6-minute Walk Distance Research Articles

The efficacy of the treat-repair-treat strategy for severe pulmonary arterial hypertension associated with congenital heart disease: a meta-analysis

BackgroundThis meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD).MethodsPubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity.ResultsA total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, − 2.50 p = < 0.001; PVR: SMD -1.27 95% CI -1.53, − 1.02 p = < 0.001; 6MWD: SMD 1.88 95% CI 1.49, 2.27 p = < 0.001; SpO2: SMD 3.72 95% CI 3.13, 4.32 p = < 0.001). Subgroup analysis showed that younger patients had better efficacy, and the change in SpO2 was an indication for patient selection. The combined mortality rate was 5% at follow-up.ConclusionsIn this meta-analysis, we demonstrated that the TRT strategy may have positive effects on haemodynamics and cardiac function in patients with severe PAH-CHD at short-term follow-up. Our analysis suggests that changes in age and SpO2 may be related to patient prognosis.Trial registrationThe protocol was registered on the PROSPERO website with the registration number CRD42022366552. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced.

Effectiveness of Qiliqiangxin Combined with Trimetazidine Hydrochloride Tablets in Treating Coronary Heart Disease with Concurrent Heart Failure: A Comparative Study

This study investigated the effect of combining qiliqiangxin with trimetazidine hydrochloride tablets in treating patients with coronary heart disease complicated by heart failure. A total of 158 patients were randomly divided into two groups: a control group with 79 patients who were given trimetazidine hydrochloride tablets and a study group, also comprising 79 patients who received qiliqiangxin capsules in addition to the tablets. Results showed that the study group had a higher total effective rate compared to the control group. After treatment, the study group exhibited a more significant decline in left ventricular end-systolic dimension and end-diastolic diameter, as well as a higher increase in left ventricular ejection fraction. Serum levels of N-terminal pro-B-type natriuretic peptide, cardiac troponin I, Angiotensin, interleukin-6, high-sensitivity C-reactive protein, and tumor necrosis factor-α were lower in the study group compared to the control group. Furthermore, the study group demonstrated a longer 6-minute walking distance and a lower incidence of adverse reactions. In conclusion, combining qiliqiangxin and trimetazidine hydrochloride tablets is highly effective and safe for treating coronary heart disease complicated with heart failure, improving clinical symptoms and heart function.

Effects of beta-blocker withdrawal in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis.

The primary chronic symptom of patients with heart failure with preserved ejection fraction (HFpEF) is severe exercise intolerance. The inability to adequately increase heart rate during exercise (chronotropic incompetence) is commonly present in HFpEF patients and contributes importantly to exercise intolerance in these patients. Since HFpEF patients often have cardiac comorbidities such as hypertension, coronary artery disease, and atrial fibrillation, beta-blockers are frequently prescribed for the treatment of these comorbidities. However, there is a concern that beta-blockers may worsen chronotropic incompetence by slowing heart rate in HFpEF patients and may further exacerbate their symptoms. There are several studies on the effects of beta-blocker withdrawal in HFpEF patients. We aim to perform the systematic review and meta-analysis of studies on the effects of beta-blocker withdrawal in HFpEF patients. This meta-analysis will include randomized controlled trials and prospective cohort studies on the effect of beta-blocker withdrawal in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome will be peak oxygen uptake (peak VO2). The secondary outcome will be 6-minute walk distance. Other outcomes of interest will be health-related quality of life, plasma BNP levels, and cardiac structure and function. This systematic review and meta-analysis will evaluate whether beta-blocker withdrawal is beneficial for HFpEF patients, providing evidence regarding beta-blocker withdrawal in these patients. Systematic review registration: INPLASY202370066.

Comparison of the 12-month impact of COVID-19 and SARS on physiological capacity and health-related quality of life

BackgroundLittle is known about the differences in medium to long-term recovery on spirometry, 6-minute walking distance (6MWD) and health-related quality of life (HRQoL) between COVID-19 and SARS.MethodsWe performed a 12-month prospective study on COVID-19 survivors. The changes in dynamic lung volumes at spirometry (%predicted FEV1, %predicted FVC), 6MWD and HRQoL at 1–3, 6 to 12 months were compared against a historical cohort of SARS survivors using the same study protocol. The residual radiological changes in HRCT in COVID-19 survivors were correlated with their functional capacity.Results108 COVID-19 survivors of various disease severity (asymptomatic 2.9%, mild 33.3%, moderate 47.2%, severe 8.3%, critical 8.3%) were recruited. When compared with 97 SARS survivors, 108 COVID-19 survivors were older (48.1 ± 16.4 vs. 36.1 ± 9.5 years, p < 0.001) and required less additional support during hospitalization; with lower dynamic lung volumes, shorter 6MWD and better physical component score. Both groups of survivors had comparable changes in these parameters at subsequent follow-ups. Both COVID-19 and SARS survivors had similar mental component score (MCS) at 6 and 12 months. COVID-19 survivors initially experienced less (between-group difference, -3.1, 95% confidence interval [CI] -5.5 to -0.7, p = 0.012) and then more improvement (between-group difference 2.9, 95%, CI 0.8 to 5.1, p = 0.007) than SARS survivors in the MCS at 1–3 to 6 months and 6 to 12 months respectively. Forty (44.0%) out of 91 COVID-19 survivors had residual abnormalities on HRCT at 12 months, with a negative correlation between the severity scores of parenchymal changes and 6MWD (r=-0.239, p < 0.05).ConclusionsCOVID-19 survivors demonstrated a similar recovery speed in dynamic lung volumes and exercise capacity, but different paces of psychological recovery as SARS survivors in the convalescent phase. The severity of parenchymal changes in HRCT is negatively correlated with the 6MWD of COVID-19 survivors.Trial registrationThis prospective study was registered at ClinicalTrials.gov on 2 November 2020 (Identifier: NCT04611243).

Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial.

Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04788511.

Effect of Early Rehabilitation Nursing on Patients with Myocardial Infarction: A Meta-analysis

Objectives: In this study, we systematically evaluated the effectiveness and safety of rehabilitation nursing in the treatment of patients with acute myocardial infarction (AMI), and its effect on improving the cardiac function and exercise tolerance of AMI patients. Methods: All relevant published articles were searched through a computer-based retrieval of PubMed, Embase, Biosis Previews, Cochrane Library, Web of Science, China National Knowledge Internet, China Biomedical Literature Service System, Weipu Information Chinese Periodical Service Platform and Wanfang databases since their establishment. Randomized controlled trials on rehabilitation nursing and exercise intervention for patients with AMI were included, and the Cochrane risk-of-bias tool was used for quality evaluation. After quality evaluation and data extraction, we conducted statistical analysis using RevMan 5.3. Results: A total of 15 English articles were included. The meta-analysis showed that the left ventricular ejection fraction (mean difference [MD] = 5.76, 95% confidence interval [CI]: 4.55-6.97, p &lt; .00001), left ventricular end-diastolic diameter (MD = 6.81, 95% CI: 8.17-5.45, p &lt; .00001) and 6-minute walking distance (MD = 2.41, 95% CI: 3.42-1.40, p &lt; .00001) showed statistically significant differences between the rehabilitation nursing group and the control group (p &lt; .0001). However, no statistically significant difference was found in systolic blood pressure (MD = 2.29, 95% CI: 2.53-7.12, p = 0.35). Conclusion: Early rehabilitation nursing can effectively improve cardiac function and exercise tolerance in patients with AMI. It has a degree of guiding significance for improving the quality of life of patients with MI and reducing complications.

Impact of Left Heart Disease Risk Factors on Outcomes in Pulmonary Arterial Hypertension Therapy

BackgroundCurrent guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with ‘cardiopulmonary comorbidities’, despite limited available evidence to guide management. Research QuestionDo left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of PAH patients? Study Design and MethodsThe AMBITION trial criteria was used to define the phenotype of PAH patients with risk factors for LHD. Treatment strategy, functional outcome, long term survival and risk discrimination were compared with a reference PAH cohort using the PHSANZ registry. Results487 incident PAH patients diagnosed between 2011-2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors with 384 (78.9%) remaining as reference group. PAH with LHD risk factors were older (66±13 vs. 58±19years, p<0.001), had lower pulmonary vascular resistance (393±266 vs 708±391dynes/sec/cm-5, p=0.031) and worse 6-minute walk distance (286±130 vs. 327±136m, p=0.005) at diagnosis. PAH with LHD risk factors were less likely to receive less initial combination therapy (27% vs. 44%, p=0.02). Changes in 6-minute walk distance at 12-months were similar in both groups, 43±77 in PAH with LHD risk factors and 50±90m in reference group (p=0.5), including when stratified by initial treatment strategy (monotherapy: 40±81 vs. 38±95m p=0.87 and combination therapy: 53±78 vs. 64±106m, p=0.511; PAH with LHD risk factors vs. reference PAH). Functional class improvements were also similar in both groups. REVEAL 2.0 risk score effectively discriminated risk in both populations (C-statistic=0.756 for PAH with LHD risk factors and C-statistic=0.750 for reference PAH). There was no difference in survival between the two groups (log-rank test p=0.29). InterpretationIn a real-word cohort, PAH patients with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected PAH patients with LHD risk factors who were treated with initial combination therapy derived similar functional response compared to reference group. Further studies are needed to phenotype PAH patients with cardiopulmonary comorbidities who may benefit from initial combination therapy.

Effect of High-Intensity Interval Training and Moderate-Intensity Continuous Training in People With Poststroke Gait Dysfunction: ARandomized Clinical Trial.

