Clinical evidence IONA (Impact of Nicorandil in Angina, 2002): this was designed to deter- mine if nicorandil could reduce the frequency of coronary events in patients with chronic s table angina and standard anti-anginal treatment at high risk of cardiovascular events. The study reported a modest reduction in the composite primary end-point of coronary heart dis ease death, non- fatal MI, or unplanned hospital admission for cardiac chest pain (15.5 % p lacebo vs. 13.1 % nicorandil ( P = 0.014)). Place in therapy Nicorandil is licensed for the prevention and long-term treatment of chron ic stable angina and also for reducing the risk of acute coronary syndromes in patients wit h chronic stable angina and at least one of the following risk factors: previous MI or CABG , or CHD on angiography or a positive exercise test together with LVH on ECG, left ventricu lar dys- function, age (cid:116) 65 years, diabetes mellitus, hypertension, or documented v ascular disease. It is most frequently used as an adjunct to \201 rst-line anti-anginal t herapies to provide additional symptomatic relief. Dosing A dose of 10 mg twice daily is recommended initially, reduced to 5 mg twice daily in patients who are predisposed to headaches. The dose should be increased gradually accordin g to clinical response, to a maximum of 30 mg twice daily. Monitoring nicorandil \200 Blood pressure should be monitored at intervals during therapy . \200 The drug dose should be adjusted to optimize symptomatic relief of angina episodes. Compelling indications for nicorandil \200 Angina : as an adjunct or alternative to \201 rst-line anti-anginal therapies to prevent angina episodes. POTASSIUM-CHANNEL ACTIVATORS 137 Contraindications and cautions \200 Contraindications : cardiogenic shock, left ventricul ar failure with low \201 lling pressures and hypotension, hypersensitivity to nicorandil, pregnancy and breast-feeding Cautions : depleted blood volume, low systolic blood pressure, acute pulmonary oedema, or acute MI with acute left ventricular failure and low \201 lling pres sures patients should be advised not to drive or operate machinery until it is established that their performance is not impaired. Adverse effects of nicorandil \200 Headache : occurs commonly, especially in the early ph ase of treatment; consider a lower starting dose Dizziness and hypotension : especially at higher doses \200 Peripheral vasodilation leadi ng to \202 ushing : occurs commonly \200 Ulceration : GI ulceration, skin ulceration, a nd ulcers of the mucosal membranes have been reported These tend to be refractory to treatm ent and most only respond to withdrawal of nicorandil treatment Angioedema : occurs uncommonly. Key drug interactions with nicorandil \200 Antihypertensives : enhanced hypotensive effec t with the addition of nicorandil Oral corticosteroids : increase of gastric erosions when used in combination with nicorandil; avoid concomitant use Sildena \201 l, tadala \201 l, vardena \201 l : due to the risk of severe hypotension, the concomitant use of nicorandil and phosphodiesterase 5 inhibitors (e.g. sildena \201 l, tadala \201 l, vardena \201 l) is contraindicated. 138 CHAPTER 2 Drugs for the heart Ivabradine Mode of action Treatment with ivabradine causes as dose-dependent reduction in h eart rate by selective and speci \201 c inhibition of the cardiac pacemaker I f current (k nown as the funny channel) that controls spontaneous depolarization in the sinus node and h ence regulates heart rate. The usual effect is a 10 bpm reduction in heart rate whether at rest or during exercise. The fall in heart rate leads to a reduction in cardiac workload an d myocardial oxygen consumption. Clinical evidence Clinical studies have shown ivabradine to be as effective as B -blockers in the prevention and treatment of angina. The BEAUTIFUL (Morbidity \200\223 Mortality Eval uation of Ivabradine in Patients with CAD and Left Ventricular Systolic Dysfunction) study investigated the role of heart-rate control with ivabradine on top of background therapy, i ncluding B -blockers in the majority in patients with CHD and left ventricular failure. Iva bradine failed to demonstrate an impact on the primary end-point, a composite of cardiovasc ular death, hospitalization for acute MI, or hospitaliza- tion for new-onset or worsening h eart failure. However, the study did con \201 rm the safety of the combination of ivabradi ne and B -blockers. The SHIFT (Systolic Heart Failure Treatment with I f Inhibitor Ivabradi ne Trial) showed reduction of hospitalization and cardiovascular mortality in heart failure patients. Place in therapy Ivabradine was initially licensed for the symptomatic treatment of chronic stable angina in patients unable to tolerate, or with a contraindication to, the use of B -blockers; following the publication of the BEAUTIFUL study, the