Medical Management of Rheumatic Heart Disease


Chronic ambulatory heart failure (HF) is usually the most common clinical manifestation of advanced rheumatic heart disease (RHD) . HF in RHD patients typically develops after a chronic, often asymptomatic, period of progressive valvular heart disease, typically manifesting clinically only when the valve disease is severe (or less than severe in mixed or multivalve disease). The pathophysiology of rheumatic valvular lesions and how this relates to the timing of cardiac surgery or catheter-based intervention, as well as the medical management of chronic HF and valvular lesions, are discussed in this chapter. Antithrombotic therapy, particularly in the context of mechanical heart valves and atrial fibrillation, also plays an important role in the medical management of RHD and is discussed in detail at the end of the chapter. Surgical ( Chapter 8 ) and catheter-based management ( Chapter 7 ), acute HF and other emergency presentations ( Chapter 16 ), and the management of pregnant women with RHD ( Chapter 9 ) are discussed in detail in their relevant chapters.

The recommendations promulgated in this chapter are based around three important groups of guidelines, each addressing different aspects of the medical management of RHD. The Australian and New Zealand guidelines define the principles of management of RHD, which apply to all patients. The American College of Cardiology, American Heart Association, and Heart Failure Society of America (ACC/AHA/HFSA), and the European Society of Cardiology (ESC) provide extensive guidance on the medical management of chronic heart failure , the main cause of death in RHD. Finally, the AHA and ACC (AHA/ACC), and the ESC provide guidance on the assessment of, and indications for, surgical or catheter-based treatment of valve disease and are discussed in the section medical management of individual valve lesions .

Each of these guidelines is updated every few years by leading world experts in the respective fields and most use class of recommendation (COR) and level of evidence (LOE) for each recommendation. It should be emphasized that the guidelines on HF and valvular heart disease reflect evidence-based management for patients in high-income countries, usually without resource restriction for medicines and complex cardiac interventions. Although the guidelines on HF are relevant to most patients with RHD, the relevance of the valvular heart disease guidelines for specific RHD lesions varies. They are highly relevant for mitral stenosis (MS), relevant for mitral regurgitation (MR) and aortic regurgitation (AR), but may be of less relevance for aortic stenosis (AS), where the guidelines have evolved in recent years from advances in the management of calcific AS in the elderly.

An important theme of the AHA/ACC and ESC valve disease guidelines is the overall strong evidence-based support for surgical and catheter-based intervention for severe or symptomatic valvular heart disease. In contrast, the guidelines acknowledge the relative lack of evidence-based support for pharmacological management of severe valvular heart disease to alter outcomes. There is also little RHD-specific evidence on optimal drug therapy in HF. The recommendation for medical therapy in RHD patients with HF and left ventricular dysfunction is therefore largely based on evidence from patients with HF with reduced ejection fraction (HFrEF). Moreover, most evidence-based management of RHD and HF is based on adult data. Management principles for RHD in the young are often extrapolated from published guidelines for adult patients. The limited specific data that underpin the guidelines on the timing of intervention in children are included.

Principles of Management of Rheumatic Heart Disease

Managing patients with RHD is complex, expensive, and requires strong national health systems. Adequate primary, secondary, and tertiary services with specialists including cardiology, cardiothoracic surgery, pediatrics, general medicine, general practice, dentistry, obstetrics, and infectious diseases are often required. A practical approach to the long-term management of RHD is provided by best practice guidelines from Australia and New Zealand and include the following: periodic clinical evaluation by a specialist experienced in RHD management, serial echocardiography for assessment of left ventricular and valve function, timely referral for heart surgery or catheter intervention, monitoring of anticoagulation for patients with atrial fibrillation (AF) or prosthetic valves, access to oral healthcare, annual influenza vaccination, and last but not least secondary prevention with penicillin prophylaxis ( Table 6.1 ). These overall management principles for RHD will always be paramount to avoid the complications of recurrences of acute rheumatic fever (ARF), infective endocarditis, and thromboembolism, and facilitate optimal ongoing care. The principles of secondary prevention, anticoagulation for prosthetic valves and AF, and optimizing oral healthcare are discussed at the end of this chapter.

Table 6.1

Best Practice Rheumatic Heart Disease Management Principles.

  • 1.

    Access to a specialist RHD physician (pediatrician, physician, cardiologist or specialized nurse/physician assistant experienced in RHD management) for regular follow-up visits

  • 2.

