Death In Hypertrophic Cardiomyopathy Research Articles

Sudden cardiac death in hypertrophic cardiomyopathy: Improved risk stratification strategies are needed

Sudden cardiac death in hypertrophic cardiomyopathy: Improved risk stratification strategies are needed

Pulmonary Hypertension is Associated with Higher In-Hospital Mortality in Patients with Hypertrophic Cardiomyopathy

Background Little is known regarding the characteristics and outcomes of patients with hypertrophic cardiomyopathy (HCM) and concomitant pulmonary hypertension (PHTN). Existing data is limited to small retrospective cohort studies performed at single centers with considerable HCM experience. In this study, we characterize the incidence and impact of PHTN in HCM patients in the United States. Methods We performed a retrospective cohort study using the Nationwide/National Inpatient Sample between 2005 and 2014. HCM and PHTN were identified using International Classification of Diseases (ICD)-9 codes. Patients under age 18 were excluded. Demographics, primary payer, hospital length of stay, hospital admission category, hospital region, bed size, location/teaching status, charges, and in-hospital death were collected. We performed univariate and multivariable modeling to find factors associated with mortality in hospitalized HCM patients. Results We identified 117,650 patients with hospital admissions for HCM from 2005 to 2014; 14,895 (12.7%) of these patients had concomitant PHTN. The median age of admitted patients with PHTN was higher than those without PHTN (73 years v. 68 years, p Conclusions In the largest contemporary study of hospitalized patients with HCM and PHTN, we found that patients admitted to U.S. hospitals with HCM and PHTN have a 1.5-fold increased odds of in-hospital mortality relative to patients with HCM without PHTN. As the risk of sudden cardiac death in HCM declines related to the success of primary prevention, the complications of advanced heart failure and PHTN-related morbidity and mortality must be recognized.

Abstract 17186: Left Atrial Strain Predicts Adverse Outcomes in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) patients are at increased risk for heart failure (HF), stroke, death, and paroxysmal atrial fibrillation (PAF) development. There is no consensus whether atrial fibrillation (AF) is a marker or mediator of adverse outcomes in HCM patients. Hypothesis: We hypothesized that PAF and left atrial (LA) remodeling predict adverse outcomes in HCM. Methods: Echocardiography (2D and speckle tracking) was used to assess LA size, function, and mechanics in a cohort of HCM patients with history of PAF (PAF group, n=45) and age/gender-matched HCM patients without history of AF (No-AF group; n=59). AF was diagnosed by review of EKGs, event recorder/holter monitor data, and ICD interrogation. Patients were followed for a mean of 53 months for development of the composite endpoint of HF, death, and stroke. Results: Clinical/demographic characteristics were similar in the 2 groups; 67% of PAF group had a CHADS 2 VASC score ≤ 1. The PAF group had higher LA volume, lower LA ejection fraction, and higher E/A ratio (reflecting LV diastolic dysfunction) compared to the No-AF group. LA contractile and reservoir strain/strain rate (SR) were significantly lower in the PAF group (Table 1). Male gender, LA reservoir and conduit strain/SR (not PAF presence) were associated with the development of the composite endpoint in univariate analysis. Only LA conduit and reservoir strain/SR independently predicted the composite endpoint in a multivariate model. Kaplan Meier survival analysis showed greater event-free survival among HCM patients with LA conduit strain >10.2% (Figure 1a) and LA reservoir strain >23.8% (p < 0.01) (Figure 1b). Conclusions: PAF is associated with greater degree of LA myopathy in HCM. LA myopathy assessed by conduit and reservoir strain/SR may be useful for risk stratification for HF, stroke, and death in HCM.

