Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes: A systematic review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction, reduced functional capacity and exercise intolerance. Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases. High intensity interval training (HIIT) seems to be superior than moderate-intensity continuous training (MICT) in cardiovascular diseases by improving brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness to a greater extent. However, the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited. AIM: To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM. METHODS: We performed a search on PubMed, PEDro and CINAHL databases, selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials (RCTs) in the English language that included community or outpatient exercise training programs in patients with T2DM. RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database (PEDro). The primary outcome was peak VO2 and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation. RESULTS: Twelve studies were included in our systematic review. The 12 RCTs resulted in 661 participants in total. HIIT was performed in 310 patients (46.8%), MICT to 271 and the rest 80 belonged to the control group. Peak VO2 increased in 10 out of 12 studies after HIIT. Ten studies compared HIIT with other exercise regimens (MICT or strength endurance) and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens. Moreover, 4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients. In 2 of them, HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed. CONCLUSION: Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients. HIIT may be superior by improving these parameters to a greater extent than MICT.

Beta-Blockers in Pregnancy: Clinical Update.

PURPOSE OF REVIEW: The aim of this review was to determine the anticipated benefits and adverse effects of beta-blockers in pregnant women with hypertension. The other issue was to assess the possible adverse effects of beta-blockers for their babies and provide current consensus recommendations for appropriate selection and individualized antihypertensive treatment with beta-blockers in pregnancy-associated hypertension. RECENT FINDINGS: Hypertensive disorders of pregnancy are a major cause of maternal and fetal morbidity, with consequences later in life. Certain beta-blockers are useful for ameliorating hypertension in pregnancy and may have a protective role in endothelial dysfunction. However, some aspects of beta-blocker use in pregnancy are contentious among providers. Evidence on their safety, although well documented, is variable, and recent research reveals areas of controversy. Besides intrauterine growth restriction, other neonatal and obstetric complications remain a concern and should be explored thoroughly. Attention is necessary when treating pregnancy-associated hypertensive disorders with beta-blockers. Specific beta-blockers are considered safe in pregnancy, although the associated effects in the fetus are not clearly known and evidence is lacking for many safety outcomes, other than intrauterine growth restriction. Nevertheless, beta-blockers with specific indications in pregnancy under individualized selection and monitoring may confer substantial improvements in pregnant women with hypertension.

Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a complex syndrome characterized by a progressive reduction of the left ventricular (LV) contractility, low exercise tolerance, and increased mortality and morbidity. Diastolic dysfunction (DD) of the LV, is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases. Also, it is well estimated that exercise training induces several beneficial effects on patients with CHF. AIM: To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction (EF) in patients with CHF. METHODS: Thirty-two stable patients with CHF (age: 56 ± 10 years, EF: 32% ± 8%, 88% men) participated in an exercise rehabilitation program. They were randomly assigned to aerobic exercise (AER) or combined aerobic and strength training (COM), based on age and peak oxygen uptake, as stratified randomization criteria. Before and after the program, they underwent a symptom-limited maximal cardiopulmonary exercise testing (CPET) and serial echocardiography evaluation to evaluate peak oxygen uptake (VO2peak), peak workload (Wpeak), DD grade, right ventricular systolic pressure (RVSP), and EF. RESULTS: The whole cohort improved VO2peak, and Wpeak, as well as DD grade (P < 0.05). Overall, 9 patients (28.1%) improved DD grade, while 23 (71.9%) remained at the same DD grade; this was a significant difference, considering DD grade at baseline (P < 0.05). In addition, the whole cohort improved RVSP and EF (P < 0.05). Not any between-group differences were observed in the variables assessed (P > 0.05). CONCLUSION: Exercise rehabilitation improves indices of diastolic and systolic dysfunction. Exercise protocol was not observed to affect outcomes. These results need to be further investigated in larger samples.

A single-center, prospective, observational study on maternal smoking during pregnancy in Greece: The HELENA study.

