Course:KIN 500C Structural Heart Disease

Allison Chun, Juan Navarro, Karine Sandilands, Natalie Yee

The authors acknowledge that this UBC Wiki page was created on the UBC Point Grey (Vancouver) Campus located on the ancestral, and unceded territory of the xʷməθkʷəy̓əm (Musqueam) Peoples.

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Introduction

Structural heart disease (SHD) refers to a broad set of conditions of cardiovascular disease processes that are non-coronary related, affecting the heart’s valves, chambers, walls, or muscles. ^16,75 Due to the immense advances of the development of diagnosis and treatment strategies, SHD has emerged as a separate specialty within interventional cardiology. ⁷⁵

Statistics

Prevalence:

SDH includes many different heart conditions that affect the hearts valves, chambers, or walls. For clarity, the following statistics encompass conditions such as valvular heart disease, congenital heart disease, cardiomyopathies, rheumatic heart disease, aortic diseases, and structural complications of heart failure.

Valvular Heart Disease:

Valvular heart disease is the most common form of SHD. ¹⁶ Globally in 2021 there were a combined 83 million cases of valvular heart disease worldwide. ¹⁴ This includes 54.8 millions cases of rheumatic heart disease, 13.3 million cases of calcific aortic valve disease, and 15.5 million cases of degenerative mitral valve disease. ¹⁴ Development of degenerative valve disease rises sharply after 70 years of age. ¹⁴ In fact, in adults over 70 years of age, the prevalence of calcific aortic valve disease exceeds 1,800 cases per 100,100 people. ¹⁴

Congenital Structural Heart Disease:

Congenital heart diseases (CHDs) are malformations of the heart that occur during fetal development and present at or before birth. ³² Congenital heart defects are the most common birth defects and are the leading cause of death for newborns in their first year of life. ³² As of 2017 there were approximately 12 million people living with congenital heart disease globally with 261,274 deaths that same year. ²⁴ The overall incidence of congenital heart disease is between 8-10 cases per 1000 births. ^24,79 Among congenital heart defects, ventricular septal defects are the most common accounting for approximately 30-35% of all cases, followed by atrial septal defects (~8-10%), patent ductus arteriosus (~5-10%), and tetralogy of Fallot (~5-7%). ²⁹

Older Adults:

There is a significant positive correlation between aging and heart disease. ¹⁴ Older adults are the age group with the largest burden of disease. ¹⁴ Degenerative valve disease is now the most common SHD in aging populations. ¹⁴ Specifically, aortic stenosis is the most common valvular heart disease among older adults, especially those over the age of 75. ^14,58 The prevalence of calcific heart disease rises sharply after age 65 and severe heart diseases are common after the age of 80. ¹⁴ Additionally, mitral regurgitation affects approximately 10% of adults over the age of 75. ¹⁴

Canadian Statistics:

Heart disease affects over 2.4 million Canadians and is the country’s second leading cause of death after cancer. ^{27, 28} In Canada, 8.2% of adults live with a diagnosed heart disease and there are over 55,000 deaths annually. ²⁷ Over 669,600 Canadians over the age of 40 have heart failure with 92,900 new diagnoses each year. ²⁷ Additionally, there are approximately 158,700 new cases of ischemic heart disease every year. ²⁸

Indigenous Populations:

In Canada, Indigenous populations face a disproportionately higher risk of developing cardiovascular disease compared with non-Indigenous Canadians. ⁷⁸ This increased burden is closely linked to longstanding social, economic, and political inequities rooted in colonialism, which continue to adversely affect Indigenous health and well-being today. ^36,78 Historical injustices, systemic racism, implicit bias within healthcare systems, and inequities in the social determinants of health collectively contribute to the persistent health disparities experienced by Indigenous peoples in Canada. ^36,78 With respect to cardiovascular disease, Indigenous peoples in Canada experience significantly higher prevalence, incidence, and mortality rates than non-Indigenous populations. ⁷⁸ Among First Nations peoples, the prevalence of cardiovascular disease is approximately 2.5 times greater than that observed in non-First Nations populations in Canada. ⁷⁸ Rheumatic heart disease also disproportionately affects Indigenous communities, reflecting broader inequities in infectious disease burden and access to timely care. ⁷⁸ Although First Nations peoples represent only 8% of the Canadian population, they account for approximately 41% of invasive Group A streptococcal infections nationally, a major contributing factor to the development of rheumatic heart disease. ⁷⁸

Structural Heart Disease by Age:


Population	Most Common Type of SHD	Prevalence/Burden	Study/Reference
Newborns	Congenital Heart Disease	8-10 per 1000 births (1.35 annually)	(van der Linde et al., 2011) ⁷⁷
Young Adults	Adult Congenital Heart Disease	Over 90% of children born with congenital heart disease survive into adulthood in high-income countries.	(GBD 2017 Congenital Heart Disease Collaborators, 2020) ²⁴
Adults > 75 Years	Aortic Stenosis	~ 3%	(Nkomo et al., 2006) ⁵⁶
Adults > 75 Years	Mitral Regurgitation	~ 10%	(Nkomo et al., 2006) ⁵⁶
Indigenous Populations	Rheumatic Heart Disease	Account for 41% of all Group A streptococcal infections in Canda	(Vervoort et al., 2022) ⁷⁸

Causes of Structural Heart Disease

Because of the wide variety of conditions that exist under the umbrella term of SHD, there is a diversity of causes. Some examples of the causes include:

· Congenital defects

· Damage from infections (ex. rheumatic fever)

· Degeneration (ex. age-related)

· Malformations

· Cardiovascular disease

· Drug or alcohol addiction

· Muscle conditions

Other Causes

Genetic Causes

A substantial proportion of SHD has a heritable genetic basis. Genetic factors can operate through single-gene mutations, chromosomal abnormalities, copy number variants (CNVs), and ocmplex polygenic interactions.

