Aortic valve sclerosis: a marker of significant obstructive coronary artery disease in patients with chest pain?

BACKGROUND: Previous reports suggested a relationship between coronary artery disease (CAD) and aortic valve sclerosis (AVS). However, whether AVS can be used as a marker of obstructive CAD (obCAD) in patients with chest pain is unknown. We hypothesized that AVS is a predictive marker for obCAD in patients hospitalized for chest pain. METHODS: We studied 93 consecutive patients with chest pain undergoing coronary angiography. All had negative cardiac enzymes and no previous diagnosis of cardiac ischemic disease. AVS was detected by transthoracic echocardiography. Resting electrocardiography, left ventricular systolic function, wall-motion abnormalities, and stress test results were considered. We calculated the diagnostic value for obCAD of AVS, stress test, and combination of the two methods. RESULTS: ObCAD was present in 29 patients (31%). Patients with obCAD had a higher prevalence of AVS (38 vs 14%, P = .02) and positive stress test (67 vs 28%, P = .02). The odds ratio for obCAD in the presence of AVS was 3.7 (95% confidence interval 1.3-10.4, P = .01). AVS (P = .01) and a positive stress test (P = .002) were independent predictors for obCAD at the multivariate analysis. AVS had sensitivity of 38% and specificity of 86%. Stress test had sensitivity of 67% and specificity of 72%. When echocardiographic detection of AVS was combined with stress test, the sensitivity and negative predictive value improved to 93% and 96%, respectively. CONCLUSIONS: AVS is an independent predictor for obCAD in patients with chest pain, thus, it should be considered in the risk stratification of these patients.

Statin use and survival in patients with chronic heart failure--results from two observational studies with 5200 patients.

BACKGROUND: There is minimal evidence that HMG-CoA reductase inhibitors (statins) are beneficial in patients with chronic heart failure (CHF). Treatment with statins may lead to a lower mortality in CHF, independent of cholesterol levels, CHF etiology and clinical status. METHODS: In a first study, we included 3132 patients with CHF from the ELITE 2 study in whom information on body mass index (BMI) and statin use at baseline were available. In a second study, we pooled the databases of 5 tertiary referral centers with 2068 CHF patients. In this cohort 705 patients were on a statin (34%), 585 of 1202 (49%) patients with ischemic etiology, and 120 of 866 (14%) patients with non-ischemic etiology (established by coronary angiography). FINDINGS: Patients in ELITE 2 who received statin therapy at baseline (n=397, 13%) had lower mortality (hazard ratio [HR] 0.61, 95% CI 0.45-0.83; p=0.0007). In univariate analysis, increasing age, NYHA class, creatinine, and decreasing BMI, LVEF, and cholesterol, as well as lack of beta-blocker treatment and ischemic etiology (all p<0.002) related to higher mortality. In multivariable analysis, statin therapy related to lower mortality independently of all these variables (adjusted HR 0.66, 95% CI 0.47-0.93; p=0.017). In the second study CHF patients on statins had lower mortality (adjusted HR 0.58, 95% CI 0.44-0.77; p=0.0001). Both in patients with ischemic (p<0.0001) and non-ischemic etiology (p=0.028) statin treatment related to better survival. INTERPRETATION: In chronic heart failure, treatment with statins is related to lower mortality, independent of cholesterol levels, disease etiology and clinical status.

Aortic stiffness correlates with an increased extracellular matrix turnover in patients with dilated cardiomyopathy.

