Unraveling the Mechanisms Behind Exercise Intolerance and Recovery in Long COVID.

BACKGROUND: Patients suffering from long COVID may exhibit autonomic dysregulation. However, the association between autonomic dysregulation and exercise intolerance and the impact of therapeutic interventions on its modulation remains unclear. This study investigated the relationship between heart rate recovery at the first minute (HRR1), a proxy for autonomic imbalance, and exercise intolerance in patients with long COVID. Additionally, the study aimed to assess the effects of a 12-week home-based inspiratory muscle training program on autonomic modulation in this patient population. METHODS: This study is a post hoc subanalysis of a randomized trial in which 26 patients with long COVID were randomly assigned to receive either a 12-week inspiratory muscle training program or usual care alone (NCT05279430). The data were analyzed using Pearson's correlation and linear mixed regression analysis. RESULTS: The mean age was 50.4 ± 12.2 years, and 11 (42.3%) were women. Baseline HRR1 was significantly correlated with maximal functional capacity (peakVO2) (r = 0.402, P = .041). Patients with lower baseline HRR1 (≤22 bpm) exhibited higher resting heart rates and lower peakVO2. Inspiratory muscle training led to a more substantial increase in peakVO2 in patients with lower HRR1 at baseline (P = .019). Additionally, a significant improvement in HRR1 was observed in the IMT group compared to the usual care group after 12-week (Δ +9.39, 95% CI = 2.4-16.4, P = .010). CONCLUSION: Lower baseline HRR1 is associated with exercise intolerance in long COVID patients and may serve as a valuable criterion for identifying individuals likely to benefit more from a home-based inspiratory muscle training program.

Carbohydrate antigen 125-guided pre-TAVI medical optimization: impact on quality of life and clinical outcomes.

INTRODUCTION AND OBJECTIVES: Carbohydrate antigen 125 (CA125), a biomarker associated with fluid overload, has proven useful in managing diuretic therapy in heart failure. We aimed to evaluate the impact of diuretic optimization guided by CA125 before transcatheter aortic valve implantation (TAVI) on outcomes. METHODS: This prospective interventional study enrolled patients scheduled for TAVI, in whom baseline CA125 was measured 2 weeks before TAVI. Patients with CA125 ≥ 20 U/mL underwent diuretic up-titration before TAVI. Three groups were included: group I) baseline CA125 <20 U/mL; IIa) CA125 ≥ 20 U/mL that decreased after treatment, and IIb) CA125 ≥ 20 U/mL that did not decrease. The primary outcome was changes in the Kansas City Cardiomyopathy Questionnaire at 3 and 12 months. The secondary endpoint was clinical events. RESULTS: The study included 184 patients (115 group I, 46 IIa, and 23 IIb). Groups I and IIa exhibited early and sustained improvements in the Kansas City Cardiomyopathy Questionnaire (group I: 18.9 points [95%CI, 15.7-22.1; P <.001] at 90 days, and 18.1 [95%CI, 14.9-21.4, P <.001] at 1 year; group IIa: 21.1 points [95%CI, 15.4-26.7; P <.001] and 19.5 [95%CI, 13.9-25.1; P <.001] respectively). In contrast, in group IIb there was no significant improvement at 90 days (P=.12), with improvement being significant only at 1 year (17.8 points, 95%CI, 5.9-29.6; P=.003). Over a median follow-up of 20.7 months, there were 63 (27.83%) deaths or heart failure admissions. Multivariate analysis showed a lower risk of events in group I vs IIb (HR, 0.28; 95%CI, 0.14-0.58; P <.001), and IIa vs IIb (HR, 0.24; 95%CI, 0.11-0.55; P <.001). CONCLUSIONS: Patients with persistently high CA125 despite diuretic therapy pre-TAVI showed slower functional recovery and poorer clinical outcomes after TAVI.

Chronotropic index and long-term outcomes in heart failure with preserved ejection fraction.

