A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

ICD Implantation Rates in Cardiac Arrest Survivors in Canada.

Background: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) are at high risk of recurrence, posing a substantial burden on healthcare systems. Despite the established benefit of implantable cardioverter defibrillator (ICD) therapy in many such patients, and recommendations by guidelines, few studies have described the proportion of OHCA patients who receive guideline-concordant care. Methods: The Canadian Institute for Health Information Discharge Abstract Database dataset was used to identify OHCA patients admitted to hospitals across Canada, excluding Quebec. We analyzed all patients without a probable ischemic or bradycardia etiology of cardiac arrest, who survived to discharge, to estimate the ICD implantation rates in patients who were potentially eligible to have an ICD. Results: Between 2013 and 2017, a total of 10,435 OHCA patients who were admitted to the hospital were captured in the database; 4486 (43%) survived to hospital discharge, and 2580 survivors (57.5%) were potentially eligible to receive an ICD. Among these potentially eligible patients, 757 (29.3%) received an ICD during their index admission or within 30 days after discharge from the hospital. The ICD implantation rate during index admission increased from 13.8% in 2013 to 19.6% in 2017 (P-value for time trend < 0.05). The rate of ICD implantations in potentially eligible patients was higher in urban than in rural settings (19.5% vs 11.1%) and in teaching vs community hospitals (34.7% vs 9.8%). Conclusions: Although ICD implantation rates show an increasing trend among patients with OHCA who are likely eligible for secondary prevention, significant underutilization of ICDs persists in these patients.

Contexte: Les patients ayant survécu à un arrêt cardiaque extra-hospitalier (ACEH) présentent un risque élevé de récidive, ce qui impose un lourd fardeau aux systèmes de soins de santé. Malgré l'avantage établi de la mise en place d'un défibrillateur cardioverteur implantable (DCI) chez un grand nombre de ces patients, et les recommandations des lignes directrices, peu d'études décrivent la proportion de patients victimes d'un ACEH ayant reçu des soins conformes aux lignes directrices. Méthodologie: Nous avons recensé les admissions à l'hôpital de patients ayant subi un ACEH au Canada, à l'exception du Québec à partir de l'ensemble de données de la Base de données sur les congés des patients de l'Institut canadien d'information sur la santé. Nous avons inclus dans notre analyse tous les patients pour lesquels la cause de l'arrêt cardiaque n'était probablement pas ischémique ou bradycardique et qui avaient survécu jusqu'à leur congé de l'hôpital, afin d'estimer les taux d'implantation d'un DCI chez les patients potentiellement admissibles à cette intervention. Résultats: Entre 2013 et 2017, un total de 10 435 patients ayant subi un ACEH ont été hospitalisés selon la base de données; 4 486 (43 %) avaient survécu jusqu'à leur congé de l'hôpital, et 2 580 survivants (57,5 %) étaient potentiellement admissibles à l'implantation d'un DCI. Parmi les patients potentiellement admissibles, 757 (29,3 %) avaient reçu un DCI au moment de leur admission initiale ou dans les 30 jours suivant leur congé de l'hôpital. Le taux d'implantation de DCI lors de l'admission initiale est passé de 13,8 % en 2013 à 19,6 % en 2017 (valeur p pour la tendance au fil du temps < 0,05). Le taux d'implantation d'un DCI chez les patients potentiellement admissibles était plus élevé en milieu urbain qu'en milieu rural (19,5 % contre 11,1 %) et dans les hôpitaux d'enseignement/universitaires par comparaison avec les hôpitaux communautaires (34,7 % contre 9,8 %). Conclusions: Bien que les taux d'implantation de DCI affichent une tendance à la hausse chez les patients ayant subi un ACEH qui sont probablement admissibles à des interventions de prévention secondaire, les DCI demeurent largement sous-utilisés chez ces patients.

Temporal Trends of Enrollment by Sex and Race in Major Cardiovascular Randomized Clinical Trials.

