Health-related quality of life and associated factors in heart failure with reduced ejection fraction patients at University of Gondar Hospital, Ethiopia

Introduction Living with heart failure poses challenges due to its poor prognosis and impact on quality of life, making it crucial to assess how it affects patients for better patient-centered management. This study aimed to assess quality of life and associated factors in heart failure with reduced ejection fraction patients at University of Gondar Comprehensive Specialized Hospital in Ethiopia, 2023. Methods An “institution-based” cross-sectional study was conducted at the University of Gondar Comprehensive Specialised Hospital. The data were collected using an interviewer-administered questionnaire. Health-related quality of life was measured using the Minnesota Living with Heart Failure Questionnaire. Sociodemographic, behavioral, clinical, biochemical, and echocardiographic characteristics were included in the questionnaire. The collected data were entered into EpiData version 4.6 and exported into SPSS version 25 for analysis. Multiple linear regression analysis (p < 0.05) was used to measure the degree of association between quality of life and independent variables. Results A total of 240 patients with heart failure and reduced ejection fraction participated in the study. The health-related quality of life scores for the physical, emotional, and total were 17.60 ± 10.33, 10.58 ± 6.33 and 46.12 ± 26.06, respectively. Health-related quality of life was significantly associated with age, marital status, occupation, income, heart failure duration, recent hospitalization, New York Heart Association functional class, heart failure etiology, atrial fibrillation comorbidity, systolic blood pressure, heart rate, heart failure medications, severe left ventricular systolic dysfunction, and severe or moderate pulmonary hypertension. Conclusion This study found that patients with heart failure and reduced ejection fraction had poor health-related quality of life, influenced by identified factors. These findings aid professionals in assessing and identifying interventions that improve these patients’ quality of life.


Introduction
Heart failure (HF) is a global public health problem with an estimated 64.3 million people suffering worldwide (1), and approximately 50% of cases are Heart Failure with reduced Ejection Fraction (HFrEF) (2).It remains a significant public health issue in many countries in Sub-Saharan Africa and is one of the top five causes of mortality in Ethiopia (3).
Health-related quality of life (HRQoL) is an assessment of how an individual's well-being may be affected over time by a disease, disability, or disorder (4,5).It is important to evaluate the impact of a disease and the effect of medical intervention as perceived by the patient through the effects on the domains of life: physical, social, psychological and environmental (6).
Health-related quality of life in patients with HF is an important patient-reported health status measure that evaluates the impact of HF and its medical interventions on various domains of life.It is an outcome measurement tool that has recently received attention for assessing the impact of HFrEF and its treatment and is one of the primary goals of HFrEF treatment guidelines (7,8).Despite current studies indicating HF patients' preferences for improved HRQoL over survival, the importance of QoL is underscored in the management of patients with heart failure (9,10).
Living with HF is challenging due to its poor prognosis and increased socioeconomic burden resulting from higher healthcare costs, debilitating symptoms such as dyspnea, edema, fatigue, and sleep disturbance, and frequent hospitalizations, all of which significantly impact HRQoL.Various studies have shown that QoL is generally poor in patients with HF and particularly in HFrEF patients (11)(12)(13)(14)(15).Despite limited and conflicting data comparing HRQoL among HF patients across the left ventricle ejection fraction (LVEF) spectrum, most evidence supports that HFrEF patients have a significantly affected QoL compared to other subgroups of heart failure patients (14, 16).
Poor HRQoL correlates with increased hospitalization and mortality rates, as well as higher costs imposed on health systems, families, and patients (17)(18)(19).
Different studies have identified determinant factors of HRQoL among patients with HF, most of which differ across the LVEF spectra.Being a younger woman, having low income, longer disease duration and higher NYHA functional class are associated with poor HRQoL in HF patients in general (11,20,21).Being an older woman, higher NYHA functional class, recent hospitalizations, having lower LVEF, lower systolic blood pressure and comorbidities are associated with poor HRQoL in HFrEF in particular (13,14,16,22).
Measuring HRQoL will help monitor treatment guidelines and improve patient HRQOL.Analysis of HRQoL can identify groups with poor HRQoL and its determinant factors, guiding interventions to improve their situation and prevent more serious consequences, allocate limited resources based on unmet needs, guide strategic plans, and monitor interventions (7,8).
Although the impact of HF on QoL and its determinants differs across the LVEF spectrum, as evidenced by available studies, there is a scarcity of studies on subgroups of HF populations.Therefore, this study aimed to assess HRQoL and associated factors among adult patients with HFrEF.

