Exercise Capacity Research Articles

Association of left atrial strain and exercise capacity among patients with hypertension: a single center study

Abstract Introduction Hypertension has been identified as one of the leading risk factors for developing cardiovascular disease in the Philippines. 1 The long term increase in afterload causes the progressive decline in both the systolic and diastolic function of hypertensive patients. There has been an increasing recognition in the role of left atrial function in the pathophysiology of several cardiac diseases, including hypertension. Purpose For patients with hypertension, exercise capacity is reduced by 30%.2 As exercise capacity is a known prognostic marker for adverse cardiovascular outcomes, identifying patients with hypertension with impaired left atrial reservoir strain may also improve cardiovascular risk stratification. With the use of two-dimensional (2D) speckle tracking echocardiography, left atrial strain can now be utilized in the evaluation of left atrial reservoir, conduit, and contractile function. Left atrial strain (LA strain) can now serve as a biomarker of adverse cardiovascular outcomes, including the exercise capacity of patients. Another goal of the study is to identify other clinical and echocardiographic factors that may affect exercise capacity Methods A single center, retrospective cross sectional study was conducted in a tertiary hospital to validate the association of left atrial strain with exercise capacity in terms of metabolic equivalent (METs) achieved during treadmill exercise echocardiography of patients diagnosed with hypertension. The primary objective of this study is to determine the left atrial strain cutoff that reliably discriminates poor, fair, average, good, or high exercise capacity. Data was obtained by conducting a chart and echocardiography review of adult patients from January 2023 to April 2023. The independent association of LA strain with METs was studied with regression analysis. Results were considered significant at p≤0.05 at 95% confidence interval. Receiver-operating characteristic curve analysis was utilized to determine the strength of the LA strain to discriminate between the different exercise capacities. Results A total of 136 patients were included in the study. LA strain, particularly the reservoir, can discriminate exercise capacity, specifically to discriminate good to high capacity from fair to average as their AUC is 0.678 (95% CI 0.58 to 0.77, p=.0001). The best cut-off is 30.2 which resulted to 80% sensitivity (95% CI 66.3 to 90) while specificity is only 51.16% (95% CI 40.1 to 62.1). Spearman rank correlation analysis showed that LA reservoir is significantly correlated with E/A and E/e’. The relationships are linear and positive. Among the other 2D echo parameters, only EDV, E/a and E/e’ were found to have a linear relationship or correlation with METS. Conclusion The study revealed that there is moderate correlation of LA reservoir strain in terms of METS achieved during treadmill stress echocardiography (rs=0.3196, p=0.0001).LA reservoir strain AUCLA strain and other echo parameters

A novel risk score based on exercise capacity to predict all-cause mortality in adults with congenital heart disease

Abstract Background Impaired exercise capacity in adults with congenital heart disease is associated with mortality. Thus, exercise capacity is a potential tool for predicting risk in this population. The present study attempts to further explore the usefulness of exercise capacity in risk assessment of all-cause mortality, together with a limited number of easily accessible clinical variables. Methods The national register of congenital heart disease was searched for adults (18-60 years of age) with at least one bicycle ergometer exercise test and follow up in the register. The exercise capacity was classified based on percent of predicted exercise capacity (EC%pred); normal (> 70%), moderately impaired (50-70%) or severely impaired (<50%). All patients were followed for 10 years or until death, if occurring earlier than 10 years after the exercise test. Data were analyzed using logistic regression modelling. A risk evaluation model was constructed based on percent of predicted exercise capacity, age, and complexity of the heart lesion. Finally, the model was converted into a 5-point (p) risk score used to predict 10-year mortality (EC%pred >70%=0p, 50-70=1p, <50%=2p, age <25=0p, 25-40=1p, 40-60=2p, simple lesion=0p, moderate/severe complexity of heart lesion=1p). Results 1171 patients (mean age at exercise test 30.5 years, 44% women) were included with 70 deaths occurring within 10 years. A score 0-1 corresponded to <1% 10-year all-cause mortality, 2p 5%, 3p 9%, 4p 21% and 5p 33% mortality risk (Table 1). The area under curve for the model was 0.75 (95% CI 0.69-0.81). Conclusion An easily performed risk assessment containing % of predicted exercise capacity, age and complexity of heart lesion performs well in detecting patients at both low and high risk of all-cause mortality within 10 years after an exercise test.

Prognostic value of peak heart rate on cardiopulmonary exercise testing in patients with chronic heart failure

Abstract Backgrounds Many factors are known to be related to impaired exercise capacity or worse clinical outcomes in patients with chronic heart failure (CHF). Peak heart rate achievement by cardiopulmonary exercise testing (CPET) can be easily obtained on CPET. However, less data is available regarding the impact of peak heart rate on exercise capacity or long-term clinical outcomes in patients with CHF. Purpose We sought to investigate whether lower heart rate during peak exercise displayed poorer exercise capacity and worse clinical outcomes in patients with CHF. Methods We examined consecutive 435 patients with CHF referred for CPET in our university hospital between 2013 and 2018. The primary outcome was a composite of all-cause death or hospitalization due to worsening heart failure. Patients were divided into two groups according to the optimal cut-off value of peak heart rate based on receiver operating characteristic curve analysis. Results Patients with lower peak heart rate (≤112/min, n=164) were older and, higher brain natriuretic peptide level compared to those with higher peak heart rate (>112/min, n=271). Heart rate during peak exercise was significantly correlated with peak oxygen consumption (peak V̇O2) (Figure 1A), peak workload achievement (Figure 1B), and ventilatory efficiency (V̇E/V̇CO2 slope) (Figure 1C). There were 80 patients with events over a median follow-up period of 3.4 (Interquartile range 0.7–5.6) years. Patients with lower peak heart rate had about 3.0-fold higher risk of events compared to those with high peak heart rate (hazard ratio [HR] 3.17; 95% confidence interval [CI], 2.01–4.98) (Figure 2). In a multivariable Cox regression, 10 bpm-decreased in peak heart rate was associated with 12% increased adverse events (HR 0.88; 95%CI, 0.78–0.98). Conclusions Peak heart rate achievement on CPET was associated with reduced exercise capacity and worse clinical outcomes, suggesting that peak heart rate is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting peak heart rate to improve the exercise capacity or clinical outcomes in patients with CHF.Figure1Figure2