Chromosomal Syndromes

Several well-characterized chromosomal syndromes are associated with structural cardiac anomalies:


Syndrome	Genetic Basis	Common Cardiac Defect	References
Down Syndrome	Trisomy 21	Atrioventricular septal defect (AVSD)	(Ko, 2025) ³⁷
Turner Syndrome	45,X	Bicuspid aortic valve, coarctation	(Ko, 2025) ³⁷
DiGeorge/22q11.2 Deletion	CNV on chr 22	Conotruncal defects (e.g., truncus arteriosus)	(Ko, 2025) ³⁷
Noonan Syndrome	RAS/MAPK pathway (RASopathy)	Pulmonary valve stenosis, HCM	(Ko, 2025) ³⁷
Marfan Syndrome	FBN1 mutations	Aortic root dilation, mitral valve prolapse	(Khera & Kathiresan, 2017) ³⁴

Marfan syndrome, caused by mutations FBN1 (fibrillin-1), was historically considered a purely structural connective tissue disease, but research has revealed that microfibrils normally bind the latent complex of transforming growth factor-β (TGF-β), loss of this function results in abnormal TGF-β signalling and progressive aortic aneurysm. ³⁴

Recessive and Multifactorial Genetics

More recent exome sequencing studies have clarified the contribution of recessive genotypes to CHD. In a large cohort of 5,424 CHD probands, recessive genotypes accounted for approximately 2.2% of cases, with founder variants in GDF1 and PLD1 accounting for 74% of the recessive burden in Ashkenazi Jewish populations. ¹⁹ Family history remains a potent risk factor for cardiovascular disease more broadly: the Framingham Heart Study demonstrated that parental history of premature cardiovascular disease substantially increases offspring risk, with "unlucky genes" capable of doubling or tripling that risk. ⁴²

Non-Genetic Causes

Teratogenic and Environmental Causes

A terogen is any environmental agent that causes permanent structural or functional malformations following fetal exposure during pregnancy. ²⁵ Teratogenic causes of SHD are most significant during the 3rd-8th weeks of gestation (the embryonic/organogensis period), when the heart is actively forming. ⁴⁴

Key teratogenic exposures associated with congenital cardiac defects include:

Rubella Virus: Congenital rubella syndrome (CRS) can cause patent ductus arteriosus and pulmonary arterial stenosis; widespread vaccination has dramatically reduced its incidence in high-income countries. ¹⁸
Thalidomide: Prescribed in the 1950s-60s for morning sickness, this drug caused cardiac and skeletal malformation in thousands of infants, leading to major reforms in drug approval and prenatal pharmacovigilance. ¹⁸
Maternal Diabetes: Poorly controlled maternal diabetes mellitus is associated with a 3-5 fold increased risk of congenital heart defects. ¹⁹

Degenerative and Acquired Causes

Beyond the congenital and infectious categories, SHD may also develop through:

Calcific aortic valve disease, driven by hemodynamic stress, lipid deposition, and chronic inflammation, mechanistically distinct from the atherosclerosis but sharing risk factors such as hypertension, dyslipidemia, and age. ⁶¹
Hypertensive heart disease, resulting in left ventricular hypertrophy, diastolic dysfunction, and increased risk of atrial fibrillation. ¹⁷
Cardiac amyloidosis, in which overproduction of specific proteins leads to deposits in myocardial tissue, progressively impairing pump function. ⁶⁸

Examples of Structural Heart Disease

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, affecting approximately 1 in 500 people in the general population in the United States. ⁵⁷ It is a genetic condition in which the heart muscle becomes abnormally thickened (hypertrophied), most commonly affecting the left ventricle and the interventricular septum. ⁵⁰ This thickening occurs without an identifiable external cause such as high blood pressure or valvular disease, which is why it described as "unexplained" hypertrophy. ⁵⁷ Despite the structural changes, the pumping function of the heart is typically preserved or even enhanced. HCM follows an autosomal dominant inheritance pattern, meaning that a person who carries the genetic mutation has a 50% chance of passing it to each of their children. In many cases, the condition is caused by mutations in genes encoding sarcomeric proteins, most commonly MYH7 (beta-myosin heavy chain) and MYBPC3 (myosin-binding protein C), which disrupt the contractile machinery of the myocardium. ⁵⁷

