Chronic heart failure

Article written and reviewed by Dr Luca Moretti

Chronic heart failure is the persistent phase of a clinical syndrome in which a structural or functional abnormality of the heart causes increased filling pressures, congestion and/or inadequate cardiac output, either persistently or during activity. The term “chronic” describes the continuity of the disease, not an unchanging equilibrium: symptoms, ventricular function, blood volume, perfusion, comorbidities, and treatment tolerance change over time and may pass through improvement, remission, subacute worsening, or acute decompensation. Diagnosis requires current or previous symptoms or signs attributable to the heart and objective confirmation of the cardiac substrate or congestion. An isolated reduction in ejection fraction identifies ventricular dysfunction, but does not encompass the entire clinical definition; likewise, a preserved ejection fraction does not exclude the syndrome when filling pressures, natriuretic peptides, imaging, or hemodynamics document a consistent abnormality. Modern management is longitudinal: it must identify the etiology, phenotype, trajectory, risk, and patient goals, introduce therapies capable of modifying the natural history early, control congestion without causing hypovolemia, and periodically reassess the need for devices, interventions targeting the cause, rehabilitation, or advanced care.

The Second Universal Definition of 2026 reinforces a classification that integrates causes, course, and manifestations, avoiding reducing heart failure to an echocardiographic threshold. In the chronic patient, the history of ejection fraction, the number and severity of episodes of worsening, residual congestion, right heart function, functional capacity, kidney and liver disease, arrhythmias, and the ability to maintain treatment all matter. An apparently stable state may conceal elevated intracardiac pressures, progressive kidney disease, loss of muscle mass, or deterioration in exercise reserve. For this reason, the absence of edema or dyspnea at rest does not equate to normal hemodynamics; true stability requires no recent worsening, euvolemia, adequate blood pressure and perfusion, optimized therapy, and a clinical trajectory without warning signs. Prognosis has been transformed by disease-modifying therapies, but remains heterogeneous. Reversible etiologies and early treatment can produce reverse remodeling; extensive fibrosis, right heart dysfunction, hypotension, organ failure, repeated hospitalizations, and drug intolerance instead indicate high risk and require decisions to be made proactively.

Etiology, pathogenesis, and pathophysiology

Ischemic heart disease causes chronic heart failure through myocardial loss after infarction, recurrent ischemia, hibernation, ventricular remodeling, secondary mitral regurgitation, and arrhythmias. The causal relationship does not depend solely on the presence of coronary stenoses: the extent of scarring, viability, inducible ischemia, and the likelihood that revascularization will improve symptoms or prognosis in the individual context must be established. Arterial hypertension produces pressure overload, hypertrophy, fibrosis, ventricular and arterial stiffness, and atrial dilation. It can lead both to phenotypes with preserved ejection fraction and, after loss of reserve and dilation, to systolic dysfunction; abrupt increases in blood pressure precipitate congestion even without a large increase in total volume. Valvular heart disease causes pressure or volume overload and may be primary or functional. Secondary mitral and tricuspid regurgitation amplifies dilation, congestion, and reduced cardiac output; identifying when valve correction offers benefit requires integrated quantification, optimization of ventricular therapy, and multidisciplinary assessment.

Dilated cardiomyopathies include genetic, inflammatory, toxic, peripartum, arrhythmia-induced, metabolic, and idiopathic forms. Variants in TTN, LMNA, FLNC, DSP, and other genes modify penetrance, arrhythmic risk, and recommendations for family members; normalization of the ejection fraction does not automatically eliminate the risk associated with the genotype or scar. Transthyretin or light-chain amyloidosis, sarcoidosis, hemochromatosis, Fabry disease, and other infiltrative cardiomyopathies require a specific etiological workup because therapies and prognosis differ radically. Increased wall thickness, low voltages, apical sparing on strain imaging, neuropathy, proteinuria, or a history of carpal tunnel syndrome are clues to be integrated, not isolated diagnostic criteria. Persistent tachycardias, rapid atrial fibrillation, a high ectopic beat burden, severe bradycardia, and nonphysiological ventricular pacing can cause or aggravate arrhythmia-induced cardiomyopathy. Recovery after rhythm control or resynchronization supports the causal component, but a predisposing myocardial substrate often coexists.

