To the Editor: Dec and Fuster (Dec. 8 issue)1 categorized theuse of beta-blockers in patients with idiopathic dilated cardiomyopathyas investigational. There is now sufficient evidence to supporttheir use as adjunctive therapy. Numerous clinical trials haveevaluated the use of beta-blockers in conjunction with angiotensin-converting–enzymeinhibitors, nitrates, diuretics, and digoxin in patients withidiopathic dilated cardiomyopathy and have found improvementsin ejection fraction, cardiac index, and New York Heart Associationclass and a decreased number of hospital admissions and cardiactransplantations.2,3,4 However, there have been trials5,6 thatdid not show such improvements. This is probably because patientswere not started on low doses with a slow upward titration,5,6the duration of the studies was short (e.g., one month),5,6the study sample was small,5 the patient populations were nothomogeneous (e.g., patients with ischemic dilated cardiomyopathy5or alcoholic cardiomyopathy6 were included), and beta-blockerswith intrinsic sympathomimetic activity were used (e.g., acebutolol).6
The authors reported that investigators in the Metoprolol inDilated Cardiomyopathy trial4 were unable to show an improvementin survival. Although this is true, it may be misleading. Sincecardiac transplantation is a well-recognized treatment for patientswith this disease, this trial compared the need for transplantationin patients on placebo with that of those taking metoprolol.Nineteen patients taking placebo underwent heart transplantation,as compared with only two patients taking metoprolol. This differencewas statistically significant. This trial also showed significantlyfewer hospital admissions for patients taking metoprolol.
Catherine E. Cooke, Pharm.D. Philadelphia College of Pharmacyand Science Philadelphia, PA 19104-4495
References
Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331:1564-1575. [Free Full Text]
Wisenbaugh T, Katz I, Davis J, et al. Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. J Am Coll Cardiol 1993;21:1094-1100.
Woodley SL, Gilbert EM, Anderson JL, et al. -Blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy. Circulation 1991;84:2426-2441. [Free Full Text]
Currie PJ, Kelly MJ, McKenzie A, et al. Oral beta-adrenergic blockade with metoprolol in chronic severe dilated cardiomyopathy. J Am Coll Cardiol 1984;3:203-209. [Abstract]
Ikram H, Fitzpatrick D. Double-blind trial of chronic oral beta blockade in congestive cardiomyopathy. Lancet 1981;2:490-493. [CrossRef][Medline]
To the Editor: Dec and Fuster provided a detailed discussionof both accepted and investigational therapies for idiopathicdilated cardiomyopathy. They failed, however, to address theimportant and expanding role of dynamic cardiomyoplasty in thetreatment of this disease. Originally described by Carpentierand Chachques1 some 10 years ago, cardiomyoplasty involves theuse of a skeletal-muscle flap, usually the left latissimus dorsi,which is wrapped around the heart and then electrically stimulatedto help augment myocardial contractility. Carpentier's group2followed 52 patients who had undergone cardiomyoplasty for severeheart failure, with idiopathic dilated cardiomyopathy beingthe primary cause in 13. There was improvement in functionalstatus in the long-term survivors, with a reduction in the meanNew York Heart Association class from 3.3 preoperatively to1.6 postoperatively. Associated with this was an improved exercisecapacity, a reduction in the number of annual hospitalizationsfrom 2.4 to 0.4, and a reduction in the need for medicationsin 62 percent of the patients. A significant decrease in latemortality was also noted, with actuarial survival of 70 percentat seven years (excluding early postoperative mortality). Studiesby other investigators have also consistently shown improvedfunctional status, decreased mortality, and an improved qualityof life, although whether there was long-term improvement inhemodynamic variables is less clear.3,4
Michael D. Greenberg, M.D. Georgetown University Medical Center Washington,DC 20007-2197
References
Carpentier A, Chachques JC. Myocardial substitution with a stimulated skeletal muscle: first successful clinical case. Lancet 1985;1:1267-1267. [Medline]
Carpentier A, Chachques JC, Acar C, et al. Dynamic cardiomyoplasty at seven years. J Thorac Cardiovasc Surg 1993;106:42-54. [Abstract]
Moreira LF, Bocchi EA, Stolf NA, Pileggi F, Jatene AD. Current expectations in dynamic cardiomyoplasty. Ann Thorac Surg 1993;55:299-303. [Abstract]
El Oakley RM, Jarvis JC. Cardiomyoplasty: a critical review of experimental and clinical results. Circulation 1994;90:2085-2090. [Free Full Text]
To the Editor: Dec and Fuster correctly noted that blacks inthe United States have a two- to threefold increase in the riskof idiopathic dilated cardiomyopathy after other factors aretaken into account.1 Two additional epidemiologic studies, witha case–control and a cohort design, have confirmed thepredominance of idiopathic dilated cardiomyopathy among blacks.2,3
It should also be noted, however, that black patients with idiopathicdilated cardiomyopathy may be substantially more likely to diein the first two years after diagnosis than white patients,even after other prognostic factors are taken into account.4The apparently poorer survival among blacks may be explainedby greater severity of disease at the time of diagnosis, decreasedcompliance with treatment regimens, or racial differences incardiac care, coexisting conditions, or biologic factors affectingsurvival.
