Ri ventricular dysfunction: An independent r of adverse outcome in patients with

myocardtiis

To 8saess the predictive value of right ventricular systolic function in patients with active myoca&tk, the echocardiograms of 23 patients with biopsy-confirmed myocardiii were revlewed. @it ventricular systolic function was evaluated qualitatively and quantiitively by descent of the right ventricutar base. Patients were divided into those with normal right ventricukr functfon, in whom right ventricular descent was 1.9 k 0.1 cm, and those with abnormat rtght ventricular function, in whom right ventricular descent was 0.8 + 0.1 cm (p < O&M), lhwa were no differences between the two groups in age, duration of symptoms, baseftne hem&ynamics, or histologic assessment. Initial left ventricutar ejection fraction was siw iower in patients with depressed right ventricular function (27.5 -+ 4.9%) compared with thet in patlent wtth normal right ventricular function (47.5 + 6.3%) @ = 0.01). The liietihood of an advease outcome, defined as death or need for cardiac transplantatiin, was greater in patlentawfth abrmmal right ventricular function (right ventricular descent _( 1.7 cm) than in patients wlth normal right ventricular function (right ventricular descent > 1.7 cm) cp < 0.03). MultivtiaPe analysis reve8fed that right ventricular dysfunction as quantified by right ventricular descent was the most powerful predictor of adverse outcome. (AM HEART J 1994;128:301-7.)

Lisa A. Mendes, MD, G. William Dee, MD, Michael H. Picard, MD, Igor F. Palacios, MD, John Newell, BA, and Ravin Davidoff, MBBCh Boston, Muss.

Patients with acute myocarditis have a variable clin- ical course, and their prognosis at the time of presen- tation is often uncertain. Spontaneous improvement in ventricular function and complete clinical and he- modynamic recovery occurs in a subgroup of indi- viduals.” However, the majority of patients have a more protracted illness, with possible clinical out- comes including life-threatening arrhythmias,2-4 per- sistent or progressive heart failure,‘9 5-7 cardiac trans- plantation,*~ g and death. Despite this wide disparity in clinical outcome, no parameters that predict prog- nosis have been identified. Improvement does not reliably correlate with the clinical characteristics at time of presentation,l initial hemodynamic parame- ters, or left ventricular (LV) ejection fraction (EF).g In addition, histologic assessment of the initial or re-

From the Evans Memorial Department of Clinical Research and the Divi- sion of Cardiology, Department of Medicine, Boston University Medical Center Hospital, and the Cardiac Unit, Massachusetts General Hospital.

Received for publication July X,1993, accepted Dec. 3,1993.

Reprint requests: Lisa A. Mendes, MD, Section of Cardiology, Boston Uni- versity Medical Center Hospital, 38 East Newton St., Boston, MA 02118. Copyright Q 1994 by Mosby-Year Book, Inc. 0002~8703/94/$3.00 + 0 4/l/56682

peated endomyocardial biopsy sample has generally not been helpful in predicting outcome.g

The therapeutic approach for patients with myo- carditis remains uncertain because of the variable nature of the illness. Most treatment is supportive and is directed at the clinical manifestations of the disease. Several small uncontrolled trials have shown clinical improvement in a subset of patients treated with corticosteroid therapy alone or in combination with other immunosuppressive agents,‘, ‘1 I1 but the utility of that therapy awaits completion of the Mul- ticenter Myocarditis Trial.12 Because immunosup- pressive therapy may be associated with significant morbidity and even mortality, it would be helpful if high-risk cases could be identified at the time of pre- sentation. Regional variation in LV function has been associated with improved prognosis in patients with idiopathic dilated cardiomyopathy,i3 but this char- acteristic has not been evaluated in patients with acute myocarditis. In addition, the predictive value of right ventricular (RV) dysfunction has not been studied in these patients even though the diagnosis is based predominantly on RV biopsy. Therefore the purpose of this study was to evaluate the prognostic value of global and regional RV and LV function in

301

302 Mendes et al. August 1994

American Hemi Journal

symptomatic patients with biopsy-proven myocardi- tis.

