Trial of an Intervention to Improve Acute Heart Failure Outcomes.

BACKGROUND: Patients with acute heart failure are frequently or systematically hospitalized, often because the risk of adverse events is uncertain and the options for rapid follow-up are inadequate. Whether the use of a strategy to support clinicians in making decisions about discharging or admitting patients, coupled with rapid follow-up in an outpatient clinic, would affect outcomes remains uncertain. METHODS: In a stepped-wedge, cluster-randomized trial conducted in Ontario, Canada, we randomly assigned 10 hospitals to staggered start dates for one-way crossover from the control phase (usual care) to the intervention phase, which involved the use of a point-of-care algorithm to stratify patients with acute heart failure according to the risk of death. During the intervention phase, low-risk patients were discharged early (in ≤3 days) and received standardized outpatient care, and high-risk patients were admitted to the hospital. The coprimary outcomes were a composite of death from any cause or hospitalization for cardiovascular causes within 30 days after presentation and the composite outcome within 20 months. RESULTS: A total of 5452 patients were enrolled in the trial (2972 during the control phase and 2480 during the intervention phase). Within 30 days, death from any cause or hospitalization for cardiovascular causes occurred in 301 patients (12.1%) who were enrolled during the intervention phase and in 430 patients (14.5%) who were enrolled during the control phase (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.78 to 0.99; P = 0.04). Within 20 months, the cumulative incidence of primary-outcome events was 54.4% (95% CI, 48.6 to 59.9) among patients who were enrolled during the intervention phase and 56.2% (95% CI, 54.2 to 58.1) among patients who were enrolled during the control phase (adjusted hazard ratio, 0.95; 95% CI, 0.92 to 0.99). Fewer than six deaths or hospitalizations for any cause occurred in low- or intermediate-risk patients before the first outpatient visit within 30 days after discharge. CONCLUSIONS: Among patients with acute heart failure who were seeking emergency care, the use of a hospital-based strategy to support clinical decision making and rapid follow-up led to a lower risk of the composite of death from any cause or hospitalization for cardiovascular causes within 30 days than usual care. (Funded by the Ontario SPOR Support Unit and others; COACH ClinicalTrials.gov number, NCT02674438.).

Ambulatory Cardiology or General Internal Medicine Assessment Prior to Scheduled Major Vascular Surgery is Associated with Improved Outcomes.

OBJECTIVE: To characterize the association between ambulatory cardiology or general internal medicine (GIM) assessment prior to surgery and outcomes following scheduled major vascular surgery. BACKGROUND: Cardiovascular risk assessment and management prior to high-risk surgery remains an evolving area of care. METHODS: This is population-based retrospective cohort study of all adults who underwent scheduled major vascular surgery in Ontario, Canada, April 1, 2004-March 31, 2019. Patients who had an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included: composite of 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; composite of 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication. RESULTS: Among 50,228 patients, 20,484 (40.8%) underwent an ambulatory assessment prior to surgery: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Compared to patients who did not, those who underwent an assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989[24.4%] vs. 4,587[15.4%], P<0.001) and more frequent pre-operative cardiac testing (N=7,772[37.9%] vs. 6,113[20.6%], P<0.001) but, lower 30-day mortality (N=551[2.7%] vs. 970[3.3%], P<0.001). After application of IPTW, cardiology or GIM assessment prior to surgery remained associated with a lower 30-day mortality (weighted Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes. CONCLUSIONS: Major vascular surgery patients assessed by a cardiology or GIM physician prior to surgery have better outcomes than those who are not. Further research is needed to better understand potential mechanisms of benefit.

Comparison of Machine Learning and Conventional Statistical Modeling for Predicting Readmission Following Acute Heart Failure Hospitalization.

INTRODUCTION: Developing accurate models for predicting the risk of 30-day readmission is a major healthcare interest. Evidence suggests that models developed using machine learning (ML) may have better discrimination than conventional statistical models (CSM), but the calibration of such models is unclear. OBJECTIVES: To compare models developed using ML with those developed using CSM to predict 30-day readmission for cardiovascular and non-cardiovascular causes in HF patients. METHODS: We retrospectively enrolled 10,919 patients with HF (> 18 years) discharged alive from a hospital or emergency department (2004-2007) in Ontario, Canada. The study sample was randomly divided into training and validation sets in a 2:1 ratio. CSMs to predict 30-day readmission were developed using Fine-Gray subdistribution hazards regression (treating death as a competing risk), and the ML algorithm employed random survival forests for competing risks (RSF-CR). Models were evaluated in the validation set using both discrimination and calibration metrics. RESULTS: In the validation sample of 3602 patients, RSF-CR (c-statistic=0.620) showed similar discrimination to the Fine-Gray competing risk model (c-statistic=0.621) for 30-day cardiovascular readmission. In contrast, for 30-day non-cardiovascular readmission, the Fine-Gray model (c-statistic=0.641) slightly outperformed the RSF-CR model (c-statistic=0.632). For both outcomes, The Fine-Gray model displayed better calibration than RSF-CR using calibration plots of observed vs. predicted risks across the deciles of predicted risk. CONCLUSIONS: Fine-Gray models had similar discrimination but superior calibration to the RSF-CR model, highlighting the importance of reporting calibration metrics for ML-based prediction models. The discrimination was modest in all readmission prediction models regardless of the methods used.