Study design and settings
The study was a cross-sectional "institutional-based" study conducted from August to November 2023 at the University of Gondar Comprehensive Specialized Hospital (UoGCSH) in North West Ethiopia.It is one of the largest hospitals in the country, providing health services to around 13 million inhabitants in its catchment area.The hospital has various follow-up clinics for major chronic illnesses, including the Cardiac clinic.Approximately 3,000 cardiac patients receive follow-up care at this clinic.

Population
All adult patients with HFrEF who had chronic follow-up at UoGCSH were source population.The study population consisted of all adult patients with HFrEF who visited the chronic follow-up clinic at UoGCSH during the study period.

Inclusion and exclusion criteria
Adult patients (aged 18 years or older) with HFrEF who had been followed up for at least three months at the cardiac clinic at UoGCSH were included in the study.
Patients with cognitive impairment, such as dementia or psychosis (who were not likely to recall their conditions well enough), concomitant acute illnesses, such as Acute HF exacerbation, severe chest infections, or other infections that could acutely influence their QoL, and coexisting diagnosis of other chronic illnesses (end-stage renal disease, decompensated chronic liver disease, chronic obstructive pulmonary disease, cerebrovascular accident, and diabetes mellitus) were excluded from the study.

Sample size and sampling procedure
The sample size was calculated based on the mean estimate from previous research conducted in Brazil (22) using the mean estimation formula.The final sample size was determined to be 253 after adding a 10% non-response rate.
A consecutive sampling technique was employed, in which every participant who met the inclusion criteria was selected until the desired sample size was reached.

Data collection tools and procedures
The data was collected using structured questionnaires.The questionnaire included sociodemographic, behavioral, clinical, biochemical, and echocardiographic parameters, as well as the Minnesota Living with Heart Failure Questionnaire (MLHFQ) tool.
The MLHFQ is one of the most widely used disease specific HRQoL questionnaires for patients with HF and has been validated in many countries worldwide (23)(24)(25).It provides scores for two dimensions, physical and emotional, as well as a total score.HFspecific health status assessments are preferred because they are more sensitive to changes in disease status and more responsive to HF therapy than generic health status measures (26)(27)(28).
The English version of the MLHFQ was translated into Amharic, a local language, and then back into English by another person to ensure consistency.Data related to clinical, biochemical, and echocardiographic parameters were obtained by reviewing patients' medical charts.Concerning the biochemical parameters, specifically Hemoglobin, Serum creatinine, Glomerular filtration rate, and Serum sodium, the average of the laboratory results obtained during the three months preceding the patient's visit is utilized.Laboratories were done via Yumizen H550 automated hematology analyzer.andAU480 chemistry analyzer.Sociodemographic, behavioral variables, and all 21 MLHFQ variables were obtained by trained interviewers who conducted face-to-face interviews.These interviewers were two nurses with experience working in a cardiac clinic service, and a general practitioner was recruited as a supervisor.
To ensure data quality, all data collectors and supervisors were trained in data collection procedures, the objective and relevance of the study, and the confidentiality of information.The Amharic version of the MLHFQ was used to ensure that study participants could easily understand it.Pretest data were collected from 15 study participants at the UoGCSH follow-up clinic to check reliability, wording, and identify any language barriers and contextual variations.During data collection, accuracy and completeness were checked daily by the supervisor and the principal investigator.

Dependent variable
Health Related Quality of Life (Physical, Emotional and Total HRQoL).

Independent variables
Socio-demographic: age, sex, residency, marital status, educational level, occupation and income.
Biochemical: Hemoglobin, Serum creatinine, Glomerular filtration rate, Serum sodium (mean of results obtained within the past 3 months).
Echocardiographic: Etiology of HF, LVEF, and severity of pulmonary hypertension on baseline echocardiography (echo) performed at the time of HFrEF diagnosis.

Operational definitions Heart failure with reduced ejection fraction patients
Heart failure patients who have echocardiographic measurement of left ventricular ejection fraction ≤40% labelled as HFrEF patients.

