Composite Endpoint Of Death Research Articles

Real-world experience of selexipag titration in pulmonary arterial hypertension.

Selexipag is an oral selective prostacyclin-receptor agonist that was approved for use in patients with World Health Organisation (WHO) functional class II-III pulmonary arterial hypertension (PAH). Treatment with individualised doses of selexipag resulted in significant reductions in the composite end point of death or a complication related to PAH in the phase III GRIPHON (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) study. In order to better understand the real-world approach to selexipag titration and to establish the individualised maintenance regimens used in our centre, we performed this retrospective study of the first 20 patients prescribed selexipag. Baseline characteristics differed from the GRIPHON study, with more combination therapy and comorbidities at drug initiation. Maintenance doses were stratified as low-dose in 10% (n=2), medium-dose in 70% (n=14) and high-dose in 20% (n=4). This study highlights that selexipag can be safely initiated, titrated and transitioned in an outpatient setting to achieve an individualised dosing regimen.

Prognostic validation of partition values for quantitative parameters to grade functional tricuspid regurgitation severity by conventional echocardiography.

Quantitative echocardiography parameters are seldom used to grade tricuspid regurgitation (TR) severity due to relative paucity of validation studies and lack of prognostic data. To assess the relationship between TR severity and the composite endpoint of death and hospitalization for congestive heart failure (CHF); and to identify the threshold values of vena contracta width (VCavg), effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFr) to define low, intermediate, and high-risk TR based on patients' outcome data. A cohort of 296 patients with at least mild TR underwent 2D, 3D, and Doppler echocardiography. We built statistical models (adjusted for age, NYHA class, left ventricular ejection fraction, and pulmonary artery systolic pressure) for VCavg, EROA, RegVol, and RegFr to study their relationships with the hazard of outcome. The tertiles of the derived hazard values defined the threshold values of the quantitative parameters for TR severity grading. During 47-month follow-up, 32 deaths and 72 CHF occurred. Event-free rate was 14%, 48%, and 93% in patients with severe, moderate, and mild TR, respectively. Severe TR was graded as VCavg > 6 mm, EROA > 0.30 cm2, RegVol > 30 mL, and RegF > 45%. This outcome study demonstrates the prognostic value of quantitative parameters of TR severity and provides prognostically meaningful threshold values to grade TR severity in low, intermediate, and high risk.

Retrospective single center cohort study: effect of intensive home hemodialysis on right ventricular systolic pressure and clinical outcomes

BackgroundIncreased right ventricular systolic pressure (RVSP), a surrogate marker for pulmonary hypertension, is common in patients with end-stage kidney disease. Limited data suggest improvement of RVSP with intensive dialysis, but it is unknown whether these improvements translate to better clinical outcomes.MethodsWe conducted a retrospective single center cohort study at the Toronto General Hospital. All patients who performed intensive home hemodialysis (IHHD) for at least a year between 1999 and 2017, and who had a baseline as well as a follow-up echocardiogram more than a year after IHHD, were included. Patients were categorized into two groups based on the RVSP at follow-up: elevated (≥ 35 mmHg) and normal RVSP. Multivariate and cox regression analyses were done to identify risk factors for elevated RVSP at follow-up and reaching the composite endpoint (death, cardiovascular hospitalization, treatment failure), respectively.ResultsOne hundred eight patients were included in the study. At baseline, 63% (68/108) of patients had normal RVSP and 37% (40/108) having elevated RVSP. After a follow-up of 4 years, 70% (76/108) patient had normal RVSP while 30% (32/108) had elevated RVSP. 8 (10%) out of the 76 patients with normal RVSP and 15 (47%) out of the 32 patients with elevated RVSP reached the composite endpoint of death, cardiovascular hospitalization or technique failure. In a multivariate analysis, age, diabetes and smoking were not associated with elevated RVSP at follow-up. Elevated RVSP at baseline was not associated with a higher likelihood in reaching the composite endpoint or mortality.ConclusionMean RVSP did not increase in patients on IHHD over time, and maintenance of normal RVSP was associated with better clinical outcomes.

