Worse Functional Capacity Research Articles

CA125 outperforms NT-proBNP in the prediction of maximum aerobic capacity in heart failure with preserved ejection fraction and kidney dysfunction.

Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60ml/min/1.73m2 versus ≥60ml/min/1.73m2). The mean age of the sample was 73.2±10.5years and 56.4% were female. The median of peak VO2 was 11.0ml/kg/min (interquartile range 9.0-13.0). A total of 67 (50.4%) patients had an eGFR <60ml/min/1.73m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r=-0.43, P<.001 and r=-0.22, P=.010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction=.045). In patients with an eGFR ≥60ml/min/1.73m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60ml/min/1.73m2, NT-proBNP was not significantly associated with peak VO2 [β=0.02 (95% confidence interval -0.19-0.23), P=.834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction=.620). In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.

Malnutrition as a potential predictor of mortality in chronic kidney disease patients on dialysis: A systematic review and meta-analysis

Background & AimsMalnutrition, a significant problem in patients with chronic kidney disease (CKD), is linked to lower health-related quality of life, longer and more frequent hospital admissions, worse functional capacity, and higher levels of morbidity. However, the extent of its impact on mortality is poorly elucidated. This systematic review and meta-analysis aimed to investigate the impact of malnutrition on mortality among CKD patients on dialysis. MethodsThis meta-analysis was designed and performed in accordance with the PRISMA guidelines (CRD42023394584). A systematic electronic literature search was conducted in PubMed, ScienceDirect, and Embase to identify relevant cohort studies. The studies that reported nutritional status and its impact on mortality in patients were considered for analysis. The generic inverse variance method was used to pool the hazard ratio effect estimates by employing a random effects model. The Newcastle-Ottawa scale was used for the quality assessment. The statistical analysis was performed by utilizing RevMan and CMA 2.0. ResultsA total of 29 studies that comprised 11063 patients on dialysis whose nutritional status was evaluated were eligible for quantitative analysis. Based on a comparison between the "malnutrition" category and the reference "normal nutrition status" category, the results showed that the overall pooled hazard risk (HR) for mortality was (HR 1.49, 95% CI: 1.36–1.64, p<0.0001). According to the subgroup analysis, the hemodialysis subgroup had greater mortality hazards (HR 1.53; 95% CI 1.38–1.70, p<0.0001), compared to the peritoneal dialysis subgroup (HR 1.26; 95% CI 1.15–1.37, p<0.00001). Additionally, the overall incidence of mortality was explored but the authors were unable to combine the results due to limitations with the data. ConclusionThe findings conclude that malnutrition is a strong predictor of mortality among patients on dialysis, with the hemodialysis subgroup having a higher mortality hazard compared to the peritoneal dialysis subgroup. The results of this study will advocate for early nutritional evaluation and timely dietary interventions to halt the progression of CKD and death.

Multidimensional frailty connection in older patients with diabetes mellitus

Background and objectivePatients with diabetes mellitus (DM) experience accelerated aging and, thus, a high prevalence of frailty. Our aim is to outline the type of frailty and prefrailty from a multidimensional perspective and the interaction of these dimensions in this scenery. Material and methodsObservational study of patients with DM over 60 years-old. Variables related to nutrition, cognitive and emotional status, physical and instrumental functional capacity and social resources were collected. They were divided into three groups (robust, prefrail and frail) according to the Fried scale. Each of the variables in the groups were compared and a correspondence analysis was carried out to see the influence of some dimensions with others in each stage of frailty. Results188 patients (mean age 72.6 + 7.5) were analysed. Of them, 105 patients had prefrailty and 66 were frail. With the exception of social resources, the rest of the variables had an increasing prevalence depending on the stage of frailty. However, in the correspondence analysis (with 22.9% of variation explained by two dimensions) it was only patients with frailty who were associated with worse functional capacity, cognitive and emotional situation and mild to moderate social incapacity. ConclusionsIn our sample there was a high prevalence of prefrailty, and frailty associated with an increase in the prevalence of other different dimensions except social resources. However, the interaction between these dimensions was only evident in the case of patients with frailty.

