The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling.

AIMS: Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group. METHODS AND RESULTS: Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing ≤90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV ≥97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV ≥97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume. CONCLUSION: In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing ≥97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271.

QRS axis and the benefit of cardiac resynchronization therapy in patients with mildly symptomatic heart failure enrolled in MADIT-CRT.

BACKGROUND: Mildly symptomatic heart failure (HF) patients derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) as shown in MADIT-CRT. The presence of QRS axis deviation may influence response to CRT-D. The objective of this study was to determine whether QRS axis deviation will be associated with differential benefit from CRT-D. METHODS: Baseline electrocardiograms of 1,820 patients from MADIT-CRT were evaluated for left axis deviation (LAD: quantitative QRS axis -30 to -90) or right axis deviation (RAD: QRS axis 90-180) in left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific interventricular conduction delay QRS morphologies. The primary endpoints were the first occurrence of a HF event or death and the separate occurrence of all-cause mortality as in MADIT-CRT. RESULTS: Among LBBB patients, those with LAD had a higher risk of primary events at 2 years than non-LAD patients (20% vs 16%; P = 0.024). The same was observed among RBBB patients (20% vs 10%; P = 0.05) but not in IVCD patients (22% vs 23%; P = NS). RAD did not convey any increased risk of the primary combined endpoint in any QRS morphology subgroup. When analyzing the benefit of CRT-D in the non-LBBB subgroups, there was no significant difference in hazard ratios for CRT-D versus ICD for either LAD or RAD. However, LBBB patients without LAD showed a trend toward greater benefit from CRT therapy than LBBB patients with LAD (HR for no LAD: 0.37, 95% CI: 0.26-0.53 and with LAD: 0.54, 95% CI: 0.36-0.79; P value for interaction = 0.18). CONCLUSIONS: LAD in non-LBBB patients (RBBB or IVCD) is not associated with an increased benefit from CRT. In LBBB patients, those without LAD seem to benefit more from CRT-D than those with LAD.

QRS fragmentation and the risk of sudden cardiac death in MADIT II.

BACKGROUND: QRS fragmentation (fQRS) has been reported as a useful ECG parameter in predicting mortality in high-risk postinfarction patients. Its prognostic value for sudden cardiac death (SCD) and ventricular arrhythmias in ischemic cardiomyopathy (ICM) remains unknown. METHODS: MADIT II enrollment 12-lead ECGs were analyzed for fQRS defined as RSR' patterns (≥1 R' or notching of S or R wave) in patients with a normal QRS duration and >2 notches on the R or S wave in patients with abnormal QRS duration, present in 2 contiguous leads. Exclusion criteria included a paced rhythm and an uninterpretable or incomplete ECG. Study endpoints included SCD, SCD or appropriate implantable cardioverter defibrillator (ICD) shock, and total mortality (TM). RESULTS: Of the 1,232 ECGs reviewed, 1,040 were of suitable quality for fQRS analysis. QRS fragmentation was found in 33% of patients in any leads, in 10% of patients in anterior leads, in 8% of patients in lateral leads and in 21% of patients in inferior leads. Anterior and lateral location of QRS fragmentation was not associated with follow-up events. Inferior location of fQRS was found to be predictive of SCD/ICD shock (hazard ratio [HR] 1.46, P = 0.032), SCD (HR 2.05, P = 0.007), and TM (HR 1.44, P = 0.036). This association was driven primarily by the increase in events found in LBBB patients: SCD/ICD shock (HR 2.05, P = 0.046), SCD (HR 4.24, P = 0.002), and TM (HR 2.82, P = 0.001). CONCLUSIONS: Fragmented QRS, especially identified in inferior leads, is predictive of SCD, SCD or appropriate ICD shock, and all-cause mortality in patients with ICM. Identifying inferior fQRS in patients with LBBB is of particular prognostic significance and should reinforce the use of ICD therapy in this high-risk group.

Risk of mortality for ventricular arrhythmia in ambulatory LVAD patients.