Abstract 13368: Clinical Impact of Heart Rate Change in Early Phase in Patients With Acute Decompensated Heart Failure

Introduction: Several studies have evaluated prognostic value of heart rate (HR) change during hospitalization in patients with acute heart failure (AHF). However, the relationship between HR change in early phase after admission and prognosis have not been fully elucidated. Hypothesis: The aim of this study was to evaluate the prognostic value of HR change in early phase in patients with AHF. Methods: We used a data of multicenter retrospective registry for the consecutive hospitalized patients due to AHF since January 2012 to March 2019. Patients were divided into three groups according to tertiles of HR at admission: lower tertile, HR <85 bpm; middle tertile, HR 85-108 bpm; higher tertile, HR >108 bpm. And, (HR [at admission] - HR [at 12 hour after admission]) * 100 / HR [at admission] was calculated as HR change (%). Results: Total of 1625 patients were analyzed. The median HR at admission was 96 bpm, and HR decreased to 81 bpm at 12 hours after admission (p < 0.001). Larger HR change was observed according to increase in HR at admission (HR change; lower tertile, 1.0%; middle tertile, 12.5%, higher tertile, 38.0%, p < 0.001). In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and re-hospitalization due to AHF showed better according to higher HR at admission (p < 0.001, log-rank) (Figure). After dividing the patient into two groups in each tertiles based on the median HR change, the cumulative event-free rates were comparable between higher HR change group and lower HR change group in all tertiles (Figure). Cox proportional hazards analysis showed that HR change was not the independent predictors of composite endpoint adjusted by covariates in each tertile (lower tertile, p = 0.81; middle tertile, p = 0.78; higher tertile, p = 0.90). Conclusions: HR decreased significantly until 12 hours after admission. However, HR change in early phase did not have prognostic value in patients with AHF.

Impact of Diabetes Mellitus on Antithrombotic Management Patterns and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndrome: Insights From the EPICOR Asia Study.

BackgroundLong‐term use of antiplatelet agents after acute coronary syndrome in diabetic patients is not well known. Here, we describe antiplatelet use and outcomes in such patients enrolled in the EPICOR Asia (Long‐Term Follow‐up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients in Asia) registry.Methods and ResultsEPICOR Asia is a prospective, observational study of 12 922 patients with acute coronary syndrome surviving to discharge, from 8 countries/regions in Asia. The present analysis included 3162 patients with diabetes mellitus (DM) and 9602 patients without DM. The impact of DM on use of antiplatelet agents and events (composite of death, myocardial infarction, and stroke, with or without any revascularization; individual components, and bleeding) was evaluated. Significant baseline differences were seen between patients with DM and patients without DM for age, sex, body mass index, cardiovascular history, angiographic findings, and use of percutaneous coronary intervention. At discharge, ≈90% of patients in each group received dual antiplatelet therapy. At 2‐year follow‐up, more patients with DM tended to still receive dual antiplatelet therapy (60% versus 56%). DM was associated with increased risk from ischemic but not major bleeding events. Independent predictors of the composite end point of death, myocardial infarction, and stroke in patients with DM were age ≥65 years and use of diuretics at discharge.ConclusionsAntiplatelet agent use is broadly comparable in patients with DM and patients without DM, although patients with DM are more likely to be on dual antiplatelet therapy at 2 years. Patients with DM are at increased risk of ischemic events, suggesting an unmet need for improved antithrombotic treatment.RegistrationURL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01361386.

Baseline ECG and Prognosis After Transcatheter Aortic Valve Implantation: The Role of Interatrial Block.

