The uptake and utility of genetic testing and genetic counseling for hypertrophic cardiomyopathy-A systematic review and meta-analysis.

Genetic testing and genetic counseling are routinely indicated for patients with hypertrophic cardiomyopathy (HCM); however, the uptake and utility of these services is not entirely understood. This systematic review and meta-analysis summarizes the uptake and utility of genetic counseling and genetic testing for patients with HCM and their at-risk family members, as well as the impact of genetic counseling/testing on patient-reported outcomes (PROs). A systematic search was performed through March 12, 2021. Meta-analyses were performed whenever possible; other findings were qualitatively summarized. Forty-eight studies met inclusion criteria (47 observational, 1 randomized). Uptake of genetic testing in probands was 57% (95% confidence interval [CI]: 40, 73). Uptake of cascade screening for at-risk relatives were as follows: 61% for cascade genetic testing (95% CI: 45, 75), 58% for cardiac screening (e.g. echocardiography) (95% CI: 40, 73), and 69% for either/both approaches (95% CI: 43, 87). In addition, relatives of probands with a positive genetic test result were significantly more likely to undergo cascade screening compared to relatives of probands with a negative result (odds ratio = 3.17, 95% CI: 2.12, 4.76). Overall, uptake of genetic counseling in both probands and relatives ranged from 37% to 84%. Multiple studies found little difference in PROs between individuals receiving positive versus negative genetic test results; however, other studies found that individuals with positive genetic test results experienced worse psychological outcomes. Genetic testing may also inform life choices, particularly decisions related to reproduction and insurance. Genetic counseling was associated with high satisfaction, increased perceived personal control and empowerment, and decreased anxiety. Approximately half to three-quarters of patients with HCM and their relatives undergo genetic testing or cascade screening. PROs after genetic testing varied and genetic counseling was associated with high satisfaction and improved PROs.

Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder which frequently leads to symptoms such as dyspnea and exercise intolerance, often due to severe dynamic left ventricular outflow tract obstruction (LVOTO). Current guideline-recommended pharmacotherapies have variable therapeutic responses to relieve LVOTO. In recent phases 2 and 3, clinical trials for symptomatic obstructive HCM (oHCM), mavacamten, a small molecule inhibitor of ß-cardiac myosin has been shown to improve symptoms, exercise capacity, health status, reduce LVOTO, along with having a beneficial impact on cardiac structure and function. METHODS: VALOR-HCM is designed as a multicenter (approximately 20 centers in United States) phase 3, double-blind, placebo-controlled, randomized study. The study population consists of approximately 100 patients (≥18 years old) with symptomatic oHCM who meet 2011 American College of Cardiology/American Heart Association and/or 2014 European Society of Cardiology HCM-guideline criteria and are eligible and willing to undergo septal reduction therapy (SRT). The study duration will be up to 138 weeks, including an initial 2-week screening period, followed by16 weeks of placebo-controlled treatment, 16 weeks of active blinded treatment, 96 weeks of long-term extension, and an 8-week posttreatment follow-up visit. The primary endpoint will be a composite of the decision to proceed with SRT prior to or at Week 16 or remain guideline eligible for SRT at Week 16. Secondary efficacy endpoints will include change (from baseline to Week 16 in the mavacamten group vs placebo) in postexercise LVOT gradient, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire clinical summary score, NT-proBNP, and cardiac troponin. Exploratory endpoints aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology. CONCLUSIONS: In severely symptomatic drug-refractory oHCM patients meeting guideline criteria of eligibility for SRT, VALOR-HCM will primarily study if a 16-week course of mavacamten reduces or obviates the need for SRT using clinically driven endpoints.

Quality of life status determinants in hypertrophic cardiomyopathy as evaluated by the Kansas City Cardiomyopathy Questionnaire.

