Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis.

BACKGROUND: Aspirin has long had a role in the primary prevention of atherosclerotic cardiovascular disease (ASCVD); however, recent randomized controlled trials (RCTs) have challenged this practice. Despite this, aspirin is still commonly recommended for high-risk primary prevention. We tested the hypothesis that aspirin is more efficacious for the primary prevention of ASCVD as the baseline risk increases. METHODS: RCTs that compared aspirin with control for primary prevention and evaluated ASCVD (composite of myocardial infarction and ischemic stroke) and major bleeding were included. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. A regression analysis was performed using the ASCVD event rate in the control arm of each RCT as the moderator. RESULTS: Twelve RCTs were identified with 963,829 patient-years of follow-up. Aspirin was associated with a reduction in ASCVD (4.7 vs 5.3 events per 1000 patient-years; RR 0.86; 95% CI, 0.79-0.92). There was increased major bleeding among aspirin users (2.5 vs 1.8 events per 1000 patient-years; RR 1.41; 95% CI, 1.29-1.54). Regression analysis found no relationship between the log RR of ASCVD or major bleeding and rate of ASCVD in the control arm of each RCT. CONCLUSION: Aspirin is associated with a reduction in ASCVD when used for primary prevention; however, it is unlikely to be clinically significant given the increase in bleeding. More importantly, aspirin's treatment effect does not increase as ASCVD risk increases, as many hypothesize. There is no suggestion from these data that use of aspirin for higher-risk primary prevention patients is beneficial.

Vitamin D supplementation, cardiac events and stroke: A systematic review and meta-regression analysis.

INTRODUCTION: Observational data has suggested a link between vitamin D deficiency and coronary heart disease (CHD). However, randomized controlled trials (RCTs) have failed to show benefit. The objective of this study is to analyze the RCTs investigating vitamin D supplementation and the risk of CHD and stroke. METHODS: All RCTs that compared vitamin D supplementation to placebo and evaluated nonfatal myocardial infarction (MI), cardiac mortality, stroke and CHD events (a composite of cardiac mortality, MI, unstable angina and revascularization) were included. Rate ratios (RR) were calculated for each endpoint and to test for heterogeneity of treatment effect (HTE) the Chi2 and I2 tests were used for younger vs. older participants, shorter vs. longer trial duration, vitamin D supplements with vs. without calcium, and daily vs. monthly dosages of vitamin D. A meta-regression was performed with baseline vitamin D concentration as the covariate. RESULTS: 22 RCTs were identified (n = 83,200). Vitamin D supplementation had no effect on nonfatal MI (RR 0.98, 95% confidence interval (CI) 0.89-1.08), cardiac death (RR 0.94, CI 0.84-1.06), CHD events (RR 1.00, CI 0.91-1.10), or stroke (RR, 0.97, CI 0.9-1.03). When performing the meta-regression with baseline circulating 25-hydroxyvitamin D (25(OH)D) concentrations as the covariate, vitamin D supplementation's treatment effect on CVD outcomes was not associated with baseline 25(OH)D. CONCLUSION: Vitamin D did not reduce CHD and stroke. A linear relationship does not exist between baseline 25(OH)D and vitamin D supplementation's effect on CVD. Vitamin D levels should be checked and repleted in those with an absolute indication.

Dataset for amiodarone adverse events compared to placebo using data from randomized controlled trials.

The dataset presented here provides a detailed description of the adverse events of amiodarone versus placebo using data from 43 randomized controlled trials. Two authors (M.M., M.R.) independently extracted the data. The dataset also includes baseline patient characteristics, amiodarone loading and maintenance doses, as well as forest plots describing the relative risk (RR) of developing an adverse event related to the pulmonary, thyroid, hepatic, cardiac, skin, gastrointestinal, neurological, and ocular systems. The Mantel-Haenszel random effects model was used to determine the relative risk of adverse events of amiodarone compared to placebo. This dataset is complementary to our article "Meta-analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo", which was published in the American Journal of Cardiology [1]. The data can be used to assess certain adverse events and their relation to amiodarone loading and/or maintenance dose.