BACKGROUND: An increased extracellular matrix (ECM) turnover has been associated with poor survival in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM). However, the influence of the accelerated collagen turnover on the progressive large artery stiffening process characterizing CHF has not been clarified. This is relevant because aortic stiffening imposes an additional systolic load and impairs exercise tolerance in CHF patients. Therefore, we investigated whether the serum aminoterminal propeptide of type III collagen (PIIINP), an established marker of ECM turnover and tissue fibrosis in DCM, was associated with aortic stiffness in DCM patients. METHODS AND RESULTS: A total of 89 patients with clinical diagnosis of DCM (age 62 +/- 9 years, 80% men, mean ejection fraction 34% +/- 8%) were selected. Aortic pulse-wave velocity (PWV), a well-established marker of aortic stiffness, was measured by Doppler ultrasonography. Serum concentration of PIIINP was determined by radioimmunoassay. Mean aortic PWV was 5.7 +/- 2.3 m/s, and PIIINP was 5.0 +/- 1.3 microg/L. The variables correlated with aortic PWV were age (r = 0.33, P = .002), PIIINP (r = 0.30, P = .005), heart rate (r = 0.27, P = .02), stroke volume (r = -0.24, P = .03) and New York Heart Association class (r = 0.25, P = .02). In a multivariate analysis, age (P = .02) and PIIINP (P = .01) were independently related with aortic PWV, accounting for 27% of its variance. CONCLUSIONS: Higher serum PIIINP levels are independently associated with a stiffer aorta in DCM patients. This suggests that abnormalities in the ECM turnover might involve the proximal elastic vasculature and could partially explain the progressive large artery stiffening process characterizing CHF.

Safety of percutaneous left heart catheterization directly performed by cardiology fellows: a cohort analysis.

BACKGROUND: No previous study has analyzed the possible responsibility of fellows-in-training in terms of the risk of complications during cardiac catheterization. Thus, we sought to identify possible risk factors for access site complications following cardiac catheterization procedures, with particular attention to the role of cardiology fellows. METHODS: A total of 1,288 left heart catheterization procedures (both diagnostic and interventional), performed over a 1-year period at a university hospital, were retrospectively evaluated to determine the incidence of local complications (pseudoaneurysm, arterio-venous fistula, major hematoma or bleeding, vascular dissection). Several clinical (age, gender, previous coronary artery bypass surgery, indication to the exam) and procedural (procedure performed by the fellow, access site, type of procedure, urgent setting, use of glycoprotein IIb/IIIa inhibitors, simultaneous right heart catheterization, use of closure devices) covariables were considered. Major adverse cardiovascular and cerebrovascular events (MACCE: death, myocardial infarction, cerebrovascular event) were also assessed. RESULTS: The overall access site complication rate was 2.6%. On multivariate regression analysis, the only two predictors of local complications were female gender (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.6-6.5) and femoral approach (OR 3.9, 95% CI 1.2-12.1). The rate of MACCE was 1.2%, mainly after percutaneous coronary interventions, with only 1 death overall (0.07%). Procedures performed by cardiology fellows were not associated with an increased incidence of either complication. CONCLUSIONS: Cardiology fellows can safely perform cardiac catheterization procedures without an increase in the rate of local and major cardiovascular complications. Of course, the presence and watchful supervision of an attending physician is still essential to ensure both patient safety and optimal training.

Impact of body mass index on short-term outcome after acute myocardial infarction: does excess body weight have a paradoxical protective role?

