Risk Of Sudden Cardiac Arrest Research Articles

In This Issue

In This Issue

EKG eponimi

Eponyms are widely represented in technical, social and natural sciences. Electrocardiography terms, named after the researcher who first described them, have not been summarized in one place until now. Wellens syndrome (Henrick Joan Joost Wellens, Dutch cardiologist) refers to a subgroup of patients with unstable angina who are at risk of developing an anterior myocardial infarction. In 2008, the Dutch cardiologist Robert Jan de Winter described a unique electrocardiographic (ECG) finding for proximal left anterior descending artery occlusion, named de Winter's pattern.Smith-Sgarbossa criteria (Elena Sgarbossa, Stephen Smith) are used to recognize acute myocardial infarction in patients with left bundle branch block. Schamroth's sign (Abraham Leo Schamroth, South African cardiologist) is an indirect ECG finding that indicates chronic obstructive pulmonary disease. Wolff-Parkinson-White syndrome (WPW) was named after the doctors who in 1930. first described the syndrome of short PR interval and abnormal QRS complexes, associated with paroxysmal tachycardia (Louis Wolff, John Parkinson, Paul Dudley White). S1Q3T3 or McGinn-White sign (Sylvester McGinn and Paul White) was first described in 1935. as an ECG finding in support of acute pulmonary heart disease. Second degree AV blocks could be type Wenckebach (Karel Frederik Wenckebach, Dutch anatomist) or type Mobitz (Woldemar Mobitz, Russian-German physician). Ashman's phenomenon (Richard F. Ashman, American physiologist) is a simple ECG manifestation of conduction disturbances, caused by a change in frequency. Bix's rule (Harold Bix) is used to recognize supraventricular tachycardia. Brugada syndrome (Pedro and Josep Brugada) is a congenital channelopathy of sodium channels, with a high risk of sudden cardiac arrest. TP segment's down-sloping in the early stage of pericarditis is called Spodick's sign (David H. Spodick, American cardiologist).

J waves in arrhythmogenic cardiomyopathy versus primary electrical disease

In case reports early repolarization (ER) is associated with arrhythmogenic cardiomyopathy. In smaller case analyses ER is a discussable risk marker. Furthermore, the association with inversions of right precordial T-waves should be analysed. Method: In a cohort of 360 patients with typical ESC/ISFC criteria of arrhythmogenic cardiomyopathy (176 males, mean age 47.3 +/- 13.7 years) the presentation with ER and the risk assessment for sudden cardiac arrest was analyzed. Results: A total of 113 cases (31%) with inferior (22%), inferolateral (3%), and lateral (6%) notching or slurring was presented as typical signs of early repolarization syndrome. Together with the results of ajmaline challenge it is in close relation with the number of right precodial T-wave inversions. Early repolarization does not identify patients at risk for sudden cardiac arrest. In single cases the risk was increased in cases with ST elevation in early repolarization pattern as primary electrical disease. Conclusions: The number of early repolarization pattern in typical arrhythmogenic cardiomyopathy is increased and relates to the number of right precordial T-wave inversions of 55% in this cohort. Early repolarization is generally not a risk marker, but in single cases overlapping primary electrical disease can be documented.

Recurrent Sudden Cardiac Arrest in the General Population

Objective: To evaluate the burden and determinants of recurrent out-of-hospital sudden cardiac arrest (SCA) in the community. Background: Despite improvements in management of SCA survivors and wide availability of implantable defibrillators for secondary prevention, a subgroup of individuals will suffer multiple distinct episodes of SCA. Methods: SCA cases were prospectively ascertained in the Oregon Sudden Unexpected Death Study. Individuals that experienced recurrent SCA were identified both prospectively and retrospectively. We conducted detailed comparisons with survivors of single SCA events. Results: We ascertained 6649 individuals with SCA from 2002-2020 and 924 (14%) survived to hospital discharge. Of these, 123 survivors (13%) experienced recurrent SCA (age 61.9 {plus minus} 14.0 at first event; 69% male; median time interval 22 months). Compared with SCA survivors who suffered a single event (n=302), patients with recurrent SCA had lower rates of receiving implantable cardioverter-defibrillators (ICD; 58%vs. 22%, p<0.001) and 60% of events occurred later than one year following initial SCA. Among a subset of individuals with recurrent SCA and no secondary prevention ICD (n=70), the majority had apparently reversible etiologies, with one-quarter undergoing coronary revascularization and over half diagnosed with non-coronary etiologies. Recurrent SCA subjects were more likely to have a history of diabetes (44% vs 25%, p<0.001) and kidney disease (35% vs 13%, p<0.001). Conclusions: A sizeable subset of SCA survivors (13%) had recurrent SCA, and diabetes and renal disease were identified as predictors of increased risk. These findings highlight the critical importance of comprehensive SCA risk prediction, and apparently reversible etiologies need renewed scrutiny.

