Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

BACKGROUND: Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. METHODS: Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. RESULTS: Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. CONCLUSIONS: Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Effect of myocardial scar size on the risk of ventricular arrhythmias in patients with chronic total coronary occlusion.

BACKGROUND: The presence of an untreated chronic total coronary occlusion (CTO) is associated with a higher risk of ventricular arrhythmias (VAs). This increased risk may be modulated by the presence of an existing scar. OBJECTIVES: To evaluate whether scar size is associated with VA in patients with an implantable cardioverter-defibrillator (ICD) and a CTO. METHODS: In this retrospective study we included patients with a CTO that received an ICD between 2005 and 2015. Scar size was estimated using the Selvester QRS score on a baseline 12­lead ECG. The primary endpoint was any appropriate ICD therapy. RESULTS: Our study population comprised 148 CTO patients with a median scar size at baseline of 18% (IQR, 9-27%). Patients with a scar size ≥18% more often had a CTO located in the left anterior descending artery and a higher proportion of poor left ventricular function (<35%) and infarct-related CTO compared to patients with a smaller scar size (<18%). During a median follow-up of 35 months (interquartile range [IQR], 8-60 months), 42 patients (28%) received appropriate ICD therapy. The cumulative 5-year event rate was higher in the patients with a large scar in comparison to those with a smaller or no scar (36% versus 19%, P = 0.04). Multivariable Cox regression analysis demonstrated that large scar and diabetes mellitus were independent factors associated with appropriate ICD therapy. CONCLUSION: In ICD recipients with an untreated CTO, a larger scar is an independent factor associated with an increased risk of VA.

Three-dimensional QCA-based vessel fractional flow reserve (vFFR) in Heart Team decision-making: a multicentre, retrospective, cohort study.

OBJECTIVES: To evaluate the feasibility of three-vessel three-dimensional (3D) quantitative coronary angiography (QCA)-based fractional flow reserve (FFR) computation in patients discussed within the Heart Team in whom the treatment decision was based on angiography alone, and to evaluate the concordance between 3D QCA-based vessel FFR (vFFR)-confirmed functional lesion significance and revascularisation strategy as proposed by the Heart Team. DESIGN: Retrospective, cohort. SETTING: 3D QCA-based FFR indices have not yet been evaluated in the context of Heart Team decision-making; consecutive patients from six institutions were screened for eligibility and three-vessel vFFR was computed by blinded analysts. PARTICIPANTS: Consecutive patients with chronic coronary syndrome or unstable angina referred for Heart Team consultation. Exclusion criteria involved: presentation with acute myocardial infarction (MI), significant valve disease, left ventricle ejection fraction <30%, inadequate quality of angiogram precluding vFFR computation in all three epicardial coronary arteries (ie, absence of a minimum of two angiographic projections with views of at least 30° apart, substantial foreshortening/overlap of the vessel, poor contrast medium injection, ostial lesions, chronic total occlusions). PRIMARY AND SECONDARY OUTCOME MEASURES: Discordance between vFFR-confirmed lesion significance and revascularisation was assessed as the primary outcome measure. Rates of major adverse cardiac events (MACE) defined as cardiac death, MI and clinically driven revascularisation were reported. RESULTS: Of a total of 1003 patients were screened for eligibility, 416 patients (age 65.6±10.6, 71.2% male, 53% stable angina) were included. The most important reason for screening failure was insufficient quality of the angiogram (43%). Discordance between vFFR confirmed lesion significance and revascularisation was found in 124/416 patients (29.8%) corresponding to 149 vessels (46/149 vessels (30.9%) were reclassified as significant and 103/149 vessels (69.1%) as non-significant by vFFR). Over a median of 962 days, the cumulative incidence of MACE was 29.7% versus 18.5% in discordant versus concordant patients (p=0.031). CONCLUSIONS: vFFR computation is feasible in around 40% of the patients referred for Heart Team discussion, a limitation that is mostly based on insufficient quality of the angiogram. Three vessel vFFR screening indicated discordance between vFFR confirmed lesion significance and revascularisation in 29.8% of the patients.

