Combined All-cause Mortality Research Articles

Abstract 12167: High BNP and NT-proBNP Level as a Poor Prognostic Indicator an Patients With Hypertrophic Cardiomyopathy: A Systematic Review and Meta-analysis

Background: Raised BNP/NT-pro BNP has been reported as a poor prognostic indicator in hypertrophic cardiomyopathy (HCM) patients. However, the unavailability of pooled data utilizing BNP/NT-proBNP as a prognostic biomarker led us to perform this systematic review and meta-analysis. Methods: Using relevant keywords, PubMed/Medline, Scopus, and EMBASE were systematically reviewed to evaluate studies reporting all-cause mortality or sudden death with BNP/NT-pro BNP through May 2022. Random effects models and I 2 statistics were used for pooled hazard ratios (HR) and heterogeneity assessment using Review Manager (RevMan) [Computer program]. Version 5.4, The Cochrane Collaboration, 2020. Results: Our systematic review included sample size of 6691 from 12 studies [Table 1]. Four publications were from China, 2 from Japan and Turkey each and 1 from USA, UK, Italy and France each. Age ranged from 46-55 years with a follow up time from 3-8 years. High NT-proBNP was associated with significantly high risk of all-cause mortality in both unadjusted (HR 1.69, 95%CI: 1.30-2.20, p<0.05, I 2 =90%) and adjusted models (HR 3.73, 95%CI: 1.36-10.21, p<0.05, I 2 =83%), and of sudden death in adjusted (HR 4.78, 95%CI: 1.49-15.34, p<0.05, I 2 =89%). Raised BNP level was associated with adjusted sudden death (HR 5.10, 95%CI: 3.03-8.61, p<0.05) (Fig. 1). Conclusions: This meta-analysis suggested that higher BNP/NT-proBNP level was associated with high risk of combined all-cause mortality and sudden death in patient with hypertrophic cardiomyopathy.

Cardiovascular Outcomes of Patients Referred to Home Based Cardiac Rehabilitation

BackgroundHome Based Cardiac Rehabilitation (HBCR) has been considered a reasonable alternative to Center-based Cardiac Rehabilitation (CBCR) in patients with established cardiovascular disease, especially in the midst of COVID-19 pandemic. However, the long-term cardiovascular outcomes of patients referred to HBCR remains unknown.ObjectivesTo compare outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR).MethodsWe performed a retrospective study of 269 patients referred to HBCR at Providence Veterans Affairs Medical Center (PVAMC). From November 2017 to March 2020, 427 patients were eligible and referred for Cardiac Rehabilitation (CR) at PVAMC. Of total patients, 158 patients were referred to CBCR and 269 patients to HBCR based on patient and/or clinician preference. The analysis of outcomes was focused on HBCR patients. We compared outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR) from 3 to 12 months of the referral date. HBCR consisted of face-to-face entry exam with exercise prescription, weekly phone calls for education and exercise monitoring, with adjustments where applicable, for 12-weeks and an exit exam. Primary outcome was composite of all-cause mortality and hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: smoking, left ventricular ejection fraction and CABG status.ResultsA total of 269 patients (mean age: 72, 98% Male) were referred to HBCR, however, only 157 (58%) patients attended HBCR. The primary outcome occurred in 30 patients (19.1%) in the HBCR group and 30 patients (30%) in the Non-HBCR group (adjusted HR=0.56, CI 0.33-0.95, P=.03). All-cause mortality occurred in 6.4% of patients in the HBCR group and 13% patients in the Non-HBCR group 3 to 12 months after HBCR referral (adjusted HR=0.43, CI 0.18-1.0, P= .05). There was no difference in cardiovascular hospitalizations (HBCR: 5.7% vs Non-HBCR: 10%, adjusted HR 0.57, CI 0.22-1.4, P= .23) or all cause hospitalizations at 3 to 12 months between the groups (HBCR: 12.7% vs Non-HBCR: 21%, adjusted HR 0.53, CI 0.28-1.01, P= .05).ConclusionCompletion of HBCR among referred patients was associated with a lower risk of the combined all-cause mortality and all-cause hospitalizations up to 12 months. Based on the outcomes, HBCR is a reasonable option that can improve access to CR for patients who are not candidates of or cannot attend CBCR. Randomized-controlled studies are needed to confirm these findings.

