Prompt Diagnosis of Heart Valve Disease is Key to Good Outcomes

Dr Yassir Javaid Explores the Recommendations in the First NICE Guideline on Valvular Heart Disease, and Outlines GPs’ Vital Role in Diagnosis and Referral

Heart valve disease is a chronic condition in which the function of one or more of the four valves of the heart is impaired.¹ The condition can lead to stenosis (narrowing or stiffening of the valve, which restricts its opening, obstructing the flow of blood forwards) or regurgitation (failure of the valve to close completely, allowing blood to flow backwards).¹ Stenosis and regurgitation can occur in the same valve (mixed valve disease), and the condition can affect more than one valve at the same time (multiple valve disease).¹ Valvular heart disease in the mitral and tricuspid valves of the heart can be categorised as primary (affecting the valve structure) or secondary (a consequence of enlargement or dysfunction of the heart in the absence of abnormal valve structure).¹

Valvular heart disease can be congenital or acquired.¹ Acquired valve degeneration is currently the predominant form of the condition, and commonly presents as calcific disease of the aortic valve leading to stenosis or calcific degeneration of the mitral valve leading to regurgitation.¹ Rheumatic heart disease, which arises following rheumatic fever, is now a very rare cause of valve disease in industrialised countries, likely as a result of improvements in living conditions and medical care;² thus rheumatic mitral valve stenosis is far less common in the UK than nonrheumatic calcific mitral valve stenosis.¹

Heart valve disease is underdiagnosed (see Figure 1),³ and is often found incidentally during the investigation of other conditions (for example, during echocardiography of a patient with suspected heart failure).⁴ The prevalence of the condition increases with age (see Figure 2)³—around 13% of people aged over 75 years have moderate or severe valvular heart disease,⁵ and more than 1.5 million people in the UK are currently living with the disease.¹ However, more than 50% of people aged 65 years or over may have asymptomatic heart valve disease; therefore, given the ageing population of the UK, the prevalence of valvular heart disease is likely to explode over the next few decades.¹

Why the Need for New NICE Guidance?

The first NICE Guideline dedicated to heart valve disease—NICE Guideline (NG) 208, Heart valve disease presenting in adults: investigation and management—is, in my opinion, a very welcome publication to help address the significant unmet need that exists in this area of medicine.¹ It’s important that heart valve disease is recognised and diagnosed in a timely fashion, as modern valve intervention can offer an excellent prognosis despite the elderly demographic in which the disease most often presents.⁶ However, prognosis worsens sharply if there is a significant delay in diagnosis—untreated severe disease can lead to valvular heart failure.¹ Sadly, there remains a huge detection gap,³ which likely worsened during the pandemic;⁷ many patients are now being diagnosed late and presenting with significant heart failure, hugely compromising prognosis.

This article will largely focus on the two most common and clinically significant valve lesions in the UK—aortic valve stenosis and mitral valve regurgitation.

Establishing a Diagnosis

Although people with heart valve disease can be asymptomatic, some may experience symptoms that differ depending on the affected valve.¹ Box 1 lists some of the signs and symptoms that can manifest in people with valvular heart disease.¹

In primary care, we can opportunistically ask about symptoms during a routine review and, if present, consider heart valve disease as a possible cause following auscultation.

Referral for Echocardiography

NICE Guideline 208 recommends that an echocardiogram should be considered in all adults with a murmur in whom heart valve disease is suspected, particularly those aged more than 75 years, those with a family history of valve disease, and those with a relevant medical history, such as a history of atrial fibrillation (AF).¹ In adults with suspected valvular heart disease, if there are associated signs (for example, peripheral oedema) or symptoms (such as angina, breathlessness, or an abnormal electrocardiogram) in addition to a murmur, then an echocardiogram should be offered.¹ In adults with a murmur and severe symptoms thought to be related to heart valve disease (such as angina or breathless on minimal exertion or at rest), an urgent assessment that includes an echocardiogram should be considered.¹ NICE states that adults with a systolic murmur and exertional syncope should be offered an urgent assessment that includes an echocardiogram (or, if an assessment is not available, an urgent echocardiogram alone).¹

The algorithm provided in Figure 3 summarises the criteria for referral set out in NG208.¹

What is the Prognostic Significance of an Incidental Murmur?

