Drug levels after sirolimus initiation and short-term outcomes in ambulatory heart transplantation recipients.

INTRODUCTION: We evaluated the effect of relative changes in combined tacrolimus and sirolimus (drug) levels, following sirolimus initiation, on outcomes in ambulatory heart transplantation (HTx) recipients. METHODS: We performed a retrospective analysis of HTx recipients who received tacrolimus, followed by sirolimus initiation, any time after HTx. We calculated the relative change in combined drug levels 1-month post-sirolimus initiation, relative to tacrolimus levels pre-initiation, and categorized patients into decreased (≥15% decrease), stable (<15% decrease to <15% increase), or increased (≥15% increase) groups. We compared, across the three groups, changes in post-initiation estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) using one-way ANOVA and Sidák's post-hoc analysis, as well as the individual and composite outcomes of new donor specific antibodies (DSA), acute cellular rejection (ACR), and all-cause mortality using Fisher's exact test. RESULTS: Amongst 99 HTx recipients included, the median age was 53 years, time to sirolimus initiation was 1.5 years post-HTx, and pre-sirolimus eGFR was 52 mL/min/1.73 m2 . Nine patients had decreased, 15 stable, and 75 increased, relative combined drug levels. Relative change in eGFR was significantly higher in patients with decreased levels compared to patients with increased levels at 6 months post-initiation (P < .05), but this was not sustained at 12 months. There were no differences in LVEF change or in individual and composite risks for developing DSA, ACR, and all-cause mortality at 12 months across the groups. CONCLUSION: Post-sirolimus initiation, a relative decrease in combined drug levels, compared to increased levels, was associated with temporarily improved renal function.

Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence.

BACKGROUND: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx). METHODS: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab. RESULTS: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab. CONCLUSION: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.

Induction therapy in heart transplantation: A systematic review and network meta-analysis for developing evidence-based recommendations.

INTRODUCTION: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA). METHODS: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework. RESULTS: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab. CONCLUSION: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients.

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.

Patients with fulminant myocarditis supported with veno-arterial extracorporeal membrane oxygenation: a systematic review and meta-analysis of short-term mortality and impact of risk factors.

Fulminant myocarditis (FM) may lead to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Results of effectiveness studies of VA-ECMO have been contradictory. We evaluated the aggregate short-term mortality after VA-ECMO and predictive factors in patients with FM. We systematically searched in electronic databases (February 2022) to identify studies evaluating short-term mortality (defined as mortality at 30 days or in-hospital) after VA-ECMO support for FM. We included studies with 5 or more patients published after 2009. We assessed the quality of the evidence using the QUIPS and GRADE tools. Mortality was pooled using random effect models. We performed meta-regression to explore heterogeneity based on a priori defined factors. We included 54 observational studies encompassing 2388 FM patients supported with VA-ECMO. Median age was 41 years (25th to 75th percentile 37-47), and 50% were female. The pooled short-term mortality was 35% (95% CI 29-40%, I2 = 69%; moderate certainty). By meta-regression, studies with younger populations showed lower mortality. Female sex, receiving a biopsy, cardiac arrest, left ventricular unloading, and earlier recruitment time frame, did not explain heterogeneity. These results remained consistent regardless of continent and the risk of bias category. In individual studies, low pH value, high lactate, absence of functional cardiac recovery on ECMO, increased burden of malignant arrhythmia, high peak coronary markers, and IVIG use were identified as independent predictors of mortality. When conventional therapies have failed, especially in younger patients, cardiopulmonary support with VA-ECMO should be considered in the treatment of severe FM.

The Polypharmacological Effects of Cannabidiol.

Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ9-tetrahydrocannabinol (∆9-THC) does. In contrast to ∆9-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a rationalized integration of the mechanisms of action of CBD on molecular targets and pharmacological implications in animal models and human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer's disease, and inflammatory diseases, are presented. We identify around 56 different molecular targets for CBD, including enzymes and ion channels/metabotropic receptors involved in neurologic conditions. Herein, we compiled the knowledge found in the scientific literature on the multiple mechanisms of actions of CBD. The in vitro and in vivo findings are essential for fully understanding the polypharmacological nature of this natural product.

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin.

