Boles S; Ashok SR;

Whilst most patients infected with COVID-19 make a full recovery, around 1 in 33 patients in the UK report ongoing symptoms post-infection, termed ‘long COVID’. Studies have demonstrated that infection with early COVID-19 variants increases postoperative mortality and pulmonary complications for around 7 weeks after acute infection. Furthermore, this increased risk persists for those with ongoing symptoms beyond 7 weeks. Patients with long COVID may therefore also be at increased postoperative risk, and despite the significant prevalence of long COVID, there are minimal guidelines on how best to assess and manage these patients perioperatively. Long COVID shares several clinical and pathophysiological similarities with conditions such as myalgic encephalitis/chronic fatigue syndrome and postural tachycardia syndrome; however, there are no current guidelines for the preoperative management of these patients to help develop something similar for long COVID patients. Developing guidelines for long COVID patients is further complicated by its heterogenous presentation and pathology. These patients can have persistent abnormalities on pulmonary function tests and echocardiography 3 months after acute infection, correlating with a reduced functional capacity. Conversely, some long COVID patients can continue to experience symptoms of dyspnoea and fatigue despite normal pulmonary function tests and echocardiography, yet demonstrating significantly reduced aerobic capacity on cardiopulmonary exercise testing even a year after initial infection. How to comprehensively risk assess these patients is therefore challenging. Existing preoperative guidelines for elective patients with recent COVID-19 generally focus on the timing of surgery and recommendations for pre-assessment if surgery is required before this time interval has elapsed. How long to delay surgery in those with ongoing symptoms and how to manage them perioperatively are less clear. We suggest that multidisciplinary decision-making is required for these patients, using a systems-based approach to guide discussion with specialists and the need for further preoperative investigations. However, without a better understanding of the postoperative risks for long COVID patients, it is difficult to obtain a multidisciplinary consensus and obtain informed patient consent. Prospective studies of long COVID patients undergoing elective surgery are urgently required to help quantify their postoperative risk and develop comprehensive perioperative guidelines for this complex patient group.

Fidalgo A; Farinatti P; Matos-Santos L; Pilon R; Rodrigues GM; Oliveira BRR; Monteiro W;

European journal of applied physiology [Eur J Appl Physiol] 2023 Jun 07.
Date of Electronic Publication: 2023 Jun 07.

Purpose: This study investigated the effects of different rest interval strategies during high-intensity interval resistance training (HIRT) on cardiorespiratory, perceptual, and enjoyment responses among trained young men.
Methods: Sixteen men experienced with HIRT underwent cardiopulmonary exercise testing and were familiarized with the exercises and HIRT protocol. On the subsequent three visits, interspaced 48-72 h, participants performed HIRT sessions with different rest intervals in a randomized order: 10 s and 30 s fixed rest intervals (FRI-10 and FRI-30), and self-selected rest interval (SSRI). Oxygen uptake (VO ₂ ), heart rate (HR), and recovery perception (Total Quality Recovery Scale) were measured during HIRT, while enjoyment responses (Physical Activity Enjoyment Scale) were assessed immediately after the sessions.
Results: The VO ₂ during exercise was greater in FRI-10 than FRI-30 (55% VO _2max and 47% VO _2max, respectively, p = 0.01), while no difference occurred between SSRI and bouts performed with fixed intervals (52% VO _2max vs. FRI, p > 0.05). HR, excess post-exercise oxygen consumption (EPOC), recovery perception, and enjoyment responses were similar across conditions (p > 0.05).
Conclusion: Exercise intensity was not affected by the rest interval strategy. High exercise intensity was maintained in sessions performed with FRI or SSRI, without negative repercussions on the duration of training sessions and enjoyment responses after exercise sessions.

Adamopoulos S; Miliopoulos D; Piotrowicz E; Snoek JA; Panagopoulou N; Nanas S; Niederseer D; Mazaheri R; Ma J; Chen Y; Popovic D; Seferovic P; Girola D; Corrà U; Coats AJ; Metra M; Rosano GMC; Volterrani M; Salvioni E;
Agostoni P; Piepoli M;

European journal of preventive cardiology [Eur J Prev Cardiol] 2023 Jun 08.
Date of Electronic Publication: 2023 Jun 08.

