Topic: Journal Club Selection

Abstract
<div><h4>Acute Coronary Occlusion in Patients With Non-ST-Segment Elevation Out-of-Hospital Cardiac Arrest.</h4><i>Spirito A, Vaisnora L, Papadis A, Iacovelli F, ... Windecker S, Räber L</i><br /><b>Background</b><br />According to current guidelines, hemodynamic status should guide the decision between immediate and delayed coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation. A delayed strategy is advised in hemodynamically stable patients, and an immediate approach is recommended in unstable patients.<br /><b>Objectives</b><br />This study sought to assess the frequency, predictors, and clinical impact of acute coronary occlusion in hemodynamically stable and unstable OHCA patients without ST-segment elevation.<br /><b>Methods</b><br />Consecutive unconscious OHCA patients without ST-segment elevation who were undergoing CAG at Bern University Hospital (Bern, Switzerland) between 2011 and 2019 were included. Frequency and predictors of acute coronary artery occlusions and their impact on all-cause and cardiovascular mortality at 1 year were assessed.<br /><b>Results</b><br />Among the 386 patients, 169 (43.8%) were hemodynamically stable. Acute coronary occlusions were found in 19.5% of stable and 24.0% of unstable OHCA patients (P = 0.407), and the presence of these occlusions was predicted by initial chest pain and shockable rhythm, but not by hemodynamic status. Acute coronary occlusion was associated with an increased risk of cardiovascular death (adjusted HR: 2.74; 95% CI: 1.22-6.15) but not of all-cause death (adjusted HR: 0.72; 95% CI: 0.44-1.18). Hemodynamic instability was not predictive of fatal outcomes.<br /><b>Conclusions</b><br />Acute coronary artery occlusions were found in 1 in 5 OHCA patients without ST-segment elevation. The frequency of these occlusions did not differ between stable and unstable patients, and the occlusions were associated with a higher risk of cardiovascular death. In OHCA patients without ST-segment elevation, chest pain or shockable rhythm rather than hemodynamic status identifies patients with acute coronary occlusion.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Feb 2023; 81:446-456</small></div>
Spirito A, Vaisnora L, Papadis A, Iacovelli F, ... Windecker S, Räber L
J Am Coll Cardiol: 07 Feb 2023; 81:446-456 | PMID: 36725173
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<div><h4>Postoperative atrial fibrillation: from mechanisms to treatment.</h4><i>Gaudino M, Di Franco A, Rong LQ, Piccini J, Mack M</i><br /><AbstractText>Postoperative atrial fibrillation (POAF) is the most common type of secondary atrial fibrillation (AF) and despite progress in prevention and treatment, remains an important clinical problem for patients undergoing a variety of surgical procedures, and in particular cardiac surgery. POAF significantly increases the duration of postoperative hospital stay, hospital costs, and the risk of recurrent AF in the years after surgery; moreover, POAF has been associated with a variety of adverse cardiovascular events (including stroke, heart failure, and mortality), although it is still unclear if this is due to causal relation or simple association. New data have recently emerged on the pathophysiology of POAF, and new preventive and therapeutic strategies have been proposed and tested in randomized trials. This review summarizes the current evidence on the pathogenesis, incidence, prevention, and treatment of POAF and highlights future directions for clinical research.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 31 Jan 2023; epub ahead of print</small></div>
Gaudino M, Di Franco A, Rong LQ, Piccini J, Mack M
Eur Heart J: 31 Jan 2023; epub ahead of print | PMID: 36721960
