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The impact of substance abuse, including alcohol abuse or illicit drug use, on outcomes after left ventricular assist device (LVAD) implantation, has not been fully elucidated. Accordingly, to test the hypothesis that such a history would be associated with worse outcomes, we analyzed the Interagency Registry for Mechanically Assisted Circulatory Support registry. All patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry who received a continuous-flow LVAD from June 2006 to December 2017 were included. The median follow-up duration was 12.9 months (interquartile range, 5.3 to 17.5). The final study group consisted of 15,069 patients, of which 1,184 (7.9%) had a history of alcohol abuse and 1,139 (7.6%) had a history of illicit drug use. The overall mortality rates in the alcohol, illicit drug, and control groups were 25%, 21%, and 29%, respectively. Cox regression analysis showed that having a history of alcohol abuse (hazard ratio, 0.97, 95% confidence interval, 0.84 to 1.13, p = 0.72) or illicit drug use (hazard ratio, 1.02, 95% confidence interval, 0.86 to 1.21, p = 0.81) was not significantly associated with increased risk of all-cause mortality when compared with general LVAD population. On the contrary, after adjusting for other covariates, a history of alcohol abuse or illicit drug use was significantly associated with increased device malfunction/pump thrombosis, device-related infection, or all-cause hospitalization (all p0.05). Furthermore, After LVAD implantation, these patients had a lower quality of life assessed by the Kansas City Cardiomyopathy Questionnaire compared with those who did not. In conclusion, our findings suggest that patients with a history of alcohol abuse or illicit drug use are at risk for adverse device-related events with a lower quality of life after continuous-flow LVAD implantation compared with the general LVAD population.

Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary.We sought to correlate 6-month CRT response assessed by clinical composite score (CCS) and left ventricular end-systolic volume index (LVESVi) with longer-term mortality and HF-related hospitalizations.Individual patient data from 5 prospective CRT studies-Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD), InSync III Marquis, predictors of response to cardiac resynchronization therapy (PROSPECT), and Adaptive CRT-were pooled. Classification of CRT response status using CCS and LVESVi were made at 6 months. Kaplan-Meier analyses were used to assess time to mortality. Cox proportional hazards regression models were used to compute hazard ratios (HRs) for the 3 levels of CRT response: improved, stabilized, and worsened. Adjusted models controlled for baseline factors known to influence both CRT response and mortality. HF-related hospitalization was compared between CRT response categories using incidence rate ratios.Among a total of 1603 patients, 1426 and 1165 were evaluated in the CCS and LVESVi outcome assessments, respectively. Mortality was significantly lower for patients in the improved (CCS: HR 0.22; 95% confidence interval [CI] 0.15-0.31; LVESVi: HR 0.40; 95% CI 0.27-0.60) and stabilized (CCS: HR 0.38; 95% CI 0.24-0.61; LVESVi: HR 0.41; 95% CI 0.25-0.68) groups than in the worsened group for both measures after adjusting for potential confounders.Patients with a worsened CRT response status have a high mortality rate and HF-related hospitalizations. Stabilized patients have a more favorable prognosis than do worsened patients and thus should not be considered CRT nonresponders.

Background Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.Methods In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged >= 40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033.Findings Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1.0 [95% CI 0.8-1.2]; p=0.85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (p(interaction)=0.002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (p(interaction)=0.012 [>= 29.7 mL/m(2), worse outcomes]), and sex (p(interaction=)0.02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0.11).Interpretation Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Background The survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long‐term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations. Methods The 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety‐four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log‐rank test was used to compare the difference in mortality between two populations and presented by the Kaplan–Meier curves. A multivariate Cox proportional hazards regression was used to determine the independent predictors of all‐cause mortality. Results The overall 30‐day, 1‐year, and 5‐year survival rates were 74%, 44.3%, and 16.6%, respectively, with a median survival of 10 months. There was no significant difference in survival rate between the two races (p‐value = 0.55). The 1‐year survival rate improved significantly during the study timeline in the AA population (13.3% during 1975–1998, 40.9% during 1999–2004, 50% during 2005–2010, and 59.7% during 2011–2016, p‐value = 0.0064). Age of diagnosis, type of tumor, disease stage, and chemotherapy administration are the main factors that predict survival outcomes of PMCT patients. Interactive nomogram was developed based on significant predictors. Conclusions PMCTs have remained one of the most lethal diseases with poor survival outcome. Survival rate improved during the timeline in AA patients, but in general, racial differences in survival outcome were not observed., Survival rate improved during the timeline in AA patients, but in general, racial differences in survival outcome were not observed. Interactive nomogram was developed based on significant predictors: age of diagnosis, type of tumor, disease stage, and chemotherapy administration.

