Antiarrhythmic effects of metformin.

Atrial fibrillation/flutter (AF) is a major public health problem and is associated with stroke, heart failure, dementia, and death. It is estimated that 20%-30% of Americans will develop AF at some point in their life. Current medications to prevent AF have limited efficacy and significant adverse effects. Newer and safer therapies to prevent AF are needed. Ventricular arrhythmias are less prevalent than AF but may have significant consequences including sudden cardiac death. Metformin is the most prescribed, first-line medication for treatment of diabetes mellitus (DM). It decreases hepatic glucose production but also reduces inflammation and oxidative stress. Experimental studies have shown that metformin improves metabolic, electrical, and histologic risk factors associated with AF and ventricular arrhythmias. Furthermore, in large clinical observational studies, metformin has been associated with a reduced risk of AF in people with DM. These data suggest that metformin may have antiarrhythmic properties and may be a candidate to be repurposed as a medication to prevent cardiac arrhythmias. In this article, we review the clinical observational and experimental evidence for the association between metformin and cardiac arrhythmias. We also discuss the potential antiarrhythmic mechanisms underlying this association. Repurposing a well-tolerated, safe, and inexpensive medication to prevent cardiac arrhythmias has significant positive public health implications.

Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The ARIC Study.

BACKGROUND: Sudden cardiac death (SCD) is a significant global public health problem accounting for 15% to 20% of all deaths. A great majority of SCD is associated with coronary heart disease, which may first be detected at autopsy. The ankle-brachial index (ABI) is a simple, noninvasive measure of subclinical atherosclerosis. The purpose of this study was to examine the relationship between ABI and SCD in a middle-aged biracial general population. METHODS AND RESULTS: Participants of the ARIC (Atherosclerosis Risk in Communities) study with an ABI measurement between 1987 and 1989 were included. ABI was categorized as low (≤0.90), borderline (0.90-1.00), normal (1.00-1.40), and noncompressible (>1.40). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual and was adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Cox proportional hazards models were used to evaluate the associations between baseline ABI and incident SCD. Of the 15 081 participants followed for a median of 23.5 years, 556 (3.7%) developed SCD (1.96 cases per 1000 person-years). Low and borderline ABIs were associated with an increased risk of SCD (demographically adjusted hazard ratios [HRs], 2.27 [95% CI, 1.64-3.14] and 1.52 [95% CI, 1.17-1.96], respectively) compared with normal ABI. The association between low ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors (HR, 1.63 [95% CI, 1.15-2.32]). CONCLUSIONS: Low ABI is independently associated with an increased risk of SCD in a middle-aged biracial general population. ABI could be incorporated into future SCD risk prediction models.

Temporary-permanent pacemakers are associated with better clinical and safety outcomes compared to balloon-tipped temporary pacemakers.

BACKGROUND: Balloon Tipped Temporary Pacemakers (BTTP) are the most used temporary pacemakers; however, they are associated with a risk of dislodgement and thromboembolism. Recently, Temporary Permanent Pacemakers (TPPM) have been increasingly used. Evidence of outcomes with TPPM compared to BTTP remains scarce. METHODS: Retrospective, chart review study evaluating all patients who underwent temporary pacemaker placement between 2014 and 2022 (N = 126) in the cardiac catheterization laboratory (CCL) at a level 1 trauma center. Primary outcome of this study is to evaluate the safety profile of TPPM versus BTTP. Secondary objectives include patient ambulation and healthcare utilization in patients with temporary pacemakers. RESULTS: Both groups had similar baseline characteristics distribution including gender, race, and age at temporary pacemaker insertion (p > .05). Subclavian vein was the most common site of access for the TPPM cohort (89.0%) versus the femoral vein in the BTTP group (65.1%). Ambulation was only possible in the TPPM group (55.6%, p < .001). Lead dislodgement, venous thromboembolism, local hematoma, and access site infections were less frequently encountered in the TPPM group (OR = 0.23 [95% CI (0.10-0.67), p < .001]). Within the subgroup of patients with TPPM, 36.6% of the patients were monitored outside the ICU setting. There was no significant difference in the pacemaker-related adverse events among patients with TPPM based on their in-hospital setting. CONCLUSION: TPPM is associated with a more favorable safety profile compared to BTTP. They are also associated with earlier patient ambulation and reduced healthcare utilization.

