Overview
Heart failure remains one of the most important cardiovascular conditions in Europe and worldwide, but it is not a single disease. Patients can have heart failure with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), or preserved ejection fraction (HFpEF). These categories reflect how well the heart pumps blood out with each beat, and they often differ in patient profile, underlying causes, and outcomes.
The ESC Heart Failure III Registry provides a contemporary, real-world picture of how patients with heart failure are doing across Europe and affiliated countries. It includes both patients admitted with acute heart failure and patients seen in outpatient clinics for chronic heart failure. The registry helps answer a practical question: what happens to these patients in the hospital and over the following year?
Why ejection fraction matters
Ejection fraction is the percentage of blood pumped out of the left ventricle with each contraction. In HFrEF, the pumping function is clearly reduced. In HFmrEF, it is only mildly reduced. In HFpEF, the pumping function is relatively preserved, but the heart is often stiff and does not relax properly.
Although these groups overlap clinically, they are not identical. HFrEF has long been the best-studied form and has several evidence-based drug treatments. HFpEF has historically had fewer proven therapies, though treatment has improved in recent years. HFmrEF often sits between the two and may share features of both.
Study design and patient population
Between 1 November 2018 and 31 December 2020, investigators enrolled 10,162 patients from 220 centers in 41 countries. The cohort included two major groups: 39% were hospitalized with acute heart failure, and 61% were seen as outpatients for heart failure management.
The acute heart failure group was older on average, with a median age of 70 years, and 36% were women. The outpatient group had a median age of 66 years, and 33% were women. Across the entire registry, 58% of patients had HFrEF, 17% had HFmrEF, and 25% had HFpEF.
This broad, multinational design is important because it reflects everyday clinical practice rather than a tightly controlled clinical trial. That makes the findings highly relevant to hospitals, clinics, and health systems.
Hospital outcomes in acute heart failure
Among patients admitted with acute heart failure, the median hospital stay was 9 days, with an interquartile range of 6 to 14 days. In-hospital mortality was 5.1% overall.
When broken down by ejection fraction, in-hospital death was slightly higher in HFrEF at 5.2%, similar in HFmrEF at 4.8%, and lower in HFpEF at 3.4%. This pattern suggests that lower ejection fraction is associated with worse short-term hospital outcomes, although all three groups carry substantial risk.
A hospital mortality rate of around 5% may seem modest, but for a common condition like heart failure it represents a major burden. It also highlights the vulnerability of patients admitted with acute decompensation, especially those with reduced systolic function, older age, and multiple comorbidities.
One-year outcomes after discharge or outpatient care
For patients who survived hospitalization and for those managed as outpatients, outcomes were assessed over a median follow-up of 376 days, roughly one year. The study reported event rates per 100 patient-years for all-cause death, cardiovascular death, and death from unknown causes.
In acute heart failure survivors with HFrEF, the rates were 19 deaths per 100 patient-years for all-cause mortality, 13 for cardiovascular mortality, and 3.0 for unknown-cause mortality. In acute HFmrEF, the corresponding rates were 22, 11, and 6.3. In acute HFpEF, they were 16, 7.0, and 4.7.
Among outpatients, the rates were lower, as expected. For outpatient HFrEF, all-cause mortality was 6.6 per 100 patient-years, cardiovascular mortality 4.3, and unknown-cause mortality 0.9. For outpatient HFmrEF, the rates were 4.0, 2.6, and 0.8. For outpatient HFpEF, the rates were 3.9, 1.7, and 1.2.
These numbers show two important themes. First, patients seen after an acute hospitalization are at especially high risk during the following year. Second, HFpEF is not benign. Even though its in-hospital and follow-up mortality rates were generally lower than those of HFrEF, patients with preserved ejection fraction still experienced meaningful mortality and rehospitalization risk.
Rehospitalization burden
Heart failure is not only a disease of survival; it is also a disease of repeated healthcare use. In this registry, at least one rehospitalization for heart failure during follow-up occurred in 44% of acute HFrEF patients, 42% of acute HFmrEF patients, and 36% of acute HFpEF patients.