INTRODUCTION: The unequivocal association between exposure to smoke and numerous complications of pregnancy, demonstrated in the last decades, has led to a significant decrease of smoking rates in pregnancy. The aim of the present study was to determine the prevalence of maternal smoking and to elucidate factors predisposing to it among pregnant women in Athens, Greece. METHODS: A population of 1700 pregnant women (mean age: 31.2±5.5 years) who visited consecutively the Cardiology Department of Helena Venizelou Maternity Hospital in Athens, Greece, between September 2016 and August 2017, was prospectively analyzed. Data regarding changes in the future mother's smoking habit as well as different sociodemographic factors potentially related to these changes were recorded. RESULTS: Of the 1700 participants, 704 (41.4%) were smokers, and of those 52.4% quit smoking after knowledge of their pregnancy status. The overall prevalence of smoking in pregnancy was 19.7%. Prevalence was higher in women who were aged <20 years (p=0.038), were multipara (p=0.032), had ≤12 years of education (p=0.044) and had a partner who was a smoker (p=0.047). Women aged ≤20 years were more likely to be persistent smokers at the beginning of pregnancy and demonstrated a higher prevalence of smoking during pregnancy (42.2% vs 19.7% in the overall study population). CONCLUSIONS: Our data demonstrate that maternal smoking during pregnancy still remains a major public health issue in Greece with a prevalence higher than most other industrialized countries.

Cardiovascular disease in women: Executive summary of the expert panel statement of women in cardiology of the hellenic cardiological society.

The perception that women represent a low-risk population for cardiovascular (CV) disease (CVD) needs to be reconsidered. Starting from risk factors, women are more likely to be susceptible to unhealthy behaviors and risk factors that have different impact on CV morbidity and mortality as compared to men. Despite the large body of evidence as regards the effect of lifestyle factors on the CVD onset, the gender-specific effect of traditional and non-traditional risk factors on the prognosis of patients with already established CVD has not been well investigated and understood. Furthermore, CVD in women is often misdiagnosed, underestimated, and undertreated. Women also experience hormonal changes from adolescence till elder life that affect CV physiology. Unfortunately, in most of the clinical trials women are underrepresented, leading to the limited knowledge of CV and systemic impact effects of several treatment modalities on women's health. Thus, in this consensus, a group of female cardiologists from the Hellenic Society of Cardiology presents the special features of CVD in women: the different needs in primary and secondary prevention, as well as therapeutic strategies that may be implemented in daily clinical practice to eliminate underestimation and undertreatment of CVD in the female population.

MicroRNAs in Preeclampsia.

Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

Respiratory drive and breathing pattern abnormalities are related to exercise intolerance in chronic heart failure patients.

BACKGROUND: Patients with chronic heart failure (CHF) are characterized by exercise intolerance and ventilatory abnormalities that are related to poor prognosis. We hypothesized that CHF patients have increased respiratory drive and abnormal breathing pattern during exercise in relation to disease severity. MATERIALS AND METHODS: The study population consisted of 219 stable CHF patients and 30 healthy control subjects. All subjects underwent a symptom-limited cardiopulmonary exercise testing (CPET), pulmonary function tests, measurement of the maximal inspiratory pressure (PImax) and respiratory drive (P0.1). Measurements included peak oxygen uptake ( [Formula: see text] peak, ml/kg/min). Respiratory drive was measured by mouth occlusion pressure P0.1 and P0.1/PImax ratio at rest, and by mean inspiratory flow (VT/TI) at rest and during exercise. CHF patients were divided into 3 groups according to [Formula: see text] peak (Group A: >20, Group B: 20-16 and Group C: <16ml/kg/min). RESULTS: CHF patients presented higher P0.1/PImax (4.1±3.6 vs 3.0±1.5, p=0.007) and VT/TI at rest (0.48±0.14 vs 0.41±0.10, L/s respectively, p=0.004) and lower VT/TI at peak exercise (2.17±0.66 vs 2.56±0.73, L/s, p=0.009) compared to controls. P0.1/PImax was higher in CHF Group C vs B vs A (4.9±2.9 vs 3.6±1.8 vs 3.1±1.8, respectively, p<0.001), while VT/TI at peak exercise was lower (1.71±0.43 vs 2.15±0.52 vs 2.65±0.64, L/s, respectively, p<0.001). CONCLUSIONS: CHF patients present increased respiratory drive at rest and abnormal breathing pattern during exercise in relation to CHF severity.

Cardiopulmonary rehabilitation enhances heart rate recovery in patients with COPD.

