Structural heart disease

Structural heart disease (SHD) is a group of cardiac disorders in which the valves, septa, chambers, myocardium or great vessels are anatomically abnormal and produce haemodynamic consequences. The category includes congenital heart disease, acquired valvular disease, cardiomyopathies and the structural components of heart failure and coronary artery disease. In interventional cardiology the term refers specifically to lesions that can be corrected by catheter-based or surgical devices, such as aortic stenosis, mitral regurgitation, atrial septal defect, patent foramen ovale and the left atrial appendage. The World Health Organization estimates that cardiovascular disease causes about 17.9 million deaths each year, 32% of all global deaths, and structural lesions are a leading substrate for heart failure and sudden cardiac death.

Terminology and classification

Structural heart disease began as an operative category for surgery and interventional cardiology, emphasising lesions of valves, septa, chambers and great vessels that can be corrected with devices rather than electrical or microvascular dysfunction.
In adult cardiology the term is used alongside congenital heart disease, acquired valve disease, cardiomyopathy and heart failure, and any lesion with a demonstrable anatomical substrate visible on imaging or at catheterisation can be placed in the category.
The distinction from congenital heart disease is temporal. Congenital disease denotes an abnormality present at birth, whereas structural heart disease also includes acquired lesions, so an adult structural clinic manages both grown-up congenital patients and elderly patients with degenerative valve disease.
ICD-10 has no single code for structural heart disease. Relevant entities are dispersed through chapter IX, with rheumatic valve disease in I05 to I09, heart failure at I50 and congenital malformations in Q20 to Q28.
ICD-11 likewise has no single entity, and relevant entries sit in chapter 11 for circulatory diseases and chapter 20 for developmental anomalies. Cross-version conversion must use the official mapping tables.
MONDO and Orphanet do not hold a generic structural heart disease entity, only individual diseases, so a review entry must use the codes of its component conditions rather than an invented umbrella code.
The Chinese terms structural heart disease and structural cardiac abnormality are often used interchangeably, but the former leans towards clinical disease and intervention while the latter describes imaging or pathology, and consistent usage matters.
Structural heart intervention is a distinct subspecialty covering transcatheter aortic valve replacement, transcatheter edge-to-edge repair, septal closure, left atrial appendage closure and valve-in-valve procedures, and its nomenclature does not map exactly onto surgical terminology.
Cardiomyopathies sit at the intersection of structural and genetic disease. Hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy have clear anatomical phenotypes together with sarcomeric or desmosomal variants, so they are managed through both structural and inherited pathways.
Coronary artery disease is primarily a luminal problem, but ischaemic cardiomyopathy, ventricular aneurysm and papillary muscle rupture are structural consequences, so it appears here as a cause rather than a synonym.
Heart failure is not a single structural disease but a common final phenotype. Reduced, mildly reduced and preserved ejection fraction forms differ in mechanism and treatment response and must be separated in classification.
Rheumatic heart disease still dominates valve disease in low-income and middle-income countries, whereas degenerative aortic stenosis and mitral regurgitation dominate in high-income countries, so the aetiological spectrum of the same label varies by region.
The grown-up congenital population is a new structural cohort. Anatomical repair is not physiological cure, and residual shunts, valve regurgitation, conduit stenosis and arrhythmia require lifelong follow-up.
Pregnancy in structural heart disease needs a separate risk framework. The World Health Organization and the European Society of Cardiology stratify risk by mechanical valves, pulmonary hypertension, aortic dilatation and cyanotic congenital disease.

