Advanced imaging for risk stratification of sudden death in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a hereditary primary myocardial disease that is most commonly due to mutations within genes encoding sarcomeric contractile proteins and is characterised by left ventricular hypertrophy in the absence of a cardiac or systemic cause. Although the overall prognosis is relatively good with an annual mortality rate <1 %, the propensity to potentially fatal ventricular arrhythmias is the most feared complication. The identification of patients at risk of arrhythmogenic sudden cardiac death (SCD) is an essential component in disease management. Aborted SCD and malignant ventricular arrhythmias are the most powerful risk factors for SCD and ICD implantation is recommended in such circumstances. The selection of patients who may benefit from ICD therapy for primary prevention purposes is more challenging. The heterogeneous nature of the disease and the variation in trigger factors provides an adequate explanation for the low predictive accuracy of most conventional risk factors in isolation. A new risk model for risk stratification proposed by the European Society of Cardiology HCM outcome group shows promise but requires validation in different cohorts. The ICD is the only effective therapy in preventing SCD for the disease with a relatively low adverse event rate, but most deaths occur in relatively young patients. However, it is also difficult to ignore the complications with the ICD, therefore, the strive to perfect risk stratification in HCM should continue to ensure that only the most high-risk patients receive an ICD.

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Myocardial Noncompaction

Revista de Chimie ◽

10.37358/rc.18.8.6500 ◽

2018 ◽

Vol 69 (8) ◽

pp. 2209-2212

Author(s):

Alexandru Radu Mihailovici ◽

Vlad Padureanu ◽

Carmen Valeria Albu ◽

Venera Cristina Dinescu ◽

Mihai Cristian Pirlog ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Specific Treatment ◽

Left Ventricular ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Genetic Transmission ◽

Asymptomatic Patients ◽

Increased Risk ◽

Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

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Effect of hypokintic transformation on the clinical phenotype and functional capacity in hypertrophic cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.2091 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Wasserstrum ◽

E Itelman ◽

R Barriales-Villa ◽

X Fernandez-Fernandez ◽

Y Adler ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Tachyarrhythmias ◽

Ventricular Ejection Fraction ◽

Icd Therapy ◽

Medical Centers ◽

Increased Risk

Abstract Background Advanced hypertrophic cardiomyopathy (HCM) may be complicated by a dilated hypokinetic transformation. Reduced left ventricular ejection fraction (HFrEF) has been described in terms of specific risks of morbidity and mortality, and specifically in terms of increased risk for fatal arrhythmias. Nevertheless, recent publications have casted doubt regarding the role of arrhythmia in non-ischemic HFrEF and questioned the role of primary prevention strategies in these cases. Methods We've reviewed clinical characteristics of 883 patients age ≥40, diagnosed with HCM who were evaluated in the cardiomyopathy clinic in two tertiary medical centers in Israel and Spain. Results Forty-five patients (5%) suffered from hypokinetic transformation. They were younger at diagnosis (median 32 [IQR 24–55] vs. 49 [35–60], p<0.001), had a lower body-mass index (28.4 [±4.7] vs. 26.0 [±3.9], p<0.001), and suffered more from strokes (19% vs 6%, p<0.001). They had lower had a lower NYHA class (p=0.001) and lower exercise capacity (7.3 [4.5–10.8] vs. 9.6 [6.7–12.0] METS, p<0.001). Patients with hypokinetic HCM had higher rates of pacemaker and implanted defibrillator (ICD) implantations (41% vs 11%, p<0.001) and (43% vs 13%, p<0.001) respectively. These patients had a higher incidence of sustained ventricular tachyarrhythmias (14% vs 2%, p<0.001). Among patients who had an ICD, patients suffering from hypokinetic transformation had received more appropriate ICD therapy (27% vs 12%, p<0.001). These patients received more heart transplantations (13% vs 1%, p<0.001), and had a trend for higher incidence rate of Sudden cardiac death (6% vs 2% p=0.06) and a higher 5-year mortality rates (21% vs. 5%, p<0.001). Conclusions HCM patients suffering from hypokinetic transformation have lower functional and exercise capacities, are more likely to suffer from ventricular tachyarrhythmias and experience appropriate ICD therapy, and undergo heart transplantation. They also have a significantly lower 5-year survival. Five-year survival Funding Acknowledgement Type of funding source: None

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Hypertrophic cardiomyopathy: prevention of sudden cardiac death

10.1093/med/9780198784906.003.0354 ◽

2018 ◽

Author(s):

Constantinos O’Mahony

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Risk Stratification ◽

Cardiac Death ◽

Clinical Care ◽

Psychological Impact ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Icd Implantation ◽

