Heart failure

Article written and reviewed by Dr Luca Moretti

Heart failure, or cardiac insufficiency, is a heterogeneous clinical syndrome in which a structural or functional disease of the heart impairs ventricular filling, blood ejection or both, generating symptoms and signs due to increased intracardiac pressures, congestion and, in more severe forms, reduced cardiac output. It is not synonymous with a single heart disease, a particular ejection fraction or the mere presence of edema: it represents the common final outcome of many myocardial, valvular, ischemic, pericardial, arrhythmic, congenital and vascular diseases. The syndrome must be interpreted along a dynamic trajectory. Patients may go through a phase of risk without demonstrated cardiac abnormalities, develop structural or biomarker abnormalities in the absence of symptoms, subsequently manifest clinical heart failure, improve with treatment, enter remission or progress to an advanced form. Improvement in ventricular function does not necessarily equate to biological recovery, because the underlying causal substrate and predisposition to relapse may persist. Contemporary classification integrates clinical course, ejection fraction, the predominantly involved ventricle, hemodynamic status, pathophysiological mechanism, etiology and severity. These dimensions are complementary rather than mutually exclusive: a person may, for example, have acute decompensated chronic heart failure, reduced ejection fraction, biventricular congestion and low cardiac output due to ischemic cardiomyopathy. A comprehensive designation is not merely a descriptive exercise, but guides investigations, treatment priorities and prognosis.

Left ventricular ejection fraction remains useful for describing the phenotype and selecting validated treatments, but it is a measurement dependent on loading conditions, geometry, image quality and analytical variability. It does not directly measure contractility, describe right ventricular function or, on its own, quantify filling pressures or the ability to increase cardiac output during exercise. For this reason, a normal ejection fraction does not rule out heart failure, and a reduced ejection fraction, in the absence of current symptoms or signs, is not sufficient to define every aspect of the clinical syndrome. The term “congestive heart failure” emphasizes a frequent but not universal component. Congestion may be pulmonary, systemic or both; it may result from an actual increase in extracellular volume, rapid venous redistribution of blood or a combination of the two mechanisms. In low-output forms, weakness, oliguria, altered mental status, cold skin and organ dysfunction may instead predominate, sometimes without obvious peripheral edema. The clinical impact stems from the high prevalence, frequent hospitalizations, still substantial mortality and progressive interaction with kidney disease, frailty, diabetes, obesity, atrial fibrillation, bronchopulmonary disease and iron deficiency. Older age increases complexity, but heart failure is not an inevitable consequence of aging: prevention of hypertension, treatment of the underlying heart diseases and early therapy for preclinical phenotypes can substantially modify its natural history.

Clinical significance, definition and trajectory of the syndrome

The clinical definition requires linking the patient’s presentation to a plausible cardiac abnormality. Dyspnea, edema and fatigability are common to many diseases; they become relevant to heart failure when the history, physical examination, natriuretic peptides, electrocardiogram and imaging demonstrate or strongly suggest a cardiac origin. In uncertain situations, especially with preserved ejection fraction, demonstration of elevated filling pressures at rest or during exercise may become decisive. The preventive continuum includes people with risk factors alone and individuals with pre-heart failure, in whom structural heart disease, cardiac dysfunction or abnormal biomarkers are already present without current or previous symptoms attributable to the syndrome. Recognizing this stage allows treatment of hypertension, diabetes, ischemia, valvular disease and cardiomyopathies before a chronic increase in filling pressures or a reduction in contractile reserve produces clinical manifestations. Current or previous symptoms or signs mark entry into the stage of overt heart failure; functional severity ranges from limitation detectable only during intense exertion to symptoms at rest. NYHA class describes the functional impact at a given time, but may change rapidly with decongestion and treatment and does not replace assessment of etiology, ventricular function, biomarkers and event risk.

The advanced stage is not simply synonymous with a low ejection fraction or an occasional high NYHA class. Advanced heart failure involves severe, persistent symptoms, recurrent hospitalizations or instability, and severe cardiac dysfunction despite optimized treatment, requiring evaluation for ventricular assist support, transplantation, palliative strategies or a proportionate combination of these interventions. The trajectory may include improvement, remission and relapse. Inflammatory, tachycardia-mediated, peripartum or toxic cardiomyopathy may show substantial recovery after removal of the cause and treatment; other forms improve without normalization of the molecular substrate. Indiscriminate withdrawal of the treatments that enabled recovery exposes some patients to relapse, which is why the history of ventricular function must remain documented even when a subsequent echocardiogram appears normal.

