Category Archives: Publications

Exercise cardiac power and the risk of heart failure in men: A population-based follow-up study.

Kurl S; Jae SY; Mäkikallio TH; Voutilainen A; Hagnäs MJ; Kauhanen J; Laukkanen JA;

Journal of sport and health science [J Sport Health Sci] 2022 Mar; Vol. 11 (2), pp. 266-271.
Date of Electronic Publication: 2020 Feb 24.

Background: Little is known about exercise cardiac power (ECP), defined as the ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, on heart failure (HF) risk. We examined the association of ECP and the risk of HF.
Methods: This was a population-based cohort study of 2351 men from eastern Finland. The average time to follow-up was 25 years. Participants participated at baseline in an exercise stress test. A total of 313 cases of HF occurred.
Results: Men with low ECP (<9.84 mL/mmHg, the lowest quartile) had a 2.37-fold (95% confidence interval (95%CI): 1.68-3.35, p < 0.0001) hazards ratio of HF as compared with men with high ECP (>13.92 mL/mmHg, the highest quartile), after adjusting for age. Low ECP was associated with a 1.96-fold risk (95%CI: 1.38-2.78, p < 0.001) of HF after additional adjustment for conventional risk factors. After further adjustment for left ventricular hypertrophy, the results hardly changed (hazards ratio = 1.87, 95%CI: 1.31-2.66, p < 0.001). One SD increase in ECP (3.16 mL/mmHg) was associated with a decreased risk of HF by 28% (95%CI: 17%-37%).
Conclusion: ECP provides a noninvasive and easily available measure from cardiopulmonary exercise tests in predicting HF. However, ECP did not provide additional value over maximal oxygen uptake .

Cardiorespiratory physiology, exertional symptoms, and psychological burden in post-COVID-19 fatigue.

Schaeffer MR; Cowan J; Milne KM; Puyat JH; Voduc N; Lavoie KL; Mulloy A; Chirinos JA; Abdallah SJ; Guenette JA;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2022 Mar 29; Vol. 302, pp. 103898.
Date of Electronic Publication: 2022 Mar 29.

Fatigue is a common, debilitating, and poorly understood symptom post-COVID-19. We sought to better characterize differences in those with and without post-COVID-19 fatigue using cardiopulmonary exercise testing. Despite elevated dyspnoea intensity ratings, V̇O 2 peak (ml/kg/min) was the only significant difference in the physiological responses to exercise (19.9 ± 7.1 fatigue vs. 24.4 ± 6.7 ml/kg/min non-fatigue, p = 0.04). Consistent with previous findings, we also observed a higher psychological burden in those with fatigue in the context of similar resting cardiopulmonary function. Our findings suggest that lower cardiorespiratory fitness and/or psychological factors may contribute to post-COVID-19 fatigue symptomology. Further research is needed for rehabilitation and symptom management following SARS-CoV-2 infection.

Utility of exercise testing to assess athletes for post COVID-19 myocarditis.

Mitrani RD; Alfadhli J; Lowery MH; Best TM; Hare JM; Fishman J; Dong C; Siegel Y; Scavo V; Basham GJ; Myerburg RJ; Goldberger JJ;

American heart journal plus : cardiology research and practice [Am Heart J Plus] 2022 Mar 31, pp. 100125.
Date of Electronic Publication: 2022 Mar 31.

Purpose: This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection.
Methods: We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days.
Results: We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2 max , left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis.
Conclusions: Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.

Cardiopulmonary Outcomes After the Nuss Procedure in Pectus Excavatum.

Jaroszewski DE; Farina JM; Gotway MB; Stearns JD; Peterson MA; Pulivarthi VSKK; Bostoros P; Abdelrazek AS; Gotimukul A; Majdalany DS; Wheatley-Guy CM;Arsanjani R;

Journal of the American Heart Association [J Am Heart Assoc] 2022 Apr 05; Vol. 11 (7), pp. e022149.
Date of Electronic Publication: 2022 Apr 04.