Causes, Complications, Risk Factors, and Symptoms

HCM is primarily a genetic disease. Mutations in genes encoding sarcomeric proteins account for approximately 40-60% of cases, with MYH7 and MYBPC3 being the most frequently implicated genes. ⁵⁷ In the remaining cases, the genetic cause is unknown or involves non-sarcomeric genes. The condition is inherited in an autosomal dominant pattern, though variable expressivity and incomplete penetrance mean that not all individuals who carry a pathogenic mutation will develop overt clinical disease. ⁵⁷

The most serious complication of HCM is sudden cardiac death (SCD), which results from malignant ventricular arrhythmias. HCM is the leading cause of SCD in young competitive athletes in the United States. ⁵⁷ Other major complications include heart failure, which may occur with either preserved or reduced ejection fraction, atrial fibrillation, and stroke secondary to thromboemolism. ⁵⁷ Progressive exercise intolerance is also common and arises from impaired stroke volume augmentation, diastolic dysfunction, chronotropic incompetence, and dynamic LVOT obstruction. ⁸ A minority of patients develop end-stage HCM, characterized by left ventricular dilation and systolic dysfunction, representing a transition to a "burned-out" phenotype associated with poor prognosis. ⁵⁷

The primary risk factor for HCM is a family history of the condition or of unexplained sudden cardiac death in a first-degree relative under the age of 50. ⁵⁷ Established risk markers for SCD in HCM include a history of unexplained syncope, non-sustained ventricular tachycardia on ambulatory ECG monitoring, massive left ventricular hypertrophy (wall thickness >30 mm), abnormal blood pressure response to exercise, and a family history of HCM-related SCD. ⁵⁷ A personal history of prior cardiac arrest or sustained ventricular arrhythmias represents the strongest predictor of future life-threatening events and is considered the highest-risk marker. ⁵⁷

Many individuals with HCM remain asymptomatic throughout life and are diagnosed incidentally during family screening or routine evaluation. ⁵⁷ When symptoms do occur, they most commonly include exertional dysponea, chest pain or pressure, palpitations, lightheadedness, and syncope. ⁵⁷ In some cases, SCD may be the first clinical manifestation of the disease. Symptom development is largely driven by left ventricular outflow tract (LVOT) obstruction, diastolic dysfunction, and impaired augmentation of cardiac output during exercise, all of which contribute to reduced stroke volume and exercise intolerance. ⁸

Types of HCM

HCM is classified based on the pattern of left ventricular hypertrophy and the hemodynamic behaviour of the left ventricular outflow tract (LVOT) at rest with provocation. Obstructive HCM (HOCM) is the most common form and is characterized by dynamic LVOT obstruction caused by basal septal hypertrophy and systolic anterior motion (SAM) of the mitral valve. A peak instantaneous LVOT gradient >30 mmHg at rest defines resting obstruction. ⁵⁷ Approximately 25-30% of patients demonstrate obstruction under resting conditions. ⁴⁶

Latent (labile) obstructive HCM refers to cases in which resting gradients are below the diagnostic threshold but become hemodynamically significant (>30 mmHg) during physiological provocation such as exercise of the Valsalva manoeuvre. When both resting and provoked gradients are considered, approximately 70% of HCM patients exhibit obstructive physiology, signifying the importance of exercise-based assessment. ⁴⁶

Non-obstructive HCM describes patients who do not develop significant LVOT obstruction at rest or with provocation. Symptoms in this group may arise from diastolic dysfunction, microvascular ischaemia, or arrhythmias, rather than outflow obstruction. ⁵⁷

Apical HCM is a morphological variant in which hypertrophy is localised to the LV apex. It is more common in Asian populations and generally carries a more favourable prognosis, although it is associated with an increased risk of apical aneurysm and ventricular arrhythmias, reflecting a distinct high-risk phenotype. ⁵⁷

Mid-ventricular obstructive HCM is a less common subtype in which obstruction occurs within the mid-cavity rather than the outflow tract. This form is associated with an elevated risk of apical aneurysm and ventricular arrhythmias, reflecting a distinct high-risk phenotype. ⁵⁷

Diagnostic Tests

Echocardiography is the primary diagnostic tool. Two-dimensional transthoracic echocardiography (TTE) assesses LV wall thickness, chamber size, ejection fraction, diastolic function, LVOT gradients at rest and with provocation (e.g., Valsalva or exercise), and the presence of systolic anterior motion (SAM) of the mitral valve. ⁵⁷

Cardiac magnetic resonance imaging (CMR) provides superior anatomical resolution and is particularly valuable for identifying apical hypertrophy, clarifying atypical morphologies, and detecting myocardial fibrosis using late gadolinium enhancement (LGE). THe presence and extent of LGE is an independent predictor of adverse outcomes in HCM. ⁵⁷

Electrocardiography (ECG) is abnormal is most patients, commonly demonstrating LV hypertrophy voltage criteria, ST-segment abnormalities, and deep T-wave inversions, although these findings are non-specific. ⁵⁷

Ambulatory ECG monitoring (Holter) is used to detect non-sustained ventricular tachycardia (NSVT) and atrial fibrillation, both of which contribute to risk stratification and management decisions. ⁵⁷

