Daniel J. Friedman

Trends and In-Hospital Outcomes Associated With Adoption of the Subcutaneous Implantable Cardioverter Defibrillator in the United States.

ImportancenTrends and in-hospital outcomes associated with early adoption of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the United States have not been described.nnnObjectivesnTo describe early use of the S-ICD in the United States and to compare in-hospital outcomes among patients undergoing S-ICD vs transvenous (TV)-ICD implantation.nnnDesign, Setting, and ParticipantsnA retrospective analysis of 393u202f734 ICD implants reported to the National Cardiovascular Data Registry ICD Registry, a nationally representative US ICD registry, between September 28, 2012 (US Food and Drug Administration S-ICD approval date), and March 31, 2015, was conducted. A 1:1:1 propensity-matched analysis of 5760 patients was performed to compare in-hospital outcomes among patients with S-ICD with those of patients with single-chamber (SC)-ICD and dual-chamber (DC)-ICD.nnnMain Outcomes and MeasuresnAnalysis of trends in S-ICD adoption as a function of total ICD implants and comparison of in-hospital outcomes (death, complications, and defibrillation threshold [DFT] testing) among S-ICD and TV-ICD recipients.nnnResultsnOf the 393u202f734 ICD implants evaluated during the study period, 3717 were S-ICDs (0.9%). A total of 109u202f445 (27.8%) of the patients were female; the mean (SD) age was 67.03 (13.10) years. Use of ICDs increased from 0.2% during the fourth quarter of 2012 to 1.9% during the first quarter of 2015. Compared with SC-ICD and DC-ICD recipients, those with S-ICDs were more often younger, female, black, undergoing dialysis, and had experienced prior cardiac arrest. Among 2791 patients with S-ICD who underwent DFT testing, 2588 (92.7%), 2629 (94.2%), 2635 (94.4%), and 2784 (99.7%) were successfully defibrillated (≤65, ≤70, ≤75, and ≤80 J, respectively). In the propensity-matched analysis of 5760 patients, in-hospital complication rates associated with S-ICDs (0.9%) were comparable to those of SC-ICDs (0.6%) (Pu2009=u2009.27) and DC-ICD rates (1.5%) (Pu2009=u2009.11). Mean (SD) length of stay after S-ICD implantation was comparable to that after SC-ICD implantation (1.1 [1.5] vs 1.0 [1.2] days; Pu2009=u2009.77) and less than after DC-ICD implantation (1.1 [1.5] vs 1.2 [1.5] days; Pu2009<u2009.001).nnnConclusions and RelevancenThe use of S-ICDs is rapidly increasing in the United States. Early adoption has been associated with low complication rates and high rates of successful DFT testing despite frequent use in patients with a high number of comorbidities.

Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study

Background Obesity is associated with altered atrial electrophysiology and a prominent risk factor for atrial fibrillation. Body mass index, the most widely used adiposity measure, has been related to atrial electrical remodeling. We tested the hypothesis that pericardial fat is independently associated with electrocardiographic measures of atrial conduction. Methods and Results We performed a cross‐sectional analysis of 1946 Framingham Heart Study participants (45% women) to determine the relation between pericardial fat and atrial conduction as measured by P wave indices (PWI): PR interval, P wave duration (P‐duration), P wave amplitude (P‐amplitude), P wave area (P‐area), and P wave terminal force (P‐terminal). We performed sex‐stratified linear regression analyses adjusted for relevant clinical variables and ectopic fat depots. Each 1‐SD increase in pericardial fat was significantly associated with PR interval (β=1.7 ms, P=0.049), P‐duration (β=2.3 ms, P<0.001), and P‐terminal (β=297 μV·ms, P<0.001) among women; and P‐duration (β=1.2 ms, P=0.002), P‐amplitude (β=−2.5 μV, P<0. 001), and P‐terminal (β=160 μV·ms, P=0.002) among men. Among both sexes, pericardial fat was significantly associated with P‐duration in analyses additionally adjusting for visceral fat or intrathoracic fat; a similar but non‐significant trend existed with P‐terminal. Among women, pericardial fat was significantly associated with P wave area after adjustment for visceral and intrathoracic fat. Conclusions Pericardial fat is associated with atrial conduction as quantified by PWI, even with adjustment for extracardiac fat depots. Further studies are warranted to identify the mechanisms through which pericardial fat may modify atrial electrophysiology and promote subsequent risk for arrhythmogenesis.

Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT-CRT Long-Term Follow-Up

BACKGROUNDnData regarding cardiac resynchronization therapy (CRT) in patients with multiple comorbidities are limited.nnnOBJECTIVESnThis study evaluated the association of multiple comorbidities with the benefits of CRT over implantable cardioverter-defibrillator (ICD) alone.nnnMETHODSnWe examined 1,214 MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) study patients with left bundle branch block (LBBB) and 0, 1, 2, orxa0≥3 comorbidities, including renal dysfunction, hypertension (HTN), diabetes, coronary artery disease, history of atrial arrhythmias, history of ventricular arrhythmias, current smoking, and cerebrovascular accident. In an adjusted analysis, we analyzed risk of heart failure (HF) events or death by comorbidity group in all patients and in patients with CRT with defibrillator (CRT-D) versus ICD. Then we examined percent change in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV ejection fraction, left atrial volume, and LV dyssynchrony at 1-year in CRT-D patients by comorbidity group.nnnRESULTSnThere was an inverse relationship between comorbidity burden and improvements in LV end-systolic volume, LV end-diastolic volume, left ventricular ejection fraction, left atrial volume, and LV dyssynchrony. In an adjusted model,xa0there was an increasing risk of death or nonfatal HF events with increasing comorbidity burden regardless of treatment group (pxa0< 0.001). During a mean follow-up of 4.65 years, there was no interaction with respect to comorbidity burden and the benefit of CRT-D versus ICD only for death or nonfatal HF events (interaction pxa0= 0.943). Inxa0the groups with greatest comorbidity burden (2 andxa0≥3), the absolute risk reduction associated with CRT-D over ICDxa0alone appeared greater than that seen for groups with less comorbidity burden (0 and 1).nnnCONCLUSIONSnDuring long-term follow-up of MADIT-CRT study patients with LBBB randomized to CRT-D, there werexa0differences in HF or death risk and in the degree of reverse remodeling among comorbidity groups. However,xa0thexa0burden of comorbidity does not appear to compromise the clinical benefits of CRT-D compared with ICD alone.

Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery

Importance The left atrial appendage is a key site of thrombus formation in atrial fibrillation (AF) and can be occluded or removed at the time of cardiac surgery. There is limited evidence regarding the effectiveness of surgical left atrial appendage occlusion (S-LAAO) for reducing the risk of thromboembolism. Objective To evaluate the association of S-LAAO vs no receipt of S-LAAO with the risk of thromboembolism among older patients undergoing cardiac surgery. Design, Setting, and Participants Retrospective cohort study of a nationally representative Medicare-linked cohort from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2012). Patients aged 65 years and older with AF undergoing cardiac surgery (coronary artery bypass grafting [CABG], mitral valve surgery with or without CABG, or aortic valve surgery with or without CABG) with and without concomitant S-LAAO were followed up until December 31, 2014. Exposures S-LAAO vs no S-LAAO. Main Outcomes and Measures The primary outcome was readmission for thromboembolism (stroke, transient ischemic attack, or systemic embolism) at up to 3 years of follow-up, as defined by Medicare claims data. Secondary end points included hemorrhagic stroke, all-cause mortality, and a composite end point (thromboembolism, hemorrhagic stroke, or all-cause mortality). Results Among 10 524 patients undergoing surgery (median age, 76 years; 39% female; median CHA2DS2-VASc score, 4), 3892 (37%) underwent S-LAAO. Overall, at a mean follow-up of 2.6 years, thromboembolism occurred in 5.4%, hemorrhagic stroke in 0.9%, all-cause mortality in 21.5%, and the composite end point in 25.7%. S-LAAO, compared with no S-LAAO, was associated with lower unadjusted rates of thromboembolism (4.2% vs 6.2%), all-cause mortality (17.3% vs 23.9%), and the composite end point (20.5% vs 28.7%) but no significant difference in rates of hemorrhagic stroke (0.9% vs 0.9%). After inverse probability–weighted adjustment, S-LAAO was associated with a significantly lower rate of thromboembolism (subdistribution hazard ratio [HR], 0.67; 95% CI, 0.56-0.81; Pu2009<u2009.001), all-cause mortality (HR, 0.88; 95% CI, 0.79-0.97; Pu2009=u2009.001), and the composite end point (HR, 0.83; 95% CI, 0.76-0.91; Pu2009<u2009.001) but not hemorrhagic stroke (subdistribution HR, 0.84; 95% CI, 0.53-1.32; Pu2009=u2009.44). S-LAAO, compared with no S-LAAO, was associated with a lower risk of thromboembolism among patients discharged without anticoagulation (unadjusted rate, 4.2% vs 6.0%; adjusted subdistribution HR, 0.26; 95% CI, 0.17-0.40; Pu2009<u2009.001), but not among patients discharged with anticoagulation (unadjusted rate, 4.1% vs 6.3%; adjusted subdistribution HR, 0.88; 95% CI, 0.56-1.39; Pu2009=u2009.59). Conclusions and Relevance Among older patients with AF undergoing concomitant cardiac surgery, S-LAAO, compared with no S-LAAO, was associated with a lower risk of readmission for thromboembolism over 3 years. These findings support the use of S-LAAO, but randomized trials are necessary to provide definitive evidence.