In my clinical experience, murmurs are a common finding in primary care, and are often found incidentally during an examination. There is limited evidence that a murmur identified in isolation and in the absence of other signs and symptoms is an indicator of heart valve disease, but there is evidence that a substantial proportion of people with a murmur do not have valve disease, as confirmed by a reference test.¹ These ‘innocent’ murmurs occur particularly during the teenage and young adult years and in pregnancy, and are difficult to differentiate from pathological murmurs by clinical examination alone.¹

The Guideline Development Committee for NG208 felt that the evidence was not strong enough to support a recommendation that everyone with a murmur should be referred for echocardiography, as this would increase pressure on echocardiography services and offer uncertain benefit.¹ As with most areas of medicine, clinical context and acumen come into play; when the nature of the murmur, family history, age, or medical history suggests possible heart valve disease, referral for echocardiography should be considered to establish a diagnosis.¹

Specialist Referral After Echocardiography

Mild valve disease is common and rarely progresses to clinical significance, but for adults with moderate or severe valve disease of any type, or adults found to have a bicuspid aortic valve (a congenital abnormality that can lead to very early aortic stenosis and aortic root pathology), referral to a specialist is recommended.^1,8

Indications for Intervention

NICE recommends that adults with symptomatic severe heart valve disease are offered an intervention.¹ Interventions for valvular heart disease are carried out in secondary care by a specialist valve team.

When determining whether an individual would benefit from intervention, it is important to be aware of the different ways in which heart valve disease can present. New-onset or worsening symptoms are a strong indication for intervention in patients with valve disease, and should be routinely asked about. B-type natriuretic peptide (BNP) level can help to differentiate between cardiac and noncardiac symptoms⁴—for example, worsening breathlessness in an elderly patient with aortic stenosis. Timely valve intervention has an excellent prognosis, even in elderly individuals,⁶ but prognosis worsens sharply if there is a significant delay between symptom onset and intervention.

Mitral Valve Regurgitation

The indicators for intervention in mitral valve regurgitation recommended by NICE are:¹

• a left ventricular ejection fraction (LVEF) of less than 60%
• an end-systolic diameter (ESD) of more than 45 mm or an ESD index of more than 22 mm/m² on echocardiography, or
• an increase of systolic pulmonary artery pressure to more than 60 mmHg on exercise testing; however, NICE states: ‘When making decisions about referral for surgery, take into account the suitability of the valve for repair and the presence of atrial fibrillation or systolic pulmonary artery pressure of more than 50 mmHg on echocardiography at rest.’

In my experience, mitral valve regurgitation can occur in patients with AF as a result of the increased volume load on the left atrium, and should be screened for in any new AF diagnosis. Similarly, I believe that AF should be screened for in patients with any degree of mitral valve regurgitation. However, although the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidance on the management of valvular heart disease states that new-onset AF in an individual with mitral regurgitation is an indication for mitral valve surgery,⁹ NICE did not consider the evidence robust enough to include AF as an indicator for referral for intervention in adults with mitral regurgitation.¹

Aortic Valve Stenosis

In patients with asymptomatic severe aortic valve stenosis, NICE states that the following findings should prompt healthcare professionals to consider intervention:¹

• a Vmax (peak aortic jet velocity) of more than 5 m/s on echocardiography
• an aortic valve area of less than 0.6 cm² on echocardiography
• an LVEF of less than 55%
• a BNP or N-terminal proBNP level of more than twice the upper limit of normal
• symptoms unmasked on exercise testing.

In addition, NICE advises healthcare professionals to consider referring adults with symptomatic low-gradient aortic valve stenosis with an LVEF of less than 50% for intervention if, during dobutamine stress echocardiography, aortic valve stenosis is shown to be severe by:¹

• a mean gradient across the aortic valve that increases to more than 40 mmHg and
• an aortic valve area that remains less than 1 cm².

Angina is not always due to coronary heart disease, and it is important to exclude aortic valve stenosis in any patient presenting with exertional chest pain,¹⁰ because its presence is likely to herald decompensation of the left ventricle as it struggles to cope with the pressure load.¹ Unfortunately, aortic valve stenosis remains a leading cause of heart failure, and urgent assessment is warranted in individuals with severe symptoms to identify the benefit of valve intervention, otherwise prognosis is very poor.¹

Interventions for Heart Valve Disease

Pharmacological Interventions

To manage heart failure in people with valve disease, healthcare professionals should consider a beta-blocker for adults with moderate to severe mitral stenosis and heart failure.¹ For adults with heart valve conditions and heart failure who also have left ventricular dysfunction, NICE refers healthcare professionals to its guideline on chronic heart failure in adults.^1,4

Valve Interventions

Mitral Valve Regurgitation

Patients with severe primary mitral valve regurgitation who are indicated for intervention should be offered surgical mitral valve repair, if surgery is appropriate.¹ If the valve is not suitable for repair, surgical mitral valve replacement should be offered to this population.¹ Consider transcatheter edge-to-edge repair, if suitable, for adults with symptomatic severe primary mitral valve regurgitation where surgery is inappropriate.¹

Surgical mitral valve repair should be considered for adults with severe secondary mitral valve regurgitation who are having cardiac surgery for another indication, if surgery is suitable.¹ In these individuals, if the valve is not suitable for repair, surgical mitral valve replacement should be considered during cardiac surgery for another indication, if surgery is suitable.¹ If surgery is not suitable, medical management should be offered to adults with heart failure and severe secondary mitral regurgitation; if these patients remain symptomatic on medical management, mitral edge-to-edge repair should be offered.¹

