Impact of Frailty on Heart Failure Prognosis: Is Sex Relevant?

PURPOSE OF REVIEW: Heart failure (HF) is one of the most frequent causes of hospital admission in elderly patients, especially in women, who present a high prevalence of geriatric syndromes like frailty. Studies have suggested that frailty and its impact may also differ between males and females. Understanding how frailty may differently affect HF patients depending on sex is therefore imperative for providing personalized care. The aim of this review is to summarize the role of sex in the prognostic impact of frailty in HF patients. RECENT FINDINGS: Numerous studies have identified frailty as a significant predictor of all-cause mortality and hospital readmissions. A recent study of elderly HF out-patients demonstrated that while women had a higher prevalence of frailty, it was an independent predictor of mortality and readmission only in men. Moreover, another study revealed that physical frailty was associated with time to first clinical event among men but not among women. These results raise the question about why frailty affects differently HF prognosis in men and women. Women with HF present a higher prevalence of frailty, especially when it is considered as physical decline. Nevertheless, frailty affects differently HF prognosis in men and women. Women with HF present lower mortality than men and frailty is related with prognosis only in men. The different severity of HF between men and women and other hormonal, psychosocial, and clinical factors might be involved in this fact.

Prognostic effect of systematic geriatric assessment on patients with acute heart failure.

AIMS: Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6 months. METHODS AND RESULTS: We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6 months after discharge. We enrolled 202 patients. The mean age was 73 ± 12.32 years, and 100 (49.5%) of the patients were elderly (>75 years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL ≥ 3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88 ± 1.48). Dependence (Barthel < 100) was observed in 65 (32.2%) patients (mean Barthel index: 94.38 ± 11.21). Frailty and dependence showed a significant association with both prognostic events at 1 and 6 months. In the multivariable analysis, frailty was associated with higher mortality at 1 month [hazard ratio (HR) 12.61, 95% confidence interval (CI) 1.57-101.47, P = 0.017] but not at 6 months (HR 2.25, 95% CI 0.61-8.26, P = 0.224) or with the combined endpoint at neither 1 month (HR 1.64, 95% CI 0.54-5.03, P = 0.384) nor 6 months (HR 1.35, 95% CI 0.75-2.46, P = 0.320). Dependence was related to higher mortality at 1 month (HR 13.04, 95% CI 1.62-104.75, P = 0.016) and 6 months (HR 7.18, 95% CI 1.99-25.86, P = 0.003) and to higher incidence of the combined event at 1 month (HR 5.93, 95% CI 1.63-21.50, P = 0.007) and 6 months (HR 2.62, 95% CI 1.49-4.61, P = 0.001). CONCLUSIONS: In AHF patients, frailty and dependence implied a worse prognosis, rising mortality, readmissions, and ER visits for AHF.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Diagnosis and Management of Malnutrition in Patients with Heart Failure.

Heart failure is a disease with an increasingly greater prevalence due to the aging population, the development of new drugs, and the organization of healthcare processes. Malnutrition has been identified as a poor prognostic factor in these patients, very often linked to frailty or to other comorbidities, meaning that early diagnosis and treatment are essential. This paper reviews some important aspects of the pathophysiology, detection, and management of malnutrition in patients with heart failure.

Fast systematic geriatric assessment in acute heart failure patients admitted in Cardiology.