BackgroundThe clinical significance of conduction disturbances after transcatheter aortic valve implantation has been described; however, little is known about the influence of baseline ECGs in the prognosis of these patients. Our aim was to study the influence of baseline ECG parameters, including interatrial block (IAB), in the prognosis of patients treated with transcatheter aortic valve implantation.Methods and ResultsThe BIT (Baseline Interatrial Block and Transcatheter Aortic Valve Implantation) registry included 2527 patients with aortic stenosis treated with transcatheter aortic valve implantation. A centralized analysis of baseline ECGs was performed. Patients were divided into 4 groups: normal P wave duration (<120 ms); partial IAB (P wave duration ≥120 ms, positive in the inferior leads); advanced IAB (P wave duration ≥120 ms, biphasic [+/–] morphology in the inferior leads); and nonsinus rhythm (atrial fibrillation/flutter and paced rhythm). The mean age of patients was 82.6±9.8 years and 1397 (55.3%) were women. A total of 960 patients (38.0%) had a normal P wave, 582 (23.0%) had partial IAB, 300 (11.9%) had advanced IAB, and 685 (27.1%) presented with nonsinus rhythm. Mean follow‐up duration was 465±171 days. Advanced IAB was the only independent predictor of all‐cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.10–1.98 [P=0.010]) and of the composite end point (death/stroke/new atrial fibrillation) (HR, 1.51; 95% CI, 1.17–1.94 [P=0.001]).ConclusionsBaseline ECG characteristics influence the prognosis of patients with aortic stenosis treated with transcatheter aortic valve implantation. Advanced IAB is present in about an eighth of patients and is associated with all‐cause death and the composite end point of death, stroke, and new atrial fibrillation during follow‐up.

Short term effect of Selexipag in comparison to parenteral prostacyclin analogues in pulmonary arterial hypertension patients started on double-combination therapy with ERA and PDE-5 inhibitors

Abstract Background The event-driven, phase 3, randomized, double-blind, placebo-controlled GRIPHON trial demonstrated that Selexipag reduces the risk of a composite end point of death or morbidity events in patients with pulmonary arterial hypertension (PAH). Despite the advantage of a per os formulation, its efficacy in comparison to parenteral prostacyclin analogues in patients already on oral double-combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5-I) is not known. Purpose The aim of this study was to compare the effects of Selexipag (S) vs subcutaneous Treprostinil (T) vs intravenous Epoprostenol (E) in PAH patients initially started with double-combination therapy with ERA and PDE5-I. Methods We enrolled patients on double combination therapy with ERA + PDE5-I starting S, T or E. Drugs were gradually uptitrated to the maximum tolerated/approved dose. All patients were systematically assessed with WHO-functional class (FC), six minute walk test (6MWT) and right heart catheterization before treatment and 3 months after reaching a stable dose of the drug. Baseline characteristics and changes in 6MWT and haemodynamic parameters were analyzed using Wilcoxon signed-rank test and compared between the 3 drugs with Kruskal-Wallis test. Results One hundred and seventy-one patients with PAH were enrolled. Results are shown in the Table. Patients with a complete re-evaluation were 61% of S, 85% of T, 79% with E. Conclusions S was prescribed to the oldest and least severe PAH patients. E was prescribed to the youngest and most severe PAH patients and led to the strongest improvement of exercise capacity and haemodynamic profile. T has intermediate characteristics. Table 1 Funding Acknowledgement Type of funding source: None

Risk stratification in hf with mid-range LVEF: the role of cardiopulmonary exercise testing

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) &amp;lt;40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF &amp;lt;50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p&amp;lt;0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p&amp;lt;0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 &amp;lt;12 mL/kg/min, VE/VCO2 &amp;gt;35 and EOV identified patients at higher risk for events (all p&amp;lt;0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p&amp;lt;0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p&amp;lt;0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 &amp;gt;16.7 and &amp;gt;15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p&amp;lt;0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None

Phenomapping a Novel Classification System for Patients with Destination LVADs: An Unsupervised Machine Learning Cluster Analysis

