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Hypertrophic cardiomyopathy: management, risk
stratification, and prevention of sudden death

William J McKenna and Elijah R Behr 2002;87;169-176 Updated information and services can be found at: These include: "Web only references" This article cites 23 articles, 16 of which can be accessed free at: 17 online articles that cite this article can be accessed at: One rapid response has been posted to this article, which you can access for free at: You can respond to this article at: Receive free email alerts when new articles cite this article - sign up in the box at the top right corner of the article Articles on similar topics can be found in the following collections To order reprints of this article go to: MANAGEMENT, RISK STRATIFICATION, AND PREVENTION OF SUDDEN DEATH *169 William J McKenna, Elijah R Behr Heart 2002;87:169–176 Hypertrophic cardiomyopathy (HCM) is an inherited cardiac muscle disorder disease that affectssarcomeric proteins, resulting in small vessel disease, myocyte and myofibrillar disorganisation,and fibrosis with or without myocardial hypertrophy. These features may result in significant car-diac symptoms and are a potential substrate for arrhythmias. Before the identification of diseasecausing genes the World Health Organization defined HCM as the presence of left or biventricularhypertrophy in the absence of any cardiac or systemic cause.w1 When these criteria are applied to awestern population the estimated prevalence of HCM is approximately 1 in 500.1 w2 Morphologicalevidence of left ventricular hypertrophy, however, may be absent in up to 20% of gene carriers.w3Adults are often asymptomatic but their estimated mortality rate may nonetheless be as high as1–2% per annum.2 w4 This article will present the natural history of HCM and relate it to the needfor medical intervention to alleviate symptoms and prevent sudden death.
The expression of disease is age related, occurring during or soon after periods of rapid somaticgrowth. Detectable cardiovascular abnormalities usually develop during adolescence.w5 For thisreason the regular evaluation of the offspring of carriers during puberty and early adulthood isnecessary for diagnosis and risk stratification. HCM has been described in infants and young chil-dren but data are limited. Children diagnosed before 14 years of age have a worse prognosis oncethey reach adolescence and early adulthood with a 2–4% annual incidence of sudden death.3 Thedevelopment of clinical features of HCM in the elderly is associated with myosin binding protein C(MyBPC) mutations.w6 Although MyBPC disease appears benign in that presentation is in the laterdecades, once disease develops patients are at risk of all the recognised complications of HCMincluding arrhythmia, stroke, and sudden death.w7 A subanalysis of data from patients who hadreceived an implantable cardioverter-defibrillator (ICD) indicated a higher proportion of individu-als (40–50%) undergoing defibrillation in the age groups 11–20 years and > 55 years compared tothe 21–55 years range.4 Aggressive management in these higher risk age groups may therefore berequired.
In adults, left ventricular hypertrophy caused by mutations in genes other than MyBPC is not progressive and in the majority is usually benign in its clinical course. Most affected individuals gounrecognised and are asymptomatic or experience only paroxysmal manifestations.w8 Chronicexertional symptoms such as chest pain and dyspnoea can be secondary to myocardial ischaemia(table 1), diastolic dysfunction and/or congestive cardiac failure, and tend to deteriorate slowlywith age. The classical pattern of asymmetric septal hypertrophy (ASH) may be accompanied bysystolic anterior motion of the mitral valve (SAM) and dynamic left ventricular outflow tract(LVOT) obstruction that can also cause exertional symptoms of impaired consciousness, dyspnoea,and chest pain. A subset of patients, however, who represent < 5% of the total, exhibit progressivesymptomatic deterioration in left ventricular systolic function with myocardial thinning anddilatation.5 This is usually accompanied by the development of systolic cardiac failure. The severityof symptoms and exercise limitation caused by obstruction and/or cardiac dysfunction will dictatesymptomatic management while the presence of arrhythmias and abnormal vascular responseswill influence the need for prevention of sudden death. The risk of stroke secondary to atrial fibril-lation (AF) must also be considered.
