<div><h4>Angiotensin-converting enzyme 2 in human plasma and lung tissue.</h4><i>Xie J, Huang QF, Zhang Z, Dong Y, ... Wang X, Wang JG</i><br /><b>Purpose</b><br />We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery.<br /><b>Materials and methods</b><br />The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (<i>n</i> = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women).<br /><b>Results</b><br />In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 <i>vs</i>. 0.98 ng/mL, <i>p</i> = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 <i>vs</i>. 53.9 a.u., <i>p</i> = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (<i>p</i> = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (<i>p</i> = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 <i>vs</i>. 0.98 ng/mL, <i>p</i> = 0.029 <i>vs</i>. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (<i>p</i> = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (<i>p</i> = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (<i>p</i> ≥ 0.20).<br /><b>Conclusion</b><br />ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary <b>What is the context?</b> • The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively. • ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection. • There is little research on ACE2 in humans, especially in the lung tissue. • In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations. <b>What is new?</b> • Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were: • In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing. • Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue. • Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs. <b>What is the impact?</b> • ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension. • A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:6-15</small></div>

<div><h4>Blood pressure responses are dependent on call type and related to hypertension status in firefighters.</h4><i>Rynne PJ, Derella CC, McMorrow C, Dickinson RL, ... Carty M, Feairheller DL</i><br /><b>Background</b><br />Impaired cardiovascular health is a concern for firefighters, with over 50% of line-of-duty deaths having cardiac causes. Many firefighters have hypertension and <25% have their blood pressure (BP) controlled. The alarm response could be an unidentified cardiac risk, but interestingly, the BP response to different calls and on-the-job activity is unknown.<br /><b>Purpose</b><br />We aimed to measure the physiological stress resulting from different call types (fire, medical) and job activity (riding apparatus, pre-alert alarms) through ambulatory BP (ABP) monitoring in a population of firefighters.<br /><b>Materials and methods</b><br />During 111 12-h work shifts firefighters wore an ABP monitor. BP was measured at 30-min intervals and manual measurements were prompted when the pager went off or whenever they felt stress.<br /><b>Results</b><br />Firefighters were hypertensive (124.3 ± 9.9/78.1 ± 6.7 mmHg), overweight (30.2 ± 4.6 kg/m<sup>2</sup>), middle-aged (40.5 ± 12.6 years) and experienced (17.3 ± 11.7 years). We calculated an average 11% increase in systolic and 10.5% increase in diastolic BP with alarm. Systolic BP (141.9 ± 13.2 mmHg) and diastolic BP (84.9 ± 11.1 mmHg) and the BP surges were higher while firefighters were responding to medical calls compared to fire calls. Between BP groups we found that medical call systolic BP (<i>p</i> = .001, <i>d</i> = 1.2), diastolic BP (<i>p</i> = .017, <i>d</i> = 0.87), and fire call systolic BP (<i>p</i> = .03, <i>d</i> = 0.51) levels were higher in the hypertensive firefighters.<br /><b>Conclusion</b><br />This is the first report of BP surge responses to alarms and to occupational activities in firefighters, and medical calls elicited the largest overall responses.PLAIN LANGUAGE SUMMARYCardiovascular disease and impaired cardiovascular health are substantially more prevalent in firefighters, with over 50% of line-of-duty deaths being cardiac related.Many firefighters are diagnosed with high blood pressure (hypertension), which is known to increase the risk of heart attacks, strokes, heart disease, and other serious health complications.Upon stress, our body enacts the \'fight or flight\' response where sympathetic nervous system activity triggers an immediate increase in heart rate and blood pressure. This response can be dangerous when surges reach extreme levels due to underlying impaired cardiovascular function. It is known that alarm sounds trigger a stress response.Firefighters respond to different alarms while on the job, each indicating different call types, such as a house fire or a medical emergency. Due to the prevalence of impaired cardiovascular health in firefighters, the physical stress resulting from these alerts is cause for concern.The blood pressure surge response to different call types and job activities in healthy and hypertensive firefighters had not been measured before this study.Through the ambulatory blood pressure monitoring of 111 on-duty firefighters, this study discovered that medical calls caused the greatest blood pressure and heart rate surge.Also, firefighters with hypertension experienced a greater blood pressure surge in response to alarms than their non-hypertensive co-workers.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2161997</small></div>

<div><h4>Current practice of blood pressure measurement in Germany: a nationwide questionnaire-based survey in medical practices.</h4><i>Beger C, Mayerböck A, Klein K, Karg T, ... Randerath O, Limbourg FP</i><br /><b>Purpose</b><br />Discrepancies exist between guideline recommendations and real-world practice of blood pressure (BP) measurements. The aim of this study was to assess, with a nationwide, questionnaire-based survey, the current practice of BP measurement and associated BP values in German medical practices.<br /><b>Material and methods</b><br />A nationwide survey in German medical practices was performed in the period from 10 May 2021 to 15 August 2021. The questionnaire was divided into five sections. The current office BP (OBP) values as well as the current drug therapy were recorded. In addition, the implementation of office BP (OBP) and home BP monitoring (HBPM) was queried. For analysis, questionnaires were scanned and automatically digitised.<br /><b>Results</b><br />A total of 7049 questionnaires were analysed, the majority of which came from general practitioners (66%) and internal medicine practices (34%). The average OBP (SD) was 140.0 (18)/82.7 (11) mmHg. 40.8% of treated patients had OBP in the controlled range, with monotherapy (34.7%) or dual combination therapy (38.2%) prescribed in most cases. OBP was taken from a single measurement in 66.3% of cases, and in 21.8% from 23 measurements. OBP was mostly measured after a rest period (87.1%) and in a separate room (80.4%). HBPM was performed in 62.3% of patients; however, in 24.9% of the participants HBP measurements were recorded once a week or less.<br /><b>Conclusion</b><br />In this nationwide survey in German medical practices, BP control remains at below 50%, while monotherapy is prescribed in around one third of patients. Moreover, office measurements and HBPM are often not performed according to current guideline recommendations.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2165901</small></div>

<div><h4>Ambulatory blood pressure monitoring in treated patients with hypertension in the COVID-19 pandemic - The study of European society of hypertension (ESH ABPM COVID-19 study).</h4><i>Wojciechowska W, Rajzer M, Weber T, Prejbisz A, ... Kreutz R, Januszewicz A</i><br /><b>Purpose</b><br />The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown profoundly affected almost all aspects of daily life including health services worldwide. The established risk factors for increased blood pressure (BP) and hypertension may also demonstrate significant changes during the pandemic. This study aims to determine the impact of the COVID-19 pandemic on BP control and BP phenotypes as assessed with 24-hour ambulatory BP monitoring (ABPM).<br /><b>Materials and methods</b><br />This is a multi-centre, observational, retrospective and comparative study involving Excellence Centres of the European Society of Hypertension across Europe. Along with clinical data and office BP, ABPM recordings will be collected in adult patients with treated arterial hypertension. There will be two groups in the study: Group 1 will consist of participants who have undergone two ABPM recordings - the second one occurring during the COVID-19 pandemic, i.e. after March 2020, and the first one 9-15 months prior to the second. Participants in Group 2 will have two repeated ABPM recordings - both performed before the pandemic within a similar 9-15 month interval between the recordings. Within each group, we will analyse and compare BP variables and phenotypes (including averaged daytime and night-time BP, BP variability, dipper and non-dipper status, white-coat and masked hypertension) between the two respective ABPM recordings and compare these changes between the two groups. The target sample size will amount to least 590 participants in each of the study groups, which means a total of at least 2360 ABPM recordings overall.<br /><b>Expected outcomes</b><br />As a result, we expect to identify the impact of a COVID-19 pandemic on blood pressure control and the quality of medical care in order to develop the strategy to control cardiovascular risk factors during unpredictable global events.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2161998</small></div>

<div><h4>Urine sodium excretion is related to extracellular water volume but not to blood pressure in 510 normotensive and never-treated hypertensive subjects.</h4><i>Taurio J, Koskela J, Sinisalo M, Tikkakoski A, ... Nevalainen P, Pörsti I</i><br /><b>Purpose</b><br />High sodium intake is an accepted risk factor for hypertension, while low Na<sup>+</sup> intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na<sup>+</sup> excretion with haemodynamics and volume status.<br /><b>Materials and methods</b><br />Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na<sup>+</sup> excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism.<br /><b>Results</b><br />The mean values of 24-h urinary Na<sup>+</sup> excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4-44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na<sup>+</sup> excretion. In regression analysis, body surface area and 24-h Na<sup>+</sup> excretion were independent explanatory variables for extracellular water volume. No differences in urine Na<sup>+</sup> excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (<i>p</i> = .003), and 24-h Na<sup>+</sup> excretion was not related with extracellular water volume.<br /><b>Conclusion</b><br />In the absence of mineralocorticoid excess, Na<sup>+</sup> intake, as evaluated from 24-h Na<sup>+</sup> excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2170869</small></div>

<div><h4>Validation of spot urine in estimating 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets in healthy adults.</h4><i>Groenland EH, Vendeville JAC, Bots ML, Visseren FLJ, Musson REA, Spiering W</i><br /><b>Purpose</b><br />To evaluate the validity of spot urine assay methods in estimating the 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets.<br /><b>Materials and methods</b><br />Twelve healthy volunteers were asked to adhere to 3 dietary sodium targets (3.3-5.0g/day,<3.3 g/day and >5.0 g/day) for three consecutive weeks and to measure salt excretion daily in spot urine samples using a self-monitoring device. On day 7 of each week, 24-h urine was collected to compare measured with estimated 24-h salt excretion (by the Kawasaki, Tanaka and INTERSALT equations).<br /><b>Results</b><br />Correlation coefficients relating measured and estimated 24-h sodium excretion were low and not significant for Kawasaki and INTERSALT and moderate for the Tanaka equation (τ 0.56-0.64,<i>p</i><.05). Bland-Altman plots showed considerable differences between estimated and measured sodium excretion across all salt diets. Over 40% of the participants showed an absolute difference between measured and estimated 24-h sodium of more than 1000 mg/day. The correlation coefficients between 24-h and spot Na/K ratio were 0.67, 0.94 and 0.85(<i>p</i><.05), and mean differences were 0.59, 0.06 and 0.48 for the intermediate, low and high sodium diets, respectively.<br /><b>Conclusion</b><br />These findings do not support estimation of individual 24-h salt excretion from spot urine by the Kawasaki, Tanaka, or INTERSALT formula. Plain language summaryAccurate monitoring of salt intake is essential to improve BP control. At present, measurement of sodium and potassium excretion in multiple non-consecutive 24-h urinary collections is considered the gold standard for measuring dietary sodium intake. However, this method is burdensome, time-consuming and error prone.Therefore, we assessed and compared the validity of three formula-based approaches to estimate 24-h urinary sodium and potassium excretion and the Na/K ratio from spot urine samples measured by a self-monitoring device under three different sodium diets using 24-h urine collections as the reference.We conclude that use of three commonly used equations that estimate 24-h urinary sodium and potassium excretion result in substantial bias, poor precision and poor accuracy and are therefore not recommended. The Na/K ratio based on multiple casual urine samples may be a useful, low-burden, low-cost alternative method to 24-h urine collection for monitoring daily salt intake.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2170868</small></div>

<div><h4>High-normal blood pressure in midlife is a stronger risk factor for incident hypertension 26 years later in women than men: the Hordaland Health Study.</h4><i>Ohldieck AE, Kringeland E, Midtbø H, Tell GS, Gerdts E</i><br /><b>Purpose</b><br />To identify modifiable risk factors in early midlife associated with incident hypertension 26 years later in women and men.<br /><b>Materials and methods</b><br />We used data from 1025 women and 703 men in the community-based Hordaland Health Study examined at the mean age of 42 years (baseline) and after a 26-year follow-up. Patients with hypertension at baseline were excluded. Blood pressure (BP) was classified according to European guidelines. Factors associated with incident hypertension were identified in logistic regression analyses.<br /><b>Results</b><br />At baseline, women had a lower average BP and a lower prevalence of high-normal BP (19% vs 37%, <i>p</i> < .05). Overall, 39% of women and 45% of men developed hypertension during follow-up (<i>p</i> < .05). Among those with high-normal BP at baseline, 72% of women and 58% of men developed hypertension (<i>p</i> < .01). In multivariable logistic regression analyses, high-normal BP at baseline was a stronger predictor of incident hypertension in women (odds ratio, OR 4.8, [95% confidence interval, CI 3.4-6.9]) than in men (OR 2.1, [95% CI 1.5-2.8]), <i>p</i> < .01 for sex interaction. A higher baseline body mass index (BMI) was associated with incident hypertension in both sexes.<br /><b>Conclusions</b><br />High-normal BP in midlife is a stronger risk factor for developing hypertension 26 years later in women than in men, independent of BMI.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2179337</small></div>

<div><h4>RAS-challenge as a first-look test for detection of primary aldosteronism in patients with treatment-resistant hypertension.</h4><i>Beger C, Karg T, Hinrichs JB, Ringe B, ... Meyer BC, Limbourg FP</i><br /><b>Purpose</b><br />Primary aldosteronism (PA), characterised by low-renin hypertension, confers a high cardiovascular risk and is the most common cause of secondary hypertension, with an increased prevalence in patients with treatment-resistant hypertension. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice. Inhibitors of the renin-angiotensin system cause an increase in renin levels in patients with intact aldosterone regulation, and inadequate low renin with concurrent RAS inhibition (RASi) may therefore indicate PA, which could serve as a first look screening test for selection for formal work-up.<br /><b>Methods</b><br />We analysed patients between 2016-2018 with treatment-resistant hypertension who had inadequate low renin in the presence of RASi (i. e. at risk for PA) and who were offered systematic work-up with adrenal vein sampling (AVS).<br /><b>Results</b><br />A total of 26 pts were included in the study (age 54.8 ± 11, male 65%). Mean office blood pressure (BP) was 154/95 mmHg on 4.5 antihypertensive drug classes. AVS had a high technical success rate (96%) and demonstrated unilateral disease in the majority of patients (57%), most of which (77%) were undetected by cross-sectional imaging.<br /><b>Conclusion</b><br />In patients with resistant hypertension, low renin in the presence of RASi is a strong indicator for autonomous aldosterone secretion. It may serve as an on-medication screening test for PA to select for formal PA work up.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2179340</small></div>

<div><h4>Kidney transplantation and kidney donation do not affect short-term blood pressure variability.</h4><i>Xagas E, Sarafidis P, Iatridi F, Theodorakopoulou MP, ... Boletis IN, Marinaki S</i><br /><b>Purpose</b><br />Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors.<br /><b>Materials and methods</b><br />Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas.<br /><b>Results</b><br />All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, <i>p</i> = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, <i>p</i> = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; <i>p</i> = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; <i>p</i> = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, <i>p</i> = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, <i>p</i> = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline.<br /><b>Conclusion</b><br />Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2181640</small></div>

<div><h4>What is resistant arterial hypertension?</h4><i>Shalaeva EV, Messerli FH</i><br /><b>Purpose</b><br />The current review is to describe the definition and prevalence of resistant arterial hypertension (RAH), the difference between refractory hypertension, patient characteristics and major risk factors for RAH, how RAH is diagnosed, prognosis and outcomes for patients.<br /><b>Materials and methods</b><br />According to the WHO, approximately 1.28 billion adults aged 30-79 worldwide have arterial hypertension, and over 80% of them do not have blood pressure (BP) under control. RAH is defined as above-goal elevated BP despite the concurrent use of 3 or more classes of antihypertensive drugs, commonly including a long-acting calcium channel blocker, an inhibitor of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a thiazide diuretic administered at maximum or maximally tolerated doses and at appropriate dosing frequency. RAH occurs in nearly 1 of 6 hypertensive patients. It often remains unrecognised mainly because patients are not prescribed ≥3 drugs at maximal doses despite uncontrolled BP.<br /><b>Conclusion</b><br />RAH distinctly increases the risk of developing coronary artery disease, heart failure, stroke and chronic kidney disease and confers higher rates of major adverse cardiovascular events as well as increased all-cause mortality. Timely diagnosis and treatment of RAH may mitigate the associated risks and improve short and long-term prognosis.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2185457</small></div>

<div><h4>Interaction between slow wave sleep and elevated office blood pressure in non-hypertensive obstructive sleep apnea patients: a cross-sectional study.</h4><i>Xia N, Wang H, Zhang L, Fan XJ, Nie XH</i><br /><AbstractText><b>Purpose:</b> Reduced slow wave sleep (SWS) has been linked to hypertension in some studies. The aim of the study is to investigate the association between SWS and office blood pressure (BP) in non-hypertensive obstructive sleep apnea (OSA). <br /><b>Methods:</b><br/>This is a retrospective study of 3350 patients who underwent polysomnography (PSG) in our hospital. Based on quartiles of percent SWS, participants were classified into four groups. BP was measured manually on the randomly chosen arm in a seated position with sphygmomanometer after PSG in the morning, and the average of the second and third measurements was used for this analysis. Elevated office BP was defined as a systolic BP≥140 mmHg or diastolic BP≥90 mmHg. <br /><b>Results:</b><br/>There were 1365 patients with OSA and 597 primary snorers included in our study. In OSA group, OSA patients with SWS <13.5% had a significant elevated risk with elevated office BP (OR,1.49[95%CI 1.05-2.10], P=0.025), compared to the highest quartile (percent SWS >39.2%). However, no significant relationship between decreased SWS and elevated office BP was found in primary snorers group. <b>Conclusion:</b> In non-hypertensive OSA patients, decreased SWS is associated with elevated office BP.</AbstractText><br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2195009</small></div>

<div><h4>A novel homozygous CYP17A1 mutation causes partial 17 α-hydroxylase/17,20-lyase deficiency in 46,XX: a case report and literature review.</h4><i>Chen H, Chen Y, Mao H, Huang H, Lou X</i><br /><AbstractText><b>Aim:</b> 17 α-hydroxylase/17,20-lyase deficiency (17-OHD) is an extremely rare autosomal recessive disorder that typically causes hypertension, hypokalaemia, primary amenorrhoea, and the absence of secondary sex characteristics in 46,XX individuals. Partial 17-OHD is even rarer than complete 17-OHD and is prone to missed diagnosis due to its subtler symptoms. The aim of this study was to help early detection and diagnosis of partial 17-OHD.<br /><b>Methods:</b><br/>We present a case of a 41-year-old female (46,XX) patient with partial 17-OHD caused by a novel missense <i>CYP17A1</i> mutation, c.391 A > C (p.T131P). This patient experienced hypertension, hypokalaemia and adrenal hyperplasia, but did not present with primary amenorrhoea or absence of secondary sex characteristics. Initially, she was misdiagnosed and underwent right and left adrenalectomy, but the procedures were ineffective. Afterward, she received a one-month treatment of 0.5 mg dexamethasone, which greatly relieved her symptoms. Additionally, we reviewed reports of thirteen other patients with partial 17-OHD in 46,XX individuals from the literature, totalling fourteen probands.<br /><b>Results:</b><br/>We found that primary amenorrhoea, hypertension, hypokalaemia, and ovarian cysts accounted for 15.4%, 42.9%, 38.5%, and 72.7% of these patients, respectively. In contrast, elevated serum progesterone was present in all patients.<b>Conclusion:</b> Based on our literature review, the absence of primary amenorrhoea, hypertension or hypokalaemia cannot rule out suspicion for 17-OHD in 46,XX individuals. However, an elevation in serum progesterone levels is a highly sensitive indicator for diagnosing 17-OHD.</AbstractText><br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2195008</small></div>

