Combinational Diuretics in Heart Failure.

PURPOSE OF REVIEW: Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy. RECENT FINDINGS: Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted.

Association between natriuretic peptides and C-reactive protein with frailty in heart failure: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) and frailty are accompanied by a bidirectional relationship, sharing common risk factors including elevated levels of natriuretic peptides and inflammation. The aim of this study was to compare biomarkers associated with poor clinical outcomes, that is, plasma brain natriuretic peptide (BNP), N-terminal-pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) in patients with HF and frailty vs. patients with HF without frailty. METHODS: From inception until July 2023, PubMed, Scopus, Web of Science, and Cochrane Library a systematic literature search was conducted. To evaluate whether frailty is linked with greater levels of BNP, NT-proBNP, and CRP, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42023446607). RESULTS: Fifty-three studies were included in this systematic review and meta-analysis. Patients with HF and frailty displayed significantly higher levels of BNP (k = 11; SMD: 0.53, 95%CI 0.30-0.76, I2 = 86%, P < 0.01), NT-proBNP (k = 23; SMD: 0.33, 95%CI 0.25-0.40, I2 = 72%, P < 0.01), and CRP (k = 8; SMD: 0.30, 95%CI 0.12-0.48, I2 = 62%, P < 0.01) vs. patients with HF without frailty. Using meta-regression, body mass index (BMI) and age were deemed potential moderators of these findings. CONCLUSIONS: Frailty in HF is linked to increased concentrations of BNP, NT-proBNP, and CRP, which have been epidemiologically associated with adverse outcomes. The increased risk of NYHA III/IV classification further emphasizes the clinical impact of frailty in this population.

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

Prevalence of Sarcopenia in chronic heart failure, and modulating role of Chronic Kidney Disease.

OBJECTIVES: Sarcopenia, heart failure (HF) and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with heart failure, possible causative factors and the additive factor of CKD. METHODS: A cross-sectional analysis of 1420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient's medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Two-year mortality was also collected. RESULTS: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73-0.93), and lower Short Physical Performance Battery score (OR, 0.81; 95% CI, 0.69-0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher two-year cardiovascular mortality risk (p=0.047). CONCLUSION: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.

Short physical performance battery is not associated with falls and injurious falls in older persons: longitudinal data of the SCOPE project.

INTRODUCTION: Falls and fall-related injuries in older persons are a major public health problem. Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. METHODS: For this sub-study of the SCOPE project participants reporting no falls at baseline, and survey data on falls at the 12-month and 24-month follow-up were included. Participant´s characteristics were assessed during the baseline interview and medical examinations. Falls as well as injurious falls and fall circumstances were obtained self-reported. SPPB and its association with fallers vs. no fallers at 12 and at 24 months were studied with logistic regression models. RESULTS: The 1198 participants had a median age of 79 years (77-82), and a median SPPB of 10 (8-11), with a 52.5% of female. A total of 227 and 277 falls (12- and 24- month visits, respectively) were reported. In the crude model, the SPPB sum scores (p < 0.001) as well as most single item scores were significant different between fallers and non-fallers over time. However, the association was attenuated in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass [e.g., 12 months; OR 0.94 (0.87-1.02)]. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p < 0.01) after 24 months. CONCLUSION: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. TRIAL REGISTRATION: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov (NCT02691546).

Diagnosis of heart failure with preserved ejection fraction: a systematic narrative review of the evidence.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a common condition in clinical practice, affecting more than half of patients with HF. HFpEF is associated with morbidity and mortality and with considerable healthcare resource utilization and costs. Therefore, early diagnosis is crucial to facilitate prompt management, particularly initiation of sodium-glucose co-transporter 2 inhibitors. Although European guidelines define HFpEF as the presence of symptoms with or without signs of HF, left ventricular EF ≥ 50%, and objective evidence of cardiac structural and/or functional abnormalities, together with elevated natriuretic peptide levels, the diagnosis of HFpEF remains challenging. First, there is no clear consensus on how HFpEF should be defined. Furthermore, diagnostic tools, such as natriuretic peptide levels and resting echocardiogram findings, are significantly limited in the diagnosis of HFpEF. As a result, some patients are overdiagnosed (i.e., elderly people with comorbidities that mimic HF), although in other cases, HFpEF is overlooked. In this manuscript, we perform a systematic narrative review of the diagnostic approach to patients with HFpEF. We also propose a comprehensible algorithm that can be easily applied in daily clinical practice and could prove useful for confirming or ruling out a diagnosis of HFpEF.

Musculoskeletal co-morbidities in patients with transthyretin amyloid cardiomyopathy: a systematic review.

The prevalence of transthyretin-associated amyloidosis cardiomyopathy (ATTR-CM) has grown because of newer non-invasive diagnosis tools. Detecting the presence of extra-cardiac ATTR manifestations such as musculoskeletal pathologies considered 'red flags', when there is minimal or non-cardiac clinical involvement is primordial to carry out an early diagnosis. The aim of this systematic review is to examine the prevalence of musculoskeletal, ATTR-deposition-related co-morbidities in patients already diagnosed with ATTR-CM, specifically carpal tunnel syndrome, ruptured biceps tendon, spinal stenosis, and trigger finger. We performed a systematic review using PRISMA guidelines. Inclusion criteria were all studies in English and Spanish language and participants had to be patients diagnosed with ATTR-CM, by any diagnostic method, with the musculoskeletal co-morbidities subject of this review. The quality of the studies was based on the Risk of Bias Tool. This systematic review included 22 studies for final analysis. Carpal tunnel syndrome is reported in 21 studies, brachial biceps tendon rupture is reported in three, and spinal stenosis in eight studies. No articles that accomplished all the inclusion criteria for trigger finger were found. Regarding to the quality of the studies, all of them were categorized as being of high and moderate quality. The frequent association between ATTR-CM and carpal tunnel syndrome, ruptured biceps tendon, and lumbar spinal is confirmed, and the onset of these co-morbidities usually precedes the diagnosis of by years. This association defines them as red flags that should be search proactively due to the current treatment possibilities and the severity of the presentation of cardiac amyloidosis.

