Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. METHODS AND RESULTS: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. CONCLUSIONS: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.

Prognostic value of natriuretic peptides in heart failure: systematic review and meta-analysis.

Risk models, informing optimal long-term medical management, seldom use natriuretic peptides (NP) in ascertaining the absolute risk of outcomes for HF patients. Individual studies evaluating the prognostic value of NPs in HF patients have reported varying effects, arriving at best estimates requires a systematic review. We systematically summarized the best evidence regarding the prognostic value of brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality and hospitalizations in ambulatory heart failure (HF) patients. We searched bibliographic databases from 2005 to 2018 and included studies evaluating the association of BNP or NT-proBNP with mortality or hospitalization using multivariable Cox proportional hazard models. We pooled hazard ratios using random-effect models, explored heterogeneity using pre-specified subgroup analyses, and evaluated the certainty of evidence using the Grading of Recommendations and Development Evaluation framework. We identified 67 eligible studies reporting on 76,178 ambulatory HF patients with a median BNP of 407 pg/mL (261-574 pg/mL). Moderate to high-quality evidence showed that a 100-pg/mL increase in BNP was associated with a 14% increased hazard of mortality (HR 1.14, 95% CI 1.06-1.22); a 1-log-unit increase was associated with a 51% increased hazard of mortality (HR 1.51, 95% CI 1.41-1.61) and 48% increased hazard of mortality or hospitalization (HR 1.48, 95% CI 1.29-1.69). With moderate to high certainty, we observed a 14% independent relative increase in mortality, translating to a clinically meaningful increase in absolute risk even for low-risk patients. The observed associations may help in developing more accurate risk models that incorporate NPs and accurately prognosticate HF patients.

Predicted heart mass for size matching in obese heart transplant donors and recipients.

INTRODUCTION: Predicted heart mass (PHM) was neither derived nor evaluated in an obese population. Our objective was to evaluate size mismatch using actual body weight or ideal body weight (IBW)-adjusted PHM on mortality and risk assessment. METHODS: We conducted a retrospective cohort study of adult recipients with BMI ≥30 kg/m2 or recipients of donors with BMI≥30 kg/m2 from the ISHLT registry. We used multivariable Cox proportional hazard models to evaluate 30-day and 1-year mortality. The two models were compared using net reclassification index. RESULTS: 10,817 HT recipients, age 55 (IQR 46-62) years, 23% female, BMI 31 kg/m2 (IQR 28-33) were included. Donors were age 34 (IQR 24-44) years, 31% female, and BMI 31 kg/m2 (IQR 26-34). There was a significant nonlinear association between mortality and actual PHM but not IBW-adjusted PHM. Undersizing using actual PHM was associated with higher 30-day and 1-year mortality (p < .01), not seen with IBW-adjusted PHM. Actual PHM better risk classified .6% (95% CI .3-.8) patients compared to IBW-adjusted PHM. CONCLUSION: Actual PHM can be used for size matching when assessing mortality risk in obese recipients or recipients of obese donors. There is no advantage to re-calculating PHM using IBW to define candidate risk at the time of organ allocation.

Association between continuous-flow left ventricular assist device infections requiring long-term antibiotic use and post-heart transplant morbidity and mortality.

BACKGROUND AND AIM OF STUDY: There exists controversy regarding the impact of infection in patients with a left ventricular assist device (LVAD) on post-heart transplant outcomes. This study evaluated the association between infections during LVAD support and the risk of early and late post-heart transplant infection, rejection, and mortality in transplant recipients bridged with an LVAD. METHODS: This is a single-center retrospective observational cohort study of consecutive adults supported with a continuous flow LVAD undergoing heart transplant between 2006 and 2019 at the Toronto General Hospital. The grade of LVAD infection was classified as per International Society of Heart and Lung Transplantation guidelines. Patients were divided into three groups: (1) patients with LVAD-specific infection confirmed with positive cultures requiring long-term antibiotic use until the time of transplant; (2) patients with any type of infection in whom antibiotics were stopped at least 1 month before transplant; (3) patients without any infections between LVAD implant and transplant. Logistic regression and Cox proportional hazard models were used to evaluate early- and late-post transplant outcomes, respectively. RESULTS: We included 75 LVAD recipients: 16 (21%) patients had a chronic LVAD-related infection on suppressive antibiotics, 30 (40%) had a resolved infection, and 29 (39%) had no infections. During a median post-transplant follow-up time of 4 (2 to 7) years, 65 (87%) patients developed infections, 43 (64%) rejections, and 17 (23%) deaths. Both short- and long-term risks of infection, rejection, and mortality did not differ significantly among the groups. CONCLUSION: LVAD patients with infections did not have a significantly higher risk of infection, rejection, or mortality at any time point after transplant.

