Richard Baillot

Impact of Valve Prosthesis-Patient Mismatch on Short-Term Mortality After Aortic Valve Replacement

Background—The prosthesis used for aortic valve replacement (AVR) can be too small in relation to body size, thus causing valve prosthesis-patient mismatch (PPM) and abnormally high transvalvular pressure gradients. This study examined if there is a relation between PPM and short-term mortality after operation. Methods and Results—The indexed valve effective orifice area (EOA) was estimated for each type and size of prosthesis being implanted in 1266 consecutive patients and used to define PPM as not clinically significant if >0.85 cm2/m2, as moderate if >0.65 cm2/m2 and ≤0.85 cm2/m2, and as severe if ≤0.65 cm2/m2; it was correlated with 30-day mortality and compared with other relevant variables. Moderate or severe PPM was present in 38% of patients. Thirty-day mortality was 4.6% (58/1266 patients) and the strongest independent predictors in multivariate analysis were left ventricular ejection fraction <40% (P =0.007), infectious endocarditis (P =0.002), emergent/salvage operation (P =0.002), cardiopulmonary bypass time >120 minutes (P =0.001), and PPM (P =0.003). Relative risk of mortality was increased 2.1-fold (95% confidence interval, 1.2 to 3.7) in patients with moderate PPM and 11.4-fold (4.4 to 29.5) in those with severe PPM. Moreover, risk of mortality for every category of PPM was higher in patients with a left ventricular ejection fraction <40% as compared with ≥40% (nonsignificant PPM, 2.7 versus 1.0; moderate PPM, 7.1 versus 1.8; severe PPM, 77.1 versus 11.3). Conclusion—PPM is a strong and independent predictor of short-term mortality among patients undergoing AVR, and its impact is related both to its degree of severity and the status of left ventricular function. In contrast to other risk factors, moderate-severe PPM can be largely avoided with the use of a prospective strategy at the time of operation.

Nonrandomized Comparison of Coronary Artery Bypass Surgery and Percutaneous Coronary Intervention for the Treatment of Unprotected Left Main Coronary Artery Disease in Octogenarians

Background— The objective of the present study was to compare the midterm follow-up results of percutaneous coronary intervention (PCI) and coronary bypass graft surgery (CABG) for the treatment of unprotected left main coronary artery disease in octogenarians. Methods and Results— A total of 249 consecutive patients ≥80 years of age diagnosed with left main coronary artery disease underwent coronary revascularization in our center between January 2002 and January 2008; 145 patients underwent CABG, and 104 patients had PCI. Major adverse cardiac and cerebrovascular events (MACCE [cardiac death, myocardial infarction, cerebrovascular event, revascularization]) were evaluated at a mean follow-up of 23±16 months. Patients who underwent PCI were older; had higher creatinine levels, lower ejection fraction, and higher EuroSCORE; and presented more frequently with an acute coronary syndrome. Drug-eluting stents were used in 48% of PCI patients. A propensity score analysis was performed to adjust for baseline differences between the 2 groups. Survival free of cardiac death or myocardial infarction (PCI, 65.4%; CABG, 69.7%) and MACCE-free survival (PCI, 56.7%; CABG, 64.8%) at follow-up were similar between the groups (adjusted hazard ratio for survival free of cardiac death or myocardial infarction, 1.28; 95% CI, 0.64 to 2.56; P=0.47; adjusted hazard ratio for MACCE-free survival, 1.11; 95% CI, 0.59 to 2.0; P=0.73). The EuroSCORE value was an independent predictor of MACCE regardless of the type of revascularization (hazard ratio, 1.17 for each EuroSCORE increase of 1 point; 95% CI, 1.09 to 1.25; P<0.0001). Conclusions— In this single-center, nonrandomized study, there were no significant differences in cardiac death or myocardial infarction and MACCE between CABG and PCI for the treatment of left main coronary artery disease in octogenarians after a mean follow-up of 2 years. Baseline EuroSCORE was the most important predictor of MACCE regardless of the type of revascularization. Randomized studies comparing both revascularization strategies in this high-risk coronary population are warranted.

