Category Archives: Publications

High-intensity interval training in cardiac resynchronization therapy: a randomized control trial.

Santa-Clara H; Abreu A; Melo X; Santos V; Cunha P; Oliveira M; Pinto R;
Carmo MM; Fernhall B.

European Journal of Applied Physiology. 119(8):1757-1767, 2019 Aug.
VI 1

AIMS: To determine the effects of high-intensity interval training (HIIT)
following cardiac resynchronization therapy (CRT) implantation in patients
with chronic heart failure (CHF), on noninvasive estimates of systolic
ventricular function, exercise performance, severity of symptoms and
quality of life.

METHODS: Cardiopulmonary exercise testing, resting transthoracic
echocardiogram and health-related quality of life assessment were obtained
before and at 6 months after CRT implantation in 37 patients with
moderate-to-severe CHF. Patients were randomized after CRT to either a
24-week HIIT group (90-95% peak heart rate, 2 days per week) or to a usual
care group (CON). Mixed design 2 x 2 repeated measures ANOVA were used to
test for differences within and in-between groups.

RESULTS: Improvements in health-related quality of life (HIIT = 98.54%,
CON = 123.47%), NYHA class (HIIT = 43.44%, CON = 38.30%) HR recovery at
minute 1 (HIIT = 32.32%, CON = 42.94%), pulse pressure at peak effort
(HIIT = 14.06%, CON = 9.52%, LVEF (HIIT = 42.17%, CON = 51.10%) and LV
Mass (HIIT = 13.26%, CON = 11.88%) were similar in both groups (p > 0.05).
Significant increases in CPET duration in the HIIT group (25.94%), and
increases in peak VO2 (HIIT = 8.64%, CON = 4.85%) and percent-predicted
VO2 (HIIT = 10.57%, CON = 4.26%) in both groups, were observed in the
intention-to-treat analysis.

CONCLUSION: Six months of HIIT in patients in CRT did not further
improved indices of functional capacity and health-related quality of
life, and LV structure and function, compared to CRT alone. However, HIIT
led to further improvements in exercise performance. It remains unclear
whether HIIT benefits patients in CRT to a similar degree as more
conventional forms of exercise training previously shown to maximize
benefits in CRT.

L-Arginine Improves Endurance to High-Intensity Interval Exercises in Overweight Men.

Daraei A; Ahmadizad S; Rahmani H; Hackney AC; Johnson KE; Laher I; Saeidi A; Zouhal H;

International journal of sport nutrition and exercise metabolism [Int J Sport Nutr Exerc Metab] 2020 Dec 01, pp. 1-9. Date of Electronic Publication: 2020 Dec 01.

The effects of acute consumption of L-Arginine (L-Arg) in healthy young individuals are not clearly defined, and no studies on the effects of L-Arg in individuals with abnormal body mass index undertaking strenuous exercise exist. Thus, we examined whether supplementation with L-Arg diminishes cardiopulmonary exercise testing responses, such as ventilation (VE), VE/VCO2, oxygen uptake (VO2), and heart rate, in response to an acute session of high-intensity interval exercise (HIIE) in overweight men. A double-blind, randomized crossover design was used to study 30 overweight men (age, 26.5 ± 2.2 years; body weight, 88.2 ± 5.3 kilogram; body mass index, 28.0 ± 1.4 kg/m2). Participants first completed a ramped-treadmill exercise protocol to determine VO2max velocity (vVO2max), after which they participated in two sessions of HIIE. Participants were randomly assigned to receive either 6 g of L-Arg or placebo supplements. The HIIE treadmill running protocol consisted of 12 trials, including exercise at 100% of vVO2max for 1 min interspersed with recovery intervals of 40% of vVO2max for 2 min. Measurements of VO2 (ml·kg-1·min-1), VE (L/min), heart rate (beat per min), and VE/VCO2 were obtained. Supplementation with L-Arg significantly decreased all cardiorespiratory responses during HIIE (placebo+HIIE vs. L-Arg+HIIE for each measurement: VE [80.9 ± 4.3 L/min vs. 74.6 ± 3.5 L/min, p < .05, ES = 1.61], VE/VCO2 [26.4 ± 1.3 vs. 24.4 ± 1.0, p < .05, ES = 1.8], VO2 [26.4 ± 0.8 ml·kg-1·min-1 vs. 24.4 ± 0.9 ml·kg-1·min-1, p < .05, ES = 2.2], and heart rate [159.7 ± 6.3 beats/min vs. 155.0 ± 3.7 beats/min, p < .05, d = 0.89]).
The authors conclude consuming L-Arg before HIIE can alleviate the excessive physiological strain resulting from HIIE and help to increase exercise tolerance in participants with a higher body mass index who may need to exercise on a regular basis for extended periods to improve their health.

