Transcatheter Left Ventricular Restoration in Patients With Heart Failure.

BACKGROUND: Left ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in patients with heart failure with reduced ejection fraction. The AccuCinch Transcatheter Left Ventricular Restoration system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to the basal free wall radius. We evaluated the echocardiographic and clinical outcomes following transcatheter left ventricular restoration. METHODS AND RESULTS: We analyzed 51 heart failure patients with a left ventricular ejection fraction between 20% and 40%, with no more than 2+ mitral regurgitation treated with optimal medical therapy, who subsequently underwent transcatheter left ventricular restoration. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire scores, and 6-minute walk test distances were measured at baseline through 12 months. Primary analysis end point was change in end-diastolic volume at 12 months compared with baseline. Patients (n = 51) were predominantly male (86%) with a mean age of 56.3 ± 13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% decrease in the free wall arc length. At 12 months, the LV end-diastolic volume decreased by 33.6 ± 34.8 mL (P < .01), with comparable decreases in the LV end-systolic volume. These decreases were associated with significant improvements in the overall Kansas City Cardiomyopathy Questionnaire score (16.4 ± 18.7 points; P < .01) and 6-minute hall walk test distance (45.9 ± 83.9 m; P < .01). There were no periprocedural deaths; through the 1-year follow-up, 1 patient died (day 280) and 1 patient received a left ventricular assist device (day 13). CONCLUSIONS: In patients with heart failure with reduced ejection fraction without significant mitral regurgitation receiving optimal medical therapy, the AccuCinch System resulted in decreases of LV volume, as well as improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).

Evaluation of Medicare Claims for the Development of Heart Failure Diagnostics.

BACKGROUND: Although claims data provide a large and efficient source of clinical events, validation is needed prior to use in heart failure (HF) diagnostic development. METHODS AND RESULTS: Data from the Multisensor Chronic Evaluations in Ambulatory Heart Failure Patients (MultiSENSE) study, used to create the HeartLogic HF diagnostic, were linked with fee-for-service (FFS) Medicare claims. Events were matched by patient ID and date, and agreement was calculated between claims primary HF diagnosis codes and study event adjudication. HF events (HFEs) were defined as inpatient visits, or outpatient visits with intravenous decongestive therapy. Diagnostic performance was measured as HFE-detection sensitivity and false-positive rate (FPR). Linkage of 791 MultiSENSE subjects returned 320 FFS patients with an average follow-up duration of 0.94 years. Although study and claims deaths matched exactly (n = 14), matching was imperfect between study hospitalizations and acute inpatient claims events. Of 239 total events, 165 study hospitalizations (69%) matched inpatient claims events, 28 hospitalizations matched outpatient claims events (12%), 14 hospitalizations were study-unique (6%), and 32 inpatient events were claims-unique (13%). Inpatient HF classification had substantial agreement with study adjudication (κ = 0.823). Diagnostic performance was not different between claims and study events (sensitivity = 75.6% vs 77.6% and FPR = 1.539 vs 1.528 alerts/patient-year). HeartLogic-detected events contributed to > 90% of the HFE costs used for evaluation. CONCLUSIONS: Acceptable event matching, good agreement of claims diagnostic codes with adjudication, and equivalent diagnostic performance support the validity of using claims for HF diagnostic development.

Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) - Phase I Evaluation of the Integration and Safety of the HeartLogic Multisensor Algorithm in Patients With Heart Failure.

BACKGROUND: Patients with heart failure (HF) and reduced ejection fraction suffer from a relapsing and remitting disease course, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multisensor index and alerts in HF care. METHODS: The Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HF and reduced ejection fraction (<35%), New York Heart Association functional class II-III symptoms, implanted with a cardiac resynchronization therapy-defibrillator or and implantable cardioverter defibrillator, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (brain natriuretic peptide [BNP] of ≥150 pg/mL or N-terminal pro-BNP [NT-proBNP] of ≥600 pg/mL). This phase included the development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety. RESULTS: The mean age of participants was 67 years, 68% were men, 81% were White, and 61% had a HF hospitalization in prior 12 months. During follow-up, there were 585 alert cases with an average of 1.76 alert cases per patient-year. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five serious adverse events (0.015 per patient-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (P < .001). CONCLUSIONS: HeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03237858).

Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

In heart failure (HF) patients, remote monitoring using implantable devices may be used to predict and reduce HF exacerbations and mortality. Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. A systematic review and meta-analysis of RCTs testing remote monitoring versus standard of care for management of HF patients was performed. Primary endpoints were all-cause mortality and a composite of cardiovascular (CV) and HF hospitalizations. Rate ratios (RRs) and 95% confidence intervals (CI) were calculated. A secondary analysis tested for heterogeneity of treatment effect (HTE) comparing right ventricular/pulmonary pressure monitoring versus impedance-based monitoring on hospitalization. A regression analysis was performed using the mean follow-up time as the moderator on each primary endpoint. Eleven RCTs (n = 6196) were identified with a mean follow-up of 21.9 months. The mean age and reported ejection fraction were 64.1 years and 27.7%, respectively. Remote monitoring did not reduce mortality (RR 0.89 [95% CI 0.77, 1.03]) or the composite of CV and HF hospitalizations (RR 0.98 [0.81, 1.19]). Subgroup analysis found significant HTE for hospitalizations between those studies that used right ventricular/pulmonary pressure monitoring versus impedance-based monitoring (I2 = 87.1%, chi2 = 7.75, p = 0.005). Regression analysis found no relationship between the log rate ratio of remote monitoring's effect on mortality, CV hospitalization or HF hospitalization, and mean follow-up time. Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations, which will need to be explored in future studies.

Letter to the editor to update the article "Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials".

Our recently published systematic review and meta-analysis of heart failure (HF) remote monitoring using implantable devices (Hajduczok et al. in HF Reviews 1-20, 1) has been updated to reflected new data from the GUIDE-HF trial (Lindenfeld et al. in Lancet 398(10304):991-1001, 2). Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. With the inclusion of the data from 1000 patients followed for 12 months in GUIDE-HF, our conclusions remain unchanged: Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations.

Ambulatory Monitoring of Heart Sounds via an Implanted Device Is Superior to Auscultation for Prediction of Heart Failure Events.

BACKGROUND: We compared the relationship between the third heart sound (S3) measured by an implantable cardiac device (devS3) and auscultation (ausS3) and evaluated their prognostic powers for predicting heart failure events (HFEs). METHODS AND RESULTS: In the MultiSENSE study, devS3 was measured daily with continuous values, whereas ausS3 was assessed at study visits with discrete grades. They were compared among patients with and without HFEs at baseline and against each other directly. Cox proportional hazard models were developed between follow-up visits and over the whole study. Simulations were performed on devS3 to match the limitations of auscultation. We studied 900 patients, of whom 106 patients experienced 192 HFEs. Two S3 sensing modalities correlated with each other, but at baseline, only devS3 differentiated patients with or without HFEs (P < 0.0001). The prognostic power of devS3 was superior to that of ausS3 both between follow-up visits (HR = 5.7, P < 0.0001, and 1.7, P = 0.047, respectively) and over the whole study (HR = 2.9, P < 0.0001, and 1.4, P = 0.216, respectively). Simulation results suggested this superiority may be attributed to continuous monitoring and to subaudible measuring capability. CONCLUSIONS: S3 measured by implantable cardiac devices has stronger prognostic power to predict episodes of future HFEs than that of auscultation.

Remote Physiologic Monitoring for Heart Failure.

PURPOSE OF REVIEW: This review will describe the process of remote monitoring in the treatment of heart failure and the clinical trials for different modalities of data collection. RECENT FINDINGS: Small studies monitoring weights, sometimes with other parameters, suggested a significant outcome benefit in meta-analysis. However, this has not been seen in larger studies. Clinical trials of remote monitoring using hemodynamic parameters seems to lead to improved outcomes, with more studies underway. Recently, multi-parameter methods with wearable or implantable devices have shown promise in detecting heart failure. The impact on clinical outcomes is being assessed. When using parameters such as daily weights, remote monitoring for heart failure has not been demonstrated to be broadly beneficial, while remote monitoring of hemodynamic parameters to guide heart failure therapy has met with initial success. Methods of combining multiple physiologic measurements appear to accurately detect worsening heart failure, and clinical trials are underway to assess the impact.

Nonhemodynamic parameters from implantable devices for heart failure risk stratification.

"Implantable devices are well suited to monitor and record several parameters that carry prognostic information. Specifically, the primary function of implantable cardioverter defibrillators (ICDs) is to monitor for changes in heart rhythm and treat both tachyarrhythmias and bradyarrhythmias. They are efficient in monitoring the heart rate, incidence of arrhythmias, and patient activity level, which provide prognostic information. Parameters such as thoracic impedance, heart sounds, and respiratory rate and patterns may further refine prognostic information available from ICDs. Combining parameters may provide a better way to interpret and use the available information."

Remote Monitoring for Heart Failure Management at Home.