History

William Harvey's description of the circulation in 1628 provided the anatomical and physiological basis for understanding valves and chambers, and for two centuries structural disease was described mainly at autopsy.
In 1948 Bailey in Boston and Harken in Philadelphia independently performed mitral commissurotomy, the first curative operation for a valve lesion, moving structural heart disease from diagnosis to treatment.
In 1953 Gibbon used cardiopulmonary bypass for closure of an atrial septal defect, making open intracardiac surgery feasible and opening the era of congenital surgical correction.
In 1954 Lillehei repaired a ventricular septal defect using cross-circulation, and the Mustard, Senning and Fontan procedures later established a surgical system for complex congenital disease.
Rashkind introduced balloon atrial septostomy in 1966, and during the 1970s catheter techniques entered structural heart disease, moving beyond diagnosis.
In 1975 Inoue reported percutaneous balloon mitral valvotomy, and from 1982 the technique was widely adopted for rheumatic mitral stenosis, becoming the first mature interventional valve procedure.
In 1988 Lock and Rome reported transcatheter closure of atrial septal defects, and Amplatzer devices spread during the 1990s, gradually replacing surgery for some septal defects.
Cribier performed the first transcatheter aortic valve replacement in 2002. The PARTNER trial began in 2007 and its 2011 high-risk results established the catheter approach for patients who could not undergo surgery<ref>J:10.1056/NEJMoa1103510</ref>.
The EVEREST II trial compared transcatheter edge-to-edge repair with surgical repair for mitral regurgitation in 2011. Efficacy was inferior to surgery but safety was better, supporting approval of MitraClip in 2013<ref>J:10.1056/NEJMoa1009355</ref>.
The CoreValve high-risk trial was published in 2014, extending transcatheter aortic valve replacement from inoperable to high-risk patients and later to intermediate and low-risk groups<ref>J:10.1056/NEJMoa1400590</ref>.
In 2018 the American College of Cardiology and American Heart Association issued a guideline for adults with congenital heart disease, published in 2019, giving grown-up congenital heart disease its own systematic chapter<ref>J:10.1161/CIR.0000000000000603</ref>.
The 2020 American valve guideline and the 2021 European Society of Cardiology and European Association for Cardio-Thoracic Surgery joint guideline established staging and heart team decisions as the modern framework<ref>J:10.1161/CIR.0000000000000923</ref><ref>J:10.1093/eurheartj/ehab395</ref>.
The 2022 American heart failure guideline integrated structural causes, comorbidity and device therapy, strengthening the link between structural intervention and medical therapy<ref>J:10.1161/CIR.0000000000001063</ref>.
After 2023 transcatheter tricuspid repair, valve-in-valve and transcatheter mitral replacement entered late-phase study, extending treatment to anatomy once considered surgically inaccessible.
These milestones show a consistent direction: each new device widened the population that could be treated, while shifting the main limitation from technical feasibility to patient selection and long-term durability.

