Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks. Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy. Methods: Patients 18 years or older with continuous-flow LVADs and ICDs were retrospectively identified within the University of Pittsburgh Medical Center system from 2006-2020. We analyzed the association between appropriate ICD shocks within 1 year pre-LVAD with a primary composite outcome of death, stroke, and pump thrombosis and secondary outcomes of post-LVAD ICD shocks and ICD shock hospitalizations. Results: Among 309 individuals, average age was 57 ± 12 years, 87% were male, 80% had ischemic cardiomyopathy, and 42% were bridge to transplantation. Seventy-one patients (23%) experienced pre-LVAD shocks, and 69 (22%) experienced post-LVAD shocks. The overall prevalence of shocks pre-LVAD and post-LVAD were not different. Pre-LVAD ICD shocks were not associated with the composite outcome. Pre-LVAD ICD shocks were found to predict post-LVAD shocks (hazard ratio [HR] 5.7; 95% confidence interval [CI] 3.42-9.48; P <.0001) and hospitalizations related to ICD shocks from ventricular arrhythmia (HR 10.34; 95% CI 4.1-25.7; P <.0001). Conclusion: Pre-LVAD ICD shocks predicted post-LVAD ICD shocks and hospitalizations but were not associated with the composite outcome of death, pump thrombosis, or stroke at 1 year. The prevalence of appropriate ICD shocks was similar before and after LVAD implantation in the entire cohort.

Role of oesophageal cooling in the prevention of oesophageal injury in atrial fibrillation catheter ablation: a systematic review and meta-analysis of randomized controlled trials.

AIMS: To evaluate the efficacy of oesophageal cooling in the prevention of oesophageal injury in patients undergoing atrial fibrillation (AF) catheter ablation. METHODS AND RESULTS: Comprehensive search of MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) evaluating the role of oesophageal cooling compared with control in the prevention of oesophageal injury during AF catheter ablation. The study primary outcome was the incidence of any oesophageal injury. The meta-analysis included 4 RCTs with a total of 294 patients. There was no difference in the incidence of any oesophageal injury between oesophageal cooling and control [15% vs. 19%; relative risk (RR) 0.86; 95% confidence interval (CI) 0.31-2.41]. Compared with control, oesophageal cooling showed lower risk of severe oesophageal injury (1.5% vs. 9%; RR 0.21; 95% CI 0.05-0.80). There were no significant differences among the two groups in mild to moderate oesophageal injury (13.6% vs. 12.1%; RR 1.09; 95% CI 0.28-4.23), procedure duration [standardized mean difference (SMD) -0.03; 95% CI -0.36-0.30], posterior wall radiofrequency (RF) time (SMD 0.27; 95% CI -0.04-0.58), total RF time (SMD -0.50; 95% CI -1.15-0.16), acute reconnection incidence (RR 0.93; 95% CI 0.02-36.34), and ablation index (SMD 0.16; 95% CI -0.33-0.66). CONCLUSION: Among patients undergoing AF catheter ablation, oesophageal cooling did not reduce the overall risk of any oesophageal injury compared with control. Oesophageal cooling might shift the severity of oesophageal injuries to less severe injuries. Further studies should evaluate the long-term effects after oesophageal cooling during AF catheter ablation.

Convolution Neural Network Algorithm for Shockable Arrhythmia Classification Within a Digitally Connected Automated External Defibrillator.

