Sudden Cardiac Death Events Research Articles

Association between Clinical and Doppler Echocardiographic Parameters with Sudden Death in Hemodialysis Patients.

Background:Sudden cardiac death (SCD) is the leading cause of death in maintenance hemodialysis (HD) patients, but there is little information about underlying risk factors.Objectives:Evaluate the association between clinical and echocardiographic variables with SCD on HD patients.Methods:Retrospective nested case-control study on chronic HD patients who were prospectively followed. The primary endpoint was SCD. Variables were compared by Student t test, Mann-Whitney or Chi-Square, and independent predictors of SCD were evidenced by multivariate logistic regression.Results:We followed 153 patients (50 ± 15 years, 58% men) for 23 ± 14 months and observed 35 deaths, 17 of which were SCD events. When compared to the control group (matched for gender, age, and body mass index) there were no differences regarding time on dialysis, traditional biochemical parameters, blood pressure, smoking, use of cardiovascular protective drugs, ejection fraction, left ventricular dimensions, and diastolic function indices. On the other hand, in the SCD group, we found a higher prevalence of previous heart failure, acute myocardial infarction and diabetes, greater left ventricular mass index, greater left atrial size and lower global myocardial performance. After multivariate logistic regression analysis, diabetes (OR = 2.6; CI = 1.3-7.5; p = 0.023) and left ventricular mass index ≥ 101 g/m2.7 (OR = 1.04; CI = 1.01-1.08; p = 0.028) showed independent association with SCD events.Conclusions:HD patients with diabetes mellitus and left ventricular hypertrophy appear to have the highest risk of SCD. Preventive and therapeutic strategies should be encouraged in addressing these risk factors to minimize the occurrence of SCD in HD patients.

T-wave reversal in the augmented unipolar right arm electrocardiographic lead is associated with increased risk of sudden death.

Repolarization abnormalities are associated with ventricular arrhythmias, and published studies report that a reversal of T wave polarity (positive or flat T wave) in lead aVR may be linked to increased cardiovascular mortality. We evaluated whether a positive or flat T wave in aVR is a risk marker for sudden cardiac death (SCD). SCD cases from the Oregon Sudden Unexpected Death Study (catchment population ~1 million) were compared to geographic controls with coronary artery disease and no history of SCD. Archived electrocardiograms performed prior and unrelated to the SCD event were evaluated. SCD cases (n = 691, 67.6 ± 14.9 years, 69% male) were more likely than controls (n = 663, 66.2 ± 11.6 years, 67% male) to have diabetes (40 vs 32%; p < 0.01), left ventricular ejection fraction (LVEF) ≤35% (27 vs 11 %; p < 0.01), prolonged QTc (≥450 ms; 54 vs 28%; p < 0.01) and positive (19 vs 13%; p < 0.01) or flat T wave (14 vs 7%; p < 0.01) in aVR. On multivariable analysis, a positive/flat T wave in aVR was independently associated with SCD (OR 1.9, 95% CI 1.3-2.8, p < 0.01). However, a positive T wave alone lost statistical significance in patients with LVEF ≤ 35% and QTc ≥ 450 ms. In a subgroup analysis among patients with normal LVEF, QTc, and no diabetes, a positive T wave in aVR (but not a flat T wave) remained associated with SCD (OR 2.8, 95% CI 1.2-6.1, p < 0.01). A positive or flat T wave in lead aVR was associated with SCD in subsets of patients. This simple ECG marker in this often-ignored lead may contribute to enhancement of SCD risk stratification, and warrants further evaluation.

