Author Archives: Paul Older

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection.

Babity M, Zamodics M, Konig A, Kiss AR, Horvath , Gregor Z, Rakoczi R, Kovacs E, Fabian A, Tokodi M, Sydo N,
Csulak E, Juhasz V, Lakatos BK, Vago H, Kovacs A, Merkely B, Kiss O;

Sci Rep. 2022 Dec 15;12(1):21686

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12-20 h/w), follow-up:93.5 days (IQR: 66.8-130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Exercise-Induced Excessive Blood Pressure Elevation Is Associated with Cardiac Dysfunction in Male Patients with Essential Hypertension.

Xia B; Cao P; Zhang L; Huang H; Li R; Yin X;

International journal of hypertension [Int J Hypertens] 2022 Nov 28; Vol. 2022, pp. 8910453.
Date of Electronic Publication: 2022 Nov 28 (Print Publication: 2022).

Objective: Cardiopulmonary exercise testing (CPET) has been used to explore the blood pressure response and potential cardiovascular system structure and dysfunction in male patients with essential hypertension during exercise, to provide a scientific basis for safe and effective exercise rehabilitation and improvement of prognosis.
Methods: A total of 100 male patients with essential hypertension (aged 18-60) who were admitted to the outpatient department of the Center for Diagnosis and Treatment of Cardiovascular Diseases of Jilin University from September 2018 to January 2021 were enrolled in this study. The patients had normal cardiac structure in resting state without clinical manifestations of heart failure or systematic regularization of treatment at the time of admission. Symptom-restricted CPET was performed and blood pressure was measured during and after exercise. According to Framingham criteria, male systolic blood pressure (SBP) ≥210 mmHg during exercise was defined as exercise hypertension (EH), and the subjects were divided into EH group ( n  = 47) and non-EH group ( n  = 53). Based on whether the oxygen pulse (VO 2 /HR) plateau appeared immediately after anaerobic threshold (AT), the EH group was further divided into the VO 2 /HR plateau immediately after AT (EH-ATP) group ( n  = 19) and EH-non-ATP group ( n  = 28). The basic clinical data and related parameters, key CPET indicators, were compared between groups.
Result: Body mass index (BMI) visceral fat, resting SBP, and SBP variability in EH group were significantly higher than those in non-EH group. Moreover, VO 2 /HR at AT and the ratio of VO 2 /HR plateau appearing immediately after AT in EH group were significantly higher than those in the non-EH group. The resting SBP, 15-minute SBP variability, and the presence of VO 2 /HR plateau were independent risk factors for EH. In addition, work rate (WR) at AT but also WR, oxygen consumption per minute (VO 2 ), VO 2 /kg, and VO 2 /HR at peak were significantly lower in the EH-ATP group compared to the EH-non-ATP group. Peak diastolic blood pressure (DBP) increment and decreased △VO 2 /△WR for AT to peak were independent risk factors for VO 2 /HR plateau appearing immediately after AT in EH patients.
Conclusion: EH patients have impaired autonomic nervous function and are prone to exercise-induced cardiac dysfunction. EH patients with exercise-induced cardiac dysfunction have reduced peak cardiac output and exercise tolerance and impaired vascular diastolic function. CPET examination should be performed on EH patients and EH patients with exercise-induced cardiac dysfunction to develop precise drug therapy and effective individual exercise prescription, to avoid arteriosclerosis and exercise-induced cardiac damage.

Optimizing exercise testing-based risk stratification to predict poor prognosis after acute heart failure.

Chen SM; Wu PJ; Wang LY; Wei CL; Cheng CI; Fang HY; Fang YN; Chen YL; SHuang DK; Lee FY; Chen MC;

ESC heart failure [ESC Heart Fail] 2022 Dec 02.
Date of Electronic Publication: 2022 Dec 02.

