Journal: J Am Heart Assoc

Sorted by: date / impact
Abstract

Endovascular Therapy for Acute Ischemic Stroke in Patients With Prestroke Disability.

Tanaka K, Yamagami H, Yoshimoto T, Uchida K, ... Sakai N, Yoshimura S

Background:
Outcomes after stroke as a result of large-vessel occlusion in patients with prestroke disability were compared between endovascular therapy (EVT) and medical management. Methods and Results Of 2420 patients with acute stroke with large-vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients with prestroke modified Rankin Scale scores 2 to 4 with occlusion of the internal carotid artery, or M1 of the middle cerebral artery were analyzed. The primary effectiveness outcome was the favorable outcome, defined as return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage. A total of 339 patients (237 women; median 85 [interquartile range (IQR), 79-89] years of age; median prestroke modified Rankin Scale score of 3 [IQR, 2-4]) were analyzed. EVT was performed in 175 patients (51.6%; mechanical thrombectomy, n=139). The EVT group was younger (p<0.01) and had lower prestroke modified Rankin Scale scores (p<0.01) than the medical management group. The favorable outcome was seen in 28.0% of the EVT group and in 10.9% of the medical management group (p<0.01). EVT was associated with the favorable outcome (adjusted odds ratio, 3.01; 95% CI, 1.55-5.85; mixed effects multivariable model with inverse probability of treatment weighting). Symptomatic intracranial hemorrhage rates were similar between the EVT (4.0%) and medical management (4.3%) groups (p=1.00).
Conclusions:
Patients who underwent EVT showed better functional outcomes than those with medical management. Given proper patient selection, withholding EVT solely on the basis of prestroke disability might not offer the best chance of favorable outcome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02419794.




J Am Heart Assoc: 20 Jul 2021:e020783; epub ahead of print
Tanaka K, Yamagami H, Yoshimoto T, Uchida K, ... Sakai N, Yoshimura S
J Am Heart Assoc: 20 Jul 2021:e020783; epub ahead of print | PMID: 34284599
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Breastfeeding in the First Days of Life Is Associated With Lower Blood Pressure at 3 Years of Age.

Miliku K, Moraes TJ, Becker AB, Mandhane PJ, ... Subbarao P, Azad MB

Background:
Breastfeeding in infancy is associated with lower cardiovascular disease risk in adulthood; however, the amount of breastfeeding required to achieve this benefit is unknown. Methods and Results In the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study, we analyzed 2382 children with complete data on early life feeding and blood pressure. Infant feeding was documented from hospital records in the first few days of life and reported by mothers throughout infancy. Blood pressure was measured at 3 years of age. Analyses controlled for birth weight, gestational age, socioeconomic status, maternal body mass index, and other potential confounders. We found that nearly all children (2333/2382; 97.9%) were ever breastfed, of whom 98 (4.2%) only briefly received breast milk during their birth hospitalization (\"early limited breastfeeding\"). At 3 years of age, blood pressure was higher in children who were never breastfed (mean systolic/diastolic 103/60 mm Hg) compared with those who were ever breastfed (99/58 mm Hg), including those who received only early limited breastfeeding (99/57 mm Hg). These differences in systolic blood pressure persisted in adjusted models (ever breastfed: -3.47 mm Hg, 95% CI, -6.14 to -0.80; early limited breastfeeding: -4.24 mm Hg, 95% CI, -7.45 to -1.04). Among breastfed children, there was no significant dose-response association according to the duration or exclusivity of breastfeeding. Associations were not mediated by child body mass index.
Conclusions:
Although the benefits of sustained and exclusive breastfeeding are indisputable, this study indicates any breastfeeding, regardless of duration or exclusivity, is associated with lower blood pressure at 3 years of age. Further research examining the bioactive components of early breast milk, underlying mechanisms, and long-term associations is warranted.




J Am Heart Assoc: 20 Jul 2021:e019067; epub ahead of print
Miliku K, Moraes TJ, Becker AB, Mandhane PJ, ... Subbarao P, Azad MB
J Am Heart Assoc: 20 Jul 2021:e019067; epub ahead of print | PMID: 34284597
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sustained Inflation During Chest Compression: A New Technique of Pediatric Cardiopulmonary Resuscitation That Improves Recovery and Survival in a Pediatric Porcine Model.

Schmölzer GM, Patel SD, Monacelli S, Kim SY, ... O\'Reilly M, Cheung PY

Background:
Chest compression (CC) during sustained inflations (CC+SI) compared with CC with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation in asphyxiated pediatric piglets will reduce time to return of spontaneous circulation (ROSC). Methods and Results Piglets (20-23 days of age, weighing 6.2-10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure <25 mm Hg with bradycardia. After cardiac arrest, piglets were randomized to CC+SI (n=12) or CCaV (n=12) or sham (n=8). Sham-operated animals had no asphyxia. Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded. There were no differences in baseline parameters or the duration and degree of asphyxiation. Median (interquartile range) Time to ROSC was 248 (41-346) seconds compared with 720 (167-720) seconds in the CC+SI group and CCaV group, respectively (P=0.0292). There was a 100% higher rate of ROSC in the CC+SI group versus CCaV group, with 10 (83%) versus 5 (42%) achieving ROSC (P=0.089), respectively. Piglets in the CC+SI and CCaV groups received intravenous epinephrine boluses to achieve ROSC (8/12 versus 10/12 P=0.639). There was a significantly higher minute ventilation in the CC+SI group, which was secondary to a 5-fold increase in the number of inflations per minute and a 1.5-fold increase in tidal volume.
Conclusions:
CC+SI reduced time to ROSC and improved survival compared with using CCaV. CC+SI allowed passive ventilation of the lung while providing chest compressions. This technique warrants further studies to examine the potential to improve outcomes in pediatric patients with cardiac arrest. Registration URL: https://www.preclinicaltrials.eu; Unique identifier: PCTE0000152.




J Am Heart Assoc: 20 Jul 2021:e019136; epub ahead of print
Schmölzer GM, Patel SD, Monacelli S, Kim SY, ... O'Reilly M, Cheung PY
J Am Heart Assoc: 20 Jul 2021:e019136; epub ahead of print | PMID: 34284596
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis.

Klein A, Cremer P, Kontzias A, Furqan M, ... Lim-Watson MZ, Magestro M

Background:
Patients with recurrent pericarditis (RP) may develop complications, multiple recurrences, or inadequate treatment response. This study aimed to characterize disease burden and unmet needs in RP. Methods and Results This retrospective US database analysis included newly diagnosed patients with RP with ≥24 months of continuous history following their first pericarditis episode. RP was defined as ≥2 pericarditis episodes ≥28 days apart. Some patients had ≥2 recurrences, while others had a single recurrence with a serious complication, ie, constrictive pericarditis, cardiac tamponade, or a large pericardial effusion with pericardiocentesis/pericardial window. Among these patients with multiple recurrences and/or complications, some had features relating to treatment history, including long-term corticosteroid use (corticosteroids started within 30 days of flare, continuing ≥90 consecutive days) or inadequate treatment response (pericarditis recurring despite corticosteroids and/or colchicine, or other drugs [excluding NSAIDs] within 30 days of flare, or prior pericardiectomy). Patients (N=2096) had hypertension (60%), cardiomegaly (9%), congestive heart failure (17%), atrial fibrillation (16%), autoimmune diseases (18%), diabetes mellitus (21%), renal disease (20%), anxiety (21%), and depression (14%). Complications included pericardial effusion (50%), cardiac tamponade (9%), and constrictive pericarditis (4%). Pharmacotherapy included colchicine (51%), NSAIDs (40%), and corticosteroids (30%), often in combination. This study estimates 37 000 US patients with RP; incidence was 6.0/100 000/year (95% CI, 5.6‒6.3), and prevalence was 11.2/100 000 (95% CI, 10.6‒11.7).
Conclusions:
Patients with RP may have multiple recurrences and/or complications, often because of inadequate treatment response and persistent underlying disease. Corticosteroid use is frequent despite known side-effect risks, potentially exacerbated by prevalent comorbidities. Substantial clinical burden and lack of effective treatments underscore the high unmet need.




J Am Heart Assoc: 20 Jul 2021:e018950; epub ahead of print
Klein A, Cremer P, Kontzias A, Furqan M, ... Lim-Watson MZ, Magestro M
J Am Heart Assoc: 20 Jul 2021:e018950; epub ahead of print | PMID: 34284595
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Out-of-Pocket Annual Health Expenditures and Financial Toxicity From Healthcare Costs in Patients With Heart Failure in the United States.

Wang SY, Valero-Elizondo J, Ali HJ, Pandey A, ... Nasir K, Khera R

Background:
Heart failure (HF) poses a major public health burden in the United States. We examined the burden of out-of-pocket healthcare costs on patients with HF and their families. Methods and Results In the Medical Expenditure Panel Survey, we identified all families with ≥1 adult member with HF during 2014 to 2018. Total out-of-pocket healthcare expenditures included yearly care-specific costs and insurance premiums. We evaluated 2 outcomes of financial toxicity: (1) high financial burden-total out-of-pocket healthcare expense to postsubsistence income ratio of >20%, and (2) catastrophic financial burden with the ratio of >40%-a bankrupting expense defined by the World Health Organization. There were 788 families in the Medical Expenditure Panel Survey with a member with HF representing 0.54% (95% CI, 0.48%-0.60%) of all families nationally. The overall mean annual out-of-pocket healthcare expenses were $4423 (95% CI, $3908-$4939), with medications and health insurance premiums representing the largest categories of cost. Overall, 14% (95% CI, 11%-18%) of families experienced a high burden and 5% (95% CI, 3%-6%) experienced a catastrophic burden. Among the two-fifths of families considered low income, 24% (95% CI, 18%-30%) experienced a high financial burden, whereas 10% (95% CI, 6%-14%) experienced a catastrophic burden. Low-income families had 4-fold greater risk-adjusted odds of high financial burden (odds ratio [OR] , 3.9; 95% CI, 2.3-6.6), and 14-fold greater risk-adjusted odds of catastrophic financial burden (OR, 14.2; 95% CI, 5.1-39.5) compared with middle/high-income families.
Conclusions:
Patients with HF and their families experience large out-of-pocket healthcare expenses. A large proportion encounter financial toxicity, with a disproportionate effect on low-income families.




J Am Heart Assoc: 19 Jul 2021; 10:e022164
Wang SY, Valero-Elizondo J, Ali HJ, Pandey A, ... Nasir K, Khera R
J Am Heart Assoc: 19 Jul 2021; 10:e022164 | PMID: 33998273
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Activation of Glucagon-Like Peptide-1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism-Independent Pathway.

Li Q, Jia M, Yan Z, Li Q, ... Zhao Z, Zhu Z

Background:
Patients with hypertension and diabetes mellitus are susceptible to dementia, but regular therapy fails to reduce the risk of dementia. Glucagon-like peptide-1 receptor agonists have neuroprotective effects in experimental studies. We aimed to assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on cognitive function and whether its effect was associated with metabolic changes in patients with type 2 diabetes mellitus. Methods and Results Fifty patients with type 2 diabetes mellitus were recruited in this prospective study. All patients underwent cognitive assessment and brain activation monitoring by functional near-infrared spectroscopy. At 12 weeks, patients in the glucagon-like peptide-1 group acquired better scores in all cognitive tests and showed remarkable improvement in memory and attention (P=0.040) test compared with the control group after multivariable adjustment. Compared with the control group, liraglutide significantly increased activation of the dorsolateral prefrontal cortex and orbitofrontal cortex brain regions (P=0.0038). After liraglutide treatment, cognitive scores were significantly correlated with changes in these activating brain regions (P<0.05), but no correlation was observed between the changes in cognitive function and changes of body mass index, blood pressure, and glycemic levels.
Conclusions:
We concluded that liraglutide improves cognitive decline in patients with type 2 diabetes mellitus. This beneficial effect is independent of its hypoglycemic effect and weight loss. The optimal intervention should be targeted to cognitive decline in the early stages of dementia. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT03707171.




J Am Heart Assoc: 19 Jul 2021; 10:e020734
Li Q, Jia M, Yan Z, Li Q, ... Zhao Z, Zhu Z
J Am Heart Assoc: 19 Jul 2021; 10:e020734 | PMID: 34250817
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Gilotra NA, Pamboukian SV, Mountis M, Robinson SW, ... Aaronson KD, Grady KL

Background:
Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (P=0.007) and less burden by both time spent (P<0.0001) and difficulty (P=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (P=0.034) and being a married caregiver (P=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; P=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; P=0.011).
Conclusions:
Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.




J Am Heart Assoc: 19 Jul 2021; 10:e019901
Gilotra NA, Pamboukian SV, Mountis M, Robinson SW, ... Aaronson KD, Grady KL
J Am Heart Assoc: 19 Jul 2021; 10:e019901 | PMID: 34250813
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Predictors of Permanent Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement - A Systematic Review and Meta-Analysis.

Ullah W, Zahid S, Zaidi SR, Sarvepalli D, ... Vishnevsky A, Fischman DL

Background:
As transcatheter aortic valve replacement (TAVR) technology expands to healthy and lower-risk populations, the burden and predictors of procedure-related complications including the need for permanent pacemaker (PPM) implantation needs to be identified. Methods and Results Digital databases were systematically searched to identify studies reporting the incidence of PPM implantation after TAVR. A random- and fixed-effects model was used to calculate unadjusted odds ratios (OR) for all predictors. A total of 78 studies, recruiting 31 261 patients were included in the final analysis. Overall, 6212 patients required a PPM, with a mean of 18.9% PPM per study and net rate ranging from 0.16% to 51%. The pooled estimates on a random-effects model indicated significantly higher odds of post-TAVR PPM implantation for men (OR, 1.16; 95% CI, 1.04-1.28); for patients with baseline mobitz type-1 second-degree atrioventricular block (OR, 3.13; 95% CI, 1.64-5.93), left anterior hemiblock (OR, 1.43; 95% CI, 1.09-1.86), bifascicular block (OR, 2.59; 95% CI, 1.52-4.42), right bundle-branch block (OR, 2.48; 95% CI, 2.17-2.83), and for periprocedural atriorventricular block (OR, 4.17; 95% CI, 2.69-6.46). The mechanically expandable valves had 1.44 (95% CI, 1.18-1.76), while self-expandable valves had 1.93 (95% CI, 1.42-2.63) fold higher odds of PPM requirement compared with self-expandable and balloon-expandable valves, respectively.
Conclusions:
Male sex, baseline atrioventricular conduction delays, intraprocedural atrioventricular block, and use of mechanically expandable and self-expanding prosthesis served as positive predictors of PPM implantation in patients undergoing TAVR.




J Am Heart Assoc: 19 Jul 2021; 10:e020906
Ullah W, Zahid S, Zaidi SR, Sarvepalli D, ... Vishnevsky A, Fischman DL
J Am Heart Assoc: 19 Jul 2021; 10:e020906 | PMID: 34259045
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Elevated Fatty Liver Index Is Independently Associated With New Onset of Hypertension During a 10-Year Period in Both Male and Female Subjects.

Higashiura Y, Furuhashi M, Tanaka M, Takahashi S, ... Hanawa N, Miura T

Background:
Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. Because of a sex difference in FLI level, we hypothesized that FLI is associated with development of hypertension to a greater extent in men or women. Methods and Results We investigated the relationship between FLI and development of hypertension during a 10-year period in a general population of subjects who received annual health examinations (n=28 990). After exclusion (44.9%) of subjects with missing data and those with hypertension at baseline, a total of 15 965 subjects (men/women: 9466/6499) were included. FLI level was significantly higher in men than in women. During the 10-year period, 2304 men (24.3%) and 745 women (11.5%) had new onset of hypertension. Multivariable Cox proportional hazard models with a restricted cubic spline showed that the hazard ratios (HRs) for development of hypertension after adjustment of age, systolic blood pressure, estimated glomerular filtration rate, habits of smoking and alcohol drinking, family history of hypertension, and diagnosis of diabetes mellitus and dyslipidemia increased gradually with increase in FLI in men and increased rapidly and then slowly with increase in FLI in women. There was a significant interaction between FLI and sex for the risk of hypertension in all of the subjects (P=0.049). The addition of FLI to traditional risk factors significantly improved the discriminatory capability.
Conclusions:
A high level of FLI predicts the development of hypertension in both men and women, although distribution patterns of HRs were different between sexes.




J Am Heart Assoc: 19 Jul 2021; 10:e021430
Higashiura Y, Furuhashi M, Tanaka M, Takahashi S, ... Hanawa N, Miura T
J Am Heart Assoc: 19 Jul 2021; 10:e021430 | PMID: 34259033
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Major Adverse Cardiovascular Events in Patients With Stroke and Cardiac Wall Motion Abnormalities.

Kamran S, Akhtar N, Singh R, Imam Y, ... Muhammad A, Perkins JD

Background:
The association of cardiac wall motion abnormalities (CWMAs) in patients with stroke who have major adverse cardiovascular events (MACE) remains unclear. The purpose of this study was to estimate the 50-month risk of MACE, including stroke recurrence, acute coronary events, and vascular death in patients with stroke who have CWMAs. Methods and Results We performed a retrospective analysis of prospectively collected acute stroke data (acute stroke and transient ischemic attack) over 50 months by electronic medical records. Data included demographic and clinical information, vascular imaging, and echocardiography data including CWMAs and MACE. Of a total of 2653 patients with acute stroke/transient ischemic attack, CWMA was observed in 355 (13.4%). In patients with CWMAs, the embolic stroke of undetermined source (50.7%) was the most frequent index stroke subtype and stroke recurrences (P=0.001). In multivariate Cox regression after adjustment for demographics, traditional risk, and confounding factors, CWMA was independently associated with a higher risk of MACE (adjusted hazard ratio [HR], 1.74; 95% CI, 1.37-2.21 [P=0.001]). Similarly, CWMA independently conferred an increased risk for ischemic stroke recurrence (adjusted HR, 1.50; 95% CI, 1.01-2.17 [P=0.04]), risk of acute coronary events (aHR, 2.50; 95% CI, 1.83-3.40 [P=0.001]) and vascular death (adjusted HR, 1.57; 95% CI, 1.04-2.40 [P=0.03]), in comparison to the patients with stroke without CWMA.
Conclusions:
In a multiethnic cohort of ischemic stroke with CWMA, CWMA was associated with 1.7-fold higher risks of MACE independent of established risk factors. Embolic stroke of undetermined source was the most common stroke association with CWMA. Patients with stroke should be screened for CWMA to identify those at higher risk of MACE.




J Am Heart Assoc: 19 Jul 2021; 10:e020888
Kamran S, Akhtar N, Singh R, Imam Y, ... Muhammad A, Perkins JD
J Am Heart Assoc: 19 Jul 2021; 10:e020888 | PMID: 34259032
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Modulation of Sirt1 and FoxO1 on Hypothalamic Leptin-Mediated Sympathetic Activation and Inflammation in Diet-Induced Obese Rats.

Liu X, Zheng H

Background:
Hypothalamic leptin-mediated signaling contributes to the exaggerated sympatho-excitation and increased blood pressure in obesity-associated hypertension. The aim of the study was to investigate the roles of energy-sensing enzyme sirtuin1 (Sirt1) and forkhead box protein O1 (FoxO1) on the hypothalamic leptin-mediated high sympathetic nerve activity and inflammation in obesity. Methods and Results Sprague Dawley rats were fed with high-fat diet (HFD) for 12 weeks. In vivo, the potential of Srit1 and FoxO1 in the sympathetic effects of leptin was investigated via siRNA injection to knockdown Sirt1 or FoxO1 gene in the arcuate nucleus (ARCN) of hypothalamus in rats. In vitro, the effects of Sirt1 or FoxO1 on leptin-mediated inflammation were observed in proopiomelanocortin (POMC) and microglial cells. Knockdown Sirt1 by siRNA significantly reduced the renal sympathetic nerve activity (RSNA) and blood pressure responses to leptin injection in the ARCN in the HFD rats. Conversely, knockdown FoxO1 significantly enhanced the RSNA and blood pressure responses to leptin injection in the HFD rats. Knockdown Sirt1 reduced the levels of pro-inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), C1q/TNF-related protein-1 (CTRP1), and immune cell infiltration in the ARCN in the HFD rats. Knockdown FoxO1 significantly increased the level of IL-6 in the ARCN of HFD rats. In cultured hypothalamic POMC and microglial cells, knockdown Sirt1 significantly reduced leptin-induced IL-6 expression, affected the levels of AMP-activated protein kinase (AMPK) and serine/threonine-specific protein kinase (Akt). Knockdown FoxO1 significantly increased leptin-induced IL-6 in both POMC cells and microglial cells.
Conclusions:
These data suggest that both Sirt1 and FoxO1 are the key modulators of leptin signaling in the hypothalamus contributed to the over sympathetic activation and inflammation in obesity.