Abstract 18559: Double or Compound Sarcomere Mutations in Hypertrophic Cardiomyopathy is Not Associated With Worsened Outcomes: A Single Center Cohort Study

Background: The presence of two or more pathogenic sarcomere mutations in patients with hypertrophic cardiomyopathy (HCM) has been reported to be associated with early disease onset, particularly marked left ventricular (LV) hypertrophy, and advanced heart failure. Objective: The aim of the study was to clarify the relationship between multiple disease-causing sarcomere mutations and major cardiovascular outcomes in a large HCM cohort. Methods and Results: Between June 1, 1995, and January 2015, 1104 probands with a diagnosis of HCM were routinely referred for systematic sarcomeric mutational screening at a single HCM center. Pathogenic mutations were identified in 273 (25%). Of these patients, 10 (3.6%) were identified with double/compound sarcomere mutations. They were mostly male (70%), presented at an average age of 33±13 years (range, 21-58), with an average maximal wall thickness of 17 mm (range, 13-26). Of the 9 patients who had a cardiac MRI, 8 (88%) had late gadolinium enhancement (LGE), none of which were considered to be extensive (&gt;20% of LV myocardium). Over a mean follow up of 17.4 ±14 years (range, 3-48 years) there were no sudden cardiac death events. Adverse cardiovascular events or severe disease progression occurred in 4 (40%) patients, with an event rate of 3.4 per 100 patient-years follow up including: 2 (20%) with stroke, 3 (30%) with progression to end-stage HCM (EF&lt;50%), and 1 (10%) with progression to New York Heart Association III/IV symptoms. One patient had myectomy for obstructive symptoms, while none required cardiac transplantation. Three (30%) patients had implantable cardioverter-defibrillator (ICD) for primary prevention. However, over a mean follow-up of 6 years (range 1-14 years), no ICD discharges were documented. Conclusion: These observations do not support the hypothesis that double (or compound) mutations confer a gene dosage effect in HCM, nor is it associated with an adverse prognosis. Mutation analysis has proven imprecise in predicting the phenotype or prognosis for patients with HCM, suggesting that genome-wide association studies and gene expression profiling may be needed for better understanding of its utility in the management of HCM patients.

Abstract 17200: Blood Alcohol in Victims of Sudden Cardiac Death in Northern Finland

Background: Momentary intake of large quantity of alcohol provokes ventricular ectopic activity increasing electrical instability. However, data on the prevalence of alcohol intake prior to a sudden cardiac death (SCD) event are limited. Methods: Victims of unexpected SCD (n=2,363, age 61±12 years, males 1,940 (82%)) included in the Finnish study of genotype and phenotype profiles of SCD (FINGESTURE) had a thorough interview of family members, medico-legal autopsy and determination of blood alcohol concentration. Because of the Finnish law, all unexpected deaths undergo medico-legal autopsy. Patients, who were admitted to a hospital due to an acute myocardial infarction (AMI) (n=128, age 63±10 years, males 100 (78%)) served as controls. Results: Based on autopsy findings, 1,691 of these victims had ischemic heart disease and were included in the present analysis. A total of 646 (38%) SCD victims with ischemic heart disease had a blood ethanol concentration above 0‰. Of these victims with blood alcohol test positive, 41% (n=264) had blood ethanol concentration ≥ 1.5‰ and 56% (n=362) ≥ 1‰. Male SCD victims had more frequently alcohol in blood than the females (40% vs. 27%, p&lt;0.001, respectively). None of the controls, who gave a consent for the blood ethanol concentration determination (n=88), had alcohol in blood. Of the controls, 40 (31%) declined to participate in the study and give the consent for blood alcohol testing. Conclusion: Almost 4/10 of the victims of unexpected SCD have evidence of alcohol intake before the fatal event in the Northern Finland autopsy population.

Abstract 16587: Tpeak-to-tend Interval Corrected for Heart Rate: A More Precise Measure of Increased Sudden Death Risk?

