The demarcation between ADHF and chronic HF is not always clear. Three types of presentations of ADHF have been described [2]: (1) progressive worsening of chronic HF into decompensation, which comprises a majority of admissions; (2) de novo ADHF, comprising ~20 % of patients; and (3) acute ADHF superimposed on the stable chronic HF state. The usual sequence of events, as previously described, is acute LV failure causing abrupt increase in LV pressure and pulmonary congestion/edema. These are followed by the compensatory mechanisms that can produce further deterioration, which, if they persist, can progress to chronic HF. The ultimate clinical outcome is determined by the reversibility of ADHF, the underlying chronic pathophysiology, the triggers of ADHF, and the interplay of these variables.

In a typical clinical scenario, a patient with chronic HF will maintain stability unless there is a circulatory disruption that requires physiologic adjustment. Activation of the latter mechanisms to restore stable cardiac output and filling pressures can ultimately overwhelm homeostatic controls and result in the development of ADHF. When a patient arrives in the ED with ADHF, the critical efforts in the therapeutic process are rapid relief of pulmonary edema and improvement in oxygenation. This goal requires prompt relief of hemodynamic dysfunction to reduce left atrial pressure and alleviate pulmonary congestion [18]. Although it is common to observe rapid resolution of the acutely decompensated state by rapid reduction of preload and/or afterload, the hemodynamic adjustments initiated by most conventional acute therapies do not provide long-term circulatory stability [18, 19]. The derangements in the neurohormonal axis and other chronic control mechanisms that led to the decompensated state usually persist after the primary therapeutic interventions. Therefore, it is essential to immediately address these factors in the secondary phase of management.

Numerous clinical factors can provoke ADHF, and one or more precipitating factors or comorbidities have been identified in a majority of patients presenting with ADHF [2, 3, 27, 28]. Among the most frequent are myocardial ischemia, respiratory pathology, arrhythmias, uncontrolled hypertension, and dietary and medication noncompliance. Any of these factors singly or in combination can initiate the pathophysiologic processes resulting in acute circulatory decompensation when superimposed on chronic HF, or this may occur in the absence of the latter if the provocation is severe enough. Although average left ventricular ejection fraction is moderately reduced (35–40 %) in patients with ADHF, it is preserved in a large minority of this population. Mortality in patients with ADHF has been reported to be 3–4 % in hospitalized patients and 8–10 % at 60–90-day follow-up, which is higher than for patients presenting with acute myocardial infarction without HF [2, 29]. Unfavorable clinical outcome in ADHF is associated with advanced age, acute coronary syndrome, renal insufficiency, respiratory processes, and hyponatremia.

Identifying precipitating factors, relieving symptoms, directly improving short- and long-term outcomes, and initiation and optimization of long-term therapies are the overall goals of therapy in ADHF. Based on the neurohormonal model of heart failure and the pharmacologic actions of current therapeutic modalities, the limitations and potentially deleterious role of some of these approaches can be appreciated. Thus, although diuretics, vasodilators, and positive inotropic agents may afford symptomatic relief and important therapeutic benefits acutely, their excessive use can exacerbate underlying detrimental neurohormonal overactivity on the myocardium, vasculature, kidney, and fluid and electrolyte balance (Fig. 7.1). Diuretics and vasodilators stimulate further activation of the sympathetic nervous system, renin–angiotensin–aldosterone system, vasopressin, and endothelin, as do direct vasodilators [9]. Additionally, the unfavorable myocardial effects of positive inotropic agents are similar to those of the endogenous catecholamines described previously [28]. In addition, inotropic agents can increase atrial and ventricular arrhythmias [29]. These considerations have stimulated concern for judicious and physiologically rational application of these therapeutic approaches based on underlying pathophysiology to mitigate their undesirable effects. Novel neurohormonal antagonists have been investigated for ADHF. The oral direct renin inhibitor, aliskiren, recently demonstrated no beneficial effect on cardiovascular death or HF rehospitalization but increased adverse effects [30]. Serelaxin is a recombinant form of human relaxin-2 found to significantly improve HF signs and symptoms and markers of congestion and end organ damage [31].

ADHF is an increasingly common and potentially lethal form of heart failure. It is usually superimposed on a background of chronic HF, but it may occur de novo. Numerous provoking factors have been identified, and most patients with ADHF have important comorbidities. Early repeat hospitalizations are common in this patient population, which has a high short-term posthospital mortality. The maladaptive compensatory neurohormonal mechanisms that contribute to chronic HF are also operative in ADHF. Although conventional therapy with diuretics and positive inotropic agents may yield early salutary clinical results, caution must be exercised with these methods because they have the potential to further augment adverse neurohormonal activation. The cardiorenal syndrome is a particularly challenging complication, the precise mechanisms of which have not been clarified. It is anticipated that current investigation of ADHF will afford enhanced approaches to its management.