Incidence and Predictors of Sudden Cardiac Arrest in Sarcoidosis: A Nationwide Analysis

Objectives:To identify electrocardiographic (ECG) and clinical predictors of sudden cardiac arrest (SCA) in sarcoidosis.Background:Sudden cardiac death (SCD) is the leading cause of death in patients with cardiac sarcoid (CS) and may be the earliest manifestation of disease. Widespread, repeated advanced imaging is an impractical solution to this problem. ECG is an affordable and widely accessible modality that could help guide diagnostic approaches and risk stratification.Methods:Data were obtained from the National Inpatient Sample from 2005 to 2017 using International Classification of Diseases, Ninth and Tenth Revisions, (ICD‐9 and ICD-10 CM). The primary outcome was to identify predictors of SCA, while predictors of SCA in young individuals and those with normal ventricular function served as secondary outcome measures. Cox regression analysis was used to calculate odds ratios following which, a multivariable Cox regression was employed to adjust for potential confounders. Results: Electrocardiographic markers of AV node dysfunction or bundle branch block are associated with a substantially increased risk of SCA in a limited proportion of patients (8.6%). This association is also observed among younger patients (<40 years) and those with normal ventricular function. Conclusions:Electrocardiographic evidence of AV nodal dysfunction or distal conduction disease should raise suspicion for cardiac involvement in patients with sarcoidosis and are associated with increased risk of SCA. Certain ECG markers could help identify patients who would benefit from advanced imaging studies. The sensitivity of electrocardiograms is however limited and the presence of a normal ECG does not reflect a low-risk of SCA.

Incidence and etiology of sudden cardiac arrest in Koreans: A cohort from the national health insurance service database.

The incidence of sudden cardiac arrest (SCA) in Asians is lower than that seen in Western populations, but there are few available data on the incidence and associated cardiac etiology of SCA in Asians. From 2002 to 2013, patients with SCA were analyzed using a cohort from the South Korean National Health Insurance Service (NHIS) coded database. Sudden unexplained death syndrome (SUDS) was defined as cryptogenic arrest, excluding that of non-cardiac origin, coronary artery disease (CAD), cardiomyopathy (CM), and valvular heart disease. During the 12-year study period, 5,973 patients (0.53%) from the total cohort of 1,125,691 had a cardiac arrest code. The overall incidence of arrest was 48.7 per 100,000 person-years (95% CI 16.6–18.0). The incidence of primary SCA excluding those of non-cardiac origin was 16.1 per 100,000 person-years (95% CI 15.4–16.8). It was higher in males than in females (18.1 vs. 14.1 per 100,000 person-years). CAD was the most common cause of SCA (59.4%), and followed by CM (13.9%). SUDS accounted for 14.7% of SCA events. The risk of SCA had increased gradually from over 25 years old. Heart failure, atrial fibrillation and hypertension are major factors associated with SCA incidence. Our findings outline epidemiologic data for SCA and the proportion of associated cardiac etiology leads SCA in a large population.

