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Sudden death and hypertrophic cardiomyopathy
CORRESPONDENCE
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Massei F, Massimetti M, Messina F, Macchia P, Maggiore G. Bartonella henselae and inflammatory bowel disease. Lancet 2000; 356: 1245–46. Anderson BE, Neuman MA. Bartonella spp as merging human pathogens. Clin Microbiol Rev 1997; 10: 203–19. Breitschwerdt EB, Kordick DL. Bartonella infection in animals: carriership, reservoir potential, pathogenicity, and zoonotic potential for human infection. Clin Microbiol Rev 2000; 13: 428–38. Zangwill KM, Hamilton DH, Perkins BA, et al. Cat scratch disease in Connecticut: epidemiology, risk factors and evaluation of a new diagnostic test. N Engl J Med 1993; 329: 8–13. Numazaki K, Ueno H, Yokoo K, Muramatsu Y, Chiba S, Morita C. Detection of serum antibodies to Bartonella henselae and Coxiella burnetii from Japanese children and pregnant women. Microb Infect (in press).
Sudden death and hypertrophic cardiomyopathy Sir—Perry Elliott and colleagues’ (Feb 10, p 420)1 analysis about the impact of magnitude of left-ventricular hypertrophy (LVH) on prognosis in hypertrophic cardiomyopathy, was apparently stimulated by our findings addressing risk stratification for sudden death.2 The investigators confirm several of our observations—the risk of sudden death in hypertrophic cardiomyopathy increases progressively with increasing wall thickness and is greatest with wall thickness of 30 mm or more.1-3 In ours and their studies, extreme LVH was more frequent in young patients with no or mild symptoms, rate of sudden death approached 20% at 10 years in Elliott and colleagues’ study and 40% at 20 years in our study, and patients with extreme hypertrophy accounted for about 25% of the sudden deaths in each study. Therefore, both studies establish extreme LVH as an unfavourable feature of hypertrophic cardiomopathy and a risk factor for sudden death. We also agree that many patients without extreme LVH die suddenly, as well as that more risk factors convey greater risk.3 However, we are uncomfortable with the conclusion that patients with extreme LVH and no additional risk factors have an excellent survival. Elliott and colleagues’ effort directed at achieving such precision in risk stratification (one vs two risk factors) in a disease as heterogeneous as hypertrophic cardiomyopathy is admirable but fraught with uncertainty and could result in undertreatment of patients at risk of sudden death. For example,
THE LANCET • Vol 357 • June 16, 2001
Elliott and colleagues arbitrarily defined family history of sudden death as a risk factor only if two or more such events occurred in relatives younger than 40 years. Syncope is a risk factor only when two or more episodes have occurred within the previous year. One sudden death in a close relative or one recent exertional syncope are thought sufficient to define risk by many experts. Non-sustained ventricular tachycardia on Holter (⭓3 beats) is effervescent in hypertrophic cardiomyopathy and absent in many young patients at high risk of sudden death.4 With use of this latter criterion, a patient with 35 mm wall thickness and ten ventricular couplets would be low risk, but the same patient with a single run of three ventricular beats would be high risk. Some flaws are implicit in the construction of a precise algorithm for risk stratification in a disease such as hypertrophic cardiomyopathy.4 Indeed, the strong conclusion that wall thickness of 30 mm or more without another risk factor never justifies implantation of a cardioverter defibrillator1 strikes us as stretching the precision of risk stratification, and ultimately the interpretation of these data. Effective therapy for prevention of sudden death has finally become available to patients.5 We are concerned that, as a consequence of Elliott and colleagues’ conclusions, some truly high-risk patients might be deprived of a lifesaving treatment. Unfortunately, the researchers make no recommendations about which patients with extreme LVH to offer preventive therapy. Many young patients with extreme wall thickness are probably at substantial long-term risk of sudden death and we recommend that they be informed of potential lifesaving protection afforded by an implantable defibrillator.5 *Paolo Spirito, Barry J Maron *Ospedaliero Ospedali Galliera, Genoa, Italy; and Minneapolis Heart Institute Foundation, Minneapolis, MN, USA
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Elliott PM, Gimeno JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001; 357: 420–24. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy, and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000; 342: 1778–85. Elliott PM, Polonlecki J, Dickle S, et al. Sudden death in hypertrophic cardiornyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36: 2212–18. Spirito P, Seidman, CE, McKenna WJ, Maron BJ. The management of hypertrophic
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cardiomyopathy. N Engl J Med 1997; 336: 775–85. Maron BJ, Shen W-K, Link MS, et al. Efficacy of implantable cardioverterdefibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000; 342: 365–73.