Aims: The timely selection of severe heart failure (HF) patients for cardiac transplantation and advanced HF therapy is challenging. Peak oxygen consumption (VO 2 ) values obtained by the cardiopulmonary exercise testing are used to determine the transplant recipient list. This study reassessed the prognostic predictability of peak VO 2 and compared it with the Heart Failure Survival Score (HFSS) in the modern optimized guideline-directed medical therapy (GDMT) era.
Methods and Results: We retrospectively selected 377 acute HF patients discharged from the hospital. The primary outcome was a composite of all-cause mortality, or urgent cardiac transplantation. We divided these patients into the more GDMT (two or more types of GDMT) and less GDMT groups (fewer than two types of GDMT) and compared the performance of their peak VO 2 and HFSS in predicting primary outcomes. The median follow-up period was 3.3 years. The primary outcome occurred in 57 participants. Peak VO 2 outperformed HFSS when predicting 1 year (0.81 vs. 0.61; P = 0.017) and 2 year (0.78 vs. 0.58; P < 0.001) major outcomes. The cutoff peak VO 2 for predicting a 20% risk of a major outcome within 2 years was 10.2 (11.8-7.0) for the total cohort. Multivariate Cox regression analyses showed that peak VO 2 , sodium, previous implantable cardioverter defibrillator (ICD) implantation, and estimated glomerular filtration rate were significant predictors of major outcomes.
Conclusions: Optimizing the cutoff value of peak VO 2 is required in the current GDMT era for advanced HF therapy. Other clinical factors such as ICD use, hyponatraemia, and chronic kidney disease could also be used to predict poor prognosis. The improvement of resource allocation and patient outcomes could be achieved by careful selection of appropriate patients for advanced HF therapies, such as cardiac transplantation.

Double blind trial of a deuterated form of linoleic acid (RT001) in Friedreich ataxia.

Lynch DR; Mathews KD; Perlman S; Zesiewicz T; Subramony S; Omidvar O; Vogel AP; Krtolica A; Litterman N;
van der Ploeg L; Heerinckx F; Milner P; Midei M;

Journal of neurology [J Neurol] 2022 Dec 03.
Date of Electronic Publication: 2022 Dec 03.

Objectives: Friedreich ataxia is (FRDA) an autosomal recessive neurodegenerative disorder associated with intrinsic oxidative damage, suggesting that decreasing lipid peroxidation (LPO) might ameliorate disease progression. The present study tested the ability of RT001, a deuterated form of linoleic acid (D2-LA), to alter disease severity in patients with FRDA in a double-blind placebo-controlled trial.
Methods: Sixty-five subjects were recruited across six sites and received either placebo or active drug for an 11-month study. Subjects were evaluated at 0, 4, 9, and 11 months, with the primary outcome measure being maximum oxygen consumption (MVO2) during cardiopulmonary exercise testing (CPET). A key secondary outcome measure was a composite statistical test using results from the timed 1-min walk (T1MW), peak workload, and MVO2.
Results: Forty-five subjects completed the protocol. RT001 was well tolerated, with no serious adverse events related to drug. Plasma and red blood cell (RBC) membrane levels of D2-LA and its primary metabolite deuterated arachidonic acid (D2-AA) achieved steady-state concentrations by 4 months. No significant changes in MVO2 were observed for RT001 compared to placebo. Similarly, no differences between the groups were found in secondary or exploratory outcome measures. Post hoc evaluations also suggested minimal effects of RT001 at the dosages used in this study.
Interpretations: The results of this study provide no evidence for a significant benefit of RT001 at the dosages tested in this Friedreich ataxia patient population.

Contribution of hemoglobin concentration to cardiorespiratory fitness in black African American patients with recently decompensated heart failure and reduced ejection fraction.

Thomas GK; Del Buono MG; Damonte JI; Moroni F; Mihalick V; Billingsley HE; Vecchiè A; Trankle CR; Talasaz A; Carbone S; Markley R; Turlington J; Duncan P; Lu J; Arena R; VAN Tassell B; Abbate A; Canada JM;

Minerva cardiology and angiology [Minerva Cardiol Angiol] 2022 Dec 05.
Date of Electronic Publication: 2022 Dec 05.

Background: Previous studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) and anemia have reduced peak oxygen consumption (VO<inf>2</inf>). Black or African American (B-AA) patients have a higher prevalence of anemia and are underrepresented in clinical studies of HFrEF. The aim of this study was to determine the contribution of hemoglobin to peak VO<inf>2</inf> in B-AA patients recently hospitalized for acute decompensated HFrEF.
Methods: We analyzed cardiopulmonary exercise testing (CPX) data measured within two weeks of discharge for acute decompensated HF in B-AA patients with HFrEF (left ventricular ejection fraction [LVEF] ≤40%) without severe anemia (Hb<8 g/dL). Blood samples were collected prior to CPX. Data are reported as median [interquartile range] and compared between groups with the Mann-Whitney, Chi-Square, and Spearman’s rank tests.
Results: We included 81 patients; 27 (33%) women, 57 [27-79] years of age, Body Mass Index of 33 [15-55] kg/m 2 and LVEF of 30 [23-36] %. Hemoglobin ranged between 9.1 to 18.1 g/dL (median= 13.3 [11.9-14.5] g/dL); 26 (32%) were considered to have anemia based on a Hb concentration of males <13 g/dL and females <12 g/dL. Peak VO<inf>2</inf> was lower in patients with anemia (11.8 [10.0-14.2] vs. 14.1 [10.6-17.0] mL·kg -1 ·min -1 ; P=0.010) with a significant correlation between peak VO<inf>2</inf> and hemoglobin concentration (R=+0.455; P<0.001).
Conclusions: Anemia is prevalent among B-AA patients with recently decompensated HFrEF and appears to be a significant contributor to reductions in peak VO<inf>2</inf>.

