Egle Corrado

POINT: Efficacy of adding mitral valve restrictive annuloplasty to coronary artery bypass grafting in patients with moderate ischemic mitral valve regurgitation: A randomized trial

OBJECTIVE Surgical management of moderate chronic ischemic mitral valve regurgitation is still debated. The aim of this study was to evaluate the effect of adding mitral valve repair to coronary artery bypass grafting on clinical outcomes and left ventricular remodeling in patients who underwent coronary artery bypass grafting alone versus coronary artery bypass grafting plus mitral valve repair in a randomized trial. METHODS Between February 2003 and May 2007, 102 patients were eligible for this study and were randomly assigned to one of 2 groups by means of card allocation: coronary artery bypass grafting plus mitral valve repair (CABG plus MVR group; 48 patients, 47%) or coronary artery bypass grafting alone (CABG group; 54 patients, 53%). The 2 groups were similar regarding demographics, perioperative clinical data, and outcomes. There were differences regarding cardiopulmonary bypass (P < .0001) and aortic crossclamp (P < .0001) times. Exercise tests were performed for all survivors to evaluate tolerance to exercise and variability on grade of mitral regurgitation and systolic pulmonary arterial pressure. The study was blinded for physicians and nurses involved in postoperative care and clinical follow-up. The mean follow-up was 32 +/- 18 months. RESULTS Overall in-hospital mortality was 3% (3 patients). One (1.8%) patient died in the CABG group, and 2 (4.1%) patients died in the CABG plus MVR group. Survival rates +/- standard error at 5 years for patients in the CABG and CABG plus MVR groups were 88.8% +/- 3.2% and 93.7% +/- 3.1%, respectively. A significant difference was found between the 2 groups with regard to mean New York Heart Association class (P < .0001), left ventricular end-diastolic diameter (P < .01), left ventricular end-systolic diameter (P < .01), pulmonary arterial pressure (P < .0001), and left atrial size (P < .01). At follow-up, coronary artery bypass grafting alone was able to reduce mitral regurgitation grade in 40% of patients, whereas in the remaining patients mitral regurgitation grade remained stable or worsened. In the CABG group, among the 17 patients with mild mitral regurgitation and 12 patients with moderate mitral regurgitation at rest, 7 (40%) and 9 (75%) patients, respectively, had worsening in mitral regurgitation grade and pulmonary artery pressure during exercise. CONCLUSIONS The efficacy of adding mitral valve repair to coronary artery bypass grafting is well demonstrated by the improvement of New York Heart Association functional class and percentage of left ventricular ejection fraction and by the decrease of mitral regurgitation grade, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, pulmonary artery pressure, and left atrial size. Moreover, coronary artery bypass grafting alone left more patients with heart failure symptoms at rest and during exercise. Combined coronary artery bypass grafting and mitral valve repair have no effect on survival at short-term follow-up, and the trends that are evident will likely become more significant with time.

MARKERS OF INFLAMMATION AND INFECTION INFLUENCE THE OUTCOME OF PATIENTS WITH BASELINE ASYMPTOMATIC CAROTID LESIONS: A 5-YEAR FOLLOW UP STUDY

BACKGROUND AND PURPOSE It is still in debate whether the evaluation of markers of infection and inflammation may be of importance for cerebrovascular and cardiovascular prevention, and we aimed to investigate this field in a prospective 5-year clinical follow-up study in patients with early stages of atherosclerosis. METHODS We studied 668 subjects divided in 3 groups according to the results of carotid ultrasound examination: (1) normal subjects, if intima-media thickness (IMT) was <0.9 mm; (2) with IMT, if IMT was between 0.9 and 1.5 mm; and (3) with asymptomatic carotid plaque, if IMT was >1.5 mm. Traditional cardiovascular risk factors were investigated, and laboratory analysis included measurement of plasma lipids, fibrinogen, C-reactive protein, IgG antibodies for helicobacter pylori (HP), cytotoxic HP, cytomegalovirus, and chlamydia pneumoniae. RESULTS Cerebrovascular or cardiovascular events were registered in 18% of patients during the follow-up, and at multivariate analysis we found that the high levels of fibrinogen (P<0.0001) and C-reactive protein (P=0.014), the seropositivity to cytotoxic HP (P=0.001) and chlamydia pneumoniae (P=0.026), the presence of IMT or asymptomatic carotid plaque (P<0.0001), and the total burden of infections (P<0.0001) were the variables predictive of the clinical events. CONCLUSIONS Beyond traditional cardiovascular risk factors, markers of inflammation and infections seem to significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline asymptomatic carotid lesions.

Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: a 24-month follow-up study.

BackgroundThe purpose of this study was to investigate whether the vasodilator response to brachial artery and the presence of carotid lesions may have a prognostic significance in patients with early stages of atherosclerosis. Methods and resultsVascular echography was performed to analyze flow-mediated vasodilatation (FMD) at the brachial artery and intima–media thickness (IMT) of carotid arteries in 84 asymptomatic patients. At baseline, we evaluated all the established traditional cardiovascular risk factors. Transient ischemic attack, stroke, effort or unstable angina, acute myocardial infarction, peripheral arterial disease and cerebrovascular and cardiovascular death served as outcome variables over a follow-up period of 24 months. Brachial FMD was correlated inversely with carotid IMT (P=0.003), systolic blood pressure (P=0.0001) and age (P=0.0001). IMT was positively correlated with systolic blood pressure (P=0.0001), waist circumference (P=0.004) and age (P=0.01). At the end of the follow-up cardiovascular and cerebrovascular events were registered in 29% of the patients and in a multivariate analysis, including all the variables evaluated at baseline, male sex [odds ratio (OR) 1.6, P=0.005], the presence of baseline carotid lesions (OR 3.5, P=0.02) and FMD below the median (OR 3.2, P=0.03) were the only variables predictive of clinical events. ConclusionIn this study, endothelial dysfunction and carotid lesions significantly increased the risk of vascular events in asymptomatic patients with early stages of atherosclerosis. Assessment of systemic vasoreactivity and carotid IMT evaluation may provide, in this category of patients, important prognostic information in addition to that derived from traditional established cardiovascular risk factors.

Soluble CD40L and Cardiovascular Risk in Asymptomatic Low-Grade Carotid Stenosis

Background and Purpose— We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques. Methods— Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years). Results— ALCS patients had higher (P<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (P=0.003) independently predicted cardiovascular risk. Conclusions— High levels of sCD40L may predict the risk of CV events in ALCS.

Superficial venous thrombosis: Prevalence of common genetic risk factors and their role on spreading to deep veins

INTRODUCTION Superficial venous thrombosis (SVT) has been considered for a long time a limited clinical condition with a low importance, but this approach has changed in recent years, when several studies demonstrated spreading to deep veins occurring from 7.3 to 44%, with high prevalence of pulmonary embolism. MATERIALS AND METHODS To evaluate the prevalence of genetic risk factors for VTE in patients suffering from SVT on both normal and varicose vein, and to understand their role on spreading to deep veins, we studied 107 patients with SVT, without other risk factors. Ultrasound examination was performed, and the presence of FV Leiden, Prothrombin G20210A mutation, and MTHFR C677T mutation was researched. RESULTS In the patients where SVT occurred in normal veins, the presence of FV Leiden was 26.3% of the non-spreading and 60% of the spreading to deep veins SVT; Prothrombin mutation was found in 7.9% of the former case and in 20% of the latter; MTHFR C677T mutation was found respectively in 23.7% and 40%. In the patients with SVT on varicose veins, the presence of these factors was less evident (6.7%, 4.4% and 6.7% respectively), but their prevalence was considerably higher (35.7%, 7.4% and 21.4% respectively) in SVT spreading to deep veins than in non-spreading. CONCLUSIONS Our data demonstrate the high prevalence of these mutations, especially FV Leiden and associations, in patients with SVT on normal veins and their role in the progression to deep vein system.

