High Risk Of Sudden Cardiac Death Research Articles

Clinical features and prognosis according to genotype variation in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition with many identified disease-causing genetic variants. However, little is known about the clinical course based on the genotype. This study investigates the relationship between the genotype and clinical outcome in patients with HCM. Method A total of 127 patients diagnosed with HCM and underwent genetic testing using a next-generation sequencing panel included ≥30 cardiomyopathy-related genes at two tertiary hospitals. The genotype-positive group (N=51) with pathogenic/likely-pathogenic variants and the genotype-negative group (N=76) were compared in terms of imaging phenotypes and clinical outcomes. The primary outcome was a composite of sudden cardiac death (SCD) and ventricular arrhythmia. Result Among the genotype-positive group, MYBPC3 (37%), MYH7 (29%) and TNNI3 (16%) variants were predominantly identified. The genotype-positive group was diagnosed at a younger age (51.1 ± 14.0 vs 59.7 ± 11.7, p<0.001), showed a higher maximal ventricular wall thickness (17.2 ± 5.1 vs 14.2 ± 4.0, p<0.001), and a higher prevalence of late gadolinium enhancement on cardiac magnetic resonance imaging (86.5% vs 54.4%, p=0.003) compared to the genotype-negative group. The genotype-positive group had a higher incidence of the primary outcome (39.2% vs 9.2%, p<0.001). Conclusion The patients with pathogenic/likely pathogenic variants exhibited morphological characteristics associated with a high risk of SCD, and experienced worse clinical outcomes.

Additional factors associated with sudden cardiac death in HCM patients

Abstract Background Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by an increase in the thickness of the left ventricular (LV) wall, which is not explained only by abnormal loading conditions. Sudden cardiac death (SCD) is the most devastating complication of HCM occurring in asymptomatic or younger patients without warning. Purpose To evaluate additional SCD risk factors in Ukrainian population of HCM patients. Materials and methods We retrospectively evaluated 350 consecutive HCM patients that were followed from 2006 to 2021 in our Cardiological Department. General clinical examination, standard 12-lead ECG, transthoracic echocardiography and 24 hours Holter ECG monitoring data were estimated. The 5-year SCD risk was calculated according to the HCM Risk-SCD score. The endpoint of the study was SCD and its surrogates, including adequate performance of the implantable cardioverter-defibrillator and successful resuscitation. Results Follow-up time was 5.0 (1.5-9.5) years. During this time, 16 patients (4.6%) reached the end point, which was 0.9%/year. According to the HCM Risk-SCD score, 5 (31.3%) of this group had a high risk of SCD (≥ 6%) and 3 (18.8%) had an intermediate risk (≥ 4% and < 6%). In multivariable Cox regression analysis adjusted for conventional SCD risk factors it was found that independent predictors of SCD were unexplained syncope (HR 3.81, 95% CI 1.11-13.12, p=0.034), systolic blood pressure (SBP) (HR 0.97 , 95% CI 0.94- 0.99, p=0.026), "infarct-like" ST elevation on ECG (HR 6.81, 95% CI 2.09-22.16, p=0.001) and PQ interval duration (HR 1.03, 95% CI 1.01-1.05, p=0.002), Harrell's C-index 0.84, 95% CI 0.73-0.95, p < 0.0001). Conclusions In our study HCM Risk-SCD score predicted SCD or surrogates only in 50% of cases. In order to improve the risk stratification some additional independent predictors of SCD can be proposed. ECG parameters ("infarct-like" ST elevation and PQ interval duration) and level of SBP were found to have SCD predictive value.

