Valvular heart disease

Article written and reviewed by Dr Luca Moretti

Valvular heart disease includes congenital and acquired disorders that impair the opening, closure or integrity of one or more heart valves. A stenotic valve resists forward flow; an incompetent valve permits retrograde flow; a mixed lesion combines both defects. These definitions describe the hydraulic behavior of the valve, but do not fully describe the disease: clinical significance also depends on etiology, speed of onset, flow, loading conditions, myocardial response and damage to chambers upstream and downstream from the valve.

The four valves function as integrated components of a pulsatile pump. The aortic valve and pulmonary valve regulate ejection from the ventricles into the great arteries; the mitral and tricuspid valves permit ventricular filling and prevent systolic reflux into the atria. Their function depends not only on the leaflets but also on annuli, commissures, arterial roots, chordae tendineae, papillary muscles and ventricular geometry. An anatomically normal valve may therefore become regurgitant when the ventricle, atrium or annulus dilates.

The prevalence of clinically relevant valvular heart disease increases with age. In a historical US population study, moderate or severe disease affected about 2.5% of adults and increased markedly after age 75; more recent global estimates confirm a high but unevenly distributed burden. In high-income countries, calcific aortic stenosis, degenerative mitral regurgitation and functional forms associated with cardiomyopathy or atrial fibrillation predominate, whereas rheumatic heart disease remains a major cause in low- and middle-income countries.

The course may remain silent for years because hypertrophy, dilation and neurohormonal adaptations initially maintain output and pressures. This compensation is not indefinite: increased wall stress, fibrosis, ventricular dysfunction, atrial dilation and pulmonary hypertension may progress before the patient recognizes a limitation. Modern management of valvular heart disease therefore aims to intervene not only when symptoms are overt, but before cardiac damage becomes irreversible.

Functional anatomy and classification

Semilunar valves normally have three pocket-shaped cusps and no chordae or papillary muscles. During ejection, the aortic and pulmonary cusps move toward the walls of their respective roots, providing a large outflow area; when the gradient reverses, the sinuses fill and promote central coaptation. Competence depends on the interaction among the cusps, ventriculoarterial junction, sinotubular junction and root dimensions.

The aortic valve separates the left ventricular outflow tract from the aorta and has right coronary, left coronary and noncoronary cusps. Progressive fibrosis and calcification may produce aortic stenosis, whereas leaflet disease or root dilation may cause regurgitation. A bicuspid morphology often leads to earlier degeneration and dysfunction and requires parallel assessment of the ascending aorta.

The pulmonary valve separates the right ventricle from the pulmonary trunk. Isolated disease in adults is less common and mainly results from congenital heart disease or previous interventions on the right ventricular outflow tract. A stenotic gradient imposes pressure overload on the right ventricle, whereas chronic regurgitation, particularly after repair of tetralogy of Fallot, causes progressive right ventricular dilation and may promote arrhythmias.

The atrioventricular valves are complex apparatuses. The mitral valve has anterior and posterior leaflets divided into scallops and supported by chordae connected to the anterolateral and posteromedial papillary muscles; the tricuspid valve has more variable morphology, a larger nonplanar annulus and leaflets commonly described as anterior, posterior and septal. Competence requires three-dimensional coordination among all components.

A lesion is defined as primary when the defect lies in the leaflets, chordae or papillary muscles, as in myxomatous degeneration, endocarditis or chordal rupture. It is secondary when the valve is structurally normal or only secondarily deformed and regurgitation results from annular dilation, leaflet tethering or papillary muscle displacement caused by ventricular or atrial remodeling.

Stenoses are classified according to location, anatomy, severity and hemodynamic consequences. Valve area, maximum velocity, mean gradient and flow are not interchangeable: the gradient depends on the square of velocity and therefore on flow, while calculated area is affected by measurement errors. Severity must therefore be established through integrated interpretation rather than a single number.

Regurgitant lesions require distinction between mechanism and severity. Vena contracta width, effective regurgitant orifice area, regurgitant volume and fraction, Doppler signals in upstream veins and chamber remodeling all contribute to quantification. Blood pressure, volume status, heart rate and rhythm may alter regurgitation during the same examination; the relationship between the lesion and hemodynamic conditions should be stated explicitly.