<div><h4>The associations of self-reported salt-intake and spot urine sodium with home blood pressure.</h4><i>Wistrand H, Niiranen T, Kaartinen NE, Langén VL</i><br /><AbstractText><b>Purpose:</b> A limited number of studies have suggested a nonlinear association between spot urine (SU) sodium concentration and office blood pressure (BP). We examined how SU sodium concentration and dietary salt obtained from a food frequency questionnaire are associated with more accurately measured home BP in a large, nationwide population sample.<b>Materials and methods:</b> We included 1398 participants in cross-sectional and 851 participants in 11-year longitudinal analyses. We investigated associations between baseline salt/sodium variables and (i) baseline and follow-up home BP; and (ii) prevalent and incident hypertension with linear and logistic regression models.<br /><b>Results:</b><br/>We observed positive associations (β ± standard error) between salt/sodium variables and BP in unadjusted models. SU sodium concentration associated with baseline systolic (0.04 ± 0.01, <i>p</i> < 0.001) and diastolic (0.02 ± 0.01, <i>p</i> < 0.001) BP and follow-up systolic (0.03 ± 0.01, <i>p</i> = 0.003) and diastolic (0.02 ± 0.01, <i>p</i> < 0.001) BP. Dietary salt intake was associated with baseline (0.52 ± 0.19, <i>p</i> = 0.008) and follow-up (0.57 ± 0.20, <i>p</i> = 0.006) systolic BP. Compared to the lowest quintile of SU sodium concentration, the highest quintile had greater odds of prevalent hypertension (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.12-2.19) and the second highest quintile with incident hypertension (OR 1.86, 95% CI 1.05-3.34). Unadjusted odds of incident hypertension were higher in the highest as compared to the lowest quintile of dietary salt intake (OR 1.83, 95% CI 1.01-3.35). After adjustments for sex, age, plasma creatinine concentration and alcohol intake, none of the aforementioned associations remained statistically significant. We found no evidence of a J-shaped association between the salt/sodium variables and BP or hypertension.<b>Conclusion:</b> SU sodium concentration and dietary salt intake are associated with home BP and hypertension only in some of the unadjusted models. Our results underscore that feasible estimation of sodium intake remains challenging in epidemiology.</AbstractText><br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2203267</small></div>

<div><h4>Cardiovascular organ damage in relation to hypertension status in patients with ankylosing spondylitis.</h4><i>Ullensvang G, Kringeland E, Ikdahl E, Provan S, ... Semb AG, Midtbø H</i><br /><b>Purpose</b><br />Hypertension is a major cardiovascular (CV) risk factor in ankylosing spondylitis (AS) patients. Less is known about the prevalence of CV organ damage in relation to hypertension status in AS patients.<br /><b>Materials and methods</b><br />CV organ damage was assessed by echocardiography, carotid ultrasound and pulse wave velocity (PWV) by applanation tonometry in 126 AS patients (mean age 49 ± 12 years, 39% women) and 71 normotensive controls (mean age 47 ± 11 years, 52% women). CV organ damage was defined as presence of abnormal left ventricular (LV) geometry, LV diastolic dysfunction, left atrial (LA) dilatation, carotid plaque or high pulse wave velocity (PWV).<br /><b>Results</b><br />Thirty-four percent of AS patients had hypertension. AS patients with hypertension were older and had higher C-reactive protein (CRP) levels compared to AS patients without hypertension and controls (<i>p</i> < 0.05). The prevalence of CV organ damage was 84% in AS patients with hypertension, 29% in AS patients without hypertension and 30% in controls (<i>p</i> < 0.001). In multivariable logistic regression analyses, having hypertension was associated with a fourfold increased risk of CV organ damage independent of age, presence of AS, gender, body mass index, CRP, and cholesterol (odds ratio (OR) 4.57, 95% confidence interval (CI) 1.53 to 13.61, <i>p</i> = 0.006). In AS patients, presence of hypertension was the only covariable significantly associated with presence of CV organ damage (OR 4.40, 95% CI 1.40 to 13.84, <i>p</i> = 0.011).<br /><b>Conclusions</b><br />CV organ damage in AS was strongly associated with hypertension, pointing to the importance of guideline-based hypertension management in AS patients.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2205956</small></div>

<div><h4>Duplicated adrenal veins in primary aldosteronism misdiagnosed with ectopic aldosteronoma due to apparent bilateral aldosterone suppression.</h4><i>Yu J, Fan C, Wei W, Liu H, ... Chen K, Zhang Y</i><br /><b>Background</b><br />Primary aldosteronism (PA) is considered the number one aetiology for secondary hypertension. Apart from confirmatory tests and localisation of PA determined by computed tomography (CT), adrenal venous sampling (AVS) is used to define whether aldosterone hypersecretion occurs inside one or both adrenal glands. However, even correctly-performed AVS may lead to undiagnostic results such as apparent bilateral adrenal suppression (apparent bilateral aldosterone suppression), in which the adrenal aldosterone-to-cortisol ratios (AC ratios) are decreased bilaterally compared to the peripheral blood sample, with several causes contributing to it.<br /><b>Case description</b><br />Here, we describe the case of a 48-year-old man who was referred to our department for further investigation with a history of refractory hypertension, hypokalaemia, and aortic dissection. His hypertension and hypokalaemia were initially attributed to ectopic aldosteronoma due to his adrenal CT scan and AVS results. However, the correct diagnosis of an adenoma with duplicated right adrenal veins (duplicated adrenal veins) due to apparent bilateral aldosterone suppression was confirmed during surgery.<br /><b>Conclusion</b><br />AVS is the gold standard accepted for PA subtyping, but sometimes when apparent bilateral aldosterone suppression is present, it can give ambiguous results. Duplicated right adrenal veins, may impact results, thus, AVS may not accurately provide evidence of unilateral hypersecretion for all PA patients. Repeat AVS or adrenal surgery can provide worthwhile diagnostic conclusions.<br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2209664</small></div>

<div><h4>Machine Learning-Based prediction of Post-Treatment ambulatory blood pressure in patients with hypertension.</h4><i>Hae H, Kang SJ, Kim TO, Lee PH, ... Lee CW, Park SW</i><br /><AbstractText><b>Purpose.</b> Pre-treatment prediction of individual blood pressure (BP) response to anti-hypertensive medication is important to determine the specific regimen for promptly and safely achieving a target BP. This study aimed to develop supervised machine learning (ML) models for predicting patient-specific treatment effects using 24-hour ambulatory BP monitoring (ABPM) data.<b>Materials and Methods</b>. A total of 1,129 patients who had both baseline and follow-up ABPM data were randomly assigned into training, validation and test sets in a 3:1:1 ratio. Utilising the features including clinical and laboratory findings, initial ABPM data, and anti-hypertensive medication at baseline and at follow-up, ML models were developed to predict post-treatment individual BP response. Each case was labelled by the mean 24-hour and daytime BPs derived from the follow-up ABPM.<b>Results.</b> At baseline, 616 (55%) patients had been treated using mono or combination therapy with 45 anti-hypertensive drugs and the remaining 513 (45%) patients had been untreated (drug-naïve). By using CatBoost, the difference between predicted vs. measured mean 24-hour systolic BP at follow-up was 8.4 ± 7.0 mm Hg (% difference of 6.6% ± 5.7%). The difference between predicted vs. measured mean 24-hour diastolic BP was 5.3 ± 4.3 mm Hg (% difference of 6.8% ± 5.5%). There were significant correlations between the CatBoost-predicted vs. the ABPM-measured changes in the mean 24-hour Systolic (<i>r</i> = 0.74) and diastolic (<i>r</i> = 0.68) BPs from baseline to follow-up. Even in the patients with renal insufficiency or diabetes, the correlations between CatBoost-predicted vs. ABPM-measured BP changes were significant.<b>Conclusion.</b> ML algorithms accurately predict the post-treatment ambulatory BP levels, which may assist clinicians in personalising anti-hypertensive treatment.</AbstractText><br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2209674</small></div>

<div><h4>Assessment of hypertension-mediated organ damage in children and adolescents with hypertension.</h4><i>Pac M, Obrycki Ł, Koziej J, Skoczyński K, Starnawska-Bojsza A, Litwin M</i><br /><AbstractText><b>Purpose:</b> Arterial hypertension (HT) is a main, potentially reversible cardiovascular risk factor. Long lasting HT leads to hypertension mediated organ damage (HMOD) of heart, vascular bed, and kidneys. Assessment of HMOD is a standard diagnostic procedure in hypertensive adults and presence of HMOD is associated with increased cardiovascular risk. The assessment of main HMOD markers includes the assessment of left ventricular mass, carotid intima-media thickness, arterial stiffness expressed as pulse wave velocity, and assessment of microcirculation. In contrast to adults, proper interpretation of obtained results of HMOD must be adjusted to age and sex referential values. In the last two decades, numerous studies describing HMOD in children with hypertension have been published, including meta-analyses evaluating various methods of HMOD assessment. Here, we present current state of the art and discuss recommendations on HMOD evaluation in hypertensive children.</AbstractText><br /><br /><br /><br /><small>Blood Pressure: 01 Dec 2023; 32:2212085</small></div>

<div><h4>C-Reactive Protein and Risk of Cardiovascular Events and Mortality in Patients with Various Cardiovascular Disease Locations.</h4><i>Burger PM, Pradhan AD, Dorresteijn JAN, Koudstaal S, ... Visseren FLJ, Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease study group</i><br /><AbstractText>Anti-inflammatory drugs reduce the risk of cardiovascular events in patients with coronary artery disease (CAD), but less is known about the relation between inflammation and outcomes in patients with cerebrovascular disease (CeVD), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA). This study assessed the association between C-reactive protein (CRP) and clinical outcomes in patients with CAD (n = 4,517), CeVD (n = 2,154), PAD (n = 1,154), and AAA (n = 424) from the prospective Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease study. The primary outcome was recurrent cardiovascular disease (CVD), defined as myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes were major adverse limb events and all-cause mortality. Associations between baseline CRP and outcomes were assessed using Cox proportional hazards models adjusted for age, sex, smoking, diabetes mellitus, body mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, and glomerular filtration rate. Results were stratified by CVD location. During a median follow-up of 9.5 years, 1,877 recurrent CVD events, 887 major adverse limb events, and 2,341 deaths were observed. CRP was independently associated with recurrent CVD (hazard ratio [HR] per 1 mg/L 1.08, 95% confidence interval [CI] 1.05 to 1.10), and all secondary outcomes. Compared with the first quintile of CRP, HRs for recurrent CVD were 1.60 (95% CI 1.35 to 1.89) for the last quintile ≤10 mg/L and 1.90 (95% CI 1.58 to 2.29) for the subgroup with CRP >10 mg/L. CRP was associated with recurrent CVD in patients with CAD (HR per 1 mg/L 1.08, 95% CI 1.04 to 1.11), CeVD (HR 1.05, 95% CI 1.01 to 1.10), PAD (HR 1.08, 95% CI 1.03 to 1.13), and AAA (HR 1.08, 95% CI 1.01 to 1.15). The association between CRP and all-cause mortality was stronger for patients with CAD (HR 1.13, 95% CI 1.09 to 1.16) than for patients with other CVD locations (HRs 1.06 to 1.08; p = 0.002). Associations remained consistent beyond 15 years after the CRP measurement. In conclusion, greater CRP is independently associated with an increased risk of recurrent CVD and mortality, irrespective of previous CVD location.</AbstractText><br /><br />Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 15 Jun 2023; 197:13-23</small></div>

<div><h4>Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2.</h4><i>Hageman SH, Petitjean C, Pennells L, Kaptoge S, ... Visseren FL, Dorresteijn JA</i><br /><b>Background</b><br />In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.<br /><b>Methods and results</b><br />Individuals without previous CVD or DM were included from the UK Biobank, ARIC, MESA, EPIC-NL and HNR studies (n=409,757) in whom 16,166 CVD events and 19,149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 (95%CI 0.0115; 0.0281) and hs-Troponin-T with 0.0100 (95%CI 0.0063; 0.0137). External validation was performed in the CPRD cohort (UK, n = 518,015, 12,675 CVD events). Adjustment of SCORE2 predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination (0.740 (95%CI 0.736-0.745) versus unimproved SCORE2 risk C-index 0.737 [95%CI 0.732-0.741]).<br /><b>Conclusions</b><br />The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 02 Jun 2023; epub ahead of print</small></div>

<div><h4>Periprocedural Mortality in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry.</h4><i>Simsek B, Rempakos A, Kostantinis S, Karacsonyi J, ... Burke MN, Brilakis ES</i><br /><b>Background</b><br />Death is a rare but devastating complication of chronic total occlusion (CTO) percutaneous coronary intervention.<br /><b>Methods</b><br />We examined the clinical characteristics and procedural outcomes of patients who died periprocedurally in the Prospective Global Registry for the Study of CTO Interventions (PROGRESS-CTO).<br /><b>Results</b><br />Of the 12 928 patients who underwent CTO percutaneous coronary intervention between 2012 and 2022, 52 (0.4%) died during the index hospitalization. Patients who died were more likely to have a history of heart failure (43% versus 28%; <i>P</i>=0.023). The J-CTO ([Multicenter CTO Registry of Japan]; 2.8±1.1 versus 2.4±1.3; <i>P</i>=0.019), PROGRESS-CTO mortality (2.6±0.9 versus 1.6±1.1; <i>P</i><0.001), and PROGRESS-CTO pericardiocentesis (2.9±1.1 versus 1.9±1.3; <i>P</i><0.001) scores were higher in patients who died. In these patients, the use of left ventricular assist devices was also higher (41% versus 3.5%; <i>P</i><0.001), and retrograde crossing was more often the first crossing strategy (33% versus 13%; <i>P</i><0.001). The cause of death was cardiac in 43 patients (83%) and noncardiac in 9 patients (17%). Complications leading to cardiac death were: tamponade in 30 patients (58%), acute myocardial infarction in 9 (17.3%), and cardiac arrest/shock in 4 (7.7%). Noncardiac causes of death were: stroke in 3 (5.8%), renal failure in 2 (3.8%), respiratory distress in 2 (3.8%), and hemorrhagic shock in 2 (3.8%).<br /><b>Conclusions</b><br />Approximately 0.4% of patients who underwent CTO percutaneous coronary intervention died during the index hospitalization. The main cause of death was tamponade in 58%. PROGRESS-CTO complication scores might help in risk stratification and procedural planning in patients undergoing CTO percutaneous coronary intervention.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique Identifier: NCT02061436.<br /><br /><br /><br /><small>Circ Cardiovasc Interv: 01 Jun 2023:e012977; epub ahead of print</small></div>

<div><h4>Coronary Microvascular Disease in Contemporary Clinical Practice.</h4><i>Smilowitz NR, Toleva O, Chieffo A, Perera D, Berry C</i><br /><AbstractText>Coronary microvascular disease (CMD) causes myocardial ischemia in a variety of clinical scenarios. Clinical practice guidelines support routine testing for CMD in patients with ischemia with nonobstructive coronary artery disease. Invasive testing to identify CMD requires Doppler or thermodilution measures of flow to determine the coronary flow reserve and measures of microvascular resistance. Acetylcholine coronary reactivity testing identifies concomitant endothelial dysfunction, microvascular spasm, or epicardial coronary spasm. Comprehensive testing may improve symptoms, quality of life, and patient satisfaction by establishing a diagnosis and guiding-targeted medical therapy and lifestyle measures. Beyond ischemia with nonobstructive coronary artery disease, testing for CMD may play a role in patients with acute myocardial infarction, angina following coronary revascularization, heart failure with preserved ejection fraction, Takotsubo syndrome, and after heart transplantation. Additional education and provider awareness of CMD and its role in cardiovascular disease is needed to improve patient-centered outcomes of ischemic heart disease.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Interv: 01 Jun 2023:e012568; epub ahead of print</small></div>

<div><h4>Interventional Versus Conservative Strategy in Patients With Spontaneous Coronary Artery Dissections: Insights From DISCO Registry.</h4><i>Benenati S, Giacobbe F, Zingarelli A, Macaya F, ... Porto I, DISCO Collaborators</i><br /><b>Background</b><br />The optimal management of patients with spontaneous coronary artery dissection remains debated.<br /><b>Methods</b><br />Patients enrolled in the DISCO (Dissezioni Spontanee Coronariche) Registry up to December 2020 were included. The primary end point was major adverse cardiovascular events, a composite of all-cause death, nonfatal myocardial infarction, and repeat percutaneous coronary intervention (PCI). Independent predictors of PCI and medical management were investigated.<br /><b>Results</b><br />Among 369 patients, 129 (35%) underwent PCI, whereas 240 (65%) were medically managed. ST-segment-elevation myocardial infarction (68% versus 35%, <i>P</i><0.001), resuscitated cardiac arrest (9% versus 3%, <i>P</i><0.001), proximal coronary segment involvement (32% versus 7%, <i>P</i><0.001), and Thrombolysis in Myocardial Infarction flow 0 to 1 (54% versus 20%, <i>P</i><0.001) were more frequent in the PCI arm. In-hospital event rates were similar. Between patients treated with PCI and medical therapy, there were no differences in terms of major adverse cardiovascular events at 2 years (13.9% versus 11.7%, <i>P</i>=0.467), all-cause death (0.7% versus 0.4%, <i>P</i>=0.652), myocardial infarction (9.3% versus 8.3%, <i>P</i>=0.921) and repeat PCI (12.4% versus 8.7%, <i>P</i>=0.229). ST-segment-elevation myocardial infarction at presentation (odds ratio [OR], 3.30 [95% CI, 1.56-7.12]; <i>P</i>=0.002), proximal coronary segment involvement (OR, 5.43 [95% CI, 1.98-16.45]; <i>P</i>=0.002), Thrombolysis in Myocardial Infarction flow grade 0 to 1 and 2 (respectively, OR, 3.22 [95% CI, 1.08-9.96]; <i>P</i>=0.038; and OR, 3.98 [95% CI, 1.38-11.80]; <i>P</i>=0.009) and luminal narrowing (OR per 5% increase, 1.13 [95% CI, 1.01-1.28]; <i>P</i>=0.037) were predictors of PCI, whereas the 2B-angiographic subtype predicted medical management (OR, 0.25 [95% CI, 0.07-0.83]; <i>P</i>=0.026).<br /><b>Conclusions</b><br />Clinical presentation and procedural variables drive the choice of the initial therapeutic approach in spontaneous coronary artery dissection. If PCI is needed, it seems to be associated with a similar risk of short-to-mid-term adverse events compared to medical treatment.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT04415762.<br /><br /><br /><br /><small>Circ Cardiovasc Interv: 01 Jun 2023:e012780; epub ahead of print</small></div>

