Norman C. Wang

Clinical Implications of QRS Duration in Patients Hospitalized With Worsening Heart Failure and Reduced Left Ventricular Ejection Fraction

CONTEXT Hospitalization for heart failure is associated with high postdischarge mortality and morbidity. The predictive value of the QRS duration during admission for heart failure has not been well studied. OBJECTIVE To investigate the predictive value of the QRS duration in patients hospitalized for heart failure with reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS Retrospective, post hoc analysis from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study in patients hospitalized for heart failure and having an LVEF of 40% or less. A total of 4133 patients were enrolled at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006. After excluding 1029 patients with a pacemaker, implantable cardioverter-defibrillator, or both at enrollment and 142 patients without a reported baseline QRS duration, 2962 patients were included in the analysis: 1641 had a normal QRS duration (< 120 ms) and 1321 had a prolonged QRS duration (> or = 120 ms). MAIN OUTCOME MEASURES Dual primary end points were all-cause mortality and the composite of cardiovascular death or hospitalization for heart failure. RESULTS During a median follow-up of 9.9 months, all-cause mortality was 18.7% for patients with a normal baseline QRS duration and 28.1% for patients with a prolonged baseline QRS duration (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.38-1.87). The composite of cardiovascular death or hospitalization for heart failure was 32.4% for patients with a baseline QRS duration less than 120 ms and 41.6% for patients with a baseline QRS duration of 120 ms or greater (HR, 1.40; 95% CI, 1.24-1.58). The increased risk associated with prolonged QRS duration was confirmed after adjusting for multiple variables for all-cause mortality (HR, 1.24; 95% CI, 1.02-1.50) and the composite of cardiovascular death or hospitalization for heart failure (HR, 1.28; 95% CI, 1.10-1.49). Only 105 patients (3.6%) who presented with a prolonged baseline QRS duration had a normal QRS duration on their last inpatient electrocardiogram. CONCLUSION A prolonged QRS duration appears common in patients with reduced LVEF who are hospitalized for heart failure and is an independent predictor of high postdischarge morbidity and mortality.

Predictive Value of Stress Myocardial Perfusion Imaging in Liver Transplant Candidates

In summary, these data indicate that SPECT imaging has a poor predictive value for CAD in OLT candidates. Coronary angiography has a primary screening role for this population, especially in patients with multiple cardiac risk factors or a known history of CAD.

Fluoroscopic Screening of Asymptomatic Patients Implanted With the Recalled Riata Lead Family

Background— The Food and Drug Administration recently issued a class I recall of the St. Jude Medical Riata implantable cardioverter-defibrillator lead presumably because of increased risk of electric failure and mechanical separation via inside-out abrasion. We sought to examine the incidence and time dependence of inside-out abrasion in asymptomatic patients implanted with the Riata lead. Methods and Results— Asymptomatic patients implanted with the Riata lead at our institution were offered voluntary fluoroscopic screening in 3 views. Electric testing of the Riata lead with provocative isometric muscle contraction was performed at the time of fluoroscopic screening. Of the 245 patients undergoing fluoroscopic screening, 53 (21.6%) patients showed clear evidence of lead separation. Of these externalized leads, 0%, 13%, and 26% had a dwell time of <3 years, 3 to 5 years, and >5 years, respectively (P=0.037). Externalized leads had a significantly pronounced decrease in R-wave amplitude (−1.7±2.9 mV versus +0.35±2.5 mV; P<0.001), and more patients with externalized leads had ≥25% decrease in R-wave amplitude from baseline (28.0% versus 8.1%; P=0.018). One patient with externalization exhibited new noise on near-field electrogram. Conclusions— The Riata lead exhibits time-dependent high rates of cable externalization exceeding 20% at >5 years of dwell time. Externalized leads are associated with a more pronounced decrease in R-wave amplitude, which may be an early marker of future electric failure. The use of fluoroscopic and electric screening of asymptomatic patients with the Riata lead remains controversial in the management of patients affected by the recent Food and Drug Administration recall.

Antirestenotic Effects of a Locally Delivered Caspase Inhibitor in a Balloon Injury Model

