Copyright © 2005, The European Society of Cardiology
Right vs. left ventricular contractile reserve in one-year prognosis of patients with idiopathic dilated cardiomyopathy: Assessment by dobutamine stress echocardiography
evi
aaaakovia,*
aDr. Aleksandar D. Popovi Cardiovascular Research Center, Dedinje Cardiovascular Institute, Belgrade University Medical School, Milana Tepi
a 1, 11040 Belgrade, Serbia and Montengro
bCNR, Institute of Clinical Physiology, Pisa, Italy
Received 1 October 2004; accepted after revision 24 January 2005.
neskovic{at}hotmail.com
* Corresponding author. Tel.: +381 63 121 63 59; fax: +381 11 266 64 45.
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Abstract |
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Aim
To determine prognostic implications of the assessment of right (RV) vs. left ventricular (LV) contractile reserve with dobutamine echocardiography in patients with idiopathic dilated cardiomyopathy.
Methods and results
Forty-eight consecutive patients (41 male, NYHA class III/IV 13 patients, LV ejection fraction 19±8%) were subjected to dobutamine stress echocardiography in incremental stages lasting 5min each. Contractile reserve was defined as the difference between the values of LV ejection fraction and RV fractional area change obtained at peak dobutamine dose and the baseline values. Patients were followed for one year after enrollment for combined end-point of cardiac death, partial left ventriculectomy and hospitalization for congestive heart failure. During the follow-up 15/48 patients reached combined end-point. Patients who reached end-point had lower RV and LV contractile reserves (14±5 vs. 8±6%, p=0.0014, and 9±5 vs. 3±2%, p<0.001, respectively). Kaplan–Meier curves demonstrated that both LV and RV contractile reserves can identify patients with dismal prognosis (log rank=17.02 and log rank=14.66, respectively, p<0.001 for both). Multivariate analysis identified dobutamine induced change in LV functional reserve as the only independent predictor of combined end-point (beta=–0.63, p=0.0035).
Conclusion
Both RV and LV contractile reserves can be used for prognostic stratification in patients with idiopathic dilated cardiomyopathy. It appears that dobutamine induced change in LV functional reserve may better identify patients with dismal prognosis.
Keywords: Dilated cardiomyopthy; Contractile reserve; Prognosis; Stress echocardiography
Prognostic assessment of subjects with heart failure plays major role in the therapeutic approach to these patients. A number of variables, such as peak exercise oxygen consumption1 and exercise tolerance,2 have been suggested for the identification of patients with poor outcome. Recently, several studies have suggested that the LV contractile reserve assessed by dobutamine stress echocardiography may improve prognostic evaluation of patients with dilated cardiomyopathy.3,4 Although RV size and function have been shown to have major prognostic implications in this group of patients,5 there are only limited reports of prognostic value of right ventricular contractile reserve.6
Therefore, the aim of this study was to determine prognostic implications of the assessment of right vs. left ventricular contractile reserve with dobutamine echocardiography in patients with idiopathic dilated cardiomyopathy during the one-year follow-up.
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Methods |
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The study group consisted of 48 consecutive patients with idiopathic dilated cardiomyopathy who met the following criteria: (1) LV end-diastolic diameter >60mm; (2) LVEF<35%; (3) adequate echocardiographic window (defined as adequate visualization of at least 13/16 segments); and (4) written informed consent after the investigative nature of the procedure was explained. The study was approved by the institutional ethical committee. Diagnosis of idiopathic dilated cardiomyopathy was established by echocardiography if there was no evidence of alcohol intake, arterial hypertension, toxin exposure, myocarditis, hypertrophic cardiomyopathy, valvular heart disease and/or significant coronary artery disease (defined as >50% diameter stenosis of the major epicardial vessel).
All examinations were performed with a Hewlett Packard Sonos 2500 machine (Andover, Massachusetts), using a 2.5MHz transducer, and stored on video tape for later analysis. LVEF was determined from apical two- and four-chamber views using the Simpson's biplane formula. RV fractional area change (FAC) was measured from apical four-chamber view using standard equation.7 For both measurements, tracing of endocardial borders in end-diastole and end-systole was performed on the Hewlett Packard Sonos 2500 machine in the technically best cardiac cycle.