Safety and efficacy of minimalist transcatheter aortic valve implantation using a new-generation balloon-expandable transcatheter heart valve in bicuspid and tricuspid aortic valves

Bicuspid aortic valve may be associated with increased complications during transcatheter aortic valve implantation (TAVI). Compare balloon-expandable transcatheter heart valve (THV) safety and efficacy in severe tricuspid (TAV) and bicuspid (BAV) aortic stenosis. Transfemoral TAVI was performed in 743 patients (Jan 2014-June 2019) using the SAPIEN 3 THV. Aortic valve morphology was determined using computed tomography. Valve Academic Research Consortium-2 (VARC-2) derived safety and efficacy endpoints at 1 year were evaluated. BAV patients (n = 78), were younger (77 [72, 81] vs. 81 [78, 85] years, p < 0.001) with lower surgical risk (EuroSCORE II 2.96% vs. 4.51% p < 0.001). Bicuspid valves were more calcified (BAV 1308mm3, TAV 848mm3 p < 0.001) with more asymmetric calcification (BAV 63/78 (81%), TAV 239/665 (36%), p < 0.001). Device success (BAV 94%, TAV 90%, p = 0.45) and major vascular complications (BAV 6%, TAV 9%, p = 0.66) were comparable. At 1 year, there was a trend toward lower combined all-cause mortality and rehospitalization for congestive heart failure in BAV patients (BAV 7%, TAV 13%, p = 0.08) with significantly lower all-cause mortality in this cohort (BAV 1%, TAV 9%, p = 0.020). VARC-2 time-related valve safety (BAV 22%, TAV 20%, p = 0.60) was comparable; however, bioprosthetic valve thrombosis remained more common in BAV patients (BAV 7%, TAV 2%, p = 0.010, Hazard ratio 3.57 [95% confidence interval 1.26, 10.10]). After propensity score matching, only bioprosthetic valve thrombosis remained significantly different. Safety and efficacy of the SAPIEN 3 balloon-expandable THV in BAV is comparable with TAV. Higher rates of bioprosthetic valve thrombosis require further investigation.

Discharge heart rate and clinical outcomes in hospitalized heart failure patients with coexisted atrial fibrillation

Abstract Background Whether discharge heart rate for hospitalized heart failure (HF) patients with coexisted atrial fibrillation (AF) is associated with long-term clinical outcomes and whether this association differs between patients with and without beta-blockers have not been well studied. Purpose We investigated the associations between discharge heart rate and clinical outcomes in hospitalized HF patients with coexisted AF, while stratified to beta-blockers at discharge. Methods The study cohort included 1631 HF patients hospitalized primarily with AF, which was from the China PEACE Prospective Heart Failure Study. Clinical outcome was 1-year combined all-cause mortality and HF hospitalization after discharge. We analyzed association between outcome and heart rate at discharge with restricted cubic spline and Cox proportional hazard ratios (HR). Results The median age was 68 (IQR: 60- 77) years, 41.9% were women, discharge heart rate was (median (IQR)) 75 (69- 84) beats per minute (bpm), and 60.2% received beta-blockers at discharge. According to the result of restricted cubic spline plot, the relationship between discharge heart rate and clinical outcome may be nonlinear (P&amp;lt;0.01). Based on above result, these patients were divided into 3 groups: lowest &amp;lt;65 bpm, middle 65–86 bpm and highest ≥87 bpm, clinical outcomes occurred in 128 (64.32%), 624 (53.42%) and 156 (59.32%) patients in the lowest, middle, and highest groups respectively. In the Cox proportional hazard analysis, the lowest and highest groups were associated with increased risks of clinical outcome compared with the middle group (HR: 1.289, 95% confidence interval (CI): 1.056 - 1.573, p=0.013; HR: 1.276, 95% CI: 1.06 - 1.537, p=0.01, respectively). And a significant interaction between discharge heart rate and beta-blocker use was observed (P&amp;lt;0.001 for interaction). Stratified analysis showed the lowest group was associated with increased risks of clinical outcomes in patients with beta-blockers (HR: 1.584, 95% confidence interval (CI): 1.215–2.066, p=0.001). Conclusion There may be a U-curve relationship between discharge heart rate and clinical outcomes in hospitalized HF patients with coexisted AF. They may have the best clinical outcomes with heart rates of 65 - 86 bpm. And strict heart rate control (&amp;lt;65 bpm) may be avoided for patients who discharge with beta-blockers. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Key Research and Development Program (2017YFC1310803) from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science (2017-I2M-B&amp;R-02); the 111 Project from the Ministry of Education of China (B16005).