BACKGROUND: Autonomic dysfunction is present early in the course of COPD, and is associated with adverse outcomes. We utilized heart rate recovery, a simple and validated index of autonomic balance, to investigate the effects of exercise training on autonomic dysfunction in patients with COPD. METHODS: We evaluated 45 stable subjects with COPD who participated in a 36-session exercise-based cardiopulmonary rehabilitation program. Subjects underwent maximal cardiopulmonary exercise testing at baseline and after completion of the rehabilitation program. We recorded exercise testing parameters and heart rate during rest, exercise, and recovery. Heart rate recovery was calculated as heart rate at peak exercise minus heart rate at the first minute of recovery. RESULTS: Thirty-nine subjects (age 66.3 ± 7.8 y, 90% male, body mass index 27.1 ± 4.1 kg/m(2), FEV(1) 45.7 ± 18.7%) completed the program. In these subjects, heart rate recovery increased from 16.2 ± 8.0 beats/min to 18.4 ± 8.4 beats/min (P = .01), resting heart rate decreased from 88.0 ± 10.7 beats/min to 83.3 ± 10.5 beats/min (P = .004), and heart rate at anaerobic threshold decreased from 109.0 ± 12.5 beats/min to 105.5 ± 11.7 beats/min (P = .040). In addition, oxygen consumption (V(O(2))) increased from 14.3 ± 3.7 mL/kg/min to 15.2 ± 3.8 mL/kg/min at peak exercise, and from 9.7 ± 2.4 mL/kg/min to 10.4 ± 2.6 mL/kg/min at anaerobic threshold (both P = .02), while the V(O(2))/t slope increased from -0.32 ± 0.16 mL/kg/min(2) to -0.38 ± 0.19 mL/kg/min(2) (P = .003). Parameters of ventilatory performance improved also. CONCLUSIONS: In subjects with COPD, exercise-based rehabilitation improves heart rate recovery, modestly though, which indicates a degree of attenuated autonomic dysfunction. Exercise and muscular oxidative capacity, as expressed by V(O(2))/t slope, is also improved.

Effects of interval cycle training with or without strength training on vascular reactivity in heart failure patients.

BACKGROUND: Exercise training confers beneficial effects on vascular reactivity in patients with chronic heart failure (CHF). This randomized study compares the effects of interval cycle training combined with strength training versus interval training alone on vascular reactivity in CHF patients. METHODS: Twenty-eight consecutive stable CHF patients (23 males, 53 ± 10 years, 28.4 ± 4.1 kg/m(2), left ventricular ejection fraction of 37 ± 12%) were randomly assigned to 3 times' weekly training sessions for 3 months, consisting of a) 40 minutes of interval cycle training (n = 14), versus b) 20 minutes of similar interval training plus 20 minutes of strength training of the quadriceps, hamstrings, muscles of the shoulder and biceps brachialis (n = 14). The work/recovery ratio of each session was 30/60 seconds. The intensity of interval training was set at 50% of the peak workload achieved at the steep ramp test (consisted of a 25-Watt increase on a cycle ergometer every 10 seconds until exhaustion). All patients underwent maximal, symptom-limited cardiopulmonary exercise testing and ultrasound evaluation of vascular reactivity by flow-mediated vasodilation (FMD) before and after the program. RESULTS: A significant improvement in FMD was observed in the combined training group (P = 0.002), in contrast to the interval training alone group (P = NS); the improvement was significantly greater in the combined training than in the interval training alone group (P < .05). Peak oxygen uptake increased significantly and similarly in both groups, in the interval training group (P = .03), and in the combined training group (P = .006). No significant correlation was found between FMD improvement and cardiopulmonary exercise parameters. CONCLUSIONS: A combined high-intensity, interval cycle exercise with strength training induces a greater beneficial effect on vascular reactivity rather than interval exercise training alone in CHF patients.