Introduction: The Tpeak-to-Tend interval (Tpe) on the 12-lead electrocardiogram (ECG) predicts increased risk of sudden cardiac death (SCD). There has been some controversy on whether Tpe would be more useful if corrected for heart rate (Tpec). Hypothesis: We hypothesize that correcting the Tpe for heart rate will improve its predictive value for SCD. Methods: Cases of sudden cardiac death (SCD) (n=725; mean age 67.4 years; 95% CI 52.7 to 82.1 years; 67.7% males) from a large ongoing population based study of SCD in the Northwest US (population approx. one million) with an ECG available prior and unrelated to the SCD event were analyzed. Comparisons were made to control subjects with and without coronary artery disease (n=898; mean age 66.9 years; 95% CI 55.5 to 78.3 years; 63.7% males). The Tpe interval was corrected for heart rate using the Bazett (TpecBa) and Fridericia (TpecFd) formulae and the predictive value of Tpec for SCD was compared in logistic regression models. Results: The area-under-curve (AUC) for predicting SCD improved with both correction formulae, TpecBa at 0.628 and TpecFd at 0.606 compared to an uncorrected Tpe at 0.544 (see Figure). The optimal cut-off value for TpecBa and TpecFd was determined using the receiver-operating characteristics (ROC) curve. A TpecBa of more than 94ms and TpecFd of more than 88ms was predictive of SCD independent of age, gender, comorbidities (hypertension, diabetes mellitus, previous myocardial infarction), electrocardiographic left ventricular hypertrophy (LVH), severe left ventricular dysfunction (LVEF ≤35%), prolonged QTc (&gt;450ms) and prolonged QRS duration (&gt;120ms) with an odds ratio of 1.88 (95% CI, 1.36 to 2.60; p &lt;0.0001) and 1.90 (95% CI, 1.38 to 2.62; p &lt;0.0001) respectively. Conclusion: Correcting the Tpeak-to-Tend interval for heart rate, using either the Bazett and Fridericia formulae, improved the independent predictive value of this marker for assessment of SCD risk in the community.

Abstract 12142: Electrolyte Abnormalities and Risk of Sudden Death in the General Population

Introduction: Electrolyte abnormalities are a substrate for arrhythmogenesis and could be the trigger for sudden cardiac death (SCD). We sought to determine the potential role of electrolyte abnormalities, irrespective of kidney function, in the occurrence of sudden death in the community. Hypothesis: Electrolyte abnormalities increases the risk for SCD in the community regardless of kidney function. Methods: SCD cases and controls from a large population based study in Northwest US (approx 1 million population, 2002-2014) were included if age ≥18 yrs with creatinine clearance (CrCl) and serum electrolytes available for analysis. For cases, CrCl and electrolytes were required to be measured within 90 days of the SCD event. Demographics and lab results were analyzed using student t-tests and chi-square tests. Multiple logistic regression was used to estimate independent association of risk factors with SCD. Results: We evaluated 483 SCD cases (65.8% male) and 886 controls (66.4% male). Cases were more likely to be older (68.8±14.3 vs 67.2±11.3, p=0.03), of black race (9.8 vs 3.2%, p&lt;0.0001) and with worse CrCl (53.4±31.3 vs. 64.0±24.9 ml/min, p&lt;0.0001). Overall, cases had lower levels of mean Na (137.3±4.2 vs 138.3±3.4 mEq/L, p&lt;0.0001), Ca (9.0±0.7 vs 9.2±0.5 mg/dl, p&lt;0.0001) and Mg (2.0±0.5 vs 2.1±0.4 mg/dl, p=0.007); and higher mean K (4.2±0.6 vs 4.1 ±0.5mEq/L, p=0.0008). Prevalence of hyponatremia (&lt;136mEq/L), hyperkalemia (&gt;5.2mEq/L), hypocalcemia (&lt;8.5 mg/dl) and hypomagnesemia (&lt;1.7 mg/dl) were also higher in cases (27.0 vs 16.2%, p&lt;0.0001; 6.1 vs 1.4%, p&lt;0.0001; 19.7 vs 7.9%, p&lt;0.0001 and 20.4 vs 8.3%, p&lt;0.0001, respectively). Adjusting for age, race and kidney function only hyperkalemia [OR 4.65 (95% CI 1.37-15.81), p=0.01], hypocalcemia [2.94 (1.68-5.13), p=0.0001] and hypomagnesemia [2.52 (1.36-4.66), p=0.003] remained significant, conferring a more than two to five-fold increase in SCD risk. Conclusions: Electrolyte abnormalities remain independently associated with increased risk of SCD in the community, even after adjusting for renal function.