Hemodynamic and Clinical Implications of Impaired Pulmonary Vascular Reserve in the Fontan Circulation.

Egbe AC; Miranda WR; Anderson JH; Borlaug BA;

Journal of the American College of Cardiology [J Am Coll Cardiol] 2020 Dec 08; Vol. 76 (23), pp. 2755-2763.

Background: Pulmonary vascular disease, pulmonary endothelial dysfunction, liver fibrosis, renal disease, and exercise intolerance are common in adults with Fontan physiology. Although the pathophysiologic mechanisms linking these phenomena have been studied, certain aspects are not well understood.
Objectives: This study hypothesized that impaired pulmonary vascular reserve (VR) plays a central role linking these abnormalities, and that patients with abnormal pulmonary VR with exercise, compared with patients with normal VR, would display poorer pulmonary endothelial function, greater liver stiffness, more renal dysfunction, and poorer exercise capacity.
Methods: Symptomatic adults with the Fontan palliation (n = 29) underwent invasive cardiopulmonary exercise testing, echocardiography, and assessment of microvascular function. Abnormal pulmonary VR was defined by the slope of increase in pulmonary pressure relative to cardiac output with exercise >3 mm Hg/l/min. Pulmonary endothelial function was assessed using reactive hyperemia index. End-organ function was assessed using magnetic resonance elastography-derived liver stiffness, glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and peak oxygen consumption (Vo 2 ).
Results: Compared with individuals with normal VR (n = 8), those with abnormal VR (n = 21) displayed higher central and pulmonary venous pressures, and more severely impaired cardiac output and stroke volume responses to exertion, but similar pulmonary vascular resistance at rest. Patients with abnormal VR displayed more severely impaired reactive hyperemia index, increased liver stiffness, lower glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and lower peak Vo 2 . As compared to pulmonary vascular resistance at rest, slope of increase in pulmonary pressure relative to cardiac output displayed stronger correlations with reactive hyperemia index (r = -0.63 vs. r = -0.31; Meng test p = 0.009), magnetic resonance elastography-derived liver stiffness (r = 0.47 vs. r = 0.29; Meng test p = 0.07), glomerular filtration rate (r = -0.52 vs. r = -0.24; Meng test p = 0.03), N-terminal pro-B-type natriuretic peptide (r = 0.56 vs. r = 0.17; Meng test p = 0.02), and peak Vo 2 (r = -0.63 vs. r = -0.26; Meng test p = 0.02).
Conclusions: Pulmonary vascular limitations in Fontan physiology are related to pulmonary endothelial and end-organ dysfunction, suggesting a mechanistic link between these commonly observed findings, and these abnormalities are more apparent during exercise testing, with little relationship at rest.

Study protocol for resolution of organ injury in acute pancreatitis (RESORP): an observational prospective cohort study.

BMJ Open. 2020 Dec 7;10(12):e040200. doi: 10.1136/bmjopen-2020-040200.