Steven S. Coughlin, Ph.D. Tulane University Medical Center NewOrleans, LA 70112-2699
References
Coughlin SS, Szklo M, Baughman K, Pearson TA. The epidemiology of idiopathic dilated cardiomyopathy in a biracial community. Am J Epidemiol 1990;131:48-56. [Free Full Text]
Coughlin SS, Neaton JD, Sengupta A, Kuller LH. Predictors of mortality from idiopathic dilated cardiomyopathy in 356,222 men screened for the Multiple Risk Factor Intervention Trial. Am J Epidemiol 1994;139:166-172. [Free Full Text]
Coughlin SS, Gottdiener JS, Baughman KL. Black-white differences in mortality in idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study. J Natl Med Assoc 1994;86:583-591. [Medline]
To the Editor: Dec and Fuster omitted reference to the importantclinical entity of reversible left ventricular dysfunction dueto chronic tachycardia.1
The first series of patients with tachycardia-induced left ventriculardysfunction was described by Phillips and Levine.2 They concludedthat "auricular fibrillation per se may produce cardiac dilationand progressive congestive heart failure . . . a truly reversibletype of heart failure." Subsequent series have demonstratedconvincingly that atrial fibrillation with a rapid ventricularresponse may be the primary cause rather than the consequenceof dilated cardiomyopathy. Furthermore, the left ventriculardysfunction may be completely reversible with control of theheart rate.3 The mechanisms of tachycardia-induced cardiomyopathyare uncertain, but theories include the depletion of phosphateenergy stores, activation of the renin–angiotensin andsympathetic nervous systems, and myocardial ischemia.3,4
The above opinion expressed in this letter represents that ofthe author and not the Department of the Air Force.
Kenneth Mishark, M.D., Maj., M.C., U.S.A.F. David Grant U.S.Air Force Medical Center Travis Air Force Base, CA 94535
References
Packer DL, Bardy GH, Worley SJ, et al. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol 1986;57:563-570. [CrossRef][Medline]
Phillips E, Levine SA. Auricular fibrillation without other evidence of heart disease: a cause of reversible heart failure. Am J Med 1949;7:478-489. [CrossRef][Medline]
Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992;69:1570-1573. [CrossRef][Medline]
Armstrong PW, Stopps TP, Ford SE, de Bold AJ. Rapid ventricular pacing in the dog: pathophysiologic studies of heart failure. Circulation 1986;74:1075-1084. [Free Full Text]
To the Editor: In their review of dilated cardiomyopathy, Decand Fuster discussed familial (or genetic) cases. Among themodes of inheritance they mentioned was "mitochondrial inheritance"in patients with multiple deletions in the mitochondrial genome.We think the use of this term to refer to such patients is inappropriate.1It is a substitute for the term "cytoplasmic or maternal inheritance,"which is generally used to describe transmission by means ofthe mitochondrial genome. Though point mutations in the mitochondrialgene are, in general, maternally transmitted,2 diseases associatedwith deletions and insertions of mitochondrial DNA, such asthose found in chronic progressive external ophthalmoplegia,are either sporadic in nature or, in cases with multiple deletions,a result of autosomal dominant inheritance.3 Since all the mitochondrial-DNAreplication enzymes are encoded by the nucleus, proteins encodedby nuclear DNA are suspected of causing these abnormalities.
