Autoimmune connective tissue diseases and aortic valve replacement outcomes: a population-based study.

Aims: Patients with autoimmune connective tissue diseases (CTDs) have a high burden of valvular heart disease and are often thought of as high surgical risk patients. Methods and results: Patients undergoing aortic valve replacement (AVR) were identified in the Nationwide Readmissions Database between January 2012 and December 2018. Patients with a history of systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, mixed C, Sjögren syndrome, polymyositis, and dermatomyositis were included in the CTD cohort. Patients undergoing coronary artery bypass grafting concomitantly with AVR were excluded. A total of 569 600 hospitalizations were included, of which16 531 (2.9%) had CTD. CTD patients were more likely to be females, with higher rates of heart failure, pulmonary hypertension, and more likely to be insured by Medicare. CTD patients had lower mortality than non-CTD patients [odds ratio (OR) 0.66; 95% confidence interval (CI): 0.59-0.74] and stroke [OR 0.87; 95% (CI): 0.79-0.97]. CTD patients undergoing SAVR had lower mortality [OR 0.69; 95% (CI): 0.60-0.80] and stroke [OR 0.86; 95% (CI): 0.75-0.98). CTD patients undergoing TAVR had lower mortality outcomes [OR 0.67; 95% (CI): 0.56-0.80]; however, they had comparable stroke outcomes [OR 0.97; 95% (CI): 0.83-1.13, P = 0.69]. Conclusions: Outcomes for patients with CTD requiring AVR are not inferior to their non-CTD counterparts. A comprehensive heart team selection of patients undergoing AVR approaches should place CTD history under consideration; however, pre-existing CTD should not be prohibitive of AVR interventions.

Clinical implications of inducible left ventricular outflow tract obstruction among patients undergoing liver transplant evaluation.

Introduction: Patients with end stage liver disease (ESLD) have a hyperdynamic state due to decreased systemic vascular resistance and increased cardiac output. Preoperative evaluation with dobutamine stress echocardiography (DSE) is used to risk-stratify patients prior to liver transplant. We sought to identify the impact of inducible left ventricular outflow tract obstruction (LVOTO) on DSE on post-operative liver transplant outcomes. Methods: Patients with ESLD who underwent liver transplant at Cleveland Clinic between January 2007 and August 2016 were identified. Pre-operative DSE data, and post-operative intensive care unit (ICU) data were extracted. Patients with inducible LVOTO were compared to those without LVOTO. Results: Of the 515 patients identified who underwent DSE prior to liver transplant, 165 (30%) were female, and 95 (18%) had LVOTO. There were no major differences in baseline characteristics between the two groups. In the LVOTO group, rest gradients were 10.8 ± 3 mm Hg while peak gradients were 90 ± 48.2 mm Hg. No significant differences in ICU length of stay or duration of mechanical ventilation between both groups were noted. There were 21 deaths at 30 days. There were 2 (2.1%) deaths in the LVOTO group, versus 19 (4.5%) deaths in the non LVOTO group (p = 0.28). Higher Model for End Stage Liver Disease (MELD) scores predicted longer duration of mechanical ventilation and ICU length of stay. Conclusion: Inducible LVOTO on DSE does not adversely affect the short-term outcomes post liver transplant. Presence of inducible LVOTO should not be the mere reason to deny liver transplant among patients with ESLD.

Effect of Aspirin Coadministration on the Safety of Celecoxib, Naproxen, or Ibuprofen.

