Death and Cardiac Arrest in U.S. Triathlon Participants, 1985 to 2016: A Case Series.

BACKGROUND: Reports of race-related triathlon fatalities have raised questions regarding athlete safety. OBJECTIVE: To describe death and cardiac arrest among triathlon participants. DESIGN: Case series. SETTING: United States. PARTICIPANTS: Participants in U.S. triathlon races from 1985 to 2016. MEASUREMENTS: Data on deaths and cardiac arrests were assembled from such sources as the U.S. National Registry of Sudden Death in Athletes (which uses news media, Internet searches, LexisNexis archival databases, and news clipping services) and USA Triathlon (USAT) records. Incidence of death or cardiac arrest in USAT-sanctioned races from 2006 to 2016 was calculated. RESULTS: A total of 135 sudden deaths, resuscitated cardiac arrests, and trauma-related deaths were compiled; mean (±SE) age of victims was 46.7 ± 12.4 years, and 85% were male. Most sudden deaths and cardiac arrests occurred in the swim segment (n = 90); the others occurred during bicycling (n = 7), running (n = 15), and postrace recovery (n = 8). Fifteen trauma-related deaths occurred during the bike segment. Incidence of death or cardiac arrest among USAT participants (n = 4 776 443) was 1.74 per 100 000 (2.40 in men and 0.74 in women per 100 000; P < 0.001). In men, risk increased substantially with age and was much greater for those aged 60 years and older (18.6 per 100 000 participants). Death or cardiac arrest risk was similar for short, intermediate, and long races (1.61 vs. 1.41 vs. 1.92 per 100 000 participants). At autopsy, 27 of 61 decedents (44%) had clinically relevant cardiovascular abnormalities, most frequently atherosclerotic coronary disease or cardiomyopathy. LIMITATIONS: Case identification may be incomplete and may underestimate events, particularly in the early study period. In addition, prerace medical history is unknown in most cases. CONCLUSION: Deaths and cardiac arrests during the triathlon are not rare; most have occurred in middle-aged and older men. Most sudden deaths in triathletes happened during the swim segment, and clinically silent cardiovascular disease was present in an unexpected proportion of decedents. PRIMARY FUNDING SOURCE: Minneapolis Heart Institute Foundation.

Ventricular Tachyarrhythmias in Patients With Hypertrophic Cardiomyopathy and Defibrillators: Triggers, Treatment, and Implications.

INTRODUCTION: Triggers and ICD interventions of ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) offer insight into mechanisms and treatment. METHODS AND RESULTS: Intracardiac ICD electrograms from 71 HCM patients in the HCM I and II studies were analyzed by three individuals. Rhythms were defined as VF (polymorphic ventricular arrhythmia), VT (monomorphic ventricular tachycardia), and ventricular flutter (VFL; VT ≥ 240 bpm). Physical activity and rhythm preceding the arrhythmia were ascertained. Of 149 arrhythmias, VF was present in 74, VT in 57, and VFL in 18. In those whose activity was known, moderate or intense physical activity was associated with over 50% of the tachycardias (57 of 111). Rhythms preceding ventricular arrhythmias were often sinus tachycardia (49 of 149; 33%) or rapid atrial fibrillation (7 of 149; 5%). VF and VFL were more likely preceded by supraventricular rhythms >100 bpm (30 of 68 with VF; 44%; 12 of 16 with VFL 75%, vs. 14 of 50 with VT 28%; P = 0.001). Antitachycardia pacing (ATP) was successful in 39 of 53 (74%). Multiple shocks were more often required to terminate VFL (10 of 18; 56%) compared to VF (10 of 72; 14%) and VT (2 of 25; 8%; P < 0.0001). Of arrhythmias requiring more than one shock to terminate, 16 of 22 were preceded by sinus tachycardia and/or moderate or extreme physical activity. CONCLUSIONS: Rapid supraventricular rhythms, and at least moderate activity, frequently precede VT and VF, and when they occur in these situations often require multiple ICD shocks to restore sinus rhythm. ATP is successful in terminating VT and VFL, and should be a programmed in all HCM patients with ICDs.

Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. METHODS AND RESULTS: We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3-38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). CONCLUSIONS: Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.

Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

AIMS: Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal). METHODS AND RESULTS: CMR was performed in 230 genotyped HCM patients (48 ± 15 years, 69% male), 30 genotype-positive/phenotype-negative (G+/P-) family members (32 ± 15 years, 30% male), and 126 controls. Left ventricular apical-basal muscle bundle was identified in 145 of 230 (63%) HCM patients, 18 of 30 (60%) G+/P- family members, and 12 of 126 (10%) controls (G+/P- vs. controls; P < 0.01). In HCM patients, the prevalence of an apical-basal muscle bundle was similar among those with disease-causing sarcomere mutations compared with patients without mutation (64 vs. 62%; P = 0.88). The presence of an LV apical-basal muscle bundle was not associated with LV outflow tract obstruction (P = 0.61). In follow-up, 33 patients underwent surgical myectomy of whom 22 (67%) were identified to have an accessory LV apical-basal muscle bundle, which was resected in all patients. CONCLUSION: Apical-basal muscle bundles are a unique myocardial structure commonly present in HCM patients as well as in G+/P- family members and may represent an additional morphologic marker for HCM diagnosis in genotype-positive status.

Risk stratification and outcome of patients with hypertrophic cardiomyopathy >=60 years of age.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is prominently associated with risk for sudden death and disease progression, largely in young patients. Whether patients of more advanced age harbor similar risks is unresolved, often creating clinical dilemmas, particularly in decisions for primary prevention of sudden death with implantable defibrillators. METHODS AND RESULTS: We studied 428 consecutive HCM patients presenting at ≥60 years of age and followed for 5.8±4.8 years; 53% were women. Of the 428 patients, 279 (65%) survived to 73±7 years of age (range, 61-96 years), most (n=245, 88%) with no/mild symptoms, including 135 with ≥1 conventional sudden death risk factors and 50 (37%) with late gadolinium enhancement. Over follow-up, 149 (35%) died at 80±8 years of age, mostly from non-HCM-related causes (n=133, 31%), including a substantial proportion from noncardiac disease (n=54). Sixteen patients (3.7%) had HCM-related mortality events (0.64%/y), including embolic stroke (n=6), progressive heart failure or transplantation (n=3), postoperative complications (n=2), and arrhythmic sudden death events (n=5, 1.2% [0.20%/y]). All-cause mortality was increased in HCM patients ≥60 years of age compared with an age-matched US general population, predominantly as a result of non-HCM-related diseases (P<0.001; standard mortality ratio, 1.5). CONCLUSIONS: HCM patients surviving into the seventh decade of life are at low risk for disease-related morbidity/mortality, including sudden death, even with conventional risk factors. These data do not support aggressive prophylactic defibrillator implantation at advanced ages in HCM. Other cardiac or noncardiac comorbidities have a greater impact on survival than HCM in older patients.

Mitral valve abnormalities identified by cardiovascular magnetic resonance represent a primary phenotypic expression of hypertrophic cardiomyopathy.

BACKGROUND: Whether morphological abnormalities of the mitral valve represent part of the hypertrophic cardiomyopathy (HCM) disease process is unresolved. Therefore, we applied cardiovascular magnetic resonance to characterize mitral valve morphology in a large HCM cohort. METHODS AND RESULTS: Cine cardiac magnetic resonance images were obtained in 172 HCM patients (age, 42±18 years; 62% men) and 172 control subjects. In addition, 15 HCM gene-positive/phenotype-negative relatives were studied. Anterior mitral leaflet (AML) and posterior mitral leaflet lengths were greater in HCM patients than in control subjects (26±5 versus 19±5 mm, P<0.001; and 14±4 versus 10±3 mm, P<0.001, respectively), including 59 patients (34%) in whom AML length alone, posterior mitral leaflet length alone, or both were particularly substantial (>2 SDs above controls). Leaflet length was increased compared with controls in virtually all HCM age groups, including young patients 15 to 20 years of age (AML, 26±5 versus 21±4 mm; P=0.0002) and those ≥60 years of age (AML, 26±4 versus 19±2 mm; P<0.001). No relation was evident between mitral leaflet length and LV thickness or mass index (P=0.09 and P=0.16, respectively). A ratio of AML length to LV outflow tract diameter of >2.0 was associated with subaortic obstruction (P=0.001). In addition, AML length in 15 genotype-positive relatives without LV hypertrophy exceeded that of matched control subjects (21±3 versus 18±3 mm; P<0.01). CONCLUSIONS: In HCM, mitral valve leaflets are elongated independently of other disease variables, likely constituting a primary phenotypic expression of this heterogeneous disease, and are an important morphological abnormality responsible for LV outflow obstruction in combination with small outflow tract dimension. These findings suggest a novel role for cardiac magnetic resonance in the assessment of HCM.

Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006.

BACKGROUND: Sudden deaths in young competitive athletes are highly visible events with substantial impact on the physician and lay communities. However, the magnitude of this public health issue has become a source of controversy. METHODS AND RESULTS: To estimate the absolute number of sudden deaths in US competitive athletes, we have assembled a large registry over a 27-year period using systematic identification and tracking strategies. A total of 1866 athletes who died suddenly (or survived cardiac arrest), 19+/-6 years of age, were identified throughout the United States from 1980 to 2006 in 38 diverse sports. Reports were less common during 1980 to 1993 (576 [31%]) than during 1994 to 2006 (1290 [69%], P<0.001) and increased at a rate of 6% per year. Sudden deaths were predominantly due to cardiovascular disease (1049 [56%]), but causes also included blunt trauma that caused structural damage (416 [22%]), commotio cordis (65 [3%]), and heat stroke (46 [2%]). Among the 1049 cardiovascular deaths, the highest number of events in a single year was 76 (2005 and 2006), with an average of 66 deaths per year (range 50 to 76) over the last 6 years; 29% occurred in blacks, 54% in high school students, and 82% with physical exertion during competition/training, whereas only 11% occurred in females (although this increased with time; P=0.023). The most common cardiovascular causes were hypertrophic cardiomyopathy (36%) and congenital coronary artery anomalies (17%). CONCLUSIONS: In this national registry, the absolute number of cardiovascular sudden deaths in young US athletes was somewhat higher than previous estimates but relatively low nevertheless, with a rate of <100 per year. These data are relevant to the current debate surrounding preparticipation screening programs with ECGs and also suggest the need for systematic and mandatory reporting of athlete sudden deaths to a national registry.

Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease characterized by a diverse clinical and phenotypic spectrum. This study reports the prevalence, morphology, clinical course, and management of an underrecognized subgroup of HCM patients with left ventricular apical aneurysms. METHODS AND RESULTS: Of 1299 HCM patients, 28 (2%) were identified with left ventricular apical aneurysms, including a pair of identical twins. Aneurysms were recognized at a wide age range (26 to 83 years), including 12 patients (43%) who were

Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy.

CONTEXT: Mutations in X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a cardiomyopathy in young patients that clinically mimics severe hypertrophic cardiomyopathy (HCM) due to sarcomere protein mutations. However, the natural history and phenotypic expression of this newly recognized disease is incompletely resolved and its identification may have important clinical implications. OBJECTIVES: To determine the clinical consequences, outcome, and phenotypic expression of LAMP2 cardiomyopathy associated with diagnostic and management strategies. DESIGN, SETTING, AND PATIENTS: Clinical course and outcome were assessed prospectively in 7 young patients (6 boys) with defined LAMP2 mutations from the time of diagnosis (age 7-17 years; median, 14 years) to October 2008. Phenotypic expression of this disease was assessed both clinically and at autopsy. MAIN OUTCOME MEASURES: Progressive heart failure, cardiac death, and transplant. RESULTS: Over a mean (SD) follow-up of 8.6 (2.6) years, and by age 14 to 24 years, the study patients developed left ventricular systolic dysfunction (mean [SD] ejection fraction, 25% [7%]) and cavity enlargement, as well as particularly adverse clinical consequences, including progressive refractory heart failure and death (n = 4), sudden death (n = 1), aborted cardiac arrest (n = 1), or heart transplantation (n = 1). Left ventricular hypertrophy was particularly marked (maximum thickness, 29-65 mm; mean [SD], 44 [15] mm), including 2 patients with massive ventricular septal thickness of 60 mm and 65 mm at ages 23 and 14 years, respectively. In 6 patients, a ventricular pre-excitation pattern at study entry was associated with markedly increased voltages of R-wave or S-wave (15-145 mm; mean [SD], 69 [39] mm), and deeply inverted T-waves. Autopsy findings included a combination of histopathologic features that were consistent with a lysosomal storage disease (ie, clusters of vacuolated myocytes) but also typical of HCM due to sarcomere protein mutations (ie, myocyte disarray, small vessel disease, myocardial scarring). CONCLUSIONS: LAMP2 cardiomyopathy is a profound disease process characterized by progressive clinical deterioration leading rapidly to cardiac death in young patients (<25 years). These observations underscore the importance of timely molecular diagnosis for predicting prognosis and early consideration of heart transplantation.