    Secondary prevention with penicillin prophylaxis (see also Chapter 11 )

  • 3.

    Access to echocardiography

  • 4.

    Access to cardiothoracic and interventional cardiology services, if required

  • 5.

    Adequate monitoring of anticoagulation therapy in patients with atrial fibrillation and/or mechanical prosthetic valves

  • 6.

    Optimise oral healthcare, including routine dentistry reviews

  • 7.

    Annual influenza vaccination

  • 8.

    Prevention of infective endocarditis

RHD, rheumatic heart disease.

Medical Management of Chronic Heart Failure in Rheumatic Heart Disease

Multivalve and mixed valve disease is the most common disease pattern seen in RHD in most age groups (see Chapter 5 ). This has important implications for the prognosis and management of RHD because multivalve and mixed valve disease carries a high risk for left ventricular dysfunction and symptomatic HF, even if the individual lesions are not classified as severe. This contrasts with single valve disease, where in general only severe lesions lead to HF.

Overview of Heart Failure Treatment

HF is a pathophysiological state in which a structural or functional cardiac disorder impairs the ability of the ventricle to fill with or eject blood at a rate that meets the requirements of metabolizing tissues. It is the final pathway for a multitude of diseases that affect the heart: for RHD, this refers to moderate to severe, usually chronic, valvular heart disease. Common symptoms of HF include dyspnea, fatigue, restricted exercise tolerance, and congestion (fluid accumulation in the lungs, abdomen, and lower extremities), all of which are discussed in Chapter 5, Chapter 16 .

All patients with HF should be classified and staged, which is important for diagnosis and management. HF classification is based on symptoms and degree of functional limitation, as defined by the New York Heart Association (NYHA—see Chapter 5 ). HF staging is based on the ACCF/AHA system, which emphasizes the progressive nature of HF (different from the NYHA classification, where the patient can move up or down classes depending on how well their symptoms are controlled) and defines the appropriate therapeutic approach for each stage ( Fig. 6.1 ) . Staging HF in this manner should help promote an approach to RHD management that reflects some of the core themes of this book—that is, the importance of identifying and treating patients at risk for RHD (history of ARF), the importance of closely monitoring patients with established RHD for evidence of HF or left ventricular dysfunction, and the importance of timely treatment of symptomatic RHD (surgical, interventional, and/or medical management).

Fig. 6.1

Staging heart failure in the context of rheumatic heart disease. Adapted from Yancy et al.

There are several different HF phenotypes, in part reflected by differences in left ventricular ejection fraction (LVEF). The LVEF is typically a key guide to medical therapy, most notably in HF patients with a LVEF ≤40% (known as heart failure with reduced ejection fraction (HFrEF)) due to the strong evidence base for disease-modifying therapies in this group. However, in patients with RHD presenting with HF symptoms, the dominant valve lesion is often a more important determinant of the choice of medical therapy than the LVEF (see also Fig. 6.1 ). For example, in patients with symptomatic severe mitral and/or aortic regurgitation, treatment is with standard guideline-based medical therapy for HFrEF, even if the LVEF is >40%. In symptomatic isolated mitral stenosis, the LVEF is usually normal and therapy is based on relieving symptoms of pulmonary congestion and controlling the heart rate. In severe symptomatic aortic stenosis, a combination of diuretics and ACEI are often used regardless of LVEF (started at low dose with gradual titration) and beta blockers are often avoided. And in patients with mixed or multivalve disease, therapy is determined by the dominant valve lesion, although is usually similar to that for HFrEF.

Because a significant number of patients with RHD who develop HF symptoms are likely to have a reduced LVEF and/or a significant regurgitant lesion (MR and/or AR), this section will focus on HFrEF guideline-directed therapy. The management of patients with isolated or predominantly stenotic lesions or asymptomatic regurgitant lesions is discussed later in the section Medical Management of Individual Valve Lesions.

Heart Failure Managment (HFrEF)

General management

The goals of management of HFrEF mainly focus on reducing morbidity (symptoms of HF, improving functional status and quality of life, decreasing hospitalization rates) and reducing mortality. Important general factors to consider include the following:

  • Lifestyle modification: this should include cessation of smoking, avoidance of obesity, restriction or abstinence from alcohol, and daily weight monitoring to detect fluid accumulation. Recommendations regarding limiting salt intake vary: the ACCF/AHA HF guidelines suggest some degree of sodium restriction (e.g., <3 g/day), whereas the 2016 ESC HF guidelines suggest avoiding excess sodium intake (<6 g/day).

