Projecting the Long-term Clinical Value of Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy in the United States: An Assessment of Net Health Benefit.

PURPOSE: The aim of the study was to project the long-term net health benefits of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States. METHODS: A Markov model with 4 mutually exclusive health states (New York Heart Association [NYHA] functional classes I, II, and III/IV and death) was developed to project the life-years (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for patients with symptomatic obstructive HCM receiving mavacamten with or without ß-blocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or without BB or CCB monotherapy. The model simulated a patient cohort with a starting age of 59 years and 41% women. Transition probabilities across NYHA functional classes were estimated using data from the Phase III Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated after week 30. The mortality risks of NYHA functional class I were assumed to be the age- and sex-specific mortality risks of the US general population. The mortality risks for NYHA class II and III/IV were estimated using those for class I in conjunction with the relative mortality risks derived using patients with obstructive HCM from a large real-world registry. Health state utilities for each treatment were estimated from EXPLORER-HCM. Both LYs and QALYs were aggregated over a lifetime for each treatment arm, discounted at 3% annually, and compared between the 2 arms. Sensitivity analyses were conducted to evaluate the robustness of the model findings. FINDINGS: Over a lifetime, treatment with mavacamten with or without BB or CCB monotherapy was associated with 3.67 incremental LYs compared with placebo with or without BB or CCB monotherapy (13.00 vs 9.33 LYs). Compared with individuals in the placebo group, patients in the mavacamten group were projected to spend 6.17 additional LYs in NYHA functional class I and 0.04 and 2.46 fewer LYs in NYHA functional classes II and III/IV, respectively. With utilities incorporated, mavacamten with or without BB or CCB monotherapy was associated with 4.17 additional QALYs compared with placebo with or without BB or CCB monotherapy (11.74 vs 7.57 QALYs). In the sensitivity analyses, incremental benefits ranged from 1.55 to 6.21 LYs and from 2.48 to 6.19 QALYs across the scenarios. IMPLICATIONS: This model projected substantial net health benefits associated with mavacamten for symptomatic obstructive HCM owing to improved patient survival and quality of life. The projected QALY gain underscored the likely long-term clinical value of mavacamten in symptomatic obstructive HCM.

Epidemiology of Pediatric Hypertrophic Cardiomyopathy in a 10-Year Medicaid Cohort.

The epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM) needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, and mortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17 years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007-2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24 months. The accrued 10-year prevalence rate for pediatric HCM was 1.2/1,000,000 and the annual incidence rate (CY 2010) was 1.3/100,000. Cardiac-related mortality was 2.9% in those who died cohort (N = 10); 70.0% of those who died were ≤ 13 months of age. Arrhythmia was diagnosed in 30.7% of the cohort, heart failure in 12.4%, and low birth weight in 8.8%. Inborn errors of metabolism were diagnosed in 8.0% of the cohort; malformation syndromes in 13.1%, and neuromuscular disorders in 2.9%; therefore, 75.9% were classified as idiopathic HCM. Our findings are somewhat higher than extant study estimates but update and augment them in representing a Southeast US statewide service system.

Cost-Effectiveness of Implantable Cardioverter-Defibrillators in Children with Cardiac Conditions Associated with Risk for Sudden Cardiac Death.

Children at high risk for sudden cardiac death (SCD) receive implantable cardioverter-defibrillators (ICD) for prevention, but the cost effectiveness of ICDs in children at intermediate risk is unclear. Our objective was to create a cost-effectiveness model to compare costs and outcomes in children at risk of SCD, with and without ICD. Utilizing hypertrophic cardiomyopathy as the proxy disease, a theoretical cohort of 8150 children was followed for 69 years. Model inputs were derived from the literature, with an incremental cost-effectiveness ratio (ICER) willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY) used to delineate cost effectiveness. Outcomes included prevalence of severe neurological morbidity (SNM), SCD, cost, and QALYs. In children at intermediate risk of SCD (4-6% over 5 years), ICD resulted in 56 fewer cases of SNM, 2686 fewer deaths. In children at high risk (> 6% over 5 years), ICD placement resulted in 74 fewer cases of SNM and 3663 fewer deaths from cardiac causes. The costs of ICD were higher, but placement was cost effective with an ICER of $3009 per QALY in intermediate risk children, but ICD therapy was a dominant strategy in high-risk children. Sensitivity analysis demonstrated ICD placement was cost-effective until the annual probability of SCD was < 0.22%. The model was robust over a wide range of values. For children at risk of SCD, prophylactic ICD implantation is cost effective, resulting in improved outcomes and increased QALYs, despite increased costs. These findings highlight the economic benefits of ICD utilization in this population.