Galectin-3: A Novel Biomarker Predicts Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is a primary cardiac disease characterized by left ventricular hypertrophy, myocyte hypertrophy and irregularities and interstitial fibrosis in the absence of any cardiac or systemic diseases and may lead to sudden cardiac death (SCD). Galectin-3 is a β-galactoside-binding lectin that has been associated with cardiac fibrosis and inflammation. In this study, we aimed to investigate the relationship between serum galectin-3 levels and the criteria for 5-year sudden death risk, recently defined in the European Society of Cardiology guidelines (2014), in patients with hypertrophic cardiomyopathy. A total of 52 hypertrophic cardiomyopathy patients were enrolled in the study. Patients were questioned for sudden death risk predictors as outlined in the 2014 European Society of Cardiology guideline. A standardized clinical evaluation was carried out on the basis of previously described prognostic variables to calculate the 5-year risk of SCD. Blood samples were taken from all patients to measure serum galectin-3 levels. A statistical significance level of P < 0.05 was accepted in all tests. We found that there was a significant correlation between the estimated 5-year risk of SCD and serum levels of galectin-3. Galectin-3 may be an inexpensive and easily accessible parameter to predict arrhythmia risk. In addition, it can be used to determine antiarrhythmic prophylaxis as a predictor of an arrhythmia storm in implantable cardioverter defibrillator-implanted patients who are not available for magnetic resonance imaging.

P1014Risk stratification scores for sudden cardiac death in hypertrophic cardiomyopathy: is volume better than diameter?

P1014Risk stratification scores for sudden cardiac death in hypertrophic cardiomyopathy: is volume better than diameter?

Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: What has Changed in The Guidelines?

BackgroundThe new European Society of Cardiology guidelines for hypertrophic cardiomyopathy (HCM) define the estimation of sudden cardiac death (SCD) risk as an integral part of clinical management. An implantable cardioverter defibrillator (ICD) is recommended (class IIa) when the risk is ≥ 6%.ObjectivesTo compare the SCD risk stratification according to the 2011 and 2014 recommendations for ICD implantation in patients with HCM.MethodsRetrospective study including 105 patients diagnosed with HCM. The indication for ICD was assessed using the 2011 and 2014 guidelines. Statistical analysis was performed using SPSS software version 19.0.0.2®. The tests performed were bilateral, considering the significance level of 5% (p < 0.05).ResultsRegarding primary prevention, according to the 2011 ACCF/AHA recommendations, 39.0% of the patients had indication for ICD implantation (level of evidence IIa). Using the 2014 guidelines, only 12.4% of the patients had an indication for ICD implantation. Comparing the two risk stratification models for patients with HCM, we detected a significant reduction in the number of indications for ICD implantation (p < 0.001). Of the 41 patients classified as IIa according to the 2011 recommendations, 68.3% received a different classification according to the 2014 guidelines.ConclusionSignificant differences were found when comparing the SCD risk stratification for ICD implantation in the two guidelines. The current SCD risk score seems to identify many low-risk patients who are not candidates for ICD implantation. The use of this new score results in a significant reduction in the number of ICD implanted.

High T2-weighted signal intensity for risk prediction of sudden cardiac death in hypertrophic cardiomyopathy

In search of improved risk stratification in hypertrophic cardiomyopathy (HCM), CMR imaging has been implicated as a potential tool for prediction of sudden cardiac death (SCD). In follow-up of the promising results with extensive late gadolinium enhancement (LGE), high signal-intensity on T2-weighted imaging (HighT2) has become subject of interest given its association with markers of adverse disease progression, such as LGE, elevated troponin and non-sustained ventricular tachycardia. In lack of follow-up cohorts, we initiated an exploratory study on the association between HighT2 and the internationally defined risk categories of SCD. In a cohort of 109 HCM patients from a multicenter study on CMR imaging and biomarkers, we estimated the 5-year SCD risk (HCM Risk-SCD model). Patients were categorized as low (< 4%), intermediate (≥ 4–<6%) or high (≥ 6%) risk. In addition, risk categorization according to the ACC/AHA guidelines was performed. HighT2 was present in 27% (29/109). Patients with HighT2 were more often at an intermediate-high risk of SCD according to the European (28 vs. 10%, p = .032) and American guidelines (41 vs. 18%, p = .010) compared to those without HighT2. The estimated 5-year SCD risk of our cohort was 1.9% (IQR 1.3–2.9%), and projected SCD rates were higher in patients with than without HighT2 (2.8 vs. 1.8%, p = .002). In conclusion, HCM patients with HighT2 were more likely to be intermediate-high risk, with projected SCD rates that were 1.5 fold higher than in patients without HighT2. These pilot findings call for corroborative studies with more intermediate-high risk HCM patients and clinical follow-up to assess whether HighT2 may have additional value to current risk stratification.