Aortic Valve Stenosis

For patients with severe aortic valve stenosis, aortic regurgitation, or mixed aortic valve disease and an indication for surgery who are at low or intermediate surgical risk, NICE recommends that surgery should be offered as the first-line intervention.¹ Transcatheter aortic valve implantation (TAVI; see the forthcoming section on TAVI) should be an option for these patients, but NICE does not consider it cost effective for people at low or intermediate surgical risk at the current list price.¹ However, TAVI should, if appropriate, be offered to adults with nonbicuspid severe aortic valve stenosis who are at high surgical risk or if surgery is not suitable.¹  

TAVI

TAVI is one of the great innovations in medicine over the past few decades, and has altered the landscape in terms of the management of aortic valve stenosis. TAVI involves the insertion of a new valve through a catheter, usually via a large blood vessel at the top of the leg, into the heart and inside the existing faulty valve. It is an alternative to surgical valve replacement by open heart surgery. Most people with aortic valve stenosis who are at the stage of requiring an intervention are in their eighth or ninth decade of life, and comorbidity is common in this population.¹¹ Many are denied intervention on account of these comorbidities and operative risk.¹² However, there are clear guidelines that state that people with severe aortic valve stenosis should be considered for TAVI if they are considered not suitable or high risk for surgery.^1,9,12

Such assessments are made within an experienced multidisciplinary team (MDT), which typically includes interventional cardiologists, cardiac surgeons, experts in cardiac imaging and, where appropriate, cardiac anaesthetists; increasingly, the MDT also includes a geriatrician, and can include other specialists if appropriate.¹² The MDT will determine the risk level for each patient, and the TAVI device most appropriate for them.¹² In patients with aortic valve stenosis that are deemed inoperable, mortality rate, hospitalisation rate, and New York Heart Association class have been shown to be superior following TAVI compared with medical management.¹² There is a move towards carrying out the procedure under local rather than general anaesthesia.¹²

Anticoagulation and Antiplatelet Therapy Following Valve Intervention

Anticoagulation is not required, and should not be offered to patients, following surgical biological valve replacement, unless there are other indications.¹ Following TAVI, however, NICE advises that aspirin (or clopidogrel if aspirin is not tolerated) should be considered.¹

In people with AF, taking into account CHA₂ DS₂-VASc score¹³ and bleeding risk, direct-acting oral anticoagulants (DOACs) are now the first-line option instead of warfarin,¹⁴ unless patients have received a surgical metallic valve replacement or have at least moderate mitral valve stenosis (which would almost always be rheumatic in origin).⁹ Regarding the use of DOACs in these patients, NICE refers healthcare professionals to its Technology Appraisal Guidance on embolism and thrombosis.^14,15

Surveillance of Patients with Valvular Heart Disease

Surveillance When There is No Current Need for Intervention

NICE recommends that patients with mild aortic or mitral valve stenosis are offered an echocardiogram.¹ Patients with asymptomatic severe valvular heart disease should be offered a clinical review, including an echocardiogram, every 6–12 months if valve intervention is suitable but not currently needed.¹

Surveillance Following Valve Intervention

All patients should be kept under surveillance following valve intervention.⁹ The type and frequency of this monitoring depends on many factors—including valve durability, comorbidities, residual valve abnormality, and patient preference¹—and will be determined by the specialist valve team.

Infective Endocarditis

Infective endocarditis (IE) is a rare but potentially devastating complication of heart valve disease, and is the cause of significant morbidity and mortality.¹⁶ Prompt diagnosis is therefore important, but can be problematic as the presentation of IE is often nonspecific. People with prosthetic valves, and those who have previously had endocarditis, are at particularly high risk of IE.^1,16 IE should be a differential diagnosis in any patient with heart valve disease and unexplained fever or constitutional symptoms such as weight loss and anorexia. A new, regurgitant murmur in such patients is sufficient to make a clinical diagnosis and indicates a need for referral. Maintaining good dental hygiene is the single most important intervention to reduce the risk of IE, as at least 50% of cases of community-acquired IE not associated with intravenous drug use are caused by viridans-group streptococci originating in the mouth.¹⁶ NICE recommends that people with valvular heart disease should be encouraged to seek advice if they feel that their condition has deteriorated; it is important to note that there is a higher risk of IE in people with replacement valves.¹

Summary

Heart valve disease is a common and often-missed condition, and comorbidity is the norm. Understanding the different ways in which valvular heart disease can present is critical to enable timely referral, which is the key to optimising outcomes.

Dr Yassir Javaid

GP with an interest in cardiology, Northampton; Cardiology Cardiovascular and Diabetes Lead, Northamptonshire CCG; past primary care council member of the British Heart Valve Society; accredited member of the British Society of Echocardiography; editorial board member for The British Journal of Cardiology