Access and Outcomes Among Hypertrophic Cardiomyopathy Patients in a Large Integrated Health System.

Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. Current guidelines endorse management in expert centers, but patient socioeconomic status can affect access to specialty care. The effect of socioeconomic status and specialty care access on HCM outcomes has not been examined. Methods and Results We conducted a retrospective cohort study that examined outcomes among HCM patients receiving care in the Yale New Haven Health System between June 2011 and December 2017. Patients were assigned to lower or higher socioeconomic status groups (LSES/HSES) based on medical insurance provider and to receivers of specialty care (SC) at Yale's Inherited Cardiomyopathy clinic or general cardiology care (GC). The primary outcome was all-cause death, and the secondary outcome was all-cause hospitalization. We identified 953 HCM patients; 820 (86%) were HSES and 133 (14%) were LSES. Forty-three (4.5%) patients died from cardiac and noncardiac causes. LSES patients within the general cardiology care cohort had significantly higher all-cause mortality compared with HSES patients (adjusted hazard ratio, [95% CI]=10.06 [4.38-23.09]; P<0.001). This was not noted in the specialty care cohort (adjusted hazard ratio, [95% CI]=2.87 [0.56-14.73]; P=0.21). The moderator effect of specialty care on mortality difference between LSES versus HSES, however, did not reach statistical significance (hazard ratio, 0.29 [0.05-1.77]; P=0.18). Specialist care was associated with increased hospitalization (adjusted hazard ratio, [95% CI]=3.28 [1.11-9.73]; P=0.03 for LSES; 2.19 [1.40-3.40]; P=0.001 for HSES). Conclusions Socioeconomically vulnerable HCM patients had higher mortality when not referred to specialty care. Further study is needed to understand the underlying causes.

Impact of gender on heart failure presentation in non-obstructive hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that represents a broad spectrum of morphologic features and clinical presentations. However, little is known about the impact of gender differences in heart failure (HF) development in non-obstructive HCM. We assessed clinical and echocardiographic parameters according to gender in patients with non-obstructive HCM and evaluated the impact of gender on HF presentation and cardiovascular (CV) outcomes in this population. We investigated 202 consecutive patients with non-obstructive HCM. Clinical parameters and conventional echocardiographic measurements including tissue Doppler measurements were evaluated and compared according to gender. Additionally, left ventricular (LV) deformation was assessed with global longitudinal strain (GLS) utilizing 2D speckle tracking software. Of the 202 patients (age = 63 ± 14 years, male: female = 141: 61), 51 patients (24.8%) presented with HF and female patients had HF more frequently (52.5% vs. 12.8%, P < 0.001). Females were older, had a higher prevalence of atrial fibrillation, had increased left atrial volume (LAV), and a higher ratio of early diastolic mitral inflow to early annular velocity (E/e') than males (70 ± 12 years vs. 59 ± 14 years, P < 0.001 for age; 51.4 ± 19.3 mL/m2 vs. 40.0 [Formula: see text] 13.4 mL/m2, P < 0.001 for indexed LAV; 17.2 [Formula: see text] 6.0 vs. 13.0 [Formula: see text] 4.3, P < 0.001 for E/e'). While LV maximal thickness and LV ejection fraction were comparable between men and women, GLS was decreased significantly in female patients (- 13.5 [Formula: see text] 3.4% vs. - 15.6 [Formula: see text] 4.0%, P = 0.001 for GLS). Even after adjusting for clinical factors, female was independently associated with HF presentation (Odd ratio 5.19, 95% CI 2.24-12.03, P < 0.001). During a median follow-up duration 34.0 months, 20 patients (9.9%) had HF hospitalization or CV death. In a multivariable analysis, female gender was associated with higher risk of the composite of HF hospitalization or CV death and HF hospitalization alone than male (Adjusted hazard ratio [HR] = 3.31, 95% CI 1.17-9.35, P = 0.024 for primary composite outcome of HF hospitalization or CV death; adjusted HR = 4.78, 95% CI 1.53-14.96, P = 0.007 for HF hospitalization). In patients with non-obstructive HCM, female patients presented with HF more frequently and showed a higher risk of CV events than male patients. LA volume, E/e' and LV mechanics were different between the genders, suggesting that these might contribute to greater susceptibility to HF in women with HCM.

