Edwards T; Tas E; Leclerc K; Børsheim E;

Frontiers in pediatrics [Front Pediatr] 2023 Apr 06; Vol. 11, pp. 1103094.
Date of Electronic Publication: 2023 Apr 06 (Print Publication: 2023).

Noninvasive cardiopulmonary exercise testing (CPET) provides the valuable capacity to analyze pulmonary gas exchange and cardiovascular responses that can be used to differentiate normal cardiopulmonary responses from abnormal. This case report highlights a proposed role for CPET in identifying potential cardiac pathologies in at-risk adolescents. An abnormal CPET response in an asymptomatic adolescent revealed a family history of early-age CAD. The significance of the abnormal CPET response was further supported by the presence of an elevated concentration of circulating high sensitivity C-reactive protein (hs-CRP). These findings emphasize the importance of a thorough clinical evaluation in at-risk adolescents, as CPET can aid in the early detection and management of cardiac pathologies, especially when combined with other relevant biomarkers such as plasma hs-CRP concentration, which can further suggest underlying pathology. Management considerations using serial CPET evaluations are recommended. Thus, CPET abnormalities combined with elevated hs-CRP should be taken seriously and provide justification for further evaluation and monitoring in adolescents at risk for cardiovascular disease.

Chung JH; Tsai YJ; Lin KL; Huang MH; Chen GB; Tuan SH;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 Apr 13; Vol. 10 (4).
Date of Electronic Publication: 2023 Apr 13.

ndividuals with mitral valve prolapse (MVP) have exercise intolerance even without mitral valve regurgitation. Mitral valve degeneration may progress with aging. We aimed to evaluate the influence of MVP on the cardiopulmonary function (CPF) of individuals with MVP through serial follow-ups from early to late adolescence. Thirty patients with MVP receiving at least two cardiopulmonary exercise tests (CPETs) using a treadmill (MVP group) were retrospectively analyzed. Age-, sex-, and body mass index-matched healthy peers, who also had serial CPETs, were recruited as the control group. The average time from the first CPET to the last CPET was 4.28 and 4.06 years in the MVP and control groups, respectively. At the first CPET, the MVP group had a significantly lower peak rate pressure product (PRPP) than the control group ( p = 0.022). At the final CEPT, the MVP group had lower peak metabolic equivalent (MET, p = 0.032) and PRPP ( p = 0.031). Moreover, the MVP group had lower peak MET and PRPP as they aged, whereas healthy peers had higher peak MET ( p = 0.034) and PRPP ( p = 0.047) as they aged. Individuals with MVP had poorer CPF than healthy individuals as they develop from early to late adolescence. It is important for individuals with MVP to receive regular CPET follow-ups.

Das BB;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 Apr 19; Vol. 10 (4).
Date of Electronic Publication: 2023 Apr 19.

Cardiopulmonary exercise testing (CPET) is the clinical standard for children with congenital heart disease (CHD), heart failure (HF) being assessed for transplantation candidacy, and subjects with unexplained dyspnea on exertion. Heart, lung, skeletal muscle, peripheral vasculature, and cellular metabolism impairment frequently lead to circulatory, ventilatory, and gas exchange abnormalities during exercise. An integrated analysis of the multi-system response to exercise can be beneficial for differential diagnosis of exercise intolerance. The CPET combines standard graded cardiovascular stress testing with simultaneous ventilatory respired gas analysis. This review addresses the interpretation and clinical significance of CPET results with specific reference to cardiovascular diseases. The diagnostic values of commonly obtained CPET variables are discussed using an easy-to-use algorithm for physicians and trained nonphysician personnel in clinical practice.

Neder JA;

Respiratory medicine [Respir Med] 2023 Apr 24, pp. 107249.
Date of Electronic Publication: 2023 Apr 24.

Cardiopulmonary exercise testing (CPET) remains poorly understood and, consequently, largely underused in respiratory medicine. In addition to a widespread lack of knowledge of integrative physiology, several tenets of CPET interpretation have relevant controversies and limitations which should be appropriately recognized. With the intent to provide a roadmap for the pulmonologist to realistically calibrate their expectations towards CPET, a collection of deeply entrenched beliefs is critically discussed. They include a) the actual role of CPET in uncovering the cause(s) of dyspnoea of unknown origin, b) peak O ₂ uptake as the key metric of cardiorespiratory capacity, c) the value of low lactate (“anaerobic”) threshold to differentiate cardiocirculatory from respiratory causes of exercise limitation, d) the challenges of interpreting heart rate-based indexes of cardiovascular performance, e) the meaning of peak breathing reserve in dyspnoeic patients, f) the merits and drawbacks of measuring operating lung volumes during exercise, g) how best interpret the metrics of gas exchange inefficiency such as the ventilation-CO ₂ output relationship, h) when (and why) measurements of arterial blood gases are required, and i) the advantages of recording submaximal dyspnoea “quantity” and “quality”. Based on a conceptual framework that links exertional dyspnoea to “excessive” and/or “restrained” breathing, I outline the approaches to CPET performance and interpretation that proved clinically more helpful in each of these scenarios. CPET to answer clinically relevant questions in pulmonology is a largely uncharted research field: I, therefore, finalize by highlighting some lines of inquiry to improve its diagnostic and prognostic yield.

Pizzuto DA; Buonsenso D; Morello R; De Rose C; Valentini P; Fragano A; Baldi F; Di Giuda D;

Pediatric pulmonology [Pediatr Pulmonol] 2023 Apr 25.
Date of Electronic Publication: 2023 Apr 25.