Introduction Patients with continuous flow destination therapy (DT) left ventricular assist devices (LVAD) are a heterogenous population that may have distinct phenotypic clusters. Hypothesis We hypothesize there will be distinct phenotypic clustering of individuals with DT LVADs by their clinical characteristics at implantation that are associated with different long-term risk profiles. Methods We analyzed 8245 patients with a continuous flow DT LVADs in INTERMACS and selected 25 baseline clinical characteristics including demographic, echocardiographic, hemodynamic, and laboratory data. Variables with >10% missingness were excluded except for left ventricular dimensions which were imputated. Unsupervised K-means clustering derived phenogroups and the optimal number of clusters was assessed by minimization of the Bayesian Information Criterion. The final dataset included 5999 patients with 18 selected variables for 4 distinct phenogroups. Survival analyses for events considered competing risk for cumulative incidence of transplant or the composite endpoint of death or heart transplant when appropriate. Results Of the 4 phenogroups, phenogroup 1 (n=1163, 19%) was older (median age 71 years), primarily white (81%), and most frail (9%). Phenogroup 4 (n=517, 9%) was younger (41 years), heavier (108 kg), and more diverse (white race 46%) with the least frailty (3%), largest left ventricles (LVEDD 7.5 cm), and highest rate of non-adherence (8%) amongst the clusters. Phenogroups 2 (n=648, 11%) and 3 (n=3671, 61%) were of intermediate age (69 & 61 years), weight (87 & 90 kg), and ventricular size (LVEDD 6.5 & 6.9 cm). The cumulative incidence of death, heart transplant, bleeding, LVAD malfunction and LVAD thrombosis differed among phenogroups (Figure A-D). The highest cumulative incidence of death and the lowest rate of heart transplant was seen in phenogroup 1 (P Conclusions Our exploratory unsupervised machine learning analysis highlighted 4 phenogroups that differed in fatal and non-fatal adverse events. These observations underscore the influence of phenotypic heterogeneity on post-LVAD implantation outcomes.

Coronary Angiography After Cardiac Arrest Without ST Segment Elevation

Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking. To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy. A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019. Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery. Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year. At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64). In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes. trialregister.nl Identifier: NTR4973.

Cognitive impairment in patients with atrial fibrillation: Implications for outcome in a cohort study

BackgroundThe impact of cognitive status on outcomes of patients with atrial fibrillation (AF) is not well defined. AimsTo assess the prevalence of cognitive impairment in AF patients and evaluate its association with: i) all-cause mortality; ii) a composite endpoint of death, stroke/systemic embolism, hemorrhages, acute coronary syndrome, pulmonary embolism, new/worsening heart failure. MethodsIn a cohort study, cognitive status was assessed at baseline by the Mini Mental State examination adjusted for age and education (aMMSE). aMMSE <24 was considered indicative of cognitive impairment. ResultsThe cohort included 437 patients (61.3% male, mean age 73.4 ± 11.7 years). Sixty-three patients (14.4%) had cognitive impairment at baseline aMMSE. Permanent AF (odds ratio [OR] 1.750; 95%CI 1.012–3.025; p = .045), haemoglobin levels (OR 0.827; 95%CI 0.707–0.967; p = .017) and previous treatment with antiplatelet drugs only, without oral anticoagulation, (OR 4.352; 95%CI 1.583–11.963; p = .004) were independently associated with cognitive impairment at baseline.After a median follow-up of 887 days (interquartile range 731–958) 30 patients died (7.1%), and 97 (22.9%) reached the composite endpoint. After adjustment for Elixhauser Comorbidy Measure, aMMSE <24 was significantly associated with all-cause mortality (hazard ratio [HR] 2.473, 95%CI 1.062–5.756, p = .036) and with the composite endpoint (HR 1.852, 95%CI 1.106–3.102, p = .019). ConclusionsIn patients with AF, cognitive impairment (aMMSE <24) is associated with worse outcomes, and the association of adverse outcomes with previous treatment with antiplatelet drugs only, without oral anticoagulation, highlights the potential role of appropriate antithrombotic treatment for improving patient prognosis.

Follow-up Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention in Patients With and Without Prior Coronary Artery Bypass Graft Surgery: Insights From the PROGRESS-CTO Registry.