Aim The objective of this study was to investigate the prognostic importance of right ventricular dysfunction (RVD) and tricuspid regurgitation (TR) in patients with moderate–severe functional mitral regurgitation (FMR) receiving MitraClip procedure. RVD and TR grade are associated with cardiovascular mortality in the general population and other cardiovascular diseases. However, there are limited data from observational studies on the prognostic significance of RVD and TR in FMR receiving MitraClip procedure. Methods and results A systemic review and meta‐analysis were performed using MEDLINE, Scopus, and Embase to assess the prognostic value of RVD and TR grade for mortality in patients with functional mitral regurgitation (FMR) receiving MitraClip procedure. Hazard ratios were extracted from multivariate models reporting on the association of RVD and TR with mortality and described as pooled estimates with 95% confidence intervals. A total of eight non‐randomized studies met the inclusion criteria with seven studies having at least 12 months follow‐up with a mean follow‐up of 20.9 months. Among the aforementioned studies, a total of 1112 patients (71.5% being male) were eligible for being included in our meta‐analysis with an overall mortality rate of 28.4% (n = 316). Of the enrolled patients, RVD was present in 46.1% and moderate–severe TR in 29.2%. RVD was significantly associated with mortality compared to normal RV function (HR, 1.79, 95% CI, 1.39–2.31, P

Background: We report 10-year follow up data from a well-established Resistant Hypertension Program. Methods and Results: Between January 2012 and December 2021, there were 976 referrals, of which 357 were excluded, due to non-adherence/no-show. Therefore, demographic and clinical data from 619 patients are summarized in Table 1. Average duration of enrollment was 8.1 months with an average of 4.3 visits. The baseline and final data are shown in Table 2. Despite no weight loss, there were significant reductions in systolic BP (150.2 to 129.5 mmHg, p< 0.05) and diastolic BP (84.8 to 76.3 mmHg, p< 0.05). Average number of antihypertensive medications increased from 1.7 to 3.4, p< 0.05). There data are very similar to those from the first year of the program. Conclusions: Ten-year data from a well-established Resistant Hypertension Program maintained significant blood pressure reductions, similar to results from the first year of program.

Objectives The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). Background There are no proven effective treatments for patients with PH-HFpEF. Methods Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. Results Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (−1.4 mm Hg; 95% confidence interval [CI]: −7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (−3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. Conclusions Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603 )

Cardiac resynchronization therapy (CRT) can improve cardiac function in patients with heart failure (HF); however, in some patients, HF worsens despite CRT. This study characterized the long-term clinical burden of patients with and without HF worsening (HFW) within 6 months post CRT implantation. A claims database (2007–2018) was used to identify two cohorts of adults: those with HFW within 180 days post-CRT and those with no HFW (NHFW). The evaluated clinical outcomes were cardiovascular events/complications, HF-related interventions, hospice enrollment, and all-cause mortality. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders; adjusted comparisons were assessed using weighted Cox proportional hazard ratios (HRs). Among the 12,753 adults analyzed (HFW: N = 4,785; NHFW: N = 7,968), the mean age was 72 years and the mean duration of follow-up was approximately 2 years. The clinical burden was greater for HFW than for NHFW in terms of all-cause mortality (19.7% vs. 12.1%) and occurrence of atrial fibrillation (57.4% vs. 51.2%). In the IPTW-adjusted Cox proportional hazard analyses, patients with HFW had a 54% higher average hazard of experiencing all-cause mortality compared to NHFW (adjusted average HR = 1.54, 95% confidence interval [CI]: 1.41–1.70; p < .001). Of the clinical events experienced by ≥5% of patients, the greatest differences in average hazard were for HF decompensation (adjusted average HR = 1.83, 95% CI: 1.60–2.09) and HF decompensation or death (HR = 1.63, 95%CI: 1.50–1.77). Patients with early HFW post-CRT experienced a significantly higher clinical burden than those without HFW. Vigilance for signs of worsening HF in the first 6 months post-CRT is warranted.

Although cardiac resynchronization therapy (CRT) has the potential to improve cardiac function in patients with heart failure (HF), a considerable portion of patients do not respond to therapy. This study assessed the economic burden among patients with and without HF worsening after receiving CRT in real-world practice. In this retrospective claims-based study using Optum’s de-identified Clinformatics® Data Mart Database (January 2007–December 2018), adults who received CRT were stratified into two cohorts based on whether they showed evidence of HF worsening within 180 days post-CRT implantation. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, accounting for demographics (e.g., age, sex), the Quan–Charlson Comorbidity Index, other clinical characteristics, healthcare resource utilization (HRU), and healthcare costs during the 180 days pre-CRT (baseline period). Annualized all-cause and congestive HF-related HRU and healthcare costs from payer and patient perspectives were assessed from day 181 post-CRT (follow-up period), and compared between cohorts using incidence rate ratios (IRRs) and cost ratios (CRs). This study included 12,753 patients (n = 4785 with HF worsening; n = 7968 without). Mean age was 72 years and roughly two-thirds were male. Baseline characteristics were balanced between cohorts post-IPTW. During follow-up, patients with HF worsening had significantly greater annual all-cause inpatient [adjusted IRR (95% confidence interval) = 1.55 (1.44, 1.66), p

Graphical abstract, Highlights • Coronary cameral fistula is a rare cardiac anomaly. • Coronary fistula can occur as complication of surgical trauma. • 3D transesophageal echocardiogram can be used in the detection of coronary fistulae.

