Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

AIMS: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. METHODS AND RESULTS: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. CONCLUSIONS: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Management strategies and prognosis of patients ineligible for transcatheter mitral valve replacement.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) faces anatomical challenges, currently limiting widespread adoption. OBJECTIVES: To describe the natural history and prognosis of patients ineligible for various TMVR devices. METHODS: During a 4-year period (2019-2023) 3 TMVR devices (SAPIEN M3, Intrepid and Alta Valve) became available at a single institution (The Christ Hospital, Cincinnati, OH) in the setting of pivotal clinical trials or early feasibility study. Consenting patients who were deemed ineligible ≥1 of these trials were prospectively studied to capture anatomical reasons for ineligibility, cross-over to alternative mitral valve therapies (surgery or high-risk mitral transcatheter edge to edge repair [M-TEER]), and clinical events. RESULTS: A total of 61 patients (out of 71 consenting patients or 85.9 %) were deemed ineligible for TMVR during the study period. The mean age was 79.2 ± 8.8 years, 65.6 % were female, with elevated surgical risk (median STS 4.3, IQR: 2.7-7.3). The 2 most common anatomical reasons for ineligibility were increased risk of left ventricular outflow tract obstruction (LVOTO) (n = 24, 39.3 %) and annular size (n = 29, 47.5 %). During follow-up (median 277 [162-555] days) there were 7 deaths (11.5 %) and 12 (19.7 %) hospitalizations for heart failure. Management strategies included high-risk M-TEER in 11 patients (1 death [9.0 %], 0 HF hospitalizations [0 %]), surgery in 9 patients (0 deaths, 1 HF hospitalizations [11.1 %]), and medical management in 41 patients (6 deaths [14.6 %], 11 HF hospitalizations [26.8 %]) (p = 0.715 for mortality and p = 0.093 for HF hospitalizations). Residual MR ≥ moderate was 0 %, 50 %, and 100 % for surgery, M-TEER and medical treatment, respectively (p < 0.001). CONCLUSIONS: One third of patients deemed ineligible for TMVR are candidates for high-risk M-TEER or surgery with acceptable morbidity and mortality. Our results have practical implications for patient management.

Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial.

BACKGROUND: Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. METHODS: This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. FINDINGS: Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. INTERPRETATION: Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. FUNDING: Medtronic.

Systolic Heart Failure is Associated with Higher Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Analysis.

Heart failure (HF) is prevalent among patients with aortic stenosis and presents a poor prognosis. In order to better portray outcomes for HF patients undergoing transcatheter aortic valve replacement (TAVR), we evaluated clinical outcomes in patients with systolic vs diastolic heart failure who underwent TAVR in a large nationwide database. We searched the National Inpatient Sample (NIS) for hospitalized adult patients who underwent TAVR with coexisting history of systolic (SHF) or diastolic heart failure (DHF) as a secondary diagnosis using the ICD-10 codes. The primary outcome was in-hospital mortality, with secondary outcomes of cardiac arrest (CA), cardiogenic shock (CS), respiratory failure (RF), Non-ST elevation myocardial infarction (NSTEMI), acute kidney injury (AKI), use of cardiac and respiratory assist device, and health care utilization defined as length of stay, average hospital cost (AHC) and patient charge (APC). Both univariate and multivariate logistic, generalized linear, and Poisson regression analyses were used to evaluate and test the outcomes. A P-value of <0.05 was significant. A total of 106,815 patients were admitted to acute care hospitals for TAVR, and 73% had a secondary diagnosis of heart failure (41% had SHF and 59% DHF). SHF group were older (mean age of 78.9 years [SD ± 8.9] vs 79.9 years [SD ± 8.3]) with more males (61.8% vs 48.2%) and white predominant (whites [85.9% vs 87.9%]). Compared to DHF, SHF had higher inpatient mortality (1.75% vs 1.14%, P = 0.003), CA (1.31% vs 0.81%, P = 0.01), NSTEMI (2.52% vs 1.0%, P = 0.001), RF (10.87% vs 8.01%, P = 0.001), and CS (3.94% vs 1.14%, P = 0.001). In addition, SHF had greater LOS (5.1 days vs. .3.9, P = 0.0001) & AHC ($52,901 vs $48,070, P = 0.0001). HF is common among patients admitted for TAVR. SHF had worse CV outcomes, greater use of hospital resources, and higher acute care hospital mortality compared to those with DHF.

