Underlying Causes and Long-Term Survival in Patients with Initially Unexplained Cardiomyopathy
G. Michael Felker, M.D., Richard E. Thompson, Ph.D., Joshua M. Hare, M.D., Ralph H. Hruban, M.D., Diedre E. Clemetson, David L. Howard, Kenneth L. Baughman, M.D., and Edward K. Kasper, M.D.
Background Previous studies of the prognosis of patients withheart failure due to cardiomyopathy categorized patients accordingto whether they had ischemic or nonischemic disease. The prognosticvalue of identifying more specific underlying causes of cardiomyopathyis unknown.
Methods We evaluated the outcomes of 1230 patients with cardiomyopathy.The patients were grouped into the following categories accordingto underlying cause: idiopathic cardiomyopathy (616 patients);peripartum cardiomyopathy (51); and cardiomyopathy due to myocarditis(111), ischemic heart disease (91), infiltrative myocardialdisease (59), hypertension (49), human immunodeficiency virus(HIV) infection (45), connective-tissue disease (39), substanceabuse (37), therapy with doxorubicin (15), and other causes(117). Cox proportional-hazards analysis was used to assessthe association between the underlying cause of cardiomyopathyand survival.
Results During a mean follow-up of 4.4 years, 417 patients diedand 57 underwent cardiac transplantation. As compared with thepatients with idiopathic cardiomyopathy, the patients with peripartumcardiomyopathy had better survival (adjusted hazard ratio fordeath, 0.31; 95 percent confidence interval, 0.09 to 0.98),and survival was significantly worse among the patients withcardiomyopathy due to infiltrative myocardial disease (adjustedhazard ratio, 4.40; 95 percent confidence interval, 3.04 to6.39), HIV infection (adjusted hazard ratio, 5.86; 95 percentconfidence interval, 3.92 to 8.77), therapy with doxorubicin(adjusted hazard ratio, 3.46; 95 percent confidence interval,1.67 to 7.18), and ischemic heart disease (adjusted hazard ratio,1.52; 95 percent confidence interval, 1.07 to 2.17).
Conclusions The underlying cause of heart failure has prognosticvalue in patients with unexplained cardiomyopathy. Patientswith peripartum cardiomyopathy appear to have a better prognosisthan those with other forms of cardiomyopathy. Patients withcardiomyopathy due to infiltrative myocardial diseases, HIVinfection, or doxorubicin therapy have an especially poor prognosis.
Despite advances in drug therapy, the prognosis of patientswith heart failure remains poor.1 The accurate assessment ofprognosis in patients with this disorder is critical, to ensurethat patients with the most severe disease receive appropriateconsideration for the limited number of hearts available fortransplantation. Although substantial research has demonstratedthe prognostic value of a variety of clinical characteristicsin patients with heart failure,2,3,4,5 few data are availableon the association between the cause of cardiomyopathy and thelong-term prognosis.6,7 Previous studies addressing the influenceof the underlying cause on prognosis have generally comparedpatients with ischemic heart disease and those with nonischemiccauses of heart failure. Although it is possible to identifya more specific cause in a substantial percentage of patientswith nonischemic cardiomyopathy,8 consensus recommendationssuggest that the underlying cause is clinically important inonly a few cases.9,10 Definitive data on the long-term prognosisof many uncommon forms of cardiomyopathy are limited. We undertookthis study to determine the prognosis associated with cardiomyopathyof different causes, as defined by an exhaustive diagnosticevaluation performed at a tertiary care center with expertisein the diagnosis and treatment of cardiomyopathy.
Methods
Selection of Patients
Between December 1982 and December 1997, 1230 patients underwentendomyocardial biopsy as part of an evaluation for heart failuredue to unexplained cardiomyopathy. The majority of these patientswere referred by other physicians, and thus some common buteasily identified causes of heart failure, such as ischemicheart disease, hypertension, and valvular heart disease, wereunderrepresented. In addition to endomyocardial biopsy, allthe patients underwent a careful history taking and physicalexamination; selected laboratory studies, including thyroid-functiontesting and measurement of antinuclear antibodies; and right-heartcatheterization. All patients with a history suggestive of ischemicheart disease or at least two standard risk factors for atherosclerosisunderwent coronary angiography. We recently reported detailedclinical characteristics of this cohort of patients and thesafety of endomyocardial biopsy in this cohort.11 The studywas approved by the Joint Committee on Clinical Investigationat Johns Hopkins Hospital. Oral informed consent to includetheir data in the study was obtained from the patients.
Endomyocardial Biopsy
All the patients underwent endomyocardial biopsy and right-heartcatheterization in a standardized manner, as previously described.11Specimens were examined at a minimum of four section levelsby an experienced cardiac pathologist. Staining with Congo redto identify amyloidosis and with Prussian blue to identify hemochromatosiswas performed when appropriate.
Cause of Cardiomyopathy
All patients were prospectively assigned an underlying causeof cardiomyopathy at the completion of the clinical evaluation,according to previously published definitions.8,11 The diagnosticclassification was based on the recommendations of the WorldHealth Organization–International Society and Federationof Cardiology Task Force for the classification of cardiomyopathy,as originally defined in 1980 and as modified in 1996.12,13In patients for whom there was more than one potential causeof heart failure, the single most likely cause was chosen. Finaldiagnoses were assigned without knowledge of the patients' statuswith respect to long-term survival or cardiac transplantation.For the purposes of analysis, patients were assigned to oneof the following categories according to the underlying causeof the cardiomyopathy: idiopathic cardiomyopathy; peripartumcardiomyopathy; or cardiomyopathy due to ischemic heart disease,infiltrative myocardial disease (i.e., amyloidosis, hemochromatosis,or sarcoidosis), myocarditis, substance abuse (i.e., cocaineor alcohol abuse), connective-tissue disease, infection withthe human immunodeficiency virus (HIV), hypertension, therapywith doxorubicin, or other causes.