Off-pump versus on-pump myocardial revascularization in patients with ST-segment elevation myocardial infarction: A randomized trial

OBJECTIVE Conventional cardioplegic arrest coronary artery bypass grafting after ST-segment elevation myocardial infarction is associated with high mortality and morbidity. The benefits of off-pump surgery have been suggested. This study randomly evaluated the impact of the off-pump technique on clinical results. METHODS Between February 2002 and October 2007, 128 patients with ST-segment elevation myocardial infarction who underwent myocardial revascularization within 48 hours from the onset of symptoms were randomly assigned to 2 groups: on-pump group (66 patients/51.5%) and off-pump group (63 patients/48.5%). The primary end point was the incidence of in-hospital death and outcomes (low cardiac output syndrome, prolonged mechanical and pharmacologic cardiac support, prolonged mechanical ventilation support, and postoperative length of stay in intensive care unit and hospital). The secondary end point was the evaluation of myocardial infarct size measured by the perioperative serum release of cardiac troponin I and the improvement of contractile cardiac function evaluated by the wall motion score index. RESULTS Overall in-hospital mortality was 4.6%. In-hospital mortality was 7.7% (5 patients) in the on-pump group and 1.6% (1 patient) in the off-pump group (P = .04). Statistically significant differences were found between the 2 groups concerning the incidence of low cardiac output syndrome (P = .001), time of inotrope drugs support (P = .001), time of mechanical ventilation (P = .006), reoperation for bleeding (P = .04), intensive care unit stay (P = .01), and in-hospital stay (P = .02). Statistically significant differences also were found between the 2 groups concerning the incidence of in-hospital death in patients who were admitted to surgery in cardiac shock (P = .0018) and patients who underwent surgery within 6 hours from the onset of symptoms (P = .0026). The procedure in 1 patient (1.6%) in the off-pump group was converted to the on-pump beating heart technique. The serum levels of cardiac troponin I were high in the on-pump group during the first 48 hours after surgery. Myocardial function was better in the off-pump group. There were no cardiac-related late deaths, and patients had no recurrent cardiac events. CONCLUSION Off-pump surgery reduced early mortality and morbidity in patients with ST-segment elevation myocardial infarction in respect to the conventional procedure. Off-pump surgery showed better results than on-pump surgery in patients who underwent surgery within 6 hours from the onset of symptoms and in patients with cardiogenic shock.

Markers of inflammation are strong predictors of subclinical and clinical atherosclerosis in women with hypertension.

Cardiovascular diseases in women still rises and remains their leading cause of death in most developed countries; yet we have less sex-specific data in women than in men as a result of lower enrollment in clinical trials and low rates of sex-specific reporting. The aim of our study was to evaluate in hypertensive postmenopausal women the potential predictive role of markers of inflammation, for example, fibrinogen and C-reactive protein (CRP), on subclinical and clinical atherosclerosis, beyond that of the other established cardiovascular risk factors. We studied 127 asymptomatic hypertensive postmenopausal women with different degrees of carotid intima–media thickness, as examined by the eco-color-doppler ultrasonography, evaluating in a 5 years follow-up cerebrovascular and cardiovascular morbidity and mortality. We preliminarily found that both fibrinogen and CRP levels were associated with the extension of carotid atherosclerosis (P<0.0001 and P=0.0445, respectively). We also found that among all established traditional cardiovascular risk factors (including obesity, diabetes, smoking habit, family history of coronary artery disease, dyslipidemia) only older age (P=0.0162), elevated fibrinogen (P=0.0298), and CRP (P=0.0345) were independent predictors of subclinical atherosclerosis. At the end of follow-up patients clinical events were registered in the 24% of patients and multivariate analysis revealed the following predictors of events: elevated CRP levels [odds ratio (OR): 12.6], the presence of family history of coronary artery disease(OR: 8.8) and older age (OR: 1.1). Beyond the utility of CRP and fibrinogen levels in the prediction of subclinical and clinical atherosclerosis, the therapeutic implications of these results remain to be evaluated by further studies.

Prediction of cardio- and cerebro-vascular events in patients with subclinical carotid atherosclerosis and low HDL-cholesterol