Early telemonitoring of weights and symptoms did not decrease heart failure hospitalizations but helped identify steps toward effective monitoring programs. A signal that is accurate and actionable with response kinetics for early re-assessment is required for the treatment of patients at high risk, while signal specifications differ for surveillance of low-risk patients. Tracking of congestion with cardiac filling pressures or lung water content has shown most impact to decrease hospitalizations, while multiparameter scores from implanted rhythm devices have identified patients at increased risk. Algorithms require better personalization of signal thresholds and interventions. The COVID-19 epidemic accelerated transition to remote care away from clinics, preparing for new digital health care platforms to accommodate multiple technologies and empower patients. Addressing inequities will require bridging the digital divide and the deep gap in access to HF care teams, who will not be replaced by technology but by care teams who can embrace it.

Implantable cardiac defibrillators and sudden death in recent onset nonischemic cardiomyopathy: results from IMAC2.

BACKGROUND: Given the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We examined the utilization of ICDs and the impact on survival for subjects with ROCM. METHODS AND RESULTS: An National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device (P = .50). CONCLUSIONS: In a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery.

Left ventricular assist device support and myocardial recovery in recent onset cardiomyopathy.

BACKGROUND: Left ventricular assist device (LVAD) support as bridge to recovery (BTR) is uncommon for subjects with chronic heart failure. Myocardial recovery is more evident in recent onset nonischemic cardiomyopathy (ROCM); however, the prevalence of BTR in this subset has not been addressed. METHODS AND RESULTS: We examined the use of LVAD support for subjects with ROCM in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) study. The overall cohort (n = 373) was 38% female, 21% black, with a mean age of 45 ± 14 years. LVAD support was used in 3.8% (n = 14, 43% female, age 32 ± 10). Of LVAD subjects, 57% (8/14) were BTR, including 73% (8/11) of subjects with symptoms ≤4 months at the time of support. Left ventricular end-diastolic diameter (LVEDD) was smaller in BTR than nonrecovered (NR) subjects (P = .04). Myocardial inflammation was more common in BTR (75% versus 0%, P = .005), whereas fibrosis was less evident (25% versus 100%, P = .005). Of BTR subjects, 7/8 (87.5%) were alive and free of transplant with median follow-up of 19 months. CONCLUSION: In a multicenter registry of ROCM, BTR was common and occurred in the majority of subjects requiring LVAD support. Histology and LVEDD may assist in predicting potential for BTR in ROCM.

Design of the remede System Therapy (reST) study: A prospective non-randomized post-market study collecting clinical data on safety and effectiveness of the remede system for the treatment of central sleep apnea.

BACKGROUND: Central sleep apnea (CSA) is a disorder defined by lack of respiratory drive from the brain stem on breathing efforts. There is a lack of established therapies for CSA and most available therapies are limited by poor patient adherence, limited randomized controlled studies, and potentially adverse cardiovascular effects. The remede System (ZOLL Respicardia, Inc., Minnetonka, Minnesota) uses transvenous phrenic nerve stimulation to stimulate the diaphragm, thereby restoring a more normal breathing pattern throughout the sleep period. METHODS: The remede System Therapy (reST) Study is a prospective non-randomized multicenter international study evaluating long-term safety and effectiveness of the remede System in the post-market setting. Up to 500 adult patients with moderate to severe CSA will be enrolled and followed up to 5 years at approximately 50 sites in the United States and Europe. Safety objectives include evaluation of adverse events related to the implant procedure, device or delivered therapy, death, and hospitalizations. Effectiveness endpoints include assessment of changes in sleep-disordered breathing metrics from polysomnograms and home sleep tests, changes in daytime sleepiness using the Epworth Sleepiness Scale, and changes in QoL using the PROMIS-29 and Patient Global Assessment questionnaires. The subgroup of patients with heart failure will undergo additional assessments including echocardiography to assess cardiac reverse remodeling, 6-min walk distance, QoL assessment by Kansas City Cardiomyopathy Questionnaire and measurement of biomarkers. CONCLUSION: This will be the largest prospective study evaluating long-term safety and effectiveness of transvenous phrenic nerve stimulation for the treatment of moderate to severe CSA in adult patients.

Long-term outcome after ICD and CRT implantation and influence of remote device follow-up: the ALTITUDE survival study.