Follow-Up
Information on the vital status of the patients was obtainedfrom clinical records and through a search of the National DeathIndex.14 The status of the patients with respect to cardiactransplantation was obtained from their clinical records.
Statistical Analysis
Comparisons among groups were made with the use of Student'st-test for continuous variables and the chi-square test forcategorical variables. Since many of the patients in this studywould have been classified as having idiopathic cardiomyopathyif they had not undergone a rigorous diagnostic evaluation,each diagnostic group was compared with the group of patientswith idiopathic cardiomyopathy (the reference group). The primaryend point was death from all causes. Data on patients who underwentcardiac transplantation were censored at the time of transplantation.Survival curves were constructed according to the method ofKaplan and Meier. Multivariate Cox proportional-hazards modelingwas used to adjust for demographic and hemodynamic variables.The following prespecified variables were tested in the multivariatemodel: cause of cardiomyopathy, age, sex, race, heart rate,pulse pressure, cardiac index, pulmonary-artery systolic bloodpressure, and pulmonary-capillary wedge pressure. A two-sidedP value of less than 0.05 was considered to indicate statisticalsignificance.
Results
Causes of Cardiomyopathy
A specific cause of cardiomyopathy was identified in 614 ofthe 1230 patients (50 percent). The remaining 616 patients wereclassified as having idiopathic cardiomyopathy despite havingundergone a comprehensive clinical evaluation. Endomyocardialbiopsy provided a specific histologic diagnosis in 188 patients(15 percent). Specific diagnoses for all 1230 patients are shownin Table 1. The complication rate of endomyocardial biopsy was8 percent, and there were two procedure-related deaths (0.2percent).
Table 1. Final Diagnoses in 1230 Patients with Initially Unexplained Cardiomyopathy.
Characteristics of the Patients
The clinical and hemodynamic characteristics of the patients,according to the cause of cardiomyopathy, are shown in Table 2.There was substantial heterogeneity among the groups withregard to age, sex, and severity of hemodynamic compromise.The mean age of the study cohort at the time of diagnosis was48 years. The patients with cardiomyopathy due to ischemic heartdisease and those with cardiomyopathy due to infiltrative myocardialdisease were significantly older than those with idiopathiccardiomyopathy, whereas the patients with HIV infection, myocarditis,substance abuse, or peripartum cardiomyopathy were younger.
Table 2. Clinical and Hemodynamic Characteristics According to Cause of Cardiomyopathy.
Association between Cause and Outcome
During a mean follow-up period of 4.4 years, 417 patients diedand 57 underwent cardiac transplantation. Unadjusted and adjustedhazard ratios for each etiologic group, as compared with thegroup with idiopathic cardiomyopathy (in which the hazard ratiofor death was 1.0, by definition), are provided in Table 3.In the unadjusted analysis, survival was substantially betteramong the patients with peripartum cardiomyopathy than amongthose with idiopathic cardiomyopathy (hazard ratio for death,0.14; 95 percent confidence interval, 0.05 to 0.44; P=0.001).In contrast, survival was significantly worse among the patientswith cardiomyopathy due to infiltrative myocardial diseases(hazard ratio, 4.79; 95 percent confidence interval, 3.36 to6.81; P<0.001), HIV infection (hazard ratio, 4.00; 95 percentconfidence interval, 2.80 to 5.74; P<0.001), therapy withdoxorubicin (hazard ratio, 2.64; 95 percent confidence interval,1.35 to 5.17; P=0.005), and ischemic heart disease (hazard ratio,2.01; 95 percent confidence interval, 1.46 to 2.77; P<0.001).Survival among the patients with cardiomyopathy due to myocarditis,substance abuse, hypertension, connective-tissue disease, orother causes did not differ significantly from that among patientswith idiopathic cardiomyopathy.
Table 3. Association between Clinical Variables and Survival.
To adjust for differences between groups, we performed multipleCox proportional-hazards analyses. The inclusion of age, sex,race, and hemodynamic variables with underlying cause in a multivariatemodel did not substantively alter the association between causeand prognosis. Adjusted estimates of survival for the groupsthat were significantly different from the group with idiopathiccardiomyopathy are shown in Figure 1. Older age (hazard ratiofor death associated with each additional decade of life, 1.20;95 percent confidence interval, 1.10 to 1.30; P<0.001) andmale sex (hazard ratio, 1.26; 95 percent confidence interval,1.00 to 1.60; P=0.05) were associated with worse survival thanyounger age and female sex (Table 3). After the inclusion ofprespecified hemodynamic variables in the multivariate model,a previous trend toward worse survival in patients with cardiomyopathydue to connective-tissue disease reached statistical significance(adjusted hazard ratio for death, 1.75; 95 percent confidenceinterval, 1.02 to 3.01; P=0.04). As shown in Table 3, the followingvariables were independently associated with survival in a multivariatemodel: cause (with the exception of hypertension, myocarditis,other causes, and substance abuse), age, sex, pulse pressure,and pulmonary-artery systolic pressure.
Figure 1. Adjusted Kaplan–Meier Estimates of Survival According to the Underlying Cause of Cardiomyopathy.
Only idiopathic cardiomyopathy and cardiomyopathy due to causes for which survival was significantly different from that in patients with idiopathic cardiomyopathy are shown.
