Valvular heart disease

Article written and reviewed by Dr Luca Moretti

Valvular heart disease is a heterogeneous group of disorders in which the structure or motion of one or more cardiac valves fails to ensure unidirectional flow with minimal resistance. Dysfunction may consist of obstruction to opening, defined as stenosis, loss of competence with backward flow, defined as regurgitation, or coexistence of both defects. The valve lesion, however, is only the starting point of a disease process that progressively involves the cardiac chambers, pulmonary circulation, rhythm, coronary circulation and systemic organs.

The function of each valve depends on an anatomical unit. For the aortic and pulmonary valves, this unit includes the cusps, ventriculoarterial junction, sinuses, sinotubular junction and root; for the mitral and tricuspid valves it includes the annulus, leaflets, commissures, chordae, papillary muscles, ventricular walls and atria. A classification based exclusively on the leaflets therefore misses important forms in which the valve becomes secondarily incompetent because of altered cardiac geometry.

The epidemiologic burden is increasing because of population aging, improved survival from heart disease and greater diagnostic capacity. Population estimates show that moderate or severe lesions become very common in older adults; worldwide, rheumatic heart disease affects tens of millions of people, whereas high-income health systems are dominated by calcific aortic degeneration, degenerative mitral disease and functional regurgitation.

The availability of three-dimensional echocardiography, CT, cardiac magnetic resonance and transcatheter procedures has changed the treatment paradigm. The question is no longer only whether a valve is severely diseased, but what the mechanism is, how much cardiac damage has already developed, whether the lesion is repairable, which procedure offers the most durable result and how the initial choice will affect future interventions.

Classification and etiology

A useful clinical classification proceeds through several levels: it identifies the valve, determines whether stenosis or regurgitation predominates, defines the cause, describes the mechanism, quantifies severity and recognizes the cardiac response. Two patients with the same grade of mitral regurgitation may have radically different prognoses and treatments if one has a focal repairable prolapse and the other has tethering due to ischemic cardiomyopathy.

Congenital malformations include bicuspid or unicuspid aortic valve, pulmonary stenosis, dysplastic tricuspid valve and abnormalities of the mitral apparatus. The bicuspid aortic valve is the most common congenital valvular abnormality in adults; it exposes the cusps and raphe to abnormal stress, accelerates stenosis or regurgitation and may be associated with aortopathy.

Calcific degeneration mainly affects the aortic valve and mitral annulus. Age, kidney disease, abnormalities of mineral metabolism and cardiometabolic factors are associated with disease, but valvular calcification has its own biology. Aortic sclerosis without significant obstruction is not yet stenosis, whereas mitral annular calcification may cause stenosis, regurgitation or both and make any intervention more complex.

Myxomatous degeneration alters the connective tissue of leaflets and chordae, especially in the mitral valve. The spectrum ranges from focal forms with thin leaflets and chordal rupture to diffuse forms with redundancy and multisegment prolapse. Inherited connective tissue syndromes may simultaneously involve the valve, aortic root and skeleton.

Rheumatic heart disease results from an immune response to streptococcal pharyngitis. Repeated scarring causes commissural fusion, leaflet thickening and retraction, and subvalvular deformity. The mitral valve is almost invariably involved in severe disease, but aortic involvement is common and right-sided involvement may occur in advanced multivalvular disease.

Infective endocarditis destroys valve tissue through vegetations, perforations, abscesses and ruptures. Dysfunction is often regurgitant and may be acute. Diagnosis and treatment follow specific criteria and guidelines, but the hemodynamic consequence must be assessed together with uncontrolled infection and embolic risk.

Ischemic lesions mainly involve the mitral valve. Papillary muscle rupture causes catastrophic acute regurgitation, whereas chronic ischemia and scar displace the papillary muscles and distort the apparatus. Regurgitation therefore does not necessarily result from infarction of the leaflet itself, but from loss of the geometry that permitted coaptation.

Dilated cardiomyopathies, atrial fibrillation, pulmonary hypertension and right ventricular dilatation cause secondary regurgitation. Distinguishing atrial from ventricular forms is essential: in the former, atrial-related annular dilatation predominates; in the latter, ventricular tethering and reduced closing force predominate. Mixed mechanisms are common in advanced stages.

