Author Archives: Paul Older

Stable Longitudinal Quality of Life in the SERVE Trial Among Adults With Transposition of the Great Arteries and a Systemic Right Ventricle.

Castiglione A; Department of Cardiology, Center for Congenital Heart Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
& many other centres in Switzerland
Schwerzmann M; Bouchardy J; Buechel RR; Engel R; Freese M; Gabriel H; Greutmann M; Heg D; Possner M; Ruperti-Repilado FJ; Rutz T; Schwitter J; Thomet C; Tobler D; Wilhelm M; Wustmann K; Schwitz F;

CJC pediatric and congenital heart disease [CJC Pediatr Congenit Heart Dis] 2024 Dec 12; Vol. 4 (2), pp. 81-91.
Date of Electronic Publication: 2024 Dec 12 (Print Publication: 2025).

Background: Adults with a transposition anatomy and a systemic right ventricle (RV) face long-term complications that may impact their quality of life (QoL). Few data are available regarding the QoL in this patient group and its evolution over time.
Methods: This study was performed in the SERVE trial’s (identifier: NCT03049540) prospective cohort of patients (n = 100) with congenitally corrected transposition of the great arteries (TGA) or dextro-TGA after the atrial switch procedure and a longitudinal follow-up of 3 years. We aimed to describe the longitudinal QoL levels and their predictors. QoL was assessed using the Linear Analog Scale. QoL parameters were collected at baseline, after 12 months, and after 36 months, together with clinical parameters and a questionnaire assessing general self-efficacy (GSE).
Results: The mean QoL on the Linear Analog Scale was 79.1 ± 13.6 at baseline, 75.5 ± 14.8 at 1 year, and 79.2 ± 13.6 at 3-year follow-up ( P  = 0.900). No significant differences in QoL were observed between congenitally corrected TGA or dextro-TGA patients. Cardiopulmonary exercise testing maximum work rate and maximum oxygen uptake, New York Heart Association class, end-diastolic RV volumes, N-terminal pro-B-type natriuretic peptide concentration, and GSE showed significant correlations with QoL levels. Multivariable regression analysis identified GSE value and New York Heart Association class ( r2  = 0.283, P < 0.001) as independent predictors of QoL at baseline.
Conclusions: Patients with a systemic RV reported a stable good QoL during 3 years of follow-up. Exercise capacity and self-efficacy were the only independent predictors of QoL.

Chronotropic incompetence and the importance of cardiopulmonary exercise testing following myocardial infarction.

Griffith GJ; Northwestern University Feinberg School of Medicine, Department of Physical Therapy and Human Movement Sciences, USA

International journal of cardiology [Int J Cardiol] 2025 May 31; Vol. 437, pp. 133445.
Date of Electronic Publication: 2025 May 31.

Chronotropic incompetence (CI) is characterized by an inadequate or blunted heart rate (HR) response to exercise, [] and the clinical and prognostic importance of CI is being increasingly recognized. Associations between CI and mortality [,] and exercise capacity [] have been demonstrated in a variety of cardiovascular disease patient populations. In this issue of the International Journal of Cardiology, the original research article by Smarz and colleagues further established the importance of CI to a population of post-myocardial infarction (MI) patients with preserved or mildly reduced ejection fraction. [] This compelling research article provides important insight into the prognostic benefit of identification of CI and importantly highlights that methodological considerations relating to the assessment of CI are of the utmost importance. Firstly, there exists a general lack of universal agreement regarding the mathematical and functional definition of CI. Secondly, implementation of cardiopulmonary exercise testing (CPET) is oftentimes underutilized, and the multitude of variables obtained from it are rarely optimized in the characterization of patient prognosis following maximal exercise testing. The aims of this article are to 1) provide insight into best methodological practices surrounding CI as identified via CPET, 2) contextualize the importance of CI in MI patients, and 3) provide recommendations for future avenues of research to continue to build the body of evidence surrounding the importance of CPET and CI.

Characterization of dysfunctional breathing using cardiopulmonary exercise testing.

Möbus SF; School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Harding CJ; Taylor CL; Sylvester KP; Fuld JP;

Physiological reports [Physiol Rep] 2025 Jun; Vol. 13 (11), pp. e70388.

