Trimetazidine improves exercise performance in patients with peripheral arterial disease.

Trimetazidine, an inhibitor of free fatty acids (FFA) oxidation, shifts cardiac and muscle metabolism from FFA to glucose utilization. This effect results in a greater production of high energy phosphates and ultimately into an anti-ischemic effect. Whether the anti-ischemic cardiac effects of trimetazidine (TMZ) can be translated to skeletal muscle in patients with claudication is unknown. We investigated the effectiveness of TMZ on functional performance in patients with peripheral arterial disease (PAD) and claudication. One hundred patients with claudication were enrolled in a parallel, double-blind, 3 months study. Patients were randomized to receive TMZ or matching placebo and were included in a domiciliary exercise program, consisting in daily sessions of aerobic and isotonic exercise for at least five days a week. All patients underwent a treadmill test, evaluating maximal walking distance (MWD), and ankle-brachial index (ABI) at baseline and after 3 months. ABI was similar in the two groups at baseline and did not significantly change at the end of the study in either groups (0.83+0.04 vs 0.85+0.03, TMZ vs placebo, respectively). MWD improved in all patients with exercise training; however, a greater improvement in MWD was observed with TMZ compared to placebo (23% vs 14%, p<0.0001). Physical training ameliorates functional performance in PAD. The adjunct of TMZ to exercise induces a greater improvement in MWD, suggesting that the inhibition of FFA oxidation improves functional capacity in patients with PAD and claudication.

B-type natriuretic peptide levels predict functional capacity in postcardiac surgery patients.

OBJECTIVE: Plasma levels of B-type natriuretic peptide (BNP) are often increased in postcardiac surgery patients. The six-minute walking test (6MWT) is useful to assess functional capacity in postcardiac surgery patients. The aim of this study was to determine whether BNP levels are associated with exercise capacity evaluated by 6MWT in patients after cardiac surgery. METHODS: Plasma BNP was measured in 101 consecutive patients referred to our center 8 ± 5 days after cardiac surgery who underwent echocardiography and 6MWT. We considered age, sex, diabetes, renal insufficiency, anemia, chronic obstructive pulmonary disease, hypertension, atrial fibrillation, beta-blocker therapy, left ventricular ejection fraction (LVEF), E/E', indexed left atrial volume (iLAV), type of surgery, and plasma BNP levels as potential predictors of reduced performance at 6MWT evaluated as percentages of the predicted values calculated according to the regression equation obtained in healthy individuals. RESULTS: The mean distance walked at 6MWT was 325 ± 100 m corresponding to 65 ± 20% of the predicted values. This was independent of the LVEF, E/E' or iLAV. Female patients or patients with atrial fibrillation had a reduced performance compared with male patients or patients with sinus rhythm (52 ± 19 vs. 70 ± 19%, P < 0.001; 50 ± 19 vs. 66 ± 19%, P = 0.017, respectively). BNP levels were inversely related to the performance at 6MWT (Pearson's correlation coefficient = -0.25, P = 0.010). At multivariate analysis, female sex (P < 0.001), atrial fibrillation (P = 0.031), and BNP levels (P = 0.040) remained the only independent predictive factors for reduced exercise capacity. CONCLUSION: The increase in BNP levels in postcardiac surgery patients is associated with reduced exercise capacity.

[Secondary cardiovascular prevention after acute coronary syndrome in clinical practice]. / Prevenzione cardiovascolare secondaria dopo sindrome coronarica acuta nella pratica clinica.

Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers.

[Functional evaluation of ultra-octogenarian patients undergoing cardiac rehabilitation: correlation between six minute walking test and Rivermead mobility index]. / Valutazione funzionale nei pazienti ultraottantenni sottoposti a ciclo di riabilitazione cardiologica: correlazione tra six minute walking test e rivermead mobility index.