Correspondence to:William J McKenna, MD, MECHANISMS OF CARDIAC ARREST Department of CardiologicalSciences, St George's Hospital Fortuitous observations have recorded several mechanisms for the generation of ventricular fibril- Medical School, Cranmer lation (VF). These include paroxysmal AF, sinus tachycardia with abnormal vascular responses Road, London SW17 0RE, UK; and/or myocardial ischaemia, sustained monomorphic ventricular tachycardia (VT), rapid atrioventricular (AV) conduction via an accessory pathway, and AV block. Recent data have Supported by the British Heart reported that appropriate discharges by ICDs (that is, probable aborted sudden death) were related to the occurrence of monomorphic VT, VF preceded by VT, and VF alone.4 ICD Holter data, however, EDUCATION IN HEART Possible mechanisms for myocardial AF, atrial fibrillation Increased myocardial oxygen ASH, asymmetric septal hypertrophy myocardial perfusion AV, atrioventricular Myocardial hypertrophy Small vessel disease HCM, hypertrophic cardiomyopathy Diastolic dysfunction Abnormal vascular responses ICD, implantable cardioverter-defibrillator Myocardial bridges LVOT, left ventricular outflow tract Left ventricular outflow obstruction Increased coronary vascularArrhythmia MyBPC, myosin binding protein CNSVT, non-sustained ventricular tachycardiaSAM, systolic anterior motion of the mitral valveSVT, supraventricular tachycardiaVF, ventricular fibrillation may not establish the importance of a trigger—for example, VT, ventricular tachycardia an abnormal vascular response or preceding ischaemia, in precipitating cardiac arrest. In the young this may be related tothe haemodynamic changes of paradoxical vasodilatation inthe presence of sinus tachycardia or primary atrial and tract, eliminating systolic mitral leaflet septal contact. There is ventricular arrhythmias. The development of a sustained ven- a success rate of > 80% that can be achieved with a tricular arrhythmia would then represent a terminal event.6 w9 perioperative mortality rate of 2% or less. Long term symptomrelief is maintained in up to 70% of patients.8 w12 The operation SYMPTOMATIC TREATMENT should be tailored to the patient's anatomy including the The diagnosis of HCM relies on the demonstration of severity of hypertrophy, the location and size of papillary otherwise unexplained electrocardiographic (ECG) and two muscles, and mitral valve anatomy. Mitral regurgitation can dimensional echocardiographic (echo) abnormalities (see develop secondary to SAM and obstruction, and cause signifi- cant dyspnoea because of pulmonary oedema. The require- 2001;86:709–14). Echo is also of use in the assessment of
ment for mitral valve surgery and/or myectomy needs to be diastolic and systolic dysfunction. The measurement of peak individualised and can be guided by careful preoperative as oxygen consumption during maximal upright exercise with well as intraoperative echocardiography.
continuous ECG and blood pressure monitoring facilitates Two other modalities have been developed for the symptomatic assessment of the HCM patient and provides an treatment of LVOT obstruction: dual chamber pacing and objective measure of functional limitation, vascular responses, alcohol septal ablation. The efficacy of pacing is controversial.
and ischaemia. This helps to identify those patients with sub- Adult HCM patients were evaluated in randomised double clinical involvement and provides a useful objective correlate blind trials of DDD or AAI pacing.9 w13 Gradient reduction for subjective symptoms that may be particularly difficult to during active DDD pacing was approximately 50%. No other evaluate in young patients. The detection of a significant LVOT differences in objective measures were detected between the gradient either at rest or during exercise will guide two pacing modalities. While 60% felt better with DDD symptomatic treament (fig 1). Angiography is usually pacing, 40% experienced symptomatic improvement with the necessary to exclude coronary artery disease in older patients pacemaker effectively turned off.9 This suggested a substan- with chest pain or ECG abnormalities.
tial placebo effect.9 w14 w15 Obstructive HCM: medical treatment Alcohol ablation in experienced hands is effective and β Blockers are the first line treatment in patients with LVOT safe.10 The technique involves injection of alcohol into the per- obstruction. The majority of patients show improvement upon forators of the left anterior descending coronary artery to treatment although high doses are often required. Side effects, cause a limited septal myocardial infarction.w16 This reduces however, can limit utility as well as induce pharmacological septal hypertrophy and the associated obstruction.w16 Experi- chronotropic incompetence, blunting the heart rate response enced centres are vital for good results as these are dependent to exercise and causing symptomatic deterioration. Verapamil on appropriate patient selection as well as good technique in is best avoided in individuals with obstruction because of pos- order to ensure the delivery of alcohol is to the correct areas.w16 sible peripheral vasodilatation and haemodynamic collapse.
