Effect of frailty on treatment, hospitalisation and death in patients with chronic heart failure

Abstract Background Frailty is common in patients with chronic heart failure (CHF) and is associated with poor outcomes. The natural history of frail patients with CHF is unknown. Methods Frailty was assessed using the clinical frailty scale (CFS) in 467 consecutive patients with CHF (67% male, median age 76 years, median NT-proBNP 1156 ng/L) attending a routine follow-up visit. Those with CFS > 4 were classified as frail. We investigated the relation between frailty and treatments, hospitalisation and death in patients with CHF. Results 206 patients (44%) were frail. Of 291 patients with HF with reduced ejection fraction (HeFREF), those who were frail (N = 117; 40%) were less likely to receive optimal treatment, with many not receiving a renin–angiotensin–aldosterone system inhibitor (frail: 25% vs. non-frail: 4%), a beta-blocker (16% vs. 8%) or a mineralocorticoid receptor antagonist (50% vs 41%). By 1 year, there were 56 deaths and 322 hospitalisations, of which 25 (45%) and 198 (61%), respectively, were due to non-cardiovascular (non-CV) causes. Most deaths (N = 46, 82%) and hospitalisations (N = 215, 67%) occurred in frail patients. Amongst frail patients, 43% of deaths and 64% of hospitalisations were for non-CV causes; 58% of cardiovascular (CV) deaths were due to advancing HF. Among non-frail patients, 50% of deaths and 57% of hospitalisations were for non-CV causes; all CV deaths were due to advancing HF. Conclusion Frailty in patients with HeFREF is associated with sub-optimal medical treatment. Frail patients are more likely to die or be admitted to hospital, but whether frail or not, many events are non-CV. Graphical abstract

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Why do frail patients with chronic heart failure die and become hospitalised?

European Heart Journal ◽

10.1093/ehjci/ehaa946.1149 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Sze ◽

P Pellicori ◽

J Zhang ◽

J Weston ◽

A.L Clark

Keyword(s):

Heart Failure ◽

Cause Of Death ◽

Hospital Admissions ◽

Average Length ◽

Significant Proportion ◽

Length Of Hospital Stay ◽

Clinical Frailty Scale ◽

Frail Patients ◽

Increased Risk

Abstract Background Frailty is common in patients with heart failure (HF) and is associated with increased morbidity and mortality. A better understanding of the causes of hospitalisations and death in frail patients might help to tailor interventional strategies for these at-risk patients. Purpose We studied the cause of death and hospitalisations in ambulatory patients with HF and frailty. Methods We assessed frailty using the clinical frailty scale (CFS) in consecutive HF patients attending a routine follow-up visit. Those with CFS ≥5 were classified as frail. Mortality and hospitalisations were ascertained from medical records (updated systematically using an NHS electronic database), discharge letters, autopsy reports and death certificates. We studied the primary cause of death and hospitalisations within one year of enrolment. Results 467 patients (67% male, median (IQR) age 76 (69–82) years, median (IQR) NT-proBNP 1156 (469–2463) ng/L) were enrolled. 206 (44%) patients were frail. Frail patients were more likely to not receive or receive suboptimal doses of ACEi/ARB and Beta-blockers; while non-frail patients were more likely to be treated with optimal doses. At 1-year follow up, there were 56 deaths and 322 hospitalisations, of which 46 (82%) and 215 (67%) occurred in frail patients. Frailty was associated with an increased risk of all-cause mortality (HR (95% CI): 4.27 (2.60–7.01)) and combined mortality/ hospitalisation (HR (95% CI): 2.85 (2.14–3.80)), all p<0.001. 57% (n=26) of frail patients died of cardiovascular causes (of which 58% were due to HF progression); although deaths due to non-cardiovascular causes (43%, n=20), especially severe infections, were also common (26%, n=12). (Figure 1) The proportion of frail patients who had non-elective hospital admissions within 1 year was more than double that of non-frail patients (46% (n=96) vs 21% (n=54); p<0.001). Compared to non-frail patients, frail patients had more recurrent (≥2) hospitalisations (28% (n=59) vs 9% (n=24); p<0.001) but median (IQR) average length of hospital stay was not significantly different (frail: 6 (4–11) vs non-frail: 6 (2–12) days, p=0.50). A large proportion of hospitalisations (64%, n=137) in frail patients were due to non-cardiovascular causes (of which 34%, 30% and 20% were due to infections, falls and comorbidities respectively). Of cardiovascular hospitalisations (36%, n=78), the majority were due to decompensated HF (67%, n=46). (Figure 1) Conclusion Frailty is common in patients with HF and is associated with an increased risk of mortality and recurrent hospitalisations. A significant proportion suffered non-cardiovascular deaths and hospitalisations. This implies that interventions targeted at HF alone can only have limited impact on outcomes in frail patients. Figure 1 Funding Acknowledgement Type of funding source: None