Epidemiology

World Health Organization data for 2021 estimate about 17.9 million cardiovascular deaths each year, 32% of global mortality, with roughly 85% occurring in low-income and middle-income countries.
The Global Burden of Disease study counted more than 485 million people living with cardiovascular disease in 2017, with high disability-adjusted life years, and structural causes contribute substantially to heart failure and stroke<ref>J:10.1016/S0140-6736(18)32279-7</ref>.
The global birth prevalence of congenital heart disease is about 9.1 per 1000 live births, according to the 2011 systematic review and meta-analysis by van der Linde and colleagues based on 114 studies, with regional estimates from 6 to 13 per 1000<ref>J:10.1016/j.jacc.2011.08.025</ref>.
Because surgical and catheter treatment has spread, adults with congenital heart disease now outnumber children, and by 2030 adults are expected to account for more than three quarters of the congenital population.
Degenerative aortic stenosis affects about 2% to 7% of people older than 65 years and more than 10% of those older than 85, and its rise tracks population ageing.
Mitral regurgitation is the most common valve disease, with moderate or greater regurgitation found in about 1.7% of community populations and increasing with age, often alongside atrial fibrillation and heart failure.
Rheumatic heart disease still affects an estimated 30 to 40 million people worldwide, with prevalence in South Asia, sub-Saharan Africa and parts of Latin America far above high-income levels.
Heart failure affects an estimated 64 million people globally. Prevalence is about 1% to 2% in developed countries and exceeds 10% above 70 years of age.
The economic burden comes from repeated admissions, devices and procedures and long-term care. Heart failure costs the United States more than 30 billion dollars each year in direct and indirect costs.
Age is the strongest non-modifiable risk factor, as valve calcification, myocardial fibrosis and reduced ventricular compliance accumulate over time, so prevalence rises in ageing societies.
Hypertension promotes left ventricular hypertrophy, atrial enlargement and aortic root dilatation and is among the most important modifiable risks for heart failure and valve regurgitation.
Diabetes and metabolic syndrome accelerate ventricular remodelling through microvascular disease, myocardial lipotoxicity and inflammation, roughly doubling the risk of heart failure.
Smoking and dyslipidaemia accelerate atherosclerosis and produce structural consequences through ischaemic cardiomyopathy and papillary muscle dysfunction, and cessation and lipid lowering partially reverse the risk.
Obesity increases preload, adipokine signalling and sleep-disordered breathing, promoting atrial enlargement and hypertrophy and standing out as a risk for preserved ejection fraction heart failure.
Rheumatic fever remains the main cause of acquired valve disease in low-income countries, linked to inadequate treatment of group A streptococcal pharyngitis, crowding and poor access to care.
Risk factors for congenital heart disease include maternal diabetes, rubella, alcohol exposure, certain anticonvulsants and chromosomal anomalies, although the cause remains unknown in most cases.
The geographical pattern is two-tracked. High-income countries are dominated by degenerative and ischaemic causes, low-income countries by rheumatic, infectious and uncorrected congenital disease, and global resource allocation reflects this divide.

Pathophysiology

The shared mechanism is an anatomical abnormality that imposes pressure load, volume load or shunting, activating the renin-angiotensin-aldosterone system, sympathetic tone and inflammation, and ending in ventricular remodelling and decompensation.
Pressure-load lesions such as aortic stenosis and hypertensive heart disease cause concentric hypertrophy that normalises wall stress, but myocardial stiffness rises, coronary reserve falls and diastolic dysfunction follows.
Volume-load lesions such as mitral and aortic regurgitation produce dilatation and eccentric hypertrophy that maintain stroke volume early, before contractile decline and irreversible dilatation appear.
A left-to-right shunt in congenital disease increases pulmonary blood flow, and shear stress and inflammatory mediators drive pulmonary vascular remodelling, which can progress to Eisenmenger physiology and loss of operability.
Valve calcification is an active process of lipid deposition, inflammatory infiltration, matrix metalloproteinase activation and osteoblast-like differentiation rather than passive wear, which changed the traditional degenerative model.
The molecular basis of cardiomyopathy includes sarcomeric variants, desmosomal defects, lysosomal storage and mitochondrial dysfunction, and genotype and phenotype are not one-to-one because penetrance depends on modifier genes and environment.
Atrial enlargement and fibrosis form the shared electrophysiological substrate. Ectopic pulmonary vein activity and re-entrant circuits sustain atrial fibrillation, creating a cycle of atrial remodelling and arrhythmia.
Neurohormonal activation preserves perfusion acutely but chronically worsens remodelling through cardiomyocyte apoptosis, interstitial fibrosis and vasoconstriction, explaining the central role of neurohormonal blockade in heart failure.
Inflammation in rheumatic disease is driven by molecular mimicry, in which streptococcal antigens cross-react with cardiac and valve proteins, causing leaflet thickening, commissural fusion and chordal shortening.
Ischaemic structural disease follows a time-dependent cascade. Coronary occlusion causes transmural necrosis, the necrotic zone thins into an aneurysm, papillary muscle rupture causes acute mitral regurgitation and septal rupture creates an acute shunt.
Preserved ejection fraction heart failure is driven by systemic inflammation, epicardial fat, microvascular dysfunction and reduced compliance, and structural intervention has limited high-quality evidence in this group.
The natural course is often silent. Symptoms appear when myocardial damage is already irreversible, so early recognition and scheduled imaging are central to altering prognosis.
Plasma volume rises by about 40% to 50% in pregnancy and haemodynamics fluctuate sharply during delivery, so structural patients can decompensate with heart failure, arrhythmia or aortic dissection, and risk stratification must precede conception.
Elderly patients often have multiple valve lesions, renal impairment and frailty, and the order of treatment must reflect symptoms, prognosis and tolerance rather than imaging severity alone.

