Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study.

Aim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.

Left ventricular hypertrophy as protective factor after bypass grafting.

Left ventricular hypertrophy (LVH) is a well established cardiovascular risk factor, accounting for an increase in cardiovascular morbid-mortality, although how much the magnitude and the kind of LVH could affect cardiovascular outcomes is in large part unknown. We speculate that mild LVH in absence of left ventricular (LV) chamber dilation, could play a protective role towards functional capacity, clinical outcome, cardiovascular and total morbi-mortality in conditions in which LV systolic function is generally reduced. Accordingly to many epidemiological observations, the availability of extra-quote of systolic function could lead to a significative improvement in the final outcome of some kinds of heart patients, as those undergoing bypass-grafting, where the stress for heart and cardiovascular system is always high. We suppose that the functional reserve available for patients with LVH could make the difference with respect to other patients undergoing myocardial revascularization. Similarly, the availability of a contractile reserve warranted by LVH could ensure a little gain in the outcome for patients after other major cardiovascular events (such as myocardial infarction or other heart surgery as surgical valve replacement). However, our hypothesis only involves mild LVH without LV chamber dilation, that is the initial stage of "non-dilated concentric" LVH and "non-dilated eccentric" LVH according to the new four-tiered classification of LVH based on relative wall thickness and LV dilation. Support for our hypothesis derives from the well-known protective role of systolic function that is a major factor in almost all cardiovascular diseases, where LV ejection fraction (LVEF) has shown to significantly improve quality of life, as well as morbidity and mortality. The knowledge that mild LVH in absence of LV chamber dilation is not as harmful in such conditions as believed at present could make avoidable some drugs prescription in some stages of the disease. Furthermore, it may allow a better evaluation of the risk profile of patients with LVH undergoing some cardiovascular major events like bypass grafting, myocardial infarction or surgical heart valve replacement.

Exercise training effects on elderly and middle-age patients with chronic heart failure after acute decompensation: A randomized, controlled trial.

BACKGROUND: The aim of this study was to evaluate the effect of exercise training on cardiac function in heart failure (HF) patients recently suffering from acute decompensation. Radionuclide ambulatory ventricular function monitoring (VEST) was used to detect variations in cardiac hemodynamics during training period. METHODS: This was a monocentric, randomized, controlled trial. We enrolled 72 HF patients [left ventricle ejection fraction (LVEF) <40%] within two weeks after acute cardiogenic pulmonary edema: 40 in the elderly group, 32 in the middle-aged group. Trained patients underwent a specific four-weeks exercise program (closed-chain resistive activities and abdominal exercises) which was supervised by a therapist in agreement with patients' characteristics. Catecholamines at rest, echocardiography, right-heart catheterization, and bicycle ergometer were performed. VEST was performed at the end of the 4weeks-training in all patients in order to assess patients' cardiac hemodynamics [LVEF, cardiac output (CO), stroke volume]. RESULTS: Exercise training significantly improved exercise duration, peak oxygen consumption, and ventilatory threshold both in elderly and middle-aged patients (p<0.0001) after the 4-week controlled training. Despite age (F=35.086, p<0.0001; F=16.967, p<0.0001; F=42.574, p=0.03, respectively), training reliably influence previous cardiopulmonary parameters (F=29.402, F=16.421, F=26.80, p<0.0001, respectively). Norepinephrine and epinephrine were significantly reduced in both trained groups. Peak LVEF (37.3±4.7% vs 34±6.2%, p=0.002), peak stroke volume (43.3±3.9% vs 37.5±4.3%, p=0.001), and peak CO (63.4±6.1% vs 48.2±4.7%, p<0.0001) increased in middle-aged patients after 4-week training. CONCLUSIONS: Exercise training improves cardiac performance indexes and pulmonary function in both middle-aged and elderly HF patients early after an acute episode of cardiac decompensation.

Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis.

BACKGROUND AND OBJECTIVES: The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. METHODS: Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. RESULTS: The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m(2). The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. CONCLUSIONS: Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

ß-adrenergic receptor responsiveness in aging heart and clinical implications.

Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called "ß-adrenergic desensitization"). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the ß-adrenergic receptor density reduction and to the ß-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of ß-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) ß1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular ß-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure.

Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure.

BACKGROUND: Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related ß-adrenergic receptor (ßAR) dysfunction. Importantly, abnormalities of ßAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac ßAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients. METHODS: For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months. RESULTS: Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome. CONCLUSIONS: Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.

Adrenergic signaling and oxidative stress: a role for sirtuins?

The adrenergic system plays a central role in stress signaling and stress is often associated with increased production of ROS. However, ROS overproduction generates oxidative stress, that occurs in response to several stressors. ß-adrenergic signaling is markedly attenuated in conditions such as heart failure, with downregulation and desensitization of the receptors and their uncoupling from adenylyl cyclase. Transgenic activation of ß2-adrenoceptor leads to elevation of NADPH oxidase activity, with greater ROS production and p38MAPK phosphorylation. Inhibition of NADPH oxidase or ROS significantly reduced the p38MAPK signaling cascade. Chronic ß2-adrenoceptor activation is associated with greater cardiac dilatation and dysfunction, augmented pro-inflammatory and profibrotic signaling, while antioxidant treatment protected hearts against these abnormalities, indicating ROS production to be central to the detrimental signaling of ß2-adrenoceptors. It has been demonstrated that sirtuins are involved in modulating the cellular stress response directly by deacetylation of some factors. Sirt1 increases cellular stress resistance, by an increased insulin sensitivity, a decreased circulating free fatty acids and insulin-like growth factor (IGF-1), an increased activity of AMPK, increased activity of PGC-1a, and increased mitochondrial number. Sirt1 acts by involving signaling molecules such P-I-3-kinase-Akt, MAPK and p38-MAPK-ß. ßAR stimulation antagonizes the protective effect of the AKT pathway through inhibiting induction of Hif-1α and Sirt1 genes, key elements in cell survival. More studies are needed to better clarify the involvement of sirtuins in the ß-adrenergic response and, overall, to better define the mechanisms by which tools such as exercise training are able to counteract the oxidative stress, by both activation of sirtuins and inhibition of GRK2 in many cardiovascular conditions and can be used to prevent or treat diseases such as heart failure.

Diffuse idiopathic skeletal hyperostosis prevalence in subjects with severe atherosclerotic cardiovascular diseases.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheseal sites. Several metabolic factors have been suggested to be involved in DISH development. We assessed the prevalence of DISH and its relationship to traditional vascular risk factors in a cohort of patients diagnosed with cardiovascular diseases. METHODS: Among the 521 consecutive patients admitted to the heart diseases rehabilitation program in our Rehabilitative Cardiology Unit, only those (n = 436) with recent coronary artery bypass grafting (CABG), a heart valve replacement (HVR), or congestive heart failure (CHF) were enrolled (45 CHF, 338 CABG, and 53 HVR). All patients underwent a rheumatologic examination, blood sample collections, and chest radiographs. Body mass index (BMI), blood pressure, and information about sex, age, smoking habit, and other vascular risk factors were recorded. DISH was established according to the Resnick and Niwayama criteria. RESULTS: In the setting (77.1% men), the mean ± SD age was 65.44 ± 9.66 years and the overall prevalence of DISH was 30.3%. A logistic regression analysis showed that both age (odds ratio [OR] 1.076, 95% confidence interval [95% CI] 1.044-1.109; P < 0.001) and obesity (OR 2.28, 95% CI 1.33-3.89; P = 0.003) were significant predictors of the presence of DISH. An increasing OR for the presence of DISH was found for increasing tertiles of age and BMI. No difference resulted according to other traditional vascular risk factors. BMI and age directly correlated with C-reactive protein levels. CONCLUSION: The overall prevalence of DISH was 30.3%. This is expected because of the study population. Obese and older individuals exhibit a higher risk of DISH development.