J Am Heart Assoc: 19 Jul 2021; 10:e020667
Liu X, Zheng H
J Am Heart Assoc: 19 Jul 2021; 10:e020667 | PMID: 34259031
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk of Physical Injury for Dispatched Citizen Responders to Out-of-Hospital Cardiac Arrest.

Andelius L, Malta Hansen C, Tofte Gregers MC, Kragh AMR, ... Torp-Pedersen C, Folke F

Background:
Citizen responder programs are implemented worldwide to dispatch volunteer citizens to participate in out-of-hospital cardiac arrest resuscitation. However, the risk of injuries in relation to activation is largely unknown. We aimed to assess the risk of physical injury for dispatched citizen responders. Methods and Results Since September 2017, citizen responders have been activated through a smartphone application when located close to a suspected cardiac arrest in the Capital Region of Denmark. A survey was sent to all activated citizen responders, including a specific question about risk of acquiring an injury during activation. We included all surveys from September 1, 2017, to May 15, 2020. From May 15, 2019, to May 15, 2020, we followed up on all survey nonresponders by phone call, e-mail, or text messages to examine if nonresponders were at higher risk of severe or fatal injuries. In 1665 suspected out-of-hospital cardiac arrests, 9574 citizen responders were dispatched and 76.6% (7334) answered the question regarding physical injury. No injury was reported by 99.3% (7281) of the responders. Being at risk of physical injury was reported by 0.3% (24), whereas 0.4% (26) reported an injury (25 minor injuries and 1 severe injury [ankle fracture]). When following up on nonresponders (2472), we reached 99.1% (2449). No one reported acquired injuries, and only 1 reported being at risk of injury.
Conclusions:
We found low risk of physical injury reported by volunteer citizen responders dispatched to out-of-hospital cardiac arrest. Risk of injury should be considered and monitored as a safety measure in citizen responder programs.




J Am Heart Assoc: 19 Jul 2021; 10:e021626
Andelius L, Malta Hansen C, Tofte Gregers MC, Kragh AMR, ... Torp-Pedersen C, Folke F
J Am Heart Assoc: 19 Jul 2021; 10:e021626 | PMID: 34259016
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Predictors of Sudden Cardiac Arrest Among Patients With Post-Myocardial Infarction Ejection Fraction Greater Than 35.

Adabag S, Zimmerman P, Lexcen D, Cheng A

Background:
Sudden cardiac arrest (SCA) risk increases after myocardial infarction (MI) in patients with a reduced ejection fraction (EF). However, the risk factors for SCA among patients with a post-MI EF >35% remain poorly understood. Methods and Results Using the Optum de-identified electronic health record data set from 2008 to 2017, we identified patients with an incident MI diagnosis and troponin elevation who had a post-MI EF >35% and underwent coronary angiography. Primary outcome was SCA within 1 year post-MI. The database was divided into derivation (70%) and validation (30%) cohorts by random selection. Cox proportional hazard regression was used to generate and validate a risk prediction model. Among 31 286 patients with an MI (median age 64.1; 39% female; 87% White), 499 experienced SCA within 1 year post-MI (estimated probability 1.8%). Lack of revascularization at MI, post-MI EF <50%, Black race, renal failure, chronic obstructive pulmonary disease, antiarrhythmic therapy, and absence of beta blocker therapy were independent predictors of SCA. A multivariable model consisting of these variables predicted SCA risk (C-statistic 0.73). Based on this model, the estimated annual probability of SCA was 4.4% (95% CI, 3.9-4.9) in the highest quartile of risk versus 0.6% (95% CI, 0.4-0.8) in the lowest quartile.
Conclusions:
Patients with a post-MI EF >35% have a substantial annual risk of SCA. A risk model consisting of acute coronary revascularization, EF, race, renal failure, chronic obstructive pulmonary disease, antiarrhythmic therapy, and beta blocker therapy can identify patients with higher risk of SCA, who may benefit from further risk stratification and closer monitoring.




J Am Heart Assoc: 19 Jul 2021; 10:e020993
Adabag S, Zimmerman P, Lexcen D, Cheng A
J Am Heart Assoc: 19 Jul 2021; 10:e020993 | PMID: 34259015
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

High Fructose-Induced Hypertension and Renal Damage Are Exaggerated in Dahl Salt-Sensitive Rats via Renal Renin-Angiotensin System Activation.

Xu L, Hu G, Qiu J, Fan Y, ... Kohzuki M, Ito O

Background:
High-fructose diet (HFr) induces hypertension and renal damage. However, it has been unknown whether the HFr-induced hypertension and renal damage are exaggerated in subjects with salt sensitivity. We tested impacts of HFr in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Methods and Results Male DS and DR rats were fed control diet or HFr (60% fructose) with normal-salt content. After 12 weeks, plasma and urinary parameters, renal histological characteristics, and renal expression of renin-angiotensin system components were examined. Furthermore, effects of renin-angiotensin system inhibitors were also examined in DS rats fed the HFr. HFr elevated blood pressure in DS rats but not in DR rats. HFr increased urinary albumin and liver type fatty acid binding protein excretions in both rats, but the excretions were exaggerated in DS rats. HFr increased plasma lipids and uric acid in both rats, whereas HFr increased creatinine clearance in DS rats but not DR rats. Although HFr decreased plasma renin activity in DS rats, HFr-induced glomerular injury, afferent arteriolar thickening, and renal interstitial fibrosis were exaggerated in DS rats. HFr increased renal expression of angiotensinogen, renin, (pro)renin receptor, angiotensin-converting enzyme, and angiotensin II type 1 receptor in DS rat, whereas HFr increased only angiotensin-converting enzyme expression and decreased renin and angiotensin II type 1 receptor expressions in DR rats. Enalapril and candesartan attenuated the HFr-induced hypertension, albuminuria, glomerular hyperfiltration, and renal damage in DS rats.
Conclusion:
HFr-induced hypertension and renal damage are exaggerated in DS rats via renal renin-angiotensin system activation, which can be controlled by renin-angiotensin system inhibitors.




J Am Heart Assoc: 19 Jul 2021; 10:e016543
Xu L, Hu G, Qiu J, Fan Y, ... Kohzuki M, Ito O
J Am Heart Assoc: 19 Jul 2021; 10:e016543 | PMID: 34259014
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Maternal Heart Failure.

Bright RA, Lima FV, Avila C, Butler J, Stergiopoulos K
Heart failure (HF) remains the most common major cardiovascular complication arising in pregnancy and the postpartum period. Mothers who develop HF have been shown to experience an increased risk of death as well as a variety of adverse cardiac and obstetric outcomes. Recent studies have demonstrated that the risk to neonates is significant, with increased risks in perinatal morbidity and mortality, low Apgar scores, and prolonged neonatal intensive care unit stays. Information on the causal factors of HF can be used to predict risk and understand timing of onset, mortality, and morbidity. A variety of modifiable, nonmodifiable, and obstetric risk factors as well as comorbidities are known to increase a patient\'s likelihood of developing HF, and there are additional elements that are known to portend a poorer prognosis beyond the HF diagnosis. Multidisciplinary cardio-obstetric teams are becoming more prominent, and their existence will both benefit patients through direct care and increased awareness and educate clinicians and trainees on this patient population. Detection, access to care, insurance barriers to extended postpartum follow-up, and timely patient counseling are all areas where care for these women can be improved. Further data on maternal and fetal outcomes are necessary, with the formation of State Maternal Perinatal Quality Collaboratives paving the way for such advances.



J Am Heart Assoc: 19 Jul 2021; 10:e021019
Bright RA, Lima FV, Avila C, Butler J, Stergiopoulos K
J Am Heart Assoc: 19 Jul 2021; 10:e021019 | PMID: 34259013
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Regulates Atherosclerosis Through C-C Motif Chemokine Ligand 2-Mediated Monocyte Infiltration.

Kong XY, Huse C, Yang K, Øgaard J, ... Halvorsen B, Dahl TB

Background:
In cardiovascular diseases, atherosclerotic disorder are the most frequent and important with respect to morbidity and mortality. Inflammation mediated by immune cells is central in all parts of the atherosclerotic progress, and further understanding of the underlying mechanisms is needed. Growing evidence suggests that deamination of adenosine-to-inosine in RNA is crucial for a correct immune response; nevertheless, the role of adenosine-to-inosine RNA editing in atherogenesis has barely been studied. Several proteins have affinity for inosines in RNA, one being ENDOV (endonuclease V), which binds and cleaves RNA at inosines. Data on ENDOV in atherosclerosis are lacking. Methods and Results Quantitative polymerase chain reaction on ENDOV mRNA showed an increased level in human carotid atherosclerotic plaques compared with control veins. Inosine-ribonuclease activity as measured by an enzyme activity assay is detected in immune cells relevant for the atherosclerotic process. Abolishing EndoV in atherogenic apolipoprotein E-deficient (ApoE-/-) mice reduces the atherosclerotic plaque burden, both in size and lipid content. In addition, in a brain stroke model, mice without ENDOV suffer less damage than control mice. Finally, lack of EndoV reduces the recruitment of monocytes to atherosclerotic lesions in atherogenic ApoE-/- mice.
Conclusions:
ENDOV is upregulated in human atherosclerotic lesions, and data from mice suggest that ENDOV promotes atherogenesis by enhancing the monocyte recruitment into the atherosclerotic lesion, potentially by increasing the effect of CCL2 activation on these cells.




J Am Heart Assoc: 19 Jul 2021; 10:e020656
Kong XY, Huse C, Yang K, Øgaard J, ... Halvorsen B, Dahl TB
J Am Heart Assoc: 19 Jul 2021; 10:e020656 | PMID: 34259011
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Interplay Between Myocardial Bridging and Coronary Spasm in Patients With Myocardial Ischemia and Non-Obstructive Coronary Arteries: Pathogenic and Prognostic Implications.

Montone RA, Gurgoglione FL, Del Buono MG, Rinaldi R, ... Crea F, Niccoli G

Background:
Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evaluating their prognostic relevance in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) or stable NOCAD. Methods and Results We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non-fatal myocardial infarction, and rehospitalization for unstable angina, was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow-up (median, 22 months; interquartile range, 13-32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P<0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis.
Conclusions:
Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long-term follow-up with a low rate of hard events.




J Am Heart Assoc: 19 Jul 2021; 10:e020535
Montone RA, Gurgoglione FL, Del Buono MG, Rinaldi R, ... Crea F, Niccoli G
J Am Heart Assoc: 19 Jul 2021; 10:e020535 | PMID: 34259010
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Inequities in Aortic Stenosis and Aortic Valve Replacement Between Black/African-American, White, and Hispanic Residents of Maryland.

Czarny MJ, Hasan RK, Post WS, Chacko M, Schena S, Resar JR

Background:
Racial and ethnic inequities exist in surgical aortic valve replacement for aortic stenosis (AS), and early studies have suggested similar inequities in transcatheter aortic valve replacement. Methods and Results We performed a retrospective analysis of the Maryland Health Services Cost Review Commission inpatient data set from 2016 to 2018. Black patients had half the incidence of any inpatient AS diagnosis compared with White patients (incidence rate ratio [IRR], 0.50; 95% CI, 0.48-0.52; P<0.001) and Hispanic patients had one fourth the incidence compared with White patients (IRR, 0.25; 95% CI, 0.22-0.29; P<0.001). Conversely, the incidence of any inpatient mitral regurgitation diagnosis did not differ between White and Black patients (IRR, 1.00; 95% CI, 0.97-1.03; P=0.97) but was significantly lower in Hispanic compared with White patients (IRR, 0.36; 95% CI, 0.33-0.40; P<0.001). After multivariable adjustment, Black race was associated with a lower incidence of surgical aortic valve replacement (IRR, 0.67; 95% CI, 0.55-0.82 P<0.001 relative to White race) and transcatheter aortic valve replacement (IRR, 0.77; 95% CI, 0.65-0.90; P=0.002) among those with any inpatient diagnosis of AS. Hispanic patients had a similar rate of surgical aortic valve replacement and transcatheter aortic valve replacement compared with White patients.
Conclusions:
Hospitalization with any diagnosis of AS is less common in Black and Hispanic patients than in White patients. In hospitalized patients with AS, Black race is associated with a lower incidence of both surgical aortic valve replacement and transcatheter aortic valve replacement compared with White patients, whereas Hispanic patients have a similar incidence of both. The reasons for these inequities are likely multifactorial.




J Am Heart Assoc: 19 Jul 2021; 10:e017487
Czarny MJ, Hasan RK, Post WS, Chacko M, Schena S, Resar JR
J Am Heart Assoc: 19 Jul 2021; 10:e017487 | PMID: 34261361
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of Experimental Interventions to Improve the Biomedical Peer-Review Process: A Systematic Review and Meta-Analysis.

Gaudino M, Robinson NB, Di Franco A, Hameed I, ... Fremes SE, Biondi-Zoccai G

Background:
Quality of the peer-review process has been tested only in small studies. We describe and summarize the randomized trials that investigated interventions aimed at improving peer-review process of biomedical manuscripts. Methods and Results All randomized trials comparing different peer-review interventions at author-, reviewer-, and/or editor-level were included. Differences between traditional and intervention-modified peer-review processes were pooled as standardized mean difference (SMD) in quality based on the definitions used in the individual studies. Main outcomes assessed were quality and duration of the peer-review process. Five-hundred and seventy-five studies were retrieved, eventually yielding 24 randomized trials. Eight studies evaluated the effect of interventions at author-level, 16 at reviewer-level, and 3 at editor-level. Three studies investigated interventions at multiple levels. The effects of the interventions were reported as mean change in review quality, duration of the peer-review process, acceptance/rejection rate, manuscript quality, and number of errors detected in 13, 11, 5, 4, and 3 studies, respectively. At network meta-analysis, reviewer-level interventions were associated with a significant improvement in review quality (SMD, 0.20 [0.06 to 0.33]), at the cost of increased duration of the review process (SMD, 0.15 [0.01 to 0.29]), except for reviewer blinding. Author- and editor-level interventions did not significantly impact peer-review quality and duration (respectively, SMD, 0.17 [-0.16 to 0.51] and SMD, 0.19 [-0.40 to 0.79] for quality, and SMD, 0.17 [-0.16 to 0.51] and SMD, 0.19 [-0.40 to 0.79] for duration).
Conclusions:
Modifications of the traditional peer-review process at reviewer-level are associated with improved quality, at the price of longer duration. Further studies are needed. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020187910.




J Am Heart Assoc: 18 Jul 2021:e019903; epub ahead of print
Gaudino M, Robinson NB, Di Franco A, Hameed I, ... Fremes SE, Biondi-Zoccai G
J Am Heart Assoc: 18 Jul 2021:e019903; epub ahead of print | PMID: 34278828
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial.

Jürgens M, Schou M, Hasbak P, Kjær A, ... Gustafsson F, Kistorp C

Background:
Sodium-glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. Methods and Results We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add-on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium-82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate-pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08-2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, -0.18 to 0.21) or placebo groups: 0.06 (95% CI, -0.15 to 0.27), with no treatment effect -0.05 (95% CI, -0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium-82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A1c by 0.76% (95% CI, 1.0-0.5; P<0.001) and increased hematocrit by 1.69% (95% CI, 0.7-2.6; P<0.001).
Conclusions:
Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short-term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials. Registration URL: https://clinicaltrialsregister.eu/; Unique identifier: 2016-003743-10.




J Am Heart Assoc: 18 Jul 2021:e020418; epub ahead of print
Jürgens M, Schou M, Hasbak P, Kjær A, ... Gustafsson F, Kistorp C
J Am Heart Assoc: 18 Jul 2021:e020418; epub ahead of print | PMID: 34278803
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Is Transposition of the Great Arteries Associated With Shortening of the Intrapericardial Portions of the Great Arterial Trunks? An Echocardiographic Analysis on Newborn Infants With Simple Transposition of the Great Arteries to Explore an Animal Model-Based Hypothesis on Human Beings.

Omer SO, Alhabshan FM, Jijeh AMZ, Caimbon NC, ... Männer J, Yelbuz TM

Background:
The pathogenesis of transposition of the great arteries (TGA) as a congenital heart defect of the outflow tract with discordant ventriculoarterial connections remains an enigma. TGA usually have parallel great arteries suggesting that deficient torsion of the embryonic arterial heart pole might cause discordant ventriculoarterial connections. It has been speculated that deficient elongation of the embryonic outflow tract might prevent its normal torsion resulting in TGA. The aim of our study was to clarify whether the intrapericardial portions of the great arteries in human patients with TGA might be indeed shorter than in normal hearts. Methods and Results Thirty-four newborns with simple TGA and 35 newborns with normal hearts were analyzed by using images of the outflow tract in their echocardiograms and the following defined lengths of the great arteries were measured: aortic length 1, (AoL-1) and aortic length 2 (AoL-2) = distance between left and right aortic valve level and origin of the brachiocephalic artery, respectively. Pulmonary trunk length 1 (PTL-1) and pulmonary trunk length 2 (PTL 2) = distance between left and right pulmonary valve level and origin of left and right pulmonary artery, respectively. All measurements of the AoL were significantly shorter in TGA compared to normal hearts (AoL-1: 1.6±0.2 versus 2.05±0.1; P<0.0001; AoL-2: 1.55±0.2 versus 2.13±0.1; P<0.0001). With regard to the pulmonary trunk (PT), PTL-1 and PTL-2 were found to be shorter and longer, respectively, in TGA compared with normal hearts, reflecting the differences in the spatial arrangement of the PT between the 2 groups as in TGA the PT is showing a mirror image of the normal anatomy. However, the overall length of the PT between the 2 groups did not differ.
Conclusions:
Our data demonstrate that, compared with normal newborns, the ascending aorta is significantly shorter in newborns with TGA whereas the overall length of the PT does not differ between the 2 groups. This finding is in accord with the animal model-based hypothesis that TGA may result from a growth deficit at the arterial pole of the embryonic heart.




J Am Heart Assoc: 18 Jul 2021:e019334; epub ahead of print
Omer SO, Alhabshan FM, Jijeh AMZ, Caimbon NC, ... Männer J, Yelbuz TM
J Am Heart Assoc: 18 Jul 2021:e019334; epub ahead of print | PMID: 34278802
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mobile Technology Improves Adherence to Cardiac Rehabilitation: A Propensity Score-Matched Study.

Imran TF, Wang N, Zombeck S, Balady GJ

Background:
Despite its established effectiveness, adherence to cardiac rehabilitation remains suboptimal. The purpose of our study is to examine whether mobile technology improves adherence to cardiac rehabilitation and other outcomes. Methods and Results We identified all enrollees of the cardiac rehabilitation program at Boston Medical Center from 2016 to 2019 (n=830). Some enrollees used a mobile technology application that provided a customized list of educational content in a progressive manner, used the patient\'s smartphone accelerometer to provide daily step counts, and served as a 2-way messaging system between the patient and program staff. Adherence to cardiac rehabilitation was defined as the number of attended sessions and completion of the program. Enrollees had a mean age of 59 years; 32% were women, and 42% were Black. Using 3:1 propensity matching for age, sex, race/ethnicity, education, smoking status, transportation time, diagnosis, and baseline depression survey score, we evaluated change in exercise capacity, weight, functional capacity, and nutrition scores. Those in the mobile technology group (n=114) attended a higher number of prescribed sessions (mean 28 versus 22; relative risk, 1.17; 95% CI, 1.04-1.32; P=0.009), were 1.8 times more likely to complete the cardiac rehabilitation program (P=0.01), and had a slightly greater weight loss (pounds) following rehabilitation (-1.71; 95% CI, -0.30 to -3.11; P=0.02) as compared with those in the standard group (n=213); other outcomes were similar between the groups.
Conclusions:
In a propensity-matched, racially diverse population, we found that adjunctive use of mobile technology is significantly associated with improved adherence to cardiac rehabilitation and number of attended sessions.




J Am Heart Assoc: 18 Jul 2021:e020482; epub ahead of print
Imran TF, Wang N, Zombeck S, Balady GJ
J Am Heart Assoc: 18 Jul 2021:e020482; epub ahead of print | PMID: 34278801
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Proteomic Signature of Dysfunctional Circulating Endothelial Colony-Forming Cells of Young Adults.