Background Recent studies have demonstrated left ventricular myocardial work (MW) is incremental in diagnosis and prognostication when compared to left ventricular ejection fraction and myocardial strain. We performed a meta-analysis of normal ranges of non-invasive MW indices including global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) and to determine confounder that may contribute to variance in reported values. Methods Four databases including Pubmed, Scopus, Embase, and Cochrane Library were searched through January 2021 using the key terms “myocardial work", "global constructive work", "global wasted work", “global work index", "global work efficiency”. Studies were included if the articles reported LV myocardial work using 2D transthoracic echocardiography in healthy normal subjects, either in control group or comprising of the entire study cohort. The weighted mean was estimated by using the random effect model with a 95% confidence interval. Heterogeneity across included studies was assessed using the I2 test. Funnel plot and Egger’s regression test were used to assess potential publication bias Results The search yielded 476 articles. After abstract and full-text screening, we included 13 datasets with 1665 patients for the meta-analysis. The reported normal mean values of GWI and GCW among the studies were 2010 mmHg% (95% CI, 1907 to 2113), and 2278 mmHg% (95% CI, 2186 to 2369) respectively. The mean GWW was 80 mmHg% (95% CI, 73 to 87), and the mean GWE was 96.0% (95% CI, 96% to 96%). Furthermore, gender significantly contributed to variations in normal values of GWI, GWW, and GWE. No evidence of significant publication bias was observed. Conclusion In this meta-analysis, we provide echocardiographic reference ranges for non-invasive indices of MW. These normal values could be served as a reference for clinical and research use.

There is a growing body of literature supporting the utilization of machine learning (ML) to improve diagnosis and prognosis tools of cardiovascular disease. The current study was to investigate the impact that the ML framework may have on the sensitivity of predicting the presence or absence of congenital heart disease (CHD) using fetal echocardiography. A comprehensive fetal echocardiogram including 2D cardiac chamber quantification, valvar assessments, assessment of great vessel morphology, and Doppler-derived blood flow interrogation was recorded. The postnatal echocardiogram was used to ascertain the diagnosis of CHD. A random forest (RF) algorithm with a nested tenfold cross-validation was used to train models for assessing the presence of CHD. The study population was derived from a database of 3910 singleton fetuses with maternal age of 28.8 ± 5.2 years and gestational age at the time of fetal echocardiography of 22.0 weeks (IQR 21-24). The proportion of CHD was 14.1% for the studied cohort confirmed by post-natal echocardiograms. Our proposed RF-based framework provided a sensitivity of 0.85, a specificity of 0.88, a positive predictive value of 0.55 and a negative predictive value of 0.97 to detect the CHD with the mean of mean ROC curves of 0.94 and the mean of mean PR curves of 0.84. Additionally, six first features, including cardiac axis, peak velocity of blood flow across the pulmonic valve, cardiothoracic ratio, pulmonary valvar annulus diameter, right ventricular end-diastolic diameter, and aortic valvar annulus diameter, are essential features that play crucial roles in adding more predictive values to the model in detecting patients with CHD. ML using RF can provide increased sensitivity in prenatal CHD screening with very good performance. The incorporation of ML algorithms into fetal echocardiography may further standardize the assessment for CHD.

Background Non-invasive global myocardial work recently emerged as new parameter to characterize left ventricle function with potential advantages over both ejection fraction and global longitudinal strain. Purpose We aimed to perform a meta-analysis of normal ranges of non-invasive left ventricular myocardial work (MW) indices including global constructive work (GCW), global work index (GWI), global wasted work (GWW), and global work efficiency (GWE) and to identify confounding factors that may contribute to variance in reported measures. Methods The authors searched four databases, Pubmed, Scopus, Embase, and Cochrane Library through January 2021 using the key terms “myocardial work”,“global constructive work”, “global wasted work”, “global work index”, “global work efficiency”. Studies were included if the articles reported LV myocardial work using 2D transthoracic echocardiography in healthy normal subjects, either in the control group or comprising the entire study cohort. The weighted mean was estimated by using the random effect model with a 95% confidence interval. Heterogeneity across studies was assessed using the I2 test. Publication bias was examined by funnel plot and Egger's regression test. Results The search yielded 476 articles. After abstract and full text screening we included 13 datasets with 1665 patients for meta-analysis. The reported normal mean values of GCW and GWI among the studies were 2278 (95% CI, 2167 to 23878; I2=95%), and 2.010 (95% CI, 1922 to 2098, I2=97%), respectively. The mean GWE was 96.0 (95% CI, 95.6% to 96.5; I2=92%), and the mean GWW was 79.7% (95% CI, 68.8% to 90.7%; I2=90%) (Figure). Furthermore, age and gender did not significantly contribute to variations in normal values. No evidence of significant publication bias was observed in the funnel plots and the Egger test. Conclusion In this meta-analysis, we provide echocardiographic reference ranges for non-invasive indices of MW. These normal values should serve as a template for clinical and research use for this promising technology. Funding Acknowledgement Type of funding sources: None.

