Multicenter Study of Survival Benefit of Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease.

BACKGROUND: Evidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. OBJECTIVES: This study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. METHODS: Both CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death. RESULTS: In total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95% CI: 0.25-0.64; P < 0.001; and HR: 0.44; 95% CI: 0.28-0.71; P = 0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P < 0.001) and shorter QRS duration (P = 0.015), sustained to 5 years. CONCLUSIONS: In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.

Estimated Glomerular Filtration Rate and Implantable Cardioverter-Defibrillator in Nonischemic Systolic Heart Failure: Extended Follow-Up of DANISH.

BACKGROUND: Patients with heart failure and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter-defibrillators (ICDs). We examined the long-term effects of primary prophylactic ICD implantation, compared with usual care, according to baseline CKD status in an extended follow-up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality). METHODS AND RESULTS: In the DANISH trial, 1116 patients with nonischemic heart failure with reduced ejection fraction were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (estimated glomerular filtration rate ≥/<60 mL/min per 1.73 m2) at baseline. In total, 1113 patients had an available estimated glomerular filtration rate measurement at baseline (median estimated glomerular filtration rate 73 mL/min per 1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual care, did not reduce the rate of all-cause mortality (no CKD, HR, 0.82 [95% CI, 0.64-1.04]; CKD, HR, 1.02 [95% CI, 0.75-1.38]; Pinteraction=0.31) or cardiovascular death (no CKD, HR, 0.77 [95% CI, 0.58-1.03]; CKD, HR, 1.05 [95% CI, 0.73-1.51]; Pinteraction=0.20), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR, 0.57 [95% CI, 0.32-1.00]; CKD, HR, 0.65 [95% CI, 0.34-1.24]; Pinteraction=0.70). CONCLUSIONS: ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce the rate of sudden cardiovascular death, regardless of baseline kidney function in patients with nonischemic heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.

Hospital admissions and outcomes for systolic and diastolic heart failure in Spain between 2016 and 2019: A population-based study. / Hospitalizaciones y eventos por insuficiencia cardiaca sistólica y diastólica en España entre 2016 y 2019. Un estudio de base poblacional.

BACKGROUND AND PURPOSE: In Spain there is a lack of population data that specifically compare hospitalization for systolic and diastolic heart failure (HF). We assessed clinical characteristics, in-hospital mortality and 30-day cardiovascular readmission rates differentiating by HF type. METHODS: We conducted a retrospective observational study of patients discharged with the principal diagnosis of HF from The National Health System' acute hospital during 2016-2019, distinguishing between systolic and diastolic HF. The source of the data was the Minimum Basic Data Set. The risk-standardized in-hospital mortality ratio and risk-standardized 30-day cardiovascular readmission ratio were calculated using multilevel risk adjustment models. RESULTS: The 190,200 episodes of HF were selected. Of these, 163,727 (86.1%) were classified as diastolic HF and were characterized by older age, higher proportion of women, diabetes mellitus, dementia and renal failure than those with systolic HF. In the multilevel risk adjustment models, diastolic HF was a protective factor for both in-hospital mortality (odds ratio [OR]: 0.79; 95% confidence interval [CI]: 0.75-0.83; P<.001) and 30-day cardiovascular readmission versus systolic HF (OR: 0.93; 95% CI: 0.88-0.97; P=.002). CONCLUSIONS: In Spain, between 2016 and 2019, hospitalization episodes for HF were mostly due to diastolic HF. According to the multilevel risk adjustment models, diastolic HF compared to systolic HF was a protective factor for both in-hospital mortality and 30-day cardiovascular readmission.

Predictors of ventricular tachyarrhythmia in patients with implantable cardioverter-defibrillator and non-ischemic systolic heart failure.

