Management of hypertrophic cardiomyopathy

BMJ 2006; 332 doi: http://dx.doi.org/10.1136/bmj.332.7552.1251 (Published 25 May 2006)
Cite this as: BMJ 2006;332:1251

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Editor,

I read with interest the excellent recent review on the management of hypertrophic cardiomyopathy (HCM) by Spirito and Autore(1). One area not touched upon by their article was the emergence of cardiovascular magnetic resonance (CMR) as a potential tool for sudden death risk stratification in these patients.

CMR is a rapidly expanding area of cardiology with increasing indications. It is currently the gold standard for the assessment of cardiac volumes and dimensions (2) and has long been an established modality for the assessment of congenital heart disease, pericardial and aortic pathology.

The development of contrast enhanced CMR, along with improved imaging techniques, allows characterisation of myocardial tissue with a degree of transmural resolution that is not possible with other imaging modalities.

The contrast agent, Gd-DTPA, accumulates in the extra-cellular space and causes tissue enhancement on CMR images. It is now known that Gd-DTPA accumulates in areas of necrosis and fibrosis, due to interstitial expansion and slowed washout kinetics (3) . This phenomenon is seen in the “late phase” (i.e. 5-10 minutes) after an intra-venous bolus and is known as delayed hyperenhancement (DHE). This has been an exploding area of cardiac imaging over recent years, mostly with respect to ischaemic heart disease. The DHE technique has also been used to assess myocardial fibrosis in HCM patients. Moon et al (4) investigated the significance of the presence of DHE in 53 HCM patients. They found a positive correlation between the percentage of the left ventricle displaying DHE and the presence of “classical” factors used to stratify for risk of sudden cardiac death (SCD) as described in the recent BMJ review. They also noted the pattern of DHE was significant with a diffuse (as opposed to confluent) pattern of distribution being associated with the presence of more SCD risk factors.

Hence it was demonstrated for the first time that the presence of the classical risk factors for SCD directly correlated to a demonstrable abnormality of the myocardial interstitium and the degree to which it is present.

A non invasive imaging technique which can assist in risk stratification in HCM patients would be a powerful tool but further work is required to ascertain how CMR could be most effectively integrated into clinical practice.

Jonathan R Dalzell,
SHO in Cardiology, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, UK.

References

(1)Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006;332:1251-55.

(2)Bellenger NG, Burgess MI, Ray SG et al. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance. Are they interchangeable? Eur Heart J 2000;21:1387-96.

(3)Judd RM, Lugo-Olivieri CH, Masazumi A et al. Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2- day old reperfused canine infarcts. Circulation 1995;92:1902-10

(4)Moon JC, McKenna WJ, McCrohon JA et al. Toward clinical risk assessment in hypertrophic cardiomyopathy with cardiovascular magnetic resonance. J Am Coll Cardiol 2003;41:1561-67.

Competing interests: None declared

Competing interests: None declared

Jonathan R Dalzell, SHO in Cardiology

Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, UK

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Because of space limitations imposed by the editor, it was difficult to squeeze into our brief review a complex and heterogeneous disease, as hypertrophic cardiomyopathy. Therefore, we are glad to have the opportunity to answer the question of Dr. Anand et al. regarding the clinical course and prognosis of the apical form of hypertrophic cardiomyopathy, an issue not addressed in the review. In centres with experience in the management of hypertrophic cardiomyopathy, it was generally perceived that patients with hypertrophy confined to the cardiac apex probably had a more favorable prognosis and a lower rate of sudden death than patients with a more standard distribution of the left ventricular hypertrophy. Recently, Eriksson et al. (JACC 2002) have investigated the clinical course of a particularly large cohort of patients with the apical form of hypertrophic cardiomyopathy, which included a total of 105 patients. The results of this study have confirmed that the apical form of hypertrophic cardiomyopathy is indeed associated with a low risk of sudden death and cardiovascular mortality.

Dr. Wald asserts that coronary artery disease, rather than hypertrophic cardiomyopathy, is the most common cause of sudden and unexpected cardiac death in the young. This criticism is based on the results of a recent paper published by Dr. Wald on this issue, as well as on a number of other studies reported in his letter. Our differing conclusions were based on the recent ACC/ESC guidelines on hypertrophic cardiomyopathy (JACC 2003) and on the results of a large and systematic evaluation of the causes of sudden death in competitive athletes (Maron et al. JAMA 1996). We believe that this discrepancy has two major explanations. First, the important age difference between the patient populations discussed. In our review, we were referring to patients in their “youth” (adolescents or young adults) and to athletes. Instead, most of the studies quoted by Dr. Wald include adult patients, some with ages ranging up to 71 years. Second, two-dimensional echocardiography, the technique which first permitted an immediate identification of the morphologic features typical of hypertrophic cardiomyopathy, became available only in the early 1980s’. However, the papers from the Liberthson review quoted by Dr. Wald in support of his thesis were based on epidemiological studies performed from the 1950s’ to the early 1980s’ (5), an age in which the diagnosis of hypertrophic cardiomyopathy remained a major clinical challenge.