BACKGROUND: Heart failure prevalence is increasing in elder adults. These patients usually present geriatric syndromes, especially frailty. The effect of frailty on heart failure is under discussion but there are few data about the clinical characterization of frail patients who are admitted for acute heart failure decompensation. OBJECTIVE: The purpose of this study was to study the differences in clinical baseline variables and geriatric scales between frail and non-frail patients admitted to the Cardiology unit via the Emergency Department for acute heart failure. METHODS: We enrolled all patients with acute heart failure who were admitted to the Cardiology unit from the Emergency Department of our hospital from July 2020 through May 2021. A multidimensional and comprehensive geriatric assessment was performed at the moment of admission. We studied differences in baseline variables and geriatric scales according to the frailty status determined by the FRAIL scale. RESULTS: A total of 202 patients were included. In the whole population, 68 (33.7%) patients presented frailty defined by a FRAIL score ≥ 3. The frail patients were older (80±9 vs. 69±12 years; p<0.001), and had a worse quality of life (58.31±12.18 vs.39.26±13.71 points; p<0.001) according to the Minnesota scale, presented high comorbidity (47 (69.1%) vs. 67 (50.4%) patients; p = 0.011) defined as ≥3 points according to the Charlson scale and were more dependent (40 (58.8%) vs. 25 (18.8%) patients; p<0.001) according to the Barthel scale. The frail patients presented higher MAGGIC risk scores (24.09±4.99 vs. 18.89±6.26; p<0.001). Despite this adverse profile, the treatments prescribed during the admission and at the hospital discharge were similar. CONCLUSIONS: The prevalence of geriatric syndromes, especially frailty, is very high in patients admitted for acute heart failure. Frail patients with acute heart failure had an adverse clinical profile with more prevalence of concomitant geriatric syndromes. Therefore, we consider that a geriatric assessment should be performed during the admission of acute heart failure patients to improve care and attention.

Differences in the prognostic value of the electrocardiographic pattern after cardiac resynchronization therapy according to age.

OBJECTIVES: In this cohort study, we analyzed if a specific pattern in three leads of the electrocardiogram (Rs in V1, Qr in aVL, or rS in I) was associated with outcomes after cardiac resynchronization therapy (CRT) depending on age. METHODS: Patients with CRT devices were included from January 2012 to April 2019. We divided the sample into 2 groups, those with age ≥ 75 years old and those younger. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalization at 1 year. RESULTS: We included 111 patients. Patients older than 75 years (26.1%, n = 29) had a significantly higher rate of hypertension and atrial fibrillation and received less frequently optimal medical therapy. The patterns were observed in 32 (39.0%) younger patients and 11 (37.9%) older patients. Patients who presented any of them had a lower incidence of the primary endpoint in the younger group (0 vs. 14%, p = 0.029), but not in the older group (9.1 vs. 27.8%, p = 0.24). The presence of a basal QRS duration greater than 160 ms was associated with a higher rate of the primary endpoint in the elderly (50 vs. 13%, p = 0.015), but not in the younger group (16.7 vs. 7.1%, p = 0.254). CONCLUSIONS: The presence of the selected patterns after CRT is associated with a lower incidence of all-cause death and hospitalization for HF in patients younger than 75 years, but not in those older than 75 years. Conversely, baseline QRS duration was associated with worse outcomes in older patients, but not in the younger group.

Utility of Genetic Testing in Patients with Transthyretin Amyloid Cardiomyopathy: A Brief Review.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed condition. Although wild-type transthyretin amyloidosis (ATTRwt) is the most common ATTR-CM, hereditary transthyretin amyloidosis (ATTRv) may also occur. Currently, genetic testing for transthyretin pathogenic variants is recommended for patients with a confirmed clinical diagnosis of ATTR-CM. In fact, confirmation of this autosomal dominant pathogenic variant prompts genetic counselling and allows early identification of affected relatives. Additionally, in the presence of an ATTR-CM-associated polyneuropathy, specific drugs targeting transthyretin can be used. In this paper, we review the utility of genetic testing for the detection of pathogenic variants among patients harboring ATTR-CM and its impact on the natural history of the disease.

A Differential Profile of Biomarkers between Patients with Atrial Fibrillation and Healthy Controls.

Atrial fibrillation (AF) is explained by anatomical and electrophysiological changes in the atria determined by high pressure, dilatation, infiltration and inflammation in the myocardium. There are some biomarkers implicated in these processes, namely, NT-proBNP, high sensitivity troponin (Hs-Tn), urate, galectin-3, ST2, C reactive protein and fibrinogen. The aim of this study was to assess differences in these biomarkers between patients with AF and healthy controls. We designed a cross-sectional study consecutively including all patients undergoing electrical cardioversion in our hospital for persistent AF and matched healthy controls. We included 115 patients with persistent non-valvular AF and 33 healthy subjects. The biomarkers NT-proBNP, ST2 and Hs-Tn T were significantly related to the presence of AF (1054 ± 833.30 vs. 58.31 ± 59.40, p < 0.001; 35.43 ± 15.89 vs. 27.43 ± 10.95, p < 0.001 and 10.25 ± 6.11 vs. 8.42 ± 6.85, p < 0.001, respectively). NT-proBNP was the best biomarker differentiating AF patients (area under the curve 0.995). The best NT-proBNP cut-off point to differentiate AF was 102 pg/mL; for Hs-Tn T it was 11.5 ng/L and for ST2 it was 37.7 ng/mL. It is possible that these biomarkers intervene at the onset of AF and have no role in AF maintenance.