Several alternative analyses were performed to test the validityof these results. To confirm the results in the group with peripartumcardiomyopathy, we repeated the multivariate analysis with ageconsidered as a categorical variable in 10-year increments ratherthan as a continuous variable. In this analysis, the improvedsurvival in the group with peripartum cardiomyopathy persisted(adjusted hazard ratio, 0.28; 95 percent confidence interval,0.08 to 0.91; P=0.04). To evaluate the potential effect of improvementsin medical therapy for heart failure over time, the multivariateanalysis was repeated with the inclusion of the calendar yearof diagnosis, in five-year increments. This analysis revealeda trend toward improved survival over time (adjusted hazardratio as compared with diagnosis in 1983 to 1987: diagnosisin 1988 to 1992, 0.88; and diagnosis in 1993 to 1997, 0.81)that did not reach statistical significance.
To assess the effect of cardiac transplantation, we reanalyzedthe data using the combined end point of death or cardiac transplantation.In this alternative analysis, the associations between specificcauses of cardiomyopathy and prognosis were unchanged, withthe exception that cardiomyopathy due to connective-tissue diseasewas no longer significant (adjusted hazard ratio for death ortransplantation, 1.44; 95 percent confidence interval, 0.84to 2.27; P=0.18). Multivariate modeling in which transplantation-freesurvival was used as an end point produced results that weresimilar to those of the analysis of absolute survival, withcause (with the exception of hypertension, myocarditis, ischemicheart disease, other causes, and substance abuse), age, sex,pulse pressure, and pulmonary-artery systolic blood pressureremaining as independent predictors of survival.
Analysis of Cardiomyopathy Due to Infiltrative Myocardial Disease
Because the group with cardiomyopathy due to infiltrative myocardialdisease was composed of patients with three distinct histologicdiagnoses (amyloidosis, hemochromatosis, and sarcoidosis), eachof these causes was analyzed separately. After adjustments weremade for demographic and hemodynamic variables, survival wasfound to be markedly worse among the patients with amyloidosis(adjusted hazard ratio for death, 7.41; 95 percent confidenceinterval, 4.45 to 12.33; P<0.001) or hemochromatosis (adjustedhazard ratio, 8.88; 95 percent confidence interval, 3.64 to21.65; P<0.001) than among those with idiopathic cardiomyopathy.The prognosis in patients with sarcoidosis was not significantlydifferent from that in the patients with idiopathic cardiomyopathy(adjusted hazard ratio, 1.72; 95 percent confidence interval,0.69 to 4.27; P=0.24). The adjusted survival curves for thepatients with cardiomyopathy due to infiltrative myocardialdisease are shown in Figure 2.
Figure 2. Adjusted Kaplan–Meier Estimates of Survival among Patients with Cardiomyopathy Due to Amyloidosis, Sarcoidosis, or Hemochromatosis, as Compared with That among Patients with Idiopathic Cardiomyopathy.
Discussion
This study examined the association between the specific causeof cardiomyopathy and long-term survival in a large group ofpatients evaluated at a single tertiary care center with expertisein the diagnosis and treatment of cardiomyopathy. The patientswith peripartum cardiomyopathy had the best prognosis of anysubgroup and were the only group to have a significantly betterrate of survival than the patients with idiopathic cardiomyopathy.As compared with the patients with idiopathic cardiomyopathy,the patients with cardiomyopathy due to infiltrative myocardialdisease, HIV infection, therapy with doxorubicin, or ischemicheart disease had significantly worse survival in the unadjustedanalysis. After multivariate adjustment, the patients with cardiomyopathydue to connective-tissue disease also had significantly worsesurvival. We did not find a significant difference in survivalbetween the patients with idiopathic cardiomyopathy and thosewith cardiomyopathy due to myocarditis, hypertension, substanceabuse, or other causes.
In our study, the patients with peripartum cardiomyopathy hada substantially better prognosis than those with other causesof heart failure, with a 94 percent survival rate at five years.Peripartum cardiomyopathy is, by definition, a disease thataffects young women, and the mean age of the patients with thisdiagnosis was substantially younger than that of the patientswith idiopathic cardiomyopathy (29 years as compared with 49years). Even after adjustments were made for differences inage and sex, however, the prognosis among the patients withperipartum cardiomyopathy remained better than that of the othergroups. In addition, a substantial portion of the patients withperipartum cardiomyopathy (26 of 51 patients) had histologicevidence of myocarditis on endomyocardial biopsy. These findingsare in contrast to those of previous studies, which generallydescribed poor outcomes and a low incidence of myocarditis inpatients with peripartum cardiomyopathy.15,16 The stricter diagnosticdefinition of peripartum cardiomyopathy used in our study mayaccount for the difference in results.
The worst prognosis was in the group with cardiomyopathy dueto infiltrative myocardial disease, which included patientswith cardiac amyloidosis, sarcoidosis, or hemochromatosis. Furtheranalysis of this subgroup indicated extremely poor long-termsurvival among the patients with amyloidosis and hemochromatosis,with one-year survival rates of 29 percent and 44 percent, respectively.Poor survival in patients with cardiac amyloidosis has beenreported previously.17 In contrast, the patients in our studywho had cardiac sarcoidosis had a prognosis similar to thatof the patients with idiopathic cardiomyopathy, with a one-yearsurvival rate of 77 percent. The natural history of cardiacsarcoidosis thus appears to be markedly different from thatof giant-cell myocarditis, a rare disorder that may be confusedwith sarcoidosis on histologic examination. Recently publisheddata confirm the extremely poor prognosis of patients with giant-cellmyocarditis, who have a one-year survival rate of less than40 percent.18
High mortality among patients with amyloidosis, hemochromatosis,HIV infection, or doxorubicin cardiotoxicity can be partiallyattributed to noncardiac causes, since each of these disordersmay be associated with decreased long-term survival independentlyof the diagnosis of cardiomyopathy. Improvements in specifictherapies for both HIV infection and cancer, however, may makethe cardiomyopathy that is associated with these conditionsmore prevalent as patients survive longer with their primaryillness. Regardless of the cause of death, these data demonstratethe extremely poor prognosis associated with cardiomyopathydue to these disorders and the potential prognostic value ofidentifying a specific cause of heart failure in patients whopresent with unexplained cardiomyopathy.