Background: Current European heart failure (HF) Guidelines suggests the use of risk score: among them, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has demonstrated to be one of the most accurate. However, the risk scores are still poorly implemented in clinical practice, also due to lack of strong evidence regarding their external validation in different populations. Thus, the current study was designed as an external validation test of the MECKI score in an international multicentre setting.
Methods: The study cohort consisted of patients diagnosed with HF with reduced ejection fraction (HFrEF) across international centres (not Italian), retrospectively recruited. Collected data included demographics, HF aetiology, laboratory testing, ECG, echocardiographic findings, cardiopulmonary exercise testing (CPET) results as described in the original MECKI score publication.
Results: 1042 patients across 8 international centres (7 European and 1 Asian) were included and followed up from 1998 till 2019. Patients were divided according to the calculated MECKI scores into 3 subgroups: (i) MECKI score <10%; (ii) 10-20%; (iii) ≥20%. Survival analysis comparison among the 3 MECKI score subgroups showed a worse prognosis in patients with higher MECKI score value: median event-free survival times were 4396 days for MECKI score <10%; 3457 days for 10-20%; 1022 days for ≥20% (p<0.0001). ROC curves and the AUC curves were like those reported in the original internal validation studies.
Conclusion: In patients diagnosed with HFrEF, the power of the MECKI score was confirmed in terms of prognosis and risk stratification, supporting its implementation as advised by the HF Guidelines.

Aronoff EB; Opotowsky AR; Mays WA; Knecht SK; Goessling J; Rice M; Shertzer J; Wittekind SG; Powell AW

Pediatric cardiology [Pediatr Cardiol] 2023 Jun 09.
Date of Electronic Publication: 2023 Jun 09.

Cardiac rehabilitation (CR) is an important tool for improving fitness and quality of life in those with heart disease (HD). Few pediatric centers use CR to care for these patients, and virtual CR is rarely used. In addition, it is unclear how the COVID-19 era has changed CR outcomes. This study assessed fitness improvements in young HD patients participating in both facility-based and virtual CR during the COVID-19 pandemic. This retrospective single-center cohort study included new patients who completed CR from March 2020 through July 2022. CR outcomes included physical, performance, and psychosocial measures. Comparison between serial testing was performed with a paired t test with P < 0.05 was considered significant. Data are reported as mean ± standard deviation. There were 47 patients (19 ± 7.3 years old; 49% male) who completed CR. Improvements were seen in peak oxygen consumption (VO ₂ , 62.3 ± 16.1 v 71 ± 18.2% of predicted, p = 0.0007), 6-min walk (6 MW) distance (401 ± 163.8 v 480.7 ± 119.2 m, p =  < 0.0001), sit to stand (16.2 ± 4.9 v 22.1 ± 6.6 repetitions; p =  < 0.0001), Patient Health Questionnaire-9 (PHQ-9) (5.9 ± 4.3 v 4.4 ± 4.2; p = 0.002), and Physical Component Score (39.9 ± 10.1 v 44.9 ± 8.8; p = 0.002). Facility-based CR enrollees were less likely to complete CR than virtual patients (60%, 33/55 v 80%, 12/15; p = 0.005). Increases in peak VO ₂ (60 ± 15.3 v 70.2 ± 17.8% of predicted; p = 0.002) were seen among those that completed facility-based CR; this was not observed in the virtual group. Both groups demonstrated improvement in 6 MW distance, sit-to-stand repetitions, and sit-and-reach distance. Completion of a CR program resulted in fitness improvements during the COVID-19 era regardless of location, although peak VO ₂ improved more for the in-person group.

Mendelson AA; Erickson D; Villar R;

Frontiers in physiology [Front Physiol] 2023 May 10; Vol. 14, pp. 1170429.
Date of Electronic Publication: 2023 May 10 (Print Publication: 2023).