Discharge heart rate and beta-blockers treatments in hospitalized heart failure patients with coexisted atrial fibrillation

Abstract Background Beta-blockers are widely used to improve clinical outcomes in heart failure (HF) patients. However, the effects of beta-blockers on clinical outcomes in those who have coexisted atrial fibrillation (AF) remains uncertain. Purpose We investigated the associations between beta-blockers and clinical outcomes according to discharge heart rate. Methods The study cohort included 1631 HF patients hospitalized primarily with AF, which was from the China PEACE Prospective Heart Failure Study. Clinical outcome was 1-year combined all-cause mortality and HF hospitalization after discharge. The associations between beta-blockers and clinical outcome were assessed using Cox proportional hazard and standardization mortality weighting regression models, with stratified discharge heart rate group predefined by restricted cubic spline. Results The median age was 68 (IQR: 60- 77) years, 41.9% were women, discharge heart rate was (median (IQR)) 75 (69- 84) beats per minute (bpm), and 60.2% received beta-blockers at discharge. According to the result of restricted cubic spline plot, these patients were divided into 3 groups: lowest &amp;lt;65 bpm, middle 65–86 bpm and highest ≥87 bpm (Fig.1). In the Cox proportional hazard analysis, a significant interaction between discharge heart rate and beta-blocker use was observed (P&amp;lt;0.001 for interaction). Stratified analysis showed beta-blocker prescription at discharge was associated with reduced risk for clinical outcomes in patients with high heart rates (hazard ratio 0.336, 95% CI: 0.144–0.786, p=0.012) but not in those with lowest and middle heart rates (hazard ratio: 1.32; 95% CI, 0.95–1.63; hazard ratio: 1.02; 95% CI, 0.68–1.55, respectively). Conclusion The associations between beta-blockers and clinical outcomes may be significantly influenced by baseline heart rate. Hospitalized HF patients with AF benefit the most from beta-blockers use if they had high heart rate (≥87 bpm) at discharge. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Key Research and Development Program (2017YFC1310803) from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science (2017-I2M-B&amp;R-02); the 111 Project from the Ministry of Education of China (B16005).

Stratification of long-term outcome in stable idiopathic pulmonary fibrosis by combining longitudinal computed tomography and forced vital capacity.

To test HRCT with either visual or quantitative analysis in both short-term and long-term follow-up of stable IPF against long-term (transplant-free) survival, beyond 2years of disease stability. Fifty-eight IPF patients had FVC measurements and HRCTs at baseline (HRCT0), 10-14months (HRCT1) and 22-26months (HRCT2). Visual scoring, CALIPER quantitative analysis of HRCT measures, and their deltas were evaluated against combined all-cause mortality and lung transplantation by adjusted Cox proportional hazard models at each time interval. At HRCT1, a ≥ 20% relative increase in CALIPER-total lung fibrosis yielded the highest radiological association with outcome (C-statistic 0.62). Moreover, the model combining FVC% drop ≥ 10% and ≥ 20% relative increase of CALIPER-total lung fibrosis improved the stratification of outcome (C-statistic 0.69, high-risk category HR 12.1; landmark analysis at HRCT1 C-statistic 0.66, HR 14.9 and at HRCT2 C-statistic 0.61, HR 21.8). Likewise, at HRCT2, the model combining FVC% decrease trend and ≥ 20% relative increase of CALIPER-pulmonary vessel-related volume (VRS) improved the stratification of outcome (C-statistic 0.65, HR 11.0; landmark analysis at HRCT1 C-statistic 0.62, HR 13.8 and at HRCT2 C-statistic 0.58, HR 12.6). A less robust stratification of outcome distinction was also demonstrated with the categorical visual scoring of disease change. Annual combined CALIPER -FVC changes showed the greatest stratification of long-term outcome in stable IPF patients, beyond 2years. • Longitudinal high-resolution computed tomography (HRCT) data is more helpful than baseline HRCT alone for stratification of long-term outcome in IPF. • HRCT changes by visual or quantitative analysis can be added with benefit to the current spirometric reference standard to improve stratification of long-term outcome in IPF. • HRCT follow-up at 12-14months is more helpful than HRCT follow-up at 23-26months in clinically stable subjects with IPF.

