Durability of left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a form of conduction system pacing. Long-term data on the safety and performance of LBBAP 1 year postdevice implantation has not been well described. METHODS AND RESULTS: Sixty-five patients (49% females) who received LBBAP for bradycardia indications using the SelectSecure 3830 lead (Medtronic) were retrospectively evaluated. Clinical variables were examined. Lead parameters were obtained at implant and during regular follow-up. Mean age of patients was 75.7 ± 10.1 years with left ventricular ejection fraction 59.8 ± 10.4%. Indications for pacing were atrioventricular block 55%, sinus node dysfunction 19%, tachy-brady syndrome 15%, atrioventricular node ablation 8%, and bail out cardiac resynchronization therapy 3%. Mean baseline QRS measured 120 ± 38 ms, paced QRS duration was 138 ± 22ms. Paced QRS narrowed by 24 ms in those with pre-existing left bundle branch block (BBB), increased by 1 ms in those with pre-existing right BBB, and increased by 42 ms in those with no BBB. LBBAP threshold at implant was 0.521 ± 0.153 V at 0.4 ms, and increased to 0.654 ± 0.186 V at 3 months (+26%), 0.707 ± 0.186 V at 6 months (+36%), and 0.772 ± 0.220 V at 12 months (+48%). Patients with left BBB showed the maximum benefit with QRS narrowing 24 ms. Pacing impedance remained unchanged with no procedure-related complications. CONCLUSION: LBBAP is a durable form of conduction system pacing with pacing thresholds remaining relatively stable over 12 months post device implantation. Patients with left BBB display the narrowest paced QRS.

Pulse pressure and prognosis in patients with heart failure with reduced ejection fraction.

BACKGROUND: A high pulse pressure (PP) is associated with adverse cardiovascular (CV) outcomes; however, this relationship may be reversed in patients with heart failure with reduced ejection fraction (HFREF). METHODS: Patients from the WARCEF trial with left ventricular ejection fraction ≤35% were included. PP was divided into tertiles: ≤42, 42-54 and >54 mm Hg. Age and ejection fraction adjusted Kaplan-Meier curves were generated to evaluate the relationship between PP and outcomes [mortality, CV mortality, stroke and HF hospitalizations (HFH)]. Cox proportional hazards models were created incorporating PP as a continuous variable. The interaction of PP with New York Heart Association (NYHA) functional class was examined. Linear and restricted cubic splines were used to study nonlinear association between PP and outcomes. RESULTS: We included 2,299 patients with a mean(±SD) follow-up of 3.5 ± 1.8 years. The lowest tertile of PP (≤42 mm Hg) was associated with significantly higher CV mortality and HFH. Cox proportional hazards models showed a reduction in CV death and HFH with higher PP, with adjusted hazard ratios (HR) of 0.91 (P = 0.02) and 0.93 (P = 0.04) per 10 mm Hg increase in PP. This relationship was more pronounced in subjects with NYHA functional class III-IV. Spline analysis showed that the association between PP and CV mortality and HFH was only seen at PP values lower than 40 mm Hg. CONCLUSIONS: In patients with advanced HFREF, a low PP (<40 mm Hg) portends a worse prognosis, whereas a high PP (>50 mm Hg) predicts a relatively favourable prognosis.

Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure.

BACKGROUND: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. METHODS: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. RESULTS: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. CONCLUSIONS: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.

Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial.

BACKGROUND AND PURPOSE: In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments. METHODS: In the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF≤35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups. RESULTS: Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of <15% (incidence rates: 2.04 versus 0.95/100 patient-years; P=0.009), which more than doubled the adjusted stroke risk (adjusted hazard ratio, 2.125; 95% CI, 1.182-3.818; P=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1.346; 95% CI, 1.044-1.737; P=0.022; P value for interaction=0.04). CONCLUSIONS: In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Impact of Annual Hospital Volume on Outcomes after Left Ventricular Assist Device (LVAD) Implantation in the Contemporary Era.

