Acute effects of high intensity interval training versus moderate intensity continuous training on haemostasis in patients with coronary artery disease.

Exercise training is associated with an acute net increase in coagulation, which may increase the risk of atherothrombosis in coronary artery disease (CAD) patients. We sought to compare the acute haemostatic effects of a bout of moderate-intensity continuous (MICT) and high-intensity interval training (HIIT) in patients with CAD. Patients after a recent myocardial infarction were randomized into a HIIT or MICT session of exercise training on a stationary bike. Blood was sampled at baseline, after the exercise bout and after a one-hour resting period. We measured overall haemostatic potential (OHP), overall coagulation potential (OCP), fibrinogen, D-dimer and von Willebrand factor (vWF) and calculated overall fibrinolytic potential (OFP). Linear mixed models for repeated measures were constructed to assess the treatment effect. A total of 117 patients were included. OCP, OHP, fibrinogen, D-dimer and vWF significantly increased after exercise and returned to baseline after a one-hour rest, OFP decreased after exercise and returned to baseline levels after a one-hour rest. Linear mixed models showed a significant difference between HIIT and MICT in fibrinogen (p 0.043) and D-dimer (p 0.042). Our study has shown that an exercise bout is associated with a transient procoagulant state in patients with CAD, with similar exercise-induced haemostatic changes for HIIT and MICT.

Effects of exercise training on heart rate variability in individuals with lower extremity arterial disease and claudication: A systematic review.

PURPOSE: To perform a systematic review of studies assessing the effects of regular exercise on heart rate variability (HRV) in individuals with lower extremity arterial disease (LEAD) and symptoms of claudication. METHODS: A systematic search in the electronic databases MEDLINE, Embase, and Scielo, was conducted and updated on January 21, 2023. Randomized clinical trials investigating patients with LEAD and IC, assessing ≥ 4 wk of exercise interventions, and reporting at least one HRV measure (e.g., time or frequency domains) at baseline and follow-up were included. Two reviewers independently screened studies for inclusion, performed data extraction, and quality assessment of included studies. RESULTS: Data from 7 trials were included (i.e., 5 walking, 1 resistance, and 1 isometric handgrip training), totaling 327 patients (66% males; range: 61 - 68 yr; ankle brachial index: 0.4 - 0.7). Following exercise training, three studies investigating walking training reported an increase in parasympathetic modulation indices and/or a decrease in sympathetic modulation indices (n = 2) as well as an increase in non-linear indices (n = 1). CONCLUSION: The current evidence is weak, and larger randomized controlled trials are needed to confirm the efficacy of exercise training in improving HRV. Additionally, the high divergence in the methodology of studies indicated the need for standard tools to improve the quality of HRV measurements in exercise trials. It is recommended to use standard procedures in future trials investigating HRV.

HFpEF and Atrial Fibrillation: The Enigmatic Interplay of Dysmetabolism, Biomarkers, and Vascular Endothelial Dysfunction.