Antonio Hernández-Madrid,1 Xiaoxiao Lu,2 Stelios I Tsintzos,3 Dedra H Fagan,2 Ruth Nicholson Klepfer,2 Roberto Matía,1 Eugene S Chung41Arrhythmia Unit, Cardiology Department, Ramón y Cajal Hospital, Alcalá University, Madrid, Spain; 2Medtronic, plc, Mounds View, MN, USA; 3Medtronic, Tolochenaz, Switzerland; 4The Christ Hospital Heart and Vascular Center, The Lindner Center for Research and Education, Cincinnati, OH, USABackground: The hOLter for Efficacy analysis (OLE) study demonstrated that current device pacing diagnostics overestimate the amount of cardiac resynchronization therapy (CRT) pacing that effectively stimulates the cardiac tissue. Sub-optimal pacing increases mortality, hospitalizations, and associated health-care costs. We sought to estimate the expected number of hospital admissions due to heart failure (HF) and its respective financial impact in patients with maximized effective pacing versus conventional pacing.Methods: A Markov model was developed to project HF hospitalizations and quantify the costs that could be avoided if pacing was maximally effective. OLE data were used to inform the prevalence of ineffective pacing among CRT patients and and average loss of pacing by causes. Adaptive CRT trial data quantified the reduction in underlying hospitalization risk by increasing effective pacing delivered. Survival was informed by a meta-analysis of 5 randomized clinical trials. Costs were analyzed from a US payer perspective.Results: Projected average hospitalizations totaled 4.58 over a lifetime horizon for CRT patients with conventional pacing. Maximizing effective pacing delivery was projected to avoid 1.83 HF admissions/patient over the lifetime. This equates to a savings of 40% (US$22,802) compared with conventional pacing from the Medicare perspective. In a sensitivity analysis, CRT with effective pacing was projected to provide cost savings in all scenarios.Conclusions: Maximized effective pacing leads to a lower number of HF hospitalizations, thus allowing significant cost offsets in the US setting.Keywords: heart failure, ventricular pacing, effective pacing, hospitalization reduction, cost savings

Objectives: This study sought to determine clinician and scientist involvement in heart failure (HF) clinical research and to describe the challenges of conducting clinical trials in the Un...

Introduction Aortic stenosis (AS) imposes a significant afterload on the left ventricle, but regional manifestations of the overall load may not be uniform, leading to mechanical dyssynchrony. Accordingly, we evaluated the prevalence of dyssynchrony in patients with severe AS at baseline as well as changes after transfemoral aortic valve replacement (TAVR). Methods This study is a retrospective analysis of 225 patients in sinus rhythm who underwent TAVR for severe AS, in whom inter-ventricular and intra-ventricular dyssynchrony were measured at baseline, discharge, 1 month, and 1 year. Inter-ventricular dyssynchrony was defined as the difference between left and right ventricular pre-ejection intervals; intra-ventricular dyssynchrony was defined as the difference between time to peak systolic velocity of the basal septal and lateral segments. Patients were further stratified into those with QRS 120 ms. Results At baseline, a quarter of patients met the criterion for significant inter-ventricular dyssynchrony, and a third had evidence of intra-ventricular dyssynchrony. Both decreased after TAVR although only the intra-ventricular dyssynchrony reached statistical significance. The interplay between QRS duration and changes in inter- and intra-ventricular dyssynchrony are also explored. Conclusions In patients with severe AS, there was evidence of mechanical dyssynchrony that is improved post-TAVR. Whether dyssynchrony is clinically and prognostically significant, and if it represents a potential target for additional therapy remains to be studied.

The impact of preoperative end-diastolic left ventricular dimension (preLVEDD) on long-term outcomes with centrifugal continuous-flow left ventricular assist device (CF-LVAD) is not well established. Accordingly, we performed an analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry to study this relationship. All patients with centrifugal CF-LVAD in the INTERMACS registry from June 2006 to December 2017 were screened. The final study group consisted of 3,304 patients. After a median follow-up of 9.0 months (interquartile range [IQR], 4.2-18.8 months), 2,596 (79%) patients were alive. After adjusting for significant covariates, increased preLVEDD was associated with lower mortality (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84-0.98; p = 0.01), stroke (HR, 0.85; 95% CI, 0.77-0.93; p < 0.001), and gastrointestinal bleeding (HR, 0.88; 95% CI, 0.80-0.97; p = 0.01), although there were more arrhythmias (HR, 1.14; 95% CI, 1.05-1.24; p = 0.003). Our study suggests that preLVEDD is an independent predictor of mortality and adverse events in patients treated with centrifugal CF-LVAD. preLVEDD should be considered an important preimplant variable for risk stratification when considering a CF-LVAD.

To investigate ventriculo-arterial coupling (VAC) and its components (Ea, Ees) in patients with stable ischemic heart disease and changes following percutaneous coronary intervention (PCI). 129 patients with stable ischemic heart disease (SIHD) undergoing PCI (study group) and 40 individuals without IHD (control group) were enrolled. VAC was calculated using echocardiography method at baseline and 1, 3, and 6 months after PCI. A linear mixed-effects models with restricted maximum likelihood were used to assess the impact of PCI on Ea, Ees, VAC over 6-month follow-up. Mean age of the SIHD group was 67.8 ± 8.1 (years), and predominantly men (73.6%). In the SIHD group, baseline median Ea, Ees and VAC were 2.52 (IQR 1.89-3.28) (mmHg/ml), 3.87 (IQR 2.90-4.95) (mmHg/ml), and 0.64 (IQR 0.54-0.79), respectively. Patients with SIHD had significantly lower Ees and higher VAC when compared to the control group (p < 0.05). Ees (p = 0.01) and VAC (p < 0.001) were significantly improved over 6 month follow-up after PCI. Notably, the degree of VAC improvement appears to be related to stented artery (Table 3). VAC obtained from echocardiographic methodology demonstrated a significant increase in patients with SIHD at baseline. This observation may represent a plausible mechanism for the benefit of PCI in SIHD. Hence, VAC may be a feasible parameter in the assessment of patients with SIHD.