<div><h4>Lifestyle patterns, genetic susceptibility, and risk of valvular heart disease: a prospective cohort study based on the UK Biobank.</h4><i>Jia C, Zeng Y, Huang X, Yang H, ... Chen W, Yang X</i><br /><b>Aims</b><br />Genetic and lifestyle factors are both major contributors to valvular heart disease (VHD). However, it is still uncertain whether genetic susceptibility alters the association between lifestyle and VHD. We aimed to investigate the association between lifestyle and VHD in different genetic risk backgrounds.<br /><b>Methods and results</b><br />A prospective cohort study was carried out on 499 341 participants without VHD at baseline. The assessment of lifestyle included smoking, alcohol consumption, diet, activity, and sleep. Genetic susceptibility was separately measured by polygenic risk scores (PRSs) and family history of cardiovascular disease (CVD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) between lifestyle and VHD, as well as aortic stenosis (AS). During a median follow-up of 10.8 years, 12 983 incident VHD cases were diagnosed (incidence rate 2.46 per 1000 person-years), including 3527 AS cases (incidence rate 0.66 per 1000 person-years). The risk of VHD and AS decreased with healthier lifestyles (P value for trend <0.001). Compared to individuals with a unhealthy lifestyle, the HRs of VHD in intermediate and healthy lifestyle groups were 0.81 (0.76-0.86) and 0.81 (0.76-0.87). The negative association between healthy lifestyle and VHD events was independent of genetic risk (P for interaction between healthy lifestyle scores and PRSs/family history of CVD was 0.723/0.763). Similar findings were obtained in analyses of AS, and a stronger negative association was found.<br /><b>Conclusion</b><br />Our study reveals that adherence to a healthy lifestyle is significantly associated with a reduced risk of VHD especially AS, irrespective of genetic susceptibility.<br /><b>Summary</b><br />Based on a cohort of around 490 000 participants, the study investigated the association between lifestyle and VHD under different stratifications of genetic risk. The study found that a healthy lifestyle was associated with a lower risk of VHD, particularly AS, independent of genetic risk. Our findings suggest that advance interventions for lifestyle may be an effective way to reduce the global burden of VHD.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur J Prev Cardiol: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Sex and age-related differences in outcomes of patients with acute myocardial infarction: MINOCA versus MIOCA.</h4><i>Canton L, Fedele D, Bergamaschi L, Foà A, ... Paolisso P, Pizzi C</i><br /><b>Background</b><br />To evaluate the impact of sex on acute myocardial infarction (AMI) patients\' clinical presentation and outcomes, comparing those with non-obstructive and obstructive coronary arteries (MINOCA vs MIOCA).<br /><b>Methods</b><br />We enrolled 2455 patients with AMI undergoing coronary angiography from January 2017 to September 2021. Patients were divided according to the type of AMI and sex: male (n=1593) and female (n=607) in MIOCA; male (n=87) and female (n=168) in MINOCA. Each cohort was further stratified based on age (≤/> 70 years). The primary endpoint (MAE) was a composite of all-cause death, recurrent AMI, and hospitalization for heart failure (HF) at follow-up. Secondary outcomes included: all-cause and cardiovascular death, recurrent AMI, HF re-hospitalization and stroke.<br /><b>Results</b><br />MINOCA patients were more likely to be females compared to MIOCA ones (p<0.001). The median follow-up was 28 [15-41] months. The unadjusted incidence of MAE was significantly higher in females compared to males, both in MINOCA [45 (26.8%) vs 12 (13.8%); p=0.018] and MIOCA cohorts [203 (33.4%) vs 428 (26.9%); p=0.002]. Age was an independent predictor of MAE in both cohorts. Among MINOCA patients, females ≤70-year-old had a higher incidence of MAE [18 (23.7%) vs 4 (5.9%); p=0.003] compared to male peers, mainly driven by a higher rate of re-hospitalization for HF (p=0.045) and recurrence of AMI (p=0.006). Only in this sub-group of MINOCA patients, female sex was an independent predictor of MAE (HR=3.09; 95%CI: 1.02-9.59; p=0.040). MINOCA females ≤70-year-old had worse outcomes than MIOCA female peers.<br /><b>Conclusion</b><br />MINOCA females ≤70-year-old had a significantly higher incidence of MAE, compared to males and MIOCA female peers, likely due to the different pathophysiology of the ischemic event.<br /><b>Trial registration</b><br />data were part of the ongoing observational study AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation. ClinicalTrials.gov Identifier: NCT03883711.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Acute Cardiovasc Care: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Intensive Blood Pressure Lowering Improves Left Ventricular Hypertrophy in Older Patients with Hypertension: The STEP Trial.</h4><i>Deng Y, Liu W, Yang X, Guo Z, ... Cai J, STEP Study Group</i><br /><b>Background</b><br />Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, its effect on cardiac remodeling remains not fully understood. This secondary analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients trial aims to determine the changes in left ventricular hypertrophy (LVH) that occur in the context of intensive SBP lowering.<br /><b>Methods</b><br />A total of 7141 older patients with hypertension were randomly assigned to intensive treatment (SBP target, 110-130 mm Hg) or standard treatment (130 to 150 mm Hg). LVH was defined according to the Peguero-Lo Presti criteria on a standard 12-lead ECG.<br /><b>Results</b><br />At baseline, the prevalence of LVH (16.6% versus 16.5%) and the mean Peguero-Lo Presti value (1811 versus 1808 μV) were comparable between the treatment groups. During a median follow-up of 3.24 years, intensive SBP lowering was associated with a significantly lower risk of new LVH occurrence (hazard ratio, 0.76 [95% CI, 0.66-0.89]; <i>P</i>=0.001) and slower progression of the mean Peguero-Lo Presti index value by -23.47 μV/y (95% CI, -34.93 to -12.01; <i>P</i>=0.000). However, the rates of regression of baseline LVH did not differ significantly. Of note, the beneficial effect of intensive SBP lowering in terms of cardiovascular events (hazard ratio, 0.75 [95% CI, 0.59-0.97]) was not markedly attenuated after adjusting for LVH as a time-varying covariate (hazard ratio, 0.76 [95% CI, 0.59-0.97]).<br /><b>Conclusions</b><br />Intensive SBP lowering protects against LVH development in older hypertensive patients, however, this favorable effect could not explain most of the reduction in cardiovascular events associated with intensive SBP lowering.<br /><br /><br /><br /><small>Hypertension: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.</h4><i>Morinaga J, Kashiwabara K, Torigoe D, Okadome Y, ... Nagai R, Oike Y</i><br /><b>Background</b><br />The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients.<br /><b>Methods</b><br />We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease]).\" From that study\'s full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization.<br /><b>Results</b><br />Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 <pmol/L, hazard ratio in Q4: 1.74, [95% CI, 1.04-2.93]).<br /><b>Conclusions</b><br />Monitoring ANGPTL8 levels over time might be useful to assess residual risk of cardiovascular secondary events in patients with cardiovascular disease undergoing statin therapy.<br /><br /><br /><br /><small>Arterioscler Thromb Vasc Biol: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Rationale and Design of the ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) Study.</h4><i>Moulson N, Petek BJ, Ackerman MJ, Churchill TW, ... Baggish AL, Drezner JA</i><br /><AbstractText><br /><b>Background:</b><br/>Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden death are based largely on expert consensus with a paucity of prospective outcomes data. Recent guidelines have taken a more permissive approach, using a shared decision-making model. However, the impact and outcomes of this strategy remain unknown. Methods The ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) study is a prospective, multicenter, longitudinal, observational cohort study designed to monitor clinical outcomes in athletes with potentially life-threatening cardiovascular conditions. The study will assess sports eligibility decision-making, exercise habits, psychosocial well-being, and long-term cardiovascular outcomes among young competitive athletes with cardiovascular conditions. Competitive athletes aged 18 to <35 years diagnosed with a confirmed cardiovascular condition or borderline finding with potential increased risk of major adverse cardiovascular events are eligible. Outcomes will be monitored for an initial 5-year follow-up period or until age 35, and metrics of psychosocial well-being and composite adverse cardiovascular events including arrhythmias, sudden cardiac arrest/sudden cardiac death, and evidence of disease progression will be compared among athletes who continue versus discontinue competitive sports participation. <br /><b>Conclusions:</b><br/>The ORCCA study aims to assess the process and results of return to sport decision-making and to monitor major adverse cardiovascular events, exercise habits, and the psychosocial well-being among young competitive athletes diagnosed with confirmed cardiovascular conditions or borderline findings with potential increased risk of major adverse cardiovascular events. The results of this work will generate an evidence base to inform future guidelines.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029052; epub ahead of print</small></div>

<div><h4>Risk of Cardiovascular Disease in Women With a History of Hyperemesis Gravidarum, With and Without Preeclampsia.</h4><i>Cécile B, Potter BJ, Lewin A, Healy-Profitós J, Brousseau É, Auger N</i><br /><AbstractText><br /><b>Background:</b><br/>Hyperemesis gravidarum is associated with preeclampsia, but it is unclear whether hyperemesis gravidarum is a risk factor for cardiovascular disease. We assessed the long-term risk of cardiovascular disease in women who experienced hyperemesis gravidarum with or without preeclampsia. Methods and Results We analyzed a longitudinal cohort of 1 413 166 pregnant women in Quebec between 1989 and 2021. Women were followed from their first pregnancy up to 3 decades later. We computed hazard ratios (HRs) and 95% CIs for the association of hyperemesis gravidarum, preeclampsia, or both conditions with subsequent risk of cardiovascular hospitalization using Cox regression models adjusted for baseline characteristics. Among 1 413 166 women, 16 288 (1.2%) had hyperemesis gravidarum only, 69 645 (4.9%) preeclampsia only, and 1103 (0.08%) had both conditions. After 32 years of follow-up, cardiovascular disease incidence was 17.7 per 100 women with hyperemesis gravidarum only, 28.2 per 100 women with preeclampsia only, 30.9 per 100 women with both exposures, and 14.0 per 100 women with neither exposure. Compared with no exposure, women with both hyperemesis and preeclampsia had the greatest risk of cardiovascular hospitalization (HR, 3.54 [95% CI, 3.03-4.14]), followed by women with preeclampsia only (HR, 2.58 [95% CI, 2.51-2.64]) and hyperemesis only (HR, 1.46 [95% CI, 1.38-1.54]). Having both hyperemesis gravidarum and preeclampsia was strongly associated with valve disease (HR, 3.38 [95% CI, 1.69-6.75]), heart failure (HR, 3.43 [95% CI, 1.79-6.59]), and cardiomyopathy (HR, 4.17 [95% CI, 1.99-8.76]). <br /><b>Conclusions:</b><br/>Hyperemesis gravidarum is associated with the development of cardiovascular disease, whether preeclampsia is present or not.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029298; epub ahead of print</small></div>

<div><h4>Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum.</h4><i>Wilkinson MJ, Lepor NE, Michos ED</i><br /><AbstractText>Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual\'s ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from \"primary\" versus \"secondary\" prevention to a \"continuum of risk.\" The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:eJAHA2022028892; epub ahead of print</small></div>

<div><h4>Comparison between ticagrelor and clopidogrel in myocardial infarction patients with high bleeding risk- A report from the SWEDEHEART registry.</h4><i>Tjerkaski J, Jernberg T, Alfredsson J, Erlinge D, ... Venetsanos D, Szummer K</i><br /><b>Aims</b><br />Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR.<br /><b>Methods and results</b><br />This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. HBR was defined as a PRECISE-DAPT score ≥ 25. Information on ischemic events, major bleeding and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25,042 HBR patients, of whom 11,848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69,040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect.<br /><b>Conclusions</b><br />We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>The impact of diabetes on the relationship of coronary artery disease and outcome: a study using multimodality imaging.</h4><i>Mäenpää M, Kujala I, Harjulahti E, Stenström I, ... Saraste A, Maaniitty T</i><br /><b>Background</b><br />Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). The aim of the present study was to study whether diabetes changes the relationship of CAD and long-term outcome.<br /><b>Methods</b><br />We retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was evaluated by <sup>15</sup>O-water PET myocardial perfusion imaging. The relationship of the phenotype of CAD and long-term outcome in patients with no diabetes, prediabetes, or type 2 diabetes was investigated. A composite endpoint included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP).<br /><b>Results</b><br />A total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of median follow-up, 164 adverse events occurred (106 deaths, 41 MIs, 17 UAPs). The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients. The event rate was lowest in patients with normal coronary arteries and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 0.2% vs. 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings.<br /><b>Conclusions</b><br />Coronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in non-diabetic and diabetic patients.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 31 May 2023; 22:129</small></div>

<div><h4>Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis.</h4><i>Ahmed AI, Al Rifai M, Alahdab F, Saad JM, ... Zoghbi WA, Al-Mallah MH</i><br /><b>Aims</b><br />Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease.<br /><b>Methods and results</b><br />Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection. Myocardial flow reserve (MFR) was calculated as the ratio of stress to rest myocardial blood flow (MBF) in mL/min/g of the left ventricle. Comparisons between cases and controls were made for the odds and prevalence of impaired MFR (MFR < 2). We included 271 cases matched to 815 controls (mean ± SD age 65 ± 12 years, 52% men). The median (inter-quartile range) number of days between COVID-19 infection and PET imaging was 174 (58-338) days. Patients with prior COVID-19 had a statistically significant higher odds of MFR <2 (adjusted odds ratio 3.1, 95% confidence interval 2.8-4.25 P < 0.001). Results were similar in clinically meaningful subgroups. The proportion of cases with MFR <2 peaked 6-9 months from imaging with a statistically non-significant downtrend afterwards and was comparable across SARS-CoV-2 variants but increased with increasing severity of infection.<br /><b>Conclusion</b><br />The prevalence of impaired MFR is similar by duration of time from infection up to 1 year and SARS-CoV-2 variants, but significantly differs by severity of infection.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 31 May 2023; epub ahead of print</small></div>

<div><h4>Status of Maternal Cardiovascular Health in American Indian and Alaska Native Individuals: A Scientific Statement From the American Heart Association.</h4><i>Sharma G, Kelliher A, Deen J, Parker T, ... American Heart Association Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology; Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Quality of Care and Outcomes Research</i><br /><AbstractText>Cardiovascular disease is the leading cause of pregnancy-related death in the United States. American Indian and Alaska Native individuals have some of the highest maternal death and morbidity rates. Data on the causes of cardiovascular disease-related death in American Indian and Alaska Native individuals are limited, and there are several challenges and opportunities to improve maternal cardiovascular health in this population. This scientific statement provides an overview of the current status of cardiovascular health among American Indian and Alaska Native birthing individuals and causes of maternal death and morbidity and describes a stepwise multidisciplinary framework for addressing cardiovascular disease and cerebrovascular disease during the preconception, pregnancy, and postpartum time frame. This scientific statement highlights the American Heart Association\'s factors for cardiovascular health assessment known collectively as Life\'s Essential 8 as they pertain to American Indian and Alaska Native birthing individuals. It summarizes the impact of substance use, adverse mental health conditions, and lifestyle and cardiovascular disease risk factors, as well as the cascading effects of institutional and structural racism and the historical trauma faced by American Indian and Alaska Native individuals. It recognizes the possible impact of systematic acts of colonization and dominance on their social determinants of health, ultimately translating into worse health care outcomes. It focuses on the underreporting of American Indian and Alaska Native disaggregated data in pregnancy and postpartum outcomes and the importance of engaging key stakeholders, designing culturally appropriate care, building trust among communities and health care professionals, and expanding the American Indian and Alaska Native workforce in biomedical research and health care settings to optimize the cardiovascular health of American Indian and Alaska Native birthing individuals.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Qual Outcomes: 31 May 2023:e000117; epub ahead of print</small></div>

<div><h4>Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft Surgery for Left Main Disease in Patients With and Without Acute Coronary Syndromes: A Pooled Analysis of 4 Randomized Clinical Trials.</h4><i>Gaba P, Christiansen EH, Nielsen PH, Murphy SA, ... Holm NR, Bergmark BA</i><br /><b>Importance</b><br />Patients with left main coronary artery disease presenting with an acute coronary syndrome (ACS) represent a high-risk and understudied subgroup of patients with atherosclerosis.<br /><b>Objective</b><br />To assess clinical outcomes after PCI vs CABG in patients with left main disease with vs without ACS.<br /><b>Design, setting, and participants</b><br />Data were pooled from 4 trials comparing PCI with drug-eluting stents vs CABG in patients with left main disease who were considered equally suitable candidates for either strategy (SYNTAX, PRECOMBAT, NOBLE, and EXCEL). Patients were categorized as presenting with or without ACS. Kaplan-Meier event rates through 5 years and Cox model hazard ratios were generated, and interactions were tested. Patients were enrolled in the individual trials from 2004 through 2015. Individual patient data from the trials were pooled and reconciled from 2020 to 2021, and the analyses pertaining to the ACS subgroup were performed from March 2022 through February 2023.<br /><b>Main outcomes and measures</b><br />The primary outcome was death through 5 years. Secondary outcomes included cardiovascular death, spontaneous myocardial infarction (MI), procedural MI, stroke, and repeat revascularization.<br /><b>Results</b><br />Among 4394 patients (median [IQR] age, 66 [59-73] years; 3371 [76.7%] male and 1022 [23.3%] female) randomized to receive PCI or CABG, 1466 (33%) had ACS. Patients with ACS were more likely to have diabetes, prior MI, left ventricular ejection fraction less than 50%, and higher SYNTAX scores. At 30 days, patients with ACS had higher all-cause death (hazard ratio [HR], 3.40; 95% CI, 1.81-6.37; P < .001) and cardiovascular death (HR, 3.21; 95% CI, 1.69-6.08; P < .001) compared with those without ACS. Patients with ACS also had higher rates of spontaneous MI (HR, 1.70; 95% CI, 1.25-2.31; P < .001) through 5 years. The rates of all-cause mortality through 5 years with PCI vs CABG were 10.9% vs 11.5% (HR, 0.93; 95% CI, 0.68-1.27) in patients with ACS and 11.3% vs 9.6% (HR, 1.19; 95% CI, 0.95-1.50) in patients without ACS (P = .22 for interaction). The risk of early stroke was lower with PCI vs CABG (ACS: HR, 0.39; 95% CI, 0.12-1.25; no ACS: HR, 0.35; 95% CI, 0.16-0.75), whereas the 5-year risks of spontaneous MI and repeat revascularization were higher with PCI vs CABG (spontaneous MI: ACS: HR, 1.74; 95% CI, 1.09-2.77; no ACS: HR, 3.03; 95% CI, 1.94-4.72; repeat revascularization: ACS: HR, 1.57; 95% CI, 1.19-2.09; no ACS: HR, 1.90; 95% CI, 1.54-2.33), regardless of ACS status.<br /><br /><b>Conclusion:</b><br/>and relevance</b><br />Among largely stable patients undergoing left main revascularization and with predominantly low to intermediate coronary anatomical complexity, those with ACS had higher rates of early death. Nonetheless, rates of all-cause mortality through 5 years were similar with PCI vs CABG in this high-risk subgroup. The relative advantages and disadvantages of PCI vs CABG in terms of early stroke and long-term spontaneous MI and repeat revascularization were consistent regardless of ACS status.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifiers: NCT00114972, NCT00422968, NCT01496651, NCT01205776.<br /><br /><br /><br /><small>JAMA Cardiol: 31 May 2023; epub ahead of print</small></div>

<div><h4>Systolic Blood Pressure Control Targets to Prevent Major Cardiovascular Events and Mortality in Patients With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.</h4><i>Yang Q, Zheng R, Wang S, Zhu J, ... Bi Y, Xu Y</i><br /><b>Background</b><br />Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included trials published before 2015. We aimed to identify the optimal SBP control targets in patients with type 2 diabetes using a systematic review and network meta-analysis of accumulating evidence.<br /><b>Methods</b><br />We systematically searched PubMed, Embase, and Cochrane Library from inception to August 29, 2022 for randomized controlled trials comparing different blood pressure targets, antihypertensive agents against placebo, or dual antihypertensive agents against single agent in patients with type 2 diabetes. Network meta-analysis was used to obtain pooled results of direct and indirect comparisons of each 5 mm Hg SBP category in association with clinical outcomes adjusted for baseline risk and intervention duration (PROSPERO [International Prospective Register of Systematic Reviews], CRD 42022316697).<br /><b>Results</b><br />We identified 30 trials including 59 934 patients with type 2 diabetes. The mean achieved SBP levels ranged from 117 mm Hg to 144 mm Hg among treatment groups. A total of 7799 major cardiovascular diseases events and 4130 deaths were reported. The lowest risk of major cardiovascular diseases was found in patients with achieved SBP level of 120 to 124 mm Hg. The hazard ratio and 95% CI were 0.73 (0.52-1.02) compared with 130 to 134 mm Hg, 0.60 (0.41-0.85) compared with 140 to 144 mm Hg, and 0.41 (0.26-0.63) compared with ≥150 mm Hg. Similar results were found for cardiovascular diseases components including stroke, myocardial infarction, heart failure, and cardiovascular mortality. All-cause mortality was reduced at an achieved SBP <140 mm Hg but further reduction did not show additional benefits.<br /><b>Conclusions</b><br />Our findings support an intensive blood pressure-lowering strategy to prevent major cardiovascular diseases in patients with type 2 diabetes.<br /><br /><br /><br /><small>Hypertension: 31 May 2023; epub ahead of print</small></div>