INTRODUCTION: Survivors of acute pancreatitis (AP) have shorter overall survival and increased incidence of new-onset cardiovascular, respiratory, liver and renal disease, diabetes mellitus and cancer compared with the general population, but the mechanisms that explain this are yet to be elucidated. Our aim is to characterise the precise nature and extent of organ dysfunction following an episode of AP.
METHODS AND ANALYSIS: This is an observational prospective cohort study in a single centre comprising a University hospital with an acute and emergency receiving unit and clinical research facility. Participants will be adult patient admitted with AP. Participants will undergo assessment at recruitment, 3 months and 3 years. At each time point, multiple biochemical and/or physiological assessments to measure cardiovascular, respiratory, liver, renal and cognitive function, diabetes mellitus and quality of life. Recruitment was from 30 November 2017 to 31 May 2020; last follow-up measurements is due on 31 May 2023. The primary outcome measure is the incidence of new-onset type 3c diabetes mellitus during follow-up. Secondary outcome measures include: quality of life analyses (SF-36, Gastrointestinal Quality of Life Index); montreal cognitive assessment; organ system physiological performance; multiomics predictors of AP severity, detection of premature cellular senescence. In a nested cohort within the main cohort, individuals may also consent to multiparameter MRI scan, echocardiography, pulmonary function testing, cardiopulmonary exercise testing and pulse-wave analysis.
ETHICS AND DISSEMINATION: This study has received the following approvals: UK IRAS Number 178615; South-east Scotland Research Ethics Committee number 16/SS/0065.
Results will be made available to AP survivors, caregivers, funders and other researchers. Publications will be open-access. TRIAL REGISTRATION NUMBERS: Registry (NCT03342716) and ISRCTN50581876;

Differential impact of a cardiac rehabilitation program in functional parameters according to patient gender.

Vilela EM; Ladeiras-Lopes R; Joao A; Braga J; Torres S; Ribeiro J; Primo J; Fontes-Carvalho R; Campos L; Miranda F; Nunes JP; Teixeira M; Braga P;

American journal of cardiovascular disease [Am J Cardiovasc Dis] 2020 Oct 15; Vol. 10 (4), pp. 367-375. Date of Electronic Publication: 2020 Oct 15 (Print Publication: 2020).

Introduction: Exercise-based cardiac rehabilitation (EBCR) programs are of paramount importance in the management of acute myocardial infarction (AMI) survivors. Albeit this, female patients tend to be less referred for these programs, while also having a poorer prognosis. We aimed at assessing the impact of a contemporary EBCR program on functional parameters after an AMI, and specifically the impact of gender on its potential benefits.
Methods: Observational, retrospective cohort study including all patients admitted to a tertiary center due to an AMI who completed a phase II EBCR program after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test (CPET). Patients were dichotomized according to gender.
Results: A total of 379 patients were included, 19% of whom were women. After the program, peak oxygen uptake (pVO2) and exercise duration increased significantly (P<0.001). Though female patients presented a lower pVO2 and completed a shorter CPET at both the beginning and end of the study, there were no differences in the magnitude of improvement in these parameters between both groups [pVO2 delta 1.37 ± 3.08 vs 1.31 ± 2.62 mL/kg/min, P=0.876; CPET duratio n delta 120 (60-167) vs 85 (60-146), P=0.176].
Conclusions: A contemporary EBCR program was associated with significant improvements in functional parameters, as assessed by CPET. Though female patients had lower levels of pVO2, the benefits of this program were similar among groups. These results highlight the importance of EBCR among this higher risk subset of patients.

Cerebral Oxygenation during Exercise in Patients with Cardiopulmonary Diseases: A Prospective Observational Study.

Tung YJ; Yen YS; Lin BS; Chou W;

Acta Cardiologica Sinica [Acta Cardiol Sin] 2020 Nov; Vol. 36 (6), pp. 667-674.

Background: The relationship between exercise and cerebral oxygenation has gained increasing attention. However, few studies have investigated the correlation between exercise and cerebral oxygenation in patients with cardiopulmonary diseases.
Objectives: To investigate the correlation between exercise and cerebral oxygenation in patients with cardiopulmonary diseases.
Methods: Thirty eligible patients with cardiopulmonary diseases underwent incremental cardiopulmonary exercising test (CPET) and near-infrared spectroscopy with both right and left sensors placed at the mid forehead to detect oxygen saturation of cerebral tissue (STO2). Parameters of cerebral oxygenation and exercise intensity were collected and analyzed.
Results: The average age of the patients was 51.17 ± 10.21 years and included 23 males and 7 females. The average maximal STO2 of the left and right brain during CPET were 51.850 ± 1.57% and 51.755 ± 1.90%, respectively. Meanwhile, mean oxygen consumption (VO2) while reaching maximal STO2 was 4.42 ± 1.05 metabolic equivalents (METs) over the left brain and 4.34 ± 1.17 METs over the right brain. The exercise intensity upon reaching maximal STO2 was 84.91 ± 11.70% over the left brain and 83.16 ± 14.64% over the right brain. Peak VO2 was significantly correlated to VO2 upon reaching maximal STO2 over the left and right brain (R = 0.805, p < 0.001 and R = 0.739, p < 0.001, respectively). Age was significantly negatively correlated to VO2 upon maximal STO2 over the left and right brain (R = -0.378, p = 0.039 and R = -0.513, p = 0.004, respectively).
Conclusions: Cerebral oxygenation increases with higher exercise intensity, and it reaches a maximal STO2 between respiratory compensation point and peak exercise. The higher the peak VO2, the better the VO2 upon reaching maximal STO2.

