Mrak M; Pavšič N; Žižek D; Ležaić L; Bunc M;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 May 26; Vol. 10 (6).
Date of Electronic Publication: 2023 May 26.

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment.
The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure.
Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II-IV) were randomized to a CSR implantation ( n = 13) or a sham procedure ( n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min ( p = 0.03) but did not change in the sham group ( p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains.
To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy.

Gryglewska-Wawrzak K; Cienkowski K; Cienkowska A; Banach M; Bielecka-Dabrowa A;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 Jun 03; Vol. 10 (6).
Date of Electronic Publication: 2023 Jun 03.

Coronavirus disease 2019 (COVID-19) is a severe respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Heart failure (HF) is associated with a worse prognosis for patients with this viral infection, highlighting the importance of early detection and effective treatment strategies. HF can also be a consequence of COVID-19-related myocardial damage. To optimise the treatment of these patients, one needs to understand the interactions between this disease and viruses. Until now, the validity of the screening for cardiovascular complications after COVID-19 has not been confirmed. There were also no patients in whom such diagnostics seemed appropriate. Until appropriate recommendations are made, diagnosis procedures must be individualised based on the course of the acute phase and clinical symptoms reported or submitted after COVID-19. Clinical phenomena are the criteria for determining the recommended test panel. We present a structured approach to COVID-19 patients with heart involvement.

Pigakis KM; Stavrou VT; Pantazopoulos I; , Greece.Daniil Z; Kontopodi-Pigaki AK; Gourgoulianis K;

Advances in respiratory medicine [Adv Respir Med] 2023 Jun 07; Vol. 91 (3), pp. 239-253.
Date of Electronic Publication: 2023 Jun 07.

Background: Exercise-induced bronchoconstriction (EIB) is a common problem in elite athletes. Classical pathways in the development of EIB include the osmotic and thermal theory as well as the presence of epithelial injury in the airway, with local water loss being the main trigger of EIB. This study aimed to investigate the effects of systemic hydration on pulmonary function and to establish whether it can reverse dehydration-induced alterations in pulmonary function.
Materials and Methods: This follow-up study was performed among professional cyclists, without a history of asthma and/or atopy. Anthropometric characteristics were recorded for all participants, and the training age was determined. In addition, pulmonary function tests and specific markers such as fractional exhaled nitric oxide (FeNO) and immunoglobulin E (IgE) were measured. All the athletes underwent body composition analysis and cardiopulmonary exercise testing (CPET). After CPET, spirometry was followed at the 3rd, 5th, 10th, 15th, and 30th min. This study was divided into two phases: before and after hydration. Cyclists, who experienced a decrease in Forced Expiratory Volume in one second (FEV ₁ ) ≥ 10% and/or Maximal Mild-Expiratory Flow Rate (MEF _25-75 ) ≥ 20% after CPET in relation to the results of the spirometry before CPET, repeated the test in 15-20 days, following instructions for hydration.
Results: One hundred male cyclists ( n = 100) participated in Phase A. After exercise, there was a decrease in all spirometric parameters ( p < 0.001). In Phase B, after hydration, in all comparisons, the changes in spirometric values were significantly lower than those in Phase A ( p < 0.001).
Conclusions: The findings of this study suggest that professional cyclists have non-beneficial effects on respiratory function. Additionally, we found that systemic hydration has a positive effect on spirometry in cyclists. Of particular interest are small airways, which appear to be affected independently or in combination with the decrease in FEV ₁ . Our data suggest that pulmonary function improves systemic after hydration.

Tomlinson OW; Barker AR; Fulford J; Wilson P; Shelley J; Oades PJ; Williams CA

Frontiers in pediatrics [Front Pediatr] 2023 Jun 14; Vol. 11, pp. 1211547.
Date of Electronic Publication: 2023 Jun 14 (Print Publication: 2023).

Background: Increased maximal oxygen uptake (V̇O _2max ) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle “quality”) and skeletal muscle size (muscle “quantity”) are both proposed as potential causes for the lower V̇O _2max , although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O _2max to address this “quality” vs. “quantity” debate.
Methods: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size – muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O _2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t -tests and effect sizes (ES) identified differences between groups in V̇O _2max , once mCSA and TMV were controlled for.
Results: V̇O _2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45).
Conclusions: A lower V̇O _2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle “quality” in CF (as muscle “quantity” is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

Althunayyan A; Alborikan S; Badiani S; Wong K; Uppal R; CPatel N; Petersen SE; Lloyd G; Bhattacharyya S;

The American journal of cardiology [Am J Cardiol] 2023 Jun 20; Vol. 201, pp. 8-15.
Date of Electronic Publication: 2023 Jun 20.