BACKGROUND: Outcome data for patients receiving implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices treated outside of clinical trials are lacking. No clinical trial has evaluated mortality after device implantation or after shock therapy in large numbers of patients with implanted devices that regularly transmit device data over a network. METHODS AND RESULTS: Survival status in patients implanted with ICD and CRT devices across the United States from a single manufacturer was assessed. Outcomes were compared between patients followed in device clinic settings and those who regularly transmit remote data collected from the device an average of 4 times monthly. Shock delivery and electrogram analysis could be ascertained from patients followed on the network, enabling survival after ICD shock to be evaluated. One- and 5-year survival rates in 185,778 patients after ICD implantation were 92% and 68% and were 88% and 54% for CRT-D device recipients. In 8228 patients implanted with CRT-only devices, survival was 82% and 48% at 1 and 5 years, respectively. For the 69,556 ICD and CRT-D patients receiving remote follow-up on the network, 1- and 5-year survival rates were higher compared with those in the 116,222 patients who received device follow-up in device clinics only (50% reduction; P<0.0001). There were no differences between patients followed on or off the remote network for the characteristics of age, gender, implanted device year or type, and economic or educational status. Shock therapy was associated with subsequent mortality risk for both ICD and CRT-D recipients. CONCLUSIONS: Survival after ICD and CRT-D implantation in patients treated in naturalistic practice compares favorably with survival rates observed in clinical trials. Remote follow-up of device data is associated with excellent survival, but arrhythmias that result in device therapy in this population are associated with a higher mortality risk compared with patients who do not require shock therapy.

Real world evaluation of dual-zone ICD and CRT-D programming compared to single-zone programming: the ALTITUDE REDUCES study.

INTRODUCTION: We evaluated the frequency of appropriate and inappropriate shocks and survival in patients using dual-zone programming versus single-zone programming. METHODS AND RESULTS: For the ALTITUDE REDUCES study, patients were followed for 1.6 ± 1.1 years. The 12-month incidence of any shock was lower for dual-versus single-zone programmed detection at rates ≤170 bpm and between 170-200 bpm (P < 0.001). Appropriate shock rates at 1 year were also lower with dual-zone programming in these rate intervals (single zone 9.1%, 5.4%, P < 0.001, dual zone 6.7%, 4.7%, P < 0.02). There were no detectable differences between single- and dual-zone shock incidence at detection rates ≥ 200 bpm (P = 0.14). Inappropriate shock incidence was less with dual- versus single-zone detection at all detect rates <200 bpm, but not at rates ≥200 bpm (P < 0.001, P = 0.37). The lowest risk of appropriate and inappropriate shock was associated with dual-zone programming and detection rates ≥200 bpm (2.1%). Dual-zone detection was associated with more nonsustained and diverted therapy episodes but these patients did not have an increased risk of death compared to patients with single-zone programming. Patients programmed to low detection rate, single-zone detection and shock-only therapy also had the highest preshock mortality risk (P = 0.05). CONCLUSIONS: Shock incidence is lowest with either single- or dual-zone detection ≥200 bpm. For detection rates <200 bpm, dual-zone programming is associated with a reduction in the incidence of total shocks, appropriate shocks, and inappropriate shocks.

Multiparameter diagnostic sensor measurements in heart failure patients presenting with SARS-CoV-2 infection.

AIMS: Implantable device-based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID-19 (Cov-19) and how these compared with those presenting with decompensated HF or pneumonia. METHODS AND RESULTS: This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov-19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT-HF, and MANAGE-HF trials. The earliest sensor changes prior to Cov-19 were observed in respiratory rate (6 days) and temperature (5 days). There was a three-fold to four-fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov-19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S1 and S3 ) amplitude in those presenting with Cov-19 or pneumonia compared with the known changes that occur in HF decompensation. CONCLUSIONS: Multi-sensor device diagnostics may provide early detection of Cov-19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3.

Small decreases in biventricular pacing percentages are associated with multiple metrics of worsening heart failure as measured from a cardiac resynchronization therapy defibrillator.