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<div><h4>Infective Endocarditis After Transcatheter Aortic Valve Replacement: JACC State-of-the-Art Review.</h4><i>Del Val D, Panagides V, Mestres CA, Miró JM, Rodés-Cabau J</i><br /><AbstractText>Infective endocarditis (IE) is a rare but serious complication following transcatheter aortic valve replacement (TAVR). Despite substantial improvements in the TAVR procedure (less invasive) and its expansion to younger and healthier patients, the incidence of IE after TAVR remains stable, with incidence rates similar to those reported after surgical aortic valve replacement. Although IE after TAVR is recognized as a subtype of prosthetic valve endocarditis, this condition represents a particularly challenging scenario given its unique clinical and microbiological profile, the high incidence of IE-related complications, the uncertain role of cardiac surgery, and the dismal prognosis in most patients with TAVR-IE. The number of TAVR procedures is expected to grow exponentially in the coming years, increasing the number of patients at risk of developing this life-threatening complication. Therefore, a detailed understanding of this disease and its complications will be essential to improve clinical outcomes.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 31 Jan 2023; 81:394-412</small></div>
Del Val D, Panagides V, Mestres CA, Miró JM, Rodés-Cabau J
J Am Coll Cardiol: 31 Jan 2023; 81:394-412 | PMID: 36697140
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<div><h4>Purine synthesis suppression reduces the development and progression of pulmonary hypertension in rodent models.</h4><i>Ma Q, Yang Q, Xu J, Sellers HG, ... Fulton DJR, Huo Y</i><br /><b>Aims</b><br />Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of pulmonary hypertension (PH). Proliferative cells utilize purine bases from the de novo purine synthesis (DNPS) pathways for nucleotide synthesis; however, it is unclear whether DNPS plays a critical role in VSMC proliferation during development of PH. The last two steps of DNPS are catalysed by the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC). This study investigated whether ATIC-driven DNPS affects the proliferation of pulmonary artery smooth muscle cells (PASMCs) and the development of PH.<br /><b>Methods and results</b><br />Metabolites of DNPS in proliferative PASMCs were measured by liquid chromatography-tandem mass spectrometry. ATIC expression was assessed in platelet-derived growth factor-treated PASMCs and in the lungs of PH rodents and patients with pulmonary arterial hypertension. Mice with global and VSMC-specific knockout of Atic were utilized to investigate the role of ATIC in both hypoxia- and lung interleukin-6/hypoxia-induced murine PH. ATIC-mediated DNPS at the mRNA, protein, and enzymatic activity levels were increased in platelet-derived growth factor-treated PASMCs or PASMCs from PH rodents and patients with pulmonary arterial hypertension. In cultured PASMCs, ATIC knockdown decreased DNPS and nucleic acid DNA/RNA synthesis, and reduced cell proliferation. Global or VSMC-specific knockout of Atic attenuated vascular remodelling and inhibited the development and progression of both hypoxia- and lung IL-6/hypoxia-induced PH in mice.<br /><b>Conclusion</b><br />Targeting ATIC-mediated DNPS compromises the availability of purine nucleotides for incorporation into DNA/RNA, reducing PASMC proliferation and pulmonary vascular remodelling and ameliorating the development and progression of PH.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 31 Jan 2023; epub ahead of print</small></div>
Ma Q, Yang Q, Xu J, Sellers HG, ... Fulton DJR, Huo Y
Eur Heart J: 31 Jan 2023; epub ahead of print | PMID: 36721994
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<div><h4>In Vivo Dissection of Chamber-Selective Enhancers Reveals Estrogen-Related Receptor as a Regulator of Ventricular Cardiomyocyte Identity.</h4><i>Cao Y, Zhang X, Akerberg BN, Yuan H, ... Kelly DP, Pu WT</i><br /><b>Background</b><br />Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined.<br /><b>Methods</b><br />We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-highly integrative chromatin immunoprecipitation on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes.<br /><b>Results</b><br />We identified 152 832 and 54 824 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs.<br /><b>Conclusions</b><br />We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.<br /><br /><br /><br /><small>Circulation: 27 Jan 2023; epub ahead of print</small></div>
Cao Y, Zhang X, Akerberg BN, Yuan H, ... Kelly DP, Pu WT
Circulation: 27 Jan 2023; epub ahead of print | PMID: 36705030