Background Diagnosis of shockable rhythms leading to defibrillation remains integral to improving out-of-hospital cardiac arrest outcomes. New machine learning techniques have emerged to diagnose arrhythmias on ECGs. In out-of-hospital cardiac arrest, an algorithm within an automated external defibrillator is the major determinant to deliver defibrillation. This study developed and validated the performance of a convolution neural network (CNN) to diagnose shockable arrhythmias within a novel, miniaturized automated external defibrillator. Methods and Results There were 26 464 single-lead ECGs that comprised the study data set. ECGs of 7-s duration were retrospectively adjudicated by 3 physician readers (N=18 total readers). After exclusions (N=1582), ECGs were divided into training (N=23 156), validation (N=721), and test data sets (N=1005). CNN performance to diagnose shockable and nonshockable rhythms was reported with area under the receiver operating characteristic curve analysis, F1, and sensitivity and specificity calculations. The duration for the CNN to output was reported with the algorithm running within the automated external defibrillator. Internal and external validation analyses included CNN performance among arrhythmias, often mistaken for shockable rhythms, and performance among ECGs modified with noise to mimic artifacts. The CNN algorithm achieved an area under the receiver operating characteristic curve of 0.995 (95% CI, 0.990-1.0), sensitivity of 98%, and specificity of 100% to diagnose shockable rhythms. The F1 scores were 0.990 and 0.995 for shockable and nonshockable rhythms, respectively. After input of a 7-s ECG, the CNN generated an output in 383±29 ms (total time of 7.383 s). The CNN outperformed adjudicators in classifying atrial arrhythmias as nonshockable (specificity of 99.3%-98.1%) and was robust against noise artifacts (area under the receiver operating characteristic curve range, 0.871-0.999). Conclusions We demonstrate high diagnostic performance of a CNN algorithm for shockable and nonshockable rhythm arrhythmia classifications within a digitally connected automated external defibrillator. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03662802; Unique identifier: NCT03662802.

Hospital outcomes of patients receiving catheter ablation of atrial fibrillation, left atrial appendage closure, or both.

BACKGROUND: Catheter ablation (CA) and left atrial appendage closure (LAAC) require transseptal access; combining both in a single procedure may have advantages. However, the safety of this approach has not been extensively studied. The objective of this study was to compare in hospital outcomes among patients receiving CA, LAAC, and combination of both treatments on the same day. METHODS: We conducted a retrospective cohort analysis of the National Inpatient Sample database. The primary outcome was the presence of major adverse cardiovascular and cerebrovascular events (MACCE) during index hospitalization. Secondary outcomes included stroke, pericardial effusion, pericardiocentesis, and bleeding. RESULTS: A total of 69,285 hospitalizations with AF were included in the analysis, of which 71.7% received LAAC, 27.8% received CA, and 0.5% received combination of both treatments on the same day. MACEE (OR, 1.63; 95% CI, 0.39-6.70), stroke (OR, 2.98; 95% CI, 0.55-16.01), pericardial effusion (OR, 0.33; 95% CI, 0.07-1.41), pericardiocentesis (OR, 1.00; 95% CI, 0.25-3.86), and bleeding (OR, 3.25; 95% CI, 0.87-12.07) did not differ significantly between CA and combination treatment. Similarly, MACCE (OR, 1.11; 95% CI, 0.28-4.41), stroke (OR, 1.03; 95% CI, 0.24-4.35), pericardial effusion (OR, 0.45; 95% CI, 0.11-1.90), pericardiocentesis (OR, 0.63; 95% CI, 0.14-2.83), and bleeding (OR, 2.04; 95% CI, 0.65-6.39) did not differ significantly between LAAC and combination treatment. CONCLUSIONS: The combined approach is infrequently used in clinical practice (< 1%). However, major life-threatening adverse events did not differ between CA and LAAC when performed in isolation or combined in a single procedural stage on the same day.

Long-Term Efficacy and Safety of Left Atrial Appendage Occlusion (LAAO) vs Direct Oral Anticoagulation (DOAC) in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Prevention of stroke by anticoagulation is essential in patients with Atrial fibrillation (AF); with direct oral anticoagulants (DOACs) being preferred over warfarin in most patients. The Long-term efficacy and safety of DOACs vs. Left Atrial Appendage Occlusion (LAAO) remain unknown. Methods: Electronic databases (PubMed, Embase, Scopus) were searched from inception to February 10th, 2021. The primary endpoint was cardiovascular mortality. Secondary outcomes included incidence of ischemic stroke/transient ischemic attack (TIA) and systemicembolism. The safety endpoint was clinically relevant bleeding (a composite of major or minor clinically relevant bleeding). Results: A total of three studies with 3039 participants (LAAO = 1465; DOACs = 1574) were included. Mean age was 74.2 and 75.3 years in the LAAO and DOAC group respectively. Average follow-up period was 2 years. There was no difference in terms of cardiac mortality (RR 0.90, 95% CI 0.40-2.03; p = 0.81), ischemic stroke/TIA (RR 1.15, 95% CI 0.80-1.65; p = 0.46; I 2 = 0) and clinically significant bleeding (RR 0.77, 95% CI 0.50-1.17; p = 0.22; I 2 = 69) between the groups. Conclusions: Among patients with AF, LAAO was comparable to DOACs with similar efficacy and safety profiles.