Background: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with ^99m Tc-MAA SPECT/CT.
Materials and Methods: lung ^99m Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed.
Results: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on ^99m Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT.
Conclusions: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.

Hager, A; (Editorial)

 JACC; Volume 81, Issue 16, 25 April 2023, Pages 1601-1604

Infants with univentricular heart have only a single ventricle and initially a parallel circulation. The mixed blood of the single ventricle serves both the pulmonary circulation and the systemic circulation. Most patients nowadays get a palliation into a serial circulation according to the Fontan principle: the central venous blood bypasses the right ventricle into the pulmonary arteries. The staged Fontan palliation is performed, with a first stage within the first weeks of age stabilizing the parallel circulation, a second-stage in infancy with a superior cavopulmonary anastomosis and a third stage in early childhood with the completion by an inferior cavopulmonary anastomosis. Up to the third stage, there is still a substantial mortality depending on the details of the primary heart defect. At and after the third stage, there is only a minimal mortality throughout childhood, and most of these patients reach adulthood……etc.

Joseph P; Singh I; Oliveira R; Capone CA; Mullen MP; Cook DB; Stovall MC; Squires J; Madsen K; Waxman AB; Systrom DM;

Chest [Chest] 2023 Apr 11.
Date of Electronic Publication: 2023 Apr 11.

Topic Importance: Post-Acute Sequelae of SARS-CoV-2 (PASC) is a long-term consequence of acute infection from coronavirus disease 2019 (COVID-19). Clinical overlap between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been observed, with shared symptoms including intractable fatigue, postexertional malaise, and orthostatic intolerance. The mechanistic underpinnings of such symptoms are poorly understood.
Review Findings: Early studies suggest deconditioning as the primary explanation for exertional intolerance in PASC. Cardiopulmonary exercise testing (CPET) reveals perturbations related to systemic blood flow and ventilatory control associated with acute exercise intolerance in PASC, which are not typical of simple detraining. Hemodynamic and gas exchange derangements in PASC have substantial overlap with those observed with ME/CFS, suggestive of shared mechanisms.
Summary: This review aims to illustrate exercise pathophysiologic commonalities between PASC and ME/CFS that will help guide future diagnostics and treatment.

Pietrzak R; Książczyk TM; Franke M; Werner B;

Scientific reports [Sci Rep] 2023 Apr 11; Vol. 13 (1), pp. 5897.
Date of Electronic Publication: 2023 Apr 11.

Premature ventricular contractions (PVC) are frequently seen in children. We evaluated left ventricular diastolic function in PVC children with normal left ventricular systolic function to detect whether diastolic function disturbances affect physical performance. The study group consisted of 36 PVC children, and the control group comprised 33 healthy volunteers. Echocardiographic diastolic function parameters such as left atrial volume index (LAVI), left atrial strains (AC-R, AC-CT, AC-CD), E wave, E deceleration time (Edt), E/E’ ratio, and isovolumic relaxation time (IVRT) were measured. In the cardiopulmonary exercise test (CPET), oxygen uptake (VO _{2 max} ) was registered. Evaluation of diastolic function parameters revealed statically significant differences between the patients and controls regarding Edt (176.58 ± 54.8 ms vs. 136.94 ± 27.8 ms, p < 0.01), E/E’ (12.6 ± 3.0 vs. 6.7 ± 1.0, p < 0.01), and IVRT (96.6 ± 19.09 ms. vs. 72.86 ± 13.67 ms, p < 0.01). Left atrial function was impaired in the study group compared to controls: LAVI (25.3 ± 8.2 ml/m ² vs. 19.2 ± 7.5 ml/m ² , p < 0.01), AC-CT (34.8 ± 8.6% vs. 44.8 ± 11.8%, p < 0.01), and AC-R-(6.0 ± 4.9% vs. -11.5 ± 3.5%, p < 0.01), respectively. VO2 max in the study group reached 33.1 ± 6.2 ml/min/kg. A statistically significant, moderate, negative correlation between VO2 max and E/E’ (r = -0.33, p = 0.02) was found. Left ventricular diastolic function is impaired and deteriorates with the arrhythmia burden increase in PVC children. Ventricular arrhythmia in young individuals may be related to the filling pressure elevation and drive to exercise capacity deterioration.

Laukkanen J; Isiozor NM; Willeit P; Kunutsor SK;

Cardiology [Cardiology] 2023 Apr 13.
Date of Electronic Publication: 2023 Apr 13.

Introduction: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study.
Methods: Haemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) measured in 1897 men aged 42-61 years during CPX from rest to peak exercise, using the formula: [(Heart rate max x SBPmax) – (Heart rate rest x SBPrest)]/(Heart rate rest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were analyzed for SCD.
Results: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p-value for non-linearity=.63). A unit (bpm/mmHg) higher HGI was associated with a decreased risk of SCD (HR 0.84; 95% CI 0.71-0.99), which was attenuated following adjustment for CRF. Cardiorespiratory fitness was inversely associated with SCD, which remained after further adjustment for HGI: (HR 0.85; 95% CI 0.77-0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change=0.0096; p=.017) and reclassification (NRI=39.40%, p=.001). The corresponding values for CRF were (C-index change=0.0178; p=.007) and (NRI=43.79%, p=.001).
Conclusion: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship, but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI.