Original ContributionsHypertrophic cardiomyopathy and sudden death in the young: Pathologic evidence of myocardial ischemia☆
Abstract
The mechanism underlying cardiac arrest in patients with hypertrophic cardiomyopathy (HC) is intriguing. In the clinical setting, myocardial ischemia has long been incriminated, particularly in the young. Among 274 cardiovascular sudden deaths in the young ([le ]35 years), 19 (7.0%), 14 males and 5 females, median age 23 years, had HC. Familial occurrence of HC was ascertained in 3 (16%). SD occurred on effort in 6 (31%). Previous syncope occurred in 5 and palpitations in 3. Basal electrocardiogram (ECG) was abnormal in 7 of 8 available cases. Hypertrophy was septal asymmetric in 14. Gross examination showed large isolated or multiple septal scars in 11 (58%); at histomorphometry, the mean percent area of fibrosis of the septal myocardium was 18.6 [plusmn] 6. Four showed a deep intramyocardial course of the left anterior descending coronary artery. At histology, myocardial disarray involved 30 [plusmn] 16% of the septal myocardium; evidence of acute-subacute myocardial necrosis was present in 14 (74%), 1 of them with a regional acute myocardial infarction. By comparing hearts with (n = 11) and without (n = 8) areas of scar-type fibrosis, we found a statistically significant difference in terms of age (25.5 [plusmn] 5.4 v 15.5 [plusmn] 12.4 years, P = .04), septal thickness (25.4 [plusmn] 5.4 v 15.4 [plusmn] 4.9 mm, P [lt ] .001), percent increase of septal thickness versus normal value for age and sex (46.2 [plusmn] 15 v 25.2 [plusmn] 13.6%, P [plusmn] .01) and mean score of small vessel disease (1.7 [plusmn] 0.4 v 1.2 [plusmn] 0.4, P = .04). Linear regression analysis showed a positive correlation of percent area of replacement fibrosis with septal thickness (P = .01) and with mean score of small vessel disease (P [lt ] .01). In conclusion, our pathologic findings of ischemic damage, either acute-subacute or in the form of fibrotic scars, support the clinical evidence that ischemia occurs in the natural history of HC and may contribute to life-threatening electrical instability. HUM PATHOL 31:988-998.
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Hypertrophic cardiomyopathy in a dog: a systematic diagnostic approach
2024, Journal of Veterinary CardiologyA seven-year-old female neutered Parson Russel terrier was referred for syncopal episodes. An electrocardiogram revealed paroxysmal atrial flutter followed by periods of sinus arrest, suggesting sick sinus syndrome. Echocardiography showed severe biventricular wall thickening (hypertrophic cardiomyopathy (HCM) phenotype) with no signs of fixed or dynamic left ventricular outflow tract obstruction. Blood pressure, abdominal ultrasound, serum total thyroxin and thyroid-stimulating hormone, and insulin-like growth factor-1 were all within normal limits. Cardiac troponin I was elevated (1.7 ng/mL, ref<0.07). Serological tests for common infectious diseases were negative. A 24-h Holter confirmed that the syncopal episodes were associated with asystolic pauses (sinus arrest after runs of atrial flutter) ranging between 8.5 and 9.6 s. Right ventricular endomyocardial biopsies (EMB) were performed at the time of pacemaker implantation to assess for storage or infiltrative diseases that mimic HCM in people. Histological analysis of the EMB revealed plurifocal inflammatory infiltrates with macrophages and lymphocytes (CD3+ > 7/mm2) associated with myocyte necrosis, but no evidence of myocyte vacuolisation or infiltrative myocardial disorders. These findings were compatible with myocardial ischaemic injury or acute lymphocytic myocarditis. Molecular analysis of canine cardiotropic viruses were negative. The dog developed refractory congestive heart failure and was euthanised 16 months later. Cardiac post-mortem examination revealed cardiomyocyte hypertrophy and disarray with diffuse interstitial and patchy replacement fibrosis, and small vessel disease, confirming HCM. We described a systemic diagnostic approach to an HCM phenotype in a dog, where a diagnosis of HCM was reached by excluding HCM phenocopies.
The Lancet Commission to reduce the global burden of sudden cardiac death: a call for multidisciplinary action
2023, The LancetDespite major advancements in cardiovascular medicine, sudden cardiac death (SCD) continues to be an enormous medical and societal challenge, claiming millions of lives every year. Efforts to prevent SCD are hampered by imperfect risk prediction and inadequate solutions to specifically address arrhythmogenesis. Although resuscitation strategies have witnessed substantial evolution, there is a need to strengthen the organisation of community interventions and emergency medical systems across varied locations and health-care structures. With all the technological and medical advances of the 21st century, the fact that survival from sudden cardiac arrest (SCA) remains lower than 10% in most parts of the world is unacceptable. Recognising this urgent need, the Lancet Commission on SCD was constituted, bringing together 30 international experts in varied disciplines. Consistent progress in tackling SCD will require a completely revamped approach to SCD prevention, with wide-sweeping policy changes that will empower the development of both governmental and community-based programmes to maximise survival from SCA, and to comprehensively attend to survivors and decedents’ families after the event. International collaborative efforts that maximally leverage and connect the expertise of various research organisations will need to be prioritised to properly address identified gaps. The Commission places substantial emphasis on the need to develop a multidisciplinary strategy that encompasses all aspects of SCD prevention and treatment. The Commission provides a critical assessment of the current scientific efforts in the field, and puts forth key recommendations to challenge, activate, and intensify efforts by both the scientific and global community with new directions, research, and innovation to reduce the burden of SCD worldwide.