Less common causes include carcinoid syndrome, serotonergic drugs, ergot derivatives, radiation therapy, lupus, antiphospholipid syndrome, rheumatoid arthritis, spondyloarthritis, Whipple disease, hypereosinophilia, amyloidosis and trauma. Identifying the etiology changes the search for systemic disease, the risk of progression, repairability and extracardiac treatment.

Temporal classification distinguishes acute, chronic and acute-on-chronic lesions. Acute regurgitation is defined by lack of chamber adaptation, not by an arbitrary duration: perforation, chordal rupture or dissection may cause very high pressures while chamber volumes remain normal. A chronic lesion may destabilize because of endocarditis, arrhythmia or ischemia and requires identification of both components.

For atrioventricular regurgitation, leaflet motion classification distinguishes normal, excessive and restricted mobility and links the jet to its mechanism. Prolapse, flail, systolic tethering and diastolic restriction are not synonyms. Segmental description helps predict repairability and communicate with the cardiac surgeon and interventionalist without reducing the report to mild, moderate or severe.

Pathogenesis and pathophysiology

The transition from risk to a valve lesion occurs through different processes. In aortic calcification, shear stress and endothelial injury promote lipoprotein entry, oxidation, inflammation and osteogenic signaling. Valvular interstitial cells, normally responsible for matrix homeostasis, may differentiate into myofibroblast-like and osteoblast-like cells through pathways involving BMP, Wnt, Runx2 and phosphate-calcium signaling.

In myxomatous tissue, the proteoglycan component increases and collagen and elastin become fragmented. Signaling pathways such as TGF-β and altered mechanical forces modify interstitial-cell behavior; the leaflet becomes thick, redundant and extensible, chordae elongate or rupture, and coaptation shifts into the atrium. Regurgitation further increases stress on the apparatus, fueling biomechanical progression.

Stenosis converts pressure energy into kinetic energy through a narrowed orifice. According to the simplified Bernoulli relationship, the gradient increases approximately as four times the square of velocity; it therefore depends on both area and flow. Anatomically severe stenosis may have a low gradient when stroke volume is reduced, whereas a high-output state may increase the gradient across less severe stenosis.

Pressure overload induces concentric hypertrophy. Increased wall thickness initially reduces wall stress as predicted by the law of Laplace, but the price is a stiffer ventricle with delayed relaxation, higher filling pressure and lower coronary reserve. Capillaries and matrix do not grow proportionally to cardiomyocytes; subendocardial ischemia, cell death and fibrosis reduce reversibility.

Regurgitation is determined by orifice area, the pressure gradient between chambers and the duration of reverse flow. Its volume can vary with pressure, afterload, heart rate and rhythm. In chronic forms the ventricle increases compliance and accommodates a larger volume at relatively low pressures; in acute forms the same amount of blood causes an abrupt pressure rise because the chamber has had no time to dilate.

Volume overload produces eccentric hypertrophy and dilatation. Increased end-diastolic volume supports stroke output through the Frank-Starling mechanism, whereas the low impedance of the regurgitant pathway facilitates ejection. Over time, wall stress rises, geometry changes and contractility declines. In mitral and aortic regurgitation, an apparently preserved ejection fraction may therefore coexist with early myocardial dysfunction.

Mitral lesions raise left atrial pressure through obstruction to filling or systolic reflux. Atrial dilatation creates the substrate for atrial fibrillation; tachycardia shortens diastole and worsens stenosis, whereas loss of atrial contraction reduces filling. Stasis and endocardial remodeling increase thrombogenicity, particularly in rheumatic mitral stenosis.

Chronic elevation of pulmonary venous pressure induces vasoconstriction and arteriolar remodeling. As pulmonary vascular resistance and right ventricular afterload rise, the right ventricle progresses from adaptation to dilatation and failure. The tricuspid annulus dilates, the leaflets become tethered and secondary regurgitation amplifies venous congestion, closing a cycle of deterioration.

Right-sided valve disease has physiology strongly influenced by respiration, volume status and the low impedance of the pulmonary circulation. Important tricuspid regurgitation raises right atrial pressure and causes systolic reversal of hepatic venous flow, whereas pulmonary stenosis or regurgitation overloads the right ventricle with pressure or volume, respectively. Right ventricular function may deteriorate late and recover incompletely.