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<div><h4>Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.</h4><i>Suverein MM, Delnoij TSR, Lorusso R, Brandon Bravo Bruinsma GJ, ... Maessen JG, van de Poll MCG</i><br /><b>Background</b><br />Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive.<br /><b>Methods</b><br />In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis.<br /><b>Results</b><br />Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups.<br /><b>Conclusions</b><br />In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 26 Jan 2023; 388:299-309</small></div>
Suverein MM, Delnoij TSR, Lorusso R, Brandon Bravo Bruinsma GJ, ... Maessen JG, van de Poll MCG
N Engl J Med: 26 Jan 2023; 388:299-309 | PMID: 36720132
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<div><h4>Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.</h4><i>Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, ... Sonawane AR, Aikawa E</i><br /><b>Aims</b><br />Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.<br /><b>Methods and results</b><br />An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.<br /><b>Conclusion</b><br />Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 20 Jan 2023; epub ahead of print</small></div>
Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, ... Sonawane AR, Aikawa E
Eur Heart J: 20 Jan 2023; epub ahead of print | PMID: 36660854
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<div><h4>Psychosocial Functioning in Transgender Youth after 2 Years of Hormones.</h4><i>Chen D, Berona J, Chan YM, Ehrensaft D, ... Tishelman AC, Olson-Kennedy J</i><br /><b>Background</b><br />Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol).<br /><b>Methods</b><br />We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children\'s Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome.<br /><b>Results</b><br />A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants.<br /><b>Conclusions</b><br />In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 19 Jan 2023; 388:240-250</small></div>
Chen D, Berona J, Chan YM, Ehrensaft D, ... Tishelman AC, Olson-Kennedy J
N Engl J Med: 19 Jan 2023; 388:240-250 | PMID: 36652355
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<div><h4>Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture.</h4><i>Major Extremity Trauma Research Consortium (METRC), O\'Toole RV, Stein DM, O\'Hara NN, ... Marvel D, Castillo RC</i><br /><b>Background</b><br />Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking.<br /><b>Methods</b><br />In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications.<br /><b>Results</b><br />A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight-heparin group (difference, 0.05 percentage points; 96.2% confidence interval, -0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight-heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups.<br /><b>Conclusions</b><br />In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT ClinicalTrials.gov number, NCT02984384.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 19 Jan 2023; 388:203-213</small></div>
Major Extremity Trauma Research Consortium (METRC), O'Toole RV, Stein DM, O'Hara NN, ... Marvel D, Castillo RC
N Engl J Med: 19 Jan 2023; 388:203-213 | PMID: 36652352
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<div><h4>The Safety of Inpatient Health Care.</h4><i>Bates DW, Levine DM, Salmasian H, Syrowatka A, ... Reynolds ME, Mort E</i><br /><b>Background</b><br />Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted.<br /><b>Methods</b><br />We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events.<br /><b>Results</b><br />In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%).<br /><b>Conclusions</b><br />Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 12 Jan 2023; 388:142-153</small></div>
Bates DW, Levine DM, Salmasian H, Syrowatka A, ... Reynolds ME, Mort E
N Engl J Med: 12 Jan 2023; 388:142-153 | PMID: 36630622
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<div><h4>Diagnosis of cardiac sarcoidosis in patients presenting with cardiac arrest or life-threatening arrhythmias.</h4><i>Hatipoglu S, Gardezi SKM, Azzu A, Baksi J, ... Pennell DJ, Mohiaddin R</i><br /><b>Objective</b><br />Cardiac sarcoidosis (CS) may present with cardiac arrest or life-threatening arrhythmias. There are limited data on this subgroup of patients with CS. Advanced imaging including cardiovascular magnetic resonance (CMR) and cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) are used for diagnosis. This study aimed to describe advanced imaging patterns suggestive of CS among patients presenting with cardiac arrest or life-threatening arrhythmias.