BACKGROUND: The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain. OBJECTIVES: The aim of this study was to compare the safety of combining NSAIDs with low-dose aspirin. METHODS: This analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) trial included 23,953 patients with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk randomized to celecoxib, ibuprofen, or naproxen. The on-treatment population was used for this study. Outcomes included composite major adverse cardiovascular events, noncardiovascular death, gastrointestinal or renal events, and components of the composite. Cox proportional hazards models compared outcomes among NSAIDs stratified by aspirin use following propensity score adjustment. Kaplan-Meier analysis was used to compare the cumulative probability of events. RESULTS: When taken without aspirin, naproxen or ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.22 to 1.90, p <0.001; and HR: 1.81; 95% CI: 1.46 to 2.26; p <0.001, respectively). Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events. Taken with aspirin, ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (HR: 1.27; 95% CI: 1.06 to 1.51; p < 0.01); this was not significantly higher with naproxen (HR: 1.18; 95% CI: 0.98 to 1.41; p = 0.08). Among patients on aspirin, major adverse cardiovascular events were similar among NSAIDs, and compared with celecoxib, ibuprofen had more gastrointestinal and renal events (p < 0.05), while naproxen had more gastrointestinal events (p < 0.05), without a difference in renal events. Similar results were seen on adjusted Kaplan-Meier analysis. CONCLUSIONS: Celecoxib has a more favorable overall safety profile than naproxen or ibuprofen when taken without aspirin. Adding aspirin attenuates the safety advantage of celecoxib, although celecoxib is still associated with fewer gastrointestinal events than ibuprofen or naproxen and fewer renal events than ibuprofen. (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen [PRECISION]; NCT00346216).

Quality of Life After Surgery or DES in Patients With 3-Vessel or Left Main Disease.

BACKGROUND: In the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, patients with 3-vessel or left main coronary artery disease (CAD) had improved long-term outcomes with coronary artery bypass graft (CABG) surgery compared with percutaneous coronary intervention (PCI) with drug-eluting stents (DES), improvements driven mainly by differences in myocardial infarction and repeat revascularization. OBJECTIVES: This study compared the long-term quality-of-life benefits of DES-PCI versus CABG for patients with 3-vessel or left main CAD. METHODS: Between 2005 and 2007, the SYNTAX trial randomized 1,800 patients with 3-vessel or left main CAD to either CABG or DES-PCI. Health status was assessed at baseline and at 1, 6, 12, 36, and 60 months by using the Seattle Angina Questionnaire (SAQ) and the 36-Item Short Form Health Survey. RESULTS: At 5-year follow-up, CABG was superior to DES-PCI on several SAQ domains including angina frequency and physical function, as well as the role physical and role emotional scales of the 36-Item Short Form Health Survey. Subgroup analysis demonstrated a significant interaction between angiographic complexity (as assessed by the SYNTAX score) and angina relief (mean difference in the SAQ angina frequency score for CABG vs. PCI of -0.9, 3.3, and 3.9 points for low, intermediate, and high SYNTAX score patients, respectively; p = 0.048 for interaction). CONCLUSIONS: Among patients with 3-vessel or left main CAD, both CABG and DES-PCI were associated with substantial and sustained quality-of-life benefits over 5 years of follow-up. In general, CABG resulted in greater angina relief, although the absolute treatment benefit was small. Angina relief at 5 years was enhanced with CABG among patients with high SYNTAX scores, a finding reinforcing the recommendation that CABG should be strongly preferred for such patients. (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972).

Cost-effectiveness of percutaneous coronary intervention versus bypass surgery from a Dutch perspective.

AIMS: Recent cost-effectiveness analyses of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) have been limited by a short time horizon or were restricted to the US healthcare perspective. We, therefore, used individual patient-level data from the SYNTAX trial to evaluate the cost-effectiveness of PCI versus CABG from a European (Dutch) perspective. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with three-vessel or left main coronary artery disease were randomised to either CABG (n=897) or PCI with drug-eluting stents (DES; n=903). Costs were estimated for all patients based on observed healthcare resource usage over 5 years of follow-up. Health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on Dutch life-tables was used to extrapolate the 5-year in-trial data to a lifetime horizon. Although initial procedural costs were lower for CABG, total initial hospitalisation costs per patient were higher (€17 506 vs €14 037, p<0.001). PCI was more costly during the next 5 years of follow-up, due to more frequent hospitalisations, repeat revascularisation procedures and higher medication costs. Nevertheless, total 5-year costs remained €2465/patient higher with CABG. When the in-trial results were extrapolated to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with gains in both life expectancy and quality-adjusted life expectancy. The incremental cost-effectiveness ratio (ICER) (€5390/quality-adjusted life year (QALY) gained) was favourable and remained <€80 000/QALY in >90% of the bootstrap replicates. Outcomes were similar when incorporating the prognostic impact of non-fatal myocardial infarction and stroke, as well as across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. However, DES-PCI was economically dominant compared with CABG in patients with a SYNTAX Score ≤22 or in those with left main disease. In patients for whom the SYNTAX Score II favoured PCI based on lower predicted 4-year mortality, PCI was also economically dominant, whereas in those patients for whom the SYNTAX Score II favoured surgery, CABG was highly economically attractive (ICER range, €2967 to €3737/QALY gained). CONCLUSIONS: For the broad population with three-vessel or left main disease who are candidates for either CABG or PCI, we found that CABG is a clinically and economically attractive revascularisation strategy compared with DES-PCI from a Dutch healthcare perspective. The cost-effectiveness of CABG versus PCI differed according to several anatomic factors, however. The newly developed SYNTAX Score II provides enhanced prognostic discrimination in this population, and may be a useful tool to guide resource allocation as well. TRIAL REGISTRATION NUMBER: Clinical trial unique identifier: NCT00114972 (http://www.clinical-trials.gov).