Background: Heart failure with preserved ejection fraction (HFpEF) has a complex pathophysiology that encompasses systemic proinflammatory state and dysregulated levels of cardiometabolic and oxidative stress biomarkers. The prevalence of both HFpEF and atrial fibrillation (AF) is continuously rising, especially in the elderly. The aim of our study was to explore if there were any differences in biomarker levels and vascular function in the elderly patients with HFpEF with and without AF and to assess interconnections between clinically relevant biomarkers and cardiac and vascular function. Methods: This was a cross-sectional study of patients ≥ 65 years with HFpEF who were divided into 2 groups based on the presence or absence of AF. We have sonographically assessed echocardiographic parameters of left ventricular systolic and diastolic function and the peripheral vascular function parameters, namely, pulse wave velocity (PWV) and flow-mediated dilation (FMD). NT-proBNP, irisin, leptin, adiponectin, insulin-like growth factor 1 (IGF-1), and malondialdehyde (MDA) blood levels were determined. Results: Fifty-two patients (mean age 80 ± 7 years, 67% females) were included. Patients with HFpEF and AF had significantly lower levels of irisin (median 4.75 vs. 13.5 ng/mL, p = 0.007), leptin (median 9.5 vs. 15.0 ng/L, p = 0.023), and MDA (median 293 vs. 450 ng/mL, p = 0.017) and significantly higher values of NT-proBNP (median 2365 vs. 529 ng/L, p < 0.001) but not vascular function parameters, as compared to HFpEF patients without AF. MDA was significantly correlated with diastolic function (r = 0.395, p = 0.007) and FMD (r = 0.394, p = 0.011), while adiponectin was inversely associated with FMD (r = -0.325, p = 0.038) and left ventricular ejection fraction (r = -0.319, p = 0.029). Conclusions: Our results have demonstrated that patients with HFpEF and AF have significantly lower leptin, irisin, and MDA levels compared to patients with HFpEF but without AF. These results offer new insights into the complexity of vascular function and cardiometabolic and oxidative stress biomarkers in the context of HFpEF, AF, and aging.

Effects of Cardiac Rehabilitation and Diet Counselling on Adherence to the Mediterranean Lifestyle in Patients after Myocardial Infarction.

Adherence to the Mediterranean lifestyle­as captured by the Medlife Index Questionnaire (i.e., encompassing a Mediterranean diet as well as other aspects of healthy living, such as food preparation, physical activity, and socializing)­has been associated with reduced cardiovascular events in healthy individuals. In the present study, we sought to determine the adherence to, and the effect of comprehensive cardiac rehabilitation on, Mediterranean lifestyle adherence in patients after myocardial infarction. We included 121 patients (mean age, 55 years; women, 37%) undergoing comprehensive cardiac rehabilitation­i.e., exercise training 3 times per week for 12 weeks plus dedicated workshops promoting the Mediterranean lifestyle. Before and after cardiac rehabilitation, patients completed the Medlife Index Questionnaire. High baseline adherence was associated with favourable glucose (5.39 vs. 6.1 mmol/L; p < 0.001), triglycerides (1.1 vs. 1.5 mmol/L; p = 0.002), and HDL cholesterol levels (1.32 vs. 1.12 mmol/L; p = 0.032). More importantly, the Medlife Score significantly improved following comprehensive cardiac rehabilitation in patients with low baseline adherence (from 13.8 to 16.7 points; p < 0.001), but not in patients with high baseline adherence (from 19.4 to 18.8 points; p = 0.205). Our findings suggested that Mediterranean lifestyle promotion during cardiac rehabilitation improved adherence to the Mediterranean lifestyle, especially in low-adherence patients.

The Correlation between the Triglyceride-Glucose Index and Coagulation Markers in Patients with Recent Acute Myocardial Infarction.

Background: Metabolic abnormalities and hypercoagulability seem to have an important predictive role in patients with coronary artery disease (CAD). The triglyceride-glucose (TyG) index has emerged as a good marker for metabolic syndrome with predictive value for cardiovascular events. Overall haemostatic potential (OHP) is a reliable global haemostatic essay to identify hypercoagulability in CAD patients. The aim of our study was therefore to evaluate a possible correlation between the TyG index and haemostatic derangements in patients with CAD. Methods: Consecutive patients referred for the first follow-up visit after acute myocardial infarction between December 1, 2018, and March 31, 2020, and did not meet exclusion criteria were included. We determined OHP, overall coagulation potential (OCP), overall fibrinolytic potential (OFP), fibrinogen, D-dimer, and von Willebrand factor from peripheral blood samples. The TyG index was calculated with the previously described and validated formula. Linear regression models were constructed for the multivariate analysis. Results: A total of 117 patients (mean age 56 ± 10 years, 20% women) were included. A correlation was found between TyG index and OCP (r = 0.229, p = 0.026), TyG index and OHP (r = 0.202, p = 0.050), and TyG index and fibrinogen (r = 0.271, p = 0.005). In the multivariate model which accounted for sex, age, and BMI, the correlation between TyG index and OCP (R 2 0.108; ANOVA for regression p = 0.035; beta 2.08 [0.79-4.01], p = 0.042) and between TyG index and fibrinogen (R 2 0.11; ANOVA for regression p = 0.015; beta 0.35 [0.08-0.62], p = 0.012) emerged as statistically significant. Conclusion: The TyG index, a marker of metabolic syndrome, has a strong correlation with a hypercoagulability state in CAD, as determined by the OCP and higher fibrinogen levels. Our findings suggest that metabolic syndrome may be an important driver of atherothrombotic risk in patients with CAD.