Invasive haemodynamic assessment shows the obesity-HFpEF phenotype is common amongst patients with symptomatic AF

Abstract Background The obesity-HFpEF phenotype is a unique form of heart failure associated with elevated LA and RA pressures, cardiac remodelling and poor exercise capacity. The influence of this HFpEF phenotype amongst patients with AF is unknown. Objective We sought to determine the influence of the obesity-HFpEF phenotype amongst patients with symptomatic AF, using invasive testing, imaging and cardiopulmonary exercise testing to assess haemodynamics, cardiac remodelling and exercise capacity in patients undergoing AF ablation. Methods Consecutive patients with symptomatic AF due to undergo an AF ablation procedure were recruited. Participants were grouped according to the presence of obesity if body mass index (BMI) exceeded 30kg/m2. Mean LA pressure (mLAP) and mean RA pressure (mRAP) were measured invasively at AF ablation and HFpEF was defined as mLAP>15mmHg at rest or after infusion of 500mls saline. Cardiac remodelling was assessed using transthoracic echocardiography. Exercise capacity was evaluated using cardiopulmonary exercise testing and AF symptoms and quality of life were assessed using the AF Symptom Severity Questionnaire. Results Of 120 participants, 44 (36.7%) were obese and 76 (63.3%) were non-obese (Table 1). Despite younger age (p=0.003), obese participants were more likely to have a coexistent diagnosis of HFpEF (84.1% vs 67.1%, p=0.043). In addition to higher mLAP (p<0.001), obesity was associated with higher mRAP (p<0.001) compared to non-obese patients. Obesity was not associated with differences in LV volume (p=0.559) or function (p=0.381) but was associated with larger LA volumes (p=0.032). On functional assessment, obese participants demonstrated a higher burden of AF symptoms (p=0.049), poorer quality of life (p=0.017) and a trend towards reduced exercise capacity (p=0.068). Conclusion Obese patients with AF demonstrate characteristic features of the obesity-HFpEF phenotype, including elevated LA and RA pressure, left atrial enlargement and poorer functional capacity. Novel treatments for the obesity-HFpEF phenotype, such as GLP-1 inhibitors, may be useful in obese patients with AF.

Importance of cardiac rehabilitation on cardiorrespiratory fitness in patients undergoing percutaneous aortic valve replacement

Abstract Background Percutaneous Aortic Valve Replacement (TAVR) significantly improves cardiac function in patients with severe aortic stenosis. However, the vast majority of these patients do not reach an adequate functional class despite the valve change, due to the deterioration of hemodynamic function and the repercussions of afterload over time. Cardiac rehabilitation (CR) program is an interdisciplinary intervention aimed at restoring functionality in Post-TAVR patients and the key to optimizing the recovery and enhancing cardiorrespiratory fitness (CRFit). The Purpose of the study is to provide an analysis of the effects of CR on exercise capacity and CRFit in TAVR patients. Methods Quasi-experimental study in TAVR patients that underwent a 4-6 week CR program, including personalized aerobic and strength training. Outcomes assessed pre- and post-rehabilitation included VO2 max, ventilatory thresholds (VT1 and VT2), and exercise capacity. The study also evaluated METs efficiency by comparing actual to predicted METs values before and after the therapy, alongside expired gas analysis test to examine exercise tolerance and its relation to VO2max gains. Results A total of 28 patients were analyzed, with an average age of 73 years (±8.1), initial weight of 68 kg (±12.32), and final weight of 65 kg (±11.13). The average ejection fraction (EF) from echocardiographic parameters was 62% (±10.1). All patients underwent cardiopulmonary exercise testing (CPET) after post-TAVR with improvements in CRFit. Initial exercise test parameters showed an average METs-load at 8.1 (±1.98), VO2max at 4.75 (±1.86), VT1 at 3.05 (±1.86), VAT at 3.85 (±1.62), VT2 at 4.5 (±2.28), and VE/VCO2 at 38 (±5.32). Final test parameters revealed VO2max at 5.8 (±2.09), VT1 at 3.2 (±1.33), VAT at 4.65 (±1.60), VT2 at 5.15 (±2.3), and VE/VCO2 at 36.4 (±69.95). Pearson's correlation analysis between CPET variables and the percentage improvement of various exercise test parameters found no statistically significant correlation. Except for METs-load and final time in Bruce, which show a significant and inversely proportional correlation (r=-0.67, p< 0.001). Conclusions The study demonstrates the effect of cardiac rehabilitation program in enhancing cardiorespiratory fitness and exercise capacity in post-TAVR patients. Notably, improvements in VO2max and ventilatory thresholds highlight the program's efficacy in promoting cardiovascular health. The inverse correlation between initial time in Bruce and METs improvement underscores the importance of baseline exercise capacity in predicting rehabilitation outcomes. Our results allow us to conclude that training volume is not the only variable to consider for proper CR. This insight could guide personalized rehabilitation strategies, making a significant contribution to the field of cardiac recovery post-TAVR.Measured METsBruce time - METs correlation