Renal tubular damage and worsening renal function in chronic heart failure: Clinical determinants and relation to prognosis (Bio-SHiFT study).

BACKGROUND: It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes. HYPOTHESIS: Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants. METHODS: During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N-acetyl-ß-d-glucosaminidase (NAG), and kidney-injury-molecule (KIM)-1. The degree of tubular injury was ranked according to NAG and KIM-1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF-hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation. RESULTS: Higher baseline NT-proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR [95%CI, 95% confidence interval] per doubling NT-proBNP: 1.26 [1.07-1.49]; per 10 mL/min/1.73 m2 eGFR decrease 1.16 [1.03-1.31]). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 [1.08-1.62]; spironolactone per 25 mg decrease: 1.76 [1.07-2.89]; per 10 mL/min/1.73 m2 eGFR increase: 1.40 [1.20-1.63]). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR [95%CI]: WRF 1.9 [1.1-3.4], tubular 8.4 [2.6-27.9]; when combined risk was highest 15.0 [2.0-111.0]). CONCLUSION: Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.

Predicting Early Mortality Among Implantable Defibrillator Patients Treated With Cardiac Resynchronization Therapy.

BACKGROUND: The beneficial effects of a cardiac resynchronization defibrillator (CRT-D) in patients with heart failure, low left ventricular ejection fraction (LVEF), and wide QRS have clearly been established. Nevertheless, mortality remains high in some patients. The aim of this study was to develop and validate a risk score to identify patients at high risk for early mortality who are implanted with a CRT-D. METHODS AND RESULTS: For predictive modelling, 1282 consecutive patients from 5 centers (74% male; median age 66 years; median LVEF 25%; New York Heart Association class III-IV 60%; median QRS-width 160 ms) were randomly divided into a derivation and validation cohort. The primary endpoint is mortality at 3 years. Model development was performed using multivariate logistic regression by checking log likelihood, Akaike information criterion, and Bayesian information criterion. Model performance was validated using C statistics and calibration plots. The risk score included 7 independent mortality predictors, including myocardial infarction, LVEF, QRS duration, chronic obstructive pulmonary disease, chronic kidney disease, hyponatremia, and anemia. Calibration-in-the-large was suboptimal, reflected by a lower observed mortality (44%) than predicted (50%). The validated C statistic was 0.71 indicating modest performance. CONCLUSION: A risk score based on routine, readily available clinical variables can assist in identifying patients at high risk for early mortality within 3 years after CRT-D implantation.

Temporal Patterns of 14 Blood Biomarker candidates of Cardiac Remodeling in Relation to Prognosis of Patients With Chronic Heart Failure-The Bio- SH i FT Study.

Background Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure ( CHF ) patients. However, temporal patterns during the course of CHF , and especially the trajectory before an adverse event, are unknown. We studied the prognostic value of temporal patterns of 14 cardiac remodeling biomarker candidates in stable patients with CHF from the Bio-SHiFT (Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis) study. Methods and Results In 263 CHF patients, we performed trimonthly blood sampling during a median follow-up of 2.2 years. For the analysis, we selected all baseline samples, the 2 samples closest to the primary end point ( PE ), or the last sample available for end point-free patients. Thus, in 567 samples, we measured suppression of tumorigenicity-2, galectin-3, galectin-4, growth differentiation factor-15, matrix metalloproteinase-2, 3, and 9, tissue inhibitor metalloproteinase-4, perlecan, aminopeptidase-N, caspase-3, cathepsin-D, cathepsin-Z, and cystatin-B. The PE was a composite of cardiovascular mortality, heart transplantation, left ventricular assist device implantation, and HF hospitalization. Associations between repeatedly measured biomarker candidates and the PE were investigated by joint modeling. Median age was 68 (interquartile range: 59-76) years with 72% men; 70 patients reached the PE . Repeatedly measured suppression of tumorigenicity-2, galectin-3, galectin-4, growth differentiation factor-15, matrix metalloproteinase-2 and 9, tissue inhibitor metalloproteinase-4, perlecan, cathepsin-D, and cystatin-B levels were significantly associated with the PE , and increased as the PE approached. The slopes of biomarker trajectories were also predictors of clinical outcome, independent of their absolute level. Associations persisted after adjustment for clinical characteristics and pharmacological treatment. Suppression of tumorigenicity-2 was the strongest predictor (hazard ratio: 7.55 per SD difference, 95% CI : 5.53-10.30), followed by growth differentiation factor-15 (4.06, 2.98-5.54) and matrix metalloproteinase-2 (3.59, 2.55-5.05). Conclusions Temporal patterns of remodeling biomarker candidates predict adverse clinical outcomes in CHF . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01851538.