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Procalcitonin (PCT) Predicts Worse Outcome in Patients with Chronic Heart Failure with Reduced Ejection Fraction (HFrEF)

Disease Markers ◽

10.1155/2018/9542784 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

J. Banach ◽

Ł. Wołowiec ◽

D. Rogowicz ◽

L. Gackowska ◽

I. Kubiszewska ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Roc Analysis ◽

Diagnostic Marker ◽

Lower Probability ◽

Reduced Ejection Fraction ◽

Probability Of Survival ◽

Kaplan Meier

Introduction. Procalcitonin (PCT) is an excellent marker of sepsis but was not extensively studied in cardiology. The present study investigated PCT plasma concentration in patients with chronic heart failure with reduced ejection fraction (HFrEF) and its prognostic value during 24-month follow-up. Material and Methods. Study group consisted of 130 patients with HFrEF (LVEF ≤ 45%) and 32 controls. PCT level was assessed on admission in all patients. Telephone follow-up was performed every three months over a period of 2 years. Endpoints were death of all causes and readmission for HFrEF exacerbation. Results. HFrEF patients had significantly higher PCT concentration than controls (166.95 versus 22.15 pg/ml; p<0.001). Individuals with peripheral oedema had increased PCT comparing to those without oedema (217.07 versus 152.12 pg/ml; p<0.02). In ROC analysis, PCT turned out to be a valuable diagnostic marker of HFrEF (AUC 0.91; p<0.001). Kaplan-Meier survival curves revealed that patients with PCT in the 4th quartile had significantly lower probability of survival than those with PCT in the 1st and 2nd quartiles. In univariate, but not multivariate, analysis, procalcitonin turned out to be a significant predictor of death during 24-month follow-up. (HR 1.002; 95% CI 1.000–1.003; p<0.03). Conclusions. Elevated PCT concentration may serve as another predictor of worse outcome in patients with HFrEF.

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Right ventricular recovery during follow-up is associated with improved survival in patients with chronic heart failure with reduced ejection fraction

European Journal of Heart Failure ◽

10.1002/ejhf.639 ◽

2016 ◽

Vol 18 (12) ◽

pp. 1462-1471 ◽

Cited By ~ 15

Author(s):

Frank Lloyd Dini ◽

Erberto Carluccio ◽

Anca Simioniuc ◽

Paolo Biagioli ◽

Gianpaolo Reboldi ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Right Ventricular ◽

Reduced Ejection Fraction

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Emerging Therapies for Acute and Chronic Heart Failure

Journal of Pharmacy Practice ◽

10.1177/1933719115615877 ◽

2016 ◽

Vol 29 (1) ◽

pp. 46-57 ◽

Cited By ~ 2

Author(s):