Background Pectus excavatum is the most common chest wall deformity. There is still controversy about cardiopulmonary limitations of this disease and benefits of surgical repair. This study evaluates the impact of pectus excavatum on the cardiopulmonary function of adult patients before and after a modified minimally invasive repair.
Methods and Results In this retrospective cohort study, an electronic database was used to identify consecutive adult (aged ≥18 years) patients who underwent cardiopulmonary exercise testing before and after primary pectus excavatum repair at Mayo Clinic Arizona from 2011 to 2020. In total, 392 patients underwent preoperative cardiopulmonary exercise testing; abnormal oxygen consumption results were present in 68% of patients. Among them, 130 patients (68% men, mean age, 32.4±10.0 years) had post-repair evaluations. Post-repair tests were performed immediately before bar removal with a mean time between repair and post-repair testing of 3.4±0.7 years (range, 2.5-7.0). A significant improvement in cardiopulmonary outcomes ( P <0.001 for all the comparisons) was seen in the post-repair evaluations, including an increase in maximum, and predicted rate of oxygen consumption, oxygen pulse, oxygen consumption at anaerobic threshold, and maximal ventilation. In a subanalysis of 39 patients who also underwent intraoperative transesophageal echocardiography at repair and at bar removal, a significant increase in right ventricle stroke volume was found ( P <0.001).
Conclusions Consistent improvements in cardiopulmonary function were seen for pectus excavatum adult patients undergoing surgery. These results strongly support the existence of adverse cardiopulmonary consequences from this disease as well as the benefits of surgical repair.

Identification of factors impairing exercise capacity after severe COVID-19 pulmonary infection: a 3-month follow-up of prospective COVulnerability cohort.

Ribeiro Baptista B; d’Humieres T; Schlemmer F; Bendib I; Justeau G;
Al-Assaad L; Hachem M; Codiat R; Bardel B; Abou Chakra L; Belmondo T;
Audureau E; Hue S; Mekontso-Dessap A; Derumeaux G; Boyer L

Respiratory Research. 23(1):68, 2022 Mar 22.

BACKGROUND: Patient hospitalized for coronavirus disease 2019 (COVID-19)
pulmonary infection can have sequelae such as impaired exercise capacity.
We aimed to determine the frequency of long-term exercise capacity
limitation in survivors of severe COVID-19 pulmonary infection and the
factors associated with this limitation.

METHODS: Patients with severe COVID-19 pulmonary infection were enrolled
3 months after hospital discharge in COVulnerability, a prospective
cohort. They underwent cardiopulmonary exercise testing, pulmonary
function test, echocardiography, and skeletal muscle mass evaluation.

RESULTS: Among 105 patients included, 35% had a reduced exercise capacity
(VO2peak < 80% of predicted). Compared to patients with a normal exercise
capacity, patients with reduced exercise capacity were more often men
(89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002)
and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in
terms of initial acute disease severity. An altered exercise capacity was
associated with an impaired respiratory function as assessed by a decrease
in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung
capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a
decrease of muscular mass index and grip test in the reduced exercise
capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of
patients with low exercise capacity had a sarcopenia, compared to 10.9% in
those with normal exercise capacity (p = 0.001). Myocardial function was
normal with similar systolic and diastolic parameters between groups
whilst reduced exercise capacity was associated with a slightly shorter
pulmonary acceleration time, despite no pulmonary hypertension.

CONCLUSION: Three months after a severe COVID-19 pulmonary infection,
more than one third of patients had an impairment of exercise capacity
which was associated with a reduced pulmonary function, a reduced skeletal
muscle mass and function but without any significant impairment in cardiac

Impact of closed loop stimulation on prognostic cardiopulmonary variables in patients with chronic heart failure and severe chronotropic incompetence: a pilot, randomized, crossover study.

Proff J; Merkely B; Papp R; Lenz C; Nordbeck P; Butter C; Meyerhoefer J;
Doering M; MacCarter DJ; Ingel K; Thouet T; Landmesser U; Roser MJ

Europace. 23(11):1777-1786, 2021 11 08.

AIMS: Clinical effects of rate-adaptive pacing in heart failure patients
with chronotropic incompetence (CI) undergoing cardiac resynchronization
therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new
rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS
in CRT patients with severe CI, focusing primarily on key prognostic
variables assessed by cardiopulmonary exercise (CPX) testing.