BACKGROUND: There are limited data regarding the incidence and prognostic significance of ventricular arrhythmias (VA) in ambulatory continuous flow left ventricular assist device (LVAD) patients. METHODS: Sixty-one consecutive patients from November 1, 2006 through December 31, 2010 with an LVAD and implantable cardioverter defibrillator that survived to discharge from the LVAD implantation admission were studied. Follow-up began from date of discharge with both devices in situ and ended with death, transplant, on June 1, 2011. Pre-LVAD VA history was related to the primary endpoints of post-LVAD VA, mortality, and the combined endpoint of post-LVAD VA/mortality. RESULTS: During a mean follow-up of 622 days 19 patients (31%) experienced VA (14 episodes of VT, 5 episodes of VF). Pre-LVAD VA was predictive of post-LVAD VA (hazard ratio [HR] 2.91, P = 0.026) and the combined post-LVAD VA/mortality endpoint (HR 2.70, P = 0.021) but only displayed a nonsignificant association with mortality (HR 2.30, P = 0.11). In multivariate analysis, pre-LVAD VA remained a significant predictor of post-LVAD VA (HR 2.84, P = 0.03) and the combined post-LVAD VA/mortality endpoint (HR 2.65, P = 0.025). Post-LVAD VA was the strongest univariate predictor of mortality (HR 13.92, P < 0.001) and remained so after multivariate adjustment (HR 9.69, P = 0.001). Post-LVAD VA occurred at a mean of 1 year from mortality events with 45% within 1 month. CONCLUSIONS: Pre-LVAD VA is a significant predictor of post-LVAD VA but not of mortality. VA in the continuous flow LVAD population carries a significant risk of mortality often within the first month.

Congenital long and short QT syndromes.

Congenital long and short QT syndromes are familial arrhythmias characterized by derangement of repolarization and a high risk of sudden cardiac death due to ventricular tachyarrhythmias. With growing understanding of these syndromes in both the medical and lay communities, diagnostic and therapeutic difficulties are increasingly faced by health care providers. Modern genomics has determined the mechanism of arrhythmia induction in these patients, resulting in specific medical therapies and improved risk stratification. This paper reviews the common presentations, genetic etiology, basic evaluation, risk stratification, and therapeutic approach for both syndromes. Particular attention is paid to the effect of the individual syndrome on the cardiac action potential and its correlate the surface 12 lead ECG. In conclusion, patients with long and short QT syndromes are at risk for sudden death, with accurate diagnosis, risk stratification, and resulting appropriate therapy favorably altering their outcome.

The downside of right ventricular apical pacing.

The right ventricular (RV) apex has been the standard pacing site since the development of implantable pacemaker technology. Although RV pacing was initially only utilized for the treatment of severe bradyarrhythmias usually due to complete heart block, today the indications for and implantation of RV pacing devices is dramatically larger. Recently, the adverse effects of chronic RV apical pacing have been described including an increased risk of heart failure and death. This review details the detrimental effects of RV apical pacing and their shared hemodynamic pathophysiology. In particular, the role of RV apical pacing induced ventricular dyssynchrony is highlighted with a specific focus on differential outcome based upon QRS morphology at implant.

Genetics of sudden cardiac death.

Advances in genetic testing technology have led to a proliferation of new genetic tests and accelerated developments in the field of cardiovascular genetic medicine. These advances enhance presymptomatic diagnosis and can establish a definitive molecular diagnosis for symptomatic patients at risk for sudden cardiac death. Most importantly, genotype-phenotype correlations can add important information for predicting outcome and selecting treatment for patients with inherited arrhythmic disorders. This paper reviews the current data regarding genotype-phenotype correlations and the role of clinical genetic testing in diagnosis, prognosis, and management of inheritable disorders leading to sudden cardiac death.

Single Day Observational Experience at High Volume Ablation Programs: What is the Impact to Practicing Electrophysiologists?

INTRODUCTION: Significant improvements in catheter technology, electro-anatomic (EA) mapping and techniques to reduce fluoroscopy during radiofrequency ablation (RFA) of atrial fibrillation (AF) are on-going.However, few educational opportunities are available post fellowship for Electrophysiologists (EPs) to understand and integrate them into their practice, preventing wide spread adoption. The impact of observational learning for adoption of new technologies and techniques in the field of cardiac electrophysiology has not been studied. We sought to report the impact of a visit to a high-volume center with experience in new technologies and fluoroscopy reductionto the clinical practice of EPs. METHODS: Between 8/2014 and 10/2017 a total of 150 EPs visited 3 hospitals that perform a high volume of AF RFAs. EPs observed a minimum of 4 RFAs, primarily AF. AF RFAs were performed without fluoroscopy, using Carto 3 Version 4 (Biosense Webster) and intracardiac Echocardiography. There was ample interaction and discussion between hosting and visiting EP. RESULTS: 73 EPs (48.6% of visitors) completed an electronic survey after the visit. The majority reported a significant reduction in fluoroscopy (>50%) and procedure (>20%).68% adopted a rigorous workflow and reported an increase in their confidence level with intracardiac echo (79%), continuous mapping (52%) and the Visitag module (61%). CONCLUSIONS: Observational experience can have an immense impact on the clinical practice of EPs. Further effort should be devoted to such programs and to study in a more systematic way their ultimate impact on patient care.