Abstract 16917: The Forgotten Prolapsed Mitral Valve in a Patient With Sudden Cardiac Arrest

Current literature suggests that the incidence of sudden cardiac arrest (SCA) attributable to mitral valve prolapse (MVP) is more common than historically presumed. Although its true incidence remains unknown, this novel realization suggests that the presence of MVP after resuscitated SCA should prompt exploratory identification of a causative association between MVP and SCA, even in the presence of other plausible explanatory findings. Case Description: A 60-year-old male with a history of hypertension presented with an out-of-hospital cardiac arrest due to ventricular fibrillation (VF). Coronary angiography revealed a 99% occluded 1st diagonal branch which was stented. TTE showed normal biventricular function and coincidentally found a myxomatous mitral valve with bileaflet prolapse. The patient was discharged without further work up under the rationale that the ischemic etiology of his arrest was reversed. 6 months later, he presented with another episode of VF arrest. EKG showed sinus bradycardia and a QTc of 534ms. Troponin was negative. Coronary angiography revealed a patent stent and coronary vessels. A cardiac MRI was obtained to investigate the arrhythmic significance of his MVP and showed late gadolinium enhancement in the basal inferolateral wall and tips of the mitral papillary muscles. A dual chamber implantable cardiac defibrillator was placed with a plan for future mitral valve repair. Discussion: Recent studies suggest that the estimated annual risk of SCA due to MVP is 0.2% to 1.9%, a figure higher than previously reported. Certain EKG, TTE and cardiac MRI findings have been associated with an increased risk of ventricular arrhythmias and SCA. In this patient, this included bileaflet MVP, mitral antral disjunction, and inferobasal wall and papillary muscle fibrosis. Currently, there are no society guidelines to assist in the identification of patients with MVP at high-risk for SCA. Nonetheless, in patients with MVP resuscitated from SCA, further workup to identify high risk features is reasonably justified to guide secondary SCA prophylaxis, even in the presence of other explanatory findings for SCA.

Abstract 282: In Hospital Outcomes of Cardiac Arrest in Patient with End Stage Renal Disease

Background: End stage renal disease (ESRD) is a well-recognized risk factor for development of sudden cardiac arrest(SCA). There is limited data on outcomes after an in-hospital SCA event in ESRD patients. Methods: Data were obtained from National Inpatient Sample from January 2007 to December 2017. In-hospital SCA was identified using International Classification of Disease, 9th Revision, Clinical Modification, and International Classification of Disease, 10th Revision, Clinical Modification codes of 99.60, 99.63, and 5A12012. ESRD patients were subsequently identified using codes of 585.6 and N18.6. Propensity -matched analysis using logistic regression with SD caliper of 0.2 was used to match patients with and without ESRD. Crude and propensity-matched (PS) cohorts outcomes were calculated. Results: A total of 1,412,985 patients sustained in-hospital SCA during our study period. ESRD patients with in-hospital SCA were younger and had a higher burden of key co-morbidities. Mortality was similar in ESRD and non-ESRD patients in PS matched cohort (70.4% vs. 70.7%, p = 0.45, figure 1) with an overall downward trend over our study years (figure 2). Conclusion: In the context of in-hospital SCA, mortality is similar in ESRD and non-ESRD patients in adjusted analysis. Adequate risk factor modification could further mitigate the risk of in-hospital SCA among ESRD patients

Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome.

Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores. A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67-0.79) and 0.71 (0.61-0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P < 0.01). No statistical difference was found in intermediate-risk patients (score 2-4). The Shanghai score does not allow to better stratify the risk of SCA. In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient.

Potential Role of Life Stress in Unexplained Sudden Cardiac Arrest

BackgroundThe etiology of sudden cardiac arrest (SCA) in individuals without known cardiovascular heart disease remains elusive in nearly half of all patients after systematic testing. We investigated the relationship between stressful life events and SCA risk in cases of explained and unexplained SCA (USCA) events. MethodsIndividuals who previously experienced SCA were enrolled prospectively and divided into a USCA or explained SCA (ESCA) subgroup dependent on whether a diagnosis was ascribed after SCA. Participants completed either the 1997 Recent Life Changes Questionnaire, Student Stress Scale, or Social Re-adjustment Rating Scale for Non-Adults recalling events during the year preceding their SCA, depending on age at SCA presentation; all measure stress in life change units (LCUs). SCA group scores were compared with an age- and sex-matched control group. ResultsWe compared 36 SCA group participants (22 USCA, 14 ESCA, age 47 ± 15 years, age at SCA 40 ± 14 years, 50% male) with 36 control participants (age 47 ± 15 years, 50% male). There was no significant difference in LCU score between the control group and the SCA group (248 ± 181 LCU vs 252 ± 227 LCU; P > .05). The ESCA subgroup had significantly lower mean LCU scores than the USCA subgroup (163 ± 183 LCU vs 308 ± 237 LCU; P = .030). ConclusionsStressful life events, especially those producing chronic stress, might predispose otherwise healthy individuals to lethal arrhythmias. Further investigation into the role of stress in SCA precipitation is warranted.