The extent of myocardial perfusion by septal vessels is variable Unfortunately much of the data on verapamil or β blockers is and may include papillary muscles and wide areas of both observational and uncontrolled.w10 ventricles. Accurate definition by contrast echo of the area Disopyramide has been evaluated more systematically and perfused is vital to avoid diffuse myocardial damage, particu- is also effective in gradient and symptom reduction, probably larly to papillary muscles.
because of negative inotropism.w11 It may have a superior effecton exercise tolerance compared to β blockers.7 They are, how- Non-obstructive HCM: medical treatment ever, best used in combination as disopyramide alone tends to Agents such as β blockers, verapamil, and diltiazem are used accelerate AV node conduction and increase the potential risk to treat chest pain and dyspnoea and improve exercise from supraventricular arrhythmias. Disopyramide should be tolerance. The mechanism probably involves improvement of administered in the maximum tolerated dose; the limiting left ventricular diastolic function and myocardial ischaemia.
factor is usually the anticholinergic side effects.
The response can be suboptimal although those patients withsevere chest pain often benefit from high doses of verapamil or Obstructive HCM: non-medical treatment diltiazem. Pulmonary congestion has been treated with Surgical septal myectomy remains the gold standard for those diuretics but there is a risk of decompensation in individuals individuals with drug refractory symptoms and a resting with severe diastolic dysfunction. Diuretics should only be gradient of > 50 mm Hg. The aim is to widen the outflow used judiciously and if possible only in the short term, as EDUCATION IN HEART Calcium antagonists Algorithm for symptomatic treatment chronic prescription tends to result in a reduction in stroke usually effective in reducing recurrences and attenuating the volume and cardiac output that ultimately lowers exercise development of permanent AF.11 The threshold for starting anticoagulation should be low to minimise embolic complica- The subset that develops systolic impairment should receive treatment for conventional cardiac failure, including angio- Established AF is uncommon in the young, while in adults tensin converting enzyme (ACE) inhibitors, β blockers, the prevalence can be up to 30%.11 It is more common in eld- digoxin, spironolactone, and if necessary cardiac transplanta- erly HCM patients and has been associated with a poorer overall prognosis, an enlarged atrial size, and increased risk ofthromboembolism including stroke.6 11 w17 w18 Its onset is associated with an acute deterioration in symptoms that usu- Supraventricular arrhythmias are common in HCM. They are ally reverses with control of the ventricular response.11 The related to left atrial enlargement and fibrosis developing in the long term outlook, with appropriate treatment to control heart context of chronically elevated filling pressures as a conse- rate and prevent emboli, is usually good.12 w17 w19 Repeated car- quence of obstruction, diastolic dysfunction, and/or mitral dioversions to restore sinus rhythm are not warranted. In most valve dysfunction.w8 Paroxysms of supraventricular tachycar- HCM patients the contribution of atrial systoles to stroke vol- dia (SVT) and AF can be detected on Holter monitoring in up ume is negligible by the time AF develops—that is, patients to 30% of adults, although the incidence in the young is closer have a palpable atrial beat but no fourth heart sound.
to 5–10%. Sustained or symptomatic episodes are much less A slurred upstroke to a broad QRS complex is a common common and warrant treatment with amiodarone, which is surface ECG finding in HCM patients. In less than 5% of these EDUCATION IN HEART The recognised markers of risk in HCM and their sensitivity, specificity, positive and negative predictive accuracy (PPA and NPA) Abnormal blood pressure response: <40 years old19 NSVT: adult <45 years old18 NSVT: <21 years old23 Inducible VT/VF: High risk populationw30 *Syncope: <45 years old3 *Family history: at least one unexplained sudden death 42 ± HCM3†LVH >3 cm17 †‡Two or more risk factors2 *Figures provided are for the risk of death from all causes rather than sudden death only.
†Figures provided are for risk of sudden death and/or appropriate ICD discharge.