The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.
Competing Interests: Declaration of Competing Interest Dr. Petersen reports a relation with Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada (SEP) that includes consulting or advisory. The remaining authors have no conflicts of interest to declare.

Batten K; Bhattacharya K; Simar D; Broderick C;

Journal of inherited metabolic disease [J Inherit Metab Dis] 2023 Jun 22.
Date of Electronic Publication: 2023 Jun 22.

Skeletal muscle is a dynamic organ requiring tight regulation of energy metabolism in order to provide bursts of energy for effective function. Several inborn errors of muscle energy metabolism (IEMEM) affect skeletal muscle function and therefore the ability to initiate and sustain physical activity. Exercise testing can be valuable in supporting diagnosis, however its use remains limited due to the inconsistency in data to inform its application in IEMEM populations. While exercise testing is often used in adults with IEMEM, its use in children is far more limited. Once a physiological limitation has been identified and the aetiology defined, habitual exercise can assist with improving functional capacity, with reports supporting favourable adaptations in adult patients with IEMEM. Despite the potential benefits of structured exercise programs, data in paediatric populations remain limited. This review will focus on the utilisation and limitations of exercise testing and prescription for both adults and children, in the management of McArdle Disease, long chain fatty acid oxidation disorders, and myopathic mitochondrial respiratory chain disorders.

Goulart CDL; Silva RN; Agostoni P; Franssen FME; Myers J; Arena R; Borghi-Silva A;

Respiratory medicine [Respir Med] 2023 Jun 23, pp. 107332.
Date of Electronic Publication: 2023 Jun 23.

Background: Exercise oscillatory ventilation (EOV) is considered an important variable for predicting poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF). However, there are no studies evaluating EOV presence in the coexistence chronic obstructive pulmonary disease (COPD) and HFrEF.
Aims: I) To compare the clinical characteristics of participants with coexisting HFrEF-COPD with and without EOV during cardiopulmonary exercise testing (CPET); and II) to identify the impact of EOV on mortality during follow-up for 35 months.
Methods: 50 stable HFrEF-COPD (EF<50%) participants underwent CPET and were followed for 35 months. The parametric Student’s t-test, chi-square tests, linear regression model and Kaplan-Meier analysis were applied.
Results: We identified 13 (26%) participants with EOV and 37 (74%) without EOV (N-EOV) during exercise. The EOV group had worse cardiac function (LVEF: 30 ± 6% vs. N-EOV 40 ± 9%, p = 0.007), worse pulmonary function (FEV ₁ : 1.04 ± 0.7 L vs. N-EOV 1.88 ± 0.7 L, p = 0.007), a higher mortality rate [7 (54%) vs. N-EOV 8 (27%), p = 0.02], higher minute ventilation/carbon dioxide production (V̇˙ _E / V̇˙ CO ₂ ) slope (42 ± 7 vs. N-EOV 36 ± 8, p = 0.04), reduced peak ventilation (L/min) (26.2 ± 16.7 vs. N-EOV 40.3 ± 16.4, p = 0.01) and peak oxygen uptake (mlO ₂ kg ^-1 min ^-1 ) (11.0 ± 4.0 vs. N-EOV 13.5 ± 3.4 ml●kg ^-1 ●min ^-1 , p = 0.04) when compared with N-EOV group. We found that EOV group had a higher risk of mortality during follow-up (long-rank p = 0.001) than patients with N-EOV group.
Conclusion: The presence of EOV is associated with greater severity of coexisting HFrEF and COPD and a reduced prognosis. Assessment of EOV in participants with coexisting HFrEF-COPD, as a biomarker for both clinical status and prognosis may therefore be warranted.

Zacca R; Castro FAS; Monteiro ASM; Pyne DB; Vilas-Boas JP; Fernandes RJP;

International journal of sports physiology and performance [Int J Sports Physiol Perform] 2023 Jun 23, pp. 1-9.
Date of Electronic Publication: 2023 Jun 23.

