Author Archives: Paul Older

Heart rate recovery after orthostatic challenge and cardiopulmonary exercise testing in older individuals: prospective multicentre observational cohort study.

James A; Department of Anaesthesia of many Hospitals in the UK – Marsden, Royal London, Plymouth Trust
Bruce D; Tetlow N; Patel ABU; Black E; Whitehead N; Ratcliff A; Jamie Humphreys A; MacDonald N; McDonnell G; Raobaikady R; Thirugnanasambanthar J; Ravindran JI; Whitehead N; Minto G; Abbott TEF; Jhanji S; Milliken D; Ackland GL;

BJA open [BJA Open] 2023 Nov 03; Vol. 8, pp. 100238.
Date of Electronic Publication: 2023 Nov 03 (Print Publication: 2023).

Background: Impaired vagal function in older individuals, quantified by the ‘gold standard’ delayed heart rate recovery after maximal exercise (HRR exercise ), is an independent predictor of cardiorespiratory capacity and mortality (particularly when HRR ≤12 beats min -1 ). Heart rate also often declines after orthostatic challenge (HRR orthostatic ), but the mechanism remains unclear. We tested whether HRR orthostatic reflects similar vagal autonomic characteristics as HRR exercise .
Methods: Prospective multicentre cohort study of subjects scheduled for cardiopulmonary exercise testing (CPET) as part of routine care. Before undergoing CPET, heart rate was measured with participants seated for 3 min, before standing for 3 min (HRR orthostatic). HRR exercise 1 min after the end of CPET was recorded. The primary outcome was the correlation between mean heart rate change every 10 s for 1 min after peak heart rate was attained on standing and after exercise for each participant. Secondary outcomes were HRR orthostatic and peak VO 2 compared between individuals with HRR exercise <12 beats min -1 .
Results: A total of 87 participants (mean age: 64 yr [95%CI: 61-66]; 48 (55%) females) completed both tests.
Mean heart rate change every 10 s for 1 min after peak heart rate after standing and exercise was significantly correlated ( R 2 =0.81; P <0.0001). HRR orthostatic was unchanged in individuals with HRR exercise ≤12 beats min -1 ( n =27), but was lower when HRR exercise >12 beats min -1 ( n =60; mean difference: 3 beats min -1 [95% confidence interval 1-5 beats min -1 ]; P <0.0001). Slower HRR orthostatic was associated with lower peak VO 2 (mean difference: 3.7 ml kg -1 min -1 [95% confidence interval 0.7-6.8 ml kg -1 min -1 ]; P =0.039).
Conclusion: Prognostically significant heart rate recovery after exhaustive exercise is characterised by quantitative differences in heart rate recovery after orthostatic challenge. These data suggest that orthostatic challenge is a valid, simple test indicating vagal impairment.

Lowered oxidative capacity in spinal muscular atrophy, Jokela type; comparison with mitochondrial muscle disease.

Ratia N; Unit of Clinical Physiology,  Helsinki University Hospital, Helsinki, Finland.
Palu E; Lantto H;Ylikallio E; Luukkonen R; Suomalainen A; Auranen M;Piirilä P;

Frontiers in neurology [Front Neurol] 2023 Nov 08; Vol. 14, pp. 1277944.
Date of Electronic Publication: 2023 Nov 08 (Print Publication: 2023).

Introduction: Spinal muscular atrophy, Jokela type (SMAJ) is a rare autosomal dominantly hereditary form of spinal muscular atrophy caused by a point mutation c.197G>T in CHCHD10 . CHCHD10 is known to be involved in the regulation of mitochondrial function even though patients with SMAJ do not present with multiorgan symptoms of mitochondrial disease. We aimed to characterize the cardiopulmonary oxidative capacity of subjects with SMAJ compared to healthy controls and patients with mitochondrial myopathy.
Methods: Eleven patients with genetically verified SMAJ, 26 subjects with mitochondrial myopathy (MM), and 28 healthy volunteers underwent a cardiopulmonary exercise test with lactate and ammonia sampling. The effect of the diagnosis group on the test results was analysed using a linear model.
Results: Adjusted for sex, age, and BMI, the SMAJ group had lower power output ( p  < 0.001), maximal oxygen consumption (VO 2 max) ( p  < 0.001), and mechanical efficiency ( p  < 0.001) compared to the healthy controls but like that in MM. In the SMAJ group and healthy controls, plasma lactate was lower than in MM measured at rest, light exercise, and 30 min after exercise ( p  ≤ 0.001-0.030) and otherwise lactate in SMAJ was lower than controls and MM, in longitudinal analysis p  = 0.018. In MM, the ventilatory equivalent for oxygen was higher ( p  = 0.040), and the fraction of end-tidal CO 2 lower in maximal exercise compared to healthy controls ( p  = 0.023) and subjects with SMAJ.
Conclusion: In cardiopulmonary exercise test, subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.