<br /><b>Methods</b><br />An imaging database of a CS referral centre (Royal Brompton Hospital, London) was screened for patients presenting with cardiac arrest or life-threatening arrhythmias and having imaging features of suspected CS. Patients diagnosed with definite or probable/possible CS were included.<br /><b>Results</b><br />Study population included 60 patients (median age 49 years) with male predominance (76.7%). The left ventricle was usually non-dilated with mildly reduced ejection fraction (53.4±14.8%). CMR studies showed extensive late gadolinium enhancement (LGE) with 5 (4-8) myocardial segments per patient affected; the right ventricular (RV) side of the septum (28/45) and basal anteroseptum (28/45) were most frequently involved. Myocardial inflammation by FDG-PET was detected in 45 out of 58 patients vs 11 out of 33 patients with oedema imaging available on CMR. When PET was treated as reference to detect myocardial inflammation, CMR oedema imaging was 33.3% sensitive and 77% specific.<br /><b>Conclusions</b><br />In patients with CS presenting with cardiac arrest or life-threatening arrhythmias, LGE was located in areas where the cardiac conduction system travels (basal anteroseptal wall and RV side of the septum). While CMR was the imaging technique that raised possibility of cardiac scarring, oedema imaging had low sensitivity to detect myocardial inflammation compared with FDG-PET.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 10 Jan 2023; epub ahead of print</small></div>
Hatipoglu S, Gardezi SKM, Azzu A, Baksi J, ... Pennell DJ, Mohiaddin R
Heart: 10 Jan 2023; epub ahead of print | PMID: 36627181
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<div><h4>Biventricular Noncompaction Cardiomyopathy in a Patient Presenting With a New Cerebrovascular Event.</h4><i>Madnawat H, Atallah I, Ahmad A, Harjai K</i><br /><AbstractText>Noncompaction (NC) cardiomyopathy (NCCM) is a rare, genetically heterogeneous cardiomyopathy (CM) caused by failure to compact the intertrabecular recesses of the myocardium. This condition usually affects the apical segment of the left ventricle, yet there are noted basal segment, biventricular, and right ventricular predominant cases. NCCM is largely diagnosed in the pediatric population; however, there is increasing recognition in older patients with heart failure and stroke and patients with arrhythmias. Treatment focuses on symptomatic management of heart failure, anticoagulation, and implantable cardiac defibrillators.</AbstractText><br /><br />Copyright © 2022 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 06 Jan 2023; 190:110-112</small></div>
Madnawat H, Atallah I, Ahmad A, Harjai K
Am J Cardiol: 06 Jan 2023; 190:110-112 | PMID: 36621285
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<div><h4>Association of sodium intake with adverse left atrial function and left atrioventricular coupling in Chinese.</h4><i>Yin L, Mei J, Dong J, Qu X, Jiang Y</i><br /><b>Objectives</b><br />High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function.<br /><b>Methods</b><br />Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging.<br /><b>Results</b><br />The average age of the participants was 55.70 ± 11.30 years old. The mean urinary sodium of the participants was 172.01 ± 80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling.<br /><b>Conclusions</b><br />Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.<br /><br />Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.<br /><br /><small>J Hypertens: 01 Jan 2023; 41:159-170</small></div>
Yin L, Mei J, Dong J, Qu X, Jiang Y
J Hypertens: 01 Jan 2023; 41:159-170 | PMID: 36453659
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<div><h4>Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction.</h4><i>Choi YJ, Kim HK, Hwang IC, Park CS, ... Cho GY, Kim YJ</i><br /><b>Objective</b><br />To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model.<br /><b>Methods</b><br />This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved (<b>≥</b>60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death.<br /><b>Results</b><br />During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death.<br /><b>Conclusions</b><br />Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM.<br /><br />© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 29 Dec 2022; epub ahead of print</small></div>