PURPOSE: The present study evaluated how heart failure (HF) negatively impacts health-related quality of life (HRQoL) in hypertrophic cardiomyopathy (HCM) patients and explored the major clinical determinants associated with HRQoL impairment in this population. METHODS: This was a cross-sectional single-center study of health-related HRQoL that included 91 consecutive patients with HCM. Evaluation was performed based on a comprehensive protocol that included the recommended diagnostic studies, as well as administration of the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (CV Outcomes Inc) as a health status measure. RESULTS: The cohort included 52 (57%) males, median age 58 (20-85) years. The median global KCCQ score was 67 (12.5-100) corresponding to a moderate impairment in HRQoL. There was an inverse correlation between the median global KCCQ score and NYHA class (Kendall's tau b coefficient r - 0.33, p = 0.001). Patients with pulmonary hypertension (PHT), defined as resting pulmonary artery systolic pressure of ≥ 45 mmHg, presented a significantly worse HRQoL as compared to those without PHT (median KCCQ score 56.2 vs 77.5, p = 0.013). The KCCQ score mildly correlated with age (r - 0.18, p = 0.014), history of syncope (r - 0.18, p = 0.045), estimated glomerular filtration rate (eGFR) (r 0.31, p < 0.001), plasmatic creatinine (r - 0.18, p = 0.017) and urea levels (r - 0.27, p < 0.001), left ventricular (LV) end-systolic dimensions (r - 0.18, p = 0.014), maximal provoked intraventricular gradient (r 0.20, p = 0.039), LV ejection fraction (r 0.15, p = 0.04), average E/e' (r - 0.16, p = 0.039), pulmonary acceleration time (r 0.21, p = 0.007), pulmonary artery systolic pressure (r - 0.20, p = 0.016). In ordinal regression, the independent predictors of HRQoL were NYHA class and eGFR. CONCLUSIONS: Patients with HCM and HF present a moderate degree of alteration in HRQoL. This is especially true for patients with PHT and more severe functional impairment. Renal failure and NYHA class are potential markers of HRQoL in clinical practice.

Participation in thrill-seeking activities by patients with hypertrophic cardiomyopathy: Individual preferences, adverse events and physician attitude.

BACKGROUND: Thrill-seeking activities are a favorite pastime for people of all ages. Patients with hypertrophic cardiomyopathy (HCM) are often barred from participation on the basis of danger for arrhythmias. Our aim was to collect information regarding the safety of thrill-seeking activities for HCM patients. METHODS: An anonymous online survey invited adult HCM patients to report participation in 11 activities (rollercoaster riding, jet skiing, rafting, bungee jumping, rappelling, paragliding, kayaking/canoeing, motor racing, snowboarding, BASE jumping and skydiving) before and after HCM diagnosis, along with major (ICD shock, syncope) or minor (nausea, dizziness, palpitations, chest pain) adverse events related to participation, and relevant physician advice. RESULTS: Six hundred forty-seven HCM patients completed the survey, with 571 (88.2%) reporting participation in ≥1 TSAs (participant age 50.85 ±â€¯14.21, 56.6% female, 8143 post-diagnosis participations). At time of survey, 457 participants (70.6%) were ICD-carriers or had ≥1 risk factor for sudden cardiac death. Nine (1.5%) participants reported a major event during or immediately after (60 minutes) of surveyed activity. Minor adverse events were reported by 181 participants (31.6%). In addition, 8 participants reported a major adverse event >60 minutes later but within the same day. Regarding physician advice, of the 213 responders (32.9%) receiving specific advice, 56 (26.2%) were told safety data is absent with no definitive recommendation, while 24 (11.2%) and 93 (43.6%) were told TSAs were respectively safe or dangerous. CONCLUSIONS: In this cohort, participation in thrill-seeking activities rarely caused major adverse events. This information can be used for shared-decision making between providers and patients.

Pacing for hypertrophic obstructive cardiomyopathy: an update and future directions.