Clinical features

Dyspnoea is the most common presenting symptom, ranging from exertional breathlessness to resting dyspnoea, and its severity usually tracks left atrial pressure and pulmonary congestion.
Chest pain may reflect coronary disease or, in aortic stenosis and hypertrophic cardiomyopathy, an imbalance between myocardial oxygen supply and demand that is typical during exertion.
Syncope in aortic stenosis, hypertrophic cardiomyopathy and pulmonary hypertension is a warning sign of fixed output or malignant arrhythmia.
Palpitations and atrial fibrillation are common in mitral and aortic regurgitation with left atrial enlargement, and atrial fibrillation in turn worsens heart failure and thromboembolic risk.
Oedema, raised jugular venous pressure, hepatojugular reflux and paroxysmal nocturnal dyspnoea indicate right or global heart failure, and rightward shift of signs usually marks advanced disease.
Cardiac murmurs are the key physical clue. Aortic stenosis gives an ejection systolic murmur radiating to the neck, mitral regurgitation a pansystolic murmur radiating to the axilla, and the hypertrophic murmur intensifies with Valsalva.
Complications include at least heart failure, atrial fibrillation, infective endocarditis, thromboembolism, pulmonary hypertension and sudden cardiac death, with endocarditis highest in regurgitant native valves and prosthetic material.
Heart failure is the common terminal pathway, and repeated decompensation drives both prognosis and cost.
Infective endocarditis can involve native valves, prostheses and implanted devices, presenting with fever, a new murmur, embolic events and positive cultures, and delay can cause perivalvular abscess and acute heart failure.
Thromboembolism is particularly common in mitral stenosis with atrial fibrillation, and stroke risk relates to left atrial size, spontaneous echo contrast and prior embolism.
Pulmonary hypertension may arise from left heart disease, left-to-right shunt or chronic thromboembolism, and right ventricular dilatation and failure under sustained afterload are central to timing of intervention.
Presentations differ by group. Children show cyanosis, feeding difficulty and poor growth, pregnant women show reduced exercise tolerance and arrhythmia, and older adults often present with fatigue, anorexia and cognitive change.
Severe disease and death result mainly from pump failure, malignant arrhythmia, aortic rupture and embolism, and survival falls steeply once symptoms appear without intervention.
A widened pulse pressure, water-hammer pulse and head bobbing suggest aortic regurgitation, while pulsus paradoxus and abnormal venous waveforms suggest tamponade or constriction and help form a pre-imaging impression.