INTRODUCTION: There are few data in the literature regarding impact of annual hospital volume on outcomes such as mortality and length of stay (LOS) post-LVAD implantation. METHODS: We queried the nationwide inpatient sample from 2008 to 2011 using International Classification of Diseases, 9th Revision procedure code 37.66. We included patients ≥18 years without primary diagnosis of orthotopic heart transplant. Annual volume of LVAD implantation was computed for each hospital. Multivariable hierarchical mixed effect logistic regression models were used to determine predictors of in-hospital mortality and LOS. RESULTS: There were 1749 LVAD implants from 2008 to 2011; patients had a mean age of 55.4 years, and 23% were female. In-hospital mortality decreased from 20.9% in the first tertile (1-22 LVADs/y) to 13.7% in the third tertile (≥35 LVADs/y) of hospital volume. Median LOS decreased from 34 days in the first tertile to 28 days in third tertile of hospital volume. The adjusted odds ratios of the highest tertile of hospital volume in predicting in-hospital mortality and LOS were 0.41 (0.26-0.64, P < .001) and 0.41 (0.23-0.73, P = .003), respectively. Restricted cubic spline analysis showed that a volume threshold of >20 LVADs/year was associated with favorable mortality rates of <10%. CONCLUSIONS: High annual LVAD volume is associated with significantly decreased in-hospital mortality and LOS after LVAD implantation. Center experience is an important determinant of optimal patient outcomes.

Clinical and Echocardiographic Factors Associated With New-Onset Atrial Fibrillation in Heart Failure　- Subanalysis of the WARCEF Trial.

BACKGROUND: Heart failure (HF) patients have a high incidence of new-onset AF. Given the adverse prognostic influence of AF in HF, identifying patients at high risk of developing AF is important. METHODS AND RESULTS: The incidence and factors associated with new-onset AF were investigated in patients in sinus rhythm with reduced LVEF enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Analyses involved clinical factors alone (n=2,219), and clinical plus echocardiographic findings (n=1,125). During 3.5±1.8 years of follow-up, 212 patients (9.6% of total cohort) developed AF. In both samples, new-onset AF was associated with age, male sex, White race, and IHD. Among echocardiographic variables, only LAD predicted AF. On multivariate Cox modeling, age (HR, 1.02; 95% CI: 1.00-1.03, P=0.008), IHD (HR, 1.37; 95% CI: 1.02-1.84, P=0.036) and LAD (HR, 1.48; 95% CI: 1.15-1.91, P=0.003) remained associated with AF onset. Patients with IHD, LAD>4.5 cm and age>50 years had a 2.5-fold higher risk of AF than patients without any of these characteristics (HR, 2.52; 95% CI: 1.72-3.69, P<0.0001). CONCLUSIONS: Age, IHD and LAD independently predict new-onset AF in HF patients in sinus rhythm, at younger age and smaller LAD than generally believed. This information may be useful to risk-stratify HF patients for AF development, allowing close monitoring and possibly early detection. (Circ J 2016; 80: 619-626).

Warfarin and aspirin in patients with heart failure and sinus rhythm.

BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.).

Cardiotoxicity of Anticancer Therapies.

Cardiovascular diseases and cancer continue to remain major causes of mortality and morbidity. However, overall cancer death rates have declined 20% from their peak in 1991. These declines reflect changing patterns in smoking, prevention, earlier diagnosis, and better treatment options in chemotherapy. It is recognized that this improved survival with better cancer therapies has put patients at risk for cardiovascular disease later in life; this may be secondary to risk factors for developing cardiovascular disease or the effect of anticancer therapies. Earlier detection, identifying patients at risk of developing cardiotoxicity, and early institution of treatment are paramount to decreasing morbidity associated with cardiotoxicity. Adverse cardiac effects have been observed and reported with a wide variety of chemotherapeutic agents. Herein we review cardiac effects of some of the common agents used in oncology.

Stroke in heart failure in sinus rhythm: the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial.

BACKGROUND: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. METHODS: We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. RESULTS: Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups. CONCLUSIONS: The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin.

Nocturia, sleep and daytime function in stable heart failure.

BACKGROUND: The aim of this study was to evaluate nocturia severity and nocturia-related differences in sleep, daytime symptoms and functional performance among patients with stable heart failure (HF). METHODS AND RESULTS: In this cross-sectional observational study, we recruited 173 patients [mean age 60.3 ± 16.8 years; female n = 60 (35%); mean left ventricular ejection fraction 32 ± 14.6%] with stable chronic HF from HF disease management programs in the northeastern United States. Participants reported nocturia and completed a 6-minute walk test (6MWT), 1 night of ambulatory polysomnography, and the SF-36 Medical Outcomes Study, Epworth Sleepiness, Pittsburgh Sleep Quality Index, Multidimensional Assessment of Fatigue, and Centers for the Epidemiological Studies of Depression scales. Participants reported 0 (n = 30; 17.3%), 1-2 (n = 87; 50.2%), and ≥3 (n = 56; 32.4%) nightly episodes of nocturia. There were decreases in sleep duration and efficiency, REM and stage 3-4 sleep, physical function, and 6MWT distance and increases in the percentage of wake time after sleep onset, insomnia symptoms, fatigue, and sleepiness across levels of nocturia severity. CONCLUSIONS: Nocturia is common, severe, and closely associated with decrements in sleep and functional performance and increases in fatigue and sleepiness in patients with stable HF.