Long-term outcomes of patients with prior coronary artery bypass graft (CABG) surgery undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study. We compared the clinical and angiographic characteristics and procedural and follow-up outcomes of patients with and without prior CABG in a multicenter international registry. Of the 1572 patients included in this analysis, a total of 498 (32%) had prior CABG. Prior CABG patients had higher J-CTO scores (2.9 ± 1.1 vs 2.2 ± 1.3; P<.001) and were less likely to undergo PCI of the left anterior descending artery (16.7% vs 29.6%; P<.001). The retrograde technique was used more often (47.4% vs 28.2%; P<.001) and was successful more often (27.4% vs 17.1%; P<.001) in the prior CABG group vs the non-prior CABG group. Technical success was lower in prior CABG patients (82.6% vs 87.9%; P<.01) with similar incidence of in-hospital major adverse cardiovascular events (3.4% vs 3%; P=.65), although in-hospital mortality was higher in the prior CABG group (2.4% vs 1.0%; P=.04). At 1-year follow-up, the composite endpoint of death, myocardial infarction, and revascularization was higher in prior CABG patients (21.79% vs 12.73%; hazard ratio, 1.76; 95% confidence interval, 1.27-2.45; P<.001). Compared with non-prior CABG patients, prior CABG patients undergoing CTO-PCI had lower technical success and higher incidence of acute and follow-up adverse cardiovascular events.

Left Ventricular Assist Device Exchange Increases Heart Transplant Wait-List Mortality

BackgroundThe new heart transplant allocation criteria prioritize inpatients who require temporary mechanical circulatory support and give lower urgency to candidates on a durable left ventricular assist device (LVAD) who require a device exchange. This study explores whether the latter group should warrant higher priority to reduce wait-list mortality. MethodsThis is a retrospective observational study of 13,113 adult heart transplant candidates in the Organ Procurement and Transplantation Network database who underwent LVAD implantation between 2007 and 2017. It evaluates the impact of LVAD exchange on the composite endpoint of death or removal from the wait list owing to worsening medical condition 1 y after device implantation. ResultsThere were 1085 pump exchanges in 954 patients (7% of candidates), of which 22% were women. The pump exchange rate was 5.92 events per 100 patient-years. One-year survival was lower for those who required a pump exchange (76.3% versus 88.5%, logrank P < 0.001). This was congruent with the risk-adjusted mortality 1-y after implantation (hazards ratio: 2.56, 95% confidence interval: 2.18-3.00, P < 0.001). ConclusionsThese findings indicate that among candidates awaiting heart transplantation with a durable LVAD, undergoing pump exchange doubles the risk of 1-y mortality. Giving priority to these candidates may reduce wait-list mortality.

Cardiac Magnetic Resonance Feature Tracking Global Longitudinal Strain and Prognosis After Heart Transplantation

ObjectivesThis study determined the long-term prognostic significance of GLS assessed using CMR-FT in a large cohort of heart transplant recipients. BackgroundIn heart transplant recipients, global longitudinal strain (GLS) assessed using echocardiography has shown promise in the prediction of clinical outcomes. We hypothesized that CMR feature tracking (CMR-FT) GLS is independently associated with long-term outcomes in heart transplant recipients. MethodsIn a cohort of consecutive heart transplant recipients who underwent routine CMR for clinical surveillance, CMR-FT GLS was calculated from 3 long-axis cine CMR images. Associations between GLS and a composite endpoint of death or major adverse cardiac events (MACE), including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization, were investigated. ResultsA total of 152 heart transplant recipients (age 54 ± 15 years; 29% women; 5.0 ± 5.4 years after heart transplantation) were included. The median GLS was −11.6% (interquartile range: −13.6% to −9.2%). Over a median follow-up of 2.6 years, 59 recipients reached the composite endpoint. On Kaplan-Meier analyses, recipients with GLS worse than the median had a higher estimated cumulative incidence of the composite endpoint compared with recipients with GLS better than the median (log rank p = 0.004). On multivariate Cox proportional hazards regression, GLS was independently associated with the composite endpoint after adjustment for cardiac allograft vasculopathy, history of rejection, left ventricular ejection fraction (LVEF), right ventricular EF, and presence of myocardial fibrosis, with a hazard ratio of 1.15 for every 1% worsening in GLS (95% confidence interval: 1.06 to 1.24; p < 0.001). Similar results were seen in subgroups of recipients with LVEF >50% and with no myocardial fibrosis. GLS provided incremental prognostic value over other variables in the multivariate model as determined by the log-likelihood chi-squared test. ConclusionsIn a large cohort of heart transplant recipients, CMR-FT GLS was independently associated with the long-term risk of death or MACE.

