Nitesh Sood

Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT

OBJECTIVE The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality. METHODS Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up. RESULTS The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks. CONCLUSION In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy. Clinical trials.gov identifier: NCT00180271.

Combination therapy for the management of hypertension: A review of the evidence

PURPOSE Evidence regarding combination therapy for the management of hypertension is reviewed. SUMMARY Numerous clinical trials have demonstrated the importance of early aggressive lowering of blood pressure, especially in patients at high cardiovascular risk. However, one of the difficulties with achieving these blood pressure goals quickly is that monotherapy is often insufficient. Many large randomized trials have shown that two or more antihypertensive agents are required for patients to reach their treatment goals. Recent data have suggested that the use of combination therapy in patients with hypertension may be beneficial in terms of improving blood-pressure-lowering efficacy, obtaining blood pressure goals earlier, and reducing major adverse cardiovascular events. Studies have found that therapy with a calcium channel blocker (CCB) combined with an angiotensin-converting-enzyme (ACE) inhibitor significantly reduces both blood pressure and major clinical events compared with an ACE inhibitor-diuretic combination. Combination ACE inhibitor-CCB therapy has also demonstrated superior blood-pressure-lowering efficacy and safety compared with either group used as monotherapy, including lower rates of peripheral edema compared with those achieved with increased doses of CCBs. The combination of an ACE inhibitor and an angiotensin II-receptor blocker has not been found to be superior to either group as monotherapy in patients with hypertension and should not be recommended at this time. CONCLUSION Combination drug therapy for the treatment of hypertension is supported by numerous randomized trials and clinical management guidelines. The addition of a diuretic or CCB to renin-angiotensin-aldosterone-system blocker therapy may provide an effective combination for reducing blood pressure and cardiovascular events.

Oral anti-diabetic drugs for the prevention of Type 2 diabetes

Diabet. Med. 28, 948–964 (2011)

Predictors of an inadequate defibrillation safety margin at ICD implantation: insights from the National Cardiovascular Data Registry.

BACKGROUND Defibrillation testing is often performed to establish effective arrhythmia termination, but predictors and consequences of an inadequate defibrillation safety margin (DSM) remain largely unknown. OBJECTIVES The aims of this study were to develop a simple risk score predictive of an inadequate DSM at implantable cardioverter-defibrillator (ICD) implantation and to examine the association of an inadequate DSM with adverse events. METHODS A total of 132,477 ICD Registry implantations between 2010 and 2012 were analyzed. Using logistic regression models, factors most predictive of an inadequate DSM (defined as the lowest successful energy tested <10 J from maximal device output) were identified, and the association of an inadequate DSM with adverse events was evaluated. RESULTS Inadequate DSMs occurred in 12,397 patients (9.4%). A simple risk score composed of 8 easily identifiable variables characterized patients at high and low risk for an inadequate DSM, including (with assigned points) age <70 years (1 point); male sex (1 point); race: black (4 points), Hispanic (2 points), or other (1 point); New York Heart Association functional class III (1 point) or IV (3 points); no ischemic heart disease (2 points); renal dialysis (3 points); secondary prevention indication (1 point); and ICD type: single-chamber (2 points) or biventricular (1 point) device. An inadequate DSM was associated with greater odds of complications (odds ratio: 1.22; 95% confidence interval: 1.09 to 1.37; p = 0.0006), hospital stay >3 days (odds ratio: 1.24; 95% confidence interval: 1.19 to 1.30; p < 0.0001), and in-hospital mortality (odds ratio: 1.96; 95% confidence interval: 1.63 to 2.36; p < 0.0001). CONCLUSIONS A simple risk score identified ICD recipients at risk for an inadequate DSM. An inadequate DSM was associated with an increased risk for in-hospital adverse events.

