Exercise training improves erectile dysfunction (ED) in patients with metabolic syndrome on phosphodiesterase-5 (PDE-5) inhibitors.

INTRODUCTION: Erectile dysfunction (ED) affects about 50% of males aged 40-70 years old. ED shares with atherosclerotic disease several common risk factors; therefore, it may be considered a surrogate marker of atherosclerosis. Since phosphodiesterase-5 inhibitors are well known pharmacologic agents capable of significant improvement in ED, we designed this study to evaluate whether exercise training is of added value in patients with ED who are already on PDE-5 inhibitors. METHODS: We recruited 20 male patients affected by ED with metabolic syndrome. At baseline, all patients underwent Cardio-Pulmonary Exercise Testing (CPET) and the International Index of Erectile Function (IIEF) test. After the initial evaluation, patients were subdivided into two groups: tadalafil group (group T, n = 10), who were maintained only on tadalafil therapy, and a tadalafil/exercise training group (T/E group, n = 10) who continued tadalafil but in addition underwent a2-month structured exercise training program. RESULTS: Basal anthropometric characteristics of study population showed no significant differences. Although both-groups showed at 2 months an improvement of the IIEF score, this was more evident in the T/E group (T group: 11.2 vs 14.2, P = 0.02; T/E group: 10.8 vs 20.1, P < 0.001). There was an improvement of oxygen consumption at peak exercise (VO(2peak)) only in the T/E group patients (T group: 13.63 +/- 2.03 vs 14.24 +/- 2.98 mL/kg/min; P = 0.521; T/E group: 13.41 +/- 2.97 vs 16.58 +/- 3.17 mL/kg/min; P = 0.006). A significant correlation was found between the changes in VO(2peak) and the modifications in IIEF score (r = 0.575; P = 0.001). CONCLUSION: Exercise training in ED patients treated with PDE-5 inhibitors is of added value since further improves ED, as evaluated by IIEF score, and increases functional capacity.

[Takotsubo syndrome in a young woman during puerperium: case report]. / Sindrome di Takotsubo nel puerperio: caso clinico.

INTRODUCTION: Takotsubo syndrome is a reversibile cardiomyopathy that often occurs during an emotional stress and is more frequent in post-menopausal women. CASE PRESENTATION: We describe a clinic case of a 42 years old woman, admitted to our emergency unit because of a thoracic pain. The ECG showed ST-T elevation in V1-V4, the echocardiography revealed akinesia of apical segment of left ventricle. Coronary arteries were free from significant stenosis and ventriculography showed akinesia of apical segment of left ventricle. In the following days, ECG evolved toward a normalization of ST-T segment with appearance of negative T wave in V2-V6, and also the echocardiography showed a normalized LV wall motion. The patient was discharged and ECG and echocardiography were normal at two months follow up. CONCLUSION: In this case report, a young woman during puerperium presented with a Takotsubo syndrome. We speculate that the high Prolactin level and her emotional state contributed to the clinical manifestation of the syndrome.

Effects of exercise training on high-mobility group box-1 levels after acute myocardial infarction.

BACKGROUND: High-mobility group box-1 (HMGB1) is a novel predictor of adverse postinfarction clinical outcomes, playing a crucial role in the appropriate postinfarction healing process. METHODS AND RESULTS: Seventy-five postinfarction patients were enrolled in a single-center randomized study (clinicaltrial.gov identifier: NCT00755131). Group T patients (training, n = 37) underwent 6-month exercise-based cardiac rehabilitation (CR) program, whereas group C patients (controls, n = 38) were discharged with generic instructions for maintaining physical activity and a correct lifestyle. After 6 months, HMGB1 levels were significantly reduced in the total population (26.1 ± 23.5 vs. 16.2 ± 12.9 ng/mL; P = .0006). After adjusting for several confounders, linear regression analysis showed that the inclusion in the training group (ß = -10.54, P = .043) was associated with marked reduction of HMGB1 levels. After 6 months, HMGB1 levels were significantly lower in trained patients compared to controls (11.7 ± 7.0 vs. 20.5 ± 15.6 ng/mL, P = .0027, respectively). In trained patients, decreased HMGB1 levels were significantly associated with the improvement in peak oxygen consumption (ß = -3.879, P = .003) and heart rate recovery (ß = -2.492, P = .002), and with reduced left ventricular end-diastolic volume (ß = 1.412, P = .001) and wall motion score index (ß = 1.138, P = .002). CONCLUSIONS: The decrease in HMGB1 levels after anterior myocardial infarction was associated with exercise training and with the improvement of cardiopulmonary and autonomic function, and with favorable cardiac remodeling.

Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction.

BACKGROUND: High mobility group box-1 (HMGB1) protein, a critical mediator of inflammatory processes, is a novel predictor of adverse post-infarction clinical outcomes, being involved in the healing process after MI. Heart rate recovery (HRR), a marker of autonomic function defined as the fall in heart rate during the first minute after exercise, is a powerful predictor of mortality in post-infarction patients. The present study was designed to test the hypothesis that HMGB1 is associated with autonomic dysfunction in post-infarction patients. METHODS: Sixty-seven consecutive patients (mean age 59.3 years, 84% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise and HMGB1 assay. RESULTS: HMGB1 levels were inversely correlated with peak oxygen consumption (VO(2peak)) (r=-0.449, P<0.001), with left ventricular ejection fraction (LVEF) (r=-0.360, P=0.003), and with HRR (r=-0.387, P<0.001). In a linear regression analysis adjusted for multiple confounders, we found a significant inverse association between HMGB1 levels and HRR independent of age, gender, body mass index, VO(2peak), slope of increase in ventilation over carbon dioxide output (VE/VCO(2slope)), and presence of diabetes (beta=-0.377, P=0.034). CONCLUSIONS: This study provided the first evidence for a significant association between increased HMGB1 levels and autonomic dysfunction expressed by post-exercise slower HRR in post-infarction patients. The prognostic implication of such association needs to be explored as well as whether HMGB1 could represent a valid marker for risk stratification either during the acute phase or long-term after MI.

Two-year multicomprehensive secondary prevention program: favorable effects on cardiovascular functional capacity and coronary risk profile after acute myocardial infarction.

BACKGROUND: Cardiac rehabilitation includes interventions aimed at facilitating physical, psychological and emotional recovery following the acute phase of myocardial infarction (AMI). To date, optimal cardiac rehabilitation program duration and frequency of patient contact has yet to be identified. OBJECTIVE: The present study was performed to evaluate the effects of two different strategies of secondary prevention (2 years, multifactorial continued educational and behavioral intervention versus usual care) implemented into a cardiac rehabilitation setting on several cardiovascular endpoints indicating cardiovascular functional exercise capacity and coronary risk profile in patients with recent AMI. METHODS: This was a prospective randomized study including 52 postinfarction patients. Initially, all patients were enrolled in a 3-month outpatient cardiac rehabilitation program. Thereafter, they were randomly subdivided into two groups (I = intervention group; C = control group), each composed of 26 patients, and followed for 24 months. RESULTS: At the end of the 3-month outpatient cardiac rehabilitation program, both groups showed a significant (P < 0.05) improvement in cardiopulmonary parameters (maximal oxygen consumption, maximal workload) and in cardiovascular risk profile (BMI, lipid profile). During the 24-month study period, group I showed stabilization or even improvement (P < 0.05) of both cardiopulmonary parameters and cardiovascular risk profile, whereas group C patients showed a deterioration or significant impairment (P < 0.05) of the same parameters. Clinical events occurred in 27% of patients in the control group (n = 7) and in 11% in the training group (n = 3) (P < 0.05). CONCLUSION: Long-term, multifactorial educational and behavioral intervention maintained for 2 years in a multicomprehensive cardiac rehabilitation setting represents a valid strategy for improving long-term cardiovascular functional capacity and cardiovascular risk profile in postinfarction patients.

Effects of exercise-based cardiac rehabilitation on high mobility group box-1 levels after acute myocardial infarction: rationale and design.