Comorbidity and Prognosis in Octogenarians with Infective Endocarditis.

Background. Infective endocarditis (IE) in older patients is associated with a high morbidity, mortality, and functional impairment. The purpose of this study was to describe the current profile of IE in octogenarians and to analyze the prognostic impact of baseline comorbidities in this population. Methods. Patients ≥ 80 years and definite IE from the Spanish IE Prospective Database were included. The effect of Charlson Comorbidity Index (CCI) on in-hospital and 12-month mortality was analyzed. Results. From 726 patients, 357 (49%) had CCI ≥ 3 and 369 (51%) CCI < 3. A total of 265 patients (36.6%) died during hospital admission and 338 (45.5%) during 1-year follow-up. CCI ≥ 3 was an independent predictor of in-hospital and 1-year mortality (odds ratio 1.46, 95% confidence interval 1.07−1.99, p = 0.017; hazard ratio 1.34, 95% confidence interval 1.08−1.66, p = 0.007, respectively). Surgical management was less common in patients with high comorbidity (CCI ≥ 3 68 [19.0%] vs. CCI < 3 112 ((30.4%) patients, p < 0.01). From 443 patients with surgical indication, surgery was only performed in 176 (39.7%). Patients with surgical indication treated conservatively had higher mortality than those treated with surgery (in-hospital mortality: 147 (55.1%) vs. 55 (31.3%), p < 0.001), (1-year mortality: 172 (64.4%) vs. 68 [38.6%], p < 0.001). Conclusion. About half of octogenarians with IE had high comorbidity with CCI ≥ 3. CCI ≥ 3 was a strong independent predictor of in-hospital and 1-year mortality. Our data suggest that the underperformance of cardiac surgery in this group of patients might have a role in their poor prognosis.

Antithrombotic Therapy in Elderly Patients with Acute Coronary Syndromes.

The treatment of acute coronary syndrome (ACS) in elderly patients continues to be a challenge because of the characteS.G.B.ristics of this population and the lack of data and specific recommendations. This review summarizes the current evidence about critical points of oral antithrombotic therapy in elderly patients. To this end, we discuss the peculiarities and differences reported referring to dual antiplatelet therapy (DAPT) in ACS management in elderly patients and what might be the best option considering these population characteristics. Furthermore, we analyze antithrombotic strategies in patients with atrial fibrillation (AF), with a particular focus on those cases that also present coronary artery disease (CAD). It is imperative to deepen our knowledge regarding the management of these challenging patients through real-world data and specifically designed geriatric studies to help resolve the questions remaining in their disease management.

Infective Endocarditis in the Elderly: Challenges and Strategies.

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term "elderly" corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population.

Genetic susceptibility to telomere shortening through the rs2293607 polymorphism is associated with a greater risk of alcohol use disorder.

Telomere shortening is usually considered a biomarker of ageing. Harmful alcohol use promotes accelerated biological ageing and alcohol use disorders (AUDs) are associated with short telomere length (TL). This study was conducted to examine the relationship of TL to AUD and determine whether single nucleotide polymorphisms (SNPs) in TERC and TERT modulate this association. For this purpose, we genotyped TERC SNPs rs2293607, rs12696304, and rs16847897 and TERT SNPs rs2735940, rs2736100, and rs2736098 in 308 male patients with AUD and 255 sex-matched healthy controls and measured TL in a subset of 99 patients and 99 controls paired by age and smoking status. Our results showed that the mean TL was shorter in patients with AUD than in controls. The area under the ROC curve was 0.70 (P < 0.001). The GG genotype of TERC rs2293607 was more common among patients with AUD than among controls (9.8% vs. 5.1%; P = 0.038). No difference was found for the other SNPs. Carriers of the GG genotype of rs2293607 had shorter telomeres than did allele A carriers. In conclusion, patients with AUD had shorter telomeres. Genetic susceptibility to telomere shortening through the rs2293607 SNP is associated with a greater risk of AUD.