The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).There are no proven effective treatments for patients with PH-HFpEF.Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages.Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (-1.4 mm Hg; 95% confidence interval [CI]: -7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (-3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo.Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603).

Introduction Chronic right ventricular pacing (RVP) has been associated with dyssynchrony, leading to increased mortality. However, there have been discrepancies in previous reports in the effect of RVP levels. Objective To sub-stratify mortality risk by age for different RVP level groups within a large real-world ICD cohort. Methods Optum® de-identified electronic health records were linked to the Medtronic Carelink data to identify dual chamber ICD recipients (2007–2017). RVP level was based on median daily pacing during the first 90 days post-implant and categorized either into groups with a cutoff of 40%, or with groups of 0–9%, 10–19%, 20–29%, 30–39%, 40–49%, and 50–100%. The endpoint was death more than 90 days post-implant. Kaplan-Meier survival curves, log-rank tests, and Cox regression were used to analyze the relationship between RVP and risk of death. Results Among 14,832 ICD patients (median age 67; 74.0% male), there were 2,602 deaths within 10 years after implant. In unadjusted comparisons, high RVP (>40%) increased the risk of death relative to low RVP (≤40%) (p Conclusions Our data from a large contemporaneous real-world source suggests that older age or characteristics associated with age make patients more sensitive to chronic RVP effects. These results help reconcile differences observed in prior studies. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic, Inc.

Background An accurate assessment of permanent pacemaker implantation (PPI) risk following transcatheter aortic valve replacement (TAVR) is important for clinical decision making. The aims of this study were to investigate the significance and utility of pre- and post-TAVR ECG data and compare machine learning approaches with traditional logistic regression in predicting pacemaker risk following TAVR. Methods Five hundred fifity seven patients in sinus rhythm undergoing TAVR for severe aortic stenosis (AS) were included in the analysis. Baseline demographics, clinical, pre-TAVR ECG, post-TAVR data, post-TAVR ECGs (24 h following TAVR and before PPI), and echocardiographic data were recorded. A Random Forest (RF) algorithm and logistic regression were used to train models for assessing the likelihood of PPI following TAVR. Results Average age was 80 ± 9 years, with 52% male. PPI after TAVR occurred in 95 patients (17.1%). The optimal cutoff of delta PR (difference between post and pre TAVR PR intervals) to predict PPI was 20 ms with a sensitivity of 0.82, a specificity of 0.66. With regard to delta QRS, the optimal cutoff was 13 ms with a sensitivity of 0.68 and a specificity of 0.59. The RF model that incorporated post-TAVR ECG data (AUC 0.81) more accurately predicted PPI risk compared to the RF model without post-TAVR ECG data (AUC 0.72). Moreover, the RF model performed better than logistic regression model in predicting PPI risk (AUC: 0.81 vs. 0.69). Conclusions Machine learning using RF methodology is significantly more powerful than traditional logistic regression in predicting PPI risk following TAVR.

Chronic afterload excess in aortic stenosis results in compensatory concentric hypertrophy which mitigates the increased systolic load. Surgical aortic valve replacement has been shown to decrease afterload and improve left ventricular (LV) ejection fraction (EF). The extent to which these changes take place in patients undergoing TAVI (transcatheter aortic valve intervention) may be different than what has been observed in the surgical aortic valve replacement patients who were generally younger with few co-morbidities. Accordingly, we analyzed indices of LV structure and ventricular mechanics pre- and 1-year after TAVI in 397 patients (mean age 81±9, 46% women) with severe symptomatic aortic stenosis, complete echocardiographic data was available in 156 patients and these patients compromised our study population. Our principal findings are: (1) LV remodeling occurs after TAVI; (2) afterload decreases significantly; (3) LV chamber and myocardial function, assessed by left ventricular ejection fraction and midwall fractional shortening, and stroke volume, respectively, remain unchanged or decrease. In conclusion, TAVI effects LV remodeling despite significant co-morbidities. Thus, TAVI reduces afterload and leads to LV remodeling. Surprisingly, however, systolic function does not improve. These data run counter to the paradigm that afterload reduction improves systolic function and suggest that the response to afterload reduction is complex in the TAVI population.

Background The aim of this study was to examine the relationship between baseline left ventricular (LV) geometry and outcomes after transcatheter aortic valve replacement (TAVR). Methods Patients undergoing TAVR (n = 206) had baseline LV geometry classified as (1) concentric hypertrophy, (2) eccentric hypertrophy, (3) concentric remodeling, or (4) normal. Descriptive statistics, Kaplan-Meier time-to-event analysis, and Cox regression were performed. Results Distribution of baseline LV geometry differed between male and female patients (χ2 = 16.83, P = .001) but not at 1 month (χ2 = 2.56, P = .47) or 1 year (χ 2 = 5.68, P = .13). After TAVR, a majority of patients with concentric hypertrophy evolved to concentric remodeling. Survival differed across LV geometry groups at 1 year (χ2[3] = 8.108, P = .044, log-rank test) and at 6.5 years (χ2[3] = 9.023, P = .029, log-rank test). Compared with patients with concentric hypertrophy, patients with normal geometry (hazard ratio, 2.25; 95% CI, 1.12–4.54; P = .023) and concentric remodeling (hazard ratio, 1.89; 95% CI, 1.12–3.17; P = .016) had higher rates of all-cause mortality. Conclusions Baseline concentric hypertrophy confers a survival advantage after TAVR. Although baseline patterns of LV geometry appear gender specific (with women demonstrating more concentric hypertrophy), this difference resolves after TAVR.