The Effect of Aquatic Exercise Training on Heart Rate Variability in Patients with Coronary Artery Disease.

(1) Background: Aquatic exercise training is a relatively understudied exercise modality in patients with CAD; with the present study, we sought to compare the impact of short-term 14-day water- and land-based exercise training on heart rate variability (HRV). (2) Methods: We randomized 90 patients after a recent CAD event (myocardial infarction and/or revascularization within 2 months prior to inclusion) to either (i) water-based or (ii) land-based exercise training (14 days, two 30 min sessions daily), or (iii) controls. Before and after the intervention period, all participants underwent 20 min 12-channel high-resolution ECG recordings with off-line HRV analysis, including conventional linear time- and frequency-domain analysis (using the Welch method for fast-Fourier transformation), and preselected non-linear analysis (Poincaré plot-derived parameters, sample entropy, and the short-term scaling exponent α1 obtained by detrended fluctuation analysis). (3) Results: Eighty-nine patients completed the study (mean age 60 ± 8 years; 20 % women). We did not detect significant differences in baseline- or age-adjusted end-of-study HRV parameters, but aquatic exercise training was associated with a significant increase in the linear LF/HF parameter (from 2.6 [1.2-4.0] to 3.0 [2.1-5.5], p = 0.046) and the non-linear α1 parameter (from 1.2 [1.1-1.4] to 1.3 [1.2-1.5], p = 0.043). (4) Conclusions: Our results have shown that a short-term 14-day aquatic exercise training program improves selected HRV parameters, suggesting this mode of exercise is safe and may be beneficial in patients with CAD.

Statin Use in Hospitalized Patients with COVID-19: A Comprehensive Analysis of the New York City Public Hospital System.

INTRODUCTION: Statins have been commonly used for primary and secondary cardiovascular prevention. We hypothesized that statins may improve in-hospital outcomes for hospitalized patients with Coronavirus disease 2019 (COVID-19) due to its known anti-inflammatory effects. METHODS: We conducted a retrospective study at the largest municipal health care system in the United States, including adult patients who were hospitalized for COVID-19 between March 1 and December 1, 2020. The primary endpoint was in-hospital death. Propensity score matching was conducted to balance possible confounding variables between patients receiving statins during hospitalization (statin group) and those not receiving statins (non-statin group). Multivariate logistic regression was used to evaluate the association of statin use and other variables with in-hospital outcomes. RESULTS: There were 8897 patients eligible for study enrollment, with 3359 patients in the statin group and 5538 patients in the non-statin group. After propensity score matching, both the statin and non-statin groups included 2817 patients. Multivariate logistic regression analysis showed that the statin group had a significantly lower risk of in-hospital mortality (odds ratio 0.71; 95% confidence interval, 0.63-0.80; P < .001) and mechanical ventilation (OR 0.80; 95% confidence interval, 0.71-0.90; P < .001) compared with the non-statin group. CONCLUSION: Statin use was associated with lower likelihood of in-hospital mortality and invasive mechanical ventilation in hospitalized patients with COVID-19.