Authors’ reply Sir—The relatively low positive predictive value of most single risk markers in patients with hypertrophic cardiomyopathy means that they are not a definite indication for implantable cardiac defibrillators. Paulo Spirito and Barry Maron have confirmed1 previous cross-sectional data which shows that severe hypertrophy, defined as a wall thickness of 30 mm or more, is associated with an increase in the risk of sudden death.2 However, in their study and ours, fewer than 20% of patients with severe hypertrophy died suddenly, which suggests that further risk stratification is needed before automatic or routine recommendation can be made for implantable cardiac defibrillators. In that study, Spirito and Maron suggest that young patients with severe LVH are at the greatest risk. They based this conclusion on the observation that five of seven patients with severe hypertrophy who died suddenly were younger than 18 years. In our own cohort (data not presented), we saw no continuous relation between age and risk of sudden death, but when the cohort was separated into those younger and older than 18 years, we noted a significant association between age and sudden death. However, no patient, young or old, who died suddenly had a wall thickness of 30 mm or more in the absence of additional risk factors. Spirito and Maron suggest that our conclusion that patients with two or more risk factors should be considered for prophylactic therapy is unrealistically precise because of difficulties in the assessment of features such as syncope and family history. We acknowledge that the importance of the risk factors used for stratification may be influenced by other features such as age, haemodynamics, and family size, but simplifications must be accepted if numerical estimates are to be produced.3 We cannot be certain that the application of the same algorithm would have generated similar results in Spirito and Maron’s population, but the similarity in the headline annual survival rates between the two papers is reassuring. Although the heterogeneity of the disease means that final management decisions depend on careful con-
1975
1
2
3
4
5
Massei F, Massimetti M, Messina F, Macchia P, Maggiore G. Bartonella henselae and inflammatory bowel disease. Lancet 2000; 356: 1245–46. Anderson BE, Neuman MA. Bartonella spp as merging human pathogens. Clin Microbiol Rev 1997; 10: 203–19. Breitschwerdt EB, Kordick DL. Bartonella infection in animals: carriership, reservoir potential, pathogenicity, and zoonotic potential for human infection. Clin Microbiol Rev 2000; 13: 428–38. Zangwill KM, Hamilton DH, Perkins BA, et al. Cat scratch disease in Connecticut: epidemiology, risk factors and evaluation of a new diagnostic test. N Engl J Med 1993; 329: 8–13. Numazaki K, Ueno H, Yokoo K, Muramatsu Y, Chiba S, Morita C. Detection of serum antibodies to Bartonella henselae and Coxiella burnetii from Japanese children and pregnant women. Microb Infect (in press).