Choi YJ, Kim HK, Hwang IC, Park CS, ... Cho GY, Kim YJ
Heart: 29 Dec 2022; epub ahead of print | PMID: 36581445
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<div><h4>Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age.</h4><i>Dellborg M, Giang KW, Eriksson P, Liden H, ... Rosengren A, Mandalenakis Z</i><br /><b>Background</b><br />The survival of children with congenital heart disease has increased substantially over the past decades, with 97% currently reaching adulthood. The total effect of advanced treatment on future mortality and morbidity in adult survivors with congenital heart disease (CHD) is less well described.<br /><b>Methods</b><br />We used data from the Swedish National Inpatient, Outpatient, and Cause of Death Register to identify patients with CHD who were born between 1950 and 1999 and were alive at 18 years of age. Ten controls identified from the Total Population Register were matched for year of birth and sex and with each patient with CHD. Follow-up was from 1968 and 18 years of age until death or at the end of the study (2017). Survival percentage with 95% CI for all-cause mortality were performed with Kaplan-Meier survival function. Cox proportional hazard regression models with hazard ratios (HRs) and 95% CI were used to estimate the risk of all-cause mortality.<br /><b>Results</b><br />We included 37 278 patients with adult CHD (ACHD) and 412 799 controls. Mean follow-up was 19.2 years (±13.6). Altogether, 1937 patients with ACHD (5.2%) and 6690 controls (1.6%) died, a death rate of 2.73 per 1000 person-years and 0.84 per 1000 person years, respectively. Mortality was 3.2 times higher (95% CI, 3.0-3.4; <i>P</i><0.001) among patients with ACHD compared with matched controls. Up to the maximum of 50 years of follow-up, >75% of patients with ACHD were still alive. Mortality was highest among patients with conotruncal defects (HR, 10.13 [95% CI, 8.78-11.69]), but also significantly higher for the more benign lesions, with the lowest risk in patients with atrial septal defects (HR, 1.36 [95% CI, 1.19-1.55]). At least 75% of patients with ACHD alive at 18 years of age lived past middle age and became sexagenerians.<br /><b>Conclusions</b><br />In this large, nationwide, register-based cohort study of patients with ACHD surviving to 18 years of age, the risk of mortality up to 68 years of age was >3 times higher compared with matched controls without ACHD. Despite this, at least 75% of patients with CHD alive at 18 years of age lived past middle age and became sexagenerians. A notable risk decline in the mortality for patients with ACHD was noted for those born after 1975.<br /><br /><br /><br /><small>Circulation: 26 Dec 2022; epub ahead of print</small></div>
Dellborg M, Giang KW, Eriksson P, Liden H, ... Rosengren A, Mandalenakis Z
Circulation: 26 Dec 2022; epub ahead of print | PMID: 36571845
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<div><h4>Acute aortic dissection: evidence, uncertainties, and future therapies.</h4><i>Rylski B, Schilling O, Czerny M</i><br /><AbstractText>Remarkable progress has become especially apparent in aortic medicine in the last few decades, leading to essential changes in how thoracic aortic dissection is understood and treated. This state-of-the-art review article addresses the mechanisms of acute aortic dissection, explaining the role of its primary entry location, proximal, and distal dissection extension in their clinical presentation and impact on the decision-making process towards the best treatment approach. The latest evidence on novel treatment methods for acute aortic syndromes is presented, and the diverse dissection classification systems that remain uncertain are discussed, which reveals the need for shared terminology and more clarity. Finally, future aspects are discussed in treating acute aortic dissection, such as the endovascular treatment of aortic dissection Type A and biomarkers for acute aortic syndromes.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 20 Dec 2022; epub ahead of print</small></div>
Rylski B, Schilling O, Czerny M
Eur Heart J: 20 Dec 2022; epub ahead of print | PMID: 36540036