METHODS Study population. Between September 2, 1980, and

June 29, 1991, 53 patients were diagnosed with active my- ocarditis, as defined by the Dallas Classification System,14 at our institution. Indications for the procedure in 95 % of the patients was new onset dilated cardiomyopathy, symp- tomatic congestive heart failure, and clinically suspected myocarditis. The others presented with unexplained tach- yarrhythmias or conduction abnormalities, a chest pain syndrome mimicking myocardial infarction without evi- dence of coronary artery disease, restrictive or constrictive hemodynamics, or suspected infiltrative disease of the my- ocardium. In 23 of these patients, satisfactory echocardio- grams were obtained within 6 + 1 days of the diagnostic biopsy; these 23 constituted the study group. Results of coronary angiography were normal in 22 patients. The pa- tient who did not undergo angiography was 18years old and did not have chest pain or other symptoms suggestive of coronary artery disease.

Transvenous endomyocardial biopsy and pathologic evaluation. Right heart catheterization was performed in all patients with a triple-lumen thermodilution catheter. RV biopsy was performed at the conclusion of hemody- namic measurements with the technique described by Ma- son,i5 Multiple biopsy specimens were obtained from the RV septum and were processed according to standard em- bedding and staining methods. Pathologic specimens were reviewed without knowledge of the patient’s clinical his- tory. The Dallas criteria were used to diagnose myocardi- tis and describe the type and degree of inffammatory cel- lular infiltrate and the extent of myocardial necrosis and fibrosis.i*

Clinical evaluation. The medical records of all 23 pa- tients were reviewed. Each patient’s clinical presentation, duration of illness, concomitant medications, and severity of heart failure were detailed. The patient’s clinical course and type of therapy were also noted. Clinical outcome and functional status according to the New York Heart Asso- ciation classification were determined by reviewing pa- tients’ medical records and interviewing patients or family members by telephone. Adverse outcome was defined as death or the need for cardiac transplant.

Left ventricular function. The patient’s initial LVEF was determined by radionuclide imaging performed by the multigated equilibrium technique. LVEF was followed se- rially by radionuclide ventriculography, and the most recent study was used to establish the patient’s final EF.

Echocardiographic technique. Two-dimensional echo- cardiography was performed with commercially available scanners with 2.5 and 3.5 mHz transducers. Standard parasternal images and orthogonal apical two- and four- chamber views aligned to maximize the long-axis length of the LV and RV were acquired. All images were stored on half-inch videotape and analyzed with an off-line analysis system (Cineview Plus, Prism Imaging, Freeland Systems, Louisville, Cola.).

Because the purpose of the study was to evaluate regional and global ventricular function, a semiquantitative wall motion scoring system was used to assess regional variation of the LV. The LV was divided into 20 segments.16 The wall motion of each segment of the LV was described and scored as follows: 1 = normal; 2 = hypokinetic; 3 = akinetic; and 4 = dyskinetic. All 20 segments were assessed in each of the 23 echocardiograms. A mean segment score was achieved by adding the individual scores and dividing by 20.

RV systolic function was assessed qualitatively for re- gional wall motion abnormalities by visual inspection and quantitatively by a modification of a previously described technique.17> l8 RV geometry does not conform to an easily described mathematic model, but the systolic shortening from apex to base has been shown to correlate with global estimates of RV function.r7 With this method an optimally oriented apical four-chamber view is acquired, and the distance between the endocardium of the RV apex and a perpendicular chord through the tricuspid value annulus is measured at end-diastole and at end-systole.ls The differ- ence in length between these two measurements is the RV descent (Fig. 1). In patients with normal RV function a de- scent of 2 -+ 0.2 cm has been reported.i8