  • Hypertension: consider antihypertensives if BP is ≥140/90 mmHg . In patients with HFrEF, hypertension should generally be managed with an angiotensin converting enzyme inhibitor (ACEI) (or an angiotensin II receptor blocker (ARB) or an angiotensin receptor-neprilysin inhibitor (ARNI)), a β-blocker, a diuretic, and/or a mineralocorticoid receptor antagonist (MRA), because these drugs are also standard therapy in HFrEF. A dihydropyridine calcium channel blocker (CCB), either amlodipine or felodipine, can be added if BP control is not achieved.

  • Anemia: has an impact on prognosis in HF. There is no universally accepted hematocrit or hemoglobin level at which a blood transfusion should be given. The historically accepted trigger for transfusion has been a hemoglobin of <10 g/dL. However, there is growing acceptance that transfusion triggers in general should be restrictive (hemoglobin trigger set at ≤7 g/dL, with a posttransfusion target hemoglobin of 9–10 g/dL) rather than liberal (hemoglobin trigger set at <10 g/dL, with a posttransfusion target hemoglobin of 10–12 g/dL), with several reports and meta-analyses showing that this approach leads to better outcomes. Iron therapy is also an important therapeutic option and both oral and intravenous iron are recommended in the presence of iron deficiency or iron deficiency anemia.

Pharmacological therapy

Established therapies for HFrEF are loop diuretics, ACEI/ARB, β-blockers, MRAs, hydralazine combined with isosorbide dinitrate (HYD-ISDN), and digoxin. Randomized control trials have shown that each of these, with the exception of loop diuretics and digoxin, reduces the burden of hospitalization and improves survival. More recent additions to the HFrEF armamentarium, valsartan/sacubitril, an ARNI, and the selective sinus node inhibitor (I f -channel blocker), ivabradine, also reduce the risk of HF hospitalizations and mortality. It is important to remember that the evidence for these drugs focuses on non-RHD causes of HF and while they may help reduce HF-related morbidity and mortality in RHD, like they do in other causes of HF, there is no evidence that they alter the natural history of RHD or the need for interventional or surgical management. It is also important to remember that symptoms relieved by medications still mean that eligible patients should be considered for surgery.

ACC/AHA/HFSA recommendations for initiating pharmacological therapy in a newly diagnosed patient with HFrEF (stage C heart failure) are summarized in Fig. 6.2 and the starting and target doses of recommended drugs are summarized in Table 6.2 . ESC guidelines, with few exceptions, make similar recommendations regarding the treatment of HFrEF. It is worth emphasizing that target doses of recommended medications should be aimed for, as far as possible, as these dosages are associated with the best evidence for improved outcomes.

Fig. 6.2

Treatment algorithm for guideline-directed medical therapy of heart failure with reduced ejection fraction. Green squares indicate Class I guideline recommendations, while the yellow square indicates a Class II recommendation. ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, ARNI angiotensin receptor-neprilysin inhibitor, eGFR estimated glomerular filtration rate, HFrEF heart failure with reduced ejection fraction, HR heart rate, NYHA New York Heart Association.

Reproduced with permission from Yancy et al.

Table 6.2

Starting and Target Doses of Disease-Modifying Drugs for Heart Failure with Reduced Ejection Fraction in Adults.

Reproduced with permission from Yancy et al.