license has been extended to include use in combination with B -blockers in patients who are inadequately controlled with an optimal B -blocker dose and whose heart rate is > 60 bpm. In clinical practice, iva bradine is often used in patients that cannot tolerate either B -blockers or rate-controlli ng calcium-channel blockers on the basis of cost. Dosing \200 Initiation : ivabradine is usually initiated at a dose of 5 mg twice daily. \200 After 3 \200\2234 weeks it may be increased to 7.5 mg twice daily if required for gre ater symptom control. If the patient is elderly or 5 mg twice daily is not tolerated, the d ose can be reduced to 2.5 mg twice daily. Monitoring ivabradine \200 Obtain baseline BP and pulse before initiation and after each change in dose. In the absence of adverse effects, review within 4 weeks and consider increasing the dose if required for better symptom control. IVABRADINE 139 Compelling indications for ivabradine \200 Angina : as an adjunct or alternative to \201 rst-line anti-anginal therapies to prevent angina episodes. Contraindications and cautions \200 Contraindications : sick sinus syndrome, bradycardia (resting heart rate <60 bpm), cardiogenic shock and acute MI, within 4 weeks of CVA, sino-a trial block and third-degree AV block, congenital QT syndrome, pacemaker-dependent patients , unstable angina, pregnancy, and breast-feeding Cautions : pre-existing cardiac arrhythmias, concurrent heart-rate- lowering agents, mild h eart failure (NYHA class I \200\223II), moderate to severe heart failure (NYHA class III \200\223IV \200\224 SHIFT study), post-CVA, retinitis pigmentosa, hypotension (avoid if BP <90/50 mmHg), hepatic insuf \201 ciency (avoid if severe), severe renal insuf \201 ciency (CrCl (creatinine clearance) <15 mL/min). Adverse effects of ivabradine \200 Visual symptoms : most commonly reported adverse effec t. Luminous phenomena occurred in 15 % of patients, and therefore new patients should be wa rned about this potential transient side-effect. The possible occurrence of such luminous p henomena should be taken into account when driving or using machines in situations where su dden variations in light intensity may occur, especially when driving at night. Blurred vis ion has also been reported Cardiac conduction effects : bradycardia, AV 1st-degree block, ventricular extrasystoles can occur during therapy Headache : generally during the early treatment phase \200 Dizziness : possibly related t o bradycardia \200 GI disturbances : nausea, vomiting, diarrhea. Key drug interactions with ivabradine \200 Antihypertensives : enhanced hypotensive effec t with the addition of nicorandil Oral coricosteroids : increase of gastric erosions when used in combination with nicorandil; avoid concomitant use Sildena \201 l, tadala \201 l, vardena \201 l : due to the risk of severe hypotension, t he concomitant use of nicorandil and phosphodiesterase 5 inhibitors (e.g. sildena \201 l, tadala \201 l, vardena \201 l) is contraindicated. 140 CHAPTER 2 Drugs for the heart Ranolazine Mode of action The mode of action of ranolazine is not well understood, despite the agent being in use in other countries for a number of years. Speculation on its mode of action focuses on inhibition of the late inward sodium current in cardiac cells. Reduced a ccumulation of sodium leads to a lower intracellular calcium load, facilitating myocardial relaxation and reducing diastolic stiffness. Ranolazine reduces the abnormalities of ventri cular repolarization and contractility seen during episodes of ischaemia, with a resultant improvement in myocardial function and perfusion. The anti- anginal effects of ranolazine a re independent of changes in blood pressure and heart rate. Clinical evidence Three placebo-controlled studies have con \201 rmed the ef \201 cacy of ranola- zine alone or as an adjunct to standard anti-anginal therapies (atenolol, amlodipi ne, or diltiazem) to improve symptomatic control in chronic stable angina (MARISA (Monother apy Assessment of Ranolazine in Stable Angina), 2004; CARISA (Combination Assessment of Ran olazine in Stable Angina), 2004; ERICA (Ef \201 cacy of Ranolazine in Chronic Angina) 2006 ). MERLIN-TIMI-36 (Metabolic Ef \201 ciency with Ranolazine for Less Ischemia in Non-ST-El evation Acute Coronary Syndromes \200\223Thrombolysis in Myocardial Infarction), the only outcome study to date, investigated the use of ranolazine compared to placebo in the treatm ent of non-ST eleva- tion in acute coronary syndrome, but failed to show an impact on the p rimary end-point of occurrence of CV death, MI, or recurrent ischaemia. Place in therapy Ranolazine is licensed and indicated as an adjunct to \201 rst-line anti -anginal therapies (such as B -blockers and/or CCBs) to improve symptomatic relief in patie nts with chronic stable angina. Due to cost, ranolazine