Background—The precise role of arterial barotrauma-mediated apoptosis in causing restenosis is unclear. The purpose of this study was to determine if a link exists between angioplasty-mediated medial smooth muscle cell apoptosis and subsequent neointimal hyperplasia. Methods and Results—Bilateral iliac artery angioplasty was performed in 25 male New Zealand White rabbits. Simultaneous with balloon injury, each artery was treated locally with either the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(Ome)-fluoromethylketone (ZVAD-fmk) or control. In the acute cohort that was survived to 4 hours (n=10, 7 high dose and 3 low dose), an apoptotic index was calculated using the terminal deoxynucleotidyl TUNEL method. In the intermediate cohort that was survived to 2 weeks (n=5), luminal reendothelialization was measured via CD-31 staining. In the chronic cohort that was survived to 4 weeks (n=10), neointimal area was measured. In the acute cohort, there was a 40% reduction in the apoptotic index with high-dose ZVAD-fmk (P =0.008) and a 33% reduction with low-dose ZVAD-fmk (P =0.08). At 2 weeks, there was no significant difference in the degree of luminal reendothelialization. However, at 4 weeks, there was a 33% (0.33±0.23 versus 0.22±0.20 mm2) (P <0.005) reduction in neointimal area in ZVAD-fmk–treated arteries. Conclusions—The local delivery of ZVAD-fmk during balloon injury inhibits smooth muscle cell apoptosis. This corresponds to a significant reduction in neointimal proliferation seen at 4 weeks without a significant change in the degree of reendothelialization at 2 weeks.

Utility of the Wearable Cardioverter-Defibrillator in Patients With Newly Diagnosed Cardiomyopathy: A Decade-Long Single-Center Experience

BACKGROUND The wearable cardioverter-defibrillator (WCD) has emerged as a means of protecting patients with newly diagnosed nonischemic cardiomyopathy (NICM) or ischemic cardiomyopathy (ICM) against sudden cardiac death while awaiting re-evaluation of cardiac function. OBJECTIVES This study sought to characterize the risk of appropriate WCD therapy in newly diagnosed NICM and ICM patients according to cardiomyopathy etiology in an independent study. METHODS Medical records of all patients prescribed a WCD between June 2004 and May 2015 at our institution (n = 639) were analyzed, focusing on 254 patients with newly diagnosed NICM and 271 patients with newly diagnosed ICM. Patients with a prior implantable cardioverter-defibrillator or sustained ventricular arrhythmias were excluded (n = 114). The primary endpoint was appropriate WCD therapy. RESULTS Median WCD wear time was 61 days (interquartile range [IQR]: 25 to 102 days) per patient and 22 h/day (IQR: 17 to 23 h/day). During 56.7 patient-years, 0 NICM patients received an appropriate WCD shock, whereas 3 (1.2%) received an inappropriate shock. During 46.7 patient-years, 6 (2.2%) ICM patients received an appropriate shock; 5 survived the episode, and 4 survived to hospital discharge. All 6 patients with an appropriate shock were male with QRS duration >120 ms. Two (0.7%) ICM patients received an inappropriate shock. CONCLUSIONS In this independent, retrospective study, the risk of appropriate WCD therapies in patients with newly diagnosed NICM was minimal. Routine use of the WCD in this population should be prospectively evaluated. The risk of appropriate therapies in newly diagnosed ICM was comparable to that observed in prior observational studies.

Health and Economic Outcomes Associated with Use of an Antimicrobial Envelope as a Standard of Care for Cardiac Implantable Electronic Device Implantation

Infection of cardiac implanted electrical devices (CIED) is a problem. In selected patients, use of an “antibacterial envelope” (AIGISRx®) is associated with low CIED infection rates. The value of this device when used as a standard of care is unclear.

Persistent sympathoexcitation long after submaximal exercise in subjects with and without coronary artery disease

There is an increased risk of cardiac events after exercise, which may, in part, be mediated by the sympathoexcitation that accompanies exercise. The duration and extent of this sympathoexcitation following moderate exercise is unknown, particularly in those with coronary artery disease (CAD). Twenty control subjects (mean age, 51 years) and 89 subjects with CAD (mean age, 58 years) underwent two 16-min bicycle exercise sessions followed by 30-45 min of recovery. Session 1 was performed under physiological conditions to peak workloads of 50-100 W. In session 2, parasympathetic blockade with atropine (0.04 mg/kg) was achieved at end exercise at the same workload as session 1. RR interval was continually recorded, and plasma catecholamines were measured at rest and selected times during exercise and recovery. Parasympathetic effect, measured as the difference in RR interval with and without atropine, did not differ between controls and CAD subjects in recovery. At 30 and 45 min of recovery, RR intervals were 12% and 9%, respectively, shorter than at rest. At 30 and 45 min of recovery, plasma norepinephrine levels were 15% and 12%, respectively, higher than at rest. A brief period of moderate exercise is associated with a prolonged period of sympathoexcitation extending >45 min into recovery and is quantitatively similar among control subjects and subjects with CAD, with or without left ventricular dysfunction. Parasympathetic reactivation occurs early after exercise and is also surprisingly quantitatively similar in controls and subjects with CAD. The role of these autonomic changes in precipitating cardiac events requires further evaluation.

