Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET.

AIM: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET). METHODS: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. RESULTS: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001). CONCLUSION: 15O-water PET might detect LV hypertrophy with high accuracy and precision.

[Experiences from a multidisciplinary cardiogenetic clinic]. / Ärftliga hjärt­kärlsjukdomar ­ ett multidisciplinärt arbetssätt krävs.

Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference.  In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.

EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM): A prospective observational study on incidence of arrhythmias.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with arrhythmias. Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death and part of the current risk stratification. Furthermore, atrial fibrillation (AF), which increases the risk of stroke, is believed to be common in HCM patients. Routine ambulatory monitoring captures the rhythm only periodically over 24-48 h; thus, the true burden of arrhythmia is unknown. The insertable cardiac monitor (ICM) should help determine a more realistic arrhythmia assessment in HCM patients. OBJECTIVE: The purpose of this study was to ascertain the incidence of NSVT, AF, and bradycardia in unselected HCM patients by the use of an ICM. METHODS: Thirty adults, mean age 49.9 ± 12.3 years, 25 (83.3%) males were implanted with a Confirm Rx ICM. The monitoring application was installed on the patient's smartphone, which allowed for patient activation in case of symptoms. The ICM was programmed as follows: ventricular tachycardia (VT) ≥ 160 beats per minute (bpm) for ≥8 intervals, AF ≥ 2 min of duration, and bradycardia ≤ 40 bpm or pause ≥ 3.0 s. RESULTS: The mean calculated 5-year risk was 2.3%, and 29/30 of the patients had a risk <4%. During follow-up, AF was found in nine patients (30.0%). At least one episode of NSVT was detected in seven patients (23.3%). In 13 patients (43.3%), sinoatrial block/sinus arrest/sinus bradycardia were seen. No arrhythmia was detected in nine patients (30.0%). CONCLUSION: In this first prospective study using an ICM, the arrhythmia burden in HCM patients yielded 30.0% AF and 23.3% NSVT.

Alcohol Septal Ablation versus Septal Myectomy Treatment of Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Surgical myectomy (SM) and alcohol septal ablation (ASA) are two invasive therapies for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), despite medical therapy. This meta-analysis aims to compare the efficacy of the two procedures. We searched all electronic databases until February 2020 for clinical trials and cohorts comparing clinical outcomes of ASA and SM treatment of patients with HOCM. The primary endpoint was all-cause mortality, cardiovascular (CV) mortality, sudden cardiac death (SCD), re-intervention, and complications. Secondary endpoints included relief of clinical symptoms and drop of left ventricular outflow tract (LVOT) gradient. Twenty studies (4547 patients; 2 CTs and 18 cohorts) comparing ASA vs. SM with a mean follow-up of 47 ± 28.7 months were included. Long term (8.72 vs. 7.84%, p = 0.42) and short term (1.12 vs. 1.27%, p = 0.93) all-cause mortality, CV mortality (2.48 vs. 3.66%, p = 0.26), SCD (1.78 vs. 0.76%, p = 0.20) and stroke (0.36 vs. 1.01%, p = 0.64) were not different between procedures. ASA was associated with lower peri-procedural complications (5.57 vs. 10.5%, p = 0.04) but higher rate of re-interventions (10.1 vs. 0.27%; p < 0.001) and pacemaker dependency (12.4 vs. 4.31%, p = 0.0004) compared to SM. ASA resulted in less reduction in LVOT gradient (-47.8 vs. -58.4 mmHg, p = 0.01) and less improvement of clinical symptoms compared to SM (New York Heart Association (NYHA) class III/IV, 82.4 vs. 94.5%, p < 0.001, angina 53.2 vs. 84.2%, p = 0.02). Thus, ASA and SM treatment of HOCM carry a similar risk of mortality. Peri-procedural complications are less in alcohol ablation but re-intervention and pacemaker implantations are more common. These results might impact the procedure choice in individual patients, for the best clinical outcome.

Positron emission tomography (15O-water, 11C-acetate, 11C-HED) risk markers and nonsustained ventricular tachycardia in hypertrophic cardiomyopathy.