is cur- rently positioned as an adj unctive therapy where \201 rst- and second-line options are not tolerated or have failed to give adequate symptomatic relief. Ranolazine may also be particularly useful in patients with hypo- tension or bradycardia, as it has minimal effects on these haemodynamic paramet ers. Dosing \200 375 mg slow release (SR) tablets twice daily initially, increasing after 2 \200\2234 weeks to 500 mg SR twice daily, and if necessary, to a maximum of 750 mg SR twi ce daily. Monitoring Blood pressure and pulse should be checked at baseline and within 4 weeks of ini tiation or dose change. Ranolazine usually has minimal effects on blood pressure and heart rate. ECG monitoring may be consid- ered after initiation to ensure no signi \201 cant QTc prolongation. Small increases in serum creatinine have been noted during treatment, but this is not linked to renal toxicity. RANOLAZINE 141 Compelling indications for ranolazine \200 Angina : as an adjunct or alternative to \201 rst- and second-line anti-anginal therapies to prevent angina episodes. Contraindications and cautions \200 Contraindications : severe renal impairment (CrCl<30 mL/min), moderate to severe hepatic impairment, pregnancy, and breast-feeding \200 Cautions : init iate and undertake dose titration carefully in patients with mild to moderate renal impairm ent (CrCl 30 \200\22380 mL/min), mild hepatic dysfunction, or moderate to severe heart fail ure (NYHA III \200\223IV), elderly patients, and patients with low body weight ( > 60 kg). Adverse effects \200 Gastrointestinal : diahorrea, constipation, nausea, and vomiting occ ur commonly. Anorexia, reduced appetite, and dehydration occur uncommonly Syncope, postural dizziness, headache : may require dose reduction \200 Skin : allergic d ermatitis, urticaria, rash, pruritis, hyperhydrosis \200 Central nervous system (CNS): so mnolence, tremor, fatigue. Rarely, disorientation, amnesia, depressed level or loss of cons ciousness Eye and ear : blurred vision, visual disturbance, vertigo, tinnitus. Key drug interactions with ranolazine \200 Anti-arrhythmics : avoid concomitant use with disopyramide \200 Antibaterials : clarithromycin and telithromycin possibly increase ranolazine levels; avoid concomitant use. Rifamipicin reduces ranolazine levels; avoid conc omitant use Antifungals : ketoconazole, itraconazole, posaconazole, voriconazole increase plasma levels of ranolazine; avoid concomitant use Antivirals : possible increase in ranolazine levels; check individual agents for details Beta-blockers : avoid concomitant use with sotalol \200 Grapefruit juice : may increase r anolazine levels; avoid concomitant consumption. This page intentionally left blank 143 Chapter 3 Valvular heart disease General considerations 144 Acute rheumatic fever 146 Mitral stenosis: clinical features 150 Mitral stenosis: investigations 152 Mitral stenosis guidelines 156 Mitral regurgitation 15 8 Mitral regurgitation guidelines 161 Mitral valve prolapse 162 Aortic stenosis 164 Managem ent of aortic stenosis 168 Aortic regurgitation 170 Aortic regurgitation guidelines 174 Tri cuspid and pulmonary disease 176 Prosthetic heart valves 180 Prosthetic valve complications 184 144 CHAPTER 3 Valvular heart disease General considerations Development Cardiac valves develop from the mesodermal germ layer be tween the 4th and 7th week of gestation. Any factors affecting embryogenesis during this ti me can affect development of valves and include infection (German measles/rubella), drugs, etc. Key points Mitral valve \200 Two lea \202 ets: anterior lea \202 et (is in \201 brous continuity with aortic valve annulus) and posterior lea \202 et \200\224 competency depe nds on large-zone coaptation \200\224 supported by annulus, posteromedial and anterolatera l papillary muscles coming off left ventricle (LV) free wall and septum, and tendinae chord ae: changes in any of above can result in mitral regurgitation (MR). The posterior lea \202 et is divided into three segments by scallops; the anterior lea \202 et not scalloped \200\224 segments are based on which parts are opposit e the posterior scallops, and each commissure is a segment, so P2 refers to the middle scal lop of the posterior lea \202 et. The posteromedial papillary muscle is supplied by the circum \202 ex or posterior descendi ng coronary artery and is most prone to ischaemic rupture, causing \202 ail posterior lea \202 et (compared to the anterolateral papillary muscle which has a dual supply). Posterior regurgitant jet is caused by posterior lea \202 et restriction (common) or anterior lea \202 et prolapse (unusual), and an anteriorly directed jet is due to posterior lea \202 et prolapse (most common) or anterior lea \202 et restriction (unu sual). Central leaks come from annular dilatatation. Eccentric jets often lead to commissur