Immunosuppressive therapy. The decision to institute immunosuppressive therapy was left to the individual re- ferring cardiologist. Fourteen of the 23 patients with my- ocarditis were treated with immunosuppressive agents. Four patients received oral prednisone alone for 6 months at dosages ranging from 20 to 40 mg/day. Seven patients received combination therapy with azathioprine and pred- nisone for 6 months according to institutional protocol; azathioprine 2 mg/kg/day was administered at, and the dosage decreased if leukopenia developed. Prednisone, 1.0 to 1.5 mg/kg/day was administered in divided doses and tapered to 0.3 mglkglday by week 12. This dosage was con- tinued for the entire 6 months and then tapered during the final 4 weeks. The remaining 3 treated patients were ran- domized to receive combined prednisone and cyclosporine therapy as part of the Multicenter Myocarditis Trial. Cy- closporine was administered initially at 10 mg/kg/day in divided doses. The dosage was then titrated to achieve a trough cyclosporine level of 50 rig/ml. All treated patients underwent reassessment of ventricular function and repeat biopsy on completion of therapy.

Statistical analysis. Whenever appropriate, group means were compared by Student’s t test, and comparisons of proportions were made with the two-tailed Fisher’s ex- act test. Group data are presented as the mean t SEM. Actuarial analysis of event-free survival was performed by Kaplan-Meier analysis. Independent predictors of adverse outcome were determined by stepwise logistic regression analysis. A p value < 0.05 was considered statistically sig- nificant.

Observer variability. Measurements of RV descent in 10 patients were determined by two independent observers. Their measurements were subtracted, and the SD of the differences was used to express interobserver variability. In a similar manner, one observer repeated the measurements to determine intraobserver variability. In addition, RV

Volume 128, Number 2

American Heart Journal Mendes et al. 303

Fig. 1. Measurement of right ventricular descent in patient with myocarditis. Left, In apical four-cham- ber view, distance between endocardium of right ventricular apex and perpendicular chord through tricus- pid annulus during diastole is 7.0 cm. Right, During systole, distance from apex to base has decreased to 6.5 cm. Right ventricular descent, or difference in length between diastolic and systolic measurements, is 0.5 cm. -

function was reassessed qualitatively in all 23 cases by both readers.

RESULTS Clinical features. To assess whether the 23 patients

who had echocardiograms at initial examination were similar to the remaining 30 myocarditis patients who did not have echocardiograms, these two groups of patients were compared (Table I). There were no differences in age, gender distribution, duration of symptoms, histologic assessment, baseline hemody- namics, initial LVEF, or immunotherapy. There was also no difference in functional class or in incidence of death or need for cardiac transplant between those patients who had echocardiograms and those who did not. Thus the patients who had echocardiograms were representative of the entire myocarditis patient group and did not represent a select subgroup with more severe disease at presentation or with worse outcome.

Table 1. Comparison of demographic, clinical, histologic, ventriculographic, and hemodynamic findings for patients with and without echocardiograms

- No P

Echocardiogram echocardiogram Value - -II__ --

n 23 30

Age (yd 48.2 i 3.3 -15.0 + 2.8 NS

Men/women 13/10 :!O/lO NS Lymphocytic 18 (78%) 25 (83 c< ) NS

Giant cell 5 (22%) 5 (17’1,) NS Immunotherapy 14 (61Oo) 18 (60% ) NS Initial LVEF ( c;. ) 36.0 t 4.0 .i2.0 2 3.9 NS

RA (mm Hg) 9.2 f 1.8 8.6 t 1.4 NS

PA, (mm Hg) 21.6 + 1.4 22.(l i 3.0 NS

PCWP (mm Hg) 14.8 + 1.5 Il.6 f 1.8 NS CO (L/min) 4.5 I 0.3 4.8 If- 0.3 NS Adverse outcome 11 (48’;) 15 r50”; ) NS

CO, Cardiac output; LVlXF, left ventricular ejecl.ion fraction; PA,, mean pulmonary artery pressure; PCWP. pulmonary capillary wedge pressure; RA, mean right atria1 pressure.