Effects of interval exercise training on respiratory drive in patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) suffer from ventilatory abnormalities. This study examined the effects of interval exercise training on the respiratory drive in CHF patients. METHODS: Forty-six clinically stable CHF patients (38 males/8 women, mean age = 53 +/- 11 years) participated in an exercise rehabilitation program (ERP) 3 times/week, for 12 weeks by interval training modality with or without the addition of resistance training. All patients underwent symptom-limited cardiopulmonary exercise testing (CPET), and measurements of mouth occlusion pressure at 100 ms (P(0.1)) and maximum inspiratory muscle strength (P(Imax)) before and after ERP. Respiratory drive was estimated by mouth occlusion pressure P(0.1) and P(0.1)/P(Imax) ratio at rest, and the ventilatory pattern by resting mean inspiratory flow (V(T)/T(I)) and by V(T)/T(I) at identical CPET workloads, before and after ERP. We also studied a control non exercising group of 11 patients (8 men and 3 women). RESULTS: P(0.1) at rest decreased from 3.04 +/- 1.52 to 2.62 +/- 0.9 cmH(2)O (p = 0.015), P(0.1)/P(Imax) % at rest from 4.56 +/- 3.73 to 3.69 +/- 2.03 (p = 0.006), resting V(T)/T(I) from 0.44 +/- 0.10 to 0.41 +/- 0.10 l/s (p = 0.014), and V(T)/T(I) at identical work rate from 2.13 +/- 0.59 to 1.93 +/- 0.58 l/s (p = 0.001) after ERP. VO(2) at peak exercise increased from 16.3 +/- 4.8 to 18.5 +/- 5.3 ml/kg/min (p < 0.001) in the exercise group. No improvement was noted in the control group. CONCLUSIONS: ERP by interval training improves the respiratory drive and ventilatory pattern at rest and during exercise in CHF patients.

Impairment of autonomic nervous system activity in patients with pulmonary arterial hypertension: a case control study.

BACKGROUND: Chronotropic response to exercise (CR) and heart rate recovery (HRR) immediately after exercise are indirect indices of sympathetic and parasympathetic activity, respectively. The aim of this study was to evaluate CR and HRR in patients with pulmonary arterial hypertension (PAH) in relation to disease severity. METHODS AND RESULTS: Ten PAH patients (6 females/4 males, mean age: 48+/-12 years) and 10 control subjects matched for age, gender, and body mass index (6 females/4 males, mean age: 46+/-6 years) performed a ramp incremental symptom-limited cardiopulmonary exercise test on a cycle ergometer. Main measurements included heart rate at rest (HR), CR=[(peak HR-resting HR/220-age-resting HR)x100, %], HRR(1)=HR difference from peak exercise to 1minute after, ventilatory efficiency during exercise (VE/VCO(2) slope), peak oxygen uptake (VO(2)p), and the first-degree slope of VO(2) for the first minute of the recovery period (VO(2)/t-slope). PAH patients had a significantly decreased CR (58+/-31 vs 92+/-13, %, P < .001) and HRR(1) (10+/-5 vs 29+/-6, beats/min, P < .001) as well as VO(2)p (11.9+/-3.5 vs 26.9+/-6.6, mL.kg.min) and VO(2)/t-slope (0.2+/-0.1 vs. 0.9+/-0.2, mL.kg.min(2)) compared with controls. CR and HRR(1) correlated well with VO(2)p (r=0.7; P < .001 and r=0.85; P < .001, respectively) and VO(2)/t-slope (r=0.66; P < .001 and r=0.85; P < .001, respectively) and had a significant inverse correlation with VE/VCO(2) slope (r=-0.47; P < .01 and r=-0.77; P < .001, respectively). CONCLUSIONS: PAH patients present a significant impairment of CR and HRR(1) in relation to disease severity, indicating profound autonomic nervous system abnormalities.

Association of passive smoking with masked hypertension in clinically normotensive nonsmokers.