Multiple valve disease involves at least two valves, whereas mixed valve disease combines stenosis and regurgitation of the same valve. Hemodynamic interactions may mask or amplify conventional parameters: for example, mitral stenosis reduces flow across aortic stenosis and lowers its gradient, while significant mitral regurgitation may reduce forward aortic stroke volume. In such settings, separate quantification of individual lesions is insufficient.

The fibrous skeleton links the aortic, mitral and tricuspid annuli, supports their insertions and electrically insulates the atria from the ventricles except for the conduction system. Mitral-aortic continuity and the proximity of the membranous septum explain why calcification, endocarditis or procedures may involve adjacent structures, produce abscesses or cause atrioventricular block.

The mitral valve and tricuspid valve depend on ventricular shape. Annular and papillary contraction brings the leaflets into coaptation; dilation, dyssynchrony or papillary muscle displacement may cause regurgitation even without a tear. The anatomical description should therefore include the chamber, annulus and subvalvular apparatus.

The behavior of the right-sided valves varies with respiration. Inspiration increases venous return and may intensify tricuspid and pulmonary murmurs, while pulmonary vascular pressures and right ventricular function modulate gradients and regurgitation. The pulmonary valve should therefore be interpreted together with the outflow tract, pulmonary arteries and history of congenital heart disease.

Modern classification adds the stage of cardiac damage to the valvular stage. Ventricular thickening or dilation, atrial involvement, secondary regurgitation, pulmonary hypertension and right ventricular dysfunction describe propagation of disease. Two lesions with identical valvular parameters may have different prognoses if one is still isolated while the other has already compromised several cardiac compartments.

Etiology, pathogenesis and pathophysiology

Calcific aortic valve disease is an active biological process, not merely passive calcium deposition. Endothelial injury on the aortic side of the cusps promotes retention and modification of lipoproteins, recruitment of inflammatory cells and activation of valvular interstitial cells, which may acquire an osteoblast-like phenotype and produce mineralized matrix. Progressive formation of calcific nodules thereby stiffens the cusps and increases obstruction, imposing increasing afterload on the left ventricle.

Rheumatic disease arises from an immune response following group A streptococcal pharyngitis. Through molecular mimicry, cardiac inflammation is triggered and, especially after recurrent episodes, leads to leaflet thickening and retraction, commissural fusion and shortening of the subvalvular apparatus. The mitral valve is most frequently involved, often together with the aortic valve, and in the chronic phase stenosis and regurgitation may coexist in different proportions.

Degenerative mitral disease spans a spectrum from fibroelastic deficiency, often focal and associated with chordal rupture in older adults, to Barlow disease with diffuse tissue excess, myxomatous thickening and multisegment prolapse. Extracellular matrix disorganization, abnormalities of collagen, elastin and proteoglycans, and abnormal mechanobiology weaken leaflets and chordae, promoting prolapse, flail and regurgitation.

Secondary regurgitation results from remodeling. In the ventricular form, dilation and increased ventricular sphericity displace the papillary muscles, increase tethering and prevent coaptation; annular dilation contributes to the defect. In the atrial form, atrial fibrillation and atrial dilation enlarge the annulus and alter the relationship between the leaflets and atrioventricular junction, even when the ventricle is relatively preserved.

Infective endocarditis, ischemia, aortic dissection, trauma and iatrogenic complications may produce acute dysfunction. The absence of time for adaptation distinguishes these forms from chronic disease: sudden regurgitation into a nondilated chamber rapidly increases upstream pressure, causing pulmonary edema, hypoperfusion or shock even when cardiac dimensions are not markedly enlarged.

In stenosis, the heart must generate higher pressure to maintain flow. A ventricle exposed to pressure overload develops concentric hypertrophy, which initially reduces wall stress but increases oxygen demand, reduces coronary reserve and impairs relaxation and compliance. Diffuse and replacement fibrosis marks the transition from compensation to dysfunction and may persist after valve correction.

In chronic regurgitation, part of stroke volume is ejected in the wrong direction. The ventricle increases end-diastolic volume and total stroke volume through eccentric remodeling, initially maintaining forward output. Apparently normal ejection fraction may be misleading because ejection also occurs toward a low-impedance chamber; contractile dysfunction may therefore already be present before ejection fraction falls below normal values.