Starting Dose Target Dose Comments
Bisoprolol 1.25 mg OD 10 mg OD Consider increasing dose every 2 weeks until maximum tolerated dose or target dose achieved
Monitor heart rate, blood pressure, and for signs of congestion after initiation and during titration
Carvedilol 3.125 mg OD 25–50 mg BID
Metoprolol succinate 12.5–25 mg OD 200 mg OD
Angiotensin Converting Enzyme Inhibitor (ACEI)
Captopril 6.25 mg TID 50 mg TID Consider increasing dose every 2 weeks until maximum tolerated dose or target dose achieved
Monitor blood pressure, renal function, and potassium after initiation and during titration
Enalapril 2.5 mg BID 10–20 mg BID
Lisinopril 2.5–5 mg OD 20–40 mg OD
Ramipril 1.25 mg OD 10 mg OD
Angiotensin II Receptor Blocker (ARB)
Candesartan 4–8 mg OD 32 mg OD Alternative in patients who cannot tolerate ACEI for reasons other than renal dysfunction or hyperkalemia (e.g., cough)
Monitoring as per ACEI
Losartan 25–50 mg OD 150 mg OD
Valsartan 40 mg BID 160 mg BID
Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
Sacubitril/valsartan 24/26 mg-49/51 mg BID 97/103 mg BID Start 24/26 mg twice daily if taking equivalent of ≤10 mg daily of ramipril or equivalent of ≤160 mg daily of valsartan
Start 49/51 mg twice daily if taking equivalent of >10 mg daily of ramipril or equivalent of >160 mg daily of valsartan
Monitoring as per ACEI
Mineralocorticoid Receptor Antagonists (MRA)
Eplerenone 25 mg OD 50 mg OD Consider increasing dose every 2 weeks until maximum tolerated dose or target dose achieved
Monitor electrolytes and renal function 2–3 days after initiation and 7 days after titration. Afterward, check monthly for 3 months and 3 monthly thereafter
Spironolactone 12.5–25 mg OD 25–50 mg OD
Hydralazine 25 mg TID 75 mg TID Consider increasing dose of ISDN and/or hydralazine every 2 weeks until maximum tolerated dose or target dose achieved
Monitor blood pressure after initiation and during titration
ISDN 20 mg TID 40 mg TID
Fixed-dose combination ISDN/hydralazine 20/37.5 mg (one tab) TID 2 tabs TID
I f- Channel Blocker
Ivabradine 2.5–5 mg BID Titrate to heart rate 50–60 bpm
Maximum dose 7.5 mg BID
If aged ≥75 years, start 2.5 mg twice daily; if aged <75 years, start 5 mg twice daily
Monitor heart rate in at least 2–4 weeks: if <50 bpm, reduce dose by 2.5 mg twice daily; if 50–60 bpm maintain current dose; if >60 bpm increase dose by 2.5 mg twice daily

OD, omne in die (once daily); BID, bis in die (twice daily); TID, ter in die (three times daily); ISDN, isosorbide dinitrate; bpm, beats per minute.

Diuretics are usually started first in volume overloaded patients. Loop diuretics are recommended and furosemide is the most commonly used, although due to superior and more predictable absorption some patients respond better to bumetanide or torsemide. Thiazide-like diuretics (e.g., indapamide, metolazone) can be added to loop diuretics if there is a suboptimal response. ACEI are typically added next, either during or after optimization of diuretic therapy, with β-blockers started once the patient is stable on ACEI therapy. Only evidence-based β-blockers should be used (see Table 6.2 ). In those patients who cannot tolerate ACEI (most often due to cough), an ARB should be offered instead.

In those patients that remain symptomatic (NYHA II–IV) after titration of an ACEI/ARB and a β-blocker, with an LVEF ≤35% and providing there are no contraindications, an MRA should be started. Inappropriate use may be harmful and the potassium and creatinine must be checked within 1 week of commencing an MRA. For patients with ongoing HF symptoms (NYHA class II–III) and who have tolerated ACEI/ARB therapy, replacement by an ARNI is recommended to further reduce morbidity and mortality. If switching an ACEI to ARNI therapy, a 36-h washout is essential first to avoid angioedema (not required with ARBs).

For black patients who remain symptomatic (NYHA class III–IV) despite optimal treatment with diuretics, ACEI/ARB or ARNI, β-blocker, and an MRA, the addition of HYD-ISDN is recommended (isosorbide mononitrate is not recommended by the ACC/AHA/HFSA guideline). This strategy is particularly relevant in Africa, which has the largest burden of RHD, although data indicate that HYD-ISDN is rarely ever used for HF in these populations, providing an opportunity for improved outcomes. HYD-ISDN can also be used in all patients who cannot tolerate an ACEI or ARB (or they are contraindicated) to reduce the risk of death. For those patients who are in sinus rhythm at a heart rate ≥70 bpm despite maximally tolerated β-blocker therapy (or in those for whom β-blockers are contraindicated or not tolerated), who remain symptomatic (NYHA class II or III) with an LVEF ≤35%, ivabradine is recommended.

Digoxin remains a therapeutic option in those patients in sinus rhythm who remain symptomatic despite an ACEI/ARB or ARNI, β-blocker, and an MRA. Although it has no effect on mortality, digoxin does reduce the risk of hospitalizations (both all-cause and HF hospitalizations). It is also indicated in patients with AF and a rapid ventricular rate (>110 bpm) , although for patients with HFrEF with AF requiring rate control, beta-blockers are preferred first line as they form part of the general treatment of HF. Should a second agent be required to achieve adequate rate control, digoxin can then be used. Digoxin is commonly used in patients with RHD (nearly 35% of patients in the REMEDY study) particularly in those with MS, regardless of the presence of AF or HF. The main rationale for this is to reduce the heart rate and transmitral gradient, with the aim of improving symptoms. However REMEDY data at 2 years from enrollment suggests a possible association of digoxin use and increased mortality, particularly among those without AF or HF.

