Simon W; Maria P; Mahabadi AA; Tienush R; Peter L;

International journal of cardiology [Int J Cardiol] 2022 Oct 08.
Date of Electronic Publication: 2022 Oct 08.

Background: Beta blockers (BB) reduce chronotropic response and exercise capacity in heart failure with preserved ejection fraction (HFpEF). To analyze the influence of BB on exercise performance and O 2 pulse increase as a surrogate for stroke volume in HFpEF.
Methods: We retrospectively analyzed the influence of BB intake (yes: n = 48/no: n = 51) on peak oxygen uptake (VO 2peak), oxygen uptake efficiency slope (OUES), and increase of O 2 pulse in HFpEF patients undergoing cardiopulmonary exercise testing (CPET). Associations of outcome variables and risk category of the algorithm of the Heart Failure Association of the European Society of Cardiology (HFA-PEFF score) were calculated.
Results: Patients on BB showed lower VO 2peak (p = .003) and OUES (p = .002), with a dominant effect in the high-risk (p = .020; 0.002), but not in the low risk-group (p = .434; p = .499). In the intermediate group BB showed a trend towards lower VO 2peak (p = .078) and lower values for OUES (p = .020). Patients on BB also demonstrated a lower increase of O 2 pulse during exercise (p = .002), without differences between HFA-PEFF risk groups (low: p = .322, intermediate: p = .269, high: p = .313).
Conclusions: BB reduce exercise capacity and O 2 pulse increase in HFpEF patients. Direct quantification of O 2 pulse increase may help to improve the discrimination of HFpEF patients.

Zannoni J; Guazzi MMilani V; Bandera F; Alfonzetti E; Arena R;

International journal of cardiology [Int J Cardiol] 2022 Oct 10.
Date of Electronic Publication: 2022 Oct 10.

Introduction: Cardiorespiratory fitness (CRF) is now considered a vital sign. Cardiopulmonary exercise testing (CPET) is the gold-standard assessment of CRF; peak oxygen consumption (VO ₂ ) and the minute ventilation/carbon dioxide production (VE/VCO ₂ ) slope are considered primary CPET measures of CRF. More work is needed to determine the role of this exercise assessment in the primary care setting.
Methods: 695 subjects (mean age: 62 ± 13 years, body mass index: 28.9 ± 5.3 kg/m ² , 375 female and 320 male) underwent CPET using a cycle ergometer. 95% of the cohort had one or more major cardiovascular risk factor (i.e., obesity, smoking, dyslipidemia, hypertension, diabetes); no subject was diagnosed with cardiovascular disease (CVD) at the time of CPET. Subjects were tracked for the composite endpoint of cardiovascular mortality or hospital admission.
Results: Mean peak VO ₂ , VE/VCO ₂ slope and peak respiratory exchange ratio were 17.8 ± 5.8 mlO ₂ •kg ^-1 •min ^-1 , 26.7 ± 4.1, and 1.18 ± 0.13, respectively. There were 42 composite events during the 64 ± 18 month tracking period. Both peak VO ₂ (Chi-square 16.3, p < 0.001) and the VE/VCO ₂ slope (Chi-square 14.9, p < 0.001) were significant univariate predictors of the composite endpoint. The VE/VCO ₂ slope added significant predictive value to peak VO ₂ and was retained in the multivariate regression (residual Chi-square 7.0, p = 0.008).
Discussion: These results support the prognostic value of CPET prior to a CVD diagnosis. The prognostic value of the VE/VCO ₂ slope, not commonly the focus of CPET trials in patients with one or more major cardiovascular risk factors but without a confirmed CVD diagnosis, is a particularly novel finding in the current study.

Haque A; Wisely N; McCollum C;

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery [Eur J Vasc Endovasc Surg] 2022 Jul 16.
Date of Electronic Publication: 2022 Jul 16.

Objective: Ruptured abdominal aortic aneurysm (AAA) carries a mortality rate of up to 80%. Elective repair prevents rupture, but peri-operative mortality remains at 2% – 3%. This mortality rate and long term survival rate are associated with impaired peak oxygen uptake (peak VO ₂ ), oxygen uptake at anaerobic threshold (AT) and ventilatory equivalent for CO ₂ (VECO ₂ ) at AT on cardiopulmonary exercise testing (CPET). Improving fitness to optimise these variables could improve peri-operative and long term survival, but the required exercise training suitable for patients with AAA has yet to be established. This randomised controlled trial aimed to evaluate the effectiveness of 24 week, patient directed, community based exercise on CPET measured fitness in AAA surveillance patients.
Methods: This was a prospective randomised controlled trial in a tertiary UK vascular centre conducted using CONSORT guidelines. Patients on AAA surveillance (n = 56) were randomly assigned to either (1) a 24 week community exercise programme (CEP) with choice of gym or home exercises, or (2) standard clinical care including advice on weight loss and exercise. The primary outcome was change in peak VO ₂ at 24 weeks, with secondary outcomes including AT, VECO ₂ , cardiovascular biomarkers (lipid profile, pro-B-type natriuretic peptide, and high sensitivity C reactive protein, body mass index, and HRQoL. Follow up was at eight, 16, 24, and 36 weeks to evaluate duration of benefit. All analyses were performed on an intention to treat basis.
Results: CEP patients (n = 28) achieved mean (95% confidence interval [CI]) improvements from baseline in peak VO ₂ of 1.5 (95% CI 0.5 – 2.5), 2.1 (95% CI 1.1 – 3.2), 2.3 (95% CI 1.2 – 3.3), and 2.2 (95% CI 1.1, 3.3) mL/kg/min at 8, 16, 24, and 36 weeks, respectively. These changes in CEP patients were significantly greater than those seen in control patients at 16 (p = .002), 24 (p = .031), and 36 weeks (p < .001). There were also significant improvements in AT, triglyceride levels, and HRQoL in CEP patients.
Conclusion: This CEP significantly improved those CPET parameters associated with impaired peri-operative and long term survival in patients following AAA repair. These improvements were maintained at 12 weeks following the end of the programme

Elbehairy AF; Geneidy NM; Elhoshy MS; Elsanhoury D; Elfeky MK; Abd-Elhameed A; Horsley A; O’Donnell DE;
Abd-Elwahab NH; Mahmoud MI;

Chest [Chest] 2022 Sep 29.
Date of Electronic Publication: 2022 Sep 29.