Cardiopulmonary exercise testing (CPET) is emerging as a useful tool in the identification of dysfunctional breathing (DB). We aimed to evaluate the prevalence and functional impact of different patterns of DB in 628 adult patients referred for CPET due to unexplained dyspnoea (August 2019-December 2023). Patients were assigned to four groups following CPET interpretation: normal, breathing pattern disorder (BPD), hyperventilation (HV), and combined BPD with HV (BPDHV). Demographic and CPET performance data were analyzed using non-parametric tests as appropriate. 94 (15.0%) patients had normal CPETs and 267 (42.5%) were identified as having DB. The remaining 267 were excluded as having alternative diagnoses. Of those with DB, 145 (54.3%) had BPD, 41 (15.4%) had HV, and 81 (30.3%) had BPDHV. VE/VCO 2 was significantly increased in HV or BPDHV only (p < 0.001). Patients in all three DB groups exhibited significantly impaired peak VO 2 compared to those with normal CPETs (p < 0.001). These CPET findings highlight DB as a common driver of symptoms in unexplained dyspnoea. Over half of patients with DB had isolated BPD, which requires visual inspection of relevant CPET plots to diagnose. Those identified with DB had significantly reduced peak VO 2 , which may be a useful classifier of functional severity in DB.

Blood Pressure Responses During Exercise Were Associated With Average Home Blood Pressure and Home Blood Pressure Variability: The Electronic Framingham Heart Study.

Wang X; Department of Biostatistics Boston University School of Public Health Boston MA USA.
Zhang Y; Pathiravasan CH; Spartano NL; Benjamin EJ; McManus DD;Lewis GD; Larson MG;Vasan RS; Murabito JM; Liu C; Nayor M;

Journal of the American Heart Association [J Am Heart Assoc] 2025 Jun 03; Vol. 14 (11), pp. e039457.
Date of Electronic Publication: 2025 Jun 03.

Background: Abnormal exercise blood pressure (BP) responses are associated with hypertension and cardiovascular disease, but their relationship with home BP over a mid- to long-term time span is unknown.
Methods: At an FHS (Framingham Heart Study) research examination (2016-2019), participants underwent maximum incremental ramp cycle ergometry cardiopulmonary exercise testing with BP measured every 2 minutes. At the same exam, English-speaking participants enrolled in the electronic FHS with an iPhone were provided with a digital BP cuff to measure home BP weekly for 1 year. Linear regression models examined associations of exercise BP with average home systolic BP (SBP), home-based hypertension, and week-to-week average real variability of home SBP, over 1-year follow-up. Participants with <3 weeks of BP return were excluded.
Results: Among 808 participants (mean age, 53 years; 58% women; 92% White individuals; 47% hypertension), higher exercise BP responses (peak SBP, SBP at 75 W, SBP/workload slope, peak diastolic BP, and diastolic BP at 75 W) were associated with higher average home SBP. Higher peak diastolic BP was associated with a greater risk for home hypertension. Additionally, higher SBP/workload slope and peak diastolic BP were associated with elevated average real variability of home SBP only in participants without antihypertensive use.
Conclusions: Higher exercise BP responses were associated with higher average home-based BP, greater home-based hypertension risk, and increased home-based BP variability over a mid- to long-term time span. However, these associations may vary by antihypertensive medication use. Exercise BP may play an important role in hypertension prevention and treatment.

Online rehabilitation in adults Fontan patients: Effects in functional capacity, lymphatic function and quality of life.

Turquetto ALR; Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Amato LP; Thorup L; Kelly B; Hjortdal VE; de Souza FR;Canêo LF; Machado DS; Filho ACB; Ligeiro MG; Mohanakumar S; Rondon E; Binotto MA; Jatene MB; Jatene FB;

International journal of cardiology [Int J Cardiol] 2025 Jun 05, pp. 133480.
Date of Electronic Publication: 2025 Jun 05.

Introduction: Survival rates for post-Fontan patients have improved, allowing many to reach adulthood with better quality of life (QOL). However, they remain at risk for reduced functional capacity (FC), skeletal muscle loss, and lymphatic dysfunction, which negatively affect clinical outcomes. This study evaluated the feasibility of an online rehabilitation program for adult Fontan patients in the late postoperative period and its effects on FC, peripheral lymphatic function (PLF), and QOL.
Methods: This prospective, non-randomized, controlled clinical trial evaluated the impact of a fitness center’s 36-session online aerobic and resistance training program. Participants were divided into a control group (CG), continuing usual activities, and an exercise group (EG). Outcomes included QOL (Short Form-36 questionnaire: SF-36), FC via cardiopulmonary exercise testing (CPET), and PLF assessed using near-infrared fluorescence imaging and venous occlusion plethysmography.
Results: A total of 26 participants (13 EG,13 CG), with a median age of 30 (25-35) years, and follow-up time after Fontan of 19 (15-21) years, were enrolled. The EG showed significant improvements in peak VO2 (ml/kg/min), predicted peak VO2 (%), peak ventilation (L/min), and oxygen pulse (mL/beat), indicating enhanced cardiovascular efficiency. Additionally, 62 % of SF-36 domains improved in the EG, while no changes were observed in the CG. However, the program did not produce significant modifications in PLF.
Conclusions: The proposed online rehabilitation program proved to be feasible and effectively improved FC and quality of life in adults after Fontan surgery; however, this training model did not significantly influence peripheral lymphatic function.