Clinical impact of diabetes mellitus on 2-year clinical outcomes following PCI with second-generation drug-eluting stents; Landmark analysis findings from patient registry: Pooled analysis of the Korean multicenter drug-eluting stent registry.

BackgroundPatients with diabetes mellitus are at an increased risk for adverse clinical events following percutaneous coronary interventions (PCI). However, the clinical impact of diabetes mellitus (DM) on second-generation drug-eluting stent (DES) implantation is not well-known. The aim of the current analysis was to examine the clinical impact of DM on clinical outcomes and the time sequence of associated risks in patients treated with second-generation DES.MethodsUsing patient-level data from two stent-specific, all-comer, prospective DES registries, we evaluated 1,913 patients who underwent PCI with second-generation DES between Feb 2009 and Dec 2013. The primary outcomes assessed were two-year major cardiac adverse events (MACE), composite endpoints of death from any cause, myocardial infarction (MI), and any repeat revascularization. We classified 0–1 year as the early period and 1–2 years as the late period. Landmark analyses were performed according to diabetes mellitus status.ResultsThere were 1,913 patients with 2,614 lesions included in the pooled dataset. The median duration of clinical follow-up in the overall population was 2.0 years (interquartile range 1.9–2.1). Patients with DM had more cardiovascular risk factors than patients without DM. In multivariate analyses, the presence of DM and renal failure were strong predictors of MACE and target-vessel revascularization (TVR). After inverse probability of treatment weighting (IPTW) analyses, patients with DM had significantly increased rates of 2-year MACE (HR 2.07, 95% CI; 1.50–2.86; P <0.001). In landmark analyses, patients with DM had significantly higher rates of MACE in the early period (0–1 year) (HR 3.04, 95% CI; 1.97–4.68; P < 0.001) after IPTW adjustment, but these findings or trends were not observed in the late period (1–2 year) (HR 1.24, 95% CI; 0.74–2.07; P = 0.41).ConclusionsIn the second-generation DES era, the clinical impact of DM significantly increased the 2-year event rate of MACE, mainly caused by clinical events in the early period (0–1 year). Careful observation of patients with DM is advised in the early period following PCI with second-generation DES.

Bayesian Interpretation of the EXCEL Trial and Other Randomized Clinical Trials of Left Main Coronary Artery Revascularization

Patients with left main coronary artery disease have improved outcomes with coronary revascularization compared with medical therapy, but the choice of optimal revascularization technique is unresolved. To use bayesian methods to analyze the risk differences for patients with left main coronary artery disease randomized to treatment with coronary artery bypass surgery (CABG) compared with those randomized to percutaneous coronary intervention (PCI) in recent randomized clinical trials (RCTs). A systematic review using the PubMed database with the query string "(left main disease) and (PCI or CABG) and (5-year follow-up) and (clinical trial)" identified all RCTs from January 1996 to January 2020 comparing CABG to PCI for treatment of patients with left main coronary artery disease and with 5-year follow-up data. With the use of bayesian methods, the largest and most publicized RCT (EXCEL; Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; 2019) was reanalyzed (1) as an isolated entity using noninformative priors and (2) in the context of previous knowledge using informative priors derived from similar trials. Published aggregate data were used with assignments from each trial following the original intention-to-treat principle. Combining EXCEL data with varying levels of prior information using Bayes theorem provided final (posterior) probability distributions for primary and secondary outcomes. A composite end point of death, nonfatal myocardial infarction, and stroke was the primary EXCEL outcome and was accordingly the primary outcome for this reanalysis. Secondary analyses were performed for isolated all-cause mortality and for the composite outcome along with repeated revascularization procedures. When EXCEL data were analyzed using the originally stated noninferiority design, the 5-year primary outcome difference reported (2.8%; 95% CI, -0.9% to 6.5%) exceeded the predefined 4.2% noninferiority margin; thus, the null hypothesis of PCI inferiority could not be rejected. By contrast, the present bayesian analysis of the EXCEL primary outcome estimated 95% probability that the 5-year primary outcome difference was increased with PCI compared with CABG and 87% probability that this difference was greater than 1 extra event per 100 patients treated. Bayesian analyses also suggested 99% probability that EXCEL total mortality was increased with PCI and 94% probability that this absolute difference exceeded 1 extra deaths per 100 treated. A systematic review identified 3 other RCTs that studied the same question. The incorporation of this prior knowledge reduced the estimated probability of any excess mortality with PCI to 85%. For the secondary composite end point, which also included repeated revascularizations, there were estimated probabilities of 98% for at least 4 extra events and of 90% for at least 5 extra events per 100 patients treated with PCI. Bayesian analysis assisted in RCT data interpretation and specifically suggested, whether based on EXCEL results alone or on the totality of available evidence, that PCI was associated with inferior long-term results for all events, including mortality, compared with CABG for patients with left main coronary artery disease.