Echocardiographic findings. Ventricular function was normal (i.e., wall motion score = 1) in 5 (22%) of 23 patients. Global LV dysfunction with diffuse hypokineses, represented as a wall motion score = 2, was present in 13 (57 % ) of the 23 study patients. In no patient was there normal wall motion in one area of the ventricle and dysfunction in another. The re- maining five patients demonstrated regional varia- tion, each with an LV wall motion score >2. LV function in all five patients was relatively preserved

at the base. For patients with depression of LV func- tion, there was no difference in survival or ultimate functional status when patients with or without regional variation were compared. Adverse outcome, defined as death or need for cardiac transplant, occurred in 6 (46 %) of 13 patients with global dysfunction and in 4 (80 % ) of 5 with regional varia- tion (p value not significant [NSl 1.

304 Mendes et al. August 1994

American Heart Journal

2.4-

2.2-

2.0-

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E 1.4-

g 1.2- v) @ 0 l.O-

' 0.8 -

0.60

0.4-

0.2-

1 Norh At&ml Qualitative RV Function

Fig. 2. Right ventricular (RV) descent in patients with normal and abnormal function by qualitative assessment. RV descent was 1.9 _+ 0.07 cm in patients with normal RV function, compared with 0.83 + 0.01 cm in patients with abnormal RV function (p < 0.001).

Evaluation of RV function revealed that 15 of 23 patients had qualitative evidence of depressed RV systolic function; this finding was confirmed by mea- surement of RV descent (Table II). In patients with RV dysfunction, RV descent measured 0.83 + 0.1 cm as compared with 1.9 + 0.1 cm in the eight patients with normal RV function (p < 0.001). In every pa- tient with abnormal RV function, RV descent was less/eq ~1.7 cm. Of the eight patients with qualita- tively normal RV function, RV descent was >1.7 cm in 6 and 1.7 cm in 2 (Fig. 2).

In Table II the clinical details of the patients with normal and abnormal RV function are compared. There were no significant differences in age, gender, duration of symptoms, histologic assessment, base- line hemodynamics, or immunotherapy between the two groups. Although mean right atria1 (RA) pressure in patients with abnormal RV function was lower than that in patients with normal RV function, this difference did not reach statistical significance (p 0.2). In addition, there was significant overlap in RA pressures between the two groups: RA pressures ranged from 3 to 25 mm Hg in patients with normal RV function and from 0 to 25 mm Hg in patients with normal RV function. Initial LVEF in patients with RV dysfunction was 27.5% + 4.0%) a value significantly lower than that of patients with normal RV function, 47.5% t 6.3% (p 0.01). Thus RV dys-

Table II. Comparison of demographic, histologic, hemody- namic, ventriculographic, and echocardiographic findings for patients stratified according to right ventricular function

RV function

Normal Abnormal p Value

8 15 48.0 + 6.1 48.3 + 4.0 NS

Men/women 414 916 NS Duration of symptoms (mo) 1.7 rt 0.8 2.2 +- 0.7 NS Lymphocytic 7 (88%) 11 (73%) NS Giant cell 1(12%) 4 (27%) NS RA (mm Hg) 12.5 z!z 2.8 7.5 + 2.1 NS PA, (mm Hg) 19.8 zk 1.0 22.5 f 1.8 NS PCWP (mm Hg) 12.9 f 2.4 15.8 f 1.9 NS CO (L/min) 4.5 + 0.4 4.9 it 0.5 NS Initial LVEF (% ) 47.5 + 6.3 27.5 f 4.0 0.01 RV descent (cm) 1.9 Ik 0.1 0.8 + 0.1 0.001

CO, Cardiac output; LVEF, left ventricular ejection fraction; PA,,,, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; RA, mean right atrial pressure; RV, right ventricular.

function was associated with worse LV systolic func- tion. However, long-term survival was significantly influenced by the presence or absence of RV dys- function and was not related to initial LVEF. When adverse outcome was defined as death or the need for cardiac transplant, the presence of abnormal RV function was associated with a poor prognosis. In 10 (67%) of 15 patients in the group with RV dysfunc- tion, outcome was adverse, as compared with 1(13 % ) of 8 patients in the group with normal RV function (p 0.04). One patient with abnormal RV function who had normal global LV systolic function (LVEF 67 % ) died of congestive heart failure after 366 days of fol- low-up.

