Impact of pregnancy on the natural history of women with hypertrophic cardiomyopathy.

AIMS: Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. METHODS AND RESULTS: Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk. CONCLUSIONS: Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.

Hypertrophic cardiomyopathy (HCM) is the most common genetic disorder of the myocardium and is characterized by important gender-related differences: women are typically 5 years older than men at diagnosis, over half are diagnosed >50 years of age and consistently show greater propensity than men for heart failure (HF)-related complications and adverse outcome. Whether pregnancy is a modifier of the long-term course and outcome of women with HCM is unknown. In this study, pregnancy was not a modifier of long-term outcome in women with HCM. In particular: At 10 ± 7 years, most patients tolerated pregnancy well and did not show a survival disadvantage compared to women without pregnancies. Only baseline heart failure symptoms and age were associated with adverse outcome.Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features. Nevertheless, cardio-obstetric counselling and close supervision are key in all instances, particularly in the peri-partum period.

The evolving paradigm and current perception of hypertrophic cardiomyopathy: Implications for management.

Recent evidence from imaging and genetic screening studies has clearly shown that hypertrophic cardiomyopathy (HCM) is more common than initially perceived, emphasizing the need to reassess its associated clinical and social burden. While clinical and academic efforts have long been focused on stratification of arrhythmic risk and management of intraventricular obstruction, progression of cardiac dysfunction and heart failure-related complications have emerged as most relevant from the epidemiological standpoint, delineating a major unmet need. Furthermore, a broader perspective of our patients' needs has become central in the care of individuals with HCM, addressing issues that are not strictly clinical but equally important to their wellbeing, such as quality of life, athletic participation, lifestyle and reproductive choices and psychological adaptation to a chronic condition often detected at a young age. The appropriate evaluation and objective assessment of disease burden associated with HCM are increasingly relevant not only to management but also to trial design and evaluation of the efficacy of emerging, targeted treatments. In this review, we discuss the evolving perception of HCM prevalence and natural history, as well as recent acquisitions regarding its true, often under-appreciated socio-economic and clinical burden.

Genetic Testing and Counselling in Hypertrophic Cardiomyopathy: Frequently Asked Questions.

Genetic counselling and genetic testing in hypertrophic cardiomyopathy (HCM) represent an integral part of the diagnostic algorithm to confirm the diagnosis, distinguish it from phenocopies, and suggest tailored therapeutic intervention strategies. Additionally, they enable cascade genetic testing in the family. With the implementation of Next Generation Sequencing technologies (NGS), the interpretation of genetic data has become more complex. In this regard, cardiologists play a central role, aiding geneticists to correctly evaluate the pathogenicity of the identified genetic alterations. In the ideal setting, geneticists and cardiologists must work side by side to diagnose HCM as well as convey the correct information to patients in response to their many questions and concerns. After a brief overview of the role of genetics in the diagnosis of HCM, we present and discuss the frequently asked questions by HCM patients throughout our 20-year genetic counselling experience. Appropriate communication between the team and the families is key to the goal of delivering the full potential of genetic testing to our patients.

Real-World Use and Predictors of Response to Disopyramide in Patients with Obstructive Hypertrophic Cardiomyopathy.

Background: Although disopyramide has been widely used to reduce left ventricular outflow obstruction (LVOTO) and to improve symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM), its use in real world as well as patient characteristics associated with a positive treatment response are still unclear. Methods: From 1980 to 2021, 1527 patients with HCM were evaluated and 372 (23%) had a LVOTO with active follow-up. The efficacy and safety of disopyramide were assessed systematically during 12 months (2-, 6-, and 12-month visits). Responders were patients with a final NYHA = I and a LVOTO < 30 mmHg; incomplete responders were those patients with NYHA > I and a LVOTO < 30 mmHg; and non-responders were symptomatic patients with no change in functional class NYHA and a LVOT gradient > 30 mmHg. Results: Two-hundred-fifty-four (66%) patients were in functional class NYHA I/II and 118 (34%) in NYHA III/IV. A total of 118/372 (32%, 55 ± 16 years) underwent disopyramide therapy. Twenty-eight (24%) patients responded to therapy, 39 (33%) were incomplete responders, and 51 (43%) did not respond. Responder were mainly patients in functional NYHA class I/II (24/28, 86%), whereas incomplete responders and non-responders were more often in functional NYHA class III/IV (50/54 (93%)). An independent predictor of response to disopyramide treatment was the presence of NYHA I/II at the initiation of therapy (HR 1.5 (95% CI 1.1-4.5), p = 0.03). No major life-threatening arrhythmic events or syncope occurred, despite 19 (16%) patients showing reduced QTc from baseline, 19 (16%) having no difference, while 80 (69%) patients had prolonged QTc interval. Thirty-one (26%) patients experienced side effects, in particular, 29 of the anticholinergic type. Conclusions: Disopyramide was underused in oHCM but effective in reducing LVOTO gradients and symptoms in slightly symptomatic patients with less severe disease phenotype with a safe pro-arrhythmic profile.