Classification according to clinical course and ejection fraction

Decompensated heart failure is the acute or gradual worsening of symptoms and signs that requires intensification of treatment; more severe presentations may require intravenous therapy or hospitalization. It may represent the onset of previously unknown heart disease or destabilization of a pre-existing syndrome. Pulmonary edema, acute right ventricular failure, cardiogenic shock and congestive exacerbation have different mechanisms and priorities, although they fall within the same clinical category. Chronic heart failure describes a persistent condition in which cardiac structure, symptoms, treatment and neurohormonal compensatory mechanisms evolve over time. “Chronic” does not mean permanently stable: prolonged periods of equilibrium may alternate with subacute deterioration, acute episodes, silent progression of organ dysfunction or clinical improvement after correction of the cause and optimization of treatment. In acute decompensated chronic heart failure, the patient has a pre-existing diagnosis and develops congestion, hypoperfusion or both beyond their usual equilibrium. Infections, ischemia, arrhythmias, uncontrolled hypertension, progression of valvular disease, drugs that promote sodium and water retention, failure to take prescribed treatment and renal deterioration are frequent precipitants, but multiple factors contribute to many hospitalizations.

The phenotype with reduced ejection fraction identifies left ventricular systolic dysfunction and has the largest body of trial evidence demonstrating reductions in mortality and hospitalizations. Current prognosis-modifying treatment is based on coordinated inhibition of the renin-angiotensin-neprilysin system, beta-blockade, mineralocorticoid antagonism and SGLT2 inhibitors, tailored to blood pressure, renal function, potassium, rhythm and tolerability. Heart failure with LVEF 41-49% is now included within HFrEF and occupies the higher-ejection-fraction portion of the HFrEF spectrum, on a biological continuum with HFpEF. It should not be interpreted as a “mild” form: symptoms, filling pressures, right ventricular dysfunction and risk may be substantial. SGLT2 inhibitors have robust evidence across the entire range, while other treatments may be particularly useful toward the lower end of the ejection fraction range and in selected phenotypes. In heart failure with preserved ejection fraction, diagnosis requires more than the simple association of dyspnea and a normal ejection fraction. Evidence of elevated filling pressures, atrial or ventricular remodeling, diastolic dysfunction, congestion and compatible comorbidities must be sought, while excluding mimics such as lung disease, anemia, obesity with deconditioning, ischemia and precapillary pulmonary hypertension.

Heart failure with improved ejection fraction retains the history of previous systolic dysfunction; the new measurement must be interpreted alongside the baseline value, the absolute change, ongoing treatment and etiology. Apparent normalization may reflect true reverse remodeling, changes in loading conditions or technical variability; continuation of treatment generally remains essential.

Hemodynamic phenotypes, ventricular involvement and related syndromes

The distinction between predominantly left-sided failure, right-sided heart failure and biventricular heart failure describes the compartment that dominates the presentation. However, ventricular interdependence makes reciprocal involvement frequent: increased left-sided pressures cause postcapillary pulmonary hypertension and right ventricular overload, while right ventricular dilation may displace the septum, limit left ventricular filling and further reduce cardiac output. The “wet” profile indicates congestion, and the “cold” profile indicates hypoperfusion; the warm-dry, warm-wet, cold-dry and cold-wet combinations help guide initial management, especially during acute phases. These are clinical categories, not invasive measurements: blood pressure, peripheral perfusion, urine output, mental status, lactate, jugular veins, crackles, edema and response to treatment must be integrated without relying on a single finding. In high-output heart failure, the heart may eject a normal or greater-than-normal amount of blood that is nevertheless inadequate for an extreme metabolic demand or very low systemic vascular resistance. Severe anemia, thyrotoxicosis, large arteriovenous fistulas, beriberi and certain liver or myeloproliferative diseases are typical causes; treatment must correct the extracardiac mechanism, rather than being limited to diuretics.

Cardiogenic pulmonary edema results from a rapid increase in pulmonary capillary hydrostatic pressure, with fluid moving into the interstitium and alveoli. It may develop because of a hypertensive crisis, ischemia, acute mitral regurgitation, tachyarrhythmia or volume overload; venous redistribution may produce severe respiratory failure before a marked increase in body weight appears. Cardiogenic shock combines a primary inability of the cardiovascular system to maintain adequate perfusion with organ injury or the risk of organ injury. Hypotension, vasoconstriction and elevated lactate are frequent but not mandatory in the early stages. Myocardial infarction, fulminant myocarditis, advanced heart failure, mechanical complications, arrhythmias and right ventricular failure require different strategies and rapid identification of the reversible cause; low cardiac output syndrome may precede overt shock or persist in a chronic form. Apparently preserved blood pressure does not guarantee adequate cardiac output, because increased systemic vascular resistance may maintain pressure at the expense of reduced perfusion. Recognition is based on the combination of peripheral and organ signs, echocardiography and, where appropriate, invasive hemodynamic assessment.

