Category Archives: Publications

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry .

Salzano A; D’Assante R; Iacoviello M; Triggiani V; Rengo G; Cacciatore F; Maiello C; Limongelli G; Masarone D; Sciacqua A; Filardi PP; Mancini A; Volterrani M; Vriz O; Castello R; Passantino A; Campo M; Modesti PA; De Giorgi A; Arcopinto M; Gargiulo P; Perticone M; Colao A; Milano S; Garavaglia A; Napoli R; Suzuki T; Bossone E; Marra AM; Cittadini A;

Cardiovascular diabetology [Cardiovasc Diabetol] 2022 Jun 16; Vol. 21 (1), pp. 108.
Date of Electronic Publication: 2022 Jun 16.

Background: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance-IR or diabetes mellitus-T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF.
Methods: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D.
Results: Compared with EU and IR, T2D was associated with increased filling pressures (E/e’ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO 2 ) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO 2 in the T2D group (+ 13% increase in RV dimension, - 21% decline in TAPSE/PAPS ratio and - 20% decrease in peak VO 2 ).
Conclusion: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis.

Risk Stratification and Outcomes in Patients With Pulmonary Hypertension: Insights into Right Ventricular Strain by MRI Feature tracking.

Zhou D; Li X; Yin G; Li S; Zhao S; Liu Z; Lu M;

Journal of magnetic resonance imaging : JMRI [J Magn Reson Imaging] 2022 Jun 17.
Date of Electronic Publication: 2022 Jun 17.

Background: Despite a recommended multidimensional approach for pulmonary hypertension (PH) risk stratification and guidance of treatment decisions, this may not always be achievable in patients with advanced disease. One issue is the lack of an imaging modality to assess right ventricular (RV) structure and function abnormalities.
Purpose: To explore the risk stratification and prognostic value of cardiac MR feature tracking (MR-FT)-derived RV strain.
Study Type: Retrospective.
Population: A total of 80 patients with idiopathic pulmonary artery hypertension (N = 52) or chronic thromboembolic PH (N = 28).
Field Strength: A 1.5 T or 3.0 T, balanced steady-state free precession sequence.
Assessment: All patients underwent laboratory testing, right heart catheterization, and MR imaging (and in 37 cases, a cardiopulmonary exercise test was also performed) within a 1-month period. Cardiac functional parameters and both global longitudinal strain (GLS) and global circumferential strain (GCS) were analyzed. Patients were stratified into low, intermediate, and high-risk groups by guideline suggested stratified values of risk factors. The combined endpoint was death or hospitalization for congestive heart failure assessed during follow-up since the date of MR examination.
Statistical Tests: Kolmogorov-Smirnov’s test, independent-sample t-tests, Wilcoxon’s rank-sum tests, one-way analysis of variance, χ 2 tests or Fisher’s exact test, receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression analysis. A P value < 0.05 was considered statistically significant.
Results: The median follow-up duration was 3.4 years. Thirty-five patients presented with combined endpoint including 10 cardiac deaths. RV structural and deformation impairments were significantly associated with combined endpoint (ejection fraction: 31.3% ± 13.2% vs. 38.0% ± 14.8%, hazard ratio [HR: 0.974; GLS: -14.5 [-18.6, -10.9] % vs. -20.4 [-26.0, -13.2] %, HR: 1.071; GCS: -9.8 [-14.5, -7.3] % vs. -12.3 [-19.9, -8.4] %, HR: 1.059). There were significant differences in RVGLS among low, intermediate, and high-risk groups (-19.3% ± 7.2% vs. -17.3% ± 9.4% vs. -11.5% ± 4.4% by cardiac functional class, -21.8% ± 7.3% vs. -19.4% ± 8.2% vs. -12.7 ± 5.3% by NT-proBNP, -19.7% ± 7.7 vs. -15.8% ± 6.5% vs. -12.6% ± 8.2% by cardiac index).
Data Conclusion: RV deformation may aid risk stratification in patients with PH, providing crucial information for RV remodeling, pulmonary hemodynamic condition and exercise capacity.