BACKGROUND: Obesity is a risk factor for acute myocardial infarction (AMI), due in part to obesity-related conditions. However, the relation between BMI (body mass index) and outcome in patients with AMI has not been completely clarified. The aim of our study was to assess the impact of BMI on short-term outcome after AMI. METHODS: We retrospectively studied 717 consecutive patients admitted to our Intensive Coronary Care Unit for AMI. The end-point of the study was all-cause mortality. RESULTS: The mean age was 64+/-12 years. Mean BMI was 26+/-3.5 kg/m2. During follow-up 15 patients died. Non-survivors were significantly older than survivors (p<0.0001); BMI (p = 0.0027) and weight (p = 0.0002) were significantly lower in non-survivors than survivors; left ventricular dimensions (end-diastolic diameter: p = 0.0023; end-systolic diameter: p = 0.0019), the number of akinetic segments (p<0.0001) and contractile efficiency (p<0.0001) were also significantly lower in non-survivors. At Cox proportional univariate analysis low BMI (p = 0.0019), female sex (p = 0.0041), age (p<0.0001), left ventricular dimensions (end-diastolic diameter = 0.0040, end-systolic diameter = 0.0053), number of akinetic segments (p = 0.0001) and degree of left ventricular dysfunction (p = 0.0002) were significant predictors of prognosis. The prognostic power of BMI remained after adjustment for age (p<0.05), left ventricular dimensions (end-diastolic diameter: p<0.0042; end-systolic diameter p = 0.04), contractile efficiency (p = 0.0045) or number of akinetic segments (p = 0.0070). CONCLUSION: Low BMI is an independent predictor of poor prognosis in the short-term outcome after AMI. The underlying mechanisms remain to be investigated.

Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques.

OBJECTIVES: To measure circulating levels of oxidized-low-density lipoproteins (ox-LDL) in patients with stable and unstable angina and controls, and to investigate their correlation with the extent of coronary artery disease (CAD) and the presence of complex plaques at coronary angiography. METHODS AND RESULTS: Circulating ox-LDL were assessed, using ELISA, in patients with unstable angina (UA, n=26), stable angina (SA, n=29) and in controls (C, n=27). All patients underwent coronary angiography. The extent of CAD was evaluated using a quantitative score, while the presence of complex, vulnerable plaques was angiographically assessed. Ox-LDL were higher in UA patients than in SA patients and in C subjects, and in SA patients than in C subjects (C, 45.6+/-12.8 U/L; SA, 58.8+/-11.0 U/L; UA, 73.7+/-13.6 U/L; p<0.001). No correlation was found with the extent of atherosclerotic disease in the coronary tree. Patients with angiographic complex lesions showed significantly higher levels of ox-LDL (68.4+/-13.9 U/L versus 55.2+/-16.4 U/L, p<0.001). Multiple regression analysis showed that ox-LDL were independent predictors of the presence of complex plaques (p<0.023). CONCLUSIONS: Ox-LDL levels are higher in unstable patients and correlate with the presence of angiographically documented complex plaques. Ox-LDL might be markers of destabilization of CAD.

Chronic heart failure with preserved left ventricular ejection fraction: diagnostic and prognostic value of left atrial size.

BACKGROUND: Almost 40% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (EF) and prognosis similar to those with reduced EF. Data on prognostic markers in such patients are limited. We analyzed the prevalence and prognostic value of left atrial (LA) size in this condition. METHODS: 89 normal subjects (Group I), 38 asymptomatic hypertensive patients (Group II) and 183 HF patients with preserved EF (EF >45%) (Group III) were studied. LA diameter (LAD), LV diastolic (LVD) and systolic (LVS) dimensions and mass (LVmass) and EF were measured. E and A wave velocities and E/A were measured. The primary end point was all cause mortality in group III patients. RESULTS: Groups did not differ in age, gender or EF. Group III patients had larger LAD (4.6+-1.0 cm) compared with both Group I (3.7+/-0.6) and Group II (3.7+/-0.5 cm) (p<0.0001). A markedly enlarged (arbitrarily defined as LAD higher or equal 5 cm) had an odds ratio of 34 (95% CI 8-144) in distinguishing HF patients from normals. After a mean follow-up period of 29+/-27 months, 40 patients (21.9%) died. In Cox univariate analysis, NYHA class (HR 2.8 95% C.I. 1.8-4.3; p<0.0001), diastolic blood pressure (DBP) (HR 0.92 95% C.I. 0.88-0.96; p<0.0001), age (HR 1.059 95% C.I. 1.01-1.11; p=0.02) and LAD (HR 1.72 95% C.I. 1.27-2.3; p=0.0005) were predictors of mortality. LAD predicted survival independently of other variables. CONCLUSION: The left atrium is frequently dilated in HF patients compared with controls despite similar EF. LAD showed powerful prognostic value independent of clinical variables.