‡In this data set from Elliott and colleagues, family history and syncope were combined in order to achievestatistical significance of relative risk.
LVH, left ventricular hypertrophy; NSVT, non-sustained ventricular tachycardia; VF, ventricular fibrillation; VT,ventricular tachycardia.
death (< 45 years old) while less than 5% had two or more Five year survival rates free of death, HCM related sudden deaths in the family. Family history of cardiac arrest or appropriate ICD discharge in studies premature sudden death is also an insensitive but relatively of HCM patients treated for secondary prevention of specific marker of risk (table 2). The combination of a history cardiac arrest or haemodynamically compromising of syncope with a family history of sudden death, however, ventricular arrhythmias does increase significantly the overall positive predictive accu- 5 year survival rates (95% CI) racy for sudden death (Cox model multivariate relative risk 5.3, 95% confidence interval (CI) 1.9 to 14.9).2 3 45% (CI unavailable) EchocardiogramEarly echocardiographic and Doppler data has not suggested CI, confidence interval.
any predictive value from the degree of hypertrophy or sever-ity of outflow tract obstruction.w21 More recent studies have, patients, however, is an accessory pathway found at electro- however, identified severe (> 3 cm) hypertrophy as a risk fac- physiological testing.13 This may then be amenable to tor for sudden death.16 17 Spirito and colleagues had concluded radiofrequency ablation. Enhanced AV nodal conduction may that severe hypertrophy alone justified ICD insertion, particu- be more frequent in HCM and may facilitate the rapid larly in the young.16 This has been criticised, however, for fail- conduction of pre-excited arrhythmias and so precipitate ing to consider the distribution of left ventricular hypertrophy (LVH) and the fact that the majority of patients with maximalwall thicknesses > 3 cm survived without prophylactic treat- SUDDEN DEATH: RISK ASSESSMENT ment. The data from Elliott and colleagues support a All patients should undergo non-invasive risk factor stratifica- significantly increased risk of sudden death or ICD discharge tion with a clinical history, Holter monitoring, and maximal associated with a maximal hypertrophy > 3 cm (Cox model exercise testing regardless of symptomatic status or the relative risk 2.1, 95% CI 1.0 to 4.2) but argues against prophy- apparent severity of morphological disease.
lactic treatment solely on the basis of left ventricular wallthickness.17 All the individuals with a mean left ventricular wall thickness > 3 cm who died suddenly had additional risk Syncope and symptoms factors, while those without other risk factors all survived.17 In Unexplained, exertion related syncope is a predictor of risk in addition, 74% of Elliott's and 82% of Spirito's subgroups who all age groups, but especially in children and adolescents with died suddenly had hypertrophy of less than 3 cm.16 17 The severe symptoms.3 This is an insensitive measure, however, as severity of wall thickness in isolation has insufficient most patients who die suddenly have no prior history of syn- predictive accuracy to guide decisions regarding prophylactic cope. In adults the severity of symptoms of chest pain and dyspnoea does not add to the predictive value (table 2).3 Prior cardiac arrest Holter monitorTwenty per cent of adult HCM patients exhibit non-sustained Early evidence suggested that the short and medium term ventricular tachycardia (NSVT) during Holter monitoring. In prognosis after a cardiac arrest was not as ominous as adults it is the most sensitive marker for increased risk of sud- expected. The data indicated that roughly one third of den death, conferring a doubled relative risk in a selected low survivors died within seven years while receiving non- risk population and an eightfold increase in relative risk in a systematic medical or surgical treatment.14 The most recent consecutive referral centre population.18 w22 The absence of ICD data, however, suggests a poorer prognosis with appropri- NSVT in adults is particularly reassuring because of its high ate discharge rates of approximately 10% in survivors of negative predictive accuracy (table 2).
cardiac arrest (table 3).4 15 NSVT, however, is seen infrequently in adolescents and rarely in children, but when detected is more ominous and Unpublished tertiary referral centre data indicates that 25% of specific with an up to eightfold increase in relative risk for HCM patients have a family history of premature sudden sudden death.18 19 The relative rarity of ventricular arrhythmias EDUCATION IN HEART Identify and treat RISK FACTOR STRATIFICATION Algorithm for risk stratification and prevention of sudden death.
in children limits its utility in this population. In the young young, in the absence of other risk factors, permits accurate little reassurance is provided by the absence of NSVT while its presence even in isolation warrants prophylactic treatment.
