For the cardiologist in general practice, until not too long ago the management of heart failure was not very difficult: Patients with dyspnea had left heart failure, those with edema right heart failure or both. If ischemia was ruled in, catheterization and intervention followed. If it was ruled out, medical treatment was the only option. On the basis of landmark trials, the implementation of diuretics, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in the treatment algorithm of systolic heart failure was the logical consequence. This was heart failure 0.1. It is labeled as HFrEF (heart failure with reduced ejection fraction). Berliner, Hallbaum, and Bauersachs bring us up to date with the most recent therapeutic options: angiotensin receptor-neprilysin inhibition (ARNI), mineralocorticoid receptor antagonists, ivabradine, and potassium binders.

In the past few years, we also learned that a large proportion of symptomatic patients did not have systolic but primarily diastolic heart failure. Cardiac biomarkers such as B‑type natriuretic peptide (BNP) or N‑terminal pro-BNP (NT-proBNP) were indicators sensitive enough to detect this form of heart failure, even when echo-Doppler examinations did not show a reduction of the ejection fraction. The label for this category of patients is HFpEF (heart failure with preserved ejection fraction). But, remarkably, the treatment strategy of systolic heart failure did not work in patients with HFpEF. This was heart failure 1.0 in a true therapeutic dilemma.

What could be done? In 2016, the European Society of Cardiology (ESC) heart failure guidelines created somewhat arbitrarily a third heart failure entity: heart failure with mid-range ejection fraction (HFmrEF). Petutschnigg and Edelmann guide us through the new definition, which stimulated research and initiated new treatment studies. It now appears that HFrEF is considered as a disease primarily of the myocardial cells, while in HFpEF, endothelial dysfunction and inflammation might play a central role. HFmrEF seems to resemble HFrEF rather than HFpEF with respect to ischemic heart disease. Since HFpEF is a heterogeneous syndrome, its underlying pathomechanisms and its clinical management remain an ongoing challenge. Treatment options apart from spironolactone could be the decompression of the left atrium by use of an interatrial shunt device (IASD). Whether the IASD—although interesting in terms of pathophysiology—will stay with us or whether it will disappear, remains to be seen. In addition, today one can also seriously doubt whether the heart failure category HFmrEF will remain or continue as heart failure 2.0.

In the treatment of end-stage heart failure, heart transplantation has the potential to offer a return to daily activities for the patient. However, Buchholz, Guenther, Michel, Schramm, and Hagl point to a major limiting factor: Heart transplantations are decreasing yearly, reaching a historic low in Germany in 2017. Heart transplantation, assist devices, and artificial hearts are high-tech but costly solutions and—regarding heart transplantation—limited by imminent organ shortage. So, can this be heart failure treatment 3.0?

Device therapy of HFrEF such as an implantable cardioverter-defibrillator (ICD) can prevent sudden death. It has long been known that ICDs improve prognosis but not function. Duncker and Veltmann show that cardiac resynchronization therapy (CRT), also an established option for many years, can achieve functional improvement but only in a limited cohort of patients with a broad QRS complex with a left bundle branch block (LBBB) configuration. However, the vast majority of heart failure patients show a narrow QRS complex.

Treating a specific disease and not the syndrome of heart failure alone has been the objective for patients with viral or autoreactive myocarditis/inflammatory cardiomyopathy. Maisch and Alter demonstrate that in autoreactive myocarditis, immunosuppressive treatment has proven to be beneficial in the TIMIC and ESETCID trials, and that in viral cardiomyopathy and myocarditis, ivIgG (intravenous immunoglobulins IgG subtype) and ivIgGAM (polyvalent intravenous immunoglobulins IgG, IgA, and IgM subtypes) can resolve inflammation effectively. Despite an effective elimination of inflammation, the eradication of parvovirus B19 and HHV6 as causative agents is still incomplete in about one third of the patients. This fact remains a challenge, which higher doses of ivIg treatment might cope with in the future.

In their contribution about peripartum cardiomyopathy, Koenig, Hilfiker-Kleiner, and Bauersachs also show that causative treatment can be very successful. Bromocriptine, a dopamine-receptor agonist, effectively blocks the release of prolactin from the pituitary gland, thus preventing damage of endothelial cells and cardiomyocytes. Together with standard heart failure treatment, maternal morbidity and mortality in patients with peripartum cardiomyopathy can thus be reduced substantially.

Our take-home message in this issue of HERZ is clear: Causative treatment of the underlying diseases of heart failure together with constantly improving and developing heart failure therapy will pave the way for heart failure treatment 20.0.

Bernhard Maisch

Johann Bauersachs