INTRODUCTION AND OBJECTIVES: Little is known about the usefulness of heart rate (HR) response to exercise for risk stratification in heart failure with preserved ejection fraction (HFpEF). Therefore, this study aimed to assess the association between HR response to exercise and the risk of total episodes of worsening heart failure (WHF) in symptomatic stable patients with HFpEF. METHODS: This single-center study included 133 patients with HFpEF (NYHA II-III) who performed maximal cardiopulmonary exercise testing. HR response to exercise was evaluated using the chronotropic index (CIx) formula. A negative binomial regression method was used. RESULTS: The mean age of the sample was 73.2± 10.5 years; 56.4% were female, and 51.1% were in atrial fibrillation. The median for CIx was 0.4 [0.3-0.55]. At a median follow-up of 2.4 [1.6-5.3] years, a total of 146 WHF events in 58 patients and 41 (30.8%) deaths were registered. In the whole sample, CIx was not associated with adverse outcomes (death, P=.319, and WHF events, P=.573). However, we found a differential effect across electrocardiographic rhythms for WHF events (P for interaction=.002). CIx was inversely and linearly associated with the risk of WHF events in patients with sinus rhythm and was positively and linearly associated with those with atrial fibrillation. CONCLUSIONS: In patients with HFpEF, CIx was differentially associated with the risk of total WHF events across rhythm status. Lower CIx emerged as a risk factor for predicting higher risk in patients with sinus rhythm. In contrast, higher CIx identified a higher risk in those with atrial fibrillation.

Effect of a home-based inspiratory muscle training programme on functional capacity in postdischarged patients with long COVID: the InsCOVID trial.

BACKGROUND: Fatigue and exercise intolerance are the most common symptoms in patients with long COVID. AIMS: This study aimed to evaluate whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in patients' long COVID after a previous admission due to SARS-CoV-2 pneumonia. METHODS: This study was a single-centre, blinded assessor, randomised controlled trial. Twenty-six patients with long COVID and a previous admission due to SARS-CoV-2 pneumonia were randomly assigned to receive either a 12-week IMT or usual care alone (NCT05279430). The physiotherapist and participants were not blinded. Patients allocated to the IMT arm were instructed to train at home twice daily using a threshold inspiratory muscle trainer and to maintain diaphragmatic breathing during the training session. The usual care arm received no intervention.The primary endpoint was the change in peak oxygen consumption (peakVO2). Secondary endpoints were changes in quality of life (QoL), ventilatory efficiency and chronotropic response during exercise (evaluated by chronotropic index-CIx- formula). We used linear mixed regression analysis for evaluating changes in primary and secondary endpoints. RESULTS: The mean age of the sample and time to first visit after discharge were 50.4±12.2 years and 362±105 days, respectively. A total of 11 (42.3%) were female. At baseline, the mean of peakVO2, ventilatory efficiency and CIx were 18.9±5 mL/kg/min, 29.4±5.2 and 0.64±0.19, respectively. The IMT arm improved their peakVO2 significantly compared with usual care (+Δ 4.46 mL/kg/min, 95% CI 3.10 to 5.81; p<0.001). Similar positive findings were found when evaluating changes for CIx and some QoL dimensions. We did not find significant changes in ventilatory efficiency. CONCLUSION: In long COVID patients with a previous admission due to SARS-CoV-2 pneumonia, IMT was associated with marked improvement in exercise capacity and QoL. TRIAL REGISTRATION NUMBER: NCT05279430.

Frailty and Hospitalization Burden in Patients With Chronic Heart Failure.