Differences According to Age in the Diagnostic Performance of Cardiac Biomarkers to Predict Frailty in Patients with Acute Heart Failure.

Frailty has traditionally been studied in the elderly population but scarcely in younger individuals. The objective of the present study is to analyze differences according to age in the diagnostic performance of cardiac biomarkers to predict frailty in patients admitted to the hospital for acute heart failure (AHF). A frailty assessment was performed with the SPPB and FRAIL scales (score > 3). We included 201 patients who were divided according to age: those older and younger than 75 years. In the younger group, no biomarker was related to the presence of frailty. This was mainly determined by age and comorbidities. In the elderly group, NT-proBNP was significantly related to the presence of frailty, but none of the baseline characteristics were. The best cut-off point in the elderly group for NT-proBNP was 4000 pg/mL. The area under the curve (AUC) for proBNP for frailty detection was 0.62 in the elderly. Another similar frailty scale, the SPPB, also showed a similar AUC in this group; however, adding the NT-proBNP (one point if NT-proBNP < 4000 pg/mL), it showed a slightly higher yield (AUC 0.65). The addition of biomarkers could improve frailty detection in members of the elderly population who are admitted to the hospital for AHF.

The Role of Galectin-3 and ST2 in Cardiology: A Short Review.

Galectin-3 is a lectin that binds beta-galactosides. It is involved in cardiac remodeling and fibrosis through the activation of macrophages and fibroblasts. ST2 is secreted by myocardial cells due to cardiac overload. These two biomarkers have been traditionally studied in the field of heart failure to guide medical therapy and detect the progression of the disease. Nevertheless, there are novel evidences that connect galectin-3 and ST2 with coronary heart disease and, specifically, with atrial fibrillation. The aim of this article is to concisely review the diagnostic and prognostic role of galectin-3 and ST2 in different cardiac diseases.

sST2 and Galectin-3 genotyping in patients with persistent atrial fibrillation.

Genotyping of ST2 and galectin-3 in atrial fibrillation (AF) is not well analyzed. The aim of our study was to analyze the possible relationship between levels of sST2 and galectin-3 and three polymorphisms in patients with AF. We included 125 patients with persistent AF undergoing electric cardioversion. We analyzed sST2 and galectin-3 levels and three polymorphisms in peripheral blood samples. Rs2274273 was significantly related with levels of galectin-3. Rs1558648 was associated with levels of sST2 but rs13019803 were not. None of the polymorphisms were connected to the variation of biomarkers levels during the follow up. We found a relationship between rs2274273 and galectin-3 levels and rs1558648 and sST2 levels in patients with AF.

Prognostic Value of Late Gadolinium Enhancement for the Prediction of Cardiovascular Outcomes in Dilated Cardiomyopathy: An International, Multi-Institutional Study of the MINICOR Group.

BACKGROUND: Dilated cardiomyopathy is associated with increased risk of major cardiovascular events. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging is a unique tissue-based marker that, in single-center studies, suggests strong prognostic value. We retrospectively studied associations between LGE presence and adverse cardiovascular events in patients with dilated cardiomyopathy in a multicenter setting as part of an emerging global consortium (MINICOR [Multi-Modal International Cardiovascular Outcomes Registry]). METHODS: Consecutive patients with dilated cardiomyopathy referred for cardiac magnetic resonance (2000-2017) at 12 institutions in 4 countries were studied. Using multivariable Cox proportional hazard and semiparametric Fine and Gray models, we evaluated the association between LGE and the composite primary end point of all-cause mortality, heart transplantation, or left ventricular assist device implant and a secondary arrhythmic end point of sudden cardiac death or appropriate implantable cardioverter-defibrillator shock. RESULTS: We studied 1672 patients, mean age 56±14 years (29% female), left ventricular ejection fraction 33±11%, and 25% having New York Heart Association class III to IV; 650 patients (39%) had LGE. During 2.3 years (interquartile range, 1.0-4.3) follow-up, 160 patients experienced the primary end point, and 88 experienced the arrhythmic end point. In multivariable analyses, LGE was associated with 1.5-fold (hazard ratio, 1.45 [95% CI, 1.03-2.04]) risk of the primary end point and 1.8-fold (hazard ratio, 1.82 [95% CI, 1.20-3.06]) risk of the arrhythmic end point. Primary end point risk was increased in patients with multiple LGE patterns, although arrhythmic risk was higher among patients receiving primary prevention implantable cardioverter-defibrillator and widening QRS. CONCLUSIONS: In this large multinational study of patients with dilated cardiomyopathy, the presence of LGE showed strong prognostic value for identification of high-risk patients. Randomized controlled trials evaluating LGE-based care management strategies are warranted.