Sudden cardiac arrest in hypertrophic cardiomyopathy in the absence of conventional criteria for high risk status.

Two patients with hypertrophic cardiomyopathy are reported from the recent experience of the Hypertrophic Cardiomyopathy Center of the Minneapolis Heart Institute Foundation, demonstrating limitations in the risk stratification algorithm currently used for this disease. One patient, an asymptomatic 21-year-old male college student, was prophylactically implanted with a cardioverter-defibrillator. This decision was based largely on the presence of apparent extensive myocardial fibrosis identified by contrast-enhanced cardiovascular magnetic resonance imaging, currently not considered a risk factor in this disease. Fifteen months later, ventricular fibrillation was interrupted by an appropriate defibrillator shock. The other patient, an asymptomatic 15-year-old male subject without any apparent high-risk markers, died suddenly at home. Necropsy examination of the heart identified scarring confined to portions of both left ventricular papillary muscles, possibly representing a substrate for ventricular tachyarrhythmias. In conclusion, these 2 cases demonstrate that present strategies for assessing high-risk status in hypertrophic cardiomyopathy are inadequate to identify all such patients. However, while the anecdotal nature of these observations cannot yet justify altering the general guidelines for implantation of defibrillators for the primary prevention of sudden death related to hypertrophic cardiomyopathy, 1 of our 2 cases suggests a future role for contrast-enhanced cardiovascular magnetic resonance in the risk stratification of this complex disease.

Significance of appropriate defibrillator shock 3 hours and 20 minutes following implantation in a patient with hypertrophic cardiomyopathy.

INTRODUCTION: Implantable defibrillators have proved effective in terminating potentially life-threatening ventricular tachyarrhythmias in hypertrophic cardiomyopathy (HCM), although the timing of appropriate shocks may be exceedingly variable. METHODS AND RESULTS: We report an unusual occurrence in a 48-year-old woman with nonobstructive HCM who experienced an appropriate shock for ventricular fibrillation only 3 hours and 20 minutes after implantation. Careful review of the clinical circumstances failed to define a specific mechanism related to the implant procedure that could have triggered the potentially lethal arrhythmia. CONCLUSION: Early device interventions are not uncommon in HCM, but (as in this case) appear unrelated to mechanisms other than the unpredictable and underlying arrhythmogenic substrate in this disease.

Identification of Fabry Disease in a Tertiary Referral Cohort of Patients with Hypertrophic Cardiomyopathy.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these 2 diseases diverge, with Fabry disease-specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy. METHODS: We studied a prospectively assembled consecutive cohort of 585 patients (71% male) from 2 hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α-galactosidase A activity levels and all females were tested for mutations in the GLA gene. RESULTS: In 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified 2 unrelated patients (0.34%), both with the GLA mutation encoding P.N215S, the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a man aged 53 years and a woman aged 69 years, and demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy. After family screening, a total of 27 new Fabry disease patients aged 2-81 years were identified in the 2 families, including 12 individuals who are now receiving enzyme replacement therapy. CONCLUSIONS: These observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease-affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy.

Evaluation of chest barriers for protection against sudden death due to commotio cordis.

Blunt precordial blows triggering ventricular fibrillation (commotio cordis) represent a leading cause of sudden death in young athletes. Attention has focused on the primary prevention of these tragedies with chest barriers. The U.S. Commotio Cordis Registry was accessed to determine the likelihood of sudden death in athletes exposed to precordial blows while wearing chest protectors. Of 182 cases of commotio cordis, 85 (47%) occurred during practice or competition in organized sports. In 32 of these 85 competitive athletes (38%), fatal chest blows occurred despite the presence of potentially protective equipment. Athletes wore standard, commercially available chest barriers made of polymer foam covered by fabric or hard shells, generally perceived as protective from arrhythmic consequences of the blows. These events occurred in 4 sports: hockey (n = 13; 1 goalie), football (n = 10), lacrosse (n = 6; 3 goalies), and baseball (n = 3; all catchers). Scenarios included the failure of the padding to cover the precordium so that blows circumvented the protective barrier (n = 25) or projectiles that struck the chest barrier directly (n = 7). In conclusion, a significant proportion (about 40%) of sudden deaths reported in young competitive athletes due to blunt chest blows (commotio cordis) occur despite the presence of commercially available sports equipment generally perceived as protective.

Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy.