Ischemic as Compared with Nonischemic Cardiomyopathy
In this study, survival was worse among the patients with cardiomyopathydue to ischemic heart disease than among those with idiopathiccardiomyopathy. This finding is consistent with the resultsof most previous studies, which have demonstrated a worse prognosisin patients with ischemic cardiomyopathy than in those withother causes of heart failure.2,7,19,20 In addition, in theplacebo groups of several large trials of therapy for heartfailure, higher mortality has been found among patients withan ischemic cause of heart failure than among patients witha nonischemic cause.21,22,23 These findings contrast, however,with those of the community-based Framingham Heart Study, whichfound worse long-term survival among patients with nonischemiccauses of heart failure.6 In our study, hemodynamic compromisewas greater in the patients with cardiomyopathy due to ischemicheart disease than in those with idiopathic cardiomyopathy,suggesting that the patients with ischemic heart disease mayhave had more advanced heart failure at the time of evaluation.
Even after adjustments were made for demographic and hemodynamicvariables, however, survival was worse among patients with cardiomyopathydue to ischemic heart disease. Because so many of the patientswith easily identifiable causes of heart failure, such as ischemicdisease and hypertension, were not referred to our study, patientswith such causes were underrepresented in our cohort, as comparedwith a general population of patients with heart failure. Thepatients in our study with cardiomyopathy due to ischemic heartdisease may therefore have differed from those seen in a communitysetting. Still, our findings support the general conclusionthat patients with cardiomyopathy due to ischemic heart diseasehave a worse prognosis than do patients with nonischemic causesof cardiomyopathy.
Previous Studies of Cause and Prognosis
Previous studies that have addressed the prognostic importanceof the underlying cause of cardiomyopathy have generally categorizedpatients according to whether they had ischemic or nonischemiccauses of heart failure. The lack of specific information aboutthe cause of heart failure in patients with cardiomyopathy dueto nonischemic causes is a limitation of such studies. Our studydiffers from others in that we performed an exhaustive clinicalevaluation of each patient, including endomyocardial biopsy,in order to identify the cause of cardiomyopathy as preciselyas possible. Our study also included a much more heterogeneouspopulation of patients with regard to cause of cardiomyopathythan did either the Framingham Study6 or the Studies of LeftVentricular Dysfunction (SOLVD) registry.19 Because of the largesize of the study cohort and the fact that all the patientshad been referred to our center, we were able to provide dataon long-term survival in patients with cardiomyopathy due tomany relatively rare nonischemic causes; such patients are oftenexcluded from randomized trials of therapy for heart failure.
The proportions of both women and members of minority groupswere higher in our series than in many previous studies of heartfailure. Forty percent of the patients in our study were women,and 34 percent were black, as compared with 26 percent and 12percent, respectively, in the SOLVD registry.19 When consideredalong with cause, age, and race, sex was an independent predictorof prognosis in this cohort, with men having worse survivalthan women. This trend persisted (P=0.05) after additional adjustmentfor hemodynamic variables. These findings are in general agreementwith epidemiologic data from the Framingham Study and the firstNational Health and Nutrition Examination Survey (NHANES I),which demonstrated better prognosis among women with heart failurethan among men.1,6 Work by Adams and colleagues suggested thatthese sex differences are most pronounced among patients withnonischemic causes of heart failure.7,24 The results of ourstudy in a cohort of patients with primarily nonischemic cardiomyopathylend further support to this finding.
Limitations of the Study
The applicability of our results to the general population ofpatients with heart failure is limited by the referral natureof this cohort. Patients with some common causes of cardiomyopathywere not referred for an exhaustive evaluation, including endomyocardialbiopsy, and thus were underrepresented in our cohort. In addition,data on the cause of death of the patients were not obtained,and we were therefore unable to differentiate between deathsdue to cardiac causes and other deaths. Clearly, survival amongpatients with cardiomyopathy due to HIV infection, infiltrativemyocardial disease, or doxorubicin therapy may be limited bythe primary illness. Drug therapy for heart failure was notcontrolled for during this study, so we are unable to speculateon the extent to which differences in therapy for heart failuremay have affected our results, although a trend toward improvedsurvival was seen in patients who received a diagnosis morerecently, as compared with those who received a diagnosis earlier.Because of the methods used to establish vital status, it ispossible that some patients who were lost to clinical follow-upmay have been classified incorrectly as long-term survivorsif they were not identified during a search of the NationalDeath Index. The accuracy of the National Death Index has beenexternally validated, but up to 5 percent of persons who havedied may be missing, particularly women and members of minoritygroups.25
Conclusions
Our study demonstrates that the underlying cause of heart failureis independently associated with survival among patients withcertain types of cardiomyopathy. Whereas peripartum cardiomyopathyhad a better long-term prognosis than idiopathic cardiomyopathy,cardiomyopathy due to infiltrative diseases of the myocardium,HIV infection, doxorubicin therapy, ischemic heart disease,and connective-tissue disease were associated with worse survival.Among patients with cardiomyopathy due to infiltrative myocardialdisease, those with amyloidosis or hemochromatosis had the worstprognosis, whereas patients with sarcoidosis had a prognosissimilar to that of patients with idiopathic cardiomyopathy.As in previous studies, older age and male sex were associatedwith a worse prognosis than younger age and female sex.
