Natural history of incidentally discovered, asymptomatic idiopathic dilated cardiomyopathy

thesis.” However, in this study by Latron et al,” oxidized LDL had no effect on t-PA synthesis, and nonoxidized LDL had no effect on either PAI- or t-PA synthesis. It was their postulate that oxidized LDL interacts with the scavenger receptor on the endothelial cell stimulating endothelial derived PAI- 1 synthesis. The results of this study suggest that lovastatin therapy reduces plasma PAI- antigen levels. There was no correlation observed between this reduction and the reduction in plasma LDL cholesterol levels; however, LDL oxidation was not measured in this study. The effect of lovastatin on PAI- 1 levels may be mediated by mechanisms other than LDL cholesterol lowering. However, before such conclusions can be drawn, it would be important to evaluate the correlation between PAIreduction and changes in LDL oxidation parameters, rather than unoxidized plasma LDL cholesterol levels, as was done in this study. Plasma fibrinogen levels have previously been shown to correlate with total cholesterol levels.6 Furthermore, in a study by Beige1 et a1,7 lovastatin therapy resulted in an increase in fibrinogen levels despite reductions in LDL cholesterol levels. These results are consistent with our findings. The significance of this effect is not established. There are now extensive data suggesting that the progression of atherosclerosis can be altered by cho-

Natural History of Incidentally Dilated Cardiomyopathy

lesterol-lowering therapy. The changes in stenosis severity, measured angiographically, are small relative to the clinical benefit noted. Other factors, in addition to changes in stenosis severity, are probably operative. Effects of cholesterol-lowering on endothelial function, perhaps mediated by reductions in PAI1 levels, may be one of these mechanisms. This uncontrolled study requires further investigation to elucidate the independent relation between lovastatin, PAI-1, and fibrinogen.

1. Ham\ten

A, Walldius G. Ssapov A. Blombach M, De Faire U, Dahlen G, Landou C. Wiman B. Plasmmogen activator mhihltor in plasma: rsk factor for recurrent myocardial infarction. Lumw 19X7:2:3-9. 2. Stiko-Rahm A. Wiman B. Hamvten A, Ndlson J. Secretion of plasminogen activator inhIbItorI from cultured human umbilical vein endothelial cells is induced hy very-low-density lipoprotein. A/-t~rro.sc/en~s~.s lY9O:lO: 1067-1073. 3. Juhan-Vague I, Valadier J, Alesv MC. Deficient t-PA release and elevated PA mhihltor level\ in patient\ with spontaneous or recurrent deep vein thrombosis. 771ronrh Hnmw,\f 1987:57:67-72. 4. Sawa H. Sohel BE. Fuji] S. Potentiation by hypercholesterolenua of the inductlon of aortlc intramural synthesis of plasminogen ilctwator inhibitor type I by endothehal injury CI~ Res lYY3:73:67 I-680. 5. Latron Y, Chutan F. Anfo\\o MC. Nalbonc G. Lafont H, Juhan-Vague. Stmv ukttmg effect of oxidved low density lipoproteins on plasma activator-l \ynthesi\ by endothehal cell\. At-wimr kf ‘/%ronh 1991: I I: 1X21&1X29. 6. Em\t E. Plnsna fibrinogen---an independent cardiovaxular risk factor. .I Inrer-n Md lY90:27:365~372. 7. Bqel Y. Fuchs J, Smr M. Lune Y. Green P. Djaldetti M. Lova\tatin therapy in heterolygow fzumhal hypercholesterolemlc patients: effect on blood rheology ;md fihrinogcn Iwcl\. .I Inrrr-n Mcd 1991:210:23~?7.