Kidney function and other associated factors of sarcopenia in community-dwelling older adults: The SCOPE study.

AIM: Sarcopenia is associated with several factors and medical conditions among older adults, though previous research has shown limitations and inconsistencies, especially regarding chronic kidney disease (CKD). We investigated the clinical and laboratory variables associated with sarcopenia and severe sarcopenia in older adults, focusing on kidney function measures. METHODS: Data from community-dwelling adults aged ≥75 years participating in the SCOPE multicenter prospective cohort study were assessed cross-sectionally. Comprehensive geriatric assessment was conducted; sociodemographic and lifestyle factors, clinical variables and comorbidities, anthropometric and bioelectrical impedance analysis, blood and urine laboratory variables were collected. EWGSOP2 revised criteria were used to define sarcopenia and its severity. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and non-creatinine-based equations, and CKD stages were defined accordingly. RESULTS: 1420 participants were included, prevalence of sarcopenia was 10.6 %, and 6 % had severe sarcopenia. Multivariate logistic regression analysis showed that age [OR =1.14; 95 %CI (1.09-1.19)], body mass index (BMI) [0.83 (0.79-0.88)], disability performing instrumental activities of daily living (IADL) [2.61 (1.69-4.06)], Mini Mental State Examination (MMSE) score <24 [2.75 (1.62-4.67)], osteoporosis [2.39 (1.55-3.67)], and stage 4 CKD defined by CKD-EPIBTP-B2M, a non-creatinine-based eGFR equation [2.88 (1.11-7.49)], were independently associated with sarcopenia; as were specifically with severe sarcopenia, with more pronounced associations. CONCLUSIONS: In community-dwelling older adults, sarcopenia is a relevant condition and is associated with severe CKD, older age, IADL, cognitive impairments, osteoporosis and low BMI. These factors should be assessed for proper identification and management of older patients with sarcopenia, and even more so with severe sarcopenia.

Diabetes and factors associated with cognitive and functional decline. The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Type 2 diabetes mellitus (DM) in older people is a heterogeneous condition that exhibits differential characteristics in comparison with younger adults. DM increases the risk of disability, is associated with dementia and loss of function, and cognition may often be interrelated and more pronounced in older patients with DM than in those without. AIMS: Our aim was to evaluate the incidence of functional and/or cognitive impairment in older adults with and without DM, and its associated factors in DM participants. METHODS: A 2-year prospective analysis was conducted in a European multicenter prospective cohort (SCOPE study). Older community-dwelling adults (aged ≥ 75 years) underwent a comprehensive geriatric assessment. New functional and/or cognitive decline was explored. RESULTS: Of 1611 participants, 335 (22.0%) had DM at baseline. The percentage of participants scoring at least one ADL impairment and/or cognitive impairment (MMSE < 24) was similar in both groups (9.6%). Factors associated with any new disability in participants with DM in the multivariate analysis were female sex (OR 3.28, 95% CI 1.42-7.56), history of stroke (OR 4.58, 95% CI 1.64-12.7), and greater IADL dependency (OR 1.08 95% CI 1.02-1.15). DISCUSSION: Association between DM and cognitive or functional decline in outpatients of 75 years and older was not found, but factors such as female gender, history of stroke, and IADL dependency could be related. CONCLUSION: Decline in functional and cognitive status of community-dwelling older adults with DM was similar to participants without DM in a short period of 2 years of follow-up, though several clinical factors may increase its risk in this population.

Machine learning for the development of diagnostic models of decompensated heart failure or exacerbation of chronic obstructive pulmonary disease.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are two chronic diseases with the greatest adverse impact on the general population, and early detection of their decompensation is an important objective. However, very few diagnostic models have achieved adequate diagnostic performance. The aim of this trial was to develop diagnostic models of decompensated heart failure or COPD exacerbation with machine learning techniques based on physiological parameters. A total of 135 patients hospitalized for decompensated heart failure and/or COPD exacerbation were recruited. Each patient underwent three evaluations: one in the decompensated phase (during hospital admission) and two more consecutively in the compensated phase (at home, 30 days after discharge). In each evaluation, heart rate (HR) and oxygen saturation (Ox) were recorded continuously (with a pulse oximeter) during a period of walking for 6 min, followed by a recovery period of 4 min. To develop the diagnostic models, predictive characteristics related to HR and Ox were initially selected through classification algorithms. Potential predictors included age, sex and baseline disease (heart failure or COPD). Next, diagnostic classification models (compensated vs. decompensated phase) were developed through different machine learning techniques. The diagnostic performance of the developed models was evaluated according to sensitivity (S), specificity (E) and accuracy (A). Data from 22 patients with decompensated heart failure, 25 with COPD exacerbation and 13 with both decompensated pathologies were included in the analyses. Of the 96 characteristics of HR and Ox initially evaluated, 19 were selected. Age, sex and baseline disease did not provide greater discriminative power to the models. The techniques with S and E values above 80% were the logistic regression (S: 80.83%; E: 86.25%; A: 83.61%) and support vector machine (S: 81.67%; E: 85%; A: 82.78%) techniques. The diagnostic models developed achieved good diagnostic performance for decompensated HF or COPD exacerbation. To our knowledge, this study is the first to report diagnostic models of decompensation potentially applicable to both COPD and HF patients. However, these results are preliminary and warrant further investigation to be confirmed.