Dr. Uriach comments that the combination of beta-blockers and verapamil may cause bradycardia and could be too risky for patients with hypertrophic cardiomyopathy. Dr. Uriach also points out that such treatment strategy is not recommended by the recent ACC/ESC Guidelines on hypertrophic cardiomyopathy (JACC 2003). In our review, as in others (Elliott P, McKenna Lancet 2004), the use of either beta blockers or verapamil, or the combination of both drugs, is suggested exclusively to control the ventricular rate in patients with HCM and chronic atrial fibrillation. Conversely, the use of the two drugs combined is not appropriate for the treatment of heart failure. The statement quoted by dr. Uriach from the ACC/ESC Guidelines, ”there is no evidence that combined medical therapy with beta-blockers and verapamil is more advantageous than the use of either drug alone.”, refers to the control of symptoms of heart failure.

Competing interests: None declared

Competing interests: None declared

Paolo Spirito, Director

Camillo Autore

Divisione di Cardiologia, Ospedali Galliera, Via Volta 8, 16128, Genoa, Italy

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Sir, we read with interest the comprehensive review on Hypertrophic cardiomyopathy (HCM) by Spirito and Autore (1). However authors do not sufficiently emphasise the apical variant of HCM, characterized by apical hypertrophy. This variant is often associated with giant negative T waves on the electrocardiogram and a “spade shaped” left ventricular cavity on angiography: it usually has a benign course(2).

References

1.Spirito P, Autore C. Hypertrophic cardiomyopathy. BMJ 2006;352:1251- 1255.

2. Wynne J,Braunwald E. Cardiomyopathy and myocarditis. Kasper DL, Braunwald E, Fauci AS, et al Eds. In; Harrison’s principles of internal medicine. 16 th Ed. Vol II. McGraw-Hill:New York. 2005:1408-1414.

Conflict of interest-none

Source of funding-nil

Kuldip Parkash Anand MD, Professor and Head, Department of Medicine, Command Hospital (Eastern Command), Kolkata 700 027, India

*Ajit Singh Kashyap MD *Corresponding author, Department of Endocrinology, Command Hospital (Central Command), Lucknow Cantt 226 002, India

Surekha Kashyap MD, Department of Hospital Administration, Command Hospital (Central Command), Lucknow Cantt 226 002, India

Competing interests: None declared

Competing interests: None declared

Kuldip P Anand, Professor and Head,Dept of Medicine

Ajit Singh Kashyap MD, Surekha Kashyap MD, Command Hospital (Central Command ), Lucknow 226 002,India

Command Hospital (Eastern Command),Kolkata 700 027,India

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Dear Sir,

In their excellent review of management of Hypertrophic Cardiomyopathy, Spirito & Autore [1] have not discussed Apical form of hypertrophic cardiomyopathy. Approximately 25% of cases of hypertrophic cardiomyopathy may belong to apical variant in Japan[2]. It is quite frequently seen in other tropical countries like India. We in Indian Armed Forces see it quite frequently as routine ECG is part of annual medical examination. A ‘horrible’ looking ECG with giant T-wave inversions (defined as more than 10 mm in depth) is the usual cause of referral to physician and confirmation of diagnosis by echocardiography. Apical hypertrophic cardiomyopathy is rare in Western Countries. Strangely mild T -wave inversions have been reported from West as compared to giant T-wave inversions in the East [3].

Does the management of Apical hypertrophic cardiomyopathy differ from other cases of hypertrophic cardiomyopathy? Sudden death has been reported to occur in Apical hypertrophic cardiomyopathy patients and in their first degree relatives in west [3]. Japanese workers have described this subgroup of hypertrophic cardiomyopathy to be relatively benign[4]. However, their long term prognosis and risk of sudden cardiac death has not been clearly defined. Perhaps the management strategies in these cases will be dictated by patient’s symptoms. Majority of these patients do not need infective endocarditis prophylaxis as they usually have no features of obstruction. Should their first degree relatives need to be aggressively screened specially in countries with scarce health resources is not very clear.

References :

1. Spirito P & Autore C. Management of Hypertrophic Cardiomyopathy. BMJ 2006; 332 : 1251-1255.

2. Wynne J & Braunwald E. The Cardiomyopathies. In Zipes DP, Libby P, Bonow RO& Braunwald E (Eds) Braunwald’s Heart Disease, 7th ed, Elsevier Saunders 2005: p1659-1696.

3. Maron BJ, Bonow RO, Seshagiri TNR, Roberts WC & Epstein SE. Hypertrophic Cardiomyopathy With Ventricular Septal Hypertrophy Localized to the Apical Region of the Left Ventricle (Apical Hypertrophic Cardiomyopathy).

Am J Cardiol 1982; 49: 1838-1848.

4. Maron BJ. Hypertrophic Cardiomyopathy in Fuster V, Alexander RW , O’Rourke RA et al (Eds) Hurst’s The Heart, 10th ed Mcgraw-Hill 2001 : p1967-1987.