P1757GLP-1 levels predict cardiovascular risk in patients with acute myocardial infarction

Abstract Background Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone, which induces post-prandial glucose-dependent insulin secretion. GLP-1 receptor agonists improve cardiovascular outcomes in patients with diabetes at high cardiovascular risk. We recently found GLP-1 levels to be increased in patients with acute myocardial infarction. Purpose The aim of this study was to assess the predictive capacity of GLP-1 for cardiovascular outcome in patients with myocardial infarction. Methods Total GLP-1 levels, NT-proBNP concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 918 patients with myocardial infarction presenting with acute chest pain. Among these 597 patients presented with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with a median follow-up of 311 days. Results Kaplan-Meier survival plots (separated by tertiles with cut-off values 35.44 and 53.45) and univariate cox regression analyses found GLP-1 values to be associated with adverse outcome (combined endpoint and all-cause mortality) (logarithmized GLP-1 values HR: 5.459; p&lt;0.0001). Further adjustment for age, sex, previous cardiovascular disease, diabetes, hypertension, hypercholesterinemia, kreatinin, CRP, troponin T and NT-proBNP levels did not affect the association of GLP-1 with adverse outcomes (p=0.0341). Receiver operating characteristic curve analyses illustrated that GLP-1 is a strong indicator for early events (area under the curve of the combined endpoint at 7 days: 0.79; 14 days: 0.81; 30 days: 0.80 and 183 days: 0.64), which proved to be superior to Troponin T, serum creatinin, NT-proBNP and CRP within the first 100 days. Adjustment of the GRACE risk estimate by GLP-1 increased the area under the receiver-operating characteristic curve (AUC) after 1 month from 0.86 to 0.89 in NSTEMI patients. Addition of GLP-1 to a model containing GRACE and NT-proBNP led to a further improvement in model performance (increase in AUC from 0.88 for GRACE + NT-proBNP to 0.90 for GRACE + NT-proBNP + GLP-1). Conclusion GLP-1 is a new biomarker of cardiovascular risk and adverse outcomes in patients with acute myocardial infarction and improves the predictive value of the GRACE score in patients with NSTEMI.

Airflow limitation more than doubles the risk for hospitalization/mortality in patients with heart failure.

Comorbid chronic obstructive pulmonary disease is found in approximately one-third of patients with heart failure. Survival in patients with chronic obstructive pulmonary disease generally decreases as lung function declines. However, the association between lung function, hospitalization and survival is less clear for patients with heart failure. The purpose of this study was to determine the predictive power of spirometry measures for event-free survival (combined all-cause hospitalization and/or mortality) in patients with heart failure. In this secondary analysis of data from three prospective, longitudinal studies, we selected patients with a confirmed diagnosis of heart failure who completed airflow limitation assessment using spirometry measures ( n=137): forced vital capacity, forced expiratory volume/second, and forced expiratory volume/second/forced vital capacity. Cox proportional hazards modeling was used to determine the relationship between spirometry and all-cause hospitalization/mortality with and without adjusting for demographic and clinical covariates over a four-year follow-up period. A majority (74%) exhibited some degree of airflow limitation (forced expiratory volume/second<80% predicted value) and 26 (19%) met the spirometric criterion for chronic obstructive pulmonary disease (forced expiratory volume/second/forced vital capacity⩽0.70). Cox proportional hazards regression models compared all-cause hospitalization/mortality between those with and without airflow limitation. Patients with airflow limitation were 2.2 times more likely to be hospitalized or die compared to those without airflow limitations (hazard ratio: 2.20, 95% confidence interval 1.06-4.53, p=0.03). Patients with comorbid heart failure and airflow limitation were at more than double the risk for an event. Spirometric measures may be useful to patients with heart failure, as tailored management of airflow limitation may impact event-free survival.

Impact of Stress Testing for Coronary Artery Disease Screening in Asymptomatic Patients With Diabetes Mellitus: A Community-Based Study in Olmsted County, Minnesota

ObjectiveTo evaluate the impact of screening stress testing for coronary artery disease in asymptomatic patients with diabetes in a community-based population. Patients and MethodsThis observational study included 3146 patients from Olmsted County, Minnesota, with no history of coronary artery disease or cardiac symptoms in whom diabetes was newly diagnosed from January 1, 1992, through December 31, 2008. With combined all-cause mortality and myocardial infarction as the primary outcome, weighted Cox proportional hazards regression was performed with screening stress testing within 2 years of diabetes diagnosis as the time-dependent covariate. For descriptive analysis, participants were classified by their clinical experience during the first 2 years postdiagnosis as screened (asymptomatic, underwent stress test), unscreened (asymptomatic, no stress test), or symptomatic (experienced symptoms or event). ResultsAmong the screened and unscreened participants, 54% (1358 of 2538) were men; the mean (SD) age at diabetes diagnosis was 55 years (13.8 years), and 97% (2442 of 2520) had type 2 diabetes. In event-free survival analysis, 292 patients comprised the screened cohort and 2246 patients comprised the unscreened cohort. Death or myocardial infarction occurred in 454 patients (32 patients in the screened cohort and 422 in the unscreened cohort [5-year rate, 1.9% and 5.3%, respectively]) during median (interquartile range) follow-up of 9.1 years (5.3-12.5 years). Screening stress testing was associated with improved event-free survival (hazard ratio, 0.61; P=.004), independent of cardiac risk factors. However, while stress test results were abnormal in 47 of the 292 screened patients (16%), only 6 (2%) underwent coronary revascularization. ConclusionAlthough screening cardiac stress testing in asymptomatic patients with diabetes in this community-based population was associated with improvement in long-term event-free survival, this result does not appear to occur by coronary revascularization alone.