Impact of mitral regurgitation on cardiovascular hospitalization and death in newly diagnosed heart failure patients.

AimsHeart failure (HF) carries a poor prognosis, and the impact of concomitant mitral regurgitation (MR) is not well understood. This analysis aimed to estimate the incremental effect of MR in patients newly diagnosed with HF.Methods and resultsData from the IBM® MarketScan® Research Databases were analysed. Included patients had at least one inpatient or two outpatient HF claims. A 6 month post‐period after HF index was used to capture MR diagnosis and severity. HF patients were separated into three cohorts: without MR (no MR), not clinically significant MR (nsMR), and significant MR (sMR). Time‐to‐event analyses were modelled to estimate the clinical burden of disease. The primary outcome was a composite endpoint of death or cardiovascular (CV)‐related admission. Secondary outcomes were death and CV hospitalization alone. All models controlled for baseline demographics and co‐morbidities. Patients with sMR were at significantly higher risk of either death or CV admission compared with patients with no MR [hazard ratio (HR) 1.26; 95% confidence interval (CI) 1.15–1.39]. When evaluating death alone, patients with sMR had significantly higher risk of death (HR 1.24; 95% CI 1.08–1.43) compared with patients with no MR. When evaluating CV admission alone, patients with MR were at higher risk of hospital admission vs. patients with no MR, and the magnitude was dependent upon the MR severity: sMR (HR 1.55; 95% CI 1.38–1.74) and nsMR (HR 1.23; 95% CI 1.08–1.40).ConclusionsEvidence of MR in retrospective claims significantly increases the clinical burden of incident HF patients. Time to death and CV hospitalizations are increased when MR is clinically significant.

Preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with major adverse cardiovascular and cerebrovascular events in coronary heart disease patients undergoing non-cardiac surgery

BackgroundPreoperative risk prediction in patients at elevated cardiovascular risk shows limited accuracy. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) indicate systemic inflammation. Both have been investigated for outcome prediction in the field of oncology and cardiovascular medicine, as well as risk prediction of adverse cardiovascular events in non-surgical patients at increased cardiovascular risk.MethodsFor this post-hoc analysis, we included all 38 coronary heart disease patients from the Leukocytes and Cardiovascular Perioperative Events cohort-1 study scheduled for elective non-cardiac surgery. We evaluated preoperative differential blood counts for association with major adverse cardiovascular and cerebrovascular events (MACCE) defined as the composite endpoint of death, myocardial ischemia, myocardial infarction, myocardial injury after non-cardiac surgery, or embolic or thrombotic stroke within 30 days after surgery. We used Youden’s index to calculate cut-off values for PLR and NLR. Additive risk-predictive values were assessed using receiver operating characteristic curve and net reclassification (NRI) improvement analyses.ResultsPatients with the composite endpoint MACCE had higher PLR and NLR (309 [206; 380] vs. 160 [132; 203], p = 0.001; 4.9 [3.5; 8.1] vs. 2.6 [2.2; 3.4]), p = 0.001). Calculated cut-offs for PLR > 204.4 and NLR > 3.1 were associated with increased risk of 30-day MACCE (OR 7, 95% CI [1.2; 44.7], p = 0.034; OR 36, 95% CI [1.8; 686.6], p = 0.001). Furthermore, NLR improved risk prediction in coronary heart disease patients undergoing non-cardiac surgery when combined with hs-cTnT or NT-proBNP (NRI total = 0.23, p = 0.008, NRI total = 0.26, p = 0.005).ConclusionsBoth PLR and NLR were associated with perioperative cardiovascular adverse events in coronary heart disease patients. NLR proved to be of additional value for preoperative risk stratification. Both PLR and NLR could be used as inexpensive and broadly available tools for perioperative risk assessment.Trial registrationNCT02874508, August 22, 2016.