Dobutamine stress echocardiography was performed in all patients in incremental stages lasting 5min each, with an initial dose of 5µg/kg/min, which was increased to 10µg/kg/min, and then to 20 and 30µg/kg/min, and finally to the maximal dose of 40µg/kg/min. The infusion was discontinued before maximal dose if 85% of the maximal predicted heart rate for age group was achieved or symptomatic non-sustained or sustained ventricular tachycardia was observed. Contractile reserve was defined as the difference between the values of LVEF and RVFAC obtained at peak dobutamine dose during the test and the baseline values. Beta-blockers were stopped 48h prior to dobutamine testing in all the patients taking these agents.
Patients were followed for one year after enrollment for combined end-point of cardiac death, partial left ventriculectomy and hospitalization for congestive heart failure. Partial left ventriculectomy was used as a substitute for cardiac transplantation which was unavailable in our country at the time.
All data are expressed as mean±standard deviation. T-test was used for comparisons between the subgroups for continuous variables (a probability value of p<0.05 was considered significant). Kaplan–Meier curves were constructed to assess cardiovascular event-free survival during the one-year follow-up, while receiver operating characteristic curves were computed to determine cut-off points for dobutamine induced change in LVEF and RVFAC (patients with change in LVEF >4% and RVFAC >9% were considered to have preserved left and right ventricular contractile reserve, respectively). Univariate and multivariate Cox model analysis was performed to assess predictors of future cardiovascular events (a probability value of p<0.1 was considered significant).
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Results |
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Patients characteristics are shown in Table 1. It should be noted that the studied patients had severely depressed LV systolic function, whereas RV systolic function was only mildly diminished. Maximal dose of dobutamine infusion averaged 37.9±3.8µg/kg/min. During dobutamine stress echocardiography couplets were noted in 10 patients, and non-sustained ventricular tachycardia was noted in six. However, no test was stopped due to ventricular arrhythmias. On peak dose dobutamine, LVEF increased from 19±8% to 26±12% (p<0.001), and RVFAC from 36±12% to 48±14% (p<0.001). Therefore, left and right ventricular contractile reserves induced by high-dose dobutamine were 7±5% and 12±6%, respectively. There was no correlation between basal LVEF and RVFAC (r=0.26, p=0.07) (Fig. 1A), whereas moderate correlation between dobutamine induced change in these indices was noted (r=0.48, p=0.001) (Fig. 2B).
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LVEF, dobutamine induced change in left ventricular ejection fraction; RVFAC, right ventricular fractional area change;
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During the one-year follow-up, 15/48 patients reached combined end-point. Namely, cardiac death was observed in five patients, partial left ventriculectomy was performed in three, and seven patients were hospitalized due to signs and symptoms of worsening congestive heart failure. Patients who reached end-point had lower right and left contractile reserve (14±5 vs. 8±6%, p=0.0014, and 9±5 vs. 3±2%, p<0.001, respectively). Linear correlation revealed significant association between the extent of LV and RV contractile reserve and one-year event-free survival (r=0.55 and r=0.50, respectively, p<0.001 for both). There was no difference in the use of digoxin, beta-blockers, ACE inhibitors, and diuretics between the groups. Cox analysis also did not show that the use of any particular medication is predictive of combined end-point during the follow-up.
Kaplan–Meier curves for one-year event-free survival demonstrated that both left and right ventricular contractile reserves can identify patients with worse prognosis (log rank=17.02 and log rank=14.66, respectively, p<0.001 for both) (Fig. 2A and B). The subgroup analysis demonstrated that the patients with preserved both LV and RV contractile reserves had the best one-year prognosis (log rank=20.10, p<0.001) (Fig. 2C). On the other hand, in the subgroup of patients with poor LV contractile reserve, Kaplan–Meier analysis failed to identify additive prognostic significance of preserved RV contractile reserve (log rank=2.00, p=0.15) (Fig. 2D). Similar analysis for patients with poor RV, but preserved LV, contractile reserve was not performed due to small number of patients in this subgroup.