Tan CMJ, Lewandowski AJ, Williamson W, Huckstep OJ, ... Leeson P, Bertagnolli M

Background:
A subpopulation of endothelial progenitor cells called endothelial colony-forming cells (ECFCs) may offer a platform for cellular assessment in clinical studies because of their remarkable angiogenic and expansion potentials in vitro. Despite endothelial cell function being influenced by cardiovascular risk factors, no studies have yet provided a comprehensive proteomic profile to distinguish functional (ie, more angiogenic and expansive cells) versus dysfunctional circulating ECFCs of young adults. The aim of this study was to provide a detailed proteomic comparison between functional and dysfunctional ECFCs. Methods and Results Peripheral blood ECFCs were isolated from 11 subjects (45% men, aged 27±5 years) using Ficoll density gradient centrifugation. ECFCs expressed endothelial and progenitor surface markers and displayed cobblestone-patterned morphology with clonal and angiogenic capacities in vitro. ECFCs were deemed dysfunctional if <1 closed tube formed during the in vitro tube formation assay and proliferation rate was <20%. Hierarchical functional clustering revealed distinct ECFC proteomic signatures between functional and dysfunctional ECFCs with changes in cellular mechanisms involved in exocytosis, vesicle transport, extracellular matrix organization, cell metabolism, and apoptosis. Targeted antiangiogenic proteins in dysfunctional ECFCs included SPARC (secreted protein acidic and rich in cysteine), CD36 (cluster of differentiation 36), LUM (lumican), and PTX3 (pentraxin-related protein PYX3).
Conclusions:
Circulating ECFCs with impaired angiogenesis and expansion capacities have a distinct proteomic profile and significant phenotype changes compared with highly angiogenic endothelial cells. Impaired angiogenesis in dysfunctional ECFCs may underlie the link between endothelial dysfunction and cardiovascular disease risks in young adults.




J Am Heart Assoc: 18 Jul 2021:e021119; epub ahead of print
Tan CMJ, Lewandowski AJ, Williamson W, Huckstep OJ, ... Leeson P, Bertagnolli M
J Am Heart Assoc: 18 Jul 2021:e021119; epub ahead of print | PMID: 34275329
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Coronary Circulatory Indexes Before and After Percutaneous Coronary Intervention in a Porcine Tandem Stenoses Model.

Chang H, Kim HK, Shin D, Lim KS, ... Kakuta T, Lee JM

Background:
In tandem stenoses, nonhyperemic pressure ratio pullback is the preferred method to fractional flow reserve (FFR), based on the assumption of stable resting coronary flow. This study aimed to evaluate temporal changes of coronary circulatory indexes in tandem stenoses before and after angioplasty for proximal stenosis. Methods and Results Coronary tandem stenoses were created by porcine restenosis model with 2 bare metal stents in the left anterior descending artery. Four weeks later, changes in distal coronary pressure (Pd), averaged peak velocity, microvascular resistance, transstenotic pressure gradient across distal stenosis, resting Pd/aortic pressure, and FFR were measured before and 1, 5, 10, 15, and 20 minutes after balloon angioplasty for proximal stenosis. After angioplasty, there were significant changes in both resting and hyperemic Pd, averaged peak velocity, microvascular resistance, and transstenotic pressure gradient across distal stenosis (all P values <0.01). After initial acute changes, hyperemic averaged peak velocity and microvascular resistance did not show significant difference from the baseline values (P=0.712 and 0.972, respectively). Conversely, resting averaged peak velocity remained increased (10.1±0.7 to 17.8±0.7; P<0.001) and resting microvascular resistance decreased (6.0±0.1 to 2.2±0.7; P<0.001). Transstenotic pressure gradient across distal stenosis was significantly increased in both resting (13.1±7.6 to 25.3±4.2; P=0.040) and hyperemic conditions (11.0±3.0 to 27.4±3.3 mm Hg; P<0.001). Actual post-percutaneous coronary intervention Pd/aortic pressure and FFR were significantly lower than predicted values (Pd/aortic pressure, 0.68±0.22 versus 0.85±0.14; P<0.001; FFR, 0.63±0.08 versus 0.81±0.08; P<0.001).
Conclusions:
After angioplasty for proximal stenosis, transstenotic pressure gradient across distal stenosis showed similar changes between resting and hyperemic conditions. Both actual post-percutaneous coronary intervention resting Pd/aortic pressure and FFR were significantly lower than predicted values.




J Am Heart Assoc: 18 Jul 2021:e021824; epub ahead of print
Chang H, Kim HK, Shin D, Lim KS, ... Kakuta T, Lee JM
J Am Heart Assoc: 18 Jul 2021:e021824; epub ahead of print | PMID: 34275325
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study.

Karunanithi Z, Andersen MJ, Mellemkjær S, Alstrup M, ... Elisabeth Hjortdal V, Hvitfeldt Poulsen S

Background:
Despite correction of the atrial septal defect (ASD), patients experience atrial fibrillation frequently and have increased morbidity and mortality. We examined physical capacity, cardiac performance, and invasive hemodynamics in patients with corrected ASD. Methods and Results Thirty-eight corrected patients with isolated secundum ASD and 19 age-matched healthy controls underwent right heart catheterization at rest and during exercise with simultaneous expired gas assessment and echocardiography. Maximum oxygen uptake was comparable between groups (ASD 32.7±7.7 mL O2/kg per minute, controls 35.2±7.5 mL O2/kg per minute, P=0.3), as was cardiac index at both rest and peak exercise. In contrast, pulmonary artery wedge v wave pressures were increased at rest and peak exercise (rest: ASD 14±4 mm Hg, controls 10±5 mm Hg, P=0.01; peak: ASD 25±9 mm Hg, controls 14±9 mm Hg, P=0.0001). The right atrial v wave pressures were increased at rest but not at peak exercise. The transmural filling pressure gradient (TMFP) was higher at peak exercise among patients with ASD (10±6 mm Hg, controls 7±3 mm Hg, P=0.03). One third of patients with ASD demonstrated an abnormal hemodynamic exercise response defined as mean pulmonary artery wedge pressure ≥25 mm Hg and/or mean pulmonary artery pressure ≥35 mm Hg at peak exercise. These patients had significantly elevated peak right and left atrial a wave pressures, right atrial v wave pressures, pulmonary artery wedge v wave pressures, and transmural filling pressure compared with both controls and patients with ASD with a normal exercise response.
Conclusions:
Patients with corrected ASD present with elevated right and in particular left atrial pressures at rest and during exercise despite preserved peak exercise capacity. Abnormal atrial compliance and systolic atrial function could predispose to the increased long-term risk of atrial fibrillation. Registration Information clinicaltrials.gov. Identifier: NCT03565471.




J Am Heart Assoc: 13 Jul 2021:e020692; epub ahead of print
Karunanithi Z, Andersen MJ, Mellemkjær S, Alstrup M, ... Elisabeth Hjortdal V, Hvitfeldt Poulsen S
J Am Heart Assoc: 13 Jul 2021:e020692; epub ahead of print | PMID: 34259012
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine-1-Phosphate.

Del Gaudio I, Rubinelli L, Sasset L, Wadsack C, Hla T, Di Lorenzo A

Background:
Most of the circulating sphingosine-1-phosphate (S1P) is bound to ApoM (apolipoprotein M) of high-density lipoprotein (HDL) and mediates many beneficial effects of HDL on the vasculature via G protein-coupled S1P receptors. HDL-bound S1P is decreased in atherosclerosis, myocardial infarction, and diabetes mellitus. In addition to being the target, the endothelium is a source of S1P, which is transported outside of the cells by Spinster-2, contributing to circulating S1P as well as to local signaling. Mice lacking endothelial S1P receptor 1 are hypertensive, suggesting a vasculoprotective role of S1P signaling. This study investigates the role of endothelial-derived S1P and ApoM-bound S1P in regulating vascular tone and blood pressure. Methods and Results ApoM knockout (ApoM KO) mice and mice lacking endothelial Spinster-2 (ECKO-Spns2) were infused with angiotensin II for 28 days. Blood pressure, measured by telemetry and tail-cuff, was significantly increased in both ECKO-Spns2 and ApoM KO versus control mice, at baseline and following angiotensin II. Notably, ECKO-Spns2 presented an impaired vasodilation to flow and blood pressure dipping, which is clinically associated with increased risk for cardiovascular events. In hypertension, both groups presented reduced flow-mediated vasodilation and some degree of impairment in endothelial NO production, which was more evident in ECKO-Spns2. Increased hypertension in ECKO-Spns2 and ApoM KO mice correlated with worsened cardiac hypertrophy versus controls.
Conclusions:
Our study identifies an important role for Spinster-2 and ApoM-HDL in blood pressure homeostasis via S1P-NO signaling and dissects the pathophysiological impact of endothelial-derived S1P and ApoM of HDL-bound S1P in hypertension and cardiac hypertrophy.




J Am Heart Assoc: 08 Jul 2021:e021261; epub ahead of print
Del Gaudio I, Rubinelli L, Sasset L, Wadsack C, Hla T, Di Lorenzo A
J Am Heart Assoc: 08 Jul 2021:e021261; epub ahead of print | PMID: 34240614
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ten-year Outcomes After Drug-Eluting Stents or Bypass Surgery for Left Main Coronary Disease in Patients With and Without Diabetes Mellitus: The PRECOMBAT Extended Follow-Up Study.

Jeong YJ, Ahn JM, Hyun J, Lee J, ... Park SJ, Park DW

Background:
Several trials reported differential outcomes after percutaneous coronary intervention with drug-eluting stents (DES) and coronary-artery bypass grafting (CABG) for multivessel coronary disease according to the presence of diabetes mellitus (DM). However, it is not well recognized how DM status affects very-long-term (10-year) outcomes after DES and CABG for left main coronary artery disease. Methods and Results In the PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) trial, patients with LMCA were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300). The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (MACCE; a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization). Outcomes were examined in patients with (n=192) and without (n=408) medically treated diabetes. The follow-up was extended to at least 10 years for all patients (median, 11.3 years). The 10-year rates of MACCE were not significantly different between DES and CABG in patients with DM (36.3% versus 26.7%, respectively; hazard ratio [HR], 1.35; 95% CI, 0.83-2.19; P=0.23) and without DM (25.3% versus 22.9%, respectively; HR, 1.15; 95% CI, 0.79-1.67; P=0.48) (P-for-interaction=0.48). There were no significant between-group differences in composite of death, MI, or stroke, and all-cause mortality, regardless of DM status. TVR rates were consistently higher after DES than CABG.
Conclusions:
In this 10-year extended follow-up of PRECOMBAT, we found no significant difference between DES and CABG with respect to the incidences of MACCE, serious composite outcome, and all-cause mortality in patients with and without DM with LMCA disease. However, owing to the limited number of patients and no adjustment for multiple testing, overall findings should be considered hypothesis-generating, highlighting the need for further research. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871127 and NCT00422968.




J Am Heart Assoc: 08 Jul 2021:e019834; epub ahead of print
Jeong YJ, Ahn JM, Hyun J, Lee J, ... Park SJ, Park DW
J Am Heart Assoc: 08 Jul 2021:e019834; epub ahead of print | PMID: 34238026
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Donor Characteristics and Recipient Outcomes After Heart Transplantation in Adult Congenital Heart Disease.

Huntley GD, Danford DA, Menachem J, Kutty S, Cedars AM

Background:
Patients with adult congenital heart disease (ACHD) experience long waitlist times for heart transplantation (HTx) while a large proportion of donor hearts are refused. The goal of this study was to inform optimal donor selection for patients with ACHD listed for HTx by examining the impact of donor characteristics on post-HTx outcomes. Methods and Results Using the Scientific Registry of Transplant Recipients, we conducted a retrospective analysis of patients aged ≥18 years listed for HTx in the United States between 2000 and 2016. We compared waitlist times between patients with ACHD and patients with noncongenital heart disease and constructed multivariate hazard models to identify donor characteristics associated with increased waitlist time. We then compared post-HTx survival between patients with ACHD and patients with noncongenital heart disease and constructed multivariate hazard models to identify donor characteristics associated with mortality. There were very few differences in donor characteristics between HTx recipients with ACHD and those with noncongenital heart disease. Status 1A-listed patients with ACHD experienced longer waitlist times compared with patients with noncongenital heart disease. Increased wait times were associated with some donor characteristics. Post-HTx outcomes varied over time, with patients with ACHD having inferior early mortality (0 to 30 days), similar intermediate mortality (31 days to 4 years), and superior late mortality (>4 years). We identified no donor characteristics associated with mortality to justify the observed differences in donor selection or waitlist time.
Conclusions:
HTx candidates with ACHD wait longer for transplant but do not require unique donor selection criteria. HTx teams should consider liberalizing donor criteria and focusing only on evidence-based selection to improve waitlist outcomes and reduce the recipient-donor disparity.




J Am Heart Assoc: 08 Jul 2021:e020248; epub ahead of print
Huntley GD, Danford DA, Menachem J, Kutty S, Cedars AM
J Am Heart Assoc: 08 Jul 2021:e020248; epub ahead of print | PMID: 34238025
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.

Rao VN, Bush CG, Mongraw-Chaffin M, Hall ME, ... Min YI, Mentz RJ

Background:
Visceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all-cause mortality in a large community cohort of Black participants. Methods and Results Among the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography-derived regional adiposity and incident HF hospitalization and all-cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow-up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography-derived adiposity measures (PAT per 10 cm3, VAT or SAT per 100 cm3) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02-1.14) and VAT 1.04 (95% CI, 1.01-1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04-1.21) and VAT 1.07 (95% CI, 1.01-1.13); for mortality, PAT 1.07 (95% CI, 1.03-1.12) and VAT 1.01 (95% CI, 0.98-1.04). SAT was not associated with either outcome.
Conclusions:
High PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.




J Am Heart Assoc: 08 Jul 2021:e020920; epub ahead of print
Rao VN, Bush CG, Mongraw-Chaffin M, Hall ME, ... Min YI, Mentz RJ
J Am Heart Assoc: 08 Jul 2021:e020920; epub ahead of print | PMID: 34238024
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Treatment Inertia in Patients With Familial Hypercholesterolemia.

Langer A, Mancini GBJ, Tan M, Goodman SG, ... Stone JA, Leiter LA

Background:
We studied care gap in patients with familial hypercholesterolemia (FH) with respect to lipid-lowering therapy. Methods and Results We enrolled patients with cardiovascular disease (CVD) or FH and low-density lipoprotein-cholesterol >2.0 mmol/L despite maximally tolerated statin therapy. During follow-up physicians received online reminders of treatment recommendations of 2009 patients (median age, 63 years, 42% women), 52.4% had CVD only, 31.7% FH only, and 15.9% both CVD and FH. Patients with FH were younger and more likely to be women and non-White with significantly higher baseline low-density lipoprotein-cholesterol level (mmol/L) as compared with patients with CVD (FH 3.92±1.48 versus CVD 2.96±0.94, P<0.0001). Patients with FH received less statin (70.6% versus 79.2%, P=0.0001) at baseline but not ezetimibe (28.1% versus 20.4%, P=0.0003). Among patients with FH only, 45.3% were at low-density lipoprotein target (≥ 50% reduction from pre-treatment level or low-density lipoprotein <2.5 mmol/L) at baseline and increasing to 65.8% and 73.6% by visit 2 and 3, respectively. Among patients with CVD only, none were at recommended level (≤2.0 mmol/L) at baseline and 44.3% and 53.3% were at recommended level on second and third visit, respectively. When primary end point was analyzed as a difference between baseline and last available follow-up observation, only 22.0% of patients with FH only achieved it as compared with 45.8% with CVD only (P<0.0001) and 55.2% with both FH+CVD (P<0.0001).
Conclusions:
There is significant treatment inertia in patients with FH including those with CVD. Education focused on patients with FH should continue to be undertaken.




J Am Heart Assoc: 08 Jul 2021:e020126; epub ahead of print
Langer A, Mancini GBJ, Tan M, Goodman SG, ... Stone JA, Leiter LA
J Am Heart Assoc: 08 Jul 2021:e020126; epub ahead of print | PMID: 34238023
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association Between Patient-Clinician Relationships and Adherence to Antihypertensive Medications Among Black Adults: An Observational Study Design.

Chang TJ, Bridges JFP, Bynum M, Jackson JW, ... Lu B, Donneyong MM

Background:
We assessed the associations between patient-clinician relationships (communication and involvement in shared decision-making [SDM]) and adherence to antihypertensive medications. Methods and Results The 2010 to 2017 Medical Expenditure Panel Survey (MEPS) data were analyzed. A retrospective cohort study design was used to create a cohort of prevalent and new users of antihypertensive medications. We defined constructs of patient-clinician communication and involvement in SDM from patient responses to the standard questionnaires about satisfaction and access to care during the first year of surveys. Verified self-reported medication refill information collected during the second year of surveys was used to calculate medication refill adherence; adherence was defined as medication refill adherence ≥80%. Survey-weighted multivariable-adjusted logistic regression models were used to measure the odds ratio (OR) and 95% CI for the association between both patient-clinician constructs and adherence. Our analysis involved 2571 Black adult patients with hypertension (mean age of 58 years; SD, 14 years) who were either persistent (n=1788) or new users (n=783) of antihypertensive medications. Forty-five percent (n=1145) and 43% (n=1016) of the sample reported having high levels of communication and involvement in SDM, respectively. High, versus low, patient-clinician communication (OR, 1.38; 95% CI, 1.14-1.67) and involvement in SDM (OR, 1.32; 95% CI, 1.08-1.61) were both associated with adherence to antihypertensives after adjusting for multiple covariates. These associations persisted among a subgroup of new users of antihypertensive medications.
Conclusions:
Patient-clinician communication and involvement in SDM are important predictors of optimal adherence to antihypertensive medication and should be targeted for improving adherence among Black adults with hypertension.




J Am Heart Assoc: 08 Jul 2021:e019943; epub ahead of print
Chang TJ, Bridges JFP, Bynum M, Jackson JW, ... Lu B, Donneyong MM
J Am Heart Assoc: 08 Jul 2021:e019943; epub ahead of print | PMID: 34238022
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cost-Utility of Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure: An Economic Evaluation.

Lau D, Sandhu RK, Andrade JG, Ezekowitz J, So H, Klarenbach S

Background:
Recent trials comparing catheter ablation to medical therapy in patients with heart failure (HF) with symptomatic atrial fibrillation despite first-line management have demonstrated a reduction in adverse outcomes. We performed an economic evaluation to estimate the cost-utility of catheter ablation as second line therapy in patients with HF with reduced ejection fraction. Methods and Results A Markov model with health states of alive, dead, and alive with amiodarone toxicity was constructed, using the perspective of the Canadian healthcare payer. Patients in the alive states were at risk of HF and non-HF hospitalizations. Parameters were obtained from randomized trials and Alberta health system data for costs and outcomes. A lifetime time horizon was adopted, with discounting at 3.0% annually. Probabilistic and 1-way sensitivity analyses were performed. Costs are reported in 2018 Canadian dollars. A patient treated with catheter ablation experienced lifetime costs of $64 960 and 5.63 quality-adjusted life-years (QALY), compared with $49 865 and 5.18 QALYs for medical treatment. The incremental cost-effectiveness ratio was $35 360/QALY (95% CI, $21 518-77 419), with a 90% chance of being cost-effective at a willingness-to-pay threshold of $50 000/QALY. A minimum mortality reduction of 28%, or a minimum duration of benefit of >1 to 2 years was required for catheter ablation to be attractive at this threshold.
Conclusions:
Catheter ablation is likely to be cost-effective as a second line intervention for patients with HF with symptomatic atrial fibrillation, with incremental cost-effectiveness ratio $35 360/QALY, as long as over half of the relative mortality benefit observed in extant trials is borne out in future studies.




J Am Heart Assoc: 08 Jul 2021:e019599; epub ahead of print
Lau D, Sandhu RK, Andrade JG, Ezekowitz J, So H, Klarenbach S
J Am Heart Assoc: 08 Jul 2021:e019599; epub ahead of print | PMID: 34238020
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Factors Associated With Health-Related Quality of Life 2 Years After Left Ventricular Assist Device Implantation: Insights From INTERMACS.

Grady KL, Fazeli PL, Kirklin JK, Pamboukian SV, White-Williams C

Background:
Factors related to health-related quality of life (HRQOL) 2 years after left ventricular assist device (LVAD) implantation are unknown. We sought to determine whether preimplant intended goal of LVAD therapy (heart transplant candidate [short-term group], uncertain heart transplant candidate [uncertain group], and heart transplant ineligible [long-term group]) and other variables were related to HRQOL 2 years after LVAD implantation. Methods and Results Our LVAD sample (n=1620) was from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Using the EuroQol-5 Dimension Questionnaire (EQ-5D-3L), a generic HRQOL measure, and the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a heart failure-specific HRQOL measure, multivariable linear regression modeling was conducted with the EQ-5D-3L Visual Analog Scale (VAS) score and KCCQ-12 overall summary score (OSS) as separate dependent variables. Two years after LVAD implant, the short-term group had a significantly higher mean VAS score versus the uncertain and long-term groups (short-term: 75.18 [SD, 20.62]; uncertain: 72.27 [SD, 20.33]; long-term: 70.87 [SD, 22.09], P=0.01); differences were not clinically meaningful. Two-year mean scores did not differ by group for the KCCQ-12 OSS (short-term, 67.85 [SD, 20.61]; uncertain, 67.79 [SD, 19.31]; long-term, 67.08 [SD, 21.49], P=0.80). Factors associated with a worse VAS score 2 years postoperatively (n=1205) included not working; not having a short-term LVAD; and postoperative neurological dysfunction, greater health-related stress, coping poorly, less VAD self-care confidence, and less satisfaction with VAD surgery, explaining 28% of variance (P<0.001). Factors associated with a worse KCCQ-12 OSS 2 years postoperatively (n=1250) included not working; history of high body mass index and diabetes mellitus; and postoperative renal dysfunction, greater health-related stress, coping poorly, less VAD self-care confidence, less satisfaction with VAD surgery, and regret regarding VAD implantation, accounting for 36% of variance (P<0.001).
Conclusions:
Factors related to HRQOL 2 years after LVAD implantation include demographic, clinical, and psychological variables.