Gender differences in cardiac rehabilitation programs from the Italian survey on cardiac rehabilitation (ISYDE-2008).

PURPOSE: In recent years epidemiological and clinical evidence has shown gender disparities in several aspects of cardiovascular disease. Aim of this study was to identify gender differences in the clinical profile and management of patients admitted to cardiac rehabilitation (CR) programs. POPULATION: Patients enrolled in the ISYDE-2008 survey were considered. RESULTS: The ISYDE-2008 survey enrolled 2281 patients; 604 (26.5%) were women. Compared to men, women were older (mean age 70.8 ± 11.5 versus men's 65.6 ± 11.5 years), had less traditional risk factors (low cardiovascular risk profile in 45.3% of women and 38.0% of men, p=0.003), were more frequently admitted after valvular surgery and heart failure, but less for post-acute myocardial infarction and post-by-pass procedure. Women were more frequently admitted to an in-hospital rehabilitation program. Women showed a more complicated acute and rehabilitative course, with 63.2% of them having at least one complication during acute-phase, compared to 52.5% of men, and 48.3% during rehabilitation, compared to 35.0% of men (p<0.0001). During rehabilitation, women underwent exercise tests less frequently, except for the 6-minute walking test. At discharge, women received ACE-inhibitors/ARBs, ß-blockers, statins, omega-3 fatty acids, antiplatelet agents less frequently, but more frequently digoxin, amiodarone, diuretics, oral anticoagulants, insulin and anti-depressive drugs. The duration of the rehabilitation program was longer for women. Mortality was very low in the entire population. CONCLUSIONS: Women are less frequently admitted to CR than men. They are older and show a greater cardiovascular burden. Women are more likely to be enrolled in CR after valvular surgery and heart failure than men.

[Standards and outcome measures in cardiovascular rehabilitation. Position paper GICR/IACPR]. / Requisiti e indicatori in cardiologia riabilitativa: documento di consenso del GICR/IACPR.

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic problem in Italy. Costs and resources required are increasing in close correlation to both the improved quality of care and to the population ageing. There is an overwhelming evidence of the efficacy of cardiac rehabilitation (CR) in terms of reduction in morbidity and mortality after acute cardiac events. CR services are by definition multi-factorial and comprehensive. Furthermore, systematic analysis and monitoring of the process of delivery and outcomes is of paramount importance. The aim of this position paper promoted by the Italian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR) is to provide specific recommendations to assist CR staff in the design, evaluation and development of their care delivery organization. The position paper should also assist health care providers, insurers, policy makers and consumers in the recognition of the quality of care requirements, standards and outcome measure, quality and performance indicators, and professional competence involved in such organization and programs. The position paper i) include comprehensive CR definition and indications, ii) describes priority criteria based on the clinical risk for admission to both inpatient or outpatient CR, and iii) defines components and technological, structural and organizing requirements for inpatient or outpatient CR services, with specific indicators and standards, performance measures and required professional skills. A specific chapter is dedicated to the requirements for highly specialized CR services for patients with more advanced cardiovascular diseases.

Six-minute walking test but not ejection fraction predicts mortality in elderly patients undergoing cardiac rehabilitation following coronary artery bypass grafting.