Health and lifestyle parameters in peripheral artery disease at two periods of the COVID-19 pandemic: comparison between men and women.

This study analyzed the impact of sex on self-reported health and lifestyle parameters in peripheral artery disease patients at two periods of the COVID-19 pandemic. In this longitudinal study, 99 patients with peripheral artery disease (53 men and 46 women) were evaluated during two periods of the COVID-19 pandemic ( i.e ., at onset: May to August 2020, and on follow-up: May to August 2021). Patients were interviewed via telephone, and information regarding lifestyle and health parameters was obtained. At the onset of the COVID-19 pandemic, health and habit parameters were similar between women and men, with 63.0% and 45.3% indicating frequent fatigue, 73.9% and 84.9% reporting increased sitting time, and 23.9% and 39.6% practicing physical activity, respectively. At follow-up, difficulties in physical mobility (women: from 26.1% to 73.9%, p<0.001; men: from 39.6% to 71.7%, p=0.001) and the frequency of hospitalization for reasons other than COVID-19 increased similarly in women and men (women: from 4.3% to 21.7%, p=0.013; men: from 9.4% to 24.5%, p=0.038). The other parameters were similar between the periods. Self-reported physical mobility difficulties and hospitalization frequency increased in women and men with peripheral artery disease. ▪ Sitting time increased in 73.9% of women and 84.9% of men at the onset of the pandemic. ▪ Physical activity was practiced by 23.9% of women and 39.6% of men at the onset of the pandemic. ▪ The prevalence of both women and men reporting physical mobility difficulties increased at follow-up. ▪ Hospitalization rates for reasons unrelated to COVID-19 have increased in both women and. While women experience more consequences related to peripheral artery disease than men, such as worse functional capacity and higher morbidity, there was a similar increase in physical mobility difficulty and frequency of hospitalization for reasons other than COVID-19 one year after the onset of the pandemic.

Anemia and Iron Deficiency Predict All-Cause Mortality in Patients with Heart Failure and Preserved Ejection Fraction: 6-Year Follow-Up Study.

The aim of this study was to assess the prevalence of anemia and iron deficiency in patients with heart failure with preserved ejection fraction (HFpEF) and its impact on clinical outcomes. We retrospectively analyzed 212 patients with HFpEF and identified anemia as a serum hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women. Additionally, ID was defined as a serum ferritin concentration < 100 ng/mL or 100-299 ng/mL with transferrin saturation < 20%. Patients were followed up for an average of 66.2 ± 12.1 months, with the endpoint being all-cause mortality among patients with HFpEF, both with and without anemia and iron deficiency. Furthermore, we explored other predictors of all-cause mortality. The average age of the entire group was 70.6 ± 10.5 years, with females comprising 55% of the patients. Anemia was present in 81 (38.2%) patients, while 108 (50.9%) had iron deficiency. At the end of the follow-up period, 60 (28.3%) of the patients had passed away. Patients with anemia displayed more heart failure (HF) symptoms, diastolic dysfunction, higher NT-pro-BNP levels, and worse baseline functional capacity than those without. Similarly, patients with iron deficiency showed more pronounced HF symptoms and worse functional capacity than those without. The results from the multivariable analyses revealed that anemia (hazard ratio [HR]: 5.401, 95% confidence interval [CI]: 4.303-6.209, log-rank p = 0.001), advanced age, iron deficiency (HR: 3.502, 95% CI: 2.204-6.701, log-rank p = 0.015), decreased left ventricular ejection fraction, chronic kidney disease, and paroxysmal nocturnal dyspnea were all independently associated with all-cause mortality. It is essential to consider anemia and iron deficiency as common comorbidities in managing and prognosis HFpEF, as they significantly increase mortality risk.