Clinical presentation and survival of childhood hypertrophic cardiomyopathy: a retrospective study in United Kingdom.

AIMS: Understanding the spectrum of disease, symptom burden and natural history are essential for the management of children with hypertrophic cardiomyopathy (HCM). The effect of changing screening practices over time has not previously been studied. This study describes the clinical characteristics and outcomes of childhood HCM over four decades in a well-characterized United Kingdom cohort. METHODS AND RESULTS: Six hundred and eighty-seven patients with HCM presented at a median age of 5.2 years (range 0-16). Aetiology was: non-syndromic (n = 433, 63%), RASopathy (n = 126, 18.3%), Friedreich's ataxia (n = 59, 8.6%) or inborn errors of metabolism (IEM) (n = 64, 9%). In infants (n = 159, 23%) underlying aetiology was more commonly a RASopathy (42% vs. 11.2%, P < 0.0001) or IEM (18.9% vs. 6.4% P < 0.0001). In those with familial disease, median age of presentation was higher (11 years vs. 6 years, P < 0.0001), 141 (58%) presented <12 years. Freedom from death or transplantation was 90.6% (87.9-92.7%) at 5 years (1.5 per 100 patient years) with no era effect. Mortality was most frequently sudden cardiac death (SCD) (n = 20, 2.9%). Children diagnosed during infancy or with an IEM had a worse prognosis (5-year survival 80.5% or 66.4%). Arrhythmic events occurred at a rate of 1.2 per 100 patient years and were more likely in non-syndromic patients (n = 51, 88%). CONCLUSION: This national study describes a heterogeneous disease whose outcomes depend on the age of presentation and aetiology. Overall mortality and SCD rates have not changed over time, but they remain higher than in adults with HCM, with events occurring in syndromic and non-syndromic patients.

Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).

Background: A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed to improve patient management and outcomes. The Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established to provide the scale of data required to address these issues, aggregating longitudinal datasets curated by eight international HCM specialty centers. Methods: Data on 4591 HCM patients (2763 genotyped), followed for a mean of 5.4±6.9 years (24,791 patient-years; median [interquartile range] 2.9 [0.3-7.9] years) were analyzed regarding cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator (ICD) therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association Functional Class III/IV symptoms (all comprising the overall composite endpoint), and left ventricular ejection fraction (LVEF)<35%. Outcomes were analyzed individually and as composite endpoints. Results: Median age of diagnosis was 45.8 [30.9-58.1] years and 37% of patients were female. Age of diagnosis and sarcomere mutation status were predictive of outcomes. Patients <40 years old at diagnosis had a 77% [95% confidence interval: 72%, 80%] cumulative incidence of the overall composite outcome by age 60, compared to 32% [29%, 36%] by age 70 for patients diagnosed >60 years. Young HCM patients (20-29 years) had 4-fold higher mortality than the general United States population at a similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had two-fold greater risk for adverse outcomes compared to patients without mutations; sarcomere variants of uncertain significance were associated with intermediate risk. Heart failure and atrial fibrillation were the most prevalent adverse events, although typically not emerging for several years after diagnosis. Ventricular arrhythmias occurred in 32% [23%, 40%] of patients <40 years at diagnosis, but in 1% [1%, 2%] >60 years. Conclusions: The cumulative burden of HCM is substantial and dominated by heart failure and atrial fibrillation occurring many years following diagnosis. Young age of diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes. These findings highlight the need for close surveillance throughout life, and the need to develop disease-modifying therapies.

Risk assessment of the occurrence of sudden death related to hypertrophic cardiomyopathy in Dakar.

AIM: The aim of this study was to assess of the risk of sudden death in a population of hypertrophic cardiomyopathy patients in Dakar. METHODS: This was a transverse study at the cardiology clinic of Aristide Le Dantec Hospital from January 2014 to June 2015. We used the European Society of Cardiology risk score to calculate this risk. RESULTS: The average age of patients was 53 years. Unexplained syncope was found in two patients and two others had a family history of sudden death. The septal hypertrophy average was 20.9 mm. Seven patients had left intraventricular obstruction. One patient had a high risk of sudden death, three had intermediate risk and 13 had low risk. Competitive sport was not allowed, 13 patients were under medical treatment, one had an implantable cardioverter defibrillator and two had no treatment. CONCLUSION: Our study highlighted a low and intermediate risk of the occurrence of sudden death at five years. One patient had a high risk of sudden death.

Assessment of the association between the presence of fragmented QRS and the predicted risk score of sudden cardiac death at 5 years in patients with hypertrophic cardiomyopathy.