“Concealed cardiomyopathy” as a cause of previously unexplained sudden cardiac arrest

Abstract Background Current genetic testing guidelines recommend against broad, multi-phenotype genetic testing in survivors of sudden cardiac arrest (SCA) where no cause is identified on clinical screening. Recent reports describe malignant arrhythmic events preceding detectable structural changes in patients with pathogenic variants in cardiomyopathy genes, who go on to demonstrate structural changes in follow up. Purpose We sought to investigate the utility of a broad genetic testing approach, sequencing genes implicated in both arrhythmia syndromes and cardiomyopathy, in SCA survivors where no cause was identified after thorough clinical evaluation. Methods We retrospectively reviewed the clinical and genetic profiles of SCA survivors referred to a specialised genetic heart disease multidisciplinary team in Australia. Multi-phenotype genetic testing included analysis of 174 cardiac genes associated with arrhythmia or cardiomyopathy. Results The cohort was comprised of 86 SCA survivors. A clinical diagnosis was made in 46 (53%) patients while 40 (47%) cases were considered idiopathic, with no cause of arrest identified despite thorough clinical investigation. Thirty-two survivors of idiopathic SCA (80%) underwent broad, multi-phenotype genetic testing through genome (n=1), exome (n=26) or extended panel (n=5) analysis. The majority of the cohort were male (62.5%, n=25) and ≤35 years of age at time of arrest (60%, n=24). Events in this group most commonly occurred at rest or sleep (65.8%, n=25) and 5 patients had a family history of sudden death (12.5%). Seven disease causing variants were identified with a testing yield of 21.9%. There was no difference in demographic or clinical factors between those with and without a disease-causing variant. Six (85.7%) of these clinically actionable variants were identified in genes associated with cardiomyopathy (PKP2, MYBPC3, DES, DSP and ACTN2) that would not have been analysed on a standard commercial cardiac arrhythmia panel. Cardiac magnetic resonance (CMR) imaging was performed prior to genetic testing in 4 of the 6 cases found to have disease-causing variants in cardiomyopathy genes (2 patients did not have CMR performed due to the presence of cardiac devices), with 2 (50%) showing sub-diagnostic changes while 2 (50%) revealed a structurally normal heart. Conclusion A broad approach to genetic testing in idiopathic SCA can improve care for patients and their families by identifying clinically actionable variants that would be missed by phenotype specific gene panels and thus significantly increase the rate of diagnosis. “Concealed cardiomyopathy” represents a clinical challenge in how to manage patients and their relatives who carry a pathogenic cardiomyopathy variant, have no overt signs of structural disease, yet have an important risk of sudden cardiac arrest. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Cardiac Society of Australia and New Zealand; National Health and Medical Research Council (Australia)

Clinical course and outcome of patients with acute pulmonary embolism rescued by veno-arterial extracorporeal membrane oxygenation: a retrospective review of 21 cases

BackgroundVeno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being utilized in patients with massive pulmonary embolism (PE). However, the efficacy and the safety remain uncertain. This study aimed to investigate clinical courses and outcomes in ECMO-treated patients with acute PE.MethodsTwenty-one patients with acute PE rescued by ECMO from January 2012 to December 2019 were retrospectively analysed. Clinical features, laboratory biomarkers, and imaging findings of these patients were reviewed, and the relationship with immediate outcome and clinical course was investigated.ResultsSixteen patients (76.2%) experienced refractory circulatory collapse requiring cardiopulmonary resuscitation (CPR) or ECMO support within 2 h after the onset of cardiogenic shock, and none could receive definitive reperfusion therapy before ECMO initiation. Before or during ECMO support, more than 90% of patients had imaging signs of right ventricular (RV) dysfunction. In normotension patients, the computed tomography (CT) value was a valuable predictor of rapid disease progression compared with cardiac troponin I level. Ultimately, in-hospital death occurred in ten patients (47.6%) and 90% of them died of prolonged CPR-related brain death. Cardiac arrest was a significant predictor of poor prognosis (p = 0.001).ConclusionsECMO appears to be a safe and effective circulatory support in patients with massive PE. Close monitoring in intensive care unit is recommended in patients with RV dysfunction and aggressive use of ECMO may reduce the risk of sudden cardiac arrest and improve clinical outcome.