METHODS AND RESULTS: In the randomized, crossover, multicentre BIO

CREATE study, 20 CRT patients with severe CI and NYHA Class II/III
(60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode,
or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode).
Patients underwent symptom-limited treadmill-based CPX test in each mode.
An improvement (decrease) of the ventilatory efficiency (VE) slope of >=5%
during CLS was regarded as positive response to CLS. Seventeen patients
with full data sets had a mean intra-individual VE slope change of -1.8
+/- 3.0 (-4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS
responders, with a -6.1 +/- 2.7 (-16.4%) slope change (P = 0.029).
Compared to non-responders, CLS responders had a higher left ventricular
(LV) ejection fraction (46 +/- 3 vs. 36 +/- 9%; P = 0.0070), smaller
end-diastolic LV volume (121 +/- 34 vs. 181 +/- 41 mL; P = 0.0085),
smaller end-systolic LV volume (65 +/- 23 vs. 114 +/- 39 mL; P = 0.0076),
and were predominantly in NYHA Class II (P = 0.0498).

CONCLUSION: The data of the present pilot study are compatible with the
notion that CLS activation may improve VE slope in CRT patients with
severe CI and less advanced heart failure. Further research is needed to
determine the long-term clinical outcomes of CLS.

Sub-maximal aerobic exercise training reduces haematocrit and ameliorates symptoms in Andean highlanders with chronic mountain sickness.

Macarlupu JL; Vizcardo-Galindo G; Figueroa-Mujica R; Voituron N;
Richalet JP; Villafuerte FC

Experimental Physiology. 106(11):2198-2209, 2021 11.

ABSTRACT: Excessive erythrocytosis is the hallmark sign of chronic
mountain sickness (CMS), a debilitating syndrome associated with
neurological symptoms and increased cardiovascular risk. We have shown
that unlike sedentary residents at the same altitude, trained individuals
maintain haematocrit within sea-level range, and thus we hypothesise that
aerobic exercise training (ET) might reduce excessive haematocrit and
ameliorate CMS signs and symptoms. Eight highlander men (38 +/- 12 years)
with CMS (haematocrit: 70.6 +/- 1.9%, CMS score: 8.8 +/- 1.4) from Cerro
de Pasco, Peru (4340 m) participated in the study. Baseline assessment
included haematocrit, CMS score, pulse oximetry, maximal cardiopulmonary
exercise testing and in-office plus 24 h ambulatory blood pressure (BP)
monitoring. Blood samples were collected to assess cardiometabolic,
erythropoietic, and haemolysis markers. ET consisted of pedalling exercise
in a cycloergometer at 60% of V O 2 peak for 1 h/day, 4 days/week for 8
weeks, and participants were assessed at weeks 4 and 8. Haematocrit and
CMS score decreased significantly by week 8 (to 65.6 +/- 6.6%, and 3.5 +/-
0.8, respectively, P < 0.05), while V O 2 peak and maximum workload
increased with ET (33.8 +/- 2.4 vs. 37.2 +/- 2.0 ml/min/kg, P < 0.05; and
172.5 +/- 9.4 vs. 210.0 +/- 27.8 W, P < 0.01; respectively). Except for an
increase in high-density lipoprotein cholesterol, other blood markers and
BP showed no differences. Our results suggest that reduction of
haematocrit and CMS symptoms results mainly from haemodilution due to
plasma volume expansion rather than to haemolysis. In conclusion, we show
that ET can effectively reduce haematocrit, ameliorate symptoms and
improve aerobic capacity in CMS patients, suggesting that regular aerobic
exercise might be used as a low-cost non-invasive and non-pharmacological
management strategy.

Impaired Ventilatory Efficiency, Dyspnea and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.

Phillips DB; Elbehairy AF; James MD; Vincent SG; Milne KM; de-Torres JP; Neder JA;Kirby M; Jensen D; Stickland MK; Guenette JA; Smith BM; Aaron SD; Tan WC; Bourbeau J; O’Donnell DE;

American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2022 Mar 25.
Date of Electronic Publication: 2022 Mar 25.

