100 Questions in Cardiology - Part 6 ppsx

49 What is the medical therapy for patients with hypertrophic cardiomyopathy, and what surgical options are of use?Krishna Prasad About 40% of patients with hypertrophic cardiomyopathy H

abnormal blood pressure response during exercise History ofmultiple sudden deaths in the family is an important risk factor

• Ambulatory monitoring of all patients with a diagnosis of HCM is

mandatory and this should be for at least 48 hours

• Exercise electrocardiography is also mandatory Patients with HCM

should undergo a metabolic exercise test with frequent bloodpressure monitoring (every minute during exercise and for 5minutes during recovery) An abnormal BP response is animportant non-invasive marker of risk The peak oxygenconsumption during the exercise also helps identify those withsignificant limitation of exercise capacity

• Non-sustained ventricular tachycardia (ⱖ5 beats rate of 120beats) especially if repetitive, is also associated with increasedrisk of sudden death

Additional investigations in patients with syncope

In these patients, additional investigations should be aimed atdetermining the mechanism

• Repetitive Holter recordings should be made

• Tilt table test and if necessary

• Electrophysiological study to exclude accessory pathway

Other investigations that may be useful but not mandatory This includes electrophysiological studies and rarely a thalliumscan for myocardial ischaemia It is necessary to exclude significantcoronary artery disease with a coronary angiogram in patients

>40 years old, smokers or those with severe chest pain

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Spirito P, Seidman CE, McKenna WJ et al The management of trophic cardiomyopathy N Engl J Med 1997;3336: 775–85.

hyper-McKenna WJ, Camm AJ Sudden death in hypertrophic

cardiomy-opathy Assessment of patients at high risk Circulation 1989;880 0: 1489–92.

Maron BJ, Bonow RO, Cannon RO III et al Hypertrophic

cardiomy-opathy Interrelations of clinical manifestations, pathophysiology, and

therapy(1) N Engl J Med 1987;3316: 780–9.

Maron BJ, Bonow RO, Cannon RO III et al Hypertrophic

cardiomy-opathy Interrelations of clinical manifestations, pathophysiology, and

therapy(2) N Engl J Med 1987;3316: 844–52.

49 What is the medical therapy for patients with hypertrophic cardiomyopathy, and what surgical options are of use?

Krishna Prasad

About 40% of patients with hypertrophic cardiomyopathy (HCM)are symptomatic and a third have risk factors for sudden death.Each situation must be individually assessed Asymptomaticpatients do not need treatment routinely unless they are at risk ofsudden death

Treatment of symptoms

Typical symptoms include dyspnoea, palpitations and chest pain.Dyspnoea is usually due to left ventricular diastolic dysfunctionwhile chest pain is frequently due to myocardial ischaemia Thepain may however be atypical and occur in the absence of demonstrable epicardial coronary disease The treatment chosenwill depend on whether there is significant outflow tractobstruction (outflow gradient ⱖ 30mmHg) In those withoutobstruction, the choice is between either a beta blocker or a calciumantagonist, such as high dose verapamil (up to 480mg/day) Inthose with obstruction a beta blocker with or without disopyramide

is usually the first choice for those patients with outflow obstruction(~25% of patients) Both drugs reduce the outflow gradient andimprove diastolic function by their negative inotropism Verapamilshould only be used with caution as it may worsen the outflowobstruction (through the increased vasodilatation and consequentventricular emptying with contraction) Palpitations may be due tosupraventricular or ventricular arrhythmias Supraventriculararrhythmias including atrial fibrillation may be controlled withbeta blockers, verapamil or amiodarone

Patients with refractory symptoms may be candidates forinvasive treatment modalities such as dual chamber pacing with ashort AV delay, alcohol septal ablation or surgical myectomy.Surgical septal myectomy is long established and can becombined with mitral valve replacement in patients with associated significant mitral regurgitation When patients presentwith progressive ventricular dilatation and reduced systolicfunction, cardiac transplantation may need to be considered

Prevention of sudden death

Identification and treatment of those at risk of sudden death is animportant part of the management of patients with HCM Theknown risk factors are family history of sudden death, recurrentsyncope, non-sustained ventricular tachycardia and abnormal BPresponse during exercise Patients with isolated risk factors need

to be monitored carefully Those with more than two risk factorsclearly need treatment Oral amiodarone and/or an implantablecardiac defibrillator are the available options

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Seggewiss H, Gleichmann U, Faber L Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute

results and 3-month follow-up in 25 patients J Am Coll Cardiol 1998;331 1: 252–8.