BACKGROUND: The benefit derived from implantable cardioverter-defibrillators (ICD) in subjects with non-ischemic systolic HF (NICM) is less well-established. AIM: The study aimed to determine the incidence, predictors, and prognostic impact of ventricular arrhythmias in patients with ICD and NICM. METHODS: The study sample included 377 consecutive patients with ICD or cardiac resynchronization cardioverter-defibrillators (CRT-D, 74% of patients) and NICM implanted and monitored remotely in a university hospital. RESULTS: During the median (interquartile range [IQR]) follow-up of 1645 (960-2675) days, sustained ventricular arrhythmia occurred in 92 patients (24.4%). Of those, ventricular fibrillation (VF), ventricular tachycardia (VT), and both VT and VF occurred in 10 (10.9%), 72 (78.3%), and 10 (10.9%) patients, respectively. Patients with vs. those without ventricular arrhythmia differed concerning sex, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), post-inflammatory etiology, atrial fibrillation/flutter occurrence, and supraventricular arrhythmia (SVT) other than AF/AFL during follow-up. In multivariable Cox regression, LVEDD (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.003-1.09; P = 0.03), AF/AFL (HR, 1.86; 95% CI, 1.21-2.85; P = 0.004), and SVT (HR, 1.77; 95% CI, 1.10-2.87; P = 0.02) were independent predictors of sustained VT, while AF/AFL (HR, 1.65; 95% CI, 1.07-2.56; P = 0.02) was independent predictor of VF. All-cause mortality in patients with VT/VF was significantly higher than in subjects without sustained ventricular arrhythmias (35.9% vs. 22.4%; P = 0.01). CONCLUSIONS: Ventricular arrhythmia occurred in every fourth patient with NICM and ICD during 4.5 years of observation and was associated with significantly worse prognosis than in subjects free of VT/VF. Higher LVEDD, atrial fibrillation/atrial flutter, and supraventricular tachycardia flag patients at risk of ventricular arrhythmia.

Adaptive servo-ventilation and mortality in patients with systolic heart failure and central sleep apnea: a single-center experience.

BACKGROUND: Central sleep apnea (CSA) is associated with increased mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Treatment of CSA with a certain type of adaptive servo-ventilation (ASV) device that targets minute ventilation (ASVmv) was found to be harmful in these patients. A newer generation of ASV devices that target peak flow (ASVpf) is presumed to have different effects on ventilation and airway patency. We analyzed our registry of patients with HFrEF-CSA to examine the effect of exposure to ASV and role of each type of ASV device on mortality. METHODS: This is a retrospective cohort study in patients with HFrEF and CSA who were treated with ASV devices between 2008 and 2015 at a single institution. Mortality data were collected through the institutional data honest broker. Usage data were obtained from vendors' and manufacturers' servers. Median follow-up was 64 months. RESULTS: The registry included 90 patients with HFrEF-CSA who were prescribed ASV devices. Applying a 3-h-per-night usage cutoff, we found a survival advantage at 64 months for those who used the ASV device above the cutoff (n = 59; survival 76%) compared to those who did not (n = 31; survival 49%; hazard ratio 0.44; CI 95%, 0.20 to 0.97; P = 0.04). The majority (n = 77) of patients received ASVpf devices with automatically adjusting end-expiratory pressure (EPAP) and the remainder (n = 13) received ASVmv devices mostly with fixed EPAP (n = 12). There was a trend towards a negative correlation between ASVmv with fixed EPAP and survival. CONCLUSION: In this population of patients with HFrEF and CSA, there was no evidence that usage of ASV devices was associated with increased mortality. However, there was evidence of differential effects of type of ASV technology on mortality.

Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.

BACKGROUND: Patients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known. METHODS AND RESULTS: In this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than -20%. The primary end point was all-cause mortality. The median RV-FWS was -18% (quartiles -23% to -14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22). CONCLUSIONS: In patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.

Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study.

BACKGROUND: Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA. METHODS: HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea-hypopnoea index (AHI) ≥15 events·h-1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed. RESULTS: 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h-1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min-1 at baseline to 44.6±11.2 bursts·min-1; ASV group: 43.0±9.0 bursts·min-1 at baseline to 42.74±9.45 bursts·min-1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective. CONCLUSIONS: Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

Impact of signal-averaged electrocardiography findings on appropriate shocks in prophylactic implantable cardioverter defibrillator patients with nonischemic systolic heart failure.