Low HDL-cholesterol concentrations are associated with increased cardiovascular risk and recent evidences suggest that HDL may aggravate the atherosclerotic process promoting inflammation: HDL are anti-inflammatory in the absence of inflammation but can become proinflammatory in the presence of atherosclerosis. Yet, no data is available on the cardiovascular outcome in subjects with low HDL-cholesterol and early stages of atherosclerosis. Therefore, we included in a prospective 5-year follow-up study 150 subjects with low HDL-cholesterol concentrations and subclinical carotid atherosclerosis, as assessed by carotid colour doppler, evaluating at baseline all the established traditional cardiovascular risk factors (e.g. male gender, older age, obesity, hypertension, diabetes, smoking, family history of coronary artery disease, hypercholesterolemia), as well as levels of two markers of inflammation (C-reactive protein and fibrinogen). At the end of the follow-up we registered vascular events in the 21% of patients and we found that lower HDL-cholesterol concentrations were associated with ischemic stroke (p=.0164), peripheral arterial disease (p=.0248) and the presence of any clinical event (p=.0105). By multivariate analysis we searched, among all baseline parameters, for independent variables associated with the events and we found a predictive role for elevated fibrinogen concentrations (OR 6.3, 95% CI 2.0-19.6, p=.0016), family history of coronary artery disease (OR 4.5, 95% CI 1.7-12.8, p=.0045) and lower HDL-cholesterol levels (OR 1.4, 95% CI 1.1-1.9, p=.0278). These findings further suggest a synergistic role of low-HDL and inflammation on the atherosclerotic disease progression from subclinical lesions to clinical events. Yet, their therapeutical implications remain to be established in future studies.

Papillary muscle relocation in conjunction with valve annuloplasty improve repair results in severe ischemic mitral regurgitation.

OBJECTIVE The incidence of recurrent mitral regurgitation (MR) after restrictive annuloplasty (RA) was 5% to 20% in several reports. There are many opinions in favor of adding subvalvular procedures to RA to reduce the tenting forces and improve the repair results. METHODS From March 2003 to May 2010, 55 patients with severe ischemic MR who had undergone papillary muscle (PPM) relocation in conjunction with mitral annuloplasty in our institutions were enrolled. The patients were matched 1:1 with those who underwent isolated RA using the propensity score. The mean left ventricular ejection fraction was 42% ± 6%. The mean tenting area and coaptation depth was 3.2 ± 0.6 cm(2) and 1.3 ± 0.2 cm, respectively. The study endpoints were early mortality and clinical and echocardiographic outcomes, freedom from cardiac-related deaths, and cardiac-related events. RESULTS In-hospital death occurred in 5 patients (4.5%), without a statistically significant difference between the 2 groups (P = .72). The 5-year freedom from cardiac-related deaths and cardiac-related events in the PPM relocation group versus the RA group was 90.9% ± 1.8% versus 89% ± 1.6% (P = .82) and 83% ± 2.1% versus 65.4% ± 1.2% (P < .001), respectively. Recurrent MR equal to or greater than moderate occurred in 2 (3.7%) and 6 (11.5%) patients in the PPM relocation group and RA group (P = .01), respectively. Moreover, we found statistically significant differences for the postoperative mean tenting area and coaptation depth in both groups (P < .001). CONCLUSIONS PPM relocation in conjunction to mitral annuloplasty is an easy and safe method and can be performed without an increase in-hospital mortality. This technique reduced the tenting area and coaptation depth compared with isolated RA, leading to improvement in the incidence of recurrent MR. The PPM group of patients experienced fewer cardiac-related events.

Preclinical carotid atherosclerosis enhances the global cardiovascular risk and increases the rate of cerebro- and cardiovascular events in a five-year follow-up.

AIM To evaluate if the intima-media thickening (IMT) and asymptomatic carotid plaque (ACP), as expression of carotid preclinical atherosclerosis (pre-ATS), can provide further information on the global cardiovascular risk (GCVR). METHODS We studied 454 asymptomatic subjects, with a cluster of risk factors (RF), and evaluated the incidence of a first cardiovascular (CV) event in a five-year follow-up. The subjects at admission were subdivided in three groups of risk. RESULTS Events occurred in 38% of subjects at high risk, in 13% and 6% of subjects at intermediate and low risk (p<0.003). Among evaluated parameters, carotid pre-ATS was a predictive marker of CV events (OR 2.7, 95% IC 1.4-5.1, p<0.0024). In subjects with GCVR<20% the prevalence of events was 8% for normal carotid ultrasound findings, 13% for increased IMT and 15% for ACP. CONCLUSIONS In primary prevention, the IMT measurement can give further information for a better stratification of GCVR. The pre-ATS of carotid arteries should be considered a strong predictor of future CV events and should suggest a more aggressive treatment of RF.