Spirito P, Seidman CE, McKenna WJ et al The management of trophic cardiomyopathy N Engl J Med 1997 Mar 13;3336: 775–85.

hyper-50 What is the role of permanent pacing in

hypertrophic cardiomyopathy?

Niall G Mahon and W McKenna

There are broadly two categories of indications for permanent maker insertion in patients with hypertrophic cardiomyopathy:

pace-• Standard indications for pacing which apply to any patient

• Reduction of left ventricular outflow tract gradient

Indications for the use of dual chamber pacing with a shortprogrammed atrioventricular delay for this purpose remain to bedetermined Gradient reduction is thought to come about through

a variety of effects on septal and papillary muscle motion andcontractility In general outflow gradients can be reduced byapproximately 50% but the translation of this benefit into clinicalimprovement is variable and unpredictable Initial enthusiasmhas been tempered by equivocal results from clinical trials Aconsiderable placebo effect of the procedure has been observed in

at least two randomised studies.1,2Anecdotally, patients who maybenefit are symptomatic elderly patients with significant leftventricular outflow tract obstruction who do not respond toconventional therapy with beta blockers, verapamil or diso-pyramide The role of pacing in young patients is unclear andmethods of identifying patients likely to benefit from theprocedure have not been established

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1 Nishimura RA, Trusty JM, Hayes DL et al Dual chamber pacing for

hypertrophic cardiomyopathy: a randomised double blind crossover

trial J Am Coll Cardiol 1997;229 9: 435–41.

2 Kappenberger L, Linde C, Daubert C et al Pacing in hypertrophic

obstructive cardiomyopathy A randomised crossover study PIC study

group Eur Heart J 1997;118 8: 1249–56.

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Elliott PM, Sharma S, McKenna WJ Hypertrophic cardiomyopathy In:

Yusuf S, Cairns JA, Camm AJ et al Evidence based cardiology London: BMJ

Books, 1998:722–43.

51 How do I investigate the relative of a patient with hypertrophic cardiomyopathy? How should they be followed up?

Niall G Mahon and W McKenna

Diagnostic criteria for the diagnosis of hypertrophic myopathy in first degree relatives have been proposed as shown

Ecch ho occa arrd diio og grra ap phy

Left ventricular wall thickness Left ventricular wall thickness of ⱖ13mm in the anterior septum 12mm in the anterior septum or

or ⱖ15mm in the posterior posterior wall or of 14mm in the

Severe systolic anterior Moderate SAM (no leaflet-septal movement of the mitral valve contact)

leaflets (SAM) (causing septal

E

Elle eccttrro occa arrd diio og grra ap phy

LVH + repolarisation changes Complete BBB or minor

interventricular conduction defect

Abnormal Q waves (>40ms or Deep S in V2 (>25mm)

>25% R wave) in at least 2 leads

from II, III, aVF (in the absence Unexplained syncope, chest pain

of left anterior hemiblock), dyspnoea

V1-V4; or I, aVL, V5-V6

S

Soou urrccee McKenna WJ, Spirito P, Desnos M et al Experience from clinical genetics

in hypertrophic cardiomyopathy Proposal for new diagnostic criteria in adult

members of affected families Heart 1997;777 7: 130–2.