Variation in patients' perceptions of elective percutaneous coronary intervention in stable coronary artery disease: cross sectional study.

OBJECTIVES: To assess the perceptions of patients with stable coronary artery disease of the urgency and benefits of elective percutaneous coronary intervention and to examine how they vary across centers and by providers. DESIGN: Cross sectional study. SETTING: 10 US academic and community hospitals performing percutaneous coronary interventions between 2009 and 2011. PARTICIPANTS: 991 patients with stable coronary artery disease undergoing elective percutaneous coronary intervention. MAIN OUTCOME MEASURES: Patients' perceptions of the urgency and benefits of percutaneous coronary intervention, assessed by interview. Multilevel hierarchical logistic regression models examined the variation in patients' understanding across centers and operators after adjusting for patient characteristics, using median odds ratios. RESULTS: The most common reported benefits from percutaneous coronary intervention were to extend life (90%, n=892; site range 80-97%) and to prevent future heart attacks (88%, n=872; site range 79-97%). Although nearly two thirds of patients (n=661) reported improvement of symptoms as a benefit of percutaneous coronary intervention (site range 52-87%), only 1% (n=9) identified this as the only benefit. Substantial variability was noted in the ways informed consent was obtained at each site. After adjusting for patient and operator characteristics, the median odds ratios showed significant variation in patients' perceptions of percutaneous coronary intervention across sites (range 1.4-3.1) but not across operators within a site. CONCLUSION: Patients have a poor understanding of the benefits of elective percutaneous coronary intervention, with significant variation across sites. No sites had a high proportion of patients accurately understanding the benefits. Coupled with the wide variability in the ways in which hospitals obtain informed consent, these findings suggest that hospital level interventions into the structure and processes of obtaining informed consent for percutaneous coronary intervention might improve patient comprehension and understanding.

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with 3-vessel or left main coronary artery disease: final results from the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial.

BACKGROUND: The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial demonstrated that in patients with 3-vessel or left main coronary artery disease, coronary artery bypass graft surgery (CABG) was associated with a lower rate of cardiovascular death, myocardial infarction, stroke, or repeat revascularization compared with percutaneous coronary revascularization with drug-eluting stents (DES-PCI)). The long-term cost-effectiveness of these strategies is unknown. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with left main or 3-vessel coronary artery disease were randomized to CABG (n=897) or DES-PCI (n=903). Costs were assessed from a US perspective, and health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on the 5-year in-trial data was used to extrapolate costs, life expectancy, and quality-adjusted life expectancy over a lifetime horizon. Although initial procedural costs were $3415 per patient lower with CABG, total hospitalization costs were $10 036 per patient higher. Over the next 5 years, follow-up costs were higher with DES-PCI as a result of more frequent hospitalizations, revascularization procedures, and higher medication costs. Over a lifetime horizon, CABG remained more costly than DES-PCI, but the incremental cost-effectiveness ratio was favorable ($16 537 per quality-adjusted life-year gained) and remained <$20 000 per quality-adjusted life-year in most bootstrap replicates. Results were consistent across a wide range of assumptions about the long-term effect of CABG versus DES-PCI on events and costs. In patients with left main disease or a SYNTAX score ≤22, however, DES-PCI was economically dominant compared with CABG, although these findings were less certain. CONCLUSIONS: For most patients with 3-vessel or left main coronary artery disease, CABG is a clinically and economically attractive revascularization strategy compared with DES-PCI. However, among patients with less complex disease, DES-PCI may be preferred on both clinical and economic grounds. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT00114972.