Background: Women and racialized minorities continue to be underrepresented in cardiovascular (CV) trial outcomes data, despite comprising a significant global burden of CV disease. This study evaluated the impact of trial characteristics on the temporal enrollment of women and racialized minorities in prominent CV trials published in the period 1986-2023. Methods: MEDLINE was searched for CV trials published in The Lancet, the Journal of the American Medical Association, and the New England Journal of Medicine. Participant and investigator demographics, types of interventions, clinical indications, and funding sources were compared according to the enrollment of women or racialized minorities. Results: From 799 studies, including 4,071,921 patients, the enrollment of women and racialized minorities significantly increased from 1986 to 2023 (both P ≤ 0.001). Although the enrollment of women varied by trial indication, comprising 25.0% of coronary artery disease, 35.2% of noncoronary and/or vascular disease, 13.8% of heart failure, 17.0% of arrhythmia, and 28.7% of other CV trials (P ≤ 0.001), it did not differ by peer-reviewed vs industry funding. First authors who were women were more likely than first authors who were men to enroll significantly more women (P = 0.01). Conclusions: Active efforts to increase diverse enrollment, along with improved reporting, including of sex and race, in future CV trials may increase the generalizability of their findings and applicability to global populations.

Contexte: Les femmes et les groupes racisés demeurent sous-représentés dans les données de résultats d'essais cliniques sur les maladies cardiovasculaires (CV) malgré l'important fardeau global associé à ces maladies. Cette étude visait à évaluer l'effet des caractéristiques des essais sur la sélection temporelle des femmes et des membres de groupes racisés dans les essais portant principalement sur les maladies CV durant la période de 1986 à 2023. Méthodologie: La base de données MEDLINE a été consultée à la recherche d'essais sur les maladies CV publiés dans The Lancet, Journal of the American Medical Association et New England Journal of Medicine. Les données démographiques des participants et des chercheurs, les types d'interventions, les indications cliniques et les sources de financement ont été comparés en fonction de la sélection des femmes ou des membres de groupes racisés. Résultats: Dans 799 études cumulant 4 071 921 patients, la sélection des femmes et des membres de groupes racisés a augmenté significativement entre 1986 et 2023 (p ≤ 0,001 dans les deux cas). Bien que la sélection des femmes variait en fonction des indications des essais, soit 25,0 % dans les essais portant sur les coronaropathies, 35,2 % pour les maladies non coronariennes et/ou vasculaires, 13,8 % pour l'insuffisance cardiaque, 17,0 % pour l'arythmie et 28,7 % pour d'autres maladies CV (p ≤ 0,001), elle ne différait pas selon que les études étaient révisées par des pairs ou qu'elles étaient financées par l'industrie. Lorsqu'une femme était l'autrice principale, le nombre de femmes sélectionnées était susceptible d'être plus élevé que lorsque l'auteur principal était un homme (p = 0,01). Conclusions: Des efforts actifs pour diversifier davantage la sélection des participants et mieux rendre compte des différences, notamment en ce qui concerne le sexe et la race, pourraient élargir la portée des conclusions des futurs essais sur les maladies CV et leur application à l'ensemble de la population.

Prognostic Value of Different Thresholds for Myocardial Scar Quantification on Cardiac MRI Late Gadolinium Enhancement Images in Patients Receiving Implantable Cardioverter Defibrillators.

Purpose: To compare the predictive value of different myocardial scar quantification thresholds using cardiac MRI for appropriate implantable cardioverter defibrillator (ICD) shock and mortality. Materials and Methods: In this retrospective, two-center observational cohort study, patients with ischemic or nonischemic cardiomyopathy underwent cardiac MRI prior to ICD implantation. Late gadolinium enhancement (LGE) was first determined visually and then quantified by blinded cardiac MRI readers using different SDs above the mean signal of normal myocardium, full-width half-maximum, and manual thresholding. The intermediate signal "gray zone" was calculated as the differences between different SDs. Results: Among 374 consecutive eligible patients (mean age, 61 years ± 13 [SD]; mean left ventricular ejection fraction, 32% ± 14; secondary prevention, 62.7%), those with LGE had a higher rate of appropriate ICD shock or death than those without (37.5% vs 26.6%, log-rank P = .04) over a median follow-up of 61 months. In multivariable analysis, none of the thresholds for quantifying scar was a significant predictor of mortality or appropriate ICD shock, while the extent of gray zone was an independent predictor (adjusted hazard ratio per 1 g = 1.025; 95% CI: 1.008, 1.043; P = .005) regardless of the presence or absence of ischemic heart disease (P interaction = .57). Model discrimination was highest for the model incorporating the gray zone (between 2 SD and 4 SD). Conclusion: Presence of LGE was associated with a higher rate of appropriate ICD shock or death. Although none of the scar quantification techniques predicted outcomes, the gray zone both in infarct and nonischemic scar was an independent predictor and may refine risk stratification.Keywords: MRI, Scar Quantification, Implantable Cardioverter Defibrillator, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2023.