Exercise capacity improvement after cardiac rehabilitation following myocardial infarction and its association with long-term cardiovascular events.

AIMS: Cardiovascular rehabilitation (CR) improves aerobic capacity and quality of life in patients after myocardial infarction (MI). The aim was to examine the associations between exercise capacity improvement and different clinically relevant cardiovascular events. METHODS AND RESULTS: This was a registry-based study of post-MI patients, referred to CR. All patients were submitted to exercise testing before and after CR (36 sessions, 2-3 times/week, and combined exercise). Patients were divided into two groups, based on the difference in exercise capacity before and after the CR programme with the cut-off of two metabolic equivalents (METs) improvement. We assessed the correlation between the extent of exercise capacity improvement and the following cardiovascular events: major adverse cardiac events (MACE), cardiovascular-related hospitalizations, and unplanned coronary angiography. A total of 499 patients were included (mean age 56 ± 10 years, 20% women). Both groups significantly improved in terms of exercise capacity, natriuretic peptide levels, resting heart rate, and resting diastolic pressure; however, lipid status significantly improved only in patients with ≥2 METs difference in exercise capacity. A total of 13.4% patients suffered MACE (median follow-up 858 days); 21.8% were hospitalized for cardiovascular reasons (median follow-up 791 days); and 19.8% had at least one unplanned coronary angiography (median follow-up 791 days). Exercise capacity improvement of ≥2 METs was associated with lower rates of MACE, cardiovascular hospitalizations, and unplanned coronary angiography in all examined univariate and multivariate models. CONCLUSION: This study has shown that exercise improvement of ≥2 METs is associated with a significant decrease in MACE, cardiac hospitalizations, and unplanned coronary angiography.

Vascular Function in Patients After Myocardial Infarction: The Importance of Physical Activity.

Background: Patients after myocardial infarction have impaired vascular function. However, effects of lifestyle, e.g., physical activity level, on endothelial function and arterial stiffness remain scarce. The aim of our study was to investigate effects of physical activity level and risk factors on endothelial function and arterial stiffness. Methods: In this cross-sectional study, we ultrasonographically assessed parameters of vascular function, namely flow mediated dilation (FMD) of the brachial artery and carotid artery stiffness in patients after myocardial infarction referred to the cardiac rehabilitation. The International Physical Activity Questionnaire (IPAQ) was obtained from all participants. Based on the IPAQ, patients were classified into three groups: vigorous, moderate, and low physical activity engagement. ANOVA was used for comparison among three groups using Bonferroni correction to determine differences between two sub-groups. Results: One hundred and eight patients after myocardial infarction (mean age 53 ± 10 years) were included. There were significant differences in terms of FMD (8.2 vs. 4.2 vs. 1.9%, p < 0.001) and pulse wave velocity (PWV), a measure of arterial stiffness (6.1 vs. 6.4 vs. 6.9 m/s, p = 0.004) among groups of vigorous, moderate, and low physical activity engagement, respectively. However, in younger patients only FMD remained associated with physical activity level, while arterial stiffness was not. Low physical activity engagement was a significant predictor of both FMD and PWV in univariate and multivariate models, adjusted for age, sex, and other risk factors. Conclusion: Low physical activity level is associated with impaired endothelial function and increased arterial stiffness in patients after myocardial infarction. Future studies are warranted to address this issue in a context of cardiac rehabilitation protocols optimization in order to improve vascular function in these patients.

Hemodynamic and Hemostatic Response to Blood Flow Restriction Resistance Exercise in Coronary Artery Disease: A Pilot Randomized Controlled Trial.