Comparative Analysis of the Effect of Renal Function on the Spectrum of Coronary Artery Disease

BackgroundWe aim to assess the differential effect of renal impairment across the spectrum of patients with ischaemic heart disease and to study if any established risk factors may modify this risk. MethodsA total of 2013 patients who underwent revascularization for ST-segment elevation myocardial infarction or invasive physiology assessment were included. Renal impairment was defined as glomerular filtration rate less than 60 ml/min/1.73m2. Clinical endpoints were prospectively collected, and the primary endpoint was defined as the composite endpoints of death, myocardial infarction, and unplanned revascularization. Results593 (30%) presented with ST-segment elevation myocardial infarction, and 1362 (70%) stable patients had invasive ischaemia assessment which resulted in 37% receiving revascularization and 63% being deferred. Renal impairment was associated with increased adverse events in myocardial infarction [HR 1.77 (95% CI 1.15 to 2.74)], but not in the revascularized stable group [(HR 1.14 (95% CI 0.62 to 2.08)] or the deferred group [HR 1.31 (95% CI 0.84 to 2.03)]. There was an exponential increase in the future risk in ST-segment elevation myocardial infarction patients with severe renal dysfunction (glomerular filtration rate < 30) compared to a linear relationship in stable patients. Age and hypertension were the only two factors that had a differential impact across three groups (P<0.05 for interactions), with inconsistent directional effect of hypertension between medically managed and revascularized groups. ConclusionsThe magnitude of risk of renal impairment varies according to the clinical presentation of coronary artery disease with more weighted risk in myocardial infarction compared to stable patients.

The Impact of HeartMate 3 Speed on Outcomes in the Momentum 3 Clinical Trial

Durable continuous flow left ventricular assist devices (LVADs) operate at a fixed speed set by the clinician. Within Momentum 3, a large multicenter clinical trial of a magnetically levitated centrifugal LVAD, we sought to characterize pump speeds utilized, identify clinical variables associated with speed selection, and determine if early speed setting was independently associated with major adverse events. Momentum 3 was a prospective randomized clinical trial comparing the HeartMate II and HeartMate 3 (HM3) in advanced heart failure. Multivariate linear regression analyses were used to identify baseline clinical factors associated with HM3 speed setting at implant and discharge. The negative binomial model was used to determine if pump speed at implant or discharge from the index hospitalization was independently associated with a composite endpoint of death, transplant for pump thrombosis, and the occurrence of hemocompatibility related adverse events: bleeding due to surgical or non-surgical causes, any stroke, suspected or confirmed pump thrombosis or peripheral arterial thromboembolism. There were 514 patients implanted with the HM3 that had speed data available for analysis. Median speed at implant was lower than all other time points through 180 days (Figure). Baseline clinical variables independently associated with higher pump speed at implant were increasing body surface area (BSA, p=0.003) and left ventricular end diastolic diameter (LVEDD, p=0.008), and at hospital discharge were BSA (p<0.001), younger age (p=0.001), male gender (p=0.01), and LVEDD (p=0.049). HM3 speed at implant and discharge were not independently associated with the composite adverse event endpoint. Within the Momentum 3 clinical trial, HM3 speed was significantly lower at implant compared to other time points up to 180 days. Younger age, male gender, larger BSA and LVEDD were associated with higher pump speeds. Early HM3 speed was not independently associated with adverse events.