Metabolic and physiological responses to graded exercise testing in individuals with type 1 diabetes using insulin pump therapy.

McCarthy OM; Birch Kristensen K; Christensen MB; Schmidt S; Ranjan AG; Nicholas C; Bain SC; Nørgaard K;
Bracken R;

Diabetes, obesity & metabolism [Diabetes Obes Metab] 2022 Dec 08.
Date of Electronic Publication: 2022 Dec 08.

Aims: 1) To profile acute glycaemic dynamics during graded exercise testing (GXT) and 2) explore the influence of glycaemic indicators on the physiological responses to GXT in adults with T1D using insulin pump therapy.
Methods: This was a retrospective analysis of pooled data from four clinical trials with identical GXT protocols. Data was obtained from 45 adults with type 1 diabetes using insulin pumps ([30 females], HbA 1c : 59.5±0.5 mmol.mol -1 [7.6±1.0 %], age: 49.7±13.0 years, diabetes duration: 31.2±13.5 years, V̇O 2peak : 29.5±8.0 mL.min -1 .kg -1 ). Integrated cardiopulmonary variables were collected continuously via spiroergometry. Plasma glucose (PG) was obtained every three minutes during GXT as well as the point of volitional exhaustion. Data were assessed via general linear modelling techniques with age and gender adjustment. Significance was accepted at P ≤0.05.
Results: Despite increasing duration and intensity, PG concentrations remained similar to rest values (8.8±2.3 mmol.L -1 ) throughout exercise (p=0.419) with an overall change of +0.3±1.1 mmol.L -1 . Starting glycaemia bore no influence on subsequent GXT responses. Per 1% increment in HbA 1c there was an associated decrease in V̇O 2peak of 3.8 mL.min -1 .kg -1 (p<0.001) and power peak of 0.33 watts.kg -1 (p<0.001) concomitant with attenuations in indices of peripheral oxygen extraction ([O 2 pulse] -1.2 mL.beat -1 , p=0.023).
Conclusion: In adults with long-standing type 1 diabetes using insulin pump therapy, circulating glucose remains stable during a graded incremental cycle test to volitional exhaustion. Glycaemic indicators are inversely associated with aerobic rate, oxygen economy and mechanical output across the exercise intensity spectrum. An appreciation of these nexuses may help guide appropriate decision making for optimal exercise management strategies.

Exercise Oscillatory Ventilation in Hypertrophic Cardiomyopathy

S. G. Sakellaropoulos, A. L. Baggish, M. A. Fifer and G. D. Lewis

Curr Probl Cardiol 2022 Vol. 47 Issue 5 Pages 100911

To assess the prevalence and clinical correlates of exercise oscillatory ventilation (EOV) in patients with hypertrophic cardiomyopathy (HCM). Retrospective single-center study. Thirty-six consecutive HCM patients who underwent cardiopulmonary exercise testing. Two patients (5.6%) had EOV. Both patients with peak oxygen consumption (VO(2)) less than or equal to 9.1 ml/kg/min had EOV. Left atrial size was greater in patients with EOV. Of the 2 patients in the study population with an abnormal blood pressure response to exercise, 1 had EOV. Both patients with New York Heart Association Class 3 heart failure had EOV. This is the first report of EOV in HCM. EOV is uncommon in patients with HCM. EOV appears to be a marker of disease severity as evidenced by overt heart failure, left atrial enlargement, and low peak VO(2).

Left Atrial Myopathy is Associated With Exercise Incapacity and Ventilatory Inefficiency in Hypertrophic Cardiomyopathy.