Atrial fibrillation in patients with heart failure: Role of catheter ablation therapies.

Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia in patients with heart failure (HF). AF in HF patients is associated with worsening of symptoms and also results in a substantial increase in mortality. Although HF patients in sinus rhythm have a better outcome than patients with AF, several randomized studies investigating pharmacological rhythm control versus rate control have shown no advantage of one strategy over the other in terms of patient outcomes. Catheter-based ablation therapy is a newer therapeutic option with a rapidly evolving and changing role in the management of this arrhythmia. In the present review, the authors discuss the epidemiology, pathophysiology and prognostic significance of AF in patients with HF. Exclusively addressed are studies investigating catheter-based ablation for rhythm-control and rate-control therapies in the management of AF in HF patients.

Suppression of ventricular tachycardia with dronedarone: a case report.

UNLABELLED: INTRODUCTION: Dronedarone is a multichannel blocker with similar electrophysiological properties to amiodarone. Dronedarone has not been studied in humans as an agent to suppress ventricular arrhythmias. METHODS: This case report describes the dramatic antiarrhythmic effects of dronedarone in a patient with nonischemic cardiomyopathy and recurrent ventricular tachycardia, which was resistant to multiple antiarrhythmic agents and endocardial catheter ablation. RESULTS: Dronedarone was effective in completely suppressing ventricular tachycardia. CONCLUSION: Further research is needed to establish a potential larger role for dronedarone in controlling ventricular arrhythmias in humans.

Novel collaborative cardiology and maternal fetal medicine practice - experience at the heart and pregnancy program.

PURPOSE: The Heart and Pregnancy Program (HPP) was created to evaluate and manage pregnant women with cardiac conditions simultaneously by cardiology and maternal-fetal medicine (MFM). The objective of our study was to describe the experience at this multidisciplinary program. METHODS: This is a retrospective review of women managed at HPP for over 4.5 years. Subjects were compared based on indication for referral. RESULTS: One hundred and seventy-three women were seen during the time period. Referral indications included cardiac complaints without history of cardiac disease (n = 49, 28.3%), known cardiac disease (n = 96, 55.5%), and other high-risk conditions (n = 28, 16.2%). Those with a known history of cardiac disease were significantly more likely to be nulliparous, and those referred for other high-risk conditions were significantly more likely to be obese. Most women underwent echocardiography (n = 137, 79.2%). For the 140 women who delivered at our hospital, the average gestational age at delivery was 38.8 weeks and the Cesarean rate was 41.4% (n = 58). No significant adverse perinatal outcomes were noted. CONCLUSIONS: In our collaborative cardiology/MFM practice, most pregnant women had known cardiac disease. No significant adverse outcomes were noted. Our experience provides support for creating a joint model of care for pregnant women with cardiac disease.

Sleep disordered breathing, daytime symptoms, and functional performance in stable heart failure.

STUDY OBJECTIVES: To evaluate characteristics of sleep disordered breathing (SDB); clinical and demographic correlates of SDB; and the extent to which SDB explains functional performance and symptoms in stable heart failure patients receiving care in structured HF disease management programs. DESIGN: Cross-sectional, observational study. SETTING: Structured heart failure disease management programs. PARTICIPANTS: 170 stable chronic heart failure patients (mean age = 60.3 +/- 16.8 years; n = 60 [35%] female; n = 50 [29%] African American; left ventricular ejection fraction mean = 32 +/- 14.6). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Full polysomnography was obtained for one night on participants in their homes. Participants completed the 6-minute walk, 3 days of actigraphy, MOS-SF 36, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Multi-Dimensional Assessment of Fatigue Scale, and the Centers for the Epidemiological Studies of Depression Scale. Fifty-one percent had significant SDB; Sixteen (9%) of the total sample had central sleep apnea. Severe SDB was associated with a 4-fold increase in the likelihood of poor self-reported physical function (OR = 4.15, 95%CI = 1.19-14.57) and CSA was associated with low levels of daytime mobility (OR = 4.09, 95%CI = 1.23-13.62) after controlling for clinical and demographic variables. There were no statistically significant relationships between SDB and daytime symptoms or self-reported sleep, despite poorer objective sleep quality in patients with SDB. CONCLUSIONS: Severe SDB is associated with poor physical function in patients with stable HF but not with daytime symptoms or self-reported sleep, despite poorer objective sleep quality in patients with SDB.