Systolic dysfunction encompasses abnormalities of contractility, excitation-contraction coupling, energy metabolism, and mechanical coordination. Dilation increases wall stress according to Laplace’s law, promotes functional valvular regurgitation, and converts part of the energy into non-ejecting work; dyssynchrony further worsens efficiency and oxygen consumption. Diastolic dysfunction results from slowed relaxation and increased stiffness due to hypertrophy, fibrosis, ischemia, titin abnormalities, or extracellular deposition. When atrial pressure must rise to maintain filling, congestion may appear particularly during tachycardia or exercise, reflecting reduced diastolic reserve that is not evident at rest. In HFpEF, the interaction among visceral adiposity, diabetes, hypertension, kidney disease, inflammation, microvascular dysfunction, arterial stiffness, and skeletal myopathy produces a multisystem syndrome. The phenotype is not uniform: obesity, atrial fibrillation, pulmonary hypertension, microvascular ischemia, and infiltration may predominate in different proportions.

Reduced effective arterial blood volume and increased pressures activate the sympathetic nervous system, the renin-angiotensin-aldosterone system, vasopressin, and endothelin. These responses initially preserve blood pressure and perfusion, but over time increase afterload, sodium retention, fibrosis, arrhythmias, and oxygen consumption; the benefit of ARNI or renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists demonstrates their causal relevance. Natriuretic peptides, nitric oxide, and adrenomedullin counteract vasoconstriction and retention, but the response is insufficient relative to maladaptive activation. BNP and NT-proBNP reflect wall stress and prognosis, although they vary with age, rhythm, kidney function, obesity, and treatment with sacubitril/valsartan. SGLT2 inhibitors produce benefits that do not depend exclusively on glycosuria: proximal natriuresis, modulation of renal hemodynamics, reduced cellular stress, and improved metabolic efficiency contribute to an early effect across the entire ejection fraction spectrum.

Chronic congestion may reflect increased total body sodium, reduced venous capacitance, or both. The splanchnic compartment is a dynamic reservoir: venoconstriction shifts blood toward the thorax and raises filling pressures even without substantial changes in weight; interstitial edema, intravascular volume, and organ congestion do not necessarily progress in parallel. Elevated venous pressure reduces the renal filtration gradient, causes renal interstitial edema, and limits natriuresis. In the liver it produces cholestasis and centrilobular fibrosis; in the intestine it promotes bowel wall edema, reduced absorption, and microbial translocation; venous congestion is therefore a mechanism of multiorgan damage and not merely a peripheral epiphenomenon. Low cardiac output induces vasoconstriction and redistribution of blood flow; normal blood pressure may mask renal, muscular, and splanchnic hypoperfusion; when compensation fails, cold extremities, oliguria, confusion, and acidosis appear. Cardiac output and cardiac index must be interpreted in relation to hemoglobin, oxygen consumption, and metabolic demand.

With chronic diuretic treatment, the kidney develops distal adaptation, hypertrophy of tubular segments, and increased post-diuretic reabsorption. This diuretic resistance may also result from poor intestinal absorption, reduced tubular secretion of the drug, hypoalbuminemia, low perfusion, or elevated venous pressure, and should not be addressed simply by increasing the dose indefinitely without reassessing the mechanism. Skeletal muscle exhibits capillary and mitochondrial loss, a predominance of glycolytic fibers, endothelial dysfunction, and deconditioning. The ergoreflex increases ventilation and vasoconstriction, explaining why functional capacity correlates only modestly with ejection fraction and improves with exercise even without marked echocardiographic changes. Iron deficiency, anemia, malnutrition, sarcopenia, and frailty reduce oxygen transport and utilization and amplify exercise intolerance. Iron is required by mitochondrial systems even in the absence of anemia; assessment must include ferritin and transferrin saturation in the clinical context.

Clinical manifestations

Exertional dyspnea results from increased pulmonary pressures, reduced cardiac output, impaired diffusion, an inefficient ventilatory response, and peripheral myopathy. It progresses from symptoms during strenuous activity to limitation in daily activities and, in severe stages, dyspnea at rest; the relationship with congestion is not linear, and pulmonary disease, anemia, obesity, and deconditioning may contribute. Orthopnea and paroxysmal nocturnal dyspnea suggest fluid redistribution and increased pulmonary pressures in the supine position. Nocturnal cough, cardiac wheezing, and the need for multiple pillows are useful when interpreted within the clinical trajectory, but are not specific; fatigability reflects low cardiac output reserve, peripheral vasoconstriction, muscle dysfunction, iron deficiency, and comorbidities. It may predominate in patients without obvious overload and must be distinguished from depression, endocrine disorders, sedating drugs, and systemic disease.