Moderate aortic stenosis (AS) confers a surprisingly adverse prognosis, approaching that of severe AS. The objective of this study was to describe the clinical course of patients with moderate AS with evidence of concomitant heart failure manifesting as elevated brain natriuretic peptide (BNP) levels.This is a single-center, retrospective cohort study of 332 patients with elevated BNP. 165 patients with moderate AS were compared with 167 controls with none-mild AS. The Median follow-up duration was 3.85 years. The primary outcome was a composite endpoint of all-cause hospitalizations and all-cause mortality.BNP levels were 530 and 515 pg/mL in the study and the control groups, respectively. Moderate AS had significantly higher rates of primary composite endpoint in both univariate analysis (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.14-1.97; p=0.004) and adjusted analysis (HR, 1.45; 95% CI, 1.05-2.01; p=0.02). Moderate AS had 1.41 (95% CI, 1.18-1.69; p0.001) times more all-cause hospitalization per patient-year of follow-up compared to controls in the univariate model. After adjustment for significant covariates, moderate AS remained an independent predictor of all-cause hospitalizations (incidence rate ratio [IRR], 1.45; 95% CI, 1.18-1.79; p=0.005). Furthermore, moderate AS was significantly associated with higher all-cause hospitalization rates in both heart failure with reduced ejection fraction (IRR, 1.33; 95% CI, 1.02-1.75; p=0.038) and heart failure with preserved ejection fraction [IRR], 1.31; 95% CI, 1.03-1.67; p=0.026).Moderate AS in conjunction with elevated BNP portends a significantly worse prognosis than those without moderate AS and should be followed closely.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong predictor of heart failure and mortality. The predictors of long-term remodeling after MI have been incompletely studied. We therefore examined the correlates of LV remodeling in patients with large ST-segment elevation myocardial infarction and a patent infarct artery after percutaneous 2coronary intervention (PCI) from the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial. Peri-infarct pacing had a neutral effect on long-term remodeling in patients with large first MI. The present analysis includes 109 patients in whom an open artery was restored after PCI, and in whom LV end-diastolic volume (LVEDV) at baseline and 18 months was assessed by transthoracic echocardiography. Multivariable models were fit to identify the independent predictors of LVEDV at baseline and 18 months. By multivariable analysis, male sex (p = 0.004) and anterior MI location (p = 0.03) were independently associated with baseline LVEDV. The following variables were independent predictors of increased LVEDV at 18 months: younger age (p = 0.01), male sex (p = 0.03), peak creatine phosphokinase (p = 0.03), shorter time from MI to baseline transthoracic echocardiography (p = 0.04), baseline LVEDV (p 0.0001), and lack of statin use (p = 0.03). In conclusion, patients with large MI and an open infarct artery after PCI, anterior MI location, and male sex were associated with greater baseline LVEDV, but MI location was not associated with 18-month LVEDV. In contrast, younger age, peak creatine phosphokinase, male sex, baseline LVEDV, and lack of statin use were associated with long-term LV remodeling.

Aims: The Biventricular vs Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) demonstrated that biventricular (BiV) pacing resulted in better clinical and structural outcomes compared to right ventricular (RV) pacing in patients with atrioventricular (AV) block and reduced left ventricular ejection fraction (LVEF; ≤50%). This study investigated the cost-effectiveness of BiV vs RV pacing in the patient population enrolled in the BLOCK-HF trial. Methods: All-cause mortality, New York Heart Association (NYHA) Class distribution over time, and NYHA-specific heart failure (HF)-related healthcare utilization rates were predicted using statistical models based on BLOCK-HF patient data. A proportion-in-state model calculated cost-effectiveness from the Medicare payer perspective. Results: The predicted patient survival was 6.78 years with RV and 7.52 years with BiV pacing, a 10.9% increase over lifetime. BiV pacing resulted in 0.41 more quality-adjusted life years (QALYs) compared to RV pacing, at an additional cost of $12,537. The “base-case” incremental cost-effectiveness ratio (ICER) was $30,860/QALY gained. Within the clinical sub-groups, the highest observed ICER was $43,687 (NYHA Class I). Patients receiving combined BiV pacing and defibrillation (BiV-D) devices were projected to benefit more (0.84 years gained) than BiV pacemaker (BiV-P) recipients (0.49 years gained), compared to dual-chamber pacemakers. Conclusions: BiV pacing in AV block patients improves survival and attenuates HF progression compared to RV pacing. ICERs were consistently below the US acceptability threshold ($50,000/QALY). From a US Medicare perspective, the additional up-front cost associated with offering BiV pacing to the BLOCK-HF patient population appears justified.