Abstract 19577: Race and Sudden Cardiac Death: Findings From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Blacks, as compared to whites, have a higher burden of cardiovascular disease (CVD) risk factors and CVD. Recent studies have reported a higher burden of sudden cardiac death (SCD) in blacks; however, it remains unclear whether this elevation in SCD risk is independent of racial differences in risk factor profiles and prevalent CVD. Methods: We examined the association between black race and SCD in participants with and without a history of CVD at baseline in the REGARDS study, a prospective, longitudinal cohort of 29,695 participants ≥45 years (55% women, 41% black) from across the United States. SCD was defined as sudden pulselessness from a presumed cardiac origin that occurred out of hospital or in the emergency room. Results: Over a median [IQR] of 6.0 [4.5-7.3] years of follow-up, 388 SCD events occurred. Compared to whites, blacks had less education, lower income and a higher burden of CVD risk factors. In the entire population, the age-adjusted SCD incidence rates per 1000 person-years were 2.6 (95% CI, 2.3-3.0) for blacks versus 1.7 (95% CI, 1.4-1.9) for whites, (HR=1.47; 95% CI 1.20-1.79). This elevated risk was attenuated after controlling for CVD risk factors and became non-significant after controlling for prevalent CVD (Table 1). Among the subgroup of 22,507 participants without CVD at baseline, SCD risk remained elevated in blacks (HR=1.90; 1.35-2.68) even after controlling for CVD risk factors and medication use (Table 1). In contrast, there was no elevation in SCD risk among the participants with prevalent CVD at baseline. The association between black race and SCD was stronger in those without compared to those with a history of CVD (p=0.001). Conclusions: The higher risk of SCD risk associated with black race, compared to whites, is partially explained by the higher prevalence of CVD and its risk factors in blacks. However, there remains a higher SCD risk associated with black race among those without CVD not explained by standard CVD risk factors.

Abstract 14767: Delayed R-Wave Peak Time on the 12-lead ECG is Associated With Increased Risk of Sudden Death

Background: Left ventricular hypertrophy (LVH) is associated with sudden cardiac death (SCD), and there is emerging evidence for unique electrical vs. ventricular myocardial mass related mechanisms. We investigated the correlation between delayed R-Wave Peak Time (DRWPT), or intrinsicoid deflection, in the lateral precordial leads and LV mass in patients who suffered SCD. Methods: In an ongoing prospective, population based study of SCD in a Northwestern US metro region (approx. 1 million population), SCD cases were compared to geographic controls with coronary artery disease (CAD) and no SCD. Archived ECGs (closest and unrelated to SCD event for cases) were evaluated for the presence of DRWPT defined as an intrinsicoid deflection of ≥ 0.05 seconds in V5 or V6. LV mass from echocardiograms and detailed clinical information was obtained for all subjects. Patients with wide QRS (&gt;100 ms) were excluded. Results: Cases (n=146, Age: 67.7 ± 14.6 yrs, Male: 55.5%) as compared to controls (n=227, Age: 66.3 ± 11.5 yrs, Male: 59.0%) were significantly more likely to have DRWPT on ECG (17.1% vs 9.2%, p=0.02). DRPWT correlated poorly with echo determined LVH (Kappa statistic 0.03) with no significant difference in mean adjusted LV Mass between those with DRWPT versus those without (104.3 ± 34.9 vs. 100.9 ± 33.5 g/m 2 , p =0.55). Multivariable analysis adjusting for diabetes, renal failure, LV dysfunction and angiotensin receptor blocker use demonstrated a significant association of DRWPT with SCD risk (OR: 2.2, 95% CI: 1.1-4.3, p=0.020). With the addition of echo LVH to the model, this risk was not significantly attenuated (OR: 2.6, 95% CI: 1.3-5.4, p=0.008). Conclusion: DRWPT was independently associated with SCD risk, and not correlated with increased LV mass. These findings suggest that abnormalities of myocardial conduction velocity should be explored as mechanisms of electrical risk in LVH and SCD.

