Author Archives: Paul Older

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.


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.

The double anaerobic threshold in heart failure: MECKI score database overview.

Rovai S; Zaffalon D; Cittar M; Felli LF; Salvioni E; Galotta A; Mattavelli I; Carriere C; Mapelli M; Merlo M; Vignati C; Sinagra G; Agostoni P;

ESC heart failure [ESC Heart Fail] 2022 May 17.
Date of Electronic Publication: 2022 May 17.

Aims: In heart failure (HF), anaerobic threshold (AT) may be indeterminable but its value held a relevant prognostic role. AT is evaluated joining three methods: V-slope, ventilatory equivalent, and end-tidal methods. The possible non-concordance between the V-slope (met AT) and the other two methods (vent AT) has been highlighted in healthy individuals and named double threshold (DT).
Methods and Results: We reanalysed 1075 cardiopulmonary exercise tests of HF patients recruited in the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score database. We identified DT in 43% of cases. Met AT precedes vent AT being met-ventΔVO 2 221 (interquartile range: 129-319) mL/min. Peak VO 2 , 1307 ± 485 vs. 1343 ± 446 mL/min (63 ± 17 vs. 63 ± 17 percentage of predicted), was similar between DT+ and DT- patients. Differently, DT+ showed a lower ventilatory vs. carbon dioxide production (VE/VCO 2 ) slope (29.6 ± 6.1 vs. 31.0 ± 6.3), a lower peak exercise end-tidal oxygen tension (PetO 2 ) 115.3 (111.5-118.9) vs. 116.4 (112.4-120.2) mmHg, and a higher carbon dioxide tension (PetCO 2 ) 34.2 (30.9-37.1) vs. 32.4 (28.7-35.5) mmHg. Vent AT showed a significant higher VO 2 , 957 ± 318 vs. 719 ± 252 mL/min, VCO 2 , 939 ± 319 vs. 627 ± 226 mL/min, ventilation, 31.0 ± 8.3 vs. 22.5 ± 6.3 L/min, respiratory exchange ratio, 0.98 ± 0.08 vs. 0.87 ± 0.07, PetO 2 , 108 (104-112) vs. 105 (101-109) mmHg, PetCO 2 , 37 (34-40) vs. 36 (33-39) mmHg, and VE/VO 2 ratio, 33.5 ± 6.7 vs. 32.6 ± 6.9, but lower VE/VCO 2 ratio, 33 (30-37) vs. 36 (32-41), compared with met AT. At 2 year survival by Kaplan-Meier analysis, even adjusted for confounders, DT resulted not associated with survival.
Conclusions: Double threshold is frequently observed in HF patients. DT+ is associated to a decreased ventilatory response during exercise.

A case report of profound atrioventricular block in an endurance athlete: how far do you go?

Abela M; Bonello J; Sammut MA;

European heart journal. Case reports [Eur Heart J Case Rep] 2022 May 02; Vol. 6 (5), pp. ytac190.
Date of Electronic Publication: 2022 May 02 (Print Publication: 2022).

Background: Athletes presenting with 1st-degree atrioventricular block (AVB) on 12-lead electrocardiogram (ECG) may present a diagnostic conundrum, especially when significantly prolonged and associated with higher degrees of block. A pragmatic stepwise approach to the evaluation of these patients is, therefore, crucial.
Case Summary: A 19-year-old waterpolo player was referred for assessment of a 1st-degree heart block and one isolated episode of syncope. All other cardiac investigations were within normal limits except for a 24-h ambulatory ECG which showed Mobitz 1 AVB and episodes of 2:1 block occurring in the context of Wenchebach. An electrophysiological study (EPS) was performed which effectively excluded infranodal conductive tissue disease, confirming physiological intranodal block.
Discussion: The increase in vagal tone is one of the physiological adaptations to an increased demand in cardiac output in athletes, which explains the presence of 1st-degree AVB in up to 7.5% of athletes. The presence of 2:1 AVB on 24 h ECG raises doubts whether the 1st-degree AVB on resting ECG is pathological or physiological, especially considering this particular patient had suffered an episode of syncope. When this diagnostic uncertainty persists despite non-invasive investigations, including cardiopulmonary exercise testing, invasive EPS may be required to assess the refractoriness of the AV node and at what level within the cardiac conductive system block occurs. The electrophysiological study can effectively rule out infranodal disease by confirming physiological intranodal block using incremental atrial pacing.

Exercise Capacity in Children and Adolescents With Congenital Heart Disease: A Systematic Review and Meta-Analysis.

Villaseca-Rojas Y; Varela-Melo J; Torres-Castro R; Vasconcello-Castillo L; Mazzucco G; Vilaró J; Blanco I;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2022 May 04; Vol. 9, pp. 874700.
Date of Electronic Publication: 2022 May 04 (Print Publication: 2022).