BACKGROUND: The objectives of the study were to describe positron emission tomography (PET) parameters, using the tracers 15O-water at rest/stress, 11C-acetate, and 11C-HED, with regard to nonsustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy (HCM). PET offers quantitative assessment of pathophysiology throughout the left ventricular segments, including the endocardium/epicardium. The potential use PET in risk stratification remains to be elucidated. NSVT provides a marker for sudden cardiac death. METHODS: Patients with a validated diagnosis of HCM who had an implantable cardioverter-defibrillator were interrogated at 12 months and independently of PET-examinations. RESULTS: In total, 25 patients (mean age 56.8 ±â€¯12.9 years, 76% males) were included and 10 reported NSVT. Mean myocardial blood flow (MBF) at rest was 0.91 ml/g/min and decreased at stress, 1.59 ml/g/min. The mean gradient (endocardium/epicardium quotient) at rest was 1.14 ±â€¯0.09, while inverse at stress (mean 0.92 ±â€¯0.16). Notably, MBF gradient at stress was significantly lower in patients with NSVT (p = 0.022) and borderline at rest (p = 0.059) while global MBF at rest and stress were not. Mean myocardial oxygen consumption (MVO2) was 0.088 ml/g/min (higher in NSVT, p = 0.023) and myocardial external efficiency 18.5%. Using 11C-HED, the mean retention index was 0.11 min-1 and a higher volume of distribution (p = 0.089) or transmural gradient of clearance rate (p = 0.061) or lower clearance rate (p = 0.052) showed a tendency of association of NSVT. CONCLUSIONS: The endocardium/epicardium MBF gradient at stress is significantly lower in HCM patients with NSVT. This provides a novel approach to further refine risk stratification of sudden cardiac death.

Current Knowledge of Hypertrophic Cardiomyopathy Among Health Care Providers in Sweden.

Introduction Hypertrophic cardiomyopathy (HCM) is a common disorder with various manifestations, including sudden cardiac death. Patients with suspected or confirmed HCM may be encountered throughout the healthcare system, especially in internal medicine and cardiology. Thus, thorough knowledge of HCM is essential among healthcare providers. Methods A web-based questionnaire was developed to assess the cross-sectional evaluation of HCM knowledge. It covered aspects such as epidemiology and diagnosis, treatment, lifestyle, risk stratification of sudden cardiac death, and implantable cardioverter-defibrillator knowledge. Results In total, 123 subjects completed the survey. The mean age was 38.5 ±10.7 years and two-thirds (n=82) were females; 43.1% were physicians (non-specialist 24.4%, cardiologists 8.9%, specialist, other than cardiology 9.8%); and the remaining were nurses (nurses within cardiology 37.4%, nurses outside cardiology 19.5%). Almost all subjects had heard about the disease (95.9%) and the vast majority (77.2%) had taken part in the management of a patient with HCM. The total mean score was 15.9 ±3.9 credits and the 25th, 50th, and 75th percentiles were 14, 15, and 18 credits, respectively. The predefined arbitrary pass score of ≥60% was reached by 61.8%, and 20.3% were considered to pass with distinction. Physicians scored higher than nurses (70.7 ±17.0% vs 58.1 ±11.8; p<0.001). Within each professional category, there was a similar score with regard to gender. Conclusions There is a considerable lack of knowledge of HCM among healthcare professionals working within the field of internal medicine/cardiology. This insufficient knowledge may contribute to less implementation of evidence-based medicine and current guidelines, although further studies are needed to confirm this.

Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy.

OBJECTIVES: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

PET med O-15-vatten påvisade myokard­ischemi där övrig utredning gick bet.

Elevation of troponin reflects myocardial infarction. The underlying causes should be assessed, as treatment and prognosis may differ widely. Myocardial damage with non-obstructive coronary arteries requires further evaluation including magnetic resonance tomography. We report a case of significant myocardial ischemia which was unnoticed by myocardial scintigraphy but detected by positron emission tomography (PET). The 15O-water tracer allows for quantitative assessment of myocardial perfusion including regional abnormalities and may thus diagnose microvascular dysfunction.

Genetic variants in cardiac calcification in Northern Sweden.