Frailty is associated with increased mortality and hospitalizations in patients with heart failure (HF). However, there is little evidence regarding the burden of morbidity. In this study, we aimed to assess the association between frailty and recurrent all-cause HF hospitalizations in patients with stable chronic HF. This was an observational and prospective study that enrolled HF outpatients followed in a specialized HF unit of a single tertiary care center from 2017 to 2019. Frailty was assessed by Fried criteria. Robustness, prefrailty, and frailty were defined as 0, 1 to 2, and ≥3, respectively. The independent association between frailty status and recurrent hospitalizations was assessed through Famoye's bivariate Poisson regression model, and risk estimates were expressed as incidence rate ratios (IRR). A total of 277 patients were included. The mean age was 74 ± 10 years, 118 were women (42.6%), and 131 patients (47.3%) had left ventricular ejection fraction ≥50. According to Fried's score 61 patients (22%) were robust, 95 patients (34%) were prefrail, and 121 patients (44%) were frail. After a median follow-up of 2.21 (1.6 to 2.8) years, 52 patients (19%) died. We registered 348 all-cause hospitalizations in 144 patients (52%) and 178 HF hospitalizations in 108 patients (39%). Compared with robust patients, frailty was associated with a higher risk of all-cause and HF recurrent hospitalizations in multivariable analysis (IRR 2.01, 95% confidence interval 1.14 to 3.57, p = 0.017 and IRR 2.25, 95% confidence interval 1.16-4.36, p = 0.016, respectively). In conclusion, in patients with chronic HF, frailty identifies patients with an increased risk of total and recurrent all-cause and HF hospitalizations.

Venous Leg Compression for Tissue Decongestion in Patients With Worsening Congestive Heart Failure.

Aims: Venous leg compression (VLC) with elastic bandages has been proposed as a potentially useful strategy for decreasing tissue congestion. We aimed to evaluate the effect of VLC on short-term changes on intravascular refill, assessed by inferior vena cava (IVC) diameter in patients with worsening heart failure (WHF) requiring parenteral furosemide. Additionally, we sought to evaluate whether early changes in IVC were related to short-term decongestion. Methods: This is a prospective study in which we included 20 consecutive ambulatory patients with WHF treated with subcutaneous furosemide and VLC for at least 72 h. The endpoints were (a) short-term changes in IVC, (b) the association between decongestion and 3-h IVC changes following VLC. Changes in continuous endpoints and their longitudinal trajectories were estimated with linear mixed regression models. All analyses were adjusted for multiple comparisons. Results: Following administration of subcutaneous furosemide and VLC, we found a significant increase in 3-h IVC diameter (ΔIVC = 1.6 mm, CI 95%: 0.7-2.5; p < 0.001), with a greater increase in those with baseline IVC≤21 mm (2.4 vs. 0.8 mm; p < 0.001). 3-h intravascular refill (increase in IVC≥2 mm) was associated with greater decongestion (natriuresis, weight, peripheral edemas, and dyspnea) in those with baseline IVC≤21 mm but not when IVC>21 mm (p < 0.05 for all comparisons). Conclusions: In this cohort of patients with congestive WHF treated with subcutaneous furosemide and VLC, we found a greater increase in short-term IVC in those with IVC ≤21 mm at baseline. In this subset of patients, a 3-h increase in IVC≥2 mm was associated with greater short-term decongestion.

Effect of a home-based inspiratory muscular training programme on functional capacity in patients with chronic COVID-19 after a hospital discharge: protocol for a randomised control trial (InsCOVID trial).

INTRODUCTION: Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID-19 after hospital discharge. Supervised exercise training programmes improve symptoms, but scarce research has been done on home-based exercise programmes on the maximal functional capacity for discharged symptomatic COVID-19 patients. This study evaluates whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in chronic COVID-19 after hospital admission. METHODS AND ANALYSIS: This single-centre, assessor-blinded randomised controlled trial, powered for superiority, seeks to evaluate maximal functional capacity as the primary endpoint. A total of 26 eligible patients with a previous admission for acute respiratory syndrome coronavirus 2 pneumonia (>3 months after hospital discharge) will be randomised (1:1) to receive a 12-week programme of IMT versus usual care alone. A blinded assessor will measure outcomes at baseline and after the intervention (12 weeks). An analysis of variance will be used to compare continuous outcomes among the two-intervention groups. As of 21 March 2022, eight patients have been enrolled. ETHICS AND DISSEMINATION: The research ethics committee (Comité Ético de Investigación con Medicamentos de l'Hospital Clínic Universitari de València) approved the protocol following the principles of the Declaration of Helsinki and national regulations (Approval Number: 021/226). Findings will be published in peer-reviewed journals and conference publications. TRIAL REGISTRATION NUMBER: NCT05279430.

