Heart Failure – Understanding Evolving Management Strategies and Moving Beyond Ejection Fraction in Heart Failure Phenotypes

– Highlights from the 14th annual Complex Cardiovascular Therapeutics: Advanced Endovascular and Coronary Intervention Global Summit (C3), Hilton Bonnet Creek, Orlando, FL, US, 17–20 June 2018 — Focus on managing heart failure.

Heart failure is a leading cause of hospitalisation worldwide – the most frequent reason in the US – and is estimated to continue to present a significant healthcare burden, particularly in light of an ageing population.^1,2

The likelihood of readmission for heart failure is widely variable, accounting for various healthcare resources like hospital size, budgets and presence of a specialist cardiac service; notably, the risk remains high at around 25%.³ Many strategies arising from large registry studies, when implemented in routine practice, have had only modest effects on hospital readmission for heart failure.⁴ These strategies included a focus on partnering with local and community healthcare resources and practitioners.⁴ Furthermore, pre-discharge patient education and telemonitoring have had little effect on readmission rates.⁵

While improvements are being made, there is clear room for further optimization in the management of patients with heart failure. The key to these improvements lies in a multidisciplinary hospital team approach, with a focus on cardiac rehabilitation and medication optimization;⁶ in addition, early follow-up following discharge has been shown to be effective in reducing readmission rates.⁷ Physicians are also encouraged to be mindful of key milestones in patients’ history that may be indicative of increased risk of worsening or fatal heart failure, such as:

• persistent or worsening signs or symptoms;
• recurrent hospitalisations;
• increasing diuretic doses;
• cutting back angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers;
• appropriate implantable cardioverter defibrillator shocks;
• need for inotropes;
• renal replacement therapies;
• new comorbidities – for example, cancer; and
• major ‘life-events’, such as the death of a spouse.

Management of heart failure typically falls into two subsets: heart failure either with a reduced (HFrEF) or preserved ejection fraction (HFpEF). Given the differing pathophysiology of the two conditions, it is unsurprising that therapeutic approaches to treating HFrEF have not been efficacious in managing HFpEF.⁸

In patients with HFrEF, there have been significant recent treatment successes with medication and devices. In the past decade, meaningful reductions in cardiovascular death or hospitalisation for heart failure have been demonstrated in the SHIFT (Effects of Ivabradine on Cardiovascular Events in Patients With Moderate to Severe Chronic Heart Failure and Left Ventricular Systolic Dysfunction. A Three-year International Multicentre Study),⁹ EMPHASIS-HF (A Comparison Of Outcomes In Patients In New York Heart Association [NYHA] Class II Heart Failure When Treated With Eplerenone Or Placebo In Addition To Standard Heart Failure Medicines),¹⁰ and PARADIGM-HF (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure) trials.¹¹ SHIFT showed 18% reduction with ivabradine versus placebo,⁹ EMPHASIS-HF showed 37% reduction with eplerenone versus placebo¹⁰ and PARADIGM-HF showed 20% reduction with sacubitril/valsartan versus enalapril.¹¹ Recently, developments in implantation strategies for HFrEF have been demonstrated: implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes than with an axial-flow pump. Benefits in outcomes were primarily due to a lower rate of reoperation to correct pump malfunction (MOMENTUM-3; MOMENTUM 3 IDE Clinical Study Protocol [HM3™]).¹²

Treatment of HFpEF may, currently, be most efficiently focused on lowering blood pressure and managing contributing aetiologies. Recently, benefits in HFpPF have been observed with spironolactone, however both physiological markers (creatinine and potassium levels) and cardiovascular mortality and hospitalisation endpoints vary by population (TOPCAT; Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function).¹³

In the continuing evolution of medication and treatment strategies, caution was urged in physicians being too preoccupied with terminology; indeed, recent research indicates there are at least four phenotypes of heart failure that may be predictive of treatment response and outcomes.¹⁴ As more research is performed into heart failure phenotyping beyond ejection fraction alone, trials may be optimized and further advances made into efficacious interventions.

References

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