al prolapse. Aortic valve \200 Trilea \202 et valve (right and left coronary cusps based on the locat ion of the coronary ostia, and non-coronary cusp), with small-zone coaptation. Increase in size of annulus, sinuses, sinotubular junction, or lea \202 et destruction can result in aortic insuf \201 ciency (AI). Conduction tissue runs between the right and non-coronary cusp. Tricuspid valve \200 Thre e lea \202 ets (septal, anterior and posterior) with a moderate zone of coaptation. The po sterior and anterior annulus are most prone to dilatation. Atrioventricular (AV) node tissue is located just below the anteroseptal commissure. This page intentionally left blank 146 CHAPTER 3 Valvular heart disease Acute rheumatic fever Epidemiology \200 <1:1000 in developed countries; 10:1000 schoolchi ldren in developing countries. It is rarer, but still accounts for half of cardiac disease in the developing world. Declining incidence is due to improved economic standards and housing, decreased crowding, and access to medical care and antimicrobials. Typically affects children aged 5 \200\22315 years from lower socio-economic class living i n crowded conditions; 20 % of cases are in adults. Incidence is higher in native Hawaiians and Maoris despite antibiotic prophylaxis. No sex difference but chorea and mitral stenosis (MS) are more common in females. Pathology \200 Typically occurs several weeks after a streptococcal pharyngitis. Usually group A beta haemolytic streptococci: Streptococcus pyogenes serotype M. Antigenic mimicry is implicated \200\224 antibodies to carbohydrate in cell wall (anti-M antibodies) of grou p A Streptococcus cross-react with protein in cardiac valves. Delay from acute infection to onset of rheumatic fever (RF) is usually 3 \200\2234 weeks. RF is thought to complicate up to 3 % of untreated streptococcal sore th roats. Previous episodes of RF predispose to further events (up to 50 % of streptococcal so re throat is complicated by RF if there has been a previous episode). Other areas of cross- reactivity may explain other signs (e.g. involvement of connective tissue in joints \200 \224 arthritis, caudate nucleus in brain \200\224 Sydenham \200\231s chorea). \200 Commo nly causes a pancarditis. Pericarditis can cause haemodynamic instability or constriction. Myocarditis may cause acute heart failure and arrhythmias. Endocarditis affects the mitral valve (65 \200\22370 % ), aortic valve (25 % ), and tricuspid valve (10 % , never in isolat ion) causing acute regurgitation and heart failure, and eventually chronic stenosis. \200 Pericardium, perivascular regions of myocardium, and endocardium develop perivascular foci of eosinophilic collagen surrounded by lymphocytes, plasma cells, and macrophages called A schoff bodies. Clinical features \200 Sore throat 1 \200\2235 weeks earlier is reported in two-thirds of cases. \200 Fever, abdominal pain, and epistaxis. \200 Migratory large-joint polyarthr itis starting in the lower limbs in 75 % of cases. Duration less than 4 weeks at each site. Severe pain and tenderness in contr ast to degree of joint swelling. Pancarditis in 50 % of cases with features of acute heart failure, mitral and aortic regurg itation, an apical, mid-diastolic \202 ow murmur (Carey Coombs murmur), and pericarditis. Chorea in 10 \200\22330 % , usually 1 \200\2236 months after the index pharyngitis. Dif \201 culty writing and speaking, generalized weakness, choreiform movements, and emotional lability. Joints hyperextended with hypotonia, diminished tendon re \202 exes, tongue fasc iculation, and a ACUTE RHEUMATIC FEVER 147 relapsing grip (alternate increases/decreases in tension). Recovery 2 \200\2233 months. Erythema marginatum is an evanescent rash with serpiginous outlines and central clearings o n the trunk and proximal limbs. Seen in 5 \200\22313 % of cases. Begins as erythematous, no n-pruritic papules or macules that spread outwards. Fades and reappears in hours and persis ts. Subcutaneous nodules in 0 \200\2238 % of cases several weeks after the onset of severe panc arditis. Mainly over bony surfaces or prominences and tendons. Commonly involves the elbows , knees, wrists, ankles, Achilles tendons, occiput, and vertebral spinous processes. Durati on 1 \200\2232 weeks. There is a danger of overdiagnosing RF in children admitted with fever, soft murmurs, and a rthralgia, all of which are common in childhood. Treatment See Table 3.1 . Table 3.1 Treatment of rheumatic fever Drug/treatment Dose Antibiotics Oral phenoxymethylpenicillin for 10 days (250 mg qds (four times a day) in children and 500 mg tds in adults) Or intramuscular benzylpenicillin (single dose of 1.2 million units) to treat the acute inf ection Oral erythromycin, if penicillin allergic, for 10 days (20 \200\22340 mg/kg/day qds in chil dren and 250 mg qds in adults) Alternatives include