Exercise Stress Testing in Athletes.

Parizher G; Emery MS;

Clinics in sports medicine [Clin Sports Med] 2022 Jul; Vol. 41 (3), pp. 441-454.

Exercise stress testing (EST) is indicated for diagnostic and prognostic purposes in the general population. In athletes, stress tests can also be useful to inform the risk of high-intensity training and competition, to assess athletic conditioning, and to refine training regimens. Many specific indications for EST are unique to athletes. Treadmill and cycle ergometer protocols each have their strengths and disadvantages; extensive protocol customization may be necessary to answer the clinical question at hand. A comprehensive understanding of the available tools for exercise testing, their strengths, and their limitations is crucial to providing cardiovascular care to athletic individuals.

Sleep behaviour and cardiorespiratory fitness in patients after percutaneous coronary intervention during cardiac rehabilitation: protocol for a longitudinal study.

Huang L; Zhou J; Li H; Wang Y; Wu X; Wu J;

BMJ open [BMJ Open] 2022 Jun 13; Vol. 12 (6), pp. e057117.
Date of Electronic Publication: 2022 Jun 13.

Introduction: Most patients with coronary heart disease experience sleep disturbances and low cardiorespiratory fitness (CRF), but their relationship during cardiac rehabilitation (CR) is still unclear. This article details a protocol for the study of sleep trajectory in patients with coronary heart disease during CR and the relationship between sleep and CRF. A better understanding of the relationship between sleep and CRF on patient outcomes can improve sleep management strategies.
Methods and Analysis: This is a longitudinal study with a recruitment target of 101 patients after percutaneous cardiac intervention from the Seventh People’s Hospital of Shanghai, China. Data collection will include demographic characteristics, medical history, physical examination, blood sampling, echocardiography and the results of cardiopulmonary exercise tests. The information provided by a 6-min walk test will be used to supplement the CPET. The Pittsburgh Sleep Quality Index will be used to understand the sleep conditions of the participants in the past month. The Patient Health Questionnaire and General Anxiety Disorder Scale will be used to assess depression and anxiety, respectively. All participants will be required to wear an actigraphy on their wrists for 72 hours to monitor objective sleep conditions. This information will be collected four times within 6 months of CR, and patients will be followed up for 1 year. The growth mixture model will be used to analyse the longitudinal sleep data. The generalised estimating equation will be used to examine the associations between sleep and CRF during CR.

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study.

Van Tassell B; Mihalick V; Thomas G; Marawan A; Talasaz AH;Lu J; Kang L; Ladd A; Damonte JI; Dixon DL; Markley R; Turlington J; Federmann E; Del Buono MG; Biondi-Zoccai G; Canada JM; Arena R; Abbate A;

Journal of translational medicine [J Transl Med] 2022 Jun 15; Vol. 20 (1), pp. 270.
Date of Electronic Publication: 2022 Jun 15.

Background: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF.
Method: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO 2 ) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO 2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes.
Discussion: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF.
Trial Registration: The trial was registered prospectively with on Jan 8, 2019, identifier NCT03797001.

Exercise Oscillatory Breathing in Heart Failure with reduced ejection fraction: clinical implication.

da Luz Goulart C; Agostoni P; Salvioni E; Kaminsky LA; Myers J; Arena R; Borghi-Silva A;

European journal of preventive cardiology [Eur J Prev Cardiol] 2022 Jun 16.
Date of Electronic Publication: 2022 Jun 16.