Low T/R ratio in inferolateral leads: A new ECG marker of sudden cardiac arrest in patients with a spontaneous type 1 Brugada pattern

Prediction of the individual risk of sudden cardiac arrest (SCA) remains the main challenge in Brugada syndrome. Several studies have shown that the surface electrocardiogram (ECG) can provide useful information that allows to estimate the risk of SCA. The T-wave amplitude is inversely correlated with the risk of ventricular fibrillation (VF) & SCA in several heart diseases. The purpose of this study was to evaluate the prognostic value of a low T/R ratio in patients with a spontaneous type-1 Brugada pattern (SBT1). In a multicenter study, we retrospectively reviewed 115 pts (105 males, 91.3%) with a SBT1. 45 had VF and/or SCA (38.7 ± 11.5 years old, all males), while 70 (49.3 ± 12.0 years, 10 women) remained free of ventricular arrhythmia. 6 ECG markers plus the lowest T/R ratio among leads V5 & II were studied. The lowest T/R ratio among leads II & V5 was significantly smaller in the VF/SCA group (0.26 ± 0.15 vs. 0.35 ± 0.16; P = 0.006). The optimized cut-off value was ≤ 0.17 by the receiver operating characteristic curve method. 44.4% of pts in the VF/SCA group had a lowest T/R ratio among leads II & V5 ≤ 0.17 compared to 11.4% in the non-VF/SCA group ( P < 0.001). In multivariate analysis, a lowest T/R ratio among leads II & V5 ≤ 0.17 was independently associated with VF/SCA (OR 6.10, 95% CI 1.92-19.40; P = 0.002). Type-1 Brugada pattern in a peripheral lead (OR 10.78) and early repolarization (OR 3.60) were the other independent ECG markers of VF/SCA ( Fig. 1 ). A low T/R ratio among leads II & V5 is independently and strongly related to the risk of VF/SCA in patients with a spontaneous type-1 Brugada pattern.

Effectiveness, efficacy, and safety of wearable cardioverter-defibrillators in the treatment of sudden cardiac arrest - Results from a health technology assessment.

To assess the effectiveness, efficacy, and safety of a wearable cardioverter-defibrillator (WCD) in adult persons with high risk for sudden cardiac arrest and for which an implantable cardioverter is currently not applicable. We performed a systematic literature search in Medline, Embase, Cochrane Library, and CRD-databases. Study selection was performed by two reviewers independently. Data were presented quantitatively; due to heterogeneity of studies no meta-analysis was performed. One randomized-controlled trial (RCT), one non-randomized comparative trial, and forty-four non-comparative trials were included. The RCT reported an overall mortality of 3.1 percent in the WCD group versus 4.9 percent in controls (relative risk [RR]: .64; 95 percent confidence interval [CI], .43-.98, p = .04), but no significant effect on arrhythmia-related mortality. The RR for arrhythmia-related mortality amounted to .67 (95 percent CI, .37-1.21, p = .18) as assessed in the RCT. Appropriate shocks were observed in 1.3 percent of patients in both comparative studies, and inappropriate shocks in .6 percent of patients in the RCT. Termination of ventricular tachycardia (VT) or ventricular fibrillation (VF) was successful in 75 to 100 percent of appropriate shocks in all studies. Adverse events assessed in the RCT showed a lower incidence of shortness of breath (38.8 percent vs. 45.3 percent; p = .004), higher incidence of rash at any location (15.3 percent vs. 7.1 percent; p < .001), and higher incidence of itching at any location (17.2 percent vs. 6.4 percent; p < .001) for WCD. Available evidence demonstrates that the WCD detects and terminates VT/VF events reliably and shows a high rate of appropriate shocks in mixed patient populations. Data of large registries confirm that the WCD is a safe intervention.