BACKGROUND: Appropriate shock therapy is associated with subsequent all-cause death in heart failure (HF) patients who receive an implantable cardioverter defibrillator (ICD) for the primary prevention of sudden cardiac death. To evaluate the impact of signal-averaged electrocardiography (SAECG) findings on appropriate shocks in prophylactic ICD patients with nonischemic systolic HF. METHODS: We studied 86 patients with nonischemic HF and a left ventricular ejection fraction ≤ 35% who underwent new ICD implantation for the primary prevention of sudden cardiac death. We excluded patients who had a previously implanted permanent pacemaker and patients who received cardiac resynchronization therapy with an ICD. SAECG was performed before implantation. Abnormal SAECG findings were defined if 2 of the following 3 conditions were identified: filtered QRS duration (fQRS) ≥ 114 ms, root-mean-square voltage during the last 40 ms of the fQRS (RMS 40) < 20 µV, and duration of the low-amplitude potentials < 40 µV (LAS 40) > 38 ms; additionally, patients with a QRS complex ≥ 120 ms who met both the RMS 40 and LAS 40 criteria were also considered to have abnormal SAECG findings. The primary outcome was the first occurrence of appropriate shock after implantation of the ICD. The secondary outcomes were the first occurrence of inappropriate shock and all-cause mortality. RESULTS: Forty-two patients met the criteria for abnormal SAECG findings (49%). During a median follow-up period of 61 months, 17 patients (20%) died, 24 (28%) received appropriate shock therapy, and 19 (22%) received inappropriate shock therapy. There was a significantly higher incidence of appropriate shocks in patients with abnormal SAECG findings than in those with normal SAECG findings (log-rank test, p = 0.025). Multivariate analysis revealed that abnormal SAECG findings were independently associated with the occurrence of appropriate shock (hazard ratio 2.67, 95% confidential interval 1.14-6.26). However, abnormal SAECG findings were not related to inappropriate shock. There was no difference in the incidence of all-cause death between patients with abnormal and normal SAECG findings. CONCLUSIONS: Our results suggest that abnormal SAECG findings are associated with a high probability of appropriate shocks in prophylactic ICD patients with nonischemic systolic HF.

Effect of adaptive servo ventilation on central sleep apnea and sleep structure in systolic heart failure patients: polysomnography data from the SERVE-HF major sub study.

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94-103 in the control group, 77-99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk.

Right heart catheterization in advanced systolic heart failure. What are the most useful haemodynamic parameters for risk stratification?

BACKGROUND: Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters. AIMS: To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure. METHODS: We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated. RESULTS: During a median (interquartile range) follow-up of 1.67 (0.49-4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 postoperative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.06-1.12; P<0.0001) and baseline pulmonary vascular resistance (PVR) (HR: 1.10; 95% CI: 1.03-1.17; P=0.002). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR: 1.06; 95% CI: 1.03-1.09; P<0.0001). The combination of PVR (≤or>3 Wood units), RAP (30mmHg) was the best predictor of major events. CONCLUSION: We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.

NT-proBNP and ICD in Nonischemic Systolic Heart Failure: Extended Follow-Up of the DANISH Trial.

OBJECTIVES: In this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. BACKGROUND: In the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation. METHODS: In the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause. RESULTS: All 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (Pinteraction = 0.28). Similarly, ICD implantation significantly reduced the rate of cardiovascular (CV) and sudden cardiovascular death (SCD) in patients with NT-proBNP levels lower than the median (CV death, HR: 0.69 [95% CI: 0.47-1.00]; SCD, HR: 0.37 [95% CI: 0.19-0.75]), but not in those with higher levels (CV death, HR: 0.94 [95% CI: 0.70-1.25]; SCD, HR: 0.86 [95% CI: 0.49-1.51]) (Pinteraction = 0.20 and 0.08 for CV death and SCD, respectively). CONCLUSIONS: Lower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945).

Impact of adaptive cardiac resynchronization therapy in patients with systolic heart failure: Beyond QRS duration and morphology.

BACKGROUND: Mechanical and electrical restoration by cardiac resynchronization therapy (CRT) with adaptive pacing algorithm (aCRT) in heart failure patients with a moderately wide (120-149 ms) QRS has not been fully evaluated. The purpose of this study was to investigate the therapeutic effect of aCRT compared with conventional biventricular CRT (BiV-CRT) regardless of QRS morphology. METHODS: Seventeen consecutive patients with a QRS ≥120 ms, regardless of morphology, underwent CRT device implantation with an aCRT pacing algorithm. Propensity score matched analysis was performed to evaluate the impact of aCRT on the improvement in mechanical and electrical parameters after CRT device implantation using historical controls (HC) from the clinical registry of BiV-CRT (START trial). RESULTS: Left ventricular (LV) volume significantly decreased after CRT in all patients in both the aCRT and HC groups. The difference in relative reduction of LV end-systolic volume (LVESV) was not significantly different between the 2 arms. QRS shortening after CRT was significantly greater in the aCRT group than in the BiV-CRT group, and the difference was prominent in patients with a moderately wide QRS (120-149 ms). In patients with a moderately wide QRS, the relative reduction in LVESV [39 (29-47)% vs. 2 (-6-20)%, p = 0.04] and proportion of LV volume responders (90% vs. 38%, p = 0.04) were significantly greater in the aCRT group than in the HC group. The proportion of volume responders was not significantly different in patients with a wide QRS (≥150 ms). CONCLUSIONS: The aCRT algorithm improved electrical and mechanical parameters in patients with a moderately wide QRS, regardless of QRS morphology.