In hypertrophic cardiomyopathy (HCM) patients with symptoms caused by left ventricular outflow tract obstruction (LVOTO), treatment options include negative inotropic drugs, myectomy, septal alcohol ablation and AV sequential pacing with or without an implantable cardioverter defibrillator (ICD). Pacing is rarely used in spite of its relative simplicity and promising results. In this review the current evidence of AV sequential pacing from observational, randomised studies and long and very long-term follow-up studies is given and put in the context of present guidelines recommendations. These studies indicate that AV sequential pacing improves symptoms and quality of life through decreases in LVOTO, systolic anterior movement and mitral regurgitation. Effects on morbidity and mortality are lacking. We describe the mechanisms of action, the prerequisites for successful pacing and provide practical advice on how to optimise therapy. Moreover, the role of the ICD for primary and secondary prevention is discussed with reference to the ESC HCM guidelines. In summary, AV sequential pacing for HOCM is underused in clinical practise despite evidence from two randomised controlled studies. This concept is currently the focus of two randomised studies: a planned randomised controlled study that will compare AV sequential pacing to TASH and an ongoing study that compares CRT to AAI pacing in HOCM patients. In this review we highlight the current evidence and the new interest for this therapy.

Examining the Psychosocial Impact of Genetic Testing for Cardiomyopathies.

Inherited cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), are the most common monogenic cause of cardiac disease and can rarely lead to sudden cardiac death (SCD). They are characterized by incomplete and age-dependent penetrance and are usually initially symptomatic in adulthood yet can present in childhood as well. Over 20 genes have been identified to cause HCM, and more than 40 genes are known to cause DCM. Genetic testing for these genes has been integrated into medical care; however, the psychological impact of genetic testing and the impact of the uncertainty that comes with receiving these results have not been well studied. This study surveyed 90 adult probands and relatives with a personal or family history of cardiomyopathy from a single hospital-based cardiac genetic program to determine the psychosocial impact of genetic testing for cardiomyopathies. Standardized psychological instruments including an adapted Multidimensional Impact of Cancer Risk Assessment (aMICRA), Impact of Event Scale (IES), and Satisfaction with Decision (SWD) scales were utilized. Patients with positive genetic test results had higher scores for intrusive thoughts, avoidance, and distress when compared to those with negative genetic test results and were also more likely to make or plan to make life changes because of the results of their genetic testing. Satisfaction with the decision to undergo genetic testing was similar regardless of genetic test results. The results of this study provide insight into the patient experience of genetic testing for cardiomyopathies and how these experiences are associated with genetic test results and cardiac history.

Living with hypertrophic cardiomyopathy and an implantable defibrillator.

BACKGROUND: ICDs efficiently terminate life-threatening arrhythmias, but complications occur during long-term follow-up. Patients' own perspective is largely unknown. The aim of the study was to describe experiences of hypertrophic cardiomyopathy (HCM) patients with implantable defibrillators (ICDs). METHODS: We analyzed 26 Swedish patient interviews using hermeneutics and latent content analysis. RESULTS: Patients (aged 27-76 years) were limited by HCM especially if it deteriorates into heart failure. The ICD implies safety, gratitude, and is accepted as a part of the body even when inappropriate ICD shocks are encountered. Nobody regretted the implant. Both the disease and the ICD affected professional life and leisure time activities, especially at younger ages. Family support was usually strong, but sometimes resulted in overprotection, whereas health care focused on medical issues. Despite limitations, patients adapted, accepted, and managed challenges. CONCLUSION: HCM patients with ICDs reported good spirit and hope even though they had to adapt and accept limitations over time.

Psychosocial adjustment and quality of life in children undergoing screening in a specialist paediatric hypertrophic cardiomyopathy clinic.