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.

Monitoring Cardiac Biomarkers with Aptamer-Based Molecular Pendulum Sensors.

Reagent-free electronic biosensors capable of analyzing disease markers directly in unprocessed body fluids will enable the development of simple & affordable devices for personalized healthcare monitoring. Here we report a powerful and versatile nucleic acid-based reagent-free electronic sensing system. The signal transduction is based on the kinetics of an electrode-tethered molecular pendulum-a rigid double stranded DNA with one of the strands displaying an analyte-binding aptamer and the other featuring a redox probe-that exhibits field-induced transport modulated by receptor occupancy. Using chronoamperometry, which enables the sensor to circumvent the conventional Debye length limitation, the binding of an analyte can be monitored as these species increase the hydrodynamic drag. The sensing platform demonstrates a low femtomolar quantification limit and minimal cross-reactivity in analyzing cardiac biomarkers in whole blood collected from patients with chronic heart failure.

Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients.

Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.

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.

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.

The risk of death or unplanned readmission after discharge from a COVID-19 hospitalization in Alberta and Ontario.

BACKGROUND: The frequency of readmissions after COVID-19 hospitalizations is uncertain, as is whether current readmission prediction equations are useful for discharge risk stratification of COVID-19 survivors or for comparing among hospitals. We sought to determine the frequency and predictors of death or unplanned readmission after a COVID-19 hospital discharge. METHODS: We conducted a retrospective cohort study of all adults (≥ 18 yr) who were discharged alive from hospital after a nonpsychiatric, nonobstetric, acute care admission for COVID-19 between Jan. 1, 2020, and Sept. 30, 2021, in Alberta and Ontario. RESULTS: Of 843 737 individuals who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction during the study period, 46 412 (5.5%) were adults admitted to hospital within 14 days of their positive test. Of these, 8496 died in hospital and 34 846 were discharged alive (30 336 discharged after an index admission of ≤ 30 d and 4510 discharged after an admission > 30 d). One in 9 discharged patients died or were readmitted within 30 days after discharge (3173 [10.5%] of those with stay ≤ 30 d and 579 [12.8%] of those with stay > 30 d). The LACE score (length of stay, acuity, Charlson Comorbidity Index and number of emergency visits in previous 6 months) for predicting urgent readmission or death within 30 days had a c-statistic of 0.60 in Alberta and 0.61 in Ontario; inclusion of sex, discharge locale, deprivation index and teaching hospital status in the model improved the c-statistic to 0.73. INTERPRETATION: Death or readmission after discharge from a COVID-19 hospitalization is common and had a similar frequency in Alberta and Ontario. Risk stratification and interinstitutional comparisons of outcomes after hospital admission for COVID-19 should include sex, discharge locale and socioeconomic measures, in addition to the LACE variables.

Relationship of frailty with excess mortality during the COVID-19 pandemic: a population-level study in Ontario, Canada.

BACKGROUND: There is a paucity of the literature on the relationship between frailty and excess mortality due to the COVID-19 pandemic. METHODS: The entire community-dwelling adult population of Ontario, Canada, as of January 1st, 2018, was identified using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. Residents of long-term care facilities were excluded. Frailty was categorized through the Johns Hopkins Adjusted Clinical Groups (ACG® System) frailty indicator. Follow-up was until December 31st, 2020, with March 11th, 2020, indicating the beginning of the COVID-19 pandemic. Using multivariable Cox models with patient age as the timescale, we determined the relationship between frailty status and pandemic period on all-cause mortality. We evaluated the modifier effect of frailty using both stratified models as well as incorporating an interaction between frailty and the pandemic period. RESULTS: We identified 11,481,391 persons in our cohort, of whom 3.2% were frail based on the ACG indicator. Crude mortality increased from 0.75 to 0.87% per 100 person years from the pre- to post-pandemic period, translating to ~ 13,800 excess deaths among the community-dwelling adult population of Ontario (HR 1.11 95% CI 1.09-1.11). Frailty was associated with a statistically significant increase in all-cause mortality (HR 3.02, 95% CI 2.99-3.06). However, all-cause mortality increased similarly during the pandemic in frail (aHR 1.13, 95% CI 1.09-1.16) and non-frail (aHR 1.15, 95% CI 1.13-1.17) persons. CONCLUSION: Although frailty was associated with greater mortality, frailty did not modify the excess mortality associated with the pandemic.