Periodic health evaluation in athletes competing in Tokyo 2020: from SARS-CoV-2 to Olympic medals.

Squeo MR; Italian National Olympic Committee, Institute of Sport Medicine and Science, Roma, Italy.
Monosilio S; Gismondi A; Perrone M;Gregorace E; Lemme E; Di Gioia G; Mango R; Prosperi S;Spataro A; Maestrini V; Di Giacinto B; Pelliccia A;

BMJ open sport & exercise medicine [BMJ Open Sport Exerc Med] 2023 Nov 29; Vol. 9 (4), pp. e001610.
Date of Electronic Publication: 2023 Nov 29 (Print Publication: 2023).

Background: The Tokyo Olympic games were the only games postponed for a year in peacetime, which will be remembered as the COVID-19 Olympics. No data are currently available on the effect on athlete’s performance.
Aim: To examine the Italian Olympic athletes who have undergone the return to play (RTP) protocol after COVID-19 and their Olympic results.
Methods: 642 Potential Olympics (PO) athletes competing in 19 summer sport disciplines were evaluated through a preparticipation screening protocol and, when necessary, with the RTP protocol. The protocol comprised blood tests, 12-lead resting ECG, transthoracic echocardiogram, cardiopulmonary exercise test, 24-hour Holter-ECG monitoring and cardiovascular MR based on clinical indication.
Results: Of the 642 PO athletes evaluated, 384 participated at the Olympic Games, 254 being excluded for athletic reasons. 120 athletes of the total cohort of 642 PO were affected by COVID-19. They were evaluated with the RTP protocol before resuming physical activity after a mean detraining period of 30±13 days. Of them, 100 were selected for Olympic Games participation, 16 were excluded for athletic reasons and 4 were due to RTP results (2 for COVID-19-related myocarditis, 1 for pericarditis and 1 for complex ventricular arrhythmias). Among athletes with a history of COVID-19 allowed to resume physical activity after the RTP and selected for the Olympic Games, no one had abnormalities in cardiopulmonary exercise test parameters, and 28 became medal winners with 6 gold, 6 silver and 19 bronze medals.
Conclusions: Among athletes with COVID-19, there is a low prevalence of cardiac sequelae. For those athletes allowed to resume physical activity after the RTP evaluation, the infection and the forced period of inactivity didn’t have a negative impact on athletic performance.

A Reference Equation for VO 2peak for Pediatric Patients Undergoing Treadmill Cardiopulmonary Exercise Testing.

Griffith GJ; Northwestern University Feinberg School of Medicine. Electronic address: garett.griffith@northwestern.edu.
Wang AP; Liem RI; Carr MR;Corson T; Ward K;

The American journal of cardiology [Am J Cardiol] 2023 Nov 30.
Date of Electronic Publication: 2023 Nov 30.

Pediatric patients are often referred to cardiopulmonary exercise testing (CPET) laboratories for assessment of exercise-related symptoms. For clinicians to understand results in the context of performance relative to peers, adequate fitness-based prediction equations must be available. However, reference equations for prediction of peak oxygen uptake (VO2peak ) in pediatrics are largely developed from field-based testing and equations derived from CPET are primarily developed using adult data. Our objective was to develop a pediatric reference equation for VO2peak .
Clinical CPET data from a validation cohort of 1,383 pediatric patients aged 6-18 years who achieved a peak RER≥1.00 were analyzed to identify clinical and exercise testing factors that contributed to the prediction of VO2peak from tests performed using the Bruce protocol.
The resultant prediction equation was applied to a cross-validation cohort of 1,367 pediatric patients. Exercise duration, sex, weight, and age contributed to the prediction of VO2peak , resulting in the following prediction equation (R 2  = 0.645, p < 0.001, SEE = 6.19mL/kg/min): VO2peak (mL/kg/min) = 16.411+ 3.423 (exercise duration [minutes]) – 5.145 (sex [0=male, 1=female]) – 0.121 (weight [kg]) + 0.179 (age [years]). This equation was stable across the age range included in the present study, with differences ≤ 0.5mL/kg/min between mean measured and predicted VO2peak in all age groups.
In conclusion, this study represents the largest pediatric CPET-derived VO2peak prediction effort to date and this VO2peak prediction equation provides clinicians who perform and interpret exercise tests on pediatric patients with a resource with which to better quantify fitness when CPET is not available.

The effects of inspiratory muscle training on cardiorespiratory functions in juvenile idiopathic arthritis: A randomized controlled trial.