BACKGROUND: We investigated ambulatory blood pressure (BP) levels among clinically normotensive nonsmokers exposed (PS) and not exposed (SF) to passive smoking aiming to evaluate the relative prevalence of masked hypertension (MH). METHODS: From 790 consecutive never-treated subjects who were self-referred to an outpatient hypertensive clinic, we excluded active smokers and those having a mean clinic BP >140/90 mm Hg. In the remaining population, echocardiography and routine biochemical profile assessment was performed, whereas by the implementation of additional exclusion criteria, all clinically normotensive subjects eligible to participate (i.e., 154 PS and 100 SF) underwent to ambulatory BP monitoring. RESULTS: PS with respect to SF subjects were younger, followed a less hygienic diet and consumed more alcohol (all P < 0.05). Moreover, PS in comparison with SF showed higher 24-h systolic BP, standing diastolic BP, and clinic heart rate (126 +/- 6 mm Hg vs. 122 +/- 5 mm Hg, 89 +/- 4 mm Hg vs. 84 +/- 4 mm Hg and 79 +/- 5 beats/min vs. 73 +/- 4 beats/min, respectively, P < 0.05 for all) and higher prevalence of MH (23% vs. 8%, P < 0.01). After adjustment for confounders determinants of MH remained passive smoking, weekly duration and intensity of passive smoke exposure, younger age, clinic heart rate, low physical activity score, and standing/sitting difference of diastolic BP and heart rate (P < 0.05 for all). CONCLUSIONS: MH is associated with passive smoking in a dose-related manner and low physical activity, increased heart rate and postural hemodynamic reaction may represent potential accelerators of that phenomenon.

Free leptin is associated with masked hypertension in nonobese subjects: a cross-sectional study.

The aim of the study was to investigate whether diverse clinical blood pressure phenotypes are associated with free leptin surrogates, as reflected by plasma leptin, human soluble leptin receptor, and their ratio (ie, free leptin index) in nonobese normoglycemic subjects. Three separate clinic blood pressure measurements and ambulatory blood pressure monitoring were implemented to divide 494 subjects (aged 44+/-5 years; 272 men; body mass index: <30 kg/m(2)) into hypertensives (n=166), white-coat hypertensives (n=82), masked hypertensives (n=66), and normotensives (n=180). Participants underwent echocardiography, while, from fasting venous blood samples, metabolic profile, plasma leptin, and its receptor levels were assessed. Hypertensives and masked hypertensives demonstrated higher levels of log (10)(leptin) and log (10)(free leptin index), as well as lower levels of log (10)(human soluble leptin receptor) with respect to normotensives. White-coat hypertensives had similar free leptin surrogates compared with normotensives. Younger age, 24-hour systolic and diastolic blood pressures, 24-hour heart rate, and left ventricle mass index were common correlates of free leptin surrogates. After adjustment for confounders, masked hypertensive and hypertensive with respect to normotensive phenotype were associated with log (10)(leptin) with odds ratios (95% CIs) of 1.31 (1.12 to 3.80) and 1.26 (1.09 to 2.24), respectively, log (10)(human soluble leptin receptor) with 0.65 (0.53 to 0.78) and 0.69 (0.57 to 0.84), respectively, and log (10)(free leptin index) with 2.46 (1.32 to 7.23) and 1.84 (1.26 to 3.73), respectively (P<0.05 for all of the cases). Free leptin surrogates are associated with masked hypertension in nonobese normoglycemic subjects. Free leptin is almost equally increased in masked and sustained hypertension, suggesting a similar leptin-related vascular impairment.

Pulmonary function at peak exercise in patients with chronic heart failure.

BACKGROUND: Various respiratory abnormalities are associated with chronic heart failure (CHF). However, changes in inspiratory capacity (IC) and breathing pattern from rest to exercise in patients with CHF have not been thoroughly investigated in these patients. MATERIALS AND METHODS: Seventy seven (66 male/11 female) patients with clinical stable CHF (age: 52+/-11 years) were studied. All the patients underwent pulmonary function tests, including measurements of IC and maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2 min. Pimax was measured again after the end of CPET. RESULTS: Percent predicted forced expiratory volume in 1 s (FEV1) was 91+/-12, %predicted forced vital capacity (FVC) was 92+/-13, %FEV1/FVC was 81+/-4, and %predicted IC was 85+/-18. Peak exercise IC was lower than resting (2.4+/-0.6 vs. 2.6+/-0.6 l, p<0.001). Analysis of variance between Weber's groups revealed statistically significant differences in peak exercise IC (p<0.001), VE/VCO2slope (p<0.001), resting Pimax (p=0.005) and post-exercise Pimax (p<0.001). At rest, there was a statistically significant difference in end-tidal CO2 (P(ETCO2)) (p=0.002), in breathing frequency (p=0.004), in inspiratory time (Ti) (p=0.04) and in total respiratory time (T(Tot)) (p=0.004) among Weber's groups. At peak exercise there was a statistically significant decrease in minute ventilation (VE) (p<0.001), tidal volume (VT) (p<0.001), respiratory cycle (VT/TI) (p<0.001) and P(ETCO2) (p<0.001). Peak IC was correlated with peak VO2 (r=0.72, p<0.001), anaerobic threshold (r=0.71, p<0.001), VO2/t slope (r=0.54, p<0.0001), and post-exercise Pimax (r=0.62, p<0.001). CONCLUSIONS: In patients with CHF, peak exercise IC is reduced in parallel with disease severity, which is probably due to respiratory muscle dysfunction.