clarithromycin, azithromycin, or cefalexin Oral aspirin 4 \200\2238 g daily until erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are normal Prednisolone 2 mg/kg/day for 2 \200\2234 weeks if moderate \200\223 severe carditis. Oral haloperidol for chorea 0.5 \200\2232 mg tds in adults and 0.05 \200\2230.15 mg/kg/day in 3 \200\22312-year-old chi ldren Use diuretics, angiotensin- converting enzyme inhibitors (ACE-Is), and digoxin for heart fa ilure Surgery for chronic, severe rheumatic valve disease (results are less durable in acute phas e) 148 CHAPTER 3 Valvular heart disease Prognosis \200 Determined by level of cardiac involvement and antibiotic prophylaxis (5 years or until 21 years old if no carditis, 10 years or well into adulthood if carditis but no valve disease, 10 years or until 40 years old if valves affected and for all dental and surgical procedures). Acute phase duration about 3 months in 80 % of cases. Mortality 1 \200\22310 % in developing countries. Recurrence rates are high. Chronic valve disease occurs in one-third without and two-thirds with recurrent infections. Murmurs resolve in 50 % of cases up to 5 years after index infection. Diagnostic criteria for rheumatic fever (Jones criteria) Evidence of group A streptococcal pharyngitis Either a positive throat culture or rapid str eptococcal antigen test, or an elevated or rising streptococcal antibody titre (samples tak en two weeks apart) Plus two major or one major and two minor Jones criteria: Major criteri a \200 Polyarthritis \200 Carditis \200 Chorea \200 Erythema marginatum \200 Subc utaneous nodules Minor criteria \200 Fever \200 Arthralgia \200 Prolonged PR interval \200 Elevated ESR and CRP This page intentionally left blank 150 CHAPTER 3 Valvular heart disease Mitral stenosis: clinical features Causes Mitral stenosis (MS) is most commonly due to rheu matic fever. Other causes are rare. They include congenital (isolated lesion or in associat ion with an atrial septal defect (ASD) \200\224 Lutembacher \200\231s syndrome), mitral an nular calci \201 cation, carcinoid heart disease, valvulitis (systemic lupus ery- thematos is), mucopolysaccharidoses (e.g. Hurler \200\231s syndrome), and endo- cardial \201 broel astosis. Stenosis occurs at three levels: the chordae (fuse, thicken, then shorten), cusps (initially rolled under edges, then thicken and eventually calcify), and commissures (progr essive fusion). Pathophysiology Elevated left atrial (LA) pressure is required to propel the blood through the narrowed mitral valve ori \201 ce. This leads to pulmonary venous pres- sure and exert ional dyspnoea due to pulmonary oedema and pulmonary compliance. Reactive pulmonary hyperte nsion occurs leading to right ventricular (RV) hypertrophy and failure. LV function is init ially unaffected. However, since \201 lling is impaired, adequate cardiac output (CO) can not always be maintained. The rise in CO during exertion is blunted. Onset of atrial \201 brillation (AF) is associated with abrupt clinical deterioration, due to both the loss of atrial systole and the fast heart rate (decreased duration of diastole). Clinical features (see also Fig. 3.1) History \200 Dyspnoea on exertion, orthopnoea, paro xysmal nocturnal dyspnoea. \200 Acute pulmonary oedema may be precipitated by uncontrolle d AF, exercise, chest infection, anesthesia, and pregnancy. AF increases the risk of thromboembolism. Systemic embolism occurs in 20 \200\22330 % and u sually originates in the dilated LA and LA appendage. Fatigue is due to reduced cardiac output reserve and is common in mild \200\223moderate stenosis. Haemoptysis can occur for a variety of reasons: alveolar capillary rupture (pink frothy pulmonary oedema); bronchial vein rupture (larger hemorrhage); blood-s tained sputum of chronic bronchitis; pulmonary infarction (low CO, immobile patients). Chest pain similar to angina may occur in patients with pulmonary hypertension and RV hyper trophy, even with normal coronaries. Rarely, the enlarging LA may compress surrounding structures producing a hoarse voice (left recurrent laryngeal nerve compression \200\224 Ortner \200 \231s syndrome), dysphagia (oesophageal compression), left lung collapse (left main bronchu s compression). Physical examination Mitral facies or malar \202 ush seen in <50 % . Prominent \200\230a \200\231 waves in jugular venous pulse (JVP). Low-amplitude arterial pulse. Irregularly ir regular pulse in AF. \200\230Tapping \200\231 apex beat \200\224 palpable S 1 . Diastolic thrill at apex. Left parasternal heave (due to right ventricular hypertrophy (RVH)). Palpa ble pulmonary closure. MITRAL STENOSIS: CLINICAL FEATURES 151 Auscultation: S 1 loud if in sinus rhythm and valve is pliable. P 2 accentuated. Opening sn ap (OS) of the MV is heard best at or medial to the apex in expiration. A 2 \200\223OS int erval varies