BACKGROUND: High-mobility group box-1 (HMGB1) is a ubiquitous nuclear protein recently recognized as a critical mediator of inflammatory processes. HMGB1 is a novel predictor of adverse postinfarction clinical outcomes, playing a crucial role in the appropriate healing process after myocardial infarction (MI). The present trial is designed in order to reveal the postinfarction HMGB1 expression pattern and its relationship with cardiac remodeling. The effects of an exercise-based cardiac rehabilitation program on HMGB1 expression pattern will be addressed as well. DESIGN: Single-center, randomized, controlled study carried out at a university hospital. METHODS: Postinfarction patients are randomized into a training group (enrolled in a 6-month exercise-based cardiac rehabilitation program) and into a control group. HMGB1 levels are evaluated by enzyme-linked immunosorbent assay. RESULTS: Postinfarction patients are enrolled from September 2008 through December 2009. Results will be available in mid-2010. CONCLUSION: Despite the importance of the inflammatory response and healing process in postinfarction left ventricular remodeling, the mechanisms that initiate and control these processes remain to be elucidated. The rationale and design of the present study is designed to test the postinfarction HMGB1 expression pattern and its relationship with cardiac remodeling as well as the effects of an exercise-based cardiac rehabilitation program.

Increased high mobility group box-1 protein levels are associated with impaired cardiopulmonary and echocardiographic findings after acute myocardial infarction.

BACKGROUND: Several markers of systemic inflammation seem to play an active role in the pathophysiology of acute coronary syndrome and its evolution. High mobility group box-1 (HMGB-1), a ubiquitous nuclear protein constitutively expressed in quiescent cells, was recently recognized as a newer critical mediator of inflammatory diseases. The present study aimed to evaluate the possible association between HMGB-1 levels and structural and functional indices of cardiovascular performance such as cardiopulmonary and Doppler-echocardiography indices in patients after acute myocardial infarction (MI). METHODS AND RESULTS: Fifty-four consecutive patients (mean age 58.3 years, 83% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise, and HMGB-1 assay. HMGB-1 levels in acute MI patients were significantly higher compared with age- and body mass index-matched controls (14.8 +/- 6.8 vs. 2.3 +/- 1.0 ng/mL, P < .0001, respectively). Postinfarction patients showed oxygen consumption at peak exercise (VO(2 peak)) = 14.4 +/- 4.2 mL x kg x min and a slope of increase in ventilation over carbon dioxide output (VE/VCO(2 slope)) = 32.1 +/- 6.2, whereas Doppler-echocardiography values were: left ventricular end-diastolic volume (LVEDV) = 53.4 +/- 8.2 mL/m(2); left ventricular ejection fraction (LVEF) = 41.7 +/- 7.0%. Multiple linear regression analysis (stepwise method) showed that VO(2 peak) (beta = -0.276, P = .012), VE/VCO(2 slope) (beta = 0.244, P = .005), LVEDV (beta = 0.267, P = .018), peak creatine kinase-MB (beta = 0.339, P = .004), peak Troponin I (beta = 0.244, P = .002), and LVEF (beta = -0.312, P = .021) were significantly associated with HMGB-1 levels. CONCLUSIONS: The present study demonstrated that in postinfarction patients, HMGB-1 levels were significantly higher compared with controls, and significantly correlated with cardiopulmonary and Doppler-echocardiography parameters.

Favourable effects of exercise-based Cardiac Rehabilitation after acute myocardial infarction on left atrial remodeling.

BACKGROUND: Left atrial enlargement is an important predictor of cardiovascular outcomes in patients after acute myocardial infarction. While the favourable effect of exercise exercise-based Cardiac Rehabilitation (CR) on postinfarction LV remodeling has been well documented, those on LA remodeling have yet to be defined. This study investigated the effects of CR on LA remodeling in postinfarction patients with moderate left ventricular (LV) dysfunction. METHODS: Sixty postinfarction patients were randomised randomized into two groups, each composed of 30 patients: group T (LV ejection fraction (EF) 43.7+/-4.2%, mean+/-SD) entered a 6-month CR program, whereas group C (EF 44.7+/-4.4%, P=ns) did not. Doppler echocardiography and cardiopulmonary exercise test were performed upon enrolment and at 6-month. RESULTS: At 6-month, trained patients showed a significant (P<0.001) improvement in peak oxygen consumption (DeltaVO(2peak)=+5.2+/-2.1 ml/kg/min) and a reduction in LA (DeltaLAV(MAX)=-1.9+/-3.7 ml/m(2)) and in LV volumes (DeltaLVEDV=-3.6+/-4.4 ml/m(2)). At 6-month, untrained patients showed LAV(MAX) (+3.6+/-4.4 ml/m(2), P<0.001) and LV dilation (+4.2+/-5.1 ml/m(2), P<0.001; group T vs. C, P<0.001); whereas no significant changes in VO(2peak) were observed. Multiple linear regression analysis showed that age (beta=0.442, P<0.001), inclusion in the training group (beta=-0.599, P<0.001), E/A ratio (beta=-0.210, P=0.038), LVEDV (beta=0.376, P<0.001), and LVEF (beta=-0.279, P=0.007) are significant predictors of LA remodeling. CONCLUSIONS: Six-month exercise-based CR in postinfarction patients with mild to moderate LV dysfunction induced a favourable LA remodeling.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