The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness () and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) have different effects on and 6-minute walk distance (6MWD). In this 24-week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT). MICT trained to target intensity at the ventilatory anaerobic threshold. HIIT trained at the maximal tolerable treadmill speed/grade using a novel program of 2 work-to-recovery protocols: 30:60 and 120:180 seconds. V̇O2 and heart rate was measured during performance of the exercise that was prescribed at 8 and 24 weeks for treatment fidelity. Main outcomes were change in and 6MWD. Assessors were blinded to the treatment group for but not 6MWD. Secondary outcomes were change in ventilatory anaerobic threshold, cognition, gait-economy, 10-meter gait-velocity, balance, stair-climb performance, strength, and quality-of-life. Among 47 participants randomized to either MICT (n=23) or HIIT (n=24) (mean age, 62±11 years; 81% men), 96% completed training. In intention-to-treat analysis, change in for MICT versus HIIT was 2.4±2.7 versus 5.7±3.1 mL·kg-1·min-1 (mean difference, 3.2 [95% CI, 1.5-4.8]; P<0.001), and change in 6MWD was 70.9±44.3 versus 83.4±53.6 m (mean difference, 12.5 [95% CI, -17 to 42]; P=0.401). HIIT had greater improvement in ventilatory anaerobic threshold (mean difference, 2.07 mL·kg-1·min-1 [95% CI, 0.59-3.6]; P=0.008). No other between-group differences were observed. During V̇O2 monitoring at 8 and 24 weeks, MICT reached 84±14% to 87±18% of while HIIT reached 101±22% to 112±14% of (during peak bouts). HIIT resulted in more than a 2-fold greater and clinically important change in than MICT. Training to target (ventilatory anaerobic threshold) during MICT resulted in ~3 times the minimal clinically important difference in 6MWD, which was similar to HIIT. These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional MICT in appropriately screened individuals. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03006731.

Continuous measurement of percutaneous oxygen saturation during 6-minute walk test is useful for stratification of the prognostic risk in patients with heart failure

Abstract Background The 6-minute walk test (6MWT) is an established test to assess the functional exercise performance and the 6-minute walk distance is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). Also, the hypoxia during 6MWT is reported to be associated with severity of pulmonary diseases. However, no study has reported the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT was not investigated in HF patients. Purpose To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF. Methods In this prospective observational study, 50 patients admitted to our hospital with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest (3 minutes just before the test) and during 6MWT by employing the wearable pulse-oximeter which are designed to record and store the SpO2 value every seconds. Alternations in SpO2 (Δ SpO2) were analyzed by subtracting the average during 6MWT from that at rest. Patients were followed 1 year for composite outcome of heart failure-hospitalization and death). Results The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of the patients with EF≧50, 50&amp;gt;EF&amp;gt;40, 40≧EF were 22, 6, and 22, respectively. Mean NT-proBNP was 4374.5pg/ml. The mean walk distance was 250 ± 112m and the mean Δ SpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and Δ SpO2; long- (&amp;gt;220m) vs. short-distance group (≦220m) and low- (&amp;lt;3.5%) vs. high-ΔSpO2 group (≧3.5%). There were no significant differences in cardiac parameters and respiratory function between long- and short-distance group as well as between low- and high-ΔSpO2 group. Kaplan-Meier analysis revealed that cardiac event rate was higher in the short-distance group than in the long-distance group (HR = 2.89, CI = 1.24-6.71, p = 0.014), and higher in the high-Δ SpO2 group than in the low-ΔSpO2 group (HR = 3.49, CI = 1.55-7.83, p = 0.002) (Figure 1A and 1B). When these classifications were combined, the patients with short-distance and low-ΔSpO2 showed remarkably high event rate of 91% (Figure 2). Conclusions This study showed that, compared to walk distance, ΔSpO2 was more predictive of prognosis of heart failure patients, and that the combination of ΔSpO2 and walk distance may identify the highest risk group. The elucidation of the usefulness of continuous SpO2monitoring during 6MWT as the marker for severity of heart failure and treatment effect warrants further investigation.Figure1Figure 2

Adults with congenital heart disease and pulmonary arterial hypertension: Quantitative assessment of haemodynamic parameters under disease targeting therapy - A retrospective multicentre analysis

Abstract Background Pulmonary arterial hypertension (PAH) occurs in approximately 10% of adults with congenital heart disease (ACHD), usually develops secondary to intra- or extra-cardiac shunts resulting in pressure and/or volume overload in the pulmonary circulation, and is associated with increased morbidity and mortality. Treatment strategies for PAH-ACHD include disease targeting therapies (DTT), such as phosphodiesterase-5 inhibitors (PDE5i) and endothelin receptor antagonists (ERA). Data regarding the impact of DTT on cardiopulmonary haemodynamics in PAH-ACHD are scarce. Purpose Aim of this study was to quantify effects of DTT on cardiopulmonary haemodynamics (assessed by right heart catheterisation [RHC]) and on key non-invasive functional parameters contributing to ESC/ERS risk status in PAH-ACHD patients, as applied in real-world clinical practice. Methods We retrospectively analysed the effect of DTT in PAH-ACHD patients who had undergone RHC in adulthood at baseline (treatment-naïve) between 2000 and 2022, with at least one follow-up RHC during DTT, in six expert centres in Europe. Clinical characteristics (WHO functional class [WHO-FC], 6-minute walking distance [6MWD], N-terminal pro-brain natriuretic peptide [NTproBNP] and measures of RHC (systemic/ pulmonary cardiac output, systolic/diastolic/mean pulmonary arterial pressure [sPAP, dPAP, mPAP], and pulmonary arterial wedge pressure [PAWP]) were collected. Pulmonary vascular resistance/arterial compliance (PVR+PAC) and stroke volume index (SVI) were calculated. Results 44 patients (70% female, mean age 45±15 years) were included. Underlying CHD was a pre- or post-tricuspid shunt in 35% and 63%, respectively. 14% had complex CHD, 7% had innate left heart disease, and 21% presented with Eisenmenger´s syndrome. At baseline 71% were in WHO-FC III/IV, 6MWD was 371±105 m, and NTproBNP was 673 [446–1021] ng/l. On RHC, mPAP was 58±15 mmHg, PVR 11 [7–17] wood units (WU), SVI 32 [27–44] ml/min/m2, CI 2.7±1.0 l/min/m2, and PAC 1.0 [0.7–1.4] ml/mmHg. DTT was started in all patients after baseline RHC. 81% received monotherapy (34% PDE5i, 66% ERA) and 19% received upfront combination therapy (PDE5i+ERA). Follow-up RHC was performed 15 [5–33] months after baseline RHC. At follow-up, WHO-FC and NTproBNP (562 [428-762] ng/l) significantly improved (p&amp;lt;0.001 and p=0.021, respectively), as did hemodynamic measures: mPAP (53±15 mmHg, p&amp;lt;0.001), PVR (9 [5–10] WU, p&amp;lt;0.001), SVI (37 [30–49] ml/min/m2, p=0.010), PAC (1.3 [1.0–1.7] ml/mmHg, p&amp;lt;0.001), and CI (3.1±1.1 l/min/m2, p=0.001). In contrast, 6MWD showed subtle change (379±111 m, p=0.164). After follow-up RHC, DTT was escalated in 78% of patients. Conclusions In PAH-ACHD patients, DTT was associated with a moderate but sustained haemodynamic and functional improvement after 15 months. Repeat RHC triggered treatment escalation in most patients. Therefore, ongoing vigilance for PAH-ACHD patients and subsequent treatment optimisation is warranted.