In symptomatic AF, cryoballoon ablation reduced progression to persistent AF vs. antiarrhythmic therapy at 3 y.

SOURCE CITATION: Andrade JG, Deyell MW, Macle L, et al. Progression of atrial fibrillation after cryoablation or drug therapy. N Engl J Med. 2023;388:105-16. 36342178.

Myocardial strain assessment using cardiovascular magnetic resonance imaging in recipients of implantable cardioverter defibrillators.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used in the evaluation of patients who are potential candidates for implantable cardioverter-defibrillator (ICD) therapy to assess left ventricular (LV) ejection fraction (LVEF), myocardial fibrosis, and etiology of cardiomyopathy. It is unclear whether CMR-derived strain measurements are predictive of appropriate shocks and death among patients who receive an ICD. We evaluated the prognostic value of LV strain parameters on feature-tracking (FT) CMR in patients who underwent subsequent ICD implant for primary or secondary prevention of sudden cardiac death. METHODS: Consecutive patients from 2 Canadian tertiary care hospitals who underwent ICD implant and had a pre-implant CMR scan were included. Using FT-CMR, a single, blinded, reader measured LV global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain. Cox proportional hazards regression was performed to assess the associations between strain measurements and the primary composite endpoint of all-cause death or appropriate ICD shock that was independently ascertained. RESULTS: Of 364 patients (mean 61 years, mean LVEF 32%), 64(17.6%) died and 118(32.4%) reached the primary endpoint over a median follow-up of 62 months. Univariate analyses showed significant associations between GLS, GCS, and GRS and appropriate ICD shocks or death (all p < 0.01). In multivariable Cox models incorporating LVEF, GLS remained an independent predictor of both the primary endpoint (HR 1.05 per 1% higher GLS, 95% CI 1.01-1.09, p = 0.010) and death alone (HR 1.06 per 1% higher GLS, 95% CI 1.02-1.11, p = 0.003). There was no significant interaction between GLS and indication for ICD implant, presence of ischemic heart disease or late gadolinium enhancement (all p > 0.30). CONCLUSIONS: GLS by FT-CMR is an independent predictor of appropriate shocks or mortality in ICD patients, beyond conventional prognosticators including LVEF. Further study is needed to elucidate the role of LV strain analysis to refine risk stratification in routine assessment of ICD treatment benefit.

Right Ventricular Function at Cardiac MRI Predicts Cardiovascular Events in Patients with an Implantable Cardioverter-Defibrillator.