Meta-Analysis of Atrial Fibrillation Ablation in Patients with Systolic Heart Failure.

Atrial fibrillation (AF) and heart failure (HF) are two common conditions that often coexist and predispose each to one another. AF increases hospitalization rates and overall mortality in patients with HF. The current available therapeutic options for AF in patients with HF are diverse and guidelines do not provide a clear consensus regarding the best management approach. To determine if catheter ablation for AF is superior to medical therapy alone in patients with coexisting HF, we conducted this systematic review and meta-analysis. The primary outcomes evaluated are left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, 6-minute walk test (6MWT) distance, heart failure hospitalizations, and mortality. The results are presented as a mean difference for continuous outcome measures and odds ratios for dichotomous outcomes (using Mantel-Haenszel random effects model). 7 full texts met inclusion criteria, including 856 patients. AF catheter ablation was associated with a significant increase in LVEF (mean difference 6.8%; 95% CI: 3.5 - 10.1; P<0.001) and 6MWT (mean difference 29.3; 95% CI: 11.8 - 46.8; P = 0.001), and improvement in MLWHFQ (mean difference -12.1; 95% CI: -20.9 - -3.3; P = 0.007). The risk of all-cause mortality was significantly lower in the AF ablation arm (OR 0.49; 95% CI: 0.31 - 0.77; P = 0.002). In conclusion, atrial fibrillation ablation in patients with systolic heart failure is associated with significant improvement in LVEF, quality of life, 6MWT, and overall mortality.

Meta-Analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo.

Amiodarone has been associated with adverse events that may restrict its use. We performed a meta-analysis of placebo-controlled trials to assess the relative risk of adverse events of amiodarone compared with placebo. In total, 43 randomized trials were included. A total of 11,395 patients were included (5,792 patients randomized to amiodarone and 5,603 patients randomized to placebo). The incident rate of adverse events per 10,000 person-years was higher in the amiodarone group compared with placebo for pulmonary (129 vs 74; relative risk (RR) 1.77, p = 0.002), thyroid (201 vs 42; RR 4.44, p <0.001), hepatic (54 vs 25; RR 2.27, p = 0.01), cardiac (771 vs 450; RR 1.94, p <0.001), neurological (140 vs 76; RR 1.93, p <0.001), and skin (81 vs 23; RR 1.99, p = 0.04) adverse events. Low-dose amiodarone was not associated with statistically significant increase in pulmonary adverse events but was still associated with thyroid and liver adverse events. In conclusion, the likelihood of experiencing adverse events related to amiodarone was higher than that of placebo. The overall rate of adverse events however, was low, and severe adverse events were rare.

SpO2 /FIO2 on Presentation as a Predictor for Early Hemodynamic Deterioration in Intermediate Risk Acute Pulmonary Embolism.

BACKGROUND: Patients with intermediate-risk acute pulmonary embolism are at risk of hemodynamic deterioration, and identification of risk factors for decompensation could guide the administration of thrombolytics. We aimed to assess whether SpO2 /FIO2 on presentation is associated with early hemodynamic deterioration in this population. METHODS: A retrospective chart review of subjects admitted between 2006 and 2018 with intermediate-risk pulmonary embolism (hemodynamically stable with right ventricle to left ventricle ratio > 0.9 or tricuspid annular plane systolic excursion < 18 mm). Early hemodynamic deterioration was defined as requirements for vasopressors or rescue thrombolytics within 48 h. Results are presented as median (interquartile range). RESULTS: A total of 178 subjects were included. Early hemodynamic deterioration occurred in 13% of the subjects and was associated with a median (interquartile range) lower SpO2 /FIO2 on presentation in univariate analysis (243 [123-275] versus 438 [335-457], P < .001) and in a multivariate analysis, including heart rate and right ventricle to left ventricle ratio as covariates (odds ratio 0.992, 95% CI 0.987-0.996; P < .001). The initial SpO2 /FIO2 predicted hemodynamic deterioration with an area under the receiver operating characteristic curve of 0.81 and a threshold of 260 was associated with a sensitivity of 74% and specificity of 88%. Sensitivity analyses restricted to subjects with hypoxemia on presentation and subjects with an elevated troponin level led to similar results. CONCLUSIONS: In intermediate-risk pulmonary embolism, SpO2 /FIO2 on presentation can help predict the risk of early hemodynamic deterioration.