Health-related quality of life
Health-Related Quality of Life serves as an outcome variable assessed through the MLHFQ instrument.This tool comprises 21 items specifically designed to evaluate HRQoL in relation to a particular disease, prompting participants to reflect on the impact of their condition over the past month.Each item is rated on a six-point Likert scale, ranging from 0 (indicating no effect) to 5 (indicating a significant effect).The individual responses are aggregated to form a composite score that reflects the overall HRQoL of the participants.Scores can vary from 0 to 105, with higher scores indicating a lower quality of life.The instrument yields a total score along with scores across two dimensions: physical (covering questions 2-7, 12, and 13, with a range of 0-40) and emotional (covering questions 17-21, with a range of 0-25).The remaining eight questions (1, 8, 9, 10, 11, 14, 15, and 16) contribute solely to the calculation of the total composite score.Heart failure patients are categorized based on their total HRQoL scores, with those scoring below 24 classified as having "Good" HRQoL, scores between 24 and 45 as "Moderate," and scores exceeding 45 as "Poor" HRQoL (29).

New York Heart Association Functional Class
Used to classify the severity of heart failure as.Class I: no limitation during ordinary activity, Class II: slight limitation during ordinary activity, Class III: marked limitation of normal activities without symptoms at rest, Class IV: unable to undertake physical activity without symptoms and symptoms may be present at rest (30).

Data processing and analysis
The completeness of the collected data was checked.Next, codes were assigned to each question and entered into EpiData version 4.6.The data was then exported to statistical software SPSS version 25 for further analysis.A reliability test (Cronbach's alpha) was conducted to assess the reliability of the items in the MLHFQ tool.The Cronbach's alpha was 0.99 for total HRQoL, 0.98 for the physical domain and also 0.98 for the emotional domain.Descriptive analyses such as frequencies, means and medians were conducted for the outcome and independent variables.In cases were an item was missing, the mean of the other items in the domain was used as a substitute.
The health-related quality of life, as measured by the MLHFQ tool, was outcome variable, consisting of three domains (physical, emotional and total HRQoL).Socio-demographic, behavioral, clinical, biochemical and echocardiographic variables were utilized as independent variables.
Bivariate analysis for categorical variables was performed using independent-samples t-test or one-way ANOVA to examine differences in mean MLHFQ score among the categories.For continuous variables, bivariate analysis using Pearson's correlation was conducted to assess their correlation with HRQoL.
Variables that showed an association with HRQoL at a significance level of p < 0.25 during bivariate analysis were included in the multivariate analysis.
Multiple linear regression analysis using a stepwise regression model was carried out for the multivariate analysis of the association between the HRQoL domains and demographic, behavioral, clinical, biochemical and echocardiographic variables.
Variables with a p-value < 0.05 after multiple linear regression were deemed statistically significant.

Sociodemographic characteristics of study participants
A total of 240 patients with heart failure with reduced ejection fraction, who were receiving follow-up at a cardiac clinic, participated in the study with a response rate of 94.9%.The mean age of the study participants was 51.04 ± 13.2 years.Among the participants, 52.1% were female, 50.8% lived in urban areas, 61.3% were married, 34.2% were housewives, and 42.9% had no formal education.The mean monthly income was 3,473.3 ± 1,605.4Ethiopian Birr (ETB).
In this study, 9.2% of participants were current smokers, 33.3% reported salt intake and 19.2% were currently drinking alcohol (Table 1).

Biochemical and echocardiographic characteristics of study participants
In this study, the mean values of laboratory results conducted within the past 3 months were included.The median (IQR) value of Hg was 14.1(2) g/dl ranging from 9.5 to 18.3 g/dl and Cr was 0.89(0.23)mg/dl ranging from 0.45 to 1.80 mg/dl.The mean value of eGFR was 92.48 ± 20.52 ml/min/1.73m 2 and Na was 136.22 ± 4.70 mEq/L.

Health-related quality of life of heart failure with reduced ejection fraction patients
In this study the MLHFQ assessed HRQoL and showed mean scores of 17.60 ± 10.33, 10.58 ± 6.33 and 46.12 ± 26.06 for physical, emotional and total QoL respectively.Approximately 43.3% of the participants were assessed as having a poor quality of life related to heart failure, while the remaining 29.2% and 27.5% were assessed as having moderate and good HRQoL, respectively (Table 4).