Risk of sudden cardiac arrest and ventricular arrhythmia with sulfonylureas: An experience with conceptual replication in two independent populations

Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardiac arrest (SCA) or ventricular arrhythmia (VA). We assessed the comparative real-world risk of SCA/VA among users of second-generation sulfonylureas: glimepiride, glyburide, and glipizide. We conducted two incident user cohort studies using five-state Medicaid claims (1999–2012) and Optum Clinformatics commercial claims (2000–2016). Outcomes were SCA/VA events precipitating hospital presentation. We used Cox proportional hazards models, adjusted for high-dimensional propensity scores, to generate adjusted hazard ratios (aHR). We identified 624,406 and 491,940 sulfonylurea users, and 714 and 385 SCA/VA events, in Medicaid and Optum, respectively. Dataset-specific associations with SCA/VA for both glimepiride and glyburide (vs. glipizide) were on opposite sides of and could not exclude the null (glimepiride: aHRMedicaid 1.17, 95% CI 0.96–1.42; aHROptum 0.84, 0.65–1.08; glyburide: aHRMedicaid 0.87, 0.74–1.03; aHROptum 1.11, 0.86–1.42). Database differences in data availability, populations, and documentation completeness may have contributed to the incongruous results. Emphasis should be placed on assessing potential causes of discrepancies between conflicting studies evaluating the same research question.

Validation and Disease Risk Assessment of Previously Reported Genome-Wide Genetic Variants Associated With Brugada Syndrome: SADS-TW BrS Registry.

Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events. We genotyped 190 unrelated BrS patients using the TWB Array, and Taiwan Biobank was used as controls. SNPs not included in the array were imputed by IMPUTE2. Cox proportional hazards model was used to evaluate the associations between each particular SNP, the collective BrS-polygenic risk score, and clinical outcomes. Of the 88 previously reported SNPs, 22 were validated in Taiwanese BrS patients (P<0.05). Of the 22 SNPs, 2 (rs10428132 and rs9388451) were linked with susceptibility to BrS, 10 were SNPs previously reaching genome-wide significance, and 10 were SNPs associated with ECG traits. For the 3 most commonly reported SNPs, disease risk increased consistently with the number of risk alleles (odds ratio, 3.54; Ptrend=1.38×10-9 for 5 risk alleles versus 1). Similar patterns were observed in both SCN5A mutation+ (odds ratio, 3.66; Ptrend=0.049) and SCN5A mutation- (odds ratio, 3.75; Ptrend=8.54×10-9) subgroups. Furthermore, BrS patients without SCN5A mutations had more risk alleles than BrS patients with SCN5A mutations regardless of the range of polygenic risk scores. Three SNPs (rs4687718, rs7784776, and rs2968863) showed significant associations with the composite outcome (sudden cardiac arrest plus syncope, hazard ratio, 2.13, 1.48, and 0.41; P=0.02, 0.006, and 0.008, respectively). Our findings suggested that some SNPs associated with BrS or ECG traits exist across multiple populations. The cumulative risk of the BrS-related SNPs is similar to that in white BrS patients, but it appears to correlate with the absence of SCN5A mutations.

Loss of ventricular preexcitation during noninvasive testing does not exclude high-risk accessory pathways: A multicenter study of WPW in children