Effects of exercise rehabilitation program on heart rate recovery in patients with chronic heart failure.

BACKGROUND: Heart rate recovery (HRR1) immediately after exercise reflects parasympathetic activity, which is markedly attenuated in chronic heart failure (CHF) patients. The aim of our study was to examine both continuous and interval exercise training effects on HRR1 in these patients. DESIGN: The population study consisted of 29 stable CHF patients that participated at a rehabilitation program of 36 sessions, three times per week. Of the 29 patients, 24 completed the program. Patients were randomly assigned to interval {n=10 [100% peak work rate (WRp) for 30 s, alternating with rest for 30 s]} and to continuous training [n=14 (50%WRp)]. METHODS: All patients performed a symptom-limited cardiopulmonary exercise test on a cycle ergometer before and after the completion of the program. Measurements included peak oxygen uptake (VO2p), anaerobic threshold (AT), WRp, first degree slope of VO2 during the first minute of recovery (VO2/t-slope), chronotropic response [% chronotropic reserve (CR)=(peak HR - resting HR)x100/(220 - age - resting HR)], HRR1 (HR difference from peak exercise to one minute after). RESULTS: After the completion of the rehabilitation program there was a significant increase of WRp, VO2p, AT and VO2/t-slope (by 30%, P=0.01; 6%, P=0.01; 10%, P=0.02; and 27%, P=0.03 respectively for continuous training and by 21%, P<0.05; 8%, P=0.01; 6%, P=NS; and 48%, P=0.02 respectively for interval training). However, only patients exercised under the continuous training regime had a significant increase in HRR1 (15.0+/-9.0 to 24.0+/-12 bpm; P=0.02) and CR (57+/-19 to 72+/-21%, P=0.02), in contrast with those assigned to interval training (HRR1: 21+/-11 to 21+/-8 bpm; P=NS and CR: 57+/-18 to 59+/-21%, P=NS). CONCLUSIONS: Both continuous and interval exercise training program improves exercise capacity in CHF patients. However, continuous rather than interval exercise training improves early HRR1, a marker of parasympathetic activity, suggesting a greater contribution to the autonomic nervous system.

Early heart rate recovery after exercise predicts mortality in patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet. METHODS: Ninety-two stable CHF patients (83M/9F, mean age: 51+/-12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %)=(peak HR-resting HR/220-age-resting HR)x100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography. RESULTS: Fatal events occurred in 24 patients (26%) during 21+/-6 months of follow-up. HRR1 was lower in non-survivors (11.4+/-6.4 vs. 20.4+/-8.1; p<0.001). All cause-mortality rate was 65% in patients with HRR112 bpm (log-rank: 32.6; p<0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (chi2=19.2; odds ratio: 0.87; p<0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10-18, ml/kg/min), HRR1 was a strong predictor of mortality (chi2: 14.3; odds ratio: 0.8; p<0.001). CONCLUSIONS: Early heart rate recovery is an independent prognostic risk indicator in CHF patients and could be used in CHF risk stratification.