Future developments in the MECKI score initiative.

Coats AJ;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec; Vol. 27 (2_suppl), pp. 72-75.

The Metabolic Exercise combined with Cardiac and Kidney Indexes [MECKI) score is a validated prognostic score for heart failure with reduced ejection fraction which combines commonly available clinical and metabolic parameters with two cardiopulmonary exercise test derived prognostic measurements. It has been validated to predict prognosis and to aid clinical decision making and it has been shown to be superior in predicting mortality compared with other commonly used prognostic scores for heart failure. In the future it would be valuable to establish whether the score holds true also in other settings, and in particular in under-represented groups – the elderly, women, and people of different ethnic backgrounds – and in other heart failure syndromes. In future it may be extended to assess its value in the presence of a range of co-morbidities such as chronic obstructive pulmonary disease, pulmonary hypertension and frailty and cachexia as well as in other conditions such as hypertrophic cardiomyopathy, amyloid, asymptomatic left ventricular dysfunction and hypertension. It may also be a candidate end-point for adaptive trials designed to prove an improvement in the MECKI score as an approvable interim end-point whilst larger mortality and morbidity trials are still underway.

Beta-blockers in heart failure prognosis: Lessons learned by MECKI Score Group papers.

Cattadori G; Di Marco S; Farina S; Limongelli G; Monda E; Badagliacca R; Papa S; Tricarico L; Correale M;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec; Vol. 27 (2_suppl), pp. 65-71.

Heart failure is a complex syndrome affecting several organs including kidney, lungs, liver, brain muscles and sympathetic system. Each of these organs might contribute to its severity and prognosis. The prognosis assessment is critical for a correct heart failure management. It has already been demonstrated that a single parameter is weaker for prognosis than different parameters combined. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has been built and validated for heart failure with reduced ejection fraction (HFrEF) patients by considering cardiopulmonary exercise test data combined with clinical, laboratory and echocardiographic measurements. The betablockers treatment is a milestone in the HFrEF management. In the MECKI score database, the association of betablockers treatment with outcome has been investigated in different settings.

Risk stratification in heart failure with mild reduced ejection fraction.

Magrì D; Gallo G; Parati G; Cicoira M; Senni M;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec; Vol. 27 (2_suppl), pp. 59-64.

Heart failure with mid-range ejection fraction represents a heterogeneous and relatively young heart failure category accounting for nearly 20-30% of the overall heart failure population. Due to its complex phenotype, a reliable clinical picture of heart failure with mid-range ejection fraction patients as well as a definite risk stratification are still relevant unsolved issues. In such a context, there is growing interest in a comprehensive functional assessment by means of a cardiopulmonary exercise test, yet considered a cornerstone in the clinical management of patients with heart failure and reduced ejection fraction. Indeed, the cardiopulmonary exercise test has also been found to be particularly useful in the heart failure with mid-range ejection fraction category, several cardiopulmonary exercise test-derived parameters being associated with a poor outcome. In particular, a recent contribution by the metabolic exercise combined with cardiac and kidney indexes research group showed an independent association between the peak oxygen uptake and pure cardiovascular mortality in a large cohort of recovered heart failure with mid-range ejection fraction patients. Contextually, the same study supplied an easy approach to identify a high-risk heart failure with mid-range ejection fraction subset by using a combination of peak oxygen uptake and ventilatory efficiency cut-off values, namely 55% of the maximum predicted and 31, respectively. Thus, looking at the above-mentioned promising results and waiting for specific trials, it is reasonable to consider cardiopulmonary exercise test assessment as part of the heart failure with mid-range ejection fraction work-up in order to identify those patients with an unfavourable functional profile who probably deserve a close clinical follow-up and, probably, more aggressive therapeutic strategies.