Discussion of other types of HF, including refractory HF (stage D) and HF with LVEF ≥50% are beyond the scope of this book but are addressed in the ACC/AHA/HFSA and ESC HF guidelines.

Medical Management of Individual Valve Lesions

The clinical features and echocardiographic assessment of individual valve lesions are both discussed in detail in Chapter 5 . Given that surgery is usually recommended for symptomatic severe valvular heart disease, it is worth emphasising here that decisions regarding surgery should be made in conjunction with cardiologists, cardiothoracic surgeons, and intensivists (as appropriate) in a multidisciplinary “heart team” approach. Risk assessment may be helped by the use of risk scores, such as those from the Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery (EuroSCORE II). It is also worth emphasizing that patients who have undergone valve surgery should undergo 6-monthly cardiology review and echocardiogram because the long-term outcomes of both mechanical and bioprosthetic valve replacement in RHD patients remain very poor. Finally, whilst the pathophysiology of valvular lesions is discussed here, the underlying valvular anatomic derangements are discussed in detail in chapter 8 .

Chronic Mitral Regurgitation

Natural History and Pathophysiology of Mitral Regurgitation

Rheumatic MR results from thickening, retraction, and distortion of both the valve itself and the supporting structures. Annular dilatation and loss of the saddle shape of the mitral annulus, elongation of the chordae tendinae (mostly the primary chords), and over the longer term, retraction of the thick intermediate chords, restricts the motion of both leaflets. Progression from mild-to-severe rheumatic MR can be halted or potentially reversed (when mild or moderate) by adherence to secondary penicillin prophylaxis.

The natural history of chronic MR has three distinct phases: compensated, transitional, and decompensated. Progression between each phase can be insidious, emphasizing the importance of regular clinical and echocardiographic monitoring to identify early deleterious LV changes and proceeding to surgical correction before the establishment of irreversible LV damage. Over time, the natural history of untreated chronic severe MR is that of myocardial damage, HF, and eventual death. The 2017 AHA/ACC update emphasize the concept that mitral regurgitation begets mitral regurgitation with a perpetual cycle of ever-increasing LV volumes and MR.

Chronic MR imposes a volume load on the LV resulting in a series of myocardial adaptions, the most important of which is LV enlargement that maintains the total stroke volume and forward stroke volume. This represents the compensated phase, which often lasts several years, and most patients are asymptomatic. LV enlargement and eccentric hypertrophy develop, normalizing the systolic wall stress. Contractility and LVEF are both normal. When the echocardiographic LV end-diastolic dimension (LVEDD) is <60 mm and the LV end-systolic dimension (LVESD) is <40 mm, surgery is not indicated.

Eventually, compensatory mechanisms start to fail and structural and functional remodeling of the LV occurs. There is a decrease in LV contractile function and increase in wall stress (increased afterload). The onset of HF symptoms and/or development of LV systolic dysfunction (defined as LVEF <60%, often with LVESD ≥40 mm) heralds onset of the transitional phase and is an indication for surgery. Many patients, however, remain asymptomatic making this phase difficult to identify. If surgery is performed during this phase, a good clinical outcome is usually possible.

The decompensated phase is characterized by the onset of symptoms and progressive LV dilatation (LVEDD >70 mm, LVESD >45 mm) and a reduction in systolic function (LVEF <50%). Corrective surgery should be performed before the establishment of the decompensated phase because patients with chronic MR and LV dysfunction have higher postoperative mortality and persistent LV dysfunction.

In the current era, cardiac catheterization is not usually indicated as severity is apparent by clinical and echocardiographic assessment. It is pertinent, however, to understand the hemodynamics of symptomatic, decompensated, severe MR. A series of 219 patients with isolated severe MR, all NYHA class III-IV, underwent cardiac catheterization prior to cardiac surgery in the 1980s in South Africa. The mean left atrial (LA) pressure was 24 ± 9 mmHg, the LA V-wave was 46 ± 18 mmHg, and LV end-diastolic pressure was 16 ± 8 mmHg. Importantly, the right ventricular systolic pressure (RVSP), and pulmonary artery systolic pressure, was 50 ± 13 mmHg, as high as patients with pure MS.

