Acute heart failure syndromes represented a significant portion of the topics presented at the 2006 ESC Working Group on Acute Cardiac Care Meeting. This is a brief summary (our interpretation) of the lectures presented at this meeting.
Epidemiology:
Acute heart failure was defined as a rapid or gradual worsening of heart failure signs and symptoms requiring emergent therapy. Although most patients initially improve in response to therapy, a post‐discharge event rate including death and hospitalization can be as high as 25–40% within the subsequent sixty day period. It was recognized that in acute heart failure syndroms significant differences exist between North America and Europe in terms of mode of presentation, therapies, hospital length of stay and outcomes. For example the prevalence of pulmonary edema, continuous positive airway pressure (CPAP) utilization, the use of inotropes, cardiac catheterization and device therapy is higher in Europe. These differences may be related to the fact that patients with less severe symptoms are being admitted in the United States rather than receiving outpatient therapies. In fact, hospitalization for heart failure in the United States does not represent acute heart failure in all cases (eg. slight worsening of the symptoms in chronic heart failure may result in hospitalization).
Pathophysiology:
Both an acute or chronic increase in preload and afterload contributes significantly to the clinical manifestations of heart failure and are important therapeutic targets.
Myocardial injury, as represented by troponin release, also plays a prominent role in these syndromes. The correlation between myocardial injury and poor prognosis, both short and long‐term, make myocardial preservation an important target for therapy.
Furthermore, it was recognized that activation of neurohormones (renin‐angiotensin‐aldosterone system, catecholamines, vasopressin) and inflammatory cytokines also contribute to the clinical presentation by negatively affecting myocytes, hemodynamics, coronary flow and renal function.
It was also reported that diastolic dysfunction, in both patients with preserved and decreased ejection fraction of primary or secondary origin, contributes to these syndromes.
Since congestion as opposed to low cardiac ouput is a major reason for hospital re‐admission, it is has become more evident that the kidneys contribute substantially to heart failure symptoms. The cardio‐renal syndrome is defined as worsening of renal function as reflected by an increase in blood urea nitrogen (BUN), not creatinine, in patients who improve clinically and continue to have edema. This syndrome is often precipitated by the use of high dose loop diuretic therapy in the setting of continued fluid overload. This is a reversible “vasomotor” disturbance, rather than a structural abnormality, and is related to high venous pressure, decrease in intravascular volume and further activation of neurohormones. Loop diuretics are known to decrease intravascular volume and further activate the neurohormones, including aldosterone, thus potentiating the renal dysfunction.
Accordingly, the pathophysiologic targets in acute heart failure syndromes are improving hemodynamics, preventing myocardial damage, modulating neurohormones including inflammatory cytokines, improving active relaxation and preventing further deterioration of renal function.
Pulmonary Edema:
The session in acute pulmonary edema recognized that a clear definition of this presentation is still lacking. This clinical entity is often the result of reactive hypertension, defined as a transient and significant increase in blood pressure as a result of sympathetic activation. It is not clear if the target for therapy is the increased blood pressure or the causes (e.g. high filling pressure and activation of neurohormones) that have contributed to this exaggerated response in blood pressure. Irrespective of the cause and effect it was agreed that aggressively treating hypertension with vasodilators, rather than diuretic therapy, will result in prompt clinical improvement. It was also recognized that most patients presenting with flash pulmonary edema have relatively preserved systolic function, a non‐compliant left ventricle and their pulmonary edema is a mismatch between an acute and severe increase in afterload superimposed on the non‐compliant ventricle.
Non‐invasive ventilation is an important therapeutic modality for patients presenting with acute pulmonary edema. In addition, cardiac catheterization is recommended in order to rule out significant coronary artery disease that may have actually precipitated the patients' presentation of acute heart failure syndrome.
Management:
The presentations focused on the emergency room evaluation and management of patients and suggested that vasodilators, particularly nitrates, are more beneficial in the initial management of this condition than high dose diuretics.