Alveolar epithelial cell-macrophage interactions affect oxygen-stimulated interleukin-8 release.

Interactions of alveolar macrophages with respiratory epithelium may play a key role in hyperoxia-induced lung inflammation. We studied the effect of cell-cell contact with epithelial cells in hyperoxia on macrophages' secretion of interleukin-8 (IL-8). A549 pulmonary epithelial cells and THP-1 monocyte/macrophage cells were cultured either singly, in contact coculture, or prevented from contact by a porous membrane, and exposed to oxygen or room air. Phorbol-12-myristate-13-acetate-(PMA)-treated THP-1 cells were exposed to the same conditions. Neither cell line cultured alone produced appreciable amounts of IL-8 in hyperoxia. Contact cocultures exposed to hyperoxia produced increased IL-8, while in the noncontact coculture it was attenuated. Both cell-cell contact and PMA increased THP-1 cell CD54 expression. Intracellular IL-8 production was increased in contact cocultured, hyperoxia exposed THP-1 cells, while the A549 sample showed no change. Increased IL-8 mRNA expression was not demonstrated in cocultured, hyperoxic exposed THP-1 cells, suggesting nontranscriptional regulation of IL-8 protein levels. Contact with epithelial cells appears to potentiate macrophage responses to hyperoxia.

Review of complementary and alternative medical treatment of arrhythmias.

Complementary and alternative medical (CAM) therapies are commonly used by patients for the treatment of medical conditions spanning the full spectrum of severity and chronicity. The use of alternative remedies, both herbal and others, for conditions lacking effective medical treatment, is on the increase. Included within this categorization, arrhythmic disease-absent effective catheter-based therapy or with medical therapy limited by the toxicities of contemporary antiarrhythmic agents is frequently managed by patients with CAM therapies without their practitioner's knowledge and in the face of potential herb-drug toxicities. This study reviews 9 CAM therapies: 7 individual herbal therapies along with acupuncture and yoga that have been studied and reported as having an antiarrhythmic effect. The primary focuses are the proposed antiarrhythmic mechanism of each CAM agent along with interactions between the CAM therapies and commonly prescribed medical therapy for arrhythmia patients. We stress persistent vigilance on the part of the provider in discussing the use of herbal or other CAM agents within the arrhythmia population.

Comparison of age (<75 Years versus ≥75 Years) to risk of ventricular tachyarrhythmias and implantable cardioverter defibrillator shocks (from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).

There are limited data regarding the effect of age on the risk of ventricular tachyarrhythmias (VTAs). The present study was designed to compare the risk for VTAs in young and older patients with left bundle branch block (LBBB) and mildly symptomatic heart failure who receive device therapy. The risk of the first ventricular tachycardia (VT) or ventricular fibrillation (VF) event and the risk of first appropriate implantable cardioverter defibrillator (ICD) shock was compared between young (<75 years, n = 1,037) and older (≥75 years, n = 227) patients with LBBB enrolled in Multicenter Automatic Implantation Trial with Cardiac Resynchronization Therapy. The cumulative incidence of a first VTA through 2 years of follow-up was significantly lower in older patients than in younger patients. Multivariate analysis showed that older patients experienced a significantly lower risk of VT/VF (hazard ratio 0.38, 95% confidence interval 0.22 to 0.64, p <0.001) and a significantly lower risk of appropriate ICD shocks (hazard ratio 0.37, 95% confidence interval 0.17 to 0.82, p = 0.014) compared with younger patients. Each increasing decade of life was associated with a 19% (p = 0.002) and 22% (p = 0.018) reduction in the risk of VT/VF and appropriate ICD shocks, respectively. The lower risk of VT/VF and appropriate ICD shocks in older patients was evident in patients implanted with an ICD only and in those implanted with a cardiac resynchronization therapy with defibrillator. In conclusion, in patients with LBBB and mild symptoms of heart failure, aging is associated with a significant decrease in the incidence of VT/VF and ICD shocks.

Predictors of spontaneous reverse remodeling in mild heart failure patients with left ventricular dysfunction.

