Category Archives: Publications

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.

Low prevalence of cardiac abnormalities in competitive athletes at return-to-play after COVID-19.

Maestrini V; Penza M; Filomena D; Birtolo LI; Monosilio S; Lemme E; Squeo MR; Mango R; Di Gioia G; Serdoz A; Fiore R; Fedele F; Pelliccia A; IDi Giacinto B

Journal of science and medicine in sport [J Sci Med Sport] 2022 Nov 01.
Date of Electronic Publication: 2022 Nov 01.

Objective: to evaluate the prevalence of cardiac involvement after COVID-19 in competitive athletes at return-to-play (RTP) evaluation, following the recommended Italian protocol including cardiopulmonary exercise test (CPET) and 24-Hour Holter monitoring.
Design and Methods: this is a single centre observational, cross-sectional study. Since October 2020, all competitive athletes (age ≥ 14 years) evaluated in our Institute after COVID-19, prior RTP were enrolled. The protocol dictated by the Italian governing bodies included: 12‑lead ECG, blood test, CPET, 24-h ECG monitoring, spirometry. Cardiovascular Magnetic Resonance (CMR) was performed based on clinical indication.
Results: 219 consecutive athletes were examined (59% male), age 23 years (IQR 19-27), 21% asymptomatic, 77% mildly symptomatic, 2% with previous pneumonia. The evaluation was performed after a median of 10 (6-17) days from negative SARS-CoV-2 swab. All athletes showed a good exercise capacity at CPET without cardiovascular and respiratory limitations. Uncommon premature ventricular contractions (PVCs) were found in 9.5% (n = 21) at CPET/Holter ECG monitoring. Two athletes (0.9%) were diagnosed with acute myocarditis (by CMR) and another one with new pericardial effusion. All the three athletes were temporally restricted from sport participation.
Conclusions: Myocarditis in competitive athletes screened after COVID-19 resolution was detected in a low minority of the cases (0.9%). However, a non-negligible prevalence of uncommon PVCs (9%) was observed, either at CPET and/or Holter ECG monitoring, including all athletes with COVID-19 related cardiovascular abnormalities.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

Di Maria MV; Goldberg DJ; Zak V; Hu C; Lubert AM; Dragulescu A; Mackie AS; McCrary A; Weingarten A;Parthiban A; Goot B; Goldstein BH; Taylor C; Lindblade C; Petit CJ; Spurney C; Harrild DM;  Urbina EM;  Schuchardt E;
Beom Kim G; Kyoung Yoon J; Colombo JN; Files MD; Schoessling M; Ermis P; Wong PC; Garg R; Swanson SK;
Menon SC; Srivastava S; Thorsson T; Johnson TR; Krishnan US; Paridon SM; .Frommelt PC;

Circulation. Cardiovascular imaging [Circ Cardiovasc Imaging] 2022 Nov; Vol. 15 (11), pp. e013676.
Date of Electronic Publication: 2022 Nov 15.

Background: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied.
Methods: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value.
Results: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index ( P =0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E ( P =0.009, 3.95 [1.50]), and A velocities ( P =0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e’ velocity ( P =0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e’ ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s’ and e’ velocity).
Conclusions: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort.

Real-time analysis of heart rate variability during aerobic exercise in patients with cardiovascular disease.

Ikura H; Katsumata Y;      Seki Y;Ryuzaki T; Shiraishi Y; Miura K; Sato K; Fukuda K;

International journal of cardiology. Heart & vasculature [Int J Cardiol Heart Vasc] 2022 Nov 11; Vol. 43, pp. 101147. Date of Electronic Publication: 2022 Nov 11 (Print Publication: 2022).

Background: Exercise therapy for cardiovascular disease (CVD) is mainly evaluated based on the heart rate (HR) or Borg scale. However, these indices can be unreliable depending on the patient’s medication or their subjective decisions; thus, alternative methods are required for easier and safer implementation of aerobic exercise. Here, we examined whether real-time analysis of HR variability (HRV) can help maintain exercise intensity at the ventilatory threshold (VT) during exercise.
Methods: Twenty-eight patients with CVD treated at Keio University Hospital between August 2018 and March 2020 were enrolled. Initially, oxygen uptake (VO 2 ) and HR at the VT were determined using the cardiopulmonary exercise test. Patients then performed aerobic exercise on a stationary bicycle for 30 min while a parameter of HRV, the high-frequency (HF) component, was monitored in real time using an electrocardiograph. The work rate during exercise was adjusted every 2 min to maintain the HF range between 5 and 10. The VO 2 and HR values, recorded every 2 min during exercise, were compared with those at VT. The Bland-Altman method was used to confirm similarity.
Results: VO 2 and HR during exercise were closely correlated with those at VT (e.g., 19 min after exercise initiation; VO 2 : r = 0.647, HR: r = 0.534). The Bland-Altman plot revealed no bias between the mean values (e.g., 19 min; VO 2 : -0.22 mL/kg/min; HR: -0.07/min).
Conclusion: Real-time HRV analysis with electrocardiograph alone during exercise can provide continuous and non-invasive exercise intensity measurements at VT, promoting safer and effective exercise strategies.

