Differing strategies for sudden death prevention in hypertrophic cardiomyopathy.

Sudden death (SD) has traditionally been the most visible and feared complication of hypertrophic cardiomyopathy (HCM). Substantial progress in reducing the occurrence of these catastrophic events represents a new paradigm in disease management. Prevention of SD in HCM has resulted from introduction of primary prevention ICDs that reliably terminate life-threatening ventricular tachyarrhythmias, as well as a matured risk stratification algorithm capable of reliably identifying those patients at highest risk. This initiative has been a major determinant of reducing HCM-related mortality to a low rate of 0.5%/year. In such a heterogeneous heart disease as HCM, no perfect risk stratification strategy is possible, and available approaches differ in terms of sensitivity and specificity for identifying patients with SD risk. Major cardiovascular societies, American Heart Association/American College of Cardiology in the USA and European Society of Cardiology in Europe have promoted different risk stratification guidelines creating the potential for judging SD risk in a given HCM patient differently based on commitment to a particular societal guideline or country of residence. In this review, we provide a critical but balanced assessment of these two divergent SD prevention strategies with regard to their respective strengths and weaknesses, as a guide to clinicians directly engaged in this important management issue.

Impact of secondary mitral valve chordal cutting on valve geometry in obstructive hypertrophic cardiomyopathy with marked septal hypertrophy.

AIMS: In patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal thickness undergoing myectomy, resecting fibrotic anterior mitral leaflet (AML) secondary chordae moves the mitral valve (MV) away from the outflow tract and ejection flow, reducing the need for a deep septal excision. Aim of the present study was to assess whether chordal resection has similarly favourable effects in patients with important hypertrophy, who represent the majority of patients with obstructive HCM. METHODS AND RESULTS: The MV position in the ventricular cavity, assessed from echocardiography as AML-annulus ratio, was compared before and after chordal resection in 150 consecutive HCM patients with important (≥20 mm) and 62 with mild (≤19 mm) septal thickness undergoing myectomy. Preoperatively, MV position was displaced towards the septum to a similar extent in both groups. Postoperatively, AML-annulus ratio increased of an equal degree in both groups, from 0.43 ± 0.05 to 0.55 ± 0.06 (P < 0.001) a 28% increase, and from 0.43 ± 0.06 to 0.55 ± 0.06 (P < 0.001) a 26% increase, respectively, indicating a similar MV shift away from the outflow tract. When AML-annulus ratio was compared in the study cohort and 124 normal subjects, MV position was within normal range in <4% of patients preoperatively and normalized in >50% postoperatively. CONCLUSIONS: In obstructive HCM, displacement of the MV apparatus into the outflow tract interferes with the ejection flow. Resection of fibrotic secondary chordae moves the MV apparatus away from the outflow tract and enlarges the outflow area independently of septal thickness, facilitating septal myectomy by reducing the need for a deep muscular excision.

Ventricular Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy (Analysis Spanning 60 Years Of Practice): AJC Expert Panel.

Surgical myectomy remains the time-honored primary treatment for hypertrophic cardiomyopathy patients with drug refractory limiting symptoms due to LV outflow obstruction. Based on >50 years experience, surgery reliably reverses disabling heart failure by permanently abolishing mechanical outflow impedance and mitral regurgitation, with normalization of LV pressures and preserved systolic function. A consortium of 10 international currently active myectomy centers report about 11,000 operations, increasing significantly in number over the most recent 15 years. Performed in experienced multidisciplinary institutions, perioperative mortality for myectomy has declined to 0.6%, becoming one of the safest currently performed open-heart procedures. Extended myectomy relieves symptoms in >90% of patients by ≥ 1 NYHA functional class, returning most to normal daily activity, and also with a long-term survival benefit; concomitant Cox-Maze procedure can reduce the number of atrial fibrillation episodes. Surgery, preferably performed in high volume clinical environments, continues to flourish as a guideline-based and preferred high benefit: low treatment risk option for adults and children with drug refractory disabling symptoms from obstruction, despite prior challenges: higher operative mortality/skepticism in 1960s/1970s; dual-chamber pacing in 1990s, alcohol ablation in 2000s, and now introduction of novel negative inotropic drugs potentially useful for symptom management.

Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history, affecting both genders and many races and cultures. Prevalence is 1:200-1:500, largely based on the disease phenotype with imaging, inferring that 750,000 Americans may be affected by HCM. However, cross-sectional data show that only a fraction are clinically diagnosed, suggesting under-recognition, with most clinicians exposed to small segments of the broad disease spectrum. Highly effective HCM management strategies have emerged, altering clinical course and substantially lowering mortality and morbidity rates. These advances underscore the importance of reliable HCM diagnosis with echocardiography and cardiac magnetic resonance. Family screening with noninvasive imaging will identify relatives with the HCM phenotype, while genetic analysis recognizes preclinical sarcomere gene carriers without left ventricular hypertrophy, but with the potential to transmit disease. Comprehensive initial patient evaluations are important for reliable diagnosis, accurate portrayal of HCM and family history, risk stratification, and distinguishing obstructive versus nonobstructive forms.

Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making.

Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry.

BACKGROUND: The X-linked Danon disease manifests by severe cardiomyopathy, myopathy, and neuropsychiatric problems. We designed this registry to generate a comprehensive picture of clinical presentations and outcome of patients with Danon disease in cardiomyopathy centers throughout Europe. METHODS: Clinical and genetic data were collected in 16 cardiology centers from 8 European countries. RESULTS: The cohort comprised 30 male and 27 female patients. The age at diagnosis was birth to 42 years in men and 2 to 65 in women. Cardiac involvement was observed in 96%. Extracardiac manifestations were prominent in men but not in women. Left ventricular (LV) hypertrophy was reported in 73% of male and 74% of female patients. LV systolic dysfunction was reported in 40% of men (who had LV ejection fraction, 34±11%) and 59% of women (LV ejection fraction, 28±13%). The risk of arrhythmia and heart failure was comparable among sexes. The age of first heart failure hospitalization was lower in men (18±6 versus 28±17 years; P<0.003). Heart failure was the leading cause of death (10 of 17; 59%), and LV systolic dysfunction predicted an adverse outcome. Eight men and 8 women (28%) underwent heart transplantation or received an LV assist device. Our cohort suggests better prognosis of female compared with male heart transplant recipients. CONCLUSIONS: Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications. Cardiomyopathy features, heart failure and arrhythmia, are similar among the sexes. Clinical diagnosis and management is extremely challenging in women due to phenotypic diversity and the absence of extracardiac manifestations.

Congenital Muscular Mitral-Aortic Discontinuity Identified in Patients With Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: The mitral valve is often structurally abnormal in hypertrophic cardiomyopathy (HCM). However, the mechanisms responsible for these abnormalities remain controversial. In 2016 we identified, at myectomy, muscular mitral-aortic discontinuity in 5 young patients with obstructive HCM. OBJECTIVES: This study sought to confirm our preliminary findings and assess the prevalence of muscular mitral-aortic discontinuity in obstructive HCM. METHODS: At our center, from January 2017 to April 2018, the area between the anterior mitral leaflet and aortic valve was inspected at myectomy in 106 consecutive patients with HCM. RESULTS: Muscular mitral-aortic discontinuity was identified in 28 (26%) patients and was significantly more common in younger than older patients (age 39 ± 13 years vs. 58 ± 11 years; p < 0.001). Muscular discontinuity was present in each of 6 patients aged <30 years but only 1 (2.7%) of 37 aged ≥60 years. Pathogenic sarcomere mutations were identified in 22 (79%) of 28 patients with and 24 (31%) of 78 without discontinuity (p < 0.001) and were associated with discontinuity independently of age (p = 0.021). Discontinuity mean length was 7.3 mm and was inversely related to age (p = 0.022). At echocardiography, the anterior mitral leaflet was longer in patients with than those without discontinuity (34 ± 4 mm vs. 29 ± 5 mm; p < 0.001). CONCLUSIONS: We report, for the first time, muscular mitral-aortic discontinuity in HCM. At myectomy, a long muscular discontinuity displaced the anterior mitral leaflet toward the apex in most young patients, was significantly associated with sarcomere mutations independent of age, and was extremely uncommon in older patients. These findings suggest that a long muscular mitral-aortic discontinuity could predispose to the development of outflow obstruction in young patients with sarcomere mutations.

Role of Preoperative Cardiovascular Magnetic Resonance in Planning Ventricular Septal Myectomy in Patients With Obstructive Hypertrophic Cardiomyopathy.