Biomarkers in atrial fibrillation and heart failure with non-reduced ejection fraction: Diagnostic application and new cut-off points.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) with non-reduced left ventricle ejection fraction (LVEF) present a diagnostic overlap. In this paper, we analyze differences in biomarkers between patients with and without HF, in a cohort of patients presenting with symptomatic AF. Differences in biomarkers between patients with medium range ejection fraction HF (HFmrEF) and those with preserved ejection fraction HF (HFpEF) are also analyzed. METHODS: A total of 115 patients with symptomatic persistent AF were included. Seven biomarkers were measured: NT-proBNP, high sensitivity T troponin (hsTNT), galectin-3, ST2, fibrinogen, urate and C-reactive protein. RESULTS: Patients with non-reduced LVEF HF had significantly higher NT-proBNP levels than those without HF. This biomarker was the only variable independently related with the presence of non-reduced LVEF HF. Troponin was the only factor independently related with the presence of HFmrEF. CONCLUSIONS: NT-proBNP showed the best diagnostic accuracy for detecting the presence of non-reduced LVEF HF. We found higher diagnostic NT-proBNP cut-off values than those previously reported. Troponin was the most accurate biomarker differentiating HFmrEF from HFpEF.

Pharmacokinetic drug evaluation of vorapaxar for secondary prevention after acute coronary syndrome.

INTRODUCTION: Vorapaxar is the first protease-activated receptor-1 inhibitor approved for clinical use. Its main indication is the reduction in thrombotic cardiovascular events in patients with previous myocardial infarction or symptomatic peripheral artery disease. Areas covered: This article reviews the pharmacokinetics of vorapaxar and its potential use in secondary prevention after an acute coronary syndrome. Expert opinion: Vorapaxar inhibits platelet aggregation mediated by thrombin. This effect is carried out without affecting to coagulation parameters and bleeding times. This drug has showed a significant reduction of cardiovascular events in patients with chronic atherosclerosis but not during the admission for an acute coronary syndrome. The rate of major bleeding found in patients treated with vorapaxar in randomized trials was consistently higher than placebo in most of the analyzed subgroups. For this reason, cautious evaluation of risk-benefit profiles should be required before prescribing this drug.

Brain natriuretic peptide levels variation after left atrial appendage occlusion.

OBJECTIVE: To explore the variations of brain natriuretic peptide (BNP) secretion after left atrial appendage occlusion. BACKGROUND: Left atrial appendage occlusion has been increasingly performed in the last few years, however little is known about the physiological consequences of left atrial appendage occlusion. Left atrial appendage regulates partially intravascular volume via release of brain natriuretic peptide. Brain natriuretic peptide levels have been related to increased risk of stroke in atrial fibrillation patients. METHODS: Venous blood samples were obtained in consecutive patients undergoing left atrial appendage occlusion before, 24 hr after device implantation and at the first visit after discharge (45-60 days) for BNP measurement. RESULTS: Left atrial appendage occlusion was performed in 34 patients with non-valvular atrial fibrillation and contraindication to long-term oral anticoagulation or at high-risk of bleeding. There were no differences in BNP levels between baseline and 24 hr after device implantation. However left atrial appendage closure resulted in a significant decrease in BNP levels at the first follow-up visit (45-60 days) compared to baseline measurements (759.90 pg ml(-1) vs. 636.90 pg ml(-1) , P = 0.013). CONCLUSIONS: Left atrial appendage occlusion modifies BNP levels. These levels decrease after left atrial appendage occlusion. The clinical consequences of these findings need to be evaluated in further studies. © 2015 Wiley Periodicals, Inc.