Incidence, Treatment and Clinical Impact of Iron Deficiency in Chronic Heart Failure: A Longitudinal Analysis.

In patients with heart failure (HF), iron deficiency (ID) is a well-recognized therapeutic target; information about its incidence, patterns of iron repletion, and clinical impact is scarce. This single-centre longitudinal cohort study assessed the rates of ID testing and diagnosis in patients with stable HF, patterns of treatment with intravenous iron, and clinical impact of intravenous iron on HF rehospitalization risk. We included 711 consecutive outpatients (4400 visits) with stable chronic HF from 2014 to 2019 (median [interquartile range] visits per patient: 2 [2−7]. ID was defined as serum ferritin <100 µg/L, or 100−299 µg/L with transferrin saturation (TSAT) < 20%. During a median follow-up of 2.20 (1.11−3.78) years, ferritin and TSAT were measured at 2230 (50.7%) and 2183 visits (49.6%), respectively. ID was found at 846 (37.9%) visits, with ferritin and TSAT available (2230/4400), and intravenous iron was administered at 321/4400 (7.3%) visits; 233 (32.8%) patients received intravenous iron during follow-up. After multivariate analyses, iron repletion at any time during follow-up was associated with a lower risk of recurrent HF hospitalization (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.28−0.88; p = 0.016). Thus, ID was a frequent finding in patients with HF, and its repletion reduced the risk of recurrent HF hospitalizations.

Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2 ): a randomized clinical trial.

AIMS: This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n = 45) or placebo (n = 45). The primary outcome was a change in peak oxygen consumption (peakVO2 ) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO2 , 6MWT and MLHFQ were 13.2 ± 3.5 ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th-75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889-2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO2 significantly increased in patients on treatment with dapagliflozin (1 month: +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14-2.04; p = 0.021, and 3 months: +Δ 1.06 ml/kg/min, 95% CI 0.07-2.04; p = 0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints. CONCLUSIONS: Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO2 at 1 and 3 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04197635.

Hospitalization following an emergency-department visit for worsening heart failure: The role of left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: Patients with worsening heart failure (WHF) are frequently hospitalized. However, some of the patients with WHF are discharged from the emergency department without hospitalization. The factors influencing the decision of admission are heterogeneous and, in most cases, remain not well-defined. This study aimed to analyze whether left ventricular ejection fraction (LVEF) influences admission decisions following a visit to the emergency department for WHF. PATIENTS AND METHODS: This is a retrospective analysis of 3168 patients discharged from a hospitalization for acute heart failure in a single-center in Spain. During follow-up, visits to the emergency department for WHF, including those hospitalized (WHF-readmissions) and episodes of WHF directly discharged without hospitalization in 24h (WHF-DDWH), were recorded. The association between the LVEF categories (<50% and ≥50%) and recurrent WHF-DDWH was evaluated by negative binomial regression. Estimates of risk were expressed as incidence rate ratios (IRR). RESULTS: The mean age (SD) of the study sample was 73.5 (11.2) years, and 1658 (52.3%) showed LVEF>50%. At a median (percentile 25% to percentile 75%) follow-up of 2.7 (1.0-5.8) years, 3341 episodes of WHF in 1439 patients were recorded. Of them, we registered 743 episodes of WHF-DDWH in 468 patients (22.2%). Compared to patients with LVEF<50%, those with LVEF≥50% exhibited an adjusted increased risk of recurrent WHF-DDWH (IRR: 1.36, CI 95%: 1.13-1.62, p=0.001). CONCLUSIONS: Following an acute heart failure admission, patients with LVEF≥50% showed an increased risk of same-day discharge for WHF.

Efficacy and Safety of Subcutaneous Infusion of Non-formulated Furosemide in Patients with Worsening Heart Failure: a Real-World Study.

