Author Archives: Paul Older

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 ClinicalTrials.gov 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 mlO2.kg-1.min-1, p < 0.05). Among P-EOV, other independent predictors of mortality were V̇E/V̇CO2 slope ≥36 and V̇O2 peak ≤12 mlO2.kg-1.min-1; 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 mlO2.kg-1.min-1, 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.

Prognostic value of 6-min walk test compared to cardiopulmonary exercise test in patients with severe heart failure.

Corrà U; Giordano A; Marcassa C; Gambarin FI; Gnemmi M; Pistono M;

Journal of cardiovascular medicine (Hagerstown, Md.) [J Cardiovasc Med (Hagerstown)] 2022 Jun 01; Vol. 23 (6),
pp. 379-386.

Aims: The 6-min walk test (6MWT) and cardiopulmonary exercise test (CPET) are both predictive in heart failure (HFrEF). Although 6MWT substitutes for CPET in HFrEF patients, as submaximal testing may be preferable, its prognostic superiority still needs to be verified, particularly in regard to beta blockers (BBs). We aimed to compare the prognostic role of CPET and 6MWT and investigate whether BB therapy influences the predictive value.
Methods: This is a single-center, retrospective study. Advanced HFrEF patients were followed up for 3 years: events were cardiovascular death or urgent heart transplantation. We analyzed the predictive capacity of CPET and 6MWT in patients, and subdivided according to use of BBs.
Results: In a group of 251 HFrEF patients, we found a correlation between meters and peak VO2 (r2 = 0.94). Over the 3-year follow-up, 74 events were recorded. Both CPET and 6MWT variables were correlated with outcome at univariate analysis (meter and VE/VCO2 slope, peak VO2, VO2 at ventilatory anaerobic threshold, percentage predicted of peak VO2), but only percentage predicted of peak VO2 (pppVO2) was an independent predictor. In 103 HFrEF patients on BBs (23 nonsurvivors), neither pppVO2 nor meter were predictive, while in 148 patients not treated with BB (51 with events) pppVO2 was selected as an independent prognostic parameter (P = 0.001).
Conclusions: 6MWT is a valid alternative to CPET, although the percentage of predicted of peak VO2 emerged as the strongest predictor. Nonetheless, our results suggest that both functional derived parameters are not predictive among those patients treated with BBs. Further studies are necessary to confirm these findings.

OLD AND NEW EQUATIONS FOR MAXIMAL HEART RATE PREDICTION IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION ON BETA-BLOCKERS TREATMENT. RESULTS FROM THE MECKI SCORE DATASET.

Magr D; Piepoli M; Gallo G; Corr U; Metra M; Paolillo S; Filardi PP; Maruotti A; Assunta.; Salvioni E; Mapelli M; Vignati C; Senni M; Limongelli G; Lagioia R; Scrutinio D; Emdin M; Passino C; Parati G; Sinagra G; Correale M; Badagliacca R; Sciomer S; Di Lenarda A; Agostoni P;

European journal of preventive cardiology [Eur J Prev Cardiol] 2022 May 17.
Date of Electronic Publication: 2022 May 17.

Background: Predicting maximal heart rate (MHR) in heart failure and reduced ejection fraction (HFrEF) still remains a major concern. In such a context, the Keteyian equation is the only one derived in a HFrEF cohort on optimized β-blockers treatment. Therefore, using the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) dataset, we looked for a possible MHR equation, for an external validation of Keteyien formula and, contextually, for accuracy of the historical MHR formulas and their relationship with the HR measured at the anaerobic threshold (AT).
Methods and Results: Data from 3,487 HFrEF outpatients on optimized β-blockers treatment from the MECKI dataset were analyzed. Besides excluding all possible confounders, the new equation was derived by using HR data coming from maximal cardiopulmonary exercise test (CPET).The simplified derived equation was [109 – (0.5*age) + (0.5*HR rest) + (0.2*LVEF) – (5 if haemoglobin < 11 g/dL)]. The R2 and the SEE were 0.24 and 17.5 beats·min-1 with a MAPE = 11.9%. The Keteyian equation had a slightly higher mean absolute percentage error (MAPE = 12.3%). Conversely the Fox and Tanaka equations showed extremely higher MAPE values. The range 75-80% of MHR according to the new and the Keteyian equations was the most accurate in identifying the HR at the AT (MAPEs 11.3% to 11.6%).
Conclusions: The derived equation to estimate the MHR in HFrEF patients, by accounting also for the systolic dysfunction degree and anemia, improved slightly the Keteyian formula. Both formulas might be helpful in identifying the true maximal effort during an exercise test and the intensity domain during a rehabilitation program.