Resting Heart Rate as an Important Predictor of Mortality and Morbidity in Ambulatory Patients With Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Resting heart rate is a risk factor of adverse heart failure outcomes; however, studies have shown controversial results. This meta-analysis evaluates the association of resting heart rate with mortality and hospitalization and identifies factors influencing its effect. METHODS AND RESULTS: We systematically searched electronic databases in February 2019 for studies published in 2005 or before that evaluated the resting heart rate as a primary predictor or covariate of multivariable models of mortality and/or hospitalization in adult ambulatory patients with heart failure. Random effects inverse variance meta-analyses were performed to calculate pooled hazard ratios. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence quality. Sixty-two studies on 163,445 patients proved eligible. Median population heart rate was 74 bpm (interquartile range 72-76 bpm). A 10-bpm increase was significantly associated with increased risk of all-cause mortality (hazard ratio 1.10, 95% confidence interval 1.08-1.13, high quality). Overall, subgroup analyses related to patient characteristics showed no changes to the effect estimate; however, there was a strongly positive interaction with age showing increasing risk of all-cause mortality per 10 bpm increase in heart rate. CONCLUSIONS: High-quality evidence demonstrates increasing resting heart rate is a significant predictor of all-cause mortality in ambulatory patients with heart failure on optimal medical therapy, with consistent effect across most patient factors and an increased risk trending with older age.

Exercise rehabilitation in cardiac resynchronization: systematic review and a meta-analysis.

The benefit of exercise training in cardiac resynchronization therapy (CRT) recipients is not well established. We conducted a systematic review and meta-analysis to determine the effect of exercise training on clinical outcomes in CRT recipients.A comprehensive search until 2019 was conducted of MEDLINE, Epub, Embase, CINAHL and Cochrane databases as well as a bibliographic hand search to identify additional studies. We included all studies that compared aerobic exercise interventions in adults treated with CRT devices with adults treated with usual CRT care. These studies evaluated patient clinical characteristics, exercise testing measures, hemodynamic measures, echocardiography parameters, biomarkers and adverse events. Independent reviewers evaluated study eligibility, abstracted data and assessed risk of bias in duplicate. We used random-effect meta-analysis methods to estimate mean differences and odds ratios. Grades of Recommendation, Assessment, Development and Evaluation system were used to quantify absolute effects and quality of evidence. I2 was used to evaluate heterogeneity.We identified seven studies, six randomized control trials and one observational study, totaling 332 CRT patients in the exercise intervention and 534 patients receiving usual care. Peak VO2 was 2.4 ml/kg/min higher in the exercise group in comparison with the control group (pooled mean difference 2.26, 95% CI 1.38-3.13, I2 = 53%, high quality). AT-VO2 improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68-5.24, I2 = 0.0%, moderate quality).Peak VO2 and AT-VO2 are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.

Risk prediction models for survival after heart transplantation: A systematic review.

Risk prediction scores have been developed to predict survival following heart transplantation (HT). Our objective was to systematically review the model characteristics and performance for all available scores that predict survival after HT. Ovid Medline and Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Clinical Trials were searched to December 2018. Eligible articles reported a score to predict mortality following HT. Of the 5392 studies screened, 21 studies were included that derived and/or validated 16 scores. Seven (44%) scores were validated in external cohorts and 8 (50%) assessed model performance. Overall model discrimination ranged from poor to moderate (C-statistic/area under the receiver operating characteristics 0.54-0.77). The IMPACT score was the most widely validated, was well calibrated in two large registries, and was best at discriminating 3-month survival (C-statistic 0.76). Most scores did not perform particularly well in any cohort in which they were assessed. This review shows that there are insufficient data to recommend the use of one model over the others for prediction of post-HT outcomes.

Post-transplant survival in adult congenital heart disease patients as compared to dilated and ischemic cardiomyopathy patients; an analysis of the thoracic ISHLT registry.