We aimed to evaluate the efficacy (short-term changes in surrogates of decongestion) and safety following the ambulatory administration of subcutaneous furosemide (SCF) in patients with WHF. Fifty-five ambulatory patients were treated with SCF administered by an elastomeric pump for at least 72 h. Surrogates of congestion were assessed at baseline, 72 h, and 30 days. Spot urinary sodium (uNa+) was assessed at baseline, 24-48-72 h, and 30 days. The median (IQI) of NT-proBNP and uNa+ at baseline was 5218 pg/mL (2856-10878) and 68±3 mmol/L, respectively. Following administration of SCF (median dose of 100 mg/daily), we found a sustained increase in uNa+ during the first 72 h of treatment compared to baseline, paralleled with evidence of decongestion at 72 h, and 30 days. No significant safety concerns were observed. SCF was an effective and safe diuretic strategy for outpatient congestion management. Non-formulated subcutaneous furosemide in patients with WHF. Efficacy and safety.

Effect of ß-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet ß-blockers are commonly used in HFpEF despite the lack of robust evidence. OBJECTIVES: This study aimed to evaluate the effect of ß-blocker withdrawal on peak oxygen consumption (peak Vo2) in patients with HFpEF and chronotropic incompetence. METHODS: This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with ß-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) ß-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo2 and percentage of predicted peak Vo2 (peak Vo2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. RESULTS: The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo2 and peak Vo2% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo2 and peak Vo2% increased significantly after ß-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively). CONCLUSIONS: ß-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. ß-blocker use in HFpEF deserves profound re-evaluation. (ß-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39).

Long-Term Prognostic Value of Cognitive Impairment on Top of Frailty in Older Adults after Acute Coronary Syndrome.

Frailty is a marker of poor prognosis in older adults after acute coronary syndrome. We investigated whether cognitive impairment provides additional prognostic information. The study population consisted of a prospective cohort of 342 older (>65 years) adult survivors after acute coronary syndrome. Frailty (Fried score) and cognitive function (Pfeiffer's Short Portable Mental Status Questionnaire-SPMSQ) were assessed at discharge. The endpoints were mortality or acute myocardial infarction at 8.7-year median follow-up. Patient distribution according to SPMSQ results was: no cognitive impairment (SPMSQ = 0 errors; n = 248, 73%), mild impairment (SPMSQ = 1-2 errors; n = 52, 15%), and moderate to severe impairment (SPMSQ ≥3 errors; n = 42, 12%). A total of 245 (72%) patients died or had an acute myocardial infarction, and 216 (63%) patients died. After adjustment for clinical data, comorbidities, and Fried score, the SPMSQ added prognostic value for death or myocardial infarction (per number of errors; HR = 1.11, 95%, CI 1.04-1.19, p = 0.002) and death (HR = 1.11, 95% 1.03-1.20, p = 0.007). An SPMSQ with ≥3 errors identified the highest risk subgroup. Geriatric conditions (SPSMQ and Fried score) explained 19% and 43% of the overall chi-square of the models for predicting death or myocardial infarction and death, respectively. Geriatric assessment after acute coronary syndrome should include both frailty and cognitive function. This is particularly important given that cognitive impairment without dementia can be subclinical and thus remain undetected.

Randomized Comparison of Exercise Intervention Versus Usual Care in Older Adult Patients with Frailty After Acute Myocardial Infarction.