Diagnosis

Diagnosis begins with history and examination, followed by transthoracic echocardiography as first-line imaging to assess valve morphology, gradients, regurgitation, chamber size and ejection fraction.
The 2020 American valve guideline uses stages A to D, separating at-risk, progressive, asymptomatic severe and symptomatic severe disease, and stage rather than a single measurement drives timing<ref>J:10.1161/CIR.0000000000000923</ref>.
The 2022 heart failure guideline uses stages A to D from at-risk through pre-heart failure, symptomatic and advanced disease, emphasising structural cause detection in stages A and B.
Transoesophageal echocardiography assesses the mitral apparatus, endocarditis vegetations, left atrial appendage thrombus and anatomical suitability for transcatheter procedures with better resolution than the transthoracic route.
Cardiac magnetic resonance quantifies ventricular volumes, ejection fraction, fibrosis and oedema, and is central to cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and cardiac sarcoidosis.
Cardiac computed tomography measures annular size, calcium score, coronary anatomy and procedural planning, and transcatheter aortic valve replacement depends on CT measurement of the annulus, sinuses and coronary height.
Catheterisation measures gradients, pulmonary vascular resistance and shunt fraction and can combine coronary angiography, which is essential for operability and reversibility of pulmonary hypertension.
Laboratory tests include brain natriuretic peptide and N-terminal prohormone, troponin, renal function, electrolytes and blood cultures, and natriuretic peptide helps exclude but not confirm heart failure.
Differential diagnosis includes at least coronary disease, pulmonary embolism, chronic obstructive pulmonary disease, anaemia, hyperthyroidism, pericardial disease and physiological murmur, and both over-reading and under-reading murmurs are common.
Coronary disease often coexists with valve disease, and preoperative coronary assessment changes surgical strategy because untreated severe disease raises perioperative risk.
Pulmonary embolism can present with acute right ventricular load and dyspnoea, and distinction from tricuspid regurgitation and right ventricular dilatation requires D-dimer, CT pulmonary angiography and venous ultrasound.
Chronic obstructive pulmonary disease and asthma cause dyspnoea and abnormal spirometry, but echocardiography and natriuretic peptide identify coexisting structural disease.
Anaemia and hyperthyroidism create a high-output murmur and palpitations that diminish after correction, which distinguishes functional from structural murmurs.
Diagnostic delay is common in asymptomatic severe aortic stenosis, valve regurgitation and grown-up congenital disease, and a single echocardiogram cannot capture progression, so lesion-specific follow-up intervals are needed.
Screening includes newborn critical congenital heart disease screening in many countries, while school-age murmur screening and secondary rheumatic prophylaxis remain the most cost-effective strategies in low-income settings.

Management

Treatment aims to relieve symptoms, interrupt remodelling, reduce mortality and embolic risk, and correct structure before myocardial damage becomes irreversible.
First-line drugs for reduced ejection fraction heart failure include an angiotensin receptor-neprilysin inhibitor, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a beta blocker, a mineralocorticoid receptor antagonist and a sodium-glucose cotransporter 2 inhibitor, and quadruple therapy is now standard.
Sacubitril with valsartan was approved in the United States in 2015, and dapagliflozin and empagliflozin were extended to heart failure in 2020 and 2021, changing long-term outcomes in structural patients<ref>J:10.1056/NEJMoa1409077</ref><ref>J:10.1056/NEJMoa1908655</ref><ref>J:10.1056/NEJMoa2022190</ref>.
Diuretics manage congestion and relieve symptoms without altering the natural course, and dosing should follow weight, renal function and electrolytes.
Transcatheter aortic valve replacement is first-line for high and intermediate risk aortic stenosis, and low-risk indications widened during the 2020s while durability and lifelong management remain debated.
Surgical aortic valve replacement suits younger, low-risk patients, bicuspid anatomy or those needing concomitant surgery, and the heart team should decide with anatomy, age, life expectancy and preference.
Transcatheter edge-to-edge repair is used for surgical high-risk mitral regurgitation, approved in the United States in 2013 and extended to selected functional regurgitation in the 2020s.
Transcatheter closure of septal defects and patent foramen ovale reduces paradoxical embolism and right ventricular load, and shunt direction and pulmonary pressure must be assessed before closure.
Left atrial appendage closure is an option for atrial fibrillation patients who cannot take long-term anticoagulation, with stroke prevention non-inferior to warfarin but requiring device follow-up.
Anticoagulation is essential for mechanical valves, atrial fibrillation and high thrombotic risk, and direct oral anticoagulants are not suitable for mechanical valves, for which warfarin remains standard.
Non-drug care includes salt restriction, fluid management, exercise rehabilitation, weight control and treatment of sleep-disordered breathing, and cardiac rehabilitation improves capacity and quality of life.
Prevention includes primary and secondary penicillin prophylaxis for rheumatic fever, antibiotic prophylaxis for endocarditis, influenza and pneumococcal vaccination and long-term control of hypertension, diabetes and dyslipidaemia.
Endocarditis prophylaxis is reserved for prosthetic valves, prior endocarditis, specific congenital lesions and implanted devices, and overuse increases resistance and adverse events.
Prognosis depends on lesion type, timing, ventricular function and comorbidity. Symptomatic severe aortic stenosis has more than 50% two-year mortality without intervention, and timely replacement substantially improves survival<ref>J:10.1161/CIR.0000000000000923</ref>.
The multidisciplinary heart team is central to complex decisions, with cardiology, surgery, imaging, anaesthesia, intensive care and palliative care, and patient preference and life expectancy must be part of the discussion.
Mechanical circulatory support bridges acute decompensation, and intra-aortic balloon counterpulsation, extracorporeal membrane oxygenation and percutaneous ventricular assist devices have distinct indications but cannot replace treating the cause.
Transplantation and durable left ventricular assist devices serve advanced heart failure, with selection based on age, comorbidity, pulmonary resistance and donor availability, followed by lifelong immunosuppression and device care.
Palliative care is not withdrawal but simultaneous symptom control, goal communication and care planning, particularly for frail older patients who are not candidates for further intervention.