Causes of death for the entire group included pro- gressive congestive heart failure in three and sudden cardiac death in five. Three of the 5 patients with sudden cardiac death were receiving antiarrhythmic therapy, as compared with 2 of the remaining 17 pa- tients. There was no difference in the type of anti- arrhythmic therapy used in patients with and with- out sudden death. Three patients underwent cardiac transplant; one of these three had survived an epi- sode of sudden cardiac death before transplantation.

The difference in outcome between patients with and without abnormal RV function is further illus- trated by comparing cumulative event-free survival during the entire follow-up period (Fig. 3). Of pa- tients with normal RV function, 60% were alive or had no need for cardiac transplantation at the end of the follow-up period (770.6 k 197.7 days) as com-

Volume 128, Number 2 Amarlcan Heart Journal Mendes et al. 305

100: '; - ';;

t

; 80-

t o--O Normal RV ‘.

h.. o---a Abnormal RV

p=o.o3

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-----a,,

ki 60- '. 0 m h %

\ 40-

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4 '.

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z$ 20- “'p . . . . . . . . . 0

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0 400 800 1200 1600 2000

Follow-Up (days)

Fig. 3. Event-free survival by Kaplan-Meier analysis for group with normal right ventricular (R V) systolic function and group with abnormal RV function.

pared with 8% of patients with abnormal RV func- tion (599.6 k 72.6 days) (p 0.03).

Quantitative assessment of RV function confirmed the prognostic value of RV dysfunction. In the 11 patients with an adverse outcome, RV descent was 0.9 + 0.2 cm compared with 1.5 f 0.2 cm in the 12 patients who survived (p 0.03). Outcome also could be predicted when patients were stratified by RV de- scent <1.7 or >1.7 cm. Eleven of 17 patients with RV descent 51.7 cm died or required cardiac transplant, whereas none of the patients with RV descent >1.7 cm experienced an adverse outcome (p = 0.03).

Although patients with abnormal RV function had a lower initial LVEF, LV function itself was not pre- dictive of outcome. In the 12 patients who survived, initial and final LVEF were 39.9% f 6.2% and 45.7% +: 6.3%, respectively, compared with 32.7 % -t 4.9% and 31.7% & 4.9% in patients with an adverse outcome (p NS). However, the net change in LVEF between initial and final radionuclide stud- ies was significantly different between the groups. In the patients with a poor outcome, LVEF demon- strated a net decrease (-1.0% + 5.0%), whereas in the patients who survived it demonstrated a net in- crease (13.5% + 3.8%) (p 0.04).

To determine the independent significance of RV dysfunction as a predictor of adverse outcome, a multivariate analysis of the given clinical, histologic, hemodynamic, and echocardiographic data was per- formed (Table III). Initial LVEF was not predictive of a poor outcome when coupled with the other given variables. RV dysfunction as quantitated by RV de- scent was the most powerful predictor of death or the need for cardiac transplant in this group of patients with myocarditis.

Table III. Predictors of death or need for cardiac trans- plantation by multivariate analysis

Variable p Value

Age NS Sex NS Histologic assessment NS Immunotherapy NS RA NS PA, NS PCWP NS co NS Initial LVEF NS Abnormal RV function 0.033 RV descent 0.016

CO, Cardiac output; LVEF, left ventricular ejection fraction; PA,, mean pulmonary artery pressure; PCWP. pulmonary capillary wedge pressure; RA, mean right atria1 pressure; RV, right ventricle.

Observer variability. The intraobserver variability in the measurement of RV descent was 0.16 cm, or 13 % of the mean value; interobserver variability was 0.09 cm or 7.5 % of the mean. When RV function was reassessed qualitatively, all patients remained in the same category of RV function in which they had been classified originally.

