Mechanisms and Management of Breathlessness in Chronic Heart Failure

Background: The pathophysiology of dyspnoea (‘breathlessness’) is poorly understood and treatment options limited. This is particularly true for heart failure in which dyspnoea is a cardinal symptom, even when the heart failure is optimally managed. This thesis aims to untangle mechanisms and utilise this knowledge to optimise heart failure management. It focuses on the potential of nebulised furosemide as an adjunct treatment, given its excellent safety record and existing evidence that it modulates dyspnoea via direct action on lungs. Methods: A multi-dimensional questionnaire was used to survey the prevalence of dyspnoea in the heart failure community. A randomised, double blind, placebo-controlled crossover trial (RCT) was then performed in healthy participants to determine the specific components of dyspnoea that are relieved by the action of furosemide on the lungs. This study led to the design of a feasibility RCT in patients with heart failure using the visual analogue scale (VAS) ratings of the ‘air hunger’ (AH) component of dyspnoea as the primary outcome measure. The RCT itself; i) addressed other issues that could account for variability in relief seen in previous studies, ii) explored blood biomarkers of heart failure in relation to dyspnoea and iii) provided guidance for future definitive clinical trials. Results: 1) 47% of patients experienced dyspnoea in the community. Dyspnoea-12 scores correlated with New York Heart Association class, with many in class III experiencing dyspnoea at rest. 2) Nebulised furosemide specifically relieved AH induced in healthy participants but did not affect the 'work/effort' component. Relief was only with nebulised, not intravenous furosemide. 3) Breathing furosemide quickly or slowly did not alter dyspnoea relief, but ventilation was not matched. 4) Cardiopulmonary exercise testing (CPET) produced an average VO2peak of 54±15% predicted, with a measurable anaerobic threshold in 73% of tests and raised dyspnoea to 42±19%VAS. 5) Nebulised furosemide resulted in no significant improvements in exercise capacity. 6) Cardiac biomarkers increased appropriately and returned to baseline within 1 hour of exercise. The maximal absorption efficiency of nebulised furosemide was 2%. Conclusion: 1) Dyspnoea is a prevalent symptom in heart failure, comparable to chronic obstructive pulmonary disease. The NYHA classification may require clarification regarding presence of breathlessness at rest. 2) Relief of dyspnoea with nebulised furosemide occurs via a mechanism within the lungs and should be targeted at those in whom ‘air hunger’ predominates. 3) CPET is a feasible method for dyspnoea assessment in heart failure. 4) Fully powered RCT of nebulised furosemide in heart failure are warranted taking on board the preliminary information gathered in this thesis to optimise treatment effect

Specialist intervention is associated with improved patient outcomes in patients with decompensated heart failure: evaluation of the impact of a multidisciplinary inpatient heart failure team

Objective. The study aimed to evaluate the impact of a multidisciplinary inpatient heart failure team (HFT) on treatment, hospital readmissions and mortality of patients with decompensated heart failure (HF). Methods A retrospective service evaluation was undertaken in a UK tertiary centre university hospital comparing 196 patients admitted with HF in the 6 months prior to the introduction of the HFT (pre-HFT) with all 211 patients seen by the HFT (post-HFT) during its first operational year. Results. There were no significant differences in patient baseline characteristics between the groups. Inpatient mortality (22% pre-HFT vs 6% post-HFT; p<0.0001) and 1-year mortality (43% pre-HFT vs 27% post-HFT; p=0.001) were significantly lower in the post-HFT cohort. Post-HFT patients were significantly more likely to be discharged on loop diuretics (84% vs 98%; p=<0.0001), ACE inhibitors (65% vs 76%; p=0.02), ACE inhibitors and/or angiotensin receptor blockers (83% vs 91%; p=0.02), and mineralocorticoid receptor antagonists (44% vs 68%; p<0.0001) pre-HFT versus post-HFT, respectively. There was no difference in discharge prescription rates of betablockers (59% pre-HFT vs 63% post-HFT; p=0.45). The mean length of stay (17±19 days pre-HFT vs 19±18 days post-HFT; p=0.06), 1-year all-cause readmission rates (46% pre-HFT vs 47% post-HFT; p=0.82) and HF readmission rates (28% pre-HFT vs 20% post-HFT; p=0.09) were not different between the groups. Conclusions. The introduction of a specialist inpatient HFT was associated with improved patient outcome. Inpatient and 1-year mortality were significantly reduced. Improved use of evidence-based drug therapies, more intensive diuretic use and multidisciplinary care may contribute to these differences in outcome