BACKGROUND: There are limited data regarding factors associated with spontaneous left ventricular reverse remodeling (S-LVRR) among mildly symptomatic heart failure (HF) patients and its prognostic implications on clinical outcomes. METHODS AND RESULTS: Best subsets logistic regression analysis was used to identify factors associated with S-LVRR (defined as ≥15% reduction in left ventricular end-systolic volume at 1-year of follow-up) among 612 patients treated with internal cardioverter defibrillator-only therapy in Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) and to create a score for the prediction of S-LVRR. Cox proportional hazards regression modeling was used to assess the clinical outcome of all internal cardioverter defibrillator-only patients (n=714) with a high S-LVRR score. S-LVRR occurred in 25% of internal cardioverter defibrillator-only patients. Predictors of S-LVRR included systolic blood pressure≥140 mm Hg, serum creatinine<1.0 mg/dL, QRS 130 to 160 ms, and nonischemic cardiomyopathy. Multivariate analysis showed that each 1-point increment in S-LVRR score (range, 0-7) was associated with an 11% (P=0.019) reduction in the risk of HF or death. Treatment with cardiac resynchronization therapy was associated with a significant reduction in the risk of HF or death only among internal cardioverter defibrillator-treated patients with a low (Q1-3) S-LVRR score (hazard ratio=0.55; P<0.001), but not among those with a higher (Q4) score (hazard ratio=1.06; P=0.72). CONCLUSIONS: Our data suggest that approximately one quarter of mild HF patients eligible for biventricular pacing experience S-LVRR. Combined assessment of clinical factors associated with S-LVRR can be used to identify mild HF patients with a low risk for clinical events without cardiac resynchronization therapy intervention. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

PR interval identifies clinical response in patients with non-left bundle branch block: a Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy substudy.

BACKGROUND: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), patients with non-left bundle branch block (LBBB; including right bundle branch block, intraventricular conduction delay) did not have clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D). We hypothesized that baseline PR interval modulates clinical response to CRT-D therapy in patients with non-LBBB. METHODS AND RESULTS: Non-LBBB patients (n=537; 30%) were divided into 2 groups based on their baseline PR interval as normal (including minimally prolonged) PR (PR <230 ms) and prolonged PR (PR ≥230 ms). The primary end point was heart failure or death. Separate secondary end points included heart failure events and all-cause mortality. Cox proportional hazards regression models were used to compare risk of end point events by CRT-D to implantable cardioverter defibrillator therapy in the PR subgroups. There were 96 patients (22%) with a prolonged PR and 438 patients (78%) with a normal PR interval. In non-LBBB patients with a prolonged PR interval, CRT-D treatment was associated with a 73% reduction in the risk of heart failure/death (hazard ratio, 0.27; 95% confidence interval, 0.13-0.57; P<0.001) and 81% decrease in the risk of all-cause mortality (hazard ratio, 0.19; 95% confidence interval, 0.13-0.57; P<0.001) compared with implantable cardioverter defibrillator therapy. In non-LBBB patients with normal PR, CRT-D therapy was associated with a trend toward an increased risk of heart failure/death (hazard ratio, 1.45; 95% confidence interval, 0.96-2.19; P=0.078; interaction P<0.001) and a more than 2-fold higher mortality (hazard ratio, 2.14; 95% confidence interval, 1.12-4.09; P=0.022; interaction P<0.001) compared with implantable cardioverter defibrillator therapy. CONCLUSIONS: The data support the use of CRT-D in MADIT-CRT non-LBBB patients with a prolonged PR interval. In non-LBBB patients with a normal PR interval, implantation of a CRT-D may be deleterious. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov; Unique Identifier: NCT00180271.

Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure.

BACKGROUND: There are limited data on the prognostic implications of brain natriuretic peptide (BNP) assessment in patients with mildly symptomatic heart failure (HF) who receive cardiac resynchronization therapy with a defibrillator (CRT-D). METHODS AND RESULTS: The effect of elevated baseline and 1-year BNP levels (dichotomized at the upper tertile BNP of 120 pg/mL) on the risk of HF or death was assessed among the cohort of 1197 patients with baseline BNP data enrolled in MADIT (Multicenter Automated Defibrillator Implantation Trial)-CRT. Elevated baseline BNP was associated with a significant 68% (P=0.007) and 58% (P=0.02) increase in the risk of HF or death among MADIT-CRT patients allocated to CRT-D and implantable cardioverter defibrillator-only therapy, respectively. At 1 year of follow-up, patients allocated to CRT-D displayed significantly greater reductions in BNP (26% reduction) levels compared with implantable cardioverter defibrillator-only patients (8% increase; P=0.005). Patients with CRT-D in whom 1-year BNP levels were reduced or remained low experienced a significantly lower risk of subsequent HF or death as compared with patients in whom 1-year BNP levels were high. Similarly, the echocardiographic response to CRT-D was highest among those who maintained low BNP levels or in whom BNP level at 1-year was reduced. CONCLUSIONS: Our findings suggest that assessment of baseline and follow-up BNP provides important prognostic implications in patients with mildly symptomatic HF who receive CRT.