The benefit of closed loop stimulation in patients with cardioinhibitory vasovagal syncope confirmed by head-up tilt table testing: a systematic review and meta-analysis.

PURPOSE: A proportion of patients with vasovagal syncope (VVS) experience recurrence despite appropriate management. Closed loop stimulation (CLS) pacing is a promising treatment for a subgroup of patients with cardioinhibitory response on head-up tilt table test (HUTT). Nonetheless, its efficacy remains uncertain. We sought to assess the efficacy of CLS pacing in patients with cardioinhibitory VVS. METHODS: We searched PubMed, Google Scholar, and the Cochrane Central Register of controlled trials for relevant studies (last search date April 23, 2018). Data were pooled using the Mantel-Haenszel fixed-effects model. For cohort studies, we used a Freeman-Tukey transformation to calculate the weighted summary proportion. Primary outcomes are syncope and presyncope. RESULTS: Eight studies were included in the final analyses (two single-blinded and one double-blinded RCT, two prospective observational studies, and three retrospective observational studies). Two hundred ninety-one patients included, with an average age of 57 years. Quality of evidence is moderate. Use of CLS pacing was associated with reduced risk of syncope (OR 0.08; 95% CI 0.03-0.18; I2 32%) and presyncope (OR 0.34; 95% CI 0.18-0.63; I2 0.00%). Using proportion meta-analysis, the summary estimate of the proportion of cases that developed syncope during CLS pacing was similar between RCTs and prospective studies (3.2% and 3.1%), respectively. This is much lower than the rate of recurrence in the control arm of RCTs at 33.7%. Sensitivity analyses yielded similar results. CONCLUSION: CLS pacing is beneficial for patients with recurrent vasovagal syncope who demonstrate a cardioinhibitory response on HUTT.

A Meta-Regression Analysis of Atrial Fibrillation Ablation in Patients with Systolic Heart Failure.

BACKGROUND: Meta-analyses of randomized controlled trials comparing atrial fibrillation (AF) ablation to medical therapy in patients with heart failure (HF) reported improvement in left ventricular ejection fraction (LVEF), quality of life using the Minnesota Living with HF Questionnaire (MLWHFQ), and 6-minute walk test (6MWT). Nonetheless, there was significant heterogeneity not accounted for suggesting that not all HF patients derive the same effect from AF ablation. OBJECTIVES: To evaluate if baseline LVEF or the etiology of the cardiomyopathy would moderate the efficacy of AF ablation. METHODS: We performed random effects meta-regression using the mean baseline LVEF and total percentage of patients with non-ischemic cardiomyopathy (NICMP) in the placebo arms as moderator variables. RESULTS: Six trials with a total of 687 patients were included. The baseline LVEF in the control arm of trials ranged from 25% - 42.9%, and the percentage of patients with NICMP within each trial varied from 35% to 100%. When baseline LVEF was used as the moderator variable, no significant change in heterogeneity was observed for any of the outcomes of interest (R2 0.00 - 0.02). However, when controlling for NICMP, heterogeneity dropped substantially for the outcomes of LVEF (I2 44.7%, R2 0.91), and MLWHFQ (I2 0.00%, R2 1.00) but not 6MWT (I2 67.4%, R2 0.00). This indicates that improvement in LVEF and MLWHFQ was greater in the AF ablation group when more patients with NICMP were included in the trials. CONCLUSIONS: In patients with systolic HF, AF ablation may be more beneficial in patients with NICMP.

Avicenna and Tremor of the Heart.

Physicians have been mesmerized by a beating heart and its relationship to the peripheral pulse since the ancient times. Although William Harvey in 1628 was credited as the first to describe "fibrillation of the auricles," chaotic irregularity of the pulse was acknowledged by some as early as in the antiquity. In fact, a close examination of history may reveal a description of cardiac arrhythmias long before the era of modern medicine.