Incidence of stroke in patients with hypertrophic cardiomyopathy in stable sinus rhythm during long-term monitoring.

INTRODUCTION: Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of stroke, but the incidence and factors associated with cardioembolic events in HCM patients without atrial fibrillation (AF) remain unresolved. We determined the incidence of stroke in patients in sinus rhythm (SR) monitored with a cardiac implantable electronic device (CIED). METHODS: All consecutive patients diagnosed with HCM and referred to CIED implantation with >16 years at diagnosis and ≥ 1 year follow-up post CIED implantation were retrospectively reviewed. Severe LA dilatation was defined as ≥48 mm. Patients were stratified by rhythm as: Pre-existing AF (AF present prior to CIED); De novo AF (AF present after CIED implantation); SR: no episodes of AF. RESULTS: Of 1651 patients, 185 (11.2%) implanted with a CIED were included (57% men, age: 54 ± 17 years). Baseline, pre-existing AF was present in 73 (39%) patients. Ischemic stroke was reported in 19 (10.3%, 1.78%/year) patients and was similar across the three groups (2.3%/year vs 1.1%/year vs 0.6%/year in patients in SR vs pre-existing AF vs de novo AF, respectively, p = 0.235). In SR patients, a LAD≥48 mm posed the greatest risk of stroke (Hazard Ratio: 10.03,95% Confidence-Interval 2.79-16.01). At Cox multivariable analysis, after adjustment for oral anticoagulation, LA was independently associated with stroke while rhythm was not. CONCLUSIONS: in HCM patients with CIED long-term monitoring and no prior history of AF, stroke rates were similar in those with de novo AF or stable SR. Severe LA dilatation was a powerful risk factor, irrespective of AF.

Prognostic value of cardiopulmonary exercise testing in patients with transthyretin cardiac amyloidosis.

The aim of this study is to evaluate the prognostic value of cardiopulmonary testing (CPET) in a cohort of patients with transthyretin cardiac amyloidosis (ATTR-CA). ATTR-CA is associated with a progressive reduction in functional capacity. The prognostic role of CPET parameters and in particular of normalized peak VO2 (%ppVO2) remains to be thoroughly evaluated. In this study, 75 patients with ATTR-CA underwent cardiological evaluation and CPET in a National Referral Center for cardiac amyloidosis (Careggi University Hospital, Florence). Fifty-seven patients (76%) had wild-type ATTR. Median age was 80 (75-83) years, 68 patients (91%) were men. Peak oxygen consumption (14.1 ± 4.1 ml/kg/min) and %ppVO2 (68.4 ± 18.8%) were blunted. Twenty-seven (36%) patients had an abnormal pressure response to exercise. After a median follow-up of 25 (12-31) months, the composite outcome of death or heart failure hospitalization was registered in 19 (25.3%) patients. At univariate analysis %ppVO2 was a stronger predictor for the composite outcome than peak VO2. %ppVO2 and NT-proBNP remained associated with the composite outcome at multivariate analysis. The optimal predictive threshold for %ppVO2 was 62% (sensitivity: 71%; specificity: 68%; AUC: 0.77, CI 0.65-0.88). Patients with %ppVO2 ≤ 62%and NT-proBNP > 3000 pg had a worse prognosis with 1- and 2-year survival of 69 ± 9% and 50 ± 10%, respectively. CPET is a safe and useful prognostic tool in patients with ATTR-CA. CPET may help to identify patients with advanced disease that may benefit from targeted therapy.

Safety and efficacy of ranolazine in hypertrophic cardiomyopathy: Real-world experience in a National Referral Center.