Cardiopulmonary exercise testing (CPET) provides objective assessment of functional capacity, including peak oxygen uptake (VO₂), ventilatory efficiency (VE/VCO₂ slope), anaerobic threshold, and blood pressure response to exercise. CPET is recommended over standard ECG stress testing because it evaluates cardiovascular and pulmonary reponses simultaneously and provides prognostic information that conventional testing cannot. ^33,8

VIDEO: HCM - Exercise Physiology, CPET Assessment & Rehabilitation

Genetic testing is recommended for all patients with HCM and their first-degree relatives. Identification of a pathogenic or likely pathogenic sarcomeric variant confirms the diagnosis, supports cascade family screening, and enables reproductive counselling when appropriate. ⁵⁷

Treatment

Treatment in HCM is directed at controlling symptoms, preventing complications, and reducing the risk of SCD. Management is individualized based on symptom burden, the presence and severity of LVOT obstruction, arrhythmia risk, and overall SCD risk profile. ⁵⁷

Pharmacological Therapy: Beta-blockers are the first-line therapy for symptomatic obstructive HCM. They reduce heart rate and myocardial contractility, thereby decreasing the LVOT gradient, particularly during exertion. ⁵⁷ Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) are recommended when beta-blockers are ineffective or not tolerated. Disopyramide, a negative inotropic class la antiarrhythmic, may be added as a third-line agent to further reduce obstruction in patients with persistent symptoms. ⁵⁷ Mavacamten, a first-in-class cardiac myosin inhibitor approved by the FDA in 2022, directly targets sarcomeric hypercontractility. Phase 3 trials have demonstrated significant reductions in LVOT gradients and improvements in symptoms and exercise capacity in obstructive HCM. ⁵⁷

Septal Reduction Therapy: For patients with sever, drug-refractory symptoms and significant LVOT obstruction (resting or provoked gradient > 50 mmHg), septal reduction therapy is recommended. Surgical septal myectomy is the gold-standard intervention, offering durable gradient reduction and excellent long-term outcomes when performed at experienced centres. ⁵⁷ Alcohol septal ablation (ASA) is a catheter-based alternative that induces a controlled infarction of the hypertrophied septum. It is appropriate for selected patients depending on coronary anatomy, comorbidities, age, and institutional expertise. ⁵⁷

Implantable Cardioverter-Defibrillator (ICD): ICD implantation is recommended for secondary prevention in patients who have survived cardiac arrest or sustained ventricular tachycardia. ⁵⁷ For primary prevention, ICD placement is considered reasonable in patients with one or more major SCD risk markers.

Lifestyle and Exercise: Physical activity recommendations have evolved substantially. The 2024 AHA/ACC guidelines support mild-to-moderate intensity recreational exercise as beneficial for most patients, with vigorous activity reasonable in appropriately selected individuals following comprehensive evaluation and shared decision-making. ⁵⁷

Heart Transplantation: For patients who progress to end-stage HCM with severe systolic dysfunction (ejection fraction < 50%) and persistent symptoms despite maximal therapy, heart transplantation is considered according to standard listing criteria. ⁵⁷

Ventricular Septal Defects

Ventricular septal defects (VSDs) are a form of congenital heart disease. ⁴⁷ They are characterized as a hole (shunt) that forms between the right and left ventricles of the heart which can lead to hemodynamic problems in the heart and lungs. ^5,47 VSDs account for approximately 37% of all congenital heart disease in children. ⁵ The prevalence of VSDs decreases significantly with age as they often undergo spontaneous closure within the first year of life. ⁵ Majority of VSDs occur in isolation; however, they can also be found with other congenital defects such as tetralogy of Fallot, or double outlet right ventricle. ⁷⁴

Types of VSDs

There are many classifications of VSDs including perimembranous, inlet, outlet, and muscular. ^5,55.62. The most common subtype of VSDs is perimembranous VSDs accounting for approximately 80% of cases. ^5,62 They are located in the membranous septum just below the aortic and tricuspid valves of the heart. ⁵ Inlet defects are located just below the mitral and tricuspid valve while outlet defects are found below the aortic and pulmonary valves. ^5,55. They account for 8% and 6% of all VSD cases respectively. ^5,55. Muscular VSDs are found in the largest part of the ventricular septum and represent between 5-20% of all VSDs. ^5,55,62

Causes, Complications, Risk Factors & Symptoms

Currently the cause of VSDs is unknown. ⁹ However it is known that they develop during pregnancy as a result of improper separation of the right and left sides of the heart. ^{5, 9}; Mayo Clinic 2022). If left untreated, VSDs can have serious health implications and complications. ⁴⁹ Common complications include arterial hypertension, Eisenmenger syndrome, ventricular dysfunction, arrythmias, endocarditis and heart failure. ^5,49 There are many risk factors associated with the development of VSDs. This includes, high maternal age, alcohol abuse, being overweight, obesity, smoking, substance abuse, and diabetes. ⁶⁹ Additionally, chromosome aberration can increase the risk of developing a VSD 6.5 times fold. ⁶⁹ Symptoms of VSDs can depend on the size of the defect. ⁴⁹ Common symptoms of VSDs include breathlessness, failure to thrive, renal failure, and hypertension. ⁵⁹

