Abstract Background Rates of referral to cardiac rehabilitation after percutaneous coronary intervention (PCI) have been historically low despite the evidence that rehabilitation is associated with ...lower mortality in PCI patients. Objectives This study sought to determine the prevalence of and factors associated with referral to cardiac rehabilitation in a national PCI cohort, and to assess the association between insurance status and referral patterns. Methods Consecutive patients who underwent PCI and survived to hospital discharge in the National Cardiovascular Data Registry between July 1, 2009 and March 31, 2012 were analyzed. Cardiac rehabilitation referral rates, and patient and institutional factors associated with referral were evaluated for the total study population and for a subset of Medicare patients presenting with acute myocardial infarction. Results Patients who underwent PCI (n = 1,432,399) at 1,310 participating hospitals were assessed. Cardiac rehabilitation referral rates were 59.2% and 66.0% for the overall population and the AMI/Medicare subgroup, respectively. In multivariable analyses, presentation with ST-segment elevation myocardial infarction (odds ratio 2.99; 95% confidence interval: 2.92 to 3.06) and non–ST-segment elevation myocardial infarction (odds ratio: 1.99; 95% confidence interval: 1.94 to 2.03) were associated with increased odds of referral to cardiac rehabilitation. Models adjusted for insurance status showed significant site-specific variability in referral rates, with more than one-quarter of all hospitals referring <20% of patients. Conclusions Approximately 60% of patients undergoing PCI in the United States are referred for cardiac rehabilitation. Site-specific variation in referral rates is significant and is unexplained by insurance coverage. These findings highlight the potential need for hospital-level interventions to improve cardiac rehabilitation referral rates after PCI.
Background Studies on outcomes among patients with heart failure (HF) with preserved left ventricular ejection fraction (HF p EF), borderline left ventricular ejection fraction (HF b EF), and reduced ...left ventricular ejection fraction (HF r EF) remain limited. We sought to characterize mortality and readmission in patients with HF in the contemporary era. Methods Get With The Guidelines–HF was linked to Medicare data for longitudinal follow-up. Patients were grouped into HF p EF (left ventricular ejection fraction EF ≥50%), HF b EF (40% ≤ EF < 50%), and HF r EF (EF <40%). Multivariable models were constructed to examine the relationship between EF and outcomes at 30 days and 1 year and to study trends over time. Results A total of 40,239 patients from 220 hospitals between 2005 and 2011 were included in the study: 18,897 (47%) had HF p EF, 5,626 (14%) had HF b EF, and 15,716 (39%) had HF r EF. In crude survival analysis, patients with HF r EF had slightly increased mortality compared with HF b EF and HF p EF. After risk adjustment, mortality at 1 year was not significantly different for HF r EF, HF b EF, and HF p EF (HF r EF vs HF p EF, hazard ratio HR 1.040 95% CI 0.998-1.084, and HF b EF vs HF p EF, HR 0.967 95% CI 0.917-1.020). Patients with HF p EF had increased risk of all-cause readmission compared with HF r EF. Conversely, risk of cardiovascular and HF readmissions were higher in HF r EF and HF b EF compared with HF p EF. Conclusions Among patients hospitalized with HF, patients with HF p EF and HF b EF had slightly lower mortality and higher all-cause readmission risk than patients with HF r EF, although the mortality differences did not persist after risk adjustment. Irrespective of EF, these patients experience substantial mortality and readmission highlighting the need for new therapeutic strategies.
Objectives The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure. Background The 2 ...most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown. Methods HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP. Results After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure. Conclusions Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.
Abstract Background Certain alleles of the CYP2C19 gene are associated with higher platelet reactivity and increased ischemic events among patients treated with clopidogrel. However, the relationship ...of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known. Objectives This study sought to assess the effect of CYP2C19 genotype on ischemic outcomes in patients with ACS initially managed medically without revascularization who were randomized to either clopidogrel or prasugrel. Methods We classified patients as extensive metabolizers (EM) or reduced metabolizers (RM) based on CYP2C19 genotype and evaluated ischemic outcomes and platelet reactivity. Among 9,326 patients enrolled from 2008 to 2011, 5,736 participated in the genetics cohort; of these, 2,236 had platelet function testing data. Results There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio HR: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction = 0.495). After adjusting for clinical and treatment variables, EM patients had a lower risk of MI versus RM patients (HR: 0.80), but risks of other outcomes were similar. RM patients had significantly higher mean P2Y12 reaction units versus EM patients when treated with clopidogrel (39.93), but not with prasugrel (3.87). Conclusions CYP2C19 metabolizer status is not associated with the composite outcome of cardiovascular death, MI, or stroke in medically managed ACS patients treated with clopidogrel or prasugrel. Our findings do not support routine CYP2C19 genetic testing in this population. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects TRILOGY ACS; NCT00699998 )
Objective Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction MI, stroke, or cardiovascular death), but differential patient characteristics, timing, ...and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. Methods We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. Results Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. Conclusions Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.