Previous studies have shown that adult congenital heart disease (ACHD) is associated with high early post-transplant mortality but improved long-term survival in comparison to the overall heart transplant population. We aimed to evaluate survival outcomes of ACHD in adult transplant recipient patients as specifically compared to ischemic (ICM) and dilated cardiomyopathy (DCM) groups. Adult heart transplant recipients between 2004 and 2014 were identified from the ISHLT registry. We used Kaplan-Meier analysis to evaluate overall survival, 1-year survival, and 1-year conditional survival among etiology groups and multivariable Cox proportional hazard (PH) models to assess the association between etiology of cardiomyopathy and 1-year and long-term all-cause mortality and cause-specific mortality. We included 30 130 heart transplant recipients. One-year survival was 78.3% in ACHD, 84.3% in ICM, and 86.2% in DCM patients (P < .001). By multivariable analysis, during first post-transplant year, ACHD and ICM patients were at significantly higher mortality risk than DCM. Adjusted post-transplant mortality risk, conditional on 1-year survival, was not statistically different in ACHD and DCM while ICM patients had 17% higher long-term mortality risk than DCM patients leading to overall worse outcomes in ICM patients. Therefore, ICM patients have poorer outcomes in comparison to both DCM and ACHD patients.

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry.

Sudden cardiac death (SCD) is responsible for ~10% of post-heart transplant deaths. We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post-transplant SCD. Adult heart transplant recipients (2004-2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and Monte Carlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25 242 recipients. During a median follow-up of 4.7 (2.3-7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36-2.31) and CAV (HR 3.32, 95% CI 2.73-4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0-4.6) and 5.4% (95% CI 3.8-7.0), respectively, at 2 years from the CAV diagnosis, and 4.9% (95% CI 3.4-6.5) and 8.0% (95% CI 6.1-10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post-transplant remains uncertain.

The effect of pre-heart transplant body mass index on posttransplant outcomes: An analysis of the ISHLT Registry Data.

We evaluated the effect of pre-heart transplant body mass index (BMI) on posttransplant outcomes using the International Society for Heart and Lung Transplantation Registry. Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. We assessed 38 498 recipients from 2000 to 2014 stratified by pretransplant BMI. Ten-year survival was 56% in underweight, 59% in normal weight, 57% in overweight, 52% in obese class I, 54% in class II, and 47% in class III patients (P < 0.001). Mortality was increased in underweight (HR 1.29, 95% CI 1.24-1.35), obese class I (HR 1.19, 95% CI 1.13-1.26), class II (HR 1.20, 95% CI 1.08-1.32), and class III patients (HR 1.45, 95% CI 1.15-1.83). Obesity was independently associated with increased death from myocardial infarction, chronic rejection, infection, and renal dysfunction. An underweight BMI lead to increased death from infection, acute and chronic rejection, malignancy, and bleeding. Obese patients had a higher incidence of renal dysfunction, diabetes, stroke, acute rejection, cardiac allograft vasculopathy, and malignancy, and underweight recipients had increased acute rejection. We have shown that pretransplant obese and underweight patients have increased post-heart transplant mortality and morbidity. This has implications for candidate selection and posttransplant management.

Predicting Survival in Patients With Heart Failure With an Implantable Cardioverter Defibrillator: The Heart Failure Meta-Score.

BACKGROUND: Prognostic evaluation in heart failure (HF) is important to predict future events and decide timely management. Many HF patients are treated with the use of an implantable cardioverter-defibrillator (ICD). This study aimed to validate a meta-analytically derived prognostic score to predict survival in ICD-HF patients. METHODS AND RESULTS: The HF Meta-score includes 14 independent mortality predictors identified in a meta-analysis, including age, sex, ethnicity, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, atrial fibrillation, ischemic cardiomyopathy, history of HF admission, New York Heart Association functional class, left ventricular ejection fraction, renal function, QRS duration, secondary prevention indication, and ICD shocks. The HF Meta-score performance was evaluated in comparison with the Seattle Heart Failure Model (SHFM) and the SHOCKED predictors in a cohort of 9860 ambulatory ICD patients from the Ontario provincial database for 2007-2011. During 3-year follow-up, 1816 patients died. The HF Meta-score showed excellent calibration, very good discrimination (c-statistic 0.74) and enhanced risk classification compared with the SHOCKED predictors, with better reclassifying in 19% and 56% of patients for 1- and 3-year survival, respectively. HF Meta-score performance was similar to the SHFM. CONCLUSIONS: The HF Meta-score is an evidence-based derived model that provides an accurate prognosis assessment in HF patients with ICDs. Its development strategy permits further incorporation of new predictors when evidence becomes available.

Impact of pretransplant recipient body mass index on post heart transplant mortality: A systematic review and meta-analysis.