Effects of Angiotensin-Converting Enzyme Inhibition in Low-Risk Patients Early After Coronary Artery Bypass Surgery

Background— Early after coronary artery bypass surgery (CABG), activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors. Methods and Results— The Ischemia Management with Accupril post–bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial tested whether early initiation (≤7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40%. The trial was a double-blind, placebo-controlled study of 2553 patients randomly assigned to quinapril, target dose 40 mg/d, or placebo, who were followed up to a maximum of 43 months. The mean (SD) age was 61 (10) years. The incidence of the primary composite end point (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary revascularization, unstable angina or heart failure requiring hospitalization, documented angina, and stroke) was 13.7% in the quinapril group and 12.2% in the placebo group (hazard ratio 1.15, 95% confidence interval 0.92 to 1.42, P=0.212) over a median follow-up of 2.95 years. The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (hazard ratio 1.52, 95% confidence interval 1.03 to 2.26, P=0.0356). Adverse events also increased in the quinapril group, particularly during the first 3 months after CABG. Conclusions— In patients at low risk of cardiovascular events after CABG, routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG; however, it increases the incidence of adverse events, particularly early after CABG. Thus, early after CABG, initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk.

Impact of deep sternal wound infection management with vacuum-assisted closure therapy followed by sternal osteosynthesis: a 15-year review of 23 499 sternotomies

OBJECTIVE This study was undertaken to examine the outcome of patients with deep sternal wound infection (DSWI) now treated with vacuum-assisted closure (VAC) therapy as a bridge to sternal osteosynthesis with horizontal titanium plate fixation. METHODS From 1992 to 2007, a consecutive cohort of 23,499 patients underwent open-heart surgery (OHS) in our institution. The period under study was divided in two according to the use of therapeutic modalities: conventional (1992-2001, N=118 DSWI): debridement/drainage with primary closure and irrigation (N=37), debridement/drainage, open packing followed by pectoralis myocutaneous flaps (PMFs) (N=81); contemporary (2002-2007, N=149 DSWI): conventional treatment (N=24) and VAC therapy (N=125/83.8%). VAC was followed by sternal osteosynthesis with horizontal titanium plates in 92 patients (61.7%). RESULTS DSWI was diagnosed in 267 out of 23 499 (1.1%) patients of our entire series according to Center for Disease Control - Atlanta (CDC) criteria, 118 out of 13 180 (0.9%) in the first and 149 out of 10 319 (1.4%) in the second period (p=0.001). Hospital mortality (N=267/23,499) has been 10.25% for the entire cohort under study without any difference between groups (1992-2001: 11.4%; 2002-2007: 9.1%, p=0.67). More recently, VAC therapy (N=125) was associated with a lower mortality (4.8% vs 14.1%, p=0.01). Stepwise multivariable logistic regression analysis for both periods revealed that prolonged intubation in the intensive care unit (ICU), use of bilateral internal thoracic artery grafting (BIMA), diabetes, re-operation for bleeding and body mass index (BMI) >30 kgm(-2) are the most powerful predictors of DSWI. In the more recently treated patients using VAC therapy, combined procedures (valve and graft) also emerged as a significant predictor. For the entire study, Staphylococcus epidermidis (49.6%) has been the most frequently identified pathogen, followed by Staphylococcus aureus (38.8%). Methicillin-resistant S.aureus (MRSA) was observed in 4.9% of the cohort. Neither of these bacteria was associated with increased mortality. Survival analysis with Cox regression model and propensity score adjustment in patients with DSWI showed freedom from all-cause mortality at 1, 5 and 10 years to be, respectively, 91.8%, 80.4% and 61.3% compared with 94.0%, 85.5% and 70.2%, respectively, for patients submitted to OHS without DSWI (p=0.01). Early adjusted survival for patients with DSWI treated with VAC therapy was 92.8%, 89.8% and 88.0%, respectively, at 1, 2 and 3 years, compared with 83.0%, 76.4% and 61.3%, respectively, for patients with DSWI treated without VAC (p=0.02). CONCLUSIONS DSWI remains a major and challenging complication of OHS. VAC therapy with sternal preservation followed by delayed sternal osteosynthesis and PMF has been recently proposed as a new therapeutic strategy. Most patients treated with VAC therapy in our second group showed decreased perioperative mortality and increased short-term survival.

Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions

Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions.

Long-term impact of diabetes and its comorbidities in patients undergoing isolated primary coronary artery bypass graft surgery.