BACKGROUND: There is an increasing need for admission of octogenarians to cardiac rehabilitation programs. The aim of this study was to evaluate if the Rivermead Mobility Index (RMI) (scale of mobility) is related to the functional capacity assessed by the 6 Minute Walking Test (6MWT). METHODS: We selected 108 consecutive patients > 80 years (M = 53, mean age 82.5 +/- 2.7 years, after cardiac surgery n = 72, heart failure n = 36) enrolled to our cardiac rehabilitation unit. All patients were evaluated with the RMI and underwent 6MWT both at admission (RMI(1) and 6MWT(1) and after a period of daily physical training (RMI2 and 6MWT(2)). The RMI(2)/RMI(1) and 6MWT(2)/6MWT(1) ratios were calculated as indexes of functional improvement (IM). RESULTS: The average in hospital stay was 20 +/- 11 days with an average of 11.9 training sessions per patient. The average distance walked at 6MWT(1) and 6MWT(2) was 193 +/- 116 and 278 +/- 122 m, respectively (p <0.001). The average score of RMI1 and RMI2 was 8.5 +/- 3.4 and 13.1 +/- 2.9, respectively (p <0.001). The values of 6MWT(1) and RMI(1) results were significantly correlated (r = 0.56, p <0.001). The RMI IM was significantly correlated to 6MWT IM (r = 0.309, p = 0.002). At multivariate analysis, RMI IM was found to be predictive of 6MWT IM even after correction for age, gender, length of hospitalization and number of sessions of training. CONCLUSIONS: In octogenarians, cardiac rehabilitation results in a significant improvement of both RMI and 6MWT. RMI IM is independently correlated to 6MWT IM. Therefore, RMI could be a useful tool for evaluating the improvement of functional capacity even in patients who cannot undergo 6MWT.

Relationship between B-type natriuretic peptide levels and echocardiographic indices of left ventricular filling pressures in post-cardiac surgery patients.

BACKGROUND: B-type natriuretic peptide (BNP) is increased in post-cardiac surgery patients, however the mechanisms underlying BNP release are still unclear. In the current study, we aimed to assess the relationship between postoperative BNP levels and left ventricular filling pressures in post-cardiac surgery patients. METHODS: We prospectively enrolled 134 consecutive patients referred to our Center 8 +/- 5 days after cardiac surgery. BNP was sampled at hospital admission and related to the following echocardiographic parameters: left ventricular (LV) diastolic volume (DV), LV systolic volume (SV), LV ejection fraction (EF), LV mass, relative wall thickness (RWT), indexed left atrial volume (iLAV), mitral inflow E/A ratio, mitral E wave deceleration time (DT), ratio of the transmitral E wave to the Doppler tissue early mitral annulus velocity (E/E'). RESULTS: A total of 124 patients had both BNP and echocardiographic data. The BNP values were significantly elevated (mean 353 +/- 356 pg/ml), with normal value in only 17 patients (13.7%). Mean LVEF was 59 +/- 10% (LVEF >or=50% in 108 pts). There was no relationship between BNP and LVEF (p = 0.11), LVDV (p = 0.88), LVSV (p = 0.50), E/A (p = 0.77), DT (p = 0.33) or RWT (p = 0.50). In contrast, BNP was directly related to E/E' (p < 0.001), LV mass (p = 0.006) and iLAV (p = 0.026). At multivariable regression analysis, age and E/E' were the only independent predictors of BNP levels. CONCLUSION: In post-cardiac surgery patients with overall preserved LV systolic function, the significant increase in BNP levels is related to E/E', an echocardiographic parameter of elevated LV filling pressures which indicates left atrial pressure as a major determinant in BNP release in this clinical setting.

'Lone' increase in C-reactive protein after cardiac surgery: prevalence, clinical characteristics, in-hospital course, and prognostic value.