The impact of left venticular filling pressure indexed to cardiac output on exercise capacity in heart failure subjects

Abstract Background/Introduction Exercise intolerance is the most common symptom of patients with heart failure (HF), regardless of the phenotypes. We aim to investigate the determinants of exercise capacity in chronic stable HF with reduced, mildly reduced, preserved, and recovered ejection fraction (EF). Methods Ambulatory HF subjects were recruited for a combined cardiopulmonary exercise test and exercise stress echocardiography. Peak oxygen consumption (peak VO2) and minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) were obtained. Impaired exercise capacity was referred to a peak VO2 of <14 ml/kg/min, and a VE/VCO2 slope of >34 was defined as ventilatory inefficiency. Results Among a total of 66 participants, there were 16 HF with reduced EF, 18 HF with mildly reduced EF, 12 HF preserved EF, and 20 HF recovered EF. While both LVEF, global longitudinal strain (GLS), E/e’ ratio and diastolic dysfunction indices were crudely associated with peak VO2 and VE/VCO2 slope, only diastolic dysfunction indices were independently predictive of impaired exercise capacity (odds ratio and 95% confidence intervals: 3.847, 1.369-10.810). GLS at rest was independently correlated with ventilatory inefficiency (1.404, 1.050-1.877). Among the exercise indices, the peak medial E/e' to cardiac output ratio was independently associated with impaired exercise capacity (3.478, 1.313-9.214) and peak GLS was best related to ventilatory inefficiency (1.403, 1.076-1.828). Conclusions Among resting and exertional echocardiographic variables, the peak medial E/e' to cardiac output ratio, a non-invasive assessment of exertional left ventricular filling pressure indexed to cardiac output, was the major determinant of exercise capacity in patients with different HF phenotypes.

Effects of pulmonary hypertension targeted therapy on haemodynamics in pulmonary arterial hypertension associated with adult congenital heart disease: a meta-analysis

Abstract Background Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. There is growing evidence that PAH drugs lead to improved hemodynamics, exercise capacity, quality of life and survival in patients with PAH. Purpose The aim of this systematic review and meta-analysis is to evaluate the effects of pulmonary hypertension (PH) medical therapy on the haemodynamic parameters as well as exercise capacity in adult patients with PAH-CHD. Methods PubMed and the Cochrane Library databases have been systematically searched. Meta-analysis was conducted using STATA and Review Manager. Results Fourteen studies including 575 patients were analyzed. Pulmonary haemodynamics improved in patients receiving PH-targeted therapy. The weighted mean reduction in mean pulmonary arterial pressure (mPAP) was -5.8mmHg (I2=0%, 95% CI [–7.55, –4.06], p<0.001).The weighted mean reduction in right atrial pressure (RAP) was -5.81mmHg (I2=0%, 95% CI [-7.55, - 4,07], p<0.001). The weighted mean reduction in pulmonary vascular resistance (PVR) was 358.5dynes/sec/cm-5 (I2 51%, 95% CI [-566.55, -150.46] and p<0.001). Cardiac index was increased by 0.61L/min/m2 (I2=6%, 95% CI [0.23,1.00], p=0.002). Six-minute walking distance increased by 47.26m, (I2=0%, CI [38.36, 56.16], p<0.001). Conclusions PH-targeted therapy improves pulmonary haemodynamics and exercise capacity in adult patients with PAH-CHD.

Comparative effects of ranolazine and trimetazidine on cardiac structure and exercise capacity in a healthy rat model: a new doping agent?

Abstract Background/Introduction Anti-anginal drugs that have been shown to improve myocardial energy use include ranolazine and trimetazidine [1]. An inquiry is warranted into their ability to impact cardiac functions and exercise capacity. Purpose This study aims to evaluate the effects of ranolazine; and trimetazidine as a positive control group on cardiac structure and exercise capacity in a rodent model in comparison with the control group. Methods In a randomized, controlled trial, 24 Sprague-Dawley rats were divided into three groups: control, ranolazine, and trimetazidine. Rats were given daily doses of ranolazine (50 mg/kg/1 ml) [2], trimetazidine (10 mg/kg/1 ml) [3], or saline (control) via gastric gavage for 30 days. At the beginning of the trial, as well as on the 15th and 30th days, the rats were weighed, placed on rotarod, and assessed using transthoracic echocardiography (Figure 1). The rats underwent 21 days of forced swimming testing. According to the guidelines for rat exercise testing [4], signs of exhaustion, lack of coordinated movements, and failure to surface for three seconds following submersion in the water were designated as grounds for terminating the test. Weight, rotarod durations, M-mode and Doppler measurements, and forced swimming test durations were recorded on the 0th, 15th, and 30th days. Results No discernible differences were found between the groups in the initial evaluations. By using echocardiography, the left ventricular masses expanded in all three, indicating the emergence of an athlete's heart. In comparison to the control group, the ranolazine and trimetazidine groups showed considerable increases in their ability to exercise. In particular, the swimming times of the trimetazidine group and the ranolazine group improved to a mean of 1889 seconds by the 21st session, 1700 seconds in the trimetazidine group, and 1548 seconds in the control group (Figure 2), respectively, indicating enhanced cardiac performance. Conclusion(s) Ranolazine exhibits significant potential to enhance exercise capacity and cardiac efficiency in rats, surpassing the effects observed with trimetazidine. Trimetazidine is already registered as a doping agent in WADA [5]. These findings highlight the potential use of ranolazine as a performance enhancing agent in healthy subjects for a malicious purpose of creating unfair advantages in professional sports. Further studies in human subjects are needed.Figure 1Figure 2