Serially measured circulating microRNAs and adverse clinical outcomes in patients with acute heart failure.

AIMS: Previous studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF). METHODS AND RESULTS: RNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)-1306-5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time-points during the study's 1-year follow-up. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR-1306-5p were positively associated with risk for reaching the primary endpoint at the same time-point [hazard ratio (HR) 4.69, 95% confidence interval (CI) 2.18-10.06], independent of clinical characteristics and NT-proBNP. Baseline miR-1306-5p did not improve model discrimination/reclassification significantly compared with NT-proBNP. For miR-320a, miR-378a-3p, miR-423-5p and miR-1254, associations with the primary endpoint were present after adjustment for age and sex (HR 1.38, 95% CI 1.12-1.70; HR 1.35, 95% CI 1.04-1.74; HR 1.45, 95% CI 1.10-1.92; HR 1.22, 95% CI 1.00-1.50, respectively). Rates of detection of myomiRs miR-208a-3p and miR-499a-5p were very low. CONCLUSIONS: Repeatedly measured miR-1306-5p was positively associated with adverse clinical outcome in AHF, even after multivariable adjustment including NT-proBNP. However, baseline miR-1306-5p did not add significant discriminatory value to NT-proBNP. Low-abundance, heart-enriched myomiRs are often undetectable, which mandates the development of more sensitive assays.

Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study.

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF.

Development and validation of a risk model for long-term mortality after percutaneous coronary intervention: The IDEA-BIO Study.

OBJECTIVES: We aimed to develop a model to predict long-term mortality after percutaneous coronary intervention (PCI), to aid in selecting patients with sufficient life expectancy to benefit from bioabsorbable scaffolds. BACKGROUND: Clinical trials are currently designed to demonstrate superiority of bioabsorbable scaffolds over metal devices up to 5 years after implantation. METHODS: From 2000 to 2011, 19.532 consecutive patients underwent PCI in a tertiary referral hospital. Patients were randomly (2:1) divided into a training (N = 13,090) and validation (N = 6,442) set. Cox regression was used to identify determinants of long-term mortality in the training set and used to develop a risk model. Model performance was studied in the training and validation dataset. RESULTS: Median age was 63 years (IQR 54-72) and 72% were men. Median follow-up was 3.6 years (interquartile range [IQR] 2.4-6.8). The ratio elective vs. non-elective PCIs was 42/58. During 88,620 patient-years of follow-up, 3,156 deaths occurred, implying an incidence rate of 35.6 per 1,000. Estimated 5-year mortality was 12.9%.Regression analysis revealed age, body mass index, diabetes mellitus, renal insufficiency, prior myocardial infarction, PCI indication, lesion location, number of diseased vessels and cardiogenic shock at presentation as determinants of mortality. The long-term risk model showed good discrimination in the training and validation sets (c-indices 0.76 and 0.74), whereas calibration was appropriate. CONCLUSIONS: A simple risk model, containing 9 baseline clinical and angiographic variables effectively predicts long-term mortality after PCI and may possibly be used to select suitable patients for bioabsorbable scaffolds.