Extensive coronary calcification without significant stenosis, described as calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischemia. There is a discrepancy in the expression pattern of CCAD compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic etiology for it.In this pilot study we studied 3 candidate genes, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1), ATP Binding Cassette Subfamily C Member 6 (ABCC6), and 5'-Nucleotidase Ecto (NT5E) involved in pyrophosphate (PPi) and inorganic phosphate (Pi) metabolism, which may predispose to coronary arterial or valvular calcification. We studied 70 patients with calcific cardiac disease; 65 with CCAD (age 43-83 years) and 5 with calcific aortic valve disease (CAVD) (age 76-82 years).Five DNA variants potentially affecting protein function were found in 6 patients. One variant is a known disease-causing mutation in the ABCC6 gene. Our findings support that disturbances in the PPi and Pi metabolism might influence the development of CCAD and CAVD. However, segregation in the families must first be performed to ascertain any damaging effect of these variants we have found.We report 4 new genetic variants potentially related to coronary calcification, through the disturbed Pi and PPi metabolism. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes particularly those involved with Pi and PPi metabolism.

Low Molecular Mass Myocardial Hyaluronan in Human Hypertrophic Cardiomyopathy.

During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.

[Management of hypertrophic cardiomyopathy - the most common inherited heart disease]. / Hypertrofisk kardiomyopati vanligaste ärftliga hjärtsjukdomen - Sjukdomsförloppet är ofta godartat ­ men risken för plötslig död i arytmi är välkänd.

Hypertrophic cardiomyopathy is the most common cardiogenetic disease affecting 1/500-1/1 000 individuals. Dyspnea is common but chest pain, dizziness or fainting may also cause considerable limitation for the patient. The diagnosis can be suspected from ECG. Echocardiography confirms hypertrophy of at least 15 mm, usually in the septum. If the obstruction of the outflow tract is severe, myectomy or alcohol ablation can relieve symptoms. Genetic evaluation of family members is advisable. To reduce symptoms, betablockers are used; verapamil or disopyramide are alternatives. Atrial fibrillation is often prevalent and requires special attention concerning anticoagulation and rhythm or rate control. An end-stage heart failure warrants advanced treatment options such as cardiac resynchronization therapy, ventricular assist devices or heart transplant. Sudden cardiac death is unpredictable and evaluation of risk markers is important to identify potential candidates for an implantable defibrillator.

EvaLuation Using Cardiac Insertable Devices And TelephonE in Hypertrophic Cardiomyopathy (ELUCIDATE HCM)-rationale and design: a prospective observational study on incidence of arrhythmias in Sweden.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with sudden cardiac death (SCD) mainly due to ventricular tachycardia (VT) or fibrillation even though life-threatening bradycardia occurs. Risk stratification takes several variables into consideration including non-sustained VT (NSVT). An implantable cardioverter defibrillator effectively prevents SCD.Atrial fibrillation (AF) is common among patients with HCM and warrants anticoagulation even without conventional risk factors according to European guidelines. Routinely, the evaluation of arrhythmias using a 48-hour ambulatory external monitor takes place every 6-24 months if patients do not report palpitations. The remaining time the potential burden arrhythmia is unknown. Therefore, the aim of the present study is to assess NSVT and AF incidence during 18 months by an insertable cardiac monitor (ICM). METHODS: Adult patients, aged 18-65 years, with a validated diagnosis of HCM are eligible for the study. The study sample is planned to include 30 patients. A Confirm Rx is implanted at the level of the fourth rib on the left side subcutaneously after local anaesthesia. The application for monitoring is installed in the patients' smartphone and symptoms registered by the patient activation and VT detection programmed as 160 bpm during ≥8 intervals. An AF episode is recorded based on ≥2 min duration. Bradycardia is recorded at ≤40 bpm or pause ≥3.0 s. The patients are followed during 18 months before explant. ETHICS AND DISSEMINATION: The study was approved by The Regional Ethical Committee in Umeå (protocol number 2017/13-31). The study protocol, including variables and prespecified research questions, the study was registered at Clinical Trial Registration NCT03259113. Each patient is informed about the study in both oral and written form by a physician and included after written consent.

Misclassification of hypertrophic cardiomyopathy: validation of diagnostic codes.

