Determining the prognosis in each patient with idiopathic dilated cardiomyopathy (IDC) has been an important goal since the introduction of cardiac transplantation. Although heart transplants continue to be limited to critically ill patients, the triage of IDC patients will assume greater importance as the era of an implantable artificial heart nears. How successful are current approaches to identifying patients with high short-term mortality rates?
The New York Heart Association-rated class IV patient who experiences repeated hospitalizations and has a need for inotropic support is clearly at a high risk of death. Thus, the consideration for a heart replacement is straightforward. Most patients with IDC are not critically ill and do not require such an urgent intervention, yet perhaps 20% of such patients will die within 1 year. Early follow-up studies (1-6) have identified a number of variables that are associated with an adverse outcome. Some of the better predictors were New York Heart Association class rating, increasing age, a low left ventricular ejection fraction (LVEF), high left ventricular filling pressures, a very dilated left ventricle, exercise peak oxygen uptake (V[O.sub.2]) of < 11 to 16 mL/kg/min, marked intraventricular conduction delay (including a permanent pacemaker), and complex ventricular arrhythmias. Later studies that included echocardiography confirmed the importance of these factors and identified additional variables associated with adverse outcomes, including a relatively low left ventricular mass, (7) the presence of moderate or greater mitral regurgitation, (8) an increased left atrial size, right ventricular enlargement, (9) and a reduced right ventricular ejection fraction. (10) Echocardiographic parameters of diastolic function that reflect a high left atrial pressure were also predictive of adverse outcomes and included a high early diastolic mitral inflow velocity, a short early diastolic mitral inflow velocity deceleration time, (11,12) and a reduced pulmonary venous inflow velocity during ventricular systole. (13) A "Doppler index," which was defined using the formula (isovolumic contraction time + isovolumic relaxation time)/ejection time, was introduced to assess both right and left ventricular function and, as would be anticipated, the reduced function of either ventricle identified patients with unfavorable outcomes. (14,15)
As each discipline examined patients with IDC, the number of variables associated with adverse outcomes or a high mortality rate grew. An increase in the late potentials of the QRS complex, as seen in the signal-averaged ECG, was shown to be an independent predictor of all-cause cardiac death. (16) The presence of chronic and excessive cardiac sympathetic stimulation implies an adverse prognosis and can be identified by high serum levels of circulating catecholamines, a decrease in the heart rate variability during Holter monitoring, (17) or down-regulation of the myocardial [beta]-adrenergic receptors, as assessed by nuclear metaiodobenzylguanidine imaging. (18) Ventricular tachycardia and complex ventricular arrhythmias during a 24-h Holter recording, when associated with a low LVEF, place patients at a higher risk of death. (19) Markers of myocardial cell death, such as an elevation of serum troponin T levels, (20) an increased ratio of creatine kinase M[B.sub.2]/M[B.sub.1], (21) and scintigraphic evidence of an abnormal myocardial uptake of a monoclonal antibody to myosin, (22) all identify IDC patients who are at high risk.
With the exception of peak V[O.sub.2], the many variables reviewed above assessed only resting cardiac function. Perhaps ventricles that are able to favorably respond to a transient inotropic stimulus (ie, contractile reserve) would be capable of long-term improvement and would be associated with a better prognosis. Conversely, the irreversibly damaged ventricle would not exhibit enhanced function, and the prognosis would be poor. The utility of assessing the contractile reserve of severely hypokinetic myocardial regions in patients with chronic ischemic heart disease is now well-established. Revascularization of the myocardial segments exhibiting contractile reserve leads to improved regional function. Whether evidence of contractile reserve in IDC patients also would identify those most likely to respond favorably to medical therapies has only been explored in the last 10 years. Dubois-Rande et al (23) studied 36 patients and reported in 1992 that patients demonstrating an increase in left ventricular dP/dt with intracoronary dobutamine infusion had favorable responses to medical therapy. Subsequently, five reports (24-28) involving a total of 223 patients have shown the utility of contractile reserve as an indicator of prognosis. Exercise was the inotropic stimulus in one study, (24) and IV dobutamine infusion was used in the others. (25-28) Protocols for the infusion of dobutamine differed, and the measurements used to assess contractile reserve varied. Nevertheless, the results of these studies are consistent in that patients exhibiting enhanced left ventricular function had better clinical outcomes over relatively short periods of follow-up (ie, 6 to 36 months). Interestingly, the report by Kitaoka et al (28) found that the LVEF during dobutamine infusion and the LVEF at follow-up were closely related.
In this issue of CHEST, Drozdz and his colleagues (see page 1216) extend these observations in a larger group of 77 patients who were observed for a remarkably long (mean [+ or -] SD) period of 63 [+ or -] 7 months. The failure of ventricular function to improve during dobutamine infusion at 10 [micro]g/kg/min was defined as either a left ventricular end-systolic volume of > 150 mL or no decrease in the left ventricular end-diastolic volume. Importantly, the failure to show improved ventricular function was a significant predictor of a fatal outcome and replaced other known clinical and echocardiographic predictors of death in a multivariate analysis. The clinical variables of male gender and atrial fibrillation remained potent indicators of a poor outcome.
Recently, Scrutinio et al (27) reported their studies of contractile reserve in 60 IDC patients. They measured contractile reserve as the percentage change in the end-systolic volume index during dobutamine infusion, and this parameter was significantly related to the patient's exercise capacity, which was expressed as peak V[O.sub.2]. Either a small percentage decrease in the end-systolic volume index or a low peak V[O.sub.2] was predictive of the occurrence of clinical events. Unfortunately, this study was underpowered to assess the utility of these variables to predict death.
Despite all these studies, the relative value of each test remains unclear, and we continue to be uncertain as to which tests should be performed routinely. The majority of the reported observations have been in relatively small numbers of patients, the variables that were measured differ, selection bias cannot always be discerned, definitions of unfavorable outcomes have differed, and the follow-up intervals generally have been brief. Nevertheless, there are some common themes running through these and other studies (29,30) that are consistent with clinical experience. A favorable prognosis is likely under the following conditions: (1) when the diseased left ventricle exhibits improved systolic function either during inotropic stimulation or in association with treatment; (2) when exercise capacity, as measured by peak V[O.sub.2] or the results of a 6-min walk test, is reasonably preserved; (3) when signs of a high left atrial pressure are absent; (4) when there is no evidence of a continued hypersympathetic state; and (5) when there are no major arrhythmic events. Although the LVEF is useful in assessing the prognosis for groups of patients, it is less helpful as a single variable in assessing the prognosis of an individual patient.
Recognition of the IDC patient who is at very high risk for death in the near term is more problematic. Confidence in our ability to identify these patients correctly will come when the many univariate predictors of death are applied to a large cohort in a multicenter trial. This will allow a robust multivariate analysis of the relative utility of our many tests and should lead to a more focused and accurate evaluation of each patient with IDC. A measure of the contractile reserve of the left ventricle is very likely to be one of the important variables in predicting outcome. The best indicator of contractile reserve needs to be identified, but it is probable that changes in end-systolic dimensions or volume will provide useful prognostic information.
Dr. Bahler is affiliated with Case Western Reserve University School of Medicine, and the Heart and Vascular Center, MetroHealth Medical Center.
Correspondence to: Robert C. Bahler, MD, Heart and Vascular Center, MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, OH 44109; e-mail: firstname.lastname@example.org
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