We conclude that the identification of the underlying causeof heart failure, beyond the differentiation between ischemicand nonischemic causes, has prognostic importance, primarilyfor patients with peripartum cardiomyopathy and those with cardiomyopathydue to infiltrative myocardial disease, doxorubicin therapy,or HIV infection. The evaluation of patients with unexplainedcardiomyopathy should include a careful search for a specificcause, and the referral of patients to a tertiary care centermay facilitate the accurate assessment of prognosis. Furtherunderstanding of the prognostic and therapeutic importance ofthe specific cause of cardiomyopathy may aid in tailoring availabletherapies to individual patients.
We are indebted to Dr. Gary Gerstenblith and Dr. Scott Zegerfor their critical review of the manuscript.
Source Information
From the Division of Cardiology, Department of Medicine (G.M.F., J.M.H., D.E.C., D.L.H., K.L.B., E.K.K.), and the Department of Pathology (R.H.H.), Johns Hopkins University School of Medicine; and the Department of Biostatistics, Johns Hopkins School of Public Health and Hygiene (R.E.T.) — both in Baltimore.
Address reprint requests to Dr. Kasper at the Division of Cardiology, Johns Hopkins Hospital, Carnegie 568, 600 N. Wolfe St., Baltimore, MD 21287-6568, or at ekasper{at}jhmi.edu.
References
Schocken DD, Arrieta MI, Leaverton PE, Ross EA. Prevalence and mortality rate of congestive heart failure in the United States. J Am Coll Cardiol 1992;20:301-306. [Abstract]
Likoff MJ, Chandler SL, Kay HR. Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am J Cardiol 1987;59:634-638. [CrossRef][Medline]
Cohn JN, Rector TS. Prognosis of congestive heart failure and predictors of mortality. Am J Cardiol 1988;62:25A-30A. [CrossRef][Medline]
Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Jr, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991;83:778-786. [Free Full Text]
Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819-823. [Abstract]
Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993;88:107-115. [Free Full Text]
Adams KF Jr, Dunlap SH, Sueta CA, et al. Relation between gender, etiology and survival in patients with symptomatic heart failure. J Am Coll Cardiol 1996;28:1781-1788. [Abstract]
Kasper EK, Agema WR, Hutchins GM, Deckers JW, Hare JM, Baughman KL. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol 1994;23:586-590. [Abstract]
Guidelines for the evaluation and management of heart failure: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation 1995;92:2764-2784. [Free Full Text]
Consensus recommendations for the management of chronic heart failure: on behalf of the membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol 1999;83:Suppl2A:1A-38A. [CrossRef][Medline]
Felker GM, Hu W, Hare JM, Hruban RH, Baughman KL, Kasper EK. The spectrum of dilated cardiomyopathy: the Johns Hopkins experience with 1,278 patients. Medicine (Baltimore) 1999;78:270-283. [CrossRef][Medline]
Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. Br Heart J 1980;44:672-673. [Free Full Text]
Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 1996;93:841-842. [Free Full Text]
Bilgrad R. National Death Index user's manual. Rev. ed. Hyattsville, Md.: National Center for Health Statistics, February 1995.
Demakis JG, Rahimtoola SH, Sutton GC, et al. Natural course of peripartum cardiomyopathy. Circulation 1971;44:1053-1061. [Free Full Text]
Homans DC. Peripartum cardiomyopathy. N Engl J Med 1985;312:1432-1437. [Medline]
Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995;32:45-59. [Medline]
Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis -- natural history and treatment. N Engl J Med 1997;336:1860-1866. [Free Full Text]
Bourassa MG, Gurne O, Bangdiwala SI, et al. Natural history and patterns of current practice in heart failure. J Am Coll Cardiol 1993;22:Suppl A:14A-19A.
Franciosa JA, Wilen M, Ziesche S, Cohn JN. Survival in men with severe chronic left ventricular failure due to either coronary heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol 1983;51:831-836. [CrossRef][Medline]
Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study. N Engl J Med 1986;314:1547-1552. [Abstract]
Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996;335:1107-1114. [Free Full Text]
Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA 1995;273:1450-1456. [Erratum, JAMA 1995;274:462.]
Adams KF Jr, Sueta CA, Gheorghiade M, et al. Gender differences in survival in advanced heart failure: insights from the FIRST study. Circulation 1999;99:1816-1821. [Free Full Text]
Boyle CA, Decoufle P. National sources of vital status information: extent of coverage and possible selectivity in reporting. Am J Epidemiol 1990;131:160-168. [Free Full Text]
Chen, L., Gong, Q., Stice, J. P., Knowlton, A. A.
(2009). Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc Res
84: 91-99
[Abstract][Full Text]
Brauch, K. M., Karst, M. L., Herron, K. J., de Andrade, M., Pellikka, P. A., Rodeheffer, R. J., Michels, V. V., Olson, T. M.