Background Right ventricular ejection fraction (RVEF) is an independent predictor of death and adverse cardiovascular outcomes in patients with various cardiac conditions. Purpose To investigate whether RVEF, measured with cardiac MRI, is a predictor of appropriate shock or death in implantable cardioverter-defibrillator (ICD) recipients for primary and secondary prevention of sudden cardiac death. Materials and Methods This retrospective, multicenter, observational study included patients who underwent cardiac MRI before ICD implantation between January 2007 and May 2017. Right ventricular end-diastolic and end-systolic volumes and RVEF were measured with cardiac MRI. The primary end point was a composite of all-cause mortality or appropriate ICD shock. The secondary end point was all-cause mortality. The association between RVEF and primary and secondary outcomes was evaluated by using multivariable Cox regression analysis. Potential interactions were tested between primary prevention, ischemic cause, left ventricular ejection fraction (LVEF), and RVEF. Results Among 411 patients (mean age ± standard deviation, 60 years; 315 men) during a median follow-up of 63 months, 143 (35%) patients experienced an appropriate ICD shock or died. In univariable analysis, lower RVEF was associated with greater risks for appropriate ICD shock or death and for death alone (log-rank trend test, P = .003 and .005 respectively). In multivariable Cox regression analysis adjusting for age at ICD implantation, LVEF, ICD indication (primary vs secondary), ischemic heart disease, and late gadolinium enhancement, RVEF was an independent predictor of the primary outcome (hazard ratio [HR], 1.21 per 10% lower RVEF; 95% CI: 1.04, 1.41; P = .01) and all-cause mortality (HR, 1.25 per 10% lower RVEF; 95% CI: 1.01, 1.55; P = .04). No evidence of significant interactions was found between RVEF and primary or secondary prevention (P = .49), ischemic heart disease (P = .78), and LVEF (P = .29). Conclusion Right ventricular ejection fraction measured with cardiac MRI was a predictor of appropriate implantable cardioverter-defibrillator shock or death. © RSNA, 2021 See also the editorial by Nazarian and Zghaib in this issue. An earlier incorrect version of this article appeared online. This article was corrected on August 24, 2021.

Prognostic value of cardiovascular magnetic resonance left ventricular volumetry and geometry in patients receiving an implantable cardioverter defibrillator.

BACKGROUND: Current indications for implantable cardioverter defibrillator (ICD) implantation for sudden cardiac death prevention rely primarily on left ventricular (LV) ejection fraction (LVEF). Currently, two different contouring methods by cardiovascular magnetic resonance (CMR) are used for LVEF calculation. We evaluated the comparative prognostic value of these two methods in the ICD population, and if measures of LV geometry added predictive value. METHODS: In this retrospective, 2-center observational cohort study, patients underwent CMR prior to ICD implantation for primary or secondary prevention from January 2005 to December 2018. Two readers, blinded to all clinical and outcome data assessed CMR studies by: (a) including the LV trabeculae and papillary muscles (TPM) (trabeculated endocardial contours), and (b) excluding LV TPM (rounded endocardial contours) from the total LV mass for calculation of LVEF, LV volumes and mass. LV sphericity and sphere-volume indices were also calculated. The primary outcome was a composite of appropriate ICD shocks or death. RESULTS: Of the 372 consecutive eligible patients, 129 patients (34.7%) had appropriate ICD shock, and 65 (17.5%) died over a median duration follow-up of 61 months (IQR 38-103). LVEF was higher when including TPM versus excluding TPM (36% vs. 31%, p < 0.001). The rate of appropriate ICD shock or all-cause death was higher among patients with lower LVEF both including and excluding TPM (p for trend = 0.019 and 0.004, respectively). In multivariable models adjusting for age, primary prevention, ischemic heart disease and late gadolinium enhancement, both LVEF (HR per 10% including TPM 0.814 [95%CI 0.688-0.962] p = 0.016, vs. HR per 10% excluding TPM 0.780 [95%CI 0.639-0.951] p = 0.014) and LV mass index (HR per 10 g/m2 including TPM 1.099 [95%CI 1.027-1.175] p = 0.006; HR per 10 g/m2 excluding TPM 1.126 [95%CI 1.032-1.228] p = 0.008) had independent prognostic value. Higher LV end-systolic volumes and LV sphericity were significantly associated with increased mortality but showed no added prognostic value. CONCLUSION: Both CMR post-processing methods showed similar prognostic value and can be used for LVEF assessment. LVEF and indexed LV mass are independent predictors for appropriate ICD shocks and all-cause mortality in the ICD population.

Left atrial volume and function measured by cardiac magnetic resonance imaging as predictors of shocks and mortality in patients with implantable cardioverter-defibrillators.