Elevated atrial pressures are transmitted to the pulmonary circulation in left-sided lesions. Reactive vasoconstriction and vascular remodeling may transform an initially post-capillary component into combined pulmonary hypertension, increasing right ventricular afterload. Right ventricular dilation and dysfunction in turn promote secondary tricuspid regurgitation, systemic venous congestion, and hepatic and renal injury.

Congenital malformations do not concern leaflet number alone. Defects in formation of the endocardial cushions, conotruncal structures, chordae or papillary muscles may produce membranes, dysplastic valves, clefts and double-orifice apparatuses. Presentation in adulthood depends on initial severity, growth and the results of previous repairs.

Among systemic etiologies, carcinoid disease forms fibrous plaques mainly on right-sided valves; radiotherapy and some drugs cause retraction and calcification; lupus and antiphospholipid syndrome may cause noninfective vegetations. The section on causes of valvular heart disease distinguishes these mechanisms because extracardiac treatment and recurrence risk modify the strategy.

Speed of onset determines the response more than regurgitant volume alone. In chronic regurgitation, the chamber increases its volume and compliance and initially limits pressure; in acute regurgitation, the same reflux enters an unadapted chamber and causes congestion and low output. A chest radiograph without cardiomegaly therefore does not exclude an extremely severe acute lesion.

Activation of the sympathetic nervous system and the renin-angiotensin system supports pressure and perfusion in the early phases but promotes retention, vasoconstriction and remodeling. Valve correction removes the mechanical stimulus, whereas fibrosis and some neurohormonal changes may persist. Recovery depends on timing of intervention and the proportion of damage that remains reversible.

Clinical manifestations

The history should establish not only whether a symptom is present, but how functional capacity has changed. Patients may unknowingly adapt their walking speed, stair climbing or daily activities and describe themselves as asymptomatic. Comparison with previous months, peers or their usual exercise level is often more informative than a generic question about dyspnea.

Exertional dyspnea is common to many valvular diseases and results from increased filling pressures, reduced output or both. Orthopnea, paroxysmal nocturnal dyspnea and pulmonary edema indicate more advanced congestion or an acute change. Fatigue and reduced endurance may reflect output that cannot increase during exercise, but should be distinguished from anemia, pulmonary disease, deconditioning and frailty.

Angina and syncope are particularly important in severe aortic stenosis. Angina may occur even without coronary artery disease because of imbalance between the demand of hypertrophied myocardium and subendocardial perfusion. Exertional syncope may result from inability to increase output in the presence of peripheral vasodilation, but arrhythmias and other causes must be excluded.

Palpitations may indicate atrial fibrillation, particularly in mitral lesions and atrial dilation, or ventricular arrhythmias. An embolic event may be the first manifestation of mitral stenosis with atrial fibrillation. In mitral valve prolapse, syncope or complex arrhythmias require specific assessment of the arrhythmic phenotype and should not automatically be attributed to the severity of regurgitation.

Right-sided congestion causes dependent edema, abdominal fullness, early satiety, weight gain, ascites and reduced urine output. In severe tricuspid disease, cervical or abdominal pulsation may occur. Renal or hepatic deterioration is not simply a comorbidity: it may result from low flow and elevated venous pressure and increase the risk of late intervention.

Physical examination begins with general condition, blood pressure, heart rate, rhythm, oxygen saturation and signs of hypoperfusion. Pulse amplitude and contour, pulse pressure, apical impulse, thrills, right ventricular impulse and jugular venous pressure provide clues to the type of load. Auscultation should define timing, site, radiation, intensity and variation with respiration and maneuvers, but cannot quantify severity by itself.

A systolic ejection murmur at the aortic area radiating to the carotids suggests aortic stenosis; a holosystolic apical murmur radiating to the axilla or back is compatible with mitral regurgitation; inspiratory augmentation of a holosystolic murmur at the lower sternal border suggests tricuspid regurgitation. The murmur of a severe lesion may be surprisingly soft in low-flow conditions.

The examination should look for consequences: crackles or pleural effusion, a third heart sound, pulsatile hepatomegaly, ascites, edema, cyanosis and cardiac cachexia. Hypotension, cold extremities, altered mental status or oliguria in the setting of acute valvular dysfunction identifies an emergency requiring stabilization and immediate interventional assessment.