inversely with severity of stenosis. Low- pitched, rumbling, mid-diastolic mur mur with pre-systolic accentuation (if in sinus rhythm) is heard best at the apex with the patient in a left lateral position. Early diastolic murmur due to pulmonary regurgitation f rom pul- monary hypertension (Graham Steell murmur) may be heard rarely. Mitral facies and central cyanosis with developing pulmonary hypertension Face \200\230V \200\231 wave in JVP 2 TR: pronounced systolic wave Low volume irregular pulse? All pulses present (emboli) Pulmonary regurgitation (Graham Steell) Inspiration Loud P2 (may be palpable) Pulmonary hypertension TR. Pan SM + RV \200\230heave \200\231 Apex beat. \200\230Tapping \200\231 if valve mobile due to palpable mitral valve closure ( S1). Not displaced Pulsatile liver Rigid valve Mobile leaflets SR AF No opening snap OS A2 A2 Loud S1 Soft S1 Loud S1 Opening snap Pansystolic additional MR Mitral diastolic murmur Rumbling axilla No S3 unless dominant regurgitation Pre-systolic accentuation (Atrial systole) Fig. 3.1 Physical signs in mitral stenosis. Reproduced with permission from Swanton H (2003 ). Pocket Consultant: cardiology . 5th ed. Oxford: Blackwell Publishing. SM = systolic murm ur; SR = sinus rhythm; TR = tricuspid regurgitation. 152 CHAPTER 3 Valvular heart disease Mitral stenosis: investigations Investigations \200 Electrocardiography (ECG): P mitrale \200\224 bi \201 d P wave (if in sinus rhythm) due to LA enlargement most prominent in le ad II. Tall and peaked P waves in pulmonary hypertension. AF is frequent. Right-axis deviat ion and RV hypertrophy. Chest X-ray (CXR): Straightening of the left heart border, prominent upper lobe veins, pulm onary artery enlargement, Kerley B lines \200\224 interstitial oedema. Large LA visible as a double shadow. Radiographic features of mitral stenosis PA \201 lm Lateral \201 lm Straight or convex L heart border \200 Double shadow of LA behind RA \200 Splaying of c arina ( > 90 o ) \200\224 rare \200 Dilated upper lobe veins \200 Prominent pulmonary conus \200 Pulmonary haemosiderosis LA or RV enlargement \200 Valvular calci \201 cation frequent \200 LA calci \201 cati on seen rarely (McCallum \200\231s patch) Oesophageal indentation on barium swallow Transthoracic ECHO (TTE): Parasternal long-axis view (LAX) shows enlarged LA and doming of the valve lea \202 ets due to commissural fusion. In short-axis view (SAX), the mitral val ve ori \201 ce can be calculated by planimetry. Calci \201 cation can be visualized. M-mo de imaging \200\224 restricted valve lea \202 et separation due to commissural fusion. Co ntinuous wave (CW) Doppler can be used to estimate the valve area and transvalvular gradien t (see b p. 15). Valve ECHO score can be calculated (based on lea \202 et mobility, lea \202 et thickening, subvalvular thickening, and calci \201 cation). Transoesophageal echocardiography (TOE): Provides better anatomic detail, can visualize small vegetations and thrombi in the LA. Cardiac catheterization: Increased pulmonary capillary wedge pressure (PCWP). Increased PCW P to LV end-diastolic pressure gradient. If the mean mitral gradient is low at rest, get th e patient to perform exercise on the cath-lab table (e.g. straight-leg raising) to calculat e gradient again. Assessment of co-existing coronary and valvular lesions. Classi \201 cation See Table 3.2 . MITRAL STENOSIS: INVESTIGATIONS 153 Table 3.2 Classi \201 cation of mitral stenosis Severity Mean gradient (mmHg) PA systolic (mmHg) Valve area (cm 2 ) Mild MS <5 <30 > 1.5 Moderate MS 5 \200\22310 30 \200\22350 1 \200\2231.5 Severe MS > 10 > 50 <1 PA = pulmonary artery. Management Medical management \200 Mild symptoms: salt intake restriction and oral diuret ics (cautious). \200 In AF: digoxin, B-blocker, or calcium-channel blocker for rate contr ol. Restoration of sinus rhythm may be attempted if appropriate. Anticoagulation: recommended for those with AF, prior thromboembolism, or LA thrombus. Patients with low-output states, right heart failure, or L A dimension (cid:2) 55 mm by echocardiography should also be anticoagulated. There is no pr oven bene \201 t if the patient is in sinus rhythm. Endocarditis prophylaxis is no longer recommended. 1 Balloon valvotomy \200 Suitable for patients with pliable valves with minimal MR, no subvalvular distortion, and without heavy calci \201 cation (ideal if valve score (cid:3) 8). Contraindicated in moderate or severe MR or atrial thrombus. \200 A guide wire is placed in the LA after trans-septal puncture, and a balloon (Inoue balloon) is directed across the valve and in \202 ated at the ori \201 ce. Indications for surgery \200 Not indicated in asymptomatic patients \200 In New York He art Association (NYHA) III \200\223IV patients: mitral valve area (MVA) (cid:3) 1.5 cm 2 if valve not suitable for percutanaous mitral balloon valvuloplasty (PMBV) \200 MVA > 1.5 but with pulmonary artery systolic pressure (PASP) > 60 mmHg, PCWP (cid:2) 25 mmHg, or MV gradient > 15 mmHg during exercise In NYHA I \200\223II patients for MVA (cid:3) 1.5 cm 2 AND pulmonary artery systolic pressure (PASP) > 60 \200\22380 mmHg if percutaneous mitral balloon valvotomy (PMB V) contraindicated. Surgical treatment \200 Indicated when morphology is not conducive to percutaneous balloo n valvotomy (see algorithms in Figs 3.2 and 3.3 ). Closed valvotomy : fused cusps separated by a dilator introduced through LV apex. No longer recommended. 