OBJECTIVE: This study aimed to assess the psychological well-being and quality of life in children with hypertrophic cardiomyopathy and the potential psychosocial impact of screening. METHODS: A total of 152 children (aged 3-18 years) attending a specialist paediatric hypertrophic cardiomyopathy clinic, and their parents completed the Generic Core Scales and Cardiac Module of the Paediatric Quality of Life Inventory (PedsQL) questionnaire as well as the Strengths and Difficulties Questionnaire; 21 patients (14%) had hypertrophic cardiomyopathy (group A); 23 children (15%) harboured hypertrophic cardiomyopathy-causing sarcomeric mutations with normal echocardiograms (group G); and 108 children (71%) had a family history of hypertrophic cardiomyopathy with normal investigations and attended for clinical cardiological screening (group S). RESULTS: In group A, mean PedsQLTM total scores reported by children and parents were lower than those reported by unaffected children (p<0.001). There was no significant difference between unaffected and gene-positive patients. Mean Cardiac module PedsQLTM total scores by children and parents were lower in children with hypertrophic cardiomyopathy compared with unaffected patients [mean child-reported total score 86.4 in group S versus 72.3 in group A (p<0.001) and 80.2 in group G (p=0.25); mean parent-reported total score 91.6 in group S versus 71.4 in group A (p<0.001) and 87 in group G (p=0.4)]. There was no significant difference between group S and group G on any of the scales, or between the three groups of patients in the mean Strengths and Difficulties Questionnaire scores. CONCLUSIONS: Children with hypertrophic cardiomyopathy have a significantly reduced quality of life. Importantly, Quality-of-Life scores among unaffected children attending for screening were not different compared with scores from a normative UK population.

Factors Associated with Uptake of Genetics Services for Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common cardiovascular disorder with variable expressivity and incomplete penetrance. Clinical guidelines recommend consultation with a genetics professional as part of an initial assessment for HCM, yet there remains an underutilization of genetics services. We conducted a study to assess factors associated with this underutilization within the framework of the Health Belief Model (HBM). An online survey was completed by 306 affected individuals and at risk family members. Thirty-seven percent of individuals (113/306) had visited a genetics professional for reasons related to HCM. Genetic testing was performed on 53 % (162/306). Individuals who had undergone testing were more likely to have seen a genetics professional (p < 0.001), had relatives with an HCM diagnosis (p = 0.002), and have a known familial mutation (p < 0.001). They were also more likely to agree that genetic testing would satisfy their curiosity (p < 0.001), provide reassurance (p < 0.001), aid family members in making healthcare decisions (p < 0.001), and encourage them to engage in a healthier lifestyle (p = 0.002). The HBM components of cues to action and perceived benefits and barriers had the greatest impact on uptake of genetic testing. In order to ensure optimal counseling and care for individuals and families with HCM, awareness and education around HCM and genetic services should be promoted in both physicians and patients alike.

Treatment of depression in an adolescent with cardiomyopathy and arrhythmia.

Patients with cardiomyopathy have a higher incidence of mood and anxiety disorders, resulting in greater probability for hospitalisation and increased risk for arrhythmia and death. We report a case of a 16-year-old boy with Danon disease, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy, who later developed depression and significant weight loss. The patient was successfully treated for his anxiety and depression with mirtazapine without any adverse cardiac effects.

Merits and pitfalls of genetic testing in a hypertrophic cardiomyopathy clinic.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM. OBJECTIVES: To analyze the impact of genetic diagnosis on the clinical management of HCM. METHODS: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation. RESULTS: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation. CONCLUSIONS: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determines the indication for genetic testing and interpretation of the results.

Exploring Health-Related Quality of Life in Children With Hypertrophic Cardiomyopathy and Relationship to Physical Activity.

BACKGROUND: Hypertrophic cardiomyopathy is a burdensome condition that inflicts both physical and psychological impairment on those with the disease, negatively impacting health-related quality of life (HRQoL). Given the abundance of evidence suggesting a role of physical activity (PA) in modulating HRQoL in healthy populations of children, we sought to determine the relationship between HRQoL and PA in children diagnosed with hypertrophic cardiomyopathy. METHODS AND RESULTS: A multicenter prospective observational cohort study was conducted, with patients with hypertrophic cardiomyopathy aged 10 to 19 years being provided a wrist-worn activity tracker (Fitbit Charge HR) to wear for 14 days. Patients self-reported on Pediatric Quality of Life 4.0 quality of life inventory items, which were associated with PA metrics following covariate adjustment using linear regression. A total of 56 participants were recruited to the study. The median age at enrollment was 15.5 years (interquartile range, 13.8-16.8), and 16 out of 56 (29%) of the cohort were girls. The cohort reported decreased metrics of physical, psychosocial, and total summary scores compared with health reference populations, with scores comparable with that of published populations with chronic disease. Increased physical HRQoL scores were significantly associated with increased daily steps taken, distance traveled, and flights of stairs climbed. CONCLUSIONS: These results show that impaired PA correlates with reduced HRQoL in children with hypertrophic cardiomyopathy, suggesting PA may partially mediate HRQoL in this population.