Predictors of risk for sudden death in childhood hypertrophic cardiomyopathy: the importance of the ECG risk score

ObjectiveTo establish which risk factors are predictive for sudden death in hypertrophic cardiomyopathy (HCM) diagnosed in childhood.MethodsA Swedish national cohort of patients with HCM diagnosed <19 years of age was...

Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Atrial fibrillation (AF), the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), is capable of producing symptoms that impact quality of life and is associated with risk for embolic stroke. However, the influence of AF on clinical course and outcome in HCM remains incompletely resolved. Records of 1558 consecutive patients followed at the Tufts Medical Center Hypertrophic Cardiomyopathy Institute for 4.8±3.4 years (from 2004 to 2014) were accessed. Of the 1558 patients with HCM, 304 (20%) had episodes of AF, of which 226 (74%) were confined to symptomatic paroxysmal AF (average, 5±5; range, 1 to >20), whereas 78 (26%) developed permanent AF, preceded by 7±6 paroxysmal AF episodes. At last evaluation, 277 patients (91%) are alive at 62±13 years of age, including 89% in New York Heart Association class I or II. No difference was found in outcome measures for patients with AF and age- and sex-matched patients with HCM without AF. Four percent of patients with AF died of HCM-related causes (n=11), with annual mortality 0.7%; mortality directly attributable to AF (thromboembolism without prophylactic anticoagulation) was 0.1% per year (n=2 patients). Patients were treated with antiarrhythmic drugs (most commonly amiodarone [n=103] or sotalol [n=78]) and AF catheter ablation (n=49) or the Maze procedure at surgical myectomy (n=72). Freedom from AF recurrence at 1 year was 44% for ablation patients and 75% with the Maze procedure (P<0.001). Embolic events were less common with anticoagulation prophylaxis (4/233, 2%) than without (9/66, 14%) (P<0.001). Transient symptomatic episodes of AF, often responsible for impaired quality of life, are unpredictable in frequency and timing, but amenable to effective contemporary treatments, and infrequently progress to permanent AF. AF is not a major contributor to heart failure morbidity or a cause of arrhythmic sudden death; when treated, it is associated with low disease-related mortality, no different than for patients without AF. AF is an uncommon primary cause of death in HCM virtually limited to embolic stroke, supporting a low threshold for initiating anticoagulation therapy.

Troponin as ischemic biomarker is related with all three echocardiographic risk factors for sudden death in hypertrophic cardiomyopathy (ESC Guidelines 2014)

BackgroundSudden cardiac death (SCD) risk stratification is the most important preventive action in patients with hypertrophic cardiomyopathy (HCM). The identification of the ischemia biomarker high sensitive troponin I (hs-TnI) role for this arrhythmic disease may provide additional information for SCD risk stratification. The aim of the study was to compare echocardiographic parameters (prognostic for risk stratification of SCD in HCM) among two subgroups of HCM patients: with elevated hs-TnI versus non-elevated hs-TnI level.MethodsIn 51 HCM patients (mean age 39 ± 8 years, 31 males and 20 females) an echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, was performed. The hs-TnI was measured 24 h later.ResultsBy comparing two subgroups of patients, 26 members with hs-TnI positive versus 25 with hs-TnI negative, the study showed that the values of all three parameters were greater: provocable left ventricular outflow tract gradient (LVOTG) – 49.1 ± 45.9 vs 25.5 ± 24.8 mmHg, p = 0.019; left atrial diameter – 50.1 ± 9.6 vs 43.9 ± 9.8 mmHg, p = 0.041; maximal LV thickness – 22.1 ± 5.3 vs 19.9 ± 34 mm, p = 0.029.ConclusionThe increased value of all three echocardiographic parameters used as risk factors for SCD (ESC Guidelines) is related to the elevated level of hs-TnI in HCM. Due to the high LVOTG – great hs-TnI relationship, exercise stress, both diagnostic and even rehabilitation/training, should be monitored by biomarker control.