Aim: I) to evaluate the impact of exertional oscillatory ventilation (EOV) in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) during cardiopulmonary exercise testing (CPET) compared with patients without EOV (N-EOV); II) to identify the influence of EOV persistence (P-EOV) and EOV disappearance (D-EOV) during CPET on the outcomes of mortality and hospitalization in HFrEF patients; and III) to identify further predictors of mortality and hospitalization in patients with P-EOV.
Methods and Results: 315 stable HFrEF patients underwent CPET and were followed for 35 months. We identified 202 patients N-EOV and 113 patients with EOV. Patients with EOV presented more symptoms (NYHA III: 35% vs. N-EOV 20%, p < 0.05), worse cardiac function (LVEF: 28 ± 6 vs. N-EOV 39 ± 1, p < 0.05), higher minute ventilation/carbon dioxide production (V̇E/V̇CO2 slope: 41 ± 11 vs. N-EOV 37 ± 8, p < 0.05) and a higher rate of deaths (26% vs. N-EOV 6%, p < 0.05) and hospitalization (29% vs. N-EOV 9%, p < 0.05). P-EOV patients had more severe HFrEF (NYHA IV: 23% vs D-EOV: 9%, p < 0.05), had worse cardiac function (LVEF: 24 ± 5 vs. D-EOV: 34 ± 3, p < 0.05) and had lower peak oxygen consumption (V̇O2) (12.0 ± 3.0 vs D-EOV: 13.3 ± 3.0, p < 0.05). Among P-EOV, other independent predictors of mortality were V̇E/V̇CO2 slope ≥36 and V̇O2 peak ≤12; a V̇E/V̇CO2 slope≥34 was a significant predictor of hospitalization. Kaplan-Meier survival analysis showed that, HFrEF patients with P-EOV had a higher risk of mortality and higher risk of hospitalization (p < 0.05) than patients with D-EOV and N-EOV.
Conclusion: In HFrEF patients, EOV persistence during exercise had a strong prognostic role. In P-EOV patients V̇E/V̇CO2 ≥36 and V̇O2 peak ≤12, had a further additive negative prognostic role.

Obese patients with long COVID-19 display abnormal hyperventilatory response and impaired gas exchange at peak exercise.

Lacavalerie MR; Pierre-Francois S; Agossou M; Inamo J; Cabie A; Barnay JL; Neviere R;

Future cardiology [Future Cardiol] 2022 Jun 06.
Date of Electronic Publication: 2022 Jun 06.

Aim: To analyze the impact of obesity on cardiopulmonary response to exercise in people with chronic post-coronavirus disease 2019 (COVID-19) syndrome.
Patients & methods: Consecutive subjects with chronic post-COVID syndrome 6 months after nonsevere acute infection were included. All patients received a complete clinical evaluation, lung function tests and cardiopulmonary exercise testing. A total of 51 consecutive patients diagnosed with chronic post-COVID-19 were enrolled in this study.
Results: More than half of patients with chronic post-COVID-19 had a significant alteration in aerobic exercise capacity (VO 2 peak) 6 months after hospital discharge. Obese long-COVID-19 patients also displayed a marked reduction of oxygen pulse (O 2 pulse).
Conclusion: Obese patients were more prone to have pathological pulmonary limitation and pulmonary gas exchange impairment to exercise compared with nonobese COVID-19 patients.

Improved Exercise Tolerance in an Adolescent Female After Failed Fontan and Subsequent Biventricular Conversion.

Tang B; Romme A; Dababneh R; Awad S;

Pediatric cardiology [Pediatr Cardiol] 2022 Jun 09.
Date of Electronic Publication: 2022 Jun 09.

We report a case of improved exercise tolerance in a single-ventricle patient following biventricular conversion. An 11 year old with a fenestrated extracardiac failing Fontan was accepted for a biventricular conversion repair at an out-of-town institution. The patient had multiple adverse cardiac events following Fontan surgery including recurrent pleural effusions, arteriovenous malformations, protein-losing enteropathy, and marked exercise intolerance. Serial cardiac catheterizations revealed chronic elevated pulmonary artery and Fontan pressures, normal left ventricular end-diastolic pressure and an adequately sized left ventricle. Cardiopulmonary exercise testing demonstrated severely reduced exercise tolerance due to ventilatory and cardiac limitations with significant arterial desaturations during exercise. Following a successful biventricular conversion, exercise tolerance improved remarkably, as evidenced by improved oxygen uptake and ventilatory efficiency. Our case demonstrates that biventricular conversion surgery may offer improvement in quality of life and exercise capacity in selected patients with failing Fontan physiology.