Zegkos T;Kamperidis V; Ntelios D; Gossios T;Parcharidou D; Tziomalos G; Papanastasiou CA; Boutou AΚ; Katranas S; Rouskas P; Karamitsos T; Giannakoulas G; Karvounis H; Efthimiadis G;

Heart, lung & circulation [Heart Lung Circ] 2022 Nov 17.
Date of Electronic Publication: 2022 Nov 17.

Background: Left atrial (LA) myopathy is an established component of hypertrophic cardiomyopathy (HCM); however, the data about its association with exercise incapacity or ventilatory inefficiency that may be seen in HCM patients are limited. This study aimed to explore the association between LA myopathy, evaluated by echocardiography LA strain, and exercise capacity and ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), in HCM patients.
Methods: This study included 241 consecutive HCM patients (aged 51.2±15.7 years 67.2% male) in sinus rhythm who underwent CPET and transthoracic echocardiography at the same visit. Exercise incapacity (maximal/predicted oxygen consumption [%peakVO 2 ] <80%) and ventilatory inefficiency (ventilation/carbon dioxide output [VE/VCO 2 ] slope >34) were assessed by CPET. Left atrial myopathy was examined by speckle-tracking myocardial deformation parameters: LA reservoir, conduit and booster strain.
Results: All three LA strain values were univariate predictors of exercise capacity and ventilatory efficiency. Among them, LA reservoir strain had the higher r correlation coefficient for predicting both %peakVO 2 and VE/VCO 2 slope. Left atrial reservoir strain, presence of angina and family history of HCM were independent predictors of exercise capacity. Left atrial reservoir strain, male gender and non-sustained ventricular tachycardia were independent predictors of ventilatory efficiency. Left atrial reservoir strain was a significant predictor of %peakVO 2 <80% with an optimal cut-off value of 27% (sensitivity 87% and specificity 31%) and VE/VCO 2 >34 with an optimal cut-off value of 18% (sensitivity 71% and specificity 83%).
Conclusion: Left atrial myopathy, as reflected by the LA strain values, was associated with exercise incapacity and ventilatory inefficiency in HCM individuals. Left atrial reservoir strain was the only common independent predictor of %peakVO 2 and VE/VCO 2 slope.

Functional exercise capacity in maximal and submaximal activities of individuals with polio sequelae.

de Lira CAB; Minozzo FC; Costa TG; de Oliveira VN; Costa GCT; Oliveira ASB; Quadros AAJ; Vancini RL; Sousa BS;
da Silva AC; Andrade MS;

European journal of applied physiology [Eur J Appl Physiol] 2022 Nov 19.
Date of Electronic Publication: 2022 Nov 19.

Purpose: Poliomyelitis is an infectious disease that can cause total paralysis. Furthermore, poliomyelitis survivors may develop new signs and symptoms, including muscular weakness and fatigue, years after the acute phase of the disease, i.e., post-polio syndrome (PPS). Thus, the objective was to compare the functional exercise capacity during maximal and submaximal exercises among individuals with polio sequelae (without PPS diagnosis), PPS, and a control group.
Methods: Thirty individuals participated in three groups: a control group (CG, n = 10); a group of individuals with polio sequelae but without PPS diagnosis (PG, n = 10); and a PPS group (PPSG, n = 10). All participants underwent (i) a cardiopulmonary exercise test to determine their maximal oxygen uptake ([Formula: see text]) and (ii) a series of functional field tests (i.e., walking test, sit-to-stand test, and stair climbing test).
Results: [Formula: see text]O 2 max was 30% lower in PPSG than in CG and PG. Regarding functional field tests, walking and stair climbing test performances were significantly different among all groups. The PPSG sit-to-stand performance was lower than CG.
Conclusion: The sequelae of paralytic poliomyelitis impair functional exercise capacity obtained from maximal and submaximal tests, especially in patients with PPS. Furthermore, submaximal variables appear to be more negatively impacted than maximal variables.

Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae.

Faria D; Moll-Bernardes R; Testa L; Rodrigues EC; Rodrigues AG; Araujo A;Alves MJNN; Ono BE; Izaias JE;
Salemi VMC; Paixão CJ;Amaro-Vicente G; Negrão CE; Sales ARK;

Hypertension (Dallas, Tex. : 1979) [Hypertension] 2022 Nov 23.
Date of Electronic Publication: 2022 Nov 23.

Background: COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress.
Methods: Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects.
Results: Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e’ ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors.
Conclusions: Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.