<div><h4>Blood Pressure and Cardiovascular Disease Mortality Among US Adults: A Sex-Stratified Analysis, 1999-2019.</h4><i>Elfassy T, German C, Muntner P, Choi E, ... Shimbo D, Yang E</i><br /><b>Background</b><br />Most research examining the association between blood pressure (BP) and cardiovascular disease (CVD) is sex-agnostic. Our goal was to assess sex-specific associations between BP and CVD mortality.<br /><b>Methods</b><br />We combined ten cycles of the National Health and Nutrition Examination Survey (1999-2018), N=53 289. Blood pressure was measured 3× and averaged. Data were linked to National Death Index data, and CVD mortality through December 31, 2019, was defined from <i>International Classification of Diseases, Tenth Revision</i> codes. We estimated sex-stratified, multivariable-adjusted incidence rate ratios (IRRs) for CVD mortality.<br /><b>Results</b><br />Over a median follow-up of 9.5 years, there were 2405 CVD deaths. Associations between categories of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with CVD mortality differed by sex (<i>P</i><0.01). Among men, compared with SBP of 100 to <110 mm Hg, CVD mortality was 76% higher with SBP ≥160 mm Hg (IRR, 1.76 [95% CI, 1.27-2.44]). Among women, compared with SBP 100 to < 110 mm Hg, CVD mortality was 61% higher with SBP 130 to 139 mm Hg (IRR, 1.61 [95% CI, 1.02-2.55]), 75% higher with SBP 140 to 159 mm Hg (IRR, 1.75 [95% CI, 1.09-2.80]), and 113% higher with SBP≥160 mm Hg (IRR, 2.13 [95% CI, 1.35-3.36]). Compared with DBP 70 to <80 mm Hg, CVD mortality was higher with DBP <70 mm Hg and DBP≥80 mm Hg among men, and higher with DBP <50 mm Hg and DBP≥80 mm Hg among women.<br /><b>Conclusions</b><br />The association between BP and CVD mortality differed by sex, with increased CVD mortality risk present at lower levels of systolic blood pressure among women compared with men.<br /><br /><br /><br /><small>Hypertension: 31 May 2023; epub ahead of print</small></div>

<div><h4>Subclinical Cardiovascular Disease in US Adults With and Without Diabetes.</h4><i>Fang M, Wang D, Tang O, McEvoy JW, ... Christenson RH, Selvin E</i><br /><AbstractText><br /><b>Background:</b><br/>We characterized the burden and prognostic value of subclinical cardiovascular disease (CVD) assessed by cardiac biomarkers among adults with and without diabetes in the general US population. Methods and Results We measured hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum samples from the 1999 to 2004 National Health and Nutrition Examination Survey. Among US adults without a history of CVD (n=10 304), we estimated the prevalence of elevated hs-cTnT (≥14 ng/L) and NT-proBNP (≥125 pg/mL) in those with and without diabetes. We examined the associations between elevated hs-cTnT and NT-proBNP with all-cause and CVD mortality after adjustment for demographics and traditional CVD risk factors. The crude prevalence of subclinical CVD (elevated hs-cTnT or NT-proBNP) was ≈2 times higher in adults with (versus without) diabetes (33.4% versus 16.1%). After age adjustment, elevated hs-cTnT, but not elevated NT-proBNP, was more common in those with diabetes, overall and across age, sex, race and ethnicity, and weight status. The prevalence of elevated hs-cTnT was significantly higher in those with longer diabetes duration and worse glycemic control. In persons with diabetes, elevated hs-cTnT and NT-proBNP were independently associated with all-cause mortality (adjusted hazard ratio [HR], 1.77 [95% CI, 1.33-2.34] and HR, 1.78 [95% CI, 1.26-2.51]) and CVD mortality (adjusted HR, 1.54 [95% CI, 0.83-2.85] and HR, 2.46 [95% CI, 1.31-4.60]). <br /><b>Conclusions:</b><br/>Subclinical CVD affects ≈1 in 3 US adults with diabetes and confers substantial risk for mortality. Routine testing of cardiac biomarkers may be useful for assessing and monitoring risk in persons with diabetes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 31 May 2023:e029083; epub ahead of print</small></div>

<div><h4>Fixed dose combination therapies in primary cardiovascular disease prevention in different groups: an individual participant meta-analysis.</h4><i>Dagenais GR, Pais P, Gao P, Roshandel G, ... Joseph P, Yusuf S</i><br /><b>Objective</b><br />To evaluate the effects of fixed dose combination (FDC) medications on cardiovascular outcomes in different age groups in an individual participant meta-analysis of three primary prevention randomised trials.<br /><b>Methods</b><br />Participants at intermediate risk (17.7% mean 10-year Framingham Cardiovascular Risk Score), randomised to FDC of two or more antihypertensives and a statin with or without aspirin, or to their respective control, were followed up for 5 years. Age groups were <60, 60-65 and ≥65 years. The primary outcome was cardiovascular death, myocardial infarction, stroke or revascularisation. Cox proportional HRs and 95% CIs were computed within each age group.<br /><b>Results</b><br />The primary outcome risk was reduced by 37% (3.3% in FDC vs 5.2% in control (HR 0.63; 95% CI 0.54 to 0.74)) in the total population of 18 162 participants with larger benefits in older groups (HR 0.58; 95% CI 0.42 to 0.78, 60 to 65 years) and (HR 0.57; 95% CI 0.47 to 0.70, ≥65 years), as were their numbers needed to treat to avoid one primary outcome: 53 and 33, respectively. The primary outcome risk was reduced in the two oldest groups with FDC with aspirin (n=8951) by 54% and 54%, and without aspirin (n=12 061) by 34% and 38%. Dizziness, the most frequent FDC adverse effects, was higher in participants aged <65 years. Aspirin was not associated with significant bleeding excess.<br /><b>Conclusions</b><br />In participants with intermediate cardiovascular risk, FDCs produce larger cardiovascular benefits in older individuals, which appear greater with aspirin.<br /><b>Trial registration number</b><br />HOPE-3, NCT00468923; TIPS-3, NCT016464137; PolyIran, NCT01271985.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 31 May 2023; epub ahead of print</small></div>

<div><h4>Evaluation of hospital readmission rates as a quality metric in adult cardiac surgery.</h4><i>Ebrahimian S, Bakhtiyar SS, Verma A, Williamson C, ... Sanaiha Y, Benharash P</i><br /><b>Objective</b><br />To assess the reliability of 30-day non-elective readmissions as a quality metric for adult cardiac surgery.<br /><b>Background</b><br />Unplanned readmissions is a quality metric for adult cardiac surgery. However, its reliability in benchmarking hospitals remains under-explored.<br /><b>Methods</b><br />Adults undergoing elective isolated coronary artery bypass grafting (CABG), surgical aortic valve replacement/repair (SAVR) or mitral valve replacement/repair (MVR) were tabulated from 2019 Nationwide Readmissions Database. Multi-level regressions were developed to model the likelihood of 30-day unplanned readmissions and major adverse events (MAE). Random intercepts were estimated, and associations between hospital-specific risk-adjusted rates of readmissions and were assessed using the Pearson correlation coefficient (r).<br /><b>Results</b><br />Of an estimated 86 024 patients meeting study criteria across 298 hospitals, 62.6% underwent CABG, 22.5% SAVR and 14.9% MVR. Unadjusted readmission rates following CABG, SAVR and MVR were 8.4%, 9.3% and 11.8%, respectively. Unadjusted MAE rates following CABG, SAVR and MVR were 35.1%, 32.3% and 37.0%, respectively. Following adjustment, interhospital differences accounted for 4.1% of explained variance in readmissions for CABG, 7.6% for SAVR and 10.0% for MVR. There was no association between readmission rates for CABG and SAVR (r=0.10, p=0.09) or SAVR and MVR (r=0.09, p=0.1). A weak association was noted between readmission rates for CABG and MVR (r=0.20, p<0.001). There was no significant association between readmission and MAE for CABG (r=0.06, p=0.2), SAVR (r=0.04, p=0.4) and MVR (r=-0.03, p=0.6).<br /><b>Conclusion</b><br />Our findings suggest that readmissions following adult cardiac surgery may not be an ideal quality measure as hospital factors do not appear to influence this outcome.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 31 May 2023; epub ahead of print</small></div>

<div><h4>Ten-Year Cardiovascular Disease Risk Score and Cognitive Function Among Older Adults: The National Health and Nutrition Examination Survey 2011 to 2014.</h4><i>Wei J, Xu H, Liese AD, Merchant AT, ... Wang T, Friedman DB</i><br /><AbstractText><br /><b>Background:</b><br/>The Framingham 10-year cardiovascular disease risk score, which is based on age, sex, smoking, total cholesterol, high-density lipoprotein-cholesterol, blood pressure, and diabetes, has been found to be associated with cognitive health, but these findings have not been validated in a representative sample in the United States. We aimed to examine the associations of Framingham risk score with cognitive function among older adults in a nationally representative sample, as well as by race or ethnicity, education, and family income. Methods and Results A total of 2254 older adults ≥60 years (57% female, 79% non-Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included in the final sample for analysis. All components of the Framingham risk score were obtained with questionnaire or measured in the laboratory. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer\'s Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test, and Animal Fluency Test. Multivariable linear regression models were used to assess the associations between Framingham risk score and test-specific and global cognition <i>Z</i> scores. Each incremental 5% in Framingham 10-year cardiovascular disease risk was associated with lower <i>Z</i> scores for Digit Symbol Substitution Test (β=-0.06 [95% CI, -0.09 to -0.03]), delayed memory (β=-0.05 [95% CI, -0.08 to -0.01]), immediate memory (β=-0.07 [95% CI, -0.10 to -0.03]), and global cognition (β=-0.05 [95% CI, -0.09 to -0.02]). Socioeconomic status, particularly race or ethnicity and monthly income levels, were strong effect measure modifiers of the associations. <br /><b>Conclusions:</b><br/>Lower cardiovascular risk factors are associated with better cognitive function.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 May 2023:e028527; epub ahead of print</small></div>

<div><h4>Cardiovascular complications in chronic kidney disease - A review from the European Renal and Cardiovascular Medicine Working Group (EURECA-m) of the European Renal Association (ERA).</h4><i>Zoccali C, Mallamaci F, Adamczak M, de Oliveira RB, ... Vanholder R, Wiecek A</i><br /><AbstractText>Chronic kidney disease (CKD) is classified into 5 stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called \"uremic toxins\" and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure occurs early in CKD and reaches a prevalence of 70%-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter- 2 (SGLT2) inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Cardiovasc Res: 30 May 2023; epub ahead of print</small></div>

<div><h4>A gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance.</h4><i>Bigossi M, Maroteau C, Dawed AY, Taylor A, ... Palmer CNA, Siddiqui MK</i><br /><b>Background:</b><br/>and aims</b><br />The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma concentration of the drug and its metabolites. Current pharmacogenetic guidelines require sequencing of the SLCO1B1 gene, which is more expensive and less accessible than genotyping. In this study we aimed to develop an easy, clinically implementable functional gene risk score (GRS) of common variants in SLCO1B1 to identify patients at risk of statin intolerance.<br /><b>Methods and results</b><br />A GRS was developed from four common variants in SLCO1B1. In statin users from Tayside Scotland, UK, those with a high-risk GRS had increased odds across three phenotypes of statin intolerance (general statin intolerance: ORGSI 2.42[95%CI:1.29, 4.31], p = 0.003; statin-related myopathy ORSRM 2.51[95%CI:1.28, 4.53], p = 0.004; statin-related suspected rhabdomyolysis: ORSRSR 2.85[95%CI:1.03, 6.65], p = 0.02). In contrast, using the Val174Ala genotype alone or the recommended OATP1B1 functional phenotypes produced weaker and less reliable results. A meta-analysis with results from adjudicated cases of statin-induced myopathy in the PREDICTION-ADR Consortium confirmed these findings (ORVal174Ala 1.99 [95%CI:1.01, 3.95], p = 0.048; ORGRS 1.76 [95%CI:1.16, 2.69], p = 0.008). For those requiring high-dose statin therapy, the high-risk GRS was more consistently associated with the time to onset of statin intolerance amongst the three phenotypes compared to Val174Ala (general statin intolerance: HRVal174Ala 2.49 [95%CI:1.09, 5.68], p = 0.03; HRGRS 2.44 [95%CI:1.46, 4.08], p < 0.001). Finally, sequence kernel association testing (SKAT) confirmed rare variants in SLCO1B1 are associated with the risk of intolerance (p = 0.02).<br /><b>Conclusions</b><br />We provide evidence that a gene risk score based on four common SLCO1B1 variants provides an easily implemented genetic tool that is more reliable than the current recommended practice in estimating the risk and predicting early onset statin intolerance.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 30 May 2023; epub ahead of print</small></div>

<div><h4>Serum uric acid to creatinine ratio and risk of preeclampsia and adverse pregnancy outcomes.</h4><i>Piani F, Agnoletti D, Baracchi A, Scarduelli S, ... Borghi C, HDP Bologna Study Group</i><br /><b>Objective</b><br />Preeclampsia is one of the most severe diseases among the hypertensive disorders of pregnancy (HDP) and the leading cause of maternal and fetal morbidity and mortality. It is of crucial importance to early identify women at a high risk for preeclampsia to implement appropriate preventive strategies. In our study, we aimed to test the hypothesis that serum uric acid to creatinine ratio (SUA/sCr) is related to the development of preeclampsia and maternal and neonatal complications.<br /><b>Methods</b><br />We searched for uric acid and creatine values in the medical records of 269 women who consecutively attended our HDP Clinic from December 2018 to December 2022. We compared the baseline characteristics of participants with normotensive pregnancy (n = 57), to those with HDP without preeclampsia (HDP-non-PE) (n = 100) and those with preeclampsia (n = 112), and we performed adjusted logistic regression analysis to test the associations between SUA/sCr and the development of preeclampsia and maternal and neonatal complications.<br /><b>Results</b><br />SUA/sCr was consistently higher in women with preeclampsia in all trimesters of pregnancy. Higher SUA/sCr at the third trimester was associated with an increased odd of developing preeclampsia [odds ratio (OR) 1.29, confidence interval (CI) 1.15-1.50, P = 0.001], preterm birth (OR 1.23, CI 1.05-1.45, P = 0.011), and composite neonatal outcome (OR 1.33, CI 1.12-1.59, P = 0.001), after adjustment for age, BMI before pregnancy, nulliparity, antihypertensive therapy, and acetylsalicylic acid therapy during pregnancy.<br /><b>Conclusions</b><br />Having higher SUA/sCr during pregnancy is associated with the development of PE and adverse pregnancy outcomes. Controlled prospective studies are warranted to clarify the predictive power of this novel marker during pregnancy.<br /><br />Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.<br /><br /><small>J Hypertens: 30 May 2023; epub ahead of print</small></div>

<div><h4>Long-Term Outcomes of Patients With Carotid and Aortic Body Tumors.</h4><i>Verghis NM, Brown JA, Yousef S, Aranda-Michel E, ... Singh M, Sultan I</i><br /><AbstractText>Chemodectomas are tumors derived from parasympathetic nonchromaffin cells and are often found in the aortic and carotid bodies. They are generally benign but can cause mass-effect symptoms and have local or distant spread. Surgical excision has been the main curative treatment strategy. The National Cancer Database was reviewed to study all patients with carotid or aortic body tumors from 2004 to 2015. Demographic data, tumor characteristics, treatment strategies, and patient outcomes were examined, split by tumor location. Kaplan-Meier survival estimates were generated for both locations. In total, 248 patients were examined, with 151 having a tumor in the carotid body and 97 having a tumor in the aortic body. Many variables were similar between both tumor locations. However, aortic body tumors were larger than those in the carotid body (477.80 ± 477.58 mm vs 320.64 ± 436.53 mm, p = 0.008). More regional lymph nodes were positive in aortic body tumors (65.52 ± 45.73 vs 35.46 ± 46.44, p <0.001). There were more distant metastases at the time of diagnosis in carotid body tumors (p = 0.003). Chemotherapy was used more for aortic body tumors (p = 0.001); surgery was used more for carotid body tumors (p <0.001). There are slight differences in tumor characteristics and response to treatment. Surgical resection is the cornerstone of management, and radiation can often be considered. In conclusion, chemodectomas are generally benign but can present with metastasis and compressive symptoms that make understanding their physiology and treatment important.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 30 May 2023; 199:78-84</small></div>

<div><h4>Aortic Root Geometry following Composite Valve Graft Implantation - Implications for Future Valve-in-valve Procedures.</h4><i>Werner P, Kuscu BS, Coti I, Puchner S, ... Andreas M, Ehrlich M</i><br /><b>Objectives</b><br />Biological composite valve grafts (CVGs) are being performed more frequently, which increases the need for interventions treating bioprosthetic valve failure. The feasibility of valve-in-valve (ViV) procedures in this population is uncertain. This study aimed to assess changes in aortic root geometry and coronary height following CVG implantation to better understand future interventions.<br /><b>Methods</b><br />We retrospectively identified 64 patients following bioprosthetic CVG replacement with pre- and postoperative computed tomography angiography. Root assessment was conducted as in preprocedural transcatheter aortic valve evaluation using a virtual valve simulation.<br /><b>Results</b><br />In 64 patients (age 67.6±9.3 years, 76.6% male) the preoperative coronary height was 14.3±6.8 mm for the left coronary artery (LCA) and 17.9±5.9 mm for the right coronary artery (RCA), which significantly decreased after CVG implantation, with 8.7±4.4 mm for the LCA and 11.3±4.4 mm for the RCA (p<0.001). The virtual valve-to-coronary distances measured 4.0±1.3 mm (LCA) and 4.6±1.4 mm (RCA). Overall, 59.4% (n=38) of patients with bio-CVGs would have been at risk for coronary obstruction, 29.7% (n=19) for LCA, 10.9% (n=7) for RCA and 18.8% (n=12) for combined LCA and RCA.<br /><b>Conclusions</b><br />Coronary height significantly decreased following CVG implantation. The majority of patients after bio-CVG were at a potential risk for coronary obstruction in future ViV procedures. Further studies are needed to identify the best possible technique for coronary reimplantation and other measures to diminish the risk for future coronary obstruction in this population.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Thorac Cardiovasc Surg: 30 May 2023; epub ahead of print</small></div>

<div><h4>SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.</h4><i>SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration </i><br /><b>Aims</b><br />To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.<br /><b>Methods and results</b><br />SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals\' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.<br /><b>Conclusion</b><br />SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 29 May 2023; epub ahead of print</small></div>