Mitral Regurgitation Medical Management

For patients with chronic asymptomatic MR, there is some evidence that β-blockers lead to possible benefit. A preliminary trial of 38 asymptomatic patients with moderate to severe isolated MR (cause of MR not specified) were randomized either to placebo or extended-release metoprolol for 2 years. LVEF and LV early diastolic filling time significantly improved with β-blocker therapy. A retrospective study of 895 patients with severe MR (of multiple etiologies and normal LVEF) found that those who were treated with β-blockers had a significantly reduced risk of mortality, independent of whether the patients were managed medically or surgically. In an Indian study looking specifically at RHD patients with chronic MR, therapy with metoprolol lowered NYHA class, left ventricular end-systolic and diastolic volumes, and brain natriuretic peptide over 3 months compared to controls. MR grade decreased from severe to moderate in 11% of those on metoprolol over 6 months of treatment (compared to none in the control group). Symptomatic patients with moderate or severe MR and LVEF <60% (stage C HF) who are either awaiting valve surgery or surgery is not an option (usually either unfit for surgery or it is unavailable) should be managed with standard HFrEF therapy, as discussed earlier.

No published guidelines support the use of vasodilators in normotensive asymptomatic patients with chronic MR and normal LV systolic function. However, there is some evidence that vasodilators may improve outcomes in symptomatic patients. A study on 47 patients with mildly symptomatic MR, 26 of whom had RHD, found that there was a significant reduction in left ventricular diameter and MR volume in those who received enalapril for 12 months, compared to placebo. A Turkish study found that addition of an ACEI lowered left ventricular end diastolic volume and atrial natriuretic peptide levels after 20 days of treatment in a cohort of patients who were being treated with digoxin at baseline. Finally, a study examined the impact of 6 months of treatment of enalapril and nicorandil, a balanced vasodilator, in 87 mildly symptomatic RHD patients with severe MR. Both drugs resulted in decreased left ventricular systolic volume and increased ejection fraction, and nicorandil was found to have a greater effect.

Summary of the medical therapy of chronic MR:

  • Mild MR is usually well tolerated and does not require any specific pharmacologic therapy

  • Asymptomatic patients with moderate or severe MR and no evidence of LV dysfunction (stage B HF):

    • Limited evidence that β-blockers therapy leads to possible benefit

    • Vasodilators (e.g., ACEI or CCBs) are not indicated if the patient is normotensive

  • Symptomatic patients with moderate or severe MR and LVEF <60% (stage C HF) that are both surgical and non-surgical candidates should be managed with standard HFrEF therapy

  • All authorities and guidelines recommend that the primary focus should be on surgical intervention. The AHA/ACC guidelines emphasize the natural history of untreated chronic severe MR, that of myocardial damage, HF, and eventual death. Correction of the MR is indicated unless LV function is significantly impaired. The guidelines also emphasize that symptoms relieved by medications still mean that the patient should be considered for mitral valve surgery.

  • Patients with hypertension without HF are treated with standard antihypertensive therapy, which may help reduce worsening of the MR.

Indications for Cardiac Surgery for Mitral Regurgitation

As a general rule, repair, if possible, is preferred over valve replacement (see Chapter 8 ). Important reasons for this include avoiding the risk of complications associated with mechanical valves (thromboembolism, bleeding, nonadherence with oral anticoagulation (OAC), and OAC in women of childbearing age). Bioprosthetic valves in the mitral position have limited durability in children but have a key role in women of childbearing age wishing to have a pregnancy.

Key points regarding indications for referral for cardiac surgery for MR are summarized in the Australian Guideline for Prevention, Diagnosis and Management of Acute Rheumatic Fever and Rheumatic Heart Disease, second edition. This is a useful checklist for health professionals such as specialist nurses, physicians, and noncardiologists regarding when to refer patients with severe MR to a cardiosurgical unit ( Table 6.3 ).

Table 6.3

Indications for Referral for Cardiac Surgery due to Mitral Regurgitation in Adults and Children.