Screening for atrial fibrillation in the elderly: A network meta-analysis of randomized trials.

BACKGROUND: Randomized controlled trials (RCTs) investigating the optimal screening strategy for atrial fibrillation (AF) have yielded conflicting results. OBJECTIVE: To examine the comparative efficacy of different AF screening strategies in older adults. METHODS: We searched MEDLINE, EMBASE and Cochrane without language restrictions through January 2022, for RCTs evaluating the outcomes of non-invasive AF screening approaches among adults ≥65 years. We conducted a pairwise meta-analysis comparing any AF screening approach versus no screening, and a network meta-analysis comparing systematic screening versus opportunistic screening versus no screening. The primary outcome was new AF detection. RESULTS: The final analysis included 9 RCTs with 85,209 patients. The weighted median follow-up was 12 months. The mean age was 73.4 years and men represented 45.6%. On pairwise meta-analysis, any AF screening (either systematic or opportunistic) was associated with higher AF detection (1.8% vs. 1.3%; risk ratio [RR] 2.10; 95% confidence interval [CI] 1.20-3.65) and initiation of oral anticoagulation (RR 3.26; 95%CI 1.15-9.23), compared with no screening. There was no significant difference between any AF screening versus no screening in all-cause mortality (RR 0.97; 95%CI 0.93-1.01) or acute cerebrovascular accident (CVA) (RR 0.92; 95%CI 0.84-1.01). On network meta-analysis, only systematic screening was associated with higher AF detection (RR 2.73; 95% CI 1.62-4.59) and initiation of oral anticoagulation (RR 5.67; 95% CI 2.68-11.99), but not with the opportunistic screening, compared with no screening. CONCLUSION: Systematic AF screening using non-invasive tools was associated with higher rate of new AF detection and initiation of OAC, but opportunistic screening was not associated with higher detection rates. There were no significant differences between the various AF screening approaches with respect to rates of all-cause mortality or CVA events. However, these analyses are likely underpowered and future RCTs are needed to examine the impact of systematic AF screening on mortality and CVA outcomes. PRIMARY FUNDING SOURCE: None.

DSPECT-specific normative limits for left ventricular size and function.

BACKGROUND: Differences in spatial resolution and image filtering between the solid-state DSPECT and traditional Anger SPECT (ASPECT) cameras are likely to result in differences in LV measurements. However, DSPECT-specific normal values are not available. The traditional approach of using patients deemed to have a low (< 5%) probability of coronary artery disease for the derivation of normative values has a number of limitations. We used healthy organ-donor subjects without known disease or medication use for derivation of normal values. METHODS: Subjects were 92 consecutive kidney or liver donors who underwent single-day rest (5 mCi)-stress (15 mCi) Tc-99m sestamibi-gated SPECT myocardial perfusion imaging (MPI) on the DSPECT camera for pre-operative evaluation and had normal perfusion and LV function. Exclusion criteria included any known cardiac disease or medications. LV measurements were made on the post-stress supine stress images using QGS®. RESULTS: Of 92 subjects (mean age 54.4 ± 15.0 and 39% men), mean EF ± 2SD for women and men was 77.2% ± 14.1% and 70.0 % ± 14.7%, respectively. Mean end-diastolic volume ± 2SD for women and men was 67.0 ± 32.2 mL and 99.6 ± 51.6 mL (indexed 38.3 ± 17.2 mL/m2 and 48.1 ± 25.9 mL/m2), respectively. Mean end-systolic volume ± 2SD for women and men was 16.1 ± 15.7 mL and 31.2 ± 29.2 mL (indexed 9.2 ± 8.8 mL/m2 and 15.0 ± 14.2 mL/m2), respectively. Mean LV wall volume ± 2SD for women and men was 95.9 ± 26.0 mL and 112.0 ± 48.8 mL (indexed 55.0 ± 13.8 mL/m2 and 54.1 ± 24.6 mL/m2), respectively. CONCLUSION: We report DSPECT-specific LV measurements from normal subjects from which limits of normality can be derived for clinic use. Organ donors who undergo pre-operative MPI are a suitable cohort for the derivation of normal values.