DISCUSSION

The prognosis of patients with active myocarditis remains uncertain, and clinical characteristics, initial hemodynamic parameters, and LV function gener- ally have not been predictive of outcome. This study is the first to identify a clinical marker that is predic- tive of a poor prognosis. Qualitative evidence of RV dysfunction by two-dimensional echocardiography

306 Mendes et al. August 1994

American Hearl Journal

was an independent risk factor for death or the need for cardiac transplantation. In a representative group of symptomatic patients with myocarditis from our institution, 67 % with abnormal RV function had an adverse outcome compared with 13% of patients with normal RV function. A more quantitative index for RV function-shortening of the RV from apex to base-also predicted outcome. All patients with RV descent > 1.7 cm had a favorable outcome; in com- parison, 65% of patients with RV descent I 1.7 cm died or required cardiac transplantation. No other hemodynamic parameter, measure of LV function, or histologic characteristic was predictive of outcome in these patients.

The identification of RV dysfunction as a predic- tor of outcome is of clinical relevance because out- come prognostication in myocarditis has proven dif- ficult. Dee et a1.l studied the clinical features and courses of 27 patients with new-onset dilated cardi- omyopathy of whom 18 had active myocarditis diag- nosed by RV biopsy. In these patients, clinical char- acteristics, duration of illness, baseline hemody- namic parameters, and use of immunotherapy were not predictive of a poor outcome, defined as death or the need for cardiac transplantation. In addition, global LV function as assessed by radionuclide imag- ing did not provide useful prognostic information.

An earlier study by Fenoglio et al.lg correlated his- tologic features of the endomyocardial biopsy speci- men with clinical presentation and outcome in pa- tients with myocarditis. However, this study was performed before the Dallas Classification System for diagnosing myocarditis was established, and therefore the prognostic importance of these histo- logic characteristics remains uncertain.

The relationship of RV dysfunction to survival has been shown in other groups of patients with cardiac disease. Polak et a1.20 found that patients with ischemic cardiomyopathy who had evidence of de- pressed RV function had a significantly higher 2-year mortality than similar patients with normal RV function. Despite the difference in the cause of my- opathy between studies, these authors also note that RV dysfunction was closely associated with more se- vere depression of LV systolic function and, as noted in the current study, that RV dysfunction is an inde- pendent predictor of an adverse outcome.

The reason for the association between RV dys- function and a poor prognosis in patients with myo- carditis is unknown. In this study, abnormal RV function identified a subgroup of patients with more severe LV dysfunction, and thus it is possible that RV dysfunction is a marker of a more diffuse or severe disease process that results in depressed biventricu-

lar function. A second possibility is that the RV may be the focus for serious ventricular arrhythmias be- cause sudden cardiac death accounted for 50 % of the adverse outcomes in patients with abnormal RV function. Structural abnormality of the RV as a cause of life-threatening ventricular arrhythmias has been well described in other patients with isolated RV disease.219 22

Although global LV function is not predictive of outcome in patients with myocarditis, the prognostic importance of segmental wall motion abnormalities has not been evaluated. Previous studies with radio- nuclide imaging and echocardiography have shown that patients with myocarditis may have segmental and diffuse wall motion abnormalities involving the LV.23> 24 Segmental contraction abnormalities are thought to represent localized regions of myocardial inflammation or necrosis.25, 26 As compared with glo- bal LV dysfunction, regional variation may identify a subset of patients with less extensive involvement of the myocardium. Wallis et a1.13 evaluated the im- portance of regional variation in LV wall motion on l-year survival in 50 patients with idiopathic dilated cardiomyopathy. In their study, 32 patients were found to have segmental wall motion abnormalities as assessed by radionuclide ventriculography and had a l-year survival rate of 90% as compared with 50% in the 19 patients with diffuse wall motion ab- normalities (p < 0.05). In contrast, the presence of regional LV dysfunction detected by echocardiogra- phy in the present study was not associated with an improved outcome. The majority (57%) of our 23 patients had global dysfunction; only 5 (22%) of 23 demonstrated minor regional variation, with relative preservation of function at the base. These segmen- tal abnormalities may reflect patchy myocardial in- flammation or injury but, in view of the invariable preservation of LV function at the base, may be re- lated to the circumferential orientation of muscle fi- bers in this portion of the heart.27, 28 This regional variation in muscle architecture may help maintain the structure and function of the basal myocardium relative to the rest of the LV.