BACKGROUND: Blood flow-restricted resistance training (BFR-RT) has been proven to be safe and efficacious in healthy older adults, but not in cardiovascular disease. OBJECTIVE: The aim of this study was to investigate the acute and training induced effects of BFR-RT on hemostatic and hemodynamic responses in patients with coronary artery disease (CAD). METHODS: Stable patients with CAD were randomized to 8 weeks of BFR-RT (30%-40% 1-repetition maximum unilateral knee extension) combined with aerobic training or aerobic training alone (control group). At baseline and after 4 and 8 weeks, blood samples were taken before and after BFR exercise, whereas hemodynamic parameters were monitored throughout the exercise. RESULTS: Twenty-four patients (12 per group; mean age, 60 ± 2 years; mostly male [75%]) completed the study. The BFR-RT significantly improved systolic blood pressure (-10 mm Hg; P = .020) and tended to lower diastolic blood pressure (-2 mm Hg; P = .066). In contrast, no posttraining alterations were observed in N-terminal prohormone B-type natriuretic hormone, fibrinogen, and D-dimer values. During BFR exercise, all hemodynamic variables significantly increased after the first and second set, whereas blood pressure immediately lowered after the cuff was released in the third set. Last, significant interaction was only observed for repetitions × intensity (P < .001; partial η2 = 0.908) of diastolic blood pressure at higher exercise intensity (40% 1-repetition maximum). CONCLUSIONS: The BFR-RT was proven to be safe, with favorable hemodynamic and hemostatic responses in patients with CAD, and can be recommended as an additional exercise modality in cardiac rehabilitation.Trial Registration:ClinicalTrial.gov Identifier: NCT03087292.

Targeted pharmacotherapy for ischemia reperfusion injury in acute myocardial infarction.

INTRODUCTION: Achieving reperfusion immediately after acute myocardial infarction improves outcomes; despite this, patients remain at a high risk for mortality and morbidity at least for the first year after the event. Ischemia-reperfusion injury (IRI) has a complex pathophysiology and plays an important role in myocardial tissue injury, repair, and remodeling. AREAS COVERED: In this review, the authors discuss the various mechanisms and their pharmacological agents currently available for reducing myocardial ischemia-reperfusion injury (IRI). They review important original investigations and trials in various clinical databases for treatments targeting IRI. EXPERT OPINION: Encouraging results observed in many preclinical studies failed to show similar success in attenuating myocardial IRI in large-scale clinical trials. Identification of critical risk factors for IRI and targeting them individually rather than one size fits all approach should be the major focus of future research. Various newer therapies like tocilizumab, anakinra, colchicine, revacept, and therapies targeting the reperfusion injury salvage kinase pathway, survivor activating factor enhancement, mitochondrial pathways, and angiopoietin-like peptide 4 hold promise for the future.

Role of gut microbiota in cardiovascular diseases.

The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.

Vorapaxar in the treatment of cardiovascular diseases.

Vorapaxar specifically and effectively inhibits protease activated receptor-1 and may reduce thrombin-mediated ischemic events without interfering primary hemostasis. In the TRA-2P-TIMI 50 trial, vorapaxar reduced the risk of primary ischemic outcome but with increased bleeding risk. In the post hoc analysis, in patients with a history of myocardial infarction, peripheral artery disease, the net clinical outcome favored vorapaxar therapy with 10% reduction in cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization and moderate or severe bleeding. Based on these favorable results, vorapaxar was approved for the reduction of thrombotic cardiovascular events in patients with prior myocardial infarction or with peripheral artery disease on top of standard antiplatelet therapy. A careful patient selection is needed to balance efficacy versus safety.

Short-Term Water- and Land-Based Exercise Training Comparably Improve Exercise Capacity and Vascular Function in Patients After a Recent Coronary Event: A Pilot Randomized Controlled Trial.