Background The AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular conduction, providing synchronized left ventricular pacing in patients with normal PR interval and adaptive BiV pacing in patients with prolonged PR interval. Previous analyses demonstrated an association between aCRT and clinical benefit. We evaluated the incidence of patient mortality and atrial fibrillation (AF) with aCRT compared with standard CRT in a real‐world population. Methods and Results Patients enrolled in the Medtronic Personalized CRT Registry and implanted with a CRT from 2013‐2018 were divided into aCRT ON or standard CRT groups based upon device‐stored data. A Frailty survival model was used to evaluate the potential survival benefit of aCRT, accounting for patient heterogeneity and center variability. Daily AF burden and first device‐detected AF episodes of various durations were recorded by the device during follow‐up. A total of 1814 CRT patients with no reported long‐standing AF history at implant were included. Mean follow‐up time was 26.1 ± 16.5 months and 1162 patients (64.1%) had aCRT ON. Patient survival probability at 36 months was 88.3% for aCRT ON and 83.7% for standard CRT (covariate‐adjusted hazard ratio [HR] = 0.71, 95% CI: 0.53‐0.96, P = .028). Mean AF burden during follow‐up was consistently lower in aCRT ON patients compared with standard CRT. At 36 months, the probability of AF was lower in patients with aCRT ON, regardless of which AF definition threshold was applied (6 minutes‐30 days, all P

Background Establishing normal values and associated variations of three-dimensional speckle-tracking echocardiography– (3DSTE-) derived left ventricular (LV) strain is necessary for accurate interpretation and comparison of measurements. We aimed to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) measurements derived by 3DSTE and to identify confounding factors that may contribute to variance in reported measures. Methods The authors searched four databases, PubMed, Scopus, Embase, and Cochrane Library, through January 2019 using the key terms “left ventricular/left ventricle/left ventricles”, “strain/deformation/speckle tracking”, and “three dimensional/three-dimensional/three-dimension/three dimension/3D”. Studies were included if the articles reported LV strain using 3DSTE in healthy normal subjects, either in the control group or comprising the entire study cohort. The weighted mean was estimated by using the random effects model with a 95% CI. Heterogeneity across studies was assessed using the I2 test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. The National Institutes of Health tools were used to assess the quality of included articles. Publication bias was examined by Begg's funnel plot and Egger's regression test. Results The search yielded 895 articles. After abstract and full-text screening we included 33 data sets with 2,346 patients for meta-analysis. The reported normal mean values of GLS among the studies varied from −15.80% to −23.40% (mean, −19.05%; 95% CI, −18.18% to −19.93%; I2 = 99.0%), GCS varied from −15.50% to −39.50% (mean, −22.42%; 95% CI, −20.96% to −23.89%, I2 = 99.7%), GRS varied from 19.81% to 86.61% (mean, 47.48%; 95% CI, 41.50%-53.46%; I2 = 99.8%), and GAS varied from –27.40% to –50.80% (mean, –35.03%; 95% CI, –33.19% to –36.87%; I2 = 99.3%). Software for strain analysis was consistently associated with variations in normal strain values (GLS: P = .016; GCS: P Conclusions Variations in the normal ranges across studies were significantly associated with the software used for strain analysis, emphasizing that this factor must be considered in the interpretation of strain data.

Background Left ventricular filling pressure (LVFP) has been demonstrated to be a major predictor of poor cardiovascular outcomes. However, estimation of LVFP in patients with aortic stenosis is limited by the high prevalence of significant mitral annular calcification. The aim of this study was to investigate the effect of transcatheter aortic valve replacement on LVFP and the relationship of LVFP to mortality and hospitalization. Methods This was a single-center, retrospective study of 140 consecutive patients in sinus rhythm with significant mitral annular calcification who underwent transcatheter aortic valve replacement for severe aortic stenosis from May 2011 to June 2015. Mean follow-up duration was 3.06 ± 1.48 years (minimum, 2.4 years; maximum, 6.5 years). Diastolic function was assessed using recently proposed criteria for those with significant mitral annular calcification. High LVFP was defined as a mitral E/A ratio > 1.8 or a ratio of 0.8 to 1.8 and isovolumic relaxation time Results At baseline, the proportion of patients with high LVFP was 40.7%, similar to 1 month (39.7%) (P = .86). However, the proportion of patients with high LVFP was significantly decreased at 1 year compared with those at baseline (26.9% vs 40.7%, P = .02). Multivariate analysis showed that high LVFP at baseline significantly increased risk for all-cause mortality compared with patients with normal LVFP (hazard ratio, 2.84; 95% confidence interval, 1.33–6.05; P = .007). Conclusions High baseline LVFP was associated with a significantly increased all-cause mortality, and LVFP does not improve in the short term but only at 1 year after transcatheter aortic valve replacement.