Left atrial (LA) volume and function (LA ejection fraction, LAEF) have demonstrated prognostic value in various cardiovascular diseases. We investigated the incremental value of LA volume and LAEF as measured by cardiovascular magnetic resonance imaging (CMR) for prediction of appropriate implantable cardioverter defibrillator (ICD) shock or all-cause mortality, in patients with ICD. We conducted a retrospective, multi-centre observational cohort study of patients who underwent CMR prior to primary or secondary prevention ICD implantation. A single, blinded reader measured maximum LA volume index (maxLAVi), minimum LA volume index (minLAVi), and LAEF. The primary outcome was a composite of independently adjudicated appropriate ICD shock or all-cause death. A total of 392 patients were enrolled. During a median follow-up time of 61 months, 140 (35.7%) experienced an appropriate ICD shock or died. Higher maxLAVi and minLAVi, and lower LAEF were associated with greater risk of appropriate ICD shock or death in univariate analysis. However, in multivariable analysis, LAEF (HR 0.92 per 10% higher, 95% CI 0.81-1.04, p = 0.17) and maxLAVi (HR 1.02 per 10 ml/m2 higher, 95% CI 0.93-1.12, p = 0.72) were not independent predictors of the primary outcome. In conclusion, LA volume and function measured by CMR were univariate but not independent predictors of appropriate ICD shocks or mortality. These findings do not support the routine assessment of LA volume and function to refine risk stratification to guide ICD implant. Larger studies with longer follow-up are required to further delineate the clinical implications of LA size and function.

Temporal Trends of Women Enrollment in Major Cardiovascular Randomized Clinical Trials.

BACKGROUND: Although it is known that women do not participate in trials as frequently as men, there are limited recent data examining how women recruitment has changed over time. METHODS: We conducted MEDLINE search using a validated strategy for randomized trials published in New England Journal of Medicine, Lancet, and Journal of the American Medical Association between 1986 and 2015, and included trials evaluating pharmacologic or nonpharmacologic therapies. We abstracted data on demographics, intervention type, clinical indication, and trial design characteristics, and examined their relationships with women enrollment. RESULTS: In total, 598 trials met inclusion criteria. Women enrollment increased significantly over time (21% between 1986 and 1990 to 33% between 2011 and 2015; Pfor trend < 0.001) and did not differ by journal or funding source. Women enrollment varied with clinical indication, comprising 37% for non-coronary artery disease vascular trials, 30% for coronary artery disease trials, 28% for heart failure trials, and 28% for arrhythmia trials (P < 0.001), which were all significantly lower than the expected proportion in disease populations (P < 0.001). Women enrollment varied with trial type (31%, 29%, and 26% for pharmacologic, device, and procedural trials, respectively; P = 0.001). These findings were corroborated using multivariable analysis. We found significant positive correlations between women enrolled, and mean age and total number of participants. Fewer women were enrolled in trials reporting statistically significant results than those who did not (P = 0.001). CONCLUSIONS: Although enrollment of women has increased over time, it remains lower than the relative proportion in the disease population. Future studies should elucidate the reasons for persistent under-representation of women in clinical trials.

Pulse pressure in acute coronary syndromes: Comparative prognostic significance with systolic blood pressure.

BACKGROUND: Pulse pressure is a readily available vital sign that has been shown to independently predict outcomes in several cardiovascular disease states. We investigated the prognostic significance of pulse pressure (PP) and systolic blood pressure (SBP) among patients with acute coronary syndromes (ACS). METHODS: A total of 14,514 patients with ACS in the prospective, multicentre Global Registry of Acute Coronary Events (GRACE), expanded GRACE (GRACE-2) and Canadian Registry of Acute Coronary Events (CANRACE) were stratified by initial PP on presentation. Patient characteristics and in-hospital outcomes were compared by PP quartiles and the independent prognostic significance of PP for in-hospital mortality was quantified. We compared the discriminative ability (c-statistic) of models incorporating either PP or SBP. RESULTS: Patients with higher PPs were older, more frequently female and had higher prevalence rates of conventional cardiovascular risk factors (all p < 0.01). Lower PP was associated with ST-segment elevation myocardial infarction presentation, higher GRACE risk scores and higher rates of adverse in-hospital outcomes (p < 0.001). PP was strongly correlated with SBP (Pearson's correlation coefficient = 0.79, p < 0.001). After adjustment for other GRACE risk model predictors, lower PP was independently associated with in-hospital mortality (first vs. fourth quartile [reference]: adjusted odds ratio 2.57, 95% confidence interval 1.80-3.67). The c-statistic was slightly higher for the multivariable model incorporating SBP as compared to the model with PP (0.868 vs. 0.864, respectively, p = 0.028) for in-hospital mortality. CONCLUSION: Higher presenting PP is associated with increased age and more prevalent cardiovascular risk factors, whereas patients with lower PP present with worse clinical characteristics and in-hospital outcomes. Lower PP is an independent adverse prognosticator in ACS. However, PP did not improve the discriminatory performance of the GRACE risk score compared with SBP.