Sarac DC; Department of Physiotherapy and Rehabilitation, Ankara, Turkiye;
Bayraktar D; Ozer Kaya D; Altug Gucenmez O; Oskay D;

Pediatric pulmonology [Pediatr Pulmonol] 2023 Dec 01.
Date of Electronic Publication: 2023 Dec 01.

Introduction: Although inspiratory muscle training (IMT) has proven effective in adult rheumatic diseases, its impact on juvenile idiopathic arthritis (JIA) remains unexplored. The present study aimed to investigate the effects of IMT in children with JIA.
Methods: Thirty-three children (13-18 years) with JIA were divided into two groups as exercise (n = 17) and control (n = 16). The exercise group performed IMT at home daily for 8 weeks. The initial IMT load was set as 60% of maximal inspiratory pressure (PI max ) and increased by %10 of the initial load every 2 weeks. The control group received no additional intervention. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), FVC/FEV 1 , PI max , and maximal expiratory pressure (PE max ) were evaluated. Peak oxygen consumption (VO 2max ), metabolic equivalents (METs), and maximal heart rate were measured with cardiopulmonary exercise test. Functional capacity and quality of life were assessed with 6-min walk distance and Pediatric Quality of Life Inventory 3.0 Arthritis Module. All participants were evaluated at baseline and post-treatment.
Results: FVC ( ↑ 0.20 (95% CI: 0.07/0.32) liters), FEV 1 ( ↑ 0.14 (95% CI: 0.02/0.25) liters), PI max (↑19.11 (95% CI: 9.52/28.71) cmH 2 O), PE max (↑12.41 (95% CI: 3.09/21.72) cmH 2 O), VO 2peak (↑158.29 (95% CI: 63.85/252.73) ml/min), and METs (↑0.92 (95% CI: 0.34/1.49) [ml/kg/min]) significantly improved only in the exercise group (p < .05). The difference over time in FVC, FEV 1 , PI max , VO 2peak , and METs were significantly higher in exercise group compared to control group (p < .05).
Conclusions: IMT seems to be an effective option for improving respiratory functions and aerobic exercise capacity in JIA.

Chronic thromboembolic pulmonary disease: Association with exercise-induced pulmonary hypertension and right ventricle adaptation over time: Chronic thromboembolic pulmonary disease and exercise pulmonary hypertension.

Madonna R; University Cardiology Division, Pisa University Hospital and University of Pisa, Italy;
Alberti M; Biondi F;Morganti R; ,Badagliacca R; Vizza CD; De Caterina R;

European journal of internal medicine [Eur J Intern Med] 2023 Dec 01.
Date of Electronic Publication: 2023 Dec 01.

Background and Aim: Chronic thromboembolic pulmonary disease (CTEPD) is a progressive condition caused by fibrotic thrombi and vascular remodeling in the pulmonary circulation despite prolonged anticoagulation. We evaluated clinical factors associated with CTEPD, as well as its impact on functional capacity, pulmonary haemodynamics at rest and after exercise, and right ventricle (RV) morphology and function.
Methods: We compared 33 consecutive patients with a history of acute pulmonary embolism and either normal pulmonary vascular imaging (negative Q-scan, group 1, n = 16) or persistent defects on lung perfusion scan (positive Q-scan) despite oral anticoagulation at 4 months (group 2, n = 17). Investigations included thrombotic load, the Pulmonary Embolism Severity Index (PESI) score, functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and at 24 months.
Results: Compared with group 1, group 2 featured a higher PESI score (p = 0.02) and a higher thrombotic load (p = 0.004) at hospital admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p < 0.001) and ESE (p < 0.001). At 24 months group 2 showed higher NT-proBNP (p < 0.001), WHO-FC (p < 0.001), systolic (p<0.001) and diastolic (p = 0.037) RV dysfunction and worse RV-arterial coupling (p < 0.001) despite maintaining a low or intermediate echocardiographic probability of PH.
Conclusions: This is the first “proof of concept” study showing that patients with a positive Q-scan frequently develop Ex-PH and RV functional deterioration as well as reduced functional capacity, generating the hypothesis that Ex-PH could help detect the progression to CTEPD.

Cardiovascular Follow-up of Patients Treated for MIS-C.

Zimmerman D; Department of Pediatrics, Children’s Hospital Los Angeles,  California;
Shwayder M; Souza A; Su JA; Votava-Smith J; Wagner-Lees S; Kaneta K; Cheng A; Szmuszkovicz J;

Pediatrics [Pediatrics] 2023 Dec 01; Vol. 152 (6).