Cognitive Function of Recipients of Primary or Secondary Defibrillator Therapy: A Comparative Study Involving Nondefibrillator Patients With Systolic Heart Failure.

BACKGROUND: The extent to which cognitive function differs between patients who receive implantable cardioverter-defibrillator (ICD) therapy and patients with heart failure (HF) who do not receive ICD therapy remains to be elucidated. OBJECTIVES: The aim of this study was to compare the cognitive function between patients with primary or secondary ICDs and patients with HF without an ICD. METHODS: This descriptive, comparative study included 116 patients who received ICDs and 74 patients with HF who did not receive ICDs. Patients underwent neuropsychological assessment for general cognition, memory, and executive function. RESULTS: Immediate recall memory loss (18.9%) occurred more often in patients with HF without an ICD than in patients with primary (3.1%) and secondary (7.1%) ICDs (P = .018). After adjusting for age and education, delayed recall memory of patients with HF without ICDs was significantly worse than that of patients with primary ICDs (4.0 vs 6.5; P < .001), whereas delayed recall memory of patients with primary ICDs was better than that of patients with secondary ICDs (6.0 vs 6.5; P = .006). Executive function of patients with HF without ICDs was significantly worse than that of patients with primary (35 vs 58 seconds; P < .001) and secondary (28 vs 58 seconds; P = .0012) ICDs. CONCLUSIONS: Patients with ICDs, regardless of primary or secondary indication, had less impairment of memory and executive function than patients with HF without ICDs, implying that ICD therapy did not interfere with cognitive performance. Cognitive screening as a part of routine care could be helpful for identifying impairment and implementing early cognitive training, especially in patients with HF.

The vasculature: a therapeutic target in heart failure?

It is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.

Efficacy of Blended Collaborative Care for Patients With Heart Failure and Comorbid Depression: A Randomized Clinical Trial.

Importance: Depression is often comorbid in patients with heart failure (HF) and is associated with worse clinical outcomes. However, depression generally goes unrecognized and untreated in this population. Objective: To determine whether a blended collaborative care program for treating both HF and depression can improve clinical outcomes more than collaborative care for HF only and physicians' usual care (UC). Design, Setting, and Participants: This 3-arm, single-blind, randomized effectiveness trial recruited 756 participants with HF with reduced left ventricular ejection fraction (<45%) from 8 university-based and community hospitals in southwestern Pennsylvania between March 2014 and October 2017 and observed them until November 2018. Participants included 629 who screened positive for depression during hospitalization and 2 weeks postdischarge and 127 randomly sampled participants without depression to facilitate further comparisons. Key analyses were performed November 2018 to March 2019. Interventions: Separate physician-supervised nurse teams provided either 12 months of collaborative care for HF and depression ("blended" care) or collaborative care for HF only (enhanced UC [eUC]). Main Outcomes and Measures: The primary outcome was mental health-related quality of life (mHRQOL) as measured by the Mental Component Summary of the 12-item Short Form Health Survey (MCS-12). Secondary outcomes included mood, physical function, HF pharmacotherapy use, rehospitalizations, and mortality. Results: Of the 756 participants (mean [SD] age, 64.0 [13.0] years; 425 [56%] male), those with depression reported worse mHRQOL, mood, and physical function but were otherwise similar to those without depression (eg, mean left ventricular ejection fraction, 28%). At 12 months, blended care participants reported a 4.47-point improvement on the MCS-12 vs UC (95% CI, 1.65 to 7.28; P = .002), but similar scores as the eUC arm (1.12; 95% CI, -1.15 to 3.40; P = .33). Blended care participants also reported better mood than UC participants (Patient-Reported Outcomes Measurement Information System-Depression effect size, 0.47; 95% CI, 0.28 to 0.67) and eUC participants (0.24; 95% CI, 0.07 to 0.41), but physical function, HF pharmacotherapy use, rehospitalizations, and mortality were similar by both baseline depression and randomization status. Conclusions and Relevance: In this randomized clinical trial of patients with HF and depression, telephone-delivered blended collaborative care produced modest improvements in mHRQOL, the primary outcome, on the MCS-12 vs UC but not eUC. Although blended care did not differentially affect rehospitalization and mortality, it improved mood better than eUC and UC and thus may enable organized health care systems to provide effective first-line depression care to medically complex patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02044211.