BACKGROUND: Older adult patients with frailty are rarely involved in rehabilitation programs after myocardial infarction. Our aim was to investigate the benefits of exercise intervention in these patients. METHODS: A total of 150 survivors after acute myocardial infarction, ≥70 years and with pre-frailty or frailty (Fried scale ≥1 points), were randomized to control (n = 77) or intervention (n = 73) groups. The intervention consisted of a 3-month exercise program, under physiotherapist supervision, followed by an independent home-based program. The main outcome was frailty (Fried scale) at 3 months and 1 year. Secondary endpoints were clinical events (mortality or any readmission) at 1 year. RESULTS: Mean age was 80 years (range = 70-96). In the intervention group, 44 (60%) out of 73 patients participated in the program and 23 (32%) completed it. Overall, there was a decrease in the Fried score in the intervention group at 3 months, with no effect at 1 year. However, in the intention-to-treat analysis, such change did not achieve statistical significance (P = 0.110). Only treatment comparisons made among the subgroups that participated in (P = 0.033) and completed (P = 0.018) the program achieved statistical significance. There were no differences in clinical events. Worse Fried score trajectory along follow-up increased mortality risk (hazard ratio [HR] = 2.38, 95% confidence interval [CI] 1.24-4.55, P = 0.009) CONCLUSIONS: Recruitment and retention for a physical program in older adult patients with frailty after myocardial infarction was challenging. Frailty status improved in the subgroup that participated in the program, although this benefit was attenuated after shifting to a home-based program. A better frailty trajectory might influence midterm prognosis. (ClinicalTrials.govNCT02715453).

Frailty Tools for Assessment of Long-term Prognosis After Acute Coronary Syndrome.

OBJECTIVE: To evaluate the 5 components of the Fried frailty phenotype (self-reported unintentional weight loss, physical activity questionnaire, gait speed, grip strength, and self-reported exhaustion) for long-term outcomes in elderly survivors of acute coronary syndrome. METHODS: A total of 342 consecutive patients (from October 1, 2010, to February 1, 2012) were included. The 5 components of the Fried score and albumin concentration, as malnutrition index, were assessed before hospital discharge. Patients were followed up until April 2020 (median follow-up, 8.7 years). The end point was postdischarge all-cause mortality. RESULTS: Mean ± SD age was 77±7 years and mean ± SD Fried score was 2.0±1.1 points. A total of 216 (63%) patients died. After adjusting for clinical covariates, the Fried phenotype was associated with mortality (per points, hazard ratio [HR], 1.35; 95% CI, 1.17 to 1.57; P<.001). Among Fried components, physical activity (HR, 2.21; 95% CI, 1.34 to 3.65; P=.002) and gait speed (HR, 1.77; 95% CI, 1.29 to 2.43; P<.001) were the deficits independendtly associated with mortality. Albumin level provided further prognostic information (per increase in g/dL; HR, 0.63, 95% CI, 0.45 to 0.88; P=.007). The model adding the components of the Fried score and albumin level to the clinical model showed the highest risk reclassification (integrated discrimination improvement, 0.040; 95% CI, 0.018 to 0.075; P=.001; continuous net reclassification improvement, 0.291; 95% CI, 0.132 to 0.397; P=.001) in comparison with the model using clinical covariates alone. CONCLUSION: Frailty assessment using the Fried phenotype has prognostic value for long-term mortality in elderly survivors of acute coronary syndrome. Physical activity and gait speed are the predictive components of the Fried score. Albumin level provides incremental prognostic information.

Clinical profile and 1-year clinical outcomes of super elderly patients admitted with acute heart failure.

INTRODUCTION: There is scarce information about the clinical profile and prognosis of acute heart failure (AHF) at the extreme ranges of age. We aimed to evaluate the 1-year death (all-cause mortality and HF-death) and HF-rehospitalizations of patients ≥85 years admitted for AHF. METHODS: We prospectively evaluated a cohort of 3054 patients admitted with AHF from 2007 to 2018 in a third-level center. Age was categorized per 10-year categories (<65 years; 65-74 years, 75-84 years, and ≥85 years). The risk of mortality and HF-rehospitalizations across age categories was evaluated with Cox regression analysis and Cox regression adapted for competing events as appropriate. RESULTS: The mean age was 73.6 ± 11.2 years, 48.9% were female, and 52.8% had preserved left ventricular ejection fraction (HFpEF). A total of 414 (13.6%) patients were ≥85 years. Among this group of age, female sex and HFpEF phenotype were more frequent. At 1-year follow-up 667 all-cause deaths (22,1%), 311 HF-deaths (10.1%) and 693 HF-hospitalizations (22,7%) were recorded. After multivariable adjustment, and compared to patients <65 years, a stepwise increased risk of all-cause mortality and HF-death was found for each decade increase in age, especially for patients ≥85 years (HR=3.47; 95% CI: 2.49 - 4.84, p<0.001, HR=3.31; 95% CI: 1.95 - 5.63; p<0.001, respectively). This subgroup of patients also showed an increased risk of HF-rehospitalization (HR=1.58; 95% CI: 1.16 - 2.16, p=0.004). CONCLUSIONS: Super elderly patients admitted with AHF showed a dramatically increased risk of 1-year death. This subset of patients also shown an increased risk of 1-year HF-readmission.

