Acute decompensated heart failure with preserved ejection fraction : haemodynamic changes, cardiorenal syndrome and short-term prognosis

Abstract

Acute decompensated heart failure with preserved ejection fraction (ADHFpEF) is a mounting global health problem, causing a significant burden on acute hospital care in the developed countries and aging societies. Although being the most common cause of acute hospital admission in Europe and the United States, this disease remains enigmatic, with little known regarding its pathogenesis, predictors of short-term prognosis and optimal management.

This study was a prospective observational study to delineate the haemodynamic changes in ADHFpEF, ascertain the incidence of cardiorenal syndrome, identify predictors of short-term prognosis and compare between continuous infusion and bolus injection of intravenous loop diuretics. Patients admitted to acute medical wards with ADHFpEF were recruited. These patients underwent serial follow-up in the first 48 hours after enrollment, assessed by clinical and biochemical methods, together with trans-thoracic echocardiography to assess haemodynamics and bioimpedance vector analysis (BIVA) to assess fluid status. Subjects were further invited to take part in a randomized trial between continuous infusion and bolus injection of loop diuretics.

Novel haemodynamic changes were presented in Chapter 3, showing a significant drop in cardiac output by 0.59 L min^(-1) and mean arterial blood pressure by 7 mmHg after 48 hours of treatment. These haemodynamic changes were associated with successful diuresis and decongestion. These findings suggest that diuretic treatment, though effective, can hamper cardiac output and possibly affect other organs.

Cardiorenal syndrome was shown to be a common phenomenon in Chapter 4. Within 48 hours, 41 of all 100 patients developed worsening renal function (WRF). Meanwhile, 54 of all 100 patients had an increase in neutrophil gelatinase-associated lipocalin level. Hypervolaemia, defined with BIVA, was associated with a lower chance (odds ratio 0.31) of developing WRF within first 24 hours. These findings suggest BIVA can be used to identify patients at risk of WRF.

Short-term prognosis was addressed in Chapter 5. In the study cohort, 3 patients died and 40 had emergency hospitalization within 60 days after enrollment. In a multivariable regression, both higher baseline BNP (hazards ratio 1.002) and lower reduction in BNP after 48 hours (hazards ratio 1.003) were associated with higher risk of reaching endpoint. These findings demonstrate the prognostic value of BNP.

Continuous infusion and bolus injection of intravenous loop diuretics were compared in Chapter 6. 96 patients were recruited into the trial, with 47 randomized to infusion arm and 49 to bolus arm. No significant difference was seen in the primary outcome of deaths or emergency hospitalization within 60 days after admission. No difference in the risk of WRF was noted. The infusion armed showed an increase in NGAL after 48 hours whilst the bolus arm showed a decrease (49 ± 90ng/mL vs. -5 ± 127 ng/mL). These findings suggest infusion may be associated with renal damage detectable by NGAL but not creatinine.

All in all, findings from this study provided novel understanding to ADHFpEF, warranting further investigations to establish the utility of these findings. There remains more work to be done to understand ADHFpEF at a level commensurate with its clinical significance.