Blood biomarkers to detect functional impairment in adult patients with repaired Tetralogy of Fallot

Abstract Background The relationship between plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumorigenicity-2 (sST2) with structural adaptions and exercise capacity remains incompletely described in patients with repaired Tetralogy of Fallot (rTOF). Methods Peripheral venous blood samples were drawn for 99 patients with repaired TOF, 59 patients with severe pulmonary regurgitation (PR) and 40 patients with no or mild PR. NT-proBNP was measured using enzyme-linked immunosorbent assays (Roche Diagnostics, Indianapolis, IN). Soluble ST2 levels were assessed on Aspect-plus ST2 quantitative rapid test. Results The mean value of NT-proBNP was 160±137 pg/ml, and sST2 was 29±13, ng/ml in the entire population. Mean NT-proBNP was significantly higher in patients with severe PR (169±150 vs145±118, pg/ml, p<0.001), while similar sST2 levels were observed in both groups (29±14 vs30±12, ng/ml, p>0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention. Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r=-.60, p<0.001) was stronger. The optimal cut-off of 90pg/ml for NT-proBNP had a sensitivity of 74% and specificity of 63% for detection of impaired exercise capacity. Conclusions Serum levels of sST2 and NT-proBNP are elevated in patients with repaired TOF, with higher values observed in those with severe PR, but also in patients undergoing transannular patch. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.

Novel CMR-assessed right ventricular-pulmonary artery coupling index independently associates with exercise capacity and clinical risk in pulmonary arterial hypertension

Abstract Background We defined a novel noninvasive right ventricle (RV)–pulmonary artery (PA) coupling index as the ratio of cardiovascular magnetic resonance (CMR)-assessed RV direct flow (RVDF) and PA pulse wave velocity (PWV), and investigated its associations with exercise capacity and clinical risk in pulmonary arterial hypertension (PAH). Method 43 PAH patients (mean age 46±12 years, M:F 7:36) and 60 healthy volunteers (mean age 46±13 years, M:F 11:48) underwent CMR and cardiopulmonary exercise test (CPET) within one week. From cine CMR, RV ejection fraction (EF) and RV end-diastolic volume (RVEDV) were calculated using volumetric analysis; and tricuspid annular plane systolic excursion (TAPSE), feature tracking. PAPWV was the ratio of early systolic DPA flow and DPA area measured from instantaneous phase and magnitude through plane 2D flow CMR images across the pulmonary trunk, respectively. RVDF was the 4D flow CMR-assessed blood volume entering and exiting the RV in one cardiac cycle, indexed to RVEDV. RV-PA coupling was RVDF/PAPWV. Based on CPET-assessed peak oxygen consumption (PVO2), all 103 participants were stratified into two groups: PVO2>15 ml/kg/min; and PVO2≤15 ml/kg/min. Based on the REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) 2.0 score, the 43 PAH patients were stratified into low risk (score ≤6) and intermediate to high risk (score >6) groups. Results RVDF/PAPWV was significantly lower in PAH vs. controls (7.9 vs. 20.4 %/(m/s), P<0.001); and in PAH patients with intermediate to high risk vs. low risk (4.6 vs. 9.4 %/(m/s), P=0.001). On multivariable analyses, RVDF/PAPWV was an independent predictor of PVO2≤15 ml/kg/min (=0.302, P=0.001) among all participants, and of REVEAL 2.0 score >6 (=0.621, P=0.009) among PAH patients. Compared to RVEF and TAPSE, RVDF/PAPWV had numerically higher discrimination (p values non-significant based on Delong test) for PVO2≤15 ml/kg/min (AUC=0.914 vs. 0.872, 0.843); and among PAH patients, REVEAL 2.0 score >6 (AUC=0.851 vs. 0.723 and 0.728) (Figure). Conclusion CMR-derived noninvasive RVDF/PAPWV independently associates with exercise capacity and PAH clinical risk, supporting its utility as an imaging marker of disease progression and therapeutic response.

