Author + information
- Gherardo Finocchiaro, MD,
- Michael Papadakis, MD,
- Gaia Tanzarella, MD,
- Harshil Dhutia, BSc,
- Chris Miles, BSc, MBBS,
- Maite Tome, MD, PhD,
- Elijah R. Behr, MA, MBBS, MD,
- Sanjay Sharma, BSc, MBChB, MD∗ ( and )
- Mary N. Sheppard, MBBCH, BAO, BSc, MD
- ↵∗Cardiology Clinical and Academic Group, St. George’s University of London, Cranmer Terrace, London SW17 0RE, United Kingdom
Hypertrophic cardiomyopathy (HCM) is an inherited cardiomyopathy that is characterized by left ventricular hypertrophy, myocyte disarray at histology, and a propensity for fatal cardiac arrhythmias (1). Sudden cardiac death (SCD) is the most feared complication, particularly among individuals in the second and third decade of life, and several clinical predictors are used to identify high-risk patients who may benefit from an implantable cardioverter-defibrillator (2). Unfortunately, SCD may be the first manifestation of the disease in apparently healthy and asymptomatic individuals, including athletes.
The aim of the study was to report the characteristics and circumstances of death in a large cohort of decedents of SCD with a diagnosis of HCM at autopsy. We reviewed a database of 5,100 consecutive cases of SCD referred to our specialist cardiac pathology center between January 1994 and March 2017 and identified 196 (4%) cases with HCM. SCD was defined as death from a cardiovascular cause within 12 h of apparent well-being. Clinical information was obtained from referring coroners who were asked to complete a questionnaire inquiring about the demographic characteristics of the deceased subject, medical history, family history, and circumstances of death. All cases underwent detailed autopsy evaluation of the heart, including histological analysis, by expert cardiac pathologists. The heart weight was recorded in grams, and ventricular wall thickness and internal cavity dimensions were measured at mid-ventricular level. A minimum of 10 blocks of tissue were taken for histological analysis as reported previously (3). Results are expressed as mean ± SD for continuous variables or as number of cases and percentage for categorical variables.
SCD was the first manifestation of HCM in the majority (78%) of cases. The majority of decedents were male (n = 143 [73%]) (Figure 1). The mean age at death was 43 ± 18 years, and 20 (10%) individuals who died suddenly were >60 years of age.
Cardiac symptoms were reported in 50 cases (26%): chest pain (n = 14 [7%]), palpitations (n = 14 [7%]), dyspnea (n = 10 [5%]), and syncope (n = 9 [5%]). A pre-mortem diagnosis of HCM was known in 43 (22%) patients, of whom 15 had previous cardiac symptoms. One patient had a concomitant diagnosis of Wolff-Parkinson-White syndrome, and one had an implantable cardioverter-defibrillator. Death during exercise or during emotional stress occurred in 46 individuals (23%), who were predominantly male (89%) and with a mean age of 30 ± 11 years (age range, 11 to 54 years). Conversely, 150 (77%) individuals died at rest or during daily activities, including 26 (13%) who died during sleep. Twenty (10%) individuals were recreational or competitive athletes.
The mean heart weight was 558 ± 186 g. The average left ventricular wall thickness was 21.4 ± 6.3 mm at the level of the interventricular septum, 19 ± 5.7 mm at the anterolateral wall, and 17.4 ± 4.7 mm at the posterior wall; 19 (10%) patients had a maximal wall thickness ≥30 mm. Left ventricular fibrosis was detected in 115 (59%) patients, mainly at the level of the interventricular septum and the anterolateral walls. Associated coronary artery stenosis (>70% of the lumen) was recorded in 5 patients (2 of whom were >60 years of age).
Our study reports on one of the largest autopsy cohorts of individuals with HCM in which the post-mortem was performed by an expert cardiac pathologist following a standardized protocol. Most deaths occurred at rest, and only 26% of subjects had reported cardiac symptoms prior to death, underscoring how HCM often remains undiagnosed in the community. SCD affected individuals with HCM at all ages (even those >60 years of age), with a peak between 30 and 50 years.
Most individuals diagnosed with HCM during life were probably not considered at sufficiently high risk to warrant an implantable cardioverter-defibrillator, which confirms the need for an improvement in risk stratification protocols and mechanisms implicated in the development of fatal arrhythmias in HCM (2). In contrast with arrhythmogenic cardiomyopathy, where there is a clear association between intense exercise and increased risk of SCD, in our case series, the majority of SCD in HCM occurred at rest or during usual activities. Current recommendations advise against competitive sport in all individuals with HCM, based on data that are derived largely from adolescents or young adults who have died during exercise (4). We observed that such deaths were confined to young male subjects and call for a more liberal approach in other exercising populations. Indeed, a recent study suggests that moderate exercise may be beneficial and safe in patients with HCM (5).
In summary, SCD was the first manifestation of HCM in the majority (78%) of cases, and only 50 (26%) decedents had reported cardiac symptoms prior to death. Death during exercise or during emotional stress occurred in 46 individuals (23%) who were predominantly male (89%) and young (age 30 ± 11 years). The diagnosis of HCM was often made only after death (78% of cases).Sudden death from HCM mostly occurred during rest or usual life activities (77% of cases) other than strenuous exercise, suggesting that exercise may be a risk factor for fatal arrhythmias only in young male subjects.
The early identification of HCM in asymptomatic individuals is the first step for risk stratification for SCD. Better strategies are required for detecting asymptomatic individuals with HCM. Although previous studies have suggested a high prevalence of HCM in athletes experiencing SCD, it is possible that this increased risk is limited to young males. Future prospective randomized studies should assess the benefits and harms/risks of exercise in patients with HCM.
It is possible that we may have overestimated the proportion of individuals with HCM who presented with SCD as the first manifestation because pathologists may not have referred decedents with an established pre-mortem diagnosis of HCM to our expert center. However, our center usually receives a high volume of referrals from SCD (>400 per year), in mostly young decedents, including athletes. In addition, given the rarity of SCD in young subjects, it is likely that our cohort provides a genuine representation of SCD in HCM.
Please note: Funding was received by Cardiac Risk in the Young (CRY) and the Charles Wolfson Charitable Trust. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2019 American College of Cardiology Foundation
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