The Association Among Blood Transfusions, White Blood Cell Count, and the Frequency of Post–Cardiothoracic Surgery Atrial Fibrillation: A Nested Cohort Study From the Atrial Fibrillation Suppression Trials I, II, and III

OBJECTIVE To evaluate the impact of postoperative red blood cell transfusions and white blood cell (WBC) counts on post-cardiothoracic surgery atrial fibrillation. DESIGN A nested cohort study of 550 patients from the Atrial Fibrillation Suppression Trials I, II, and III. SETTING A large urban teaching hospital. PARTICIPANTS Patients undergoing cardiothoracic surgery. MEASUREMENTS AND RESULTS Endpoints included postoperative atrial fibrillation occurrence and maximum white blood cell counts during the first 5 days postoperatively. Multivariate logistic regression was used to control for potential confounders and calculate adjusted odds ratios (AOR) with 95% confidence intervals (95% CIs). Of the 173 patients (31.5%) who developed postoperative atrial fibrillation, 110 patients (63.5%) received postoperative transfusions and 63 patients (36.5%) did not (crude odds ratio = 1.89; 95% CI, 1.31-2.74; p = 0.001). Postoperative white blood cell counts were significantly greater in patients who developed atrial fibrillation on postoperative days 3 to 5. There were no differences in WBC between patients who did and did not receive transfusions. Upon multivariate logistic regression, the use of postoperative red blood cell transfusions was found to be associated with a 2-fold increase in postoperative atrial fibrillation (AOR 1.95; 95% CI, 1.24-3.06; p = 0.004). Similarly, the maximum white blood cell count also was associated with increased atrial fibrillation odds (AOR 1.09 K/microL; 95% CI, 1.04-1.13; p < 0.001). CONCLUSIONS Postoperative red blood cell transfusion use was found to be a strong independent predictor for the development of postoperative atrial fibrillation, although no direct link between red blood cell transfusion and an increased white blood cell count was seen.

Lack of effect of statins on maintenance of normal sinus rhythm following electrical cardioversion of persistent atrial fibrillation

Randomised controlled trials evaluating the effect of statin use on maintenance of normal sinus rhythm (NSR) after electrical cardioversion (ECV) of persistent atrial fibrillation (AF) have demonstrated conflicting results. However, many of these trials were of relatively small size and thus underpowered to adequately evaluate this end‐point. The aim of this study was to conduct a meta analysis evaluating the effect of statin use on maintenance of NSR after ECV of persistent AF. Randomised controlled trials evaluating the use of statins to maintain NSR after ECV of AF were identified through a systematic search including Medline (1950 through December 2009), the Cochrane CENTRAL Register (4th quarter, 2009) and a manual review of references without any language restrictions. Pooled estimates of effect are reported as relative risks (RRs) with accompanying 95% confidence intervals (CIs) using a random‐effects model. Four trials (n = 424; range: 48–212) were identified and subject to meta analysis. Evaluated statins included atorvastatin 10 and 80 mg and pravastatin 40 mg/day. Over a mean of 2.1 months (range: 1–3 months) statins did not increase the likelihood of maintaining NSR following ECV (RR, 1.12; 95%CI, 0.85–1.46) compared with control. Current evidence does not suggest that statins are associated with an increased probability of maintaining NSR following ECV of persistent AF.

Intravenous magnesium sulfate enhances the ability of dofetilide to successfully cardiovert atrial fibrillation or flutter: results of the Dofetilide and Intravenous Magnesium Evaluation

AIMS A previous study found that the adjunctive use of intravenous magnesium sulfate with ibutilide could increase the odds of a patient chemically cardioverting from atrial fibrillation (AF) or flutter (AFL) to normal sinus rhythm (NSR) by 78%. Whether or not intravenous magnesium has the same effect on dofetilides ability to chemically cardiovert patients from AF/AFL to NSR is not known. METHODS AND RESULTS This was a retrospective cohort evaluation of consecutive eligible patients receiving dofetilide for chemical cardioversion of AF or AFL at a single institution. All AF or AFL patients received dofetilide according to the institutions standard protocol, which required patients to remain as an inpatient for a minimum of 3 days or 6 doses after the initiation of dofetilide therapy. Patients receiving any dose of intravenous magnesium starting on the same day as dofetilide constituted the treatment group. Controls received dofetilide, but no intravenous magnesium any time prior to chemical cardioversion. Patients underwent continuous electrocardiographic monitoring throughout their hospital admission. Multivariable logistic regression analysis was used to determine the impact of intravenous magnesium on dofetilides efficacy. A total of 160 patients in persistent AF or AFL (mean age 66.6 +/- 11.0 years, 70.0% male, 30.0% in AF or AFL >15 days, 54.4% hypertension, 37.5% heart failure, 16.3% valvular disease, 16.3% previous myocardial infarction, and baseline serum magnesium levels 2.1 +/- 0.26 mg/dL) and receiving dofetilide (mean dose 428 +/- 118 microg/dose) were included in this analysis. The overall chemical cardioversion rate with dofetilide irrespective of adjunctive intravenous magnesium utilization was 41.9%. The concurrent administration of intravenous magnesium (n = 50) was associated with a 107% increased odds of successful chemical cardioversion [adjusted odds ratio: 2.07 (95% confidence intervals: 1.00-4.33)] compared with those who did not receive magnesium (n = 110). Only one case of torsade de pointes occurred in the no magnesium group during the index hospital admission. CONCLUSION Concurrent use of intravenous magnesium is associated with an enhanced ability of dofetilide to successfully convert AF or AFL.