CONTEXT: Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. OBJECTIVE: To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. DESIGN, SETTING, AND PATIENTS: Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. MAIN OUTCOME MEASURE: Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. RESULTS: The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). CONCLUSIONS: In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management.

BACKGROUND: A previously under-recognized subset of hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) apical aneurysms is being identified with increasing frequency. However, risks associated with this subgroup are unknown. OBJECTIVES: The authors aimed to clarify clinical course and prognosis of a large cohort of HCM patients with LV apical aneurysms over long-term follow-up. METHODS: The authors retrospectively analyzed 1,940 consecutive HCM patients at 2 centers, 93 of which (4.8%) were identified with LV apical aneurysms; mean age was 56 ± 13 years, and 69% were male. RESULTS: Over 4.4 ± 3.2 years, 3 of the 93 patients with LV apical aneurysms (3%) died suddenly or of heart failure, but 22 (24%) survived with contemporary treatment interventions: 18 experienced appropriate implantable cardioverter-defibrillator discharges, 2 underwent heart transplants, and 2 were resuscitated after cardiac arrest. The sudden death (SD) event rate was 4.7%/year, which includes sudden death, successful resuscitation from cardiac arrest or appropriate ICD interventions triggered by VF or rapid VT. Notably, recurrent monomorphic ventricular tachycardia requiring ≥2 implantable cardioverter-defibrillator shocks occurred in 13 patients, including 6 who underwent successful radiofrequency ablation of the arrhythmic focus without ventricular tachycardia recurrence. Five non-anticoagulated patients experienced nonfatal thromboembolic events (1.1%/year), whereas 13 with apical clots and anticoagulation did not incur embolic events. There was no consistent relationship between aneurysm size and adverse HCM-related events. Rate of HCM-related deaths combined with life-saving aborted disease-related events was 6.4%/year, 3-fold greater than the 2.0%/year event rate in 1,847 HCM patients without aneurysms (p < 0.001). CONCLUSIONS: HCM patients with LV apical aneurysms are at high risk for arrhythmic sudden death and thromboembolic events. Identification of this phenotype expands risk stratification and can lead to effective treatment interventions for potentially life-threatening complications.

Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (ß-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy.

BACKGROUND: The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (ß-myosin heavy chain) and MYBPC3 (ß-myosin-binding protein C). Phenotypic differences between patients with mutations in these 2 genes have been inconsistent. Scarce data exist on the genotype-phenotype association as assessed by tomographic imaging using cardiac magnetic resonance imaging. METHODS AND RESULTS: Cardiac magnetic resonance imaging was performed on 358 consecutive genotyped hypertrophic cardiomyopathy probands at 5 tertiary hypertrophic cardiomyopathy centers. Genetic testing revealed a pathogenic mutation in 159 patients (44.4%). The most common genes identified were MYH7 (n=53) and MYBPC3 (n=75); 33.1% and 47% of genopositive patients, respectively. Phenotypic characteristics by cardiac magnetic resonance imaging of these 2 groups were similar, including left ventricular volumes, mass, maximal wall thickness, morphology, left atrial volume, and mitral valve leaflet lengths (all P=non-significant). The presence of late gadolinium enhancement (65% versus 64%; P=0.99) and the proportion of total left ventricular mass (%late gadolinium enhancement; 10.4±13.2% versus 8.5±8.5%; P=0.44) were also similar. CONCLUSIONS: This multicenter multinational study shows lack of phenotypic differences between MYH7- and MYBPC3-associated hypertrophic cardiomyopathy when assessed by cardiac magnetic resonance imaging. Postmutational mechanisms appear more relevant to thick-filament disease expression and outcome than the disease-causing variant per se.

Demographics and Epidemiology of Sudden Deaths in Young Competitive Athletes: From the United States National Registry.