Carotid atherosclerotic plaque instability in patients with acute myocardial infarction.

UNLABELLED: The instability of atherosclerotic plaque is partly determined by local factors, but systemic factors such as infection, inflammation, autoimmunity or genes might also be important. We aimed to analyze whether patients with acute myocardial infarction (AMI) might have a higher proportion of unstable plaques in the carotid arteries compared with patients who had had no acute coronary events. METHODS: Sixty-nine consecutive patients with AMI (Group 1) and 95 patients without acute coronary events (Group 2) had carotid artery duplex ultrasounds. Carotid atherosclerosis was quantified by number of plaques in the two carotid arteries, intimal media thickening and degree of maximal stenosis. According to their morphology, plaques were divided into stable (fibrocalcific) and unstable (soft and/or not homogeneous). RESULTS: The two groups did not differ as regards age (66+/-8 vs. 68+/-19; p=0.3), female sex (13% vs. 21%; p=0.3), mean number of carotid plaques (2.8+/-1 vs. 2.5+/-2; p=0.2), degree of stenosis (59+/-2% vs. 36+/-1%; p=0.2) or intimal media thickening (1.04+/-0.2 vs. 1.06+/-0.2; p=0.8). However, Group 1 pts more frequently had unstable carotid plaques compared with Group 2 (43% vs. 15%; p=0.004), and had a greater number of unstable carotid plaques (0.51+/-0.6 vs. 0.16+/-0.4: p<0.0001) and a higher ratio of unstable to stable plaque (19% vs. 8%; p=0.005). In the overall population, logistic regression analysis showed that after adjustment for degree of maximal stenosis, the presence of coronary artery event (AMI pts) predicted the presence of unstable carotid plaque (OR: 4.3 95% CI: 2.0-9.2; p=0.0002). CONCLUSION: Patients with unstable coronary artery disease expressed clinically as AMI, frequently had unstable atherosclerotic plaques in other arterial sites such as carotid arteries. This finding supports the hypothesis that plaque instability might reflect a systemic process.

Safety and efficacy of the percutaneous radial artery approach for coronary angiography and angioplasty in the elderly.

BACKGROUND: The transradial approach to coronary interventions has been accepted as a safe and effective alternative to the femoral approach due to fewer access site complications and improved patient comfort. In the present study we aimed to investigate the safety and efficacy of transradial procedure in the elderly. METHODS: We analyzed 850 patients who underwent transradial coronary angiography and/or angioplasty. All patients were divided into two groups, according to age. The first group consisted of patients < 70 years (600; 70.5%) and the second group consisted of patients greater than or equal to 70 years (250; 29.5%). RESULTS: Baseline characteristics did not differ between the two groups, except for diabetes mellitus which affected more patients greater than or equal to 70 years of age. Procedure duration, X-ray time and number of catheters used were similar in the two groups. No deaths or acute myocardial infarctions occurred. There were some vascular complications in both groups, with no statistically significant difference between groups. In Group 2 (the older group) 2 TIAs and 1 stroke occurred, whereas in Group 1, there was 1 TIA (p = 0.08). CONCLUSIONS: From our experience, we conclude that the transradial catheterization is a safe and effective technique in the elderly, with a reduced risk of local vascular complications and a noteworthy increase in patient comfort, especially in view of the age-related diseases that frequently affect older patients.

Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity.