Efficacy of intravenous iron therapy in iron-deficient patients with heart failure: an updated systematic review and meta-analysis

Abstract Background/Introduction Iron deficiency is a common finding in chronic diseases such as heart failure (HF), as well as being a predictor of worse functional class and a higher risk of death in patients with a reduced/moderated reduced left ventricular ejection fraction (HFrEF/HFmrEF). Despite numerous trials evaluating iron supplementation in patients with HF and iron deficiency, the impact on mortality and hospitalisations is not well-established. Purpose The aim of our study was to assess the efficacy of IV iron supplementation on clinical and blood biochemical outcomes in iron-deficient patients with heart failure (HFmrEF and HFrEF). Methods We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) studying the effects of iron therapy in patients with HF. Statistical analysis was performed using RevMan 5.1.7. Heterogeneity was assessed with I² statistics; p-values inferior to 0.10 and I²&amp;gt;25% were classified with significant heterogeneity. Results Ten RCTs were included comprising a total of 3447 participants, of whom 1810 (52.5%) have received iron infusion. The 6-minute walk distance after 12 weeks of treatment was significantly higher in those who received iron supplementation (MD 54.23; 95% CI 25.41-83.05; p = 0.0002; I² = 64%; Fig. number 1A). Hospital admissions for heart failure were significantly lower in patients randomised to iron therapy when compared with the control group (OR 0.57; 95% CI 0.46-0.70; p &amp;lt;0.001; I² = 17%; Fig. number 1B). There was no statistically significant difference among groups regarding cardiovascular death (OR 0.87; 95% CI 0.71-1.07; p = 0.19; I² = 0%; Fig. number 2A ), all-cause hospitalisations (OR 1.00; 95% CI 0.37-2.73; p = 1.00; I² = 81%; Fig. number 2B), and hospital admissions for cardiovascular causes (OR 0.72; 95% CI 0.4-1.33; p = 0.3; I² = 77%). Ferritin levels have shown a significant increase (MD 212.34; 95% CI 127.05-297.62; I² = 98%). Conclusion(s) This meta-analysis suggests that intravenous iron supplementation in patients with heart failure and iron deficiency was associated with a lower risk of hospital admissions for heart failure and improved exercise capacity, albeit with inconclusive data about the reduction in cardiovascular mortality.Relevant clinical outcomesSecondary relevant clinical outcomes

Clinical impact of residual pulmonary hypertension based on revised criteria after balloon pulmonary angioplasty

Abstract Background Balloon pulmonary angioplasty (BPA) improves haemodynamics, exercise capacity, and prognosis in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the treatment goal of BPA is not well established. The European Society of Cardiology guidelines published in 2022 revised the diagnosis of pulmonary hypertension from resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg to mPAP &amp;gt;20 mmHg because mild elevation of pulmonary hypertension has decreased exercise capacity and worsened the prognosis. The clinical impact of normalization in resting pulmonary hypertension after balloon pulmonary angioplasty is not investigated. Purpose The purpose of this study is to clarify the clinical impact of mPAP normalization after BPA as a treatment goal in patients with CTEPH. Methods We retrospectively reviewed consecutive 236 CTEPH patients (68 [55,75] yrs., Male 52 (22%)) who completed BPA procedures from July 2009 to December 2020 and had haemodynamics evaluation after the procedures and had mPAP &amp;lt;30 mm Hg after BPA. We extracted two groups with mPAP &amp;lt;20 mmHg (Non-PH group) and 21≤ mPAP &amp;lt;30 mmHg (Residual-PH group) after BPA. Results The median follow-up period from the final BPA session was 38 [22,61] months. In both the Non-PH and Residual-PH groups, BPA significantly improved mPAP (37 [29,43] to 18 [16,19] mmHg, P&amp;lt;0.01 and 38 [34,45] to 23 [22,26], P&amp;lt;0.01, respectively) and cardiac index (CI) (2.15 [1.86,2.63] to 2.39 [2.11,2.80] L/min/m2, P&amp;lt;0.01 and 2.25 [1.87,2.63] to 2.50 [2.23,2.88] L/min/m2, P&amp;lt;0.01, respectively). There were no significant differences in CI after BPA between the Non-PH and Residual-PH groups. The 6-minute walk distance (6MWD) after BPA was shorter in the Residual-PH group than in the Non-PH group (435m and 480m, P&amp;lt;0.01). However, the estimated 5-year survival in the Non-PH and Residual-PH groups was comparable (96.3% and 99.1%, P=0.23, Figure 1). Patients in the Residual-PH group showed significantly shorter 6MWD and higher mPAP before BPA, and required more procedures (P&amp;lt;0.01, 0.02, 0.03, respectively). Additional multivariate logistic regression analysis revealed that shorter 6MWD before BPA was a significant predictor of residual PH (odds ratio=1.03, P=0.04). Conclusions The Residual-PH group had lower exercise capacity than the Non-PH group, although the prognosis in the Residual-PH group was similar to that in the Non-PH group.Figure 1