Atrioventricular delay programming and the benefit of cardiac resynchronization therapy in MADIT-CRT.

BACKGROUND: The optimal atrioventricular pacing delay (AVD) in cardiac resynchronization therapy (CRT) remains to be determined. OBJECTIVE: To determine whether programming CRT devices to short AVD (S-AVD) will improve clinical response secondary to greater reductions in dyssynchrony. METHODS: The study population comprised 1235 patients with left bundle branch block enrolled in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy (MADIT-CRT). We assessed the relationship between AVD and outcomes. Patients programmed to S-AVD (median value of <120 ms; n = 337) vs long AVD (L-AVD; ≥120 ms; n = 390) were assessed for the end points of heart failure (HF) or death, death alone, and echocardiographic response to the CRT at 1-year follow-up. Outcomes were also compared to the left bundle branch block implantable cardioverter-defibrillator-only group (n = 508). RESULTS: Multivariate analysis showed that patients programmed to S-AVD experienced a significant 33% (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.44-0.85; P = .037) reduction in the risk of HF or death and a 47% (HR 0.53; 95% CI 0.29-0.94; P = .031) reduction in death alone as compared with those programmed to L-AVD. Patients with CRT-programmed S-AVD and L-AVD experienced 63% (HR 0.37; 95% CI 0.26-0.53; P < .001) and 46% (HR 0.54; 95% CI 0.31-0.96; P < .001) reduction, respectively, in the risk of HF or death compared to patients with implantable cardioverter-defibrillator alone. At 1 year of follow-up, S-AVD vs L-AVD was associated with a greater reduction in left ventricular end-systolic volume (34.2% vs 30.8%; P = .002) along with a significantly greater improvement in dyssynchrony (22.3% vs 9.4%; P = .036). CONCLUSIONS: Our findings indicate that in MADIT-CRT programming, the CRT AVD <120 ms was associated with a greater clinical and echocardiographic response to CRT.

Sex-related differences in patients' responses to heart failure therapy.

Men and women with heart failure display important differences in clinical characteristics that might affect their responses to pharmacological and nonpharmacological therapies. In women, heart failure is associated with a higher frequency of hypertension, nonischemic cardiomyopathy and left bundle branch block than in men. Subgroup analyses of data from randomized clinical trials suggest that these differences result in a differential response to heart failure therapies, including a somewhat better response to ß-blockers, a worse prognosis with digoxin therapy, and a lower survival benefit with implantable cardioverter-defibrillators in women. Importantly, female patients with heart failure also derive significantly greater improvements in cardiac volumes from cardiac resynchronization therapy than do male patients, and this treatment is associated with reduced risks of all-cause mortality and heart failure events among women with mild symptoms. These data suggest that sex-related differences might exist in response to both medical and device therapies for patients with heart failure.

Baseline functional capacity and the benefit of cardiac resynchronization therapy in patients with mildly symptomatic heart failure enrolled in MADIT-CRT.

BACKGROUND: Mildly symptomatic heart failure (HF) patients were shown to derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. However, the relationship between functional capacity (FC) and CRT-D benefit in the trial was not assessed. OBJECTIVE: To evaluate the association between FC and response to CRT-D in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. METHODS: We evaluated the association between preimplantation FC and the benefit of CRT-D in reducing the risk of HF or death in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. Functional status was assessed by a 6-minute walk test (6MWT), dichotomized at the median value as poor (<350 m) or good (≥350 m). RESULTS: Implantable cardioverter-defibrillator-only patients with a poor FC had an adjusted 73% increased risk for HF or death (P <.001) and a 2.4-fold (P = .001) increased risk for all-cause mortality. CRT-D therapy was associated with 63% (P <.001) and 44% (P <.001) reductions in the risk of HF or death among left bundle branch block patients with a poor FC and a good FC, respectively (P for interaction = .10). Among left bundle branch block patients with a poor FC, CRT-D was also associated with a significant reduction in the risk of all-cause mortality (hazard ratio 0.52; P = .015) whereas the survival benefit of CRT-D was not observed among those who had a higher FC at enrollment (hazard ratio 1.01; P = .98; P for interaction = .10). CONCLUSIONS: Poor FC is a strong independent predictor for mortality and HF events in patients with mildly symptomatic HF. Left bundle branch block patients with poor baseline FC derive a pronounced benefit from CRT-D, manifest by a significant reduction in mortality.