Supervised high-intensity interval training reduces the negative effect of chemotherapy on cardiorespiratory fitness in young breast cancer women: a randomised controlled study.

Dudek M; 1 st Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland.
Górecki M; Marszałek S; Kufel-Grabowska J; Litwiniuk M; et al

European journal of applied physiology [Eur J Appl Physiol] 2025 Jun 05.
Date of Electronic Publication: 2025 Jun 05.

Purpose: Younger women are diagnosed more often with aggressive breast cancer (BC) subtypes, the treatment of which usually incorporates chemotherapy. Physical training plays a significant role in mitigating the adverse effects of systemic cancer therapy, improving quality of life, and potentially enhancing treatment efficacy. High-intensity interval training (HIIT) emerged as a promising intervention to counteract the fatigue induced by chemotherapy, which in younger women often causes depression and disruption of employment. This study aimed to investigate whether supervised HIIT employed concurrently with chemotherapy impacts the cardiorespiratory fitness of young BC patients.
Methods: Twenty-six young (18-40 years old) BC patients scheduled for chemotherapy were randomised to intervention comprising supervised HIIT employed concurrently with chemotherapy or no supervised training (control) for 6 months. Outcomes measured using cardiopulmonary exercise testing (CPET) and non-invasive cardiac output testing were cardiorespiratory fitness and cardiac output.
Results: Compared to control, employment of HIIT mitigated the decrease in relative peakVO 2 from 33.630 to 29.540 ml/kg/min for HIIT group and from 29.679 to 22.571 ml/kg/min for control group (ANCOVA p = 0.018, ES = 0.469), and also a mitigated the decrease in exercise time from 685.600 to 666.500 s for HIIT group and from 703.357 to 555.500 s for control group (ANCOVA p = 0.008, ES = 0.815) measured during CPET.
Conclusions: Supervised HIIT implemented alongside chemotherapy can mitigate the decline in cardiorespiratory fitness caused by BC chemotherapy in young patients.

Preoperative submaximal cardiopulmonary exercise testing and its association with early postoperative complications.

Carr ZJ; Yale University, School of Medicine, New Haven, CT, USA.; Department of Anesthesiology, Yale New Haven Hospital, New Haven, CT, USA.
Charchaflieh J; Brenes-Bastos A; He H;  Lin HM; Jankelovits A; Gu E; Zafar J; Ghali F; Tan WS; Heerdt P;

BJA open [BJA Open] 2025 Apr 24; Vol. 14, pp. 100407.
Date of Electronic Publication: 2025 Apr 24 (Print Publication: 2025).