Abstract 622: High-density Lipoprotein Cholesterol Efflux Does Not Predict Cardiovascular Risk in Hemodialysis Patients

The cardioprotective effect of HDL (High-Density Lipoprotein) is largely determined by its cholesterol efflux capacity, which was shown to correlate inversely with atherosclerotic cardiovascular disease in populations with normal kidney function. Patients with end-stage renal disease suffer an exceptionally high cardiovascular risk not fully explained by traditional risk factors. Here, we investigated in a post-hoc analysis in 1147 patients with type 2 diabetes mellitus on hemodialysis participating in the 4D Study (The German Diabetes Dialysis Study), if the HDL cholesterol efflux capacity is predictive of cardiovascular risk. Efflux capacity was quantified by incubating human macrophage foam cells with apolipoprotein B-depleted serum. During a median follow-up of 4.1 years n=423 patients reached the combined primary endpoint (composite of cardiac death, nonfatal myocardial infarction and stroke), n=410 experienced cardiac events and n=561 died (all-cause mortality). Strikingly, in Cox regression analysis we found no association of efflux capacity with the combined primary endpoint (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88 – 1.06, p =0.417), cardiac events (HR, 0.92; CI, 0.83-1.02; p =0.108) or all-cause mortality (HR 0.96; 95% CI, 0.88-1.05; p =0.390). In conclusion, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in diabetic patients on hemodialysis.

Left Ventricular Hypertrophy in Asymptomatic Nonsevere Aortic Stenosis

Increased biomechanical stress on cardiomyocytes because of outflow obstruction secondary to aortic stenosis (AS) is thought to induce reexpression of the fetal gene program, which modifies myocyte efficiency, sarcomere composition, and regulation of extracellular matrix, as well as various nuclear signal transduction pathways resulting in autocrine production and secretion of cytokines, neurohormones and growth factors that ultimately promote ventricular hypertrophy.1,2 See Article by Gerdts et al The traditional view of adaptative concentric left ventricular hypertrophy (LVH) because of parallel replication of new sarcomeres is that wall thickness increases to normalize LV systolic wall stress and preserve systolic performance. This view, accepted for the past 40 years3 and perhaps counterintuitively expected to mitigate the effects of LV pressure overload on cardiovascular morbidity and mortality, has begun to be challenged by new clinical data, suggesting that moderate or severe LVH may be associated with adverse outcomes in AS4,5 and that inappropriately increased LV mass, found in 17% of patients with mild to moderate AS6 and in 67% of patients with asymptomatic severe AS, was associated with a 4.5-fold increased risk of cardiovascular events.7 Conversely, the absence of hypertrophy in one third of the patients with severe AS seems to have no adverse effects on systolic function or survival.8,9 Experimental studies in genetically modified animal models are consistent with clinical observations.10 In addition, no association was found between AS severity and the magnitude or pattern of LVH using cardiac magnetic resonance.11 Thus, it seems that the presence, severity, and the geometric pattern of LVH in AS vary widely, are …

Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50.

The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as ≥50%. Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction ≥50% (age 77±11 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; P<0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). In heart failure with ejection fraction ≥50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

Association Between Use of β-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). β-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF. To test the hypothesis that β-blockers are associated with reduced all-cause mortality in HFPEF. Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for β-blocker use were derived from 52 baseline clinical and socioeconomic variables. Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012. From a consecutive sample of 41,976 patients, 19,083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for β-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22,893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients. β-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization. Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P = .04). β-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; P = .46). In the matched HFREF cohort, β-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; P = .001). In patients with HFPEF, use of β-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. β-Blockers in HFPEF should be examined in a large randomized clinical trial.

Adherence to dabigatran therapy and longitudinal patient outcomes: Insights from the Veterans Health Administration

Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.