Acute presentation differs from chronic progression: sudden dyspnea, hypotension, pain, fever or an ischemic event requires investigation for destructive endocarditis, papillary muscle rupture, dissection or a procedural complication. Murmur intensity may be modest because pressures equalize rapidly; instability and echocardiographic findings take precedence over auscultation.

In chronic disease, the most sensitive test is often the patient's personal trajectory. Slower walking, postprandial fatigue, slower recovery and abandonment of activities are functional signs that precede orthopnea or edema. Questionnaires, walk testing and cardiopulmonary exercise testing may objectively document limitation when the history and echocardiographic severity do not agree.

Extracardiac findings guide the etiologic diagnosis: signs of connective tissue disease and aortic dilation, stigmata of endocarditis, rheumatic manifestations, flushing and diarrhea from carcinoid disease, thoracic radiation exposure or use of valvulotoxic drugs. Investigation should be guided by clinical probability because indiscriminate screening produces incidental findings without clarifying the mechanism.

Clinical severity emerges from integrating symptoms, signs of congestion, output and organ function. A patient may have severe parameters with preserved reserve or apparently intermediate values with advanced heart failure due to multiple lesions. Assessment should explain whether valvular disease is the cause, a contributing cause or an incidental finding in relation to the observed syndrome.

Investigations and diagnosis

After clinical suspicion, transthoracic echocardiography with Doppler is the first-line test. It should describe leaflet morphology, cause and mechanism, severity, chamber size and function, pulmonary pressures, the aorta and other valves. Quantification should integrate qualitative, semiquantitative and quantitative parameters, checking their consistency and the hemodynamic conditions at the time of the examination.

The electrocardiogram may document hypertrophy, overload, ischemia, conduction disorders and arrhythmias; chest radiography may show cardiomegaly, congestion, edema, effusions or calcification. These tests complete the picture but do not replace valvular imaging. Complete blood count, renal and liver function, electrolytes and biomarkers are selected according to the presentation and treatment planning.

When the transthoracic window is inadequate, the mechanism remains uncertain or repair must be planned, transesophageal echocardiography, preferably three-dimensional, defines anatomy and relationships. It also has a central role in suspected endocarditis, thrombosis or prosthetic dysfunction and guides many transcatheter atrioventricular procedures.

Cardiac computed tomography measures calcium and valvular anatomy, characterizes the aorta and coronary arteries, defines the annulus, root and vascular access, and is the reference for TAVI planning. Cardiac magnetic resonance reproducibly quantifies ventricular volumes, flow and regurgitation and characterizes fibrosis and infiltration; it is particularly useful when echocardiography and the clinical picture are discordant.

Exercise testing is indicated in selected apparently asymptomatic patients, especially in severe aortic stenosis, to unmask symptoms, a fall in blood pressure or reduced capacity. Exercise echocardiography may clarify the cause of dyspnea and show dynamic changes in gradient, regurgitation or pulmonary pressure. It should not be performed in symptomatic patients with unstable severe aortic stenosis.

Coronary angiography by CT or invasive technique is performed when the probability of coronary artery disease and procedural planning require it. Cardiac catheterization for direct measurement of pressures and output is reserved for cases in which noninvasive data are inconclusive or discordant and the result may change the decision; routine use to confirm well-characterized valvular disease is not justified.

A complete diagnosis is not merely a label for the lesion. It should specify etiology and mechanism, severity, flow state, attributable symptoms, ventricular and atrial response, pulmonary pressure, involvement of other valves and the aorta, arrhythmias, coronary artery disease, frailty and organ dysfunction. This synthesis determines risk and the appropriate timing of intervention.

The differential diagnosis of symptoms includes ischemic heart disease, cardiomyopathies, pericardial disease, non-valvular heart failure, pulmonary disease, anemia and deconditioning. Doppler findings must be distinguished from subvalvular or supravalvular obstruction, high-flow states, alignment errors and changes related to blood pressure or volume status. When the data and clinical picture do not agree, the correct next step is to reassess acquisition and physiology before classifying the disease.

Multiparametric interpretation first checks the quality of each measurement, then seeks concordance among anatomy, flow and consequences. If data diverge, blood pressure, rhythm, hemoglobin, volume status and technique are checked; an independent modality is then selected. Averaging parameters that measure different phenomena does not resolve discordance.