European Society Of Cardiology

Sudden cardiac death (SCD) secondary to ventricular arrhythmias is the most common mode of death in hypertrophic cardiomyopathy (HCM) and can be effectively prevented with an implantable cardioverter defibrillator (ICD). The risk of SCD in HCM relates to the severity of the phenotype and regular risk stratification is an integral part of routine clinical care. For the primary prevention of SCD, risk stratification involves the assessment of seven readily available clinical parameters (age, maximal left ventricular wall thickness, left atrial diameter, left ventricular outflow tract gradient, non-sustained ventricular tachycardia, unexplained syncope, and family history of SCD) which are used to estimate the risk of SCD within 5 years of clinical evaluation using a statistical risk prediction model (HCM Risk-SCD). The 2014 European Society of Cardiology Guidelines provide a framework to aid clinical decisions and consider patients with a 5-year risk of SCD of less than 4% as low risk and recommend regular assessment while those with a risk of 6% or higher should be considered for an ICD. In patients with an intermediate risk (4% to <6%) ICD implantation may also be considered after taking into account age, co-morbid conditions, socioeconomic factors, and the psychological impact of therapy. Survivors of ventricular fibrillation arrest should receive an ICD for secondary prevention unless their life expectancy is less than 1 year. Following device implantation, patients should be followed up for device- and disease-related complications, particularly heart failure and cerebrovascular disease.

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Hypertrophic cardiomyopathy: prevention of sudden cardiac death

ESC CardioMed ◽

10.1093/med/9780198784906.003.0354_update_001 ◽

2018 ◽

pp. 1462-1466

Author(s):

Constantinos O’Mahony

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Risk Stratification ◽

Cardiac Death ◽

Clinical Care ◽

Psychological Impact ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Icd Implantation ◽

European Society Of Cardiology

Sudden cardiac death (SCD) secondary to ventricular arrhythmias is the most common mode of death in hypertrophic cardiomyopathy (HCM) and can be effectively prevented with an implantable cardioverter defibrillator (ICD). The risk of SCD in HCM relates to the severity of the phenotype and regular risk stratification is an integral part of routine clinical care. For the primary prevention of SCD, risk stratification involves the assessment of seven readily available clinical parameters (age, maximal left ventricular wall thickness, left atrial diameter, left ventricular outflow tract gradient, non-sustained ventricular tachycardia, unexplained syncope, and family history of SCD) which are used to estimate the risk of SCD within 5 years of clinical evaluation using a statistical risk prediction model (HCM Risk-SCD). The 2014 European Society of Cardiology Guidelines provide a framework to aid clinical decisions and consider patients with a 5-year risk of SCD of less than 4% as low risk and recommend regular assessment while those with a risk of 6% or higher should be considered for an ICD. In patients with an intermediate risk (4% to <6%) ICD implantation may also be considered after taking into account age, co-morbid conditions, socioeconomic factors, and the psychological impact of therapy. Survivors of ventricular fibrillation arrest should receive an ICD for secondary prevention unless their life expectancy is less than 1 year. Following device implantation, patients should be followed up for device- and disease-related complications, particularly heart failure and cerebrovascular disease.

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ICD Therapy for Primary Prevention in Hypertrophic Cardiomyopathy

Arrhythmia & Electrophysiology Review ◽

10.15420/aer.2016:30:2 ◽

2016 ◽

Vol 5 (3) ◽

pp. 188 ◽

Cited By ~ 13

Author(s):

Amar Trivedi ◽

Bradley P Knight ◽

◽

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Primary Prevention ◽

Ventricular Arrhythmias ◽

Genetic Basis ◽

Icd Implantation ◽

Subcutaneous Icd ◽

Icd Therapy ◽

European Guidelines ◽

Relevant Factors

Hypertrophic cardiomyopathy (HCM) is a common and heterogeneous disorder that increases an individual’s risk of sudden cardiac death (SCD). This review article discusses the relevant factors that are involved in the challenge of preventing SCD in patients with HCM. The epidemiology of SCD in patients is reviewed as well as the structural and genetic basis behind ventricular arrhythmias in HCM. The primary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy is the cornerstone of modern treatment for individuals at high risk of SCD. The focus here is on the current and emerging predictors of SCD as well as risk stratification recommendations from both North American and European guidelines. Issues related to ICD implantation, such as programming, complications and inappropriate therapies, are discussed. The emerging role of the fully subcutaneous ICD and the data regarding its implantation are reviewed.