A Review of Heart Failure in Patients with COVID-19.

The interplay of COVID-19 and heart failure is complex and involves direct and indirect effects. Patients with existing heart failure develop more severe COVID-19 symptoms and have worse clinical outcomes. Pandemic-related policies and protocols have negatively affected care for cardiovascular conditions and established hospital protocols, which is particularly important for patients with heart failure.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

Moderate Aortic Stenosis in Patients With Heart Failure.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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; p<0.001) 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). CONCLUSIONS: Moderate AS in conjunction with elevated BNP portends a significantly worse prognosis than those without moderate AS and should be followed closely.

Left Ventricular Assist Device in Patients With Alcohol Abuse or Illicit Drug Use.

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 p <0.05). 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.

Real-world clinical burden among patients with and without heart failure worsening after cardiac resynchronization therapy.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial.

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 (pinteraction=0·002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=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%. FUNDING: Corvia Medical.

Application of machine learning in screening for congenital heart diseases using fetal echocardiography.

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.

Ventriculo-arterial coupling in patients with stable ischemic heart disease undergoing percutaneous coronary intervention.

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.

Left Ventricular End-Diastolic Dimension and Clinical Outcomes After Centrifugal Flow Left Ventricular Assist Device Implantation.

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.

Normal Ranges of Global Left Ventricular Myocardial Work Indices in Adults: A Meta-Analysis.

BACKGROUND: Recent studies have demonstrated that left ventricular myocardial work (MW) is incremental in diagnosis and prognostication compared with left ventricular ejection fraction and myocardial strain. The authors performed a meta-analysis of normal ranges of noninvasive MW indices including global work index, global constructive work, global wasted work, and global work efficiency and determined confounders that may contribute to variance in reported values. METHODS: Four databases (PubMed, Scopus, Embase, and the Cochrane Library) were searched through January 2021 using the key terms "myocardial work," "global constructive work," "global wasted work," "global work index," and "global work efficiency." Studies were included if the articles reported LV MW using two-dimensional transthoracic echocardiography in healthy normal subjects, either in a control group or comprising the entire study cohort. The weighted mean was estimated by using the random-effect model with a 95% CI. Heterogeneity across included studies was assessed using the I2 test. Funnel plots and the Egger regression test were used to assess potential publication bias. RESULTS: The search yielded 476 articles. After abstract and full-text screening, we included 13 data sets with 1,665 patients for the meta-analysis. The reported normal mean values of global work index and global constructive work among the studies were 2,010 mm Hg% (95% CI, 1,907-2,113 mm Hg%) and 2,278 mm Hg% (95% CI, 2,186-2,369 mm Hg%), respectively. Mean global wasted work was 80 mm Hg% (95% CI, 73-87 mm Hg%), and mean global work efficiency was 96.0% (95% CI, 96%-96%). Furthermore, gender significantly contributed to variations in normal values of global work index, global wasted work, and global work efficiency. No evidence of significant publication bias was observed. CONCLUSIONS: In this meta-analysis, the authors provide echocardiographic reference ranges for noninvasive indices of MW. These normal values could serve as a reference for clinical and research use.

The importance of early evaluation after cardiac resynchronization therapy to redefine response: Pooled individual patient analysis from 5 prospective studies.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Long-term outcomes of primary cardiac malignant tumors: Difference between African American and Caucasian population.

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.

Right ventricular dysfunction and tricuspid regurgitation in functional mitral regurgitation.

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 < 0.001, I2  = 0). Patients with moderate-severe TR showed increased risk of mortality compared with those in the none-mild TR group (HR, 1.61. 95% CI, 1.11-2.33, P = 0.01, I2  = 14). CONCLUSIONS: This meta-analysis demonstrates the prognostic importance of RVD and TR grade in predicting all-cause mortality in patients with significant FMR. RV function and TR parameters may therefore be useful in the risk stratification of patients with significant FMR undergoing MitraClip procedure.

Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial.

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 0.1 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. 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).