Unicuspid aortic valve : an interesting presentation

A 52-year-old male presented with acute onset chest pain and ST-segment elevation myocardial infarction (Panel A). An urgent cardiac catheterization was performed which showed a filling defect in the left anterior descending (LAD) artery (Panel B). After failure at attempts to reperfuse the LAD, the patient underwent emergent cardiopulmonary bypass surgery with a left internal mammary graft to LAD. He was found …

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Background Frailty predicts poorer outcomes and decreased anticoagulation use in patients with nonvalvular atrial fibrillation. We sought to assess the effectiveness and safety of apixaban, dabigatran and rivaroxaban versus warfarin in frail nonvalvular atrial fibrillation patients. Methods and Results Using US MarketScan claims data from November 2011 to December 2016, we identified frail oral anticoagulant‐naïve nonvalvular atrial fibrillation patients with ≥12 months of continuous insurance coverage before oral anticoagulant initiation. Frailty status was determined using the Johns Hopkins Claims‐based Frailty Indicator score (≥0.20 indicating frailty). Users of apixaban, dabigatran, or rivaroxaban were separately 1:1 matched to warfarin users via propensity‐scores, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed for up to 2 years or until an event, insurance disenrollment or end of follow‐up. Rates of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 2700, 2784, and 5270 patients were included in the apixaban, dabigatran, and rivaroxaban 1:1 matched analyses to warfarin. At 2 years, neither apixaban nor dabigatran were associated with differences in the hazard of stroke or systemic embolism (HR=0.78; 95% CI=0.46–1.35 and HR=0.94; 0.60–1.45) or major bleeding (HR=0.72; 95% CI=0.49–1.06 and HR=0.87; 95% CI=0.63–1.19) versus warfarin. Rivaroxaban was associated with reduced stroke or systemic embolism at 2 years (HR=0.68; 95% CI=0.49–0.95) without significantly altering major bleeding risk (HR=1.07; 95% CI=0.81–1.32). Conclusions Our study found rivaroxaban but not apixaban or dabigatran to be associated with reduced SSE versus warfarin in frail nonvalvular atrial fibrillation patients. No direct‐acting oral anticoagulants demonstrated a significant difference in major bleeding versus warfarin.

Incidence and Predictors of Perioperative Complications With Transvenous Lead Extractions: Real-World Experience With National Cardiovascular Data Registry

Background: Transvenous lead extraction is an integral part of management of patients with cardiovascular implantable electronic devices. Real-world incidence and predictors of perioperative complications in extractions involving implantable cardioverter-defibrillator leads have not been described in detail. Methods and Results: Data from the National Cardiovascular Data Registry Implantable Cardioverter-Defibrillator Registry were analyzed. Lead extraction was defined as removal of leads implanted for >1 year. Predictors of major perioperative complications for all extraction procedures (11 304) and for high-voltage lead (8362, 74%), across 762 centers, were analyzed using univariate and multivariate logistic regression. Major complication occurred in 258 (2.3%) extraction procedures. Of these 258 with a complication, 41 (16%) required urgent cardiac surgery. Of these 41, 14 (34%) died during surgery. Among the total 98 (0.9%) deaths reported, 18 (0.16% of total) occurred during transvenous lead extraction. In multivariable logistic regression analysis, female sex, admission other than electively for procedure, ≥3 leads extracted, longer implant duration, dislodgement of other leads, and patient’s clinical status requiring lead extraction (infection/perforation) were associated with increased risk of complications. Smaller lead diameter, flat versus round coil shape, and greater proximal surface coil area were multivariate predictors of major perioperative complications specific to high-voltage leads. Conclusions: The rate of major complications and mortality with transvenous lead extraction is similar in the real-world outcomes to that reported in recent single-center studies from high-volume centers. There is significant risk of urgent cardiac surgery, which carries a high mortality, and planning for appropriate cardiothoracic surgery backup is imperative.