In multiple lesions, behavior is not the arithmetic sum of the components. An upstream lesion limits flow through a downstream lesion; regurgitation reduces the forward stroke volume available to generate a gradient; correcting one valve instantly changes loading conditions on the others. Planning must therefore anticipate the new physiology after each intervention.

The interaction between the valve and arterial system determines ventriculoarterial coupling. A stenotic valve, a stiff aorta and hypertension jointly increase load; a regurgitant pathway lowers the apparent impedance to ejection but wastes stroke volume. After correction, the ventricle faces a new load and may reveal previously masked dysfunction, especially after correction of mitral regurgitation.

Atrial remodeling is not merely a marker of chronicity. Fibrosis, mechanical dysfunction and endothelial changes promote atrial fibrillation and stasis; loss of sinus rhythm accelerates annular dilatation and atrial functional regurgitation. This bidirectional relationship explains why rhythm control may reduce part of the regurgitation in selected patients, but cannot repair an organic lesion.

Clinical manifestations

Clinical history should reconstruct onset, progression and context. Fever, invasive procedures, intravenous drug use or intracardiac devices suggest endocarditis; sudden chest or back pain with aortic regurgitation suggests dissection; pulmonary edema after myocardial infarction requires exclusion of papillary muscle rupture. Previous rheumatic fever, radiation therapy and potentially valvulotoxic drugs may precede presentation by years.

In chronic forms, the earliest symptom is often a subtle reduction in exercise capacity. Patients may report walking more slowly, avoiding hills or stopping activities they previously tolerated. Concrete functional assessment reduces the risk of classifying as asymptomatic someone who has unconsciously adapted their lifestyle.

Dyspnea appears when filling pressures rise during exertion; with progression it may occur at rest, when supine or during the night. Cough, hemoptysis and hoarseness are less common but may accompany substantial congestion or atrial enlargement. Acute pulmonary edema indicates a critical change in physiology or a sudden lesion.

Chest pain in aortic stenosis may result from coronary artery disease or ischemia of hypertrophied myocardium. Exertional syncope is a high-risk manifestation but requires a differential diagnosis including arrhythmias, orthostatic hypotension and neurologic causes. In chronic regurgitant lesions, awareness of pulsations and palpitations may precede dyspnea.

Atrial fibrillation causes palpitations, sudden dyspnea or worsening exercise tolerance. In mitral stenosis, an increase in heart rate abruptly shortens filling time and may precipitate congestion. In other valve diseases, the arrhythmia often signals advanced atrial remodeling and is associated with a less favorable prognosis.

Right-sided symptoms include edema, abdominal distension, early satiety, nausea, ascites and fatigue. Right upper quadrant pain may result from stretching of the hepatic capsule. Intestinal congestion contributes to malabsorption and cachexia; fatigue reflects both low output and inflammation and multiorgan dysfunction.

Pulse examination may show a slow-rising low-amplitude pulse in aortic stenosis or a bounding, collapsing pulse in chronic aortic regurgitation. A sustained apical impulse suggests pressure overload, whereas a displaced hyperdynamic impulse suggests volume overload. A parasternal heave and accentuated pulmonary component of the second heart sound suggest pulmonary hypertension.

Heart murmurs must be interpreted in the context of flow. A loud murmur does not necessarily equal a severe lesion, and a soft murmur does not exclude one. Reduced cardiac output, obesity, emphysema or an unfavorable acoustic window may attenuate it; fever, anemia, pregnancy and fistulas may intensify it without corresponding anatomical severity.

Jugular venous pressure provides information about the right heart. Prominent v waves suggest tricuspid regurgitation, whereas a large a wave may accompany tricuspid stenosis or reduced compliance. Hepatojugular reflux, pulsatile hepatomegaly, ascites and edema define the severity of congestion and should enter risk assessment.

In end-stage disease, hypotension, hypoperfusion, oliguria, confusion, loss of body mass and hepatic or renal dysfunction appear. These findings do not merely represent symptom severity; they identify a patient in whom procedural risk is increased and benefit may be limited by irreversible injury. Preventing this stage is one of the main goals of follow-up.