It is also important to recognize the use of CPAP in patients who continue to have dyspnea and are not successfully responding to therapy.
During hospitalization both non‐invasive (echo doppler, MRI, nuclear) and invasive cardiac approaches should be employed particularly in patients with known coronary artery disease (CAD) or those with significant risk factors. Proper clinical assessment of acute heart failure patients will result in the use of life‐saving therapies, which includes beta‐blockers, ACE inhibitors, angiotensin II receptor blockers, aldosterone blocking agents, statins, anti‐platelet agents, cardiac resynchronization therapy (CRT), implantable cardiac defibrillators (ICD), percutaneous coronary intervention (PCI), surgical procedures including mitral valve replacement, coronary artery bypass and Dor Procedure. It is more than likely that pre‐discharge use of these modalities will result in improvement in mortality and morbidity.
The role of biomarkers, particularly b‐type natriuretic peptide (BNP), was addressed and has been found to be useful in assessing the severity of hemodynamic congestion (high filling pressure) without clinical signs of congestion, such as edema and jugular venous distention.
New Therapies:
Vasopressin antagonists when added to loop diuretics will result in a further and significant decrease in body weight and congestion without decreasing blood pressure, nor increasing heart rate and renal abnormalities. In addition, they appear to normalize hyponatremia. This is important since approximately 25% of patients presenting with acute heart failure have hyponatremia, which is an independent and major predictor of prognosis. The recently completed EVEREST Trial, which enrolled greater than 4,000 patients with acute heart failure, will provide outcome data regarding the role of vasopressin antagonists in this syndrome.
The calcium sensitizer, levosimendan, was associated with symptomatic improvement, via enhanced contractility, at the expense of significant side effects, including hypotension, arrhythmias and a possible increase in post‐discharge mortality. However, it appears that it is somewhat safer as compared with dobutamine and milrinone, particularly when no loading dose is employed, and when not used concomitantly with dobutamine.
Ularitide, a new natriuretic peptide that is produced by the kidney, has a beneficial hemodynamic effect without worsening renal function. The worth of ularitide is now being studied in a large multi‐center international trial.
Istaroxime, both a lusitropic and inotropic agent, is currently being studied in a Phase II trial and would become a novel treatment option based on its hemodynamic and biochemical profile for acute heart failure.
In addition to old and new therapies for this syndrome, it was established that metabolic and nutritional support is extremely important for patients admitted with heart failure. This was substantiated by the fact that some of the available heart failure therapies may cause nutritional deficiences, such as loop diuretics resulting in vitamin B1 deficiency and statins leading to a loss of coenzyme Q10.
Conclusion:
Despite the poor prognosis associated with acute heart failure syndromes it is evident that patients admitted are often not fully evaluated and that all available therapeutic options are not being implemented. The proper clinical assessment and utilization of many new treatments and therapeutic targets including pharmacologic agents, magnetic resonance imaging for myocardial viability assessment, CRT, ICD, CPAP and surgical procedures can improve symptoms, decrease morbidity and improve mortality in patients afflicted with acute heart failure syndromes.
Suggested Articles:
- Gheorghiade M., Zannad F., Sopko G., Klein L., Pina I. L., Konstam M. A., Massie B. M., Roland E., Targum S., Collins S. P., Filippatos G., Tavazzi L., International Working Group on Acute Heart Failure Syndromes. Acute heart failure syndromes: current state and framework for future research. Circulation 2005; 112: 3958–68
- Nieminen M. S., Brutsaert D., Dickstein K., Drexler H., Follath F., Harjola V. P., Hochadel M., Komajda M., Lassus J., Lopez‐Sendon J. L., Ponikowski P., Tavazzi L. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J 2006; Sep 25, [Epub ahead of print]
- Tavazzi L., Maggioni A. P., Lucci D., Cacciatore G., Ansalone G., Oliva F., Porcu M. Nationwide survey on acute heart failure in cardiology ward services in Italy. Eur Heart J 2006; 10: 1207–15