Diagnostic Tests

Colour Doppler transthoracic echocardiography (TTE) is the primary diagnostic tool used to identify VSDs. ^5,23 TTE is a very sensitive test as it can diagnose up to 95% of cases. ⁵ Its main function is to help locate and determine the size of the defect. ⁵ If TTE results are inconclusive, transesophageal echocardiography can be used to diagnose VSDs. ^5,23 Other potentially useful diagnostic tools include electrocardiography (ECG), chest radiography, cardiac magnetic resonance imaging (MRI), computed tomography, and cardiac catheterization. ^5,49 ECGs are normal in approximately half of patients with VSDs, but they can detect abnormalities in those with large shunts. ⁵ Similarly, chest radiography is useful in detecting large defects. ⁵ MRI and CT are used to located complex forms of VSDs which may be in abnormal locations. ⁵ Finally, cardiac catheterization helps provide hemodynamic information which is used to help evaluate patients who may need surgical closure of their VSD. ⁵

Treatment

Treatment of VSDs generally involves open-heart surgery or a transcatheter procedure to close the defect. ⁷³ Surgical repair though open-heart surgery is considered the gold standard of treatment for VSDs and is the most common procedure performed in pediatric cardiac surgery. ^65,73 Surgical repair involves closing the hole with a sutures or a patch. Although traditional surgical repair is viewed as the preferred treatment option for many patients, there are other emerging treatments which show high success rates. ⁷³ Transcatheter closure of VSDs use an occlusion device to close the defect. ^41,71 It is a minimally invasive procedure with success rates often exceeding 90%. ^30,11,66,26 Transcatheter closure of VSDs is associated with a lower complication rates and incidence of myocardial injury. ^22,71,82 Additionally, patients who underwent transcatheter closure had a shorter hospital stay compared to individuals who had open-heart surgery. ^22,71 In some cases, hospital stay decreased by up to five days. ^22,71 Despite the benefits of transcatheter closure, surgical repair is still considered the standard practice, especially for pediatric patients with large defects or low birth weight. ⁷¹ However, transcatheter closure is an effective alternative to surgical repair, and counteracts the some of the drawbacks of a surgical approach. ^22,71,82 Overall, both treatments have high success rates. ^22,31,71 However, the transcatheter approach demonstrates a shift towards more minimally invasive procedures within medicine. ⁶⁷

VIDEO: Biodegradable Occluders for Trasncatheter Closures of VSDs.

Valvular Heart Disease

Aortic Valve (AV) Disease

Aortic valve disease entails conditions that affect the aortic valve of the heart, which is between the lower left ventricle and the aorta. ⁵³

Types of Aortic Valve Diseases

The two main types of aortic valve disease involve aortic regurgitation and aortic stenosis. Furthermore, congenital defects, such as a bicuspid aortic valve, are also considered an aortic valve disease. For the purposes of this article, the focus will be on aortic stenosis.

Causes, Complications, Risk Factors & Symptoms

If left untreated, aortic stenosis is associated with a high rate of death. ⁷² However, this is complicated by the fact that the pathology may continue to develop over several years, but the symptoms may not appear until the condition deteriorates severely. ⁸⁰ Symptoms that may be experienced include chest pain or tightness, dizziness, shortness of breath, fatigue, and palpitations – which can occur with or without activity. ⁵⁴ This is further complicated by some patients who are asymptomatic. Aortic stenosis occurs due to aortic valve leaflet stiffness, leading to a reduced orifice area and causing an increased pressure gradient with decreased anterograde systolic flow. ⁸⁰ The main cause of aortic stenosis is due to calcification, which is age-related, and likely due to progressive endothelial damage over a period of time. ⁸⁰ Because of this, risk factors for aortic stenosis include age, congenital heart defects, long-term kidney disease, infections, and risk factors for heart disease. ⁵⁴ Some complications that may arise due to aortic stenosis include stroke, blood clots, heart failure, and arrhythmias. ⁵⁴

Diagnostic Tests

The initiation of diagnostic tests usually occur after a reasonable suspicion of aortic stenosis is obtained from an in-depth history, subjective symptoms, and thorough physical exam. ⁸⁰ The 2D echocardiogram with Doppler study is considered the gold standard test, with cardiac contrast tomography (CT) and magnetic resonance imaging (MRI) utilized only if needed. ⁸⁰

Treatment

An innovative replacement technique, known as the transcatheter aortic valve replacement (TAVR), has emerged. It is inserted via transfemorally or transapically via catheter, essentially displacing and functionally replacing the damaged valve with a bioprosthesis. ⁷² Evidence that advocates for the use of TAVR, as opposed to traditional, open-heart surgical replacement, include the series of PARTNER (Placement of AoRtic TraNscathetER Valve) trials.