Echocardiographic technique. This is the first study to evaluate the prognostic value of RV function as assessed by echocardiography in patients with myo- carditis. Although RV geometry does not conform to an easily described mathematic model, RV descent has been shown to correlate with estimates of RV ejection fraction by radionuclide angiography.17 In addition, a previous study involving patients with RV infarction has shown that RV descent correlates with hemodynamically significant RV dysfunction. Echo- cardiography also provides information about valvu-

Volume 128, Number 2

American Heart Journal

lar function and biventricular wall motion and is a simple noninvasive method of monitoring these pa- rameters during the course of illness.

Limitations. Although this study is limited by small sample size, it currently is the largest series of patients in which ventricular function as assessed by echocardiography has been correlated with clinical outcome. With the recent completion of the Multi- center Myocarditis Trial,12 a larger number of pa- tients with echocardiographic examinations at the time of diagnosis will be available to assess further the prognostic importance of RV function. In addi- tion, the type of inflammatory infiltrate found by ex- amination of endomyocardial biopsy specimens in this study did not provide prognostic information. This limitation probably also relates to the small sample size because a previous study from this insti- tution, which included five additional patients with giant cell myocarditis has shown that histologic find- ings of giant cells is a univariate predictor of adverse outcome.8

Conclusions. The presence of RV dysfunction as- sessed qualitatively or quantitatively by two-dimen- sional echocardiography provided a clinical marker predictive of adverse outcome in patients who pre- sented with symptomatic cardiomyopathy caused by active myocarditis. Although depressed RV function was associated with more severe LV dysfunction, it was the only independent predictor of death or pro- gressive heart failure leading to cardiac transplanta- tion. These findings, if confirmed by additional studies of myocarditis patients, may have important implications regarding the appropriate therapy for patients with active myocarditis.

REFERENCES

1.

2.

3.

4.

5. 6.

I.

Dee GW, Palacios IF, Fallon JT, Aretz HT, Mills J, Lee DC-S, Johnson RA. Active myocarditis in the spectrum of acute di- lated cardiomyopathies: clinical features, histologic correlates, and clinical outcome. N Engl J Med 1985;312:885-90. Strain, JE, Grose RM, Factor SM, Fisher JD. Results of en- domyocardial biopsy in patients with spontaneous ventricular tachycardia but without apparent structural heart disease. Circulation 1983;68:1171-81. Vignola PA, Aonuma K, Swaye PS, Rozanski JJ, Blankstein RL, Benson J, Gosselin AJ, Lister JW. Lymphocytic myo- carditis presenting as unexplained ventricular arrhythmias: diagnosis with endomyocardial biopsy and response to immu- nosuppression. J Am Co11 Cardiol 1984;4:812-9. Hosenuud JD. McAnultv JH. Niles NR. Unexnected mvocar-

dial disease in patients with life threatening arrhythmias. Br Heart J 1986;56:55-61. Abelmann WH. Myocarditis. N Engl J Med 1966;275:832-34. Zee-Chang CS, Tsai CC, Palmer DC, Codd JE, Pennington DG, Williams GA. High incidence of myocarditis by endom- yocardial biopsy in patients with idiopathic congestive cardi- omyopathy. J Am Co11 Cardiol 1984;3:63-70. Quigley PJ, Richardson PJ, Meany BT, Olsen EGJ, Monaghan MJ, Jackson G, Jewitt DE. Long-term follow-up of active my-