Correlations between physician-perceived functional status, patient-perceived health status, and cardiopulmonary exercise results in hypertrophic cardiomyopathy.

BACKGROUND: Dyspnea and the resulting functional impairment are a common complication in hypertrophic cardiomyopathy (HCM). The relationship between physician-perceived functional status, patient-perceived health status, and objective exercise test results has not been evaluated in this condition. PURPOSE: To evaluate the correlation between the Kansas City Cardiomyopathy Questionnaire (KCCQ) and (1) physician's perceived (NYHA class) and (2) objective measurement (cardiopulmonary exercise test) of functional capacity in patients with HCM. METHODS: In 24 outpatients with HCM at a single, referral center, the KCCQ instrument was administered and cardiopulmonary exercise testing (CPX) was performed. Severity of symptoms as determined by physician (NYHA classification) and patient (KCCQ instrument) was obtained before exercise test results were known. Pearson correlation was used to assess the independent correlation between KCCQ score and the various exercise parameters; Spearman correlation was used to assess correlation between KCCQ score and NYHA class. RESULTS: KCCQ results demonstrated moderate reductions in all domains, with greatest reduction in quality-of-life domain. CPX testing showed reduction in peak oxygen consumption (mean absolute VO2 20.5 ± 7.8 ml/kg/min and percent predicted VO2 76.8 ± 4.1 %). There were negative correlations between NYHA class and all KCCQ components except the self-efficacy score. The strongest correlations were between NYHA class and the overall summary score (r = -0.623, p = 0.001) as well as the physical limitation score (r = -0.604, p = 0.002). Similarly, there were statistically significant positive correlations between the KCCQ components and percent predicted peak VO2. The strongest correlation was between percent predicted peak VO2 and the physical limitation score (r = 0.474, p = 0.019), but there was also correlation between percent predicted peak VO2 and the quality-of-life score (r = 0.456, p = 0.025), the functional status score (r = 0.455, p = 0.025), and the clinical summary score (r = 0.444, p = 0.030). CONCLUSIONS: The multiple domains of the KCCQ provide data on patient-perceived health status, which correlate with physician-perceived and objective measurement of functional capacity in HCM. Additional studies are needed to evaluate the sensitivity of the KCCQ to changes in functional capacity over time or in response to therapies for this condition.

Living with hypertrophic cardiomyopathy.

PURPOSE: The purpose of this study is to provide an insider's account of what it is like to live with hypertrophic cardiomyopathy (HCM), a genetic cardiovascular illness that carries the risk for sudden cardiac death. This study aims to reveal how HCM impacts the family and guides the decision whether or not to pursue genetic testing, how the physical limitations associated with HCM alter being-in-the-world, and how HCM alters social relationships. DESIGN: Fifteen adults with HCM were recruited for a longitudinal, phenomenological, qualitative study through purposive sampling and word of mouth. A total of 45 interviews were conducted by the researcher at a time and place designated by the participant between August 2011 and January 2012. The first interview with each participant was conducted in person. While efforts were made to conduct all interviews in person, a total of three interviews were conducted by telephone as requested by three participants due to scheduling conflicts. METHODS: Through methods of interpretive phenomenology, three audio-recorded, semistructured interviews occurred over the course of 3 months. Detailed narratives were solicited and transcribed verbatim. Methodological and analytical documentation was supported with the identification of key phrases, similar experiences, themes, and documentation of the rationale for decisions throughout the research process. CONCLUSIONS: Participation in genetic testing carries a multitude of personal, familial, financial, and emotional implications. The results of a genetic test elicited an emotional response regardless of whether the results were negative, positive, or inconclusive. Living with a potentially life-threatening illness altered identity, disrupted social relationships, and generated chronic fear and uncertainty. A new normal was re-ordered or transformed by the demands and limitations posed by HCM, and by the person's concerns, priorities, and the meaning of the illness. CLINICAL RELEVANCE: Results from this study underscore the need for healthcare professionals to learn more about HCM and to conduct screenings that will facilitate a prompt and accurate diagnosis. In doing so, the risk for sudden cardiac death may be averted. There is a need to educate and to advocate for genetic testing of HCM. It is necessary for healthcare providers to move beyond their biomedical understanding of genetic illness and to address the lived experience of the illness, how the illness impacts the family, and the multifaceted concerns of people who have a genetic illness as well as the concerns of their family members.