(2009). Mutations in ribonucleic Acid binding protein gene cause familial dilated cardiomyopathy.. J Am Coll Cardiol
54: 930-941
[Abstract][Full Text]
Cresci, S., Kelly, R. J., Cappola, T. P., Diwan, A., Dries, D., Kardia, S. L.R., Dorn, G. W. II
(2009). Clinical and genetic modifiers of long-term survival in heart failure.. J Am Coll Cardiol
54: 432-444
[Abstract][Full Text]
Medi, C., Kalman, J. M., Haqqani, H., Vohra, J. K., Morton, J. B., Sparks, P. B., Kistler, P. M.
(2009). Tachycardia-mediated cardiomyopathy secondary to focal atrial tachycardia: long-term outcome after catheter ablation.. J Am Coll Cardiol
53: 1791-1797
[Abstract][Full Text]
RAMARAJ, R., SORRELL, V. L.
(2009). Peripartum cardiomyopathy: Causes, diagnosis, and treatment. Cleveland Clinic Journal of Medicine
76: 289-296
[Abstract][Full Text]
Yumino, D, Wang, H, Floras, J S, Newton, G E, Mak, S, Ruttanaumpawan, P, Parker, J D, Bradley, T D
(2009). Relationship between sleep apnoea and mortality in patients with ischaemic heart failure. Heart
95: 819-824
[Abstract][Full Text]
Chrustowicz, A., Simonis, G., Matschke, K., Strasser, R. H., Gackowski, A.
(2009). Right ventricular dilatation predicts survival after mitral valve repair in patients with impaired left ventricular systolic function. Eur J Echocardiogr
10: 309-313
[Abstract][Full Text]
de Jong, J. S.S.G., Rietveld, K., van Lochem, L. T., Bouma, B. J.
(2009). Rapid left ventricular recovery after cabergoline treatment in a patient with peripartum cardiomyopathy. Eur J Heart Fail
11: 220-222
[Abstract][Full Text]
Rossi, J. S., Flaherty, J. D., Fonarow, G. C., Nunez, E., Gattis Stough, W., Abraham, W. T., Albert, N. M., Greenberg, B. H., O'Connor, C. M., Yancy, C. W., Young, J. B., Davidson, C. J., Gheorghiade, M.
(2008). Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: A report from OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure). Eur J Heart Fail
10: 1215-1223
[Abstract][Full Text]
Calvin, A. D., Geske, J. B., Bell, M. R.
(2008). 69-Year-Old Woman With Rapid Heartbeat. Mayo Clin Proc.
83: 1392-1395
[Full Text]
le Polain de Waroux, J.-B., Pouleur, A.-C., Goffinet, C., Pasquet, A., Vanoverschelde, J.-L., Gerber, B. L.
(2008). Combined coronary and late-enhanced multidetector-computed tomography for delineation of the etiology of left ventricular dysfunction: comparison with coronary angiography and contrast-enhanced cardiac magnetic resonance imaging. Eur Heart J
29: 2544-2551
[Abstract][Full Text]
Leonardi, B., Margossian, R., Colan, S. D., Powell, A. J.
(2008). Relationship of magnetic resonance imaging estimation of myocardial iron to left ventricular systolic and diastolic function in thalassemia.. J Am Coll Cardiol Img
1: 572-578
[Abstract][Full Text]
Kindermann, I., Kindermann, M., Kandolf, R., Klingel, K., Bultmann, B., Muller, T., Lindinger, A., Bohm, M.
(2008). Predictors of Outcome in Patients With Suspected Myocarditis. Circulation
118: 639-648
[Abstract][Full Text]
Dorn, G. W. II, Matkovich, S. J.
(2008). Put Your Chips on Transcriptomics. Circulation
118: 216-218
[Full Text]
Heidecker, B., Kasper, E. K., Wittstein, I. S., Champion, H. C., Breton, E., Russell, S. D., Kittleson, M. M., Baughman, K. L., Hare, J. M.
(2008). Transcriptomic Biomarkers for Individual Risk Assessment in New-Onset Heart Failure. Circulation
118: 238-246
[Abstract][Full Text]
Dube, M. P., Lipshultz, S. E., Fichtenbaum, C. J., Greenberg, R., Schecter, A. D., Fisher, S. D., for Working Group 3,
(2008). Effects of HIV Infection and Antiretroviral Therapy on the Heart and Vasculature. Circulation
118: e36-e40
[Full Text]
Wu, K. C., Weiss, R. G., Thiemann, D. R., Kitagawa, K., Schmidt, A., Dalal, D., Lai, S., Bluemke, D. A., Gerstenblith, G., Marban, E., Tomaselli, G. F., Lima, J. A.C.
(2008). Late gadolinium enhancement by cardiovascular magnetic resonance heralds an adverse prognosis in nonischemic cardiomyopathy.. J Am Coll Cardiol
51: 2414-2421
[Abstract][Full Text]
Takeda, K., Matsumiya, G., Matsue, H., Sakaki, M., Sakaguchi, T., Fujita, T., Sawa, Y.
(2008). Left Ventricular Reconstructive Surgery in Ischemic Dilated Cardiomyopathy Complicated With Cardiogenic Shock. Ann. Thorac. Surg.
85: 1339-1343
[Abstract][Full Text]
Cooper, L. T., Baughman, K. L., Feldman, A. M., Frustaci, A., Jessup, M., Kuhl, U., Levine, G. N., Narula, J., Starling, R. C., Towbin, J., Virmani, R.
(2007). The role of endomyocardial biopsy in the management of cardiovascular disease: A Scientific Statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. Eur Heart J
28: 3076-3093
[Full Text]
Cooper, L. T., Baughman, K. L., Feldman, A. M., Frustaci, A., Jessup, M., Kuhl, U., Levine, G. N., Narula, J., Starling, R. C., Towbin, J., Virmani, R.