BACKGROUND: Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. METHODS: Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). RESULTS: The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4+/-4.2 versus 17.8+/-4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1+/-6.8 versus 34+/-5.3, p<0.0001). In the univariate model, age (r=-0.36, p<0.0001), female sex (r=-0.21, p=0.001), ischemic CHF etiology (r=-0.26, p<0.0001) and NYHA class (r=-0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology (beta=-0.23, p=0.001) was a predictor of peak VO2 (R(2)=0.49) independently of age (beta=-0.23, p=0.001), female sex (beta=-0.25, p=0.0006) and NYHA class (beta=-0.31, p<0.0001). Similarly, ischemic etiology (beta=0.29, p=0.001) predicted the VE/VCO2 slope (R(2)=0.38) independently of E/A ratio (beta=0.27, p=0.01) and resting heart rate (beta=0.22, p=0.01). CONCLUSIONS: Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.

Is bare-metal stenting superior to balloon angioplasty for small vessel coronary artery disease? Evidence from a meta-analysis of randomized trials.

AIMS: To compare, by meta-analytical techniques, the clinical impact of bare-metal stenting vs. balloon angioplasty for the treatment of lesions in small coronary arteries. METHODS AND RESULTS: We included trials with random allocation and prospective comparison of angioplasty vs. stenting, reference vessel diameter<3 mm, and follow-up>or=6 months. Random effect odds ratios (OR) for death, myocardial infarction (MI), repeat revascularization (RR), and major adverse cardiac events (MACEs) were computed. In a pre-specified subgroup analysis, we compared stenting with optimal (post-procedural stenosis<20%) and suboptimal (>20%) angioplasty. Thirteen studies (4383 patients) were selected. No differences were found in terms of death and MI, while MACEs, mainly driven by RR, were significantly less common after stenting (17.6%) than after angioplasty (22.7%), OR 0.71 (0.57-0.90). Heterogeneity among trials was present. When considering only optimal angioplasty, MACE rates were homogeneously similar, 17.9 vs. 21.1%, OR 0.86 (0.66-1.11). If angioplasty were suboptimal, MACEs were significantly more common after angioplasty (24%) than after stenting (17.3%), OR 0.62 (0.44-0.88). CONCLUSION: Stenting is superior to balloon angioplasty for the treatment of small vessels, in particular after suboptimal angioplasty. However, MACE and RR rates remain high after stenting, and the advantage of stent over angioplasty is moderate. An optimal balloon angioplasty strategy (with provisional stenting) may achieve results not inferior to routine stenting.

Independent and additional prognostic value of aminoterminal propeptide of type III procollagen circulating levels in patients with chronic heart failure.

BACKGROUND: In chronic heart failure (CHF), changes in the extracellular space contribute to cardiac dysfunction. We aimed to determine whether aminoterminal-propeptide of type III procollagen (PIIINP), a marker of extracellular matrix turnover, might provide prognostic information in CHF patients. METHODS AND RESULTS: A total of 101 consecutive CHF patients (mean age 61.7 +/- 8.7 years, 88% males) were followed up between 1999 and 2001. The combined endpoint of the study was death and hospitalization for heart failure. During follow-up there were 15 deaths and 11 hospitalizations for worsening heart failure. At the survival analysis, age (P = .02), New York Heart Association class (P = .014), s-creatinine (P = .014), plasma-PIIINP (p-PIIINP) levels (P = .005), left ventricular ejection fraction (LVEF) (P = .0002), and a restrictive mitral filling pattern (P = .0003) predicted event-free survival. At the multivariate analysis, p-PIIINP levels predicted outcome independently of other clinical variables, hormones, and echocardiographic and exercise testing variables (P < .05 in all models). In patients with LVEF <31%, the presence of p-PIIINP >4.7 microg/L levels was significantly associated with a higher risk of death and hospitalization as compared with the other patients (event-free survival rate at 12 months: 45% versus 95%; at 24 months: 27% versus 88%; at 36 months: 18% versus 85%, P < .0001). CONCLUSIONS: In patients with CHF, PIIINP levels predict outcome independently of clinical status, hemodynamics and hormonal activation. PIIINP levels provide additional prognostic information to that of left ventricular function alone, suggesting that it may reflect more than cardiac extracellular matrix turnover.