Patient experiences of implantable cardiac monitoring in hypertrophic cardiomyopathy: an exploratory study.

AIMS: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Insertable cardiac monitors (ICMs) are increasingly used in this population to provide closer monitoring, with the potential for notification systems. However, little is known regarding the psychological impact this information may have on patients. The Abbott Confirm Rx™ ICM has the capability of connecting to the patient's smartphone to enable active participation in their care, as well as two-way communication between the patient and their care providers. This study aimed to explore individuals' experiences of having a smartphone-enabled ICM to monitor for arrhythmias in HCM. METHODS AND RESULTS: Semi-structured interviews were conducted with 10 participants. Utilizing a grounded theory approach, the interview guide was modified based on emerging themes throughout the study. Reflexive thematic analysis was applied to categorize interview data into codes and overacting themes, with each interview independently coded by two study members. Analysis revealed three key themes: (i) psychological impact, (ii) educational needs, and (iii) technology expectations. Participants reported that receiving feedback from ICM transmissions resulted in improved symptom clarity, providing reassurance, and aiding implantable cardioverter defibrillator decision-making. Some participants reported uncertainty regarding when to send manual transmissions. Lastly, participants reported the app interface did not meet expectations with regard to the amount of data available for patients. CONCLUSION: Overall, utilizing a smartphone app to facilitate two-way communication of ICM transmissions was well accepted. Future directions include addressing gaps in educational needs and improvements in the patient interface with increased access to data.

Predictors of heart-focused anxiety in patients undergoing genetic investigation and counseling of long QT syndrome or hypertrophic cardiomyopathy: a one year follow-up.

Since Long QT syndrome and Hypertrophic cardiomyopathy are inherited cardiac disorders that may cause syncope, palpitations, serious arrhythmias, and sudden cardiac death, at-risk individuals may experience heart-focused anxiety. In a prospective multi-site study, 126 Norwegian patients attending genetic counseling were followed 1 year with multiple administration of questionnaires, including the Cardiac Anxiety Questionnaire, measuring three distinct symptoms of heart-focused anxiety- avoidance, attention, and fear-in mixed linear analyses. Overall, at 1-year follow-up, patients with clinical diagnosis as compared to patients at genetic risk had significantly higher scores of avoidance (p < .002), attention (p < .005), and fear (p < .007). Sudden cardiac death in close relatives, uncertainty whether other relatives previously had undergone genetic testing, patients' perceived general health, self-efficacy expectations and procedural satisfaction with genetic counseling were influential in predicting the different symptoms of heart-focused anxiety over time.

General anxiety, depression, and physical health in relation to symptoms of heart-focused anxiety- a cross sectional study among patients living with the risk of serious arrhythmias and sudden cardiac death.

OBJECTIVE: To investigate the role of three distinct symptoms of heart-focused anxiety (cardio-protective avoidance, heart-focused attention, and fear about heart sensations) in relation to general anxiety, depression and physical health in patients referred to specialized cardio-genetics outpatient clinics in Norway for genetic investigation and counseling. METHODS: Participants were 126 patients (mean age 45 years, 53.5% women). All patients were at higher risk than the average person for serious arrhythmias and sudden cardiac death (SCD) because of a personal or a family history of an inherited cardiac disorder (familial long QT syndrome or hypertrophic cardiomyopathy). Patients filled in, Hospital Anxiety and Depression Scale, Short-Form 36 Health Survey, and Cardiac Anxiety Questionnaire, two weeks before the scheduled counseling session. RESULTS: The patients experienced higher levels of general anxiety than expected in the general population (mean difference 1.1 (p < 0.01)). Hierarchical regression analyses showed that avoidance and fear was independently related to general anxiety, depression, and physical health beyond relevant demographic covariates (age, gender, having children) and clinical variables (clinical diagnosis, and a recent SCD in the family). In addition to heart-focused anxiety, having a clinical diagnosis was of importance for physical health, whereas a recent SCD in the family was independently related to general anxiety and depression, regardless of disease status. CONCLUSION: Avoidance and fear may be potentially modifiable symptoms. Because these distinct symptoms may have important roles in determining general anxiety, depression and physical health in at-risk individuals of inherited cardiac disorders, the present findings may have implications for the further development of genetic counseling for this patient group.