NYHA class is useful for describing limitation but depends on the activity a patient attempts. A sedentary adult may formally remain in class I despite very limited reserve. Walking tests, oxygen consumption and ventilatory threshold provide reproducible measures and help distinguish cardiac dyspnea from pulmonary limitation and deconditioning.

Auscultation retains value for recognizing dynamic changes. Inspiration, posture, Valsalva and post-extrasystolic beats modify flow and intensity, but a response is not a quantitative measurement. Prostheses or devices add expected clicks and sounds; a new murmur or change in a sound requires comparison and imaging.

Diagnostic evaluation

The diagnostic pathway begins by confirming that valve dysfunction is present and proceeds to definition of etiology, mechanism, severity and cardiac damage. Transthoracic echocardiography should be quantitative and comprehensive, not an examination focused only on the murmur. Heart rate, rhythm, blood pressure and clinical conditions at the time of acquisition should be recorded because they affect gradients and regurgitation.

Morphology identifies calcification, commissural fusion, prolapse, flail, perforation, restriction, tethering, vegetations and annular dilatation. Mechanism links anatomy and flow. Severity is then assessed with lesion-specific measures: velocity and gradients for stenosis; vena contracta, PISA, effective regurgitant orifice area, regurgitant volume and regurgitant fraction for regurgitation.

Every parameter has limitations. Valve area calculated with the continuity equation amplifies error in measurement of the outflow tract; PISA assumes a geometry that may not be hemispheric; jet area depends on machine settings; pressure half-time depends on compliance and pressures. Robust diagnosis arises from multiparametric concordance and technical quality control of the images.

Cardiac consequences include hypertrophy, dilatation, systolic and diastolic function, strain, atrial volume, pulmonary pressure and right ventricular function. Intervention thresholds are often based on dimensions or ejection fraction and require reproducible measurements. Borderline values should be confirmed, indexed when appropriate and interpreted longitudinally.

Transesophageal echocardiography is indicated when transthoracic imaging does not adequately define anatomy or severity, when endocarditis or thrombosis is suspected, and before or during repair procedures. Three-dimensional datasets provide a surgical view of the mitral and tricuspid valves and more direct assessment of anatomy, commissures and irregular orifices.

Cardiac CT quantifies aortic valve calcium in discordant stenosis and provides three-dimensional measurements for TAVI and complex interventions. It identifies the aorta, coronary arteries, annulus, calcium distribution and relationships with the outflow tract and coronary ostia. Contrast and radiation exposure should be balanced against renal function and the expected information gain.

Cardiac magnetic resonance is the reference standard for ventricular volumes and function and allows independent quantification of regurgitation using phase-contrast flow. Late gadolinium enhancement and tissue mapping identify scar and diffuse fibrosis, contributing prognostic information. It is particularly useful in regurgitant lesions and when echocardiographic volumes are discordant with the clinical picture.

Exercise testing unmasks symptoms and abnormal blood pressure responses in apparently asymptomatic patients. Objective measurement of functional capacity avoids decisions based solely on perception. Stress echocardiography can also distinguish true from pseudo-severe aortic stenosis in low-flow states, demonstrate dynamic changes in regurgitation and document increases in pulmonary pressure.

BNP and NT-proBNP reflect wall stress but are not specific; a repeatedly elevated value interpreted in relation to age, sex, rhythm and renal function may indicate subclinical decompensation. Troponin, blood cultures, inflammatory markers, evaluation for systemic disease or genetic testing are driven by the specific etiology and do not constitute uniform screening for all valve diseases.

Pre-intervention assessment includes the coronary arteries, vascular access, aorta, surgical risk, frailty, nutritional status, cognition, renal and hepatic function and life expectancy. EuroSCORE II and STS-PROM are helpful but do not capture porcelain aorta, radiation injury, hostile anatomy or futility. The diagnostic conclusion is a team synthesis, not the automatic output of a calculator.

Major sources of diagnostic error include Doppler misalignment, underestimation of the outflow tract, uncontrolled blood pressure, irregular rhythm, anemia, high-output states, low flow, multiple lesions and comparison of studies acquired with different techniques. In discordant cases, the original data must be reviewed and an independent modality used before deciding on intervention.