Implantable Cardioverter-defibrillators in Patients Hospitalized for Heart Failure With Chronically Reduced Left Ventricular Ejection Fraction

The aim of this study was to investigate the association between implantable cardioverter-defibrillator (ICD) status at the time of hospitalization for worsening heart failure (HF) with postdischarge events in patients with reduced left ventricular ejection fraction. We conducted an analysis of 4133 patients hospitalized for HF with left ventricular ejection fraction 40% or less in EVEREST. The final analysis included patients without an electrophysiological device (n = 3102) and those with an ICD (n = 600) at the time of enrollment. During a median follow-up of 300 days, all-cause mortality was 22.9% in the no device group and 35.2% in the ICD group (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.39-1.89). Rehospitalization for HF was 27.0% in the no device group and 46.8% in the ICD group (HR, 2.20; 95% CI, 1.92-2.52). After adjustment for multiple variables, the rates for all-cause mortality were similar (HR, 1.01; 95% CI, 0.83-1.22), but the ICD group had elevated rates of HF hospitalizations compared with the no device group (HR, 1.35; 95% CI, 1.14-1.60). In patients with reduced left ventricular ejection fraction, an ICD at presentation for hospitalization for worsening HF was associated with similar rates of death but higher rates of rehospitalization for HF. Given our findings, further studies should investigate optimization of care in patients already implanted with an ICD as well as the role of ICD implantation during or soon after hospitalization for HF in patients not yet implanted.

Incidence and Predictors of Complications During Cryoballoon Pulmonary Vein Isolation for Atrial Fibrillation

Background Cryoballoon pulmonary vein isolation (PVI) has emerged as an alternative to radiofrequency PVI for atrial fibrillation (AF). Data are lacking to define the rates and predictors of complications, particularly phrenic nerve injury (PNI). Methods and Results We evaluated a single‐center prospective registry of 450 consecutive patients undergoing cryoballoon PVI between 2011 and 2015. Patients were 59±10 years old, 26% were women, 58% had hypertension, their mean CHA 2 DS 2 VASc score was 1.7±1.3, 30% had persistent atrial fibrillation, and 92% received a second‐generation 28‐mm balloon. Predefined major complications were persistent PNI, pericardial effusion, deep vein thrombosis, arteriovenous fistula, atrioesophageal fistula, bleeding requiring transfusion, stroke, and death. PNI was categorized as persistent if it persisted after discharge from the laboratory. Logistic regression was performed to identify predictors of complications and specifically PNI. We identified a major complication in 10 (2.2%) patients. In 49 (10.8%) patients, at least transient PNI was observed; only 5 persisted beyond the procedure (1.1%). All cases of PNI resolved eventually, with the longest time to resolution being 48 days. We also describe 2 cases of PNI manifesting after the index hospitalization. Regression analysis identified 23‐mm balloon use (16.3% versus 5.2%, odds ratio 2.94, P=0.011) and increased age (62.8±7.7 versus 58.7±0.12 years, odds ratio 1.058, P=0.014) as independent significant predictors of PNI. There were no significant predictors of major complications. Conclusions In a large contemporary cohort, cryoballoon PVI is associated with low procedural risk, including lower rates of PNI than previously reported. Older age and 23‐mm balloon use were associated with PNI. Our low rate of PNI may reflect more sensitive detection methods, including compound motor action potential monitoring and forced double‐deflation.

Frequency of Toxicity With Chemical Conversion of Atrial Fibrillation With Dofetilide

Dofetilide is a class III antiarrhythmic agent approved for the maintenance of sinus rhythm in patients with persistent atrial fibrillation (AF). The goal of this study was to determine if chemical cardioversion (CCV) suggests a greater sensitivity to dofetilide and, therefore, portends a higher risk of proarrhythmia. We analyzed 99 consecutive patients with persistent AF who were loaded on dofetilide before cardioversion. CCV occurred after 2 ± 1.5 doses of dofetilide in 46 patients whereas electrical cardioversion (ECV) was required in the remaining 53 patients after 4.7 ± 1.3 doses. During index hospitalization, there were higher rates of dofetilide discontinuation because of QT prolongation or torsades de pointes (TdP) in the CCV group compared with the ECV group (24% vs 2%, p = 0.001). All patients with CCV requiring drug discontinuation converted after a single dose of dofetilide. Additionally, all 3 patients with TdP were in the CCV group. Furthermore, 15 of the 21 patients with CCV (71%) who converted after the first dose of dofetilide developed significant QT prolongation, requiring dose adjustment or discontinuation of drug. Among patients discharged on drug, AF recurrence and drug discontinuation rates were similar between groups at 2-year follow-up. In patients hospitalized for initiation of dofetilide, CCV occurs in almost 50% and is associated with higher rates of pathologic QT prolongation and TdP compared with those who require ECV. Once discharged on dofetilide, safety and efficacy is similar in both groups. In conclusion, patients with CCV may require closer monitoring for proarrhythmia.