Capacidade funcional pós-COVID-19 com teste de argola e de caminhada: estudo transversal

Abstract Introduction COVID-19 can cause persistent symptoms even in mild cases, such as fatigue and dyspnea, which can reduce functional capacity and make it difficult to perform activities of daily living. Objective To compare functional capacity using the pegboard and ring test and the six-minute walk test responses in post-COVID-19 patients according to the ventilatory support used. Methods Cross-sectional study including 40 adults of both sexes after SARS-CoV2 infection between June 2020 and June 2021, with assessment of functional capacity using the pegboard and ring test (upper limbs) and the six-minute walk (lower limbs). Those who reported comprehension deficit or neuromuscular disease were excluded. All participants were evaluated between 15 and 90 days after the onset of symptoms, diagnosed by nasal swab and classified according to the ventilatory support used during the infection. Results The mean age of the participants (n = 40) was 54.30 (±12.76) years, with BMI 28.39 (±4.70) kg/m2 and pulmonary involvement in 51.49 (±17.47)%. A total of 37 participants were hospitalized with a stay of 14.33 (±15.44) days, and 30% were previously immunized, while 7.5% reached the predicted distance covered. The average achieved was 46.44% (398.63 ± 130.58 m) in the distance covered and 39.31% (237.58 ± 85.51) in the movement of rings. Participants who had invasive mechanical ventilation (n = 10) had the worst functional capacity in both tests 265.85 ± 125.11 m and 181.00 ± 90.03 rings, compared to 472.94 ± 88.02 m and 273.25 ± 66.09 rings in non-invasive ventilation (n = 8), 410.32 ± 90.39 m and 257.68 ± 62.84 rings in oxygen therapy (n = 19), 569.00 ± 79.50 m and 203.00 ± 169.00 rings when there was no hospitalization (n = 3). Conclusion Participants who required invasive mechanical ventilation had worse functional capacity, 46% of what was expected in the walk test and 39% of what was expected in the pegboard and ring test.

Sarcopenia: Inflammatory and Humoral Markers in Older Heart Failure Patients.

Sarcopenia is highly prevalent in heart failure (HF) patients, and the involvement of biomarkers in its pathophysiology is suggested, but little has been studied concerning HF sarcopenic patients. To evaluate the association between inflammatory and humoral markers with sarcopenia, as well as the impact of sarcopenia on quality of life and functional capacity in older HF patients. In this cross-sectional study, 90 outpatient HF patients, aged ≥ 60 years, were evaluated for sarcopenia (EWGSOP2 diagnostic criteria), inflammation (high-sensitive C-reactive protein [hs-CRP], Interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and humoral markers (total testosterone and insulin-like growth factor-1 [IGF-1]), physical activity (International Physical Activity Questionnaire), quality of life (Minnesota Living with Heart Failure Questionnaire), and functional capacity (6-minute walk test). The adopted level of significance was p<0.05. Patients had a mean age of 69.4 ± 7.2 years, 67.8% were male, with left ventricular ejection fraction (LVEF) of 35.9 ± 11.9% and 22 (24.4%) were sarcopenic. Age (73.1 ± 8.1 and 68.3 ± 6.5 years; p= 0.006), body mass index (BMI) (23.1 ± 2.8 and 28.2 ± 4.2 kg/m2; p <0.001), and LVEF (29.9 ± 8.8 and 37.9 ± 12.1%; p= 0.005) were different between groups with and without sarcopenia, respectively. After adjusting for age, ethnicity, BMI, LVEF, and the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers, sarcopenia was associated with higher serum levels of IL-6 and worse functional capacity. In HF patients, sarcopenia was associated with IL-6 levels and functional capacity.

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients’ insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet’s agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients’ and informants’ ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative.