Macitentan tadalafil Fixed Dose Combination (FDC) in treatment-naive and prior monotherapy patients with Pulmonary Arterial Hypertension (PAH): insights from A DUE

Abstract Background Combination therapy is recommended for the management of pulmonary arterial hypertension (PAH). The A DUE study showed that M/T FDC, a fixed dose combination (FDC) of the endothelin receptor antagonist (ERA) macitentan 10mg (M) and the phosphodiesterase type 5 inhibitor (PDE5i) tadalafil 40mg (T), led to a clinically relevant improvement in pulmonary vascular resistance (PVR) vs macitentan and tadalafil monotherapies in PAH patients. A clinically meaningful trend for improvement in 6-minute walk distance (6MWD) in favor of M/T FDC vs macitentan and tadalafil was observed. Purpose Here we analysed the effect of M/T FDC in the subgroups of treatment-naïve and prior monotherapy patients. Methods In A DUE 187 adult PAH patients in WHO functional class II / III were randomised 2:1:1 to M/T FDC, macitentan or tadalafil if treatment-naïve, 2:1 to M/T FDC or macitentan if on prior ERA, and 2:1 to M/T FDC or tadalafil if on prior PDE5i. The treatment effect of M/T FDC vs macitentan and M/T FDC vs tadalafil was calculated using ANCOVA models for PVR (geometric mean ratios [95% CL]) and for 6MWD (mean change [95% CL]) in treatment-naïve patients and in patients on prior monotherapy (ERA or PDE5i) at randomisation. Results Treatment effects for M/T FDC versus macitentan and versus tadalafil on the change in PVR and 6MWD are reported in the table for each subgroup, along with those for the overall population. The safety profile of M/T FDC was in line with the safety profiles of macitentan and tadalafil. Conclusions In A DUE, the effect of M/T FDC vs both monotherapies on PVR and 6MWD in treatment-naïve and prior ERA/PDE5i patients was consistent with that observed in the overall population.

Ebsteins anomaly management in Central and South Eastern European (CESEE) countries: current status and improvement needed

Abstract Background Ebstein anomaly (EA) of the tricuspid valve (TV) as a rare congenital heart disease (CHD) is characterized by variable morphology, hemodynamics and clinical course, associated heart defects as well. Moreover, whether and when to intervene on TV remains a big challenge. Patients with EA should therefore be managed in expert centres equipped with all diagnostic and treatment tools according to ESC guidelines (ESC-GL), including cardiac magnetic resonance (CMR) as the gold standard. Aim of the study The aim of the study was to characterize EA patient population from selected countries within Central-Southern-Eastern Europe (CESEE), evaluate the management in relation to ESC-GL and determine optimal parameters for long-term follow-up (FU) feasible in CESEE. Material and methods In retrospective cross-sectional study from 9 CESEE countries, 203 adult patients with EA were included: median age 39y, 58% women. Determined were age at diagnosis, EA complications (associated CHD, arrythmias), cardiosurgery. ECHO and CMR right ventricular (RV) characteristics, NTproBNP, 6-minute walking distance (6MWD) were analysed as follows: ECHO parameters: long-axis RV end-diastolic dimension (RVEDD,mm), long-axis end-diastolic right to left ventricle diameter ratio (RV/LV), tricuspid annular plane systolic excursion (TAPSE,mm), RV fractional area change (FAC,%), RV tissue Doppler myocardial velocity (m/s). CMR-derived analysed parameters were: ejection fraction (EF,%), indexed end-diastolic volume (EDVi,ml/m²). Results Patients were diagnosed at age &amp;lt;1y/1-18y/&amp;gt;18y in: 29,6%/31.1%/39.3%. NYHA I/II/III/IV was as follows: 41.6%/37%/22.5%/0%, median NTproBNP: 160ng/l, 6MWD: 473m. CMR-characteristics were: median RVEF: 43.2%, EDVi: 118ml/m². CMR was absent in 60% cases. Associated CHD/arrhythmias were present at 46,7%/64,4. TV surgery were indicated / underwent 30,7% patients at mean age 32y. Performed was daSilva cone-repair/other valvuloplasty/valve replacement in 36,4%/25,5%/38,2%. CMR-derived EDV correlates significantly (P&amp;lt;0.001) with ECHO-based RVEDD and RV/LV ratio. No correlations between CMR-derived EF and ECHO functional parameters were found. Conclusion Although patients with EA in CESSE region are diagnosed late, the characteristics correspond to data published so far. Despite large heterogeneity including various associated complications, patient´s care in the CESEE region does not fully meet the requirements of ESC-GL. Mainly, CMR as a golden standard for EA evaluation is not widely accessible and so not performed. Therefore, an inconsistency in management and differences in therapeutic approach is a consequence. In these conditions in view of our previously proven experience, that the RV/LV ratio correlates significantly with CMR volume parameters, ECHO could serve as a reliable and decisive imaging method in FU, however insufficient in relation to ESC-GL.