Abstract Background Electronic health records (EHRs) may be key tools for improving the quality of health care, particularly for conditions for which guidelines are rapidly evolving and timely care ...is critical, such as ischemic stroke. Objectives The goal of this study was to determine whether hospitals with EHRs differed on quality or outcome measures for ischemic stroke from those without EHRs. Methods We studied 626,473 patients from 1,236 U.S. hospitals in Get With the Guidelines-Stroke (GWTG-Stroke) from 2007 through 2010, linked with the American Hospital Association annual survey to determine the presence of EHRs. We conducted patient-level logistic regression analyses for each of the outcomes of interest. Results A total of 511 hospitals had EHRs by the end of the study period. Hospitals with EHRs were larger and were more often teaching hospitals and stroke centers. After controlling for patient and hospital characteristics, patients admitted to hospitals with EHRs had similar odds of receiving “all-or-none” care (odds ratio OR: 1.03; 95% CI: 0.99 to 1.06; p = 0.12), of discharge home (OR: 1.02; 95% CI: 0.99 to 1.04; p = 0.15), and of in-hospital mortality (OR: 1.01; 95% CI: 0.96 to 1.05; p = 0.82). The odds of having a length of stay >4 days was slightly lower at hospitals with EHRs (OR: 0.97; 95% CI: 0.95 to 0.99; p = 0.01). Conclusions In our sample of GWTG-Stroke hospitals, EHRs were not associated with higher-quality care or better clinical outcomes for stroke care. Although EHRs may be necessary for an increasingly high-tech, transparent healthcare system, as currently implemented, they do not appear to be sufficient to improve outcomes for this important disease.
Background Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among ...medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. Methods Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 39%) and men (n = 5,676 61%) randomized to prasugrel 10 mg/d (5 mg/d for patients ≥75 years and/or <60 kg) versus clopidogrel 75 mg/d. Sex-specific differences in 30-day platelet reactivity were analyzed in 2,564 (27%) patients participating in a platelet function substudy. Results Compared with men, women were older, weighed less, were less likely to have prior myocardial infarction or revascularization, and had lower baseline creatinine clearance and hemoglobin level values. Rates of the composite of cardiovascular death/myocardial infarction/stroke (20.2% vs 19.1%; P = .56), all-cause mortality (12.2% vs 11.7%; P = .88), and Global Use of Strategies to Open Occluded Arteries severe/life-threatening/moderate bleeding (3.8% vs 2.8%; P = .74) through 30 months were similar in women versus men. After adjustment, women had significantly lower risk for ischemic outcomes and all-cause mortality. There were no sex-specific, treatment-related differences in 30-day platelet reactivity. Conclusions Long-term ischemic and bleeding outcomes in medically managed ACS patients were similar for women versus men, as was treatment-related platelet reactivity. Women had a higher baseline risk profile and, after adjustment, significantly lower risk of the primary composite end point and all-cause death through 30 months.