PARTNER Ia Trial: A multi-center, randomized study involving patients with severe aortic stenosis, considered high risk due to clinical and/or anatomical factors. 699 patients were randomized to either TAVR or surgical replacement, with death from any cause at 1 year being the primary outcome measure. This initial trial demonstrated that subjects experienced similar rates of survival at the 1 year mark, with differences noted in periprocedural risks. ⁷²
PARTNER Ib Trial: A multi-center, randomized study involving patients with severe aortic stenosis, considered inoperable due to clinical and/or anatomical factors. 358 patients were randomized to either TAVR or standard therapy (including balloon aortic valvuloplasty). Several outcome measures were assessed at the 2 year mark, including death by any cause, death or stroke, death by cardiac causes, and rehospitalization. The results showed reduced rates of death, hospitalization and symptoms, with an improvement in valve hemodynamics in the TAVR group. ⁴⁵
PARTNER II Trial: A multi-center, randomized study with intermediate risk patients, 2032 patients were randomized to TAVR and surgical aortic valve replacement. Assessment of the rate of death from any cause or disabling stroke was similar in both groups. Further, TAVR was found to result in lower rates of acute kidney injury (AKI), severe bleeds, new onset atrial fibrillation; while surgery led to less vascular complications and paravavlular aortic regurgitation. ⁴⁰
PARTNER II Sapien 3: A prospective, multi-center study involving symptomatic patients with severe AS, deemed inoperable, received TAVR with the next-generation SAPIEN 3 transcatheter heart valve. This newer system was associated with low rates (2.2%) of 30-day mortality, decreased rates of disabling stroke (0.9%) and low rates of moderate to severe (0.0-3.4%) paravalvular regurgitation. ³⁸
PARTNER III Trial: A multi-center, randomized trial involving 1,000 patients with severe aortic stenosis but low surgical risk were randomized to either TAVR or surgical replacement. The primary end point assessed was the composite of death, stroke, or rehospitalization after 1 year, which was found to be significantly lower in TAVR patients. ⁴³

In addition to these, a systematic review and meta-analysis involving 1,148 patients from 7 studies, showed the utility of TAVR compared to the surgical procedure in patients who previously received cardiac surgery. Promising results were shown, with no significant differences in one-year mortality and overall mortality between surgical and TAVR, therefore offering a safe alternative redo procedure for patients with previous cardiac surgery. ⁷⁰

VIDEO: Transcatheter Aortic Valve Replacements

Myocarditis

Myocarditis is an inflammatory disease of the myocardium, or heart muscle. It can reduce the heart’s ability to pump blood effectively and may present with chest pain, shortness of breath, palpitations, arrhythmias, or heart failure. ⁵² Although myocarditis is primarily an inflammatory myocardial disease, it is relevant to SHD because ongoing inflammation can lead to ventricular dysfunction, myocardial injury, and fibrosis that alter cardiac structure and function. ²⁰

Causes, Complications, Risk Factors & Symptoms

Myocarditis is most commonly linked to viral infection, but it can also result from bacterial, fungal, or parasitic infections, autoimmune or inflammatory diseases, medication reactions, illicit drug use, toxins, or radiation exposure. Symptoms can range from none at all to severe cardiogenic illness, but common presentations include chest pain, fatigue, dyspnea, rapid or irregular heartbeat, lightheadedness, swelling, and flu-like symptoms. Important complications include persistent cardiac dysfunction, arrhythmias, heart failure, thromboembolic events, and sudden cardiac death. ⁵¹

Types of Myocarditis

Myocarditis can be classified in more than one way. One common approach is by histologic subtype, meaning the dominant inflammatory cells seen in the heart tissue. In this classification, the main subtypes include:

File:Histopathology of lymphocytic myocarditis with myocyte necrosis, annotated.jpg

Histopathology of Lymphocytic Myocarditis

Lymphocytic myocarditis (Most common)
Eosinophilic myocarditis
Giant cell myocarditis (most rare and more severe)
Granulomatous myocarditis.

Myocarditis can also be described by its clinical presentation.

Acute myocarditis: recent episode of myocardial inflammation

Fulminant myocarditis: severe and rapidly progressive presentation that may lead to cardiogenic shock or the need for mechanical circulatory support.

Chronic active or chronic persistent myocarditis: longer-lasting inflammatory disease

Diagnostic Tests

The initial assessment of suspected myocarditis commonly includes electrocardiography, cardiac troponin testing, and echocardiography. Cardiac magnetic resonance imaging is especially valuable because it can identify myocardial edema, necrosis, fibrosis, pericardial inflammation, and ventricular dysfunction. Endomyocardial biopsy is not routinely performed in every suspected case, but it may be used when a specific diagnosis is needed to guide treatment or rule out mimics.^1,20

Treatment

Treatment depends on the cause, severity, and clinical presentation. Mild cases may improve with rest, monitoring, and medications, while more severe cases may require hospitalization, intravenous therapies, mechanical circulatory support, or heart transplantation. ⁵¹ Because exercise during active myocardial inflammation may increase risk, current guidance recommends avoiding strenuous physical activity for 3 to 6 months, followed by repeat imaging, rhythm monitoring, and exercise assessment before return to intense activity. ^1,20

VIDEO: Myocarditis: The Precision Paradox

Prevention of Structural Heart Disease

Because SHD includes abnormalities of the heart’s valves, walls, chambers, and muscle, prevention depends on the underlying cause. Some forms, particularly those related to genetic syndromes, congenital abnormalities, or age-related degeneration, cannot be fully prevented. However, many risks and complications can still be reduced through prenatal care, infection prevention, healthy lifestyle habits, and early medical follow-up. ¹⁶