Reproducibility is part of diagnosis. Small changes may reflect the observer, acoustic window, blood pressure or rhythm and may not represent biological progression. Comparison should retrieve original images and measurements, maintain conventions and assess whether multiple parameters change in the same direction; values that determine intervention are confirmed when the context allows.

Invasive hemodynamics measures pressures, cardiac output and vascular resistance when imaging and clinical findings remain incongruent. Sedation, tachycardia, vasodilation and calculation method can alter the data, and the peak-to-peak gradient is not the same as the maximum Doppler gradient. Catheterization is a targeted test, not an arbiter automatically superior to a technically correct noninvasive examination.

Treatment and prognosis

Treatment must be directed at the mechanism. In organic stenosis and severe primary regurgitation, definitive therapy is mechanical; in secondary regurgitation, optimization of ventricular or atrial disease is the first step and may reduce the lesion. In every setting, hypertension, ischemia, infection, arrhythmias and heart failure should be treated without confusing control of consequences with correction of the cause.

Diuretics reduce congestion and filling pressures, but excessive diuresis may lower preload and cardiac output in severe stenosis. Vasodilators and heart-failure therapies are selected according to physiology and blood pressure. Heart rate should be controlled in atrioventricular stenosis; in aortic regurgitation, marked bradycardia prolongs the time available for regurgitation.

Anticoagulation depends on atrial fibrillation, rheumatic mitral stenosis, prostheses and other factors. DOACs do not replace vitamin K antagonists in mechanical prostheses and are not the choice in clinically significant rheumatic mitral stenosis with atrial fibrillation. Therapy must clearly distinguish native valves, bioprostheses, repairs and devices.

Surgical repair is preferred when it preserves geometry and offers low mortality and high durability, especially in degenerative mitral regurgitation. It requires a realistic prediction of the result and appropriate center expertise. An incomplete repair or one destined to fail may be worse than a well-chosen replacement.

Surgical replacement permits removal or exclusion of the diseased valve, treatment of the aorta and concomitant revascularization. Mechanical prostheses prioritize durability, whereas bioprostheses reduce the need for permanent anticoagulation but may degenerate. The choice should consider life expectancy, bleeding risk, pregnancy, adherence and reintervention strategy.

TAVI has become a fundamental treatment for severe aortic stenosis. The 2025 ESC/EACTS guidelines favor SAVR in low-risk patients younger than 70 years and transfemoral TAVI in patients aged at least 70 years with a tricuspid aortic valve and suitable anatomy, leaving other patients to individualized decision-making. Bicuspid valve anatomy, aortopathy, complex coronary disease and the need for other procedures may favor surgery.

Transcatheter mitral and tricuspid techniques include edge-to-edge repair, annuloplasty, replacement and interventions on prostheses or rings. Selection requires confirmation of severity, optimized medical therapy when relevant, favorable anatomy and a reasonable expectation of clinical benefit. Echocardiographic reduction in regurgitation is not sufficient if extracardiac damage makes functional improvement unlikely.

Timing of intervention is critical. Waiting until overt ventricular dysfunction may leave irreversible fibrosis and pulmonary hypertension; intervening too early exposes the patient to procedural risk and limited prosthesis durability. Attributable symptoms, exercise-test response, progression rate, biomarkers, strain and chamber damage complement traditional thresholds.

The Heart Team assesses appropriateness and treatment modality, but the patient should understand differences in recovery, durability, anticoagulation, pacemaker risk, leak, coronary access and future procedures. A lifetime strategy considers not only the first intervention but also realistic options when the repair or bioprosthesis eventually fails.

Prognosis after correction is better when ventricular function and the pulmonary circulation are still preserved. Reverse remodeling may reduce volumes and pressures, but fibrosis, enlarged atria and arrhythmias may persist. Benefit should be measured in survival, hospitalizations, functional capacity and quality of life, not merely technical success.

Post-procedural follow-up documents baseline function and looks for abnormal gradient, residual or paravalvular regurgitation, thrombosis, infection, hemolysis and conduction disturbances. Rehabilitation, oral hygiene, education, adherence to antithrombotic therapy and early recognition of symptoms are as much part of treatment as the implantation itself.