Abrupt loss of ventricular preexcitation on noninvasive evaluation, or nonpersistent preexcitation, in Wolff-Parkinson-White syndrome (WPW) is thought to indicate a low risk of life-threatening events. The purpose of this study was to compare accessory pathway (AP) characteristics and occurrences of sudden cardiac arrest (SCA) and rapidly conducted preexcited atrial fibrillation (RC-AF) in patients with nonpersistent and persistent preexcitation. Patients 21 years or younger with WPW and invasive electrophysiology study (EPS) data, SCA, or RC-AF were identified from multicenter databases. Nonpersistent preexcitation was defined as absence/sudden loss of preexcitation on electrocardiogram, Holter monitoring, or exercise stress test. RC-AF was defined as clinical preexcited atrial fibrillation with shortest preexcited R-R interval (SPERRI) ≤ 250 ms. AP effective refractory period (APERP), SPERRI at EPS , and shortest preexcited paced cycle length (SPPCL) were collected. High-risk APs were defined as APERP, SPERRI, or SPPCL ≤ 250 ms. Of 1589 patients, 244 (15%) had nonpersistent preexcitation and 1345 (85%) had persistent preexcitation. There were no differences in sex (58% vs 60% male; P=.49) or age (13.3±3.6 years vs 13.1±3.9 years; P=.43) between groups. Although APERP (344±76 ms vs 312±61 ms; P<.001) and SPPCL (394±123 ms vs 317±82 ms; P<.001) were longer in nonpersistent vs persistent preexcitation, there was no difference in SPERRI at EPS (331±71 ms vs 316±73 ms; P=.15). Nonpersistent preexcitation was associated with fewer high-risk APs (13% vs 23%; P<.001) than persistent preexcitation. Of 61 patients with SCA or RC-AF, 6 (10%) had nonpersistent preexcitation (3 SCA, 3 RC-AF). Nonpersistent preexcitation was associated with fewer high-risk APs, though it did not exclude the risk of SCA or RC-AF in children with WPW.

The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: real-world evidence on thiazolidinedione safety

BackgroundThe low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA).MethodsWe conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999–2012) and a commercial health insurance plan (Optum Clinformatics | 2000–2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset.ResultsThe adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75–1.10) in Medicaid and 0.88 (0.61–1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54–0.93] and 1.16 [0.89–1.52] in men and women respectively, interaction term p-value = 0.01).ConclusionsRosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.

Postoperative high-sensitivity troponin T as a predictor of sudden cardiac arrest in patients undergoing cardiac surgery.

The usefulness of high-sensitivity troponin T (hs-TnT) as a predictor of sudden cardiac arrest (SCA) in patients undergoing valve surgery is currently unknown. A prospective study was conducted on a group of 815 consecutive patients with significant valvular heart disease that underwent elective valve surgery. The primary end-point was postoperative SCA. The postoperative SCA occurred in 26 patients. At multivariate analysis of hs-TnT measured immediately after surgery (hs-TnT I) and age remained independent predictors of the primary end-point. Elevated postoperative hs-TnT was associated with a higher risk of postoperative SCA.

Clinical risk prediction with random forests for survival, longitudinal, and multivariate (RF-SLAM) data analysis

BackgroundClinical research and medical practice can be advanced through the prediction of an individual’s health state, trajectory, and responses to treatments. However, the majority of current clinical risk prediction models are based on regression approaches or machine learning algorithms that are static, rather than dynamic. To benefit from the increasing emergence of large, heterogeneous data sets, such as electronic health records (EHRs), novel tools to support improved clinical decision making through methods for individual-level risk prediction that can handle multiple variables, their interactions, and time-varying values are necessary.MethodsWe introduce a novel dynamic approach to clinical risk prediction for survival, longitudinal, and multivariate (SLAM) outcomes, called random forest for SLAM data analysis (RF-SLAM). RF-SLAM is a continuous-time, random forest method for survival analysis that combines the strengths of existing statistical and machine learning methods to produce individualized Bayes estimates of piecewise-constant hazard rates. We also present a method-agnostic approach for time-varying evaluation of model performance.ResultsWe derive and illustrate the method by predicting sudden cardiac arrest (SCA) in the Left Ventricular Structural (LV) Predictors of Sudden Cardiac Death (SCD) Registry. We demonstrate superior performance relative to standard random forest methods for survival data. We illustrate the importance of the number of preceding heart failure hospitalizations as a time-dependent predictor in SCA risk assessment.ConclusionsRF-SLAM is a novel statistical and machine learning method that improves risk prediction by incorporating time-varying information and accommodating a large number of predictors, their interactions, and missing values. RF-SLAM is designed to easily extend to simultaneous predictions of multiple, possibly competing, events and/or repeated measurements of discrete or continuous variables over time.Trial registration: LV Structural Predictors of SCD Registry (clinicaltrials.gov, NCT01076660), retrospectively registered 25 February 2010