Efficacy and Safety of Catheter Ablation vs Antiarrhythmic Drugs as Initial Therapy for Management of Symptomatic Paroxysmal Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: Catheter ablation is an effective treatment for atrial fibrillation (AF), primarily performed in patients who fail antiarrhythmic drugs. Whether early catheter ablation, as first-line therapy, is associated with improved clinical outcomes remains unclear. METHODS: Electronic databases (PubMed, Scopus, Embase) were searched until March 28th, 2021. Randomized controlled trials (RCTs) compared catheter ablation vs antiarrhythmic drug therapy as first-line therapy were included. The primary outcome of interest was the first documented recurrence of any atrial tachyarrhythmia (symptomatic or asymptomatic; AF, atrial flutter, and atrial tachycardia). Secondary outcomes included symptomatic atrial tachyarrhythmia (AF, atrial flutter, and atrial tachycardia) and serious adverse events. Unadjusted risk ratios (RR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance considered if the confidence interval (CI) excludes one and p < 0.05. RESULTS: A total of six RCTs with 1212 patients (Ablation n = 609; Antiarrhythmic n = 603) were included. Follow- up period ranged from 1-2 years. Patients who underwent ablation were less likely to experience any recurrent atrial tachyarrhythmia when compared to patients receiving antiarrhythmic drugs (RR 0.63; 95% CI 0.55-0.73; p < 0.00001). Symptomatic atrial tachyarrhythmia was also lower in the ablation arm (RR 0.53; 95% CI 0.32-0.87; p = 0.01). No statistically significant differences were noted for overall any type of adverse events (RR 0.93; 95% CI 0.68-1.27; p = 0.64) and cardiovascular adverse events (RR 0.90; 95% CI 0.56-1.44; p = 0.65) respectively. CONCLUSIONS: Catheter ablation, as first-line therapy, was associated with a significantly lower rate of tachyarrhythmia recurrence compared to conventional antiarrhythmic drugs, with a similar adverse effect risk profile. These findings support a catheter ablation strategy as first-line therapy among patients with symptomatic paroxysmal atrial fibrillation.

A Validated Model to Identify Patients With Low Likelihood of High-Risk Coronary Artery Disease Anatomy.

In stable coronary artery disease (CAD), revascularization improves outcomes only for patients with high-risk coronary anatomy (HRCA). We sought to derive and validate a prediction model, incorporating clinical and exercise stress test characteristics, to identify patients with HRCA. We conducted a retrospective analysis of patients undergoing exercise stress testing at Cleveland Clinic (2005 to 2014), followed by invasive coronary angiography within 3 months. We excluded patients with acute coronary syndrome, known CAD or ejection fraction <50%. HRCA was defined as left main, 3-vessel, or 2-vessel disease involving the proximal left anterior descending artery. Clinical and stress test predictors of HRCA were identified in a multivariable logistic regression model, internally validated with 1,000-fold bootstrapping. The model was then externally validated at the University of Pittsburgh Medical Center (2017 to 2019). The model was derived from 2,758 patients with complete data. HRCA was identified in 418 patients (15.2%) in the derivation cohort. The model consisted of 10 variables: age, male gender, hypertension, hypercholesterolemia, diabetes mellitus, family history of premature CAD, high-density lipoprotein, chest pain, exercise time, and Duke Treadmill Score. Bias-corrected c-statistic was 0.79 (95% confidence interval 0.77 to 0.81) with excellent calibration. In all, 762 patients (27.6%) had a predicted probability and observed prevalence of HRCA <5%. In the validation cohort, the model had a c-statistic of 0.79 (95% confidence interval 0.74 to 0.85) and 210 patients had an observed prevalence of HRCA <5% (40%). In conclusion, an externally validated prediction model, based on clinical characteristics and exercise stress test variables, can identify stable patients with CAD who have HRCA.