Background: Early postoperative complication risk prediction would enhance perioperative surveillance and resource allocation. Reports have described brief submaximal cardiopulmonary exercise testing (CPET) for the routine assessment of cardiopulmonary disease. Compared with conventional CPET, it can be performed in 6 min and is used to predict peak CPET measurements. We aimed to determine whether submaximal CPET-derived measures outperform structured surveys in early postoperative complication detection.
Methods: An institutional review board-approved, single-centre, open-label, clinical device trial was conducted. A total of 101 participants undergoing noncardiac surgery, aged >60 yr, with revised cardiac risk index ≤2, self-reported metabolic equivalents >4 (METs in ml O 2 kg -1 min -1 ; self-endorsed reliably climbing two flights of stairs), were enrolled. Participants completed a subjective METs assessment, Duke Activity Status Index, and submaximal CPET that derived peak oxygen uptake (VO 2 , ml O 2 kg -1 min -1 ), METs, and gas exchange-derived pulmonary capacitance (GXCAP, in ml O 2 beat -1 kPa -1 ). Elastic net regularisation machine learning identified feature importance among study measures for the primary endpoint (Postoperative Morbidity Survey [POMS] ≥1), secondary endpoints (cardiac, pulmonary and renal domains of the POMS [POMS-CPR ≥1]), and length of stay. Adjusted multivariable regression models were used to identify significance.
Results: Of 101 participants, 53 (52.4%) had POMS ≥1. GXCAP to peak VO 2 slope (GXCAP-VO 2 ) was associated with POMS ≥1 (OR adj 0.94; 95% CI 0.89-0.99; P =0.011) and increasing length of stay (OR adj 0.98; 95% CI 0.96-0.99; P =0.01). GXCAP-VO 2 slope (OR adj 0.93; 95% CI 0.88-0.99; P =0.015) was associated with POMS-CPR ≥1.
Conclusions: Compared with structured surveys (subjective METs or Duke Activity Status Index) or conventional peak CPET values (VO 2 or METs), a novel measure, GXCAP-VO 2 slope, offered superior early postoperative complication discrimination in low-morbidity subjects. These preliminary findings support GXCAP-VO 2 slope as a compelling investigational target for early postoperative complication risk, supporting the use of CPET to enhance early postoperative complication prediction.
Competing Interests: ZJC declares partial research funding from Shape Medical Systems, Inc (MN, USA). PMH declares consulting for Cardiage LLC and Baudax Bio, consulting and sponsored research for Edwards Lifesciences, and equity interest in emka Medical.

V o2peak , Ve/V CO2 , and Cardiac Remodeling Correlate with Long-Term Cardiovascular Outcome in Heart Failure Patients.

Pagliaro A; Division of Cardiology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Cavigli L; Molle R; Iardino E; Anselmi F; Righini F; Martini L; Zacà V; Mandoli GE; Pastore MC; Focardi M; Cameli MBernazzali S; Maccherini M; Chiostri M; D’Ascenzi F; Valente S;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2025 May 02; Vol. 12 (5).
Date of Electronic Publication: 2025 May 02.

Background Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV ejection fraction (LVEF) is the most used parameter in clinical practice.
Aims This study aimed to analyze CPET and echocardiographic data in patients under evaluation for heart transplantation (HTx) to identify the parameter that best correlates with cardiac events.
Methods and Results. Echocardiography and CPET were performed in patients with HFrEF under evaluation for HTx. The population comprised 170 patients (mean age: 55 ± 9 years; 88% male; non-ischemic etiology: 63%). LVEF was 30.4 ± 7.6%, peak oxygen uptake (Vo 2peak ) was 17.08 ± 4.6 mL/Kg/min; minute ventilation (VE)/carbon dioxide production (Vco 2 ) slope was 34.8 ± 8.7. During a follow-up of 4 ± 1 years, 37 hospitalizations, 4 deaths, 14 HTx, and 5 LV assist device implantation occurred. Patients who experienced major events had a lower Vo 2peak ( p < 0.005), higher VE/Vco 2 slope ( p < 0.005), greater LV end-systolic diameter ( p < 0.005), and RV end-diastolic diameter ( p < 0.005) than patients without events. Conversely, LVEF did not differ between these two groups. VE/Vco 2 slope and RV dimensions significantly correlated with hard cardiac events ( p = 0.019 and p = 0.008, respectively).
Conclusions. In patients with HFrEF, parameters quantifying the system reserve (i.e., Vo 2peak and VE/Vco 2 slope) and those demonstrating advanced biventricular remodeling may help stratify the risk of cardiac events. Conversely, LVEF showed a limited prognostic value in this setting.

Evaluating cardiovascular risk factors in breast cancer survivors: The role of echocardiography and cardiopulmonary exercise testing in the Munich Cardio-Oncology-Exercise retrospective Registry.

Wernhart S; Department for Preventive Sports Medicine and Sports Cardiology, Munich, Germany.
Fiorentini C; Glowka S; Madl B;Grill S; Kiechle M;Mueller S; Schmid V; Foulkes S; Haykowsky MJ; Halle M;

International journal of cardiology [Int J Cardiol] 2025 May 25; Vol. 436, pp. 133421.
Date of Electronic Publication: 2025 May 25.