In obstructive hypertrophic cardiomyopathy (HC), extreme heterogeneity of septal morphology makes septal myectomy particularly challenging. Although cardiovascular magnetic resonance (CMR) reconstructs ventricular anatomy with high spatial resolution, CMR is not used systematically to plan preoperatively septal myectomy. In this study, we report our results with using CMR to plan the extent of septal excision in 112 consecutive HC patients who subsequently underwent myectomy. Depth and length of the myectomy planned at CMR were compared with those of the septal muscle excised in a single piece in all patients. Anterior septum maximal thickness at CMR was 22 ± 5 mm and excised muscle thickness 9 ± 3 mm. Planned myectomy length was 35 ± 11 mm (range 17 to 65) and excised muscle length 38 ± 10 mm (range 10 to 70), indicating extension of septal resection to mid-cavity. Thickness and length of the planned myectomy showed a significant correlation with the excised muscle (R2 = 0.345; p <0.001; and R2 = 0.358; p <0.001, respectively). Deep septal crypts were identified at CMR in 12(11%) patients, preventing muscle excision from areas at increased risk of iatrogenic septal defect. Large aberrant muscle bundles that could decrease mid-cavity dimension were identified at CMR and excised in 26(23%) patients. In the 55 patients with postoperative CMR, qualitative comparison of pre and postoperative ventricular morphology showed a smooth and apically extended myectomy. In conclusion, CMR planning of septal myectomy provided high resolution images of septal morphology and allowed us to perform a standardized and apically extended septal excision that was associated with favorable outcome. Our novel approach could make myectomy more accessible to cardiovascular surgeons.

Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators.

BACKGROUND: High-risk patients with hypertrophic cardiomyopathy (HCM) are identified by contemporary risk stratification and effectively treated with implantable cardioverter-defibrillators (ICDs). However, long-term HCM clinical course after ICD therapy for ventricular tachyarrhythmias is incompletely understood. METHODS AND RESULTS: Cohort of 486 high-risk HCM patients with ICDs was assembled from 8 international centers. Clinical course and device interventions were addressed, and survey questionnaires assessed patient anxiety level and psychological well-being related to ICD therapy. Of 486 patients, 94 (19%) experienced appropriate ICD interventions terminating ventricular tachycardia/ventricular fibrillation, 3.7% per year for primary prevention, over 6.4±4.7 years. Of 94 patients, 87 were asymptomatic or only mildly symptomatic at the time of appropriate ICD interventions; 74 of these 87 (85%) remained in classes I/II without significant change in clinical status over the subsequent 5.9±4.9 years (up to 22). Among the 94 patients, there was one sudden death (caused by device failure; 1.1%); 3 patients died from other HCM-related processes unrelated to arrhythmic risk (eg, end-stage heart failure). Post-ICD intervention, freedom from HCM mortality was 100%, 97%, and 92% at 1, 5, and 10 years, distinctly lower than in ischemic or nonischemic cardiomyopathy ICD trials. HCM patients with ICD interventions reported heightened anxiety in expectation of future shocks, but with intact general psychological well-being and quality of life. CONCLUSIONS: In HCM, unlike ischemic heart disease, prevention of sudden death with ICD therapy is unassociated with significant increase in cardiovascular morbidity or mortality, or transformation to heart failure deterioration. ICD therapy does not substantially impair overall psychological and physical well-being.

Alcohol septal ablation: in which patients and why?

At present, surgical septal myectomy is regarded as the "gold standard" treatment for most patients with obstructive hypertrophic cardiomyopathy (HCM) and drug-refractory symptoms. However, the best results are obtained by those surgeons who have extensive experience with this operation at a small number of referral centers. In the mid-1990s, percutaneous alcohol septal ablation was introduced as an alternative to myectomy to reduce LV outflow gradient and heart failure symptoms in patients with obstructive HCM. However, certain features of alcohol ablation limit its applicability to carefully selected patients. Because this procedure involves the injection of 1-4 mL of 96% ethanol into a septal perforator of the left anterior coronary artery to produce a myocardial infarction (with septal thinning, outflow tract widening and gradient reduction), alcohol ablation is limited by the size and distribution of the septal perforator branches. In addition, rich blood supply from other septal branches not occluded by the balloon and from the posterior descending coronary artery may restrict myocardial ischemia to portions of the septum that do not contribute to outflow obstruction. Septal hypertrophy may be either mild or particularly marked, and abnormalities of mitral valve apparatus may also play a major role in outflow obstruction. When such features are present, alcohol-induced septal thinning is unlikely to significantly reduce the gradient. In addition, persisting uncertainties regarding the risk for ventricular tachyarrhythmias after alcohol ablation suggest this procedure should be limited to patients of advanced age, patients at unacceptable operative risk due to comorbidities, or those with strong aversion to surgery. Further progress in the treatment for patients with obstructive HCM and severe refractory symptoms will come from assuring proper patient selection for alcohol septal ablation, as well as increasing the number of surgeons and centers experienced in performing septal myectomy.