Systemic congestion produces dependent edema, weight gain, jugular venous distention, hepatojugular reflux, hepatomegaly, ascites, early satiety, and abdominal discomfort. Edema may be absent in patients with elevated venous pressure or may result from venous insufficiency, nephrosis, cirrhosis, hypoalbuminemia, or drugs; symmetry, evolution, and central findings increase its specificity. Pulmonary congestion may cause crackles, hypoxemia, and pleural effusions, but crackles disappear in chronic forms because of lymphatic adaptation, and their absence does not exclude elevated pressures. A third heart sound, a displaced apex beat, valvular murmurs, and pulsus alternans suggest structural or hemodynamic abnormalities. Signs of hypoperfusion include cold extremities, a narrowed pulse pressure, drowsiness, confusion, oliguria, and worsening kidney function; they may appear late and require comparison with usual values. Orthostatic hypotension may indicate excessive diuresis, autonomic dysfunction, or low reserve and affects titration.

The NYHA class describes functional limitation from I to IV and retains prognostic value, but shows interobserver variability and changes with decongestion, training, and patient perception. It should be supplemented by walking distance, peak oxygen consumption, the VE/VCO2 slope, KCCQ, or other quality-of-life instruments when the clinical question requires it. Frailty encompasses physical, cognitive, and social domains and is not synonymous with age. Falls, reduced gait speed, weakness, weight loss, and difficulty managing treatment influence hospitalization, tolerability, and eligibility for procedures; some components are reversible with rehabilitation and nutritional support. Depression, anxiety, sleep disorders, and cognitive deficits affect symptoms, adherence, and quality of life; the care burden often falls on caregivers and must be considered when simplifying treatment and in advance care planning.

The course may remain stable for months or years, improve with treatment, or be interrupted by episodes of worsening heart failure treated in an outpatient setting, the emergency department, or during hospitalization. An increase in the diuretic dose, a need for intravenous therapy, or an urgent visit are prognostically relevant events even without hospitalization. Early signs include reduced usual exercise tolerance, weight gain, increased orthopnea, nocturia, edema, early satiety, increased jugular venous pressure, or a growing need for diuretics. However, rapid redistribution may precede weight gain, and loss of appetite may mask fluid accumulation; a patient with an improved ejection fraction may become asymptomatic but retains a historical diagnosis and a risk of relapse. Withdrawal of the therapies that produced recovery, as shown in recovered dilated cardiomyopathy, may reactivate remodeling and dysfunction.

Investigations and diagnosis

Assessment begins with a complete history of etiologies, medications, substances, infections, pregnancy, cancer treatments, and family history. Previous ejection fraction values, hospitalizations, dry weight, tolerated doses, arrhythmias, devices, and procedures must be reconstructed, because an isolated snapshot does not identify the trajectory. Physical examination integrates supine and standing blood pressure, heart rate and rhythm, oxygen saturation, perfusion, jugular veins, hepatojugular reflux, lungs, heart, liver, ascites, and edema. No single sign has sufficient sensitivity; the combination and the change from baseline are more informative; the electrocardiogram may show previous infarction, hypertrophy, conduction blocks, dyssynchrony, atrial fibrillation, or arrhythmias. An entirely normal tracing makes significant heart disease less likely, but does not exclude HFpEF or intermittent forms.

A complete blood count, creatinine, estimated glomerular filtration rate, sodium, potassium, bicarbonate, glucose, HbA1c, liver function, TSH, ferritin, and transferrin saturation form a frequently used core laboratory panel. Persistently elevated troponin may reflect chronic injury, ischemia, infiltration, or stress; proteinuria and the albumin/creatinine ratio define cardiorenal risk. BNP and NT-proBNP support diagnosis and prognosis. Low values have high rule-out value in the appropriate context, but obesity may lower them; age, atrial fibrillation, kidney disease, pulmonary hypertension, and other heart diseases increase them. BNP, unlike NT-proBNP, is directly affected by neprilysin inhibition; serial changes in peptides may complement assessment but do not replace clinical evaluation. A titration strategy guided exclusively by the biomarker is not universally recommended; rhythm, kidney function, treatment, and phenotype must be understood.