Background: Congenital heart disease (CHD) entails structural defects in the morphogenesis of the heart or its main vessels. Analyzing exercise capacity of children and adolescents with CHD is important to improve their functional condition and quality of life, since it can allow timely intervention on poor prognostic factors associated with higher risk of morbidity and mortality.
Objective: To describe exercise capacity in children and adolescents with CHD compared with healthy controls.
Methods: A systematic review was carried out. Randomized clinical trials and observational studies were included assessing exercise capacity through direct and indirect methods in children and adolescents between 5 and 17 years-old. A sensitive analysis was performed including studies with CHD repaired participants. Additionally, it was sub-analyzed by age range (< and ≥ 12 years old). Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of the evidence.
Results: 5619 articles were found and 21 were considered for the review. Eighteen articles used the direct exercise capacity measurement method by cardiopulmonary exercise test (CPET). The CHD group showed significant differences in peak oxygen consumption (VO 2 peak) with a value of -7.9 ml/Kg/min (95% CI: -9.9, -5.9, p = 0.00001), maximum workload (Wmax) -41.5 (95% CI: -57.9, -25.1 watts, p = 0.00001), ventilatory equivalent (VE/VCO 2) slope 2.6 (95% CI: 0.3, 4.8), oxygen pulse (O 2 pulse)-2.4 ml/beat (95% CI: -3.7, -1.1, p = 0.0003), and maximum heart rate (HRmax) -15 bpm (95% CI: -18, -12 bpm, p = 0.00001), compared with healthy controls. Adolescents (≥ 12 yrs) with CHD had a greater reduction in VO 2 peak (-10.0 ml/Kg/min (95% CI: -12.0, -5.3), p < 0.00001), Wmax (-45.5 watts (95% CI: -54.4, -36.7), p < 0.00001) and HRmax (-21 bpm (95% CI: -28, -14), p <0.00001).
Conclusion: Suffering CHD in childhood and adolescence is associated with lower exercise capacity as shown by worse VO 2 peak, Wmax, VE/VCO 2 slope, O 2 pulse, and HRmax compared with matched healthy controls. The reduction in exercise capacity was greater in adolescents.

The effect of medium-term recovery status after COVID-19 illness on cardiopulmonary exercise capacity in a physically active adult population.

Ladlow P; O’Sullivan O; Bennett AN; Barker-Davies R; Houston A; Chamley R; May S; Mills D; Dewson D;
Rogers-Smith K; Ward C; TayloJ;Mulae J; Naylor J; Nicol ED; Holdsworth DA;

Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2022 May 19.
Date of Electronic Publication: 2022 May 19.

Background: A failure to fully recover following coronavirus disease 2019 (COVID-19) may have a profound impact on high functioning populations ranging from front-line emergency services to professional or amateur/recreational athletes.
Aim: To describe the medium-term cardiopulmonary exercise profiles of individuals with ‘persistent symptoms’ and individuals who feel ‘recovered’ after hospitalization or mild-moderate community infection following COVID-19 to an age, sex and job-role matched control group.
Methods: 113 participants underwent cardiopulmonary functional tests at a mean 159±7 days (~5 months) following acute illness; 27 hospitalized with persistent symptoms (hospitalized-symptomatic), 8 hospitalized and now recovered (hospitalized-recovered); 34 community managed with persistent symptoms (community-symptomatic); 18 community managed and now recovered (community-recovered), and 26 controls.
Results: Hospitalized groups had the least favorable body composition (body mass, body mass index and waist circumference) compared to controls. Hospitalized-symptomatic and community-symptomatic individuals had a lower oxygen uptake (V̇O 2 ) at peak exercise (hospitalized-symptomatic, 29.9±5.0ml/kg/min; community-symptomatic, 34.4±7.2ml/kg/min; vs. control 43.9±3.1ml/kg/min, both p<0.001). Hospitalized-symptomatic individuals had a steeper V̇E/V̇CO 2 slope (lower ventilatory efficiency) (30.5±5.3 vs. 25.5±2.6, p=0.003) vs. controls. Hospitalized-recovered had a significantly lower oxygen uptake at peak (32.6±6.6ml/kg/min vs. 43.9 ±13.1ml/kg/min, p=0.015) compared to controls. No significant differences were reported between community-recovered individuals and controls in any cardiopulmonary parameter.
Conclusion: Medium term findings suggest community-recovered individuals did not differ in cardiopulmonary fitness from physically active healthy controls. This suggests their readiness to return to higher levels of physical activity. However, the hospitalized-recovered group and both groups with persistent symptoms had enduring functional limitations, warranting further monitoring, rehabilitation and recovery.