J Am Heart Assoc: 08 Jul 2021:e021196; epub ahead of print
Grady KL, Fazeli PL, Kirklin JK, Pamboukian SV, White-Williams C
J Am Heart Assoc: 08 Jul 2021:e021196; epub ahead of print | PMID: 34238018
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk Prediction in Women With Congenital Long QT Syndrome.

Goldenberg I, Bos JM, Yoruk A, Chen AY, ... J Ackerman M, Zareba W

Background:
We aimed to provide personalized risk estimates for cardiac events (CEs) and life-threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and β-blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome-related sudden cardiac death), and was applied with the end point of life-threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow-up duration among the 767 enrolled women was 22 243 patient-years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype-phenotype data, we identified 3 risk groups with 10-year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10-year projected rates of life-threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65-0.71) and 0.71 (95% CI 0.66-0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60-0.70) and 0.77 (95% CI 0.70-0.84).
Conclusions:
This is the first risk prediction model that provides absolute risk estimates for CEs and life-threatening events in women with type 1 or type 2 long QT based on personalized genotype-phenotype data. The projected risk estimates can be used to guide female-specific management in long QT syndrome.




J Am Heart Assoc: 08 Jul 2021:e021088; epub ahead of print
Goldenberg I, Bos JM, Yoruk A, Chen AY, ... J Ackerman M, Zareba W
J Am Heart Assoc: 08 Jul 2021:e021088; epub ahead of print | PMID: 34238014
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Root Dilatation Is More Malignant Than Ascending Aortic Dilation.

Kalogerakos PD, Zafar MA, Li Y, Mukherjee SK, ... Rizzo JA, Elefteriades JA

Background:
Data from the International Registry of Acute Aortic Dissection indicate that the guideline criterion of 5.5 cm for ascending aortic intervention misses many dissections occurring at smaller dimensions. Furthermore, studies of natural behavior have generally treated the aortic root and the ascending aorta as 1 unit despite embryological, anatomical, and functional differences. This study aims to disentangle the natural histories of the aforementioned aortic segments, allowing natural behavior to define specific intervention criteria for root and ascending segments of the aorta. Methods and Results Diameters of the aortic root and mid-ascending segment were measured separately. Long-term complications (dissection, rupture, and death) were analyzed retrospectively for 1162 patients with ascending thoracic aortic aneurysm. Cox regression analysis suggested that aortic root dilatation (P=0.017) is more significant in predicting adverse events than mid-ascending aortic dilatation (P=0.087). Short stature posed as a serious risk factor. The dedicated risk curves for the aortic root and the mid-ascending aorta revealed hinge points at 5.0 and 5.25 cm, respectively.
Conclusions:
The natural histories of the aortic root and mid-ascending aorta are uniquely different. Dilation of the aortic root imparts a significant higher risk of adverse events. A diameter shift for intervention to 5.0 cm for the aortic root and to 5.25 cm for the mid-ascending aorta should be considered at expert centers.




J Am Heart Assoc: 08 Jul 2021:e020645; epub ahead of print
Kalogerakos PD, Zafar MA, Li Y, Mukherjee SK, ... Rizzo JA, Elefteriades JA
J Am Heart Assoc: 08 Jul 2021:e020645; epub ahead of print | PMID: 34238012
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Contemporary National Patterns of Eligibility and Use of Novel Cardioprotective Antihyperglycemic Agents in Type 2 Diabetes Mellitus.

Nargesi AA, Jeyashanmugaraja GP, Desai N, Lipska K, Krumholz H, Khera R

Background:
SGLT-2 (sodium glucose transporter-2) inhibitors and GLP-1RAs (glucagon-like peptide-1 receptor agonists) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes mellitus at high risk for these complications, and have been recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice. Methods and Results In the National Health and Nutrition Examination Survey for 2017 to 2018, we defined compelling indications for SGLT-2 inhibitors by the presence of atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, and for GLP-1RAs by the presence of established or high-risk atherosclerotic cardiovascular disease, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology and American Diabetes Association. We then evaluated use of these medications among patients with physician-diagnosed type 2 diabetes mellitus. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes mellitus, representing 10.6% (95% CI, 9.7%-11.6%) of the US population or 33.2 million adults nationally. Of these, 52.6% (95% CI, 47.7%-57.5%) had an indication for SGLT-2 inhibitors, 32.8% (95% CI, 28.8%-37.2%) for GLP-1RAs, and 26.6% (95% CI, 22.2%-31.7%) for both medications. During 2017 to 2018, 4.5% (95% CI, 2.4%-8.2%) were treated with SGLT-2 inhibitors and 1.5% (95% CI, 0.7%-3.2%) with GLP-1RAs. Atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease were not independently associated with SGLT-2 inhibitor or GLP-1RA use in patients with diabetes mellitus.
Conclusions:
Despite a large number of patients being eligible for guideline-recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT-2 inhibitors and GLP-1RAs, limiting their public health benefits.




J Am Heart Assoc: 05 Jul 2021; 10:e021084
Nargesi AA, Jeyashanmugaraja GP, Desai N, Lipska K, Krumholz H, Khera R
J Am Heart Assoc: 05 Jul 2021; 10:e021084 | PMID: 33998258
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mediterranean Diet Score, Dietary Patterns, and Risk of Sudden Cardiac Death in the REGARDS Study.

Shikany JM, Safford MM, Soroka O, Brown TM, ... Durant RW, Judd SE

Background:
Sudden cardiac death (SCD) is a common cause of death in the United States. Few previous studies have investigated the associations of diet scores and dietary patterns with risk of SCD. We investigated the associations of the Mediterranean diet score and various dietary patterns with risk of SCD in participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study cohort. Methods and Results Diet was assessed with a food frequency questionnaire administered at baseline in REGARDS. The Mediterranean diet score was derived based on the consumption of specific food groups considered beneficial or detrimental components of that diet. Dietary patterns were derived previously using factor analysis, and adherence to each pattern was scored. SCD events were ascertained through regular contacts. Cox proportional hazards regression was used to examine the risk of SCD events associated with the Mediterranean diet score and adherence to each of the 5 dietary patterns overall and stratifying on history of coronary heart disease at baseline. The analytic sample included 21 069 participants with a mean 9.8±3.8 years of follow-up. The Mediterranean diet score showed a trend toward an inverse association with risk of SCD after multivariable adjustment (hazard ratio [HR] comparing highest with lowest group, 0.74; 95% CI, 0.55-1.01; Ptrend=0.07). There was a trend toward a positive association of the Southern dietary pattern with risk of SCD (HR comparing highest with lowest quartile of adherence, 1.46; 95% CI, 1.02-2.10; Ptrend=0.06).
Conclusions:
In REGARDS participants, we identified trends toward an inverse association of the Mediterranean diet score and a positive association of adherence to the Southern dietary pattern with risk of SCD.




J Am Heart Assoc: 05 Jul 2021; 10:e019158
Shikany JM, Safford MM, Soroka O, Brown TM, ... Durant RW, Judd SE
J Am Heart Assoc: 05 Jul 2021; 10:e019158 | PMID: 34189926
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pulseless Electrical Activity as the Initial Cardiac Arrest Rhythm: Importance of Preexisting Left Ventricular Function.

Ambinder DI, Patil KD, Kadioglu H, Wetstein PS, ... Agnetti G, Halperin HR

Background:
Pulseless electrical activity (PEA) is a common initial rhythm in cardiac arrest. A substantial number of PEA arrests are caused by coronary ischemia in the setting of acute coronary occlusion, but the underlying mechanism is not well understood. We hypothesized that the initial rhythm in patients with acute coronary occlusion is more likely to be PEA than ventricular fibrillation in those with prearrest severe left ventricular dysfunction. Methods and Results We studied the initial cardiac arrest rhythm induced by acute left anterior descending coronary occlusion in swine without and with preexisting severe left ventricular dysfunction induced by prior infarcts in non-left anterior descending coronary territories. Balloon occlusion resulted in ventricular fibrillation in 18 of 34 naïve animals, occurring 23.5±9.0 minutes following occlusion, and PEA in 1 animal. However, all 18 animals with severe prearrest left ventricular dysfunction (ejection fraction 15±5%) developed PEA 1.7±1.1 minutes after occlusion.
Conclusions:
Acute coronary ischemia in the setting of severe left ventricular dysfunction produces PEA because of acute pump failure, which occurs almost immediately after coronary occlusion. After the onset of coronary ischemia, PEA occurred significantly earlier than ventricular fibrillation (<2 minutes versus 20 minutes). These findings support the notion that patients with baseline left ventricular dysfunction and suspected coronary disease who develop PEA should be evaluated for acute coronary occlusion.




J Am Heart Assoc: 05 Jul 2021; 10:e018671
Ambinder DI, Patil KD, Kadioglu H, Wetstein PS, ... Agnetti G, Halperin HR
J Am Heart Assoc: 05 Jul 2021; 10:e018671 | PMID: 34121419
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ascending Aortic Length and Its Association With Type A Aortic Dissection.

Eliathamby D, Gutierrez M, Liu A, Ouzounian M, ... Tan KT, Chung J

Background:
The aim of this study was to determine the role of ascending aortic length and diameter in type A aortic dissection. Methods and Results Computed tomography scans from patients with acute type A dissections (n=51), patients with proximal thoracic aortic aneurysms (n=121), and controls with normal aortas (n=200) were analyzed from aortic annulus to the innominate artery using multiplanar reconstruction. In the control group, ascending aortic length correlated with diameter (r2=0.35, P<0.001), age (r2=0.17, P<0.001), and sex (P<0.001). As a result of immediate changes in aortic morphology at the time of acute dissection, predissection lengths and diameters were estimated based on models from published literature. Ascending aortic length was longer in patients immediately following acute dissection (median, 109.7 mm; interquartile range [IQR], 101.0-115.1 mm), patients in the estimated predissection group (median, 104.2 mm; IQR, 96.0-109.3 mm), and patients in the aneurysm group (median, 107.0 mm; IQR, 99.6-118.7 mm) in comparison to controls (median, 83.2 mm; IQR, 74.5-90.7 mm) (P<0.001 all comparisons). The diameter of the ascending aorta was largest in the aneurysm group (median, 52.0 mm; IQR, 45.9-58.0 mm), followed by the dissection group (median, 50.3 mm; IQR, 46.6-57.5 mm), and not significantly different between controls and the estimated predissection group (median, 33.4 mm [IQR, 30.7-36.7 mm] versus 35.2 mm [IQR, 32.6-40.3 mm], P=0.09). After adjustment for diameter, age, and sex, the estimated predissection aortic lengths were 16 mm longer than those in the controls and 12 mm longer than in patients with nondissected thoracic aneurysms.
Conclusions:
The length of the ascending aorta, after adjustment for age, sex, and aortic diameter, may be useful in discriminating patients with type A dissection from normal controls and patients with nondissected thoracic aneurysms.




J Am Heart Assoc: 05 Jul 2021; 10:e020140
Eliathamby D, Gutierrez M, Liu A, Ouzounian M, ... Tan KT, Chung J
J Am Heart Assoc: 05 Jul 2021; 10:e020140 | PMID: 34121418
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of Underlying Cardiometabolic Diseases on the Association Between Sedentary Time and All-Cause Mortality in a Large Japanese Population: A Cohort Analysis Based on the J-MICC Study.

Koyama T, Ozaki E, Kuriyama N, Tomida S, ... Wakai K, Japan Multi‐Institutional Collaborative Cohort (J‐MICC) Study Group

Background:
This study aimed to determine the association between sedentary time and mortality with regard to leisure-time physical activity with or without cardiometabolic diseases such as hypertension, dyslipidemia, and diabetes mellitus. Methods and Results Using data from the J-MICC (Japan Multi-Institutional Collaborative Cohort) Study, 64 456 participants (29 022 men, 35 434 women) were analyzed. Hazard ratios (HRs) and 95% CIs were used to characterize the relative risk of all-cause mortality to evaluate its association with sedentary time (categorical variables: <5, 5 to <7, 7 to <9, ≥9 h/d and 2-hour increments in exposure) according to the self-reported hypertension, dyslipidemia, and diabetes mellitus using a Cox proportional hazards model. A total of 2257 participants died during 7.7 years of follow-up. The corresponding HRs for each 2-hour increment in sedentary time among participants with all factors, no factors, hypertension, dyslipidemia, and diabetes mellitus were 1.153 (95% CI, 1.114-1.194), 1.125 (95% CI, 1.074-1.179), 1.202 (95% CI, 1.129-1.279), 1.176 (95% CI, 1.087-1.273), and 1.272 (95% CI, 1.159-1.396), respectively. Furthermore, when analyzed according to the combined different factors (hypertension, dyslipidemia, and diabetes mellitus), HRs increased with each additional factor, and participants reporting all 3 conditions had the highest HR of 1.417 (95% CI, 1.162-1.728) independently of leisure-time metabolic equivalents.
Conclusions:
The association between sedentary time and increased mortality is stronger among patients with hypertension, dyslipidemia, and diabetes mellitus regardless of leisure-time physical activity in a large Japanese population.




J Am Heart Assoc: 05 Jul 2021; 10:e018293
Koyama T, Ozaki E, Kuriyama N, Tomida S, ... Wakai K, Japan Multi‐Institutional Collaborative Cohort (J‐MICC) Study Group
J Am Heart Assoc: 05 Jul 2021; 10:e018293 | PMID: 34121417
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Electrophysiological Characteristics of Intra-Atrial Reentrant Tachycardia in Adult Congenital Heart Disease: Implications for Catheter Ablation.

Kahle AK, Gallotti RG, Alken FA, Meyer C, Moore JP

Background:
Ultra-high-density mapping enables detailed mechanistic analysis of atrial reentrant tachycardia but has yet to be used to assess circuit conduction velocity (CV) patterns in adults with congenital heart disease. Methods and Results Circuit pathways and central isthmus CVs were calculated from consecutive ultra-high-density isochronal maps at 2 tertiary centers over a 3-year period. Circuits using anatomic versus surgical obstacles were considered separately and pathway length <50th percentile identified small circuits. CV analysis was used to derive a novel index for prediction of postablation conduction block. A total of 136 supraventricular tachycardias were studied (60% intra-atrial reentrant, 14% multiple loop). Circuits with anatomic versus surgical obstacles featured longer pathway length (119 mm; interquartile range [IQR], 80-150 versus 78 mm; IQR, 63-95; P<0.001), faster central isthmus CV (0.1 m/s; IQR, 0.06-0.25 versus 0.07 m/s; IQR, 0.05-0.10; P=0.016), faster non-isthmus CV (0.52 m/s; IQR, 0.33-0.71 versus 0.38 m/s; IQR, 0.27-0.46; P=0.009), and fewer slow isochrones (4; IQR, 2.3-6.8 versus 6; IQR 5-7; P=0.008). Both central isthmus (R2=0.45; P<0.001) and non-isthmus CV (R2=0.71; P<0.001) correlated with pathway length, whereas central isthmus CV <0.15 m/s was ubiquitous for small circuits. Non-isthmus CV in tachycardia correlated with CV during block validation (R2=0.94; P<0.001) and a validation map to tachycardia conduction time ratio >85% predicted isthmus block in all cases. Over >1 year of follow-up, arrhythmia-free survival was better for homogeneous CV patterns (90% versus 57%; P=0.04).
Conclusions:
Ultra-high-density mapping-guided CV analysis distinguishes atrial reentrant patterns in adults with congenital heart disease with surgical obstacles producing slower and smaller circuits. Very slow central isthmus CV may be essential for atrial tachycardia maintenance in small circuits, and non-isthmus conduction time in tachycardia appears to be useful for rapid assessment of postablation conduction block.




J Am Heart Assoc: 05 Jul 2021; 10:e020835
Kahle AK, Gallotti RG, Alken FA, Meyer C, Moore JP
J Am Heart Assoc: 05 Jul 2021; 10:e020835 | PMID: 34121415
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Measures of Left Ventricular Diastolic Function and Cardiorespiratory Fitness According to Glucose Metabolism Status: The Maastricht Study.

Veugen MGJ, Linssen PBC, Henry RMA, Koster A, ... Stehouwer CDA, Brunner-La Rocca HP

Background:
This cross-sectional study evaluated associations between structural and functional measures of left ventricular diastolic function and cardiorespiratory fitness (CRF) in a well-characterized population-based cohort stratified according to glucose metabolism status. Methods and Results Six hundred seventy-two participants from The Maastricht Study (mean±SD age, 61±9 years; 17.4% prediabetes and 25.4% type 2 diabetes mellitus) underwent both echocardiography to determine left atrial volume index, left ventricular mass index, maximum tricuspid flow regurgitation, average e\' and E/e\' ratio; and submaximal cycle ergometer test to determine CRF as maximum power output per kilogram body mass. Associations were examined with linear regression adjusted for cardiovascular risk and lifestyle factors, and interaction terms. After adjustment, in normal glucose metabolism but not (pre)diabetes, higher left atrial volume index (per 1 mL/m2), left ventricular mass index (per 1 g/m2.7), maximum tricuspid regurgitation flow (per 1 m/s) were associated with higher CRF (maximum power output per kilogram body mass; β in normal glucose metabolism 0.015 [0.008-0.023], Pinteraction (pre)diabetes <0.10; 0.007 [-0.001 to 0.015], Pinteraction type 2 diabetes mellitus <0.10; 0.129 [0.011-0.246], Pinteraction >0.10; for left atrial volume index, left ventricular mass index, maximum tricuspid regurgitation flow, respectively). Furthermore, after adjustment, in all individuals, higher average E/e\' ratio (per unit), but not average e\', was associated with lower CRF (normal glucose metabolism -0.044 [-0.071 to -0.016]), Pinteraction >0.10).
Conclusions:
In this population-based study, structural and functional measures of left ventricular diastolic function were independently differentially associated with CRF over the strata of glucose metabolism status. This suggests that deteriorating left ventricular diastolic function, although of small effect, may contribute to the pathophysiological process of impaired CRF in the general population. Moreover, the differential effects in these structural measures may be the consequence of cardiac structural adaptation to effectively increase CRF in normal glucose metabolism, which is absent in (pre)diabetes.




J Am Heart Assoc: 05 Jul 2021; 10:e020387
Veugen MGJ, Linssen PBC, Henry RMA, Koster A, ... Stehouwer CDA, Brunner-La Rocca HP
J Am Heart Assoc: 05 Jul 2021; 10:e020387 | PMID: 34121414
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

MEDI6012: Recombinant Human Lecithin Cholesterol Acyltransferase, High-Density Lipoprotein, and Low-Density Lipoprotein Receptor-Mediated Reverse Cholesterol Transport.

George RT, Abuhatzira L, Stoughton SM, Karathanasis SK, ... Koren M, Hirshberg B

Background:
MEDI6012 is recombinant human lecithin cholesterol acyltransferase, the rate-limiting enzyme in reverse cholesterol transport. Infusions of lecithin cholesterol acyltransferase have the potential to enhance reverse cholesterol transport and benefit patients with coronary heart disease. The purpose of this study was to test the safety, pharmacokinetic, and pharmacodynamic profile of MEDI6012. Methods and Results This phase 2a double-blind study randomized 48 subjects with stable coronary heart disease on a statin to a single dose of MEDI6012 or placebo (6:2) (NCT02601560) with ascending doses administered intravenously (24, 80, 240, and 800 mg) and subcutaneously (80 and 600 mg). MEDI6012 demonstrated rates of treatment-emergent adverse events that were similar to those of placebo. Dose-dependent increases in high-density lipoprotein cholesterol were observed with area under the concentration-time curves from 0 to 96 hours of 728, 1640, 3035, and 5318 should be: mg·h/mL in the intravenous dose groups and 422 and 2845 mg·h/mL in the subcutaneous dose groups. Peak mean high-density lipoprotein cholesterol percent change was 31.4%, 71.4%, 125%, and 177.8% in the intravenous dose groups and 18.3% and 111.2% in the subcutaneous dose groups, and was accompanied by increases in endogenous apoA1 (apolipoprotein A1) and non-ATP-binding cassette transporter A1 cholesterol efflux capacity. Decreases in apoB (apolipoprotein B) were observed across all dose levels and decreases in atherogenic small low-density lipoprotein particles by 41%, 88%, and 79% at the 80-, 240-, and 800-mg IV doses, respectively.
Conclusions:
MEDI6012 demonstrated an acceptable safety profile and increased high-density lipoprotein cholesterol, endogenous apoA1, and non-ATP-binding cassette transporter A1 cholesterol efflux capacity while reducing the number of atherogenic low-density lipoprotein particles. These findings are supportive of enhanced reverse cholesterol transport and a functional high-density lipoprotein phenotype. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601560.