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<div><h4>Massively Hypertrophied Right-Sided Heart with Hypoplastic Left-Sided Heart in a Neonate (A Rare Type of Hypertrophic Cardiomyopathy).</h4><i>Roberts WC, Chinta S, Guileyardo JM</i><br /><AbstractText>Described herein is a newborn boy with likely right-sided hypertrophic cardiomyopathy (HC), who survived for 18 hours after birth. At necropsy, he had a severely thickened right ventricular free wall, ventricular septum, right atrial wall and a hypoplastic left-sided heart. There was a large fossa ovale type atrial septal defect and also a patent ductus arteriosus. During peak systole, the right ventricular outflow tract was obstructed, and its contents were pushed into the thick-walled right atrium, then rapidly into the thin-walled left atrium via a large fossa ovale atrial septal defect. The contents were then pushed into the thin-walled left ventricle and finally into the small ascending aorta and into the lungs via a large patent ductus arteriosus. We were unable to find a similar published case.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>Am J Cardiol: 15 Dec 2022; epub ahead of print</small></div>
Roberts WC, Chinta S, Guileyardo JM
Am J Cardiol: 15 Dec 2022; epub ahead of print | PMID: 36528398
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<div><h4>Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.</h4><i>Ishani A, Cushman WC, Leatherman SM, Lew RA, ... Ferguson RE, Diuretic Comparison Project Writing Group</i><br /><b>Background</b><br />Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.<br /><b>Methods</b><br />In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.<br /><b>Results</b><br />A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001).<br /><b>Conclusions</b><br />In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).<br /><br />Copyright © 2022 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 14 Dec 2022; epub ahead of print</small></div>
Ishani A, Cushman WC, Leatherman SM, Lew RA, ... Ferguson RE, Diuretic Comparison Project Writing Group
N Engl J Med: 14 Dec 2022; epub ahead of print | PMID: 36516076
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<div><h4>Incidence and Burden of Tricuspid Regurgitation in Patients With Atrial Fibrillation.</h4><i>Patlolla SH, Schaff HV, Nishimura RA, Stulak JM, ... Pislaru SV, Nkomo VT</i><br /><b>Background</b><br />Atrial fibrillation (AF) is considered a risk factor for isolated tricuspid valve regurgitation (TR) in the absence of other known etiologies.<br /><b>Objectives</b><br />This study sought to identify the incidence of clinically significant isolated TR and its impact in patients with AF.<br /><b>Methods</b><br />A population-based record linkage system was used to identify adult patients with new-onset AF. Patients with evidence of moderate or greater tricuspid valve disease, left-sided valve disease, pulmonary hypertension, prior cardiac surgery, impaired left ventricular systolic/diastolic function at baseline were excluded. The remaining patients (n = 691) were followed over time to identify development of moderate or greater TR and assess its impact on subsequent survival.<br /><b>Results</b><br />A total of 232 patients (33.6%) developed moderate or greater TR. Among these, 73 patients (10.6%) had isolated TR without significant underlying structural heart disease. Incidence rate of any moderate or greater TR was 3.9 cases and that of isolated TR was 1.3 cases per 100 person-years. Permanent/persistent AF and female sex were associated with increased risk of developing TR, whereas rhythm control was associated with lower risk of TR. Over a median clinical follow-up of 13.3 years (IQR: 10.0-15.9 years), development of any moderate or greater TR (HR: 2.92; 95% CI: 2.29-3.73; P < 0.001) and isolated significant TR (HR: 1.51; 95% CI: 1.03-2.22; P = 0.03) were associated with an adjusted increased risk of subsequent mortality.<br /><b>Conclusions</b><br />In this population-based cohort of patients with AF, nearly one-third developed moderate or greater TR over time. Incident significant TR and incident isolated significant TR portend a worse survival in patients with AF.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Dec 2022; 80:2289-2298</small></div>
Patlolla SH, Schaff HV, Nishimura RA, Stulak JM, ... Pislaru SV, Nkomo VT
J Am Coll Cardiol: 13 Dec 2022; 80:2289-2298 | PMID: 36480971