In-hospital outcomes of transesophageal versus intracardiac echocardiography guided left atrial appendage closure.

BACKGROUND: Transesophageal echocardiogram (TEE) is the preferred imaging modality to guide transcatheter left atrial appendage closure (LAAC). Intracardiac echocardiography (ICE) has evolved as a less invasive alternative to TEE. Several observational studies have shown similar success rates and perioperative complications between TEE and ICE for LAAC. OBJECTIVES: We sought to examine the temporal trends and patient characteristics of TEE versus ICE use in LAAC using a national database. We also evaluated hospital outcomes including periprocedural complications, mortality, and length of hospital stay. METHODS: This is a retrospective analysis of data from the National Readmission Database, collected from 2016 to 2018. The primary outcome was major adverse events (MAE) defined as in-hospital mortality, cardiac arrest, pericardial effusion with or without tamponade, pericardiocentesis or window pericardiocentesis and pericardial window, pericardial effusion and tamponade, and hemorrhage requiring transfusion. RESULTS: Trend analysis showed that TEE-guided LAAC increased from 96.6% in 2016 to 98.4% in 2018 (relative increase, 1.9%), while ICE-guided LAAC decreased from 3.4% to 1.6% during the same period (relative decrease, 53%, p for trend = 0.08). In the unmatched cohorts, the MAE was significantly lower in TEE-guided LAAC compared to ICE-guided LAAC (6.5% vs. 9.3%, p = 0.022). In the propensity score matching analysis, MAE remained significant (5.6% vs. 9.4%, p < 0.001). The incidence of pericardial effusion with or without tamponade remained significantly lower in the TEE group (2.3% vs. 5.8%, p < 0.001). Length of stay (3.4 vs. 1.9 days, p < 0.001) and hospitalization cost ($34,826 vs. $20,563, p < 0.001) remained significantly lower for TEE-guided LAAC. CONCLUSIONS: Compared to ICE, the incidence of MAE was significantly lower for TEE-guided LAAC, driven mainly by less pericardial effusion events. Large-scale randomized trials are needed to confirm the findings of the current and previous studies.

Bayesian network meta-analysis comparing cryoablation, radiofrequency ablation, and antiarrhythmic drugs as initial therapies for atrial fibrillation.