Beta-blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve-HR trial).

BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients. HYPOTHESIS: We postulate beta-blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short-term effect of beta-blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI. METHODS: This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II-III, chronic treatment with beta-blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD ± 2.0)] of 52 patients is necessary to test our hypothesis. RESULTS: Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020. CONCLUSIONS: Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta-blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03871803.

Relation of Low Lymphocyte Count to Frailty and its Usefulness as a Prognostic Biomarker in Patients >65 Years of Age With Acute Coronary Syndrome.

Low lymphocyte count, as a marker of inflammation and immunosuppression, may be useful for identifying frail patients. In this work, we aimed to evaluate the association between low-relative lymphocyte count (Lymph%) and frailty status in patients >65 years old with acute coronary syndromes (ACS), and whether Lymph% is associated with morbimortality beyond standard prognosticators and frailty. In this prospective observational study, we included 488 hospital survivors of an episode of an ACS >65 years old. Total and differential white blood cells and frailty status were assessed at discharge. Frailty was evaluated using the Fried score at discharge and defined as Fried≥3. The independent association between Lymph% and Fried≥3 was evaluated by multivariate logistic regression analysis. The associations between Lymph% with long-term all-cause mortality and recurrent admission were evaluated with Cox regression and shared frailty regression, respectively. The mean age of the sample was 78 ± 7 years and 41% were females. The median (interquartile range) of the Lymph% was 21% (15 to 27) and 41% showed Fried≥3. In multivariate analysis, Lymph% was inversely related to the odds of frailty with an exponential increase risk from values below 15% (p = 0.001). Likewise, Lymph% was inverse and independently associated with a higher risk of long-term mortality (p = 0.011), recurrent all-cause (p = 0.020), and cardiovascular readmissions (p = 0.024). In conclusion, in patients >65 years with a recent ACS, low Lymph% evaluated at discharge is associated with a higher risk of frailty. Low Lymph% was also associated with a higher risk of long-term mortality and recurrent admissions beyond standard prognosticators and Fried score.

Sex-differential effect of frailty on long-term mortality in elderly patients after an acute coronary syndrome.

BACKGROUND: The potential sex-differential effect of frailty in patients with acute coronary syndromes (ACS) has not been well-evaluated. We sought to examine the sex-differential association between frailty status on long-term mortality in elderly patients with an ACS. METHODS AND RESULTS: This is a prospective observational single-center study that included 488 elderly patients (>65 years) hospitalized for ACS who survived the index hospitalization. Multivariate Cox regression was used to determine the association among the exposures (interaction of sex with Fried score and sex with Fried ≥ 3) and all-cause mortality. The mean age of the sample was 78 ±â€¯7 years; 41% were female and the median Fried score was higher in women [3 (2-3) vs. 2 (1-2) points, p < 0.001]. At a median follow-up of 3.12 years (IQR:1.38-5.13), 182 deaths (37.3%) were registered. The association of Fried ≥ 3 with mortality varied across sex (p-value for interaction = 0.022). In males, Fried ≥ 3 was independently associated with all-cause death (HR = 1.89; CI 95%:1.25-2.85, p = 0.003). However, it showed a neutral effect on women (HR = 0.92; CI 95%:0.57-1.49, p = 0.726). CONCLUSIONS: In this work, we found that the frailty status assessed by Fried score was independently associated with mortality in elderly males but not in females with ACS.