J Am Heart Assoc: 05 Jul 2021; 10:e014572
George RT, Abuhatzira L, Stoughton SM, Karathanasis SK, ... Koren M, Hirshberg B
J Am Heart Assoc: 05 Jul 2021; 10:e014572 | PMID: 34121413
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cumulative Serum Uric Acid and Its Time Course Are Associated With Risk of Myocardial Infarction and All-Cause Mortality.

Tian X, Wang A, Wu S, Zuo Y, ... Mo D, Luo Y

Background:
Serum uric acid (SUA) has been demonstrated as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the impact of cumulative SUA (cumSUA) remains unclear. We aimed to investigate the association of cumSUA with MI risk and all-cause mortality, and to further explore the effects of SUA accumulation time course. Methods and Results The study enrolled 53 463 participants without a history of MI, and these participants underwent 3 examinations during 2006 to 2010. cumSUA from baseline to the third examination was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Cox models estimated hazard ratios (HRs) and 95% CIs of MI and all-cause mortality for cumSUA quartiles, hyperuricemia exposure duration, and SUA accumulation time course. During a median follow-up of 7.04 years, 476 incident MIs and 2692 deaths occurred. In the fully adjusted model, a higher MI risk was observed in the highest cumSUA quartile (HR, 1.48; 95% CI, 1.10-1.99), in participants with longer hyperuricemia exposure duration (HR, 1.71; 95% CI, 1.06-2.73), and in participants with cumSUA≥median and a negative slope (HR, 1.58; 95% CI, 1.18-2.11). Similar associations persisted for all-cause mortality.
Conclusions:
The risk of MI and all-cause mortality increased with higher cumSUA and was affected by the SUA accumulation time course. Early SUA accumulation contributed more to MI risk and all-cause mortality than later SUA accumulation with the same overall cumulative exposure, emphasizing the importance of optimal SUA control early in life.




J Am Heart Assoc: 05 Jul 2021; 10:e020180
Tian X, Wang A, Wu S, Zuo Y, ... Mo D, Luo Y
J Am Heart Assoc: 05 Jul 2021; 10:e020180 | PMID: 34120449
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Causal Effect of Adiposity Measures on Blood Pressure Traits in 2 Urban Swedish Cohorts: A Mendelian Randomization Study.

Giontella A, Lotta LA, Overton JD, Baras A, ... Gill D, Fava C

Background:
Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. Methods and Results In this study, we used 4 different genetic risk scores (GRS; GRS-BMI565, GRS-WHR324, GRS-VAT208, GRS-BF81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive 795Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist-to-hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow-up in the Malmö Preventive Project.
Conclusions:
We support a causal link between genetically mediated adiposity, especially waist-to-hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.




J Am Heart Assoc: 05 Jul 2021; 10:e020405
Giontella A, Lotta LA, Overton JD, Baras A, ... Gill D, Fava C
J Am Heart Assoc: 05 Jul 2021; 10:e020405 | PMID: 34120448
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Compliance in Primary Prevention With Statins and Associations With Cardiovascular Risk and Death in a Low-Risk Population With Type 2 Diabetes Mellitus.

Malmborg M, Schmiegelow MDS, Gerds T, Schou M, ... Torp-Pedersen C, Gislason G

Background:
We examined whether primary prevention with statins and high adherence to statins reduce the associated risk of cardiovascular events or death in a low-risk population with type 2 diabetes mellitus (T2D). Methods and Results Using Danish nationwide registers, we included patients with new-onset T2D, aged 40 to 89 years, between 2005 and 2011, who were alive 18 months following the T2D diagnosis (index date). In patients who purchased statins within 6 months following T2D diagnosis, we calculated the proportion of days covered (PDC) within 1 year after the initial 6-month period. We studied the combined end point of myocardial infarction, stroke, or all-cause mortality, whichever came first, with Cox regression. Reported were standardized 5-year risk differences for fixed comorbidity distribution according to statin treatment history, stratified by sex and age. Among 77 170 patients, 42 975 (56%) were treated with statins, of whom 31 061 (72%) had a PDC ≥80%. In men aged 70 to 79 years who were treated with statins, the standardized 5-year risk was 22.9% (95% CI, 21.5%-24.3%), whereas the risk was 29.1% (95% CI, 27.4%-30.7%) in men not treated, resulting in a significant risk reduction of 6.2% (95% CI, 4.0%-8.4%), P<0.0001. The risk reduction associated with statins increased with advancing age group (women: age 40-49 years, 0.0% [95% CI, -1.0% to 1.0%]; age 80-89 years, 10.8% [95% CI, 7.2%-14.4%]). Standardizing to all patients treated with statins, PDC <80% was associated with increased risk difference (reference PDC ≥80%; PDC <20%, 4.2% [95% CI, 2.9%-5.6%]).
Conclusions:
This study supports the use of statins as primary prevention against cardiovascular diseases or death in 18-month surviving low-risk patients with T2D, with the highest effect in the elderly and adherent patients.




J Am Heart Assoc: 05 Jul 2021; 10:e020395
Malmborg M, Schmiegelow MDS, Gerds T, Schou M, ... Torp-Pedersen C, Gislason G
J Am Heart Assoc: 05 Jul 2021; 10:e020395 | PMID: 34151606
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Vascular Calcification as a Novel Risk Factor for Kidney Function Deterioration in the Nonelderly.

Park S, Cho NJ, Heo NH, Rhee EJ, Gil H, Lee EY

Background:
The relationship between vascular calcification and chronic kidney disease is well known. However, whether vascular calcification affects renal function deterioration remains unclear. We investigated whether kidney function deteriorated more rapidly in individuals with higher vascular calcification indicated by the coronary artery calcium score (CACS). Methods and Results Individuals with a normal estimated glomerular filtration rate (>60 mL/min per 1.73 m2) who underwent cardiac computed tomography in our institution (a tertiary teaching hospital in Cheonan, Korea) from January 2010 to July 2012 were retrospectively reviewed. All participants were aged 20 to 65 years. Among 739 patients, 447, 175, and 117 had CACSs of 0, 1 to 99, and ≥100 units, respectively. The participants were followed for 7.8 (interquartile range, 5.5-8.8) years. The adjusted annual estimated glomerular filtration rates declined more rapidly in patients in the CACS ≥100 group compared with those in the CACS 0 group (adjusted-β, -0.40; 95% CI, -0.80 to -0.03) when estimated using a linear mixed model. The adjusted hazard ratio in the CACS ≥100 group for Kidney Disease: Improving Global Outcomes criteria (a drop in estimated glomerular filtration rate category accompanied by a 25% or greater drop in estimated glomerular filtration rate) was 2.52 (1.13-5.61). After propensity score matching, more prevalent renal outcomes (13.2%) were observed in patients with a CACS of ≥100 compared with those with a CACS of 0 (1.9%), with statistical significance (P=0.004).
Conclusions:
Our results showed that renal function declined more rapidly in patients with higher CACSs, suggesting that vascular calcification might be associated with chronic kidney disease progression.




J Am Heart Assoc: 05 Jul 2021; 10:e019300
Park S, Cho NJ, Heo NH, Rhee EJ, Gil H, Lee EY
J Am Heart Assoc: 05 Jul 2021; 10:e019300 | PMID: 34151587
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Aleksandric SB, Djordjevic-Dikic AD, Dobric MR, Giga VL, ... Ostojic MC, Beleslin BD

Background:
Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 μg/kg per minute) and dobutamine (10-50 μg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia.
Conclusions:
Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.




J Am Heart Assoc: 05 Jul 2021; 10:e020597
Aleksandric SB, Djordjevic-Dikic AD, Dobric MR, Giga VL, ... Ostojic MC, Beleslin BD
J Am Heart Assoc: 05 Jul 2021; 10:e020597 | PMID: 34151580
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Burden of Ischemic Stroke in Patients With Congenital Heart Disease: A Nationwide, Case-Control Study.

Giang KW, Fedchenko M, Dellborg M, Eriksson P, Mandalenakis Z

Background:
Patients with congenital heart disease (CHD) are at increased risk of developing ischemic stroke (IS) compared with controls without CHD. However, the long-term outcomes after IS, including IS recurrence and mortality risk, remain unclear. Methods and Results We identified all patients with CHD in Sweden who were born between 1930 and 2017 using the Swedish National Patient Register and the Cause of Death Register. Ten controls without CHD were randomly selected from the general population and matched for birth year and sex for each patient with CHD. The follow-up of the study population was performed between January 1970 and December 2017. In total, 88 700 patients with CHD (50.6% men) and 890 450 matched controls (51.0%) were included in this study. During a mean follow-up of 25.1±22.0 years, patients with CHD had a 5-fold higher risk of developing an index IS (hazard ratio [HR], 5.01; 95% CI, 4.81-5.22) compared with controls. However, the risk of developing a recurrent IS was lower in patients with CHD compared with controls (HR, 0.66; 95% CI, 0.56-0.78), an observation that persisted after adjustment for cardiovascular risk factors and comorbidities. Patients with CHD were also at a significantly lower risk of all-cause mortality after index IS than controls (HR, 0.53; 95% CI, 0.49-0.58).
Conclusions:
Patients with CHD had a 5-fold higher risk of developing index IS compared with matched controls. However, the risk of recurrent IS stroke and all-cause mortality were 34% and 47% lower, respectively, in patients with CHD compared with controls.




J Am Heart Assoc: 05 Jul 2021; 10:e020939
Giang KW, Fedchenko M, Dellborg M, Eriksson P, Mandalenakis Z
J Am Heart Assoc: 05 Jul 2021; 10:e020939 | PMID: 34139861
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Antenatal Exposure to UV-B Radiation and Preeclampsia: A Retrospective Cohort Study.

Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, ... Dibben C, Pell JP

Background:
Risk of preeclampsia varies by month of delivery. We tested whether this seasonal patterning may be mediated through maternal vitamin D concentration using antenatal exposure to UV-B radiation as an instrumental variable. Methods and Results Scottish maternity records were linked to antenatal UV-B exposure derived from satellites between 2000 and 2010. Logistic regression analyses were used to explore the association between UV-B and preeclampsia, adjusting for the potential confounding effects of month of conception, child\'s sex, gestation, parity, and mean monthly temperature. Of the 522 896 eligible singleton deliveries, 8689 (1.66%) mothers developed preeclampsia. Total antenatal UV-B exposure ranged from 43.18 to 101.11 kJ/m2 and was associated with reduced risk of preeclampsia with evidence of a dose-response relationship (highest quintile of exposure: adjusted odds ratio, 0.57; 95% CI, 0.44-0.72; P<0.001). Associations were demonstrated for UV-B exposure in all 3 trimesters.
Conclusions:
The seasonal patterning of preeclampsia may be mediated through low maternal vitamin D concentration in winter resulting from low UV-B radiation. Interventional studies are required to determine whether vitamin D supplements or UV-B-emitting light boxes can reduce the seasonal patterning of preeclampsia.




J Am Heart Assoc: 05 Jul 2021; 10:e020246
Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, ... Dibben C, Pell JP
J Am Heart Assoc: 05 Jul 2021; 10:e020246 | PMID: 34155917
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Improving Efficiency of the Barbershop Model of Hypertension Care for Black Men With Virtual Visits.

Blyler CA, Ebinger J, Rashid M, Moy NP, ... Albert CM, Rader F

Background:
The LABBPS (Los Angeles Barbershop Blood Pressure Study) developed a new model of hypertension care for non-Hispanic Black men that links health promotion by barbers to medication management by pharmacists. Barriers to scaling the model include inefficiencies that contribute to the cost of the intervention, most notably, pharmacist travel time. To address this, we tested whether virtual visits could be substituted for in-person visits after blood pressure (BP) control was achieved. Methods and Results We enrolled 10 Black male patrons with systolic BP ≥140 mm Hg into a proof-of-concept study in which barbers promoted follow-up with pharmacists who initially met each patron in the barbershop, where they prescribed BP medication under a collaborative practice agreement with the patrons\' physician. Medications were titrated during bimonthly in-person visits to achieve a BP goal of ≤130/80 mm Hg. Once BP goal was reached, visits were done by videoconference. Final BP and safety outcomes were assessed at 12 months. Nine patients completed the intervention. Baseline BP of 155±14/83.9±11 mm Hg decreased by -28.7±13/-8.9±15 mm Hg (P<0.0001). These data are statistically indistinguishable from prior LABBPS data (P=0.8 for change in systolic BP and diastolic BP). Hypertension control (≤130/80 mm Hg) was 67% (6 of 9), numerically greater than the 63% observed in LABBPS (P=not significant). As intended, the mean number of in-person visits decreased from 11 in LABBPS to 6.6 visits over 12 months. No treatment-related serious adverse events occurred.
Conclusions:
Virtual visits represent a viable substitute for in-person visits, both improving pharmacist efficiency and reducing cost while preserving intervention potency. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03726710.




J Am Heart Assoc: 05 Jul 2021; 10:e020796
Blyler CA, Ebinger J, Rashid M, Moy NP, ... Albert CM, Rader F
J Am Heart Assoc: 05 Jul 2021; 10:e020796 | PMID: 34155907
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms.

Igase M, Igase K, Okada Y, Ochi M, ... Sadamoto K, Ohyagi Y

Background:
We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31-91 years) without cerebro- or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial-ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0-8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low-density lipoprotein cholesterol.
Conclusions:
The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low-density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low-density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.




J Am Heart Assoc: 05 Jul 2021; 10:e018626
Igase M, Igase K, Okada Y, Ochi M, ... Sadamoto K, Ohyagi Y
J Am Heart Assoc: 05 Jul 2021; 10:e018626 | PMID: 34155906
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex Differences in Prehospital Delays in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Stehli J, Dinh D, Dagan M, Duffy SJ, ... Stub D, Zaman S

Background:
Women with ST-segment-elevation myocardial infarction experience delays in reperfusion compared with men with little data on each time component from symptom onset to reperfusion. This study analyzed sex discrepancies in patient delays, prehospital system delays, and hospital delays. Methods and Results Consecutive patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention across 30 hospitals in the Victorian Cardiac Outcomes Registry (2013-2018) were analyzed. Data from the Ambulance Victoria Data warehouse were used to perform linkage to the Victorian Cardiac Outcomes Registry for all patients transported via emergency medical services (EMS). The primary end point was EMS call-to-door time (prehospital system delay). Secondary end points included symptom-to-EMS call time (patient delay), door-to-device time (hospital delay), 30-day mortality, major adverse cardiovascular events, and major bleeding. End points were analyzed according to sex and adjusted for age, comorbidities, cardiogenic shock, cardiac arrest, and symptom onset time. A total of 6330 (21% women) patients with ST-segment-elevation myocardial infarction were transported by EMS. Compared with men, women had longer adjusted geometric mean symptom-to-EMS call times (47.0 versus 44.0 minutes; P<0.001), EMS call-to-door times (58.1 versus 55.7 minutes; P<0.001), and door-to-device times (58.5 versus 54.9 minutes; P=0.006). Compared with men, women had higher 30-day mortality (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P=0.02) and major bleeding (OR, 1.54; 95% CI, 1.08-2.20; P=0.02).
Conclusions:
Female patients with ST-segment-elevation myocardial infarction experienced excess delays in patient delays, prehospital system delays, and hospital delays, even after adjustment for confounders. Prehospital system and hospital delays resulted in an adjusted excess delay of 10 minutes compared with men.




J Am Heart Assoc: 05 Jul 2021; 10:e019938
Stehli J, Dinh D, Dagan M, Duffy SJ, ... Stub D, Zaman S
J Am Heart Assoc: 05 Jul 2021; 10:e019938 | PMID: 34155902
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation.

Chavkin NW, Sano S, Wang Y, Oshima K, ... Gokce N, Walsh K

Background:
A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase-like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage.
Conclusions:
Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.




J Am Heart Assoc: 05 Jul 2021; 10:e019904
Chavkin NW, Sano S, Wang Y, Oshima K, ... Gokce N, Walsh K
J Am Heart Assoc: 05 Jul 2021; 10:e019904 | PMID: 34155901
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mitral Valve Prolapse and Its Motley Crew-Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition.

Morningstar JE, Nieman A, Wang C, Beck T, Harvey A, Norris RA
Mitral valve prolapse (MVP) is a commonly occurring heart condition defined by enlargement and superior displacement of the mitral valve leaflet(s) during systole. Although commonly seen as a standalone disorder, MVP has also been described in case reports and small studies of patients with various genetic syndromes. In this review, we analyzed the prevalence of MVP within syndromes where an association to MVP has previously been reported. We further discussed the shared biological pathways that cause MVP in these syndromes, as well as how MVP in turn causes a diverse array of cardiac and noncardiac complications. We found 105 studies that identified patients with mitral valve anomalies within 18 different genetic, developmental, and connective tissue diseases. We show that some disorders previously believed to have an increased prevalence of MVP, including osteogenesis imperfecta, fragile X syndrome, Down syndrome, and Pseudoxanthoma elasticum, have few to no studies that use up-to-date diagnostic criteria for the disease and therefore may be overestimating the prevalence of MVP within the syndrome. Additionally, we highlight that in contrast to early studies describing MVP as a benign entity, the clinical course experienced by patients can be heterogeneous and may cause significant cardiovascular morbidity and mortality. Currently only surgical correction of MVP is curative, but it is reserved for severe cases in which irreversible complications of MVP may already be established; therefore, a review of clinical guidelines to allow for earlier surgical intervention may be warranted to lower cardiovascular risk in patients with MVP.



J Am Heart Assoc: 05 Jul 2021; 10:e020919
Morningstar JE, Nieman A, Wang C, Beck T, Harvey A, Norris RA
J Am Heart Assoc: 05 Jul 2021; 10:e020919 | PMID: 34155898
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Temporal Trends and Drivers of Heart Team Utilization in Transcatheter Aortic Valve Replacement: A Population-Based Study in Ontario, Canada.

Marcus G, Qiu F, Manoragavan R, Ko DT, ... Fremes SE, Wijeysundera HC

Background:
The multidisciplinary Heart Team (HT) is recommended for management decisions for transcatheter aortic valve replacement (TAVR) candidates, and during TAVR procedures. Empiric evidence to support these recommendations is limited. We aimed to explore temporal trends, drivers, and outcomes associated with HT utilization. Methods and Results TAVR candidates were identified in Ontario, Canada, from April 1, 2012 to March 31, 2019. The HT was defined as having a billing code for both a cardiologist and cardiac surgeon during the referral period. The procedural team was defined as a billing code during the TAVR procedure. Hierarchical logistical models were used to determine the drivers of HT. Median odds ratios were calculated to quantify the degree of variation among hospitals. Of 10 412 patients referred for TAVR consideration, 5489 (52.7%) patients underwent a HT during the referral period, with substantial range between hospitals (median odds ratio of 1.78). Utilization of a HT for TAVR referrals declined from 69.9% to 41.1% over the years of the study. Patient characteristics such as older age, frailty and dementia, and hospital characteristics including TAVR program size, were found associated with lower HT utilization. In TAVR procedures, the procedural team included both cardiologists and cardiac surgeons in 94.9% of cases, with minimal variation over time or between hospitals.
Conclusions:
There has been substantial decline in HT utilization for TAVR candidates over time. In addition, maturity of TAVR programs was associated with lower HT utilization.




J Am Heart Assoc: 05 Jul 2021; 10:e020741
Marcus G, Qiu F, Manoragavan R, Ko DT, ... Fremes SE, Wijeysundera HC
J Am Heart Assoc: 05 Jul 2021; 10:e020741 | PMID: 34155897
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Meal and Snack Patterns With Mortality of All-Cause, Cardiovascular Disease, and Cancer: The US National Health and Nutrition Examination Survey, 2003 to 2014.