BACKGROUND: We hypothesized that a 2-week twice daily aquatic endurance plus calisthenics exercise training program: (i) increases aerobic exercise capacity (peak oxygen uptake/ V ˙ O2peak), (ii) improves endothelium-dependent flow-mediated vasodilation (FMD), and (iii) reduces circulating markers of low-grade inflammation and hemostasis, as compared to land-based endurance plus calisthenics exercise training or no exercise in patients undergoing short-term residential cardiac rehabilitation after a recent coronary artery disease (CAD) event. METHODS: Patients with a recent myocardial infarction or revascularization procedure were randomized into two interventional groups and a control group. The interventional groups underwent supervised aerobic endurance plus calisthenics exercise training either in thermo-neutral water or on land at moderate intensity (60-80% of the peak heart rate achieved during symptom-limited graded exercise testing) for 30 min twice daily for 2 weeks (i.e., 24 sessions). The control group was deferred from supervised exercise training for the 2-week duration of the intervention, but was advised low-to-moderate intensity physical activity at home while waiting. At baseline and after the intervention period, all participants underwent estimation of aerobic exercise capacity, brachial artery flow-mediated dilatation (FMD, measured ultrasonographically at rest and during reactive hyperemia after 4.5 min of forearm cuff inflation), markers of cardiac dysfunction (NT-proBNP), inflammation (hsCRP, IL-6, IL-8, IL-10), cell adhesion (ICAM, P-selectin), and hemostasis (fibrinogen, D-dimer). RESULTS: A total of 89 patients (mean age 59.9 ± 8.2 years, 77.5% males, V ˙ O2peak at baseline 14.8 ± 3.5 ml kg-1 min-1) completed the study. Both exercise modalities were safe (no significant adverse events recorded) and associated with a significant improvement in V ˙ O2peak as compared to controls: age and baseline V ˙ O2peak-adjusted end-of-study V ˙ O2peak increased to 16.7 (95% CI 16.0-17.4) ml kg-1 min-1 with land-based training (p < 0.001 for change from baseline) and to 18.6 (95% CI 17.9-19.3) ml kg-1 min-1 with water-based training (p < 0.001 for change from baseline), but not in controls (14.9 ml kg-1 min-1; 95% CI 14.2-15.6; p = 0.775 for change from baseline). FMD also increased in both intervention groups (from 5.5 to 8.8%, p < 0.001 with land-based, and from 7.2 to 9.2%, p < 0.001 with water-based training, respectively), as compared to controls (p for change 0.629). No significant changes were detected in biomarkers of inflammation, cell adhesion or hemostasis, whereas levels of NT-proBNP (marker of cardiac dysfunction) decreased in the water-based training group (p = 0.07 vs. controls). CONCLUSION: Endurance plus calisthenics exercise training in thermo-neutral water is safe, and improves aerobic exercise capacity and vascular function in patients undergoing short-term residential cardiac rehabilitation after a recent CAD event. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02831829.

Blood Flow Restriction Resistance Exercise Improves Muscle Strength and Hemodynamics, but Not Vascular Function in Coronary Artery Disease Patients: A Pilot Randomized Controlled Trial.

Resistance training may be associated with unfavorable cardiovascular responses (such as hemodynamic alterations, anginal symptoms or ventricular arrhythmias). In healthy adults, blood flow-restricted (BFR) resistance training improves muscle strength and hypertrophy improvements at lower loads with minimal systemic cardiovascular adverse responses. The aim of this study was to assess the safety and efficacy of BFR resistance training in patients with coronary artery disease (CAD) compared to usual care. Patients with stable CAD were randomized to either 8 weeks of supervised biweekly BFR resistance training (30-40% 1RM unilateral knee extension) or usual exercise routine. At baseline and after 8 weeks, patients underwent 1-RM knee extension tests, ultrasonographic appraisal of vastus lateralis (VL) muscle diameter and of systemic (brachial artery) flow-mediated dilation, and determination of markers of inflammation (CD40 ligand and tumor necrosis factor alfa), and fasting glucose and insulin levels for homeostatic model assessment (HOMA). A total of 24 patients [12 per group, mean age 60 ± 2 years, 6 (25%) women] were included. No training-related adverse events were recorded. At baseline groups significantly differ in age (mean difference: 8.7 years, p < 0.001), systolic blood pressure (mean difference: 12.17 mmHg, p = 0.024) and in metabolic control [insulin (p = 0.014) and HOMA IR (p = 0.014)]. BFR-resistance training significantly increased muscle strength (1-RM, +8.96 kg, p < 0.001), and decreased systolic blood pressure (-6.77 mmHg; p = 0.030), whereas VL diameter (+0.09 cm, p = 0.096), brachial artery flow-mediated vasodilation (+1.55%; p = 0.079) and insulin sensitivity (HOMA IR change of 1.15, p = 0.079) did not improve significantly. Blood flow restricted resistance training is safe and associated with significant improvements in muscle strength, and may be therefore provided as an additional exercise option to aerobic exercise to improve skeletal muscle functioning in patients with CAD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03087292.