WEARABLE CARDIOVERTER DEFIBRILLATOR IN PATIENT WITH TRANSIENT RISK OF SUDDEN CARDIAC DEATH : SINGLE CENTRE EXPERIENCE

Abstract Background Cardiovascular disease is still the first cause of death, with sudden cardiac death ( SCD) as a first presentation in 25% of cases, related to coronary artery disease. Implantable cardioverter defibrillator (ICD) demontrated a reduction of SCD in high risk patients with good functional status. However the risk of SCD should be transient, so the use of a wearable cardioverter defibrillator (WCD) is considered in current guidelines and in clinical practice. The purpose of this study was to investigate the safety and the adherence to WCD in a real world population; moreover we reviewed the rate of ICD implantation after WCD use. Methods We considered consecutively 96 patients discharged from Piacenza cardiology department for potentially transient high risk of SCD, weared a WCD from August 2017 to June 2023. The patients were discharged in high risk mode of SCD with WCD protection and followed through remote monitoring or outpatient.A clinical and echocardiographic evalutation was performed at baseline and repeated at the end of the WCD use period. Results Out of 95 patients , with average age 66,0 ±11,1 years old and baseline average left ventricular ejection fraction (LVEF) 28,6±7,5, 81,2% were males, 72,9% suffered from arterial hypertension, 26% diabetes mellitus, 13,5% peripheral vascular disease, 14,6% chronic renal failure, 4,1% previous stroke.66% of these patients weared WCD for severe systolic disfunction in ischemic cardiac disease after recent myocardial infarction, after percutaneous coronary intervention or coronary artery bypass graft, 4% after removal of an infected ICD, 6% whilst awaiting completion of diagnostic tests (chanalopathies/right arrhythmogenic ventricular cardiomyopathy), 24% newly diagnosed cardiomyopathy. The average wearing time of WCD was 22,7±3,1 hours daily. We received these events: 1 sustained ventricular tachicardia, 2 non sustained ventricular tachicardia, 5 atrial fibrillation with 3 T wave oversensing. One patient recedived inappropriate shock. One death was detected due to severe heart failure. After 56,0±37,8 days of average wearing time 52% of patients were scheduled for ICD implantation. Conclusions In our experience we may consider that WCD use is effective, safe and with a good adherence in all patients. The WCD allows saving resources preventing inapprpriate ICD implantation in patient with transient SCD risk.

Left atrial and left ventricular strain in feature-tracking cardiac magnetic resonance for predicting patients at high risk of sudden cardiac death in hypertrophic cardiomyopathy.

Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). The risk stratification of SCD in patients with HCM remains a subject of ongoing debate, and the utility of left atrial (LA) and left ventricular (LV) myocardial strain for risk stratification of also SCD remains uncertain. Through use of feature-tracking cardiac magnetic resonance (FT-CMR), this study aimed to investigate the attenuation of LA and LV strain in HCM and to assess their predictive value in SCD. This retrospective and cross-sectional study included patients with HCM who underwent 3.0 T cardiac magnetic resonance (CMR) at a single institution. Feature-tracking strain analysis was conducted to obtain the strain rate (SR) and LV strain and to evaluate LV function. LA strain was measured during different functional phases including left atrial reservoir strain (LARS), LA conduit strain (LACS), and LA booster strain. All patients were categorized into high- and low-risk groups for SCD as defined by the 2020 American Heart Association/American College HCM implantable cardioverter defibrillator class of recommendation algorithm. Comparison between the two groups was conducted using the independent samples t test and the nonparametric rank sum test. Multivariate logistic regression analysis was performed to further identify the factors influencing SCD risk in HCM. Compared with those in the low-risk group, patients in the high-risk group had lower left ventricular ejection fraction (LVEF), LV stroke volume index (LVSVI), and LA stroke volume index (LASVI) but a higher LV end-systolic volume index (LVESVI), LV maximum wall thickness, and late gadolinium enhancement (LGE) (P<0.001). LV strain, SR, and LA strain all showed significant differences between the high- and low-risk groups (LARS: P=0.04; LACS: P=0.02; all other P values <0.001). The LV global circumferential strain (LVGCS) had a strong negative correlation with LVEF in patients with HCM (r=-0.76; P<0.001). Multivariate analysis showed that LV global radial strain (LVGRS) and LARS could be used for categorizing the patients into the high-risk group [LVGRS: odds ratio (OR) =0.69; 95% confidence interval (CI): 0.55-0.87, P<0.001; LARS: OR =1.39; 95% CI: 1.02-1.90, P=0.03]. The combined LVGRS-LARS model exhibited a superior diagnostic value for high risk of SCD [area under the curve (AUC) =0.95; 95% CI: 0.90-1.00; P<0.001] compared to LARS alone (AUC =0.63; 95% CI: 0.51-0.76; P=0.04). LA and LV strain measured by FT-CMR can accurately identify those patients with HCM at a high risk of SCD. This approach may prove considerably value in guiding early therapeutic intervention with implantable cardioverter-defibrillators (ICDs) to prevent adverse clinical outcomes.

Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial

BackgroundComprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries.MethodsPatients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD.ResultsWe enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116–0.343, p < 0.0001) lower SCD risk.ConclusionsThere was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent.Trial registrationClinicalTrials.gov, NCT02099721.

Ventricular Arrhythmias and Hemodynamic Collapse During Acute Coronary Syndrome- Increased Risk for Sudden Cardiac Death?

In acute phase of acute coronary syndrome (ACS), ventricular tachycardia (VT) and/or ventricular fibrillation (VF) leading to resuscitation are not considered to be associated with increased long-term sudden cardiac death (SCD) because the cause - acute ischemia - is believed to be reversible.Aim of this study was to investigate whether ventricular arrhythmias leading to sudden cardiac arrest during ACS associate with the risk of incident SCD in patients with normal or mildly impaired left ventricular ejection fraction (LVEF). This study is based on a retrospective analysis of all 8,062 consecutive ACS patients undergoing coronary angiography with baseline LVEF ≥40% between 2007-2018 (follow-up until December 31st, 2021). The primary outcome was SCD equivalent life-threatening ventricular arrhythmias (LTVA) composing of true SCDs, aborted SCDs by successful resuscitation or appropriate ICD therapy. The risk of sudden LTVA was estimated with multivariate subdistribution hazard model using other deaths as competing events. Two-hundred and thirteen (n=211, 2.6%) patients suffered acute phase VF/VT leading to resuscitation and survived to discharge and most happened before angiography (80.6%, N=170) and were VF (92.9%, N=196). During a median follow-up of 7.6 years, 3.9% (N=316) of all the patients had LTVA (10.0% in VF/VT group vs 3.8% in other patients). VF/VTs during ACS associated with an increased risk for future SCD (HR 3.07; 95% CI 1.94-4.85, p<0.001). Most LTVAs occurred in patients without ICDs. VF/VT in ACS associates with remarkably high long-term risk for SCD in patients with LVEF ≥40%.

Prognostic value of morphological, biochemical, molecular markers of fibrosis in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) at the cellular level is characterized by hypertrophy, cardiomyocyte disorganization and myocardial fibrosis areas. The leading death cause in HCM remains sudden cardiac death (SCD). Despite the existing risk scores for SCD in HCM, there are still patients with uncertain SCD risk. In addition, SCD cases are also recorded among low-risk patients. From the above, search for novel markers for a more accurate risk assessment should be continued. Fibrosis is currently suspected to be a substrate of potentially life-threatening ventricular arrhythmias. Despite the increasingly widespread use of cardiac magnetic resonance imaging in the diagnosis of myocardial fibrosis and stratification of patients at high SCD risk, the determination of myocardial fibrosis biomarkers remains a relevant and promising area. The article presents the results of studies proving the diagnostic significance and relationship with the risk of life-threatening cardiac arrhythmias of the following markers: C-propeptide of type I procollagen, matrix metalloproteinase proteins, tissue inhibitor of metalloproteinases 1, microRNA family, soluble suppression of tumorigenicity 2, galectin-3, apelin. Evaluation of these biomarkers can be used to improve risk stratification of patients with HCM.