BACKGROUND: Sudden deaths in young competitive athletes are tragic events, with high public visibility. The importance of race and gender with respect to sport and the diagnosis and causes of sudden death in athletes has generated substantial interest. METHODS: The US National Registry of Sudden Death in Athletes, 1980-2011, was accessed to define the epidemiology and causes of sudden deaths in competitive athletes. A total of 2406 deaths were identified in young athletes aged 19 ± 6 years engaged in 29 diverse sports. RESULTS: Among the 842 athletes with autopsy-confirmed cardiovascular diagnoses, the incidence in males exceeded that in females by 6.5-fold (1:121; 691 vs 1:787,392 athlete-years; P ≤.001). Hypertrophic cardiomyopathy was the single most common cause of sudden death, occurring in 302 of 842 athletes (36%) and accounting for 39% of male sudden deaths, almost 4-fold more common than among females (11%; P ≤.001). More frequent among females were congenital coronary artery anomalies (33% vs 17% of males; P ≤.001), arrhythmogenic right ventricular cardiomyopathy (13% vs 4%; P = .002), and clinically diagnosed long QT syndrome (7% vs 1.5%; P ≤.002). The cardiovascular death rate among African Americans/other minorities exceeded whites by almost 5-fold (1:12,778 vs 1:60; 746 athlete-years; P <.001), and hypertrophic cardiomyopathy was more common among African Americans/other minorities (42%) than in whites (31%; P ≤.001). Male and female basketball players were 3-fold more likely to be African American/other minorities than white. CONCLUSIONS: Within this large forensic registry of competitive athletes, cardiovascular sudden deaths due to genetic and/or congenital heart diseases were uncommon in females and more common in African Americans/other minorities than in whites. Hypertrophic cardiomyopathy is an under-appreciated cause of sudden death in male minority athletes.

Comparison of the Frequency of Sudden Cardiovascular Deaths in Young Competitive Athletes Versus Nonathletes: Should We Really Screen Only Athletes?

The issue of sudden death in young athletes and consideration for the most practical and optimal strategy to identify those genetic and/or congenital heart diseases responsible for these tragic events continues to be debated. However, proponents of broad-based and mandatory national preparticipation screening, including with 12-lead electrocardiograms have confined the focus to a relatively small segment of the youthful population who choose to engage in competitive athletic programs at the high school, college, and elite-professional level. Therefore, lost in this discussion of preparticipation screening of athletes is that the larger population of young people not involved in competitive sports (and, therefore, a priori are excluded from systematic screening) who nevertheless may die suddenly of the same cardiovascular diseases as athletes. To substantiate this hypothesis, we accessed the forensic Hennepin County, Minnesota registry in which cardiovascular sudden deaths were 8-fold more common in nonathletes (n = 24) than athletes (n = 3) and threefold more frequent in terms of incidence. The most common diseases responsible for sudden death were hypertrophic cardiomyopathy (n = 6) and arrhythmogenic right ventricular cardiomyopathy (n = 4). These data raise ethical considerations inherent in limiting systematic screening for unsuspected genetic and/or congenital heart disease to competitive athletes.

Relation of Doppler Tissue Imaging Parameters With Heart Failure Progression in Hypertrophic Cardiomyopathy.

Refractory progressive heart failure (HF) is becoming the predominant cause of mortality in nonobstructive hypertrophic cardiomyopathy (HC). To anticipate development of this important and often unpredictable clinical course, we investigated whether left ventricular diastolic dysfunction, assessed by echocardiographic Doppler parameters, could identify a subset of patients with HC without obstruction at rest who would experience progression of HF. Diastolic function parameters, assessed by Doppler tissue imaging (DTI), mitral inflow, and pulmonary venous flow were measured in 274 consecutive adult patients with HC evaluated from 2003 to 2007. DTI and other diastolic and clinical/demographic parameters were measured against the composite end point of HF/death, heart transplantation, or progression to advanced New York Heart Association functional class III/IV symptoms and sudden death (SD)/implantable defibrillator (ICD) interventions. HF end points were reached in 19 of 274 patients (7%) over a follow-up period of 4.0 ± 2.3 years. Variables significantly associated with HF outcome by univariate analysis included male gender, initial New York Heart Association class II, lower ejection fraction, and reduced septal and lateral e' mitral annular tissue velocities. Multivariable analysis showed only a reduced lateral e' mitral annular tissue velocity to be independently associated with the composite HF end points (HR 0.77; 95% CI 0.65 to 0.91; p = 0.003). In addition, estimated pulmonary arterial systolic pressure and extensive late gadolinium enhancement by magnetic resonance were also associated with HF outcome (p = 0.04 and p <0.001, respectively). No Doppler (or clinical) variable was associated with SD/appropriate ICD interventions. In conclusion, in HC without outflow obstruction at rest, diastolic dysfunction, evidenced by DTI-reduced lateral e' mitral annular tissue velocity, was associated with adverse long-term HF outcome but was unrelated to SD. This echocardiographic marker provides a potential noninvasive strategy for anticipating progressive HF in this HC patient group.