Factors associated with health-related quality of life
Multivariate analysis was conducted using a multiple linear regression model, with categorical variable (after conversion to dummy variables) and continuous variables as independent variables, and HRQoL domains (physical, emotional, total QoL) as outcome variables.
The analysis revealed that the total HRQoL domain was significantly associated with Age, Marital status, Occupation, Monthly income, SBP, HR, Duration of HF, NYHA class, Recent Hospitalization, Etiology of HF, AF comorbidity, Anticoagulant and furosemide use as HF medications, Baseline echo systolic dysfunction and PH severity.The final R-square value was 0.879, indicating that 87.9% of the variation in total HRQoL was explained by the identified associated factors.
As age increased, the scores of physical and total HRQoL domains also increased.Specifically, for every one-year increase in age, the total HRQoL score increased by 0.37 (95% CI = 0.24, 0.50), and the physical domain HRQoL score increased by 0.15 (95% CI = 0.10, 0.20).
Compared to married individuals, single and widowed participants had higher HRQoL scores in all domains.Employed respondents (both governmental and non-governmental) had higher physical and total HRQoL scores compared to housewives, while farmers had only a higher physical HRQoL score.As income increased, the score of all HRQoL domains decreased.For every 1000ETB increase in monthly income, the total HRQoL score decreased by 2.00 (95% CI = −2.20,−1.20), the physical HRQoL score decreased by 2.00 (95% CI = −3.20,−1.20), and the emotional HRQoL score decreased by 3.00 (95% CI = −5.10,−1.10).
As HR increased, the score of physical and total HRQoL domains increased.For every one bpm increase in HR, the total HRQoL score increased by 0.19 (95% CI = 0.07, 0.31), and the physical domain HRQoL score increased by 0.11 (95% CI = 0.06, 0.15).
An increase in the duration of HFrEF was associated with a decrease in total HRQoL domain score.Specifically, for every one-year increase in duration, the total HRQoL score decreased by 1.73 (95% CI = −3.05,−0.40).
Participants with DCMP as the etiology of HFrEF had an increased total HRQoL score compared to those with CRVHD, while those with DVHD had a higher emotional HRQoL score.
Participants using diuretics (furosemide) and anticoagulant medication had increased HRQoL score in all domains compared to those not using them.
Respondents with LV severe systolic dysfunction at baseline echocardiography had an increased total HRQoL score by 3.41 (95% CI = 0.38, 6.43) compared to those with moderate LV systolic dysfunction.
The total adjusted R 2 in this model was 0.879 for total HRQoL.Most of the significant correlates of total HRQoL were related to echocardiographic factors (partial R 2 = 0.644) followed by Clinical factors (partial R 2 = 0.120), Sociodemographic factors (partial R 2 = 0.062), Comorbidity and etiology related factors (partial R 2 = 0.041), and Treatment related factors (partial R 2 = 0.010) (Table 5 and Figure 1).This finding underscores the importance of including HRQoL as an additional measure when evaluating patients with HFrEF, as other clinical variables used to assess risk may not capture the same information as instruments that gauge the patients' perception of health.This approach can help identify patients who require special interventions.
Providing more personalized education and adjusting medical treatments/interventions can assist patients with poor HRQoL in managing their daily lives effectively.

TABLE 1
Socio-Demographic and behavioral characteristics of patients with heart failure with reduced ejection fraction attending cardiac clinic at UoGCSH North West Ethiopia, 2023 (n = 240).

TABLE 2
Clinical characteristics of patients with heart failure with reduced ejection fraction attending cardiac clinic at UoGCSH North West Ethiopia, 2023 (n = 240).

TABLE 4
Health-Related quality of life of patients with heart failure with reduced ejection fraction attending cardiac clinic at UoGCSH north west Ethiopia, 2023 (n = 240).

TABLE 3
Biochemical and echocardiographic characteristics of patients with heart failure with reduced ejection fraction attending cardiac clinic at UoGCSH North West Ethiopia, 2023 (n = 240).

TABLE 5
Factors associated with health-related quality of life among patients with heart failure with reduced ejection fraction attending cardiac clinic at UoGCSH, northwest Ethiopia, 2023 (n = 240)., recent hospitalization, DCMP as the etiology of HF, AF as a comorbidity of HF, medication use (furosemide & anticoagulants), severe LV systolic dysfunction, and severe/moderate PH were all associated with poor HRQoL.