QRS-T angle: is it a specific parameter associated with sudden cardiac death in type 2 diabetes? Results from the SURDIAGENE and the Mini-Finland prospective cohorts.

Type 2 diabetes is associated with a high risk of sudden cardiac death (SCD), but the risk of dying from another cause (non-SCD) is proportionally even higher. The aim of the study was to identify easily available ECG-derived features associated with SCD, while considering the competing risk of dying from non-SCD causes. In the SURDIAGENE (Survie, Diabete de type 2 et Genetique) French prospective cohort of individuals with type 2 diabetes, 15 baseline ECG parameters were interpreted among 1362 participants (mean age 65 years; HbA1c 62±17 mmol/mol [7.8±1.5%]; 58% male). Competing risk models assessed the prognostic value of clinical and ECG parameters for SCD after adjusting for age, sex, history of myocardial infarction, N-terminal pro b-type natriuretic peptide (NT-proBNP), HbA1c and eGFR. The prospective Mini-Finland cohort study was used to externally validate our findings. During median follow-up of 7.4 years, 494 deaths occurred including 94 SCDs. After adjustment, frontal QRS-T angle ≥90° (sub-distribution HR [sHR] 1.68 [95% CI 1.04, 2.69], p=0.032) and NT-proBNP level (sHR 1.26 [95% CI 1.06, 1.50] per 1 log, p=0.009) were significantly associated with a higher risk of SCD. Nevertheless, frontal QRS-T angle was the only marker not to be associated with causes of death other than SCD (sHR 1.08 [95% CI 0.84, 1.39], p=0.553 ). These findings were replicated in the Mini-Finland study subset of participants with diabetes (sHR 2.22 [95% CI 1.05, 4.71], p=0.04 for SCD and no association for other causes of death). QRS-T angle was specifically associated with SCD risk and not with other causes of death, opening an avenue for refining SCD risk stratification in individuals with type 2 diabetes.

The China Hypertrophic Cardiomyopathy Project (CHCMP): The Rationale and Design of a Multicenter, Prospective, Registry Cohort Study.

Hypertrophic cardiomyopathy (HCM) is associated with adverse outcomes, such as heart failure, arrhythmia, and mortality. Sudden cardiac death (SCD) is a common cause of death in HCM patients, and identification of patients at a high risk of SCD is crucial in clinical practice.The China Hypertrophic Cardiomyopathy Project is a hospital-based, multicenter, prospective, registry cohort study of HCM patients, covering a total of 3000 participants and with a 5-year follow-up plan. A large number of demographic characteristics and clinical data will be fully collected to identify prognostic factors in Chinese HCM patients. Furthermore, the main purpose of this study is to integrate demographic and clinical characteristics to establish new 5-year SCD risk predictive equations for Chinese HCM patients by the use of machine learning technologies.The project has crucial clinical significance for risk stratification and determination of HCM patients with high risk of adverse outcomes. CLINICAL TRIALS REGISTRATION: ChiCTR2300070909.

Assessment of Sudden Cardiac Death Risk in Pediatric Primary Electrical Disorders: A Comprehensive Overview

Sudden cardiac death (SCD) in children is a devastating event, often linked to primary electrical diseases (PED) of the heart. PEDs, often referred to as channelopathies, are a group of genetic disorders that disrupt the normal ion channel function in cardiac cells, leading to arrhythmias and sudden cardiac death. This paper investigates the unique challenges of risk assessment and stratification for channelopathy-related SCD in pediatric patients—Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, long QT syndrome, Anderson–Tawil syndrome, short QT syndrome, and early repolarization syndrome. We explore the intricate interplay of genetic, clinical, and electrophysiological factors that contribute to the complex nature of these conditions. Recognizing the significance of early identification and tailored management, this paper underscores the need for a comprehensive risk stratification approach specifically designed for pediatric populations. By integrating genetic testing, family history, and advanced electrophysiological evaluation, clinicians can enhance their ability to identify children at the highest risk for SCD, ultimately paving the way for more effective preventive strategies and improved outcomes in this vulnerable patient group.