Abstract 162: Procedural and 1-Year Outcomes between PCI Centers with and without On-Site CT Surgery: Insights from the VA CART Program

Background: Clinical trials demonstrate that percutaneous coronary intervention (PCI) can be safely performed at medical centers without on-site cardiothoracic (CT) surgery, and current PCI guidelines support this practice with effective quality oversight. Translation of these trial findings and guideline recommendations into clinical practice has not been described. In 2005, the VA initiated a policy to expand PCI access by performing procedures at centers without on-site CT surgery under strict quality standards. The impact of this policy on procedural and longer-term patient outcomes has not been evaluated. Methods: We studied all PCIs conducted in the VA health care system between 2007-2010. We used data from the VA Clinical Assessment, Reporting, and Tracking (CART) Program, a national clinical quality program that collects real-time data on coronary procedures, procedural complications, and outcomes. Procedural complications (need for emergent CABG and in-lab death), 1-year all-cause mortality, myocardial infarction (MI), and rates of repeat revascularization procedures were compared by presence of on-site CT surgery. We used multivariate survival analysis to assess the association between the presence of on-site CT surgery and 1-year outcomes. The analyses were further stratified by procedural indication (ACS vs. elective) and cath lab PCI volume (≥ vs. &lt;165 PCIs/year). Results: 24,387 patients received a PCI at 59 centers in the VA health care system between 2007-2010. 6,900 (28.3%) patients underwent PCI at 19 centers without on-site CT surgery. Rates of procedural complications were similar for PCI centers with and without on-site CT surgery (emergent CABG: 13 (0.1%) at PCI centers with on-site CT surgery vs. 2 (&lt;0.05%) at PCI centers without on-site CT surgery, p-value 0.26; deaths: 15 (0.1%) at PCI centers with on-site CT surgery vs. 5 (0.1%) at PCI centers without on-site CT surgery, p-value 0.74). Adjusted 1-year combined all-cause mortality and MI rates were similar between centers (HR 0.995, 95% CI 0.84, 1.17), but revascularization rates were higher at sites without on-site CT surgery centers (HR 1.20, 95% CI 1.05, 1.33). Neither PCI indication nor cath lab volume significantly modified these results. Conclusions: Our findings demonstrate that procedural and 1-year patient outcomes are similar between PCI centers with and without on-site CT surgery. These results indicate that the clinical trial evidence of PCI safety without on-site CT surgery can be effectively translated to clinical practice. The VA’s policy allowing for PCI centers without on-site CT surgery in the setting of a quality oversight program may serve as a potential model for improving PCI access in large, integrated health care systems.

Systemic review/Meta-analysis Pregnancy-associated plasma protein A predicts adverse vascular events in patients with coronary heart disease: a systematic review and meta-analysis

IntroductionProspective studies about the association between elevated circulating pregnancy-associated plasma protein A (PAPP-A) and adverse vascular events in patients with coronary heart diseases (CHD) are inconsistent. We performed a meta-analysis to clarify this issue.Material and methodsWe identified prospective studies by searching MEDLINE. The vascular outcomes included all-cause mortality, combination of all-cause mortality and non-fatal myocardial infarction (MI), and combined cardiovascular events. Prospective studies providing multivariable adjusted relative risks (RRs) and their 95% confidence intervals (CIs) of pre-mentioned outcomes were included. A random-effects model was used to calculate the pooled RRs. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity or modifiable factors.ResultsFourteen studies with a total of 12 830 participants were included. Elevated PAPP-A level was associated with all-cause mortality (pooled RR 1.74, 95% CI: 1.45 to 2.09, p < 0.001), combined all-cause mortality and non-fatal MI (RR 1.59, 95% CI: 1.37 to 1.85, p < 0.001) and combined cardiovascular events (RR 1.50, 95% CI: 1.22 to 1.85, p < 0.001). There was no significant heterogeneity. Subgroup and sensitivity analyses showed that the positive association was not affected by follow-up term, CHD type, different assay methods of PAPP-A, or studies with less than 5 adjusted variables.ConclusionsElevated serum PAPP-A level is associated with adverse vascular outcomes in patients with CHD.

ACHTUNG-Rule: a new and improved model for prognostic assessment in myocardial infarction