OBJECTIVE: It has been shown that the presence of fragmented QRS (fQRS) is associated with poor prognosis in many cardiovascular diseases and in patients with hypertrophic cardiomyopathy (HCM). However, no study has shown an association with the absolute risk score of sudden cardiac death. The aim of this study was to determine the relationship between QRS and the predicted risk score of sudden cardiac death at 5 years (HCM Risk-SCD) in HCM patients. METHODS: In total, 115 consecutive HCM patients were included in this prospective observational study. The patients were divided into two groups according to the presence [fQRS(+) group (n=65)] or absence [fQRS(-) group (n=50)] of fQRS on a 12-lead electrocardiogram (ECG). RESULTS: The HCM Risk-SCD (%) HCM Risk-SCD (>6%) values and some echocardiographic parameters, including ventricular extrasystole, ventricular tachycardia, cardiopulmonary resuscitation, implantable cardioverter defibrillator implantation, appropriate shock, and heart failure at the time of admission, were significantly higher in the fQRS(+) group than in the fQRS(-) group (all p<0.05). Both univariate and multivariate analyses revealed fQRS and New York Heart Association (NYHA) class as independent predictors of HCM Risk-SCD. In a receiver operating characteristic (ROC) curve analysis, an HCM Risk-SCD value of >4 was identified as an effective cut-off point in fQRS for HCM. An HCM Risk-SCD value of >4 yielded a sensitivity of 77% and a specificity of 76%. CONCLUSION: fQRS is determined to be an independent high-risk indicator of HCM Risk-SCD. It seems to be associated with increased ventricular arrhythmias and some echocardiographic parameters.

Cardiac CT assessment of left ventricular mass in mid-diastasis and its prognostic value.

AIMS: To determine the influence of cardiac motion on measurements of left ventricular (LV) mass obtained with 64-slice computed tomography (CT) and to elucidate the prognostic value of LV mass on major adverse cardiac events (MACE) and all-cause mortality. Increased LV mass has been linked with MACE. Although Cardiac CT allows measurement of LV anatomy, it is susceptible to motion artefacts often requiring image acquisition during diastasis. There is a need to understand variability in LV mass measurements across phases of the cardiac cycle, and whether mid-diastolic measurements have prognostic value. METHODS AND RESULTS: The study comprised two equally sized cohorts of patients that had undergone retrospectively gated cardiac CT: patients who had MACE and/or all-cause death at follow-up and a matched (age, sex, and risk factors) event-free cohort. LV mass was measured at mid-diastole, end-diastole, and end-systole. Correlation and agreement between phases were determined. The incremental value of mid-diastolic hypertrophy (LVH) over the National Cholesterol Education Programme (NCEP) risk was performed for LV mass indices normalized to body surface area (LVMIBSA) or weight (LVMIWeight). Of 166 patients, 31.3% experienced MACE and 28.9% died of any cause (follow-up 22.9 ± 13.4 months). LV mass at all cardiac phases were strongly correlated (r > 0.94). Mean mid-diastolic LVMIBSA was higher in the cohort with events (93.7 vs. 80.7 g/m2, P= 0.008) as was LVMIWeight (2.26 vs. 1.88 g/kg, P = 0.001). LVMIBSA and LVMIWeight had prognostic value incremental to NCEP with 1.85 and 2.47 hazard ratios, respectively. CONCLUSIONS: Measurement of LV mass can be obtained by cardiac CT images obtained at mid-diastasis. LV mass measurements obtained at mid-diastasis have prognostic value.

Septal Ablation and Hypertrophic Obstructive Cardiomyopathy: 7 Years US Experience.

BACKGROUND: Septal ablation (SA) is a key modality for left ventricular outflow tract gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM) patients with refractory symptoms. The primary objective of our study was to evaluate post-procedural mortality, complications, length of stay (LOS), and cost of hospitalization following SA. METHODS: We queried the Nationwide Inpatient Sample (NIS) between 2005 and 2011 using the ICD9 procedure code of 37.34 for ablation of heart tissue. Only adult patients with HOCM (ICD-9-CM: 425.1) were included. Patients with any arrhythmia diagnosis or open surgical ablation procedure code were excluded. Hierarchical mixed effects models were generated in order to identify the independent multivariate predictors of outcomes. RESULTS: A total of 358 SAs were available for analysis. There was no reported mortality during the study period; permanent pacemaker implantation rate was 8.7%. Highest hospital volume tertile (OR, 95%CI, P- value) predicted significantly lower post-procedural complications (0.51, 0.26-0.98, P = 0.04). Univariate analysis of highest versus lowest tertile of hospital volume showed significant decrease in LOS (2.6 days vs. 3.8 days, P<0.01) and non-significant decrease hospitalization costs (16,800$ vs. 19,500$, P = 0.29). CONCLUSIONS: SA is a safe procedure and associated with low peri- procedural mortality rate. A higher burden of baseline comorbidities is associated with worse outcomes while higher annual hospital volume is associated with lower rate of post-procedural complications, length of stay, and cost of care following SA.