Background Sustained right ventricular (RV) apical pacing may lead to deterioration in ventricular function and an increased risk of heart failure, especially in patients with pre-existing systolic dysfunction. The BLOCK HF (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block) trial demonstrated that biventricular-paced patients had a reduced incidence of a composite endpoint of death, heart failure–related urgent care, and adverse left ventricular remodeling. Objectives In a pre-specified analysis, this study examined clinical outcomes, including clinical composite score, quality of life (QOL), and change in New York Heart Association (NYHA) functional classification. Methods The BLOCK HF trial randomized patients with atrioventricular block, NYHA symptom class I to III heart failure, and left ventricular ejection fraction ≤50% to biventricular or RV pacing. NYHA functional classification, QOL, and clinical composite score were assessed at 6, 12, 18, and 24 months. Bayesian statistical methods were used, with the pre-specified metric of benefit being a posterior probability ≥0.95. Results Patients with biventricular pacing showed greater improvement in NYHA functional class at 12 months, with 19% improved, 61% unchanged, and 17% worsened, compared with 12%/62%/23% in the RV arm. QOL was improved through 12 months. At 6 months, clinical composite score was improved/unchanged/worsened in 53%/24%/24% in the biventricular arm compared with 39%/33%/28% in the RV arm. This improvement in clinical composite score was sustained through 24 months. Conclusions For patients with atrioventricular block and systolic dysfunction, biventricular pacing not only reduces the risk of mortality/morbidity, but also leads to better clinical outcomes, including improved QOL and heart failure status, compared with RV pacing. (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block [BLOCK HF]; NCT00267098 )

Objectives The aim of our work is to investigate the clinical characteristics of coronary artery fistula (CAF) anomalies in South Vietnam. Methods This is a retrospective analysis of 119 patients with diagnosis of definite CAF between January 1992 and April 2016. The demographic, clinical, echocardiographic, and angiographic characteristics and management of CAF with short-term outcomes are described. Results The median age was 15 years (range, 1-79 years), with 49 male (41%) and 70 female (59%). There were 77 symptomatic patients (64.7%) and 91 patients (76.5%) who presented with a murmur. The electrocardiogram was abnormal in 45.4% and cardiac enlargement or increased pulmonary vasculature were seen in 76 patients (63.9%) on chest X-ray. The sensitivity of echocardiography for CAF diagnosis was 79%. The source of the fistula was most often from the RCA (54%), most commonly to right atrium (34.5%) or right ventricle (31.1%). In comparison with surgery, transcatheter closure had a shorter hospital length of stay (5.4 ± 3.8 days vs 12.6 ± 6.5 days, P = .02) and better postprocedural left ventricular ejection fraction (67.9 ± 8.1% vs 62.9 ± 6.0%, P = .03). Conclusion The majority of fistula in this study originated from the RCA and terminated in the right atrium or the right ventricle. Transcatheter and surgical closure are both relatively safe and effective, with the potential for shortened length of hospital stay following transcatheter closure.

Background The conduct of rigorous HF clinical trials requires participation from a wide variety of institutions and partnerships across academic, non-academic, Veterans Affairs, and industry. We aimed to examine differences between academic and non-academic centers in the conduct of HF clinical trials in North America. Methods HFSA distributed an electronic survey to examine the current state of HF clinical trial activity. Surveys were distributed to current or past HFSA members and affiliates, HF members of AHA and ACC. Pearson's chi-squared test was applied to categorical data. Results A total of615 surveys were returned. Of these, 410 respondents reported being currently active in the conduct of HF trials and were included in this analysis. Respondents represented 45 states and 331 distinct institutions. Most respondents were physicians (n=269, 66%), followed by nurses or nurse practitioners (n=83, 20%) and pharmacists (n=20, 5%). The majority of respondents were from academic centers (n=311, 75.5%), followed by non-academic (n=59, 14%), industry (n=22, 5%), and Veterans Affairs (n=18, 4%). Academic and non-academic institutions participated in a similar number of trials per year and reported similar numbers of subjects enrolled per year (Table). In addition, regulatory and staff resources including time to Institutional Review Board (IRB) approval, access to a central IRB, timeline for execution of contracts and number of study coordinators were not different between academic and non-academic institutions. Respondents from academic institutions did report more publications per year than those from non-academic institutions and participation differed in types of trials. Involvement as a lead national primary investigator or co-investigator for multi-centered trials was higher in academic institutions than non-academic institutions (40% vs 29%). Conclusion Academic and non-academic institutions contributed similarly to the conduct of HF clinical trials across North America. Regulatory and staff resources were also comparable. Opportunities exist to better engage non-academic investigators in publications and other leadership opportunities within multi-centered HF clinical trials.

Background Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. Methods The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 μg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group. Those randomized to a device will be blinded to the pacing mode, but randomization to a device or control cannot be blinded. Subjects randomized to pacing will have the device implanted within 10 days of MI. The primary objective is to assess the change in left ventricular end-diastolic volume from baseline to 18 months. Secondary objectives are to assess changes in clinical and mechanistic parameters between the groups, including rates of hospitalization for heart failure and cardiovascular events, the incidence of sudden cardiac death and all-cause mortality, New York Heart Association functional class, 6-minute walking distance, and quality of life. Conclusions The PRomPT trial will provide important evidence regarding the potential of peri-infarct pacing to interrupt adverse remodeling in patients with large MI.

Background Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). Methods Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. Results Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met ( P = 0.89). For the patients treated with pSDF-1, there was a trend toward an improvement in LVEF at 12 months (placebo vs. 15 mg vs. 30 mg ΔLVEF: −2 vs. −0.5 vs. 1.5%, P = 0.20). A pre-specified analysis of the effects of pSDF-1 based on tertiles of LVEF at entry revealed improvements in EF and LVESV from lowest-to-highest LVEF. Patients in the first tertile of EF (