Three-dimensional echocardiography, CT and magnetic resonance answer different questions. The first reconstructs moving leaflets and apparatuses; CT offers high spatial resolution for calcium, aorta, coronary arteries and devices; magnetic resonance measures volumes and flow and characterizes the myocardium. The best modality is the one that resolves the uncertainty that would change management, not the most technologically complex one.

In selected cases, genetic testing and family assessment are indicated for bicuspid valve with aortopathy, connective tissue syndromes or familial clustering of prolapse and sudden death. Blood cultures precede antibiotics when endocarditis is suspected; monoclonal protein testing and scintigraphy are reserved for suspected amyloidosis. Etiologic investigations follow testable hypotheses.

The final assessment in a Heart Valve Clinic includes operability and expected benefit: anatomical risk, frailty, cognition, nutrition, autonomy, renal and liver function, life expectancy and patient goals. A technically feasible procedure may be futile; conversely, high risk does not imply futility if the valve dominates prognosis and an appropriate treatment pathway exists.

Treatment, follow-up and prognosis

Most valvular heart disease is mechanical, and no drug can restore a calcified leaflet, a fused commissure or a ruptured chord. Medical therapy treats hypertension, heart failure, congestion, ischemia, arrhythmias and thromboembolic risk and may stabilize the patient, but should not delay an indicated intervention. Exceptions depend on the mechanism, such as secondary regurgitation that may improve with optimized heart failure therapy and resynchronization when indicated.

Follow-up of lesions not yet requiring intervention should be scheduled according to the valve, severity, progression and cardiac response. Each visit compares symptoms, functional capacity, rhythm, dimensions, function and quantitative parameters with previous studies. Acceleration of progression, symptom onset or approach to thresholds requires shorter intervals and assessment in a Heart Valve Clinic.

The decision to intervene integrates prognostic benefit, symptom relief and the risk of waiting with mortality, complications and durability of the procedure. Repairing a valve preserves native tissue and may avoid a prosthesis, but is appropriate only when the probability of a durable result is high. Replacement is required when anatomy and pathology do not permit reliable repair.

Surgery allows simultaneous treatment of multiple valves, the aorta and coronary arteries and remains essential in younger patients, complex anatomies and when repair requires reconstructive expertise. Transcatheter procedures have transformed treatment of aortic stenosis and some mitral and tricuspid regurgitant lesions, extending treatment options to patients at high surgical risk and, in selected indications, to those at lower risk.

The choice between surgical and transcatheter procedures cannot be reduced to a score. Age, life expectancy, frailty, anatomy, access, risk of bleeding or pacemaker implantation, need for anticoagulation, probability of mismatch, future coronary access and strategy for possible reinterventions together form lifetime management. Informed patient preference is central after a balanced presentation of the alternatives.

Mechanical prostheses offer excellent durability but require anticoagulation with vitamin K antagonists; bioprostheses generally avoid permanent anticoagulation in the absence of other indications but are subject to structural degeneration. Biological age, desired pregnancy, contraindications, adherence, access to monitoring and potential future procedures should all enter the decision.

After intervention, a baseline echocardiographic value should be documented, early complications recognized, antithrombotic therapy adjusted and persistent heart failure or arrhythmias treated. Follow-up does not end with correction: prostheses, repairs and devices may develop degeneration, thrombosis, endocarditis, leaks or nonstructural dysfunction and require lifelong surveillance.

Prognosis is favorable when a significant lesion is recognized and corrected before advanced fibrosis, right or left ventricular dysfunction and organ damage develop. Recovery of volumes and pressures may be substantial, but myocardial fibrosis, pulmonary hypertension, atrial fibrillation and tricuspid regurgitation may persist and explain why normalization of the valve does not always mean normalization of risk.

The timing of intervention is established before compensation is exhausted. Reproducible symptoms, ventricular function and dimensions, pulmonary pressure, progression and markers of damage carry different weight for different valves. Thresholds are not interchangeable and must be applied to the correct measurement obtained under appropriate conditions.

Anticoagulation requires strict distinction. Mechanical prostheses and clinically significant rheumatic mitral stenosis with atrial fibrillation require vitamin K antagonists; in other valvular diseases with atrial fibrillation, DOACs may be appropriate according to indications and contraindications. Repair, recent bioprostheses and TAVI follow specific time-dependent regimens.