Skeletal muscle dysfunction after critical illness, defined as ICU-acquired weakness (ICU-AW), is a complex and multifactorial syndrome that contributes significantly to long-term morbidity and reduced quality of life for ICU survivors and caregivers. Historically, research in this field has focused on pathological changes within the muscle itself, without much consideration for their in vivo physiological environment. Skeletal muscle has the widest range of oxygen metabolism of any organ, and regulation of oxygen supply with tissue demand is a fundamental requirement for locomotion and muscle function. During exercise, this process is exquisitely controlled and coordinated by the cardiovascular, respiratory, and autonomic systems, and also within the skeletal muscle microcirculation and mitochondria as the terminal site of oxygen exchange and utilization. This review highlights the potential contribution of the microcirculation and integrative cardiovascular physiology to the pathogenesis of ICU-AW. An overview of skeletal muscle microvascular structure and function is provided, as well as our understanding of microvascular dysfunction during the acute phase of critical illness; whether microvascular dysfunction persists after ICU discharge is currently not known. Molecular mechanisms that regulate crosstalk between endothelial cells and myocytes are discussed, including the role of the microcirculation in skeletal muscle atrophy, oxidative stress, and satellite cell biology. The concept of integrated control of oxygen delivery and utilization during exercise is introduced, with evidence of physiological dysfunction throughout the oxygen delivery pathway – from mouth to mitochondria – causing reduced exercise capacity in patients with chronic disease (e.g., heart failure, COPD). We suggest that objective and perceived weakness after critical illness represents a physiological failure of oxygen supply-demand matching – both globally throughout the body and locally within skeletal muscle. Lastly, we highlight the value of standardized cardiopulmonary exercise testing protocols for evaluating fitness in ICU survivors, and the application of near-infrared spectroscopy for directly measuring skeletal muscle oxygenation, representing potential advancements in ICU-AW research and rehabilitation.

Monfort A; Thevenet E; Enette L; Fagour C; Inamo J; Neviere R;

Frontiers in physiology [Front Physiol] 2023 May 15; Vol. 14, pp. 1174645.
Date of Electronic Publication: 2023 May 15 (Print Publication: 2023).

Background: The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise. Abnormal exercise pressor reflex response has been associated with exaggerated ventilatory drive, sympathovagal imbalance and exercise limitation in chronic heart failure patients. Whether metaboreflex is over-activated and participate to poor aerobic capacity in patients with hereditary transthyretin cardiac amyloidosis (CA-TTR) is unknown.
Methods: Twenty-two CA-TTR patients (aged 76 ± 7, 68% male) with the V122I (p.Val142Ile) transthyretin underwent a thorough evaluation including heart rate variability metrics, electrochemical skin conductance (ESC), physical function cardiopulmonary exercise testing, and muscle metaboreflex assessment. Eleven control subjects were chosen for muscle metaboreflex assessment.
Results: Age-matched controls ( n = 11) and CA-TTR patients ( n = 22) had similar metaboreflex sensitivity for heart rate, stroke volume, cardiac index and mean systemic arterial pressure. Compared with age-matched controls, metaboreflex sensitivity for systemic vascular resistance (-18.64% ± 6.91% vs 3.14% ± 23.35%) and minute-ventilation responses (-9.65% ± 14.83% vs 11.84% ± 23.1%) was markedly increased in CA-TTR patients. Values of ESC displayed positive correlations with stroke volume ( r = 0.53, p = 0.011) and cardiac index ( r = 0.51, p = 0.015) components of metaboreflex sensitivity, an inverse correlation with systemic vascular resistance ( r = -0.55, p = 0.008) and a trend with mean arterial ( r = -0.42, p = 0.052) components of metaboreflex sensitivity. Peak aerobic capacity (peak VO ₂ %) displayed an inverse correlation with the ventilation component of metaboreflex sensitivity ( r = -0.62, p = 0.015).
Conclusion: Consistent with the “muscle hypothesis” in heart failure, it is proposed that deterioration of skeletal muscle function in hereditary CA-TTR patients may activate muscle metaboreflex, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and overall sympathetic activation.

Aly S; Mertens L; Friedberg MK; Dragulescu A;

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography [J Am Soc Echocardiogr] 2023 May 24.
Date of Electronic Publication: 2023 May 24.

