Maleszewski, Joseph J.

Background— The incidence and cause of sudden cardiac death (SCD) in athletes is debated with hypertrophic cardiomyopathy often reported as the most common cause. Methods and Results— A database of all National Collegiate Athletic Association deaths (2003–2013) was developed. Additional information and autopsy reports were obtained when possible. Cause of death was adjudicated by an expert panel. There were 4 242 519 athlete-years (AY) and 514 total student athlete deaths. Accidents were the most common cause of death (257, 50%, 1:16 508 AY) followed by medical causes (147, 29%, 1:28 861 AY). The most common medical cause of death was SCD (79, 15%, 1:53 703 AY). Males were at higher risk than females 1:37 790 AY versus 1:121 593 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9–5.5; P <0.00001), and black athletes were at higher risk than white athletes 1:21491 AY versus 1:68 354 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9–5.2; P <0.00001). The incidence of SCD in Division 1 male basketball athletes was 1:5200 AY. The most common findings at autopsy were autopsy-negative sudden unexplained death in 16 (25%), and definitive evidence for hypertrophic cardiomyopathy was seen in 5 (8%). Media reports identified more deaths in higher divisions (87%, 61%, and 44%), whereas the percentages from the internal database did not vary (87%, 83%, and 89%). Insurance claims identified only 11% of SCDs. Conclusions— The rate of SCD in National Collegiate Athletic Association athletes is high, with males, black athletes, and basketball players at substantially higher risk. The most common finding at autopsy is autopsy-negative sudden unexplained death. Media reports are more likely to capture high-profile deaths, and insurance claims are not a reliable method for case identification.

Background— Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology. Methods and Results— We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size–expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm 2 ) than control ( P <0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls ( r =–0.28, P =0.004) and HFpEF ( r =–0.26, P =0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD. Conclusions— In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.

The advent of induced pluripotent stem cell (iPSC) technology creates new opportunities for transplant-based therapeutic strategies. The potential for clinical translation is currently hindered by the risk of dysregulated cell growth. Pluripotent stem cells reprogrammed by three-factor (Sox2, Klf, and Oct4) and four-factor (Sox2, Klf, Oct4, and c-Myc) strategies result in the capacity for teratogenic growth from residual pluripotent progeny upon in vivo transplantation. However, these pluripotent stem cells also have a stage-specific hypersensitivity to DNA-damaging agents that may allow separation of lineage-specific therapeutic subpopulation of cells. We aimed to demonstrate the selective effect of DNA topoisomerase II inhibitor, etoposide, in eliminating pluripotent cells in the early cardiac progenitor population thus decreasing the effect of teratoma formation. Immunodeficient murine hearts were infarcted and received implantation of a therapeutic dose of cardiac progenitors derived from partially differentiated iPSCs. Etoposide-treated cell implantation reduced mass formation in the intracardiac and extracardiac chest cavity compared with the same dose of iPSC-derived cardiac progenitors in the control untreated group. In vivo bioluminescence imaging confirmed the localization and engraftment of transplanted cells in the myocardium postinjection in both groups. Comparatively, the equivalent cell population without etoposide treatment demonstrated a greater incidence and size of teratoma formation. Hence, pretreatment with genotoxic etoposide significantly lowered the threat of teratogenicity by purging the contaminating pluripotent cells, establishing an adjunctive therapy to further harness the clinical value of iPSC-derived cardiac regeneration.

Background— The pathogenesis of sudden cardiac death in college athletes has not been defined by systematic case identification. Methods and Results— A total of 45 cases of sudden cardiac death were identified in National Collegiate Athletic Association (NCAA) athletes from 2004 to 2008 based on an internal reporting system and review of media reports. Autopsy reports were reviewed and adjudicated by a multidisciplinary panel. Cause of death could be reasonably determined in 36 cases; 3 athletes had no autopsy, 5 autopsy reports could not be obtained, and 1 autopsy had insufficient information to determine cause of death. The most common finding at death was a structurally normal heart or autopsy-negative sudden unexplained death (11, 31%), followed by coronary artery abnormalities (5, 14%), dilated cardiomyopathy (3, 8%), myocarditis related (3, 8%), aortic dissection (3, 8%), and idiopathic left ventricular hypertrophy/possible hypertrophic cardiomyopathy (HCM; 3, 8%). There was 1 case each (3%) of hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, commotio cordis, and Kawasaki disease. There was 1 case of death in a sickle cell positive athlete who also had left ventricular hypertrophy. The adjudicated diagnosis agreed with the official pathology report in only 59% of cases. Conclusions— Unexplained death with a structurally normal heart is the most common finding after suspected sudden cardiac death in NCAA athletes. Hypertrophic cardiomyopathy is infrequently seen, and conclusions in autopsy reports may not accurately reflect the pathological findings. Standardized protocols for cardiovascular autopsies in athletes are needed, including postmortem genetic testing, particularly in autopsy-negative cases.