The ISHLT's 2016 Guidelines on the selection of heart transplant (HT) candidates recommends weight loss prior to listing for persons with body mass (BMI) index greater than 35 kg/m2 . We conducted a systematic review to assess the impact of BMI on all-cause mortality. We searched to identify eligible observational studies that followed HT recipients. We used the GRADE system to quantify absolute effects and quality of evidence, and meta-analyzed survival curves to assess post-transplant mortality across BMI categories. We found a significantly increased risk of mortality in patients with BMI > 30 kg/m2 across all age categories, independently of transplant era and study source (BMI 30-34.9: HR 1.10, 95% CI 1.04-1.17; BMI ≥ 35: HR 1.24, 95% CI 1.12-1.38). We also found an increased risk of death in underweight (BMI < 18.5 kg/m2 ) candidates over 39 years of age (Age 40-65: HR 1.24, 95% CI 1.02-1.53; Age > 65: HR 1.70, 95% 1.13-2.57). We found obesity and underweight BMI to be associated with mortality post-HT. The similar and overlapping increased risk of mortality in patients with BMI 30-34.9 and BMI ≥ 35 does not support the recently updated ISHLT guidelines. Future evidence in the form of randomized controlled trials is required to assess effectiveness of interventions targeting obesity-related comorbidities and weight management.

The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.

Frailty assessment has become an integral part of the evaluation of potential candidates for heart transplantation and ventricular assist device (HTx/VAD). The impact of frailty, as a heart failure risk factor or to identify those who will derive the greatest benefit with HTx/VAD remains unclear. The aim of this study was to evaluate the independent prognostic relevance of frailty assessment from peak oxygen consumption (peak VO2 ) or B-type natriuretic peptide (BNP) on mortality in patients referred for advanced heart failure therapies. Frailty was measured using modified Fried frailty criteria. In 201 consecutive patients, during a median follow-up of 17.5 months (IQR 11-29.2), there were 25 (12.4%) deaths. One-year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail patients, respectively (log rank P = .0001). Frailty was associated with a twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42-2.84). When adjusted for BNP or peak VO2 , frailty was not associated with a significant risk of all-cause death. However, when peak VO2 is stratified into two categories (≥12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased mortality in patients with a lower peak VO2 (HR 1.72, P = .006).

Incidence and predictors of sudden cardiac death after heart transplantation: A systematic review and meta-analysis.

PURPOSE: Sudden cardiac death (SCD) is an important post-transplant problem being responsible for ~10% of deaths. We conducted a systematic review and meta-analysis to evaluate incidence and predictors of post-heart transplant SCD and the use of implantable cardiac defibrillator (ICD). METHODS: Citations were identified in electronic databases and references of included studies. Observational studies on adults reporting on incidence and predictors of post-transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years using random effects models. We qualitatively summarized predictors. RESULTS: This study includes 55 studies encompassing 47 901 recipients. The pooled incidence rate of SCD was 1.30 per 100 person-years (95% CI: 1.08-1.52). Cardiac allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100 patient-years, 95% CI: 1.46-3.34). Independent predictors of SCD identified by two moderate-quality studies were older donor age, younger recipient age, non-Caucasian race, reduced left ventricular ejection fraction, rejection, infection, and cancer. Authors rarely reported on ICD use. CONCLUSION: This meta-analysis found that post-transplant SCD risk in heart transplant recipients is higher than that in the general population. CAV was associated with increased SCD risk. Observational studies reporting on absolute risk of SCD are needed to better identify populations at a clinically significant increased risk.

An Appraisal of Biomarker-Based Risk-Scoring Models in Chronic Heart Failure: Which One Is Best?

PURPOSE OF REVIEW: While prediction models incorporating biomarkers are used in heart failure, these have shown wide-ranging discrimination and calibration. This review will discuss externally validated biomarker-based risk models in chronic heart failure patients assessing their quality and relevance to clinical practice. RECENT FINDINGS: Biomarkers may help in determining prognosis in chronic heart failure patients as they reflect early pathologic processes, even before symptoms or worsening disease. We present the characteristics and describe the performance of 10 externally validated prediction models including at least one biomarker among their predictive factors. Very few models report adequate discrimination and calibration. Some studies evaluated the additional predictive value of adding a biomarker to a model. However, these have not been routinely assessed in subsequent validation studies. New and existing prediction models should include biomarkers, which improve model performance. Ongoing research is needed to assess the performance of models in contemporary patients.

Cost-effectiveness of ventricular assist device therapy as a bridge to transplantation compared with nonbridged cardiac recipients.