Background: Reduced exercise capacity has been previously reported in patients with obstructive sleep apnea hypopnea syndrome (OSAHS); though the underlying mechanisms are unclear.
Research Question: What are the underlying mechanisms of reduced exercise capacity in untreated patients with OSAHS? Is there a role for systemic or pulmonary vascular abnormalities?
Study Design and Methods: This is a cross-sectional observational study in which 14 patients with moderate-severe OSAHS and 10 control subjects (matched for age, body mass index (BMI), smoking history and FEV ₁ ) underwent spirometry, incremental cycle cardiopulmonary exercise test (CPET) with arterial line, resting echocardiogram and assessment of arterial stiffness (pulse wave velocity (PWV) and augmentation index (AIx)).
Results: Patients (age:50±11 years, BMI: 30.5±2.7kg/m ² , smoking: 2.4±4.0 pack-years, FEV ₁ /FVC: 0.78±0.04%, FEV ₁ :85±14 %predicted; mean±SD) had apnea hypopnea index of 43±19/hour. At rest, PWV, AIx, and mean pulmonary artery pressure (mPAP) were higher in patients vs. control subjects, P<.05. During CPET, patients had lower peak work rate (WR) and oxygen uptake; and greater dyspnea ratings compared with control subjects, all P<.05. Minute ventilation (V _E ), ventilation/CO ₂ output (V _E /VCO ₂ ), and dead space/tidal volume (V _D /V _T ) were greater in patients vs. control subjects during exercise (all P<.05). Reduction in V _D /V _T from rest to peak exercise was greater in control subjects compared with patients (0.24±0.08 vs. 0.04±0.14, P=.001). Dyspnea intensity at the highest equivalent WR correlated with corresponding values of V _E /VCO ₂ (r=0.65, P=.002), and dead space ventilation (r=0.70, P=.001). Age, PWV and mPAP explained ∼70% of the variance in peak WR, while predictors of dyspnea during CPET were rest-to-peak change in V _D /V _T and PWV (Rsqr=0.50, P<.001).
Interpretation: Patients with OSAHS had evidence of pulmonary gas exchange abnormalities during exercise (in the form of increased dead space) and resting systemic vascular dysfunction which may explain reduced exercise capacity and increased exertional dyspnea intensity.

Bayonas-Ruiz A; Muñoz-Franco FM; Sabater-Molina M; Oliva-Sandoval MJ; Gimeno JR; Bonacasa B;

ESC heart failure [ESC Heart Fail] 2022 Oct 01.
Date of Electronic Publication: 2022 Oct 01.

Aims: The aim of this study was to synthesize the evidence on the effect of the current therapies over the pathophysiological and clinical characteristics of patients with hypertrophic cardiomyopathy (HCM).
Methods and Results: A systematic review and meta-analysis of 41 studies identified from 1383 retrieved from PubMed, Web of Science, and Cochrane was conducted. Therapies were grouped in pharmacological, invasive and physical exercise. Pharmacological agents had no effect on functional capacity measured by VO2max (1.11 mL/kg/min; 95% CI: -0.04, 2.25, P < 0.05). Invasive septal reduction therapies increased VO2max (+3.2 mL/kg/min; 95% CI: 1.78, 4.60, P < 0.05). Structured physical exercise programmes did not report contraindications and evidenced the highest increases on functional capacity (VO2max + 4.33 mL/kg/min; 95% CI: 0.20, 8.45, P < 0.05). Patients with left ventricular outflow tract (LVOT) obstruction at rest improved their VO2max to a greater extent compared with those without resting LVOT obstruction (2.82 mL/kg/min; 95% CI: 1.97, 3.67 vs. 1.18; 95% CI: 0.62, 1.74, P < 0.05). Peak LVOT gradient was reduced with the three treatment options with the highest reduction observed for invasive therapies. Left ventricular ejection fraction was reduced in pharmacological and invasive procedures. No effect was observed after physical exercise. Symptomatic status improved with the three options and to a greater extent with invasive procedures.
Conclusions: Invasive septal reduction therapies increase VO2max, improve symptomatic status, and reduce resting and peak LVOT gradient, thus might be considered in obstructive patients. Physical exercise emerges as a coadjuvant therapy, which is safe and associated with benefits on functional capacity. Pharmacological agents improve reported NYHA class, but not functional capacity.

Kulej-Lyko K; Niewinski P; Tubek S; Krawczyk M; Kosmala W; Ponikowski P;

Frontiers in physiology [Front Physiol] 2022 Aug 30; Vol. 13, pp. 911636.
Date of Electronic Publication: 2022 Aug 30 (Print Publication: 2022).

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance ( p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia ( p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO ₂ comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO ₂ on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO ₂ during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO ₂ was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO ₂ , whereas PChT predicts an improvement in V˙E/V˙CO ₂ after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.