Competing interests: None declared

Competing interests: None declared

Kuldip P Anand, Head Dept of Medicine

Ajit S Kashyap, Surekha Kashyap

Command Hospital Kolkata 70027, India

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Sudden death is rare in young people with hypertrophic cardiomyopathy

Spirito and Autore, in their review on the management of hypertrophic cardiomyopathy (HCM),1 claim that HCM is the most common cause of sudden death in young asymptomatic people. This is incorrect. The table summarises the results of 12 studies that provided data on the number of deaths due to HCM in young people,2-5 (nine of which were summarised by Liberthson3). Less than 10% of all sudden deaths in young people were due to HCM. The commonest cause, despite the young age, was coronary artery disease.3,4

Most deaths from HCM, contrary to perception, occur in older people.2 In the general young adult population the annual death rate from previously undiagnosed HCM is one per million or less (table). Among asymptomatic people known to have the disorder the death rate (case-fatality) is 0.2% per year or less. These results are important with respect to advising patients of their prognosis.

Spirito and Autore recommend screening for the disorder in families of affected cases but provide no quantitative evidence to show that this would be worthwhile. It would undoubtedly lead to a large number of diagnosed cases, but few would die unexpectedly from the disorder and there is no treatment that could reasonably be offered to all.

David S Wald, Senior Lecturer

d.s.wald{at}qmul.ac.uk

Malcolm Law, Professor

Wolfson Institute of Preventive Medicine, Barts and The London, Queen Mary's School of Medicine , London EC1M 6BQ
References

  1. Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006;332:1251-5
  2. Wald DS, Law M, Morris JK. Mortality from hypertrophic cardiomyopathy in England and Wales: clinical and screening implications. Int J Cardiol 2004;97:479-84
  3. Liberthson RR. Suden death from cardiac causes in children and young adults. N Engl J Med 1996;334:1039-44
  4. Corrado D, Basso C, Maurizio S, et al. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998;339:364-9
  5. Takagi E, Yamakado T, Nakano T. Prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1999;33:206-11

Sudden deaths from hypertrophic cardiomyopathy (HCM) in young people


Cases Age (years) Number of sudden
deaths from HCM
Annual death rate in general population Case-fatality rate % of all sudden deaths attributed to HCM






Asymptomatic people with HCM in England & Wales2 <_55 _="_" font="font"/> 37 4 per million 0.06 % per year -
Asymptomatic and symptomatic people with HCM from 9 populations in 4 countries3
(USA, Sweden Israel and Italy)


49 - - 6%
(10% of cardiac sudden deaths)
Asymptomatic and symptomatic people with HCM in Veneto ( Italy ):4 ≤35 -
Athletes������� 1 0.3 per million 2%
Non-athletes 16 0.5 per million - 7%
Asymptomatic people in Tsu ( Japan ):5 with HCM 20-71 1 - 0.2% per year -

Competing interests: None declared



Competing interests: None declared

David S Wald, Senior Lecturer

Malcolm Law

Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ

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EDITOR - Doctors Spirito and Autore recommend beta- blockers or verapamil, or the two drugs combined to control heart rate in patients with hypertrophic cardiomyopathy and chronic atrial fibrillation (1). To recommend the combination of beta-blockers and verapamil without more specifications is, in our opinion, too risky. As it is well known, both beta-blockers and verapamil have negative inotropic effects, which can be additive. Given together they can cause marked bradycardia and may depress ventricular contraction (2) as well as increase the risk of AV block (3). Verapamil can also raise the serum levels of beta-blokers that are extensively metabolised in the liver (e.g. metoprolol, propranolol), possibly by inhibiting their metabolism (2). Moreover, as was mentioned in the ACC/ESC Expert Consensus Document on Hypertrophyc Cardiomyopathy, published in 2003 (4), there is no evidence that combined medical therapy with beta-blockers and verapamil is more advategeous that the use of either drug alone. In our knowledge, the situation has not changed.

We think that currently, when drug safety is an important concern, authors of medical papers should be very cautious when making this kind of recommendation.

1.- Spirito P, Autore C. Management of hypertrophyc cardiomyopathy. Br Med J 2006; 332: 1251-5.

2.- Baxter K (ed.). Stockley's Drug Interactions, 7th ed., London, Pharmaceutical Press.2006.

3.- López-Sendón J, Swedberg K, McMurray J, Tamargo J, Maggioni A P, Dargie H, et al. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 2004; 25: 1341-62.

4.- Maron B J, McKenna W J, Danielson G K, Kappemberger L J, Kuhn H J, Seidman C E, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. J Am Coll Cardiol 2003; 42: 1687-713.

Competing interests: None declared

Competing interests: None declared

Javier Borja, Drug Safety Manager

Iñaki Izquierdo, Josep Guindo

J. Uriach y Compañía, S.A. Av. Camí Reial, 51-57. 08184 Palau-solità i Plegamans. Barcelona. Spain

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