Ranolazine--treatment of ventricular tachycardia and symptomatic ventricular premature beats in ischemic cardiomyopathy.

Premature ventricular complexes (PVCs) are a frequent occurrence in the presence of ischemic heart disease. A very high PVC load can be symptomatic or occasionally result in a cardiomyopathy (CMP). Treatment options include pharmacologic agents and radiofrequency ablation (RFA). RFA has been successful in treating PVCs in symptomatic patients or in the presence of unexplained CMP. Ranolazine is a piperazine derivative used for treating chronic stable angina. It also has antiarrhythmic properties. We report a patient with ischemic CMP, symptomatic PVCs, and monomorphic ventricular tachycardia (VT) despite attempts to control symptoms with two antiarrhythmic drugs. Initiation of ranolazine led to marked reduction in PVCs along with control of VT and symptoms.

Is there a role for cardiac magnetic resonance imaging during pregnancy?

Purpose: To assess the role of cardiac magnetic resonance imaging (CMR) for the evaluation and management of women with cardiac disorders in pregnancy and postpartum.Methods: Retrospective record review of women at a university-affiliated, single institution referred for CMR without contrast due to known or suspected cardiac disorders between January 2010 and December 2015. Medical records, echocardiogram and CMR reports were reviewed. Instances where clinical management was changed based on CMR findings were identified.Results: There were 17 peripartum CMR studies performed without contrast in 17 pregnancies from 16 women. Indications for CMR included congenital heart disease (N = 8, 47.1%), Marfan syndrome or strong family history of Marfan syndrome (N = 5, 29.4%), cardiomyopathy (N = 1, 5.9%), cardiac mass (N = 1, 5.9%), persistent dyspnea with a normal echocardiogram (N = 1, 5.9%), and hypertension with suspected aortic root dilation (N = 1, 5.9%). CMR confirmed the echocardiogram diagnosis in eight (47.1%) and improved the diagnosis in five (29.4%). Availability of CMR findings changed the delivery management in 2/17 (11.8%) women. CMR was especially helpful in assessing the size of the aortic root in women at risk for dilation.Conclusions: Although echocardiogram imaging of the heart is considered the first-line method for assessing the maternal cardiac status, CMR can provide information about cardiac anatomy and function in pregnant women with complex cardiac disease or suspected aortic pathology. Management may be changed based on results.

Alcohol use and congestive heart failure: incidence, importance, and approaches to improved history taking.

Alcohol use, abuse, and dependence have the potential to result in alcoholic cardiomyopathy (ACM). This distinct form of congestive heart failure (CHF) is responsible for 21-36% of all cases of nonischemic dilated cardiomyopathy in Western society. Without complete abstinence, the 4-year mortality for ACM approaches 50%. Therefore, accurate and detailed assessment of alcohol use in congestive heart failure is essential. The prevalence of problematic alcohol use is unrecognized by many clinicians. Clinical assessment of alcohol intake is often reduced to a simple question such as, "Do you drink?" Denial and minimization are hallmarks of alcohol abuse, with many individuals underreporting their use of alcohol. Clinicians can overcome these hurdles by implementing practical history taking measures to improve the accuracy of self-reported alcohol use. The data regarding the dangers of ongoing alcohol use in individuals with ACM make attempts to engage individuals in treatment to support abstinence essential. Suggestions for detailed and accurate assessment are discussed.

Association between mortality and implantable cardioverter-defibrillators by aetiology of heart failure: a propensity-matched analysis of the WARCEF trial.