Abstract 11013: Predictive Role of Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy: An Updated Meta-Analysis

Background: Myocardial fibrosis detected by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is currently used to predict adverse cardiovascular events in patients with hypertrophic cardiomyopathy (HCM). However, controversies remain about its prediction value of sudden cardiac death (SCD). Objective: The aim of this study was to perform an updated meta-analysis of the prediction value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for future events and death in hypertrophic cardiomyopathy (HCM). Methods: We searched PubMed and Web of Science for clinical trials that investigated the prognosis indexes of LGE in HCM patients. The outcomes of interest comprised all-cause mortality, cardiac death, SCD, aborted SCD and heart failure death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the role of LGE CMR in the risk stratification of HCM. Results: Seven studies were retrieved from 393 citations for the analysis, and in total, 3423 patients (mean age: 52.3 years; median follow up: 37.7 months) were included in the analysis. After synthesizing data, the meta-analysis showed that LGE by CMR was associated with SCD/Aborted SCD (OR=2.921, 95%CI=1.760-4.848; P&lt;0.001) and all cause mortality (OR=1.715, 95%CI=1.013-2.901; P=0.044), and showed a trend toward significance of predicting cardiac death (OR=2.174, 95%CI=1.000-4.727; P=0.05). However, we did not observe a correlation between LGE and heart failure death (OR=2.066, 95%CI=0.788-5.416; P=0.14). Conclusions: LGE by CMR exhibited a substantial prognostic value in SCD events prediction. Significant associations were found between LGE and SCD, and all cause mortality. Moreover, LGE displayed a trend toward significance on cardiac death but not on heart failure death. Myocardial fibrosis assessed by LGE is effective in SCD risk stratification in patients with HCM.

Electrocardiographic Markers and Left Ventricular Ejection Fraction Have Cumulative Effects on Risk of Sudden Cardiac Death

ObjectivesThis study assessed potential improvement in predicting risk of sudden cardiac death (SCD) by adding selected risk markers from the 12-lead electrocardiogram (ECG) to the measurement of left ventricular ejection fraction (LVEF). BackgroundNovel strategies to improve risk stratification for SCD are needed. Given the modest odds associated with most individual risk markers, combining multiple markers may be a useful approach. MethodsFrom the ongoing Oregon Sudden Unexpected Death Study, SCD cases with pre-event LVEF data available were compared with those of matched control subjects with coronary artery disease. Resting heart rate, QRS duration (QRSD), and JTc intervals were measured from archived ECGs prior to and unrelated to the SCD event. Independent odds of SCD for individual and combined ECG markers were calculated. ResultsSCD cases (n = 317; 67.9 ± 12.9 years of age) were more likely than controls (n = 317; 67.9 ± 12.8 years of age) to have LVEF ≤35% (26% vs. 11%, respectively). Mean heart rate, QRSD, and JTc were significantly higher in cases (all p < 0.0001). In adjusted analyses, higher heart rate (odds ratio [OR]: 2.6 [95% confidence interval [CI]: 1.8 to 3.7]), QRSD (OR: 1.5 [95% CI: 1.0 to 2.5]), and JTc (OR: 2.3 [95% CI: 1.6 to 3.4]) were independently associated with SCD. When ECG markers were combined, SCD odds progressively increased with 1 (OR: 3.4 [95% CI: 2.1 to 5.4]) and ≥2 elevated markers (OR: 6.3 [95% CI: 3.3 to 12.1]). Addition of ECG markers to an adjusted model with LVEF improved discrimination (C statistic improved from 0.642 to 0.724) and net reclassification (by 22.7%; p < 0.0001). ConclusionsCombining selected 12-lead ECG markers with LVEF improves SCD risk prediction and warrants further investigation in prospective studies.

NOS1AP Polymorphisms Modify QTc Interval Duration But Not Cardiac Arrest Risk in Hypertrophic Cardiomyopathy.