1 Wilson W, Taubert KA, Gewitz M, et al (2007). Prevention of infective endocarditis: guide lines from the American Heart Association: a guideline from the American Heart Association Rheuma tic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 116 (15): 1736 \200\22354. 154 CHAPTER 3 Valvular heart disease Open valvotomy with cardiopulmonary bypass is preferred to closed valvotomy. Cusps are sepa rated under direct vision. Any fusion of subvalvular apparatus is loosened. Mitral repair is occasionally possible in advanced rheumatic stenosis using pericardium to augment lea \202 ets, but durability is 5 \200\22310 years. Mitral valve replacement if repair is not possible: 2 \200\2234 % annual risk of major thromboembolic or haemorrhagic event, including stroke w ith mechanical valve (so very high lifetime risk in young patients), and small risk of reop eration for non-structural valve dysfunction third-generation bioprosthetic valves \200\231 durability is dependent on age of patient \200\224 around 80 % freedom from structural valve degeneration at 10 years in 40 \200\2235 0 year olds, versus over 90 % freedom at 10 years in > 65 year olds surgical ablation for AF has 60 \200\22370 % freedom from AF at one year: preoperative AF is not an indication for a mechanical valve. Risk of surgery : 1 \200\2232 % mortality and stroke in 65-year-old patient with no other major morbidity and good LV function. This page intentionally left blank 156 CHAPTER 3 Valvular heart disease Mitral stenosis guidelines Mitral stenosis History, Physical exam CXR, ECG, 2D echo/Doppler Symptoms? Symptomatic Asymptomatic Moderate or severe stenosis* MVA \211 1.5 cm2 Mild stenosis MVA >1.5 cm2 Yearly follow-up History, Physical exam, CXR, ECG Valve morphology favorable for PMBV? No \200 Yes PASP > 50 mm Hg? Yes \200 No Class I Exercise Consider PMBV Poor exercise tolerance or PASP >60 mm Hg or PAWP \211 25 mm Hg Class I Exclude LA clot, 3+ to 4+ MR Yes No No Class IIb Yes New-onset AF? Fig. 3.2 Management strategy for patients with mitral stenosis. *The writing committee reco gnizes that there may be variability in the measurement of mitral valve area (MVA) and that the mean transmitral gradients, pulmonary artery wedge pressure (PAWP), and pulmonary arte ry systolic pressure (PASP) should also be taken into consideration. \200 There is controv ersy as to whether patients with severe mitral stenosis (MVA less than 1.0 cm 2 ) and sever e pulmonary hypertension (pulmonary artery pressure greater than 60 mm Hg) should undergo p ercutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement to prevent right ve ntricular failure. \200 Assuming no other cause for pulmonary hypertension is present. AF indicates atrial \201 brillation; CXR, chest X-ray; ECG, electrocardiogram; echo, echoca rdiography; LA, left atrial; MR, mitral regurgitation; and 2D, 2-dimensional. Reproduced wi th permission from Journal of the American College of Cardiology , Vol 48 , No.3, 2006. Aug ust 1, 2006:e1 \200\223148. Bonow et al, AHA/ACC Best Practice Guidelines. MITRAL STENOSIS GUIDELINES 157 Symptomatic mitral stenosis NYHA functional class II History, Physical exam CXR, ECG, 2D echo/Doppler Mild stenosis MVA >1.5 cm2* Moderate or severe stenosis MVA \211 1.5 cm2* Exercise PASP >60 mm Hg PAWP \211 25 mm Hg MVG >15 mm Hg Valve morphology favorable for PMBV? Yes No Valve morphology favorable for PMBV? Yes No Yearly follow-up Severe PH PAP >60 \200\22380 mm Hg No Yes Class IIb Class I No Yes Consider PMBV Class IIa 6-month follow-up 6-month follow-up \200 Consider commissurotomy or MVR Exclude LA clot, 3+ to 4+ MR Fig. 3.3 Management strategy for patients with mitral stenosis and mild symptoms. *The comm ittee recognizes that there may be variability in the measurement of mitral valve area (MVA ) and that the mean transmitral gradient, pulmonary artery wedge pressure (PAWP), and pulmo nary artery systolic pressure (PASP) should also be taken into consideration. \200 There is controversy as to whether patients with severe mitral stenosis (MVA less than 1.0 cm 2 ) and severe pulmonary hyperten- sion (PH; PASP greater than 60 to 80 mm Hg) should undergo percutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement (MVR) to prevent r ight ventricular failure. CXR indicates chest X-ray; ECG, electrocardiogram; echo, echocard iography; LA, left atrial; MR, mitral regurgitation; MVG, mean mitral valve pressure gradie nt; NYHA, New York Heart Association; PAP, pulmonary artery pressure; and 2D, 2-dimensional . Reproduced with permission from Journal of the American College of Cardiology , Vol 48 , No.3, 2006. August 1, 2006:e1 \200\223148. Bonow et al , AHA/ACC Best Practice Guidelines. 