AIMS: To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. METHODS: Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. RESULTS: At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). CONCLUSIONS: Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Favourable effects of exercise training on N-terminal pro-brain natriuretic peptide plasma levels in elderly patients after acute myocardial infarction.

BACKGROUND: regional or global impairment of left ventricular (LV) systolic or diastolic function leading to increased LV wall stress results in increased circulating levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP). OBJECTIVE: this study aims at evaluating the effect of exercise training (ET) on NT-pro-BNP plasma levels in older patients recovering from acute myocardial infarction (AMI). DESIGN: prospective randomised study. SETTING: Academic Medical Centre. SUBJECTS: forty older patients (33 males and 7 females) who experienced AMI. METHODS: patients were randomised into two groups, each composed of 20 patients: Group A were enrolled in a 3-month exercise-based cardiac rehabilitation (CR) programme and Group B were discharged home with generic instructions to continue physical activity. NT-pro-BNP, cardiopulmonary and Doppler-echocardiographic parameters were measured at baseline and at 3-month follow-up. RESULTS: in Group A, ET reduced NT-pro-BNP levels (from 1446 +/- 475 to 435 +/- 251 pg/ml, P<0.001) and increased maximal exercise parameters; there was also an inverse correlation between changes in NT-pro-BNP levels and in VO(2peak) (r = -0.67, P<0.01), E-wave (r = -0.42, P<0.01) and E/A ratio (r = -0.60, P<0.01). In Group B, after 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. LV volumes and left ventricular ejection fraction (LVEF) were unchanged after 3 months in both groups. CONCLUSIONS: three months ET in older patients after AMI was associated with a reduction in NT-pro-BNP levels and an overall improvement of exercise capacity, without negative LV remodelling and with improvement in early LV filling. Further investigation is required to evaluate whether in these patients the reduction of NT-pro-BNP levels at 3 months could be useful as a surrogate marker of favourable LV remodelling at a later follow-up.

Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction.

BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone that is a powerful predictor of mortality in patients with coronary artery disease. DESIGN: This study aims at evaluating the effects of long-term exercise training on HRR after acute myocardial infarction (AMI), in order to clarify whether prolonged exercise training could maintain a long-term improvement of HRR. METHODS: Forty-four patients after AMI were enrolled in a 3-month hospital-based exercise training programme. At the end, patients were subdivided into two groups: group A (n=22), patients discharged with a specific home-based exercise training programme and instructions for improving leisure-time physical activity; group B (n=22), patients discharged with generic instructions to maintain physical activity. All patients underwent a cardiopulmonary exercise test before, at the end of 3 months exercise training and at 6 months follow-up. RESULTS: At the end of the hospital-based exercise training programme we observed an increase in peak oxygen consumption [VO2peak; from 13.9+/-3.6 to 18+/-2.7 ml/kg per min (A) and from 14.1+/-3.9 to 17.9+/-2.1 ml/kg per min (B), P<0.001] and in HRR [from 17.1+/-1.8 to 23.4+/-1.4 beats/min (A), and from 18.8+/-2.1 to 24.3+/-1.9 beats/min (B), P<0.001]. At 6 months' follow-up we observed a further improvement in VO2peak (from 18.0+/-2.7 to 20.3+/-2.7 ml/kg per min, P<0.001) and in HRR (from 23.4+/-1.4 to 27.8+/-2.1 beats/min, P<0.001) in group A, but a significant decrease in VO2peak and in HRR in group B (P<0.001). CONCLUSION: Long-term exercise training is useful for maintaining or improving the beneficial results of the standard 3-month exercise training programme on cardiovascular capacity and HRR. This observation may bear beneficial prognostic effects on patients after AMI.