Early invasive coronary angiography and acute ischaemic heart failure outcomes.

AIMS: While myocardial ischaemia plays a major role in the pathogenesis of heart failure (HF), the indications for coronary angiography during acute HF are not established. We determined the association of early coronary angiography during acute HF hospitalization with 2-year mortality, cardiovascular death, HF readmissions, and coronary revascularization. METHODS AND RESULTS: In a two-stage sampling process, we identified acute HF patients who presented to 70 emergency departments in Ontario (April 2010 to March 2013) and determined whether they underwent early coronary angiography within 14 days after presentation using administrative databases. After clinical record review, we defined a cohort with acute ischaemic HF as patients with at least one factor suggesting underlying ischaemic heart disease, including previous myocardial infarction, troponin elevation, or angina on presentation. We oversampled patients undergoing angiography. We used inverse-probability-of-treatment weighting (IPTW) to adjust for baseline differences. Of 7239 patients with acute HF, 2994 met inclusion criteria [median age 75 (interquartile range 65-83) years; 40.9% women]. Early angiography was performed in 1567 patients (52.3%) and was associated with lower all-cause mortality [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.61-0.90, P = 0.002], cardiovascular death (HR 0.72, 95% CI 0.56-0.93, P = 0.012), and HF readmissions (HR 0.84, 95% CI 0.71-0.99, P = 0.042) after IPTW. Those undergoing early angiography experienced higher rates of percutaneous coronary intervention (HR 2.58, 95% CI 1.73-3.86, P < 0.001) and coronary artery bypass grafting (HR 2.94, 95% CI 1.75-4.93, P < 0.001) within 2 years. CONCLUSIONS: Early coronary angiography was associated with lower all-cause mortality, cardiovascular death, HF readmissions, and higher rates of coronary revascularization in acute HF patients with possible ischaemia.

Rationale and design of the comparison of outcomes and access to care for heart failure (COACH) trial: A stepped wedge cluster randomized trial.

BACKGROUND: Heart failure (HF) is an ambulatory care sensitive condition and a leading reason for emergency department (ED) visits and hospitalizations. Improved decision-making and care may enhance safety and efficiency for patients presenting to the ED with acute HF. OBJECTIVES: We will evaluate an intervention comprised of 2 complementary components: (1) the Emergency Heart Failure Mortality Risk Grade simultaneous 7- and 30-day (EHMRG30-ST) risk scores, which will inform admission-discharge decisions, and (2) a rapid outpatient follow-up (RAPID-HF) clinic for low-to-intermediate risk patients on cardiovascular readmissions or death. STUDY DESIGN: Stepped wedge cluster randomized trial with cross-sectional measurement at 10 acute care hospitals in Ontario, Canada. Patients presenting during control and intervention periods are eligible if they have a primary ED diagnosis of HF. In the intervention periods, access to the EHMRG30-ST web calculator will become available to hospitals' internet protocol (IP) addresses, and referral to the RAPID-HF clinic will be facilitated by a study nurse navigator. Patients with a high risk EHMRG30-ST score will be admitted to hospital. The RAPID-HF clinic will accept referrals for patients: (1) with low risk 7- and 30-day EHMRG30-ST scores who are discharged directly from the ED, or (2) intermediate risk patients with hospital length of stay < 72 hours. The RAPID-HF clinic, staffed by a nurse-clinician and cardiologist, will provide care during the 30-day transition after hospital separation. CONCLUSION: This trial will determine whether novel risk stratification coupled with rapid ambulatory care achieves better outcomes than conventional decision-making and care for patients with HF.

The associations between direct and delayed critical care unit admission with mortality and readmissions among patients with heart failure.