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy and future perspectives.

The hypertrophic cardiomyopathy (HCM) risk- sudden cardiac death (SCD) model provides a convenient tool for determining the risk of SCD in patients with HCM even though some patients with low-risk scores still remain at risk of SCD. Hence, the aim of our study was to assess the performance of HCM Risk-SCD in a large series of consecutive patients with HCM who had been followed up in a tertiary center. The study population consisted of 389 consecutive HCM patients who had been followed up between 2004 and 2021. Demographic and clinical characteristics, estimated 5-year risk using the HCM Risk-SCD model, were compiled, and survival data were collected during follow-up. Patients were divided into 2 groups according to their long-term survival, and HCM risk-SCD scores of these two groups were compared. The long-term mortality was observed in 47 patients out of 389 patients in the during a mean follow-up of 55.5 ± 12.7 months. The mean HCM Risk-SCD score of surviving patients was significantly lower than that of non-survivors (1.8% vs. 3.0%, p < .001). The HCM Risk-SCD score was above 6% in nine (2.6%) survivors and nine (19.1%) non-survivors (p < .001). The ROC curve based on the HCM Risk-SCD score had 61% sensitivity and 61% specificity for risk threshold of for 2.0%, 38% sensitivity and 99% specificity a threshold of ≥4%, 17% sensitivity, and 99% specificity for a threshold of ≥6%. A new risk algorithm with higher sensitivity is needed, although the HCM risk-SCD model is still quite useful in identifying patients at a high risk for SCD.

Plasma Ceramides and Sphingomyelins and Sudden Cardiac Death in the Cardiovascular Health Study

Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known. To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk. In this cohort study, multivariable Cox proportional hazards regression models were used to examine the association of sphingolipid species with SCD risk. The study population included 4612 participants in the Cardiovascular Health Study followed up prospectively for a median of 10.2 (IQR, 5.5-11.6) years. Baseline data were collected from January 1992 to December 1995 during annual examinations. Data were analyzed from February 11, 2020, to September 9, 2023. Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons. Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk. Among the 4612 CHS participants included in the analysis (mean [SD] age, 77 [5] years; 2724 [59.1%] women; 6 [0.1%] American Indian; 4 [0.1%] Asian; 718 [15.6%] Black; 3869 [83.9%] White, and 15 [0.3%] Other), 215 SCD cases were identified. In adjusted Cox proportional hazards regression analyses, plasma ceramides and sphingomyelins with palmitic acid (Cer-16 and SM-16) were associated with higher SCD risk per higher SD of log sphingolipid levels (hazard ratio [HR] for Cer-16, 1.34 [95% CI, 1.12-1.59]; HR for SM-16, 1.37 [95% CI, 1.12-1.67]). Associations did not differ by baseline age, sex, race, or body mass index. No significant association of SCD with sphingolipids with very-long-chain saturated fatty acids was observed after correction for multiple testing (HR for ceramide with arachidic acid, 1.06 [95% CI, 0.90-1.24]; HR for ceramide with behenic acid, 0.92 [95% CI, 0.77-1.10]; HR for ceramide with lignoceric acid, 0.92 [95% CI, 0.77-1.09]; HR for sphingomyelin with arachidic acid, 0.83 [95% CI, 0.71-0.98]; HR for sphingomyelin with behenic acid, 0.84 [95% CI, 0.70-1.00]; HR for sphingomyelin with lignoceric acid, 0.86 [95% CI, 0.72-1.03]). The findings of this large, population-based cohort study of SCD identified that higher plasma levels of Cer-16 and SM-16 were associated with higher risk of SCD. Future studies are needed to examine the underlying mechanism of these associations.