Skeletal and respiratory muscle weakness contributes to decreased exercise capacity in hypertrophic cardiomyopathy

Abstract Background and Aims Although decreased exercise capacity (due to dyspnea or angina-like symptoms) constitutes the fundamental characteristics of hypertrophic cardiomyopathy (HCM), the pathophysiology of these symptoms remains only partly understood. We investigated clinical and functional determinants of decreased exercise capacity in a broad range of HCM patients irrespective of primary disease aetiology (either genetic disorder or e.g. infiltrative phenocopies in the course of cardiac amyloidosis), overt heart failure (HF) and the presence of haemodynamically significant left ventricular outflow tract obstruction (LVOTO). Further, we deterimined the contribution of skeletal and respiratory muscle weakness to decresed exercise capacity. Methods We analyzed clinical data and functional assessments (skeletal and respiratory muscle strength, physical fitness) in relation to symptomatology and sub-maximal exercise capacity in 82 clinically stable patients with HCM (females: 32 %; age: 62±16 years; left ventricular ejection fraction [LVEF] 59±7%; intraventricular septum wall thickness [IVS] 19±4 mm; median plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 818 pg/mL [lower and upper quartile: 208-1917]; New York Heart Association [NYHA] class 0/I/II/III: 38/18/33/11 % [0 indicates no HF]; significant LVOTO: 29%). Results HCM patients with more severe symptomatology (NYHA class II-III vs 0-I) were older, had more frequently significant LVOTO and greater comorbidity burden, and had higher NT-proBNP and worse estimated renal function (all p≤0.03). Gender distribution, percentage of beta-blocker therapy and implanted device, body mass index, major echocardiography parameters (including LVEF, left ventricular end-diastolic diameter and IVS), high-sensitive (hs) cardiac troponin type I and hs-C-reactive protein were comparable in these 2 groups of subjects (all p>0.05). In multivariable linear regression models more advanced age, higher circulating natriuretic peptides (NT-proBNP) and previous coronary revascularization were independent predictors of more advanced NYHA class (standardized β-coefficient=0.30, p<0.01; β=0.27, p<0.01; and β=0.22, p<0.05; respectively). Similarly, more advanced age, female sex and higher NT-proBNP were independent correlates of shorter distance in 6-minute walking test (6MWT) (β=-0.46, p<0.001; β=-0.26, p<0.001; and β=-0.36, p<0.001; respectively). All analyzed muscle parameters (including respiratory muscle strength parameters) and objective measures of physical fitness (Functional Fitness Test for older adults) remained independently associated with 6MWT distance (all p<0.001) when adjusted for aforementioned clinical and laboratory correlates of 6MWT. Conclusions Muscle weakness and low physical fitness are related to decreased exercise capacity in HCM and may be potential therapeutic targets to alleviate disease symptoms also in non-obstructive HCM phenotype.

Efficacy of specific drug class therapy in pulmonary arterial hypertension associated with HIV, portal hypertension or both: a single Center experience

Abstract Background Pulmonary arterial hypertension (PAH) is a rare complication of both HIV infection (HIV-PAH) and portal hypertension (Po-PAH); it can occur in patients with both diseases (HIV/Po-PAH). The use of the PAH-specific drug classes (prostanoids, endothelin-1 receptor antagonists [ERA] and phosphodiesterase-5 inhibitors [PDE5-i]) is largely justified by retrospective and observational case reports since, to date, there are no randomized clinical trials except for the PORTICO trial which demonstrated the efficacy of macitentan in Po-PAH. Purpose the aim of the study was to evaluate the efficacy of PAH-specific drugs, both monotherapy and dual oral upfront therapy (ERA + PDE5i started within 1 month apart), in patients with Po-PAH, HIV/Po-PAH and HIV-PAH. Methods Between 1998 and 2023 we enrolled patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to our Center and undergoing monotherapy with prostanoid, ERA and PDE5-I or dual upfront oral therapy. The efficacy of the drugs was assessed by comparing clinical parameters (NYHA functional class), exercise capacity (six-minute walking test) and hemodynamic parameters at baseline and after a treatment period of 3-6 months. The data are expressed as mean and standard deviation and were compared with Student's t-test for paired data. Results 128 patients were enrolled (83 Po-PAH, 23 HIV/Po-PAH and 22 HIV-PAH). 20 were treated with ERA monotherapy, 90 with PDE5-I, 13 with prostanoids and 5 treated with dual oral upfront therapy. Conclusions Prostanoids, ERAs and PDE5-Is, both in monotherapy and as dual upfront oral therapy, are associated with a significant improvement in functional class, exercise capacity and hemodynamic parameters. The effect of such drugs is similar to patients suffering from other forms of PAH.

Endothelial dysfunction in acute coronary syndrome: a complex association with cardiovascular risk factors, sleep quality and cardiorespiratory capacity

Abstract Introduction It is widely acknowledged that normal endothelial function plays a pivotal role in conferring cardioprotective effects against ischemia-reperfusion injury following acute myocardial infarction (AMI) treated by a primary percutaneous coronary intervention (PCI), thereby limiting infarct size (1). However, endothelial dysfunction (ED) has been extensively documented in patients with cardiovascular (CV) risk factors (2). This study proposes a novel perspective, positing that ED could be intricately linked not only with traditional CV risk factors, but also it can be associated with poor sleep quality. Consequently, this interplay might significantly contribute to the attenuation of exercise capacity. Objective The aim of this study was to assess endothelial function following AMI treated with a PCI and investigate the link between endothelial function, CV risk factors, sleep quality and exercise capacity. Furthermore, the study aimed to determine if endothelial function could serve as a predictive factor for future major adverse acute cardiac events (MAACE) following AMI. Materials and methods Sixty-three patients with AMI (56.21 ± 7.6 years) volunteered to participate in this study, . Endothelial function was assessed using the Endothelium Quality Index (EQI) . Sleep quality was evaluated using both actigraphy and the PSQI (Pittsburgh Sleep Quality Index) questionnaire. Exercise capacity was quantified through the 6-minute walking test (6mwt). Results ED was evident, as indicated by an EQI of 1.4 ± 0.7. Furthermore, ED was notably influenced by CV risk factors such as low physical activity level, age, and smoking. A significant correlation was found between EQI and both sleep efficiency (r = 0.340; p = 0.006) and PSQI score (r = -0.533; p < 0.001). Additionally, a strong association was observed between endothelial function and the results of the 6mwt (r = 0.291; p = 0.021). Furthermore, during a follow up period ( near 4 months) following PCI, MAACE were observed in patients with severe ED only. Conclusion In summary, findings of this study may emphasize the importance of enhancing sleep quality and advocating for an active lifestyle as modifiable elements to enhance endothelial function, which can be regarded as a prognostic tool subsequent to AMI, ultimately contributing to improved clinical outcomes. Moreover, this study concluded that AMI patients with severe endothelial dysfunction were more likely to develop MAACE.Endothelial Dysfunction after AMIED following AMI : Causes and effect