Wei W, Jiang W, Huang J, Xu J, ... Li Y, Han T

Background:
Although accumulating evidence has demonstrated that consumption time of energy and macronutrients plays an important role in maintaining health, the association between consumption time of different foods and cardiovascular disease, cancer, and all-cause mortalities is still largely unknown. Methods and Results A noninstitutionalized household population of the US 21 503 participants from National Health and Nutrition Examination Survey was included. Meal patterns and snack patterns throughout a whole day were measured using 24-hour dietary recall. Principal component analysis was performed to establish dietary patterns. Cox proportional hazards models were used to evaluate the association between dietary patterns across meals and cardiovascular disease (CVD), cancer, and all-cause mortalities. During the 149 875 person-years of follow-up, 2192 deaths including 676 deaths because of CVD and 476 because of cancer were documented. After adjusting for potential confounders, participants consuming fruit-lunch had lower mortality risks of all-cause (hazard ratio [HR], 0.82; 95% CI, 0.72-0.92) and CVD (HR, 0.66; 95% CI, 0.49-0.87); whereas participants who consumed Western-lunch were more likely to die because of CVD (HR, 1.44; 95% CI, 1.10-1.89). Participants who consumed vegetable-dinner had lower mortality risks of all-cause, CVD, and cancer (HRall-cause, 0.69; 95% CI, 0.60-0.78; HRCVD, 0.77; 95% CI, 0.61-0.95; HRcancer, 0.63; 95% CI, 0.48-0.83). For the snack patterns, participants who consumed fruit-snack after breakfast had lower mortality risks of all-cause and cancer (HRall-cause, 0.78; 95% CI, 0.66-0.93; HRcancer, 0.55; 95% CI, 0.39-0.78), and participants who consumed dairy-snack after dinner had lower risks of all-cause and CVD mortalities (HRall-cause, 0.82; 95% CI, 0.72-0.94; HRCVD, 0.67; 95% CI, 0.52-0.87). Participants who consumed a starchy-snack after main meals had greater mortality risks of all-cause (HRafter-breakfast, 1.50; 95% CI, 1.24-1.82; HRafter-lunch, 1.52; 95% CI, 1.27-1.81; HRafter-dinner, 1.50; 95% CI, 1.25-1.80) and CVD (HRafter-breakfast, 1.55; 95% CI, 1.08-2.24; HRafter-lunch, 1.44; 95% CI, 1.03-2.02; HRafter-dinner, 1.57; 95% CI, 1.10-2.23).
Conclusions:
Fruit-snack after breakfast, fruit-lunch, vegetable-dinner, and dairy-snack after dinner was associated with lower mortality risks of CVD, cancer, and all-cause; whereas Western-lunch and starchy-snack after main meals had greater CVD and all-cause mortalities.




J Am Heart Assoc: 05 Jul 2021; 10:e020254
Wei W, Jiang W, Huang J, Xu J, ... Li Y, Han T
J Am Heart Assoc: 05 Jul 2021; 10:e020254 | PMID: 34157852
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Activation of Aryl Hydrocarbon Receptor by ITE Improves Cardiac Function in Mice After Myocardial Infarction.

Seong E, Lee JH, Lim S, Park EH, ... Chung WS, Chang K

Background:
The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2-[1\'H-indole-3\'-carbonyl]-thiazole-4-carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T-cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE-treated mice exhibited significantly improved systolic function (P<0.001) and reduced infarct size compared with control mice (P<0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3+ (forkhead box protein P3-positive) regulatory T cells and tolerogenic dendritic cell populations.
Conclusions:
Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post-MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.




J Am Heart Assoc: 05 Jul 2021; 10:e020502
Seong E, Lee JH, Lim S, Park EH, ... Chung WS, Chang K
J Am Heart Assoc: 05 Jul 2021; 10:e020502 | PMID: 34157850
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Discordance Between Severity of Heart Failure as Determined by Patient Report Versus Cardiopulmonary Exercise Testing.

Michelis KC, Grodin JL, Zhong L, Pandey A, ... Thibodeau JT, Drazner MH

Background:
Patient-reported outcomes may be discordant to severity of illness as assessed by objective parameters. The frequency of this discordance and its influence on clinical outcomes in patients with heart failure is unknown. Methods and Results In HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), participants (N=2062) had baseline assessment of health-related quality of life via the Kansas City Cardiomyopathy Clinical Summary score (KCCQ-CS) and objective severity by cardiopulmonary stress testing (minute ventilation [VE]/carbon dioxide production [VCO2] slope). We defined 4 groups by median values: 2 concordant (lower severity: high KCCQ-CS and low VE/VCO2 slope; higher severity: low KCCQ-CS and high VE/VCO2 slope) and 2 discordant (symptom minimizer: high KCCQ-CS and high VE/VCO2 slope; symptom magnifier: low KCCQ-CS and low VE/VCO2 slope). The association of group assignment with mortality was assessed in adjusted Cox models. Symptom magnification (23%) and symptom minimization (23%) were common. Despite comparable KCCQ-CS scores, the risk of all-cause mortality in symptom minimizers versus concordant-lower severity participants was increased significantly (hazard ratio [HR], 1.79; 95% CI, 1.27-2.50; P<0.001). Furthermore, despite symptom magnifiers having a KCCQ-CS score 28 points lower (poorer QOL) than symptom minimizers, their risk of mortality was not increased (HR, 0.79; 95% CI, 0.57-1.1; P=0.18, respectively).
Conclusions:
Severity of illness by patient report versus cardiopulmonary exercise testing was frequently discordant. Mortality tracked more closely with the objective data, highlighting the importance of relying not only on patient report, but also objective data when risk stratifying patients with heart failure.




J Am Heart Assoc: 05 Jul 2021; 10:e019864
Michelis KC, Grodin JL, Zhong L, Pandey A, ... Thibodeau JT, Drazner MH
J Am Heart Assoc: 05 Jul 2021; 10:e019864 | PMID: 34180246
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Intensive Lifestyle Intervention Increases Plasma Midregional Proatrial Natriuretic Peptide Concentrations in Overweight Children.

Thomsen CF, Goharian TS, Larsen KT, Goetze JP, Andersen LB, Jeppesen JL

Background:
Overweight adults have low circulating concentrations of ANP (atrial natriuretic peptide) and proANP fragments. We tested the hypothesis that an intensive lifestyle intervention with an intended weight loss would increase plasma concentrations of a proANP fragment in overweight children. Methods and Results We measured MR-proANP (midregional proANP) concentrations in plasma from overweight children who participated in the OOIS (Odense Overweight Intervention Study). OOIS randomized 115 overweight children (11-13 years, 55% girls) to an intensive day-camp intervention arm with increased physical activity and healthy diet or to a less intensive standard intervention arm for 6 weeks. We used linear mixed-effects modeling for repeated measures to estimate the difference in the mean change with 95% CIs in fasting plasma MR-proANP concentrations between the 2 arms, and we used partial least squares regression analysis to identify candidate mediators. Differences in weight, fitness, and metabolic factors were also analyzed. At baseline, fasting plasma MR-proANP concentrations were (median [interquartile range]) 35.0 pmol/L (26.8-42.0) in the day-camp intervention arm and 37.2 pmol/L (31.7-44.7) in standard intervention arm participants, respectively. After 6 weeks intervention, children in the day-camp intervention arm had increased their MR-proANP (5.4 pmol/L [0.8-10.0], P=0.022) and their fitness (2.33 mL O2/min per kg [0.52-4.14], P=0.012) and they had deceased their body mass index (-2.12 kg/m2 [-2.59 to -1.65], P<0.001) as compared with children in standard intervention arm. In the partial least squares analysis, decreases in fasting insulin and in estimated insulin resistance were associated with the observed increase in MR-proANP concentrations.
Conclusions:
An intensive lifestyle intervention increases plasma MR-proANP among overweight children. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01574352.




J Am Heart Assoc: 05 Jul 2021; 10:e020676
Thomsen CF, Goharian TS, Larsen KT, Goetze JP, Andersen LB, Jeppesen JL
J Am Heart Assoc: 05 Jul 2021; 10:e020676 | PMID: 34180245
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lower In-Hospital Mortality With Beta-Blocker Use at Admission in Patients With Acute Decompensated Heart Failure.

Tamaki Y, Yaku H, Morimoto T, Inuzuka Y, ... Kimura T, KCHF Study Investigators

Background:
It remains unclear whether beta-blocker use at hospital admission is associated with better in-hospital outcomes in patients with acute decompensated heart failure. Methods and Results We evaluated the factors independently associated with beta-blocker use at admission, and the effect of beta-blocker use at admission on in-hospital mortality in 3817 patients with acute decompensated heart failure enrolled in the Kyoto Congestive Heart Failure registry. There were 1512 patients (39.7%) receiving, and 2305 patients (60.3%) not receiving beta-blockers at admission for the index acute decompensated heart failure hospitalization. Factors independently associated with beta-blocker use at admission were previous heart failure hospitalization, history of myocardial infarction, atrial fibrillation, cardiomyopathy, and estimated glomerular filtration rate <30 mL/min per 1.73 m2. Factors independently associated with no beta-blocker use were asthma, chronic obstructive pulmonary disease, lower body mass index, dementia, older age, and left ventricular ejection fraction <40%. Patients on beta-blockers had significantly lower in-hospital mortality rates (4.4% versus 7.6%, P<0.001). Even after adjusting for confounders, beta-blocker use at admission remained significantly associated with lower in-hospital mortality risk (odds ratio, 0.41; 95% CI, 0.27-0.60, P<0.001). Furthermore, beta-blocker use at admission was significantly associated with both lower cardiovascular mortality risk and lower noncardiovascular mortality risk. The association of beta-blocker use with lower in-hospital mortality risk was relatively more prominent in patients receiving high dose beta-blockers. The magnitude of the effect of beta-blocker use was greater in patients with previous heart failure hospitalization than in patients without (P for interaction 0.04).
Conclusions:
Beta-blocker use at admission was associated with lower in-hospital mortality in patients with acute decompensated heart failure. Registration URL: https://www.upload.umin.ac.jp/; Unique identifier: UMIN000015238.




J Am Heart Assoc: 05 Jul 2021; 10:e020012
Tamaki Y, Yaku H, Morimoto T, Inuzuka Y, ... Kimura T, KCHF Study Investigators
J Am Heart Assoc: 05 Jul 2021; 10:e020012 | PMID: 34180244
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.

Ernst ME, Ryan J, Chowdhury EK, Margolis KL, ... McNeil JJ, Murray AM

Background:
Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P=0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P=0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32).
Conclusions:
High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.




J Am Heart Assoc: 05 Jul 2021; 10:e019613
Ernst ME, Ryan J, Chowdhury EK, Margolis KL, ... McNeil JJ, Murray AM
J Am Heart Assoc: 05 Jul 2021; 10:e019613 | PMID: 34176293
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Tailored Versus Standard Hydration to Prevent Acute Kidney Injury After Percutaneous Coronary Intervention: Network Meta-Analysis.

Moroni F, Baldetti L, Kabali C, Briguori C, ... Bagur R, Azzalini L

Background:
Contrast-induced acute kidney injury (CI-AKI) is a serious complication after percutaneous coronary intervention. The mainstay of CI-AKI prevention is represented by intravenous hydration. Tailoring infusion rate to patient volume status has emerged as advantageous over fixed infusion-rate hydration strategies. Methods and Results A systematic review and network meta-analysis with a frequentist approach were conducted. A total of 8 randomized controlled trials comprising 2312 patients comparing fixed versus tailored hydration strategies to prevent CI-AKI after percutaneous coronary intervention were included in the final analysis. Tailored hydration strategies included urine flow rate-guided, central venous pressure-guided, left ventricular end-diastolic pressure-guided, and bioimpedance vector analysis-guided hydration. Primary endpoint was CI-AKI incidence. Safety endpoint was incidence of pulmonary edema. Urine flow rate-guided and central venous pressure-guided hydration were associated with a lower incidence of CI-AKI compared with fixed-rate hydration (odds ratio [OR], 0.32 [95% CI, 0.19-0.54] and OR, 0.45 [95% CI, 0.21-0.97]). No significant difference in pulmonary edema incidence was observed between the different hydration strategies. P score analysis showed that urine flow rate-guided hydration is advantageous in terms of both CI-AKI prevention and pulmonary edema incidence when compared with other approaches.
Conclusions:
Currently available hydration strategies tailored on patients\' volume status appear to offer an advantage over guideline-supported fixed-rate hydration for CI-AKI prevention after percutaneous coronary intervention. Current evidence suggests that urine flow rate-guided hydration as the most convenient strategy in terms of effectiveness and safety.




J Am Heart Assoc: 05 Jul 2021; 10:e021342
Moroni F, Baldetti L, Kabali C, Briguori C, ... Bagur R, Azzalini L
J Am Heart Assoc: 05 Jul 2021; 10:e021342 | PMID: 34169747
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Daily Mean Temperature and Temperature Variability With Onset Risks of Acute Aortic Dissection.

Yu X, Xia L, Xiao J, Zheng J, ... Feng X, Wei X

Background:
The association between ambient temperature and cardiovascular diseases has been well established, but evidence of temporal changes in the risk of acute aortic dissection (AAD) onset is lacking. Methods and Results We conducted an 8-year time-series study based on data from 2120 patients diagnosed with AAD at Tongji Hospital (Wuhan, China). Daily meteorological parameters were measured in the study area. Spearman\'s rank correlation analysis was applied to measure the associations between daily meteorological data and air pollution indicators. A distributed lag nonlinear model following quasi-Poisson regression was used to express the nonlinear exposure-response relationships and lag effects of daily mean temperature and temperature variability on the occurrence of AAD. Considering a 25-day lag effect, lower or higher temperatures with reference to 25°C did not alter the onset risk of AAD. The lag effect of daily mean temperature on the incidence of AAD is statistically significant within 2 days, and the impact of daily mean temperature on the risk is most influential on the day. The exposure-response curve between daily mean temperature and onset risks of AAD at lag 0 showed that the extremely cold temperature (2.5th percentile, 0.5°C) significantly increased the AAD risk for the total (relative risk, 1.733; 95% CI, 1.130-2.658) and type A dissection (relative risk, 3.951; 95% CI, 1.657-9.418). Temperature variability within 1 week did not affect the onset risks of AAD for the total.
Conclusions:
We confirmed that extremely cold temperatures significantly increased the AAD risk, which could contribute to early prevention and timely diagnosis of the disease.




J Am Heart Assoc: 05 Jul 2021; 10:e020190
Yu X, Xia L, Xiao J, Zheng J, ... Feng X, Wei X
J Am Heart Assoc: 05 Jul 2021; 10:e020190 | PMID: 34169738
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of Sodium-Glucose Linked Transporter 2 Inhibition With Ertugliflozin on Mitochondrial Function, Energetics, and Metabolic Gene Expression in the Presence and Absence of Diabetes Mellitus in Mice.

Croteau D, Luptak I, Chambers JM, Hobai I, ... Qin F, Colucci WS

Background:
Inhibitors of the sodium-glucose linked transporter 2 improve cardiovascular outcomes in patients with or without type 2 diabetes mellitus, but the effects on cardiac energetics and mitochondrial function are unknown. We assessed the effects of sodium-glucose linked transporter 2 inhibition on mitochondrial function, high-energy phosphates, and genes encoding mitochondrial proteins in hearts of mice with and without diet-induced diabetic cardiomyopathy. Methods and Results Mice fed a control diet or a high-fat, high-sucrose diet received ertugliflozin mixed with the diet (0.5 mg/g of diet) for 4 months. Isolated mitochondria were assessed for functional capacity. High-energy phosphates were assessed by 31P nuclear magnetic resonance spectroscopy concurrently with contractile performance in isolated beating hearts. The high-fat, high-sucrose diet caused myocardial hypertrophy, diastolic dysfunction, mitochondrial dysfunction, and impaired energetic response, all of which were prevented by ertugliflozin. With both diets, ertugliflozin caused supernormalization of contractile reserve, as measured by rate×pressure product at high work demand. Likewise, the myocardial gene sets most enriched by ertugliflozin were for oxidative phosphorylation and fatty acid metabolism, both of which were enriched independent of diet.
Conclusions:
Ertugliflozin not only prevented high-fat, high-sucrose-induced pathological cardiac remodeling, but improved contractile reserve and induced the expression of oxidative phosphorylation and fatty acid metabolism gene sets independent of diabetic status. These effects of sodium-glucose linked transporter 2 inhibition on cardiac energetics and metabolism may contribute to improved structure and function in cardiac diseases associated with mitochondrial dysfunction, such as heart failure.




J Am Heart Assoc: 05 Jul 2021; 10:e019995
Croteau D, Luptak I, Chambers JM, Hobai I, ... Qin F, Colucci WS
J Am Heart Assoc: 05 Jul 2021; 10:e019995 | PMID: 34169737
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Safety and Efficacy of Leadless Pacemakers: A Systematic Review and Meta-Analysis.

Ngo L, Nour D, Denman RA, Walters TE, ... Woodman RJ, Ranasinghe I

Background:
Leadless pacemaker is a novel technology, and evidence supporting its use is uncertain. We performed a systematic review and meta-analysis to examine the safety and efficacy of leadless pacemakers implanted in the right ventricle. Methods and Results We searched PubMed and Embase for studies published before June 6, 2020. The primary safety outcome was major complications, whereas the primary efficacy end point was acceptable pacing capture threshold (≤2 V). Pooled estimates were calculated using the Freedman-Tukey double arcsine transformation. Of 1281 records screened, we identified 36 observational studies of Nanostim and Micra leadless pacemakers, with most (69.4%) reporting outcomes for the Micra. For Micra, the pooled incidence of complications at 90 days (n=1608) was 0.46% (95% CI, 0.08%-1.05%) and at 1 year (n=3194) was 1.77% (95% CI, 0.76%-3.07%). In 5 studies with up to 1-year follow-up, Micra was associated with 51% lower odds of complications compared with transvenous pacemakers (3.30% versus 7.43%; odds ratio [OR], 0.49; 95% CI, 0.34-0.70). At 1 year, 98.96% (95% CI, 97.26%-99.94%) of 1376 patients implanted with Micra had good pacing capture thresholds. For Nanostim, the reported complication incidence ranged from 6.06% to 23.54% at 90 days and 5.33% to 6.67% at 1 year, with 90% to 100% having good pacing capture thresholds at 1 year (pooled result not estimated because of the low number of studies).
Conclusions:
Most studies report outcomes for the Micra, which is associated with a low risk of complications and good electrical performance up to 1-year after implantation. Further data from randomized controlled trials are needed to support the widespread adoption of these devices in clinical practice.




J Am Heart Assoc: 05 Jul 2021; 10:e019212
Ngo L, Nour D, Denman RA, Walters TE, ... Woodman RJ, Ranasinghe I
J Am Heart Assoc: 05 Jul 2021; 10:e019212 | PMID: 34169736
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term Survival and Freedom From Coronary Artery Reintervention After Arterial Switch Operation for Transposition of the Great Arteries: A Population-Based Nationwide Study.

Koubský K, Gebauer R, Tláskal T, Matějka T, ... Janoušek J, Chaloupecký V

Background:
The aim of this study was to evaluate long-term survival and freedom from coronary artery reintervention after the arterial switch operation (ASO). Methods and Results This single-center nationwide retrospective study included consecutive children who underwent ASO between 1990 and 2016 (n=605). Long-term outcomes were obtained by cross-mapping individual data with the National Death Registry and the National Registry of Cardiovascular Interventions for adults. A control group was randomly retrieved at a 1:10 ratio from the National Birth and Death Registries. Early mortality was 3.3% and late mortality was 1.7% during a median follow-up of 10 (interquartile range, 5-16) years. The probability of overall survival at 20 years after ASO was 94.9% compared with 99.5% in the background population (hazard ratio [HR] 15.6; 95% CI, 8.9-27.5, P<0.001). Independent multivariable predictors of worse survival were an intramural coronary artery (HR, 5.2; 95% CI, 1.8-15.2, P=0.002) and period of ASO 1990 to 1999 (HR, 4.6; 95% CI, 1.5-13.6, P<0.001). Fourteen patients (2.3%) required 16 coronary artery reoperations. Freedom from coronary artery reintervention at 20 years after ASO was 96%. The only independent multivariable predictor associated with a higher hazard for coronary artery reintervention was an intramural coronary artery (HR, 33.9; 95% CI, 11.8-97.5, P<0.001).
Conclusions:
Long-term survival after ASO is excellent. Coronary artery reinterventions are rare. An intramural coronary artery was an independent predictor associated with a higher risk for coronary artery reintervention and death, regardless of the surgical period.




J Am Heart Assoc: 05 Jul 2021; 10:e020479
Koubský K, Gebauer R, Tláskal T, Matějka T, ... Janoušek J, Chaloupecký V
J Am Heart Assoc: 05 Jul 2021; 10:e020479 | PMID: 34169727
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Depression as a Risk Factor for Incident Ischemic Stroke Among HIV-Positive Veterans in the Veterans Aging Cohort Study.