Association Between a Prolonged PR Interval and Outcomes of Cardiac Resynchronization Therapy: A Report From the National Cardiovascular Data Registry.

Background: A prolonged PR interval is common among cardiac resynchronization therapy (CRT) candidates; however, the association between PR interval and outcomes is unclear, and the data are conflicting. Methods: We conducted inverse probability weighted analyses of 26u2009451 CRT-eligible (ejection fraction ⩽35, QRS ≥120 ms) patients from the National Cardiovascular Data Registry ICD Registry to assess the association between a prolonged PR interval (≥230 ms), receipt of CRT with defibrillator (CRT-D) versus implantable cardioverter defibrillator (ICD), and outcomes. We first tested the association between a prolonged PR interval and outcomes among patients stratified by device type. Next, we performed a comparative effectiveness analysis of CRT-D versus ICD among patients when stratified by PR interval. Using Medicare claims data, we followed up with patients up to 5 years for incident heart failure hospitalization or death. Results: Patients with a PR≥230 ms (15%; n=4035) were older and had more comorbidities, including coronary artery disease, atrial arrhythmias, diabetes mellitus, and chronic kidney disease. After risk adjustment, a PR≥230 ms (versus PR<230 ms) was associated with increased risk of heart failure hospitalization or death among CRT-D (hazard ratio, 1.23; 95% confidence interval, 1.14–1.31; P<0.001) but not ICD recipients (hazard ratio, 1.08; 95% confidence interval, 0.97–1.20; P=0.17) (Pinteraction=0.043). CRT-D (versus ICD) was associated with lower rates of heart failure hospitalization or death among patients with PR<230 ms (hazard ratio, 0.79; 95% confidence interval, 0.73–0.85; P<0.001) but not PR≥230 ms (hazard ratio, 1.01; 95% confidence interval, 0.87–1.17; P=0.90) (Pinteraction=0.0025). Conclusions: A PR≥230 ms is associated with increased rates of heart failure hospitalization or death among CRT-D patients. The real-world comparative effectiveness of CRT-D (versus ICD) is significantly less among patients with a PR≥230 ms in comparison with patients with a PR<230 ms.Background: A prolonged PR interval is common among cardiac resynchronization therapy (CRT) candidates; however, the association between PR interval and outcomes is unclear, and the data are conflicting.nnMethods: We conducted inverse probability weighted analyses of 26u2009451 CRT-eligible (ejection fraction ≤35, QRS ≥120 ms) patients from the National Cardiovascular Data Registry ICD Registry to assess the association between a prolonged PR interval (≥230 ms), receipt of CRT with defibrillator (CRT-D) versus implantable cardioverter defibrillator (ICD), and outcomes. We first tested the association between a prolonged PR interval and outcomes among patients stratified by device type. Next, we performed a comparative effectiveness analysis of CRT-D versus ICD among patients when stratified by PR interval. Using Medicare claims data, we followed up with patients up to 5 years for incident heart failure hospitalization or death.nnResults: Patients with a PR≥230 ms (15%; n=4035) were older and had more comorbidities, including coronary artery disease, atrial arrhythmias, diabetes mellitus, and chronic kidney disease. After risk adjustment, a PR≥230 ms (versus PR<230 ms) was associated with increased risk of heart failure hospitalization or death among CRT-D (hazard ratio, 1.23; 95% confidence interval, 1.14–1.31; P <0.001) but not ICD recipients (hazard ratio, 1.08; 95% confidence interval, 0.97–1.20; P =0.17) ( P interaction=0.043). CRT-D (versus ICD) was associated with lower rates of heart failure hospitalization or death among patients with PR<230 ms (hazard ratio, 0.79; 95% confidence interval, 0.73–0.85; P <0.001) but not PR≥230 ms (hazard ratio, 1.01; 95% confidence interval, 0.87–1.17; P =0.90) ( P interaction=0.0025).nnConclusions: A PR≥230 ms is associated with increased rates of heart failure hospitalization or death among CRT-D patients. The real-world comparative effectiveness of CRT-D (versus ICD) is significantly less among patients with a PR≥230 ms in comparison with patients with a PR<230 ms.nn# Clinical Perspective {#article-title-32}

