How Important is the Time Factor in the Treatment of Heart Failure?
Current guidelines emphasize the importance of early diagnosis and immediate treatment for patients with heart failure (HF). These patients are most vulnerable immediately after the decompensation of chronic HF, and intensive treatment can therefore reduce the risk of further hospitalization and mortality. The prognosis for these patients is unfavorable, and any delay in initiating therapy further worsens it. The treatment of chronic HF is often postponed if the symptoms are stable, and the risk of adverse outcomes and sudden death is underestimated. The time factor thus plays a significant role in all stages of HF.
Early Therapy Saves the Myocardium
Despite significant improvements in the management of cardiovascular (CV) diseases in recent decades, these illnesses remain the most common cause of death worldwide. The critical role of time-to-treatment initiation as a risk factor has already been demonstrated in the therapy of acute myocardial infarction with ST-segment elevation (STEMI). The management of STEMI has significantly changed with this understanding, and it is now known that the sooner therapy is initiated from the onset of symptoms, the better the prognosis for patients.
Chronic HF, by its designation, may lead to the misconception that immediate pharmacotherapy is unnecessary. This approach frequently results in its delayed implementation. However, the risk of acute decompensation rapidly increases, and it is important to remember that acute HF is already associated with irreversible cardiomyocyte damage. After an episode of HF decompensation, mortality remains very high.
Hospital Treatment of Acute HF
In 70–80% of cases, acute HF is caused by decompensation of a chronic condition. In-hospital mortality is approximately 4–6%, and the risk of rehospitalization or death within the following year reaches 10–30%. Several studies have already addressed the time factor in initiating treatment.
The ADHERE registry analysis introduced the concept of door-to-diuretic (D2D). It was found that delaying diuretic administration by every 4 hours significantly increased mortality in patients with decompensated HF, prolonged hospitalization, and increased the risk of ICU admission and symptoms at discharge.
These findings were confirmed about 20 years later in the first prospective study including 1291 patients presenting to the emergency department for acute HF. Patients who received diuretics within 60 minutes of arrival had lower overall in-hospital mortality (2.3% vs. 6.0% in others; p = 0.002). The D2D threshold was determined to be 100 minutes, beyond which mortality significantly increases.
Observational studies KorAHF and FAST-FURO also looked into this issue. However, their results did not show a significant difference in prognosis depending on D2D. This difference might be explained by the observational nature of the data and various procedures and different quality of care across global regions.
The Most Vulnerable Moment is at Hospital Discharge
The ASCEND-HF registry examined the impact of hospitalization length on patient prognosis. The data indicate that with each additional day of hospital stay, the risk of rehospitalization for HF decreases by 21% (14% for rehospitalization from any cause). Another significant risk factor is the total number of HF hospitalizations (e.g., after the 3rd HF hospitalization, 50% of patients die within 1 year). Mortality remains elevated for up to 18 months. The early phase after hospital discharge represents the highest risk period for rehospitalizations and mortality, especially in patients with persistent congestion. Therefore, identifying these patients during hospitalization and their early and intensive treatment is crucial.
According to recommendations, patients should have initiated and optimized chronic HF treatment at the time of hospital discharge. The GREAT study found that starting therapy with beta-blockers (BB), renin-angiotensin-aldosterone system (RAAS) inhibitors, and mineralocorticoid receptor antagonists (MRA) before discharge significantly reduced mortality. Optimizing HF treatment also includes sodium-glucose cotransporter 2 inhibitors (SGLT2i, i.e., gliflozins), dual angiotensin II receptor and neprilysin inhibitors (ARNI), diuretics, ivabradine, etc.
Chronic HF Must Not Be Underestimated
Long-standing and worsening symptoms of inadequately compensated HF predict a poor prognosis. Chronic HF is often accompanied by other comorbidities, particularly chronic kidney disease (CKD) and type 2 diabetes mellitus, which further increase mortality. Studies have confirmed the association between the duration of HF symptoms and the number of comorbidities, as well as the impact of comorbidity count on HF treatment outcomes. Therefore, HF treatment optimization should occur as soon as possible regardless of symptom duration. This principle applies to both pharmacotherapy and resynchronization therapy or implantable cardioverter-defibrillator (ICD) implantation.
„There Is No Time to Waste“
Heart failure should be considered an urgent condition requiring rapid and comprehensive treatment in all its stages. Early symptom recognition, prompt therapy initiation, appropriate hospitalization duration, and well-adjusted subsequent chronic treatment crucially impact disease prognosis. Any delay is wasted time that can lead to irreversible myocardial damage and further complications.
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Source: Abdin A., Anker S. D., Butler J. et al. 'Time is prognosis' in heart failure: time-to-treatment initiation as a modifiable risk factor. ESC Heart Failure 2021; 8: 4444–4453, doi: 10.1002/ehf2.13646.
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