SVT and AF have been observed as antecedent events in the Other investigations development of VF and sudden death. Prophylaxis may there- Thallium cardiac perfusion scanning reveals reversible thal- fore have an additional benefit in the reduction of the risk of lium defects in young HCM patients with histories of prior sudden death.
cardiac arrest or syncope.w26 These findings have not beenborne out in larger mixed groups of prospectively studied Blood pressure response to exercise testing patients although in a small subset of patients ischaemia is During upright exercise HCM patients commonly demon- strate an abnormal blood pressure response, with either a fall An angiographic study of children with HCM suggested or failure of blood pressure to rise.w23 w24 Inappropriate arterial that myocardial bridging was a significant risk factor for sud- vasodilatation in non-exercising muscles has been docu- den death.w28 These children were a highly selected group by mented and it is postulated that this is related to activation of virtue of having to undergo angiography and were examined left ventricular baroreceptors by wall stress or ischaemia.w23 w25 retrospectively, making these findings difficult to extrapolate An abnormal blood pressure response during exercise is to the general paediatric HCM population. The significance of defined as a failure to either augment and/or sustain a systolic myocardial bridging and ischaemia in triggering secondary blood pressure of > 25 mm Hg above the resting systolic blood arrhythmias remains unknown but the available data do not pressure during exercise. It can be detected in 25% of HCM provide sufficient justification for routine angiography.
patients and thus its positive predictive accuracy for sudden Other non-invasive electrophysiological investigations have death is low at 15% (table 2).20 w24 It is a more sensitive indica- been assessed in risk stratification with little success.w8 Signal tor of risk in younger patients (< 40 years old) and is associ- averaged ECGs and heart rate variability studies are com- ated with sudden death, although the relative risk is low monly abnormal in HCM patients, but there is no association (1.8).2 20 Therefore a positive result should be used in conjunc- with increased risk. QT interval analysis, including QT disper- tion with other risk factors. The absence of an abnormal blood sion, has provided contradictory results. Beat to beat QT vari- pressure response is reassuring, however, as its negative ability has been studied in β myosin mutations and was found predictive value for sudden death is 97% (table 2) and in the to be increased in patients with Arg403Gln mutations of the β EDUCATION IN HEART Recognised markers of increased risk of Triggers for sudden death and their sudden death in HCM associated treatment 1. Previous cardiac arrest Paroxysmal atrial fibrillation Amiodarone ± anticoagulation 2. Non-sustained VT on Holter or exercise Sustained monomorphic VT ICD ± amiodarone 3. Abnormal exertional blood pressure response Conduction system disease Permanent pacemaker 4. Unexplained syncope Accessory pathway Radiofrequency ablation 5. Family history of premature sudden death Myocardial ischaemia High dose verapamil 6. Severe left ventricular hypertrophy >3 cm There are several recognised markers for risk of sudden myosin heavy chain gene, but there are no data as yet on fol- death (table 4). Individually they all have low positive predic- low up and outcomes.w29 tive accuracy (table 2). The proposed risk management Invasive electrophysiological investigations have been used algorithm (fig 2) advocates reassurance of individuals with no as research and potential clinical tools. Programmed stimula- risk factors and no evidence of ischaemia. This is justifiable tion studies using aggressive protocols have suggested that given the high negative predictive accuracy seen in patients inducible VT is associated with a higher risk of future sudden without risk factors (table 2).2 Individuals with two or more death (table 2).w30 These protocols, however, result in a low risk factors have annual sudden death rates of 3% (95% CI 2% positive predictive accuracy similar to non-invasive methods.
to 7%) and should be offered prophylaxis with ICD and/or Therefore the hazard and inconvenience of electrophysiologi- amiodarone.2 Individuals with only one risk factor have cal studies cannot be justified.