BACKGROUND: Serum C-reactive protein (CRP) is involved in the acute phase reaction after surgery, even though its clinical significance remains a matter of debate. We evaluated CRP levels in cardiac surgery patients without clinical or laboratory signs of infection. METHODS: We screened 737 consecutive patients referred to our center 8+/-5 days after cardiac surgery. Patients with fever (>37.2 degrees C), elevated white blood cell count (>11,000/ml), neutrophilia (>70%), or any inflammatory, infective or malignant disease were excluded. CRP levels were measured on admission and at discharge and the values were related to the following variables: age, sex, diabetes mellitus, renal failure, type of surgery, postoperative atrial fibrillation, pericardial or pleural effusion, and length of hospital stay. Follow-up (mean: 23+/-8.5 months) was available for 175 patients (94%). RESULTS: In the 187 patients enrolled in the study, the CRP values were significantly elevated (median: 4.23 mg/dl, interquartiles range: 2.68-6.64) independent of any variable analyzed. At discharge, CRP levels were significantly reduced compared with values on admission (median: 1.55 mg/dl, interquartiles range: 0.84-2.37, P<0.001). At follow-up, 19 events (10.8%) occurred (two noncardiac deaths, 17 hospital readmissions for cardiac reasons); nonetheless, no correlation was found with CRP values either on admission or at discharge. CONCLUSION: Early after cardiac surgery, in patients without clinical or laboratory signs of acute infection, CRP levels are significantly elevated, do not correlate with clinical variables, and decrease at discharge. These findings suggest a systemic inflammatory response to surgery-related stress, which carries a favorable prognosis at follow-up.

Time since menopause influences the acute and chronic effect of estrogens on endothelial function.

OBJECTIVE: We evaluated whether time since menopause influences the acute and chronic effect of Estradiol (E) on vascular endothelial function. METHODS AND RESULTS: We studied flow-mediated dilatation (FMD) in 134 postmenopausal women (PMW) before and after acute and chronic E administration. At baseline FMD was inversely associated to time from menopause (r=-0.67, P<0.001) and age (r=-0.43, P<0.05), in exogenous estrogen naïve but not in previous users. Acute and chronic E improved endothelial function in all women. E administration improved FMD more in women within 5 years since menopause than in those with more than 5 years since menopause (76% and 74% versus 45% and 48%, acute and chronic E, respectively; P<0.05). Among women with more than 5 years since menopause acute and chronic E increased FMD more in previous E users than in nonusers (59% and 63% versus 31% and 38%, acute and chronic E, respectively; P<0.01). Multivariate analysis showed that time from menopause was a predictor of impaired FMD and of its improvement after acute and chronic E. CONCLUSIONS: Time from menopause influences FMD in PMW. The acute and chronic effect of E on FMD is time dependent and is reduced by a longer time since menopause.

[Car driving after cardiac surgery: clinical aspects, regulations, and legal implications]. / Impatto degli esiti di interventi cardiochirurgici sulla guida dell'automobile: aspetti clinici, medico-legali e normativi.

BACKGROUND: Car driving is one of the most perceived problems by patients after cardiac surgery. The aim of this study was to evaluate the influence of cardiac surgery and median sternotomy on driving performance after a cardiac rehabilitation program. METHODS: Seventy-four consecutive patients, usual car drivers, admitted to our Cardiac Rehabilitation Center after cardiac surgery, were evaluated 60 days from discharge using a five-item questionnaire. Questions were related to resume of car driving, problems related to car driving, and seatbelt wearing. RESULTS: The analysis of the answers indicated that 36% of patients (62% females, 26% males; p = 0.01) stopped car driving after cardiac surgery, owing to the lack of security or fear of either the patients or their relatives. Sixty-four patients continued to drive, however 39% of them reported problems related to driving (irritation, poor concentration, fear, parking maneuvers). Because of persistent post-surgical chest pain, 15% of patients avoided wearing seatbelts, and 7% asked for exclusion following unconventional procedures. CONCLUSIONS: After cardiac surgery, 1 out of 3 patients stops car driving, particularly among female gender; 1 out of 7 patients is seatbelt no wearers and about half of them claim for exemption following procedures not codified. Thus, common rules and recommendations from Scientific Societies are highly warranted.

Bedside diagnosis and follow-up of patients with pleural effusion by a hand-carried ultrasound device early after cardiac surgery.