Adult Patients with Moderate or Severe MR and:

  • NYHA class II-IV symptoms or

  • Impaired LV systolic function (LVEF <60%) or

  • LVESD ≥40 mm in adults or enlarged LVESD Z-score in children or

  • Pulmonary hypertension (PASP >50 mmHg) or

  • New onset atrial fibrillation

Children a with severe MR and:

  • Symptoms of breathlessness or

  • Asymptomatic plus one of the following:

    • Impaired LV function (LVEF <60%)

    • LVESV z -score > +2.5

    • Pulmonary hypertension (PASP >50 mmHg)

MR, mitral regurgitation; NYHA, New York Heart Association; LV, left ventricular; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; LVESV, left ventricular end-systolic volume; PASP, pulmonary artery systolic pressure.

a Children defined as <16 years, or those with nonadult body habitus.

Data for the LV end-systolic volume (LVESV) Z -score threshold is based on data from RHD patients in New Zealand, where the higher the preoperative LVESV Z-score the higher the risk of late postoperative LV dysfunction.

More detailed descriptions of specific patient subsets and their indications for mitral valve surgery, as used by cardiologists assessing patients, and for decision-making at cardiosurgical units, are published in the extensively referenced AHA/ACC guidelines and ESC guidelines, using COR and LOE for each recommendation. It should be reemphasized that these guidelines are updated every few years and reflect evidence-based management for patients in high-income countries, usually without resource restrictions for complex cardiac interventions. Although there are no class 1A indications for mitral valve surgery, AHA/ACC class IB indications include the following:

  • Mitral valve surgery is recommended for symptomatic patients with chronic severe primary MR and LVEF >30%

    When assessing LV function preoperatively and considering the timing of surgery, it is important to remember that the true extent of intrinsic systolic dysfunction may not manifest fully until after surgery, which can lead to a “paradoxical” worsening of LVEF. This relates to preoperative LV mechanics, including end-systolic stress and afterload. For example, severe MR “unloads” the LV by providing a low-resistance pathway into the LA during systole. Therefore, in the presence of severe MR, a normally functioning LV should appear hyperdynamic. When LV function is depressed preoperatively, therefore, it may not recover and outcomes may be poor despite relief of symptoms due to the MR. Outcomes following cardiac surgery are discussed in more detail in Chapter 8 .

  • Mitral valve surgery is recommended for asymptomatic patients with chronic severe primary MR and LV dysfunction (LVEF 30%–60% and/or LVESD ≥40 mm)

  • Mitral valve repair is recommended in preference to mitral valve replacement (MVR) when surgical treatment is indicated for patients with chronic severe primary MR limited to the posterior leaflet

  • Mitral valve repair is recommended in preference to MVR when surgical treatment is indicated for patients with chronic severe primary MR involving the anterior leaflet or both leaflets when a successful and durable repair can be accomplished

  • Concomitant mitral valve repair or MVR is indicated in patients with chronic severe primary MR undergoing cardiac surgery for other indications

Serial evaluation

Detecting any change in clinical status, as determined by history and physical examination, and any change in the severity of MR and LV function on echocardiography, are important goals of monitoring. See Table 5.10 , Chapter 5 for further details on frequency of follow-up.

Mitral Stenosis

Natural History and Pathophysiology of Mitral Stenosis

Mitral stenosis is almost always rheumatic in origin; rare exceptions to this are seen in the elderly, where extensive calcification of the mitral valve apparatus can result in a similar syndrome. Commissural fusion is the pathognomonic lesion that underpins rheumatic MS. Females are more frequently affected, with 80% of those with MS in the REMEDY study being female.

The normal mitral valve area is 4–6 cm 2 but obstructive symptoms only typically occur at ≤2 cm 2 . The natural history of MS therefore begins with a typically prolonged asymptomatic period with little effect on mortality. This asymptomatic phase varies significantly between different populations. In some low- and middle-income countries, it may progress rapidly and lead to symptoms in teenagers or even children. For example, 20% of 275 patients with pure MS undergoing cardiac surgery in the 1980s in a South African series were under 20 years old. On the other hand, the latency period can be as long as 5–40 years from ARF to symptoms in high-income countries.

Patients with MS and NYHA class I or II have an excellent prognosis, with 10-year survival >80% at diagnosis. However, MS with NYHA classes III and IV symptoms are associated with a sharp decline in survival: without intervention this was estimated at 0%–15% over the ensuing 10 years in an earlier era.

The hemodynamic hallmark of MS is an elevated transmitral pressure gradient resulting in elevated mean LA pressures and reduced LV filling. Pressure gradients are typically ≤5 mmHg at rest in mild MS and up to 25 mmHg in those with severe disease. The reduced mitral inflow usually “protects” the left ventricle from volume over load and its size will usually remain normal unless other conditions that cause overload coexist. These conditions may include hypertension, mixed mitral valve disease with MR, or multivalve disease with AR.