Real-Life Use of Neurohormonal Antagonists and Loop Diuretics in Chronic Heart Failure: Analysis of Serial Biomarker Measurements and Clinical Outcome.

We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardiorenal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) were inversely associated with cardiac impairment, inflammation, and renal tubular damage, but not with glomerular dysfunction. Diuretics were associated with worse biomarker profiles and with a hazard ratio for adverse clinical outcome of 1.12 (95% confidence interval: 1.03-1.22) per 40 mg higher doses. ACE-inhibitors/ARBs were more frequently downtitrated and diuretics more frequently uptitrated in patients who experienced endpoints than in those who did not. In conclusion, a decrease or withholding of ACE-inhibitors/ARBs solely based on glomerular function is not justified because of the beneficial effects on the heart, inflammation, and renal tubules. Higher and increased diuretic doses mark progression towards endstage CHF.

Serially measured circulating miR-22-3p is a biomarker for adverse clinical outcome in patients with chronic heart failure: The Bio-SHiFT study.

BACKGROUND: Several studies have suggested circulating microRNAs (miRs) are associated with heart failure, but these studies were small, and limited to single miR measurements. We examined 7 miRs which were previously linked to heart failure, and tested whether their temporal expression level predicts prognosis in a prospective cohort of chronic heart failure (CHF) patients. METHODS AND RESULTS: In 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3months, we measured 7miRs. The primary endpoint (PE) comprised heart failure hospitalization, cardiovascular mortality, cardiac transplantation and LVAD implantation. Associations between temporal miR patterns and the PE were investigated by joint modelling, which combines mixed models with Cox regression. Mean age was 67±13years, 72% were men and 27% NYHA classes III-IV. We obtained 873 blood samples (median 3 [IQR 2-5] per patient). The PE was reached in 41 patients (16%) during a median follow-up of 0.9 [0.6-1.4] years. The temporal pattern of miR-22-3p was independently associated with the PE (HR [95% CI] per doubling of level: 0.64 [0.47-0.77]). The instantaneous change in level (slope of the temporal miR pattern) of miR-22-3p was also independently associated with the PE (HR [95% CI] per doubling of slope: 0.33 [0.20-0.51]). These associations remained statistically significant after adjustment for temporal patterns of NT-proBNP, Troponin T and CRP. CONCLUSIONS: The temporal pattern of circulating miR-22-3p contains important prognostic and independent information in CHF patients. This concept warrants further investigation in larger series with extended follow-up.

Stent thrombosis in early-generation drug-eluting stents versus newer-generation everolimus-eluting stent assorted by LVEF.

OBJECTIVE: Everolimus drug-eluting stents (EES) are superior to early-generation drug-eluting stents (DES), releasing sirolimus (SES) or paclitaxel (PES) in preventing stent thrombosis (ST). Since an impaired LVEF seems to increase the risk of ST, we aimed to investigate the difference in outcome of patients with varying LVEF using EES versus early-generation DES. METHODS: In a prospective cohort study, we compared the risk of ST in patients in three LVEF subgroups: normal (LVEF >50%), mildly impaired (LVEF >40% and ≤50%) and moderate-severely impaired (LVEF ≤40%). Within these various LVEF groups, we compared EES with SES and PES after adjustment for baseline differences. RESULTS: We assessed a cohort of 5363 patients, with follow-up of up to 4 years and available LVEF. Overall definite ST occurred in 123 (2.3%) patients. ST rates were higher in the LVEF moderate-severely impaired group compared with the normal LVEF group (2.8% vs 2.1%; HR 1.82; CI 1.10 to 3.00). Especially early ST (EST) was more frequent in the moderate-severely impaired LVEF group (HR 2.20; CI 1.06 to 4.53). Overall rates of definite ST were lower in patients using EES compared with patients using SES or PES in all LVEF groups. Interaction terms were not statistically significant. ST rates were higher in the moderate-severely impaired LVEF group compared with the normal LVEF group when using SES or PES, but not significantly different when using EES. CONCLUSIONS: EES was associated with a lower risk of definite ST compared with early-generation DES. This lower risk was independent of LVEF, even though ST rates were higher in patients with a moderate-severely impaired LVEF. TRIAL REGISTRATION NO: MEC-2013-262.

