Characteristics And Outcomes Of Acute Heart Failure In Sub Saharan Africa

Abstract

Background:

Heart failure (HF) is one of the most important causes of morbidity and mortality

both in the developed and the developing nations. Acute heart failure (AHF) is a

syndrome characterized by hospital admission for heart failure as defined by the

presence of acute dyspnea and the presence of heart failure signs by physical

examination with at least 2 of the following: rales, edema, elevated JVP,

hepatomegaly and ascites. AHF can occur de novo or as worsening of symptoms in

patients with chronic systolic or diastolic HF. In most sub Saharan African (SSA)

countries, AHF has not been well studied and the incidence, prevalence, treatment

and outcome of AHF are not well defined. HF in Africa affects young people in their

prime of life and as such pose a huge economic burden on the population. There is

also limited information on the characteristics, outcome and predictors of HF in

general and AHF in particular. Study of clinical characteristics of AHF patients

including the role of conventional and novel biomarkers in prognostication is

therefore a research priority in this region. The findings will guide appropriate

clinical decisions on treatment and proper monitoring.

Methods:

This work involved two cohorts of acute heart failure patients. The first included

patients enrolled into a multicenter prospective observational clinical registry for

hospitalized patients with AHF while the second included patients recruited for a

prospective, placebo controlled double blind randomized study to compare treatment

with hydralazine – isosorbide dinitrate versus placebo on top of standard care in

African patients admitted with AHF. Data from each subject were obtained using a

uniform and standardized case report forms (CRF) for the particular study. In both

cases we collected demographic data, date of diagnosis of HF and pre-admission

history (previous heart failure related admissions). Others included New York Heart

Association (NYHA) functional class, symptoms, signs, self reported cardiovascular

risk factors, aetiology of HF, precipitating factors, co-morbidities, blood

investigations (including brain natriuretic peptide (BNP) and galectin-3 (Gal3) in the

second cohort), Chest X-ray , 12-lead ECG, echocardiography and medications.

The main objective of this thesis was to study the clinical characteristics and shortterm

(6 months) outcome of acute heart failure as well as determine the role of

conventional biomarker BNP and the novel biomarker Gal3 in the prognostication of

acute heart failure patients. To achieve this, we investigated in the first cohort; 1) the

demographic and clinical characteristic of patients with AHF, 2) their

echocardiographic parameters and how they predict outcome, 3) the predictors of

readmission and mortality, 4) the prevalence and impact of renal dysfunction on AHF

and 5) the electrocardiographic pattern in AHF. The outcome measures were

worsening renal function (WRF), length of hospital stay, HF readmissions and

cardiovascular death within 60 days and all cause, cardiovascular or HF death

through 180 days. In the second cohort, we investigated the demographics, clinical

characteristics as well as the relationship between plasma levels of BNP and galectin

3 and outcomes (cardiovascular (CV) death or HF hospitalization through week 24)

as well as the relationship between the plasma levels of BNP and Gal3 and both left

ventricular (LV) and right ventricular (RV) remodeling in patients with AHF.

Results:

The first cohort enrolled 1006 patients with AHF. The mean age was 52.3 years,

50.8% were women, and the predominant race was black African (98.5%). HF was

most commonly due to hypertension (45.4%), dilated cardiomyopathy (DCM)

(18.8%) and rheumatic heart disease (RHD) (14.3%). Ischemic heart disease (IHD)

was the cause of AHF in only 7.7%. The median hospital stay was 7 days, with an inhospital

mortality of 4.2% and estimated 180-day mortality was 17.8%

The main predictors of 60-day re-admission or death in a model excluding the

geographic region were a history of malignancy, severe lung disease, admission

systolic blood pressure, and signs of congestion (rales) and kidney function, i.e.

abnormal blood urea nitrogen (BUN). In a model including region, the Southern

region had a higher risk. Predictors of 180-day mortality included malignancy, severe

lung disease, smoking history, systolic blood pressure, heart rate, and symptoms and

signs of congestion (orthopnoea, peripheral oedema and rales) at admission, kidney

dysfunction (BUN), anaemia, and HIV positivity. The echocardiographic predictors

of 60-day readmission or death were left atrial size and heart rate while heart rate, LV

posterior wall thickness in diastole (PWTd), and presence of aortic stenosis (AS)

were associated with the risk of death through 180 days. Renal dysfunction was found

in 31 % of the AHF patients. WRF was seen in 9.8 % of those with follow up

creatinine values available, and has different predictors compared with Western

cohorts. It was nevertheless, associated with the severity of congestion and clinical

outcome. Atrial Fibrillation (AF) is present in 20.8% of AHF patients, 44% of whom

had valvular AF. Having valvular AF predicted death through day 180.

The second cohort randomized 133 patients; mean age was 53.2 years and 50.8 %

were males. Eighty patients had data for biomarkers available for analysis. In this

cohort, both BNP and galectin-3 predicted CV death or HF hospitalization through

week 24. While BNP was not associated both with changes in markers of LV and RV

remodeling, Gal3 at baseline predicted changes (week 24 to baseline) in left

ventricular ejection fraction (LVEF), left ventricular end systolic and end diastolic

diameters as well as tricuspid annular systolic excursion (TAPSE).

Conclusion:

AHF in Africa affects middle-aged men and women in their productive ages, has a

predominantly non-ischaemic cause and is associated with high mortality. Except for

HIV status association with mortality, the main predictors of outcome are largely

similar in sub-Saharan Africa as in the rest of the world; both renal dysfunction and

AF are prevalent in AHF patients as they are in western cohorts. Novel biomarker

Gal3 is valuable in predicting changes (week 24 to baseline) in markers of LV and RV remodeling in African AHF patients.