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [V̇E/V̇CO2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD).
Objectives: To determine: 1) the association between high V̇E/V̇CO2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort.
Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing and chest computed tomography (CT). Impaired exercise ventilatory efficiency was defined by a nadir V̇E/V̇CO2 above the upper limit of normal (V̇E/V̇CO2>ULN), using population-based normative values.
Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with GOLD 1 COPD, and 200 with GOLD 2-4 COPD. Participants with V̇E/V̇CO2>ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale≥2, odds ratio=1.77[1.31-2.39]) and abnormally low peak oxygen uptake (V̇O2peak<LLN, odds ratio=4.58[3.06-6.86]). The carbon monoxide transfer coefficient (KCO) had a stronger correlation with nadir V̇E/V̇CO2 (r=-0.38, p<0.001) than other relevant lung function and CT metrics. The prevalence of V̇E/V̇CO2>ULN was 24% in COPD (similar in GOLD 1 and 2-4), which was greater than in never-smokers (13%) and ever-smokers (12%).
Conclusions: V̇E/V̇CO2>ULN was associated with greater dyspnea and low VO2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

Impact of accelerated washout of Technetium-99m-sestamibi on exercise tolerance in patients with acute coronary syndrome: single-center experience.

Kato T; Noda T; Tanaka S; Yagasaki H; Iwama M;Tanihata S; Arai M; Minatoguchi S; Okura H

Heart and vessels [Heart Vessels] 2022 Mar 27.
Date of Electronic Publication: 2022 Mar 27.

Technetium-99m-sestamibi ( 99m Tc-sestamibi) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with acute coronary syndrome (ACS) could be used to assess area-at-risks, as well as myocardial infarct or saved sizes. In patients with ACS, accelerated washout of 99m Tc-sestamibi during early and delayed imaging in the acute phase may suggest mitochondrial dysfunction in the injured but salvaged myocardium. However, the link between 99m Tc-sestamibi accelerated washout and exercise tolerance is unknown. The purpose of this study was to investigate a possible association between 99m Tc-sestamibi accelerated washout and exercise tolerance in acute ACS patients as they progressed into the chronic phase. One hundred and sixty-five patients with ACS who underwent 99m Tc-sestamibi SPECT MPI during the acute phase were recruited. On this basis, we calculated the total perfusion deficits (TPDs) for early (1 h after tracer injection) and delayed (4 h after tracer injection) images using automated quantification software. We then subtracted the early TPDs from the delayed TPDs to calculate the ΔTPD. We conducted a cardiopulmonary exercise test in acute and chronic phases. We divided two groups according to the median ΔTPD (the ΔTPD ≥ 4 group and the ΔTPD < 4 group) and compared anaerobic threshold (AT; ml/kg/min) between the groups. For anaerobic threshold (AT) improvement in data analysis, we employed multivariate logistic regression analysis. A total of 101 ST-segment elevation myocardial infarctions, 36 non-ST-elevation myocardial infarctions, and 28 unstable angina pectoris events were reported as ACS. From acute phase (10.8 ± 4.2 ml/kg/min) to chronic phase (11.9 ± 2.3 ml/kg/min), the AT in the ΔTPD ≥ 4 group was significantly increased (p < 0.0001). This trend was also seen in the ΔTPD < 4 group from acute (11.4 ± 1.8 ml/kg/min) to chronic phase (12.1 ± 2.2 ml/kg/min, p = 0.015). AT was lower in the ΔTPD ≥ 4 group in the acute phase (p = 0.027), but there was no difference in AT between the two groups in the chronic phase (p = 0.60). ΔTPD and the absence of diabetes were both independent predictors of AT improvement in multivariate logistic regression analysis. Receiver-operating characteristic curve analysis determined that ΔTPD = 6 was the best cut-off value, with 60.0% sensitivity and 71.4% specificity, respectively. The accelerated washout of 99m Tc-sestamibi in patients with ACS during the acute phase could help to predict improvement in exercise tolerance in the chronic phase.