Treatment outcome and its predictors among patients of acute heart failure at a tertiary care hospital in Ethiopia: a prospective observational study

Acute heart failure (AHF) is a rapid onset of new or worsening of signs and symptoms of heart failure (HF) that is associated with elevated plasma levels of natriuretic peptides [1]. AHF syndromes manifestas new-onset ‘de novo’ or recurrence of acute decompensated heart failure (ADHF) requiring emergency treatment and hospitalization [2, 3]. The incidences of AHF vary in the different part of the world. Its increasing incidence is due to an increasing aging, population, complications arising from cardiovascular diseases like acute coronary syndrome (ACS) and increasing prevalence of lifestyle-related risk factors [4]. AHF patients who attended at hospitals in Africa are young and have severe symptoms due to late presentation. Thus, we should address the young people who are affected by the burden of an acute attack of HF. These younger age group had a significant impact on the economy of the society [5, 6].

Adherence to medication predicts health outcomes. Failure to adhere to HF medication was associated with poor treatment outcomes [7]. Patients should receive appropriate therapy as early as possible to achieve good treatment outcomes.

Evaluating reasons for hospitalization in AHF is important to give due attention to precipitating factors. The most common precipitating factors are non -compliance to salt restriction, pulmonary infections, arrhythmias and misuse of HF medications [8].The study conducted by Blecker S et.al has shown hospitalized AHF patients didn’t receive appropriate therapy [9]. Besides worsening, AHF was common in hospitalized patients and it was associated with higher mortality rates [10]. Therefore, managing AHF patients according to guideline recommendation could reduce patient hospitalization, decrease morbidity and mortality.

Limited studies and literatures are available in Africa and other developing countries that describe the clinical characteristics, management, and treatment outcome of AHF patients. Therefore, the present study could provide valuable insights to the patient’s treatment outcome and predictors of in- hospital mortality among patients hospitalized with AHF in Ethiopia.

AHF patients presenting to a tertiary care hospital were young and had pneumonia as a major precipitating factor. The leading underlying disease was chronic rheumatic heart disease (RHD) and major co-morbid disease was chronic kidney disease (CKD). 17.2% of the patients had died in the hospital.

More than half of the AHF patients in this study were female 92 (54.4%) which was comparable to registry studies in sub-Saharan Africa Survey on Heart Failure (50.8%), the 5 year retrospective cohort study of African patients admitted with heart failure (54.4%), Acute Decompensated Heart Failure Registry (ADHERE) (52.0%) and the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) (52.0%) [5, 12‐14]. However, the European registries Euro Heart Failure Survey II (EHFS II) (39.0%), Heart Failure Pilot Study (ESC-HF pilot) (47.0%) and the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF) (37.6) studies females had lower frequency as compared to males [15‐18].

Patients admitted in this study were young (median = 34 years). This was contrary to registries in ADHERE (mean = 72.4), OPTIMIZE-HF (mean = 73), OFICA (median = 79.0), Korean Acute Heart Failure Registry (KorAHF) (mean = 68.5) and the sub-Saharan Africa Survey of Heart Failure cohort (mean = 52.3) [5, 12, 15, 19, 20]. Reason for younger age admission could be related to the high prevalence of RHD in Ethiopia [21]. Similarly, in the study by Abdissa and his colleagues the peak age of diagnosis with VHD among Ethiopian patients was in their third decade mean ± (SD) = 24.4 ± 9.7 years [22]. AHF in Tikur Anbessa Specialized Hospital pediatric ward was primarily due to RHD [21]. Supported by Soweto study 2006/07 South Africa, RHD was peaked predominantly in the third decade of life [23].

In the present study leading precipitating factors were pneumonia, atrial fibrillation, anemia and drug discontinuation. Similar to our study, in the OPTIMIZE-HF registry study pneumonia, ischemia/acute coronary syndrome and arrhythmia were leading precipitating factors [13].. This was also comparable with the ALARM-HF registry study where arrhythmia, infection and non-compliance to medication were the most frequent precipitating factors [18].

In the current study drug discontinuation as precipitating factor was reported in 22.5% of the patients, and almost 101 (59.8%) patients had a primary school and no formal education. Adherence to heart failure medication regimens could be influenced by inadequate support, lack of education and illiteracy. In addition to optimal pharmacologic treatment patient education on medication adherence had improved outcomes, [2]. Thus, clinical pharmacists had key role in medication adherence of heart failure patients as demonstrated by the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) study. Interventions made by clinical pharmacists lowered readmission/death by more than 50.0% through closer follow-up [24].