122Left atrial diameter predicted from left atrial volume in the risk assessment of sudden cardiac death in hypertrophic cardiomyopathy - potential clinical consequence for the individual patient

122Left atrial diameter predicted from left atrial volume in the risk assessment of sudden cardiac death in hypertrophic cardiomyopathy - potential clinical consequence for the individual patient

Comparison of two European models estimating risk of ­sudden cardiac death in hypertrophic cardiomyopathy

Objective Hypertrophic cardiomyopathy (HCM) is associated with a risk of sudden cardiac death (SCD). Several models have been developed to estimate SCD risk and guide preventive therapy. The comparison of the previous 2003 with novel 2014 SCD risk models have never been studied. MethodsOver a year we included 103 consecutive HCM patients without previous cardiac arrest and/or ICD implanted (65% males; aged 53.3 ± 13.9 years; mean EF 62.3 ± 18%). The SCD risk was calculated for each patient.Results Based on the 2003 model, patients had following scores: 0 points -15 (15%) patients, 1-28 (27%), 2-34 (33%), 3-18 (17%), ≥ 4-8 (8%). According to the 2014 model 83 (80%) had low risk, 12 (12%) intermediate risk, and only 8 (8%) high risk. Patients who had an intermediate or high risk in the 2003 model but a low risk in 2014 model were the oldest, experienced less frequently syncope and nsVT, but had more often abnormal blood pressure response to exercise and an intermediate LVOT gradient in comparison to the patients who had consistently low or high risk in both models.Conclusions Calculation of SCD risk using two models provides completely different risk estimates and consequently different guidance on SCD primary prevention. According to the 2003 model up to 85% of patients have indications for ICD, whereas based on the 2014 risk model only 20% of the patients had non-negligible SCD risk and are candidates for ICD therapy. SCD risk markers, used in the 2003 and 2014 models, have various discriminating power.

Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model.

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and among the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential (AP) duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na+ and Ca2+ in the development of HCM, but the role of repolarizing K+ currents has not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by myosin-binding protein C (MyBPC) knockout (KO), and to test the hypothesis that remodeling of repolarizing K+ currents causes APD prolongation in MyBPC KO myocytes. We demonstrated that MyBPC KO mice developed severe hypertrophy and cardiac dysfunction compared with wild-type (WT) control mice. Telemetric electrocardiographic recordings of awake mice revealed prolongation of the corrected QT interval in the KO compared with WT control mice, with overt ventricular arrhythmias. Whole cell current- and voltage-clamp experiments comparing KO with WT mice demonstrated ventricular myocyte hypertrophy, AP prolongation, and decreased repolarizing K+ currents. Quantitative RT-PCR analysis revealed decreased mRNA levels of several key K+ channel subunits. In conclusion, decrease in repolarizing K+ currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility.NEW & NOTEWORTHY Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K+ currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy.