Pregnancy increases plasma volume, heart rate and cardiac output and may decompensate significant stenosis or ventricular dysfunction. Preconception assessment identifies lesions that should be corrected, teratogenic medications, maternal risk and mode of delivery. A mechanical prosthesis requires complex anticoagulation choices and an experienced cardio-obstetric team.

Prevention includes oral hygiene, prompt treatment of infections and endocarditis prophylaxis only in the indicated groups and procedures. Exercise and work are adapted to severity, symptoms, ventricular function, aortic disease and arrhythmias. A generic prohibition may worsen deconditioning and quality of life; individualized prescription should instead avoid loads incompatible with the patient’s physiology.

Complications

Heart failure results from failure of adaptation to pressure or volume overload. Left-sided congestion causes dyspnea and pulmonary edema, whereas right-sided congestion causes edema, ascites and organ dysfunction. In acute disease deterioration may be immediate; in chronic disease the patient passes through a phase of reduced reserve before symptoms develop at rest.

Ventricular dysfunction may become only partially reversible. Replacement fibrosis does not regress when loading conditions are normalized and provides a substrate for heart failure and arrhythmias. Reduced strain and CMR-detected fibrosis may precede a fall in ejection fraction and explain interest in earlier intervention.

Atrial fibrillation is promoted by atrial pressure, dilatation and fibrosis. It worsens hemodynamics and symptoms, increases thromboembolic risk and often persists after correction. In mitral lesions, its onset may mark an advanced stage; in atrial functional disease it is also part of the mechanism that sustains regurgitation.

Pulmonary hypertension progresses from passive pressure transmission to vasoconstriction and vascular remodeling. Once high pulmonary vascular resistance develops, correction of the left-sided valve may not normalize pressure. The right ventricle dilates, tricuspid regurgitation increases and prognosis worsens.

Endocarditis, thrombosis and embolism are distinct complications. Endocarditis destroys the valve and disseminates infected emboli; atrial or prosthetic thrombosis causes systemic embolism or obstruction; noninfective vegetations may accompany malignancy or autoimmune disease. Treatment depends on correct identification of the substrate.

Acute mechanical complications include chordal rupture, papillary muscle rupture, perforation, dehiscence and dissection with aortic regurgitation. The abrupt rise in upstream pressures causes pulmonary edema and shock. An apparently high ejection fraction does not indicate normal function when much of the stroke volume is lost through a regurgitant orifice.

Procedures carry specific risks: bleeding, stroke, kidney injury, infection, atrioventricular block, pacemaker implantation, vascular injury, paravalvular leak, mismatch and early dysfunction. Their distribution differs between surgical and transcatheter approaches and should be weighed individually rather than summarized as a generic interventional risk.

Over the long term, a repair may recur and a bioprosthesis may undergo structural deterioration. Thrombosis and pannus can obstruct prostheses, whereas a leak may cause heart failure or hemolysis. Serial surveillance distinguishes expected variation from progressive dysfunction and allows reintervention to be planned before instability develops.

Chronic venous congestion causes liver disease, renal dysfunction, intestinal abnormalities and malnutrition. Multiorgan damage increases risk and may render a technically feasible procedure futile. Early assessment of right-sided valve disease is aimed primarily at preventing progression to this stage.

Death may result from heart failure, shock, arrhythmia, embolism, endocarditis or procedural complications. Risk depends not only on defect severity but also on its duration and the patient’s reserve. Complete diagnosis, reliable surveillance and intervention before irreversible damage are the main modifiable determinants.

Cardiorenal and hepatic syndrome may destabilize diuretic treatment and increase bleeding, infection and mortality. Creatinine may underestimate dysfunction in sarcopenic patients, whereas bilirubin and INR reflect congestion and impaired synthetic function. Correcting the valve before multiorgan dysfunction improves the likelihood of complete recovery.

Sudden death may be caused by tachyarrhythmia, heart block, ischemia, embolism or hemodynamic collapse. Risk varies with lesion type, symptoms, fibrosis and ventricular function and cannot be predicted from the murmur. A syncopal episode, complex arrhythmia or rapidly worsening dysfunction requires reassessment of the cause and timing of intervention, not merely intensified surveillance.