Complications of Implantable Cardioverter Defibrillator and Their Potential Risk Factors in Patients with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has different complications such as cardiac arrhythmia and sudden cardiac death (SCD). Insertion of an implantable cardioverter defibrillator (ICD) is recommended for HCM patients who are at high risk of SCD and malignant arrhythmias, despite having their own potential complications. Hypothesis. We aimed to investigate the prevalence of different complications of ICD insertion and the impact of the potential influential baseline characteristics in a one-year follow-up period. This was a retrospective study with a total of 71 HCM patients with ICD insertion. We evaluated the prevalence of different complications of ICD implantation and the impact of baseline characteristics on the occurrence of ICD complications using multivariate regression analysis in three 4-month periods. In a one-year follow-up, 13 patients (18.3%) experienced at least one of the complications including pneumothorax, lead failure, ICD infection, inappropriate shocks, perforation, and upper limb deep vein thrombosis (DVT) with no mortality. Inappropriate shocks were reported as the most common (11.3%) complication during this period, with a gradual increase in the second (4.2%) and third (5.6%) follow-up sessions. Among all of the baseline characteristics that were investigated in this study, a positive history of hypertension was the only risk factor with significant impact on the occurrence of complications (P = 0.01). We demonstrated the occurrence of complications during a one-year follow-up as 18.3% in HCM patients with ICD insertion. A positive history of hypertension was the only baseline characteristic affecting the occurrence of complications, and inappropriate shocks were the most common complication.

Abstract 16842: Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy

Background: There is limited data on the progression of the scar on LGE in patients with hypertrophic cardiomyopathy (HCM) stratified by age and its relationship with sudden cardiac death (SCD). Objectives: We compared LGE progression as stratified by age and examined the relationship of this risk to SCD. Methods: A total of 102 HCM patients (age &lt;60 years; n=75, age ≥60 years; n=27) undergoing two consecutive cardiovascular magnetic resonance (CMR) at an interval of 4.3 ± 3.3 years from two medical centers were evaluated. LGE was quantified semi-automatically using a 6-SD threshold followed by manual adjustment. Median follow-up from study entry to the most recent evaluation was 7.3 years. The primary endpoint was the composite of resuscitated cardiac arrest and SCD. Results: At the first CMR, LGE was detected in 61 (60%) patients. At the follow-up, 25 patients developed a new LGE; thus, 86 (84%) patients had LGE by the follow-up CMR. Overall, the progression rate was 0.7 ± 1.0%/year, including 21 patients (21%) with LGE progression ≥1% /year and 5 (5%) with LGE &gt;15% at follow-up. The risk of LGE progression ≥1%/year was significantly higher in patients &lt;60 years (25% vs. 7%, p=0.02). There was a trend for the highest risk of LGE progression ≥1%/year in patients &lt;60 years with LGE &gt;10% at baseline scan. LGE progression ≥1%/year was a strong predictor of the primary outcomes (HR 1.88 [95% CI; 1.08-3.26], p=0.03). LGE progression moderately correlated with changes in LV mass, indexed LV mass index, and maximal LV end-diastolic wall thickness (p&lt;0.001 for all). Conclusions: Progressive fibrosis occurs more frequently in young to middle-aged HCM patients and identifies a cohort at high risk of SCD. One-quarter of young to middle-aged patients exhibit LGE progression ≥1%/year, underscoring the importance of repeating CMR to re-evaluate for potential LGE progression in this age group.

Reversed Septal Curvature Is Associated With Nonsustained Ventricular Tachycardia in Hypertrophic Cardiomyopathy