Previous and New Onset Atrial Fibrillation and Associated Outcomes in Acute Coronary Syndromes (from the Global Registry of Acute Coronary Events).

Atrial fibrillation (AF) is a frequent complication of acute coronary syndromes (ACS) and is associated with an increased risk of in-hospital and long-term mortality. Our objective was to determine whether patients with previous AF and those who presented with or developed AF during their ACS hospitalization (new onset) have an associated increased risk of short- and mid-term cardiovascular events, death, or a composite. We included 7,228 patients from the Global Registry of Acute Coronary Events electrocardiogram core laboratory substudy, who presented with an ACS. Associated multivariable-adjusted risk of death and major adverse cardiovascular events (MACE) of death, re-infarction, or stroke in-hospital and at 6 months were estimated. New-onset AF and previous AF patients had higher rates of in-hospital mortality (14.9% and 10.9%, respectively) compared with patients without AF (3.8%; both p < 0.001). New-onset AF and previous AF patients had higher rates of 6-month mortality (22.3% and 21.3%, respectively) compared with patients without AF (7.0%; both p <0.001). After adjustment for clinical prognosticators, including those in the Global Registry of Acute Coronary Events risk model, new-onset AF was associated with higher mortality in-hospital (ORadj 1.87, 95% CI 1.30 to 2.70) and at 6 months (ORadj 1.75, 95% CI 1.29 to 2.39) as well as MACE at 6 months (ORadj 1.43, 95% CI 1.12 to 1.81) compared with patients without AF, but were at similar risk compared to those with previous AF (all p > 0.40). In conclusion, the risk of death and MACE after ACS in patients with new-onset and previous AF appears similar and significantly increased compared with patients without AF.

Out-of-Hospital Cardiac Arrest in the Presence of Ischemic Heart Disease: What Is the Long-term Arrhythmic Risk After Revascularization?

Patients resuscitated from out-of-hospital cardiac arrest (OHCA) frequently have underlying coronary artery disease (CAD), but the relationship between the arrest and myocardial ischemia or infarction due to CAD can be difficult to discern in clinical practice. Patients often present with clinical profiles that guideline recommendations for appropriate implantable cardioverter-defibrillator use do not address. In cases of incomplete revascularization or mild but sustained impairment of ventricular function, it is not clear if the cause of the cardiac arrest is completely "reversible." We describe distinct phenotypes of patients with OHCA and concomitant CAD and highlight current knowledge gaps in their management and outcomes.

Cardiovascular disease in the Eastern Mediterranean region: epidemiology and risk factor burden.

The Eastern Mediterranean region (EMR) comprises 22 countries or territories spanning from Morocco in the west to Pakistan in the east, and contains a population of almost 600 million people. Like many other developing regions, the burden of disease in the EMR has shifted in the past 30 years from primarily communicable diseases to noncommunicable diseases such as cardiovascular disease (CVD). Cardiovascular mortality in the EMR, mostly attributable to ischaemic heart disease, is expected to increase more dramatically in the next decade than in any other region except Africa. The most prominent CVD risk factors in this region include tobacco consumption, physical inactivity, depression, obesity, hypertension, and diabetes mellitus. Many individuals living in the EMR are unaware of their risk factor status, and even if treated, these risk factors are often poorly controlled. Furthermore, infrequent use of emergency medical services, delays in access to care, and lack of access to cardiac catheterization affects the timely diagnosis of CVD. Treatment of CVD is also suboptimal in this region, consisting primarily of thrombolysis, with insufficient provision of timely revascularization. In this Review, we summarize what is known about CVD burden, risk factors, and treatment strategies for individuals living in the EMR. This information will hopefully aid decision-makers when devising strategies on how to improve CVD prevention and management in this region.