BACKGROUND: Antiarrhythmic drugs (AADs) and catheter ablation are first line treatments of paroxysmal atrial fibrillation (PAF), however, there exists a paucity of data regarding the potential benefit of different catheter ablation technologies versus AADs as an early rhythm strategy. OBJECTIVE: To assess the safety and efficacy of cryoablation versus radiofrequency ablation (RFA) versus AADs as a first line therapy of PAF. METHODS: MEDLINE, Embase, Scopus and CENTRAL were searched to retrieve randomized clinical trials (RCTs) comparing cryoablation, RFA or AADs to one another as first line therapies for atrial fibrillation (AF). The primary outcome was overall freedom from arrhythmia recurrence (AF, atrial flutter [AFL], atrial tachycardia). Secondary outcomes included freedom from symptomatic arrhythmia recurrence, hospitalization, and serious adverse events. A random-effects Bayesian network meta-analysis was used to calculate odds ratios (OR) and 95% credible intervals (CrI). RESULTS: Six RCTs (N = 1212) met the inclusion criteria (605 AADs, 365 Cryoablation, and 245 RFA). Compared with AADs, overall recurrence was reduced with RFA (OR: 0.31; 95% CrI: 0.10-0.71) and cryoablation (OR: 0.39; 95% CrI: 0.16-1.00). Comparing ablation (cryoablation and RFA) with AADs in respect to freedom from symptomatic AF recurrence, neither cryoablation (OR: 0.35; 95% CrI: 0.06-1.96) nor RFA (OR: 0.34; 95% CrI: 0.07-1.27) resulted in statistically significant reductions individually compared to AADs, though pooled ablation with both technologies showed lower odds of arrhythmia recurrence (OR: 0.35; 95% CrI: 0.13-0.79). In terms of serious adverse events rates, neither cryoablation (OR: 0.77; 95% CrI: 0.44-1.39) nor RFA (OR: 1.45; 95% CrI: 0.67-3.23) were significantly different to AADs. RFA resulted in a statistically significant reduction in hospitalizations compared to AAD (OR: 0.08; 95% CrI: 0.01-0.99), whereas cryoablation did not (OR: 0.77; 95% CrI: 0.44-1.39). The surface under the cumulative ranking curve showed RFA to be the most effective treatment at reducing overall rates of recurrence, symptomatic recurrence and hospitalizations; whereas cryoablation was most likely to reduce serious adverse events. CONCLUSION: Cryoablation and RFA are both effective and safe first line therapies for AF compared to AADs, with RFA being the most effective at reducing recurrences.

Venous thromboembolism during pregnancy and postpartum period.

Venous thromboembolism (VTE) is one of the leading causes of maternal mortality. Rates of VTE during pregnancy and the postpartum period have not decreased over the past two decades and pregnancyassociated VTE continues to pose a significant health challenge. Pregnant and postpartum women are at a higher risk for VTE owing to many factors. There are hormonally mediated and pregnancy-specific alterations of coagulation that favor thrombosis, including increased production of clotting factors. There are physiologic and anatomic mechanisms that also contribute, including a decreased rate of venous blood flow from the lower extemities as pregnancy progresses. Cesarean delivery also introduces VTE risk. In addition, studies have demonstrated that pregnancy-associated complications such as pre-eclampsia or peri-partum infections are associated with increased VTE rates. In this review, we discuss the recent epidemiological studies, pathogenesis, risk factors and clinical presentation as well as therapeutic options for VTE during pregnancy and the postpartum period. We also provide proposed diagnostic algorithms for diagnosis and management of VTE during pregnancy and the postpartum period based on updated evidence. Finally, we highlight knowledge gaps to guide future research.

Methodological Rigor and Temporal Trends of Cardiovascular Medicine Meta-Analyses in Highest-Impact Journals.

Background Well-conducted meta-analyses are considered to be at the top of the evidence-based hierarchy pyramid, with an expansion of these publications within the cardiovascular research arena. There are limited data evaluating the trends and quality of such publications. The objective of this study was to evaluate the methodological rigor and temporal trends of cardiovascular medicine-related meta-analyses published in the highest impact journals. Methods and Results Using the Medline database, we retrieved cardiovascular medicine-related systematic reviews and meta-analyses published in The New England Journal of Medicine, The Lancet, Journal of the American Medical Association, The British Medical Journal, Annals of Internal Medicine, Circulation, European Heart Journal, and Journal of American College of Cardiology between January 1, 2012 and December 31, 2018. Among 6406 original investigations published during the study period, meta-analyses represented 422 (6.6%) articles, with an annual decline in the proportion of published meta-analyses (8.7% in 2012 versus 4.6% in 2018, Ptrend=0.002). A substantial number of studies failed to incorporate elements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses or Meta-Analysis of Observational Studies in Epidemiology guidelines (51.9%) and only a minority of studies (10.4%) were registered in PROSPERO (International Prospective Register of Systematic Reviews). Fewer manuscripts failed to incorporate the Preferred Reporting Items for Systematic Reviews and Meta-Analyses or Meta-Analysis of Observational Studies in Epidemiology elements over time (60.2% in 2012 versus 40.0% in 2018, Ptrend<0.001) whereas the number of meta-analyses registered at PROSPERO has increased (2.4% in 2013 versus 17.5% in 2018, Ptrend<0.001). Conclusions The proportion of cardiovascular medicine-related meta-analyses published in the highest impact journals has declined over time. Although there is an increasing trend in compliance with quality-based guidelines, the overall compliance remains low.