Physical capacity determines physical and mental health in patients with chronic heart failure - a case control study

Abstract Background Chronic heart failure (CHF) is associated with reduced quality of life (QoL), but underlying mechanisms are incompletely understood. In this study we aimed to assess determinants of both physical and mental functioning in patients with and without chronic heart failure and investigated the impact of physical capacity (PC). Methods This is a cross-sectional analysis conducted in two cohorts using a case-control design. Both, the case cohort (RoC-HF, n=205) and the control cohort (BioPersMed, n=1022) were prospective, single center cohort studies. The case cohort included patients with diagnosed CHF with a current left ventricular ejection fraction (LVEF) &amp;lt;50%, while the control cohort included apparently healthy individuals with at least one cardiovascular risk factor. Laboratory parameters, transthoracic echocardiography, PC (Biopersmed: 6-minute walking distance [6MWD]; RoC-HF: 4-meter gait speed [4MGS]), and SF-36 health survey parameters as the main read-out of this study, were available in all participants. Results Cases and controls were matched by age, sex and body mass index yielding a study sample of 188 vs. 188 individuals. Medians with interquartile range of NT-proBNP and LVEF were 985 (325 – 2183) pg/dl and 37 (30 – 44) % in cases, and 72 (33 - 118) pg/dl and 64 (60 – 68) % in controls. Cases had lower levels than controls regarding all eight QoL aspects of the SF-36 HS (Figure 1). Both within the case and the control cohort, measures of heart failure severity (LVEF, NT-proBNP, TAPSE) were not or only marginally associated with SF-36 HS scales. PC parameters correlated significantly with physical component summary score (PCS) both within cases and controls, and with mental component summary score (MCS) only in cases (Figure 2). Multivariate linear regression analyses with adjustment for age, sex, eGFR, LVEF, NT-proBNP and TAPSE were conducted in each cohort, respectively. Within cases, 4MGS, but not LVEF, NT-proBNP and TAPSE, was significantly associated with MCS (adjusted beta 0.228, P=0.011) and PCS (beta = 0.318, P&amp;lt;0.001). Within controls, 6MWD was significantly associated with PCS (beta = 0.332, P&amp;lt;0.001), but not with MCS (beta = -0.62, P=0.472). Conclusion In patients with CHF, impairment of both physical and mental functioning is determined by physical capacity, but not by measures of cardiac function and congestion. By contrast, only physical functioning, but not mental functioning, can be explained by PC in healthy controls. Given the increasing relevance of QoL as a patient-oriented outcome in CHF, assessment and improvement of PC should be considered essential aspects in CHF care, besides biomarker-guided improvements in cardiac function and congestion. Whether targeting PC, for instance by medical and device therapies, translates into better physical and mental well-being in CHF should be specifically addressed in randomized controlled trials.

Prognostic value of modified ADMIIRE-HF risk score in patients with implantable cardioverter defibrillator: a prospective comparative study with 6-minute walk distance

Abstract Background ADIMIRE-HF risk score is a novel risk score that combines clinical characteristics and MIBG imaging variables to predict serious arrhythmic risk in patients with chronic heart failure (CHF) and recent studies showed that highest occurrence of severe arrhythmic events (SAE) was seen in patients with an intermediate decrease in MIBG uptake rather than the lowest values. Six-minute walk distance (6MWD) has also been shown to detect high risk patients with CHF. However, there is no information available on the long-term prognostic value of these indices for the prediction of ventricular tachyarrhythmias in patients with implantable cardioverter defibrillator (ICD). Methods and Results We prospectively enrolled 231 consecutive outpatients with ICD (age: 65±14 years, male: 81%, NYHA class: 1.7±0.7, LVEF: 47±17%). At entry, cardiac MIBG imaging, echocardiography and 6-minute walk test were performed. Modified ADMIRE-HF risk score was derived from the sum of the point values of the following parameters: LVEF (&amp;lt;25%:5 points), MIBG heart-to-mediastinum ratio on delayed planar image (HMR 1.4-1.9: 12 points) and systolic blood pressure (&amp;lt;120: 3 points, 120-139: 0 point, &amp;gt;140: -3 points). During a follow-up period of 4.4±2.8 years, 72 patients had appropriate ICD therapy (ATx). At multivariate Cox analysis, modified ADMIRE-HF risk score and 6MWD were significantly and independently associated with ATx after adjustment of age, sex, non-sustained ventricular tachycardia and NYHA functional class. ATx was significantly more frequently observed in patients with both higher modified ADMIRE HF risk score (&amp;gt;9: median value) and shorter 6MWD (&amp;lt;300m) and with either, than with none of them (54% vs 34% vs 18%, respectively p&amp;lt;0.0001). Conclusion Combination of modified ADMIRE-HF risk score and 6MWD would be strongly associated with an increased risk for ventricular tachyarrhythmias in ICD patients.