The accurate prediction of the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains elusive. Corrected QT interval (QTc) duration is a known risk factor in various cardiac conditions. Single nucleotide polymorphisms (SNPs) have been linked to QTc length, and to SCD. Here we investigated the role of 21 candidate SNPs in QTc duration and SCD events in patients with HCM. This HCM registry-based study included patients with an ECG, medical history, first SCD event data, and DNA available. Each individual SNP was assessed using logistic regression for associations with 2 outcomes: a prolonged QTc ( ≥440 milliseconds), and first SCD event (SCD, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock for ventricular fibrillation/ventricular tachycardia (VF/VT). In 272 HCM patients, there were 31 SCD events (8 SCD, 9 resuscitated cardiac arrest, 14 ICD shocks for VF/VT; 11%). A QTc ≥ 500 milliseconds was associated with SCD events on multivariate analysis (odds ratio [OR] = 4.0, 95% confidence interval [CI], 1.19-12.02, P = 0.016). In 228 Caucasian patients, 2 SNPs in the NOS1AP gene (rs10494366 and rs12143842) were associated with a prolonged QTc after correction for multiple testing. This remained significant after adjustment for current age, sex, and ≥1 SCD risk factor (OR 1.59 per copy of the minor allele, 95% CI 1.08-2.39, P = 0.022, and OR 1.63, 95% CI 1.09-2.49, P = 0.020, respectively). No SNPs were directly associated with SCD events. SNPs in the NOS1AP gene influence QTc interval duration but we have not demonstrated a direct association with the risk of SCD.

Distribution of Ventricular Fibrosis Associated With Life-Threatening Ventricular Tachyarrhythmias in Patients With Nonischemic Dilated Cardiomyopathy.

Current guidelines recommend the implantation of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) in a subgroup of patients with nonischemic cardiomyopathy (NICM) who have a left ventricular ejection fraction (LVEF) ≤ 30-35%, and are NYHA functional class II or III. However, the majority of patients with an ICD implantation for primary prevention did not receive appropriate ICD therapy. The purpose of this study was to evaluate the association between myocardial fibrosis detected by cardiovascular magnetic resonance (CMR) imaging and life-threatening ventricular arrhythmic events in NICM patients. One hundred and seventy-five NICM patients with an LVEF ≦ 35 % and NYHA functional class II or III, (60 ± 15 years, LVEF 29 ± 5.4%) were studied. Myocardial fibrosis was identified with a late gadolinium enhancement (LGE) on CMR. Clinical events were defined as SCD or life-threatening ventricular arrhythmic events and were followed up for 5.1 ± 3.3 years. The presence of an LGE was detected in 122 patients (70%). No life-threatening ventricular arrhythmia events occurred in patients with the absence of an LGE. A total of 18 ventricular tachycardia and 8 ventricular fibrillation events were found in patients with the presence of an LGE (P < 0.01). Sensitivity, specificity, and positive and negative predictive value of LGE in predicting life-threatening ventricular arrhythmia events were 100%, 34%, and 15% and 100%, respectively. Multivariate analysis showed that the presence of both septal and lateral mid-wall LGE was associated with life-threatening ventricular arrhythmic events (hazard ratio 23.1 CI; 2.88-184.9, P = 0.003). The absence of an LGE predicts a low potential risk of SCD and life-threatening ventricular arrhythmia events in the near future. CMR may be a useful tool for selecting suitable patients for primary ICD implantations in NICM patients.