Background— The objective of this study was to identify the impact of diabetes and related comorbidities, namely chronic renal failure, peripheral vascular disease, and low ejection fraction (<35%), on long-term survival of patients undergoing coronary artery bypass graft surgery. Methods and Results— A unicenter study was conducted on 9125 survivors of isolated coronary artery bypass graft surgery between 1992 and 2002. There were 6581 nondiabetic patients and 2544 diabetics, including 1809 patients with noninsulin-dependent diabetes mellitus and 735 patients with insulin-dependent diabetes mellitus. Cardiac-specific survival at 5 and 10 years was lower in insulin-dependent diabetes mellitus compared with both nondiabetic mellitus patients and patients with noninsulin-dependent diabetes mellitus (P<0.0001). However, freedom from cardiac-related death was similar for patients with noninsulin-dependent diabetes mellitus and nondiabetes mellitus patients up to 6 years (P=0 0.08) after surgery and was significantly lower thereafter (P=0.004). Cardiac-specific survival after coronary artery bypass graft surgery in patients with one or more comorbidities was comparable (P=0.4) for both nondiabetes mellitus patients and patients with noninsulin-dependent diabetes mellitus, but was significantly lower for those requiring insulin therapy (P<0.0001). Noninsulin-dependent diabetes mellitus was not an independent predictor of long-term cardiac death (hazard ratio: 1.09, P=0.41); however, insulin-dependent diabetes mellitus, chronic renal failure, peripheral vascular disease, and low ejection fraction were all independent risk factors for late cardiac death (all P<0.0001). The impact of comorbidities on the long-term risk of cardiac death was similar for the 3 groups. Conclusions— Noninsulin-dependent diabetes is not an independent predictor of late cardiac death after coronary artery bypass graft surgery, because cardiac-related survival is similar to that of nondiabetic patients for 6 years after surgery. In diabetic and nondiabetic patients, cardiac survival is adversely affected by the need for insulin therapy and/or the presence and number of comorbidities such as chronic renal failure, peripheral vascular disease, and low ejection fraction.

Impact of residual regurgitation after aortic valve replacement

OBJECTIVES Mild-to-moderate aortic regurgitation (AR) is not infrequently encountered after standard aortic valve replacement, and reportedly more often following transcatheter aortic valve implantation. Patients are usually managed by observational follow-up, but the clinical significance and natural history of residual AR are unknown. The goal of this study was to determine its impact on the outcome of these patients. METHODS Between 1992 and 2011, 3201 consecutive patients underwent isolated standard aortic valve replacement in our institution. Of these, 135 patients (4.2%) were found to have paravalvular leak >1/4. Clinical, intraoperative as well as early and late postoperative outcome variables were studied. Factors associated with residual AR and their impact on survival were assessed by multivariate analysis. RESULTS Mean follow-up was 4.5 ± 3.4 years. The use of a bioprosthesis, longer cardiopulmonary bypass duration and preoperative atrial fibrillation were associated with a higher risk of presenting residual AR. Survival was negatively affected by commonly identified comorbidities (diabetes, stroke, pulmonary disease, renal failure, peripheral vascular disease) but also by the presence of >1/4 residual AR. Survival in the latter group was lower than for patients with ≤1/4 AR at all time points: 91.4 vs 96.7%, 77.5 vs 82.4% and 44.1 vs 54.5% at 1, 5 and 10 years, respectively (P < 0.01). CONCLUSIONS Postoperative residual AR >1/4 is an independent predictor of postoperative mortality and should be considered in the selection of surgical approach and management strategy for patients in need of standard and transcatheter aortic valve replacement.

Sustained postoperative anaemia is associated with an impaired outcome after coronary artery bypass graft surgery: insights from the IMAGINE trial