Markers of Iron Metabolism and Outcomes in Patients with Heart Failure: A Systematic Review

Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron supplementation for patients with HF has demonstrated benefits in quality of life (QoL) and HF-related hospitalizations. The aim of this systematic review was to summarize the evidence linking iron metabolism biomarkers with outcomes in patients with HF to assist in the optimal use of these biomarkers for patient selection. A systematic review of observational studies in English from 2010 to 2022 was conducted using PubMed, with keywords of "Heart Failure" and respective iron metabolism biomarkers ("Ferritin", "Hepcidin", "TSAT", "Serum Iron", and "Soluble Transferrin Receptor"). Studies pertaining to HF patients, with available quantitative data on serum iron metabolism biomarkers, and report of specific outcomes (mortality, hospitalization rates, functional capacity, QoL, and cardiovascular events) were included, irrespective of left ventricular ejection fraction (LVEF) or other HF characteristics. Clinical trials of iron supplementation and anemia treatment were removed. This systematic review was conducive to formal assessment of risk of bias via Newcastle-Ottawa Scale. Results were synthesized based on their respective adverse outcomes and iron metabolism biomarker(s). Initial and updated searches identified 508 unique titles once duplicates were removed. The final analysis included 26 studies: 58% focused on reduced LVEF; age range was 53-79 years; males composed 41-100% of the reported population. Statistically significant associations of ID were observed with all-cause mortality, HF hospitalization rates, functional capacity, and QoL. Increased risk for cerebrovascular events and acute renal injury have also been reported, but these findings were not consistent. Varying definitions of ID were utilized among the studies; however, most studies employed the current European Society of Cardiology criteria: serum ferritin < 100 ng/mL or the combination of ferritin between 100-299 ng/mL and transferrin saturation (TSAT) < 20%. Despite several iron metabolism biomarkers demonstrating strong association with several outcomes, TSAT better predicted all-cause mortality, as well as long-term risk for HF hospitalizations. Low ferritin was associated with short-term risk for HF hospitalizations, worsening functional capacity, poor QoL, and development of acute renal injury in acute HF. Elevated soluble transferrin receptor (sTfR) levels were associated with worse functional capacity and QoL. Finally, low serum iron was significantly associated with increased risk for cardiovascular events. Considering the lack of consistency among the iron metabolism biomarkers for association with adverse outcomes, it is important to incorporate additional biomarker data, beyond ferritin and TSAT, when assessing for ID in HF patients. These inconsistent associations question how best to define ID to ensure proper treatment. Further research, potentially tailored to specific HF phenotypes, is required to optimize patient selection for iron supplementation therapy and appropriate targets for iron stores replenishment.

S-29-3: THE RELATIONSHIP BETWEEN VENTRICULAR-ARTERIAL COUPLING AND AEROBIC CAPACITY ACROSS THE CARDIOVASCULAR DISEASE CONTINUUM: FOCUS ON PROXIMAL AORTIC STIFFNESS

Objective: Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). We evaluated VAC across the cardiovascular disease continuum. Design and method: We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and 3D-GLS in: We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results: aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p &lt; 0.01). PWVs were directly related and increased with age (all p &lt; 0.0001). cf-PWV/3D-GLS was similarly compromised in HFrEF (1.08 ± 0.36) and HFpEF (1.05 ± 0.22), while aa-PWV/3D-GLS was more impaired in HFpEF (0.69 ± 0.11) than HFrEF (0.60 ± 0.15; p &lt; 0.01). Stage A-B had values of cf-PWV/3D-GLS and aa-PWV/3D-GLS (0.66 ± 0.25 and 0.47 ± 0.12) higher than controls (0.47 ± 0.10 and 0.40 ± 0.10) but lower than Stage C (all p &lt; 0.01). Peak AVO2diff was inversely related with cf-PWV/3D-GLS and aa-PWV/3D-GLS (all p &lt; 0.01). cf-PWV/3D-GLS and aa-PWV/3D-GLS independently predicted peak VO2 in the overall population (adjusted R2 = 0.32 and 0.35; all p &lt; 0.0001) but only aa-PWV/3D-GLS was independently associated with flow reserve during exercise (R2 = 0.51; p &lt; 0.0001). Conclusion: Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/3D-GLS.