Prognostic significance of QRS duration and morphology.

QRS duration and morphology, evaluated via a standard 12-lead electrocardiogram (ECG), represent an opportunity to derive useful prognostic information regarding the risk of subsequent cardiac events or therapeutic outcomes. Prolonged QRS duration, and the presence of intraventricular conduction abnormalities, usually indicate the presence of changes in the myocardium due to underlying heart disease. Prolonged QRS duration is often associated with depressed ejection fraction or enlarged left ventricular volumes, but several studies have demonstrated that this simple ECG measure provides independent prognostic value, after adjusting for relevant clinical covariates. Post-infarction patients with prolonged QRS duration have a significantly increased risk of mortality, although data associating QRS prolongation specifically with sudden death is less supportive. In non-ischemic cardiomyopathy, there is no evidence that QRS duration has prognostic significance in predicting mortality or sudden death. Prolonged QRS duration, and especially presence of left bundle branch block, seems to predict a benefit from cardiac resynchronization therapy in both ischemic and non-ischemic cardiomyopathy patients. Therefore, QRS duration and morphology should not only be considered a predictor of death or sudden death in patients after myocardial infarction, and in those suspected of coronary artery disease, but also as a predictor of benefit from cardiac resynchronization therapy in patients with heart failure, whether of an ischemic or non-ischemic origin.

Non-pharmacologic management of atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice today. Contemporary medical treatment options include atrioventricular nodal blocking agents to control heart rates during AF, antiarrhythmic drugs aimed at maintaining normal sinus rhythm, and anticoagulation therapies to reduce stroke risk. Invasive treatment of AF has emerged because of the toxicities and lack of long-term efficacy of available antiarrhythmic medications along with the lack of improvement in symptoms for rate-controlled patients. The investigators review the evolution of the current catheter-delivered AF procedures, starting with surgical maze up to and including left atrial appendage occlusion devices. Individual catheter ablation targets, anatomic and electrophysiologic, are discussed, with a particular focus on the use of an incremental ablation target strategy dependent on the type of AF being treated. In conclusion, the history of invasive AF therapy provides a basic understanding of contemporary ablation strategies and a backdrop for the cutting-edge rhythm and stroke prevention therapies of today.

Wearable defibrillator in congenital structural heart disease and inherited arrhythmias.

Patients with congenital structural heart disease (CSHD) and inherited arrhythmias (IAs) are at high risk of ventricular tachyarrhythmias and sudden cardiac death. The present study was designed to evaluate the short- and long-term outcomes of patients with CSHD and IA who received a wearable cardioverter-defibrillator (WCD) for the prevention of sudden cardiac death. The study population included 162 patients with CSHD (n = 43) and IA (n = 119) who were prospectively followed up in a nationwide registry from 2005 to 2010. The mortality rates were compared using Kaplan-Meier survival analysis. The mean age of the study patients was 38 ± 27 years. The patients with CSHD had a greater frequency of left ventricular dysfunction (ejection fraction <30%) than did the patients with IA (37% vs 5%, respectively; p = 0.002). The predominant indication for WCD was pending genetic testing in the IA group and transplant listing in the CSHD group. Compliance with the WCD was similar in the 2 groups (91%). WCD shocks successfully terminated 3 ventricular tachyarrhythmias in the patients with IA during a median follow-up of 29 days of therapy (corresponding to 23 appropriate WCD shocks per 100 patient-years). No arrhythmias occurred in the patients with CSHD during a median follow-up of 27 days. No patients died while actively wearing the WCD. At 1 year of follow-up, the survival rates were significantly lower among the patients with CSHD (87%) than among the patients with IA (97%, p = 0.02). In conclusion, our data suggest that the WCD can be safely used in high-risk adult patients with IA and CSHD. Patients with IA showed a greater rate of ventricular tachyarrhythmias during therapy but significantly lower long-term mortality rates.