Exercise Capacity in Patients with Pulmonary Atresia with Intact Ventricular Septum: Does the Type of Surgical Repair Matter?

Konduri A; Sriram C; Mahadin D; Aggarwal S;

Pediatric cardiology [Pediatr Cardiol] 2022 Jun 09.
Date of Electronic Publication: 2022 Jun 09.

Two standard surgical palliative options for neonates born with pulmonary atresia and intact ventricular septum (PA/IVS) include uni-or biventricular repair. Whenever feasible, the biventricular repair is considered to have better exercise capacity (XC) and outcomes. However, there is a paucity of data comparing objective XC between these two surgical techniques. Our aim was to compare XC, including longitudinal changes in patients with PA/IVS following uni-biventricular repair. We performed a single-center retrospective study of survivors with repaired PA/IVS who underwent comprehensive treadmill cardiopulmonary exercise testing. Initial and latest exercise parameters were compared for longitudinal analysis. Demographic and exercise parameters were collated. Peak oxygen uptake (VO 2 in ml/kg/min), an indicator of maximal aerobic capacity, peak heart rate, and other measures of spirometry performed at the same time were collected. Recorded parameters included, (a) Percentage of predicted VO 2 (% VO2) normalized for age, weight, height, and gender, (b) % oxygen (O 2 ) pulse, (c) anaerobic threshold (AT), (d) Chronotropic index (CI), (e) % Breathing reserve, (f) Forced vital capacity (FVC), (g) % Forced Expiratory volume in 1 s (FEV1), (h) Maximum voluntary ventilation (MVV), and (i) VE/VCO 2 . Appropriate statistical tests were performed, and a p value < 0.05 was considered significant. A total of 35 patients (43% male, 57% univentricular repair) were included, with a mean (SD) age of 20.1(7.5) years. Patients with univentricular palliation demonstrated significantly impaired peak heart rate, chronotropic index (0.50 ± 0.2 vs. 0.90 ± 0.1, p = 0.02), VE/VCO 2 (35.4 ± 5.0 vs. 30.2 ± 2.8, p = 0.001), and %FVC (78.3 ± 8.3 vs. 88.6 ± 15.1, p = 0.02). There was a trend towards reduction in % VO 2 in the Fontan patients though it was statistically similar between the groups (68.4 ± 21.4 vs. 81.2 ± 18.9, p = 0.07). Longitudinal data were available for 11 patients in each group, and there was no longitudinal decline in their exercise parameters over similar intermediate follow-up duration [6.8 (UV) vs. 5.3 (BV) years]. We conclude that young survivors with PA/IVS with prior univentricular palliation demonstrated an objective impairment in their chronotropic parameters compared with the biventricular repair. However, this did not translate into a significant difference in their exercise capacity. There was no longitudinal decline in exercise capacity or other parameters over intermediate follow-up.

Cardiopulmonary exercise testing and efficacy of percutaneous coronary intervention: a substudy of the ORBITA tria

Ganesananthan S; Rajkumar CA; Foley M; Thompson D; Nowbar AN; Seligman H; Petraco R; Sen S; Nijjer S;
Thom SA; Wensel R;Davies J; Francis D; Shun-Shin M; Howard J; Al-Lamee R;

Aims: Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. The aim of this analysis was to examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome and to determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI).
Methods and Results: Patients with severe single-vessel coronary artery disease (CAD) were randomized 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomization treadmill CPET, dobutamine stress echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period.A total of 195 patients with CPET data were randomized (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score [+0.82 segments; 95% confidence interval (CI): 0.40 to 1.25, P = 0.0068] and lower fractional flow reserve (-0.07; 95% CI: -0.12 to -0.02, P = 0.011) compared with those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score [oxygen-pulse plateau presence (Pinteraction = 0.026) and oxygen-pulse gradient (Pinteraction = 0.023)] and Seattle angina physical-limitation score [oxygen-pulse plateau presence (Pinteraction = 0.037)]. Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse, and oxygen uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI.
Conclusion: Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel CAD.