Endocan Is an Independent Predictor of Heart Failure-Related Mortality and Hospitalizations in Patients with Chronic Stable Heart Failure.

BACKGROUND: Heart failure (HF) is characterized by unfavorable prognosis. Disease trajectory of HF, however, may vary, and risk assessment of patients remains elusive. In our study, we sought to determine the prognostic impact of endocan-a novel biomarker of endothelial dysfunction and low-grade inflammation-in patients with heart failure. METHODS: In outpatients with chronic HF, baseline values of endocan were determined and clinical follow-up for a minimum of 18 months obtained. A multivariate Cox proportional hazard model was built for HF-related death or hospitalization requiring inotropic support. RESULTS: A total of 120 patients (mean age 71 years, 64% male, mean LVEF 36%) were included. During a mean follow-up of 656 ± 109 days, 50 patients (41.6%) experienced an event. On Cox multivariate analysis, endocan values emerged as an independent predictor of HF prognosis (HR, 1.471 CI 95% 1.183-1.829, p = 0.001, for each 1 ng/mL increase) even after adjustment for age, gender, HF etiology, LVEF, NYHA class, NT-proBNP, and exercise tolerance. CONCLUSIONS: Endocan is an independent predictor of HF-related events in chronic HF individuals and represents a promising tool for risk assessment of HF patients.

Moderate-pain versus pain-free exercise, walking capacity, and cardiovascular health in patients with peripheral artery disease.

OBJECTIVE: Supervised exercise training (walking) is recommended in patients with intermittent claudication, both as a means to improve symptoms (walking distance and quality of life [QoL]) and as a means to improve general cardiovascular health (including vascular function and heart rate variability [HRV]). Our aim was to compare two types of supervised training (moderate-pain and pain-free walking) with comparable intensity based on heart rate, in terms of walking capacity, QoL, vascular function, biomarkers, and HRV in patients with intermittent claudication. METHODS: Thirty-six adults with intermittent claudication were randomized to either moderate-pain or pain-free exercise training (36 sessions, two or three times a week) or usual care (no supervised exercise). Initial walking distance and absolute walking distance using treadmill testing, flow-mediated vasodilation and pulse wave velocity using ultrasound, N-terminal pro-B-type natriuretic peptide and fibrinogen levels, HRV, and QoL (36-Item Short Form Health Survey questionnaire) were determined at baseline and after the intervention period. RESULTS: Twenty-nine patients (mean age, 64 ± 9 years; 72% male) completed the study. Both training programs similarly improved walking capacity. Initial walking distance and absolute walking distance significantly increased with either moderate-pain walking (median, 50 m to 107 m [P = .005] and 85 m to 194 m [P = .005], respectively) or pain-free walking (median, 53 m to 128 m [P = .003] and 92 m to 163 m [P = .003], respectively). QoL also similarly improved with both training modalities, whereas only moderate-pain walking was also associated with a statistically significant improvement in the vascular parameters flow-mediated vasodilation (4.4% to 8.0%; P = .002) and pulse wave velocity (6.6 m/s to 6.1 m/s; P = .013). Neither training program was associated with changes in biomarker levels and HRV. CONCLUSIONS: Both moderate-pain and pain-free training modalities were safe and similarly improved walking capacity and health-related QoL. Conversely, vascular function improvements were associated with only moderate-pain walking.