Transthoracic echocardiography measures volumes, ejection fraction, right heart function, valves, atria, and the pericardium, and estimates pulmonary pressures. Ejection fraction must be interpreted in light of the method, image quality, and loading conditions; a modest change may fall within analytical variability. Global longitudinal strain, stroke volume, cardiac output, the E/e’ ratio, annular e’ velocity, atrial volume, tricuspid regurgitation, and the vena cava provide additional information, but no isolated diastolic parameter demonstrates or excludes elevated pressures. Specific algorithms are needed in valvular disease or atrial fibrillation. Lung ultrasound documents B-lines and effusions and can track decongestion; assessment of the vena cava and organ veins may support the venous profile. Ultrasound evidence of congestion must be integrated with pulmonary, jugular venous, and renal findings and the therapeutic response.

Cardiac magnetic resonance imaging provides reproducible measurements of volumes and function and characterizes scar, edema, infiltration, iron, and ischemic or nonischemic patterns. Late gadolinium enhancement has etiological and prognostic value; T1/T2 mapping and extracellular volume increase sensitivity for diffuse processes, subject to image quality and kidney function. Coronary assessment with CT, functional imaging, or angiography depends on probability, symptoms, function, and eligibility for revascularization; the test must address a clinical question, avoiding equating every incidental finding of coronary artery disease with the cause of heart failure. Bone-tracer scintigraphy, serum and urine immunofixation, and light-chain testing enable the amyloidosis workup; PET, genetic testing, and endomyocardial or extracardiac biopsy are reserved for specific indications. Endomyocardial biopsy is not a routine test and should be performed when the result can modify treatment.

Cardiopulmonary exercise testing quantifies peak VO2, anaerobic threshold, the VE/VCO2 slope, oscillatory ventilation, and the chronotropic response. It is useful for distinguishing cardiac, pulmonary, and peripheral limitations, assessing prognosis, and selecting patients for transplantation or mechanical support; a submaximal effort requires cautious interpretation of peak VO2. Right heart catheterization is indicated when the hemodynamic profile remains uncertain, treatment produces no response, pulmonary hypertension or constriction is suspected, or advanced therapies are being evaluated. Resting pressures may be normal in early HFpEF; exercise or fluid challenge in selected cases may demonstrate the abnormality. Implantable pulmonary pressure monitors reduce events in selected populations when embedded in a system capable of responding to the data. Home measurements of weight, blood pressure, heart rate, and symptoms remain useful, but the effectiveness of telemonitoring depends on the protocol, timeliness, and clinical accountability.

The differential diagnosis includes COPD, interstitial lung disease, chronic embolism, anemia, obesity, deconditioning, venous insufficiency, cirrhosis, nephrosis, and edema-inducing drugs. In suspected HFpEF, the H2FPEF and HFA-PEFF scores can be used to structure the probability assessment, remembering that they do not replace judgment and that intermediate cases often require diastolic stress testing or invasive hemodynamics. The final classification should report the likely etiology, current and previous ejection fraction phenotype, stage, functional class, right heart function, rhythm, valves, congestion, and perfusion. A complete designation facilitates treatment selection and reduces inertia. Echocardiographic reassessment is indicated after clinical changes or treatment sufficient to alter function and device eligibility, not at rigid intervals in every patient. Laboratory tests and visits are more frequent during titration, diuretic changes, or renal instability.

Treatment and prognosis

The goals are to reduce mortality and worsening events, relieve symptoms, preserve organ function, improve capacity and quality of life, and treat the cause. Therapy must be built around the phenotype, but decongestion applies across phenotypes: loop diuretics are titrated to the lowest dose capable of maintaining euvolemia, with monitoring of weight, blood pressure, creatinine, sodium, and potassium. A modest rise in creatinine during effective decongestion may reflect hemodynamic changes and does not mandate withdrawal of beneficial therapies; residual congestion, hypotension, oliguria, or signs of injury are what matter. Conversely, pursuing a creatinine value at the cost of leaving the patient congested worsens prognosis; resistance requires checking medication intake, sodium intake, interactions, and perfusion, increasing the dose or frequency, and sometimes sequential nephron blockade. Thiazides, acetazolamide, or other combinations require close monitoring; ultrafiltration is not a routine solution and is reserved for selected refractory cases.