Hence first degree relatives should undergo history, physicalexamination, standard 2-D echocardiography, and 12-lead electrocardiography Relatives are considered affected in thepresence of one major criterion or two minor echocardiographiccriteria or one minor echocardiographic plus two minor electro-cardiographic criteria These criteria do not apply when otherpotential causes such as athletic training, systemic arterial hyper-tension or obesity are present Young children with no evidence

of disease should be re-evaluated every 5 years until their teensand then annually until aged 21 Diagnosis in a child under 10years requires a body surface area corrected left ventricular wallthickness of >10mm Affected relatives should additionallyundergo risk stratification, which includes 48 hour Holter monitoring and exercise testing, looking especially forventricular arrhythmias and abnormal blood pressure responsesrespectively

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McKenna WJ, Spirito P, Desnos M et al Experience from clinical genetics

in hypertrophic cardiomyopathy Proposal for new diagnostic criteria in

adult members of affected families Heart 1997;777 7: 130–2.

52 What investigation protocol should a patient with dilated cardiomyopathy undergo?

Niall G Mahon and W McKenna

A protocol for the investigation of dilated cardiomyopathy shouldaim to confirm the diagnosis, rule out treatable causes, preventpotential complications and determine prognosis The followinginvestigations are routinely used:

1

1 Echocardiography Two-dimensional echocardiography is the major

diagnostic test Cardiac dimensions and systolic function are also

of prognostic value, with an approximately 2-fold increase inrelative risk of mortality for every 10% decline in ejectionfraction.1 The presence of intracardiac thrombi, as well as poorsystolic function itself, may be indications for anticoagulation.2

2 Electrocardiography Twelve-lead electrocardiography and Holter

monitoring for arrhythmias should be performed Occasionally

a diagnosis of incessant tachycardia as a cause of the myopathy may be made The signal averaged ECG may be auseful predictor of risk of sudden death and progressive heartfailure and should be performed where available.2, 3

cardio-3

3 Metabolic exercise testing is of prognostic value, particularly in

advanced disease, and may guide referral for cardiac plantation

trans-4

4 Screens for metabolic causes should routinely include liver function

tests for unsuspected alcohol excess, thyroid function tests andiron studies including transferrin saturations Further investigation (such as for sarcoid or amyloid) should be guided

by history and examination

Other tests may also be performed, but are not indicated inevery case:

1

1 Coronary angiography should be performed in patients over the

age of 40 years, or who have risk factors or symptoms or signssuggestive of coronary disease

2

2 Coxsackie and adenoviral titres should be tested where there is a

history of recent suspected myocarditis or recent viral illness, butthe value of these in established cardiomyopathy is questionable

3 Serology may be performed to detect the presence of markers of

myocardial inflammation and myocyte damage

4

4 Endomyocardial biopsy may have a role, but the risks and

benefits are debated What is, however, clear is that a tissuehistological diagnosis provides important prognostic information which may (as in the case of sarcoidosis) have animpact on treatment.4 Biopsy may be recommended toexclude treatable causes such as sarcoidosis and giant cellmyocarditis, if these are thought likely In research centres,biopsy specimens may be analysed by immunohistochemicaland molecular biological techniques to determine thepresence or absence of low grade inflammation and viralpersistence

Frequency of follow up will depend on the severity ofinvolvement at initial presentation The course of the disease atearly follow up is a useful indicator of long term prognosis withimprovement or deterioration occurring in most cases within sixmonths to one year of diagnosis

The possibility that the patient’s cardiomyopathy may befamilial should be explored by taking a detailed family history,but incomplete and age-related penetrance make familyscreening problematic The decision to evaluate (usually firstdegree) relatives should be individualised, based on the extent ofdisease within a family, the levels of anxiety among patients andrelatives, the presence of suggestive symptoms and the extent oflocal experience in the evaluation of dilated cardiomyopathy R

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1 Sugrue DD, Rodeheffer RJ, Codd MB et al The clinical course of pathic dilated cardiomyopathy A population-based study Ann Intern Med 1992;1117: 117–23.

idio-2 Mancini DM, Fleming K, Britton N, Simson MB Predictive value of abnormal signal-averaged electrocardiograms in patients with non-

ischemic cardiomyopathy J Am Coll Cardiol 1992;119 9: 72A.

3 Yi G, Keeling PJ, Goldman JH et al Comparison of time domain and

spectral turbulence analysis of the signal-averaged electrocardiogram for the prediction of prognosis in idiopathic dilated cardiomyopathy.

Clin Cardiol 1996;119 9: 800–8.