OBJECTIVES: We assessed the efficacy and safety of ranolazine in real-world patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Ranolazine is an anti-anginal drug that inhibits the late phase of the inward sodium current. In a small prospective trial, ranolazine reduced the arrhythmic burden and improved biomarker profile in HCM patients. However, systematic reports reflecting real-world use in this setting are lacking. METHODS: Changes in clinical and instrumental features, symptoms and arrhythmic burden were evaluated in 119 patients with HCM before and during treatment with ranolazine at a national referral centre for HCM. RESULTS: Patients were treated with ranolazine for 2 [1-4] years; 83 (70%) achieved a dosage ≥1000 mg per day. Treatment interruption was necessary in 24 patients (20%) due to side effects (n = 10, 8%) or disopyramide initiation (n = 8, 7%). Seventy patients (59%) were treated with ranolazine for relief of angina. Among them, 51 (73%) had total symptomatic relief and 47 patients (67%) showed ≥2 Canadian Cardiovascular society (CCS) angina grade improvement. Sixteen patients (13%) were treated for recurrent ventricular arrhythmias, including 4 with a clear ischemic trigger, who experienced no further arrhythmic episodes while on ranolazine. Finally, 33 patients (28%) were treated for heart failure associated with severe diastolic dysfunction: no symptomatic benefit could be observed in this group. CONCLUSION: Ranolazine was safe and well tolerated in patients with HCM. The use of ranolazine may be considered in patients with HCM and microvascular angina.

Arrhythmic Burden in Cardiac Amyloidosis: What We Know and What We Do Not.

Cardiac amyloidosis (CA), caused by the deposition of insoluble amyloid fibrils, impairs different cardiac structures, altering not only left ventricle (LV) systo-diastolic function but also atrial function and the conduction system. The consequences of the involvement of the cardiac electrical system deserve more attention, as well as the study of the underlying molecular mechanisms. This is an issue of considerable interest, given the conflicting data on the effectiveness of conventional antiarrhythmic strategies. Therefore, this review aims at summarizing the arrhythmic burden related to CA and the available evidence on antiarrhythmic treatment in this population.

Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis.

Cardiac amyloidosis is an infiltrative disease characterized by extracellular deposition of insoluble amyloid fibrils in the heart leading to organ dysfunction. Despite recent diagnostic advances, the diagnosis of cardiac amyloidosis is often delayed or even missed. Furthermore, a long diagnostic delay is associated with adverse outcomes, with the early diagnosed patients showing the longest survival. In this narrative review we aimed to summarize the 'red flags' that may facilitate the correct diagnosis. The red flags may be classified as clinical, biohumoral, electrocardiographic, echocardiographic, and cardiac magnetic resonance features and should promptly raise the suspicion of cardiac amyloidosis in order to start a correct diagnostic pathway and targeted treatment strategies that may improve patients' outcomes.

Sex-related differences in clinical presentation and all-cause mortality in patients with cardiac transthyretin amyloidosis and light chain amyloidosis.

We aimed to ascertain whether sex-related differences are relevant to clinical presentation, cardiac phenotype and all-cause mortality in different types of cardiac amyloidosis, a field still poorly investigated. Medical files from consecutive patients diagnosed with cardiac amyloidosis between 2000 and 2020, at Careggi University Hospital, were retrospectively evaluated. Over this period, 259 patients (12% females) were diagnosed with wild type transthyretin amyloidosis (wtATTR), 52 (25% females) with hereditary transthyretin amyloidosis (hATTR) and 143 (47% females) with light chain amyloidosis (AL). Women with wtATTR, compared to men, were significantly older at the time of diagnosis and showed higher National Amyloidosis Centre score, thicker normalized interventricular septum, higher diastolic dysfunction and worse right ventricular function. Females with hATTR and AL had lower normalized cardiac mass compared to men, otherwise, bio-humoral parameters, NYHA class, and ECG characteristics were similar. Comparing females and male with wtATTR, hATTR and AL, no differences in Kaplan-Meier curves for all-cause mortality were observed with regard to sex, p-value >0.05. In conclusion, we did not observe major differences in clinical expression related to sex in different types of cardiac amyloidosis: specifically, all-cause mortality was not affected. Nevertheless, women with wtATTR had echocardiographic signs of more advanced disease and higher NAC score at diagnosis suggesting a possible later recognition of disease compared to men.