THROMBOLYSIS IN MYOCARDIAL INFARCTION (TIMI), PLATELET GLYCOPROTEIN IIB/IIIA IN UNSTABLE ANGINA: Receptor Suppression Using Integrilin (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores have been developed for risk stratification in myocardial infarction (MI). The latter is the most validated score, yet active research is ongoing for improving prognostication in MI. Derivation and validation of a new model for intrahospital, post-discharge and combined/total all-cause mortality prediction - ACHTUNG-Rule - and comparison with the GRACE algorithm. 1091 patients admitted for MI (age 68.4 ± 13.5, 63.2% males, 41.8% acute MI with ST-segment elevation (STEMI)) and followed for 19.7 ± 6.4 months were assigned to a derivation sample. 400 patients admitted at a later date at our institution (age 68.3 ± 13.4, 62.7% males, 38.8% STEMI) and followed for a period of 7.2 ± 4.0 months were assigned to a validation sample. Three versions of the ACHTUNG-Rule were developed for the prediction of intrahospital, post-discharge and combined (intrahospital plus post-discharge) all-cause mortality prediction. All models were evaluated for their predictive performance using the area under the receiver operating characteristic (ROC) curve, calibration through the Hosmer-Lemeshow test and predictive utility within each individual patient through the Brier score. Comparison through ROC curve analysis and measures of risk reclassification - net reclassification improvement index (NRI) or Integrated Discrimination Improvement (IDI) - was performed between the ACHTUNG versions for intrahospital, post-discharge and combined mortality prediction and the equivalent GRACE score versions for intrahospital (GRACE-IH), post-discharge (GRACE-6PD) and post-admission 6-month mortality (GRACE-6). Assessment of calibration and overall performance of the ACHTUNG-Rule demonstrated a good fit (p value for the Hosmer-Lemeshow goodness-of-fit test of 0.258, 0.101 and 0.550 for ACHTUNG-IH, ACHTUNG-T and ACHTUNG-R, respectively) and high discriminatory power in the validation cohort for all the primary endpoints (intrahospital mortality: AUC ACHTUNG-IH 0.886 ± 0.035 vs. AUC GRACE-IH 0.906 ± 0.026; post-discharge mortality: AUC ACHTUNG-R 0.827 ± 0.036 vs. AUC GRACE-6PD 0.811 ± 0.034; combined/total mortality: AUC ACHTUNG-T 0.831 ± 0.028 vs. AUC GRACE-6 0.815 ± 0.033). Furthermore, all versions of the ACHTUNG-Rule accurately reclassified a significant number of patients in different, more appropriate, risk categories (NRI ACHTUNG-IH 17.1%, p (2-sided) = 0.0021; NRI ACHTUNG-R 22.0%, p = 0.0002; NRI ACHTUNG-T 18.6%, p = 0.0012). The prognostic performance of the ACHTUNG-Rule was similar in both derivation and validation samples. All versions of the ACHTUNG-Rule have shown excellent discriminative power and good calibration for predicting intrahospital, post-discharge and combined in-hospital plus post-discharge mortality. The ACHTUNG version for intrahospital mortality prediction was not inferior to its equivalent GRACE model, and ACHTUNG versions for post-discharge and combined/total mortality demonstrated apparent superiority. External validation in wider, independent, preferably multicentre, registries is warranted before its potential clinical implementation.

TCT-843 Transcatheter Aortic Valve Implantation with Edwards SAPIEN XT™ versus Medtronic CoreValve Revalving System® with AccuTrak™: The SAPERE Pilot Study

Background: To our knowledge no data exists comparing new generation commercially available devices for transfemoral (TF) transcatheter aortic valve implantation (TAVI). Methods: All consecutive patients from our single-center prospective registry with AS treated with TAVI with from Edwards SAPIEN XTTM (SXT) vs. Medtronic CoreValve® with AccuTrakTM delivery sy stem (MCVAT) when the devices became commercially available were included. The study endpoints were according to the Valve Academic Research Consortium (VARC) definitions. Results: In total, 235 patients treated in our center by TF TAVI for severe AS were included: 142 (60.4%) underwent SXT vs. 93 (39.6%) MCVAT. More females (60.6% vs. 43.0%; p 0.008) and smaller annulus size (23.2 1.9 vs. 24.3 2.0; p 0.001) were present in the SXT group. There were no differences between valves in 30-day combined safety endpoint (SXT 26.1% vs. MCVAT 29.7%; p 0.558), all-cause mortality (3.1% vs. 6.5%; p 0.218), cardiovascular mortality (2.3% vs. 5.4%; p 0.214), myocardial infarction (1.4% vs. 2.2%; p 0.683) or stroke (0.7% vs. 1.1%; p 0.774). Additionally, no differences were observed in life-threatening bleeding (12.4% vs. 20.4%; p 0.100) or major vascular complications (12.0% vs. 9.7%; p 0.583). Conversely, with SXT there was a lower occurrence of conduction disturbances/arrhythmia (16.5% vs. 36.6%; p 0.001) and pacemaker implantation (5.8% vs. 33.3%; p 0.001). Of note, a higher device success (96.5% vs. 88.2%; p 0.013) was observed with SXT. At median follow-up of 328 (IQR 83-401) days, there was no difference in combined efficacy endpoint (14.8% vs. 9.8%; p 0.265) or mortality (8.0% vs. 6.5%; p 0.654). Conclusions: In our single center experience, there was a lower incidence of arrhythmia and pacemaker, with higher device success with SXT. Differences in the characteristics of the patients treated with each valve may explain some of these findings.