4 Felker GM, Thompson RE, Hare JM et al Underlying causes and

long-term survival in patients with initially unexplained cardiomyopathy.

N Engl J Med 2000;3342: 1077–84.

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Dec GW, Fuster V Idiopathic dilated cardiomyopathy (review) N Engl J Med 1994;3331: 1564–75.

53 Which patients with impaired ventricles should receive an ACE inhibitor? What are the survival advantages? Do AT1-receptor antagonists confer the same advantages?

Lionel H Opie

Not all impaired left ventricular (LV) function is an indication forACE-inhibitor treatment Specifically, left ventricular hyper-trophy due to hypertension or aortic stenosis may be associatedwith diastolic dysfunction, yet ACE inhibition is only one ofseveral therapies that will regress LV hypertrophy, even thoughsome believe that for this purpose it is one of the best Similarly,the defects of ventricular function seen in hypertrophic cardio-myopathy are not a clear indication for ACE inhibition

The following patients shouldbe treated with an ACE inhibitor

Symptomatic patients

All patients with clinically diagnosed heart failure should receive

an ACE inhibitor The survival advantages are consistent(mortality reduction of about 20%) and far outweigh the relatively small risk of serious side effects In post-infarct clinically diagnosed heart failure, ACE inhibition reducedmortality by 27% at an average follow up of 15 months, and 36%with a mean follow up of nearly 5 years.1

Post-infarct patients without overt heart failure but with impairedleft ventricular systolic function

These patients should receive an ACE inhibitor This will givethem benefit even in the absence of symptoms, as shown in theSOLVD prevention trial.2 Most patients were post-infarct, andmost were New York Heart Association (NYHA) class 1, despitethe low ejection fraction of 35% or less

Benefit to risk ratios

In the SAVE study3 of post-infarct patients with an ejectionfraction of ⱕ40%, the chief treatment-related adverse effects of

captopril were cough, taste abnormally, dizziness or hypotension.Calculations suggest that a reduction in mortality could beachieved without side effects after treating only 24 patients.4Yetnearly 200 patients would have to be treated before encounteringone case in which side effects were found without a mortalitybenefit This makes ACE inhibition a very safe form of therapy.

Do AT1-receptor blockers confer the same advantages?

These agents are not currently (1999) licenced for use in heartfailure in the USA nor in the UK There are some key theoreticaldifferences from ACE inhibitors, such as decreased breakdown

of the protective vasodilator bradykinin during ACE inhibition,versus the likelihood that AT1 blockade gives more completeinhibition of the renin-angiotensin system than does ACE inhibition The ELITE II trial showed losartan to be no moreeffective than captopril in reducing mortality in the elderly Inthe subgroup of patients taking beta blockers, mortalitydecreased in those taking captopril, compared with losartan.ACE inhibitors, therefore, remain the cornerstone of the therapy

of heart failure.5

It should be noted that data support the use of spironolactoneadministration (25mg/day) in those with severe heart failure.Concerns about hyperkalaemia relating to concomitant use withACE inhibition were generally unfounded in this study, althoughpotassium levels in the order of 6mmol/l were accepted.6

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1 Hall AS, Murray GD, and Ball SG Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study Acute

Infarction Ramipril Efficacy Lancet 1997;3349: 1493–7.

2 The SOLVD Investigators Effects of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced

left ventricular ejection fractions N Engl J Med 1992;3327: 685–91.

3 Pfeffer MA, Braunwald E, Moye LA et al Effect of captopril on

mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction Results of the survival and ventricular

enlargement trial N Engl J Med 1992;3327: 669–77.

4 Mancini GB, Schulzer M Reporting risks and benefits of therapy by use of the concepts of unqualified success and unmitigated failure: applications to highly cited trials in cardiovascular medicine.

Circulation 1999;999 9: 377–83.

5 Topol E ACE inhibitors still the drug of choice for heart failure – and

more Lancet 1999;3354: 1797.

6 Pitt B, Zannad F, Remme WJ et al The effect of spironolactone on

morbidity and mortality in patients with severe heart failure.

Randomized Aldactone Evaluation Study Investigators N Engl J Med

1999;3 341: 709–17.