[Assessment of risk of sudden cardiac death in patients with hypertrophic cardiomyopathy]. / Risikostratifizierung bei familiärer hypertropher Kardiomyopathie anhand der neuen ESC-Leitlinien.

Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterized by left ventricular hypertrophy with or without concomitant outflow tract obstruction. Identification of patients with HCM who are at high risk of sudden cardiac death (SCD) is crucial as those patients are likely to benefit from an implantable cardioverter defibrillator (ICD). Based on the HCM Risk-SCD study published in 2013, that included 3675 HCM patients with 24 313 years of follow up, a new clinical risk prediction model for sudden cardiac death was developed. This model was included in the recently released 2014 ESC guidelines. This review summarizes the changes in the prediction model and the resulting recommendations and discusses potential risks and limitations of the new score.

Independent Assessment of the European Society of Cardiology Sudden Death Risk Model for Hypertrophic Cardiomyopathy.

Risk stratification for sudden death (SD) is an essential component of hypertrophic cardiomyopathy (HC) management, given the proven effectiveness of implantable cardioverter-defibrillators (ICD) for preventing SD. Although highly effective in identifying high-risk patients, current stratification algorithms remain incomplete and novel strategies are encouraged. In this regard, reliability of the statistical model to predict SD risk in HC, as recommended by the recent European Society of Cardiology (ESC) guidelines, was retrospectively tested in an independent cohort of 1,629 consecutive patients with HC aged ≥16 years. Of the 1,629 patients, 35 incurred SD events, but only 4 of these (11%) had high predictive risk scores >6%/5 years consistent with an ICD recommendation, and most (60%; n = 21) had scores <4%/5 years that would not justify ICDs. Of 46 high-risk patients with appropriate ICD interventions for ventricular fibrillation/tachycardia, 27 (59%) had low SD risk scores of <4%/5 years, regarded by ESC as insufficient to recommend ICDs, and only 12 (26%) had scores >6%/5 years, considered an ICD indication; 11 of these 12 had already met conventional criteria warranting implantation with 2 to 3 risk markers. Of 414 patients with ICDs but without appropriate interventions, 258 (62%) had low risk scores (<4%/5 years) that would argue against implant. In conclusion, primary risk stratification using the ESC prognostic score applied retrospectively to a large independent HC cohort proved unreliable for prediction of future SD events. Most patients with HC with SD or appropriate ICD interventions were misclassified with low risk scores and therefore would have remained unprotected from arrhythmic SD without ICDs.

Apical hypertrophic cardiomyopathy--a benign condition?

Apical hypertrophic cardiomyopathy (ApHCM) is a less common type of hypertrophic cardiomyopathy (HCM) and is often characterized as benign. However, more recent publications indicate that there is significant heterogeneity among individuals with ApHCM and that for many the condition is less than benign. This review will discuss the most recent understanding of ApHCM in the context of a case presentation and will provide a basic framework for risk stratification.

Assessment of left atrial appendage function during sinus rhythm in patients with hypertrophic cardiomyopathy: transesophageal echocardiography and tissue doppler study.