Efficacy of intravenous iron therapy compared to usual treatment in iron deficient adult cyanotic congenital heart disease patients for improvement in clinical outcomes at three months

Abstract Background Iron deficiency is frequent in CCHD patients and is associated with poorer outcomes. Patients with iron deficiency anaemia are treated with oral iron which results in improved clinical outcomes. The use of intravenous iron in CCHD patients is not well studied. Purpose We aimed to compare effectiveness of intravenous iron with usual care (i.e., no therapy for CCHD patients with iron deficiency without anemia, and oral iron therapy for CCHD patients with iron deficiency anemia) on 6-minute walk distance(6MWD) after 3 months of treatment, improvement in arterial Haemoglobin saturation, Quality of life, WHO functional class and safety of intravenous Iron. Methods We enrolled 27 patients of which 13 were randomized to IV iron arm and 14 to usual treatment arm. The mean age (±SD) of enrolled patient was 23.3 (±5.55) years. 24 out of 27 patients (88.9%) were Eisenmenger Syndrome patients, while the other three patients were TOF with pulmonary atresia, DORV with pulmonary atresia and post-Fontan. 6MWD was performed to access functional capacity and WHOQOL-BREF questionnaire was used for assessment of quality of life. All the clinical findings, data and test recordings were repeated after three months. Results The mean (±SD) haemoglobin(Hb) of patients included in the study was 16.7 (±2.0) g/dl. The Hb levels improved by 0.91 (±0.85) g/dl in patients who received any form of iron therapy (IV or oral iron). Hb improvement was not significantly different between those who received IV or oral iron [IV iron: 1.15 (±0.88) g/dl, Oral iron: 0.59 (±0.79) g/dl; p= 0.12]. The baseline 6MWD was not different in both the arms (p= 0.639). The mean (±SD) 6MW distance covered in IV iron arm and usual treatment arm was 401 (±35.2) m and 408.6 (±46.5) m respectively at baseline, which improved to 425 (±28.7) m and 421.5 (±43.2) m respectively at 3 months follow up. The change in 6MWD in IV iron arm and usual treatment arm was 24 (±22.3) m and 13.1 (±16.4) m respectively. The difference of change in 6MWD between the two arms was non-significant (p= 0.157). There was a significant improvement in WHOQOL-BREF Score Domains 2,3 and 4 and there was a trend towards improvement on Domain 1 score in IV iron arm compared to usual treatment arm. WHO functional class was similar at baseline in both arms (p= 0.534). The change in WHO functional class at follow up was similar in both arms (p= 0.082) Conclusion This study demonstrated no improvement in clinical outcomes of 6MW distance, arterial hemoglobin saturation and WHO functional class. However, there was significant improvement in quality of life and iv iron was found safe and equally efficacious as oral iron for correcting iron deficiency. Further studies for determining ideal hemoglobin levels and dose of iron in CCHD patients are pertinent.

Treatment with sacubitril/valsartan and improvement of ventricular-arterial coupling in heart failure with reduced ejection fraction

Abstract Background Treatment with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) in patients with heart failure and reduced ejection fraction (HFrEF) reduces mortality and heart failure (HF) hospitalizations. The specific hemodynamic mechanisms underlying these beneficial effects are currently unclear. Purpose This study aimed to assess the effects of S/V treatment on left ventricular (LV) end-systolic elastance (Ees), effective arterial elastance (Ea), and the ventricular-arterial coupling ratio (Ea/Ees) in patients with HFrEF using non-invasive pressure-volume analysis. Methods 117 patients with symptomatic HF and LVEF &amp;lt;40% in whom treatment with S/V was initiated were enrolled in this multicenter German prospective study. We used transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements for non-invasive pressure-volume loop analyses. Primary endpoints were changes in Ees, Ea, and Ea/Ees ratio after six months of S/V treatment. Results The mean age was 65 (±13) years and 30% were female. In 54.7% of the patients, the etiology of HF was ischemic, and 45.3% was non-ischemic. 58.4% had first HF diagnosis at baseline. 102 patients with complete clinical and echocardiographic data at baseline and after six months of follow-up were analyzed. Among those, 62% were on target dose of S/V. Six months of S/V treatment resulted in a significant increase of Ees (0.66 mmHg/ml, IQR [0.45;0.94] vs. 0.78 mmHg/ml [0.57;1.10], p=0.001) and decrease of Ea (1.76 mmHg/ml [1.48;2.13] vs. 1.62 mmHg/ml [1.36;1.96], p=0.014). Hence, the Ea/Ees ratio significantly improved (2.52 [1.88;4.05] vs. 1.93 [1.50;2.63], p&amp;lt;0.001). In addition, LV volumes and pressure improved significantly with a regression of the LV end-systolic volume (LVESV: 142 ml [115;180] vs. 96 ml [65;124]), end-diastolic volume (LVEDV: 216 ml [179;247] vs. 165 ml [132;200]) and LV end-diastolic pressure (LVEDP: 19.6 mmHg [18.2;22.4] vs. 17.8 mmHg [16.6;19.9]), p&amp;lt;0.001 respectively. The LVEF increased from a median of 33% (27;37) to 43% (36;49), p&amp;lt;0.001. NT-proBNP level decreased from (median) 1771 pg/ml [838;5211] to 724 pg/ml [300;1575] and mean 6-minute walking distance increased from 371m (±125) to 423 m (±122), p&amp;lt;0.001 respectively. The percentage of patients with NYHA class III changed from 25.6% to 5.9%. Conclusion In a 6-months treatment period, initiation of sacubitril/valsartan in patients with heart failure and reduced ejection fraction was associated with reduction of LV volumes, improved LV function, reduction in afterload and fewer heart failure symptoms. These new data indicate that beyond reverse LV remodeling, improvement of LV contractility and ventricular-arterial coupling may contribute to the favorable clinical outcomes on treatment with sacubitril/valsartan in chronic heart failure.