QT prolongation predicts all-cause mortality above and beyond a validated risk score.

INTRODUCTION: QT prolongation is a risk factor for life-threatening arrhythmias and sudden cardiac death. In large cohorts, QT interval was associated with all-cause mortality, but these analyses may contain residual confounding. Whether the QT interval provides prognostic information above and beyond a validated mortality risk score is unknown. We hypothesized that QT interval on ECG will independently predict mortality after adjustment for the Care Assessment Needs (CAN) score, which was validated to predict mortality nationwide at the Veterans Administration (VA) (c-index 0.86). METHODS: Outpatients with an ECG at the Minneapolis VA from 2012 to 2016 were included in this retrospective cohort study. ECGs with ventricular rate < 50 or > 100 beats/min and those with QRS > 120 ms were excluded. QT intervals were corrected (QTc) using the Bazett's formula. CAN score, calculated within 1-week of the ECG, was obtained from the VA Corporate Data Warehouse. RESULTS: Of the 31,201 patients, 427 (1.4%) had QTc ≥ 500 ms, 1799 (5.8%) had QTc 470-500 ms and 28,975 (92.9%) had QTc < 470 ms. Compared to those with QTc < 470 ms, CAN-adjusted odds ratios (OR) for 1-year mortality (1.76 for QTc 470-500 and 2.70 for QTc > 500 ms; p < 0.0001 for both) and for 5-year mortality (1.75 for QTc 470-500 and 2.48 for QTc > 500 ms; p < 0.0001 for both) were significantly higher in those with longer QTc. C-index for CAN score and QTc predicting 1-year mortality was 0.837. CONCLUSIONS: QT prolongation predicts all-cause mortality independently of a validated mortality risk prediction score.

Cardiovascular disease burden in the Middle East and North Africa region.

INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death globally, including the Middle East and North Africa (MENA) region. However, limited research has been conducted on the burden of CVD in this region. Our study aims to investigate the burden of CVD and related risk factors in the MENA. METHODS: We used data from the Global Burden of Disease (GBD) 2019 to examine CVD prevalence in 21 MENA countries. Prevalence and mortality were analyzed using Bayesian regression tools, demographic methods, and mortality-to-incidence ratios. Disability-adjusted life years (DALYs) were calculated, and risk factors were evaluated under the GBD's comparative risk assessment framework. RESULTS: Between 1990 and 2019, CVD raw accounts in the MENA increased by 140.9%, while age standardized prevalence slightly decreased (-1.3%). CVD raw mortality counts rose by 78.3%, but age standardized death rates fell by 28%. Ischemic heart disease remained the most prevalent condition, with higher rates in men, while women had higher rates of CVA. Age standardized DALYs decreased by 32.54%. DALY rates varied across countries and were consistently higher in males. Leading risk factors included hypertension, high LDL-C, dietary risks, and elevated BMI.  The countries with the three highest DALYs in 2019 were Afghanistan, Egypt, and Yemen. CONCLUSIONS: While strides have been made in lessening the CVD burden in the MENA region, the toll on mortality and morbidity, particularly from ischemic heart disease, remains significant. Country-specific variations call for tailored interventions addressing socio-economic factors, healthcare infrastructure, and political stability.

Cardiovascular Autonomic Function and Incident Chronic Obstructive Pulmonary Disease Hospitalizations in Atherosclerosis Risk in Communities.

Rationale: The autonomic nervous system extensively innervates the lungs, but its role in chronic obstructive pulmonary disease (COPD) outcomes has not been well studied. Objective: We assessed relationships between cardiovascular autonomic nervous system measures (heart rate variability [HRV] and orthostatic hypotension [OH]) and incident COPD hospitalization in the multicenter ARIC (Atherosclerosis Risk In Communities) study. Methods: We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals between baseline (1987-1989) autonomic function measures (HRV measures from 2-minute electrocardiograms and OH variables) and incident COPD hospitalizations through 2019. Adjusted analyses included demographic data, smoking status, lung function, comorbidities, and physical activity. We also performed analyses stratified by baseline airflow obstruction. Results: Of the 11,625 participants, (mean age, 53.8 yr), 56.5% were female and 26.3% identified as Black. Baseline mean percentage predicted forced expiratory volume in 1 second was 94 ± 17% (standard deviation), and 2,599 participants (22.4%) had airflow obstruction. During a median follow-up time of 26.9 years, there were 2,406 incident COPD hospitalizations. Higher HRV (i.e., better autonomic function) was associated with a lower risk of incident COPD hospitalization. Markers of worse autonomic function (OH and greater orthostatic changes in systolic and diastolic blood pressure) were associated with a higher risk of incident COPD hospitalization (hazard ratio for the presence of OH, 1.5; 95% confidence interval, 1.25-1.92). In stratified analyses, results were more robust in participants without airflow obstruction at baseline. Conclusions: In this large multicenter prospective community cohort, better cardiovascular autonomic function at baseline was associated with a lower risk of subsequent hospitalization for COPD, particularly among participants without evidence of lung disease at baseline.