Sudden cardiac death (SCD) is associated with nonsustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HCM). Recently, differences regarding septal morphology have been reported, with an increased probability of sudden death in HCM patients who had reverse septal curvature (RSC). The aim of this study was to examine the relationship between RSC and NSVT in HCM. A total of 138 patients with HCM were enrolled. Of 138 patients, 47 (34.1%) were diagnosed with RSC and 42 patients (30.4%) had NSVT. Compared with the non-RSC group, those with RSC were much younger and had an increased incidence of NSVT, thicker septal thickness, larger mass, and a higher proportion of HCM or SCD family history. Furthermore, patients with RSC had a higher risk of SCD according to the European Society of Cardiology calculator (2.5 (1.6, 4.6) vs. 1.6(1.1, 2.3)(%/5 year), p <0.001). Multivariate analysis showed that RSC was a strong and independent risk factor for NSVT (odds ratio = 2.756, 95% confidence interval: 1.164-6.525, p = 0.021). In conclusion, the presence of RSC in HCM patients is independently associated with NSVT. Further studies are needed to evaluate the role of RSC as a risk factor for SCD in this population.

The Role of miRNA Expression Profile in Sudden Cardiac Death Cases.

Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a SCD case and the available methods used for diagnosis cannot always give an exhaustive answer. In addition, the molecular analysis of genes does not lead to a clear conclusion, but it could be interesting to focus attention on the expression level of miRNAs, a class of non-coding RNA of about 22 nucleotides. The role of miRNAs is to regulate the gene expression through complementary binding to 3'-untraslated regions of miRNAs, leading to the inhibition of translation or to mRNA degradation. In recent years, several studies were performed with the aim of exploring the use of these molecules as biomarkers for SCD cases, and to also distinguish the causes that lead to cardiac death. In this review, we summarize experiments, evidence, and results of different studies on the implication of miRNAs in SCD cases. We discuss the different biological starting materials with their respective advantages and disadvantages, studying miRNA expression on tissue (fresh-frozen tissue and FFPE tissue), circulating cell-free miRNAs in blood of patients affected by cardiac disease at high risk of SCD, and exosomal miRNAs analyzed from serum of people who died from SCD.

Improving sudden cardiac death risk stratification in hypertrophic cardiomyopathy using established clinical variables and genetic information

Background and aimsThe cardiac societies of Europe and the United States have established different risk models for preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). The aim of this study is to validate current SCD risk prediction methods in a German HCM cohort and to improve them by the addition of genotype information.MethodsHCM patients without prior SCD or equivalent arrhythmic events ≥ 18 years of age were enrolled in an expert cardiomyopathy center in Germany. The primary endpoint was defined as SCD/-equivalent within 5 years of baseline evaluation. 5-year SCD-risk estimates and recommendations for ICD implantations, as defined by the ESC and AHA/ACC guidelines, were analyzed. Multivariate cox proportional hazards analyses were integrated with genetic findings as additive SCD risk.Results283 patients were included and followed for in median 5.77 years (2.92; 8.85). A disease-causing variant was found in 138 (49%) patients. 14 (5%) patients reached the SCD endpoint (5-year incidence 4.9%). Kaplan–Meier survival analysis shows significantly lower overall SCD event-free survival for patients with an identified disease-causing variant (p < 0.05). The ESC HCM Risk-SCD model showed an area-under-the-curve (AUC) of 0.74 (95% CI 0.68–0.79; p < 0.0001) with a sensitivity of 0.29 (95% CI 0.08–0.58) and specificity of 0.83 (95% CI 0.78–0.88) for a risk estimate ≥ 6%/5-years. By comparison, the AHA/ACC HCM SCD risk stratification model showed an AUC of 0.70 (95% CI 0.65–0.76; p = 0.003) with a sensitivity of 0.93 (95% CI, 0.66–0.998) and specificity of 0.28 (95% CI 0.23–0.34) at the respective cut-off. The modified SCD Risk Score with genetic information yielded an AUC of 0.76 (95% CI 0.71–0.81; p < 0.0001) with a sensitivity of 0.86 (95% CI 0.57–0.98) and specificity of 0.69 (95% CI 0.63–0.74). The number-needed-to-treat (NNT) to prevent 1 SCD event by prophylactic ICD-implantation is 13 for the ESC model, 28 for AHA/ACC and 9 for the modified Genotype-model.ConclusionThis study confirms the performance of current risk models in clinical decision making. The integration of genetic findings into current SCD risk stratification methods seem feasible and can add in decision making, especially in borderline risk-groups. A subgroup of patients with high SCD risk remains unidentified by current risk scores.Graphical abstract