Sico JJ, Kundu S, So-Armah K, Gupta SK, ... Freiberg MS, Stewart JC

Background:
HIV infection and depression are each associated with increased ischemic stroke risk. Whether depression is a risk factor for stroke within the HIV population is unknown. Methods and Results We analyzed data on 106 333 (33 528 HIV-positive; 72 805 HIV-negative) people who were free of baseline cardiovascular disease from an observational cohort of HIV-positive people and matched uninfected veterans in care from April 1, 2003 through December 31, 2014. International Classification of Diseases, Ninth Revision (ICD-9) codes from medical records were used to determine baseline depression and incident stroke. Depression occurred in 19.5% of HIV-positive people. After a median of 9.2 years of follow-up, stroke rates were highest among people with both HIV and depression and lowest among those with neither condition. In Cox proportional hazard models, depression was associated with an increased risk of stroke for HIV-positive people after adjusting for sociodemographic characteristics and cerebrovascular risk factors (hazard ratio [HR], 1.18; 95% CI: 1.03-1.34; 0.014). The depression-stroke relationship was attenuated by alcohol use disorders, cocaine use, and baseline antidepressant use, and unaffected by combined antiretroviral therapy use or individual antiretroviral agents. A numerically higher HR of depression on stroke was found among those younger than 60 years.
Conclusions:
Depression is associated with an increased risk of stroke among HIV-positive people after adjusting for sociodemographic characteristics, traditional cerebrovascular risk factors, and HIV-specific factors. Alcohol use disorders, cocaine use, and baseline antidepressant use accounted for some of the observed stroke risk. Depression may be a novel, independent risk factor for ischemic stroke in HIV, particularly among younger people.




J Am Heart Assoc: 05 Jul 2021; 10:e017637
Sico JJ, Kundu S, So-Armah K, Gupta SK, ... Freiberg MS, Stewart JC
J Am Heart Assoc: 05 Jul 2021; 10:e017637 | PMID: 34169726
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Time-Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above-Normal Blood Pressure.

Craighead DH, Heinbockel TC, Freeberg KA, Rossman MJ, ... Bailey EF, Seals DR

Background:
High-resistance inspiratory muscle strength training (IMST) is a novel, time-efficient physical training modality. Methods and Results We performed a double-blind, randomized, sham-controlled trial to investigate whether 6 weeks of IMST (30 breaths/day, 6 days/week) improves blood pressure, endothelial function, and arterial stiffness in midlife/older adults (aged 50-79 years) with systolic blood pressure ≥120 mm Hg, while also investigating potential mechanisms and long-lasting effects. Thirty-six participants completed high-resistance IMST (75% maximal inspiratory pressure, n=18) or low-resistance sham training (15% maximal inspiratory pressure, n=18). IMST was safe, well tolerated, and had excellent adherence (≈95% of training sessions completed). Casual systolic blood pressure decreased from 135±2 mm Hg to 126±3 mm Hg (P<0.01) with IMST, which was ≈75% sustained 6 weeks after IMST (P<0.01), whereas IMST modestly decreased casual diastolic blood pressure (79±2 mm Hg to 77±2 mm Hg, P=0.03); blood pressure was unaffected by sham training (all P>0.05). Twenty-four hour systolic blood pressure was lower after IMST versus sham training (P=0.01). Brachial artery flow-mediated dilation improved ≈45% with IMST (P<0.01) but was unchanged with sham training (P=0.73). Human umbilical vein endothelial cells cultured with subject serum sampled after versus before IMST exhibited increased NO bioavailability, greater endothelial NO synthase activation, and lower reactive oxygen species bioactivity (P<0.05). IMST decreased C-reactive protein (P=0.05) and altered select circulating metabolites (targeted plasma metabolomics) associated with cardiovascular function. Neither IMST nor sham training influenced arterial stiffness (P>0.05).
Conclusions:
High-resistance IMST is a safe, highly adherable lifestyle intervention for improving blood pressure and endothelial function in midlife/older adults with above-normal initial systolic blood pressure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03266510.




J Am Heart Assoc: 05 Jul 2021; 10:e020980
Craighead DH, Heinbockel TC, Freeberg KA, Rossman MJ, ... Bailey EF, Seals DR
J Am Heart Assoc: 05 Jul 2021; 10:e020980 | PMID: 34184544
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk Factors for Severe Primary Graft Dysfunction in Infants Following Heart Transplant.

Singh TP, Profita EL, Rycus P, Thiagarajan R, Gauvreau K

Background:
Previous studies suggest that infant heart transplant (HT) recipients are at higher risk of developing severe primary graft dysfunction (PGD) than older children. We sought to identify risk factors for developing severe PGD in infant HT recipients. Methods and Results We identified all HT recipients aged <1 year in the United States during 1996 to 2015 using the Organ Procurement and Transplant Network database. We linked their data to ELSO (Extracorporeal Life Support Organization) registry data to identify those with severe PGD, defined by initiation of extracorporeal membrane oxygenation support for PGD within 2 days following HT. We used multivariable logistic regression to assess risk factors for developing severe PGD. Of 1718 infants analyzed, 600 (35%) were <90 days old and 1079 (63%) had congenital heart disease. Overall, 134 (7.8%) developed severe PGD; 95 (71%) were initiated on extracorporeal membrane oxygenation support on the day of HT, 34 (25%) the next day, and 5 (4%) the following day. In adjusted analysis, recipient congenital heart disease, extracorporeal membrane oxygenation, or biventricular assist device support at transplant, recipient blood type AB, donor-recipient weight ratio <0.9, and graft ischemic time ≥4 hours were independently associated with developing severe PGD whereas left ventricular assist device support at HT was not. One-year graft survival was 48% in infants with severe PGD versus 87% without severe PGD.
Conclusions:
Infant HT recipients with severe PGD have poor graft survival. Although some recipient-level risk factors are nonmodifiable, avoiding modifiable risk factors may mitigate further risk in infants at high risk of developing severe PGD.




J Am Heart Assoc: 05 Jul 2021; 10:e021082
Singh TP, Profita EL, Rycus P, Thiagarajan R, Gauvreau K
J Am Heart Assoc: 05 Jul 2021; 10:e021082 | PMID: 34184543
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Genetic Evidence for Repurposing of GLP1R (Glucagon-Like Peptide-1 Receptor) Agonists to Prevent Heart Failure.

Daghlas I, Karhunen V, Ray D, Zuber V, ... Vujkovic M, Gill D

Background:
This study was designed to investigate the genetic evidence for repurposing of GLP1R (glucagon-like peptide-1 receptor) agonists to prevent heart failure (HF) and whether the potential benefit exceeds the benefit conferred by more general glycemic control. Methods and Results We applied 2-sample Mendelian randomization of genetically proxied GLP1R agonism on HF as the main outcome and left ventricular ejection fraction as the secondary outcome. The associations were compared with those of general glycemic control on the same outcomes. Genetic associations were obtained from genome-wide association study summary statistics of type 2 diabetes mellitus (228 499 cases and 1 178 783 controls), glycated hemoglobin (n=344 182), HF (47,309 cases and 930 014 controls), and left ventricular ejection fraction (n=16 923). Genetic proxies for GLP1R agonism associated with reduced risk of HF (odds ratio per 1 mmol/mol decrease in glycated hemoglobin 0.75; 95% CI, 0.64-0.87; P=1.69×10-4), and higher left ventricular ejection fraction (SD change in left ventricular ejection fraction per 1 mmol/mol decrease in glycated hemoglobin 0.22%; 95% CI, 0.03-0.42; P=0.03). The magnitude of these benefits exceeded those expected from improved glycemic control more generally. The results were similar in sensitivity analyses, and we did not find evidence to suggest that these associations were mediated by reduced coronary artery disease risk.
Conclusions:
This genetic evidence supports the repurposing of GLP1R agonists for preventing HF.




J Am Heart Assoc: 05 Jul 2021; 10:e020331
Daghlas I, Karhunen V, Ray D, Zuber V, ... Vujkovic M, Gill D
J Am Heart Assoc: 05 Jul 2021; 10:e020331 | PMID: 34184541
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prevalence and Course of Depression During the First Year After Mild to Moderate Stroke.

Dong L, Williams LS, Brown DL, Case E, Morgenstern LB, Lisabeth LD

Background:
This study examined the prevalence and longitudinal course of depression during the first year after mild to moderate stroke. Methods and Results We identified patients with mild to moderate ischemic stroke or intracerebral hemorrhage (National Institutes of Health Stroke Scale score <16) and at least 1 depression assessment at 3, 6, or 12 months after stroke (n=648, 542, and 533, respectively) from the Brain Attack Surveillance in Corpus Christi project (2014-2016). Latent transition analysis was used to examine temporal profiles of depressive symptoms assessed by the 8-item Patient Health Questionnaire between 3 and 12 months after stroke. Mean age was 65.6 years, 49.4% were women, and 56.7% were Mexican Americans. The prevalence of depression after stroke was 35.3% at 3 months, decreased to 24.9% at 6 months, and remained stable at 25.7% at 12 months. Approximately half of the participants classified as having depression at 3 or 6 months showed clinical improvement at the next assessment. Subgroups with distinct patterns of depressive symptoms were identified, including mild/no symptoms, predominant sleep disturbance and fatigue symptoms, affective symptoms, and severe/all symptoms. A majority of participants with mild/no symptoms retained this symptom pattern over time. The probability of transitioning to mild/no symptoms was higher before 6 months compared with the later period, and severe symptoms were more likely to persist after 6 months compared with the earlier period.
Conclusions:
The observed dynamics of depressive symptoms suggest that depression after stroke tends to persist after 6 months among patients with mild to moderate stroke and should be continually monitored and appropriately managed.




J Am Heart Assoc: 05 Jul 2021; 10:e020494
Dong L, Williams LS, Brown DL, Case E, Morgenstern LB, Lisabeth LD
J Am Heart Assoc: 05 Jul 2021; 10:e020494 | PMID: 34184539
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heterogeneity of Cardiovascular Disease Risk Factors Among Asian Immigrants: Insights From the 2010 to 2018 National Health Interview Survey.

Koirala B, Turkson-Ocran RA, Baptiste D, Koirala B, ... Himmelfarb CD, Commodore-Mensah Y

Background:
The Asian population is the fastest-growing immigrant population in the United States. Prior studies have examined the Asian immigrant population as a homogenous group. We hypothesized that there will be heterogeneity in cardiovascular disease risk factors among Asian immigrant subgroups (Indian subcontinent, Southeast Asia, Asia) compared with the non-Hispanic White population. Methods and Results A cross-sectional analysis of the 2010 to 2018 National Health Interview Survey was conducted among 508 941 adults who were born in Asian regions or were non-Hispanic White and born in the United States. Generalized linear models with Poisson distribution were fitted to compare the prevalence of self-reported hypertension, overweight/obesity, diabetes mellitus, high cholesterol, physical inactivity, and current smoking among Asian immigrants compared with White adults, adjusting for known confounders. We included 33 973 Asian immigrants from Southeast Asia (45%), Asia (29%), the Indian subcontinent (26%), and 474 968 White adults. Compared with non-Hispanic White adults, Indian subcontinent immigrants had the highest prevalence of overweight/obesity (prevalence ratio, 1.22; 95% CI, 1.19-1.25); Southeast Asian immigrants had the highest prevalence of high cholesterol (prevalence ratio, 1.16; 95% CI, 1.10-1.23); Indian subcontinent (prevalence ratio, 1.69; 95% CI, 1.49-1.93) and Southeast Asian (prevalence ratio, 1.38; 95% CI, 1.26-1.52) immigrants had a higher prevalence of diabetes. All Asian immigrant subgroups were more likely to be physically inactive and less likely to smoke than White adults.
Conclusions:
We observed significant heterogeneity in cardiovascular disease risk factors among Asian immigrants and a varied prevalence of risk factors compared with non-Hispanic White adults. Providers caring for Asian immigrants should provide tailored and culturally informed care to improve the cardiovascular health of this diverse group.




J Am Heart Assoc: 05 Jul 2021; 10:e020408
Koirala B, Turkson-Ocran RA, Baptiste D, Koirala B, ... Himmelfarb CD, Commodore-Mensah Y
J Am Heart Assoc: 05 Jul 2021; 10:e020408 | PMID: 34182790
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Adenosine-Induced Coronary Steal Is Observed in Patients Presenting With ST-Segment-Elevation Myocardial Infarction.

Aetesam-Ur-Rahman M, Brown AJ, Jaworski C, Giblett JP, ... West NEJ, Hoole SP

Background:
Adenosine is used to treat no-reflow in the infarct-related artery (IRA) during ST-segment-elevation myocardial infarction intervention. However, the physiological effect of adenosine in the IRA is variable. Coronary steal-a reduction of blood flow to the distal coronary bed-can occur in response to adenosine and this is facilitated by collaterals. We investigated the effects of adenosine on coronary flow reserve (CFR) in patients presenting with ST-segment-elevation myocardial infarction to better understand the physiological mechanism underpinning the variable response to adenosine. Methods and Results Pressure-wire assessment of the IRA after percutaneous coronary intervention was performed in 93 patients presenting with ST-segment-elevation myocardial infarction to calculate index of microvascular resistance, CFR, and collateral flow index by pressure. Modified collateral Rentrop grade to the IRA was recorded, as was microvascular obstruction by cardiac magnetic resonance imaging. Coronary steal (CFR <0.9), no change in flow (CFR=0.9-1.1), and hyperemic flow (CFR >1.1) after adenosine occurred in 19 (20%), 15 (16%), and 59 (63%) patients, respectively. Patients with coronary steal had higher modified Rentrop score to the IRA (1 [0, 1.75] versus 0 [0, 1], P<0.001) and a higher collateral flow index by pressure (0.25±0.10 versus 0.15±0.10, P=0.004) than the hyperemic group. The coronary steal group also had significantly higher index of microvascular resistance (61.68 [28.13, 87.04] versus 23.93 [14.67, 37.00], P=0.006) and had more disease (stenosis >50%) in the donor arteries (52.63% versus 22.03%, P=0.02) than the hyperemic group.
Conclusions:
Adenosine-induced coronary steal may be responsible for a reduction in coronary flow reserve in a proportion of patients presenting with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03145194. URL: https://www.isrctn.com; Unique identifier: ISRCTN3176727.




J Am Heart Assoc: 05 Jul 2021; 10:e019899
Aetesam-Ur-Rahman M, Brown AJ, Jaworski C, Giblett JP, ... West NEJ, Hoole SP
J Am Heart Assoc: 05 Jul 2021; 10:e019899 | PMID: 34187187
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mitral Regurgitation International Database (MIDA) Score Predicts Outcome in Patients With Heart Failure Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair.

Kavsur R, Spieker M, Iliadis C, Metze C, ... Becher MU, of the Heart Failure Network Rhineland

Background:
Optimizing risk stratification in patients undergoing transcatheter mitral valve repair is an ongoing challenge. The Mitral Regurgitation International Database (MIDA) score represents a user-friendly mortality risk stratification tool that is validated on a large-scale registry of patients with degenerative mitral regurgitation (MR). We here assessed the potential benefit of the MIDA risk score for patients with functional or degenerative MR undergoing transcatheter mitral valve repair. Methods and Results In total, 680 patients undergoing MitraClip implantation were stratified according to MIDA score tertiles into a low (0-7), intermediate (8-9), and a high (10-12) MIDA score group. MR was assessed in follow-up echocardiograms in 416 patients at 323±169 days after transcatheter mitral valve repair. During 2-year follow-up, 8.2% (15/182) of patients with low, 21.3% (64/300) with intermediate, and 26.3% (52/198) with high MIDA score died (log-rank test P<0.001). Hazard of all-cause mortality increased by 13% (95% CI, 3%-25%) with every additional point of the MIDA score. Subanalysis of 431 patients with functional MR showed similar results. Furthermore, rates of a combined end point of mortality and hospitalization for heart failure were higher with increasing MIDA score (30% [54/182], 38% [113/300] and 48% [94/198], respectively, log-rank test P=0.001). Frequency of residual MR ≥II at follow-up increased with increasing MIDA score group (33%, 44%, and 59%, respectively, P<0.001).
Conclusions:
The MIDA mortality risk score maintains its predictive utility in patients undergoing transcatheter mitral valve repair, regardless of MR cause. Moreover, it was predictive of worse event-free survival regarding a combined end point of mortality and hospitalization for heart failure, and was associated with postprocedural residual MR ≥II and MR recurrence.




J Am Heart Assoc: 05 Jul 2021; 10:e019548
Kavsur R, Spieker M, Iliadis C, Metze C, ... Becher MU, of the Heart Failure Network Rhineland
J Am Heart Assoc: 05 Jul 2021; 10:e019548 | PMID: 34187184
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Midregional N-Terminal Pro-Atrial Natriuretic Peptide and Soluble Suppression of Tumorigenicity 2 Levels on Heart Rhythm in Patients Treated With Catheter Ablation for Atrial Fibrillation: The Biorhythm Study.

Badoz M, Serzian G, Favoulet B, Sellal JM, ... Schiele F, Meneveau N

Background:
We assessed the impact of preprocedural plasma levels of MRproANP (midregional N-terminal pro-atrial natriuretic peptide) and sST2 (soluble suppression of tumorigenicity 2) on recurrence of atrial fibrillation (AF) at 1 year after catheter ablation of AF. Methods and Results This was a prospective, multicenter, observational study including patients undergoing catheter ablation of AF. MRproANP and sST2 were measured in a peripheral venous blood preprocedure, and MRproANP was assessed in the right and left atrial blood during ablation. The primary end point was recurrent AF between 3 and 12 months postablation, defined as a documented (>30 seconds) episode of AF, flutter, or atrial tachycardia. We included 106 patients from December 2017 to March 2019; 105 had complete follow-up, and the mean age was 63 years with 74.2% males. Overall, 34 patients (32.1%) had recurrent AF. In peripheral venous blood, MRproANP was significantly higher in patients with recurrent AF (median, 192.2; [quartile 1-quartile 3, 155.9-263.9] versus 97.1 [60.9-150.7] pmol/L; P<0.0001), as was sST2 (median, 30.3 [quartile 1-quartile 3, 23.3-39.3] versus 23.4 [95% CI, 17.4-33.0] ng/mL; P=0.0033). In the atria, MRproANP was significantly higher than in peripheral blood and was higher during AF than during sinus rhythm. Receiver operating characteristic curve analysis identified a threshold of MRproANP>107.9 pmol/L to predict AF recurrence at 1 year and a threshold of >26.7 ng/mL for sST2. By multivariate analysis, MRproANP>107.9 pmol/L was the only independent predictor of recurrent AF (OR, 24.27; 95% CI, 4.23-139.18). MRproANP<107.9 pmol/L identified subjects at very low risk of recurrence (negative predictive value >95%).
Conclusions:
Elevated MRproANP level independently predicts recurrent AF, whereas sST2 levels do not appear to have any prognostic value in assessing the risk of recurrence of AF up to 1 year after catheter ablation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03351816.




J Am Heart Assoc: 05 Jul 2021; 10:e020917
Badoz M, Serzian G, Favoulet B, Sellal JM, ... Schiele F, Meneveau N
J Am Heart Assoc: 05 Jul 2021; 10:e020917 | PMID: 34187182
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Left Atrial Strain to Predict Stroke in Patients With Acute Heart Failure and Sinus Rhythm.

Park JH, Hwang IC, Park JJ, Park JB, Cho GY

Background:
Stroke is a major comorbidity in patients with heart failure (HF), especially in those with decreased left atrial (LA) function, and thus, identifying patients highly at risk of stroke can prevent its occurrence. We evaluated the predictive value of global longitudinal strain of LA (LAGLS) in patients with acute HF and sinus rhythm. Methods and Results In this retrospective study, 2461 patients (53.3% men, 69.7±14.4 years old) with sinus rhythm and LAGLS among 4312 consecutive patients with acute HF from 3 tertiary hospitals were included. HF phenotypes were defined as HF with reduced ejection fraction (EF) (left ventricular EF ≤40%), HF with midrange EF (40% <left ventricular EF <50%), and HF with preserved ejection fraction (left ventricular EF ≥50%). Primary outcome was new-onset stroke. The mean left ventricular EF was 39.4%±15.6%. Moreover, 1388 (57.5%), 342 (14.2%), and 682 (28.3%) were classified with HF with reduced EF, HF with midrange EF, and HF with preserved EF, retrospectively. LAGLS was 17.2%±10.4%. During the follow-up duration (mean: 30.3±25.4 months), 100 patients experienced stroke. Patients with stroke had higher LA diameter (P=0.031) and lower LAGLS (P=0.010) than those without stroke. In the univariate analysis, age, diabetes mellitus, LA diameter, LA volume index, and LAGLS were significant risk factors for stroke. In the multivariate analysis, each 1% decrease in LAGLS was associated with a 3.8% increased risk for stroke (hazard ratio [HR], 1.038; 95% CI, 1.013-1.065; P=0.003). When applying a LAGLS cutoff point of 14.5%, patients with LAGLS <14.5% had approximately twice the risk for stroke after adjusting other significant variables (HR, 1.940; 95% CI, 1.269-2.965; P=0.002).
Conclusions:
In patients with acute HF and sinus rhythm, decreased LAGLS (<14.5%) was associated with an increased risk for stroke, with an annual incidence of 2.38%.