Mortality associated with antiarrhythmic medication for atrial fibrillation among patients with left ventricular hypertrophy.

BACKGROUND: Atrial fibrillation (AF) guidelines recommend amiodarone as the preferred antiarrhythmic medication (AAM) in patients with left ventricular hypertrophy (LVH), due to potential pro-arrhythmic risk with other AAM. However, there are limited data to support this assertion. METHODS: We retrospectively analyzed the records of 8204 patients who were prescribed AAM for AF and had transthoracic echocardiogram (TTE) at the multicenter, VA Midwest Health Care Network from 2000 to 2021. We excluded patients without LVH (septal or posterior wall dimension ≤1.4 cm). The primary outcome variable was all-cause mortality during antiarrhythmic therapy or within 6 months after stopping it. Propensity-stratified analyses were performed between amiodarone versus non-amiodarone (Vaughan-Williams Class I and III) AAM. RESULTS: A total of 1277 patients with LVH (mean age 70.2 ± 9.5 years) were included in the analysis. Of these, 774 (60.6%) were prescribed amiodarone. Baseline characteristics of the two comparison groups were similar after propensity adjustment. After a median 1.40 years of follow-up, 203 (15.9%) patients died. Incidence rates per 100 patient-year follow-up was 9.02 (7.58-10.66) for amiodarone and 4.98 (3.91-62.56) for non-amiodarone. In propensity-stratified analysis, amiodarone use was associated with 1.58 times higher risk of mortality (95% CI 1.03-2.44; p = .038). Sub-group analysis in 336 (26.3%) patients with severe LVH showed no difference in mortality (HR 1.41, 95% CI 0.82-2.43, p = .21). CONCLUSION: Among patients with AF and LVH, amiodarone was associated with a significantly higher mortality risk than other AAM.

Academic cardiac electrophysiologists' perspectives on sleep apnea care.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an important, modifiable risk factor in the pathophysiology of arrhythmias including atrial fibrillation (AF). The purpose of the study was to evaluate cardiac electrophysiologists' (EPs) perception of OSAS. METHODS: We designed a 27-item online Likert scale-based survey instrument entailing several domains: (1) relevance of OSAS in EP practice, (2) OSAS screening and diagnosis, (3) perception on treatments for OSAS, (4) opinion on the OSAS care model. The survey was distributed to 89 academic EP programs in the USA and Canada. While the survey instrument questions refer to the term sleep apnea (SA), our discussion of the diagnosis, management, and research on the sleep disorder is more accurately described with the term OSAS. RESULTS: A total of 105 cardiac electrophysiologists from 49 institutions responded over a 9-month period. The majority of respondents agreed that sleep apnea (SA) is a major concern in their practice (94%). However, 42% reported insufficient education on SA during training. Many (58%) agreed that they would be comfortable managing SA themselves with proper training and education and 66% agreed cardiac electrophysiologists should become more involved in management. Half of EPs (53%) were not satisfied with the sleep specialist referral process. Additionally, a majority (86%) agreed that trained advanced practice providers should be able to assess and manage SA. Time constraints, lack of knowledge, and the referral process are identified as major barriers to EPs becoming more involved in SA care. CONCLUSIONS: We found that OSAS is widely recognized as a major concern for EP. However, incorporation of OSAS care in training and routine practice lags. Barriers to increased involvement include time constraints and education. This study can serve as an impetus for innovation in the cardiology OSAS care model.

Perioperative changes in left ventricular systolic function following surgical revascularization.