Oral hygiene and treatment of infections reduce the risk of endocarditis; antibiotic prophylaxis is reserved for high-risk patients undergoing relevant procedures. Physical activity, pregnancy and noncardiac surgery should be planned according to severity, symptoms, function and risk. Stable valvular disease does not automatically justify inactivity or prophylactic procedures.

Rehabilitation and continuity of care restore strength, adherence and autonomy after intervention. The pathway links the primary care physician, cardiologist, imaging specialists, cardiac surgery and interventional cardiology and should specify who monitors prostheses, anticoagulation and symptoms. Loss to follow-up may negate the benefit of an initially successful procedure.

Complications

Heart failure is the most common final pathway. Pressure or volume overload exceeds compensatory capacity, raises filling pressures and reduces output. Pulmonary congestion and left ventricular dysfunction predominate in left-sided lesions; systemic congestion and right ventricular dysfunction predominate in right-sided lesions, often overlapping in advanced stages.

Atrial dilation and elevated pressures promote atrial fibrillation. Loss of atrial contraction and irregularity may precipitate symptoms in stenotic lesions, in which filling depends on the duration of diastole, and increase thromboembolic risk. Management requires rate or rhythm control and anticoagulation according to the specific valvular disease and risk profile.

Pulmonary hypertension initially results from backward transmission of left-sided pressures; vascular remodeling may introduce a precapillary component. The resulting increase in right ventricular afterload causes dilation, secondary tricuspid regurgitation and reduced output. When advanced, this cascade may limit benefit and increase the risk of intervention.

Infective endocarditis may affect native, repaired or prosthetic valves and cause perforation, destruction, abscesses, dehiscence, emboli and acute regurgitation. Fever, positive blood cultures, new valvular findings or embolic phenomena require a dedicated pathway. Antibiotic prophylaxis is reserved for high-risk groups undergoing procedures specified by guidelines, not every patient with a murmur.

Severe acute lesions may cause pulmonary edema and cardiogenic shock without the dilation typical of chronic disease. Papillary muscle rupture, chordal rupture, destructive endocarditis and aortic dissection require immediate recognition, targeted hemodynamic support and urgent correction of the cause.

Ventricular arrhythmias may result from ischemia, hypertrophy, dilation and fibrosis. Risk is not uniform: some conditions, such as arrhythmic mitral valve prolapse with annular disjunction and fibrosis, require specific stratification. Unexplained syncope, complex ectopy or ventricular tachycardia should not be considered a nonspecific consequence of a murmur.

Embolic events may originate from atrial thrombi in atrial fibrillation or mitral stenosis, infected vegetations, prosthetic material or prosthetic valve thrombosis. Consequences include stroke, peripheral ischemia and organ infarction. The mechanism determines prevention and treatment; empirical anticoagulation does not replace diagnosis.

Advanced disease may ultimately cause renal failure, congestive hepatopathy, malnutrition, frailty and cachexia. These complications increase procedural mortality and reduce the likelihood of functional recovery. Their development indicates late correction and reinforces the need for structured surveillance before valvular heart disease becomes a multiorgan disease.

Prosthetic heart valves introduce their own complications: thrombosis, endocarditis, structural deterioration, pannus, leak and mismatch. Suspicion arises from new symptoms, a change in murmur, hemolysis or increasing gradients. Comparison with the baseline echocardiogram distinguishes a stable characteristic from evolving dysfunction.

Anticoagulants and antiplatelet drugs may cause bleeding, whereas inadequate therapy exposes the patient to thrombosis and embolism. Management after a bleeding event considers the indication, prosthesis type, bleeding site and control of the source. Stopping or restarting therapy without assessing valvular risk may have serious consequences.

Sudden death and cardiac arrest may result from arrhythmia, ischemia, embolism, critical obstruction or prosthetic dysfunction. Absolute risk varies enormously across lesions and stages and does not justify uniform alarm. Syncope, ventricular tachycardia and rapid deterioration instead require urgent reassessment of the substrate and timing of treatment.

The most difficult complication to correct is irreversible damage. Fibrosis, pulmonary vasculopathy, right ventricular dysfunction, liver disease and frailty may persist after flow is normalized. Prevention does not mean treating every lesion early, but recognizing the point at which the risk of waiting exceeds that of a durable intervention.