Background: Ventricular dysfunction is a significant clinical challenge in the long-term follow-up of patients with single ventricle (SV) physiology. Ventricular function and myocardial mechanics can be studied using speckle-tracking echocardiography (STE) which provides information on myocardial deformation. Limited information is available on serial changes in SV myocardial mechanics after the Fontan operation.
Aims: In this study, we wanted to describe serial changes in myocardial mechanics in children after the Fontan operation and the relationship of these changes with myocardial fibrosis markers as obtained by cardiac magnetic resonance (CMR) and exercise performance parameters.
Hypothesis: We hypothesized that ventricular mechanics declines in SV patients over time and is associated with increased myocardial fibrosis and reduced exercise performance.
Methods: Single-center retrospective cohort study including adolescents after the Fontan operation. Ventricular strain and torsion were assessed using STE. CMR and cardiopulmonary exercise testing data closest to the latest echocardiograms were obtained. The most recent follow-up echocardiographic and CMR data were compared to sex and age-matched controls as well as to individual patients’ early post-Fontan data.
Results: 50 SV patients (31 LV, 13 RV, and 6 co-dominant) were included. Median time at follow-up echocardiogram from the time of Fontan was 12.8 (10.6-16.6) years. Compared to early post-Fontan echocardiograms, follow-up assessment showed reduced global longitudinal strain [-17.5% (-14.5 to -19.5) vs -19.8% (-16.0 to -21.7), p=0.01], circumferential strain [-15.7% (-11.4 to -18.7) vs -18.9% (-15.2 to -25.0), p=0.009], reduced torsion [1.28˚/cm (0.51 to 1.74) vs 1.72˚/cm (0.92 to 2.34), p= 0.02] with decreased apical rotation but no significant change in basal rotation. Single RVs had lower torsion compared to single LVs [1.04 ˚/cm (0.12 to 2.20) vs 1.25 ˚/cm (0.25 to 2.51), p=0.01]. T1 values were higher in SV compared to controls [1009±36ms vs 958±40ms, p=0.004], and in single RV compared to LV (1023±19ms vs 1006±17ms, p=0.02). T1 correlated circumferential strain (r=0.59, p=0.04) and inversely correlated with O ₂ saturation (r=-0.67, p<0.001), and torsion (r=-0.71, p=0.02). Peak oxygen consumption correlated with torsion (r=0.52, p=0.001) and untwist rates (r=0.23, p=0.03) CONCLUSION: Post Fontan, there is a progressive decrease in myocardial deformation parameters. The progressive decrease in SV torsion is related to a decrease in apical rotation, which is more pronounced in single RVs. Decreased torsion is associated with increased markers of myocardial fibrosis and lower maximal exercise capacity. Torsional mechanics may be an important parameter to monitor after Fontan palliation but further prognostic information is required.

Phan V; Hershenson J; Caldarera L; Larkin SK; Wheeler K; Cortez AL; Dulman R; Briere N; Lewis A; Kuypers FA;
Yang E;

Pediatric blood & cancer [Pediatr Blood Cancer] 2023 May 29, pp. e30423.
Date of Electronic Publication: 2023 May 29.

Background: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.
Methods: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO ₂ ), anaerobic threshold, O ₂ pulse, VE/VCO ₂ slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO ₂ . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.
Results: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P ₅₀ left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO ₂ . The change in % predicted peak VO ₂ from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.
Conclusion: In a pilot study of 10 youths with SCA, voxelotor treatment did not improve peak VO ₂ in 9 out of 10 patients.

Tobita K; Goda A; Teruya K; Nishida Y; Takeuchi K; Kikuchi H; Inami T; Kohno T; Tashiro S;Yamada S; .Satoh T; Soejima K;

Journal of the American Heart Association [J Am Heart Assoc] 2023 Jun 01, pp. e026890.
Date of Electronic Publication: 2023 Jun 01.

Background The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment.
Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39-51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6-minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17-25) mm Hg, and the 6-minute walk distance was 530 (458-565) m, whereas the peak oxygen consumption was 18.8 (14.8-21.6) mLꞏmin ^-1 ꞏkg ^-1 . The multivariate model that best predicted 6-minute walk distance included peak arterial mixed venous oxygen content difference (β=0.46, P <0.001), whereas the best peak oxygen consumption predictors included peak cardiac output (β=0.72, P <0.001), peak arterial mixed venous oxygen content difference (β=0.56, P <0.001), and resting mean pulmonary arterial pressure (β=-0.25, P =0.026). The parameter that best predicted minute ventilation versus carbon dioxide output slope was the resting mean pulmonary arterial pressure (β=0.35, P =0.041). Quadriceps muscle strength was moderately correlated with exercise capacity (6-minute walk distance; ρ=0.57, P <0.001; peak oxygen consumption: ρ=0.56, P <0.001) and weakly correlated with ventilatory efficiency (ρ = -0.32, P =0.007).
Conclusions Central and peripheral factors are closely related to impaired exercise tolerance in patients with hemodynamically normalized PAH.

Bilak JM; Yeo JL; Gulsin GS; Marsh AM; Sian M; Dattani A; Ayton SL; Parke KS; Bain M; Pang W; Boulos S; Pierre TGS; Davies MJ; Yates T; McCann GP; Brady EM;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 Apr 24; Vol. 10 (5).
Date of Electronic Publication: 2023 Apr 24.

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D ( n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls ( n = 25). T2D remission was associated with a lower leptin-adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.