Prevalence of anxiety and depression symptoms in a sample of outpatients with ATTR cardiac amyloidosis.

Patients with ATTR cardiac amyloidosis (ATTR-CA) face rare disease that could negatively influence psychological well-being with consequences on the course of the disease and quality of life. However, to date, no study analyzed the prevalence of anxiety and depression in patients with ATTR-CA and which clinical and sociodemographic characteristics are linked with these psychopathological conditions. A total of 109 consecutive patients (83% males) aged 62-90 years with ATTR-CA were recruited. In order to better understand the prevalence of anxiety and depression in ATTR-CA, a control group composed by 33 individuals equaling gender, education, and age were recruited. The level of anxiety and depression was measured using the Italian version of the Hospital Anxiety and Depression Scale (HADS). Sociodemographic and clinic characteristics were registered. Almost half of patients (49%) reported a clinical level of depression or anxiety, or both. ATTR-CA patients reported higher levels of anxiety and depression than control group. Results showed that older patients with ATTR-CA, especially females, with more advanced disease could be more at risk to develop an anxious disorder. Furthermore, being a woman, and presenting with a greater severity of symptoms, would appear to be a risk factor for developing a depressive disorder. Overall, these results highlighted the high presence of anxiety and depression in ATTR-CA patients, suggesting to physicians to pay attention to the psychological well-being of ATTR-CA patients. In fact, a psychological support for patients with high level of psychopathological disease could reduce disease burden and improve quality of life in ATTR-CA population.

Early Diagnosis and Outcome in Patients With Wild-Type Transthyretin Cardiac Amyloidosis.

Whether diagnostic timing in transthyretin (TTR) cardiac amyloidosis (CA) predisposes patients to worse outcomes is unresolved. We aimed to describe the long-term association of diagnostic timing (time from first onset of symptoms consistent with CA leading to medical contact to definitive diagnosis) with mortality in patients with wild-type TTR-CA (ATTRwt-CA). Overall, we reviewed the medical records of 160 patients seen at a tertiary care amyloidosis unit from January 1, 2016, to January 1, 2020 (median [interquartile range] follow-up, 21 [10 to 34] months), and compared them by survival. Median diagnostic timing was 4 (2 to 12) months and was longer in nonsurvivors (9 [3 to 15] vs 3 [1 to 7] months; P<.001). Patients diagnosed 6 or more months after symptom onset had higher mortality, with a median survival of 30 months (95% CI, 22 to 37 months). On Cox multivariable analysis, timing was independently associated with all-cause mortality (hazard ratio per month increase, 1.049 [95% CI, 1.017 to 1.083]) together with age at diagnosis, disease stage, New York Heart Association class, and coronary artery disease. In conclusion, diagnostic timing of ATTRwt-CA is associated with mortality. Timely diagnosis is warranted whenever "red flags" are present.

Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy.

PURPOSE OF REVIEW: Pharmacological treatment options for hypertrophic cardiomyopathy (HCM) are currently limited and comprise non-disease specific therapies such as ß-blockers, non-dihydropyridine calcium channel blockers, and disopyramide. These agents that offer a variable degree of symptomatic relief, often suboptimal, are often limited by side-effects and fail to address the key molecular abnormalities of the disease. RECENT FINDINGS: Mavacamten is a novel, first-in-class, allosteric inhibitor of cardiac myosin ATPase, which reduces actin-myosin cross-bridge formation, thereby reducing myocardial contractility and improving myocardial energetic consumption in experimental HCM models. Following a successful Phase 2 study, the recently published phase III, placebo-controlled, randomized EXPLORER-HCM trial demonstrated the efficacy and safety of mavacamten in reducing left ventricular outflow tract obstruction and ameliorating exercise capacity, New York Heart Association functional class and health status in patients with obstructive HCM. Mavacamten represents the first agent specifically developed for HCM successfully tested in a Phase III trial, to be registered soon for clinical use, representing a radical change of paradigm in the pharmacological treatment of HCM.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. METHODS: Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. RESULTS: 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /µl vs CSI-: 3000 /µl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. CONCLUSIONS: CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.

Myocardial blood flow in patients with hypertrophic cardiomyopathy receiving perindopril (CARAPaCE): a pilot study.

