Novel insights in HFrEF and HFpEF: patient characteristics, remote monitoring, and management

As we all know, cardiovascular disease remains the most common cause of premature death in the patient population at large, but particularly in those with chronic kidney disease,1 even in those with optimal treatment.2–5 Such patients are at 10–20 times greater risk of cardiac death than those without chronic kidney disease, despite stratification for age, race, sex, and diabetes. Thus, clinical investigations and trials in this population are of great need, as Murray Epstein and Bertram Pitt from the University of Miami Miller School of Medicine in Florida and the University of Michgan at Ann Arbor, USA argue in their Current Opinion ‘A propitious time for initiating clinical trials in patients with heart failure with reduced ejection fraction and an estimated glomerular filtration rate <30 mL/min with an mineralocorticoid receptor antagonist and a K+ binder: “the forbidden fruit”’.6 They note that patients with heart failure and reduced ejection fraction and an estimated glomerular filtration rate (eGFR) <30 mL/min have the greatest absolute benefit from treatment,7 although the relative benefit is similar among those with and without chronic kidney disease and an eGFR <30 mL/min. Regretfully this cohort has long been excluded in all the major trials. Based on recent evidence, the absolute benefit of mineralocorticoid receptor antagonists is—contrary to common belief—maintained in patients with a reduced eGFR. The authors thus argue that the time is right to evaluate the role of mineralocorticoid receptor antagonists in patients with heart failure and reduced ejection and a reduced eGFR of 15–30 mL/min. These patients are at the highest risk of death, but paradoxically receive the least effective therapy due to the common fears of inducing hyperkalaemia and worsening renal failure. The promising results of the new non-absorbable K+ binders in such patients strongly suggest that treatment with mineralocorticoid receptor antagonists in combination with these new K+ binders would substantially facilitate the use of mineralocorticoid receptor antagonsist with consequent improved cardiovascular outcomes. In contrast to patients with heart failure and reduced ejection fraction, those with preserved ejection fraction8 represent nearly half of the population with chronic heart failure9 but they have few evidence-based medical therapies for their use.10 The neutral results of the TOPCAT trial with spironolactone in these patients11 leave clinicians with an ongoing clinical dilemma. In a subsequent review ‘After TOPCAT: what to do now in heart failure with preserved ejection fraction?’ Akshay Desai and colleagues from the Brigham and Women’s Hospital in Boston, MA outline an approach to the clinical management of patients with heart failure and preserved ejection fraction based on data from available clinical trials and an expert consensus.12 Prevalence of risk factors by ethnicity. (from Lam CS, Teng TK, Tay WT, Anand I, Zhang S, Shimizu W, Narasimhan C, Park SW, Yu CM, Ngarmukos T, Omar R, Reyes EB, Siswanto BB, Hung CL, Ling LH, Yap J, MacDonald M, Richards AM. Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure registry. See pages 3141–3153.) Kaplan–Meier plots of endpoints according to region. (from Kristensen SL, Martinez F, Jhund PS, Arango JL, Belohlavek J, Boytsov S, Cabrera W, Gomez E, Hag禥 AA, Huang J, Kiatchoosakun S, Kim KS, Mendoza I, Senni M, Squire IB, Vinereanu D, Wong RC, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, Packer M, McMurray JJ. Geographic variations in the PARADIGM-HF heart failure trial. See pages 3167–3174.) The clinical presentation and outcome of heart failure may differ based on ethnicity, economy, and geography. In a FAST TRACK paper ‘Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure (ASIAN-HF) registry’, Carolyn S.P. Lam and colleagues from the National Heart Centre Singapore characterized regional and ethnic differences in heart failure across Asia.20 They prospectively studied 5276 patients with stable heart failure and reduced ejection fraction ≤40% from 11 Asian regions with a mean age of ∼60 years. Two-thirds had two or more co-morbid conditions such as hypertension, coronary artery disease, and/or diabetes. The prevalence of coronary artery disease was highest in South-east Asians. In contrast to Koreans and Japanese, those of Chinese ethnicity, Malays, and Indians had higher odds of coronary artery disease. The prevalence of hypertension and diabetes was highest in South-east Asians and high-income regions. Lam et al. conclude that these first prospective multinational data from Asia highlight the significant heterogeneity among Asian patients with heart failure, and the important influence of both ethnicity and regional income level on patient characteristics. This aspect has been further studied in the paper entitled ‘Geographic variations in the PARADIGM-HF heart failure trial’ by John J.J.V. Mcmurray and colleagues from the Western Infirmary in Glasgow, Scotland.21 They analysed patients from North America, Western Europe, Central and Eastern Europe with Russia, Latin America, and the Asia-Pacific region. Of note, patients from Western Europe and North America were somewhat older than those from Asia-Pacific and Latin America and they had more coronary disease. Further, patients living in North America, and Central or Eastern Europe and Russia had the worst signs, symptoms, and functional status. On the other hand, patients from North American were the most likely to have a defibrillating device and least likely to be prescribed a mineralocorticoid receptor antagonist. Other evidence-based therapies were used most frequently in North America and Western Europe. The rates of the primary composite outcome of cardiovascular death or heart failure hospitalization also varied among regions: in North America it was 13.5 per 100 patient-years, in Western Europe 9.6, in Central and Eastern Europe including Russia 12.3, in Latin America 11.2, and in the Asia-Pacific regions 12.5. After adjustment for prognostic variables, relative to North America, the risk of cardiovascular death was higher in Latin America and the Asia-Pacific region, while the risk of heart failure hospitalizations was lower in Western Europe. Importantly, the benefit of LCZ696 or sacubitril/valsartan was consistent across regions. The authors therefore conclude that there are were substantial regional differences in PARADIGM-HF as regards age, symptoms, co-morbidity, background therapy, and event rates, although these did not modify the benefit of LCZ696. These interesting results are discussed in a well thought out Editorial by Faiez Zannad from the Centre Hospitalier Universitaire de Nancy in France.22 The editors hope that the readers of the European Heart Journal will find this issue of great interest