Objectives This study compared prognoses of myocardial infarction related to percutaneous coronary intervention (PCI, procedural MI) using increasing creatine kinase-myocardial band (CK-MB) ...thresholds with spontaneous MI. Background Procedural MI usually is defined by a CK-MB elevation of more than 3 times the upper limit of normal (ULN), but higher thresholds have been proposed. Methods Patients from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndrome) study and the SYNERGY (Superior Yield of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa inhibitors) study treated with PCI were included. The primary end point was 1-year all-cause mortality from 24 h after PCI. To determine an enzymatic threshold for procedural MI with a prognosis similar to that of spontaneous MI, we redefined procedural MI using increasing CK-MB thresholds and compared corresponding hazard ratios with those of spontaneous MI (CK-MB more than twice the ULN). Hazard ratios for mortality for procedural and spontaneous MI were calculated using Cox proportional hazards regression and Global Registry of Acute Cardiac Events covariates for risk adjustment. Results Nine thousand eighty-seven patients who underwent PCI (46.8%) were included; 773 procedural MI and 239 spontaneous MI occurred within 30 days. Adjusted hazard ratios for 1-year death were 1.39 (95% confidence interval CI: 1.01 to 1.89) for procedural MI and 5.37 (95% CI: 3.90 to 7.38) for spontaneous MI. The CK-MB threshold for procedural MI that achieved the same prognosis as spontaneous MI was 27.7 times the ULN (95% CI: 13.9 to 58.4), but this differed between the SYNERGY study (57.9 times the ULN, 95% CI: 17.9 to 63.6) and the EARLY-ACS study (20.4 times the ULN, 95% CI: 5.16 to 24.2). Of all procedural MI, 49 (6%) had CK-MB elevations of 27.7 or more times the ULN. Conclusions The current enzymatic definition of procedural MI (CK-MB more than 3 times the ULN) used in clinical trials is less strongly associated with death than that of spontaneous MI. Procedural MI achieves similar prognosis for 1-year mortality when much higher CK-MB thresholds are applied.
Introduction Public reporting (PR) is a policy mechanism that may improve clinical outcomes for percutaneous coronary intervention (PCI). However, prior studies have shown that PR may have an adverse ...impact on patient selection. It is unclear whether alternatives to PR, such as collaborative quality improvement (CQI), may drive improvements in quality of care and outcomes for patients receiving PCI without the unintended consequences seen with PR. Methods Using National Cardiovascular Data Registry CathPCI Registry data from January 2011 through September 2012, we evaluated patients who underwent PCI in New York (NY), a state with PR (N = 51,983), to Michigan, a state with CQI (N = 53,528). We compared patient characteristics, the quality of care delivered, and clinical outcomes. Results Patients undergoing PCI in NY had a lower-risk profile, with a lower proportion of patients with ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, or cardiogenic shock, compared with Michigan. Quality of care was broadly similar in the 2 states; however, outcomes were better in NY. In a propensity-matched analysis, patients in NY were less likely to be referred for emergent, urgent, or salvage coronary artery bypass surgery (odds ratio OR 0.67, 95% CI 0.51-0.88, P < .0001) and to receive blood transfusion (OR 0.7, 95% CI 0.61-0.82, P < .0001), and had lower in-hospital mortality (OR 0.72, 95% CI 0.63-0.83, P < .0001). Conclusions Public reporting of PCI data is associated with fewer high-risk patients undergoing PCI compared with CQI. However, in comparable samples of patients, PR is also associated with a lower risk of mortality and adverse events. The optimal quality improvement method may involve combining these 2 strategies to protect access to care while still driving improvements in patient outcomes.
Acute perivascular rejection (AR) is common in lung recipients and increases the risk for chronic lung allograft dysfunction (CLAD). Hyaluronan (HA), an extracellular matrix constituent, accumulates ...in experimental AR and can act as an innate immune agonist, breaking tolerance and potentiating alloimmunity. We previously demonstrated HA accumulates in CLAD after human-lung transplantation. We sought to determine if HA accumulates in the bronchoalveolar lavage fluid (BALF) concurrent with AR in lung recipients.
The cohort consisted of 126 first adult lung recipients at 5 transplant centers with a total of 373 BALF samples collected within the first posttransplant year. All samples were paired with a lung biopsy from the same bronchoscopy. BALF HA (ng/mL) was quantified by ELISA and log-transformed for analysis. Linear-mixed effect models, adjusted for potential confounders, were used to estimate the association between BALF HA concentration and the presence of AR on biopsy. The association between early posttransplant BALF HA levels and the development of CLAD was explored utilizing tertiles of maximum BALF HA level observed within the first 6 months of transplant.
In analyses adjusted for potential confounders, BALF HA concentration was significantly increased in association with AR (change in means on log-scale 0.31; 95% CI, 0.01-0.60;
= 0.044). When considered on the original scale (ng/mL), BALF HA concentrations were 1.36 times (36%) higher, on average, among samples with, versus without, AR. The cumulative incidence of CLAD was numerically higher in individuals in the highest tertiles of BALF HA level within the first 6 months after transplant, as compared with those in the lowest tertile; however, this difference was not statistically significant (
= 0.32).
These results demonstrate accumulation of HA in clinical AR and suggest a mechanism by which innate and adaptive immune activation might interact in the development of AR and CLAD.
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