BACKGROUND: Current available treatment options for advanced heart failure include heart transplantation and ventricular assist device (VAD) therapy. This project aimed to evaluate the cost-effectiveness of a bridge-to-transplantation (BTT)-VAD approach relative to direct heart transplantation in transplant-eligible patients. METHODS AND RESULTS: A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients' baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio. CONCLUSIONS: BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonly accepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances.

Right ventricular function and prognosis in stable heart failure patients.

BACKGROUND: Right ventricular ejection fraction (RVEF) is a mortality predictor in heart failure (HF) patients. There are controversial results regarding the influence of RVEF on other important prognostic variables. The purpose of this study was to investigate the effect of RVEF on exercise parameters obtained during cardiopulmonary exercise testing (CPET), creatinine and B-type natriuretic peptide (BNP) levels, and a composite outcome of death, heart transplantation, or ventricular assist device implantation in ambulatory HF patients. METHODS AND RESULTS: This retrospective cohort study included 246 ambulatory HF patients with CPET and RVEF evaluated with the use of first-pass radionuclide angiography. We analyzed the impact of RVEF on other prognostic factors with the use of multivariable linear regression. The mean age was 49 ± 12 years. The mean peak VO2 was 16.4 ± 5.7 mL kg(-1) min(-1), mean peak VE/VCO2 34.1 ± 9.1, mean creatinine 1.17 ± 0.40 mg/dL, and median BNP 158 pg/mL (interquartile range 374 pg/mL). The mean left ventricular ejection fraction was 35 ± 12% and the mean RVEF 38 ± 10%. For every 10% decrease in RVEF, peak VO2 decreased 0.97 mL kg(-1) min(-1) (P < .05), creatinine increased 0.12 mg/dL (P < .01), and log BNP increased 0.26 (P < .05). CONCLUSIONS: We found an independent association between RVEF and prognostic markers in HF patients. Worsening RV function may exert its negative effect on prognosis through increasing congestion (elevated BNP), affecting renal blood flow (increased creatinine) and limiting left ventricular preload, thereby reducing exercise tolerance.

How to use a subgroup analysis: users' guide to the medical literature.

Clinicians, when trying to apply trial results to patient care, need to individualize patient care and, potentially, manage patients based on results of subgroup analyses. Apparently compelling subgroup effects often prove spurious, and guidance is needed to differentiate credible from less credible subgroup claims. We therefore provide 5 criteria to use when assessing the validity of subgroup analyses: (1) Can chance explain the apparent subgroup effect; (2) Is the effect consistent across studies; (3) Was the subgroup hypothesis one of a small number of hypotheses developed a priori with direction specified; (4) Is there strong preexisting biological support; and (5) Is the evidence supporting the effect based on within- or between-study comparisons. The first 4 criteria are applicable to individual studies or systematic reviews, the last only to systematic reviews of multiple studies. These criteria will help clinicians deciding whether to use subgroup analyses to guide their patient care.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Clinical differences between continuous flow ventricular assist devices: a comparison between HeartMate II and HeartWare HVAD.

BACKGROUND: The HeartWare ventricular assist device (HVAD) is a new generation centrifugal flow VAD recently introduced in Canada. The objective of this study was to compare the HVAD device to the HeartMate II (HMII) axial flow device. Very few studies have compared clinical outcomes between newer generation VADs. METHODS: All perioperative and follow-up data on LVAD recipients were collected prospectively in our institutional database. Between January 2006 and April 2012, 46 consecutive patients underwent implantation of either an HVAD (n=13) or a HMII (n=33) device. Pre-implant demographics, perioperative and postoperative clinical outcomes were reviewed between groups. RESULTS: Overall, the baseline characteristics, demographics, co-morbidities and laboratory values were comparable between the two groups. The majority of the patients were Interagency Registry for Mechanical Assisted Circulatory Support 3-4 (92% in both groups) and most of the patients were bridge to transplant (75% in HMII vs. 79% in HVAD). Survival and the incidence of perioperative bleeding, renal dysfunction, liver dysfunction, and infection were similar between the groups. However, HVAD devices had a significantly higher incidence of gastrointestinal (GI) bleeding (31% vs. 0% in HMII patients, p<0.01) and stroke (44% vs. 10% in HMII patients, at one year p=0.04). Hemorrhagic strokes were more frequent in patients with HVAD (three of the five episodes vs. one of the three episodes in HMII patients, p=0.06). CONCLUSION: While device complications were comparable, patients with HVAD experienced a significantly higher incidence of stroke and GI bleeding and therefore refinement in patients' management may decrease incidence of these complications.