Comparative Effectiveness of CRT-D Versus Defibrillator Alone in HF Patients With Moderate-to-Severe Chronic Kidney Disease

BACKGROUNDnPatients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT).nnnOBJECTIVESnThis study sought to assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD.nnnMETHODSnWe conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models.nnnRESULTSnAfter risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages.nnnCONCLUSIONSnIn a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates.

Catheter ablation of ventricular tachycardia: Lessons learned from past clinical trials and implications for future clinical trials

Catheter ablation of ventricular tachycardia (VT) has evolved in recent years, especially in patients with ischemic heart disease. Data from prospective studies show that VT catheter ablation reduces the risk of recurrent VT; however, there is a paucity of data on the effect of VT catheter ablation on mortality and patient-centered outcomes such as quality of life. Performing randomized clinical trials of VT catheter ablation can be fraught with challenges, and, as a result, several prior trials of VT catheter ablation had to be stopped prematurely. The main challenges are inability to blind the patient to therapy to obtain a traditional control group, high crossover rates between the 2 arms of the study, patient refusal to participate in trials in which they have an equal chance of receiving a pill vs an invasive procedure, heterogeneity of mapping and ablation techniques as well as catheters and equipment, rapid evolution of technology that may make findings of any long trial less relevant to clinical practice, lack of consensus on what constitutes acute procedural and long-term success, and presentation of patients to electrophysiologists late in the course of their disease. In this article, a panel of experts on VT catheter ablation and/or clinical trials of VT catheter ablation review challenges faced in conducting prior trials of VT catheter ablation and offer potential solutions for those challenges. It is hoped that the proposed solutions will enhance the feasibility of randomized clinical trials of VT catheter ablation.

Progressive ventricular dysfunction among nonresponders to cardiac resynchronization therapy: baseline predictors and associated clinical outcomes.