Masato Odawara, M.D. Kamejiro Yamashita, M.D. University ofTsukuba Tsukuba, Ibaraki, 305 Japan
References
Suomalainen A, Paetau A, Leinonen H, Majander A, Peltonen L, Somer H. Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA. Lancet 1992;340:1319-1320. [CrossRef][Medline]
Kadowaki T, Kadowaki H, Mori Y, et al. A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med 1994;330:962-968. [Free Full Text]
Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S. An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 1989;339:309-311. [CrossRef][Medline]
To the Editor: In Table 1 of their article on idiopathic dilatedcardiomyopathy, Dec and Fuster list the known causes of dilatedcardiomyopathy. The table lists doxorubicin and bleomycin asthe chemotherapeutic agents known to cause dilated cardiomyopathy.Although doxorubicin is a well-known cause of cardiomyopathy,bleomycin is not known to cause any clinical cardiac toxicity.The only known organ toxicity of bleomycin is pulmonary toxicity,resulting in lung fibrosis. Mitoxantrone (Novantrone) is anotherchemotherapeutic agent (which should have been listed instead)known to cause cardiomyopathy, although it is clearly less cardiotoxicthan doxorubicin and rarely produces dilated cardiomyopathywhen used alone.
Sewa S. Legha, M.D. University of Texas M.D. Anderson CancerCenter Houston, TX 77030
The authors reply:
To the Editor: Dr. Mishark has correctly pointed out that chronicrapid atrial fibrillation may occasionally result in a dilatedcardiomyopathy that is reversible with adequate rate control.Our experience, as well as a review of the published literature,1suggests that this is an extremely uncommon event.
Dr. Legha has correctly pointed out that bleomycin was erroneouslyincluded in Table 1 of our article. Cyclophosphamide and mitoxantroneshould have been included as cardiotoxic agents.
Dr. Coughlin has made important contributions to our understandingof the racial differences in the incidence of idiopathic dilatedcardiomyopathy. We agree with his observation that black patientshave not only a greater likelihood of idiopathic dilated cardiomyopathy,but also a poorer survival than whites. It is our suspicionthat these apparent differences in survival are explainableon the basis of more advanced disease at the time of presentationrather than an underlying biologic difference in response totherapy or the rate of disease progression.
Drs. Odawara and Yamashita have correctly stated that multipledeletions in mitochondrial DNA have been seen in both familialand sporadic cases of idiopathic dilated cardiomyopathy.2 Disease-specificpoint mutations have been reported in fatal infantile cardiomyopathyand maternally inherited myopathy–cardiomyopathy.3 Bothmaternal and autosomal patterns of inheritance have been suggested.Whether these mitochondrial abnormalities produce a dilatedcardiomyopathy directly or are simply associated with otheryet-to-be-defined mutations in nuclear DNA is uncertain.
More effective treatments are certainly needed for patientswith idiopathic dilated cardiomyopathy and symptoms of advancedheart failure. We disagree with Dr. Cooke that beta-adrenergicblockers should no longer be considered investigational therapy.Her analysis of the Metoprolol in Dilated Cardiomyopathy trialis erroneous. This carefully designed trial failed to detecta survival benefit of metoprolol. The suggestion that metoprololmay have decreased the need for cardiac transplantation failsto recognize that the timing of transplantation is dictatedby the availability of donor hearts and a patient's positionon the waiting list rather than on the severity of disease.Doughty et al. have provided a recent detailed review of boththe benefits and risks of this form of adjunctive therapy.4Although we agree with Dr. Greenberg's assessment that the roleof dynamic cardioplasty is expanding, we believe that his representationof the experience of Dr. Carpentier and colleagues with thistechnique5 is overly optimistic. Their report of a 70 percentrate of actuarial survival at seven years is misleading, sinceit excluded 23 percent of the patients who died in the earlyperioperative period. Current recommendations limit its useto patients with New York Heart Association class 3 heart failurerather than those with more advanced symptoms. It is well recognizedthat medical therapy for this degree of heart failure may oftenameliorate symptoms and produce long-term survival rates thatequal or exceed those of cardiomyoplasty. Although cardiomyoplastyis now available in Europe, the Food and Drug Administrationhas mandated that a prospective, randomized study be undertakento determine its safety and efficacy.
Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992;69:1570-1573.
Suomalainen A, Paetau A, Leinonen H, Majander A, Peltonen L, Somer H. Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA. Lancet 1992;340:1319-1320.
Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet 1993;342:1441-1446. [CrossRef][Medline]
Doughty RN, MacMahon S, Sharpe N. Beta-blockers in heart failure: promising or proved? J Am Coll Cardiol 1994;23:814-821. [Abstract]
Carpentier A, Chachques JC, Acar C, et al. Dynamic cardioplasty at seven years. J Thorac Cardiovasc Surg 1993;106:42-54.
Correction
to
Dec and Fuster, 
-Blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy. Circulation 1991;84:2426-2441. 
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