BACKGROUND: Lower BiVentricular (BiV) pacing percentages have been associated with significantly worse survival in patients with chronic heart failure (HF). However, the pathophysiology behind this observation has not been further delineated. This analysis evaluated whether small incremental decreases in BiV pacing percentages were associated with worse measures, related to HF physiology using individual sensor trends and the HeartLogic composite index. METHODS: Sensor data was obtained from 900 ambulatory HF patients with implanted CRT devices. The percent of cardiac cycles with BiV pacing was assessed for periods (median = 7.3 days) between data downloads (median = 55 periods/patient). RESULTS: The third heart sound (S3), respiration rate, RSBI, and night-time heart rate were significantly elevated with sub-optimal pacing (<98%), while the first heart sound (S1), thoracic impedance, and activity were significantly lower. All sensor changes were in the direction associated with worsening HF. While IN the HeartLogic alert state (threshold above an Index of 16) the odds of optimal BiV pacing (≥98%) were less than when OUT of the HeartLogic alert state for a given subject (OR: 0.655; 95% CI: 0.626-0.686; p < 0.0001). The percent BiV pacing was reduced and the HeartLogic Index was increased in the periods surrounding HFhospitalizations. CONCLUSION: Lower BiV pacing percent is associated with multiple sensor changes indicative of worsening HF, and patients in HeartLogic alert are more likely to have suboptimal BiV pacing. Collectively, these data provide strong evidence that even small decreases in BiV percent pacing can lead to worsening HF.

Multiparameter diagnostic sensor measurements during clinically stable periods and worsening heart failure in ambulatory patients.

AIMS: This study aims to characterize the range of implantable device-based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events. METHODS AND RESULTS: The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT-D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT-proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P < 0.001), thoracic impedance (45.66 ± 8.78 Ohm vs. 50.33 ± 8.43 Ohm, P < 0.001), respiratory rate (19.09 ± 3.10 br/min vs. 17.66 ± 2.39 br/min, P = 0.002), night time heart rate (73.39 ± 8.36 b.p.m. vs. 69.56 ± 8.09 b.p.m., P = 0.001), patient activity (1.69 ± 1.84 h vs. 2.56 ± 2.20 h, P = 0.006), and HeartLogic index (11.07 ± 12.14 vs. 5.31 ± 5.13, P = 0.001). Sensor parameters measured worsening status leading up to HF events with recovery of values following treatment. CONCLUSIONS: Device-based physiologic sensors not only revealed progressive worsening leading up to HF events but also differentiated patients at increased risk of HF events when presumed to be clinically stable.

Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the sudden cardiac death in heart failure trial.

BACKGROUND: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. METHODS AND RESULTS: SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. CONCLUSIONS: ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected] CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

HFSA 2010 Comprehensive Heart Failure Practice Guideline.

Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, reduced quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly that individual clinicians may be unable to readily and adequately synthesize new information into effective strategies of care for patients with this syndrome. Trial data, though valuable, often do not give direction for individual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2010 Heart Failure Society of America comprehensive practice guideline addresses the full range of evaluation, care, and management of patients with HF.

Impact of Degree of Left Ventricular Remodeling on Clinical Outcomes From Cardiac Resynchronization Therapy.

OBJECTIVES: This study tested the hypothesis that the extent of left ventricular (LV) eccentric structural remodeling in heart failure with reduced ejection fraction (HFrEF) is directly associated with clinical event responses to cardiac resynchronization therapy (CRT). BACKGROUND: Whether the severity of LV structural remodeling influences CRT treatment effects is unknown. METHODS: COMPANION (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure) trial data were analyzed retrospectively. Left ventricular internal dimensions at end diastole indexed by body surface area (LVEDDI) were measured pre-randomization by 2-dimensional echocardiography. LVEDDI values were stratified around the median value of 35 mm/m2, and CRT (including CRT-P [CRT with only pacing capability] and/or CRT-D [CRT with an implantable defibrillator]) treatment effects were assessed and compared by LVEDDI group. Patients assigned to these treatments were compared to those undergoing optimal pharmacologic therapy (OPT) for the outcomes of all-cause mortality (ACM) or ACM and heart-failure hospitalization (ACM/HFH). RESULTS: In the LVEDDI ≥35 mm/m2 group (n = 614), CRT vs. OPT was associated with a lower ACM/HFH hazard ratio (HR) (HR: 0.53; 95% confidence interval [CI]: 0.40 to 0.70; p <0.001), whereas in the LVEDDI <35 mm/m2 group, the CRT vs. OPT ACM/HFH hazard ratio was not statistically significant (HR: 0.80; 95% CI: 0.59 to 1.08; p = 0.15). For ACM alone, in the LVEDDI ≥35 mm/m2 group, the hazard ratio for CRT-P was 0.59 (95% CI: 0.39 to 0.90; p = 0.012) and for CRT-D 0.50 (95% CI: 0.32 to 0.77; p = 0.002). Neither of the CRT groups showed a statistically significant reduction in ACM in the LVEDDI <35 mm/m2 group. CONCLUSIONS: Larger versus smaller LVEDDIs are associated with a reduction in ACM with CRT-P or CRT-D treatment, and with a more effective reduction in ACM/HFH for the combined CRT treatment groups.