Atrial fibrillation in cardiac resynchronization therapy with a defibrillator: a risk factor for mortality, appropriate and inappropriate shocks.

INTRODUCTION: Knowledge about predictive factors for mortality and (in)appropriate shocks in cardiac resynchronization therapy with a defibrillator (CRT-D) should be available and updated to predict clinical outcome. METHODS: We retrospectively analyzed 543 consecutive patients assigned to CRT-D in 2 tertiary medical centers. The aim of this study was to assess risk factors for all-cause mortality, appropriate and inappropriate shocks. RESULTS: Mean follow-up time was 3.2 (±1.8) years. A total of 110 (20%) patients died, 71 (13%) received ≥1 appropriate shocks, and 33 (6.1%) received ≥1 inappropriate shocks. No patients received a His bundle ablation and biventricular pacing percentage was not analyzed. Multivariable Cox regression analysis showed that a history of atrial fibrillation (AF) (HR 1.74 CI 1.06-2.86), higher creatinine (HR 1.12; CI 1.08-1.16), and a poorer left ventricular ejection fraction (LVEF) (HR 0.97; CI 0.94-1.01) independently predict all-cause mortality. In the entire cohort, history of AF and secondary prevention were independent predictors of appropriate shocks and variables associated with inappropriate shocks were history of AF and QRS ≥150 milliseconds. In primary prevention patients, history of AF also predicted appropriate shocks as did ischemic cardiomyopathy and poorer LVEF. History of AF, QRS ≥150 milliseconds, and lower creatinine were associated with inappropriate shocks in this subgroup. Appropriate shocks increased mortality risk, but inappropriate shocks did not. CONCLUSION: In symptomatic CHF patients treated with CRT-D, history of AF is an independent risk factor not only for mortality, but also for appropriate and inappropriate shocks. Further efforts in AF management may optimize the care in CRT-D patients.

Functional response to cardiac resynchronization therapy is associated with improved clinical outcome and absence of appropriate shocks.

INTRODUCTION: We evaluated clinical outcome and incidence of (in)appropriate shocks in consecutive chronic heart failure (CHF) patients treated with CRT with a defibrillator (CRT-D) according to functional response status. Furthermore, we investigated which factors predict such functional response. METHODS AND RESULTS: In a large teaching hospital, 179 consecutive CHF patients received CRT-D in 2005-2010. Patients were considered functional responders if left ventricular ejection fraction (LVEF) increased to ≥ 35% postimplantation. Analysis was performed on 142 patients, who had CRT-D as primary prevention, complete data and a baseline LVEF <35%. Endpoints consisted of all-cause mortality, heart failure (HF) hospitalizations, appropriate shocks and inappropriate shocks. Median follow-up was 3.0 years (interquartile range [IQR] 1.6-4.4) and median baseline LVEF was 20% (IQR 18-25%). The functional response-group consisted of 42 patients. In this group no patients died, none were hospitalized for HF, none received appropriate shocks and 3 patients (7.1%) received ≥ 1 inappropriate shocks. In comparison, the functional nonresponse group consisted of 100 patients, of whom 22 (22%) died (P = 0.003), 17 (17%) were hospitalized for HF (P = 0.007), 17 (17%) had ≥ 1 appropriate shocks (P = 0.003) and 8 (8.1%) received ≥ 1 inappropriate shocks (P = 0.78). Multivariable analysis showed that left bundle branch block (LBBB), QRS duration ≥ 150 milliseconds and no need for diuretics at baseline are independent predictors of functional response. CONCLUSION: Functional responders to CRT have a good prognosis and rarely need ICD therapy. LBBB, QRS duration ≥ 150 milliseconds and lack of chronic diuretic use predict functional response.