In HFrEF, foundational therapy comprises an ARNI or, if it cannot be used, an ACE inhibitor/ARB, an evidence-based beta-blocker, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor. The four pillars should be introduced rapidly at low doses and then titrated, avoiding a slow sequence that postpones complementary classes for months; blood pressure, heart rate, kidney function, and potassium guide the individual order. Sacubitril/valsartan must not be combined with an ACE inhibitor and requires a 36-hour washout to reduce the risk of angioedema. Beta-blockers are started or increased in euvolemia and stability; mineralocorticoid receptor antagonists require appropriate kidney function and potassium thresholds; SGLT2 inhibitors can be used independently of diabetes, with education on genital infections, ketoacidosis, and perioperative withholding. Hydralazine-nitrate, ivabradine, digoxin, and vericiguat have selective roles. Vericiguat is supported in high-risk HFrEF patients after recent worsening, whereas the absence of benefit in a stable setting without a recent event prevents its indiscriminate extension.

In HFrEF and HFpEF, SGLT2 inhibitors reduce worsening events across the entire spectrum. The benefit of finerenone on heart failure events at ejection fractions of at least 40% adds an option, to be positioned according to regulatory approvals, kidney function, potassium, and the individual profile; mineralocorticoid receptor antagonists are recommended in symptomatic heart failure regardless of ejection fraction, while ARNI and ARB may be considered in appropriate subgroups. Treatment of obesity targets a cause in the adipose HFpEF phenotype. Semaglutide improves symptoms, capacity, and weight; tirzepatide has reduced worsening events and improved health status in patients with obesity and HFpEF. Selection must consider muscle mass, frailty, gastrointestinal tolerability, and the risk of unintentional weight loss. Hypertension, diabetes, kidney disease, obstructive sleep apnea, and atrial fibrillation require integrated targets. In HFpEF, the phenotype-based strategy also includes identifying and treating amyloidosis, valvular disease, ischemia, pulmonary hypertension, and chronotropic incompetence.

Sinus rhythm and atrioventricular synchronization may improve symptoms in patients with atrial fibrillation, particularly when tachycardia is causal. Anticoagulation is based on thromboembolic risk, not solely on the presence of heart failure; digoxin may contribute to rate control, using low doses and paying attention to kidney function, age, and interactions. Revascularization is indicated according to coronary anatomy, ischemia, symptoms, and prognosis, not as an automatic treatment for reduced ejection fraction. Primary valvular diseases follow specific criteria; in secondary mitral regurgitation, transcatheter repair offers benefit to selected patients who remain symptomatic despite optimal therapy and have suitable anatomy. Cardiac resynchronization therapy reduces events and induces remodeling in selected patients with reduced ejection fraction, a wide QRS, and particularly left bundle branch block; a defibrillator prevents arrhythmic death in appropriate candidates after optimization, balancing competing risk, comorbidities, and preferences.

Adapted aerobic and resistance exercise improves capacity, quality of life, and peripheral function. Cardiac rehabilitation includes exercise, education, psychological support, nutrition, smoking cessation, and management of cardiometabolic factors; prolonged rest promotes sarcopenia and is not a treatment for stable heart failure. Sodium and fluid restriction must be individualized. Excess sodium hinders decongestion, but extreme restrictions may reduce caloric intake, activate neurohormonal systems, and worsen quality of life; fluid restriction is particularly useful in hyponatremia or selected cases of severe congestion. Vaccinations, oral health, moderation of or abstinence from alcohol according to etiology and safety, and review of NSAIDs and edema-inducing drugs are part of prevention. Education must define warning signs, a diuretic plan, contact details, and how to manage vomiting, diarrhea, or procedures.

Follow-up after hospitalization must be early and intensive. STRONG-HF supported a strategy of rapid optimization with closely spaced checks in stabilized patients; weight, blood pressure, congestion, creatinine, and potassium should be reassessed after every substantial change. Adherence is influenced by costs, polypharmacy, literacy, adverse effects, and fragmentation of care. Medication reconciliation must eliminate duplication and explain the function of each class, without automatically attributing symptoms caused by congestion to therapy or vice versa. Multidisciplinary programs, dedicated nurses, pharmacists, rehabilitation, and primary care reduce discontinuity; remote monitoring has value when it generates defined actions; merely collecting data without responding does not change outcomes.