Prediction of mortality in chronic heart failure from peak oxygen consumption adjusted for either body weight or lean tissue.

BACKGROUND: Peak oxygen consumption (pVO2) reflects oxygen extraction from the skeletal muscles, but is routinely corrected for body weight. We hypothesized that correcting pVO2 for lean tissue rather than total body weight would improve the prediction of prognosis in patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 272 CHF outpatients (mean age 61 +/- 12 years, New York Heart Association [NYHA] class 2.3 +/- 0.8) underwent a cardiopulmonary exercise testing and body composition assessment by dual-energy X-ray absorptiometry. During a median follow-up of 608 days (range 8-3656), 75 patients died. Univariate survival analysis showed strong survival prediction from pVO2 adjusted for total weight or lean tissue (chi2 17.7, P < .001; chi2 27.5, P < .0001, respectively). Both predicted survival significantly in bivariate analysis, (chi2 4.6, P = .032; chi2 16.6, P < .0001). The predictive effects were independent of exercise protocol (treadmill versus cycle ergometer) (both P < .001). Multivariate analysis showed that pVO2 adjusted for lean tissue had prognostic importance independently of NYHA class, ejection fraction, and ventilation and carbon dioxide production slope (P < .05 for each). In patients with NYHA class I and II (n = 160), pVO2 adjusted for lean tissue predicted outcome (P = .03). CONCLUSION: Adjustment for lean tissue instead for body weight increases the prognostic power of pVO2, particularly in patients with mild heart failure.

Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures; Systematic overview and meta-analysis of randomized trials.

OBJECTIVES: We sought to compare, through a meta-analytic process, the transradial and transfemoral approaches for coronary procedures in terms of clinical and procedural outcomes. BACKGROUND: The radial approach has been increasingly used as an alternative to femoral access. Several trials have compared these two approaches, with inconclusive results. METHODS: The MEDLINE, CENTRAL, and conference proceedings from major cardiologic associations were searched. Random-effect odds ratios (ORs) for failure of the procedure (crossover to different entry site or impossibility to perform the planned procedure), entry site complications (major hematoma, vascular surgery, or arteriovenous fistula), and major adverse cardiovascular events (MACE), defined as death, myocardial infarction, emergency revascularization, or stroke, were computed. RESULTS: Twelve randomized trials (n = 3,224) were included in the analysis. The risk of MACE was similar for the radial versus femoral approach (OR 0.92, 95% confidence interval [CI] 0.57 to 1.48; p = 0.7). Instead, radial access was associated with a significantly lower rate of entry site complications (OR 0.20, 95% CI 0.09 to 0.42; p < 0.0001), even if at the price of a higher rate of procedural failure (OR 3.30, 95% CI 1.63 to 6.71; p < 0.001). CONCLUSIONS: The radial approach for coronary procedures appears as a safe alternative to femoral access. Moreover, radial access virtually eliminates local vascular complications, thanks to a time-sparing hemostasis technique. However, gaining radial access requires higher technical skills, thus yielding an overall lower success rate. Nonetheless, a clear ongoing trend toward equalization of the two procedures, in terms of procedural success, is evident through the years, probably due to technologic progress of materials and increased operator experience.

Effects of ACE gene insertion/deletion polymorphism on response to spironolactone in patients with chronic heart failure.

