Complexities of managing heart failure

The latest ESC Guidelines on heart failure (HF) were published in 2016. New in this version were a diagnostic algorithm for suspected HF, a novel mid-range ejection fraction (EF) category referred to as HFmrEF, the role and position of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan, and more focus on comorbidities.

HFmrEF refers to an EF of 40-49%. This is a category of patients that is currently underserved, and less is known about these patients because they are not often included in studies. Diagnosis of HFmrEF and HFpEF is more complicated than of HFrEF, and for diagnosis of the first two conditions, additional testing (natriuretic peptides) and an additional criterion (relevant structural heart disease and/or diastolic dysfunction) is required.

A patient case served as a means to discuss which therapies may give benefit to HF patients: although the data are somewhat controversial, statins do not seem to reduce major CV outcomes in older patients with systolic HF. When in doubt, Van der Meer considers whether a patient matches the trial population. In the case of statins, he would not actively stop statin therapy if the patient does not experience side-effects. It will not harm the patient, but the benefit is limited. Eplerenone, on the other hand, has been shown to provide a benefit in patients with systolic HF.

As a next step, additional tests may be performed, but this is only useful if it something can be done afterwards, which improves symptoms. This is not always clear. For instance, the STITCH trial compared CABG vs optimal medical therapy (OMT) in patients with EF<35% and CAD suitable for CABG. Only in the 10-years follow-up data, a benefit of CABG was seen when compared with OMT. The benefit of digoxin therapy is also unclear: an old study showed no mortality benefit, but a trend towards benefit for mortality due to worsening HF. Later analyses suggested that digoxin therapy may be beneficial at lower digoxin serum concentrations. A Dutch study will further investigate the effect of low-dose digoxin on morbidity and mortality.

A new treatment option that has entered the Guidelines, is sacubitril/valsartan. In the PARADIGM-HF trial, this ARNI reduced the relative risk of both the primary endpoint and death from CV causes by 20%. Based on the trial evidence, the Guidelines therefore recommend switching to ARNI in patients who remain symptomatic and have EF <35% despite ACEi, beta-blocker and MR antagonist therapy, in those who tolerate ACEi or ARB. It is important to note that ACEi therapy should be stopped 36 hours before initiation of ARNI.

Van der Meer devoted part of his presention to management of comorbidities in HF, the most relevant of which are chronic kidney disease (CKD), cancer, gout, erectile dysfunction and COPD/Asthma, along with hypertension and diabetes, which were discussed in detail in other sessions of the Summit.

CKD, or renal dysfunction, generally defined as eGFR <60 mL/min/1.73m² and/or presence of albuminuria, is relevant for the prognosis in HF. The cardiorenal syndrome is recognised in HF, which refers to HF leading to decreased renal perfusion, but also that the latter negatively impacts the heart. Diuretic therapy can sometimes dampen the effect of HF on renal function, but it may also negatively affect renal function. 5 stages of CKD are recognised, and most patients included in HF trials have CKD stage 2/3 (eGFR >30). The evidence on the best treatment for HF patients with CKD stage 4/5 is limited.

Cancer is relevant in light of HF, because some chemotherapies can cause or aggravate LV systolic dysfunction and HF. It may be wise to check EF every 3 months. Moreover, an echocardiogram may be done before starting treatment, to establish a baseline, and repeat it after the first dose. Alternative therapies may be considered if a decline in EF is seen. Cardio-oncology is now getting more attention, and haematologists/oncologists are communicating more with cardiology. A study assessed the prevalence of long-term cardiac dysfunction in general practices by echocardiography of women treated with chemotherapy, radiotherapy or both for early breast cancer and found an odds ratio of 2.5 for having LVEF <54%, as compared with matched controls without such therapy. Biomarkers in blood were also assessed in these women, which revealed a pro-inflammatory profile 10 years after their treatment for cancer.

Regarding gout, it should be known that there is a strong recommendation against the use of NSAIDs or COX-2 inhibitors, as they increase the risk of HF worsening and HF hospitalisation. In case of erectile dysfunction, PDE5 inhibitors can safely be used in HF, although not in combination with nitrates. With regard to lung diseases, there are no (longer) absolute contraindications for use of beta-blockers in those with asthma, and COPD is no reason to withhold lifesaving beta-blocker therapy. The long-term safety of inhaled drugs for lung disease in HF patients is uncertain. Importantly, it is now known that adaptive servo-ventilation is not recommended in patients with HFreF: it relieves symptoms, but it increases mortality.

Van der Meer ended with listing gaps in the evidence on how to manage comorbities in HF patients. They relate to specific patient populations, such as the very elderly, the young, those with eGFR <30 mL/min/1.73m², diabetic patients, and those with cardiotoxic chemotherapy-induced HF, muscular dystrophies, or cachexia and depression. Moreover, more information is needed on therapies for HF-related sleep-disordered breathing in all HF subtypes.

Read impressions of other sessions during the CV summit