The leading underlying disease found was chronic RHD this was supported by different studies. In developing countries heart failure was primarily due to VHD whereas developed countries it was mainly due to ischemic disease [25]. Studies in the African population showed RHD was the commonest diagnosis among patients with cardiovascular diseases. The study at Jimma Specialized Hospital in Ethiopia showed RHD was the commonest diagnosis among patients presented to the cardiac clinic [26]. In Tikur Anbessa Specialized Hospital, the VHD was the commonest diagnosis among patients with cardiovascular diseases [22]. This was also similar to studies done in sub-Saharan Africa where cardiomyopathy and RHD accounted for almost half of all cases presented to hospitals [27‐29]. However, this was different from THESUS–HF study where hypertensive and ischemic heart disease(IHD) were the primary causes [5].

This study showed that treatment was targeted mainly towards symptom relief, the underlying and/or co-morbid disease were most commonly treated by frusemide, spironolactone, digoxin and warfarin. In the current study, warfarin and digoxin had higher consumption rates which were used for the management of VHD and atrial fibrillation [2, 30, 31].

The present study showed in-hospital mortality of 17.2% which is comparable with the mortality of THESUS–HF cohort study [5]. This was higher than the study of systematic review and meta-analysis in low and middle income countries that a 2.2% of hospital admission was AHF with mean in-hospital mortality of 8% [32].Globally, hospitalized patients had higher mortality (30.6%) and African patients had the highest adjusted hazard of death (34%) within 1 year. This variation in mortality might be related to the difference in health-care infrastructure, quality of care, environmental and genetic factors in different regions of the world [33].

Adverse drug events were a predictor of in-hospital mortality that occurred in 27.8% of the patients. This study found hypokalemia in 27.6% and hyperkalemia in 6.0% of the patients. Use of loop diuretic could lead to hypokalemia and drugs that increase potassium level especially in renal dysfunction such as a combination of angiotensin converting enzyme inhibitors, potassium chloride and spironolactone could lead to hyperkalemia. Use of non-potassium sparing diuretics was significantly associated with increased risk of arrhythmic death. Diuretic-induced electrolyte disturbance might ultimately resulted in fatal arrhythmia in patients using non-potassium sparing diuretics [34].

In our study AHF patients with pulmonary hypertension had higher mortality. Similarly, Lowe and colleagues showed patients with pulmonary hypertension had twofold risk of mortality [35]. The increased mortality in patients with pulmonary hypertension might be due to an aggressive afterload reduction with vasodilator or diuretics treatment that could finally end up in cardiovascular collapse as these patients could not increase their forward blood through flow restricted valve [36].

Patients with heart failure and preserved (≥ 50%) ejection fraction have multiple co-morbidities including diabetes mellitus, atherosclerosis, renal dysfunction, chronic obstructive lung disease, and anemia. The presence of those co-morbidities were associated with increased all-cause mortality among patients [14].The co-morbidities of heart failure patients (preserved EF) were significantly associated with unique clinical, structural, functional and prognostic profiles [37]. The poor clinical outcome of heart failure patients with preserved ejection fraction can not merely be explained by age, sex, presence of co-morbidity, low blood pressure and left ventricular remodeling rather than additional involvement of heart failure related mechanisms explained the worse outcome of patients [38]. The variation in cardiac and non-cardiac co-morbid conditions, underlying diseases, and clinical profile at presentation, diagnostic and treatment in AHF were heterogeneous across different countries [5, 12, 13, 15, 16, 39].

There are limited studies on the causes, treatments and outcomes of AHF in Africa. The present study provides information on the clinical characteristics, underlying and co-morbid disease, adverse drug events and treatment outcome and its predictors in AHF in Ethiopia. Ultimately the findings are useful for the policymaker to develop strategies to improve treatment outcomes, quality of care, preventive and diagnostic services of AHF.

High in-hospital mortality rate (17.2%) was observed among acute heart failure patients admitted to a Tertiary Care Hospital in Ethiopia. Chronic RHD and pneumonia were the leading underlying disease and precipitating factors found in patients admitted with AHF, respectively. Smoking, diabetes mellitus, pulmonary hypertension and the presence of adverse drug events were predictors of poor treatment outcomes. Due attention should be given to co-morbid diseases while patients presented with AHF syndromes. Clinicians should also pay more attention to the management of adverse drug events.