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.

Orlandi R; Rinaldo RF; Mazzucco A; Baccelli A; Mondoni M; Marchetti F; Zagaria M; Cefalo J; Leporati A;
Montoli M;Ghilardi G; Baisi A; Centanni S;

Frontiers in surgery [Front Surg] 2023 Mar 16; Vol. 10, pp. 1130919.
Date of Electronic Publication: 2023 Mar 16 (Print Publication: 2023).

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO ₂ peak). Patients with VO ₂ peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing.
Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period.
Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO ₂ peak above target for safe surgery.
Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO ₂ peak in identifying higher risk patients, even in this subgroup.

Campos NE; Vendrusculo FM; Pérez-Ruiz M; Donadio MVF;

Respiratory care [Respir Care] 2023 Apr 04.
Date of Electronic Publication: 2023 Apr 04.

Background: Whereas pulmonary exacerbations and aerobic fitness play a key role in the prognosis of cystic fibrosis (CF), the use of ventilatory threshold data as markers of exacerbation risk has been scarcely addressed. This study sought to examine the association between aerobic fitness, assessed through ventilatory threshold variables recorded during cardiopulmonary exercise testing (CPET), and the risk of exacerbations in individuals with CF.
Methods: Participants of this retrospective cohort study were subjects from 6 y of age. Over a 4-y period, the following data were recorded: lung function indicators, CPET variables, time to first exacerbation and antibiotic use, along with demographic, clinical, and anthropometric data.
Results: The mean age of 20 subjects included was 16 ± 5.4 y. Univariate regression analysis revealed that lung function (FEV ₁ : Cox hazard ratio [HR] 0.97 , P = .03; and forced expiratory flow between 25-75% of vital capacity [FEF _25-75 ]: Cox HR 0.98 , P = .036) and aerobic fitness (oxygen consumption [V̇ _{O 2} ] at ventilatory threshold: Cox HR 0.94 , P = .01; and ventilatory equivalent for carbon dioxide [V̇ _E /V̇ _{CO 2} ] at ventilatory threshold: Cox HR 1.13 , P = .049) were associated with exacerbation risk, whereas in the multivariate model, only V̇ _{O 2} at the ventilatory threshold (%max) (Cox HR 0.92 , P = .01) had a significant impact on this risk. Consistently, individuals experiencing exacerbation had significantly lower V̇ _{O 2} values (%max) at the ventilatory threshold ( P = .050) and higher ventilatory equivalent for oxygen consumption (V̇ _E /V̇ _{O 2} ) ( P = .040) and V̇ _E /V̇ _{O 2} ( P = .037) values at the ventilatory threshold. Time to exacerbation was significantly correlated with V̇ _{O 2} at the ventilatory threshold (r = 0.50, P = .02), V̇ _E /V̇ _{O 2} (r = -0.48, P = .02), and V̇ _E /V̇ _{CO 2} (r = -0.50, P = .02).
Conclusions: Our results suggest an association between CPET variables at the ventilatory threshold and exacerbations. Percentage V̇ _{O 2} at the ventilatory threshold could serve as a complementary variable to monitor exacerbations in people with CF.

Cavalcante S; Viamonte S; Cadilha RS; Ribeiro IP; Gonçalves AC; Sousa-Venâncio J; Gouveia M; Teixeira M; Santos M; Oliveira J; Ribeiro F;

Current issues in molecular biology [Curr Issues Mol Biol] 2023 Feb 28; Vol. 45 (3), pp. 1950-1960.
Date of Electronic Publication: 2023 Feb 28.

The impact of exercise on the levels of endothelial progenitor cells (EPCs), a marker of endothelial repair and angiogenesis, and circulating endothelial cells (CECs), an indicator of endothelial damage, in heart failure patients is largely unknown. This study aims to evaluate the effects of a single exercise bout on the circulating levels of EPCs and CECs in heart failure patients. Thirteen patients with heart failure underwent a symptom-limited maximal cardiopulmonary exercise test to assess exercise capacity. Before and after exercise testing, blood samples were collected to quantify EPCs and CECs by flow cytometry. The circulating levels of both cells were also compared to the resting levels of 13 volunteers (age-matched group). The maximal exercise bout increased the levels of EPCs by 0.5% [95% Confidence Interval, 0.07 to 0.93%], from 4.2 × 10 ^-3 ± 1.5 × 10 ^-3 % to 4.7 × 10 ^-3 ± 1.8 × 10 ^-3 % ( p = 0.02). No changes were observed in the levels of CECs. At baseline, HF patients presented reduced levels of EPCs compared to the age-matched group ( p = 0.03), but the exercise bout enhanced circulating EPCs to a level comparable to the age-matched group (4.7 × 10 ^-3 ± 1.8 × 10 ^-3 % vs. 5.4 × 10 ^-3 ± 1.7 × 10 ^-3 %, respectively, p = 0.14). An acute bout of exercise improves the potential of endothelial repair and angiogenesis capacity by increasing the circulating levels of EPCs in patients with heart failure.

Ito W; Uchiyama K; Mitsuno R; Sugita E; Nakayama T; Ryuzaki T; Takahashi R; Katsumata Y; Hayashi K; Kanda T; Washida N; Sato K; IItoh H;

Frontiers in physiology [Front Physiol] 2023 Mar 07; Vol. 14, pp. 1155281.
Date of Electronic Publication: 2023 Mar 07 (Print Publication: 2023).

Objective: Diminished physical capacity is common and progressive in patients undergoing dialysis, who are also prone to deficiency in carnitine, which plays a pivotal role in maintaining skeletal muscle and cardiac function. The present study aimed to evaluate the association of carnitine profile with exercise parameters in patients with incident dialysis.
Design and Methods: This was a single-center cross-sectional study including 87 consecutive patients aged 20-90 years who were initiated on dialysis in Keio University Hospital between December 2019 and December 2022 and fulfilled the eligibility criteria. Exercise parameters were evaluated via cardiopulmonary testing (CPX) using the electronically braked STRENGTH ERGO 8 ergometer, whereas the carnitine profile was assessed by determining serum free carnitine (FC), acylcarnitine (AC) levels and AC/FC ratio.
Results: The mean cohort age was 62.1 ± 15.2 years, with male and hemodialysis predominance (70% and 73%, respectively). AC/FC was 0.46 ± 0.15, and CPX revealed peak oxygen consumption (VO ₂ ) of 13.9 ± 3.7 (mL/kg/min) with percent-predicted peak VO ₂ of 53.6% ± 14.7% and minute ventilation (VE)/carbon dioxide output (VCO ₂ ) slope of 35.1 ± 8.0. Fully-adjusted multivariate linear regression analysis showed that AC/FC was significantly associated with decreased peak VO ₂ (β, -5.43 [95% confidence interval (CI), -10.15 to -0.70]) and percent-predicted peak VO ₂ (β, -19.98 [95% CI, -38.43 to -1.52]) and with increased VE/VCO ₂ slope (β, 13.76 [95% CI, 3.78-23.75]); FC and AC did not exhibit similar associations with these parameters. Moreover, only AC/FC was associated with a decreased peak work rate (WR), percent-predicted WR, anaerobic threshold, delta VO ₂ /delta WR, and chronotropic index.
Conclusion: In patients on incident dialysis, exercise parameters, including those related to both skeletal muscle and cardiac function, were strongly associated with AC/FC, a marker of carnitine deficiency indicating altered fatty acid metabolism. Further studies are warranted to determine whether carnitine supplementation can improve exercise capacity in patients on incident dialysis.