Abstract 3420: High-sensitivity Troponin T Improves Cardiovascular Risk Prediction In Patients With Cerebral Ischemia

Background Patients with a cerebral ischemic event are at high risk of recurrent ischemia and other cardiovascular events. Clinical scores are recommended to predict cardiovascular risk in patients with cerebral ischemia to inform secondary preventive measures. Biomarkers may improve risk prediction beyond clinical scores and therefore secondary prevention. Methods Within the observational Find-AF trial (ISRCTN 46104198), 197 patients aged &gt;18 years with cerebral ischemia and without atrial fibrillation had blood sampled at baseline and completed 1-year follow-up. Predictive value of 5 novel cardiovascular biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2), National Institutes of Health Stroke Scale (NIH-SS) and Modified Rankin Scale (MRS). Results There were 23 vascular events (11.7%) and 13 deaths (6.6%) during 1 year. In multivariate analyses of all 5 markers, only high-sensitivity Troponin T (hs-TropT) remained significantly predictive of vascular events (p=0.045) and all-cause mortality (p=0.004). Hs-TropT was higher in patients with a vascular event (median 12.7 [6.8; 49.6] ng/mL vs. 5.1 [1.5; 11.7] ng/mL) and patients with hs-TropT above the median of 6.15 ng/mL were more likely to have a vascular event (Hazard Ratio 4.0, p=0.006 on log-rank test). For prediction of vascular events as well as all-cause mortality, hs-TropT significantly contributed to multivariate Cox-regression models with ESRS, SPI-2, or each combined with NIH-SS or MRS as covariates. C-statistic increased numerically from 0.689 (ESRS) to 0.743 (ESRS+hs-TropT) and 0.696 (SPI-2) to 0.758 (SPI-2+hs-TropT) (p=n.s.). Areas under the receiver-operator characteristics curves for vascular events were 0.694 (SPI-2), 0.712 (ESRS), 0.743 (ESRS+hs-TropT), 0.755 (hs-TropT) and 0.760 (SPI-2+hs-TropT). No patient with a low-risk ESRS ≤2 and a hs-TropT below the median had a vascular event during 1 year follow-up. Conclusion Hs-TropT is predictive of major vascular events and all-cause mortality in patients with cerebral ischemia and improves prediction by established clinical scores.

Impact of Abciximab in Elderly Patients with High-Risk Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged ≥70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged <70 years with high-risk ACS undergoing PCI, but conflicting findings relating to its effects in the elderly have been reported. The aim of this study was to evaluate the effect of abciximab in elderly high-risk ACS patients undergoing PCI. From our dedicated PCI registry we identified 2068 ACS patients with high-risk lesions that were treated with PCI. Baseline data were collected prospectively. All-cause mortality, target vessel revascularization (TVR), myocardial infarction (MI), and the combination of these were primary study endpoints. All endpoints within 1 year after PCI were registered and validated. The population was subsequently stratified according to age and use of abciximab. Elderly patients constituted 42% of the total population. They presented with more co-morbidities, were less frequently treated with abciximab and had a higher risk of reaching the combined endpoint and higher all-cause mortality than younger patients. The age/abciximab stratified analysis revealed no effect of abciximab on any of the endpoints in elderly patients (combined endpoint: no abciximab 22.6% vs abciximab 23.4%, p=0.85; all-cause mortality: no abciximab 15.4% vs abciximab 15.9%, p=0.91; TVR: no abciximab 3.4% vs abciximab 5.5%, p=0.21; MI: no abciximab 7.0% vs abciximab 8.5%, p=0.54), whereas all-cause mortality and the risk of reaching the combined endpoint were significantly reduced in younger patients (combined endpoint: no abciximab 14.0% vs abciximab 9.4%, p=0.03; all-cause mortality: no abciximab 4.5% vs abciximab 1.7%, p=0.02; TVR: no abciximab 5.5% vs abciximab 4.3%, p=0.39; MI: no abciximab 7.2% vs abciximab 6.6%, p=0.80). These findings were confirmed in our adjusted analyses. In this large observational study we found no benefit of abciximab treatment in elderly high-risk ACS patients who underwent PCI. These findings should be taken into consideration when deciding on the treatment strategy for elderly ACS patients undergoing PCI.