OBJECTIVES: The aim of this study was to assess the potential value of hand-carried ultrasound (HCU) devices in the diagnosis and follow-up of patients with pleural effusion (PE) after cardiac surgery. METHODS: Seventy consecutive patients were evaluated at bedside early after cardiac surgery, in the upright sitting position, using an HCU device on hospital admission and every 3 days until hospital discharge. The posterior chest wall was scanned along the paravertebral, scapular, and posterior axillary lines. For each hemithorax, an effusion index was derived as the sum of the intercostal spaces between the lower and upper limits of the PE along the lines of scanning, divided by 3. A standard chest radiograph was performed in all patients on hospital admission and at hospital discharge, and was qualitatively scored (0, absent; 1, small; 2, large PE). The findings of the HCU device and radiograph were compared using kappa statistics and the Kruskal-Wallis test. RESULTS: A chest ultrasound was feasible in all patients (mean [+/- SD] time, 5 +/- 2 min). Compared with the chest ultrasound, a physical examination showed a sensitivity of 69% and a specificity of 77%. On hospital admission, the HCU device detected a PE in 72 of 140 hemithoraxes. Agreement with the finding of the radiograph was 76% (kappa = 0.52). In 15 hemithoraxes, the HCU device revealed a PE that had not been diagnosed using the radiograph. Conversely, in 18 hemithoraxes a PE that had been diagnosed with a radiograph was not confirmed by the HCU device. The correlation between ultrasound and radiographic scores was statistically significant (p < 0.001). At hospital discharge, a PE was present in 31 of 140 hemithoraxes according to the findings of the HCU device, and in 38 of 140 hemithoraxes according to the findings of the radiograph (agreement, 78%; kappa = 0.44). CONCLUSIONS: In patients early after cardiac surgery, HCU devices allow rapid PE detection and improve the clinical diagnosis. Compared to a radiograph, this method offers the unique advantage of the bedside evaluation of patients without the need for radiation exposure.

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy.

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.

Comparison of trimetazidine plus sildenafil to chronic nitrates in the control of myocardial ischemia during sexual activity in patients with coronary artery disease.

A large proportion of patients who have erectile dysfunction also have coronary artery disease (CAD). In these patients, nitrate therapy is a contraindication to the use of sildenafil. To assess whether the metabolic anti-ischemic agent, trimetazidine, is effective in controlling episodes of myocardial ischemia during sexual activity in patients who have CAD and use long-term nitrate therapy, we studied 38 men (57 +/- 6 years of age) who had proved CAD. Patients underwent 24-hour ambulatory electrocardiographic monitoring at baseline, after 1 week of oral nitrate therapy (20 mg 3 times a day), and after 1 week of trimetazidine (20 mg 3 times a day). Patients were asked to engage in >/=1 session of sexual intercourse during each session of ambulatory electrocardiographic monitoring. They were instructed to take sildenafil (100 mg) 1 hour before sexual intercourse performed at baseline and during therapy with trimetazidine and sildenafil or placebo (blinded) during therapy with nitrates. A decrease in total ischemic burden was observed with nitrates and trimetazidine compared with baseline (-3 +/- 1.2 episodes/patient/24 hours vs -5 +/- 1.3 episodes/patient/24 hours and -6 +/- 5 min/patient/24 hours vs -8 +/- 3 min/patient/24 hours, p <0.01 for nitrates and trimetazidine vs baseline). Trimetazidine plus sildenafil was more effective in controlling episodes of myocardial ischemia during sexual activity than nitrates alone (-45 +/- 11% vs -18 +/- 7%, p <0.04). In conclusion, in patients who have CAD, combination therapy with sildenafil and trimetazidine is more effective than nitrate therapy in the control of ischemic episodes during sexual activity, suggesting that long-term nitrate therapy may be safely switched to trimetazidine therapy when therapy for erectile dysfunction is required.

Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk.