Purpose: To compare ventilatory and cardiorespiratory responses between the COSMED AquaTrainer coupled with the K4b2 and K5 wearable metabolic systems in breath-by-breath mode over a wide range of swimming speeds.
Methods: Seventeen well-trained master swimmers performed 2 front-crawl 7 × 200-m incremental intermittent protocols (increments of 0.05 m·s-1 and 30-s rest intervals, with a visual pacer) with AquaTrainer coupled with either K4b2 or K5.
Results: Post hoc tests showed that swimming speed was similar (mean diff.: -0.01 to 0.01 m·s-1; P = .73-.97), repeatable (intraclass correlation coefficient: .88-.99; P < .001), highly accurate, and precise (agreement; bias: -0.01 to 0.01 m·s-1; limits: -0.1 to 0.1 m·s-1) between all conditions. Ventilatory and cardiorespiratory responses were highly comparable between all conditions, despite a “small” effect size for fraction of expired carbon dioxide at the sixth 200-m step (0.5%; ηp2=.12; P = .04) and carbon dioxide production at the fifth, sixth, and seventh 200-m steps (0.3-0.5 L·min-1; ηp2=.11-.17; P = .01-.05). We also observed high accuracy, which was greater for tidal volume (0.0-0.1 L), minute ventilation (-3.7 to 5.1 L·min-1), respiratory frequency (bias: -2.1 to 1.9 beats·min-1), and oxygen uptake (0.0-0.2 L·min-1). Bland-Altman plots showed that the distribution inside the limits of agreement and their respective 95% CIs were consistent for all ventilatory and cardiorespiratory data. The repeatability (intraclass correlation coefficient) of tidal volume (.93-.97), minute ventilation (.82-.97), respiratory frequency (.68-.96), fraction of expired carbon dioxide (.85-.95), carbon dioxide production (.77-.95), fraction of expired oxygen (.78-.92), and oxygen uptake (.94-.98) data ranged from moderate to excellent (P < .001-.05).
Conclusions: Swimming with the AquaTrainer coupled with K5 (breath-by-breath mode) yields accurate, precise, and repeatable ventilatory and cardiorespiratory responses when compared with K4b2 (previous gold standard). Swimming support staff, exercise and health professionals, and researchers can now relate differences between physiological capacities measured with the AquaTrainer while coupled with either of these 2 devices.

Caruso FR; Goulart CDL;Jr JCB; de Oliveira CR; Mendes RG; Arena R; Borghi-Silva A;

Heart & lung : the journal of critical care [Heart Lung] 2023 Jun 24; Vol. 62, pp. 95-100.
Date of Electronic Publication: 2023 Jun 24.

Background: Weber classification stratifies cardiac patients based on peak oxygen consumption (V̇O ₂ ), the gold-standard measure of exercise capacity.
Objective: To determine if Weber classification is a useful tool to discriminate clinical phenotypes in COPD patients and to evaluate if disease severity and other clinical measures can predict V̇O _2peak .
Methods: Three hundred and six COPD patients underwent cardiopulmonary exercise testing (CPX) and were divided according to Weber class: 1) Weber A (n = 34); 2) Weber B (n = 88); 3) Weber C (n = 138); and 4) Weber D (n = 46).
Results: Weber class D patients demonstrated a reduced V̇O _{2 peak} , heart rate (HR), minute ventilation (V̇ _E ) _, oxygen (O ₂ ) pulse, circulatory power (CP), oxygen uptake efficiency slope (OUES), oxygen saturation (SpO ₂ %), delta (Δ)HR and ΔSpO ₂ when compared to Weber A and B (p<0.05). Moreover, Dyspnea and the V̇ _E /carbon dioxide production (V̇CO ₂ ) slope were higher in Weber D compared with Weber C and A (p<0.001). Hierarchical regression analysis demonstrated significant predictors of V̇O _2peak (R ² = 0.131; Adj R ²  = 1.25), including HR (β=0.5757; t = 5.7; P<0.001) and forced expiratory volume in one second (FEV ₁ ) (β=0.119; t = 2.16; P<0.03). Among the Weber C + D groups, predictors of V̇O _2peak (R = 0.78; R ² = 0.60; Adj R ² =0.59), dyspnea (β=0.076; t = 1.111; P<0.27) and maximal voluntary ventilation (MVV) (β=0.75; t = 1.14; P<0.00).
Conclusion: Weber classification may be a useful tool to stratify cardiorespiratory fitness in COPD patients. Other clinical measures may be useful in predicting peak V̇O ₂ in mild-to-severe COPD, moreover different phenotypes may be important tool to improve physical capacity of chronic disease patients.

Mapelli M; Mattavelli I; Paolillo S; Salvioni E; Magrì D; Galotta A; De Martino F; Mantegazza V; Vignati C; Esposito I; Dell’Aversana S; Paolillo R; Capovilla T; Tamborini G; Nepitella AA; Filardi PP; Agostoni P

European journal of clinical pharmacology [Eur J Clin Pharmacol] 2023 Jun 27.
Date of Electronic Publication: 2023 Jun 27.

Purpose: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses.
Methods: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose.
Results: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003.
Conclusions: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.