Electrocardiographic Findings in Patients With Acute Coronary Syndrome Presenting With Out-of-Hospital Cardiac Arrest.

We sought to characterize presenting electrocardiographic findings in patients with acute coronary syndromes (ACSs) and out-of-hospital cardiac arrest (OHCA). In the Global Registry of Acute Coronary Events and Canadian ACS Registry I, we examined presenting and 24- to 48-hour follow-up ECGs (electrocardiogram) of ACS patients who survived to hospital admission, stratified by presentation with OHCA. We assessed the prevalence of ST-segment deviation and bundle branch blocks (assessed by an independent ECG core laboratory) and their association with in-hospital and 6-month mortality among those with OHCA. Of the 12,040 ACS patients, 215 (1.8%) survived to hospital admission after OHCA. Those with OHCA had higher presenting rates of ST-segment elevation, ST-segment depression, T-wave inversion, precordial Q-waves, left bundle branch block (LBBB), and right bundle branch block (RBBB) than those without. Among patients with OHCA, those with ST-segment elevation had significantly lower in-hospital mortality (20.9% vs 33.0%, p = 0.044) and a trend toward lower 6-month mortality (27% vs 39%, p = 0.060) compared with those without ST-segment elevation. Conversely, among OCHA patients, LBBB was associated with significantly higher in-hospital and 6-month mortality rates (58% vs 22%, p <0.001, and 65% vs 28%, p <0.001, respectively). ST-segment depression and RBBB were not associated with either outcome. Sixty-three percent of bundle branch blocks (RBBB or LBBB) on the presenting ECG resolved by 24 to 48 hours. In conclusion, compared with ACS patients without cardiac arrest, those with OHCA had higher rates of ST-segment elevation, LBBB, and RBBB on admission. Among OHCA patients, ST-segment elevation was associated with lower in-hospital mortality, whereas LBBB was associated with higher in-hospital and 6-month mortality.

Coronary vasospasm-induced polymorphic ventricular tachycardia: a case report and literature review.

INTRODUCTION: Coronary vasospasm is an uncommon but important cause of myocardial ischaemia and ventricular arrhythmias. CASE PRESENTATION: In this report, we present a striking example of vasospasm manifesting as ST-segment elevation and ventricular tachycardia on Holter monitoring. Later, spasm occurred during a procainamide challenge performed for suspected Brugada syndrome. The patient underwent implantable cardioverter-defibrillator insertion and was successfully treated with oral calcium channel blocker. DISCUSSION: We review contemporary data regarding management and outcomes in coronary vasospasm and discuss the use of implantable defibrillator therapy in patients who have sustained a significant arrhythmic event.

Temporal Trends in Use of Composite End Points in Major Cardiovascular Randomized Clinical Trials in Prominent Medical Journals.

BACKGROUND: Cardiovascular mortality has decreased over the past 5 decades, making it increasingly difficult to demonstrate significant benefits of new therapies in randomized clinical trials. We sought to determine whether the use of composite end points in major cardiovascular trials has changed over time and examine temporal trends in the clinical importance of individual components of these composite end points. METHODS AND RESULTS: Using a validated search strategy, we searched MEDLINE for randomized trials of therapies for primary or secondary cardiovascular prevention published in New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association between 1986 and 2015. We abstracted and categorized study population demographics, type of intervention, and primary and secondary outcomes. Composite end point components were ranked according to importance (minor, moderate, major, critical, and death) and temporal trends analyzed. In total, 604 of 2607 trials retrieved met inclusion criteria. Use of composite end points increased significantly over time from 18.8% between 1986 and 1990 to 83.0% between 2011 and 2015 (P<0.001). The number of components in the primary end point also increased significantly (median 1 in 1986-1990, median 3 in 2011-2015; P<0.001). Contemporary trials were more likely to include end points of lesser importance to patients (minor 3.1% and moderate 6.3% in 1986-1990, minor 4.5% and moderate 44.6% in 2011-2015; P<0.001). Use of death as the sole primary end point declined significantly over time (53.1% in 1986-1990, 17.9% in 2011-2015; P<0.001). CONCLUSIONS: Contemporary cardiovascular randomized clinical trials are more likely to use primary composite end points that contain a larger number of components. Furthermore, these composite end points have increasingly incorporated components of lesser clinical importance. Clinicians and policymakers interpreting results of randomized trials should recognize that the significance of individual components in a composite end point is often heterogeneous.