The aim of the present study was to evaluate the effect of increased serum uric acid (UA) levels and their therapeutic reduction with allopurinol on endothelium-dependent dilation in subjects with a high cardiovascular (CV) risk but who were free from clinical CV disease. Patients with hyperuricemia had impaired flow-mediated dilation (FMD) compared with matched controls with normal UA levels and elevated CV risk. Three-month therapy with allopurinol improved FMD in hyperuricemic subjects, showing an intrinsic negative effect of elevated UA levels on the arterial wall; conversely, FMD remained unchanged in controls, thus suggesting that the reduction of UA to less than a certain value does not affect endothelial function.

Acute myocardial infarction from spontaneous coronary artery dissection a case report and review of the literature.

Spontaneous coronary artery dissection is a rare event as a cause of acute myocardial infarction. Optimal treatment remains unclear. In this report, we describe a case of spontaneous acute coronary artery dissection presenting as recurrent acute myocardial infarction in a postmenopausal woman, successfully treated with systemic thrombolysis. The case is discussed with review of the pertinent literature.

In patients with coronary artery disease endothelial function is associated with plasma levels of C-reactive protein and is improved by optimal medical therapy.

BACKGROUND: Endothelial function is impaired in patients with coronary artery disease (CAD); in these patients plasma levels of C-reactive protein (CRP) and impaired endothelial function are related to future cardiac events. The aim of the present study was to evaluate the effects of medical therapy on endothelial function and CRP in patients with CAD. METHODS: Seventy-three patients (52 men, 21 women, mean age 66 +/- 9 years) with CAD and 32 control subjects (25 men, 7 women, mean age 65 +/- 11 years) were enrolled in the study. The endothelial function was evaluated by means of flow-mediated dilation (FMD) of the brachial artery following ischemia and CRP by means of a high-sensitivity assay. After baseline evaluation of CRP and FMD all patients received full medical therapy for 3 months and were then again tested for endothelial function and CRP. RESULTS: Compared to healthy controls, patients had significantly more impaired endothelial function (FMD 3.6 +/- 3.2 vs 8 +/- 2.4%, p < 0.01) and higher CRP plasma levels (1.6 +/- 0.9 vs 0.9 +/- 0.56 mg/dl, p < 0.05). At baseline a significant negative correlation was found between CRP plasma levels and FMD in patients with CAD (r = -0.56, p < 0.05) while no correlation was found in controls. Medical therapy resulted in a significant improvement in endothelial function (3.64 +/- 3 vs 7.2 +/- 3.5%, p < 0.01), and a decrease of CRP (-0.26 +/- 0.19, p < 0.01); the changes in CRP and FMD were independent of the drug used. A positive correlation was found between the improvement in FMD and the degree of CRP reduction (r = 0.57, p < 0.01). CONCLUSIONS: In patients with CAD plasma levels of CRP are associated with an impaired endothelial function suggesting a correlation between inflammation and the integrity of the endothelium. Full medical therapy reduces CRP with a parallel improvement in endothelial function.

Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo.

AIMS: Patients with cardiovascular diseases frequently complain of erectile dysfunction especially when treated with beta-blockers. In order to assess whether the effect of beta-blockers on erectile dysfunction is in part related to patient knowledge of the drug side effects, 96 patients (all males, age 52+/-7 years) with newly diagnosed cardiovascular disease and not suffering from erectile dysfunction entered a two phase, single cross over study. METHODS AND RESULTS: During the first phase of the study patients received atenolol 50mg o.d. (A), 32 patients were blinded on the drug given (group A), 32 were informed on the drug given but not on its side effects (group B) and 32 took A after being informed on its side effects on erectile function (group C). After 3 months the incidence of erectile dysfunction was 3.1% in the group A, 15.6% in group B and 31.2% in group C (P<0.01). All patients reporting ED entered the second phase of the study and were randomised to receive Sildenafil 50mg and placebo in a cross over study. Sildenafil citrate and placebo were equally effective in reversing erectile dysfunction in all but one patient reporting ED with Atenolol. CONCLUSION: Our results show that the knowledge and prejudice about side effects of beta-blockers can produce anxiety, that may cause erectile function.