BACKGROUND: Age-related effects on the ability of 6-min walking test (6MWT) and ejection fraction (EF) to predict mortality in coronary artery bypass grafting (CABG) patients undergoing cardiac rehabilitation (CR) is still debated. DESIGN AND METHODS: In order to verify the role of 6MWT and EF on all-cause mortality in patients undergoing CR following CABG, 882 CABG patients undergoing CR stratified in adults (<65 years) and elderly (≥65 years) were studied. RESULTS: At the admission, EF was 52.6 ± 9.1% in adults and 51.3 ± 8.9% in elderly (p = 0.234, NS) while 6MWT was 343.8 ± 93.5 m in adults and 258.9 ± 95.7 m in elderly (p < 0.001). After 42.9 ± 14.1 months follow up, mortality was 8.2% in adults and 10.9% in elderly (p = 0.176, NS). Cox regression analysis shows that EF ≥ 50% and 6MWT ≥300 m are protective on mortality in all CABG patients before CR. However, EF ≥50% in adults (HR 0.18, 95% CI 0.06-0.49, p < 0.005) but not in elderly (HR 1.16, 95% CI 0.45-3.42, p = 0.354, NS) and 6MWT ≥300 m in elderly (HR 0.34, 95% CI 0.10-0.79, p = 0.033) but not in adults (HR 0.76, 95% CI 0.31-2.12, p = 0.654, NS) exert a protective role on mortality. CONCLUSIONS: Our results indicate that both EF ≥ 50% and 6MWT ≥ 300 m independently protect against mortality in CABG patients before CR. However, their protective role is age dependent. In fact, EF ≥ 50% is protective in adults but not in elderly while 6MWT ≥ 300 m is protective in elderly but not in adult patients.

Reproducibility of heart rate turbulence indexes in heart failure patients.

Cardiovascular oscillations following spontaneous ventricular premature complexes (VPC) are characterized by a short-term heart rate fluctuation known as heart rate turbulence (HRT) described by the so-called turbulence onset (TO) and slope (TS). Despite a recent written consensus on the standard of HRT measurement, reproducibility data are lacking. Aim of the paper was a reproducibility study of HRT indexes in heart failure patients (HF). Eleven HF patients underwent two 24h ECG Holter recordings, spaced 7 ± 5 days. A paired t test was used to assess the clinical stability of patients during the study period and the number of PVC in Holter recordings' couples. Both TO and TS indexes were calculated for each isolated VPC, and due to their skewed distribution, reproducibility of median and mean TO and TS was studied by Bland-Altman technique. Results showed that median HRT indexes might be preferred to commonly suggested mean values and that, although TO showed lower bias value than TS, TS can be considered much more reproducible than TO, comparing limits of agreements with normal values. This preliminary results suggest the use of medians instead of mean HRT indexes values and a reliability of the turbulence slope greater than the turbulence onset index.

An active lifestyle prior to coronary surgery is associated with improved survival in elderly patients.

BACKGROUND: An active lifestyle is associated with a reduced cardiovascular risk in middle-aged as well as in elderly patients. In the present study, we investigated the association between physical activity habits of elderly participants prior to coronary artery bypass grafting (CABG) and survival free from both all-cause and cardiac death. METHODS AND RESULTS: Study population consisted of 587 elderly patients (>or=70 years) CABG patients stratified, according to the Physical Activity Scale for the Elderly (PASE), into less active (low PASE) and exercised (high PASE) groups. At follow-up (mean: 44.3 +/- 21.0 months), 33 (37.1%) of 89 total deaths occurred for cardiac causes. Sixty-month survival rate was 65% and 96% for low-PASE and high-PASE groups, respectively (log rank = 49.460, p < .0001). Cox survival analysis indicated a significant (p < .0001) nonlinear association between PASE score increments and improved survival with the most evident differences in the lowest score categories. A robust association was also found between low PASE score and increased cardiac-related mortality (p < .0001). CONCLUSIONS: Our data indicate that a more active lifestyle is significantly associated with improved survival in elderly CABG patients. The nonlinearity of the relation suggests that more sedentary patients could have the most benefit on survival by increasing their exercise lifestyle habits. The improved outcome is explained by both cardiac and overall mortality reduction.

Hypermagnesemia predicts mortality in elderly with congestive heart disease: relationship with laxative and antacid use.

The aim of this study was to evaluate the role of magnesium levels on 3-year survival in the elderly with congestive heart failure (CHF) admitted to the Rehabilitative Cardiology Unit of S. Maugeri Foundation Scientific Institute of Telese/Campoli. All elderly patients > or = 65 years old with a diagnosis of CHF underwent clinical and instrumental examination, and their demographics, co-morbidity, and in-hospital and 3-year mortality rates were recorded. Hypomagnesemia was found in 4.8%, normomagnesemia in 67.5%, and hypermagnesemia in 27.8% of subjects. The hypomagnesemic group was excluded for numerical exiguity; the analysis was performed on a total of 199 elderly patients. Hypermagnesemia was found in 29.1% and normomagnesemia in 70.9%. At the univariate analysis no differences were found in hypermagnesemia in respect to normomagnesemia group, except for slightly higher levels of creatininemia (1.35 +/- 0.61 vs. 1.13 +/- 0.55 mg/dL, respectively; p < 0.02), greater disability (lost ADL, 2.69 +/- 1.57 vs. 2.15 +/- 1.56, respectively; p < 0.05), more mortality for CHF (32.6 vs. 48.3%; p < 0.05), and higher antacid and laxative use (82.7 vs. 24.8%, respectively; p < 0.0001). Patients with higher magnesium showed less probability to survive at a 3-year follow-up than did patients with lower levels (17.32 +/- 15.93 vs. 22.46 +/- 16.16 months; p < 0.05), and this finding remained significant in the multivariate analysis after adjusting for some confounders. Finally hypermagnesemia should also be considered in the absence of pre-existing renal failure clinical evidence because of its negative prognostic value, especially in elderly patients with CHF. The shown relationship between hypermagnesemia and laxative/antacid use should induce physicians to pay more attention to abuse of these drugs.

Effect of losartan in treatment of exercise-induced myocardial ischemia.

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease. Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind). At the end of each phase a new exercise stress test was performed. At baseline, systolic blood pressure was significantly decreased after losartan 100 mg compared with losartan placebo. At submaximal exercise, systolic blood pressure and rate-pressure product were lower after losartan 100 mg administration compared with losartan placebo, and these findings remained significant at 1-mm ST depression and at peak exercise. Losartan 100 mg administration versus losartan placebo significantly delayed the time to 1-mm ST-depression onset and decreased ST-segment depression at peak exercise and time to recovery of ST-segment depression. Losartan 100 mg administration compared with losartan placebo was able to significantly increase exercise duration and maximal workload during exercise stress testing. In conclusion, in our study, losartan decreased electrocardiographic parameters of myocardial ischemia in patients with coronary artery disease, suggesting a possible role of this drug in treatment of patients with effort myocardial ischemia.

Cardiac rehabilitation in the elderly: patient selection and outcomes.

In Western countries, the aging and improving survival of patients with coronary heart disease are responsible for an increasing number of older adults (65 years of age and older) who are eligible for cardiac rehabilitation. The elderly with coronary heart disease represent a special population with changes induced by aging and lifestyle, comorbidity, cognitive dysfunction, and high risk of disability. Although the elderly account for the majority of cardiac admissions and procedures, studies on cardiac rehabilitation have traditionally focused on younger patients. In aged experimental animals, there is evidence that exercise training is able to improve hemodynamic parameters and biologic markers. Moreover, in older patients, exercise improves functional capacity and reduces myocardial work, similar to that seen in younger patients. As for younger patients, cardiac rehabilitation requires a multidisciplinary approach, including comprehensive assessment, treatment of risk factors and comorbidity, and psychosocial assessment. Cardiac rehabilitation is safe and helpful for elderly coronary patients. Physicians must be encouraged to prescribe cardiac rehabilitation programs for the elderly following major coronary events and coronary revascularization procedures.

Distance walked in the 6-minute test soon after cardiac surgery: toward an efficient use in the individual patient.