Sarah Hanigan ◽

Robert J. DiDomenico

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Cardiovascular Death ◽

Phase 3 ◽

Reduced Ejection Fraction ◽

Emerging Therapies ◽

Treat Heart Failure ◽

Novel Drugs ◽

The Us ◽

History Of

Although the period from 1953 to 2001 resulted in the approval of more than 30 medications currently used to treat heart failure (HF), few novel drugs have been approved in the last decade. However, the investigational pipeline for HF medications once again appears promising. In patients with chronic heart failure with reduced ejection fraction (HFrEF), ivabradine and valsartan/sucubitril (LCZ696) were recently approved by the US Food and Drug Administration. Both agents have been shown to reduce the risk of cardiovascular death and HF hospitalization. In the treatment of acute HF, serelaxin and ularitide are the farthest along in development. Both agents have demonstrated favorable effects on surrogate end points and preliminary data suggest a possible mortality benefit with serelaxin. Consequently, phase 3 trials are ongoing to evaluate the effect of serelaxin and ularitide on clinical outcomes. Given the poor history of recent investigational acute HF drugs that have advanced to phase 3/4 studies, enthusiasm for both serelaxin and ularitide must be tempered until these trials are completed.

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Participation in a Heart Failure Clinical Trial: Perspectives and Opportunities From the VICTORIA Trial and VICTORIA Simultaneous Registry

Circulation Heart Failure ◽

10.1161/circheartfailure.120.008242 ◽

2021 ◽

Author(s):

Justin Ezekowitz ◽

Robert J. Mentz ◽

Cynthia M. Westerhout ◽

Nancy K. Sweitzer ◽

Michael M. Givertz ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Risk Score ◽

Meta Analysis ◽

The United States ◽

Unique Identifier ◽

Eligibility Criteria ◽

Reduced Ejection Fraction

Background: Randomized controlled trials (RCTs) often target enrollment of patients with demographics and outcomes less representative of the broader population of interest. To provide context for the VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), we designed a registry of hospitalized patients with worsening heart failure to characterize their clinical profile, outcomes, and reasons for their nonparticipation in a RCT. Methods: Fifty-one RCT sites in Canada and the United States participated. Eligible patients included those with chronic heart failure, hospitalized for heart failure, and an ejection fraction <45%; no other exclusions were applied. Sites identified patients between 2017 and 2019 during the RCT enrollment period. RCT eligibility criteria were applied, and non–mutually exclusive reasons for nonenrollment were captured. Mortality at 1 year was estimated via the Meta-Analysis Global Group in Chronic Heart Failure risk score or as observed in the RCT. Results: Overall, 2056 patients were enrolled in the registry; 61% (n=1256) were ineligible for the RCT, 37% (n=766) were eligible but not enrolled, and 2% (n=34) were also enrolled in the RCT. Registry participants had a median age of 70, 33% were women, and 63% were White. The median risk score predicted a 20.9% 1-year mortality, higher than in the RCT (predicted 14.7% and observed 11.5%). Major reasons for ineligibility in the RCT included the use of nitrates (23%), systolic blood pressure <100 mm Hg (12%), and substance use (11%) with other exclusion criteria <10%. For eligible patients, reasons for nonparticipation in the RCT included lack of interest in participating (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (20%), unable to provide consent (17%), and distance from site (15%). Conclusions: Patients with worsening heart failure in routine clinical practice exhibit high-risk features, and approximately one-third were eligible for an RCT but excluded. The majority of these nonparticipating patients had modifiable reasons. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02861534.

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P974 Sacubitril/valsartan is well tolerated in patients with heart failure and a history of cancer

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.1197 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

M K Frey ◽

E Han ◽

H Arfsten ◽

N Pavo ◽

M Huelsmann ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cancer Patients ◽