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<div><h4>Pathophysiology, Echocardiographic Diagnosis, and Treatment of Atrial Functional Mitral Regurgitation: JACC State-of-the-Art Review.</h4><i>Farhan S, Silbiger JJ, Halperin JL, Zhang L, ... Sharma S, Lerakis S</i><br /><AbstractText>The conventional view holds that functional mitral regurgitation (MR) is caused by restriction of leaflet motion resulting from displacement of the papillary muscle-bearing segments of the left ventricle. In the past decade, evidence has accrued suggesting functional MR can also be caused by left atrial enlargement. This underrecognized cause of secondary MR-atrial functional MR (AF-MR)-is mechanistically linked to annular enlargement, perturbations of annular contraction, and atriogenic leaflet tethering. AF-MR has been described in patients with atrial fibrillation and heart failure with preserved ejection fraction. Preliminary data suggest rhythm control may decrease MR severity in patients with atrial fibrillation. Additionally, several studies have reported reductions in MR and symptomatic improvement with restrictive annuloplasty and transcatheter edge-to-edge repair. This review discusses the pathophysiology, echocardiographic diagnosis, and treatment of AF-MR. AF-tricuspid regurgitation is also discussed.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Dec 2022; 80:2314-2330</small></div>
Farhan S, Silbiger JJ, Halperin JL, Zhang L, ... Sharma S, Lerakis S
J Am Coll Cardiol: 13 Dec 2022; 80:2314-2330 | PMID: 36480974
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<div><h4>Cardiopulmonary Exercise Testing in Athletes With Hypertrophic Cardiomyopathy.</h4><i>Newman DB, Garmany R, Contreras AM, Bos JM, ... Ommen SR, Ackerman MJ</i><br /><AbstractText>Patients with hypertrophic cardiomyopathy (HCM) have historically been restricted from athletic participation because of the perceived risk of sudden cardiac death. More contemporary research has highlighted the relative safety of competitive athletics with HCM. However, lack of published data on reference values for cardiopulmonary exercise testing (CPET) complicates clinical management and counseling on sports participation in the individual athlete. We conducted a single-center, retrospective cohort study to investigate CPET in athletes with HCM and clinical characteristics associated with objective measures of aerobic capacity. We identified 58 athletes with HCM (74% male, mean age 18 ± 3 years, mean left ventricular (LV) wall thickness 20 ± 7 mm). LV outflow tract obstruction was present in 22 (38%). A total of 15 (26%) athletes were taking a β blocker (BB), but only 4 (7%) reported exertional symptoms. Overall, exercise capacity was mildly reduced, with a peak myocardial oxygen consumption (peak VO<sub>2</sub>) of 37.9 ml/min/kg (83% of predicted peak VO<sub>2</sub>). Both LV outflow tract obstruction and BB use were associated with reduced exercise capacity. Limited peak heart rate was more common in athletes taking BB (47% vs 9%, p = 0.002). At a mean 5.6 years follow-up, 5 patients underwent myectomy (9%), and 8 (14%) received an implantable cardioverter defibrillator (ICD) for primary prevention. One individual with massive LV hypertrophy experienced recurrent ICD shocks for ventricular fibrillation and underwent myectomy 7 years after initial evaluation and was no longer participating in sports. There were no deaths over the follow-up period. In conclusion, the prognostic role of CPET remains unclear in athletes with HCM. Mildly reduced exercise capacity was common; however, reduced peak VO<sub>2</sub> did not correlate with symptom status or clinical outcomes. A significant proportion went on to require myectomy and/or ICD, thus highlighting the need for close follow-up. These data provide some initial insight into the clinical evaluation of \"real world\" athletes with HCM; however, further study is warranted to help guide shared decision-making, return-to-play discussions, and the potential long-term safety of competitive athletic participation.</AbstractText><br /><br />Copyright © 2022 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 09 Dec 2022; 189:49-55</small></div>
Newman DB, Garmany R, Contreras AM, Bos JM, ... Ommen SR, Ackerman MJ
Am J Cardiol: 09 Dec 2022; 189:49-55 | PMID: 36508762
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This program is still in alpha version.