Transforming growth factor-ß and inflammation in vascular (type IV) Ehlers-Danlos syndrome.

BACKGROUND: Vascular Ehlers-Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene, COL3A1, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments. METHODS AND RESULTS: We studied inflammatory and transforming growth factor-ß (TGF-ß) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype-phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-ß1, TGF-ß2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-ß2, whereas downstream canonical/noncanonical TGF-ß signaling was not different. Patients with COL3A1 exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity. CONCLUSIONS: These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-ß signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-ß1. Finally, we found a novel role for dysregulated TGF-ß2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.

Adoption and effectiveness of internal mammary artery grafting in coronary artery bypass surgery among Medicare beneficiaries.

OBJECTIVES: The aim of this study was to assess the pattern of the adoption of internal mammary artery (IMA) grafting in the United States, test its association with clinical outcomes, and assess whether its effectiveness differs in key clinical subgroups. BACKGROUND: The effect of IMA grafting on major clinical outcomes has never been tested in a large randomized trial, yet it is now a quality standard for coronary artery bypass graft (CABG) surgery. METHODS: We identified Medicare beneficiaries ≥66 years of age who underwent isolated multivessel CABG between 1988 and 2008, and we documented patterns of IMA use over time. We used a multivariable propensity score to match patients with and without an IMA and compared rates of death, myocardial infarction (MI), and repeat revascularization. We tested for variations in IMA effectiveness with treatment × covariate interaction tests. RESULTS: The IMA use in CABG rose slowly from 31% in 1988 to 91% in 2008, with persistent wide geographic variations. Among 60,896 propensity score-matched patients over a median 6.8-year follow-up, IMA use was associated with lower all-cause mortality (adjusted hazard ratio: 0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The association between IMA use and lower mortality was significantly weaker (p ≤ 0.008) for older patients, women, and patients with diabetes or peripheral arterial disease. CONCLUSIONS: Internal mammary artery grafting was adopted slowly and still shows substantial geographic variation. IMA use is associated with lower rates of death, MI, and repeat coronary revascularization.

Comparative effectiveness of multivessel coronary bypass surgery and multivessel percutaneous coronary intervention: a cohort study.

BACKGROUND: Randomized trials of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) suggest that patient characteristics modify the effect of treatment on mortality. OBJECTIVE: To assess whether clinical characteristics modify the comparative effectiveness of CABG versus PCI in an unselected, general patient population. DESIGN: Observational treatment comparison using propensity score matching and Cox proportional hazards models. SETTING: United States, 1992 to 2008. PATIENTS: Medicare beneficiaries aged 66 years or older. INTERVENTION: Multivessel CABG or multivessel PCI. MEASUREMENTS: The CABG-PCI hazard ratio (HR) for all-cause mortality, with prespecified treatment-by-covariate interaction tests, and the absolute difference in life-years of survival in clinical subgroups after CABG or PCI, both over 5 years of follow-up. RESULTS: Among 105 156 propensity score-matched patients, CABG was associated with lower mortality than PCI (HR, 0.92 [95% CI, 0.90 to 0.95]; P < 0.001). Association of CABG with lower mortality was significantly greater (interaction P ≤ 0.002 for each) among patients with diabetes (HR, 0.88), a history of tobacco use (HR, 0.82), heart failure (HR, 0.84), and peripheral arterial disease (HR, 0.85). The overall predicted difference in survival between CABG and PCI treatment over 5 years was 0.053 life-years (range, -0.017 to 0.579 life-years). Patients with diabetes, heart failure, peripheral arterial disease, or tobacco use had the largest predicted differences in survival after CABG, whereas those with none of these factors had slightly better survival after PCI. LIMITATION: Treatments were chosen by patients and physicians rather than being randomly assigned. CONCLUSION: Multivessel CABG is associated with lower long-term mortality than multivessel PCI in the community setting. This association is substantially modified by patient characteristics, with improvement in survival concentrated among patients with diabetes, tobacco use, heart failure, or peripheral arterial disease. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Use of medications for secondary prevention after coronary bypass surgery compared with percutaneous coronary intervention.

OBJECTIVES: This study sought to compare use of evidence-based secondary preventive medications after coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI). BACKGROUND: Use of cardioprotective medication after coronary revascularization has been inconsistent and relatively low in older studies. METHODS: We studied patients in a large integrated healthcare delivery system who underwent CABG or PCI for new onset coronary disease. We used data from health plan databases about prescriptions dispensed during the first year after initial coronary revascularization to identify patients who never filled a prescription and to calculate the medication possession ratio among patients who filled at least 1 prescription. We focused on angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), beta-blockers, and statins. RESULTS: Between 2000 and 2007, 8,837 patients with new onset coronary disease underwent initial CABG, and 14,516 underwent initial PCI. Patients receiving CABG were more likely than patients receiving PCI to not fill a prescription for a statin (7.1% vs. 4.8%, p < 0.0001) or for an ACEI/ARB (29.1% vs. 22.4%, p < 0.0001), but similar proportions never filled a prescription for a beta-blocker (6.4% vs. 6.1%). Among those who filled at least 1 prescription post-revascularization, patients receiving CABG had lower medication possession ratios than patients receiving PCI for ACEI/ARBs (69.4% vs. 77.8%, p < 0.0001), beta-blockers (76.1% vs. 80.6%, p < 0.0001), and statins (82.7% vs. 84.2%, p < 0.001). CONCLUSIONS: Patients who received CABG were generally less likely than patients who received PCI to fill prescriptions for secondary preventive medications and to use those medications consistently in the first year after the procedure.

Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD.

Thirty to sixty percent of patients with ESRD on dialysis have coronary heart disease, but the optimal strategy for coronary revascularization is unknown. We used data from the United States Renal Data System to define a cohort of 21,981 patients on maintenance dialysis who received initial coronary revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1997 and 2009 and had at least 6 months of prior Medicare coverage as their primary payer. The primary outcome was death from any cause, and the secondary outcome was a composite of death or myocardial infarction. Overall survival rates were consistently poor during the study period, with unadjusted 5-year survival rates of 22%-25% irrespective of revascularization strategy. Using multivariable-adjusted proportional hazards regression, we found that CABG compared with PCI associated with significantly lower risks for both death (HR=0.87, 95% CI=0.84-0.90) and the composite of death or myocardial infarction (HR=0.88, 95% CI=0.86-0.91). Results were similar in analyses using a propensity score-matched cohort. In the absence of data from randomized trials, these results suggest that CABG may be preferred over PCI for multivessel coronary revascularization in appropriately selected patients on maintenance dialysis.

Procedural complications, rehospitalizations, and repeat procedures after catheter ablation for atrial fibrillation.

OBJECTIVES: The purpose of this study was to estimate rates and identify predictors of inpatient complications and 30-day readmissions, as well as repeat hospitalization rates for arrhythmia recurrence following atrial fibrillation (AF) ablation. BACKGROUND: AF is the most common clinically significant arrhythmia and is associated with increased morbidity and mortality. Radiofrequency or cryotherapy ablation of AF is a relatively new treatment option, and data on post-procedural outcomes in large general populations are limited. METHODS: Using data from the California State Inpatient Database, we identified all adult patients who underwent their first AF ablation from 2005 to 2008. We used multivariable logistic regression to identify predictors of complications and/or 30-day readmissions and Kaplan-Meier analyses to estimate rates of all-cause and arrhythmia readmissions. RESULTS: Among 4,156 patients who underwent an initial AF ablation, 5% had periprocedural complications, most commonly vascular, and 9% were readmitted within 30 days. Older age, female, prior AF hospitalizations, and less hospital experience with AF ablation were associated with higher adjusted risk of complications and/or 30-day readmissions. The rate of all-cause hospitalization was 38.5% by 1 year. The rate of readmission for recurrent AF, atrial flutter, and/or repeat ablation was 21.7% by 1 year and 29.6% by 2 years. CONCLUSIONS: Periprocedural complications occurred in 1 of 20 patients undergoing AF ablation, and all-cause and arrhythmia-related rehospitalizations were common. Older age, female sex, prior AF hospitalizations, and recent hospital procedure experience were associated with a higher risk of complications and/or 30-day readmission after AF ablation.

The effect of internal thoracic artery grafts on long-term clinical outcomes after coronary bypass surgery.

OBJECTIVES: We sought to compare long-term outcomes after coronary bypass surgery with and without an internal thoracic artery graft. METHODS: We analyzed clinical outcomes over a median follow-up of 6.7 years among 3,087 patients who received coronary bypass surgery as participants in one of 8 clinical trials comparing surgical intervention with angioplasty. We used 2 statistical methods (covariate adjustment and propensity score matching) to adjust for the nonrandomized selection of internal thoracic artery grafts. RESULTS: Internal thoracic artery grafting was associated with lower mortality, with hazard ratios of 0.77 (confidence interval, 0.62-0.97; P = .02) for covariate adjustment and 0.77 (confidence interval, 0.57-1.05; P = .10) for propensity score matching. The composite end point of death or myocardial infarction was reduced to a similar extent, with hazard ratios of 0.83 (confidence interval, 0.69-1.00; P = .05) for covariate adjustment to 0.78 (confidence interval, 0.61-1.00; P = .05) for propensity score matching. There was a trend toward less angina at 1 year, with odds ratios of 0.81 (confidence interval, 0.61-1.09; P = .16) in the covariate-adjusted model and 0.81 (confidence interval, 0.55-1.19; P = .28) in the propensity score-adjusted model. CONCLUSIONS: Use of an internal thoracic artery graft during coronary bypass surgery seems to improve long-term clinical outcomes.