679 PROGNOSTIC IMPACT OF ECHOCARDIOGRAPHIC DERIVED PRECAPILLARY WEDGE PRESSURE AND PULMONARY VASCULAR RESISTANCES IN PATIENTS WITH HEART FAILURE

Abstract Background A reliable echocardiographic algorithm for the estimation of precapillary wedge pressure (PCWP) and pulmonary vascular resistances (PVR) has been recently validated by our group in a large cohort of patients undergoing right heart catheterization (RHC). Those metrics may add relevant clinical and prognostic information in patients with heart failure (HF). Objective To assess the clinical/prognostic significance of echocardiographic derived PCWP and PVR in a large cohort of chronic HF patients on modern treatments. Methods Outpatients with chronic HF with either reduced (≤40%) or mildly reduced LVEF (41-49%) underwent a thorough clinical multiparametric assessment and were followed-up for a composite endpoint of cardiac death, appropriate ICD shock, or first HF hospitalization. Results Out of 1,483 patients prospectively enrolled (70±12 years, 73% males, 42% ischemic etiology, LVEF 35±8%, 74% HFrEF), PCWP (16.4±5.8 mmHg) was elevated (&amp;gt;15 mmHg) in 53% of cases, while PVR (1.7±0.7) was elevated (&amp;gt;2 WU) in 25% of cases. Of the latter group, most (83%) had also elevated PCWP. Patients with increased PCWP were older, had a higher heart rate and lower cardiac output, showed a higher degree of left and right chamber remodeling, had a higher neurohormonal activation, worse renal function, worse functional capacity and ventilatory efficiency on effort, particularly when also PVR were elevated (all p&amp;lt;0.001). The optimal prognostic cut-point was identified for both PCWP (16.2 mmHg) and PVR (2 WU) by log-rank maximal likelihood ratio. Over a median follow-up of 27 (12-43) months, both measures significantly stratified patients for the risk of the primary endpoint at Kaplan-Meier analysis (Log Rank 99.5, p&amp;lt;0.001 for PCWP; Log Rank 18.4, p&amp;lt;0.001 for PVR). While both increased PCWP and PVR were associated with a higher risk of events in the HFrEF subgroup (both p&amp;lt;0.001), only increased PCWP significantly stratified the outcome in HFmrEF patients (Figure). At multivariable Cox regression analysis (adjusted for age, sex, ischemic HF etiology, glomerular filtrate, LVEF, and NT-proBNP), increased PCWP (hazard ratio, HR 1.67 [95%CI 1.28-2.18], p&amp;lt;0.001) but not PVR (HR 1.25 [95%CI 0.98-1.60], p=0.07) remained an independent predictor of the primary outcome. Conclusion The estimation of PCWP and PVR by echocardiography add relevant clinical and prognostic information and may help in the decision making in patients with HF.

Biomarker-based clustering of patients with chronic obstructive pulmonary disease.

COPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways. 213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster. Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load. These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.

The impact of ventricular-arterial coupling on aerobic capacity across the heart failure spectrum

Abstract Background Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). Objectives To evaluate VAC across the spectrum of heart failure (HF). Methods We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and 3D-GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n=104) or reduced ejection fraction (HFrEF, n=132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p&amp;lt;0.01). PWVs were directly related and increased with age (all p&amp;lt;0.0001). cf-PWV/3D-GLS was similarly compromised in HFrEF (1.08±0.36) and HFpEF (1.05±0.22), while aa-PWV/3D-GLS was more impaired in HFpEF (0.69±0.11) than HFrEF (0.60±0.15; p&amp;lt;0.01). Stage A-B had values of cf-PWV/3D-GLS and aa-PWV/3D-GLS (0.66±0.25 and 0.47±0.12) higher than controls (0.47±0.10 and 0.40±0.10) but lower than Stage C (all p&amp;lt;0.01). Peak AVO2diff was inversely related with cf-PWV/3D-GLS and aa-PWV/3D-GLS (all p&amp;lt;0.01). cf-PWV/3D-GLS and aa-PWV/3D-GLS independently predicted peak VO2 in the overall population (adjusted R2=0.32 and 0.35; all p&amp;lt;0.0001) but only aa-PWV/3D-GLS was independently associated with flow reserve during exercise (R2=0.51; p&amp;lt;0.0001). Conclusion Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/3D-GLS. Funding Acknowledgement Type of funding sources: None.