A 25-Year-Old Man with Refractory Schizophrenia and Clozapine-Induced Myocarditis Diagnosed by Non-Invasive Cardiovascular Magnetic Resonance.

BACKGROUND Clozapine, a second-generation antipsychotic, is often prescribed for refractory schizophrenia; however, it can cause life-threatening adverse events including agranulocytosis and myocarditis. Making the diagnosis of clozapine-induced myocarditis can be challenging given the non-specific presentation as well as risk involved in obtaining an endomyocardial biopsy. As clozapine-induced myocarditis carries a mortality risk of up to 30%, timely recognition, diagnosis, and management are vital. This report presents a case of clozapine-induced myocarditis in a 25-year-old man with refractory schizophrenia who was diagnosed using non-invasive imaging with cardiovascular magnetic resonance (CMR). CASE REPORT A 25-year-old man with refractory schizophrenia was admitted with severe psychotic symptoms and started on a rapid titration of clozapine. During his hospitalization he developed somnolence, fever, and tachycardia with leukocytosis, elevated inflammatory markers, and cardiac biomarkers concerning for clozapine-induced myocarditis. Alternative etiologies were ruled out and CMR was used to confirm the diagnosis. The patient's symptoms resolved following discontinuation of clozapine and initiation of supportive therapies. CONCLUSIONS Clozapine-induced myocarditis is challenging to diagnose due to a lack of consensus on diagnostic criteria, reliance on voluntary reporting, and non-specific presentation. This report highlights that myocarditis can be associated with clozapine pharmacotherapy in patients with schizophrenia and demonstrates the value of diagnosis using non-invasive CMR. Additional studies are needed to understand the mechanism of clozapine-induced myocarditis and how clozapine titration may affect risk.

Outcomes of Direct Oral Anticoagulants in Atrial Fibrillation Patients Across Different Body Mass Index Categories.

OBJECTIVES: This study sought to evaluate direct oral anticoagulant (DOAC) outcomes (vs. warfarin) in patients with atrial fibrillation (AF) across body mass index (BMI) categories, including ≥40 and <18.5 kg/m2. BACKGROUND: Clinical trials have not systematically tested the fixed DOAC dosing in underweight and morbidly obese patients. METHODS: We retrospectively included consecutive patients with nonvalvular AF with CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke/transient ischemic attack/systemic thromboembolism, Vascular disease, Age 65-74, Sex) of ≥1 receiving OACs at our hospital system (2010-2018). Patients were categorized into groups 1 (underweight: BMI of <18.5 kg/m2), 2 (normal/overweight: BMI of 18.5 to <30 kg/m2), 3 (grade 1/2 obesity: BMI of 30 to <40 kg/m2), and 4 (grade 3 obesity: BMI of ≥40 kg/m2). We further classified patients by DOAC versus warfarin use. Outcomes were ischemic stroke, significant bleeding events (i.e., resulting in hospitalization), and mortality. RESULTS: We included 36,094 patients with a mean age of 74 ± 11 years and CHA2DS2-VASc of 3.4 ± 1.5. Groups 1 through 4 included 455 (1.3%), 18,339 (50.8%), 13,376 (37.1%), and 3,924 (10.9%) patients, respectively. DOAC use ranged from 49% to 56%. At 3.8 follow-up years, with multivariable Cox regression, DOACs (vs. warfarin) were associated with lower risk of ischemic stroke, bleeding, and mortality across all BMI groups, with hazard ratios (HRs) of 0.73 (95% confidence interval [CI]: 0.63 to 0.85), 0.75 (95% CI: 0.64 to 0.87), 0.75 (95% CI: 0.65 to 0.88), and 0.75 (95% CI: 0.64 to 0.87) (p < 0.001 for all) for ischemic stroke; 0.42 (95% CI: 0.19 to 0.92), 0.41 (95% CI: 0.19 to 0.89), 0.45 (95% CI: 0.20 to 1.00), and 0.43 (95% CI: 0.20 to 0.94) (p < 0.05 for all) for bleeding; and 0.90 (95% CI: 0.68 to 1.19; p = 0.5), 0.70 (95% CI: 0.66 to 0.75; p < 0.0001), 0.65 (95% CI: 0.60 to 0.71; p < 0.0001), and 0.66 (95% CI: 0.56 to 0.77; p < 0.0001) for mortality, in groups 1 to 4, respectively. CONCLUSIONS: In patients with nonvalvular AF, DOACs compared to warfarin were associated with better safety and effectiveness across all BMI categories, including underweight and morbidly obese patients.