BACKGROUNDnCardiac resynchronization therapy (CRT) nonresponders have poor outcomes. The significance of progressive ventricular dysfunction among nonresponders remains unclear.nnnOBJECTIVEnWe sought to define predictors of and clinical outcomes associated with progressive ventricular dysfunction despite CRT.nnnMETHODSnWe conducted an analysis of 328 patients undergoing CRT with defibrillator for standard indications. On the basis of 6-month echocardiograms, we classified patients as responders (those with a ≥5% increase in ejection fraction) and progressors (those with a ≥5% decrease in ejection fraction), and all others were defined as nonprogressors. Coprimary end points were 3-year (1) heart failure, left ventricular assist device (LVAD), transplantation, or death and (2) ventricular tachycardia (VT) or ventricular fibrillation (VF).nnnRESULTSnMultivariable predictors of progressive ventricular dysfunction were aldosterone antagonist use (hazard ratio [HR] 0.23; P = .008), prior valve surgery (HR 3.3; P = .005), and QRS duration (HR 0.98; P = .02). More favorable changes in ventricular function were associated with lower incidences of heart failure, LVAD, transplantation, or death (70% vs 54% vs 33%; P < .0001) and VT or VF (66% vs 38% vs 28%; P = .001) for progressors, nonprogressors, and responders, respectively. After multivariable adjustment, progressors remained at increased risk of heart failure, LVAD, transplantation, or death (HR 2.14; P = .0029) and VT or VF (HR 2.03; P = .046) as compared with nonprogressors. Responders were at decreased risk of heart failure, LVAD, transplantation, or death (HR 0.44; P < .0001) and VT or VF (0.51; P = .015) as compared with nonprogressors.nnnCONCLUSIONnPatients with progressive deterioration in ventricular function despite CRT represent a high-risk group of nonresponders at increased risk of worsened clinical outcomes.

Prescription of Guideline-Recommended Implantable Cardioverter Defibrillator and Cardiac Resynchronization Therapy Among Patients Hospitalized With Heart Failure and Varying Degrees of Renal Function

Implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) reduce mortality in many patients with heart failure (HF), but the current use and effectiveness of ICD/CRT in patients with chronic kidney disease (CKD) are uncertain. We examined associations between kidney function and guideline-recommended prescription of ICD/CRT in the Get With The Guidelines-Heart Failure registry, a performance improvement program for hospitalized patients with HF. We compared differences in ICD and CRT prescription between the following categories of estimated glomerular filtration rate (eGFR; mL/min/1.73xa0m2): ≥60, 59 to 30, <30, and dialysis dependent. From 2008 through 2014, 26,286 patients were eligible for ICD or CRT, and 16,123(61%) had an eGFR <60. De novo ICD and CRT prescription in this group was low at 45% and 30.5%, respectively. Compared to patients with eGFR ≥60, patients with eGFR 30 to 59 were more likely to receive an ICD (adjusted odds ratio [aOR] 1.08, 95% confidence intervals [CI] 1.01 to 1.14), whereas dialysis patients were less likely (aOR 0.61, 95% CI 0.5 to 0.76). Worse kidney function was associated with a decreased likelihood of CRT prescription (aOR 0.97 per 10xa0ml/min eGFR decrease, pxa0= 0.03). During the study period, the likelihood of both ICD and CRT prescription increased over time among patients with CKD (ICD aOR 1.12, 95% CI 1.07 to 1.18; CRT aOR 1.14, 95% CI 1.06 to 1.23, per year). Prescription of an ICT/CRT was associated with greater 1-year survival in all eGFR groups. In conclusion, there are significant CKD-based differences in prescription of ICD and CRT in HF. However, given the current state of evidence, it is unclear whether improved prescription of ICD and CRT in the CKD population will result in improvement in outcomes.

Measuring quality in electrophysiology

The evolving healthcare environment demands optimally measured quality of care. Performance measures are increasingly being used for quality improvement, public reporting, and reimbursement determinations. The National Quality Forum has created rigorous criteria for the evaluation of potential performance measures across medical fields. The Heart Rhythm Society has championed the development of four separate electrophysiology (EP)-specific performance measures: implantable cardioverter defibrillator complication rate, cardiac tamponade and/or pericardiocentesis following atrial fibrillation ablation, infection within 180xa0days of a cardiac implantable electronic device implantation, replacement, or revision, and in-person evaluation following a cardiac implantable electronic device implantation. National registries serve a key role in developing performance measures and facilitating quality improvement, particularly as they provide improved granularity and accuracy of data compared with administrative claims data. All performance measures demand continued reassessment as technology and performance gaps change and as unintended consequences may arise.