PURPOSE: To validate diagnostic codes for hypertrophic cardiomyopathy (HCM), analyze misclassfications, and estimate the prevalence of HCM in an unselected Swedish regional cohort. PATIENTS AND METHODS: Using the hospitals' electronic medical records (used for the Swedish National Patient Register), we identified 136 patients from 2006 to 2016 with the HCM-related codes 142.1 and 142.2 (International Classification of Diseases). RESULTS: Of a total of 129 residents in the catchment area, 88 patients were correctly classified as HCM (positive predictive value 68.2%) and 41 patients (31.8%) were misclassified as HCM. Among the 88 HCM patients (52.2% males), 74 were alive and 14 were dead (15.9%). This yields an HCM prevalence of 74/183,337, that is, 4.0 diagnosed cases per 10,000 in the adult population aged ≥18 years. The underlying diagnoses of misclassified cases were mainly hypertension (31.7%) and aortic stenosis (22.0%). Other types of cardiomyopathies accounted for several cases of misclassification: dilated (nonischemic or ischemic), left ventricular noncompaction, and Takotsubo. Miscellaneous diagnoses were amyloidosis, pulmonary stenosis combined with ventricular septal defect, aortic insufficiency, athelete's heart, and atrioventricular conduction abnormality. The mean age was not significantly different between HCM and misclassified patients (65.8±15.8 vs 70.1±13.4 years; P=0.177). There were 47.8% females among HCM and 60.8% females among misclassified (P=0.118). CONCLUSION: One-third of patients diagnosed as HCM are misclassified, so registry data should be interpreted with caution. A correct diagnosis is important for decision-making and implementation of optimal HCM care; efforts should be made to increase awareness of HCM and diagnostic competence throughout the health care system.

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.

Health-related quality of life in hypertrophic cardiomyopathy patients with implantable defibrillators.

BACKGROUND: Health-related quality of life (HRQL) in hypertrophic cardiomyopathy (HCM) patients with implantable cardioverter-defibrillators (ICDs) is largely unknown. The aim was to assess HRQL, including comparisons between groups, using the questionnaire SF-36, and compare it to a Swedish age- and sex-matched population. METHODS AND RESULTS: Validated data on adult HCM patients with ICDs were used. The SF-36 response rate was 82.5 % and 245 patients (mean age 55.9 years, 70.2 % men) were analyzed using the Mann-Whitney U-test, t-test, Spearman correlation and effect size calculations. In all SF-36 domains the patients' score was lower (p-value of <0.0001) than norms except for bodily pain. The general health domain showed the highest effect size (0.77) and the impact was more pronounced in the SF-36 physical component summary score (0.62) than the mental component summary score (0.46). Older age was correlated with lower scores on the physical component and higher scores on the mental component. Atrial fibrillation and/or systolic heart failure were associated with worse physical health. HRQL was similar in primary vs secondary prevention cases. Inappropriate ICD shock was associated with worse mental health while appropriate therapy trended toward better mental health. CONCLUSION: HCM patients with ICDs suffer from poor HRQL regardless of age, sex, or primary vs secondary prevention indication. Atrial fibrillation and systolic heart failure are determinants of poor physical health. Inappropriate shocks, but not appropriate therapies, are associated with poorer mental health.

Long mitral valve leaflets determine left ventricular outflow tract obstruction during exercise in hypertrophic cardiomyopathy.

BACKGROUND: Development of left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM) is important for explaining symptoms and designing management. LVOTO is mostly caused by a combination of septal hypertrophy and systolic anterior movement of the mitral valve (SAM). The aim of the present study was to determine predictors of exercise induced LVOTO in a group of HCM patients. METHODS: We performed supine exercise Doppler echocardiography, including measurements of LV morphology and function and anterior mitral leaflet length, in 51 mildly symptomatic HCM (septal thickness≥15mm) and compared them with 50 healthy controls. Measurements were made at 1) rest, 2) Valsalva maneuver, 3) peak exercise and 4) post exercise. LVOTO was diagnosed as a LVOT gradient of >30mmHg at rest, after Valsalva and after exercise or ≥50mmHg at peak exercise. RESULTS: All patients stopped exercise because of exhaustion. 35% of the patients had resting LVOTO and 48% during Valsalva. At peak exercise, only 37% had LVOTO, who increased to 64% post exercise. Patients who developed LVOTO at peak exercise were more prone to continue having it post exercise (p<0.001), to have attenuated systolic blood pressure rise (p=0.011) and to have long anterior mitral valve leaflets (p<0.001). Backward multiple regression analysis showed the anterior mitral leaflet length as the strongest single independent predictor (ß=0.36, p=0.010) for increased LVOT velocities, followed by basal septal thickness. CONCLUSION: In patients with HCM, LV outflow tract obstruction seems to be relatively uncommon during exercise but rather occurring minutes after stopping exercise. Exercise LVOTO seems to be determined by long anterior mitral leaflets in addition to the well established septal hypertrophy.

Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden.

AIMS: Implantable defibrillators (ICDs) successfully terminate ventricular arrhythmias in hypertrophic cardiomyopathy (HCM), protect against bradycardia, and monitor atrial arrhythmias. This may alter the natural history and causes of death. METHODS: This nationwide observational longitudinal retrospective study of all HCM patients implanted during 1995-2012 obtained data from the Swedish ICD Registry, the National Patient Register, the Cause of Death Register, and were validated by review of medical records. RESULTS: Of 342 patients (mean age 51.8 years, 70.8% males), 45 died during a total follow-up of 1847 years (mean 5.4 years). Mean age at death was 68.2 years (range 21-83 years; 12 were ≥75 years). Mean follow-up time among the deceased was 4.9 years (quartiles 1.4-7.4 years). All-cause mortality was higher in HCM patients compared with the age and sex-matched Swedish general population (standardized mortality ratio 3.4; 95% confidence interval 2.4-4.5; P < 0.001). Main cause of death was heart failure (n = 27), stroke (n = 5), cancer (n = 3), myocardial infarction (n = 2), sepsis (n = 2), and others (n = 4). Two patients died suddenly, one after the ICD was turned off because of inappropriate shocks, and one patient whose device system was removed after infection. HCM was the main cause of death in 76% of the cases, mainly because of progressive heart failure. CONCLUSION: For HCM patients, ICDs almost eliminate premature arrhythmic death and result in a shift to heart failure as the cause of death in the majority of cases. Still, mortality in HCM patients remains elevated and management of heart failure and comorbidities must be improved to increase survival.

Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy.

BACKGROUND: Risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is mainly based on evaluations from patients at highly specialized centers. AIM: To evaluate risk markers for appropriate implantable cardioverter defibrillator (ICD) therapy in an unselected, nationwide cohort of HCM. METHODS: Patients with an ICD due to HCM were identified from the Swedish ICD Registry since its start in 1995, merged with Patient Register data, and medical records were retrieved. Risk markers for ventricular arrhythmias leading to appropriate ICD therapy were analyzed using Cox proportional hazard ratio (HR). RESULTS: Of 321 patients (70.1% males), at least one appropriate therapy occurred in 77 (24.0%) during a mean follow-up of 5.4 years (5.3% per year; primary prevention 4.5%, secondary prevention 7.0%). Cumulative incidences at 1 year, 3 years, and 5 years were 8.1%, 15.3%, and 21.3%, respectively. Cardioversion effectively restored rhythm in 52% of the first episode and antitachycardia pacing was sufficient in the remaining. For the whole cohort, ejection fraction (EF) <50% (HR 2.63; P < 0.001) was associated with appropriate ICD therapy. In primary prevention, patients with established risk markers experienced appropriate therapy; atrial fibrillation (AF; HR 2.54; P = 0.010), EF < 50% (HR 2.78; P = 0.004), and nonsustained ventricular tachycardia (HR 1.80; P = 0.109) had the highest HR, and wall thickness ≥ 30 mm, syncope, exercise blood pressure response, or family history of SCD had weaker associations. CONCLUSION: ICD therapy successfully terminates ventricular arrhythmias in HCM. In addition to conventional risk markers, a history of AF or EF < 50% may be considered in risk stratification.

Genetic screening in sudden cardiac death in the young can save future lives.

BACKGROUND: Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. METHODS AND RESULTS: From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40%). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). CONCLUSION: Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.