The consumption of Cannabis sativa plant, known as marijuana in the Western world, for different purposes (therapeutic, intoxicating, and spiritual) due to its psychoactive effects, can be traced back to ancient times. Cannabis is the most used illicit drug worldwide; however, its legal status is changing rapidly. Cannabis regulation will allow a better understanding of its effects as a misused drug, including new challenges, such as the availability of highly potent Cannabis extracts. Furthermore, scientific research is making significant efforts to take advantage of the potential therapeutic uses of Cannabis active compounds. The science of Cannabis derivatives started with the identification of the phytocannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), allowing the formal study of the complex set of effects triggered by Cannabis consumption and the deciphering of its pharmacology. Δ9-THC is recognized as the compound responsible for the psychoactive and intoxicating effects of Cannabis. Its study led to the discovery of the endocannabinoid system, a neuromodulatory system widespread in the human body. CBD does not induce intoxication and for that reason, it is the focus of the search for cannabinoid potential clinical applications. This review examines the current state of knowledge about contrasting perspectives on the effects of Cannabis, Δ9-THC, and CBD: their abuse liability and potential therapeutic use; two sides of the same coin.

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.

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis.

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥ 50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91-0.95, I2 = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88-0.93, I2 = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91-0.94, I2 = 86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF > 40%, higher average SBP (> 130 mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence.

Impact of serial measurements of tricuspid annular plane systolic excursion on mortality and morbidity after heart transplantation.

The impact of right ventricular (RV) dysfunction on long-term post-HTx outcomes remains uncertain. We assessed the impact of serial measurements of Tricuspid Annular Plane Systolic Excursion (TAPSE) on post-HTx mortality and morbidity. This two-center retrospective cohort study included consecutive adult HTx recipients (2000-2017). We used multivariable extended hazard regression models to evaluate the association between TAPSE and left ventricular ejection fraction (LVEF), entered as time-dependent variables, and all-cause mortality, cardiac allograft vasculopathy (CAV), acute cellular rejection (ACR), and chronic kidney disease (CKD). TAPSE was modelled using cubic splines. We included 485 HTx recipients (9461 TAPSE measurements), median (25th- 75th percentile) 19 (10-27) mm; median age was 52 (41-59) years, and 71.3% were male. During a follow-up of 6.7 (3.0-10.8) years, 92 patients died, 225 had ACR >2R, 234 CAV, and 91 CKD. By multivariable analysis, for each 1-mm decrease in patients with a TAPSE value <15mm, mortality increased by 22% (P<.001). For the average HTx recipient with a TAPSE of 15mm, 10mm, and 6mm, 1-year mortality was 3%, 7%, and 17%, and 5-year mortality was 8%, 20%, and 43%, respectively. Reduced TAPSE was significantly associated with increased CAV but notACR and CKD. A decrease in TAPSE below 15mm represents clinically significant graft dysfunction, warranting close monitoring.

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.

The role of character strengths in predicting gains in informal caregivers of dementia.

OBJECTIVES: Although providing care to a person with dementia can have a negative impact, caregivers may also perceive certain benefits and gains through the tasks they perform. Our aim here was to study caregiver gains within the framework of positive psychology, exploring the predictive power of character strengths, while controlling for sociodemographic variables and variables related to the dementia and caring. METHODS: A sample of 105 main caregivers of people diagnosed with dementia completed a sociodemographic questionnaire, the Gain in Alzheimer care Instrument and the Values in Action Inventory of Strengths. Correlational analysis and hierarchical regression were conducted. RESULTS: Eighteen character strengths were positively and significantly correlated with gain scores. Regression analysis indicated that level of education was negatively related to gain scores. In addition, hope was the character strength which best predicted the gain score, such that caregivers who scored higher on hope tended to perceive greater benefits from their role. CONCLUSION: The results suggest that hope may play an important role in relation to the perceived gains of caregiving. Intervention programmes based on positive psychology and aimed at enhancing character strengths, especially hope, could help caregivers to identify the positive aspects of their caring role.

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.

Utility of the INTERMACS profile at the time of assessment for heart transplant.

The Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) profiles are associated with mortality in heart failure patients undergoing ventricular assist device (VAD) implantation and heart transplantation (HTx). We assessed the prognostic value of the INTERMACS profile at the time of assessment for HTx or durable VAD implantation as bridge to candidacy (BTC). A total of 503 consecutive patients considered for HTx or VAD between 2006 and 2016 were included. The associations between INTERMACS profile and (a) waitlist mortality or delisting, (b) probability of HTx, and (c) overall mortality or delisting were evaluated using multivariable analysis. Median follow-up time was 2.9 years (IQR: 0.9-5.5) during which 184 received VAD, 347 received HTx, and 73 died (27 waitlist, 46 post-transplant). INTERMACS I-II profile was associated with higher waitlist mortality or delisting (HR: 3.83, 95% CI: 1.22-12.03), and this risk was reversed by VAD implantation (HR: 0.12, 95% CI: 0.03-0.50). INTERMACS III-IV profile was associated with a higher probability of HTx (HR: 1.82, 95% CI: 1.37-2.40). INTERMACS profile was not associated with the composite outcome of overall mortality or delisting. These results emphasize the prognostic utility of INTERMACS at time of decision for advanced therapies and its potential value in selecting patients for different interventions.