Discovered, Asymptomatic

Idiopathic

Margaret M. Redfield, MD, Bernard J. Gersh, MB, ChB, DPhil, Kent R. Bailey, PhD, and Richard J. Rodeheffer, MD

L

eft ventricular (LV) dysfunction associated with con- toms is increasing as noninvasive means to assess sysgestive symptoms is characterized by significant tolic function are more widely used. We further hypothmorbidity and mortality despite aggressive medical ther- esized that patients with incidentally discovered asympapy.l 4 Recent studies have demonstrated that sympto- tomatic IDC should enjoy a better outcome than class I matic LV dysfunction is preceded by an asymptomatic patients who are well compensated with treatment but phase and that treatment of asymptomatic LV dysfunc- who have a history of congestive heart failure. tion reduces the morbidity and mortality associated with Patients diagnosed as having IDC at the Mayo Clinovert congestive heart failure.“,” Although these recent ic hemeen 1976 and 1987 were identijied retrospecstudies identified large numbers of patients with coro- tii‘ely. Patients with IDC wlere divided into 2 groups nary artery disease and asymptomatic LV dysfunction, according to the year of diagnosis. The 1976 to 1981 little is known about the prevalence and natural history referral group included patients jirst identijied as havof asymptomatic LV dysfunction in patients with idioing IDC at the Mayo Clinic hetieen I976 and 1981, and pathic dilated cardiomyopathy (IDC). The current study the 1982 to 1987 referral group included patients j?rst was designed to determine the frequency with which identified he&seen 1982 and 1987. The history was reIDC is diagnosed in the asymptomatic state in a large viewed to determine if the patient had symptoms of heart referral population of patients with IDC. The study was failure currently or in the past. Symptoms of heart failfurther designed to determine the outcome of these ure included dyspnea on exertion, orthopnea, paroxyspatients. We hypothesized that the frequency with which mal nocturnal dyspnea, fatigue, or edema. Patients who IDC is diagnosed before the onset of congestive symp- complairzed of palpitations or atypical chest pain in the absence of congestil’e symptoms were included in the From the Division of Cardiovascular Disease and Internal Medicine, asymptomatic LV [email protected] group. Although these Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, Minsymptoms ma! he related to cardiomyopathy, palpitanesota 55905. This study was funded in part by grants from the Mayo tions and aryplcal chest pain arefr-eyuent in patients Mith Foundation, Rochester, Minnesota. and the Joseph P. and Jeanne Sullinormal systolic,fl4rlction, and the detection of signlfificant van Foundation, Chicago. Illinois. Manuscript received November 8, 1003: revised manuscript received April 22. 1494. and accepted April 25. systolic dysfunction was considered incidental in these BRIEF REPORTS 737

r TABLE

coronary angiography to exclude coronary artery disease. Patients wjho did not undergo coronary angiography but who were still considered to have IDC by their cardiologist were included unless they had 2 risk factors for coronary artery disease other than age and sex or symptoms of coronary artery disease. Patients with a history of excess alcohol consumption, recent viral illness, recent pregnancy, or,family history of IDC were not e,xeluded from the study. However, the prevalence of these risk factors for ventricular dysfunction were recorded. Follow-up as of October 1991 was conducted,from a questionnaire with telephone,follow-up when necessary. Only the date of death or cardiac transplantation (which was treated as death) was recorded, and no e#ort was made to determine cause of’ death. Medication at the time of diagnosis and at the time of the follow)-up questionnaire was recorded. Group comparisons of the baseline characteristics of the asymptomatic LV dysfunction and class I groups were based on chi-square tests,for dichotomous variables and t tests jar continuous variables. Surviltal among the 2 groups was estimated by the Kaplan-Meier method and differences in survival were assessed using log-rank tests. Follow-up was performed in 222 patients with IDC. There w’ere (35 patients in the 1976 to 1981 cohort and 137 patients in the 1982 to 1987 cohort. Fij+fout patients (24%)~filjilled the criteria for class I congestive heart failure. Thirty-two of the 222 patients (14%) fulfilled the criteria for asymptomatic LV dy$mction. Seven percent of patients (6 of 85) in the I976 to 1981 cohort and 1990 of patients (26 of 137) in the 1982 to 1987 cohort had asymptomatic LV dysfunction (p = 0.02). The clinical characteristics of patients with asymptomatic LV dysfunction and class I congestive heartfailme are compared in Table I. A history of a viral illness was more frequently recorded in class I patients. Whereas the physical findings were generally consistent with a well-compensated state in both groups, more class I patients had a third heart sound. Patients with asymptomatic LV dysfunction had a lower prevalence of cardiomegaly on chest radiography and a smaller left v’entricle and better ejection fraction on echocardiography than did class I patients.