BACKGROUND: Angiotensin-converting enzyme (ACE) is involved in the pathophysiology of chronic heart failure, and its activity is determined in part by a polymorphism of the ACE gene. We hypothesized that the benefits of spironolactone, which inhibits downstream elements of ACE-mediated abnormalities, may depend on ACE genotype. METHODS: We randomly assigned 93 chronic heart failure patients to treatment with spironolactone (n = 47) or to a control group (n = 46) and followed them for 12 months. Genotype for the insertion/deletion polymorphism of the ACE gene was determined by polymerase chain reaction. An echocardiographic examination was performed at baseline and at the end of the 12 months. RESULTS: The mean (+/- SD) age of the 93 patients was 62 +/- 9 years, and the mean New York Heart Association class was 2 +/- 1. The genotype was DD in 26 patients (28%). Forty-seven patients were assigned to spironolactone treatment (mean dose, 32 +/- 16 mg). In the treated group, only patients with a non-DD genotype showed significant improvement in left ventricular ejection fraction (3.0%; 95% confidence interval [CI]: 1.2% to 4.8%; P = 0.002), end-systolic volume (-23 mL; 95% CI: -36 to -11; P = 0.0005), and end-diastolic volume (-27 mL; 95% CI: -43 to -12; P = 0.001). In the multivariate analysis, the estimated net effect of treatment was 29 mL better (95% CI: -20 to 78 mL) for end-diastolic volume, 20 mL better (95% CI: -18 to 58 mL) for end-systolic volume, but 1.4% worse (95% CI: -3.4% to 6.2%) for left ventricular ejection fraction in patients with non-DD versus DD genotypes. CONCLUSION: The effects of spironolactone treatment on left ventricular systolic function and remodeling may in part depend on ACE genotype.

The role of angiotensin-converting enzyme polymorphism in congestive heart failure.

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase, with primary known functions of converting angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and inactivating bradykinin. There is high variability among individuals in ACE concentrations, mainly due to the presence of a genetic polymorphism. The ACE gene has, in fact, insertion/deletion polymorphism in intron 16, consisting of a 287-base pair Alu repeat sequence, with three genotypes: insertion polymorphism, insertion/deletion polymorphism, and deletion polymorphism. The genetic effect accounts for 47% of the total variance of serum ACE. The determination of this polymorphism has allowed researchers to study the implications of the ACE gene in many case-control studies of cardiovascular disease, including myocardial infarction and hypertrophic and dilated cardiomyopathy. We review the current knowledge about the ACE gene polymorphism and its implications in heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Interpretation of the results of studies about the role of this polymorphism are controversial. The repetition of epidemio-genetic studies and the creation of adequate experimental studies will help to definitively establish the pathogenetic role of the permanent increase in ACE expression associated with the deletion polymorphism genotype.

Feasibility and safety of transeophageal atrial pacing stress echocardiography in patients with known or suspected coronary artery disease.

To investigate the feasibility and safety of the transesophageal atrial pacing stress test combined with echocardiography (TAPSE) 1,727 TAPSE tests were performed on 1,641 patients consecutively referred to our echocardiographic laboratory for nonexercise stress testing (1,319 men; mean age 60 +/- 9 years; 34% of whom were outpatients). Wall motion abnormalities were present at baseline echocardiography in 975 cases (56%). TAPSE was feasible in 1,648 cases (95.4%). It was not feasible in 79 patients due to failure of positioning the transnasal catheter (n=11), the patient's intolerance of esophageal stimulation (n=24), failure to obtain any or stable atrial capture (n=36), or because the echocardiogram could not be evaluated at the peak of the test (n=8). TAPSE was diagnostic in 1,584 cases (96% of the feasible tests, 92% of all attempts). TAPSE was nondiagnostic in 64 cases (4% of the feasible tests) due to second-degree atrioventricular type I block resistance to atropine administration with failure to achieve 85% of the age-predicted maximum heart rate (n=59) or due to side effects, such as arrhythmias (n=3) or hypertension (n=2), which required premature interruption of the test. There were no major complications (death, myocardial infarction, or life-threatening arrhythmias). There were 28 instances of minor complications that comprised transient arrhythmias, including atrial fibrillation (n=8), paroxysmal supraventricular tachycardia (n=6), automatic atrial tachycardia (n=1), sinus arrest (n=1), atrioventricular junctional rhythm (n=2), ectopic atrial rhythm (n=2), nonsustained ventricular tachycardia (maximum 6 beats, n=3), hypotension (n=1), and hypertension (n=4) leading to interruption of the test. Only 5 complications hampered a diagnostic result, whereas 18 occurred during or after a positive test and 5 during a negative, but diagnostic, test. Thus, TAPSE is a highly feasible and very safe stress test. It gives high percentage of diagnostic tests and may represent a valid alternative to pharmacologic stressors.