Because the transvalvular pressure gradient is a function of the square of the transvalvular flow rate (i.e. doubling the flow rate quadruples the pressure gradient), conditions which increase the heart rate (such as exercise, atrial fibrillation, sepsis) and/or cardiac output (such as pregnancy or anemia) can precipitously increase the transmitral pressure gradient, leading to acute worsening of obstruction at the mitral valve in those with moderate or severe MS. These increased LA pressures are then reflected back into the pulmonary venous system, resulting in pulmonary congestion (or even frank pulmonary oedema) and, in some, hypotension (see also Chapter 16 for acute HF). Chronic elevation of LA pressures also leads to increased risk of thrombosis in situ, pulmonary hypertension, and eventually right HF. More than 60% of patients who die from MS do so from progressive right HF and/or pulmonary edema, with the remaining deaths mostly secondary to systemic thromboembolism. Important strategies in the medical management of rheumatic MS therefore may include rate and/or rhythm control, OAC in the setting of an enlarged LA or AF (see later), and treatment of pulmonary edema, pulmonary hypertension, and right HF.

Medical Management of Mitral Stenosis

The purpose of medical management of MS is broadly twofold: firstly, prevention and treatment of symptoms and complications and secondly, monitoring for timing of intervention.

Heart rate control can be an effective strategy in symptomatic MS, regardless of whether the patient is in sinus rhythm or AF. Both selective and nonselective β-blockers achieve this well. β-Blockers are often used as first-line therapy, but nondihydropyridine CCBs with negative inotropic and chronotropic effects, such as diltiazem or verapamil, can also be used. The effect of these drugs on exercise tolerance however is uncertain.

Digoxin exerts a weakly positive inotropic and negative chronotropic effect on the heart, especially at rest. Because of its lack of effect on heart rate control during exercise and because many patients with MS have normal LV systolic function, the role of digoxin in MS is limited. It may be more beneficial as a second line agent for rate control in patients with AF or in select patients with symptomatic left or right ventricular systolic dysfunction (see HFrEF, above).

More recently, ivabradine has been shown to have similar efficacy in hemodynamic improvement, exercise performance, and dyspnea when compared to metoprolol in patients with MS who are in sinus rhythm. Therefore, ivabradine may be a useful adjunct to β-blockers for symptom management in MS or used as an alternative if β-blockers are contraindicated or not tolerated. The use of rate-limiting agents in truly asymptomatic patients with MS is more controversial. Although clinical practice varies, many patients, even with severe MS, do not require any specific treatment. Rate control in patients with MS who develop an acute tachyarrhythmia is discussed in Chapter 16 .

Diuretics are useful when there is evidence of pulmonary congestion or right heat failure as they reduce preload. Loop diuretics are often used first-line but MRAs (spironolactone and eplerenone) and thiazide or thiazide-like diuretics (e.g., metolazone and chlorthalidone) can also be added.

Summary of the medical management of mitral stenosis:

  • 1.

    Asymptomatic MS (any degree of severity)

    • Usually does not require any specific therapy

  • 2.

    Symptomatic MS (usually moderate or severe)—see also Chapter 16

    • Heart rate control (β-blockers or nondihydropyridine CCBs)

    • Consider digoxin second-line for heart rate control

    • Ivabradine is an alternative to β-blockers if the patient is in sinus rhythm

    • Diuretics for pulmonary vascular congestion or right heart failure

  • 3.

    Diuretics, β-blockers, digoxin and CCBs may only transiently improve symptoms.

  • 4.

    Symptoms are an indication to refer to a cardiosurgical unit.

  • 5.

    Anticoagulation with a target international normalized ratio (INR) between 2-3 is indicated in patients with evidence of AF, significant LA dilatation, or spontaneous LA contrast (see later)

Indications for Percutaneous Mitral Balloon Commissurotomy and Cardiac Surgery

In brief, any patient, child or adult, with severe symptomatic MS, a mitral valve area (MVA) of <1.5 cm 2 , or pulmonary hypertension (RVSP 50 mmHg), meets the requirement for intervention (i.e., percutaneous mitral balloon commissurotomy (PMBC) or surgery) (Table 6.4).

Feb 2, 2021 | Posted by in RHEUMATOLOGY | Comments Off on Medical Management of Rheumatic Heart Disease
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