Frequency of Appropriate and Low-Risk Noncardiac Preoperative Stress Testing Across Medical Specialties.

Preoperative stress testing in asymptomatic patients is considered rarely appropriate in patients with: (1) moderate to good functional capacity (≥4 metabolic equivalent (METs)), (2) no clinical risk factors, or who are (3) asymptomatic after revascularization, normal stress test, or normal coronary angiography within 1 year. Preoperative stress testing is also not recommended in patients at low risk (<1%) for adverse cardiac events. We investigated the frequency of rarely appropriate and low-risk preoperative stress testing across medical specialties at our institution in asymptomatic patients when applying appropriate use criteria and two different perioperative risk models. We reviewed preoperative stress tests for noncardiac surgeries performed at Hershey Medical Center from January 1, 2012 to December 31, 2014. Perioperative cardiac risk was estimated using the National Surgical Quality Improvement Program Myocardial Infarction and Cardiac Arrest risk calculator and the Revised Cardiac Risk Index (RCRI) score. We analyzed 501 preoperative stress tests meeting the study criteria. When applying appropriate use criteria, we found that 336 of 501 studies (67%) were rarely appropriate. When applying the risk score models, 369 of 501 studies (74%) were determined to be low risk by the RCRI (RCRI score ≤1), and 248 of 361 stress tests (69%) were determined to be low risk by the National Surgical Quality Improvement Program Myocardial Infarction and Cardiac Arrest risk calculator. Low risk and rarely appropriate preoperative stress testing was common across all ordering specialties reviewed. In conclusion, these findings suggest that preoperative stress testing is broadly overused in asymptomatic patients and that interventions to reduce rarely appropriate and low-risk preoperative stress testing require a multispecialty approach.

Fluoroscopy pulse rate reduction during diagnostic and therapeutic imaging in the cardiac catheterization laboratory: An evaluation of radiation dose, procedure complications and outcomes.

OBJECTIVES: To evaluate radiation reduction by reducing fluoroscopy pulse rate in diagnostic cardiac catheterizations and percutaneous coronary interventions (PCI) as well as outcomes at 30 days and six months. BACKGROUND: Radiation exposure to the public at large has increased dramatically over the past three decades, and the cardiac catheterization laboratory is a large contributor. Fluoroscopy pulse rate is one way to decrease radiation exposure. METHODS: Fluoroscopy pulse rate was reduced from 10 pulses/sec (p/s) to 7.5 p/s as part of an internal quality improvement project. A retrospective analysis of all cardiac catheterizations was performed, evaluating Air KERMA at the interventional reference point (Ka, r ), Air KERMA area product (PKA ), procedural complications and major adverse cardiac events at 30 days and 6 months. RESULTS: In diagnostic catheterization median PKA (µGy·m2 ) and Ka,r (mGy) were significantly reduced (PKA - 5,613.3 vs. 4,400, P < 0.001; Ka,r - 703.0 vs. 621.0, P = 0.041). In PCI, median PKA and Ka,r were further reduced (PKA - 13,481.6 vs. 10,648.0, P < 0.001; Ka,r - 1787.0 vs. 1,459.0, P = 0.002). There was no difference in complications, fluoroscopy time or number of stents placed. There was no difference in MACE after adjustment for number of STEMIs. CONCLUSIONS: Reducing fluoroscopy pulse rates to 7.5 from 10 is an effective way to reduce patient radiation exposure across meaningful dose indices. A pulse rate of 7.5 p/s is safe, with no difference in complications or outcomes. A fluoroscopy pulse rate of 7.5 p/s should be given strong consideration for a new standard. © 2016 Wiley Periodicals, Inc.

Usefulness of the Myocardial Infarction and Cardiac Arrest Calculator as a Discriminator of Adverse Cardiac Events After Elective Hip and Knee Surgery.