Temporal distribution of arrhythmic events in chronic kidney disease: Highest incidence in the long interdialytic period

Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of sudden cardiac death (SCD). A unique risk factor may be a longer interval between HD sessions (interdialytic period). Inherent in conventional HD (thrice-weekly) are two 48-hour short breaks (SIDP) and one 72-hour long break (LIDP) between HD sessions. We used an implantable cardiac monitor (ICM) to define the incidence and timing of significant arrhythmias in an HD population. Fifty CKD patients undergoing HD with left ventricular ejection fraction >35% had an ICM inserted, with intensive follow-up to record SCD events and predefined bradyarrhythmias and tachyarrhythmias. Mean age of the patients was 67 ± 11 years; 72% were male, and the mean follow-up was 18 ± 4 months. There were 8 unexpected SCDs (16%), all during the LIDP. The terminal event was severe bradycardia with asystole in each recorded case. No episodes of polymorphic ventricular tachycardia (VT) occurred. A total of 7686 arrhythmia events were recorded in 43 patients (86%), including bradycardia in 15 patients (30%), sinus arrest in 14 (28%), second-degree atrioventricular block in 4 (8%), nonsustained VT in 10 (20%), and new-onset paroxysmal atrial fibrillation in 14 (28%). The LIDP was the highest-risk period for all arrhythmias (P < .001). The arrhythmia event rate per hour was greatest during the first pre-HD period of the week compared with any other peri-HD period (P < .001). Risk of SCD and significant arrhythmias is greatest during the LIDP. SCD was attributable to severe bradycardia and asystole. Interventions to prevent this type of SCD or shorten the LIDP deserve further evaluation. URL: https://www.anzctr.org.au (Unique identifier: ACTRN12613001326785).

Noncompaction cardiomyopathy

Noncompaction cardiomyopathy (NCCM) is a genetic myocardial disorder, which is characterized by a two-layered ventricle wall with a thin compact outer layer and a noncompacted inner layer, with prominent trabeculations and deep intratrabecular recesses communicating with the ventricle cavity without any contact to the coronary system. Before the initial description as isolated left ventricle cardiomyopathy (ILVCN) in 1984 by Engberding and Bender, the morphological characteristics had been described only in association with other congenital cardiac disorders, such as atresia of the semilunar valves. The disease usually involves the myocardium of the left ventricle but involvement of the right ventricular has recently been shown. Due to delayed diagnosis and therapy, in advanced stages NCCM can result in heart failure. Life-threatening complications, such as malignant arrhythmia with sudden cardiac death and embolic events have been observed in patients with NCCM. A multimodal investigation including echocardiography and cardiac magnet resonance tomography (CMR) as well as a focused analysis of symptoms can allow a valid diagnosis.

Validation of the 2014 European Society of Cardiology Guidelines Risk Prediction Model for the Primary Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy

The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57-0.82; P=0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47-0.63; P=0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50-0.70; P=0.07). The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD.

Implantable cardioverter defibrillators: state of the art

Implantable cardioverter defibrillators: state of the art Jordan C Ray, Harrison M Goodall, Thomas E Pascual, Fred M Kusumoto Electrophysiology and Pacing Service, Division of Cardiovascular Disease, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA Abstract: It has been estimated that 180,000&ndash;450,000 people die suddenly in the US every year. Currently, the most effective method for reducing the risk of sudden death in those patients at highest risk is implantation of an internal cardioverter defibrillator (ICD). The evidence base for the benefit of the ICD has matured over the last two decades, and large studies have consistently shown reduced mortality or sudden cardiac death (SCD) in selected patient populations. Since its initial application in the early 1980s in patients who had already suffered an episode of SCD (secondary prevention), ICD use has expanded dramatically and now includes patients who are at high risk for a first event of SCD (primary prevention). More recent studies have focused on new technology, optimal programming, and other gaps in our understanding of the use of ICDs. Keywords: sudden cardiac death, primary prevention, secondary prevention, myocardial infarction, ventricular fibrillation, ventricular tachycardia, LVEF, subcutaneous implantable cardioverter-defibrillator

Abstract P170: The Association of Serum Potassium with Mortality in Older Community-Dwelling Individuals: The Cardiovascular Health Study (CHS)