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The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab046 ◽

2021 ◽

Author(s):

Gabrielle Norrish ◽

Cristian Topriceanu ◽

Chen Qu ◽

Ella Field ◽

Helen Walsh ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Risk Stratification ◽

Risk Score ◽

Cardiac Death ◽

Left Ventricular ◽

Predictive Values ◽

Arrhythmic Event ◽

Ecg Abnormalities

Abstract Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

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Abstract 4683: Risk Stratification in Hypertrophic Cardiomyopathy: Evidence that Syncope is a Marker for Sudden Death

Circulation ◽

10.1161/circ.118.suppl_18.s_929-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Paolo Spirito ◽

Camillo Autore ◽

Claudio Rapezzi ◽

Paola Bernabo ◽

Robert Badagliacca ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Death ◽

Risk Stratification ◽

Age Groups ◽

Left Ventricular ◽

Adult Patients ◽

Patient Evaluation ◽

Death Risk ◽

Increased Risk ◽

Unexplained Syncope

Risk stratification and identification of those patients with hypertrophic cardiomyopathy (HCM) at the highest risk for sudden death is a major issue for patient management, given the effective option of the implantable defibrillator in this disease. For example, the prognostic significance of syncope has not been investigated systematically in large HCM cohorts, and therefore treatment strategies related to this symptom have been based largely on intuition and experience. We assessed the relationship between syncope and sudden death in 1511 consecutive HCM patients. Unexplained (n=153) or neurally-mediated (n=52) syncope occurred in 205 (14%) of patients. Over a 5.6±5.2 year follow-up, 74 patients died suddenly. Relative risk of sudden death was 1.78 (95% CI 0.88 –3.51; p=0.08) in patients with unexplained syncope, and 0.91 (95% CI 0.00 –3.83; p=1.0) in those with neurally-mediated syncope, compared to patients without syncope. However, the time interval between unexplained syncope and initial patient evaluation proved to have a strong impact on sudden death risk. Patients with recent syncope (≤6 months from initial evaluation) showed a 5-fold increase in risk compared to patients without syncope (adjusted HR=4.89; CI 2.19 –10.94; p=0.006), a relationship maintained throughout all age groups (<18, 18 –39 and ≥40 years). Conversely, adult patients (18 –39 and ≥40 years) with remote syncope (>6 months from evaluation) showed no increase in sudden death rate (4.8; 95% CI 0.1–26.7 and 3.2; 95% CI 0.1–17.8 per 1000 person-years, respectively), compared to patients of similar age without syncope (11.8; 95% CI 7.6 –17.6 and 5.7%; 95% CI 3.8 – 8.3 per 1000 person-years). Left ventricular outflow obstruction was not associated with sudden death risk (p=0.29). In this large HCM cohort, unexplained syncope proved to be a risk factor for sudden death. In addition, the temporal proximity of syncopal events to patient evaluation is of clinical relevance. Recent unexplained syncope is associated with an increased risk for sudden death in all age groups, while remote syncopal events do not convey increased risk to adult patients.

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The Role of Cardiac MRI in the Diagnosis and Risk Stratification of Hypertrophic Cardiomyopathy

Arrhythmia & Electrophysiology Review ◽

10.15420/aer.2016:13:3 ◽

2016 ◽

Vol 5 (3) ◽

pp. 197 ◽

Cited By ~ 19

Author(s):

Ethan J Rowin ◽

Martin S Maron ◽

◽

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Death ◽

Imaging Modality ◽

Management Strategies ◽

Phenotypic Expression ◽

Left Ventricular ◽

Contrast Enhanced ◽

Increased Risk ◽

Wide Range

Hypertrophic cardiomyopathy (HCM), the most common genetic cardiomyopathy, is a disease characterised by substantial heterogeneity. Although the majority of patients with HCM remain asymptomatic with near-normal longevity, a small, but important, subset remain at risk for a wide range of clinical outcomes including sudden death. Cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as an imaging modality particularly well suited to characterise the phenotypic expression of HCM. CMR helps in the diagnosis of HCM by identifying areas of hypertrophy not well visualised by echocardiography, providing more accurate wall thickness measurements and differentiating HCM from other causes of left ventricular (LV) hypertrophy. CMR has led to the identification of novel subgroups of patients with HCM, including those with LV apical aneurysms (a subgroup at increased risk for ventricular arrhythmias and thromboembolic stroke), as well as abnormalities that contribute to LV outflow obstruction. Additionally, contrast-enhanced CMR with late-gadolinium enhancement (LGE) has recognised patients with extensive LGE (≥15 % LV myocardium) as individuals who may be at increased risk of sudden death, independent of other high-risk features, with implications on management strategies including consideration for primary prevention implantable cardioverter defibrillator therapy. These observations justify an expanded role of CMR in the routine clinical assessment of patients with HCM.

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Risk stratification in hf with mid-range LVEF: the role of cardiopulmonary exercise testing

European Heart Journal ◽

10.1093/ehjci/ehaa946.0940 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B.M.L Rocha ◽

G.J Lopes Da Cunha ◽

P.M.D Lopes ◽

P.N Freitas ◽

F Gama ◽

...

Keyword(s):

Risk Stratification ◽

Exercise Testing ◽

Primary Endpoint ◽

Prognostic Significance ◽

Cardiopulmonary Exercise Testing ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Cardiopulmonary Exercise

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) <40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF <50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p<0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p<0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 <12 mL/kg/min, VE/VCO2 >35 and EOV identified patients at higher risk for events (all p<0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p<0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p<0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 >16.7 and >15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p<0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None

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