Sudden death and hypertrophic cardiomyopathy Sir—Perry Elliott and colleagues’ (Feb 10, p 420)1 analysis about the impact of magnitude of left-ventricular hypertrophy (LVH) on prognosis in hypertrophic cardiomyopathy, was apparently stimulated by our findings addressing risk stratification for sudden death.2 The investigators confirm several of our observations—the risk of sudden death in hypertrophic cardiomyopathy increases progressively with increasing wall thickness and is greatest with wall thickness of 30 mm or more.1-3 In ours and their studies, extreme LVH was more frequent in young patients with no or mild symptoms, rate of sudden death approached 20% at 10 years in Elliott and colleagues’ study and 40% at 20 years in our study, and patients with extreme hypertrophy accounted for about 25% of the sudden deaths in each study. Therefore, both studies establish extreme LVH as an unfavourable feature of hypertrophic cardiomopathy and a risk factor for sudden death. We also agree that many patients without extreme LVH die suddenly, as well as that more risk factors convey greater risk.3 However, we are uncomfortable with the conclusion that patients with extreme LVH and no additional risk factors have an excellent survival. Elliott and colleagues’ effort directed at achieving such precision in risk stratification (one vs two risk factors) in a disease as heterogeneous as hypertrophic cardiomyopathy is admirable but fraught with uncertainty and could result in undertreatment of patients at risk of sudden death. For example,
THE LANCET • Vol 357 • June 16, 2001
Elliott and colleagues arbitrarily defined family history of sudden death as a risk factor only if two or more such events occurred in relatives younger than 40 years. Syncope is a risk factor only when two or more episodes have occurred within the previous year. One sudden death in a close relative or one recent exertional syncope are thought sufficient to define risk by many experts. Non-sustained ventricular tachycardia on Holter (⭓3 beats) is effervescent in hypertrophic cardiomyopathy and absent in many young patients at high risk of sudden death.4 With use of this latter criterion, a patient with 35 mm wall thickness and ten ventricular couplets would be low risk, but the same patient with a single run of three ventricular beats would be high risk. Some flaws are implicit in the construction of a precise algorithm for risk stratification in a disease such as hypertrophic cardiomyopathy.4 Indeed, the strong conclusion that wall thickness of 30 mm or more without another risk factor never justifies implantation of a cardioverter defibrillator1 strikes us as stretching the precision of risk stratification, and ultimately the interpretation of these data. Effective therapy for prevention of sudden death has finally become available to patients.5 We are concerned that, as a consequence of Elliott and colleagues’ conclusions, some truly high-risk patients might be deprived of a lifesaving treatment. Unfortunately, the researchers make no recommendations about which patients with extreme LVH to offer preventive therapy. Many young patients with extreme wall thickness are probably at substantial long-term risk of sudden death and we recommend that they be informed of potential lifesaving protection afforded by an implantable defibrillator.5 *Paolo Spirito, Barry J Maron *Ospedaliero Ospedali Galliera, Genoa, Italy; and Minneapolis Heart Institute Foundation, Minneapolis, MN, USA
1
2
3
4
Elliott PM, Gimeno JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001; 357: 420–24. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy, and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000; 342: 1778–85. Elliott PM, Polonlecki J, Dickle S, et al. Sudden death in hypertrophic cardiornyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36: 2212–18. Spirito P, Seidman, CE, McKenna WJ, Maron BJ. The management of hypertrophic
5
cardiomyopathy. N Engl J Med 1997; 336: 775–85. Maron BJ, Shen W-K, Link MS, et al. Efficacy of implantable cardioverterdefibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000; 342: 365–73.
Authors’ reply Sir—The relatively low positive predictive value of most single risk markers in patients with hypertrophic cardiomyopathy means that they are not a definite indication for implantable cardiac defibrillators. Paulo Spirito and Barry Maron have confirmed1 previous cross-sectional data which shows that severe hypertrophy, defined as a wall thickness of 30 mm or more, is associated with an increase in the risk of sudden death.2 However, in their study and ours, fewer than 20% of patients with severe hypertrophy died suddenly, which suggests that further risk stratification is needed before automatic or routine recommendation can be made for implantable cardiac defibrillators. In that study, Spirito and Maron suggest that young patients with severe LVH are at the greatest risk. They based this conclusion on the observation that five of seven patients with severe hypertrophy who died suddenly were younger than 18 years. In our own cohort (data not presented), we saw no continuous relation between age and risk of sudden death, but when the cohort was separated into those younger and older than 18 years, we noted a significant association between age and sudden death. However, no patient, young or old, who died suddenly had a wall thickness of 30 mm or more in the absence of additional risk factors. Spirito and Maron suggest that our conclusion that patients with two or more risk factors should be considered for prophylactic therapy is unrealistically precise because of difficulties in the assessment of features such as syncope and family history. We acknowledge that the importance of the risk factors used for stratification may be influenced by other features such as age, haemodynamics, and family size, but simplifications must be accepted if numerical estimates are to be produced.3 We cannot be certain that the application of the same algorithm would have generated similar results in Spirito and Maron’s population, but the similarity in the headline annual survival rates between the two papers is reassuring. Although the heterogeneity of the disease means that final management decisions depend on careful con-
1975