Hydrophilic polymer coated introducer sheaths and medical devices are widely used in interventional cardiology. Despite the potential procedural advantages that these provide, a risk of polymer embolization has been recently reported. We describe the first reported case of hydrophilic polymer induced acute transcatheter aortic valve thrombosis. © 2014 Wiley Periodicals, Inc.

Objective Bicuspid aortic valve (BAV) is associated with a higher risk of type A aortic dissection (AD) compared with tricuspid aortic valve (TAV). We sought to study differences between patients with BAV and TAV with AD. Design and setting Observational descriptive analysis of clinical, imaging and pathological characteristics of all patients with confirmed BAV and AD from 1980–2010, compared with a consecutive TAV group with AD. Results Of 47 patients with BAV (mean age 58±14, 77% male), 31 (66%) had acute AD, 16 (34%) had chronic AD, 40 (85%) had typical BAV, 32 (68%) had hypertension and 11 (23%) had previous aortic coarctation repair. Of 53 patients with TAV (mean age 66±13 (p=0.007), 76% male), 34 (66%) had acute AD (p=1.0) and 46 (87%) had hypertension (p=0.03). More patients with BAV had known aortic dilatation prior to AD (49% versus 17%, p=0.001). Presentation symptoms were identical between groups (p=NS). Maximal ascending aortic diameter at AD was higher in patients with BAV (66±15 mm vs 56±11 mm, p=0.0004). Previous aortic valve replacement (AVR) was more common in BAV (23% vs 6%, p=0.02). Of 11 patients with BAV with previous isolated AVR, 7 had ≥moderate ascending aorta dilatation at the time of surgery. Patients with BAV had increased aortic jet velocity (28% vs 10%) and more severe aortic stenosis (19% vs 0%) at presentation (p=0.04 and 0.002, respectively). In acute AD, aortic medial degeneration affected 75% of BAV specimens and 41% TAV specimens (p=0.01) while aortic atherosclerosis was more frequent in TAV (56% vs 26%, p=0.02). Conclusions Compared with patients with TAV, patients with BAV with type A AD are younger, have less hypertension, more valve stenosis and previous AVR, higher maximal aortic dimension, worse aortic medial degeneration, high prevalence of aortic coarctation, and 1 out of 2 have known aortic dilatation prior to AD. Implementation of current guidelines could have theoretically prevented AD in several patients with BAV.

Papillary fibroelastomas (PFEs) are benign cardiac tumors arising from endocardium. They are commonly found on valvular surfaces and average 1.0–1.5 cm in size. Though often asymptomatic, PFEs can lead to potentially severe complications, primarily due to their embolic potential. Surgical resection is recommended for all symptomatic or large PFEs. We report the case of a patient presenting with cardiovascular symptoms who was found to have a very large aortic valve PFE, as diagnosed by histopathologic examination following surgical resection. Multimodality cardiovascular imaging demonstrates the classic morphologic findings, including a pedunculated appearance and oscillating “frond-like” surface projections.

ABSTRACT Microbiological diagnosis is pivotal to the appropriate management and treatment of infective endocarditis. We evaluated PCR-electrospray ionization mass spectrometry (PCR/ESI-MS) for bacterial and candidal detection using 83 formalin-fixed paraffin-embedded heart valves from subjects with endocarditis who had positive valve and/or blood cultures, 63 of whom had positive valvular Gram stains. PCR/ESI-MS yielded 55% positivity with concordant microbiology at the genus/species or organism group level (e.g., viridans group streptococci), 11% positivity with discordant microbiology, and 34% with no detection. PCR/ESI-MS detected all antimicrobial resistance encoded by mecA or vanA / B and identified a case of Tropheryma whipplei endocarditis not previously recognized.