In the outpatient group, at least one heart failure rehospitalization occurred in 21% of HFrEF patients, 14% of HFmrEF patients, and 18% of HFpEF patients.
This difference is clinically important. Patients leaving the hospital after an acute heart failure episode remain at high risk of deterioration, fluid overload, and repeat admission. This often reflects the severity of the underlying disease, incomplete recovery, medication intolerance, poor functional reserve, or limited access to timely follow-up.
What the results mean in practice
The study confirms that heart failure remains a high-risk syndrome across the full range of ejection fractions. It also reinforces several practical points for clinicians and care teams.
First, acute hospitalization identifies a particularly vulnerable group. These patients need careful discharge planning, early follow-up, medication optimization, and monitoring for congestion, renal dysfunction, and worsening symptoms.
Second, HFrEF continues to carry the highest burden of adverse outcomes in many settings, especially in the hospital. This is consistent with the idea that reduced pumping ability often reflects advanced myocardial disease.
Third, HFpEF and HFmrEF should not be viewed as mild conditions. Their mortality rates are substantial, and their rehospitalization rates remain high. In routine care, these patients often have older age, hypertension, obesity, atrial fibrillation, kidney disease, diabetes, and other comorbidities that make management complex.
Fourth, cause-specific mortality matters. Distinguishing cardiovascular death from death of unknown cause helps clinicians and researchers understand where improvements in care may have the biggest impact. The fact that unknown-cause deaths were not negligible also shows the challenge of long-term follow-up in real-world populations.
Clinical implications for care pathways
The registry supports a more proactive heart failure care model. For patients discharged after acute heart failure, the first weeks and months are a crucial period. Strategies that may improve outcomes include early outpatient review, rapid titration of guideline-directed medical therapy, patient education on daily weight monitoring and symptom recognition, sodium and fluid management when appropriate, vaccination, and coordination with primary care and specialists.
For HFrEF, established therapies include beta-blockers, renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, along with diuretics for congestion. For HFpEF and HFmrEF, treatment focuses on symptom relief, volume management, control of blood pressure, treatment of atrial fibrillation and ischemia when present, management of diabetes and obesity, and use of therapies with proven benefit where appropriate, especially sodium-glucose cotransporter 2 inhibitors.
The registry does not test treatment strategies directly, but its findings support aggressive risk reduction and close follow-up across all heart failure phenotypes.
Strengths and limitations
A major strength of the ESC HF III Registry is its size and geographic breadth. More than 10,000 patients from 41 countries provide a realistic snapshot of contemporary heart failure care in Europe and affiliated regions.
Another strength is that the registry included both inpatients and outpatients, allowing comparison across stages of clinical severity. The cause-specific outcome analysis also adds useful detail beyond simple all-cause mortality.
As with all registry studies, however, there are limitations. Observational data cannot prove cause and effect. Patient management was not randomized, and there may be differences in treatment intensity, comorbidity burden, and local care pathways. In addition, registry populations may still differ from the broader heart failure population if some patients were not captured or if follow-up was incomplete.
Even with these limitations, the findings are highly informative because they reflect what is happening in actual practice rather than idealized trial conditions.
Bottom line
The ESC HF III Registry shows that heart failure continues to impose a major burden across Europe and affiliated countries. In-hospital mortality was 5.1% overall and was higher when ejection fraction was lower. Over one year, death and rehospitalization remained common in both acute and outpatient settings.
Patients hospitalized with acute heart failure had particularly high event rates, with roughly twice the risk of rehospitalization compared with outpatient patients. Although HFrEF generally had worse outcomes, HFmrEF and HFpEF also carried substantial risk and deserve equally serious clinical attention.
For clinicians, the message is clear: heart failure management should not stop at discharge. It requires ongoing, phenotype-aware care, close monitoring, and timely treatment adjustment to reduce death, rehospitalization, and the long-term burden of this chronic condition.