In univariate analysis, dobutamine induced changes in both the right and left ventricular functional reserves have been shown to be predictors of combined end-point (beta=–0.12, p=0.01, and beta=–0.49, p=0.007, respectively). However, multivariate analysis that included age, sex, NYHA class on admission, basal and peak dobutamine LVEF and RVFAC, as well as LV and RV contractile reserves, identified dobutamine induced change in left ventricular functional reserve as the only independent predictor of combined end-point (beta=–0.63, p=0.0035).
Both right and left ventricular contractile reserves had good overall specificity (87% and 89%, respectively), but rather poor overall sensitivity (62% and 65%, respectively), for combined end-point during the one-year follow-up. Specificity and sensitivity were augmented in the subgroup of patients in whom both LV and RV contractile reserves were either preserved or diminished (95% and 75%, respectively).
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Discussion |
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This study demonstrates that both left and right ventricular contractile reserves can reliably identify patients with dismal prognosis during the one-year follow-up. Our findings regarding LV contractile reserve are in accordance with a large body of evidence suggesting prognostic usefulness of changes in LV functional reserve induced by either exercise or dobutamine infusion.8,9 Because of its dependance on loading conditions, usefulness of LVEF in the assessment of contractile reserve has been questioned. However, it has been demonstrated that exercise induced changes in LVEF, measured by radionuclide scintigraphy, was the most powerful predictor of survival in patients with idiopathic dilated cardiomyopathy without overt heart failure.10
RV contribution to global cardiac performance is minor in subjects with normal or mildly depressed LV systolic function, but may become more important in patients with advanced left heart failure.11,12 Previous studies have suggested that RV enlargement is a strong marker for adverse prognosis in patients with idiopathic dilated cardiomyopathy, and that the patients with similar level of right and left ventricular dilatation have lower overall survival and higher degrees of mitral and tricuspid regurgitation.13 Additionally, it has been demonstrated that RV long axis excursion is predictive of exercise tolerance14 and that tricuspid annular plane systolic excursion adds significant prognostic information to traditional clinical, hemodynamic and echocardiographic prognostic variables.15
DiSalvo and colleagues have demonstrated that an increase in RVEF to >35% during exercise is the only independent predictor of event-free survival in patients with advanced heart failure.16 Gorcsan and coworkers have elegantly demonstrated that preserved RV contractile reserve (measured by pressure–area relations) in response to low-dose dobutamine was associated with a good 30-day outcome in patients with NYHA class IV heart failure.6 In our study this observation was extended to: (1) larger group of patients, (2) patients with wider spectrum of heart failure severity, (3) longer follow-up, and (4) harder end-points, including cardiac death and partial left ventriculectomy. Although the use of pressure–area relations may be theoretically more sound, they are difficult to obtain, rendering this approach far too complex for everyday use in a busy clinical practice. We showed that a simple and easily obtained non-invasive index, such as RVFAC, may be used for the assessment of contractile reserve despite its heavy dependance on loading conditions.
Our data suggest prognostic primacy of left over right ventricular contractile reserve. The reasons for this are not clear, but may be partly explained by increased left-to-right systolic interaction in dilated cardiomyopathy as compared to normal heart.17 Also, an experimental study has demonstrated variable effects of heart failure on calcium handling in left and right ventricles, which may affect the extent of dobutamine induced change in ventricular functional reserve.18
Subgroup analysis showed that the best separation in terms of outcome was achieved when preservation of both left and right ventricular contractile reserves was taken into account. Indeed, using this approach specificity for combined end-point during the one-year follow-up reached 95%, but more importantly sensitivity also increased to 75%. On the other hand, it appears that preserved RV contractile reserve has no additive prognostic significance in patients with poor LV contractile reserve, suggesting that the outcome of patients with idiopathic dilated cardiomyopathy is primarily dependent on LV systolic performance reserve.
Limitations of the study
The present study included relatively small number of patients who were followed for a year after index examination. During the follow-up only a limited number of hard end-points, such as cardiac death and partial left ventriculectomy, were noted, suggesting that the prognostic importance of RV functional reserve should be further validated in a larger group of patients.
In conclusion, our data indicate that both right and left ventricular contractile reserves can be used for prognostic stratification in patients with idiopathic dilated cardiomyopathy. Dobutamine induced change in LV functional reserve may better identify patients with dismal prognosis. However, it appears that the combination of these variables may yield the best prognostic significance.
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References |
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