BACKGROUND: Although greater than 20% of patients hospitalized with heart failure (HF) are admitted to a critical care unit, associated outcomes, and costs have not been delineated. We determined 30-day mortality, 30-day readmissions, and hospital costs associated with direct or delayed critical care unit admission. METHODS: In a population-based analysis, we compared HF patients who were admitted to critical care directly from the emergency department (direct), after initial ward admission (delayed), or never admitted to critical care during their hospital stay (ward-only). RESULTS: Among 178,997 HF patients (median age 80 [IQR 71-86] years, 49.6% men) 36,175 (20.2%) were admitted to critical care during their hospitalization (April 2003 to March 2018). Critical care patients were admitted directly from the emergency department (direct, 81.9%) or after initial ward admission (delayed, 18.1%). Multivariable-adjusted hazard ratios (HR) for all-cause 30-day mortality were: 1.69 for direct (95% confidence interval [CI]; 1.55, 1.84) and 4.92 for delayed (95% CI; 4.26, 5.68) critical care-admitted compared to ward-only patients. Multivariable-adjusted repeated events analysis demonstrated increased risk for all-cause 30-day readmission with both direct (HR 1.04, 95% CI; 1.01, 1.08, P = .013) and delayed critical care unit admissions (HR 1.20, 95% CI; 1.13, 1.28, P < .001). Median 30-day costs were $12,163 for direct admissions, $20,173 for delayed admissions, and $9,575 for ward-only patients (P < .001). CONCLUSIONS: While critical care unit admission indicates increased risk of mortality and readmission at 30 days, those who experienced delayed critical care unit admission exhibited the highest risk of death and highest costs of care.

The effect of antiplatelet therapy on survival and cardiac allograft vasculopathy following heart transplantation: A systematic review and meta-analysis.

Cardiac allograft vasculopathy (CAV) is mediated by endothelial inflammation, platelet activation and thrombosis. Antiplatelet therapy may prevent the development of CAV. This systematic review and meta-analysis summarizes and appraises the evidence on the effect of antiplatelet therapy after heart transplantation (HT). CENTRAL(Ovid), MEDLINE(Ovid), Embase(Ovid) were searched from inception until April 30, 2020. Outcomes included CAV, all-cause mortality, and CAV-related mortality. Data were pooled using random-effects models. Seven observational studies including 2023 patients, mean age 52 years, 22% female, 47% with ischemic cardiomyopathy followed over a mean 7.1 years proved eligible. All studies compared acetylsalicylic acid (ASA) to no treatment and were at serious risk of bias. Data from 1911 patients in 6 studies were pooled in the meta-analyses. The evidence is very uncertain about the effect of ASA on all-cause or CAV-related mortality. ASA may reduce the development of CAV (RR 0.75, 95% CI: 0.44-1.29) based on very low certainty evidence. Two studies that conducted propensity-weighted analyses showed further reduction in CAV with ASA (HR 0.31, 95% CI: 0.13-0.74). In conclusion, there is limited evidence that ASA may reduce the development of CAV. Definitive resolution of the impact of antiplatelet therapy on CAV and mortality will require randomized clinical trials.

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.

Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS). METHODS: Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV. RESULTS: Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non-Caucasian race (HR = 1.98, p = .011), BMI < 18 kg/m2 (HR = 4.596, p = .042), longer ischemic time (HR = 1.374, p = .028), older donor age (HR = 1.158, p = .009), and rejection with hemodynamic compromise within the first year (HR = 2.858, p = .043). Prednisone discontinuation within 1 year was associated with a lower risk of CAV (HR 0.58 p = .047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p < .001). CONCLUSION: In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.

Readmission rates following heart failure: a scoping review of sex and gender based considerations.

BACKGROUND: Although hospital readmission for heart failure (HF) is an issue for both men and women, little is known about differences in readmission rates by sex. Consequently, strategies to optimize readmission reduction programs and care strategies for women and men remain unclear. Our study aims were: (1) to identify studies examining readmission rates according to sex, and (2) to provide a qualitative overview of possible considerations for the impact of sex or gender. METHODS: We conducted a scoping review using the Arksey and O'Malley framework to include full text articles published between 2002 and 2017 drawn from multiple databases (MEDLINE, EMBASE), grey literature (i.e. National Technical information, Duck Duck Go), and expert consultation. Eligible articles included an index heart failure episode, readmission rates, and sex/gender-based analysis. RESULTS: The search generated 5887 articles, of which 746 underwent full abstract text consideration for eligibility. Of 164 eligible articles, 34 studies addressed the primary outcome, 103 studies considered sex differences as a secondary outcome and 25 studies stratified data for sex. Good inter-rater agreement was reached: 83% title/abstract; 88% full text; kappa: 0.69 (95%CI: 0.53-0.85). Twelve of 34 studies reported higher heart failure readmission rates for men and six studies reported higher heart failure readmission rates for women. Using non composite endpoints, five studies reported higher HF readmission rates for men compared to three studies reporting higher HF readmission rates for women. Overall, there was heterogeneity between studies when examined by sex, but one observation emerged that was related to the timing of readmissions. Readmission rates for men were higher when follow-up duration was longer than 1 year. Women were more likely to experience higher readmission rates than men when time to event was less than 1 year. CONCLUSIONS: Future studies should consider different time horizons in their designs and avoid the use of composite measures, such as readmission rates combined with mortality, which are highly skewed by sex. Co-interventions and targeted post-discharge approaches with attention to sex would be of benefit to the HF patient population.