Selection of endpoints for heart failure clinical trials.

In assessing the efficacy and the safety of a new drug, randomized clinical trials represent the standard scientific method. The selection of the best response variables in a clinical trial of a treatment in congestive heart failure patients is often not straightforward; the primary end point of a trial should be clinically relevant, directly related to the primary goal of the trial, and with favorable distributional properties. All-cause mortality is undoubtedly the most unbiased endpoint, but there is interest both in assessing cause-specific mortality and hospitalization rate and in evaluating 'soft' endpoints (functional status, exercise tolerance); the latter, in fact, are clinically relevant and potentially more useful in mild heart failure patients. Physiopathologic variables (e.g. left ventricular function) could provide information on drug action mechanism. In this paper, several recent large clinical trials are reviewed and the advantages and drawbacks of the response variables used, are analyzed.

Association of aortic valve sclerosis and coronary artery disease in patients with severe nonischemic mitral regurgitation.

BACKGROUND: The presence of aortic valve sclerosis accounts for a higher rate of ischemic events and increased cardiovascular mortality. It may reflect coronary artery disease (CAD) because of a shared pathologic background. HYPOTHESIS: We aimed to analyze whether the presence of aortic valve sclerosis might help in identifying patients with coronary atherosclerosis among those with severe nonischemic mitral regurgitation (MR), who undergo coronary angiography before surgery for screening, and not because of suspected ischemic heart disease. METHODS: In all, 84 patients (mean age 64 +/- 9 years; 71% men) with mitral valve prolapse and severe regurgitation underwent echocardiography and coronary angiography. Aortic valve sclerosis was defined as focal areas of increased echogenicity and thickening of the leaflets without restriction of leaflet motion on echocardiography. Coronary artery disease was defined by the presence/absence of atherosclerotic plaques, independent of the degree of stenosis. RESULTS: Coronary artery disease was diagnosed in 47.6% of patients with and 15.8% of those without aortic valve sclerosis (p = 0.008). On logistic regression analysis, the presence of aortic valve sclerosis predicted CAD (odds ratio 3.3, 95% confidence interval 1.03-10.5; p = 0.04) independent of age. In female patients, the risk ratio for CAD in the presence of aortic valve sclerosis was 9. CONCLUSIONS: Coronary artery atherosclerosis and aortic valve sclerosis are closely associated in patients with severe nonischemic MR.

Is vasopressin superior to adrenaline or placebo in the management of cardiac arrest? A meta-analysis.

Vasopressin is currently recommended in the management of patients with cardiac arrest, but its efficacy is still incompletely established. We systematically reviewed randomized trials comparing vasopressin to control treatment in the management of cardiac arrest in humans and animals. Two human and 33 animal studies were retrieved. At pooled analysis vasopressin appeared equivalent to adrenaline (epinephrine) in the management of human cardiac arrest (N=240), with, respectively 63 (78/124) vs 59% (68/116) ROSC (P=0.43), and 16 (20/124) vs 14% (16/116) survival to hospital discharge (P=0.52). In animal trials (N=669) vasopressin appeared instead significantly superior to both placebo (ROSC, respectively 93 [98/105] vs 19% [14/72], P<0.001) or adrenaline (ROSC, respectively 84 [225/268] vs 52% [117/224], P<0.001). In conclusion, vasopressin is superior to both placebo or adrenaline in animal models of cardiopulmonary resuscitation. Evidence in humans is still limited and confidence intervals estimates too wide to reliably confirm or disprove results obtained in experimental animal settings.