Background: High serum potassium (K) is associated with death in chronic kidney disease (CKD) patients, and in acute illness. Associations in other settings are uncertain. We determined associations between K concentrations and total mortality, coronary heart disease (CHD) death, and sudden cardiac death (SCD) in an older, community-dwelling population. Methods: Among 5137 CHS participants aged ≥ 65 years at baseline, we evaluated associations between serum K categories [&lt; 4.0, 4.0-4.5, 4.5-5.0, &amp; ≥ 5.0 mMol/dL] with CHD death, SCD, and all-cause mortality using Cox proportional hazards models. We also evaluated whether associations differed by angiotensin converting enzyme (ACE) inhibitor / angiotensin II receptor blocker (ARB) use, diuretic use, and CKD status [eGFR &lt; 60 vs. higher]. All CHD and SCD events were adjudicated by committee. Results: Mean age was 72 years, 39% were male, and 17% were Black. Individuals in the ≥ 5.0 mMol/dL category were older, more frequently men, diabetic, to have CKD, and to use ACE/ARBs. They were also less likely to use diuretics. Mean follow-up was 14 ± 6 years during which there were 4122 total deaths including 971 CHD deaths. Follow-up for SCD was 12 ± 5 years during which there were 162 SCD events. In models adjusted for demographics, CVD risk factors, eGFR, and use of ACE/ARBs, diuretics and K supplements, those with K ≥ 5.0 mMol/dL had 32% higher risk of all-cause mortality (HR 1.32; 95% CI: 1.07-1.63) than the 4.0-4.5mMol/dL reference category. The association was similar irrespective of diuretic or ACE/ARB use or by CKD status (p interaction all &gt; 0.18). Those with K &lt; 4.0 mMol/dL had 14% higher risk of all-cause mortality (HR 1.14; 95% CI: 1.05-1.23) than the reference category; and this association was limited to those with K &lt; 4.0 mMol/dL and were not on diuretics and did not have CKD (p interaction both &lt; 0.02). No association of K &lt; 4.0 mMol/dL with mortality was observed in those on diuretics or with CKD. There was no significant association of either high or low K with either CHD death (HR 1.08; 95% CI: 0.71-1.65; and HR 0.96; 95% CI: 0.81-1.13, respectively) or SCD (HR 1.13; 95% CI: 0.41-3.11; and HR 1.01; 95% CI: 0.68-1.50, respectively) in adjusted models. Conclusions: Higher and lower serum K are independently associated with all-cause mortality but not CHD death or SCD in older community-dwelling individuals. Mechanisms linking high and low K with mortality from diseases other than CHD and SCD require future study.

A founder MYBPC3 mutation results in HCM with a high risk of sudden death after the fourth decade of life

BackgroundMutations in the cardiac myosin binding protein C (MYBPC3) gene account for a significant proportion of patients affected with hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate...

Application of Next Generation Sequencing for personalized medicine for sudden cardiac death.

Sudden cardiac death (SCD) is a serious public health problem. In the United States, more than 300,000 people are affected by SCD every year. Significantly, sudden deaths represent 20% of the total mortality and 50% of cardiovascular mortality in Western countries. In addition, SCD constitutes one of the most important unsolved challenges in the practice of forensic pathology because of the failure to determine the exact cause of sudden death. In young individuals, SCD is frequently caused by cardiomyopathies and channelopathies, that have generally an autosomal dominant pattern of inheritance. The impact of genetics and genetic testing on the clinical management of these diseases is unquestioned. In particular, genetic tests are an important tool for identifying pre-symptomatic individuals carrying genetic variant that predisposes them to SCD. High-throughput sequencing technologies offer novel opportunities to deeper investigate the genetic background underlying these fatal diseases and to early identify individuals at risk for SCD. In this review, we provide an overview of the development of Next-Generation Sequencing (NGS) technologies and of guidelines useful to design an efficient sequencing protocol and to perform an accurate data analysis. We suggest a flow chart to follow for the set up of a genetic screening protocol for the prevention of cardiac pathologies, in particular SCD events, in young athletes.

Analysis of temporal and spatial variability of spontaneous type 1 brugada ECG: correlation with symptoms and sudden cardiac death events

Analysis of temporal and spatial variability of spontaneous type 1 brugada ECG: correlation with symptoms and sudden cardiac death events