<div><h4>Outcomes of Transcatheter Aortic Valve Implantation in Nonagenarians and Octogenarians (Analysis from the National Inpatient Sample Database).</h4><i>Ismayl M, Aboud Abbasi M, Al-Abcha A, Robertson S, ... Guerrero M, Anavekar NS</i><br /><AbstractText>Risks among nonagenarian (age ≥90 years) and octogenarian (age 80 to 89 years) patients who underwent transcatheter aortic valve implantation (TAVI) compared with clinically similar septuagenarian (age 70 to 79 years) patients remain unclear. This study aimed to assess the outcomes of TAVI in nonagenarians and octogenarians compared with septuagenarians. We conducted a retrospective cohort study using the National Inpatient Sample database to identify patients aged ≥70 years hospitalized for TAVI from 2016 to 2020 and to compare outcomes in nonagenarians and octogenarians versus septuagenarians. The primary outcome was in-hospital mortality. Secondary outcomes included procedural complications, length of stay (LOS), and total costs. The trends in in-hospital outcomes were evaluated. Results were adjusted for demographic/clinical factors. The total cohort included 263,325 patients hospitalized for TAVI, of whom 11.9% were nonagenarians, 51.1% octogenarians, and 37.0% septuagenarians. After adjustment, nonagenarians and octogenarians had higher odds of in-hospital mortality (adjusted odds ratio 1.80, 95% confidence interval 1.34 to 2.41 for nonagenarians; adjusted odds ratio 1.65, 95% confidence interval 1.35 to 2.01 for octogenarians), heart block, permanent pacemaker insertion, stroke, major bleeding, blood transfusion, and palliative care consultation than septuagenarians (all p <0.01). LOS was longer and the total costs were higher for nonagenarians and octogenarians (both p <0.01). Over the study period, in-hospital mortality decreased in nonagenarians (p<sub>trend</sub> = 0.04), and major bleeding, permanent pacemaker insertion, LOS, and costs decreased in all patients aged ≥70 years (p<sub>trend</sub> <0.01). In conclusion, nonagenarians and octogenarians who underwent TAVI have higher rates of mortality and procedure-related complications than clinically similar septuagenarians. Further research is necessary to optimize outcomes in this frail population.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 29 May 2023; 199:59-70</small></div>

<div><h4>Effect of prior anticoagulation therapy on stroke severity and in-hospital outcomes in patients with acute ischemic stroke and atrial fibrillation.</h4><i>Zhou L, Li Y, Yang X, Gu H, ... Wang C, Wang Y</i><br /><b>Background</b><br />We aimed to assess the prevalence of prior anticoagulation therapy (warfarin or non-vitamin K antagonist oral anticoagulants [NOACs]) among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) in China and investigate the associations between prior anticoagulation therapy and initial stroke severity and in-hospital outcomes.<br /><b>Methods</b><br />We included consecutive patients with AIS and known history of AF admitted to hospitals in the China Stroke Center Alliance (CSCA) program from January 2019 to July 2019. Multivariate logistic regression analyses were performed to determine the associations between prior anticoagulation therapy and initial stroke severity and in-hospital outcomes.<br /><b>Results</b><br />Of 7181 patients (median [IQR] age, 75.0 [68.0-81.0] years; 48.7% men), 700 (9.7%), 129 (1.8%), and 255 (3.6%) patients received prior subtherapeutic warfarin (international normalized ratio [INR] <2.0), therapeutic warfarin (INR ≥2.0), and NOACs therapy, respectively. A total of 6499 patients had a preadmission CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥ 2, among whom 94.6% were not adequately anticoagulated. Compared with no prior anticoagulation therapy, prior NOACs therapy was associated with reduced risk of moderate or severe stroke at admission (odds ratio [95% CI], 0.64 [0.43-0.94], P = 0.023) and in-hospital mortality or discharge against medical advice (DAMA) (0.46 [0.24-0.86], P = 0.015). However, no significant association was observed between prior therapeutic warfarin therapy and stroke severity or in-hospital mortality or DAMA.<br /><b>Conclusions</b><br />Among patients with AIS and AF in China, the proportion of patients with inadequate anticoagulation prior to stroke remained substantially high. Prior NOACs therapy was associated with reduced stroke severity and less in-hospital mortality or DAMA.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 May 2023; epub ahead of print</small></div>

<div><h4>Coronary artery disease is associated with impaired atrial function regardless of left ventricular filling pressure.</h4><i>Sharifov O, Denney TS, Girard AA, Gupta H, Lloyd SG</i><br /><b>Background</b><br />Left atrial (LA) strain is impaired in left ventricular (LV) diastolic dysfunction, associated with increased LV end diastolic pressure (LVEDP). In patients with preserved LV ejection fraction (LVEF), coronary artery disease (CAD) is known to impair LV diastolic function. The relationship of LVEDP with CAD and impact on LA strain is not well studied.<br /><b>Methods and results</b><br />Patients with LVEF >50% (n = 37, age 61 ± 7 years) underwent coronary angiography, high-fidelity LV pressure measurements and cardiac magnetic resonance imaging. LA volumes, LA emptying fraction (LAEF), LA reservoir strain (LARS) and LA long-axis shortening (LALAS) were measured. By coronary angiography, patients were assigned into 3 groups: severe-CAD (n = 19, with obstruction of major coronary arteries >70% and/or history of coronary revascularization), mild-to-moderate-CAD (n = 10, obstruction of major coronary arteries 30-60%), and no-CAD (n = 8, obstruction of major coronary arteries and branches <30%). Overall, LVEF was 65 ± 8% and LVEDP was 14.4 ± 5.6 mmHg. Clinical characteristics, LVEDP and LV function measurements were similar in 3 groups. Severe-CAD group had lower LAEF, LALAS and LARS than those in no-CAD group (P < 0.05 all). In regression analysis, LARS and LALAS were associated with CAD severity and treatment with Nitrates, whereas LAEF and LAEF<sub>active</sub> were associated with CAD severity, treatment with Nitrates and LA minimum volume (P < 0.05 all). LAEF<sub>passive</sub> was associated with LVED volume (P < 0.05).<br /><b>Conclusions</b><br />LA functional impairment may be affected by coexistent CAD severity, medications, in particular, Nitrates, and loading conditions, which should be considered when assessing LA function and LA-LV interaction. Our findings inspire exploration in a larger cohort.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 May 2023; epub ahead of print</small></div>

<div><h4>Epinephrine dosing strategies during pediatric extracorporeal cardiopulmonary resuscitation reveal novel impacts on survival: a multicenter study utilizing time-stamped epinephrine dosing records.</h4><i>Ortmann LA, Reeder RW, Raymond TT, Brunetti MA, ... di Bari S, Lasa JJ</i><br /><b>Objectives</b><br />To describe epinephrine dosing distribution using time-stamped data and assess the impact of dosing strategy on survival after ECPR in children.<br /><b>Methods</b><br />This was a retrospective study at five pediatric hospitals of children < 18 years with an in-hospital ECPR event. Mean number of epinephrine doses was calculated for each 10-minute CPR interval and compared between survivors and non-survivors. Patients were also divided by dosing strategy into a frequent epinephrine group (dosing interval of ≤ 5 min/dose throughout the first 30 minutes of the event), and a limited epinephrine group (dosing interval of ≤ 5 min/dose for the first 10 minutes then > 5 min/dose for the time between 10 and 30 minutes).<br /><b>Results</b><br />A total of 191 patients were included. Epinephrine was not evenly distributed throughout ECPR, with 66% of doses being given during the first half of the event. Mean number of epinephrine doses was similar between survivors and non-survivors the first 10 minutes (2.7 doses). After 10 minutes, survivors received fewer doses than non-survivors during each subsequent 10-minute interval. Adjusted survival was not different between strategy groups [OR of survival for frequent epinephrine strategy: 0.78 (95% CI 0.36 - 1.69), p=0.53].<br /><b>Conclusions</b><br />Survivors received fewer doses than non-survivors after the first 10 minutes of CPR and although there was no statistical difference in survival based on dosing strategy, the findings of this study question the conventional approach to EPCR analysis that assumes dosing is evenly distributed.<br /><br />Copyright © 2023 Elsevier B.V. All rights reserved.<br /><br /><small>Resuscitation: 29 May 2023:109855; epub ahead of print</small></div>

<div><h4>Pediatric in-hospital cardiac arrest: respiratory failure characteristics and association with outcomes.</h4><i>Shepard LN, Reeder RW, O\'Halloran A, Kienzle M, ... Sutton RM, Morgan RW</i><br /><b>Aims</b><br />To characterize respiratory failure prior to pediatric in-hospital cardiac arrest (IHCA) and to associate pre-arrest respiratory failure characteristics with survival outcomes.<br /><b>Methods</b><br />This is a single-center, retrospective cohort study from a prospectively identified cohort of children <18 years in intensive care units (ICUs) who received cardiopulmonary resuscitation (CPR) for ≥ 1 minute between January 1, 2017 and June 30, 2021, and were receiving invasive mechanical ventilation (IMV) in the hour prior to IHCA. Patient characteristics, ventilatory support and gas exchange immediately pre-arrest were described and their association with the return of spontaneous circulation (ROSC) was measured.<br /><b>Results</b><br />In the 187 events among 154 individual patients, the median age was 0.9 [0.2, 2.4] years, and CPR duration was 7.5 [3, 29] minutes. Respiratory failure was acute prior to 106/187 (56.7%) events, and the primary indication for IMV was respiratory in nature in 107/187 (57.2%) events. Immediately pre-arrest, the median positive end-expiratory pressure was 8 [5,10] cmH<sub>2</sub>O; mean airway pressure was 13 [10,18] cmH<sub>2</sub>O; peak inspiratory pressure was 28 [24, 35] cmH<sub>2</sub>O; and fraction of inhaled oxygen (FiO2) was 0.40 [0.25, 0.80]. Pre-arrest FiO2 was lower in patients with ROSC vs. without ROSC (0.30 vs 0.99; p<0.001). Patients without ROSC had greater severity of pre-arrest oxygenation failure (p<0.001) as defined by oxygenation index, oxygen saturation index, P/F ratio or S/F ratio.<br /><b>Conclusions</b><br />There was substantial heterogeneity in respiratory failure characteristics and ventilatory requirements pre-arrest. Higher pre-arrest oxygen requirement and greater degree of oxygenation failure were associated with worse survival outcomes.<br /><br />Copyright © 2023 Elsevier B.V. All rights reserved.<br /><br /><small>Resuscitation: 29 May 2023:109856; epub ahead of print</small></div>

<div><h4>Cardiovascular Brain Circuits.</h4><i>Mohanta SK, Yin C, Weber C, Godinho-Silva C, ... Chang RB, Habenicht AJR</i><br /><AbstractText>The cardiovascular system is hardwired to the brain via multilayered afferent and efferent polysynaptic axonal connections. Two major anatomically and functionally distinct though closely interacting subcircuits within the cardiovascular system have recently been defined: The artery-brain circuit and the heart-brain circuit. However, how the nervous system impacts cardiovascular disease progression remains poorly understood. Here, we review recent findings on the anatomy, structures, and inner workings of the lesser-known artery-brain circuit and the better-established heart-brain circuit. We explore the evidence that signals from arteries or the heart form a systemic and finely tuned cardiovascular brain circuit: afferent inputs originating in the arterial tree or the heart are conveyed to distinct sensory neurons in the brain. There, primary integration centers act as hubs that receive and integrate artery-brain circuit-derived and heart-brain circuit-derived signals and process them together with axonal connections and humoral cues from distant brain regions. To conclude the cardiovascular brain circuit, integration centers transmit the constantly modified signals to efferent neurons which transfer them back to the cardiovascular system. Importantly, primary integration centers are wired to and receive information from secondary brain centers that control a wide variety of brain traits encoded in engrams including immune memory, stress-regulating hormone release, pain, reward, emotions, and even motivated types of behavior. Finally, we explore the important possibility that brain effector neurons in the cardiovascular brain circuit network connect efferent signals to other peripheral organs including the immune system, the gut, the liver, and adipose tissue. The enormous recent progress vis-à-vis the cardiovascular brain circuit allows us to propose a novel neurobiology-centered cardiovascular disease hypothesis that we term the neuroimmune cardiovascular circuit hypothesis.</AbstractText><br /><br /><br /><br /><small>Circ Res: 26 May 2023; 132:1546-1565</small></div>

<div><h4>Sex-Associated Differences in the Clinical Outcomes of Left Ventricular Assist Device Recipients: Insights From Interagency Registry for Mechanically Assisted Circulatory Support.</h4><i>Shetty NS, Parcha V, Abdelmessih P, Patel N, ... Arora G, Arora P</i><br /><b>Background</b><br />Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking.<br /><b>Methods</b><br />Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21-30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups.<br /><b>Results</b><br />Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HR<sub>adj</sub>], 1.75 [1.23-2.47]) females had the highest risk of death followed by non-Hispanic White females (HR<sub>adj</sub>, 1.15 [1.07-1.25]; <i>P</i><sub>interaction</sub>=0.02). Hispanic (HR<sub>adj</sub>, 0.60 [0.40-0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HR<sub>adj</sub>, 0.76 [0.67-0.86]), and non-Hispanic White females (HR<sub>adj</sub>, 0.88 [0.80-0.96]) compared with their male counterparts (<i>P</i><sub>interaction</sub><0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HR<sub>adj</sub>, 1.32 [1.18-1.48]) had the highest risk of death (<i>P</i><sub>interaction</sub>=0.01). The risk of death (<i>P</i><sub>interaction</sub>=0.44) and cumulative incidence of heart transplantation (<i>P</i><sub>interaction</sub>=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups.<br /><b>Conclusions</b><br />Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.<br /><br /><br /><br /><small>Circ Heart Fail: 26 May 2023:e010189; epub ahead of print</small></div>

<div><h4>Reducing Long-Term Mortality Post Transcatheter Aortic Valve Replacement Requires Systemic Differentiation of Patient-Specific Coronary Hemodynamics.</h4><i>Khodaei S, Garber L, Abdelkhalek M, Maftoon N, Emadi A, Keshavarz-Motamed Z</i><br /><AbstractText><br /><b>Background:</b><br/>Despite the proven benefits of transcatheter aortic valve replacement (TAVR) and its recent expansion toward the whole risk spectrum, coronary artery disease is present in more than half of the candidates for TAVR. Many previous studies do not focus on the longer-term impact of TAVR on coronary arteries, and hemodynamic changes to the circulatory system in response to the anatomical changes caused by TAVR are not fully understood. Methods and Results We developed a multiscale patient-specific computational framework to examine the effect of TAVR on coronary and cardiac hemodynamics noninvasively. Based on our findings, TAVR might have an adverse impact on coronary hemodynamics due to the lack of sufficient coronary blood flow during diastole phase (eg, maximum coronary flow rate reduced by 8.98%, 16.83%, and 22.73% in the left anterior descending, left circumflex coronary artery, and right coronary artery, respectively [N=31]). Moreover, TAVR may increase the left ventricle workload (eg, left ventricle workload increased by 2.52% [N=31]) and decrease the coronary wall shear stress (eg, maximum time averaged wall shear stress reduced by 9.47%, 7.75%, 6.94%, 8.07%, and 6.28% for bifurcation, left main coronary artery, left anterior descending, left circumflex coronary artery, and right coronary artery branches, respectively). <br /><b>Conclusions:</b><br/>The transvalvular pressure gradient relief after TAVR might not result in coronary flow improvement and reduced cardiac load. Optimal revascularization strategy pre-TAVR and progression of coronary artery disease after TAVR could be determined by noninvasive personalized computational modeling.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029310; epub ahead of print</small></div>

<div><h4>Relationship Between Endothelial Dysfunction and the Outcomes After Atrial Fibrillation Ablation.</h4><i>Okawa K, Sogo M, Morimoto T, Tsushima R, ... Ozaki M, Takahashi M</i><br /><AbstractText><br /><b>Background:</b><br/>Endothelial dysfunction (ED) is associated with cardiovascular events in patients with atrial fibrillation (AF). However, the utility of ED as a prognostic marker after AF ablation supplementary to the CHA<sub>2</sub>DS<sub>2</sub>-VASc score is unclear. This study aimed to investigate the relationship between ED and 5-year cardiovascular events in patients undergoing AF ablation. Methods and Results We conducted a prospective cohort study of patients who underwent a first-time AF ablation and for whom the endothelial function was assessed by the peripheral vascular reactive hyperemia index (RHI) before ablation. We defined ED as an RHI of <2.1. Cardiovascular events included strokes, heart failure requiring hospitalization, arteriosclerotic disease requiring treatment, venous thromboses, and ventricular arrhythmias or sudden cardiac death. We compared the 5-year incidence of cardiovascular events after AF ablation between those with and without ED. Among the 1040 patients who were enrolled, 829 (79.7%) had ED, and the RHI value was found to be associated with the CHA<sub>2</sub>DS<sub>2</sub>-VASc score (<i>P</i>=0.004). The 5-year incidence of cardiovascular events was higher among patients with ED than those without ED (98 [11.8%] versus 13 [6.2%]; log-rank <i>P</i>=0.014). We found ED to be an independent predictor of cardiovascular events after AF ablation (hazard ratio [HR], 1.91 [95% CI, 1.04-3.50]; <i>P</i>=0.036) along with a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of ≥2 (≥3 for women) (HR, 3.68 [95% CI, 1.89-7.15]; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>The prevalence of ED among patients with AF was high. Assessing the endothelial function could enable the risk stratification of cardiovascular events after AF ablation.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028482; epub ahead of print</small></div>

<div><h4>Impact of Preoperative Quantitative Flow Ratio of the Left Anterior Descending Artery on Internal Mammary Artery Graft Patency and Midterm Patient Outcomes After Coronary Artery Bypass Grafting.</h4><i>Wang C, Hu Z, Hou Z, Wang Y, ... Feng W, Zhang Y</i><br /><AbstractText><br /><b>Background:</b><br/>In coronary artery bypass grafting, grafting a target vessel with nonsignificant stenosis increases the risk of graft failure. The present study aims to investigate the impact of preoperative quantitative flow ratio (QFR), a novel functional assessment of the coronary artery, on internal mammary artery graft failure rate and midterm patient outcomes. Methods and Results Between January 2016 and January 2020, we retrospectively included 419 patients who underwent coronary artery bypass grafting who had received preoperative angiography and postoperative coronary computed tomographic angiography in our center. QFR of the left anterior descending (LAD) artery was computed based on preoperative angiograms. The primary end point was the failure of the graft on the LAD artery assessed by coronary computed tomographic angiography at 1 year, and the secondary end point was major adverse cardiac and cerebrovascular events including death from any cause, myocardial infarction, stroke, or repeat revascularization. Grafts on functionally nonsignificant LAD arteries (QFR >0.80) had a significantly higher failure rate than those on functionally significant LAD arteries (31.4% versus 7.2%, <i>P</i><0.001). QFR outperforms degree of stenosis in discriminating graft failure (C statistic, 0.76 versus 0.58). Clinical follow-up (3.6 years, interquartile range [3.3-4.1]) was accomplished in 405 patients, and the rate of major adverse cardiac and cerebrovascular events was significantly higher among patients with functionally nonsignificant LAD arteries (10.1% versus 4.2%; adjusted hazard ratio, 3.08 [95% CI, 1.18-8.06]; <i>P</i>=0.022). <br /><b>Conclusions:</b><br/>In patients receiving internal mammary artery to LAD artery coronary artery bypass grafting, preoperative QFR of the LAD artery of >0.80 was associated with a higher graft failure rate at 1 year and worse patient outcomes at the 3.6-year follow-up.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029134; epub ahead of print</small></div>