Associations of different definitions of iron deficiency with cardiac structure and function, congestion, exercise capacity and prognosis in heart failure

Abstract Background It is uncertain how best to diagnose iron deficiency (ID) in patients with heart failure (HF) as different ID definitions have been proposed with discordant results. Objectives To assess the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in outpatients with HF. Methods ID was defined according to guidelines (G-ID: ferritin <100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation [TSAT] <20%) or as TSAT <20%. Alternative definitions (iron <13 ¼mol/L, ferritin <100 and <300 ng/mL) were explored. Relationship with rest and exercise ultrasound findings, cardiopulmonary exercise testing and a composite endpoint of cardiovascular hospitalisations or all-cause mortality were assessed. Results Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT <20%, while 728 (48%) had G-ID. Compared to those without ID, patients with TSAT <20% or G-ID showed impaired cardiac structure and function at rest and peak exercise and lower peak oxygen consumption; they were also more likely to display a discontinuous renal venous flow pattern and more lung B-lines. Only TSAT <20% was associated with significant inferior vena cava dilatation. Lower TSAT, iron and haemoglobin were associated with more severe effort intolerance and ultrasound signs of congestion, while ferritin and LVEF were not (Picture 1). During a median follow-up of 16 months, 62 (4%) patients died, and 244 (16%) were hospitalised for cardiovascular reasons. No patients were hospitalised immediately after the enrolment visit because of clinical findings. At Kaplan-Meier analyses, TSAT <20% was associated with a greater risk of adverse events, as were iron ≤13 ¼mol/L, ferritin ≥300 ng/mL and <100 ng/mL (p <0.01 vs ferritin 100-299 ng/mL) and G-ID (Picture 2). After adjusting for age, sex, diabetes, haemoglobin, estimated glomerular filtration rate (eGFR), NT-proBNP, rest LVEF and peak VO2 <16 mL/kg/min, TSAT <20% and iron ≤13 ¼mol/L were associated with worse outcomes (hazard ratio 2.41, 95% confidence interval 1.85-3.14 and 1.90, 1.46-2.47), while G-ID or ferritin <100 or <300 ng/mL were not (Picture 1). Conclusions In outpatients with HF, TSAT <20% is more consistently associated with echocardiographic signs of poorer functional capacity and multi-organ congestion than other ID definitions. TSAT <20% and iron ≤13 ¼mol/L, but not G-ID or ferritin-based ID, seem to predict a worse prognosis.Picture 1Picture 2

DPD quantification correlates with ECV and disease severity in patients with ATTR-CM

Abstract Background The pathophysiological hallmark of transthyretin amyloid cardiomyopathy (ATTR-CM) is the deposition of amyloid within the myocardium. However, the association between myocardial amyloid load and quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) uptake is barely investigated. Purpose We aimed to investigate the relationship between quantitative cardiac 99mTc-DPD uptake and myocardial amyloid load, assessed by extracellular volume (ECV) on cardiac magnetic resonance (CMR) imaging, along with cardiac function in patients with ATTR-CM. Methods Forty ATTR-CM patients underwent 99mTc-DPD single-photon emission computed tomography/computed tomography (SPECT/CT) and CMR imaging. Results We observed significant correlations (r, Spearman's correlation coefficient) between the standardized uptake value (SUV) retention index and myocardial amyloid load (ECV: r=0.677, p<0.001; native T1 time: r=0.430, p=0.006), longitudinal cardiac function [right ventricular longitudinal strain (RV-LS): r=0.472, p=0.002], cardiac biomarkers (NT-proBNP: r=0.543, p<0.001; troponin T: r=0.401, p=0.011), exercise capacity [6-min walking distance (6MWD): r=-0.410, p=0.010] and disease stage [National Amyloidosis Centre (NAC) ATTR stage: r=0.479, p=0.002]. ATTR-CM patients were divided into two cohorts based on the median of the SUV retention index (low cardiac uptake: <5.19 mg/dL, n=20; high cardiac uptake: ≥5.19 mg/dL, n=20). We observed significant between-cohort differences in terms of ECV (p<0.001), native T1 time (p=0.011), RV-LS (p=0.007), NT-proBNP (p<0.001), troponin T (p=0.030), 6MWD (p=0.002) and NAC ATTR stage (I: p<0.001, II: p=0.030, III: p=0.021). Conclusions In ATTR-CM, quantitative cardiac 99mTc-DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage. DPD quantification may provide a valuable tool for quantifying and monitoring cardiac disease burden in affected individuals.Table.Baseline Characteristics.Figure.Correlations.