P1597QT rate dependence in risk stratification for sudden death in hypertrophic cardiomyopathy

P1597QT rate dependence in risk stratification for sudden death in hypertrophic cardiomyopathy

Feasibility of the 2014 European guidelines risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy in Chinese patients

Objective: Exploring the feasibility of the 2014 European Society of Cardiology(ESC)guideline's risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD) in Chinese patients. Methods: The study population consisted of a consecutive cohort of 172 Chinese patients with HCM without prior sudden cardiac death (SCD) event who were in patients in Nanjing Drum Tower Hospital from December 2010 to October 2015.The endpoint event was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.Clinical data were collected to calculate the 5-year SCD risk using the HCM Risk-SCD formula and to observe the actual risk during the follow-up.Receiver operating characteristic curves (ROC) and the area under curve (AUC) were calculated for the HCM Risk-SCD and risk stratification methods of the 2011 American Heart Association (AHA) guideline. Results: During follow-up of (2.69±1.36) years, five patients achieved the endpoint event.The predicated rate of SCD event using HCM Risk-SCD was (2.36±1.73)%, (1.93±0.78)%, (5.18±0.65)%, (8.77±2.38)% for all patients, low-risk group, medium-risk group and high-risk group respectively.However, the actual rate of SCD event was 2.91%, 1.27%, 25.00% and 14.29%, respectively.The AUC of 2014 ESC guideline and 2011 AHA guidelinewas 0.93(95%CI 0.85-1.00) vs. 0.87(95%CI 0.75-0.98). Conclusion: The predicated rate of SCD event calculated by HCM Risk-SCD is lower than actual rate of SCD, but the prediction efficiency and indication for ICD implantation of HCM Risk-SCD are better than that of 2011 AHA guideline.

Predicting risk of sudden death in hypertrophic cardiomyopathy: Can additional simple markers help?

Predicting risk of sudden death in hypertrophic cardiomyopathy: Can additional simple markers help?

QT spatial dispersion and sudden cardiac death in hypertrophic cardiomyopathy: Time for reappraisal

BackgroundThe 12-lead surface electrocardiographic (ECG) analysis is able to provide independent predictors of prognosis in several cardiovascular settings, including hypertrophic cardiomyopathy (HCM). The present single-center study investigated the possible ability of several ECG-derived variables in stratifying sudden cardiac death (SCD) risk and, possibly, in improving the accuracy of the 2014 European Society of Cardiology guidelines. MethodsA total of 221 consecutive HCM outpatients were recruited and prospectively followed. All of them underwent a full clinical and instrumental examination, including a 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QT), Q-Tpeak (QTp), Tpeak-Tend (TpTe), J-Tpeak (JTp), and J-Tend (JT). The study composite end-point was SCD, aborted SCD, and appropriate implantable cardioverter defibrillator (ICD) interventions. ResultsDuring a median follow-up of 4.4 years (25th–75th interquartile range: 2.4–9.4 years), 23 patients reached the end-point at 5-years (3 SCD, 3 aborted SCD, 17 appropriate ICD interventions). At multivariate analysis, the spatial QT dispersion corrected according to Bazett's formula (QTcd) remains independently associated to the study endpoint over the HCM Risk-SCD score (C-index 0.737). A QTcd cut-off value of 93ms showed the best accuracy in predicting the SCD endpoint within the entire HCM study cohort (sensitivity 56%, specificity 75%, positive predictive value 22%, negative predictive value 97%). ConclusionOur data suggest that the QTcd might be helpful in SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to the contemporary guidelines.

The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy.

IntroductionSevere right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH.MethodsHCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM) were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared.ResultsCompared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI): 1.43-52.87, p = 0.019) and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026). Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9%) were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82%) patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73%) patients.ConclusionsHCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations.

Predicting risk of sudden death in hypertrophic cardiomyopathy: Can additional simple markers help?

Predicting risk of sudden death in hypertrophic cardiomyopathy: Can additional simple markers help?

THE RELATIONSHIP BETWEEN THE QUANTITATIVE EXTENT OF MYOCARDIAL FIBROSIS AND BURDEN OF NON-SUSTAINED VENTRICULAR TACHYCARDIA IN HYPERTROPHIC CARDIOMYOPATHY: A DELAYED CONTRAST ENHANCED MRI STUDY

Background: Non-sustained ventricular tachycardia (NSVT) has been shown to be independently associated with sudden death in hypertrophic cardiomyopathy (HCM). Previous studies have found late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) to be independently associated with the