I Clinical Characteristics in Patients with Asymptomatic Left Ventricular Dysfunction Versus Patients with Class I Congestive Heart Failure Asymptomatic Dysfunction (n = 32)

LV Class I (n = 54)

History Men (%) 75 Mean age (years)(range) 52 (14-75) Excessive alcohol (%) 9 Recent viral illness (%) 3 Recent pregnancy (%) 3 12 Family history of IDC (%) Physical examination Third heart sound (%) 9 Rales (%) 3 Edema (%) 3 Elevated jugular 22 venous pressure (%) Laboratory data 13 Electrocardiographic atrial fibrillation (%) 47 Conduction delay on electrocardiogram (%) Cardiomegaly on 31 chest radiograph (%) Mean ejection fraction 33 i: 10 (%) (+ SD) Mean LV diastolic 65 k 8 (n = 26) dimension (mm) ‘Statistically significant IDC = idiopathic dilated

at p ~0.05. cardiomyopathy;

p Valut

70 53 (23-73) 22 20 2 4

NS NS NS 0.03* NS NS

30 2 15 17

0.03’ NS NS NS

15

NS

57

NS

57

0.02*

29 f 9

0.05’

70 f 9 (n = 40)

0.02*

LV = left ventricular.

patients. Patients who had no congestive symptoms when first seen hut who had a history of congestive symptoms were identtjied as “class I.” Patients who had no congestive symptoms in the past or present and who were not being treated specifically for heartfailure were identified as “asymptomatic LV dysfunction.” Characteristics and outcome were compared between the 2 groups. The criterion for IDC was global LV dilatation with impaired systolic function in the absence of a known cardiac or systemic cause. Systolic dysfunction was defined as an ejection fraction ~50%. The clinical record was screened to exclude possible etiologies for ventricular dysfunction. Approximately 70% of patients underwent

Expected

ALVD Class I

20-

01 0

1

2

3

4

5

6

7

25 33

20 26

15 21

lt3

FIGURE 1. Survival curves for patients with asymptomatic left ventricular dysfunction (AND), class I congestive heart failure, and age and sex-matched control subjects. The number of patients at risk in each of the study groups at each year is indicated at bottom. The survival curves for asymptomatic left ventricular dysfunction and class I patients are not significantly different (p q 0.29).

Years ALVD (n) Cl;w I (n)

32 52

32 45

30 42

@ cumwxwJ,*

738

THE

AMERICAN JOURNAL OF CARDIOLOGY@ VOLUME 74

OCTOBER 1, 1994

ed cardiomyopathy diagnostic code because of variation in phrasing by the physician or the data base coder. Importantly, this method of patient identification will miss patients who have IDC but are asymptomatic, and are not evaluated and diagnosed because of the absence of symptoms. The study was conducted in a referral population and survival in both groups may be worse than that in patients diagnosed with IDC in a primary care setting.7 Although efforts were made to characterize the patterns of medication use in the 2 groups, detailed information regarding the length of therapy and dosage of medications known to impact on survival in patients with IDC were not available.

This study did not demonstrate an improved survival in patients with asymptomatic dysfunction when compared with patients who were currently well compensated but who had a history of congestive symptoms, although there was a trend toward such an improved survival. This is surprising as one would expect that identification of patients before the onset of congestive symptoms should represent diagnosis earlier in the natural history of the illness and result in an improved survival. It may be that the numbers of patients with IDC and no congestive symptoms in the current study are insufficient to demonstrate statistical significance. More patients with class I IDC were treated with vasodilators, and this may have masked a difference in the natural history of the 2 groups. Alternatively, larger doses of vasodilators may have been used in patients with a history of congestive symptoms, and this also could have narrowed the differences between the 2 groups. Because this was a referral population, a similar rate of noncardiac disease may also have contributed to the similar survival curves. The current study is a retrospective review and relies on the accuracy of the recorded history to classify patients as symptomatic or asymptomatic. The method of patient identiiication used in this study may miss some patients who have IDC but who did not receive the dilat-

Radiographic John Portelli,

In conclusion, this study demonstrates that the frequency with which IDC is diagnosed in the asymptomatic state is increasing. The true prevalence of asymptomatic IDC remains unclear. Whereas the short and intermediate prognosis for asymptomatic IDC is relatively good, the Fyear mortality rate approaches 50%. In a disease that often affects people early in life, asymptomatic IDC cannot be considered a benign diagnosis. An aggressive approach to the diagnosis and treatment of asymptomatic patients with IDC is clearly warranted.