AIMS: There is debate on whether the beneficial effect of implantable cardioverter-defibrillators (ICDs) is attenuated in patients with non-ischaemic cardiomyopathy (NICM). We assess whether any ICD benefit differs between patients with NICM and those with ischaemic cardiomyopathy (ICM), using data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. METHODS AND RESULTS: We performed a post hoc analysis using WARCEF (N = 2293; ICM, n = 991 vs. NICM, n = 1302), where participants received optimal medical treatment. We developed stratified propensity scores for having an ICD at baseline using 41 demographic and clinical variables and created 1:2 propensity-matched cohorts separately for ICM patients with ICD (N = 223 with ICD; N = 446 matched) and NICM patients (N = 195 with ICD; N = 390 matched). We constructed a Cox proportional hazards model to assess the effect of ICD status on mortality for patients with ICM and those with NICM and tested the interaction between ICD status and aetiology of heart failure. During mean follow-up of 3.5 ± 1.8 years, 527 patients died. The presence of ICD was associated with a lower risk of all-cause death among those with ICM (hazard ratio: 0.640; 95% confidence interval: 0.448 to 0.915; P = 0.015) but not among those with NICM (hazard ratio: 0.984; 95% confidence interval: 0.641 to 1.509; P = 0.941). There was weak evidence of interaction between ICD status and the aetiology of heart failure (P = 0.131). CONCLUSIONS: The presence of ICD is associated with a survival benefit in patients with ICM but not in those with NICM.

Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF.

OBJECTIVES: This study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF). BACKGROUND: Despite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established. METHODS: This study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable and a 2-point decrease. To account for a loss to follow-up, data at the baseline and at the 12-month visit were analyzed separately (sensitivity analysis). RESULTS: A total of 1,846 patients were included. In linear regression, MMSE decrease was independently associated with higher baseline MMSE score (p < 0.0001), older age (p < 0.0001), nonwhite race/ethnicity (p < 0.0001), and lower education (p < 0.0001). In logistic regression, CD was independently associated with higher baseline MMSE scores (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.07 to 1.20]; p < 0.001), older age (OR: 1.37; 95% CI: 1.24 to 1.50; p < 0.001), nonwhite race/ethnicity (OR: 2.32; 95% CI: 1.72 to 3.13 for black; OR: 1.94; 95% CI: 1.40 to 2.69 for Hispanic vs. white; p < 0.001), lower education (p < 0.001), and New York Heart Association functional class II or higher (p = 0.03). Warfarin and other medications were not associated with CD. Similar trends were seen in the sensitivity analysis (n = 1,439). CONCLUSIONS: CD in HF is predicted by baseline cognitive status, demographic variables, and NYHA functional class. The possibility of intervening on some of its predictors suggests the need for the frequent assessment of cognitive function in patients with HF. (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF]; NCT00041938).

Risk of thromboembolism in heart failure: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: In patients with heart failure, rates of clinically apparent stroke range from 1.3% to 3.5% per year. Little is known about the incidence and risk factors in the absence of atrial fibrillation. In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), 2521 patients with moderate heart failure were randomized to receive amiodarone, implanted cardioverter-defibrillators (ICDs), or placebo. METHODS AND RESULTS: We determined the incidence of stroke or peripheral or pulmonary embolism in patients with no history of atrial fibrillation (n=2114), predictors of thromboembolism and the relationship to left ventricular ejection fraction. Median follow-up was 45.5 months. Kaplan-Meier estimates (95% CIs) for the incidence of thromboembolism by 4 years were 4.0% (3.0% to 4.9%), with 2.6% (1.1% to 4.1%) in patients randomized to amiodarone, 3.2% (1.8% to 4.7%) in patients randomized to ICD, and 6.0% (4.0% to 8.0%) in patients randomized to placebo (approximate rates of 0.7%, 0.8%, and 1.5% per year, respectively). By multivariable analysis, hypertension (P=0.021) and decreasing left ventricular ejection fraction (P=0.023) were significant predictors of thromboembolism; treatment with amiodarone or ICD treatment was a significant predictor of thromboembolism-free survival (P=0.014 for treatment effect; hazard ratio [95% CI] versus placebo, 0.57 [0.33 to 0.99] for ICD; 0.44 [0.24 to 0.80] for amiodarone). Inclusion of atrial fibrillation during follow-up in the multivariable model did not affect the significance of treatment assignment as a predictor of thromboembolism. CONCLUSIONS: In the SCD-HeFT patient cohort, which reflects contemporary treatment of patients with moderately symptomatic systolic heart failure, patients experienced thromboembolism events at a rate of 1.7% per year without antiarrhythmic therapy. Those treated with amiodarone or ICDs had lower risk of thromboembolism than those given placebo. Hypertension at baseline and lower ejection fraction were independent predictors of risk.