annual sudden death rates of approximately 1% but with wideconfidence limits (95% CI 0.3% to 1.5%); their management Genetic testingRecent studies have suggested that some mutations in HCM should therefore be tailored according to age, genotype, inten- may carry prognostic significance. Troponin T mutations can sity of the risk factor, and the acceptability of risk for each be exceptionally lethal and appear to be more homogenous in individual.2 For example, a patient's only risk factor may be a their high level of risk than the prognostic allelic heterogen- family history of premature sudden death, but if the proportion of affected individuals in a pedigree who suffer abnormalities.21 Troponin T patients tend to exhibit subtle or premature sudden death is high the justification for pro- absent hypertrophy but with significant myocyte disarray, and phylaxis is greater than if the proportion was low.
thus may be at risk without conspicuous evidence of disease.w31 β Myosin mutations are heterogeneous in their In approximately 30% of patients risk factor stratification associated levels of risk. Arg403Glu and Arg453Cys mutations identifies potential triggers for sudden death which are appear to predispose to sudden death while the Val606Met usually amenable to specific treatments (table 5).
mutation appears to carry a better prognosis.21 Nevertheless the genotype–phenotype relation has to be clarified further to allow proband risk prediction as the exist- Over 60% of cases of sudden death in HCM die during or ing data have been elicited from selected groups of patients immediately after mild to moderate exertion.w21 In addition, and their families. In addition there may be pronounced necropsy studies of sudden death in young athletes have heterogeneity of disease within a family with the same muta- shown that the majority had HCM and that two thirds of them tion. For example, a MyBPC mutation has demonstrated a died during or immediately after exertion.22 It is therefore rea- wide variation in expression in a large German family.w7 Only sonable to advise those at risk of sudden death not to under- a minority of the family exhibited full expression, which was take strenuous exercise or competitive sports which require partly age related, and once disease developed placed them at extreme physical exertion.22 high risk of syncope, arrhythmias, and sudden death. In addi-tion, DNA diagnosis is limited by the lack of clinical testing Drug and device treatment outside of research institutions.
In the absence of a recognised trigger, treatment of high risk Recently mutations in the gene PRKAG2 encoding the patients is limited to ICD and/or amiodarone.4 23 There are gamma-2 subunit of an AMP activated protein kinase have limited data to define who should receive which treatment. In been identified in families with Wolff-Parkinson-White those at the highest risk an ICD is appropriate while amiodar- (WPW) syndrome with premature conduction disease and one may be prescribed in lower risk patients. Amiodarone is HCM.w32 w33 Genetic testing may prove useful as this phenotype also recommended if there is evidence of additional features has a high incidence of pre-excitation, paroxysmal AF, and that require prophylaxis such as paroxysmal supraventricular flutter and the development of premature conduction disease.
The use of amiodarone in children and adolescents may be SUDDEN DEATH: PROPHYLAXIS complicated by anxiety about the potential dose/duration side It is accepted practice to treat aggressively those patients who effects. It can be used temporarily, however, as bridging have experienced cardiac arrest and/or sustained or sympto- therapy to delay ICD insertion in high risk young individuals matic ventricular arrhythmias (secondary prevention) using in whom a device is thought to be the long term treatment of ICDs because of their high risk (table 3).4 15 Most cardiac arrest choice. In addition it can provide prophylaxis during a period victims with HCM do not survive the initial event, making it of high risk until adulthood is reached and a lower risk profile imperative to evaluate all HCM patients for risk and institute is achieved.4 w34 A recent retrospective and non-randomised primary prevention accordingly (fig 2).
paediatric study suggested a 5–10 fold reduction in risk with EDUCATION IN HEART It is still necessary to determine which prophylactic Management of HCM: key points treatment is appropriate for which patient. Thus a continued c Symptomatic relief: registry of ICD and amiodarone treatment in HCM, incorpo- – in non-obstructive HCM treatment relies on calcium rating genetic testing and risk stratification, may be the only channel antagonists and β blockers definitive way to guide therapy in relation to genotype and – in obstructive HCM pharmacological treatment relies on β blockers and disopyramide initially – myectomy, alcohol ablation, and dual chamber pacing are alternative interventions in obstructive The management of HCM remains an important clinical chal- HCM in the drug refractory patient lenge necessitating regular longitudinal follow up of young c Atrial fibrillation should be treated aggressively to minimise individuals. Treatment of obstruction offers several effective the risks of thromboembolism options but symptom relief can be difficult, particularly in c Sudden death prophylaxis: non-obstructive patients. Stratification of the risk of sudden – all HCM patients should undergo risk stratification for death is feasible using available non-invasive techniques. Ulti- mately, genotyping may further refine our predictive abilities.