For genetic and congenital causes, direct prevention is often limited because inherited mutations and chromosomal syndromes cannot usually be avoided. In these cases, prevention focuses more on early recognition, family history assessment, genetic counselling, and timely screening. Reducing modifiable maternal risk factors before and during pregnancy may also help lower the risk of some congenital heart defects, while newborn screening can support earlier diagnosis and treatment. ^12,13

Prevention is also important for non-genetic causes related to teratogenic, environmental, and infectious exposures. Avoiding harmful exposures during pregnancy, such as teratogenic drugs, ionizing radiation, and other substances that disrupt fetal development, may reduce the risk of congenital cardiac abnormalities. Proper prenatal care, vaccination, and management of maternal conditions such as diabetes are also important preventive strategies ²⁵ National Centre for Biotechnology Information, 2008; Gelb et al., 2025). In addition, rheumatic heart disease can often be prevented through prompt treatment of streptococcal sore throat, while the risk of infective endocarditis may be reduced through good oral hygiene and regular dental care. ^3,81 For myocarditis, prevention is more variable, but infection-prevention behaviours such as handwashing, avoiding viral illness when possible, staying up to date on vaccines, and avoiding recreational drug use may help reduce some risk (AHA, 2024; ¹⁵ ; WHO, 2025).

Many prevention strategies for degenerative and acquired SHD overlap with general cardiovascular disease prevention. Conditions such as calcific aortic valve disease and hypertensive heart disease may develop over time through chronic cardiovascular strain and other long-term risk factors. As a result, regular physical activity, not smoking, maintaining a healthy weight, eating a heart-healthy diet, limiting alcohol, and controlling blood pressure, cholesterol, and blood sugar may help reduce the risk of acquired structural damage and slow disease progression (CDC, 2026; ¹⁶ Exercise & Rehab in Patients with Structural Heart Disease

Exercise and cardiac rehabilitation can play an important role in the care of many patients with SHD, but recommendations must be individualized to the specific condition and the patient’s clinical status. In general, cardiac rehabilitation is a medically supervised program that combines exercise training, heart-healthy education, risk factor management, and psychosocial support. Recent American Heart Association guidance also emphasizes patient assessment, aerobic and strength training, physical activity counselling, nutrition and weight management, and program quality as core parts of cardiac rehabilitation. ^2,4,10

Because SHD includes a wide range of conditions, exercise prescription is not one-size-fits-all. The type, intensity, and amount of activity should be guided by the patient’s diagnosis, symptom severity, ventricular function, arrhythmia risk, oxygen saturation, pulmonary pressures, prior surgery or catheter-based intervention, and current medications. The European Society of Cardiology (ESC) recommends shared decision-making and notes that exercise testing, ideally with cardiopulmonary exercise testing when available, can help determine safe activity limits and guide recommendations for sport and exercise participation. ⁶⁰

For many patients with congenital or repaired SHD, regular physical activity is both safe and beneficial when appropriately supervised. The AHA notes that routine moderate exercise can benefit most people with congenital heart disease, including some patients with complex disease, although certain individuals require more personalized limits. This is especially important for patients with pacemakers or implantable cardioverter defibrillators, those taking anticoagulants, or those with residual hemodynamic problems after repair. In these cases, consultation with a health care professional experienced in congenital heart disease is recommended before beginning vigorous physical activity (AHA, 2025).

Exercise recommendations are also important in valvular and acquired SHDs. In general, remaining physically active is encouraged, but some cases require greater caution. For example, ESC valvular heart disease guidance states that patients with severe symptomatic aortic stenosis, as well as some patients with moderate stenosis due to bicuspid aortic valve and a dilated aorta, should avoid isometric exercise and high-intensity sports, while patients with milder disease may tolerate more activity after appropriate assessment. After heart valve surgery, cardiac rehabilitation can improve exercise capacity and quality of life and can help patients return to daily activities with minimal risk of serious negative effects. ^35,76

One important exception is active myocarditis, where exercise restriction is often necessary during recovery. Current American College of Cardiology guidance recommends that patients with Stage C or D myocarditis avoid strenuous physical activity for 3 to 6 months. ¹ Before returning to strenuous exercise, follow-up testing such as repeat imaging, rhythm monitoring, and exercise stress testing is recommended to confirm recovery and reduce risk. Overall, exercise in SHD should be viewed as beneficial in many cases, but safest when it is individualized, medically guided, and integrated into a structured rehabilitation plan when appropriate. ¹

Indigenous Approaches to Health and Wellness

Indigenous peoples globally bear a disporportionate burden of cardiovascular disease, including SHD. In Canada, Indigenous peoples, including the First Nations, Métis, and Inuit, experience significantly higher rates of CVD than the non-Indigenous population. Indigenous peoples in Canada have approximately 2.5 times the cardiovascular disease prevalence of non-Indigenous Canadians, with age-standardized CVD mortality rates 30% higher among Indigenous men and 76% higher among Indigenous women. ⁷⁸ Métis people in Ontario have CVD prevalence rates 25-77% higher than the general population across multiple conditions, including acute coronary syndromes, congestive heart failure, atrial fibrillation, and hypertension. ⁷⁸ In Australia, cardiovascular disease onset occurs 10-20 years earlier among Aboriginal and Torres Strait Islander peoples compared to non-Indigenous Australians. ⁶ These disparities reflect the ongoing impacts of colonization, including dispossession, disruption of traditional food systems, the Indian Residential School system, systemic racism, and structural inequality, rather than biological inevitability. ³⁹

Effective responses to these disparities require approaches that integrate Indigenous knowledge systems with Western biomedical evidence. Two prominent frameworks for achieving this integration are described below.