J Am Heart Assoc: 05 Jul 2021; 10:e020414
Park JH, Hwang IC, Park JJ, Park JB, Cho GY
J Am Heart Assoc: 05 Jul 2021; 10:e020414 | PMID: 34187174
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Targeting Hypertension Screening in Low- and Middle-Income Countries: A Cross-Sectional Analysis of 1.2 Million Adults in 56 Countries.

Kirschbaum TK, Theilmann M, Sudharsanan N, Manne-Goehler J, ... Jaacks LM, Geldsetzer P

Background:
As screening programs in low- and middle-income countries (LMICs) often do not have the resources to screen the entire population, there is frequently a need to target such efforts to easily identifiable priority groups. This study aimed to determine (1) how hypertension prevalence in LMICs varies by age, sex, body mass index, and smoking status, and (2) the ability of different combinations of these variables to accurately predict hypertension. Methods and Results We analyzed individual-level, nationally representative data from 1 170 629 participants in 56 LMICs, of whom 220 636 (18.8%) had hypertension. Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or reporting to be taking blood pressure-lowering medication. The shape of the positive association of hypertension with age and body mass index varied across world regions. We used logistic regression and random forest models to compute the area under the receiver operating characteristic curve in each country for different combinations of age, body mass index, sex, and smoking status. The area under the receiver operating characteristic curve for the model with all 4 predictors ranged from 0.64 to 0.85 between countries, with a country-level mean of 0.76 across LMICs globally. The mean absolute increase in the area under the receiver operating characteristic curve from the model including only age to the model including all 4 predictors was 0.05.
Conclusions:
Adding body mass index, sex, and smoking status to age led to only a minor increase in the ability to distinguish between adults with and without hypertension compared with using age alone. Hypertension screening programs in LMICs could use age as the primary variable to target their efforts.




J Am Heart Assoc: 05 Jul 2021; 10:e021063
Kirschbaum TK, Theilmann M, Sudharsanan N, Manne-Goehler J, ... Jaacks LM, Geldsetzer P
J Am Heart Assoc: 05 Jul 2021; 10:e021063 | PMID: 34212779
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Gut Microbiome of Heart Failure With Preserved Ejection Fraction.

Beale AL, O\'Donnell JA, Nakai ME, Nanayakkara S, ... Marques FZ, Kaye DM

Background:
Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial-derived metabolites such as short-chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α-diversity (eg, number of microbes) and β-diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF (P=0.001). We did not find an association between β-diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so (P=0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short-chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P=0.016).
Conclusions:
We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.




J Am Heart Assoc: 05 Jul 2021; 10:e020654
Beale AL, O'Donnell JA, Nakai ME, Nanayakkara S, ... Marques FZ, Kaye DM
J Am Heart Assoc: 05 Jul 2021; 10:e020654 | PMID: 34212778
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Secondary Stroke Prevention Following Embolic Stroke of Unknown Source in the Absence of Documented Atrial Fibrillation: A Clinical Review.

Kotadia ID, Sim I, Mukherjee R, O\'Hare D, ... O\'Neill M, Williams SE
Approximately one-third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one-third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.



J Am Heart Assoc: 05 Jul 2021; 10:e021045
Kotadia ID, Sim I, Mukherjee R, O'Hare D, ... O'Neill M, Williams SE
J Am Heart Assoc: 05 Jul 2021; 10:e021045 | PMID: 34212774
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical Outcomes of Autologous Stem Cell-Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy.

Domae K, Miyagawa S, Yoshikawa Y, Fukushima S, ... Yamada T, Sawa Y

Background:
Clinical effectiveness of autologous skeletal cell-patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty-four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure-related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%], P<0.05, 6-minute walk test; 471 m [370-541 m] to 525 m [425-555 m], P<0.05, left ventricular stroke work index; 31.1 g·m2·beat [22.7-35.5 g·m2·beat] to 32.8 g·m2·beat [28-38.5 g·m2·beat], P=0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B-type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B-type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: ​OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic-area under the curve, 0.96, P<0.001).
Conclusions:
This clinical trial demonstrated that autologous skeletal stem cell-patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/. Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.




J Am Heart Assoc: 05 Jul 2021; 10:e008649
Domae K, Miyagawa S, Yoshikawa Y, Fukushima S, ... Yamada T, Sawa Y
J Am Heart Assoc: 05 Jul 2021; 10:e008649 | PMID: 34212772
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives.

De Luca L, Steg PG, Bhatt DL, Capodanno D, Angiolillo DJ
Cangrelor is the only currently available intravenous platelet P2Y12 receptor inhibitor. It is characterized by potent, predictable, and rapidly reversible antiplatelet effects. Cangrelor has been tested in the large CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program, where it was compared with different clopidogrel regimens, and it is currently indicated for use in patients with coronary artery disease undergoing percutaneous coronary intervention. However, the uptake of cangrelor use varies across the globe and may also include patients with profiles different from those enrolled in the registration trials. These observations underscore the need to fully examine the safety and efficacy of cangrelor in postregistration studies. There are several ongoing and planned studies evaluating the use of cangrelor in real-world practice which will provide important insights to this extent. The current article provides a review on the pharmacology, clinical studies, contemporary use of cangrelor in real-world practice, a description of ongoing studies, and futuristic insights on potential strategies on how to improve outcomes of patients undergoing percutaneous coronary intervention.



J Am Heart Assoc: 05 Jul 2021; 10:e022125
De Luca L, Steg PG, Bhatt DL, Capodanno D, Angiolillo DJ
J Am Heart Assoc: 05 Jul 2021; 10:e022125 | PMID: 34212768
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Psychological Distress, Contextual Factors, and Individual Differences Among Citizen Responders.

Ries ES, Kragh AR, Dammeyer J, Folke F, Andelius L, Malta Hansen C

Background:
Little is known about the psychological risks of dispatched citizen responders who have participated in resuscitation attempts. Methods and Results A cross-sectional survey study was performed with 102 citizen responders who participated in a resuscitation attempt from July 23, 2018, to August 22, 2018, in the Capital Region of Denmark. Psychological distress, defined as symptoms of posttraumatic stress disorder, was assessed 3 weeks after the resuscitation attempt and measured with the Impact of Event Scale-Revised. Perceived stress was measured with the Perceived Stress Scale. Individual differences were assessed as the personality traits of agreeableness, conscientiousness, extraversion, neuroticism, and openness to experience with the Big Five Inventory, general self-efficacy, and coping mechanisms (Brief Coping Orientation to Problems Experienced Inventory). Associations between continuous variables were examined with the Pearson correlation. The associations between psychological distress levels and contextual factors and individual differences were analyzed in multivariable linear regression models to determine factors independently associated with psychological distress levels. The mean overall posttraumatic stress disorder score was 0.65 of 12; the mean perceived stress score was 7.61 of 40. The most common coping mechanisms were acceptance and emotional support. Low perceived stress was significantly associated with high general self-efficacy, and high perceived stress was significantly associated with high scores on neuroticism and openness to experience. Non-healthcare professionals were less likely to report symptoms of posttraumatic stress disorder.
Conclusions:
Citizen responders who participated in resuscitation reported low levels of psychological distress. Individual differences were significantly associated with levels of psychological distress and should be considered when engaging citizen responders in resuscitation.




J Am Heart Assoc: 05 Jul 2021; 10:e020378
Ries ES, Kragh AR, Dammeyer J, Folke F, Andelius L, Malta Hansen C
J Am Heart Assoc: 05 Jul 2021; 10:e020378 | PMID: 34212765
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Nonacute Opioid Use and Cardiovascular Diseases: A Scoping Review of the Literature.

Singleton JH, Abner EL, Akpunonu PD, Kucharska-Newton AM

Background:
In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes.
Methods and results:
We defined NOU to include both long-term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of injection drug use (with opioids being the most commonly injected type of drug) and community prevalence of infective endocarditis, and between (primarily medically indicated) NOU and myocardial infarction. There was less consensus about the relationship between NOU and congestive heart failure, cardiac arrhythmia, and stroke. CONCLUSIONS There is a dearth of high-quality evidence on the relationship between NOU and cardiovascular disease. Innovative approaches to the assessment of opioid exposure over extended periods of time will be required to address this need.




J Am Heart Assoc: 05 Jul 2021; 10:e021260
Singleton JH, Abner EL, Akpunonu PD, Kucharska-Newton AM
J Am Heart Assoc: 05 Jul 2021; 10:e021260 | PMID: 34212763
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Double Deletion of Angiotensin II Type 2 and Mas Receptors Accelerates Aging-Related Muscle Weakness in Male Mice.

Takeshita H, Yamamoto K, Mogi M, Wang Y, ... Horiuchi M, Rakugi H

Background:
The activation of AT2 (angiotensin II type 2 receptor ) and Mas receptor by angiotensin II and angiotensin-(1-7), respectively, is the primary process that counteracts activation of the canonical renin-angiotensin system (RAS). Although inhibition of canonical RAS could delay the progression of physiological aging, we recently reported that deletion of Mas had no impact on the aging process in mice. Here, we used male mice with a deletion of only AT2 or a double deletion of AT2 and Mas to clarify whether these receptors contribute to the aging process in a complementary manner, primarily by focusing on aging-related muscle weakness. Methods and Results Serial changes in grip strength of these mice up to 24 months of age showed that AT2/Mas knockout mice, but not AT2 knockout mice, had significantly weaker grip strength than wild-type mice from the age of 18 months. AT2/Mas knockout mice exhibited larger sizes, but smaller numbers and increased frequency of central nucleation (a marker of aged muscle) of single skeletal muscle fibers than AT2 knockout mice. Canonical RAS-associated genes, inflammation-associated genes, and senescence-associated genes were highly expressed in skeletal muscles of AT2/Mas knockout mice. Muscle angiotensin II content increased in AT2/Mas knockout mice.
Conclusions:
Double deletion of AT2 and Mas in mice exaggerated aging-associated muscle weakness, accompanied by signatures of activated RAS, inflammation, and aging in skeletal muscles. Because aging-associated phenotypes were absent in single deletions of the receptors, AT2 and Mas could complement each other in preventing local activation of RAS during aging.




J Am Heart Assoc: 05 Jul 2021; 10:e021030
Takeshita H, Yamamoto K, Mogi M, Wang Y, ... Horiuchi M, Rakugi H
J Am Heart Assoc: 05 Jul 2021; 10:e021030 | PMID: 34212761
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Stroke-Related Mortality in the United States-Mexico Border Area of the United States, 1999 to 2018.

Khan SU, Kalra A, Yedlapati SH, Dani SS, ... Michos ED, Alkhouli M

Background:
The United States (US)-Mexico border is a socioeconomically underserved area. We sought to investigate whether stroke-related mortality varies between the US border and nonborder counties.
Methods and results:
We used death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to examine stroke-related mortality in border versus nonborder counties in California, Texas, New Mexico, and Arizona. We measured average annual percent changes (AAPCs) in age-adjusted mortality rates (AAMRs) per 100 000 between 1999 and 2018. Overall, AAMRs were higher for nonborder counties, older adults, men, and non-Hispanic Black adults than their counterparts. Between 1999 and 2018, AAMRs reduced from 55.8 per 100 000 to 34.4 per 100 000 in the border counties (AAPC, -2.70) and 64.5 per 100 000 to 37.6 per 100 000 in nonborder counties (AAPC, -2.92). The annual percent change in AAMR initially decreased, followed by stagnation in both border and nonborder counties since 2012. The AAPC in AAMR decreased in all 4 states; however, AAMR increased in California\'s border counties since 2012 (annual percent change, 3.9). The annual percent change in AAMR decreased for older adults between 1999 and 2012 for the border (-5.10) and nonborder counties (-5.01), followed by a rise in border counties and stalling in nonborder counties. Although the AAPC in AAMR decreased for both sexes, the AAPC in AAMR differed significantly for non-Hispanic White adults in border (-2.69) and nonborder counties (-2.86). The mortality decreased consistently for all other ethnicities/races in both border and nonborder counties. CONCLUSIONS Stroke-related mortality varied between the border and nonborder counties. Given the substantial public health implications, targeted interventions aimed at vulnerable populations are required to improve stroke-related outcomes in the US-Mexico border area.




J Am Heart Assoc: 05 Jul 2021; 10:e019993
Khan SU, Kalra A, Yedlapati SH, Dani SS, ... Michos ED, Alkhouli M
J Am Heart Assoc: 05 Jul 2021; 10:e019993 | PMID: 34212760
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Area Deprivation Index and Cardiac Readmissions: Evaluating Risk-Prediction in an Electronic Health Record.

Johnson AE, Zhu J, Garrard W, Thoma FW, ... Kershaw KN, Magnani JW

Background:
Assessment of the social determinants of post-hospital cardiac care is needed. We examined the association and predictive ability of neighborhood-level determinants (area deprivation index, ADI), readmission risk, and mortality for heart failure, myocardial ischemia, and atrial fibrillation. Methods and Results Using a retrospective (January 1, 2011-December 31, 2018) analysis of a large healthcare system, we assess the predictive ability of ADI on 30-day and 1-year readmission and mortality following hospitalization. Cox proportional hazards models analyzed time-to-event. Log rank analyses determined survival. C-statistic and net reclassification index determined the model\'s discriminative power. Covariates included age, sex, race, comorbidity, number of medications, length of stay, and insurance. The cohort (n=27 694) had a median follow-up of 46.5 months. There were 14 469 (52.2%) men and 25 219 White (91.1%) patients. Patients in the highest ADI quintile (versus lowest) were more likely to be admitted within 1 year of index heart failure admission (hazard ratio [HR], 1.25; 95% CI, 1.03‒1.51). Patients with myocardial ischemia in the highest ADI quintile were twice as likely to be readmitted at 1 year (HR, 2.04; 95% CI, 1.44‒2.91]). Patients with atrial fibrillation living in areas with highest ADI were less likely to be admitted within 1 year (HR, 0.79; 95% CI, 0.65‒0.95). As ADI increased, risk of readmission increased, and risk reclassification was improved with ADI in the models. Patients in the highest ADI quintile were 25% more likely to die within a year (HR, 1.25 1.08‒1.44).
Conclusions:
Residence in socioeconomically disadvantaged communities predicts rehospitalization and mortality. Measuring neighborhood deprivation can identify individuals at risk following cardiac hospitalization.




J Am Heart Assoc: 05 Jul 2021; 10:e020466
Johnson AE, Zhu J, Garrard W, Thoma FW, ... Kershaw KN, Magnani JW
J Am Heart Assoc: 05 Jul 2021; 10:e020466 | PMID: 34212757
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Socioeconomic Disadvantage With Mortality and Readmissions Among Older Adults Hospitalized for Pulmonary Embolism in the United States.

Wadhera RK, Secemsky EA, Wang Y, Yeh RW, Goldhaber SZ

Background:
In the United States, hospitalizations for pulmonary embolism (PE) are increasing among older adults insured by Medicare. Although efforts to reduce health disparities have intensified, it remains unclear whether clinical outcomes differ between socioeconomically disadvantaged and nondisadvantaged Medicare beneficiaries hospitalized with PE. Methods and Results In this study, there were 53 386 Medicare fee-for-service beneficiaries age ≥65 years hospitalized for PE between October 2015 and January 2017. Of these, 5494 (10.3%) were socioeconomically disadvantaged and 47 892 (89.7%) were nondisadvantaged. Socioeconomically disadvantaged adults were of similar age as nondisadvantaged adults (77.1 versus 77.0), more likely to be female (68.5% versus 54.2%), and less likely to receive advanced therapies (11.0% versus 12.1%). After adjustment for demographics, 90-day all-cause mortality rates were similar between disadvantaged and nondisadvantaged adults. In contrast, 1-year mortality rates were higher among socioeconomically disadvantaged adults (hazard ratio [HR], 1.16; 95% CI, 1.10-1.22), although these differences were partially attenuated after additional adjustments for comorbidities and PE severity (HR, 1.09; 95% CI, 1.02-1.16). Risk-adjusted 30-day and 90-day all-cause readmission rates were substantially higher among socioeconomically disadvantaged patients (30-day HR, 1.14 [95% CI, 1.06-1.22]; 90-day HR, 1.18 [95% CI, 1.12-1.25]). In addition, 90-day readmissions attributed to PE, deep vein thrombosis, and/or bleeding were higher among socioeconomically disadvantaged patients (HR, 1.16; 95% CI, 1.02-1.32).
Conclusions:
Socioeconomically disadvantaged older adults hospitalized with PE have higher 1-year mortality rates compared with their nondisadvantaged counterparts. Nearly 1 in 3 socioeconomically disadvantaged older adults was readmitted within 90 days of a hospitalization for PE. Targeted strategies are needed to improve transitional and ambulatory care for this vulnerable population.




J Am Heart Assoc: 05 Jul 2021; 10:e021117
Wadhera RK, Secemsky EA, Wang Y, Yeh RW, Goldhaber SZ
J Am Heart Assoc: 05 Jul 2021; 10:e021117 | PMID: 34210156
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Inactivation of Interleukin-4 Receptor α Signaling in Myeloid Cells Protects Mice From Angiotensin II/High Salt-Induced Cardiovascular Dysfunction Through Suppression of Fibrotic Remodeling.

Song J, Frieler RA, Vigil TM, Ma J, ... Goldstein DR, Mortensen RM

Background:
Hypertension-induced cardiovascular remodeling is characterized by chronic low-grade inflammation. Interleukin-4 receptor α (IL-4Rα) signaling is importantly involved in cardiovascular remodeling, however, the target cell type(s) is unclear. Here, we investigated the role of myeloid-specific IL-4Rα signaling in cardiovascular remodeling induced by angiotensin II and high salt. Methods and Results Myeloid IL-4Rα deficiency suppressed both the in vitro and in vivo expression of alternatively activated macrophage markers including Arg1 (arginase 1), Ym1 (chitinase 3-like 3), and Relmα/Fizz1 (resistin-like molecule α). After angiotensin II and high salt treatment, myeloid-specific IL-4Rα deficiency did not change hypertrophic remodeling within the heart and aorta. However, myeloid IL-4Rα deficiency resulted in a substantial reduction in fibrosis through the suppression of profibrotic pathways and the enhancement of antifibrotic signaling. Decreased fibrosis was associated with significant preservation of myocardial function in MyIL4RαKO mice and was mediated by attenuated alternative macrophage activation.
Conclusions:
Myeloid IL-4Rα signaling is substantially involved in fibrotic cardiovascular remodeling by controlling alternative macrophage activation and regulating fibrosis-related signaling. Inhibiting myeloid IL-4Rα signaling may be a potential strategy to prevent hypertensive cardiovascular diseases.




J Am Heart Assoc: 05 Jul 2021; 10:e017329
Song J, Frieler RA, Vigil TM, Ma J, ... Goldstein DR, Mortensen RM
J Am Heart Assoc: 05 Jul 2021; 10:e017329 | PMID: 34132103
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Coronary Microvascular Dysfunction in Systemic Lupus Erythematosus.

Weber BN, Stevens E, Barrett L, Bay C, ... Costenbader K, Di Carli MF

Background:
Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disorder associated with premature atherosclerosis and increased cardiovascular risk. Systemic inflammation is an emerging risk factor for coronary microvascular dysfunction (CMD). We aimed to test whether CMD, defined as abnormal myocardial flow reserve (MFR) by positron emission tomography-computed tomography, would be independently associated with SLE after adjusting for nonobstructive atherosclerotic burden and common cardiovascular risk factors. Methods and Results Consecutive patients with SLE who underwent symptom-prompted stress cardiac positron emission tomography-computed tomography were included (n=42). Obstructive coronary artery disease and systolic dysfunction were excluded. MFR was quantified by positron emission tomography-computed tomography, and CMD was defined as MFR <2. We frequency matched patients who did not have SLE and had symptom-prompted positron emission tomography studies on age, sex, and key cardiovascular risk factors (n=69). The attenuation correction computed tomography scans were reviewed for qualitative assessment of coronary artery calcium. Patients with SLE had a more severe reduction in global MFR compared with controls and a higher prevalence of CMD, despite a similar degree of nonobstructive atherosclerotic burden (1.91±0.5 versus 2.4±0.7, respectively, P<0.0001; CMD, 57.1% versus 33.3%, respectively, P=0.017).
Conclusions:
We demonstrated that patients with SLE with cardiac symptoms without obstructive coronary artery disease have a high prevalence of coronary vasomotor abnormalities. In comparison with symptomatic matched controls, patients with SLE have a more severe reduction in MFR that is not accounted for by common cardiovascular factors or atherosclerotic burden.




J Am Heart Assoc: 05 Jul 2021; 10:e018555
Weber BN, Stevens E, Barrett L, Bay C, ... Costenbader K, Di Carli MF
J Am Heart Assoc: 05 Jul 2021; 10:e018555 | PMID: 34132099
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Older ...

This program is still in alpha version.