STUDY OBJECTIVES: To describe the results of the 6-min walking test performed on admission to an intensive rehabilitation program after cardiac surgery and to develop, through an algorithm based on a few clinical indicators, reference tables in order to apply distance walked values more efficiently in the individual patient at his/her entry into a cardiac rehabilitation program. SETTING: Intensive cardiac rehabilitation units. PATIENTS AND INTERVENTION: A total of 2,555 consecutive patients admitted between January 2001 and December 2002 to the Cardiac Rehabilitation Department of the S. Maugeri Foundation early after cardiac surgery performed a 6-min walking test within the fourth day of hospital admission. RESULTS: The mean walked distance was 296 +/- 111 m (+/- SD). At multiple regression analysis, age, sex, and comorbidity were independent predictors of walking test performance. The left ventricular ejection fraction only influenced the walked distance in men. Starting from these variables, we propose an algorithm and specific reference tables. CONCLUSIONS: Reference values for gender-, age-, comorbidity-, and systolic function-related test performance in patients after cardiac surgery at the beginning of the rehabilitative phase are provided. Once a new patient has been categorized through simple parameters, the actual distance walked could be compared with the matched reference value, thus making the interpretation of the result more efficient. The walked distance might be used to define different levels of disability and to personalize therapeutic exercise prescriptions.

A randomized, double-blind comparison of lercanidipine 10 and 20 mg in patients with stable effort angina: clinical evaluation of cardiac function by ambulatory ventricular scintigraphic monitoring.

We evaluated the antiischemic action and the effects on left ventricular response to exercise of lercanidipine, a long-acting dihydropyridine calcium antagonist, in 23 patients with stable effort angina in a randomized, double-blind, parallel trial. Left ventricular function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed under control conditions before (run-in placebo period) and after 2-week treatment with lercanidipine 10 or 20 mg once daily. During the placebo run-in period and at the study end, patients underwent clinical examination, ECG, exercise tests, ambulatory ventricular scintigraphic monitoring (VEST). Results showed that both drug doses increased time to onset of ST segment depression >/=1 mm and peak ST segment depression, with improvement of total exercise duration. Heart rate, blood pressure, and the rate-pressure product did not significantly change with respect to pretreatment value. The left ventricular ejection fraction, indicating contractility state of myocardium, was unchanged at rest and during exercise after both lercanidipine doses. In conclusion, lercanidipine is safe and effective in reducing ischemia in patients with stable effort angina without any deterioration of cardiac function.

Angiotensin II-receptor antagonist losartan does not prevent nitroglycerin tolerance in patients with coronary artery disease.

The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo (p < 0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in (p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001) or Losartan-placebo (p < 0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001, p < 0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p < 0.001). The AT(1) antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.

A randomized, double-blind comparison of 10 and 20 mg lercanidipine in patients with stable effort angina: effects on myocardial ischemia and heart rate variability.

We evaluated the anti-ischemic action and the effects on autonomic function of lercanidipine, a long-acting dihydropyridine calcium antagonist, in 25 patients with stable effort angina in a randomized, double-blind, parallel trial. After a 2-week placebo run-in period, patients entered a 2-week treatment period with 10 or 20 mg of lercanidipine once daily. During the placebo run-in period and at the study end, the patients underwent clinical examination, electrocardiography, exercise tests, 24-hour Holter electrocardiography for long-term heart rate variability evaluation, and short-term spectral analysis of heart rate and systolic blood pressure variability and plasma epinephrine and norepinephrine levels at rest and during tilting. Results showed that time to onset of ST segment depression > or =1 mm was significantly increased by both drug doses. No significant change was recorded in the average hourly heart rate after treatment with both 10 and 20 mg of lercanidipine. During the 24-hour recordings, no significant change was observed in low-frequency power, high-frequency power, or low frequency/high frequency. In the standing position, there was a significant increase in plasma norepinephrine and epinephrine concentration in both groups, and no change in the supine position after 10 and 20 mg of lercanidipine. When considering short-term heart rate variability, no significant difference was observed in either treatment group in low frequency, high frequency, or their ratio on electrocardiographic R-R spectra. The blood pressure spectral component was also unchanged. In conclusion, lercanidipine is effective in reducing ischemia in patients with stable effort angina. Moreover, lercanidipine does not cause adrenergic activation, which is the main mechanism hypothesized to explain the negative effect on cardiovascular mortality assigned to short-acting dihydropyridine calcium antagonists.