Comprehensive Risk Management in Arrhythmogenic Cardiomyopathy Associated With Autosomal Dominant Carvajal Syndrome

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.

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

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

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

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

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 I and a LVOTO 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

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

Long-term outcomes of pediatric-onset hypertrophic cardiomyopathy and age-specific risk factors for lethal arrhythmic events

IMPORTANCE Predictors of lethal arrhythmic events (LAEs) after a pediatric diagnosis of hypertrophic cardiomyopathy (HCM) are unresolved. Existing algorithms for risk stratification are limited to patients older than 16 years because of a lack of data on younger individuals. OBJECTIVE To describe the long-term outcome of pediatric-onset HCM and identify age-specific arrhythmic risk factors. DESIGN, SETTING, AND PARTICIPANTS This study assessed patients with pediatric-onset hypertrophic cardiomyopathy diagnosed from 1974 to 2016 in 2 national referral centers for cardiomyopathies in Florence, Italy. Patients with metabolic and syndromic disease were excluded. EXPOSURES Patients were assessed at 1-year intervals, or more often, if their clinical condition required. MAIN OUTCOMES AND MEASURES Lethal arrhythmic events (LAEs) and death related to heart failure. RESULTS Of 1644 patients with HCM, 100 (6.1%) were 1 to 16 years old at diagnosis (median [interquartile range], 12.2 [7.3-14.1] years). Of these, 63 (63.0%) were boys. Forty-two of the 100 patients (42.0%) were symptomatic (defined as an New York Heart Association classification higher than 1 or a Ross score greater than 2). The yield of sarcomere gene testing was 55 of 70 patients (79%). During a median of 9.2 years during which a mean of 1229 patients were treated per year, 24 of 100 patients (24.0%) experienced cardiac events (1.9%per year), including 19 LAEs and 5 heart failure-related events (3 deaths and 2 heart transplants). Lethal arrhythmic events occurred at a mean (SD) age of 23.1 (11.5) years. Two survivors of LAEs with symptoms of heart failure experienced recurrent cardiac arrest despite an implantable cardioverter defibrillator. Risk of LAE was associated with symptoms at onset (hazard ratio [HR], 8.2; 95%CI, 1.5-68.4; P = .02) and Troponin I or Troponin T gene mutations (HR, 4.1; 95%CI, 0.9-36.5; P = .06). Adult HCM risk predictors performed poorly in this population. Data analysis occurred from December 2016 to October 2017. CONCLUSIONS AND RELEVANCE Pediatric-onset HCM is rare and associated with adverse outcomes driven mainly by arrhythmic events. Risk extends well beyond adolescence, which calls for unchanged clinical surveillance into adulthood. In this study, predictors of adverse outcomes differ from those of adult populations with HCM. In secondary prevention, the implantable cardioverter defibrillator did not confer absolute protection in the presence of limiting symptoms of heart failure