– patients suffering prior cardiac arrest or sustained The potential benefit of risk assessment also includes the ventricular arrhythmia warrant prophylactic treatment reassurance of low risk individuals, while for high risk – patients with two or more recognised risk factors war- individuals there are prophylactic treatments available. The rant prophylaxis (table 4) weight of evidence supports the judicious use of amiodarone – patients with one risk factor require individualised decision making in relation to the strength of the risk and ICD therapy in primary prevention. Secondary prevention data support ICD therapy as mandatory. Data on treatment in – effective prophylactic treatment includes the use of ICD the younger age groups are limited despite their relatively high and/or amiodarone risk of sudden death.
c Clarification of the genotype–phenotype relation in HCM may ultimately assist decision making 1 Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults.
high dose β blockade.w35 Interpretation of these data is limited Echocardiographic analysis of 4111 subjects in the CARDIA study.
Coronary artery risk development in (young) adults. Circulation by the small sample size derived from a heterogeneous popu- lation of young patients (all diagnosed < 19 years old), which 2 Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol included a high proportion of patients with "HCM" unrelated to sarcomeric contractile protein gene mutations (38% c This study demonstrated the clinical utility and statistical validity of Noonan's syndrome). The sudden death risk of "HCM" caused risk stratification using recognised risk factors to identify high riskpatients.
by mitochondrial disease, Noonan's, Freidrich's ataxia, and 3 McKenna W, Deanfield J, Faruqui A, et al. Prognosis in hypertrophic Fabry's disease is likely to be different to the risk of HCM cardiomyopathy: role of age and clinical, electrocardiographic andhemodynamic features. Am J Cardiol 1981;47:532–8.
caused by mutations in contractile protein genes.
4 Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable More recently retrospective registry data on ICD therapy cardioverter-defibrillators for the prevention of sudden death in patientswith hypertrophic cardiomyopathy. N Engl J Med 2000;342:365–73.
have become available from US and Italian investigators.4 The c The registry data presented, although retrospective, are the first to risk profile of the patients is incomplete but the primary pre- describe the utility and complications of ICD treatment in a large vention data suggest that individuals not at excessively high group of HCM patients.
5 Spirito P, Maron BJ, Bonow RO, et al. Occurrence and significance of risk were treated. Extrapolation to a 10 year period suggested progressive left ventricular wall thinning and relative cavity dilatation in an annual appropriate discharge rate of 2.5%. This correlates hypertrophic cardiomyopathy. Am J Cardiol 1987;60:123–9.
6 Nicod P, Polikar R, Peterson KL. Hypertrophic cardiomyopathy and with the experience of the European ICD registry (M sudden death. N Engl J Med 1988;318:1255–7.
Borggrefe MD, personal communication).
7 Pollick C. Disopyramide in hypertrophic cardiomyopathy. II. Noninvasive assessment after oral administration. Am J Cardiol 1988;62:1252–5.
The complications of ICD therapy, however, appear to be 8 McCully RB, Nishimura RA, Tajik AJ, et al. Extent of clinical improvement greater in patients with HCM compared to high risk dilated after surgical treatment of hypertrophic obstructive cardiomyopathy.
Circulation 1996;94:467–71.
cardiomyopathy or coronary artery disease patients. For c A comprehensive retrospective assessment of the efficacy and safety example, 25% of the whole Italo-American group and 22% of of surgical myectomy according to the Mayo Clinic experience.