(2007). The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol
50: 1914-1931
[Full Text]
Cooper, L. T., Baughman, K. L., Feldman, A. M., Frustaci, A., Jessup, M., Kuhl, U., Levine, G. N., Narula, J., Starling, R. C., Towbin, J., Virmani, R., Endorsed by the Heart Failure Society of America a,
(2007). The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation
116: 2216-2233
[Full Text]
Mayosi, B. M
(2007). Contemporary trends in the epidemiology and management of cardiomyopathy and pericarditis in sub-Saharan Africa. Heart
93: 1176-1183
[Abstract][Full Text]
Caforio, A. L.P., Calabrese, F., Angelini, A., Tona, F., Vinci, A., Bottaro, S., Ramondo, A., Carturan, E., Iliceto, S., Thiene, G., Daliento, L.
(2007). A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J
28: 1326-1333
[Abstract][Full Text]
Assomull, R. G., Prasad, S. K., Lyne, J., Smith, G., Burman, E. D., Khan, M., Sheppard, M. N., Poole-Wilson, P. A., Pennell, D. J.
(2006). Cardiovascular Magnetic Resonance, Fibrosis, and Prognosis in Dilated Cardiomyopathy. J Am Coll Cardiol
48: 1977-1985
[Abstract][Full Text]
Zannad, F., Mebazaa, A., Juilliere, Y., Cohen-Solal, A., Guize, L., Alla, F., Rouge, P., Blin, P., Barlet, M.-H., Paolozzi, L., Vincent, C., Desnos, M., Samii, K., for the EFICA Investigators,
(2006). Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study. Eur J Heart Fail
8: 697-705
[Abstract][Full Text]
Ginsburg, G. S., Seo, D., Frazier, C.
(2006). Microarrays Coming of Age in Cardiovascular Medicine: Standards, Predictions, and Biology. J Am Coll Cardiol
48: 1618-1620
[Full Text]
Marcu, C. B., Beek, A. M., van Rossum, A. C.
(2006). Clinical applications of cardiovascular magnetic resonance imaging.. CMAJ
175: 911-917
[Abstract][Full Text]
Toyama, M., Usui, A., Abe, T., Oshima, H., Akita, T., Ueda, Y.
(2006). Mitral Valve Surgery for Dilated Cardiomyopathy with Mitral Regurgitation. Asian Cardiovasc. Thorac. Ann.
14: 371-376
[Abstract][Full Text]
Sola, S., Khan, B. V.
(2006). Reply. J Am Coll Cardiol
48: 1284-1284
[Full Text]
Gheorghiade, M., Sopko, G., De Luca, L., Velazquez, E. J., Parker, J. D., Binkley, P. F., Sadowski, Z., Golba, K. S., Prior, D. L., Rouleau, J. L., Bonow, R. O.
(2006). Navigating the Crossroads of Coronary Artery Disease and Heart Failure. Circulation
114: 1202-1213
[Full Text]
Guarneri, V., Lenihan, D. J., Valero, V., Durand, J.-B., Broglio, K., Hess, K. R., Michaud, L. B., Gonzalez-Angulo, A. M., Hortobagyi, G. N., Esteva, F. J.
(2006). Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience. JCO
24: 4107-4115
[Abstract][Full Text]
Kadish, A., Schaechter, A., Subacius, H., Thattassery, E., Sanders, W., Anderson, K. P., Dyer, A., Goldberger, J., Levine, J.
(2006). Patients With Recently Diagnosed Nonischemic Cardiomyopathy Benefit From Implantable Cardioverter-Defibrillators. J Am Coll Cardiol
47: 2477-2482
[Abstract][Full Text]
Purek, L, Laule-Kilian, K, Christ, A, Klima, T, Pfisterer, M E, Perruchoud, A P, Mueller, C
(2006). Coronary artery disease and outcome in acute congestive heart failure. Heart
92: 598-602
[Abstract][Full Text]
Magnani, J. W., Dec, G. W.
(2006). Myocarditis: Current Trends in Diagnosis and Treatment. Circulation
113: 876-890
[Full Text]
Sliwa, K., Forster, O., Libhaber, E., Fett, J. D., Sundstrom, J. B., Hilfiker-Kleiner, D., Ansari, A. A.
(2006). Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. Eur Heart J
27: 441-446
[Abstract][Full Text]
Baughman, K. L.
(2006). Diagnosis of Myocarditis: Death of Dallas Criteria. Circulation
113: 593-595
[Full Text]
Mahrholdt, H., Wagner, A., Judd, R. M., Sechtem, U., Kim, R. J.
(2005). Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J
26: 1461-1474
[Abstract][Full Text]
Kittleson, M. M., Minhas, K. M., Irizarry, R. A., Ye, S. Q., Edness, G., Breton, E., Conte, J. V., Tomaselli, G., Garcia, J. G. N., Hare, J. M.
(2005). Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure. Physiol. Genomics
21: 299-307
[Abstract][Full Text]
Elkayam, U., Akhter, M. W., Singh, H., Khan, S., Bitar, F., Hameed, A., Shotan, A.
(2005). Pregnancy-Associated Cardiomyopathy: Clinical Characteristics and a Comparison Between Early and Late Presentation. Circulation
111: 2050-2055
[Abstract][Full Text]
Osterziel, K. J., Perrot, A.