Moderate intensity exercise training ameliorates the heart failure with preserved ejection fraction phenotype in a preclinical model by improving cardiometabolic fitness

Abstract Introduction and Aim Exercise intolerance is a hallmark feature of patients with heart failure with preserved ejection fraction (HFpEF).While clinical evidence suggests potential benefits of exercise training in HFpEF, its mechanisms remain largely unknown.In this study, we used a translationally relevant murine model of cardiometabolic HFpEF(1) to assess whether moderate intensity continuous training(MICT) can ameliorate the HFpEF phenotype in mice and promote cardiometabolic health. Methods Twenty-five adult, male C57BL/6N were fed with the combination of high fat diet(HFD;D12492,Research diet)and L-NAME(0.5 g/L,in drinking water) for 15 weeks to elicit HFpEF as previously described(1).After the establishment of the HFpEF phenotype, mice were randomized in two groups:sedentary(SED,n= 10) and exercised(MICT,n=15)mice.MICT was carried out according to the protocol:running on 10-degree positive inclination treadmill for 8 consecutive weeks,5 times/week,60 minutes/day,at a speed gradually increasing from 0.1 to 0.2 m/sec on a weekly basis.Morphometry, echocardiography(TTE),isoproterenol-induced stress echocardiography(SE),time domain nuclear magnetic resonance, and treadmill exhaustion tests were performed at the beginning and end of MICT.Additionally, at the end of MICT blood and tissues were collected for proteomics analysis(Fig1).Non-trained male C57BL/6N mice(37w) were used as controls for the HFpEF mice. Results Before randomization, all HFpEF mice were similar in terms of phenotypic characteristics. Compared to SED mice, MICT induced a significantly decrease in body weight driven by a reduction of total fat mass with an increased in lean mass(Fig2A+B).Interestingly, MICT had no impact on skeletal muscle mass for all different muscle groups evaluated (extensor digitorum longus, soleus and tibialis anterior).Importantly, MICT led to a significant improvement in exercise capacity in HFpEF mice, as shown by increased running distance and time, surpassing even the running distance seen in non-HFpEF mice (SED:62.8±18.7,MICT:305.7±13.9,non-HFpEF mice: 129.72±15.2meters,p<0.001).Preclinical surrogate of HFpEF such as pulmonary congestion, evaluated by index lung weights, improved after aerobic training.Following MICT there was a marked improvement in diastolic dysfunction(measured by E/E’ratio) both at rest(SED:36.5±3.3,MICT:23.3±5.09,p<0.001) and after isoproterenol challenge(SED:42.6±15.1,MICT:26.09±3.75,p<0.001)(Fig2C).Moreover, the wet cardiac mass was lower in the MICT group(Fig2A), suggesting potential amelioration in cardiac hypertrophy following aerobic training. Conclusion Eight weeks of supervised MICT on treadmill improves functional status, exercise capacity, and diastolic function in a cardiometabolic HFpEF murine model.The most significant effects were seen on weight loss and fat mass reduction.Our findings suggest a beneficial impact of aerobic exercise in mitigating HFpEF by improving metabolic fitness in the preclinical HFpEF model.Fig1-Study DesignFig2-Characteristics SED vs MICT groups

The role of digital health intervention in improving physical activity in cardiac rehabilitation center: a randomised controlled trial

Abstract Background Physical activity plays a crucial role in cardiac rehabilitation for secondary prevention. Despite its importance, participation rates in cardiac rehabilitation programs remain low. Telemedicine, particularly telerehabilitation, presents a viable solution by offering remote access to cardiac rehabilitation services. This innovative approach has the potential to significantly enhance patient outcomes. Purpose This study aimed to assess the effectiveness of digital health intervention in improving physical activity in cardiac rehabilitation center. Methods A prospective randomised controlled trial was conducted, enrolling 80 eligible cardiac rehabilitation patients. Participants were 1:1 randomised into two groups: a 12-week center-based cardiac rehabilitation program (control group), and a 12-week center-based cardiac rehabilitation program combined with a digital health intervention (intervention group). This digital health intervention consists of smartphone, web, and tablet applications to monitor physical activity outside of rehabilitation sessions and motivate patients to engage in more physical activities. Results Of the initial 80 patients, 70 completed the study, and the results are presented in Table 1. In the intervention group, there was a statistically significant improvement in peak rate of oxygen consumption (VO2 peak) (p < 0.01) and peak power output (W peak) (p < 0.01), as measured by cardiopulmonary exercise testing between the end and the beginning of the study at the significance level of 0.05. Similar improvements were also observed in the control group (p = 0.0002 for VO2 peak and p < 0.01 for W peak). After 12 weeks of intervention, significant between-group differences were found: We observe a greater improvement in VO2 peak, on average 1.39 (95% CI: 0.23-2.54) ml/kg, and in W peak, on average, 12.29 (95% CI: 4.12-20.45), higher in the intervention group compared to the control group. Regarding physical activity, the intervention group showed a significant improvement in step count (P = 0.002), measured by an accelerometer, whereas no significant improvement was observed in the control group (P = 0.9714). There is a statistically significant difference in the change of step count between the intervention and control group at the significance level of 0.05. We observe a greater improvement, on average 14 788 steps (95% CI: 4 246 – 25 331), in the intervention group compared to the control group. Conclusion This study shows that a combination of a digital health intervention based telerehabilitation with a center-based cardiac rehabilitation is more effective in increasing patient’s exercise capacity and physical activity compared with a center-based cardiac rehabilitation.Table 1:results

