Kodangudi B. Ramanathan

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Graft Surgery for Patients With Medically Refractory Myocardial Ischemia and Risk Factors for Adverse Outcomes With Bypass: A Multicenter, Randomized Trial

Abstract BACKGROUND Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction RESULTS A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Left ventricular hypertrophy: Effect on survival

OBJECTIVES The aim of the study was to determine whether left ventricular hypertrophy has an independent adverse effect on survival. BACKGROUND Left ventricular hypertrophy is considered to be a significant risk factor for coronary heart disease mortality; however, the impact of coexisting coronary artery stenosis on survival statistics is not clear. METHODS The relations among electrocardiographic (ECG) left ventricular hypertrophy, ST-T segment abnormality, coronary artery disease and survival were examined in 18,969 patients undergoing coronary arteriography between 1972 and 1985. Patients were excluded if they underwent coronary revascularization or had unstable angina, rheumatic or congenital heart disease, cardiomyopathy, pericardial disease or ECG changes other than left ventricular hypertrophy or repolarization abnormalities, leaving 4,824 patients for analysis. RESULTS Left ventricular hypertrophy was present in 249 patients, whereas 4,575 were free of left ventricular hypertrophy. Five-year survival was 90.2% in the group without left ventricular hypertrophy and was significantly lower (81.9%, p < 0.001) in the group with left ventricular hypertrophy. Five-year survival was significantly lower in patients with left ventricular hypertrophy, regardless of whether coronary artery disease was present: 84.4% versus 94.5% (p = 0.016) in the absence of coronary artery disease and 81.0% versus 87.7% (p < 0.001) in the presence of coronary artery disease. The presence of ST segment abnormalities was not associated with a significant reduction in survival in patients without coronary disease, although mortality was less in those without ST changes who had coronary disease (p = 0.012). CONCLUSIONS It is concluded that ECG left ventricular hypertrophy has an adverse effect on survival, even in patients who are free of coronary artery disease.

Effect on Survival of Estrogen Replacement Therapy After Coronary Artery Bypass Grafting

We examined the relation between postmenopausal estrogen placement therapy (ERT) and survival in 1,098 women who underwent coronary artery bypass grafting (CABG). Patients were selected for the study if their age was > or = 55 years at the time of preoperative coronary angiography or if they had previously undergone bilateral oophorectomy. Life-table analysis was used to compare survival after surgery in 92 women who received ERT and 1,006 women who did not. Five-year survival was 98.8% in the estrogen users and 82.3% in the non-users. Ten-year survival was 81.4% in the users and 65.1% in the nonusers (p = 0.0001 by Lee Desu test). The women who did not take estrogen were significantly older (p < 0.001), had more vessels with significant stenosis (p = 0.033), lower ejection fractions (p = 0.051), and more prior myocardial infarctions (p = 0.054). However, a Cox proportional-hazards model selected the number of coronary arteries narrowed (RR 1.43, p < 0.0001), estrogen use (RR 0.38, p = 0.001), left main coronary stenosis (RR 1.83, p = 0.001), and diabetes mellitus (RR 1.57, p = 0.003) as the significant independent predictors of survival. These data suggest that ERT improves survival significantly after CABG in postmenopausal women with coronary artery disease.

Association between the severity of diabetes mellitus and coronary arterial atherosclerosis

The relation between the severity of diabetes mellitus (DM) and the risk of significant coronary artery lesions were studied in 7,655 patients undergoing coronary arteriography for suspected coronary artery disease (CAD) between 1972 and 1982. The principal treatment regimen for DM was used to estimate the severity of DM. DM treated with insulin was defined as the most severe (n = 244), followed by DM treated with oral agents (n = 344) and with diet only (n = 380); 6,687 patients did not have DM. Severity of DM in patients with CAD (70% or greater diameter stenosis) was compared with that in control subjects without CAD (0% stenosis) for each of 9 anatomic locations (proximal, middle and distal portions of right, anterior descending and circumflex coronary arteries) using a retrospective case-control approach. The risk of CAD was highest in patients with DM treated with insulin (odds ratio estimate of the relative risk [OR = 3.0]), followed by patients with DM treated with oral agents (OR = 1.8) and lastly in those treated with diet alone (OR = 1.4). Severity of DM was a significant (p less than 0.05) independent predictor of CAD in a multivariate logistic regression model, whereas age at onset and duration of DM were not. The relative risk of CAD was the same (p greater than 0.05) for each of the 9 coronary segments. The data suggest that the risk of CAD increases with the severity of DM, which was a stronger predictor of CAD than duration of DM.(ABSTRACT TRUNCATED AT 250 WORDS)

Comprehensive cardiovascular risk factor control improves survival: The BARI 2D trial

Background It is unclear if achieving multiple risk factor (RF) goals through protocol-guided intensive medical therapy is feasible or improves outcomes in type 2 diabetes (T2DM).