Oxygen Uptake Efficiency Slope as a Predictor of Mortality Risk: THE BALL STATE ADULT FITNESS LONGITUDINAL LIFESTYLE STUDY (BALL ST).

Peterman JE; Novelli DS; Fleenor BS; Whaley MH; Kaminsky LA; Harber MP

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2022 Nov 17.
Date of Electronic Publication: 2022 Nov 17.

Purpose: Oxygen uptake efficiency slope (OUES), defined as the slope of the linear relationship between oxygen uptake and the semilog transformed ventilation rate measured during an incremental exercise test, may have prognostic utility. The objective of this investigation was to examine the relationship between assessments of OUES and all-cause mortality in a cohort of apparently healthy adults.
Methods: The sample included 2220 apparently healthy adults (48% females) with a mean age of 44.7 ± 12.9 yr who performed cardiopulmonary exercise testing. The OUES was calculated from the entire test, using data from the initial 50% (OUES50) and 75% (OUES75) of test time, and normalized to body surface area. Cox proportional hazard models assessed the relationship between measures of OUES and mortality. Prognostic peak oxygen uptake (V˙o2peak) and OUES models were compared using the concordance index.
Results: There were 310 deaths (29% females) over a follow-up period of 19.8 ± 11.1 yr. For males, OUES, OUES75, and normalized OUES had an inverse association with mortality, even after adjusting for traditional risk factors (P < .05). For females, only the unadjusted OUES, OUES75, and normalized OUES models were associated with mortality (P < .05). The concordance index values indicated that unadjusted OUES50 and OUES75 models had lower discrimination than the unadjusted OUES and V˙o2peak models (P < .05). Furthermore, OUES did not complement the fully adjusted V˙o2peak model (P≥ .32).
Conclusions: Assessments of OUES are related to all-cause mortality in males but not in females. These findings suggest that OUES can have prognostic utility in apparently healthy males. Moreover, submaximal determinations of OUES could have value when measuring V˙o2peak is not feasible.


Cardiopulmonary Exercise Testing Interpretation in Athletes: What the Cardiologist Should Know.

Husaini M; Emery MS;

Cardiology clinics [Cardiol Clin] 2023 Feb; Vol. 41 (1), pp. 71-80.
Date of Electronic Publication: 2022 Oct 21.

The noninvasive assessment of oxygen consumption, carbon dioxide production, and ventilation during a cardiopulmonary exercise test (CPET) provides insight into the cardiovascular, pulmonary, and metabolic system’s ability to respond to exercise. Exercise physiology has been shown to be distinct for competitive athletes and highly active persons (CAHAPs), thus creating more nuanced interpretations of CPET parameters. CPET in CAHAP is an important test that can be used for both diagnosis (provoking symptoms during a truly maximal test) and performance.

Lack of concordance between the different exercise test measures used in the risk stratification of patients with pulmonary arterial hypertension.

Mora Cuesta VM; Martínez Meñaca A; Iturbe Fernández D; Tello Mena S; Alonso Lecue P; Fernández Márquez D; Gallardo Ruiz MJ; Cifrián Martínez JM;

Pulmonary circulation [Pulm Circ] 2022 Oct 01; Vol. 12 (4), pp. e12149.
Date of Electronic Publication: 2022 Oct 01 (Print Publication: 2022).

In pulmonary arterial hypertension (PAH) patients it is essential to perform a prognostic assessment to optimize the treatment. The aim of this study is to evaluate the risk stratification concordance assessed with different exercise test variables in a cohort of PAH patients. A retrospective analysis was performed using patient data registered in the PAH unit. Only those patients in whom the mean time elapsed between the 6-min walking test (6MWT) and the cardiopulmonary exercise test (CPET) was a maximum of 6 months were selected. A total of 140 records from 40 patients were finally analyzed. When it came to assessing the concordance between the two exercise tests in the guidelines (CPET and 6MWT), up to 84.3% of the records did not coincide in terms of the risk stratification. Exclusively considering the CPET parameters, most of the records (75%) failed to include all three variables in the same risk category. When analyzing the VO 2 alone, up to 40.7% of the tests yielded different risk classifications depending on whether the parameter was expressed. In conclusion, there is a low concordance between the two proposed exercise tests. These results should be a call for reflection on whether the cut-off points set for the exercise tests proposed for the current risk stratification are adequate to achieve a correct risk stratification or whether they require an appropriate revision.