Maternal Stroke: A Call for Action.

Maternal mortality rates have been steadily increasing in the United States, and cardiovascular mortality is the leading cause of death among pregnant and postpartum women. Maternal stroke accounts for a significant burden of cardiovascular mortality. Data suggest that rates of maternal stroke have been increasing in recent years. Advancing maternal age at the time of birth and the increasing prevalence of traditional cardiovascular risk factors, and other risk factors, as well, such as hypertensive disorders of pregnancy, migraine, and infections, may contribute to increased rates of maternal stroke. In this article, we provide an overview of the epidemiology of maternal stroke, explore mechanisms that may explain increasing rates of stroke among pregnant women, and identify key knowledge gaps for future investigation in this area.

Coronary artery calcium score and risk of cardiovascular events without established coronary artery disease: a systemic review and meta-analysis.

BACKGROUND: Coronary artery calcium (CAC) is an indicator of atherosclerosis, and the CAC score is a useful noninvasive assessment of coronary artery disease. OBJECTIVE: To compare the risk of cardiovascular outcomes in patients with CAC > 0 versus CAC = 0 in asymptomatic and symptomatic population in patients without an established diagnosis of coronary artery disease. METHODS: A systematic search of electronic databases was conducted until January 2018 for any cohort study reporting cardiovascular events in patients with CAC > 0 compared with absence of CAC. RESULTS: Forty-five studies were included with 192 080 asymptomatic 32 477 symptomatic patients. At mean follow-up of 11 years, CAC > 0 was associated with an increased risk of major adverse cardiovascular and cerebrovascular events (MACE) compared to a CAC = 0 in asymptomatic arm [pooled risk ratio (RR) 4.05, 95% confidence interval (CI) 2.91-5.63, P < 0.00001, I2 = 80%] and symptomatic arm (pooled RR 6.06, 95% CI 4.23-8.68, P < 0.00001, I2 = 69%). CAC > 0 was also associated with increased risk of all-cause mortality in symptomatic population (pooled RR 7.94, 95% CI 2.61-24.17, P < 0.00001, I2 = 85%) and in asymptomatic population CAC > 0 was associated with higher all-cause mortality (pooled RR 3.23, 95% CI 2.12-4.93, P < 0.00001, I2 = 94%). In symptomatic population, revascularization in CAC > 0 was higher (pooled RR 15, 95% CI 6.66-33.80, P < 0.00001, I2 = 72) compared with CAC = 0. Additionally, CAC > 0 was associated with more revascularization in asymptomatic population (pooled RR 5.34, 95% CI 2.06-13.85, P = 0.0006, I2 = 93). In subgroup analysis of asymptomatic population by gender, CAC > 0 was associated with higher MACE (RR 6.39, 95% CI 3.39-12.84, P < 0.00001). CONCLUSION: Absence of CAC is associated with low risk of cardiovascular events compared with any CAC > 0 in both asymptomatic and symptomatic population without coronary artery disease.