The PRELIEVE trial:Final 1-year outcomes of the prospective atrial flow regulator study

Abstract Background Implantation of the Atrial Flow Regulator (AFR) with an 8 or 10mm interatrial fenestration reduces left sided filling pressures in symptomatic heart failure (HF). Here, we report the final one-year results on safety and efficacy of the AFR in HF patients. Methods PRELIEVE is a prospective, non-randomized, multi-center, single-arm study in HF patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Patients with elevated fillings pressure at rest received an 8mm shunt device while those with exercise-induced rise in filling pressure received a 10mm AFR shunt device. Results Out of 109 enrolled patients 106 patients (n=62 HFrEF and n=44 HFpEF) received a successful device implantation (n=86 8mm AFR and n=20 10mm AFR). All-cause and cardiovascular mortality were 21% and 14% respectively in HFrEF and 7% and 0% respectively in HFpEF. HF hospitalization rate was 19% in HFrE and 9% in HFpEF. In 85 patients (n=44 HFrEF and n=41 HFpEF) with completed follow-up, device patency was documented in all patients having adequate image quality at 1-year follow-up (n=78). NYHA class &amp;gt;1 increase was noted in 67.5% HFrEF and 63.7% HFpEF patients. Quality of life assessed from the KCCQ score (overall summary score) increased from 49 + 23 to 72+24 in HFrEF and from 41+20 to 55+26 in HFpEF patients. Improved KCCQ&amp;gt;5 points was noted in 67.4% HFrEF and 44.7% in HFpEF patients. Six minute walking distance increased from 203+101m to 269+108m in HFrEF and from 228+121 m to 253+109m in HFpEF. Improved walking distance by either 50 m or by 50% was noted in 59.5% in HFrEF and 41.2% in HFpEF patients. Among echocardiography parameters, right ventricular diameter tended to increase in patients receiving 10 mm shunt device (Delta 1year vs. baseline 3.1 +11.2 mm), no changes were observed in patients treated with 8 mm shunt device. Note, pacemaker presence or resting pulmonary vascular resistance were similar. Conclusions Implantation of AFR device with either 8 or 10 mm shunt size in HF patients was safe and feasible irrespective of baseline ejection fraction. Signals of clinical efficacy were observed in the majority of patients. This study warrants further clinical evaluation of the AFR device in HF.Clinical efficacy parameters

Abstract 17131: Association of Objectively Measured Sleep With 6-minute Walk Distance in Older Adults

Background: Decline in physical function in older adults is associated with higher risk of cardiovascular diseases. While disturbances in sleep may contribute to declines in physical function with aging, prior research is limited by the use of subjective sleep measures. Hypothesis: Older adults with sleep disturbance will have impaired functional capacity measured via 6-minute walk test. Aim: This study aimed to examine the association between objectively measured sleep parameters and 6-minute walk distance (6MWD), a marker of functional capacity, in a diverse sample of older adults aged ≥55 years. Methods: This analysis included 96 participants who were enrolled in the Disparities in Sleep and Cognitive Outcomes (DISCO) study, a prospective cohort study of older adults with objective measurement of sleep and functional capacity. Sleep duration (minutes), efficiency (%), and fragmentation (%) were measured using 7 days-wrist actigraphy. Sleep stages including non-REM stage 3 (N3) duration (minutes) and REM duration (minutes) were measured using an overnight home sleep monitor. Total distance (meters) completed in 6-minutes was the primary outcome. Covariates included age, sex, race, ethnicity, body mass index, smoking status, and pain/ inflammation. Linear regression models were used for analysis. Results: Mean age of participants was 69.1 ± 5.4 years (range 56-82 years), 69.8% were women, 72% were White and 97% were Non-Hispanic/Latino. The average 6MWD was 495.6 ± 87 meters. Sleep duration, N3 duration, and REM duration were not statistically associated with total distance walked. In the fully adjusted models, higher sleep efficiency was associated with higher total 6MWD (p&lt;0.001), and greater sleep fragmentation was associated with lower total 6MWD (p=0.016) (see Table 1). Conclusions: Less favorable sleep quality, as indicated by lower sleep efficiency and more fragmented sleep, was associated with poorer functional capacity in older adults.