Symptoms and angiographic findings of patients undergoing elective coronary angiography without prior stress testing.

Many patients undergo elective coronary angiography without preprocedural stress testing that may be suitable if performed in patients with more angina pectoris or more frequently identified obstructive coronary artery disease (CAD). Patients in the National Cardiovascular Data Registry CathPCI Registry undergoing elective coronary angiography from July 2009 to April 2013 were assessed for differences in angina (Canadian Cardiovascular Society [CCS] class) and severity of obstructive CAD in those with and without preprocedural stress testing, stratified by CAD history. Given the large sample size, differences were considered clinically meaningful if the standardized difference (SD) was >10%. Of 790,601 patients without CAD history, 36.9% did not undergo preprocedural stress testing. Compared with patients with preprocedural stress testing, patients without preprocedural stress testing were more frequently angina free (CCS class 0; 28.2% with stress test vs 38.5% without, SD = 14.8%) and had similar rates of obstructive CAD (40.1% with stress test vs 35.7% without, SD = 9.0). Of 449,579 patients with CAD history, 44.2% did not undergo preprocedural stress testing. Patients without preprocedural stress testing reported more angina (CCS class III/IV angina: 17.8% vs 13.4%; SD = 11.3%) but were not more likely to have obstructive CAD (78.7% vs 81.1%; SD = 5.8%) than patients with preprocedural stress testing. In conclusion, approximately 40% of patients undergoing elective coronary angiography did not have preprocedural risk stratification with stress testing. For these patients, the clinical decision to proceed directly to invasive evaluation was not driven primarily by severe angina and did not result in higher detection rates for obstructive CAD.

Patterns and predictors of intensive statin therapy among patients with diabetes mellitus after acute myocardial infarction.

Intensive statin therapy is a central component of secondary prevention after acute myocardial infarction (AMI), particularly among high-risk patients, such as those with diabetes mellitus (DM). However, the frequency and predictors of intensive statin therapy use after AMI among patients with DM have not been described. We examined patterns of intensive statin therapy use (defined as a statin with expected low-density lipoprotein cholesterol lowering of >50%) at discharge among patients with AMI with known DM enrolled in a 24-site US registry. Predictors of intensive statin therapy use were evaluated using multivariable hierarchical Poisson regression models. Among 1,300 patients with DM after AMI, 22% were prescribed intensive statin therapy at hospital discharge. In multivariable models, ST-elevation AMI (risk ratio [RR] 1.48, 95% confidence interval [CI] 1.29 to 1.70), insurance for medications (RR 1.28, 95% CI 1.00 to 1.63), and higher low-density lipoprotein cholesterol levels (RR 1.05 per 1 mg/dl, 95% CI 1.02 to 1.07) were independent predictors of intensive statin therapy, whereas higher Global Registry of Acute Coronary Events scores were associated with lower rates of intensive statin therapy (RR 0.94 per 10 points, 95% CI 0.91 to 0.98). In conclusion, only 1 in 5 patients with DM was prescribed intensive statin therapy at discharge after an AMI. Predictors of intensive statin therapy use suggest important opportunities to improve quality of care in this patient population.

Quality of life after PCI vs CABG among patients with diabetes and multivessel coronary artery disease: a randomized clinical trial.