BACKGROUND: Nearly 1/3rd of patients undergoing coronary artery bypass graft surgery (CABG) have left ventricular systolic dysfunction. However, the extent, direction and implications of perioperative changes in left ventricular ejection fraction (LVEF) have not been well characterized in these patients. METHODS: We studied the changes in LVEF among 549 patients with left ventricular systolic dysfunction (LVEF <50%) who underwent CABG as part of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Patients had pre- and post-CABG (4 month) LVEF assessments using identical cardiac imaging modality, interpreted at a core laboratory. An absolute change of >10% in LVEF was considered clinically significant. RESULTS: Of the 549 patients (mean age 61.4±9.55 years, and 72 [13.1%] women), 145 (26.4%) had a >10% improvement in LVEF, 369 (67.2%) had no change and 35 (6.4%) had >10% worsening of LVEF following CABG. Patients with lower preoperative LVEF were more likely to experience an improvement after CABG (odds ratio 1.36; 95% CI 1.21-1.53; per 5% lower preoperative LVEF; p <0.001). Notably, incidence of postoperative improvement in LVEF was not influenced by presence, nor absence, of myocardial viability (25.5% vs. 28.3% respectively, p = 0.67). After adjusting for age, sex, baseline LVEF, and NYHA Class, a >10% improvement in LVEF after CABG was associated with a 57% lower risk of all-cause mortality (HR: 0.43, 95% CI: 0.26-0.71). CONCLUSIONS: Among patients with ischemic cardiomyopathy undergoing CABG, 26.4% had >10% improvement in LVEF. An improvement in LVEF was more likely in patients with lower preoperative LVEF and was associated with improved long-term survival.

Mortality and readmission risk in relation to QRS duration among patients hospitalized for heart failure with preserved ejection fraction.

BACKGROUND: In ambulatory patients with heart failure (HF) with preserved ejection fraction (HFpEF), QRS prolongation (QRS > 120 msec) and left bundle branch block (LBBB) each carry an increased risk of cardiovascular mortality and/or HF hospitalization. Less is known about implications of conduction abnormalities following an acute HF hospitalization for HFpEF. METHODS AND RESULTS: A retrospective cohort of 1454 patients discharged from after a HF hospitalization between 2015 and 2019 with ejection fraction (EF) ≥ 45% were identified (age 75.1 ± 10.8 years, EF 58.5% ± 10.2%). All patients' electrocardiograms were classified by QRS duration (prolonged - 545 [37.5%] vs. normal [QRS ≤ 120 msec] 909 [62.5%]). QRS prolongation was comprised of: LBBB (4.2%), right bundle branch block (RBBB, 18.3%), intraventricular conduction delay (9.7%), and ventricularly paced (9.7%). Over 4.09 ± 1.00 years, 769 (52.9%) patients died. Survival was similar between normal and prolonged QRS cohorts with an age and sex adjusted hazard ratio of 1.01 (95%CI: 0.87-1.17, p = 0.16). Recurrent HF hospitalization occurred in 91 (16.7%) with QRS prolongation vs. 90 (9.9%) without (odds ratio: 1.82 [95%CI: 1.33-2.50, p < 0.001]). RBBB carried 2.26 higher odds of recurrent HF hospitalization (95%CI: 1.56-3.28). CONCLUSIONS: Following a HF hospitalization, QRS prolongation increased the odds of re-admission for HF in patients with HFpEF without differences in overall mortality.

Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial.

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD. Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment. Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group. Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.

Improvement of left ventricular function with surgical revascularization in patients eligible for implantable cardioverter-defibrillator.

INTRODUCTION: Left ventricular ejection fraction (EF) ≤ 35% is the cornerstone criterion for implantable cardioverter-defibrillator (ICD) eligibility. Improvement in EF may occur in ICD-eligible patients after coronary artery bypass graft surgery (CABG). However, the incidence, predictors, and outcomes of this process are unclear. METHODS AND RESULTS: We studied 427 patients with EF ≤ 35% who underwent CABG in the Surgical Treatment for Ischemic Heart Failure (STICH) trial and had a systematic pre- and postoperative (4 months) EF assessment using the identical cardiac imaging modality. All imaging studies were interpreted at a core laboratory. Improvement in EF was defined as postoperative EF > 35% and >5% absolute improvement from baseline. Of the 427 patients (mean age 61.8 ± 9.5 and 50 women), 125 (29.2%) had EF improvement. Their mean EF increased from 26.8% (±5.8%) to 43.3% (±6.5%) (p < .0001). EF improvement occurred in only 20% of patients with a preoperative EF < 25%. The odds of EF improvement were 1.96 times higher (95% confidence interval [CI]: 0.91-4.23, p = .09) in patients with myocardial viability. In adjusted analyses, EF improvement was associated with a significantly lower risk of all-cause mortality (hazard ratio [HR]: 0.58, 95% CI: 0.35-0.96; p = .03) and heart failure mortality (HR: 0.31, 95% CI: 0.11-0.87; p = .027). CONCLUSION: Nearly 1/3rd of ICD-eligible patients undergoing CABG had significant improvement in EF, obviating the need for primary prevention ICD implantation. These results provide patients and clinicians data on the likelihood of ICD eligibility after CABG and support the practice of reassessment of EF after revascularization.