1. Cohn

JN. Archibald DC. Zleschc S. Franciou JA. Iianton WE. Tristani FE, Dunkman WB, Jacobs W. Fran& GS, Flohr KH, Goldman S, Cobh FR. Shah PM, Saunders R. Fletcher RD. Loeb HS. Hughe\ VC. Baker B. Effect of vasod~lator therapy on mortality 111chronic congestive heart fallurs: rewIl\ of a Veteran\ Adminiwation Cooperative Study. N Engi .I Mell lY86:114.1547-1552. 2. Cohn Jti. Johnson G. Ziexhc S, Cobh F. Francis C. Triami I:. Smith R. Dunkman WB. Loch H, Wang M, Bhat G. Goldman S, Fletcher RD. Doherty J. Hugha CV. Carwn P, Cmtron G. Shabetai R, Haakcnxm C. A compariwn 01 enalapnl with hydraln/lnr~l\o\orhIde d~mtrate in the treatment of chronic conge\he heat1 falurc. n; Eqql.I Mcd 1901;325:301-110. 3. The SOLVD Inve?tlgators. Effect of enalapnl on wrwval m pahents wiih reduced left ventricular e.jectlon fraclions and cc,nge\tlvc hcan failure. I’ /:II,~/ .I Mcc/ lYOl:3?5:2Y1-302. 4. Xx Conwnu\ Trial Study Group. Effects of cnalapnl on mortality in xwrc congratiw hean failure. N I:‘q/ .I Mtv/ I%73 l&1429-1435. S. Pfeller MA. Brnunwald E. Moyc: LA. Basla 1, Brown EJ. Cuddy TE. Daw\ BR. Gcltman EM. Goldman S, Flaker CC. Klein M, Lamas GA, Pa&r M. Rouleau J, Rouleau JL, Ruthetiord J. Weflhennsr JH, Hawkins CM, on Behalf of Ihe SAVE Investigatora. Effect of captopril on mortality and morhldlty in pst~rnt\ wth left ventricular dy\functlon after myocardial mfarction Y t’n:r/ .I Mcc/ lY92;327:

669-677. 6. The SOLVD of hcan failure

Invectl_rators. Etfect 01 enalapril on mortahty and the development m aaymptomatic pawn& with ~reduccd left ven~ncular c.jxtion fract,on\. rli Ewgl J k’ed lYY2:327:6XS--691. 7. Sugrue DD. Rodehcffer RJ, Codd MB. Ballard DUJ, Fuster V. Gush BJ. The clm~cal cwrse of &>pathlc ddated urdiomyopathy: a population-haed Judy. AI~I! 1,1rcr ,i i2lcd IW: I 17. t 17-l 23.

Contrast Waste in Cardiac Catheterization

MD, and Andrew A. Ziskind,

Laboratories

MD

W

ith the growing emphasison cost-consciousdelivery of medical care, there is an even greater need to identify ways to reduce costs without compromising patient care. One area of interest in the cardiac catheter-

From the Division of Cardiology. Department of Medicine. University of Maryland, 22 South Greene Street, Room N3W77, Baltimore. Mary land 2 I20 I, Manuscript received January 25. 1994: revised manuscript received April I?. 1994. and accepted Aprd 14.

ization laboratory is limiting the use of expensive lowosmolality contrast agentsthat cost 15to 20 times more than conventional high-osmolality agents. Studies that have evaluated the safety and cost-effectiveness of both agents suggestthat a reasonableapproach would be to limit the use of low-osmolality agentsto selectedhighrisk patients.ld5 In an etfort to identify other potential sourcesof cost savings, we investigated the inefficiency of contrast use by studying the quantity of radiographic contrast discarded in our laboratory. BRIEF REPORTS 739