Exercise training in adults with repaired tetralogy of Fallot: A randomized controlled pilot study of continuous versus interval training.

INTRODUCTION: Adults with repaired tetralogy of Fallot (ToF) have impaired exercise capacity, vascular and cardiac autonomic function, and quality of life (QoL). Specific effects of high-intensity interval or moderate continuous exercise training on these parameters in adults with repaired ToF remain unknown. METHODS AND RESULTS: Thirty adults with repaired ToF were randomized to either high-intensity interval, moderate intensity continuous training (36 sessions, 2-3 times a week) or usual care (no supervised exercise). Exercise capacity, flow-mediated vasodilation, pulse wave velocity, NT-proBNP and fibrinogen levels, heart rate variability and recovery, and QoL (SF-36 questionnaire) were determined at baseline and after the intervention period. Twenty-seven patients (mean age 39±9years, 63% females, 9 from each group) completed this pilot study. Both training groups improved in at least some parameters of cardiovascular health compared to no exercise. Interval-but not continuous-training improved VO2peak (21.2 to 22.9ml/kg/min, p=0.004), flow-mediated vasodilation (8.4 to 12.9%, p=0.019), pulse wave velocity (5.4 to 4.8m/s, p=0.028), NT-proBNP (202 to 190ng/L, p=0.032) and fibrinogen levels (2.67 to 2.46g/L, p=0.018). Conversely, continuous-but not interval-training improved heart rate variability (low-frequency domain, 0.32 to 0.22, p=0.039), heart rate recovery after 2min post-exercise (40 to 47 beats, p=0.023) and mental domain of SF-36 (87 to 95, p=0.028). CONCLUSION: Both interval and continuous exercise training modalities were safe. Interval training seems more efficacious in improving exercise capacity, vascular function, NT-proBNP and fibrinogen levels, while continuous training seems more efficacious in improving cardiac autonomic function and QoL. (Clinicaltrials.gov, NCT02643810).

Cardiovascular autonomic dysfunction and carotid stiffness in adults with repaired tetralogy of Fallot.

PURPOSE: Adults after surgical repair of tetralogy of Fallot (ToF) may have impaired vascular and cardiac autonomic function. Thus, we wanted to assess interrelations between heart rate variability (HRV) and heart rate recovery (HRR), as parameters of cardiac autonomic function, and arterial stiffness, as a parameter of vascular function, in adults with repaired ToF as compared to healthy controls. METHODS: In a case-control study of adults with repaired ToF and healthy age-matched controls we measured: 5-min HRV variability (with time and frequency domain data collected), carotid artery stiffness (through pulse-wave analysis using echo-tracking ultrasound) and post-exercise HRR (cycle ergometer exercise testing). RESULTS: Twenty-five patients with repaired ToF (mean age 38 ± 10 years) and 10 healthy controls (mean age 39 ± 8 years) were included. Selected HRR and HRV (time-domain) parameters, but not arterial stiffness were significantly reduced in adults after ToF repair. Moreover, a strong association between late/slow HRR (after 2, 3 and 4 min) and carotid artery stiffness was detected in ToF patients (r = -0.404, p = 0.045; r = -0.545, p = 0.005 and r = -0.545, p = 0.005, respectively), with statistical significance retained even after adjusting for age, gender, resting heart rate and ß-blockers use (r = -0.393, p = 0.024 for HRR after 3 min). CONCLUSION: Autonomic cardiac function is impaired in patients with repaired ToF, and independently associated with vascular function in adults after ToF repair, but not in age-matched healthy controls. These results might help in introducing new predictors of cardiovascular morbidity in a growing population of adults after surgical repair of ToF.