BACKGROUND: The incidence of systemic thromboembolism is high in patients with hypertrophic cardiomyopathy (HCM). The authors hypothesized that vulnerability to such vascular events could be caused by depressed left atrial appendage (LAA) function during normal sinus rhythm (SR). The aim of this cross-sectional study was to investigate LAA contractile function during SR in patients with HCM. METHODS: LAA function was assessed in 62 patients with HCM in SR and compared with that in 53 age-matched and sex-matched controls. Patients with histories of atrial fibrillation and documented episodes of paroxysmal atrial fibrillation on 24-hour Holter monitoring and depressed left ventricular ejection fractions (<50%) were excluded. Multiplane transesophageal echocardiography was performed for determination of the morphology and function of the LAA. RESULTS: LAA thrombi were present in five patients (8%) with HCM. LAA emptying and filling Doppler velocities were significantly depressed in the HCM group. LAA emptying and filling velocities were negatively correlated with age in controls (r = -0.4, P = .005), but these velocities were not associated with age in the HCM group. Moreover, LAA velocities were not associated with left ventricular mass index, left ventricular outflow tract gradient, or the degree of diastolic dysfunction in the HCM group. All Doppler tissue imaging velocities obtained from LAA walls were also significantly depressed in the HCM group. CONCLUSIONS: LAA thrombus formation was not rare in this patient population. The significantly depressed LAA filling and emptying velocities in SR may predispose patients with HCM to thromboembolic events. The depressed Doppler tissue imaging LAA parameters in patients with HCM may indicate the presence of a possible intrinsic atrial myopathy. Thromboembolic risk should be taken into account, and the evaluation of LAA morphology and function by transesophageal echocardiography might become a component of routine workup in patients with HCM in the future.

Life expectancy gains and cost-effectiveness of implantable cardioverter/defibrillators for the primary prevention of sudden cardiac death in patients with hypertrophic cardiomyopathy.

BACKGROUND: Sudden cardiac death (SCD) is a devastating complication of hypertrophic cardiomyopathy (HCM). The optimal strategy for the primary prevention of SCD in HCM remains controversial. METHODS: Using a Markov model, we compared the health benefits and cost-effectiveness of 3 strategies for the primary prevention of SCD: implantable cardioverter/defibrillator (ICD) insertion, amiodarone therapy, or no therapy. We modeled hypothetical cohorts of 45-year-old patients with HCM with no history of cardiac arrest but at significant risk of SCD (3%/y). RESULTS: Over a lifetime, compared with no therapy, ICD therapy increased quality-adjusted survival by 4.7 quality-adjusted life years (QALYs) at an additional cost of $142,800 ($30,000 per QALY), whereas amiodarone increased quality-adjusted survival by 2.8 QALYs at an additional cost of $104,900 ($37,300 per QALY). Compared with no therapy, ICD therapy would cost < $50,000 per QALY for patients (i) aged 25, with > or = 1 risk factors for SCD, and (ii) aged 45 or 65, with > or = 2 risk factors for SCD. CONCLUSIONS: An ICD strategy is projected to yield the greatest increase in quality-adjusted life expectancy of the 3 treatment strategies evaluated. Combined consideration of age and the number of risk factors for SCD may allow more precise tailoring of ICD therapy to its expected benefits.

Hypertrophic cardiomyopathy: risk factors for life and living benefits insurance.

BACKGROUND: The clinical course of hypertrophic cardiomyopathy (HCM) is highly variable. Patients may remain asymptomatic throughout life, develop progressive and ultimately fatal heart failure, or die prematurely due to sudden death. This article reviews Western and Asian literature on HCM, including recent studies of large, regionally based cohorts that reflect the full spectrum of disease. The intent is to estimate HCM-related morbidity and mortality rates in the general population and identify risk factors for life and living benefits insurance. RESULTS: Clinical studies have identified risk factors that are associated with a higher incidence of sudden death, such as non-sustained ventricular tachycardia, left ventricular wall thickness, and family history of sudden death. For many of these factors, there was a nonlinear relationship between mortality risk and the number of risk factors (ie, each additional risk factor was associated with a disproportionately greater risk of sudden death). Natural history studies of patients with HCM reported total HCM-related mortality rates of 1.8% per year for ages 5 to 15 years, 1.0% to 1.5% for ages 16 to 65, 3.9% for ages 66 to 75, and 4.7% for ages above 75 years. Sudden death rates varied from 0.5% to 1.5% per year for most age groups, with children and adolescents experiencing sudden death rates near the top of this range. With regard to morbidity, patients progressed from New York Heart Association functional class I or II to III/IV at a rate of 1% to 2% per year, with higher progression rates in people aged 65 years or older. Risk varied with genotype and was generally similar in Western and Asian populations. CONCLUSION: Despite improvements in diagnosis and treatment, HCM is still associated with considerable morbidity and mortality.

Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population.

BACKGROUND: Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients. AIMS: To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community. METHODS: Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low. doses (220 (44) mg/day). RESULTS: Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple (> or = 2 runs) and repetitive bursts (on > or = 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up. CONCLUSIONS: In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low doses, did not carry an independent and additive risk for cardiac mortality. Amiodarone may have contributed to the absence of sudden cardiac death in patients believed to be at higher risk because of multiple repetitive NSVT.