European registry patients suffered inappropriate discharges 9 Nishimura RA, Trusty JM, Hayes DL, et al. Dual-chamber pacing for hypertrophic cardiomyopathy: a randomized, double-blind, crossover trial.
and 15% had significant complications caused by lead failure J Am Coll Cardiol 1997;29:435–41.
or local effects of insertion (for example, infection, haemor- 10 Seggewiss H, Faber L, Gleichmann U. Percutaneous transluminal septal ablation in hypertrophic obstructive cardiomyopathy. Thorac Cardiovasc rhage, and subclavian thrombosis). Amiodarone may reduce the frequency and rate of ventricular and supraventricular c The largest series to demonstrate clearly the safety and efficacy of alcohol ablation.
tachycardias and hence reduce the number of inappropriate 11 Cecchi F, Olivotto I, Montereggi A, et al. Hypertrophic cardiomyopathy in and appropriate discharges. In the Italo-American popula- Tuscany: clinical course and outcome in an unselected regional tion, however, it was used less frequently than one might population. J Am Coll Cardiol 1995;26:1529–36.
12 Robinson K, Frenneaux MP, Stockins B, et al. Atrial fibrillation in have expected (25%). In addition the young are also more at hypertrophic cardiomyopathy: a longitudinal study. J Am Coll Cardiol risk of complications. Children are more likely to require 13 Fananapazir L, Tracy CM, Leon MB, et al. Electrophysiologic insertion in an abdominal position with redundant intra- abnormalities in patients with hypertrophic cardiomyopathy. A consecutive atrial loops of lead required to allow for further growth.w34 analysis in 155 patients. Circulation 1989;80:1259–68.
14 Cecchi F, Maron BJ, Epstein SE. Long-term outcome of patients with Adolescents often have psychological problems adapting to hypertrophic cardiomyopathy successfully resuscitated after cardiac arrest.
the device, while young people in general will require multi- J Am Coll Cardiol 1989;13:1283–8.
ple box and lead placements resulting in difficult vascular Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest orsustained ventricular tachycardia in patients with hypertrophic access and an increase in complications.w34 cardiomyopathy. J Am Coll Cardiol 1999;33:1596–601.
EDUCATION IN HEART 16 Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular c An abnormal blood pressure response to exercise was shown to be hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N a useful predictor of risk of sudden death, particularly in the young.
Engl J Med 2000;342:1778–85.
21 Watkins H, McKenna WJ, Thierfelder L, et al. Mutations in the genes for 17 Elliott PM, Gimeno BJ, Mahon NG, et al. Relation between severity of cardiac troponin T and alpha-tropomyosin in hypertrophic left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. N Engl J Med 1995;332:1058–64.
cardiomyopathy. Lancet 2001;357:420–4.
22 Maron BJ, Roberts WC, McAllister HA, et al. Sudden death in young c Elliott and colleagues provide convincing evidence that hypertrophy athletes. Circulation 1980;62:218–29.
alone should not be used as an indicator of high risk but as part of 23 McKenna WJ, Oakley CM, Krikler DM, et al. Improved survival with full risk stratification.
amiodarone in patients with hypertrophic cardiomyopathy and ventricular 18 Maron BJ, Savage DD, Wolfson JK, et al. Prognostic significance of 24 tachycardia. Br Heart J 1985;53:412–16.
hour ambulatory electrocardiographic monitoring in patients withhypertrophic cardiomyopathy: a prospective study. Am J Cardiol1981;48:252–7.
19 McKenna WJ, Franklin RC, Nihoyannopoulos P, et al. Arrhythmia and prognosis in infants, children and adolescents with hypertrophiccardiomyopathy. J Am Coll Cardiol 1988;11:147–53.
20 Sadoul N, Prasad K, Elliott PM, et al. Prospective prognostic assessment of blood pressure response during exercise in patients with hypertrophic Additional references appear on the Heart website—



ESSEX PALLIATIVE AND SUPPORTIVE CARE NETWORK FORMULARY AND GUIDELINES FOR MANAGEMENT Updated April 2010 CONTENTS Introduction General Principles Principles of Prescribing in Palliative care Syringe Drivers Emergencies in Palliative Care Steroids in Palliative Care Care of the Dying Pain Control Gastrointestinal Symptoms Anorexia and Cachexia Nausea and Vomiting Constipation Diarrhoea Bowel Obstruction Malignant Ascites Mouth Care Respiratory Symptoms Breathlessness Cough Hiccups Other Common Symptoms Urinary Symptoms Agitation Skin Care (including pressure and wound care) Lymphoedema General References and Further Reading


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