Diagnostic pathway and principles of treatment

The diagnostic pathway begins with clinical probability and must answer four questions: is the syndrome truly present, which hemodynamic phenotype predominates, which heart disease caused it, and which factors are driving its deterioration? Electrocardiography, echocardiography, complete blood count, renal function, electrolytes, liver function, blood glucose, iron studies, TSH and natriuretic peptides are frequent components of the initial assessment, adjusted to the context. BNP and NT-proBNP are particularly useful because of their high rule-out value when low in an untreated patient with an appropriate clinical suspicion. Elevated values are not specific: age, atrial fibrillation, renal dysfunction, pulmonary embolism, pulmonary hypertension and critical illness may increase them, while obesity and sacubitril/valsartan treatment modify their interpretation. The result must be considered alongside symptoms, signs and imaging; echocardiography defines volumes, systolic and diastolic function, valves, atria, right ventricle, pericardium, estimated pulmonary pressures and possible mechanical causes. Magnetic resonance imaging characterizes tissue, scar, infiltration, edema and function when echocardiography is insufficient; CT and coronary imaging clarify anatomy and ischemia; right heart catheterization, cardiopulmonary exercise testing and genetic assessment are reserved for selected diagnostic questions.

Treatment includes correction of the etiology, removal of precipitants, relief of congestion, and drugs or devices capable of modifying prognosis in the appropriate phenotype. Diuretics control overload and symptoms but do not replace neurohormonal therapy; the four pillars of HFrEF should be introduced early and titrated in a coordinated manner; SGLT2 inhibitors also reduce events in HFrEF with LVEF 41-49% and in HFpEF; valvular disease, ischemia, arrhythmias and specific cardiomyopathies require interventions directed at the cause. Education, adapted physical activity, rehabilitation, vaccination, smoking cessation, alcohol moderation when indicated, and management of blood pressure, diabetes, obesity, renal function and iron status are part of treatment. Indiscriminate, very severe sodium or fluid restrictions are not appropriate for every patient; they must be individualized according to congestion, hyponatremia, requirements, diuretic therapy and the risk of malnutrition. Early follow-up after hospitalization is a particularly valuable phase of treatment. Weight, blood pressure, heart rate, symptoms, renal function, potassium, congestion status, adherence and drug doses must be reassessed promptly. In stabilized patients, a strategy of intensive optimization of treatment and close follow-up reduces the risk of death or rehospitalization compared with slow, fragmented titration.

Systemic progression, complications and continuity of care

Heart failure is a cardiovascular and systemic syndrome; cardiorenal syndrome arises from the interaction of reduced perfusion, elevated renal venous pressure, neurohormonal activation, inflammation, drugs and pre-existing kidney disease. A modest increase in creatinine during effective decongestion does not automatically equate to tubular injury and should not prompt discontinuation of useful treatment without assessment of the overall clinical status. In cardiohepatic syndrome, venous congestion may cause cholestasis, increased bilirubin and centrilobular fibrosis, while abrupt hypoperfusion may produce hypoxic hepatocellular injury with a marked rise in aminotransferases. The liver may in turn contribute to sodium and water retention and hemostatic abnormalities, requiring a pathophysiological interpretation of laboratory results rather than a simple label of “liver disease”. Cardiac cachexia is an involuntary loss of body tissue that cannot be explained solely by the removal of edema. Reduced intake, malabsorption due to intestinal congestion, inflammation, adrenergic activation, anabolic abnormalities and increased energy expenditure contribute to catabolism. It should be distinguished from sarcopenia and frailty, although the three conditions may coexist and worsen treatment tolerance and prognosis.

Atrial fibrillation, ventricular tachycardias and bradyarrhythmias may be a cause, consequence or precipitant. Functional mitral and tricuspid regurgitation amplify congestion; thromboembolism, stroke, infections, iron deficiency, sleep-disordered breathing and depression increase disability and hospitalizations. Effective management therefore requires multidisciplinary care that keeps the underlying heart disease at its center without neglecting the organs and conditions that modify its course. Individual prognosis varies widely. Repeated hospitalizations, hypotension, hyponatremia, progressive renal or hepatic dysfunction, right ventricular impairment, persistently elevated natriuretic peptides, treatment intolerance, arrhythmias and reduced functional capacity identify increasing risk. No single value predicts the course on its own; serial assessment of the trajectory is more informative than an isolated snapshot. Continuity of care must include discharge planning, medication reconciliation, rapid access to follow-up, education on warning signs, rehabilitation and reassessment of goals of care. In advanced stages, palliative care and symptom control may coexist with active treatments, devices and assessment for replacement therapies. Discussing preferences, delegation of decision-making and future device management does not mean abandoning care, but making it proportionate and consistent with the patient’s wishes.