Prognostic impact of echocardiographic derived precapillary wedge pressure and pulmonary vascular resistances in patients with heart failure

Abstract Background A reliable echocardiographic algorithm for the estimation of precapillary wedge pressure (PCWP) and pulmonary vascular resistances (PVR) has been recently validated by our group in a large cohort of patients undergoing right heart catheterization (RHC) (1). Those metrics may add relevant clinical and prognostic information in patients with heart failure (HF). Objective To assess the clinical/prognostic significance of echocardiographic derived PCWP and PVR in a large cohort of chronic HF patients on modern treatments. Methods Outpatients with chronic HF with either reduced (≤40%) or mildly reduced LVEF (41–49%) underwent a thorough clinical multiparametric assessment and were followed-up for a composite endpoint of cardiac death, appropriate ICD shock, or first HF hospitalization. Results Out of 1,483 patients prospectively enrolled (70±12 years, 73% males, 42% ischemic etiology, LVEF 35±8%), PCWP (16.4±5.8 mmHg) was elevated (&amp;gt;15 mmHg) in 53% of cases, while PVR (1.7±0.7) was elevated (&amp;gt;3 WU) in 6% of cases. Of the latter group, most (92%) had also elevated PCWP. Patients with increased PCWP were older, had a higher heart rate and lower cardiac output, showed a higher degree of left and right chamber remodeling, had a higher neurohormonal activation, worse renal function, worse functional capacity and ventilatory efficiency on effort (all p&amp;lt;0.001). Those patients with high PCWP and PVR showed higher heart rate and pulmonary pressures, lower cardiac output, and right ventricular function, higher neurohormonal activation, lower functional capacity and ventilatory efficiency on effort compared to patients with high PCWP but normal PVR (all p&amp;lt;0.01). The optimal prognostic cut-point was identified for both PCWP (16.2 mmHg) and PVR (2 WU) by log-rank maximal likelihood ratio. Over a median follow-up of 22 (8–37) months, both measures significantly stratified patients for the risk of the primary endpoint at Kaplan-Meier analysis (log-rank 92.9, p&amp;lt;0.001 for PCWP; log-rank 17.3, p&amp;lt;0.001 for PVR). At multivariable Cox regression analysis (adjusted for age, sex, ischemic HF etiology, renal function, LVEF, and NT-proBNP), PCWP (hazard ratio, HR 1.77 [95% CI 1.30–2.40], p&amp;lt;0.001) but not PVR (HR 1.15 [95% CI 0.88–1.51], p=0.31) remained an independent predictor of the primary outcome. Conclusion The estimation of PCWP and PVR by echocardiography add relevant clinical and prognostic information and may help in the decision making in patients with HF. Funding Acknowledgement Type of funding sources: None.

Characterisation of pulmonary arterial hypertension patients with cardiovascular comorbidities treated with selexipag: real-world evidence from the EXPOSURE study