Health status in patients at risk of inherited arrhythmias and sudden unexpected death compared to the general population.

BACKGROUND: The possibilities in the molecular genetics of long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) has made family screening, with diagnostic and predictive genetic testing part of the health care offer in genetic counselling of inherited arrhythmias, potentially affecting the subjective health among these individuals. The study compared health status among patients at risk of arrhythmia because of family history or clinical diagnosis of LQTS and HCM with reference health status scores of the general population. METHODS: In the period 2005-2007, 127 patients (mean age 45 years, 53.5% women), with a family history of arrhythmia (n = 95) or a clinical diagnosis of LQTS (n = 12) or HCM (n = 19) referred for genetic counselling at the medical genetic departments in Norway filled in a questionnaire (Short Form Health Survey SF-36) measuring health status on eight domains. The patient SF-36 scores were compared to expected scores of the general population by t-test, and the relationship between the socio-demographic variables, clinical status, and SF-36 domains were analysed by multiple linear regression. RESULTS: The total sample reported significant lower SF-36 score as compared to the general population scores for the domain of general health (mean difference -7.3 (<0.001). When analysing the sample in subgroups according to clinical status, the general health was still significant lower for the group of family risk and in the group of HCM. In addition the physical functioning, role physical, vitality and role emotional domains were reduced for the latter group. In general, employment, higher education and being referred to genetic counselling through a family member were associated with better scores on the health status domains. CONCLUSIONS: Having a genetic risk of arrhythmia affects general health significantly. In addition, patients with a clinical diagnosis of HCM demonstrate a significantly poorer health in both physical and mental domains.

Emotional stress triggers symptoms in hypertrophic cardiomyopathy: a survey of the Hypertrophic Cardiomyopathy Association.

BACKGROUND: Symptoms are among the most important factors impacting quality of life (QOL) in hypertrophic cardiomyopathy (HCM) patients, and reflect a poor prognosis. Whether emotional stress can trigger symptoms of chest pain, dyspnea, palpitations, and lightheadedness has not been described. METHODS: Members of the Hypertrophic Cardiomyopathy Association (HCMA) received an electronic link via e-mail to an ongoing online survey, also accessed via links on the HCMA message-board and homepage. Between May 2007 and November 2008, there were 1,297 respondents. The survey queried demographic and self-reported clinical information, and types and triggers of symptoms. Respondents reported physical and emotional QOL on a 1-10 Likert scale. RESULTS: Symptoms reported included chest pain (49%), dyspnea (70%), palpitations (61%), and syncope/lightheadedness (59%). The most common symptom trigger was exertion, 64% describing symptoms while climbing stairs or hills. Forty-nine percent described experiencing symptoms during emotional stress. Those reporting chest pain were more likely to report emotion triggering (60%) than those reporting palpitations, syncope/lightheadedness, or dyspnea (50-54% each). Both physical and emotional QOL were significantly decreased in those describing emotion-triggered symptoms. Women were more likely than men to report symptoms overall, as well as emotion-triggered symptoms (50% vs 35%, P < 0.001) and exertion-triggered symptoms (79% vs 58%, P < 0.001). After controlling for presence of symptoms, both emotion- and exertion-triggered symptoms remained significantly more common in women. CONCLUSIONS: Triggering of symptoms by emotion is common in individuals with HCM. Further studies will determine pathways linking emotional stressors with chest pain, dyspnea, palpitations, and lightheadedness in these 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.