VE/VCO2 slope is associated with abnormal resting haemodynamics and is a predictor of long-term survival in chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) present with exercise-induced hyperpnea, but its pathophysiological mechanism has not been thoroughly investigated. We aimed to determine the relationship between exercise-induced hyperpnea, resting haemodynamic measurements and the validity of ventilatory response (V(E)/V(CO(2)) slope) as a mortality predictor in CHF patients. METHODS: Ninety-eight CHF patients (90M/8F) underwent a symptom-limited treadmill cardiopulmonary exercise test (CPET). Right heart catheterization and radionuclide ventriculography were performed within 72 h of CPET. RESULTS: Twenty-seven patients died from cardiac causes during 20+/-6 months follow-up. Non-survivors had a lower peak oxygen consumption (V(O(2)p)), (16.5+/-4.9 vs. 20.2+/-6.1, ml/kg/min, p=0.003), a steeper V(E)/V(CO(2)) slope (34.8+/-8.3 vs. 28.9+/-4.8, p<0.001) and a higher pulmonary capillary wedge pressure (PCWP) (19.5+/-8.6 vs. 11.7+/-6.5 mm Hg, p=0.008) than survivors. By multivariate survival analysis, the V(E)/V(CO(2)) slope as a continuous variable was an independent prognostic factor (chi(2): 8.5, relative risk: 1.1, 95% CI: 1.03-1.18, p=0.004). Overall mortality was 52% in patients with V(E)/V(CO(2)) slope > or =34 and 18% in those with V(E)/V(CO(2)) slope <34 (log rank: 18.5, p<0.001). In a subgroup of patients (V(O(2)p): 10-18 ml/kg/min), V(E)/V(CO(2)) slope was a significant predictor of mortality (relative risk: 6.2, 95% CI: 1.7-22.2, p=0.002). Patients with high V(E)/V(CO(2)) slope had higher resting PCWP (19.9+/-9.1 vs. 11.3+/-5.7 mmHg, p<0.001) and V(E)/V(CO(2)) slope correlated significantly with PCWP (r: 0.57, p<0.001). CONCLUSIONS: The V(E)/V(CO(2)) slope, as an index of ventilatory response to exercise, improves the risk stratification of CHF patients. Interstitial pulmonary oedema may be a pathophysiological mechanism of inefficient ventilation during exercise in these patients.

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure.

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.

Ventilatory response to exercise and kinetics of oxygen recovery are similar in cardiac transplant recipients and patients with mild chronic heart failure.

BACKGROUND: Exercise capacity, assessed by cardiopulmonary exercise treadmill testing (CPET), does not return to normal following heart transplantation. This study evaluated the ventilatory response to exercise and the kinetics of oxygen (O(2)) recovery in heart transplant recipients (HTR) compared to healthy volunteers (HV) and heart failure patients. METHODS: Eighteen patients with end-stage heart failure (ESHF), 12 with mild heart failure (MHF) matched for peak oxygen consumption (Vo(2)) with the HTR, 12 HTR and 12 HV underwent CPET for measurements of peak Vo(2), Vo(2) at anaerobic threshold (AT), first-degree slope of Vo(2) decline during early recovery (Vo(2)/t-slope), time required for a 50% fall from peak Vo(2) (T(1/2) of Vo(2)) and the slopes of VE/Vco(2) and VE/Vo(2). RESULTS: The MHF and HTR groups had similar ventilatory responses to exercise and O(2) recovery kinetics. Peak Vo(2) (18.5 +/- 5.7 vs 9.4 +/- 0.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 6.7 +/- 1.8 ml/kg/min, p < 0.001) and Vo(2)/t-slope (0.6 +/- 0.2 vs 0.3 +/- 0.2 liter/min/min, p = 0.055) were higher in the HTR than in the ESHF group. In contrast, HTR had lower VE/Vco(2)-slope (31.4 +/- 3.8 vs 39.2 +/- 9.9, p = 0.015) and T(1/2) Vo(2) (1.5 +/- 0.3 vs 2.4 +/- 1.1 minute, p = 0.014) than the ESHF group. Compared to HV, HTR had lower Vo(2) peak (18.5 +/- 5.7 vs 28.4 +/- 6.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 19.8 +/- 4.5 ml/kg/min, p = 0.04), Vo(2)/t-slope (0.6 +/- 0.2 vs 1.0 +/- 0.4 liter/min/min, p = 0.005) and steeper VE/Vco(2) slope (31.4 +/- 3.8 vs 23.6 +/- 2.7, p = 0.062). Heart rate deceleration during recovery was significantly slower in HTR than in all other groups. CONCLUSIONS: Exercise intolerance and delayed O(2) recovery kinetics were only partially reversed after heart transplantation. This finding suggests that some of the pathophysiologic mechanisms of heart failure persist after heart transplantation.