<div><h4>Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?</h4><i>Kalogeras K, Jabbour RJ, Pracon R, Kabir T, ... Dalby M, Panoulas V</i><br /><AbstractText><br /><b>Background:</b><br/>No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (<i>P</i><sub>log-rank</sub>=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; <i>P</i><0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (<i>P</i><sub>log-rank</sub>=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), <i>P</i><sub>log-rank</sub>=0.096). <br /><b>Conclusions:</b><br/>Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years\' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028038; epub ahead of print</small></div>

<div><h4>Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.</h4><i>Park HB, Arsanjani R, Sung JM, Heo R, ... Min JK, Chang HJ</i><br /><b>Aims</b><br />To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA).<br /><b>Methods and results</b><br />We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020).<br /><b>Conclusion</b><br />In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov NCT02803411.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 26 May 2023; epub ahead of print</small></div>

<div><h4>Valve-Sparing Root Replacement vs. Composite Valve Graft Root Replacement: Analysis of >1500 Patients from Two Aortic Centers.</h4><i>Levine D, Patel P, Wang C, Pan C, ... Chen E, Takayama H</i><br /><b>Objectives</b><br />The long-term outcomes comparing valve-sparing root replacement (VSRR), composite valve graft with bioprosthesis (b-CVG) and mechanical prosthesis (m-CVG) have yet to be explored. We investigated long-term survival and reintervention rates after undergoing one of three major aortic root replacements in both tricuspid and bicuspid aortic valve (AV) patients.<br /><b>Methods</b><br />A total of 1507 patients underwent VSRR (n=700), b-CVG (n=703), or m-CVG (n=104) between 2004-2021 from two aortic centers, excluding those with dissection, endocarditis, stenosis, or prior AV surgery. Endpoints included mortality over time and cumulative incidence of AV/proximal aorta reintervention. Multivariable Cox Regression compared adjusted 12-year survival. Fine and Gray competing risk regression compared risk and cumulative incidence of reintervention. Propensity score matched (PSM) subgroup analysis balanced the two major groups (b-CVG and VSRR), and landmark analysis isolated outcomes beginning four years postoperatively.<br /><b>Results</b><br />On multivariable analysis, both b-CVG (HR 1.91, p=0.001) and m-CVG (HR 2.62, p=0.005) had increased 12-year mortality risk vs VSRR. After PSM, VSRR displayed improved 12-year survival vs b-CVG (87.9% vs 78.8%, p=0.033). Adjusted 12-year reintervention risk in b-CVG or m-CVG vs VSRR patients was similar [(b-CVG sHR 1.49, p=0.170); (m-CVG sHR 0.28, p=0.110)], with cumulative incidence 7% in VSRR, 17% in b-CVG, and 2% in m-CVG (p=0.420). Landmark analysis at four years showed increased incidence of late reintervention in b-CVG vs VSRR (p=0.008).<br /><b>Conclusions</b><br />VSRR, m-CVG, and b-CVG have excellent 12-year survival, with VSRR associated with better survival. All three groups have low incidence of reintervention, with VSRR showing decreased late post-operative need for reintervention compared to b-CVG.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Thorac Cardiovasc Surg: 26 May 2023; epub ahead of print</small></div>

<div><h4>Hypothermia after Extracorporeal Cardiopulmonary Resuscitation Not Associated with Improved Neurologic Complications or Survival in Children: an Analysis of the ELSO Registry.</h4><i>Sanford EL, Bhaskar P, Li X, Thiagarajan R, Raman L</i><br /><b>Aim</b><br />To analyze the association between hypothermia and neurologic complications among children who were treated with extracorporeal cardiopulmonary resuscitation (ECPR) using the Extracorporeal Life Support Organization (ELSO) international registry <br /><b>Methods:</b><br/>We conducted a retrospective, multicenter, database study utilizing ELSO data for ECPR encounters from January 1, 2011, through December 31, 2019. Exclusion criteria included multiple ECMO runs and lack of variable data. The primary exposure was hypothermia under 34 degrees Celsius for greater than 24 hours. The primary outcome, determined a priori, was a composite of neurologic complications defined by ELSO registry including brain death, seizures, infarction, hemorrhage, diffuse ischemia. Secondary outcomes were mortality on ECMO and mortality prior to hospital discharge. Multivariable logistic regression determined the odds of neurologic complications, mortality on ECMO or prior to hospital discharge associated with hypothermia after adjustment for available pertinent covariables.<br /><b>Results</b><br />Of the 2,289 ECPR encounters, no difference in odds of neurologic complications were found between the hypothermia and non-hypothermia groups (AOR 1.10, 95% CI 0.80-1.51). However, hypothermia exposure was associated with decreased odds of mortality on ECMO (AOR 0.76, 95% CI 0.59-0.97), but no difference in mortality prior to hospital discharge (AOR 0.96, 95% CI 0.76-1.21) <br /><b>Conclusion:</b><br/>Analysis of a large, multicenter, international dataset demonstrates that hypothermia for greater than 24 hours among children who undergo ECPR is not associated with decreased neurologic complications or mortality benefit at time of hospital discharge.<br /><br />Published by Elsevier B.V.<br /><br /><small>Resuscitation: 26 May 2023:109852; epub ahead of print</small></div>

<div><h4>Hospital ECMO capability is associated with survival in pediatric cardiac arrest.</h4><i>Pollack B, Barbaro RP, Gorga SM, Carlton EF, Gaies M, Kohne JG</i><br /><b>Aim</b><br />Extracorporeal membrane oxygenation (ECMO) provides temporary support in severe cardiac or respiratory failure and can be deployed in children who suffer cardiac arrest. However, it is unknown if a hospital\'s ECMO capability is associated with better outcomes in cardiac arrest. We evaluated the association between pediatric cardiac arrest survival and the availability of pediatric extracorporeal membrane oxygenation (ECMO) at the treating hospital.<br /><b>Methods</b><br />We identified cardiac arrest hospitalizations, including in- and out-of-hospital, in children (0-18 years old) using data from the Health Care Utilization Project (HCUP) National Inpatient Sample (NIS) between 2016-2018. The primary outcome was in-hospital survival. Hierarchical logistic regression models were built to test the association between hospital ECMO capability and in-hospital survival.<br /><b>Results</b><br />We identified 1276 cardiac arrest hospitalizations. Survival of the cohort was 44%; 50% at ECMO-capable hospitals and 32% at non-ECMO hospitals. After adjusting for patient-level factors and hospital factors, receipt of care at an ECMO- capable hospital was associated with higher in-hospital survival, with an odds ratio of 1.49 [95% CI 1.09, 2.02]. Patients who received treatment at ECMO-capable hospitals were younger (median 3 years vs 11 years, p<0.001) and more likely to have a complex chronic condition, specifically congenital heart disease. A total of 10.9% (88/811) of patients at ECMO-capable hospitals received ECMO support.<br /><b>Conclusion</b><br />A hospital\'s ECMO capability was associated with higher in-hospital survival among children suffering cardiac arrest in this analysis of a large United States administrative dataset. Future work to understand care delivery differences and other organizational factors in pediatric cardiac arrest is necessary to improve outcomes.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Resuscitation: 26 May 2023:109853; epub ahead of print</small></div>

<div><h4>An estimation of the consequences of reinforcing the 2016 and 2019 ESC/EAS guidelines on current lipid-lowering treatment in patients with type 2 diabetes in tertiary care - a SwissDiab study.</h4><i>Singeisen H, Renström F, Laimer M, Lehmann R, Bilz S, Brändle M</i><br /><b>Background</b><br />In 2019, the ESC/EAS updated the 2016 guidelines for the management of dyslipidaemias recommending more stringent LDL-cholesterol (LDL-C) targets in diabetes mellitus type 2 (DM2). Based on a real-world patient population, this study aimed to determine the feasibility and cost of attaining guideline-recommended LDL-C targets, and assess cardiovascular benefit.<br /><b>Methods</b><br />The Swiss Diabetes Registry is a multicentre longitudinal observational study of outpatients in tertiary diabetes care. Patients with DM2 and a visit 01.01.2018-31.08.2019 that failed the 2016 LDL-C target were identified. The theoretical intensification of current lipid-lowering medication needed to reach the 2016 and 2019 LDL-C target was determined and the cost thereof extrapolated. The expected number of MACE prevented by treatment intensification was estimated.<br /><b>Results</b><br />294 patients (74.8%) failed the 2016 LDL-C target. The percentage of patients that theoretically achieved the 2016 and 2019 target with the indicated treatment modifications were: high-intensity statin, 21.4% and 13.3%; ezetimibe, 46.6% and 27.9%; PCSK9 inhibitor (PCSK9i), 30.6% and 53.7%; ezetimibe and PCSK9i, 1.0% and 3.1%, whereas one (0.3%) and five patients (1.7%) failed to reach target, respectively. Achieving the 2016 versus 2019 target would reduce the estimated 4-year MACE from 24.9 to 18.6 versus 17.4 events, at an additional annual cost of medication of 2,140 CHF versus 3,681 CHF per patient, respectively.<br /><b>Conclusions</b><br />For 68% of the patients, intensifying statin treatment and/or adding ezetimibe would be sufficient to reach the 2016 target, whereas 57% would require cost-intensive PCSK9i therapy to reach the 2019 target, with limited additional medium-term cardiovascular benefit.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 25 May 2023; epub ahead of print</small></div>

<div><h4>Association of HIV Infection and Incident Abdominal Aortic Aneurysm Among 143 001 Veterans.</h4><i>Filipkowski AM, Kundu S, Eden SK, Alcorn CW, ... Freiberg MS, Aday AW</i><br /><b>Background</b><br />People with HIV (PWH) have an increased risk of cardiovascular disease. Previous cross-sectional data suggest there is a higher prevalence of abdominal aortic aneurysm (AAA) in PWH than in those without HIV. Whether PWH have an increased risk of incident AAA compared with those without HIV is unknown.<br /><b>Methods</b><br />We analyzed data among participants without prevalent AAA from the Veterans Aging Cohort Study, a prospective, observational, longitudinal cohort of veterans with HIV matched 1:2 with veterans without HIV infection. We calculated AAA rates by HIV status and assessed the association between HIV infection and incident AAA using Cox proportional hazards models. We defined AAA using the International Classification of Diseases, 9th or 10th revision, or Current Procedural Terminology codes and adjusted all models for demographic characteristics, cardiovascular disease risk factors, and substance use. Secondary analyses examined the association between time-varying CD4+ T-cell count or HIV viral load and incident AAA.<br /><b>Results</b><br />Among 143 001 participants (43 766 with HIV), over a median follow-up of 8.7 years, there were 2431 incident AAA events (26.4% among PWH). Rates of incident AAA per 1000 person-years were similar among PWH (2.0 [95% CI, 1.9-2.2]) and people without HIV (2.2 [95% CI, 2.1-2.3]). There was no evidence that HIV infection increased the risk of incident AAA compared with no HIV infection (adjusted hazard ratio, 1.02 [95% CI, 0.92-1.13]). In adjusted analyses with time-varying CD4+ T-cell counts or HIV viral load, PWH with CD4+ T-cell counts <200 cells/mm<sup>3</sup> (adjusted hazard ratio, 1.29 [95% CI, 1.02-1.65]) or HIV viral load ≥500 copies/mL (adjusted hazard ratio, 1.29 [95% CI, 1.09-1.52]) had an increased risk of AAA compared with those without HIV.<br /><b>Conclusions</b><br />HIV infection is associated with an increased risk of AAA among those with low CD4+ T-cell counts or elevated HIV viral load over time.<br /><br /><br /><br /><small>Circulation: 25 May 2023; epub ahead of print</small></div>

<div><h4>Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry (Sarcomeric Human Cardiomyopathy).</h4><i>Alaiwi SA, Roston TM, Marstrand P, Claggett BL, ... Vissing CR, Ho CY</i><br /><b>Background</b><br />The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children.<br /><b>Methods</b><br />Data from patients with HCM in the international, multicenter SHaRe Registry (Sarcomeric Human Cardiomyopathy) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models.<br /><b>Results</b><br />We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe Registry site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]).<br /><b>Conclusions</b><br />Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.<br /><br /><br /><br /><small>Circulation: 25 May 2023; epub ahead of print</small></div>

<div><h4>Relation of Life\'s Essential 8 to the Genetic Predisposition for Cardiovascular Outcomes and All-cause Mortality: Results from a National Prospective Cohort.</h4><i>Zhang J, Chen G, Habudele Z, Wang X, ... Lip GYH, Lin H</i><br /><b>Aims</b><br />To evaluate the independent, mediating, interactive, and associated effects of Life\'s Essential 8 (LE8) and genetic predisposition on the risk of cardiovascular outcomes and all-cause mortality.<br /><b>Methods</b><br />We retrieved a total of 254,783 individuals from the UK Biobank. LE8 was determined by 8 metrics (nicotine exposure, physical activity, diet, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and was characterized as low, moderate, and high cardiovascular health (CVH). Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations between LE8, PRS and outcomes.<br /><b>Results</b><br />During a median follow-up of 12.53 years, all-cause mortality occurred in 10,257 of 197,473 participants, cardiovascular mortality in 2,074 of 215,675, and incident CVD in 71,774 of 215,675. Individuals with moderate or high CVH experienced a lower risk (HRs 0.33 to 0.81) of adverse health outcomes compared with their counterparts with low CVH. A substantial proportion (16.1∼69.8%) of health outcomes could be attributable to moderate or high LE8, and up to 51.2% of the associations between PRS and adverse outcomes were mediated by LE8. In high PRS group, individuals with high CVH had lower CVD mortality (HR: 0.26, 95% CI: 0.18, 0.39), compared to those with low CVH.<br /><b>Conclusion</b><br />Ideal CVH was associated with lower risks of cardiovascular outcomes and all-cause mortality, with a more pronounced association observed in individuals with high PRS for CVD. Improving CVH according to LE8 guidelines should be encouraged, especially for those with PRS that indicate high CVD risk.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur J Prev Cardiol: 25 May 2023; epub ahead of print</small></div>

<div><h4>Surgical outcomes of aortic valve repair for specific aortic valve cusp characteristics; retraction, calcification and fenestration.</h4><i>Mathari SE, Boulidam N, de Heer F, de Kerchove L, ... Kluin J, Aortic Valve Research Network Investigators</i><br /><b>Objectives</b><br />We investigated the predictive value of aortic valve cusp retraction, calcification and fenestration for aortic valvuloplasty feasibility.<br /><b>Methods</b><br />Multicenter data was collected for 2082 patients who underwent surgical aortic valvuloplasty or aortic valve replacement. The study population had retraction, calcification or fenestration in at least one aortic valve cusp. Controls had normal or prolapsed cusps.<br /><b>Results</b><br />All cusp characteristics demonstrated significantly increased OR\'s for switch to valve replacement. This effect was strongest for cusp retraction, followed by calcification and fenestration (OR = 25.14, p=<.001; OR = 13.50, p=<.001; OR 12.32, p=<.001). Calcification and retraction displayed increased odds for developing grade 4 aortic regurgitation compared to grade 0 or 1 combined on average over time (OR = 6.67, p=<.001; OR = 4.13, p=.038). Patients with cusp retraction showed increased risk for reintervention at 1- and 2-years follow-up after aortic valvuloplasty (HR = 5.66, p=<.001; HR = 3.22, p=.007). Cusp fenestration was the only group showing neither an increased risk of postoperative severe aortic regurgitation (p=0.57) or early reintervention (p=0.88) compared to the control group.<br /><b>Conclusions</b><br />Aortic valve cusp retraction, calcification and fenestration were all related to increased rates of switch to valve replacement. Calcification and retraction were associated with recurrence of severe aortic regurgitation. Retraction was related to early reintervention. Fenestration was neither associated with recurrence of severe aortic regurgitation or reintervention. This indicates that surgeons are well able to distinguish aortic valve repair candidates in patients with cusp fenestration.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Thorac Cardiovasc Surg: 25 May 2023; epub ahead of print</small></div>

<div><h4>Is exercise a viable therapy for anxiety? Systematic review of recent literature and critical analysis.</h4><i>Stonerock GL, Gupta RP, Blumenthal JA</i><br /><b>Objectives</b><br />Exercise has been promoted as a treatment for a variety of psychiatric conditions. The benefits of exercise for depression are widely recognized, but the benefits of exercise for anxiety are uncertain. Although several reviews promoted exercise as a treatment for anxiety, concerns about the quality of studies prompted us to provide a critical review of the recent literature to re-assess the value of exercise for treating anxiety.<br /><b>Methods and materials</b><br />We conducted a systematic review of all peer-reviewed randomized clinical trials (RCTs) among adults, published between January 2014 and December 2021, with an exercise intervention and anxiety as the a priori primary outcome. Two reviewers independently extracted data from studies meeting inclusion criteria, including sample characteristics, exercise intervention, control conditions, primary anxiety measure, relevant findings, and methodological quality quantified by PEDro scores.<br /><b>Results</b><br />7240 published studies from CINAHL, EMBASE, MEDLINE, and PsycINFO were screened in April 2022, with 1831 participants across 25 eligible RCTs, of which 13 included elevated anxiety at study entry as an eligibility criterion. Only two of these 13 studies, and five of 12 studies of non-anxious individuals, found anxiety to be reduced unequivocally with exercise. Most studies suffered from significant methodological limitations including concurrent therapies and lack of intention-to-treat analyses.<br /><b>Conclusion</b><br />There remains considerable uncertainty about the value of exercise in reducing symptoms of anxiety, particularly among anxious individuals. The paucity of methodologically sound studies of patients with anxiety represents a significant gap in our knowledge and calls for more research in the area. Word count: 249.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 25 May 2023; epub ahead of print</small></div>

<div><h4>Magnetic resonance analysis of ventricular volumes in bicuspid and trileaflet aortic regurgitation.</h4><i>Sevilla T, Rojas G, González-Bartol E, Candela J, ... Gomez Salvador I, San Román Calvar JA</i><br /><b>Objective</b><br />To identify differences in left ventricular (LV) remodelling between patients with bicuspid aortic valve (BAV) and trileaflet aortic valve (TAV) with chronic aortic regurgitation (AR).<br /><b>Methods</b><br />Retrospective cohort study of 210 consecutive patients undergoing cardiac magnetic resonance for AR evaluation. We divided the study population according to valvular morphology. Independent predictors of LV enlargement AR were evaluated.<br /><b>Results</b><br />There were 110 patients with BAV and 100 patients with TAV. Patients with BAV were younger (mean age BAV vs TAV: 41±16 years vs 67±11 years; p<0.01), mostly male (% male BAV vs TAV: 84.5% vs 65%, p=0.01) and presented milder degrees of AR (median regurgitant fraction BAV vs TAV: 14 (6-28)% vs 22 (12-35)%, p=0.002). Both groups presented similar indexed LV volumes and ejection fraction. According to the degree of AR, at mild AR, patients with BAV presented larger LV volumes (BAV vs TAV: indexed end diastolic left ventricular volumes (iEDV): 96.5±19.7 vs 82.1±19.3 mL, p<0.01; indexed end systolic left ventricular volumes (iESV): 39.4±10.3 mL vs 33.2±10.5 mL, p=0.01). These differences disappeared at higher degrees of AR. Independent predictors of LV enlargement were regurgitant fraction (EDV: OR 1.118 (1.081-1.156), p<0.001; ESV: OR 1.067 (1.042-1.092), p<0.001), age (EDV: OR 0.940 (0.917-0.964), p<0.001, ESV: OR 0.962 (0.945-0.979), p<0.001) and weight (EDV: OR 1.054 (1.025-1.083), p<0.001).<br /><b>Conclusions</b><br />In chronic AR, LV enlargement is an early finding. LV volumes display a direct correlation with regurgitant fraction and an inverse association with age. Patients with BAV present larger ventricular volumes, especially at mild AR. However, these differences are attributable to demographic disparities; valve type is not independently associated with LV size.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 25 May 2023; epub ahead of print</small></div>