Solving the Riddle of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: The Added Role of Cardiac Magnetic Resonance

Cardiac magnetic resonance (CMR) has been recently implemented in clinical practice to refine the daunting task of establishing the risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We present an exemplificative case highlighting the practical clinical utility of this imaging modality in a 24-year-old man newly diagnosed with an apical HCM. CMR was essential in unmasking a high risk of SCD, which appeared low-intermediate after traditional risk assessment. A discussion examines the essential role of CMR in guiding the patient’s therapy and underlines the added value of CMR, including novel and potential CMR parameters, compared to traditional imaging assessment for SCD risk stratification.

Sudden cardiac death after heart transplantation: a population-based study.

The epidemiology of sudden cardiac death (SCD) after heart transplantation (HTx) remains imprecisely described. We aimed to assess the incidence and determinants of SCD in a large cohort of HTx recipients, compared with the general population. Consecutive HTx recipients (n = 1246, 2 centres) transplanted between 2004 and 2016 were included. We prospectively assessed clinical, biological, pathologic, and functional parameters. SCD was centrally adjudicated. We compared the SCD incidence beyond the first year post-transplant in this cohort with that observed in the general population of the same geographic area (registry carried out by the same group of investigators; n = 19 706 SCD). We performed a competing risk multivariate Cox model to identify variables associated with SCD. The annual incidence of SCD was 12.5 per 1,000 person-years [95% confidence interval (CI), 9.7-15.9] in the HTx recipients cohort compared with 0.54 per 1,000 person-years (95% CI, 0.53-0.55) in the general population (P < 0.001). The risk of SCD was markedly elevated among the youngest HTx recipients with standardized mortality ratios for SCD up to 837 for recipients ≤30 years. Beyond the first year, SCD was the leading cause of death. Five variables were independently associated with SCD: older donor age (P = 0.003), younger recipient age (P = 0.001) and ethnicity (P = 0.034), pre-existing donor-specific antibodies (P = 0.009), and last left ventricular ejection fraction (P = 0.048). HTx recipients, particularly the youngest, were at very high risk of SCD compared with the general population. The consideration of specific risk factors may help identify high-risk subgroups.

ANMCO position paper: guide to the appropriate use of the wearable cardioverter defibrillator in clinical practice for patients at high transient risk of sudden cardiac death.

Extended risk stratification and optimal management of patients with a permanently increased risk of sudden cardiac death (SCD) are becoming increasingly important. There are several clinical conditions where the risk of arrhythmic death is present albeit only transient. As an example, patients with depressed left ventricular function have a high risk of SCD that may be only transient if there will be a significant recovery of function. It is important to protect the patients while receiving and titrating to the optimal dose the recommended drugs that may lead to an improved left ventricular function. In several other conditions, a transient risk of SCD can be observed even if the left ventricular function is not compromised. Examples are patients with acute myocarditis, during the diagnostic work-up of some arrhythmic conditions or after extraction of infected catheters while eradicating the associated infection. In all these conditions, it is important to offer a protection to these patients. The wearable cardioverter defibrillator (WCD) is of particular importance as a temporary non-invasive technology for both arrhythmia monitoring and therapy in patients with increased risk of SCD. Previous studies have shown the WCD to be an effective and safe therapy for the prevention of SCD caused by ventricular tachycardia/fibrillation. The aim of this ANMCO position paper is to provide a recommendation for clinical utilization of the WCD in Italy, based upon current data and international guidelines. In this document, we will review the WCD functionality, indications, clinical evidence, and guideline recommendations. Finally, a recommendation for the utilization of the WCD in routine clinical practice will be presented, in order to provide physicians with a practical guidance for SCD risk stratification in patients who may benefit from this device.