Association of gender with morbidity and mortality after isolated coronary artery bypass grafting. A propensity score matched analysis

INTRODUCTION There is conflicting evidence about the impact of gender on outcomes after coronary artery bypass grafting (CABG). METHODS We performed a multivariate logistic regression and propensity score matched analyses in 13,115 patients (75% men) who underwent CABG between January 1, 1995 and December 31, 2009. The primary outcome was in-hospital mortality. Secondary outcomes included post-operative respiratory failure, stroke, myocardial infarction, sternal and leg wound infections, atrial fibrillation (AF), renal failure, need for postoperative intra-aortic balloon pump (IABP) support, and length of hospital stay. RESULTS A higher proportion of women (184; 5.6%) suffered in-hospital death compared to men (264; 2.7%), p<0.0001. After propensity score matching (n=3600 total, 1800 in each group), female gender was an independent predictor of mortality after isolated CABG (odds ratio [OR]=1.84; 95% confidence interval [CI] 1.22-2.78). Women also experienced a higher incidence of postoperative complications including stroke (3.8% vs. 2.3%, OR 1.37; 95% CI 1.08-1.73) and leg wound infection (3.4% vs. 1.7%, OR 1.75; 95% CI 1.36-2.54) on multivariate regression analyses. However, these differences were not significant after propensity score matching. We also observed a lower risk of post-operative AF (21.2% vs. 22.1%, OR 0.78; 95% CI 0.70-0.86) in women that remained significant after propensity matching (O.R. 0.76; 95% C.I. 0.65-0.90). Length of hospital stay was longer in women compared with men (11.9 ± 9.0 vs. 10.4 ± 9.2 days, p<0.0001). CONCLUSIONS Female gender is an independent predictor of increased mortality and a lower incidence of post-operative AF after isolated CABG.

The Effect of Age on Clinical Outcomes and Health Status: BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes)

OBJECTIVES The purpose of this study was to determine the extent to which effectiveness of cardiac and diabetes treatment strategies varies by patient age. BACKGROUND The impact of age on the effectiveness of revascularization and hyperglycemia treatments has not been thoroughly investigated. METHODS In the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial, 2,368 patients with documented stable heart disease and type 2 diabetes were randomized to receive prompt revascularization versus initial medical therapy with deferred revascularization and insulin sensitization versus insulin provision for hyperglycemia treatment. Patients were followed for an average of 5.3 years. Cox regression and mixed models were used to investigate the effect of age and randomized treatment assignment on clinical and health status outcomes. RESULTS The effect of prompt revascularization versus medical therapy did not differ by age for death (interaction p = 0.99), major cardiovascular events (interaction p = 0.081), angina (interaction p = 0.98), or health status outcomes. After intervention, participants of all ages had significant angina and health status improvement. Younger participants experienced a smaller decline in health status during follow-up than older participants (age by time interaction p < 0.01). The effect of the randomized glycemia treatment on clinical and health status outcomes was similar for patients of different ages. CONCLUSIONS Among patients with stable heart disease and type 2 diabetes, the relative beneficial effects of a strategy of prompt revascularization versus initial medical therapy and insulin-sensitizing versus insulin-providing therapy on clinical endpoints, symptom relief, and perceived health status outcomes do not vary by age. Health status improved significantly after treatment for all ages, and this improvement was sustained longer among younger patients. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

The effect of age on clinical outcomes and health status in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial (BARI 2D)

OBJECTIVES The purpose of this study was to determine the extent to which effectiveness of cardiac and diabetes treatment strategies varies by patient age. BACKGROUND The impact of age on the effectiveness of revascularization and hyperglycemia treatments has not been thoroughly investigated. METHODS In the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial, 2,368 patients with documented stable heart disease and type 2 diabetes were randomized to receive prompt revascularization versus initial medical therapy with deferred revascularization and insulin sensitization versus insulin provision for hyperglycemia treatment. Patients were followed for an average of 5.3 years. Cox regression and mixed models were used to investigate the effect of age and randomized treatment assignment on clinical and health status outcomes. RESULTS The effect of prompt revascularization versus medical therapy did not differ by age for death (interaction p = 0.99), major cardiovascular events (interaction p = 0.081), angina (interaction p = 0.98), or health status outcomes. After intervention, participants of all ages had significant angina and health status improvement. Younger participants experienced a smaller decline in health status during follow-up than older participants (age by time interaction p < 0.01). The effect of the randomized glycemia treatment on clinical and health status outcomes was similar for patients of different ages. CONCLUSIONS Among patients with stable heart disease and type 2 diabetes, the relative beneficial effects of a strategy of prompt revascularization versus initial medical therapy and insulin-sensitizing versus insulin-providing therapy on clinical endpoints, symptom relief, and perceived health status outcomes do not vary by age. Health status improved significantly after treatment for all ages, and this improvement was sustained longer among younger patients. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Clinical Outcomes of Percutaneous Interventions in Saphenous Vein Grafts Using Drug‐Eluting Stents Compared to Bare‐Metal Stents: A Comprehensive Meta‐Analysisof All Randomized Clinical Trials

Clinical outcomes of percutaneous coronary intervention (PCI) in patients with saphenous vein grafts (SVGs) remain poor despite the use of drug‐eluting stents (DES). There is a disparity in clinical outcomes in SVG PCI based on various registries, and randomized clinical data remain scant. We conducted a meta‐analysis of all existing randomized controlled trials (RCTS) comparing bare‐metal stents (BMS) and DES in SVGPCIs.

Oxidative Stress and Cardiomyocyte Necrosis With Elevated Serum Troponins: Pathophysiologic Mechanisms

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca2+ accumulation and mitochondria Ca2+ overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca2+ accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.