<div><h4>Associations of Menstrual Cycle Regularity and Length With Cardiovascular Diseases: A Prospective Study From UK Biobank.</h4><i>Huang C, Lin B, Yuan Y, Li K, ... Huang Y, Zhang H</i><br /><AbstractText><br /><b>Background:</b><br/>The association between menstrual cycle characteristics and cardiovascular outcomes remains unclear. This study was undertaken to evaluate whether menstrual cycle regularity and length throughout the life course are associated with cardiovascular outcomes. Methods and Results This cohort study included 58 056 women who had no cardiovascular disease (CVD) at baseline and reported their menstrual cycle regularity and length. Hazard ratios (HRs) and 95% CIs for CVD events were estimated using Cox proportional hazards models. During the median 11.8 years of follow-up, 1623 incident CVD cases were documented, including 827 incident cases of coronary heart disease, 199 myocardial infarctions, 271 strokes, 174 cases of heart failure, and 393 cases of atrial fibrillations. Compared with women with regular menstrual cycles, the HRs for women with irregular menstrual cycles were 1.19 (95% CI, 1.07-1.31) for CVD events and 1.40 (95% CI, 1.14-1.72) for atrial fibrillation. The multivariable-adjusted HRs for short (≤21 days) or long (35 days) menstrual cycles during follow-up were 1.29 (95% CI, 1.11-1.50) and 1.11 (95% CI, 0.98-1.56) for CVD events, respectively. Similarly, long or short cycle length were more likely to be associated with increased risk of atrial fibrillation (HR, 1.30 [95% CI, 1.01-1.66]; and HR, 1.38 [95% CI, 1.02-1.87]), and short cycle length was more likely to be associated with increased risk of coronary heart disease and myocardial infarction. However, these associations for stroke and heart failure were not significant. <br /><b>Conclusions:</b><br/>Long or short menstrual cycle length was associated with increased risks of CVD and atrial fibrillation but not myocardial infarction, heart failure, or stroke. Short cycle length was associated with a greater risk of coronary heart disease and myocardial infarction.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 May 2023:e029020; epub ahead of print</small></div>

<div><h4>Increasing Equity of Physical Activity Promotion for Optimal Cardiovascular Health in Adults: A Scientific Statement From the American Heart Association.</h4><i>Jerome GJ, Boyer WR, Bustamante EE, Kariuki J, ... Barone Gibbs B, American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Peripheral Vascular Disease</i><br /><AbstractText>Fewer than 1 in 4 adults achieves the recommended amount of physical activity, with lower activity levels reported among some groups. Addressing low levels of physical activity among underresourced groups provides a modifiable target with the potential to improve equity in cardiovascular health. This article (1) examines physical activity levels across strata of cardiovascular disease risk factors, individual level characteristics, and environmental factors; (2) reviews strategies for increasing physical activity in groups who are underresourced or at risk for poor cardiovascular health; and (3) provides practical suggestions for physical activity promotion to increase equity of risk reduction and to improve cardiovascular health. Physical activity levels are lower among those with elevated cardiovascular disease risk factors, among certain groups (eg, older age, female, Black race, lower socioeconomic status), and in some environments (eg, rural). There are strategies for physical activity promotion that can specifically support underresourced groups such as engaging the target community in designing and implementing interventions, developing culturally appropriate study materials, identifying culturally tailored physical activity options and leaders, building social support, and developing materials for those with low literacy. Although addressing low physical activity levels will not address the underlying structural inequities that deserve attention, promoting physical activity among adults, especially those with both low physical activity levels and poor cardiovascular health, is a promising and underused strategy to reduce cardiovascular health inequalities.</AbstractText><br /><br /><br /><br /><small>Circulation: 24 May 2023; epub ahead of print</small></div>

<div><h4>Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.</h4><i>Fischer U, Koga M, Strbian D, Branca M, ... Dawson J, ELAN Investigators</i><br /><b>Background</b><br />The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.<br /><b>Methods</b><br />We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.<br /><b>Results</b><br />Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.<br /><b>Conclusions</b><br />In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 24 May 2023; epub ahead of print</small></div>

<div><h4>Modifiable cardiovascular risk factors and genetics for targeted prevention of dementia.</h4><i>Juul Rasmussen I, Frikke-Schmidt R</i><br /><AbstractText>Dementia is a major global challenge for health and social care in the 21st century. A third of individuals >65 years of age die with dementia, and worldwide incidence numbers are projected to be higher than 150 million by 2050. Dementia is, however, not an inevitable consequence of old age; 40% of dementia may theoretically be preventable. Alzheimer\'s disease (AD) accounts for approximately two-thirds of dementia cases and the major pathological hallmark of AD is accumulation of amyloid-β. Nevertheless, the exact pathological mechanisms of AD remain unknown. Cardiovascular disease and dementia share several risk factors and dementia often coexists with cerebrovascular disease. In a public health perspective, prevention is crucial, and it is suggested that a 10% reduction in prevalence of cardiovascular risk factors could prevent more than nine million dementia cases worldwide by 2050. Yet this assumes causality between cardiovascular risk factors and dementia and adherence to the interventions over decades for a large number of individuals. Using genome-wide association studies, the entire genome can be scanned for disease/trait associated loci in a hypothesis-free manner, and the compiled genetic information is not only useful for pinpointing novel pathogenic pathways but also for risk assessments. This enables identification of individuals at high risk, who likely will benefit the most from a targeted intervention. Further optimization of the risk stratification can be done by adding cardiovascular risk factors. Additional studies are, however, highly needed to elucidate dementia pathogenesis and potential shared causal risk factors between cardiovascular disease and dementia.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 24 May 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular complications of diabetes: role of non-coding RNAs in the crosstalk between immune and cardiovascular systems.</h4><i>Spinetti G, Mutoli M, Greco S, Riccio F, ... Devaux Y, Martelli F</i><br /><AbstractText>Diabetes mellitus, a group of metabolic disorders characterized by high levels of blood glucose caused by insulin defect or impairment, is a major risk factor for cardiovascular diseases and related mortality. Patients with diabetes experience a state of chronic or intermittent hyperglycemia resulting in damage to the vasculature, leading to micro- and macro-vascular diseases. These conditions are associated with low-grade chronic inflammation and accelerated atherosclerosis. Several classes of leukocytes have been implicated in diabetic cardiovascular impairment. Although the molecular pathways through which diabetes elicits an inflammatory response have attracted significant attention, how they contribute to altering cardiovascular homeostasis is still incompletely understood. In this respect, non-coding RNAs (ncRNAs) are a still largely under-investigated class of transcripts that may play a fundamental role. This review article gathers the current knowledge on the function of ncRNAs in the crosstalk between immune and cardiovascular cells in the context of diabetic complications, highlighting the influence of biological sex in such mechanisms and exploring the potential role of ncRNAs as biomarkers and targets for treatments. The discussion closes by offering an overview of the ncRNAs involved in the increased cardiovascular risk suffered by patients with diabetes facing Sars-CoV-2 infection.</AbstractText><br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 May 2023; 22:122</small></div>

<div><h4>Sodium-glucose cotransporter 2 inhibitor may not prevent atrial fibrillation in patients with heart failure: a systematic review.</h4><i>Ouyang X, Wang J, Chen Q, Peng L, Li S, Tang X</i><br /><b>Background</b><br />Atrial fibrillation (AF) and heart failure (HF) frequently coexist because of their similar pathological basis. However, whether sodium-glucose cotransporter 2 inhibitor (SGLT2i), a novel class of anti-HF medication, decreases the risk of AF in HF patients remains unclear.<br /><b>Objectives</b><br />The aim of this study was to assess the relationship between SGLT2i and AF in HF patients.<br /><b>Methods</b><br />A meta-analysis of randomized controlled trails evaluating the effects of SGLT2i on AF in HF patients was performed. PubMed and ClinicalTrails.gov were searched for eligible studies until 27 November 2022. The risk of bias and quality of evidence were assessed through the Cochrane tool. Pooled risk ratio of AF for SGLT2i versus placebo in eligible studies was calculated.<br /><b>Results</b><br />A total of 10 eligible RCTs examining 16,579 patients were included in the analysis. AF events occurred in 4.20% (348/8292) patients treated with SGLT2i, and in 4.57% (379/8287) patients treated with placebo. Meta-analysis showed that SGLT2i did not significantly reduce the risk of AF (RR 0.92; 95% CI 0.80-1.06; p = 0.23) in HF patients when compared to placebo. Similar results remained in the subgroup analyses, regardless of the type of SGLT2i, the type of HF, and the duration of follow-up.<br /><b>Conclusions</b><br />Current evidences showed that SGLT2i may have no preventive effects on the risk of AF in patients with HF.<br /><b>Translational perspective</b><br />Despite HF being one of the most common heart diseases and conferring increased risk for AF, affective prevention of AF in HF patients is still unresolved. The present meta-analysis demonstrated that SGLT2i may have no preventive effects on reducing AF in patients with HF. How to effectively prevent and early detect the occurrence of AF is worth discussing.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 May 2023; 22:124</small></div>

<div><h4>Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography.</h4><i>Hommels TM, Hermanides RS, Fabris E, Kedhi E</i><br /><AbstractText>In this review, we summarise new insights into diagnostic approaches and treatment strategies for coronary artery disease (CAD) in patients with diabetes mellitus (DM). Despite the improvements in therapy, the clinical management of DM patients remains challenging as they develop more extensive CAD at a younger age and consistently have worse clinical outcomes than non-DM patients. Current diagnostic modalities as well as revascularisation treatments mainly focus on ischemic lesions. However, the impact of plaque morphology and composition are emerging as strong predictors of adverse cardiac events even in the absence of identified ischemia. In particular, the presence of vulnerable plaques such as thin-cap fibroatheroma (TCFA) lesions has been identified as a very strong predictor of future adverse events. This emphasises the need for an approach combining both functional and morphological methods in the assessment of lesions. In particular, optical coherence tomography (OCT) has proven to be a valuable asset by truly identifying TCFAs. New treatment strategies should consist of individualised and advanced medical regimens and may evolve towards plaque sealing through percutaneous treatment.</AbstractText><br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 May 2023; 22:123</small></div>

<div><h4>Heart failure and obesity: The latest pandemic.</h4><i>Aryee E, Ozkan B, Ndumele CE</i><br /><AbstractText>The marked rise in rates of obesity, which is most prominent among individuals from socio-economically disadvantaged circumstances, has been a powerful contributor to the rising prevalence of heart failure (HF). Obesity has indirect effects on HF through the development of several metabolic risk factors, but also direct adverse effects on the myocardium. Obesity contributes to myocardial dysfunction and HF risk through multiple mechanisms, including hemodynamic changes, neurohormonal activation, endocrine and paracrine effects of adipose tissue, ectopic fat deposition and lipotoxicity. These processes principally result in concentric left ventricular (LV) remodeling and predominant increase in the risk for HF with preserved LV ejection fraction (HFpEF). Despite the excess risk for HF associated with obesity, there is a well described obesity paradox in which individuals with overweight and grade I obesity have better survival than those with normal weight and overweight. Despite the obesity paradox among individuals with prevalent HF, intentional weight loss is associated with improvements in metabolic risk factors, myocardial dysfunction and quality of life, in a dose-response fashion. In matched observational studies of bariatric surgery patients, marked weight loss is associated with decreased risk for developing HF, as well as improved cardiovascular disease (CVD) outcomes in those with existing HF. Ongoing clinical trials using powerful new obesity pharmacotherapies in individuals in with obesity and CVD may provide definitive information regarding the cardiovascular impact of weight loss. Given the powerful contribution of rising obesity prevalence to rates of HF, addressing these intertwined epidemics is a clinical and public health priority.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 24 May 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular risk factors and major recurrent coronary events: A genetic liability study in patients with coronary artery disease in the UK Biobank.</h4><i>Noordam R, Brochard TA, Drewes YM, Gussekloo J, ... Jukema JW, van Heemst D</i><br /><b>Background:</b><br/>and aims</b><br />Mendelian randomization confirmed multiple risk factors for primary events of coronary artery disease (CAD), but no such studies have been performed on recurrent major coronary events despite interesting insights derived from other designs. We examined the associations between genetically-influenced classical cardiovascular risk factors and the risk of recurrent major coronary events in a cohort of CAD patients.<br /><b>Methods</b><br />We included all first-time CAD cases (defined as angina pectoris, chronic ischemic heart disease or acute myocardial infarction) of European ancestry from the UK Biobank. Cases were followed till the end of follow-up, death or when they developed a recurrent major coronary event (chronic ischemic heart disease or acute myocardial infarction). Standardized weighted genetic risk scores were calculated for body mass index (BMI), systolic blood pressure, LDL cholesterol and triglycerides.<br /><b>Results</b><br />From a total of 22,949 CAD patients (mean age at first diagnosis 59.8 (SD 7.3) years, 71.1% men), 12,539 (54.6%) reported a recurrent major coronary event within a period of maximum 17.8 years. One standard deviation higher genetically-determined LDL cholesterol was associated with a higher risk of a recurrent major coronary event (odds ratio: 1.08 [95% confidence interval: 1.05, 1.11]). No associations were observed for genetically-influenced BMI (1.00 [0.98, 1.03]), systolic blood pressure (1.01 [0.98, 1.03]) and triglycerides (1.02 [0.995, 1.05]).<br /><b>Conclusions</b><br />Despite the use risk-reducing medications following a first coronary event, this study provided genetic evidence that, of the classical risk factors, mainly high LDL cholesterol was associated with a higher risk of developing recurrent major coronary events.<br /><br />Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Atherosclerosis: 24 May 2023; 376:19-25</small></div>

<div><h4>Vegetarian or vegan diets and blood lipids: a meta-analysis of randomized trials.</h4><i>Koch CA, Kjeldsen EW, Frikke-Schmidt R</i><br /><b>Aims</b><br />Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular diseases, the leading cause of death worldwide, is thus highly relevant. Therefore, a systematic review and meta-analysis were conducted to estimate the effect of vegetarian and vegan diets on blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B.<br /><b>Methods and results</b><br />Studies published between 1980 and October 2022 were searched for using PubMed, Embase, and references of previous reviews. Included studies were randomized controlled trials that quantified the effect of vegetarian or vegan diets vs. an omnivorous diet on blood lipids and lipoprotein levels in adults over 18 years. Estimates were calculated using a random-effects model. Thirty trials were included in the study. Compared with the omnivorous group, the plant-based diets reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels with mean differences of -0.34 mmol/L (95% confidence interval, -0.44, -0.23; P = 1 × 10-9), -0.30 mmol/L (-0.40, -0.19; P = 4 × 10-8), and -12.92 mg/dL (-22.63, -3.20; P = 0.01), respectively. The effect sizes were similar across age, continent, duration of study, health status, intervention diet, intervention program, and study design. No significant difference was observed for triglyceride levels.<br /><b>Conclusion</b><br />Vegetarian and vegan diets were associated with reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-effects that were consistent across various study and participant characteristics. Plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 24 May 2023; epub ahead of print</small></div>

<div><h4>Plasma TSH and cardiovascular disease in the general population: A Mendelian randomization study of 105,224 individuals.</h4><i>Dalila N, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A</i><br /><b>Background:</b><br/>and aims</b><br />The association between thyroid stimulating hormone (TSH) and cardiovascular disease has mainly been determined using clinical categories of disease. We tested the hypothesis that TSH on a continuous scale is associated with risk of atrial fibrillation (AF), myocardial infarction (MI), stroke, heart failure (HF), aortic valve stenosis (AVS), and major adverse cardiovascular events (MACE) and whether these associations are likely to be causal.<br /><b>Methods</b><br />We first tested whether plasma TSH on a continuous scale was observationally associated with incident cardiovascular events in a prospective cohort study of 105,224 individuals from the Copenhagen General Population Study followed for a median 7 years. Next, we tested whether a genetic risk score weighted on TSH was associated with cardiovascular endpoints. Finally, using Mendelian randomization, we tested whether the observed associations were likely to be causal.<br /><b>Results</b><br />Using restricted cubic splines, lower concentrations of TSH relative to the population median (=1.53 mIU/L) were associated with higher risk of AF, MI, stroke, HF, AVS, and MACE. Comparing individuals with TSH ≤5th percentile (≤0.54 mIU/L) versus >50th percentile (>1.53 mIU/L), hazard ratios (HRs) ranged from 1.12 (1.00-1.26) for stroke to 1.27 (1.11-1.46) for HF. Genetic risk estimates per standard deviation decrease in TSH were 1.28 (1.08-1.52) for AF, 1.35 (1.06-1.71) for MI, 1.06 (0.89-1.26) for stroke, 1.19 (0.94-1.52) for HF, 1.53 (1.03-2.26) for AVS, and 1.09 (0.97-1.23) for MACE.<br /><b>Conclusions</b><br />In 105,224 individuals from the general population low plasma TSH was observationally and genetically associated with increased risk of AF, MI, and AVS suggesting that these observations may reflect causal pathways.<br /><br />Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.<br /><br /><small>Atherosclerosis: 24 May 2023; 376:26-33</small></div>

<div><h4>Risk for Bleeding-Related Hospitalizations During Use of Amiodarone With Apixaban or Rivaroxaban in Patients With Atrial Fibrillation : A Retrospective Cohort Study.</h4><i>Ray WA, Chung CP, Stein CM, Smalley W, ... Dickson AL, Murray KT</i><br /><b>Background</b><br />Amiodarone, the most effective antiarrhythmic drug in atrial fibrillation, inhibits apixaban and rivaroxaban elimination, thus possibly increasing anticoagulant-related risk for bleeding.<br /><b>Objective</b><br />For patients receiving apixaban or rivaroxaban, to compare risk for bleeding-related hospitalizations during treatment with amiodarone versus flecainide or sotalol, antiarrhythmic drugs that do not inhibit these anticoagulants\' elimination.<br /><b>Design</b><br />Retrospective cohort study.<br /><b>Setting</b><br />U.S. Medicare beneficiaries aged 65 years or older.<br /><b>Patients</b><br />Patients with atrial fibrillation began anticoagulant use between 1 January 2012 and 30 November 2018 and subsequently initiated treatment with study antiarrhythmic drugs.<br /><b>Measurements</b><br />Time to event for bleeding-related hospitalizations (primary outcome) and ischemic stroke, systemic embolism, and death with or without recent (past 30 days) evidence of bleeding (secondary outcomes), adjusted with propensity score overlap weighting.<br /><b>Results</b><br />There were 91 590 patients (mean age, 76.3 years; 52.5% female) initiating use of study anticoagulants and antiarrhythmic drugs, 54 977 with amiodarone and 36 613 with flecainide or sotalol. Risk for bleeding-related hospitalizations increased with amiodarone use (rate difference [RD], 17.5 events [95% CI, 12.0 to 23.0 events] per 1000 person-years; hazard ratio [HR], 1.44 [CI, 1.27 to 1.63]). Incidence of ischemic stroke or systemic embolism did not increase (RD, -2.1 events [CI, -4.7 to 0.4 events] per 1000 person-years; HR, 0.80 [CI, 0.62 to 1.03]). The risk for death with recent evidence of bleeding (RD, 9.1 events [CI, 5.8 to 12.3 events] per 1000 person-years; HR, 1.66 [CI, 1.35 to 2.03]) was greater than that for other deaths (RD, 5.6 events [CI, 0.5 to 10.6 events] per 1000 person-years; HR, 1.15 [CI, 1.00 to 1.31]) (HR comparison: <i>P</i> = 0.003). The increased incidence of bleeding-related hospitalizations for rivaroxaban (RD, 28.0 events [CI, 18.4 to 37.6 events] per 1000 person-years) was greater than that for apixaban (RD, 9.1 events [CI, 2.8 to 15.3 events] per 1000 person-years) (<i>P</i> = 0.001).<br /><b>Limitation</b><br />Possible residual confounding.<br /><b>Conclusion</b><br />In this retrospective cohort study, patients aged 65 years or older with atrial fibrillation treated with amiodarone during apixaban or rivaroxaban use had greater risk for bleeding-related hospitalizations than those treated with flecainide or sotalol.<br /><b>Primary funding source</b><br />National Heart, Lung, and Blood Institute.<br /><br /><br /><br /><small>Ann Intern Med: 23 May 2023; epub ahead of print</small></div>