(2005). Dilated cardiomyopathy: more genes means more phenotypes. Eur Heart J
26: 751-754
[Full Text]
Kittleson, M. M., Ye, S. Q., Irizarry, R. A., Minhas, K. M., Edness, G., Conte, J. V., Parmigiani, G., Miller, L. W., Chen, Y., Hall, J. L., Garcia, J. G.N., Hare, J. M.
(2004). Identification of a Gene Expression Profile That Differentiates Between Ischemic and Nonischemic Cardiomyopathy. Circulation
110: 3444-3451
[Abstract][Full Text]
Chan, S., Davidson, N., Juozaityte, E., Erdkamp, F., Pluzanska, A., Azarnia, N., Lee, L. W.
(2004). Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann Oncol
15: 1527-1534
[Abstract][Full Text]
Wang, A., Bashore, T. M.
(2004). Undercover and Overlooked. NEJM
351: 1014-1019
[Full Text]
Ray, P., Murphy, G. J., Shutt, L. E.
(2004). Recognition and management of maternal cardiac disease in pregnancy. Br J Anaesth
93: 428-439
[Abstract][Full Text]
Cade, W T., Peralta, L., Keyser, R. E
(2004). Aerobic Exercise Dysfunction in Human Immunodeficiency Virus: A Potential Link to Physical Disability. ptjournal
84: 655-664
[Full Text]
Walker, N L, Cobbe, S M, Birnie, D H
(2004). Tachycardiomyopathy: a diagnosis not to be missed. Heart
90: e7-7
[Abstract][Full Text]
Michels, V V, Driscoll, D J, Miller, F A, Olson, T M, Atkinson, E J, Olswold, C L, Schaid, D J
(2003). Progression of familial and non-familial dilated cardiomyopathy: long term follow up. Heart
89: 757-761
[Abstract][Full Text]
Limat, S., Demesmay, K., Voillat, L., Bernard, Y., Deconinck, E., Brion, A., Sabbah, A., Woronoff-Lemsi, M. C., Cahn, J. Y.
(2003). Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma. Ann Oncol
14: 277-281
[Abstract][Full Text]
Jessup, M.
(2003). The less familiar face of heart failure. J Am Coll Cardiol
41: 224-226
[Full Text]
Okura, Y., Dec, G. W., Hare, J. M., Kodama, M., Berry, G. J., Tazelaar, H. D., Bailey, K. R., Cooper, L. T.
(2003). A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. J Am Coll Cardiol
41: 322-329
[Abstract][Full Text]
Lewis, W.
(2003). Defective mitochondrial DNA replication and NRTIs: pathophysiological implications in AIDS cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol.
284: H1-H9
[Full Text]
Laissy, J.-P., Messin, B., Varenne, O., Iung, B., Karila-Cohen, D., Schouman-Claeys, E., Steg, P. G.
(2002). MRI of Acute Myocarditis: A Comprehensive Approach Based on Various Imaging Sequences. Chest
122: 1638-1648
[Abstract][Full Text]
Sato, M., Toyozaki, T., Odaka, K., Uehara, T., Arano, Y., Hasegawa, H., Yoshida, K., Imanaka-Yoshida, K., Yoshida, T., Hiroe, M., Tadokoro, H., Irie, T., Tanada, S., Komuro, I.
(2002). Detection of Experimental Autoimmune Myocarditis in Rats by 111In Monoclonal Antibody Specific for Tenascin-C. Circulation
106: 1397-1402
[Abstract][Full Text]
Suter, T. M., Meier, B.
(2002). Detection of anthracycline-induced cardiotoxicity: is there light at the end of the tunnel?. Ann Oncol
13: 647-649
[Full Text]
Anderson, L.J., Holden, S., Davis, B., Prescott, E., Charrier, C.C., Bunce, N.H., Firmin, D.N., Wonke, B., Porter, J., Walker, J.M., Pennell, D.J.
(2001). Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J
22: 2171-2179
[Abstract]
Mehta, N. J., Mehta, R. N., Khan, I. A.
(2001). Peripartum Cardiomyopathy: Clinical and Therapeutic Aspects. ANGIOLOGY
52: 759-762
[Abstract]
Elkayam, U., Tummala, P. P., Rao, K., Akhter, M. W., Karaalp, I. S., Wani, O. R., Hameed, A., Gviazda, I., Shotan, A.
(2001). Maternal and Fetal Outcomes of Subsequent Pregnancies in Women with Peripartum Cardiomyopathy. NEJM
344: 1567-1571
[Abstract][Full Text]
Reimold, S. C., Rutherford, J. D.
(2001). Peripartum Cardiomyopathy. NEJM
344: 1629-1630
[Full Text]
Hare, J.M., Baughman, K.L.
(2001). Fulminant and acute lymphocytic myocarditis: the prognostic value of clinicopathological classification. Eur Heart J
22: 269-270
MARSHALL, D., SACK, M. N
(2000). Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?. Heart
84: 355-356
[Full Text]
(2000). Cause of Cardiomyopathy Associated with Survival. Journal Watch Cardiology
2000: 6-6
[Full Text]
Givertz, M. M.
(2000). Underlying Causes and Survival in Patients with Heart Failure. NEJM
342: 1120-1122
[Full Text]
Luscher, T. F
(2000). Diagnosis of CHF -- often a trap In Itself. Journal of Renin-Angiotensin-Aldosterone System
1: 7-11
[Abstract]
Cappola, T. P., Felker, G. M., Kao, W.H. L., Hare, J. M., Baughman, K. L., Kasper, E. K.
(2002). Pulmonary Hypertension and Risk of Death in Cardiomyopathy: Patients With Myocarditis Are at Higher Risk. Circulation
105: 1663-1668
[Abstract][Full Text]
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