Objective To investigate the association between sustained postoperative anaemia and outcome after coronary artery bypass graft (CABG) surgery. Design Retrospective analysis of the IMAGINE trial, which tested the effect of the ACE inhibitor quinapril on cardiovascular events after CABG. Setting Thoracic surgery clinic/outpatient department. Patients 2553 stable patients with left ventricular ejection fraction >40% 2–7 days after scheduled CABG. Interventions Randomisation to quinapril or placebo. Main outcome measures Cox regression analysis for the association between postoperative anaemia and cardiovascular events and the effect of quinapril on the incidence of anaemia. Results Postoperative anaemia was sustained for >50 days in 44% of patients. Sustained postoperative anaemia was associated with an increased incidence of cardiovascular events during the first 3 months (adjusted HR (adjHR) 1.77, 95% CI 1.10 to 2.85, p=0.012) and during the maximum follow-up of 43 months (adjHR 1.37, 95% CI 1.14 to 1.65, p=0.008). When haemoglobin (Hb) was considered as a continuous variable, every 1 mg/dl decrease in Hb was associated with a 13% increase in cardiovascular events (adjHR 0.87, 95% CI 0.81 to 0.95, p=0.003) and a 22% increase in all-cause mortality (adjHR 0.78, 95% CI 0.60 to 0.99, p=0.034). Quinapril was associated with a slower postoperative recovery of Hb levels and a higher incidence of cardiovascular events in patients with anaemia (adjHR 1.60, 95% CI 1.1 to 2.4, p=0.024). Conclusions Postoperative anaemia is common, frequently persists for months after CABG surgery and is associated with an impaired outcome. In patients with anaemia, ACE inhibitors slowed recovery from postoperative anaemia and increased the incidence of cardiovascular events after CABG.

Age cut-off for the loss of benefit from bilateral internal thoracic artery grafting §

OBJECTIVES To identify the age-related benefit of single and bilateral internal thoracic artery (ITA) grafting on long-term cardiac-related survival in patients who survived from primary isolated coronary artery bypass grafting (CABG). METHODS A unicenter study was conducted on 12,231 consecutive survivors from primary isolated CABG who received single (n=9566 patients) or bilateral (n=1388 patients) ITA grafts, or vein grafts only (n=1277 patients) between 1992 and 2005. Data was collected prospectively. The Cox regression model estimates the hazard ratio of each independent variable on cardiac-specific survival over the entire length of follow-up. Age was a significant covariate into the statistical model. The mean follow-up was 5.7+/-3.7 years and 100% complete as of December 2005. The date and cause of death were obtained from the regional statistical institute. RESULTS After adjustments for different risk factors, the cardiac-related survival benefit in patients undergoing CABG with two ITAs was superior to that of single ITA grafting up to 60 years of age, displaying a constant decrease over time. The use of a single ITA was beneficial on cardiac-related survival in all age groups, including octogenarians, compared to patients receiving only vein grafts. CONCLUSIONS The use of at least one ITA is associated with increased long-term cardiac-specific survival in all age groups compared to venous-only CABG, even in octogenarians. The additional survival benefit of using a second ITA decreases gradually with age, and is lost after 60 years of age.

Permanent pacemaker implantation following isolated aortic valve replacement in a large cohort of elderly patients with severe aortic stenosis

Objectives To assess the incidence of conduction disturbances leading to permanent pacemaker implantation (PPI) following isolated aortic valve replacement (AVR) in a large cohort of elderly patients with severe symptomatic aortic stenosis, and to determine the predictive factors and prognostic value of PPI following AVR in such patients. Methods A total of 780 consecutive elderly patients (age 77±4 years, logistic EuroSCORE 10.4±8.5%, STS score 3.5±1.5%) with severe aortic stenosis and no previous pacemaker were analysed. Main outcome measures The incidence, clinical indications, timing and predictive factors of PPI within 30 days after AVR and their prognostic value were evaluated. Results Baseline ECG showed the presence of conduction abnormalities in 37.1% of the patients. Twenty-five patients (3.2%) needed PPI during the index hospitalisation due to the occurrence of complete atrioventricular block (2.6%) or severe bradycardia (0.6%). The presence of preprocedural left bundle branch block (OR 4.65, 95% CI 1.62 to 13.36, p=0.004) or right bundle branch block (OR 4.21, 95% CI 1.47 to 12.03, p=0.007) predicted the need for PPI after AVR. The need for PPI was associated with a longer hospital stay (p<0.0001). Thirty-day mortality rates were similar between patients with and without PPI (4% vs 3.2%, p=0.56). Survival rate at 5-year follow-up was 75%, with no differences between patients with and without PPI (p=0.12). Conclusions The need for PPI following isolated AVR in elderly patients with severe symptomatic aortic stenosis was low. Pre-existing bundle branch block predicted the need for PPI. PPI determined a longer hospital stay, but had no effect on acute and long-term mortality.