Functional Class ◽

Reduced Ejection Fraction ◽

Non Hodgkin Lymphoma ◽

Patients With Heart Failure ◽

History Of ◽

History Of Cancer

Abstract Introduction Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalisations due to heart failure in patients with reduced ejection fraction when compared to enalapril. Until now, sacubitril/valsartan has not been evaluated in patients with a history of cancer, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. Methods We retrospectively enrolled all patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan and had a history of cancer. Fifteen patients receiving sacubitril/valsartan had a diagnosis of histologically confirmed cancer: 26.7% breast cancer (n = 4), 13.3% osteosarcoma (n = 2), 13.3% colorectal cancer (n = 2), 13.3% renal cell carcinoma (n = 2), 6.7% non-Hodgkin lymphoma (n = 1), 6.7% lung cancer (n = 1), 6.7% prostate cancer (n = 1), 6.7% bladder carcinoma and 6.7% myeoloproliferative syndrome (n = 1). Surgery due to cancer was performed in 80% of patients (n = 12), 26.7% previously received chemotherapy (n = 6) and 40% radiation therapy (n = 4). Results Sacubitril/valsartan was withdrawn in 2 patients (13.3%) because of dizziness and pruritus respectively. After a mean follow-up of 13 ±8 months, NYHA functional class improved significantly (mean -0.5, p = 0.001), ejection fraction as assassed by echocardiography increased (mean +6.8%, p = 0.018) and NT-proBNP was significantly decreased (mean -1552pg/ml, p = 0.026). There was no significant change in creatinine levels (+0.046 mg/dl, p = 0.564 ). Conclusions In this pilot study we were able to show that sacubitril/valsartan is generally well tolerated in patients with a history of cancer. Patients with cardiotoxicity induced heart failure can be treated and uptitrated with sacubitril/valsartan to usual dosages similarly as in other causes of heart failure. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.

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Why do patients fail to receive β-blockers for chronic heart failure over time? A “real-world” single-center, 2-year follow-up experience of β-blocker therapy in patients with chronic heart failure

American Heart Journal ◽

10.1016/j.ahj.2004.07.026 ◽

2005 ◽

Vol 149 (5) ◽

pp. 921-926 ◽

Cited By ~ 16

Author(s):

Anoop C. Parameswaran ◽

W.H. Wilson Tang ◽

Gary S. Francis ◽

Ritesh Gupta ◽

James B. Young

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Real World ◽

Single Center ◽

Blocker Therapy ◽

Β Blocker ◽

Β Blockers ◽

To Receive ◽

Over Time

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Cardiovascular outcomes of ferric carboxymaltose supplementation for the management of iron-deficient acute and chronic heart failure- a meta analysis

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.049 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

A Abdul Razzack ◽

S Kumar ◽

R Kumar ◽

HT Khokhar ◽

S Pothuru ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Iron Deficiency ◽

Clinical Outcomes ◽

Statistical Significance ◽

Ferric Carboxymaltose ◽

Cardiac Mortality ◽

Reduced Ejection Fraction ◽

Iron Deficient

Abstract Funding Acknowledgements Type of funding sources: None. Background-Iron deficiency is prevalent in heart failure patients and is associated with unfavorable clinical outcomes, irrespective of anemia status. The 2016 European Society of Cardiology (ESC) guidelines recommended intravenous ferric carboxymaltose (FCM) for the management of acute and chronic heart failure in symptomatic HF with reduced ejection fraction (EF). Objective- To determine whether the correction of iron deficiency with ferric carboxymaltose confers better clinical outcomes in patients with acute and chronic heart failure Methods-Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to December 28th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05. The primary outcome of interest was cardiac mortality. Secondary outcomes included first hospitalisation due to worsening heart failure and any other cardiovascular (CV) reason. Results-A total of five studies with 2091( FCM = 1125; placebo = 966) patients were included. Average follow-up period was 2 years. There was no difference in terms of cardiac mortality (RR 0.93, 95% CI 0.71–1.21; p = 0.57; I2 = 0) and hospitalizations for any CV reason (RR 0.83, 95% CI 0.32–2.16; p = 0.70; I2 = 83) with either group at the end of follow-up. As compared to placebo, FCM was associated with significant reduction in hospitalization due to worsening heart failure (RR 0.64; 95% CI 0.41-0.99; p = 0.04; I2 = 56) Conclusion- Amongst patients with iron-deficient acute and chronic heart failure, treatment with ferric carboxymaltose reduced the risk of heart failure hospitalizations, with no apparent effect on the risk of cardiac mortality and hospitalizations for any other CV cause. Abstract Figure. A)CV death B&C)Hospitalizations-HF,CV

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