Abstract Background A recent post-hoc analysis of the GRIPHON randomised controlled trial [1] showed that selexipag reduces the risk of a morbidity/mortality event versus placebo in pulmonary arterial hypertension (PAH) patients, irrespective of comorbidity burden. Real-world evidence is needed on the management of PAH patients with cardiovascular comorbidities receiving selexipag. Purpose To describe characteristics, treatment patterns and outcomes of PAH patients with cardiovascular comorbidities receiving selexipag in the real world. Methods EXPOSURE is an ongoing, multicentre, prospective, observational study of PAH patients initiating a PAH-specific therapy in Europe and Canada. Patients initiating selexipag were grouped by number of cardiovascular comorbidities present prior to or at therapy initiation: BMI ≥30 kg/m2, systemic hypertension, diabetes mellitus, and coronary artery disease. Results As of November 2020, 382 selexipag-treated patients had follow-up and comorbidity data available: 44% (n=169) had 0, 30% (n=114) had 1, 18% (n=70) had 2, and 8% (n=29) had ≥3 comorbidities. At selexipag initiation, patients with comorbidities were older, more likely to have idiopathic/heritable PAH and had worse functional capacity (lower median 6-minute walk distance, higher proportion in WHO functional class III/IV) vs those without comorbidities (Table 1). Overall, haemodynamic parameters were similar across groups (Table 1). Patients with a higher comorbidity burden were more likely to be at high-risk of 1-year mortality (COMPERA method) vs those with a lower comorbidity burden (Table 1). Patients predominantly initiated selexipag as part of triple combination therapy (mainly in addition to an endothelin receptor antagonist and phosphodiesterase type 5 inhibitor), regardless of comorbidity burden (76–79% across groups). The duration of exposure and the median selexipag maintenance dose were similar across groups (Table 2). The proportion of patients hospitalised and the proportion who discontinued selexipag during the exposure period are shown in Table 2. 5% (n=8) of patients in the 0 comorbidities group, 12% (n=14) in the 1 comorbidity group, 0% in the 2 comorbidities group, and 10% (n=3) in the ≥3 comorbidities group died during the exposure period. Conclusions These real-world data from Europe and Canada suggest that more than 50% of patients who initiated selexipag had ≥1 cardiovascular comorbidity. Patients with comorbidities had more severe functional impairment vs those without. Overall haemodynamic profiles reflected Group 1 Pulmonary Hypertension and were similar across groups. Selexipag was initiated predominantly as part of triple combination therapy in all groups and most patients remained on selexipag, regardless of comorbidity burden. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson &amp; Johnson

Right ventricular strain related to pulmonary artery pressure predicts clinical outcome in patients with pulmonary arterial hypertension.

In pulmonary arterial hypertension (PAH), the right ventricle (RV) is exposed to an increased afterload. In response, RV mechanics are altered. Markers which would relate RV function and afterload could therefore aid to understand this complex response system and could be of prognostic value. The aim of our study was to (i) assess the RV-arterial coupling using ratio between RV strain and systolic pulmonary artery pressure (sPAP), in patients with PAH, and (ii) investigate the prognostic value of this new parameter over other echocardiographic parameters. Echocardiograms of 65 pre-capillary PAH patients (45 females, age 61 ± 15 years) were retrospectively analysed. Fractional area change (FAC), sPAP, tricuspid annular plane systolic excursion, and RV free-wall (FW) longitudinal strain (LS) were measured. A primary endpoint of death or heart/lung transplantation described clinical endpoint. Patients who reached a clinical endpoint had worse functional capacity (New York Heart Association), reduced RV function, and higher sPAP. Left ventricle function was similar in both groups. Only RVFW LS/sPAP ratio was found as an independent predictor of clinical endpoint in multivariable analysis (hazard ratio 8.3, 95% confidence interval 3.2-21.6, P < 0.001). The RWFW LS/sPAP (cut-off 0.19) demonstrated a good accuracy for the prediction of reaching the clinical endpoint, with a sensitivity of 92% and specificity of 82.5%. RVFW LS/sPAP ratio significantly predicts all-cause mortality and heart-lung transplantation, and was superior to other well-established parameters, in patients with pre-capillary PAH. We therefore propose RVFW LS/sPAP as a new prognostic echocardiographic marker.

Reduced frequencies of Foxp3+GARP+ regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype

BackgroundExpression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism.ObjectiveTo investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD.MethodsGARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed.ResultsPatients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3+GARP+ Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3+GARP− Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood.ConclusionDecreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage.