Sudden Death Risk Assessment in Hypertrophic Cardiomyopathy Across the Lifespan: Reconciling the American and European Approaches
2023, Cardiac Electrophysiology ClinicsHigh-Sensitivity Cardiac Troponin T Elevation in Hypertrophic Cardiomyopathy Is Associated With Ventricular Arrhythmias
2023, Mayo Clinic ProceedingsTo investigate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) levels and sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM).
A referral HCM population with prospectively obtained hs-cTnT concentration from March 1, 2018, to April 23, 2020, was reviewed. Patients with end-stage renal disease or an abnormal hs-cTnT level not collected in an outpatient protocolled fashion were excluded. The hs-cTnT level was compared with demographic characteristics, comorbidities, conventional HCM-associated SCD risk factors, imaging, exercise testing, and prior cardiac events.
Of 112 included patients, 69 (62%) had an elevated hs-cTnT concentration. The level of hs-cTnT correlated with known risk factors for SCD, including nonsustained ventricular tachycardia (P=.049) and septal thickness (P=.02). When patients were stratified by having a normal vs an elevated hs-cTnT concentration, patients with elevated hs-cTnT concentration were more likely to have experienced an implantable cardioverter-defibrillator discharge for ventricular arrhythmia, ventricular arrhythmia with hemodynamic instability, or cardiac arrest (incidence rate ratio, 2.96; 95% CI, 1.11 to 10.2). When sex-specific hs-cTnT cutoffs were removed, this association was no longer present (incidence rate ratio, 1.50; 95% CI, 0.66 to 3.60).
In a protocolized, outpatient HCM population, hs-cTnT elevations were common and were associated with more arrhythmic expressivity of the HCM substrate as indicated by previous ventricular arrhythmias and appropriate implantable cardioverter-defibrillator shocks only when sex-specific hs-cTnT cutoffs were used. Further research should use different hs-cTnT reference values by sex to determine whether an elevated hs-cTnT value is an independent risk factor for SCD in patients with HCM.
Detecting Regional Fibrosis in Hypertrophic Cardiomyopathy: The Utility of Myocardial Strain Based on Cardiac Magnetic Resonance
2023, Academic RadiologyThe value of myocardial strain for reflecting fibrosis in patients with hypertrophic cardiomyopathy (HCM) on cardiac magnetic resonance (CMR) has not been definite. We aim to explore whether there are underlying non-contrast parameters to evaluate myocardial fibrosis and screen which may be the best.
We retrospectively included 127 HCM patients (89 men; average age 46.6 ± 15.6 years) and 30 healthy controls (20 men; average age 52.0 ± 13.2 years) who have undergone late gadolinium enhancement (LGE) CMR. Next, 127 HCM patients were divided randomly into two sets including training cohort and validation cohort. Strain and imaging parameters were measured and analyzed statistically.
Based on univariate and multivariate analysis, segmental circumferential strain (SCS) (p < 0.001) and maximal wall thickness (MWT) (p < 0.001) may differentiate myocardial segments with or without LGE as significant biomarkers for both sets. The area under the curve (AUC) was 0.803 (95% CI 0.785-0.820) for SCS and 0.777 (95% CI 0.759-0.795) for MWT to identify myocardial fibrosis. When combining SCS >-13.9% and MWT >16.4mm, the specificity of the model (AUC = 0.779; 95% CI 0.760-0.796) achieved the highest 93.9%, with a sensitivity of 61.8%.
Strain analysis in HCM holds promise for myocardial fibrosis detection and SCS is the best strain parameter based on CMR. Nevertheless, the model of combining SCS and MWT could achieve the highest specificity for fibrotic diagnosis.
Effect of beta-blockers and exercise restriction on the prevention of sudden cardiac death in pediatric hypertrophic cardiomyopathy
2023, Journal of CardiologyRisk assessment tools and effective prevention strategies for sudden cardiac death (SCD) in pediatric patients with hypertrophic cardiomyopathy (HCM) have not been established. This study aimed to evaluate the efficacy of beta-blockers and exercise restriction for SCD prevention in this population.
We retrospectively reviewed the medical records of patients aged <18 years who were diagnosed with HCM at our center between January 1996 and December 2021. SCD and aborted SCD were defined as SCD equivalents. We divided patients based on whether they were prescribed beta-blockers or exercise restriction and compared the outcomes among the groups. The primary outcome was the overall survival (OS), and the secondary outcome was the cumulative SCD equivalent rate. Outcomes were analyzed using Kaplan–Meier curves and Cox proportional hazard analysis. We also compared patients according to the occurrence of SCD equivalents to identify SCD risk predictors.
Among the 43 included patients [mean age, 7.7 (1.6–12.1) years; 23 male individuals], SCD equivalents occurred in 13 patients over 11.2 (4.5–15.6) years of follow-up, among whom 12 were resuscitated and 1 died. The OS rate was significantly higher in the beta-blocker and exercise restriction groups than in the non-beta-blocker and non-exercise restriction groups (81.3 % vs. 19.1 %, p < 0.01 and 57.4 % vs. 12.7 %, p < 0.01, respectively). Among the 13 patients with SCD equivalents, 5 had 9 recurrent SCD equivalents. A significant difference was observed between the SCD equivalent and non-SCD equivalent groups in the history of suspected arrhythmogenic syncope (p < 0.01) in the univariable but not in the multivariable analysis.
Beta-blockers and exercise restriction may decrease the risk of SCD in pediatric patients with HCM and should be considered for SCD prevention in this population, particularly because predicting SCD in these patients remains challenging.
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Supported by the Veneto Region, Venice, and MURST, Rome, Italy