158 CHAPTER 3 Valvular heart disease Mitral regurgitation Causes Acute: Infective endocarditis, acute myocardial infarction (MI) , trauma. Chronic: Most common \200\224 myxomatous degeneration (mitral valve prolapse), chronic rhe umatic heart disease, left ventricular or annular dilatation of any cause (e.g. chronic isc haemia, cardiomyopathy, annular calci \201 cation), degeneration of valve cusps, collagen vascular disease, hypertrophic cardiomyopathy. Nomenclature \200 Essentially there is a spectrum of myxomatous degenerative disease from single-segment prolapse in small valves ( \201 broelastic de \201 ciency) to multise gment prolapse in large valves (Barlow \200\231s disease). Mitral regurgitation (MR) can be classi \201 ed by mechanism according to Carpentier \200\231s classi \201 cation: \200 type I \200\224 normal lea \202 et motio n, e.g. dilated annulus from dilated cardiomyopathy, lea \202 et perforation due to endocarditis \200 type II \200\224 lea \202 et prolapse, e.g. myxomatous degeneration \200 type IIIa \200\224 restricted lea \202 et opening, e.g. rheumatic disease \200 type IIIb \200\224 restricted lea \202 et closing, e.g. ischaemic dilated cardiomyopathy (functional). Pathophysiology \200 Damage to lea \202 ets, chordae, papillary muscles, or LV can cause MR. \200 The LV ejects into the LA during systole, as well as antegrade into the aorta. In acute MR: there is little enlargement of the LA due to normal compliance. This results in raised LA p ressure and can result in pulmonary oedema \200 there is no compensatory LV enlargement, so the forward ejection fraction (EF) is reduced, leading to low CO. In longstanding severe MR, there is enlargement of the LA, which accommodates the volume overload with minimal rise in LA pressure. The LV dilates, and larg e stroke volume compensates for regurgitation, maintaining the forward EF. LV failure resul ts from longstanding volume overload. The low-pressure regurgitant pathway masks LV failure : EF is often normal even when LV is very impaired. Clinical features In acute severe MR \200\224 pulmonary oedema is common, hypotension, car dio- genic shock. This is a medical emergency. See b p. 728. History \200 Chronic MR \200\224 initially asymptomatic. Fatigue (due to d forward CO), exertional dyspnoea, orthopnoea, systemic embolization (less common than MS). Palpitations ( i stroke volume/associated AF). Right heart failure in later stages Symptoms and risk factors of endocarditis, ischaemic heart disease. MITRAL REGURGITATION 159 Physical examination Rapid upstroke in arterial pulse. Irregularly irregular pulse in AF. P rominent \200\230a \200\231 waves in JVP in patients in sinus rhythm. Large \200\230v \200\231 waves if there is asso- ciated tricuspid regurgitation (TR). Forceful apex displac ed laterally (LV dilatation). Systolic thrill at apex. Auscultation: Pansystolic murmur loudest at the apex and radiating into the axilla. Soft \201 rst heart sound. Loud mitral valve closure sound helpful in excluding severe MR. Wide splitting of S 2 due to premature aortic valve closure. Prominent low-pitched S 3 . A mid-d iastolic \202 ow murmur may follow S 3 even in the absence of MS. Investigations \200 ECG: LA enlargement, left ventricular hypertrophy (LVH), RA enlargement in pulmonary hypertension. AF common in chronic MR. \200 CXR: Cardiomegaly, L A and LV enlargement, and pulmonary venous congestion. Calci \201 ed mitral annulus may be seen. TTE: Demonstrates MV anatomy (lesion and type of MR). Color Doppler to detect and quantify the MR (Table 3.3 ). Assessment of LV function from EF, end- systolic dimension and end-diastolic dimension ( Note: In compensated MR, EF is always over estimated because of the low-resistance retrograde pathway). TOE: Shows the anatomy in greater detail and allows accurate assessment of the feasibility of valve repair. Should be performed pre- or intra-operativel y. Cardiac catheterization: Not always required. Ventriculogram can quantify MR severity and EF. Detection of co-existing valve lesions and coronary artery dis ease. Classi \201 cation of organic mitral regurgitation See Table 3.3 . Table 3.3 Classi \201 cation of mitral regurgitation Severity Angiographic grade Jet area ( % of LA area) Jet width (cm) Regurgitant fraction ( % ) ERO (cm 2 ) Mild MR Contrast seen entering LA <20 <0.3 <30 <0.2 20 \200\22340 0.3 \200\2230.69 30 \200\22349 0.2 \200\2230.39 Moderate MR