The 2014 American College of Cardiology and American Heart Association guidelines on perioperative evaluation recommend differentiating patients at low risk (<1%) versus elevated risk (≥1%) for cardiac complications to guide appropriate preoperative testing. Among the tools recommended for estimating perioperative risk is the National Surgical Quality Improvement Program (NSQIP) Myocardial Infarction and Cardiac Arrest (MICA) risk calculator. We investigated whether the NSQIP MICA risk calculator would accurately discriminate adverse cardiac events in a cohort of adult patients undergoing elective orthopedic surgery. We retrospectively reviewed 1,098 consecutive, elective orthopedic surgeries performed at Hershey Medical Center from January 1, 2013, to December 31, 2014. Adverse cardiac events were defined as myocardial infarction or cardiac arrest within 30 days of surgery. The mean estimated risk for adverse cardiac events using the NSQIP MICA risk calculator was 0.54%, which was not significantly different (p = 1) compared with the observed incidence of 0.64% (7 of 1,098 procedures). The c-statistic for discriminating adverse cardiac events was 0.85 (95% CI 0.67 to 1) for the NSQIP MICA risk calculator and 0.9 (95% CI 0.75 to 1) for the Revised Cardiac Risk Index. In conclusion, the NSQIP MICA risk calculator is a good discriminator of adverse cardiac events in patients undergoing elective hip and knee surgery, performing comparably to the Revised Cardiac Risk Index.

International survey of nephrologists' perceptions and attitudes about rewards and compensations for kidney donation.

BACKGROUND: Payment for organ donation, whether in the form of incentives, rewards or compensation is highly debated and has been denounced by many professional and legislative bodies. Despite the passionate discussion in the literature, there is very limited data on attitudes and perceptions of physicians about providing rewards or compensation to organ donors. We investigated the relationship between demographic and practice characteristics of nephrologists and their perceptions and attitudes about rewards and compensations for organ donation. METHODS: Using a web-based survey, we explored the views of nephrologists around the world about rewards and compensations for kidney donation. The relationship between attitudes and demographic characteristics of 1280 nephrologists from 74 countries was examined by univariate and multivariable analyses. RESULTS: Seventy-five percent agreed with donor health insurance, 26% favored direct financial compensation and 31% agreed with financial rewards for unrelated donors. Sixty-six percent believed that rewards will lead to increased donation. Seventy-three percent indicated that rewards will lead to exploitation of the poor and 78% agreed with legislation prohibiting organ sales. Thirty-seven percent believed that rewards will negatively impact deceased-donor transplantation. Nephrologists from India/Pakistan and the Middle East had more favorable views about rewards, while respondents from Latin America and Europe, older than 50, female nephrologists and those practicing in rural areas had less favorable views. CONCLUSIONS: We conclude that a minority of nephrologists favor rewards for donation, many agree with some compensation and a considerable majority favor donor health insurance. Perceptions of nephrologists about rewards and compensation are influenced by age, sex, urban versus rural location and geographic region of practice.

Nephrologists' perceptions of renal transplant as treatment of choice for end-stage renal disease, preemptive transplant, and transplanting older patients: an international survey.

OBJECTIVES: To explore the relation between nephrologists' characteristics and their views of transplant as the treatment of choice for end-stage renal disease, preemptive transplant, and transplant of older patients. MATERIALS AND METHODS: A comprehensive international Web-based survey explored the relation between nephrologists' characteristics and their views of transplant as the treatment of choice for end-stage renal disease, preemptive transplant, and transplant of older patients. RESULTS: A total of 1448 nephrologists completed the survey. The majority of respondents agreed with transplant as the treatment of choice for end-stage renal disease (75%), preemptive transplant (71%), and transplant for patients > 60 years of age (59%). The likelihood of agreement was higher among transplant and academic nephrologists, and practice at hospitals with ≥ 50 transplants per year. Urban location and ≥ 10 years in practice were associated with higher likelihood of viewing transplant as treatment of choice and favoring preemptive transplant. CONCLUSIONS: Demographic and practice characteristics influence nephrologists' attitudes about transplant as the treatment of choice for end-stage renal disease, preemptive transplant, and transplant as an option for older patients. Detailed studies exploring the determinants of nephrologists' attitudes are likely to identify sources of variations in perceptions of patient suitability for transplant. Our findings underscore the need for continuing educational programs addressing evolving aspects of transplant particularly targeting nephrologists practicing within nonacademic centers and in rural areas.