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analysis of renal flow pattern in acute heart failure and associate study of the right heart

Aims\ud \ud Pulmonary hypertension (PHT) may complicate heart failure with reduced ejection fraction (HFrEF) and is associated with a substantial symptom burden and poor prognosis. Sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, might have beneficial effects on pulmonary haemodynamics, cardiac function and exercise capacity in HFrEF and PHT. The aim of this study was to determine the safety, tolerability, and efficacy of sildenafil in patients with HFrEF and indirect evidence of PHT.\ud \ud \ud \ud Methods and results\ud \ud The Sildenafil in Heart Failure (SilHF) trial was an investigator-led, randomized, multinational trial in which patients with HFrEF and a pulmonary artery systolic pressure (PASP) ≥40 mmHg by echocardiography were randomly assigned in a 2:1 ratio to receive sildenafil (up to 40 mg three times/day) or placebo. The co-primary endpoints were improvement in patient global assessment by visual analogue scale and in the 6-min walk test at 24 weeks. The planned sample size was 210 participants but, due to problems with supplying sildenafil/placebo and recruitment, only 69 patients (11 women, median age 68 (interquartile range [IQR] 62–74) years, median left ventricular ejection fraction 29% (IQR 24–35), median PASP 45 (IQR 42–55) mmHg) were included. Compared to placebo, sildenafil did not improve symptoms, quality of life, PASP or walk test distance. Sildenafil was generally well tolerated, but those assigned to sildenafil had numerically more serious adverse events (33% vs. 21%).\ud \ud \ud \ud Conclusion\ud \ud Compared to placebo, sildenafil did not improve symptoms, quality of life or exercise capacity in patients with HFrEF and PHT.

Supplemental material, 4_Supplementary_material for Extracorporeal membrane oxygenation without therapeutic anticoagulation in adults: A systematic review of the current literature by Dario Fina, Matteo Matteucci, Federica Jiritano, Paolo Meani, Valeria Lo Coco, Mariusz Kowalewski, Jos Maessen, Marco Guazzi, Andrea Ballotta, Marco Ranucci and Roberto Lorusso in The International Journal of Artificial Organs

Background The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a prognostic model to identify heart failure (HF) patients at risk for cardiovascular mortality (CVM) and urgent heart transplantation (uHT) based on 6 routine clinical parameters: hemoglobin, sodium, kidney function by the Modification of Diet in Renal Disease (MDRD) equation, left ventricle ejection fraction (LVEF), percentage of predicted peak oxygen consumption (VO2) and VE/VCO2 slope. Objectives MECKI score must be generalizable to be considered useful: therefore, its performance was validated in a new sequence of HF patients. Methods Both the development (MECKI-D) and the validation (MECKI-V) cohorts were composed of consecutive HF patients with LVEF < 40% able to perform a symptom-limited cardiopulmonary exercise testing. The CVM or uHT rates were analyzed at one, two and three years in both cohorts: all patients with a censoring time shorter than the scheduled follow-up were excluded, while those with events occurring after 1, 2 and 3 years were considered as censored. Results MECKI-D and MECKI-V consisted of 2009 and 992 patients, respectively. MECKI-V patients had a higher LVEF, higher peak VO2 and lower VE/VCO2 slope, higher prescription of beta-blockers and device therapy: after the 3-year follow-up, CVM or uHT occurred in 206 (18%) MECKI-D and 44 (13%) MECKI-V patients (p < 0.000), respectively. MECKI-V AUC values at one, two and three years were 0.81 ± 0.04, 0.76 ± 0.04, and 0.80 ± 0.03, respectively, not significantly different from MECKI-D. Conclusions MECKI score preserves its predictive ability in a HF population at a lower risk.

From an evidence-based perspective, cardiopulmonary exercise testing (CPX) is a well-supported assessment technique in both the United States (US) and Europe. The combination of standard exercise testing (ET) [i.e. progressive exercise provocation in association with serial electrocardiograms (ECGs), haemodynamics, oxygen saturation, and subjective symptoms] and measurement of ventilatory gas exchange amounts to a superior method to: (i) accurately quantify cardiorespiratory fitness (CRF), (ii) delineate the physiologic system(s) underlying exercise responses, which can be applied as a means to identify the exercise-limiting pathophysiological mechanism(s) and/or performance differences, and (iii) formulate function-based prognostic stratification. Cardiopulmonary ET certainly carries an additional cost as well as competency requirements and is not an essential component of evaluation in all patient populations. However, there are several conditions of confirmed, suspected, or unknown aetiology where the data gained from this form of ET is highly valuable in terms of clinical decision making.1

From an evidence-based perspective, cardiopulmonary exercise testing (CPX) is a well-supported assessment technique in both the United States (US) and Europe. The combination of standard exercise testing (ET) (ie, progressive exercise provocation in association with serial electrocardiograms [ECG], hemodynamics, oxygen saturation, and subjective symptoms) and measurement of ventilatory gas exchange amounts to a superior method to: 1) accurately quantify cardiorespiratory fitness (CRF), 2) delineate the physiologic system(s) underlying exercise responses, which can be applied as a means to identify the exercise-limiting pathophysiologic mechanism(s) and/or performance differences, and 3) formulate function-based prognostic stratification. Cardiopulmonary ET certainly carries an additional cost as well as competency requirements and is not an essential component of evaluation in all patient populations. However, there are several conditions of confirmed, suspected, or unknown etiology where the data gained from this form of ET is highly valuable in terms of clinical decision making

Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission.We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ± 13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78).In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.

Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures ("backward" failure), which may or may not coexist with reduced cardiac output ("forward" failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes. Dr Verbrugge is supported by a Fellowship of the Belgian American Educational Foundation and by the Special Research Fund of Hasselt University (grant no. BOF19PD04). Dr Borlaug is supported by grants R01 HL128526 and U01 HL125205, both from the US National Heart, Lung, and Blood Institute. Borlaug, BA (corresponding author), Mayo Clin & Mayo Fdn, 200 First St SW, Rochester, MN 55905 USA. borlaug.barry@mayo.edu

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. Interpretation: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Methods and results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577–2304) days in the entire population, 1203 (614–2420) and 1325 (569–2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001). Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

Although still underutilized, cardiopulmonary exercise testing (CPET) allows the most accurate and reproducible measurement of cardiorespiratory fitness and performance in athletes. It provides functional physiologic indices which are key variables in the assessment of athletes in different disciplines. CPET is valuable in clinical and physiological investigation of individuals with loss of performance or minor symptoms that might indicate subclinical cardiovascular, pulmonary or musculoskeletal disorders. Highly trained athletes have improved CPET values, so having just normal values may hide a medical disorder. In the present review, applications of CPET in athletes with special attention on physiological parameters such as VO2max, ventilatory thresholds, oxygen pulse, and ventilatory equivalent for oxygen and exercise economy in the assessment of athletic performance are discussed. The role of CPET in the evaluation of possible latent diseases and overtraining syndrome, as well as CPET-based exercise prescription, are outlined.

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A. INTRODUCTION A.1. The sympathetic nervous system. A.1.1. General considerations and historical perspective. A.1.1.1. Historical perspective A.1.1.2. Reflex regulation of the autonomic nervous system A.1.1.3. Central control of the autonomic nervous system A.1.1.4. Sympathetic and parasympathetic components of the autonomic nervous system A.1.1.5. Organisation of the sympathetic nervous system A.1.1.6. Functions of the sympathetic nervous system A.1.1.7. Neurotransmitters of the sympathetic nervous system A.1.1.8. Neurotransmitter secretion at effectors organ synapse A.1.1.9. Adrenoreceptors A.1.2. Control mechanisms A.1.2.1. Aortic arch and carotid baroreceptors A.1.2.2. Low pressure baroreceptors A.1.2.3. Chemoreceptors A.1.2.4. Effects of exercise on sympathetic nervous system activation A.1.2.5. Effects of left ventricular dysfunction on sympathetic nervous system activation A.1.2.6. Effects of right ventricular dysfunction and heart transplantation on sympathetic nervous system activity A.2. Methodological considerations. A.2.1. Assessment of sympathetic activity in humans A.2.2. Circulating catecholamines A.2.3. Microneurography A.3. Ergospirometry A.3.1. Several aspects of physiology of exercise A.3.2. Principles of exercise testing A.3.3. Exercise ventilation A.4. Assessment of chemoreceptor regulation in humans A.4.1. Peripheral chemoreceptor inhibition A.4.2. Peripheral and central chemoreceptor activation A.5. Brief summary of still unresolved questions A.5.1. Pulmonary arterial hypertension A.5.2. Heart transplantation B. SYMPATHETIC CONTROL IN PULMONARY ARTERIAL HYPERTENSION B.1. Hypothesis tested B.2. Study populations B.2.1. Study investigating sympathetic activity in PAH patients B.2.2. Study investigating the effects of atrial septostomy on MSNA in PAH patients B.3. Material, methods and study protocols B.3.1. Particular measurements in the study investigating sympathetic activity in PAH patients B.3.2. Particular measurements in the study investigating effects of atrial septostomy on MSNA in PAH patients B.4. Sympathetic nervous activity in PAH and effects of disease severity B.5. Effects of chemoreflex activation B.6. Effects of atrial septostomy C. SYMPATHETIC CONTROL AFTER HEART TRANSPLANTATION C.1. Hypothesis tested C.2. Patient population C.3. Material and methods C.4. Effects of chemoreflex activation on sympathetic activity and blood pressure C.5. Effects of chemoreflex activation on exercise intolerance D. DISCUSSION D.1. Sympathetic nervous system activation in patients with pulmonary arterial hypertension D.2. Effects of atrial septostomy on sympathetic nervous system activation D.3. Chemoreceptors in heart transplant recipients D.3.1. Peripheral chemoreceptors deactivation D.3.2. Peripheral and central chemoreceptors sensitivity E. CONCLUSIONS F. REFERENCE LIST G. ANNEXES G.1. Publications G.1.1. Velez-Roa and Ciarka et al, Increased sympathetic nerve activity in pulmonary artery hypertension, Circulation. 2004 Sep 7;110(10):1308- 12. G.1.2. Ciarka et al, Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension, Chest. 2007 Jun;131(6):1831-7. G.1.3. Ciarka et al, Effects of peripheral chemoreceptors deactivation on sympathetic activity in heart transplant recipients. Hypertension. 2005 May;45(5):894-900. G.1.4. Ciarka et al, Increased peripheral chemoreceptors sensitivity and exercise ventilation in heart transplant recipients. Circulation. 2006 Jan 17;113(2):252-7. G.2. Annexe thesis title. G.3. Brief summary in French of described research, Doctorat en Sciences médicales, info:eu-repo/semantics/published