Prognosis is estimated by integrating hospitalizations and urgent visits, NYHA class, blood pressure, rhythm, ejection fraction, right heart function, valves, peptides, sodium, kidney function, liver function, iron status, cardiopulmonary capacity, and frailty. Risk models can support but do not replace the clinical trajectory and tend to lose accuracy when treatment rapidly changes the profile. Signs of advanced heart failure include persistent symptoms, refractory congestion or low cardiac output, repeated hospitalizations, hypotension, organ deterioration, and inability to maintain therapies. Early referral to an advanced heart failure center allows assessment for ventricular assist support or transplantation before biological age and multiorgan failure make these options unfeasible. Palliative care is compatible with active treatment at every stage and addresses dyspnea, pain, anxiety, communication, and family support. Advanced stages require advance care planning, preferences regarding hospitalization and resuscitation, and device management, with decisions that can be revisited.

Complications

Acute congestive decompensations increase mortality and the risk of further events, and each episode may leave a loss of kidney, muscle, or cognitive function. Residual congestion at discharge is a strong prognostic determinant; the transition from intravenous to oral therapy must demonstrate effectiveness before the patient returns home. Cardiogenic pulmonary edema results from a rapid rise in pulmonary pressures and may occur because of a hypertensive crisis, ischemia, arrhythmia, or acute valvular regurgitation. Hypoperfusion and organ damage predominate in cardiogenic shock; the distinction determines the use of vasodilators, diuretics, inotropes, or support; chronic low cardiac output produces asthenia, hypotension, oliguria, confusion, and catabolism without necessarily meeting shock criteria. Indiscriminate introduction of chronic inotropes increases risk and is reserved as a bridge to advanced therapies or for selected palliation.

Cardiorenal syndrome arises from the interaction among venous pressure, perfusion, neurohormonal activation, drugs, and intrinsic kidney disease. A rise in creatinine must be interpreted in relation to volume status, urine output, urinary sediment, and timing; hyperkalemia and hypotension are frequent causes of treatment underuse and require correction of reversible factors. Hepatic congestion causes cholestasis, elevated bilirubin, and fibrosis; abrupt hypoperfusion produces hypoxic hepatitis with a marked increase in aminotransferases; cardiohepatic syndrome alters coagulation, metabolism, and eligibility for advanced therapies. Hyponatremia indicates excess vasopressin and water relative to sodium, often in severe disease; hypokalemia and hypomagnesemia promote arrhythmias, while hyperkalemia limits RAASi use. Correction must be gradual and directed at the cause, avoiding dangerous osmotic shifts.

Atrial fibrillation, ventricular tachycardia, bradyarrhythmias, and sudden death are major complications. Scar, adrenergic activation, ischemia, and electrolyte imbalances form the substrate; arrhythmic risk does not coincide perfectly with ejection fraction and persists in some cardiomyopathies even after recovery. Intracardiac thrombi, stasis, and atrial fibrillation increase thromboembolism and stroke, but heart failure in sinus rhythm does not justify routine anticoagulation without another indication. Bleeding and interactions must be reassessed in frail patients. Functional mitral and tricuspid regurgitation increase pressures, congestion, and dilation in a self-perpetuating cycle; the right ventricle deteriorates because of pulmonary hypertension, ischemia, arrhythmias, and ventricular interdependence, often marking a transition to a worse prognosis.

Iron deficiency, anemia, sarcopenia, and cachexia reduce capacity and treatment tolerance. Cardiac cachexia is an involuntary loss of tissue not explained by decongestion alone and results from anorexia, malabsorption, inflammation, and catabolism; it must not be confused with a simple reduction in weight due to diuretics. Frailty and cognitive decline increase falls, treatment errors, and institutionalization; assessment must seek reversible causes, simplify the regimen, involve caregivers, and maintain activity and nutrition compatible with congestion and kidney function. Anxiety, depression, sexual dysfunction, and social isolation impair quality of life; comprehensive specialist care includes patient-reported outcomes, personal goals, and caregiver burden, not only survival and hospitalizations.

Respiratory infections, acute anemia, thyrotoxicosis, pregnancy, surgery, and cancer treatments can destabilize the balance; prevention must include vaccinations, perioperative planning, cardio-oncology, and preconception counseling when relevant. Obstructive sleep apnea may aggravate hypertension and arrhythmias; treatment improves sleepiness and respiratory control in indicated cases. Adaptive servo-ventilation is not recommended in HFrEF with predominantly central sleep apnea; it may instead be considered when sleep-disordered breathing is predominantly obstructive, to improve sleep quality, quality of life, and symptoms. Progression toward multiorgan failure must not be recognized only in the terminal phase. Repeated hospitalizations, increasing diuretic requirements, hypotension, hyponatremia, right heart dysfunction, and weight loss are opportunities to reassess strategy, eligibility, and the proportionality of care early.