Frameworks

Two-Eyed Seeing (Etuaptmumk)

Etuaptmumk, the Mi'kmaw word for "the gift of multiple perspectives," is a guiding principle introduced to the academic community in 2004 by Mi'kmaw Elders Albert and Murdena Marshall and Dr. Cheryl bartlett of Cape Breton University. In English, it is most commonly called Two-Eyed Seeing. ⁶³

Elder Albert Marshall describes Two-Eyed Seeing as learning to see "from one eye with the strengths of Indigenous knowledges and ways of knowing, and using both these eyes together, for the benefit of all". ⁶⁴

A scoping review of 80 articles applying Two-Eyed Seeing in Indigenous health research identified seven core thematic categories undermining the approach: guide for life; responsibility for the greater good and future generations; co-learning journey; multiple or diverse perspectives; spirit; decolonization and self-determinationo; and humans as part of ecosystems. ⁶³

In cardiovascular health research, Two-Eyed Seeing has been applied to:

Design community-based research that integrates Indigenous health knowledge without subordinating it to Western biomedical paradigms.
Develop culturally safe communication tools and care pathways for Indigenous patients with cardiac disease.
Inform health policy advocacy that centres Indigenous self-determination and lived experience expertise.

A critical concern raised by Elder Marshall himself is the risk that Two-Eyed Seeing can be tokenized or trivialized, deployed as "mere jargon" without genuine spirit of co-learning and relationship-building. ⁶⁴ Thoughtful application requires that Indigenous voices, values, and priorities genuinely shape research design, not merely provide cultural window-dressing.

The Medicine Wheel

The Medicine Wheel is a sacred symbol and holistic health framework used by many Indigenous peoples across Turtule Island (North America), including Anishinaabe, Cree, Lakota, Plains, and many other nations, among others. It is not a pan-Indigenous symbol, teachings, colours, animals, and directional associations differ significantly by Nation, and should always be engaged with in accordance with the cultural protocols of specific communities. ⁴⁸

In its most general contemporary public health application, the Medicine Wheel is organized around four quadrants representing dimensions of human well-being:


Direction	Domain
East	Spiritual
South	Emotional
West	Physical
North	Mental/Intellectual

(Note: specific associations vary by Nation and teaching tradition)

Medicine Wheel teachings emphasize that health requires balance across all four domains simultaneously, physical health cannot be separated from emotional, mental, or spiritual well-being. This holistic model predates Western integrative medicine and maps onto evidence-based recognition of the connections between psychosocial stress, chronic disease, and cardiovascular outcomes. ⁴⁸

In cardiovascular public health, the Medicine Wheel has been applied as:

A conceptual framework to organize the multiple dimensions of lifestyle change interventions (physical activity, nutrition, mental health, cultural connection).
An evaluation framework to assess outcomes across spiritual, emotional, physical, and mental domains.
A data analysis tool enabling researchers to identify patterns and connections not visible in linear positivistic research methods. ⁴⁸

Dietary Adaptations and Traditional Foods

Colonization profoundly disrupted the traditional food systems of Indigenous peoples in Canada and globally. Government policies forced displacement from traditional lands, restricted hunting and fishing rights, and introduced nutritionally poor commodity foods (processed, high in salt, fat, and refined carbohydrates) as replacements for traditional diets. Research has documented a direct relationship between the loss of traditional foods and the rise of chronic diseases, including type 2 diabetes and cardiovascular disease, in Indigenous communities. ⁷

Traditional Indigenous diets on Canada's Pacific coast, for example, were rich in wild salmon, shellfish, herring, seaweed, game, and berries, foods with high protein, omega-3 fatty acids, and antioxidant content, and low saturated fat. In inland and northern communities, diets traditionally centred on game (moose, caribou, beaver), freshwater fish, and foraged plants. Traditional food is recognized to be of superior nutritional quality compared to market foods, contributing to spiritual, cultural, and physical health. ⁷

A 2025 non-randomized clinical trial, the MUTTON-HF study (Medically Utilized Tailored Traditional Foods to Optimize Nutrition in Heart Failure), tested a medically tailored meal delivery program in corporating Indigenous recipes and locally sourced traditional Navajo foods for patients with heart failure in rural Navajo Nation. The intervention significantly improved food security (participants who were food secure increased from 40% to 85%) and physical limitation scores, demonstrating the feasibility and acceptability of traditional food-as-medicine programs for Indigenous cardiac patients. ²¹

Key barriers to traditional food access documented in the literature include environmental degradation, government regulatory restrictions on hunting and fishing, geographic remoteness, limited income, and erosion of integenerational knowledge. ⁷ Promoters include extended family networks, traditional knowledge transmission, community programs, land access, and food sovereignty movements.

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