AIMS: Coronary microvascular dysfunction (CMD) represents a powerful independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). No treatment for CMD exists. The angiotensin-converting enzyme (ACE)-inhibitor perindopril improves myocardial blood flow (MBF) in animal models of cardiac hypertrophy and in hypertensive patients. Whether HCM patients with CMD may benefit is unknown. METHODS: Fourteen HCM patients aged 18-60 years with CMD [MBF post 0.56 mg/kg dipyridamole (Dip) infusion <2.1 ml/min∗g] were included. Presence of left ventricular outflow obstruction, hypertension and coronary artery disease were exclusion criteria. Perindopril was administered after the initial Dip 13N-NH3 PET study at 10 mg for 6 months. After wash-out, a second PET was performed. MBF before and after treatment was compared. RESULTS: No relevant associations were found between baseline MBF values and sex, genetics, history of angina, type of HCM (apical/classic), maximum left ventricular thickness and left ventricular mass. No significant improvement in Dip-MBF was observed with treatment (1.79 ±â€Š0.30 vs.1.76 ±â€Š0.26 ml/min∗g at baseline; P = 0.59). A limited but significant improvement in Dip-MBF was seen only in the subset without evidence of fibrosis at cardiac MRI (n = 4; 28%; 2.03 ±â€Š0.13 vs.1.77 ±â€Š0.26 ml/min∗g at baseline; P = 0.014). The drug was generally well tolerated: only one patient temporarily stopped the drug, because of cough. CONCLUSION: A 6-month perindopril treatment course in HCM patients with CMD was not associated with significant improvement in Dip-MBF. A limited but significant improvement was observed only in the subset of patients without myocardial fibrosis, suggesting potential utility in early disease stages.

Doctor-patient care relationship in genetic cardiomyopathies: An exploratory study on clinical consultations.

BACKGROUND: The present study aims to explore the setting of consultation and communication between physicians and patients affected by genetic cardiomyopathies, investigating how the two parts of the therapeutic relationship participate and share information. METHODS AND RESULTS: 45 adult patients affected by various cardiomyopathies took part in a prospective case study while attending consultations at a cardiologic outpatient clinic constituting an Italian referral centre for cardiomyopathies. A researcher observed the consultations, which were audio-recorded and transcribed. Transcripts were coded and an analysis of setting, type of communication implemented and participation of doctors and patients in terms of word-count and type of questions/answers was carried out. Overall word-count was significantly higher for physicians than for patients (t(44) = 9,506; p<0.001). Doctors were prone to ask closed questions (t(44) = -11,90; p<0.001) while patients preferred open answers (t(44) = 5.58; p<0.001), enriched with subjective issues related to their illness experience. Partial correlation highlights a significant positive relation between doctors' closed question and patients' open answers (r = .838; p<0.001). CONCLUSIONS: Findings emphasize patients' need for adequate time and space to share their subjective illness experience with the physician, within an approach informed by the insights and recommendations of Narrative Medicine. These findings are instrumental to improving the specific clinical setting for individuals with genetic cardiomyopathies.

Prevalence, causes and predictors of cardiovascular hospitalization in patients with hypertrophic cardiomyopathy.

BACKGROUND: Despite numerous studies assessing the natural history of patients with hypertrophic cardiomyopathy (HCM), there is lack of data regarding the burden of hospitalization. Aim of this study was to describe prevalence, causes and predictors of cardiovascular hospitalization in patients with HCM. METHODS: We retrospectively included 253 patients with HCM undergoing first evaluation at our center. Enrolment criteria included cardiac magnetic resonance imaging (CMRI) at baseline and > 1-year follow-up. All hospital admissions were recorded during follow-up and adjudicated as acute vs elective and cardiovascular (CV) vs non-cardiovascular (non-CV). RESULTS: During 6.4 ± 4.0 years there were 187 hospitalizations in 92 patients (36%, at a rate of 5.7%/year). Most were CV-related (158/187,84.5%; 4.8%/year) while non-CV admissions were 29/187 (15.5%, 0.88%/year). There was a slight predominance of elective (n = 96, 58%, 2.8%/year) vs acute (n = 62, 41.8%, 2.0%/year) CV hospitalizations. Independent predictors of CV hospitalization were baseline symptoms (NYHA class II vs I: HR 2.06; 95% CI 1.24-3.43, NYHA III-IV vs I: HR 3.05; 95% CI 1.40-6.65, p = .004), indexed left atrial (LA) volume (HR 1.03; 95% CI 1.01-1.04, p < .001), and lower indexed right ventricular end-diastolic volume iRVEDV) at cardiac magnetic resonance (HR 0.99; 95% CI 0.97-0.99, p = .03). CONCLUSIONS: In little over 6 years, CV hospitalization was required in over one-in-three of our HCM patients, often unplanned and due to acute disease-related complications. Symptomatic status, larger LA volume and reduced iRVEDV at baseline were independently associated with CV admissions. Strategies aimed at preventing hospitalizations are an important target to reduce the burden of disease in HCM patients.