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

Men&s et al. 307

ocarditis: correlation with ventricular function and outcome. Eur Heart J 1987;8:39-42. Davidoff R, Palacios IF, Southern 3, Fallon tJT, Newell J, Dee GW. Giant cell versus lymphocytic myocarditis: a comparison of their clinical features and long-term outcomes. Circulation 1991;17:953-61. Dee GW. Fallon JT. Southern JF. Palacios IF. Relation between histological findings on early repeat right ventricular biopsy and ventricular function in patients with myocarditis. Br Heart J 1988;60:32-7. Mason JW, Billingham ME, Rich DR. Treatment of acute in- flammatory myocarditis assisted by endomyocardial biopsy. Am J Cardiol 1980;45:1037-44. O’Connell JB, Robinson JA, Henkin PE, Gunner RM. Immu- nosuppressive therapy in patients with congestive cardiomy- opathy and myocardial uptake of gallium-67. Circulation 1984;64:780-6. Mason JW, O’Connell JB. Clinical merit of endomyocardial biopsy. Circulation 1989;79:971-9. Wallis DE, O’Connell JB, Henkin RE, Costanzo-Nordin MR, Scanlon PJ. Segmental wall motion abnormalities in dilated cardiomyopathy: a common finding and good prognostic sign. J Am Co11 Cardiol 1984;4:674-9. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JT, Olsen EGJ, Schoen FJ. Myocarditis: a histo- pathologic definition and classification. Am J Cardiovasc Path01 1987;1:3-14. Mason JW. Techniques for right and left ventricular endom- yocardial biopsy. Am J Cardiol 1978;41:887-92. Mann DL, Gillam LD, Weyman AE. Cross-sectional echocar- diographic assessment of regional left ventricular performance and myocardial perfusion. Prog Cardiovasc Dis 1986;29:1-52. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular function using two-dimensional echocardiogra- phy. AM HEART J 1984;107:526-31. Goldberger 35, Himelman RB, Wolfe CL, Schiller NB. Right ventricular infarction: recognition and assessment of its he- modynamic significance by two-dimensional echocardiogra- phy. J Am Sot Echo 1991;4:140-6. Fenoglio JJ, Ursell PC, Kellogg CF, Drusin RE, Weiss MB. Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med 1983;308I12-8. Polak JF. Holman BL. Wvnne J. Colucci WS. Rieht ventric- ular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease. J -Am Co11 Cardiol 1983;2:217-24. Proclemer A. Cisni R. Feruelio GA. Rieht ventricular tachv-

I I

cardia with ventricular dysplasia: clinical features, diagno& techniques, and current management. AM HEART J 1982; 103:415-20. Wichter T, Borggrefe M, Haverkamp W, Chen X, Breithardt G. Efficacv of antiarrhvthmic drugs in natients with arrhvth- mogenic right ventricular disease:-es&s in patients with in- ducible and noninducible ventricular tachycardia. Circulation 1992;86:29-37. Miklozek CL, Crumpacker CS, Royal HD, Come PC, Sullivan JL, Abelmann WH. Myocarditis presenting as acute myocar- dial infarction. AM HEART J 1988;115:768-76. Pinamonti B. Alberti E. Ckalotto A. Dreas L. Salvi A. Silves- tri F, Came&i F. Echocardiographic findings in myocarditis. Am J Cardiol 1988;62:285-91. Gardiner AJS, Short D. The four faces of acute myocarditis. Br Heart J 1973;35:433-42. Case Records of the Massachusetts General Hospital (case 20-19’72). N Engl J Med 1972;286:1100-7. Greenbaum RA, Ho S, Gibson DG, Becker AE, Anderson RH. Left ventricular fibre architecture in man. Br Heart J 1981;45:248-63. Streeter DD. Handbook of physiology. section 2. The heart. In: Berne RM. ed. The cardiovascular svst.em, vol. 1. Baltimore: Williams & Wilkins, 1979:61-112. ”