ANALYSIS OF THE VENTRICULAR-ARTERIAL COUPLING DERIVED FROM PROXIMAL AORTIC STIFFNESS: IMPACT ON AEROBIC CAPACITY ACROSS THE HEART FAILURE SPECTRUM

Objective: Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). We aimed at evaluating VAC across the spectrum of heart failure (HF). Design and method: We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n = 104) or reduced ejection fraction (HFrEF, n = 132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results: aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p &lt; 0.01). PWVs were directly related and increased with age (all p &lt; 0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.08 ± 0.36) and HFpEF (1.05 ± 0.22), while aa-PWV/GLS was more impaired in HFpEF (0.69 ± 0.11) than HFrEF (0.60 ± 0.15; p &lt; 0.01). Stage A-B had values of cf-PWV/GLS and aa-PWV/GLS (0.66 ± 0.25 and 0.47 ± 0.12) higher than controls (0.47 ± 0.10 and 0.40 ± 0.10) but lower than Stage C (all p &lt; 0.01). Peak AVO2diff was inversely related with cf-PWV/GLS and aa-PWV/GLS (all p &lt; 0.01). cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO2 in the overall population (adjusted R2 = 0.32 and 0.35; all p &lt; 0.0001) but only aa-PWV/GLS was independently associated with flow reserve during exercise (R2 = 0.51; p &lt; 0.0001). Conclusions: Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.

Ventricular-Arterial Coupling Derived From Proximal Aortic Stiffness and Aerobic Capacity Across the Heart Failure Spectrum

BackgroundVentricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulsed wave velocity [PWV]) and myocardial deformation (global longitudinal strain [GLS]). ObjectivesThis study aimed to evaluate VAC across the spectrum of heart failure (HF). MethodsThe authors introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). They measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 236 patients in stage C heart failure with preserved ejection fraction (HFpEF) (n = 104) or heart failure with reduced ejection fraction (HFrEF) (n = 132). They evaluated peak oxygen consumption and peripheral extraction using combined cardiopulmonary-echocardiography exercise stress. Resultsaa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (P < 0.01). PWVs were directly related and increased with age (all P < 0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.09 ± 0.35) and HFpEF (1.05 ± 0.21), whereas aa-PWV/GLS was more impaired in HFpEF (0.70 ± 0.10) than HFrEF (0.61 ± 0.14; P < 0.01). Stage A-B had values of cf-PWV/GLS and aa-PWV/GLS (0.67 ± 0.27 and 0.48 ± 0.14, respectively) higher than controls (0.46 ± 0.11 and 0.39 ± 0.10, respectively) but lower than stage C (all P < 0.01). Peak arteriovenous oxygen difference (AVO2diff) was inversely related with cf-PWV/GLS and aa-PWV/GLS (all P < 0.01). Although cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO2 in the overall population (adjusted R2 = 0.33 and R2= 0.36; all P < 0.0001), only aa-PWV/GLS was independently associated with flow reserve during exercise (R2 = 0.52; P < 0.0001). ConclusionsAbnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.

Ventricular-arterial coupling derived from proximal aortic stiffness: impact on aerobic capacity across the heart failure spectrum

Abstract Funding Acknowledgements Type of funding sources: None. Background Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). Objectives To evaluate VAC across the spectrum of heart failure (HF). Methods We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n=104) or reduced ejection fraction (HFrEF, n=132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p&amp;lt;0.01). PWVs were directly related and increased with age (all p&amp;lt;0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.08±0.36) and HFpEF (1.05±0.22), while aa-PWV/GLS was more impaired in HFpEF (0.69±0.11) than HFrEF (0.60±0.15; p&amp;lt;0.01). Stage A-B had values of cf-PWV/GLS and aa-PWV/GLS (0.66±0.25 and 0.47±0.12) higher than controls (0.47±0.10 and 0.40±0.10) but lower than Stage C (all p&amp;lt;0.01). Peak AVO2diff was inversely related with cf-PWV/GLS and aa-PWV/GLS (all p&amp;lt;0.01). cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO2 in the overall population (adjusted R2=0.32 and 0.35; all p&amp;lt;0.0001) but only aa-PWV/GLS was independently associated with flow reserve during exercise (R2=0.51; p&amp;lt;0.0001). Conclusion Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.