Clinical presentation and outcomes in women and men with advanced heart failure.

OBJECTIVE: To examine clinical characteristics and outcomes in women and men referred for advanced heart failure (HF) therapies such as left ventricular assist device (LVAD) or heart transplantation (HTx). Design: A retrospective study of 429 (23% women) consecutive adult HF patients not on inotropic or mechanical circulatory support with left ventricular ejection fraction ≤45% referred for assessment of advanced HF therapies at a single tertiary institution between 2002 and 2016. Clinical characteristics and outcomes were compared in women and men, and all patients underwent right heart catheterization (RHC). Results: At evaluation, women were younger than men (48 ± 13 vs. 51 ± 12 years, p = .02), and less likely to have ischemic cardiomyopathy. There were no significant differences in NYHA class, contemporary HF therapy use, or physical examination findings, except for lower jugular vein distension and body surface area in women. On RHC, women had lower cardiac filling pressures, but similar pulmonary vascular resistance and cardiac index. Peak oxygen uptake from cardiopulmonary exercise testing was similar in both sexes. At total follow-up time, there were 164 deaths (21% vs. 44%, p < .0001), 46 LVADs (3% vs. 13%, p = .005), 110 HTxs (32% vs. 25%, p = .15), and 82 HTxs without requiring LVAD (29% vs. 16%, p = .03) in women and men. The time from RHC to HTx (±LVAD) was significantly shorter in women compared to men. Female sex was significantly associated with higher survival independent of time-trend, age, and comorbidities. Conclusion: At evaluation, hemodynamics were less deranged in women. A higher proportion of women received HTx, their waitlist time was shorter, and survival greater.

Evaluation of a Heart Failure Telemonitoring Program Through a Microsimulation Model: Cost-Utility Analysis.

BACKGROUND: Heart failure (HF) is a major public health issue in Canada that is associated with high prevalence, morbidity, and mortality rates and high financial and social burdens. Telemonitoring (TM) has been shown to improve all-cause mortality and hospitalization rates in patients with HF. The Medly program is a TM intervention integrated as standard of care at a large Canadian academic hospital for ambulatory patients with HF that has been found to improve patient outcomes. However, the cost-effectiveness of the Medly program is yet to be determined. OBJECTIVE: This study aims to conduct a cost-utility analysis of the Medly program compared with the standard of care for HF in Ontario, Canada, from the perspective of the public health care payer. METHODS: Using a microsimulation model, individual patient data were simulated over a 25-year time horizon to compare the costs and quality-adjusted life years (QALYs) between the Medly program and standard care for patients with HF treated in the ambulatory care setting. Data were sourced from a Medly Program Evaluation study and literature to inform model parameters, such as Medly's effectiveness in reducing mortality and hospitalizations, health care and intervention costs, and model transition probabilities. Scenario analyses were conducted in relation to HF severity and TM deployment models. One-way deterministic effectiveness analysis and probabilistic sensitivity analysis were performed to explore the impact on the results of uncertainty in model parameters. RESULTS: The Medly program was associated with an average total cost of Can $102,508 (US $77,626) per patient and total QALYs of 5.51 per patient compared with the average cost of Can $97,497 (US $73,831) and QALYs of 4.95 per patient in the Standard Care Group. This led to an incremental cost of Can $5011 (US $3794) and incremental QALY of 0.566, resulting in an incremental cost-effectiveness ratio of Can $8850 (US $6701)/QALY. Cost-effectiveness improved in relation to patients with advanced HF and with deployment models in which patients used their own equipment. Baseline and alternative scenarios consistently showed probabilities of cost-effectiveness greater than 85% at a willingness-to-pay threshold of Can $50,000 (US $37,718). Although the results showed some sensitivity to assumptions about effectiveness parameters, the intervention was found to remain cost-effective. CONCLUSIONS: The Medly program for patients with HF is cost-effective compared with standard care using commonly reported willingness-to-pay thresholds. This study provides evidence for decision makers on the use of TM for HF, supports the use of a nurse-led model of TM that embeds clinically validated algorithms, and informs the use of economic modeling for future evaluations of early-stage health informatics technology.