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

INTRODUCTION: N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. METHODS: Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. RESULTS: In Group A, exercise training reduced NT-pro-BNP levels (from 1498+/-438 to 470+/-375 pg/ml, P=0.0026), increased maximal (VO2peak+4.3+/-2.9 ml/kg per min, P<0.001; Powermax+38+/-7, P<0.001) exercise parameters and work efficiency (Powermax/VO2peak+1.3+/-0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in VO2peak (r=-0.72, P<0.001), E-wave (r=-0.51, P<0.001) and E/A ratio (r=0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. CONCLUSION: Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.

Exercise-based cardiac rehabilitation improves heart rate recovery in elderly patients after acute myocardial infarction.

BACKGROUND: Heart rate recovery (HRR), defined as the fall in HR during the first minute after exercise, is a marker of vagal tone, which is a powerful predictor of mortality in patients with coronary artery disease and in older patients. Whether exercise training (ET) modifies HRR in elderly patients recovering from acute myocardial infarction (AMI) is still unknown. Therefore, this study aims at evaluating the effect of ET on HRR in elderly AMI patients. METHODS: This was a prospective observational study including 268 older patients after AMI (217 men, 51 women), subdivided in two groups: Group A (n = 104), enrolled in an ET program; Group B (n = 164), discharged with generic instructions to continue physical activity. At baseline and at 3-month follow-up, all Group A and 54/164 Group B patients underwent a cardiopulmonary exercise stress test, whereas 110/164 Group B patients underwent an exercise stress test. RESULTS: After completion of the ET program, in Group A we observed an improvement in oxygen consumption at peak exercise (VO2peak; from 14.7 +/- 1.3 to 17.6 +/- 1.9 mL/kg/min, p < .001), in the rate of increase of ventilation per unit of increase of carbon dioxide production (VE/VCO2slope; from 34.2 +/- 3.8 to 30.4 +/- 3.0, p < .001), and in HRR (from 13.5 +/- 3.7 to 18.7 +/- 3.5 beats/min, p < .001). The changes in VO2peak and in VE/VCO2slope after ET were correlated with the improvement of HRR (r = -0.865, p < .01; r = -0.594, p < .01, respectively). No changes in these parameters were observed in Group B patients. CONCLUSIONS: In older AMI patients, ET results in HRR improvement, which was correlated to the improvement in cardiopulmonary parameters. These findings may shed additional light on the possible mechanisms of the beneficial prognostic effects of ET in this patient population.

Role of smokers in the household and of cardiac rehabilitation in smoking behaviour after acute myocardial infarction.

OBJECTS: This study aims to evaluate the influence of household smokers and of a prolonged, comprehensive home-based Cardiac Rehabilitation Program (CRP) on patient's long term smoking behaviour after AMI. METHODS: 164 male post-AMI patients, all smokers until the day of AMI, were subdivided into three groups: Group A (n=54): patients with recent AMI, discharged from hospital without enrolment in CRP; Group B (n=55): similar to Group A but enrolled in an 8 weeks hospital-based CRP and then discharged home with routine care; Group C (n=55) enrolled in an 8 weeks hospital-based CRP followed by a further 10 months of formal home-based CRP, with scheduled hospital follow-up visits. RESULTS: Smoking resumption at 12 months was influenced by the presence of household smokers (HS): 38% of patients with HS resumed smoking compared to 27% of patients without HS (p <0.01). Adherence to a CRP was inversely correlated to smoking resumption: there were fewer smoking patients at 12 months from AMI in Group C than in Groups A or B (11% in C vs. 29% and 55% in B and A, respectively, p <0.001). CONCLUSIONS: Long term maintenance of CRP seems to be the best way to achieve a reduction of long term smoking habit and maintain adherence to prescription in patients after AMI. Counselling and behavioural intervention should also be extended to family members in order to maximize the benefit of secondary prevention.