<div><h4>Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events.</h4><i>Khan SS, Post WS, Guo X, Tan J, ... Greenland P, Kavousi M</i><br /><b>Importance</b><br />Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts.<br /><b>Objective</b><br />To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model.<br /><b>Design, setting, and participants</b><br />Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands.<br /><b>Exposure</b><br />Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score.<br /><b>Main outcomes and measures</b><br />Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed.<br /><b>Results</b><br />The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.<br /><br /><br /><br /><small>JAMA: 23 May 2023; 329:1768-1777</small></div>

<div><h4>Effect of Adapted Mindfulness Training in Participants With Elevated Office Blood Pressure: The MB-BP Study: A Randomized Clinical Trial.</h4><i>Loucks EB, Schuman-Olivier Z, Saadeh FB, Scarpaci MM, ... Britton WB, Kronish IM</i><br /><AbstractText><br /><b>Background:</b><br/>Hypertension is a leading risk factor for cardiovascular disease. Despite availability of effective lifestyle and medication treatments, blood pressure (BP) is poorly controlled in the United States. Mindfulness training may offer a novel approach to improve BP control. The objective was to evaluate the effects of Mindfulness-Based Blood Pressure Reduction (MB-BP) versus enhanced usual care control on unattended office systolic BP. Methods and Results Methods included a parallel-group phase 2 randomized clinical trial conducted from June 2017 to November 2020. Follow-up time was 6 months. Outcome assessors and data analyst were blinded to group allocation. Participants had elevated unattended office BP (≥120/80 mm Hg). We randomized 201 participants to MB-BP (n=101) or enhanced usual care control (n=100). MB-BP is a mindfulness-based program adapted for elevated BP. Loss-to-follow-up was 17.4%. The primary outcome was change in unattended office systolic BP at 6 months. A total of 201 participants (58.7% women; 81.1% non-Hispanic White race and ethnicity; mean age, 59.5 years) were randomized. Results showed that MB-BP was associated with a 5.9-mm Hg reduction (95% CI, -9.1 to -2.8 mm Hg) in systolic BP from baseline and outperformed the control group by 4.5 mm Hg at 6 months (95% CI, -9.0 to -0.1 mm Hg) in prespecified analyses. Plausible mechanisms with evidence to be impacted by MB-BP versus control were sedentary activity (-350.8 sitting min/wk [95% CI, -636.5 to -65.1] sitting min/wk), Dietary Approaches to Stop Hypertension diet (0.32 score [95% CI, -0.04 to 0.67]), and mindfulness (7.3 score [95% CI, 3.0-11.6]). <br /><b>Conclusions:</b><br/>A mindfulness-based program adapted for individuals with elevated BP showed clinically relevant reductions in systolic BP compared with enhanced usual care. Mindfulness training may be a useful approach to improve BP. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03256890 and NCT03859076.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e028712; epub ahead of print</small></div>

<div><h4>Branched-Chain Amino Acids in Computed Tomography-Defined Adipose Depots and Coronary Artery Disease: A PROMISE Trial Biomarker Substudy.</h4><i>Zhao E, Giamberardino SN, Pagidipati NJ, Voora D, ... Foldyna B, Shah SH</i><br /><AbstractText><br /><b>Background:</b><br/>The interplay between branched-chain amino acid (BCAA) metabolism, an important pathway in adiposity and cardiometabolic disease, and visceral adipose depots such as hepatic steatosis (HS) and epicardial adipose tissue is unknown. We leveraged the PROMISE clinical trial with centrally adjudicated coronary computed tomography angiography imaging to determine relationships between adipose depots, BCAA dysregulation, and coronary artery disease (CAD). Methods and Results The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial randomized 10 003 outpatients with stable chest pain to computed tomography angiography versus standard-of-care diagnostics. For this study, we included 1798 participants with available computed tomography angiography data and biospecimens. Linear and logistic regression were used to determine associations between a molar sum of BCAAs measured by nuclear magnetic resonance spectroscopy with body mass index, adipose traits, and obstructive CAD. Mendelian randomization was then used to determine if BCAAs are in the causal pathway for adipose depots or CAD. The study sample had a mean age of 60 years (SD, 8.0), body mass index of 30.6 (SD, 5.9), and epicardial adipose tissue volume of 57.3 (SD, 21.3) cm<sup>3</sup>/m<sup>2</sup>; 27% had HS, and 14% had obstructive CAD. BCAAs were associated with body mass index (multivariable beta 0.12 per SD increase in BCAA [95% CI, 0.08-0.17]; <i>P</i>=4×10<sup>-8</sup>). BCAAs were also associated with HS (multivariable odds ratio [OR], 1.46 per SD increase in BCAAs [95% CI, 1.28-1.67]; <i>P</i>=2×10<sup>-8</sup>), but BCAAs were associated only with epicardial adipose tissue volume (odds ratio, 1.18 [95% CI, 1.07-1.32]; <i>P</i>=0.002) and obstructive CAD (OR, 1.18 [95% CI, 1.04-1.34]; <i>P</i>=0.009) in univariable models. Two-sample Mendelian randomization did not support the role of BCAAs as within the causal pathways for HS or CAD. <br /><b>Conclusions:</b><br/>BCAAs have been implicated in the pathogenesis of cardiometabolic diseases, and adipose depots have been associated with the risk of CAD. Leveraging a large clinical trial, we further establish the role of dysregulated BCAA catabolism in HS and CAD, although BCAAs did not appear to be in the causal pathway of either disease. This suggests that BCAAs may serve as an independent circulating biomarker of HS and CAD but that their association with these cardiometabolic diseases is mediated through other pathways.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e028410; epub ahead of print</small></div>

<div><h4>A RANDOMISED CONTROLLED TRIAL TO INVESTIGATE THE USE OF ACUTE CORONARY SYNDROME THERAPY IN PATIENTS HOSPITALISED WITH COVID-19: THE C19-ACS TRIAL.</h4><i>Kanagaratnam P, Francis DP, Chamie D, Coyle C, ... Cornelius V, Shun-Shin M</i><br /><b>Background</b><br />Patients hospitalised with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease.<br /><b>Objectives</b><br />To investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with COVID-19 and coronary disease risk factors.<br /><b>Patients/methods</b><br />A randomised controlled open-label trial across acute hospitals (UK and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death).<br /><b>Results</b><br />320 patients from 9 centres were randomised. The trial terminated early due to low recruitment. At 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted OR 0.73, 95%CI 0.38 to 1.41, p=0.355). Significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR 1.46, 95% CrI 0.88 to 2.37, Pr(Beta>0)=93%; adjusted OR 1.50, 95% CrI 0.91 to 2.45, Pr(Beta>0)=95%) and median time to discharge home was two days shorter (95% CrI -4 to 0, 2% probability that it was worse).<br /><b>Conclusions</b><br />Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Thromb Haemost: 23 May 2023; epub ahead of print</small></div>

<div><h4>Racial and Ethnic Disparities in the Treatment and Outcomes for Witnessed Out-of-Hospital Cardiac Arrest in Connecticut.</h4><i>Sutton TS, Bailey DL, Rizvi A, Al-Araji R, ... Hashim S, McKay RG</i><br /><b>Background</b><br />Racial and ethnic disparities in the treatment and outcomes for witnessed out-of-hospital cardiac arrest (OHCA) in the United States have been previously described. We sought to characterize disparities in pre-hospital care, overall survival, and survival with favorable neurological outcomes following witnessed OHCA in the state of Connecticut.<br /><b>Methods</b><br />We performed a cross-sectional study to compare pre-hospital treatment and outcomes for White versus Black and Hispanic (Minority) OHCA patients submitted from Connecticut to the Cardiac Arrest Registry to Enhance Survival (CARES) between 2013 and 2021. Primary outcomes included bystander CPR use, bystander automated external defibrillator (AED) use with attempted defibrillation, overall survival, and survival with favorable cerebral function.<br /><b>Results</b><br />2,809 patients with witnessed OHCA were analyzed (924 Black or Hispanic; 1885 White). Minorities had lower rates of bystander CPR (31.4% vs 39.1%, P=0.002) and bystander AED placement with attempted defibrillation (10.5% vs 14.4%, P=0.004), with lower rates of survival to hospital discharge (10.3% vs 14.8%, P=0.001) and survival with favorable cerebral function (65.3% vs 80.2%, P=0.003). Minorities were less likely to receive bystander CPR in communities with median annual household income >$80, 000 (OR, 0.56; 95% CI, 0.33 - 0.95; P=0.030) and in integrated neighborhoods (OR, 0.70; 95% CI, 0.52 - 0.95; P=0.020).<br /><b>Conclusions</b><br />Black and Hispanic Connecticut patients with witnessed OHCA have lower rates of bystander CPR, attempted AED defibrillation, overall survival, and survival with favorable neurological outcomes compared to White patients. Minorities were less likely to receive bystander CPR in affluent and integrated communities.<br /><br />Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.<br /><br /><small>Resuscitation: 23 May 2023:109850; epub ahead of print</small></div>

<div><h4>Long-Term Outcomes of Early Coronary Artery Disease Testing After New-Onset Heart Failure.</h4><i>Zheng J, Heidenreich PA, Kohsaka S, Fearon WF, Sandhu AT</i><br /><b>Background</b><br />Coronary artery disease (CAD) testing remains underutilized in patients with newly diagnosed heart failure (HF). The longitudinal clinical impact of early CAD testing has not been well-characterized. We investigated changes in clinical management and long-term outcomes after early CAD evaluation in patients with incident HF.<br /><b>Methods</b><br />We identified Medicare patients with incident HF from 2006 to 2018. The exposure variable was early CAD testing within 1 month of initial HF diagnosis. Covariate-adjusted rates of cardiovascular interventions after testing, including CAD-related management, were modeled using mixed-effects regression with clinician as a random intercept. We assessed mortality and hospitalization outcomes using landmark analyses with inverse probability-weighted Cox proportional hazards models. Falsification end points and mediation analysis were employed for bias assessment.<br /><b>Results</b><br />Among 309 559 patients with new-onset HF without prior CAD, 15.7% underwent early CAD testing. Patients who underwent prompt CAD evaluation had higher adjusted rates of subsequent antiplatelet/statin prescriptions and revascularization, guideline-directed therapy for HF, and stroke prophylaxis for atrial fibrillation/flutter than controls. In weighted Cox models, 1-month CAD testing was associated with significantly reduced all-cause mortality (hazard ratio, 0.93 [95% CI, 0.91-0.96]). Mediation analyses indicated that ≈70% of this association was explained by CAD management, largely from new statin prescriptions. Falsification end points (outpatient diagnoses of urinary tract infection and hospitalizations for hip/vertebral fracture) were nonsignificant.<br /><b>Conclusions</b><br />Early CAD testing after incident HF was associated with a modest mortality benefit, driven mostly by subsequent statin therapy. Further investigation on clinician barriers to testing and treating high-risk patients may improve adherence to guideline-recommended cardiovascular interventions.<br /><br /><br /><br /><small>Circ Heart Fail: 22 May 2023:e010426; epub ahead of print</small></div>

<div><h4>Age Dependency of Cardiovascular Outcomes With the Amyloidogenic pV142I Transthyretin Variant Among Black Individuals in the US.</h4><i>Selvaraj S, Claggett BL, Quarta CC, Yu B, ... Falk RH, Solomon SD</i><br /><b>Importance</b><br />Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.<br /><b>Objective</b><br />To estimate age-dependent risks for cardiovascular events with the variant.<br /><b>Design, settings, and participants</b><br />This cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up until 2019; median follow-up, 27.6 years). Data analyses were completed from June 2022 to April 2023.<br /><b>Exposure</b><br />pV142I carrier status.<br /><b>Main outcomes</b><br />The association between the variant and AF, HF hospitalization, mortality, and a composite of HF hospitalization or mortality was modeled by generating 10-year absolute risk differences for each year between ages 53 (the median age at visit 1) and 80 years, adjusting for the first 5 principal components of ancestry and sex. As an example, 5- and 10-year risk differences were specifically estimated for the composite outcome among participants surviving to age 80 years.<br /><b>Results</b><br />Among 3856 Black participants (including 124 carriers) at visit 1, 2403 (62%) were women, 2140 (56%) had hypertension, and 740 (20%) had diabetes, with no differences between groups. The 10-year absolute risk difference between ages 53 and 80 years increased over time for each outcome. Statistical significance for increased 10-year risk difference emerged near ages 65 years for AF, 70 years for HF hospitalization, and 75 years for mortality. Among participants surviving to age 80 years, carriers had a 20% (95% CI, 2%-37%) and 24% (95% CI, 1%-47%) absolute increased risk for HF hospitalization or death at 5 and 10 years, respectively. Thus, at age 80 years, only 4 carriers would need to be identified to attribute 1 HF hospitalization or death over the following decade to the variant.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, age-specific risks were provided for relevant outcomes with the pV142I variant. Despite a relatively benign course during earlier years, Black individuals who carry the pV142I variant surviving into later life may be particularly vulnerable. These data may inform timing for screening, risk counseling to patients, and potential strategies for early targeted therapy.<br /><br /><br /><br /><small>JAMA Cardiol: 22 May 2023; epub ahead of print</small></div>

<div><h4>Body Weight Time in Target Range and Cardiovascular Outcomes in Adults with Overweight/Obesity and Type 2 Diabetes.</h4><i>Liu M, Xu X, Chen X, Guo Y, ... Zhuang X, Liao X</i><br /><b>Aims</b><br />Prescription of weight loss to individuals is often characterized by weight fluctuations. However, current body weight management metrics may have difficulty characterizing the changes in body weight over time. We aims to characterize the long-term changes using body weight time in target range (TTR) and test its independent association with cardiovascular outcomes.<br /><b>Methods</b><br />We included 4,468 adults from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the percentage of time during which body weight was within the Look AHEAD weight loss goal range. The associations of body weight TTR with cardiovascular outcomes were analyzed using multivariable Cox modeling and restricted cubic spline function.<br /><b>Results</b><br />Among the participants (mean age 58.9 years, 58.5% women, 66.5% White), there were 721 incident primary outcomes (cumulative incidence: 17.5%, 95% confidence interval [CI]: 16.3%-18.8%) during a median of 9.5 years of follow-up. Each 1-SD (standard deviation) increase in body weight TTR was significantly associated with a decreased risk of the primary outcome (hazard ratio [HR]: 0.84, 95% CI: 0.75-0.94) after adjusting for mean and variability of body weight and traditional cardiovascular risk factors. Further analyses using restricted cubic spline indicated the inverse association between body weight TTR and primary outcome in a dose-dependent manner. Similar associations remained significant among the participants with a lower baseline or mean body weight.<br /><b>Conclusion</b><br />In adults with overweight/obesity and type 2 diabetes, higher body weight TTR was independently associated with lower risks of cardiovascular adverse events in a dose-response manner.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur J Prev Cardiol: 22 May 2023; epub ahead of print</small></div>

<div><h4>Risk of serious hypoglycemia in patients with atrial fibrillation and diabetes concurrently taking antidiabetic drugs and oral anticoagulants: A nationwide cohort study.</h4><i>Huang HK, Liu PP, Lin SM, Yeh JI, ... Loh CH, Tu YK</i><br /><b>Aims</b><br />Evidence regarding the risks of serious hypoglycemia for patients with atrial fibrillation (AF) and diabetes mellitus (DM) taking antidiabetic medications with concurrent non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin is limited. This study aimed to investigate this knowledge gap.<br /><b>Methods and results</b><br />This retrospective cohort study used nationwide data from Taiwan\'s National Health Insurance Research Database and included a total of 56,774 adult patients treated with antidiabetic medications and oral anticoagulants between January 1, 2012 and December 31, 2020. The incidence rate ratios (IRRs) of serious hypoglycemia were estimated for patients taking antidiabetic drugs with NOACs versus warfarin. Poisson regression models with generalized estimating equations accounting for intra-individual correlation across follow-up periods were used. Stabilized inverse probability of treatment weighting was used to create treatment groups with balanced characteristics for comparisons. Compared to concurrent use of antidiabetic drugs with warfarin, those with NOACs showed a significantly lower risk of serious hypoglycemia (IRR = 0.73, 95% CI: 0.63-0.85, p<0.001). In the analyses of each NOAC, patients taking dabigatran (IRR = 0.76, 95% CI: 0.63-0.91, p = 0.002), rivaroxaban (IRR = 0.72, 95% CI: 0.61-0.86, p<0.001), and apixaban (IRR = 0.71, 95% CI: 0.57-0.89, p = 0.003) showed a significantly lower risk of serious hypoglycemia than those taking warfarin.<br /><b>Conclusion</b><br />In patients with AF and DM taking antidiabetic drugs, concurrent use of NOACs was associated with a lower risk of serious hypoglycemia than concurrent use of warfarin.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 22 May 2023; epub ahead of print</small></div>

<div><h4>Long-term Outcomes of Tricuspid Valve Intervention During Stage 2 Palliation in Patients with a Single Right Ventricle.</h4><i>Smerling JL, Goldstone AB, Bacha EA, Liberman L</i><br /><b>Objectives</b><br />In single ventricle patients with a systemic right ventricle, tricuspid valve regurgitation increases the risk of adverse outcomes, and tricuspid valve intervention at the time of staged palliation further increases that risk in the post-operative period. Long-term outcomes of valve intervention in patients with significant regurgitation during stage 2 palliation, however, have not been established. The purpose of this study is to evaluate long-term outcomes after tricuspid valve intervention during stage 2 palliation in patients with RV dominant circulation in a multicenter study.<br /><b>Methods</b><br />The study was performed using the SVR and SVR II datasets. Survival analysis was performed to describe the association between valve regurgitation, intervention, and long-term survival. Cox proportional-hazards modeling was used to estimate the longitudinal association of tricuspid intervention and transplant-free survival.<br /><b>Results</b><br />Patients with tricuspid regurgitation at either stage 1 or 2 had worse transplant-free survival (HR 1.61, 95% CI 1.12-2.32; HR 2.3, 95% CI 1.39-3.82). Those with regurgitation who underwent concomitant valve intervention at stage 2 were significantly more likely to die or undergo heart transplantation compared to those with regurgitation who did not (HR 2.93, CI 2.16-3.99). Patients with tricuspid regurgitation at the time of Fontan had favorable outcomes regardless of valve intervention.<br /><b>Conclusions</b><br />The risks associated with tricuspid regurgitation in single ventricle patients do not appear to be mitigated by valve intervention at the time of stage 2 palliation. Patients who underwent valve intervention for tricuspid regurgitation at stage 2 had significantly worse survival compared with patients with tricuspid regurgitation who did not.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Thorac Cardiovasc Surg: 22 May 2023; epub ahead of print</small></div>