Objectives: To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C).
Methods: Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram.
Results: Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups.
Conclusions: The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

Incidental Cardiovascular Abnormalities in the Abdominal Aortic Aneurysm (AAA) Surveillance Population During the AAA Get Fit Trial: A Case Series and Review of the Literature

Flaherty D. J.;  Haque A.; Vascular Surgery, University of Manchester, Manchester, GBR.

Cureus 2023 Vol. 15 Issue 11 Pages e48271

Background The prevalence of cardiovascular disease and incidence of major adverse cardiovascular events (MACEs) is very high among the abdominal aortic aneurysm (AAA) surveillance population. Formal assessments of and interventions to reduce cardiovascular risk are not a routine part of the surveillance programme at present. However, its potential importance is highlighted by incidental findings during the AAA Get Fit Trial, a randomised controlled trial which included baseline cardiopulmonary exercise testing (CPET). We speculate that CPET can act as an opportunistic screening programme to identify cardiovascular disease in AAA surveillance patients.
Methods The AAA Get Fit Trial was a prospective, randomised controlled trial at a tertiary vascular centre, Manchester University NHS Foundation Trust, conducted between November 2017 and August 2019. Patients underwent CPET at baseline, 8, 16, 24 and 36 weeks as well as clinical history and examination and blood tests. We report on incidental cardiovascular abnormalities diagnosed during the trial.
Results Of the 59 participants in the trial, four (6.8%) were identified to have abnormal findings suggestive of unstable cardiovascular disease. On subsequent further investigation, two patients were diagnosed and treated for severe coronary artery disease after abnormal ECG findings were noted during CPET. One patient was diagnosed with unstable angina after obtaining a detailed history on baseline assessment which was treated medically before going on to have a successful elective AAA repair. Conclusions There is a high incidence of MACEs among this high-risk population both pre and perioperatively. Identifying and treating cardiovascular disease among t

Correction to article by Dr Shanmugakumar Chinnappa MRCP PhD et al

The paper:

“The Interpretation of Standard Cardiopulmonary Exercise Test Indices of Cardiac Function in Chronic Kidney Disease” in the special issue “New Insights from Cardiopulmonary Exercise Testing and Cardiac Rehabilitation—Part II

Was wrongly ascribed to Taiwan University.

It originated from Doncaster and Bassetlaw Teaching Hospitals in the UK

My apologies to all concerned

Paul Older

The Interpretation of Standard Cardiopulmonary Exercise Test Indices of Cardiac Function in Chronic Kidney Disease

J. Clin. Med. 2023, 12(23), 7456
Background and Aims: As there is growing interest in the application of cardiopulmonary exercise test (CPX) in chronic kidney disease (CKD), it is important to understand the utility of conventional exercise test parameters in quantifying the cardiopulmonary fitness of patients with CKD. Merely extrapolating information from heart failure (HF) patients would not suffice. In the present study, we evaluated the utility of CPX parameters such as the peak O2-pulse and the estimated stroke volume (SV) in assessing the peak SV by comparing with the actual measured values. Furthermore, we compared the anaerobic threshold (AT), peak circulatory power, and ventilatory power with that of the measured values of the peak cardiac power (CPOpeak) in representing the cardiac functional reserve in CKD. We also performed such analyses in patients with HF for comparison.
Method: A cross sectional study of 70 asymptomatic male CKD patients [CKD stages 2–5 (pre-dialysis)] without primary cardiac disease or diabetes mellitus and 25 HF patients. A specialized CPX with a CO2 rebreathing technique was utilized to measure the peak cardiac output and peak cardiac power output. The peak O2 consumption (VO2peak) and AT were also measured during the test. Parameters such as the O2-pulse, stroke volume, arteriovenous difference in O2 concentration [C(a-v)O2], peak circulatory power, and peak ventilatory power were all calculated. Pearson’s correlation, univariate, and multivariate analyses were applied.
Results: Whereas there was a strong correlation between the peak O2-pulse and measured peak SV in HF, the correlation was less robust in CKD. Similarly, the correlation between the estimated SV and the measured SV was less robust in CKD compared to HF. The AT only showed a modest correlation with the CPOpeak in HF and only a weak correlation in CKD. A stronger correlation was demonstrated between the peak circulatory power and CPOpeak, and the ventilatory power and CPOpeak. In HF, the central cardiac factor was the predominant determinant of the standard CPX-derived surrogate indices of cardiac performance. By contrast, in CKD both central and peripheral factors played an equally important role, making such indices less reliable markers of cardiac performance per se in CKD.
Conclusion: The results highlight that the standard CPX-derived surrogate markers of cardiac performance may be less reliable in CKD, and that further prospective studies comparing such surrogate markers with directly measured cardiac hemodynamics are required before adopting such markers into clinical practice or research in CKD.