Research and controversies

Long-term transcatheter versus surgical aortic valve replacement remains the central controversy. Five-year low-risk trial results support non-inferiority or superiority on some endpoints, but durability and reintervention need longer follow-up.
Valve-in-valve procedures and annular rupture have produced the concept of lifetime valve management, and the first choice between surgical and transcatheter valves in younger patients depends on future reintervention and coronary obstruction risk.
Timing of intervention in asymptomatic severe aortic stenosis is disputed. One side argues for early surgery to prevent irreversible damage, the other for waiting for symptoms to avoid overtreatment, and randomised trials are adding evidence.
Benefit of transcatheter repair in functional mitral regurgitation has been inconsistent across trials, and patient selection, ventricular remodelling and medical background explain much of the difference.
Tricuspid intervention is the fastest-growing field, with edge-to-edge repair and annuloplasty entering practice in the 2020s, although right ventricular function, pulmonary pressure and device durability lack consensus.
Long-term follow-up for grown-up congenital heart disease is fragmented, with high loss to follow-up after transfer from paediatric care, and residual lesions and arrhythmia often appear only in adulthood.
Artificial intelligence is expanding rapidly in automated echocardiography and CT measurement, valve segmentation and risk prediction, but bias, privacy and limited validation restrict adoption.
Overdiagnosis and overtreatment are real risks in mild regurgitation, bicuspid valves and frail elderly patients, and inconsistency between imaging thresholds and symptom assessment is a major source.
Global access is markedly unequal, with transcatheter devices concentrated in high-income countries while rheumatic valve disease remains unmet in low-income settings, and price and training are the main barriers.
Synergy between medical therapy and structural intervention lacks high-quality evidence, and optimisation of quadruple therapy in patients awaiting or declining surgery remains an opportunity.
Registries and real-world data complement randomised trials, but endpoint definitions, follow-up completeness and centre heterogeneity limit interpretation.
Induced pluripotent stem cells and gene editing in cardiomyopathy models offer individualised therapy, but safety, tumorigenicity and ethical issues remain unresolved.
Guideline disagreement centres on screening age, intervention thresholds and anticoagulation, and European and American documents differ on asymptomatic severe disease and low-risk transcatheter indications, so local resources and patient values must guide decisions.
Paravalvular leak and device haemolysis are inherent complications of transcatheter valve replacement, more frequent with annular calcification and complex anatomy, and follow-up requires echocardiography and haemoglobin monitoring.
Patient-reported outcomes and quality of life are increasingly important endpoints, because haemodynamic improvement does not always translate into functional benefit, and frailty and comorbidity blunt surgical gain.
Health economic analyses suggest cost-effectiveness for transcatheter approaches in some high-risk groups, but device price and reintervention costs make results sensitive to the health system, and affordability in low-income countries remains unresolved.