Predictors of Sudden Cardiac Arrest Among Patients With Post-Myocardial Infarction Ejection Fraction Greater Than 35.

Background Sudden cardiac arrest (SCA) risk increases after myocardial infarction (MI) in patients with a reduced ejection fraction (EF). However, the risk factors for SCA among patients with a post-MI EF >35% remain poorly understood. Methods and Results Using the Optum de-identified electronic health record data set from 2008 to 2017, we identified patients with an incident MI diagnosis and troponin elevation who had a post-MI EF >35% and underwent coronary angiography. Primary outcome was SCA within 1 year post-MI. The database was divided into derivation (70%) and validation (30%) cohorts by random selection. Cox proportional hazard regression was used to generate and validate a risk prediction model. Among 31 286 patients with an MI (median age 64.1; 39% female; 87% White), 499 experienced SCA within 1 year post-MI (estimated probability 1.8%). Lack of revascularization at MI, post-MI EF <50%, Black race, renal failure, chronic obstructive pulmonary disease, antiarrhythmic therapy, and absence of beta blocker therapy were independent predictors of SCA. A multivariable model consisting of these variables predicted SCA risk (C-statistic 0.73). Based on this model, the estimated annual probability of SCA was 4.4% (95% CI, 3.9-4.9) in the highest quartile of risk versus 0.6% (95% CI, 0.4-0.8) in the lowest quartile. Conclusions Patients with a post-MI EF >35% have a substantial annual risk of SCA. A risk model consisting of acute coronary revascularization, EF, race, renal failure, chronic obstructive pulmonary disease, antiarrhythmic therapy, and beta blocker therapy can identify patients with higher risk of SCA, who may benefit from further risk stratification and closer monitoring.

Implantable Cardioverter-Defibrillator Shocks During COVID-19 Outbreak.

Background COVID-19 was temporally associated with an increase in out-of-hospital cardiac arrests, but the underlying mechanisms are unclear. We sought to determine if patients with implantable defibrillators residing in areas with high COVID-19 activity experienced an increase in defibrillator shocks during the COVID-19 outbreak. Methods and Results Using the Medtronic (Mounds View, MN) Carelink database from 2019 and 2020, we retrospectively determined the incidence of implantable defibrillator shock episodes among patients residing in New York City, New Orleans, LA, and Boston, MA. A total of 14 665 patients with a Medtronic implantable defibrillator (age, 66±13 years; and 72% men) were included in the analysis. Comparing analysis time periods coinciding with the COVID-19 outbreak in 2020 with the same periods in 2019, we observed a larger mean rate of defibrillator shock episodes per 1000 patients in New York City (17.8 versus 11.7, respectively), New Orleans (26.4 versus 13.5, respectively), and Boston (30.9 versus 20.6, respectively) during the COVID-19 surge. Age- and sex-adjusted hurdle model showed that the Poisson distribution rate of defibrillator shocks for patients with ≥1 shock was 3.11 times larger (95% CI, 1.08-8.99; P=0.036) in New York City, 3.74 times larger (95% CI, 0.88-15.89; P=0.074) in New Orleans, and 1.97 times larger (95% CI, 0.69-5.61; P=0.202) in Boston in 2020 versus 2019. However, the binomial odds of any given patient having a shock episode was not different in 2020 versus 2019. Conclusions Defibrillator shock episodes increased during the higher COVID-19 activity in New York City, New Orleans, and Boston. These observations may provide insights into COVID-19-related increase in cardiac arrests.