IMPORTANCE: The FREEDOM trial demonstrated that among patients with diabetes mellitus and multivessel coronary artery disease, coronary artery bypass graft (CABG) surgery resulted in lower rates of death and myocardial infarction but a higher risk of stroke when compared with percutaneous coronary intervention (PCI) using drug-eluting stents. Whether there are treatment differences in health status, as assessed from the patient's perspective, is unknown. OBJECTIVES: To compare the relative effects of CABG vs PCI using drug-eluting stents on health status among patients with diabetes mellitus and multivessel coronary artery disease. DESIGN, SETTING, AND PARTICIPANTS: Between 2005 and 2010, 1900 patients from 18 countries with diabetes mellitus and multivessel coronary artery disease were randomized to undergo either CABG surgery (n = 947) or PCI (n = 953) as an initial treatment strategy. Of these, a total of 1880 patients had baseline health status assessed (935 CABG, 945 PCI) and comprised the primary analytic sample. INTERVENTIONS: Initial revascularization with CABG surgery or PCI. MAIN OUTCOMES AND MEASURES: Health status was assessed using the angina frequency, physical limitations, and quality-of-life domains of the Seattle Angina Questionnaire at baseline, at 1, 6, and 12 months, and annually thereafter. For each scale, scores range from 0 to 100 with higher scores representing better health. The effect of CABG surgery vs PCI was evaluated using longitudinal mixed-effect models. RESULTS: At baseline, mean (SD) scores for the angina frequency, physical limitations, and quality-of-life subscales of the Seattle Angina Questionnaire were 70.9 (25.1), 67.3 (24.4), and 47.8 (25.0) for the CABG group and 71.4 (24.7), 69.9 (23.2), and 49.2 (25.7) for the PCI group, respectively. At 2-year follow-up, mean (SD) scores were 96.0 (11.9), 87.8 (18.7), and 82.2 (18.9) after CABG and 94.7 (14.3), 86.0 (19.3), and 80.4 (19.6) after PCI, with significantly greater benefit of CABG on each domain (mean treatment benefit, 1.3 [95% CI, 0.3-2.2], 4.4 [95% CI, 2.7-6.1], and 2.2 [95% CI, 0.7-3.8] points, respectively; P < .01 for each comparison). Beyond 2 years, the 2 revascularization strategies provided generally similar patient-reported outcomes. CONCLUSIONS AND RELEVANCE: For patients with diabetes and multivessel CAD, CABG surgery provided slightly better intermediate-term health status and quality of life than PCI using drug-eluting stents. The magnitude of benefit was small, without consistent differences beyond 2 years, in part due to the higher rate of repeat revascularization with PCI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00086450.

Insulin resistance is associated with significant clinical atherosclerosis in nondiabetic patients with acute myocardial infarction.

OBJECTIVE: The prevalence of insulin resistance (IR) is increasing worldwide because of increasing age, obesity, and physical inactivity. Emerging evidence supports a direct proatherogenic effect of IR on the coronary vasculature, but the relation between IR and angiographic atherosclerosis in a real-world clinical setting is uncertain. In this work, we assessed whether IR is independently associated with clinically significant angiographic atherosclerosis in nondiabetic individuals. APPROACH AND RESULTS: We examined the association between IR and the extent of coronary atherosclerosis determined by angiography in 1073 nondiabetic patients surviving acute myocardial infarction. Patients were divided into quartiles on the basis of the homeostasis model assessment grading of IR, and associations between IR and multivessel coronary artery disease, defined as ≥ 2 arteries with ≥ 70% stenosis (or ≥ 50% left main stenosis), were analyzed in bivariate and multivariable modeling. Overall, the cohort had a median age of 56 years; 28.9% women and 21.8% nonwhite. The crude prevalence of multivessel coronary artery disease was 37.8%, 42.3%, 47.2%, and 48.0% for homeostasis model assessment grading of IR quartiles 1, 2, 3, and 4, respectively (P(trend) = 0.009). In multivariable modeling, compared with quartile 1, both quartile 3 (relative risk [95% confidence interval], 1.31 [1.07-1.60]) and quartile 4 (1.29 [1.03-1.60]) were independently associated with multivessel coronary artery disease. Covariates in the model included patient demographic and clinical characteristics and metabolic factors (low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglyceride, glycosylated hemoglobin, and high-sensitivity C-reactive protein). CONCLUSIONS: We demonstrate an independent association between IR and multivessel coronary artery disease in nondiabetic postmyocardial infarction patients. Our findings strengthen the experimental evidence for a direct atherogenic effect of IR independent of glucose control and other components of the metabolic syndrome.