Background: Breast cancer survivors (BCS) have an increased risk of developing cardiovascular disease risk factors (CVDRF). However, the role of cardiopulmonary fitness, echocardiography and treatment regimen e.g. anthracycline, HER2-targeted therapy (AC/H) or endocrine therapy (ET) are uncertain.
Methods: This single-center, retrospective study included BCS without visceral metastases, who had been treated with either AC/H or ET and assessed by echocardiography, cardio-pulmonary exercise testing (CPET) and the H 2 FPEF score at baseline. We included BCS with a left ventricular ejection fraction ≥50 % and absence of CVDRF at baseline. The primary outcome was the incidence of CVDRF.
Results: A total of 112 BCS were included (mean age of 54.6 ± 9.9 years, BC stage I-III). After a median follow-up of 21 months new-onset arterial hypertension was the most common CVDRF observed (n = 17). New onset hypertension was related to higher baseline resting systolic blood pressure (127.4 ± 9.2 mmHg vs. 117.3 ± 13.1 mmHg, p = 0.002) and H 2 FPEF scores (1.2 ± 0.8 vs. 0.8 ± 1.1, p = 0.043). Echocardiographic and CPET findings associated with new-onset arterial hypertension included greater left ventricular mass index (77.3 ± 24.2 g/m 2 vs. 65.6 ± 15.5 g/m 2 , p = 0.007), higher peak systolic blood pressure (193.1 ± 19.5 mmHg vs. 173.3 ± 21.2 mmHg, p = 0.017) and ventilatory power (6.4 ± 1.3 mmHg vs. 5.7 ± 1.2 mmHg, p = 0.022). Treatment regimen had no influence on the development of CVDRF.
Conclusions: The most common CVDRF among BCS is hypertension, underscoring the importance of monitoring this outcome irrespective of breast cancer treatment regimens. The H 2 FPEF score, CPET and echocardiography may help identify BCS at risk of developing hypertension. Strain and biomarkers were not available, impeding detection of cardiotoxicity.
Competing Interests: Declaration of competing interest Simon Wernhart has received honoraria for lectures from Bristol-Myers Squibb. Stephan Mueller has received personal fees from Bristol-Myers Squibb (consulting services). Mark Haykowsky is funded, in part, by a Research Chair in Aging in the Faculty of Nursing, College of Healthy Sciences at UofA. Martin Halle reports honoraria for lectures beyond this cancer topic from Abbott, Amgen, Astra-Zeneca, Boehringer-Ingelheim, BMW, Bristol-Myers Squibb, Daiichi-Sankyo, Lilly, Medi, MSD Sharp & Dohme GmbH, Norsan, Novartis, Pfizer and Roche, consulting fees from Medical Park. Sabine Grill has received honoraria for lectures from AstraZeneca, Roche, Pfizer and Daiichi Sankyo. No other potential conflicts of interest are reported.

Changes in cardiopulmonary exercise testing variables after surgery for primary mitral regurgitation.

Afoke J; Imperial College Healthcare, Hammersmith Hospital, London, UK.; Imperial College, London, UK.
Gibbs S; Kanaganayagam S; Bruno D; Howard L; Punjabi P;

Perfusion [Perfusion] 2025 May 27, pp. 2676591251346035.
Date of Electronic Publication: 2025 May 27.

Aims Describe differences in changes in cardiopulmonary exercise testing after surgery for severe primary mitral regurgitation between class I and class II indications for surgery.
Methods Prospective observational study of patients who underwent transthoracic echocardiogram and cardiopulmonary exercise testing pre-operatively and six months after surgery.
Results Forty three of the fifty patients recruited between February 2017 and October 2018 were included in per protocol analysis. Seven patients were excluded-two patients did not meet inclusion criteria after further investigation, two patients were unable to perform pre-operative cardiopulmonary exercise testing, two patients had post-operative mortality, one patient declined post-operative cardiopulmonary exercise testing. Median age was 64 years and 15 patients (34.9%) were female. Thirty five patients had impaired post-operative functional capacity defined as post-operative left ventricular ejection fraction on echocardiogram <50% and/or post-operative percentage predicted peak VO2 ≤ 84%). In patients with class I indication for surgery (n = 30), there was no significant change post-operatively in ppVO2 (81 (69-88) % vs. 79 (60-87) %, p = 0.09). In patients with class II indication for surgery (n = 13), there was a significant fall post-operatively in ppVO2 (82 (79-92) % vs. (74 (68-86) %, p < 0.01). In the univariate analysis, pre-operative ppVO2 ≤ 84% (p < 0.01) was a predictor for impaired post-operative functional capacity.
Conclusions Patients with class I indication have persistently abnormal exercise performance six months after surgery. Patients with class II indication for surgery have worse exercise performance parameters six months after surgery. Pre-operative ppVO2 ≤84% is an independent predictor of impaired post-operative functional capacity at six months.