Design of the SILICOFCM study: Effect of sacubitril/valsartan vs lifestyle intervention on functional capacity in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease with a broad spectrum of disease severity. HCM ranges from a benign course to a progressive disorder characterized by angina, heart failure, malignant arrhythmia, syncope, or sudden cardiac death. So far, no medical treatment has reliably shown to halt or reverse progression of HCM or to alleviate its symptoms. While the angiotensin receptor neprilysin inhibitor sacubitril/valsartan has shown to reduce mortality and hospitalization in heart failure with reduced ejection fraction, data on its effect on HCM are sparse. HYPOTHESIS: A 4-month pharmacological (sacubitril/valsartan) or lifestyle intervention will significantly improve exercise tolerance (ie, peak oxygen consumption) in patients with nonobstructive HCM compared to the optimal standard therapy (control group). METHODS: SILICOFCM is a prospective, multicenter, open-label, randomized, controlled, three-arm clinical trial (NCT03832660) that will recruit 240 adult patients with a confirmed diagnosis of nonobstructive HCM. Eligible patients are randomized to sacubitril/valsartan, lifestyle intervention (physical activity and dietary supplementation with inorganic nitrate), or optimal standard therapy alone (control group). The primary endpoint is the change in functional capacity (ie, peak oxygen consumption). Secondary endpoints include: (a) Change in cardiac structure and function as assessed by transthoracic echocardiography and cardiac magnetic resonance (MRI imaging), (b) change in biomarkers (ie, CK, CKMB, and NT-proBNP), (c) physical activity, and (d) quality of life. RESULTS: Until December 2019, a total of 41 patients were recruited into the ongoing SILICOFCM study and were allocated to the study groups and the control group. There was no significant difference in key baseline characteristics between the three groups. CONCLUSION: The SILICOFCM study will provide novel evidence about the effect of sacubitril/valsartan or lifestyle intervention on functional capacity, clinical phenotype, injury and stretch activation markers, physical activity, and quality of life in patients with nonobstructive HCM.

Targeted Medical Therapies for Hypertrophic Cardiomyopathy.

PURPOSE OF REVIEW: The management of hypertrophic cardiomyopathy (HCM) has changed considerably over the years, although molecular therapies targeting core mechanisms of the disease are still lacking. This review provides an overview of the contemporary medical approach to patients with HCM, and of promising novel developments hopefully soon to enter the clinical arena. RECENT FINDINGS: Our perception of therapeutic targets for medical therapy in HCM is rapidly evolving. Novel approaches include myocardial metabolic modulation, late sodium current inhibition, and allosteric myosin inhibition, actively pursued to reduce and hopefully prevent the development of severe HCM phenotypes, improve symptom control, and preserve patients from disease-related complications. Clinical management of patients with HCM should be guided by in-depth knowledge of the complex mechanisms at the energetic, metabolic, and electrophysiologic level. Until new experimental therapies become available, tailored management of modifiable disease manifestations should be pursued, including lifestyle counseling and prevention of comorbidities.

Comprehensive Risk Management in Arrhythmogenic Cardiomyopathy Associated With Autosomal Dominant Carvajal Syndrome: Protecting Families.

In a 37-year-old cardiac arrest survivor with autosomal dominant Carvajal syndrome and arrhythmogenic cardiomyopathy, a desmoplakin mutation was identified. Cascade screening identified 2 affected family members and 2 healthy children carrying the mutation. Strategies for primary and secondary risk prevention emphasize the role of genetic testing in rare cardiomyopathies. (Level of Difficulty: Advanced.).