Impact of inpatient cardiac rehabilitation on hospital-associated disability for older patients undergoing transcatheter aortic valve implantation: insight from the JROAD/JROAD-DPC database

Abstract Background Hospital-associated disability (HAD), a decline in the ability to perform activities of daily living (ADL) during hospitalization, is a modifiable target in the integrated care for older adults. Inpatient rehabilitation during the perioperative period is a part of a comprehensive cardiac rehabilitation (CR) program and plays a pivotal role in functional recovery and smooth reintegration into the home, community, and workplace after surgery. Prior research, including meta-analyses, have shown that outpatient CR participation after discharge of patients who underwent transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement is associated with a significant improvement in exercise capacity and indexes of ADL. However, the impact of inpatient CR on the occurrence of HAD remains unexplored. Purpose Using a large real-world nationwide database in Japan, the aim of this study was to determine the prevalence of HAD and the impact of inpatient CR participation on the development of HAD in older patients undergoing TAVI. Methods Older patients undergoing TAVI were extracted from the Japanese nationwide database (JROAD-DPC) from April 2014 to March 2021 and were divided into patients receiving inpatient CR (CR group) and non-CR group. HAD was defined as a decrease in the Barthel Index score ≥ 5 points at discharge relative to admission. Results Of 19,789 eligible patients, 17,066 (86%) underwent inpatient CR (average age, 84.3 ± 4.9 years; Woman, 65%). The overall prevalence of HAD was 9.6%, with a lower incidence in the CR group than those in the non-CR group (8.8% vs. 14.2%, p < 0.01). Participation in inpatient CR was associated with a significantly lower odds ratio (OR) of HAD in multivariate logistic regression analysis (adjusted OR, 0.62; 95% confidence interval [CI], 0.54–0.70; p < 0.01) and in inverse probability of treatment weighting-adjusted logistic regression analyses (adjusted OR, 0.82; 95% CI, 0.77–0.88; p < 0.01; Table). Analyses in subgroups of interest showed heterogeneity of the effects of inpatient CR with possible loss in patients with a body mass index of less than 18.5 kg/m² or BI score of less than 60 points at admission (Figure). Conclusions A substantial number of older patients undergoing TAVI developed HAD during perioperative period. Participation in inpatient CR was associated with a lower likelihood of HAD in TAVI recipients, but the benefit of inpatient CR for development of HAD was possibly lost in patients with a low BMI and low a BI score at admission, indicating the necessity of HAD-targeted multidisciplinary CR for lean patients with ADL disability before TAVI.Figure

The impact of exogenous ketone body suppletion on energy and pH balance in skeletal muscle during exercise in chronic heart failure patients: a prospective randomized double-blind cross-over study

Abstract Background Heart Failure (HF) is characterized by impediments in exercise capacity. Disruptions in the energy metabolism of skeletal muscle contribute to this condition. Pre-clinical and clinical evidence showed that reductions in carbohydrate and FA metabolism in HF may be partially overcome by a compensatory increase in ketone body oxidation and suggest that suppletion of ketone bodies (KB) may improve energy metabolism in HF. Purpose We tested the effect of exogenous KB suppletion on energy and pH balance during cycling exercise using 31P Magnetic Resonance (MR) Spectroscopy of the exercising quadriceps muscle in patients with HF. Methods In a randomized, double-blind, placebo-controlled cross-over study, 14 stable HF patients with reduced ejection fraction and diminished exercise capacity underwent maximal exercise testing in a MR scanner fitted with a cycling ergometer after KB or placebo treatment. Phosphocreatine (PCr) and inorganic phosphate (Pi) resonance amplitudes and frequencies were measured continuously in the quadriceps muscle during rest, exercise and recovery using in-vivo 31P MR spectroscopy (Figure 1). Results Patients had a median age of 66 [53 – 75] years, were 14% female, had a median LVEF of 37% [27 – 40] and circulating NT-pro BNP levels of 411 [182 – 946] pg/mL. Peak oxygen uptake (VO2) was 18.2 [15.2 – 20.3] ml/kg/min, which is 68% [62 – 78%] of predicted. After treatment, exercise performance in terms of cycling duration and workload were comparable between treatment arms (Figure 2). Quadriceps acidification during exercise was larger after KB suppletion compared to placebo (ΔpH: -0.2 [-0.3 - -0.1] vs -0.1 [-0.3 - -0.1] respectively; p=0.041) while quadriceps energy depletion during exercise was not altered by treatment (ΔPi/PCr 0.77 [0.55 – 2.51] vs 0.66 [0.46 – 0.81] respectively; p=0.087). Post-exercise mitochondrial oxidative function was similar between treatment arms (KB: PCr resynthesis rate 48 sec [25 – 59] versus placebo: 42 sec [36 – 63]; p=0.767). Conclusions Ketone body suppletion increased acidification and did not improve energy balance in skeletal muscle during exercise or mitochondrial function during recovery in patients with chronic HF. These results question the value of ketone bodies as treatment to boost muscular energy metabolism during exercise in HF.31P MRS Spectrum during exercise in HFExercise and energy parameters

Effects of Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors on Health-Related Quality of Life and Exercise Capacity in Heart Failure Patients With a Preserved Ejection Fraction: A Scoping Review

Effects of Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors on Health-Related Quality of Life and Exercise Capacity in Heart Failure Patients With a Preserved Ejection Fraction: A Scoping Review