Effects of Late Sodium Current Blockade on Ventricular Refibrillation in a Rabbit Model.

BACKGROUND: After defibrillation of initial ventricular fibrillation (VF), it is crucial to prevent refibrillation to ensure successful resuscitation outcomes. Inability of the late Na+ current to inactivate leads to intracellular Ca2+ dysregulation and arrhythmias. Our aim was to determine the effects of ranolazine and GS-967, inhibitors of the late Na+ current, on ventricular refibrillation. METHODS AND RESULTS: Long-duration VF was induced electrically in Langendorff-perfused rabbit hearts (n=22) and terminated with a defibrillator after 6 minutes. Fibrillating hearts were randomized into 3 groups: treatment with ranolazine, GS-967, or nontreated controls. In the treated groups, hearts were perfused with ranolazine or GS-967 at 2 minutes of VF. In control experiments, perfusion solution was supplemented with isotonic saline in lieu of a drug. Inducibility of refibrillation was assessed after initial long-duration VF by attempting to reinduce VF. Sustained refibrillation was successful in fewer ranolazine-treated (29.17%; P=0.005) or GS-967-treated (45.83%, P=0.035) hearts compared with that in nontreated control hearts (84.85%). In GS-967-treated hearts, significantly more spontaneous termination of initial long-duration VF was observed (66.67%; P=0.01). Ca2+ transient duration was reduced in ranolazine-treated hearts compared with that in controls (P=0.05) and also Ca2+ alternans (P=0.03). CONCLUSIONS: Late Na+ current inhibition during long-duration VF reduces the susceptibility to subsequent refibrillation, partially by mitigating dysregulation of intracellular Ca2+. These results suggest the potential therapeutic use of ranolazine and GS-967 and call for further testing in cardiac arrest models.

Prognostic value of dynamic electrocardiographic T wave changes in non-ST elevation acute coronary syndrome.

OBJECTIVE: To assess the relationship between the evolution of T wave inversion (TWI) on the 24-48 h postadmission ECG and the patient characteristics, management and clinical outcomes among those with non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: We evaluated admission and 24-48 h follow-up ECGs of 7201 patients with NSTE-ACS from the prospective, multicentre Global Registry of Acute Coronary Events (GRACE) and Canadian ACS Registry I. We performed multivariable analyses to determine the association between new TWI (on follow-up ECG only), resolved TWI (on admission ECG only) and persistent TWI (on both admission and follow-up ECG) and inhospital and cumulative 6-month all-cause mortality. RESULTS: Patients with TWI were older, more likely to have cardiovascular risk factors, higher Killip class and GRACE risk scores. After adjustment for known prognostic factors, compared with patients presenting without TWI, new TWI was associated with significantly lower inhospital mortality (OR=0.60, 95% CI 0.38 to 0.95, p=0.029), whereas resolved (OR=1.06, 95% CI 0.65 to 1.75, p=0.81) and persistent (OR=0.73, 95% CI 0.48 to 1.11, p=0.14) TWI did not predict inhospital mortality. No TWI pattern independently predicted inhospital adverse cardiovascular events or cumulative 6-month mortality. In contrast, ST depression on the admission and follow-up ECG were independent predictors of inhospital and 6-month mortality. CONCLUSIONS: Across the spectrum of NSTE-ACS, TWI within 48 h of presentation was associated with high-risk clinical features, but its presence or dynamic change did not provide additional prognostic value beyond other established clinical predictors.