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Role of Echocardiography in Predicting Onset of Heart Failure in Patients With Stable Coronary Artery Disease

Is the Whole Greater Than the Sum of its Parts?^_*

Department of Cardiology, Methodist Hospital and the Methodist DeBakey Heart and Vascular Center, Houston, Texas

Key Words: echocardiography • heart failure • coronary artery disease

In this issue of iJACC, Stevens et al. (6) explored the hypothesis that findings derived from a resting transthoracic echocardiogram in patients with CAD can be combined to develop a risk-stratification index that predicts HF hospitalization. They studied 1,024 ambulatory subjects participating in the Heart and Soul Study, all of whom had clinical characteristics that placed them in stage A or B heart failure (known CAD, previous MI [>6 months], hypertension). More than 80% of the participants had never experienced a hospitalization for HF, and the majority (92.7%) had an EF >45% (mean EF: 62 ± 10%; range: 13% to 83%).

Using the Cox proportional hazard model, the authors assessed the association of 15 transthoracic echocardiogram measurements with subsequent HF hospitalization. Although most of the variables were identified as predictors of HF hospitalization by univariate analysis, only 5 were independent predictors: mitral regurgitation (MR), left atrial volume index (LAVI), LV mass index, the integral of the velocity in the LV outflow tract by pulsed-wave Doppler (VTI_LVOT), and diastolic dysfunction (i.e., pseudonormal or restrictive mitral inflow pattern indicative of elevated filling pressures). The authors applied a point-scoring system to the 5 variables to develop a HF risk index (RI) with a scale ranging from 0 to 8 (1 point each given for mild MR, LAVI >29 ml/m², VTI_LVOT <22 cm; 2 points for diastolic dysfunction; and 3 points for LV mass index >90 g/m²). During an average follow-up of 4.4 years, HF hospitalizations were observed in 4% of participants with an RI of 0 to 2 compared with 10% with an RI of 3 to 4 (p = 0.003); 24% with an RI of 5 to 6 (p < 0.0001); and 48% with an RI of 7 to 8 (p < 0.0001). The association between the RI and HF hospitalization remained significant even after adjusting for several comorbidities. Results were similar, but with lower risks in the 831 participants without a previous history of HF.

Four of the 5 components of the HFRI have been identified previously as predictors of outcome in patients with CAD and/or LV dysfunction. In MI survivors, the presence of functional/ischemic MR, even if mild, is associated with higher mortality and worsening of HF (7). Left atrium (LA) enlargement and diastolic dysfunction have been shown to predict worse outcomes in patients with CAD, hypertension, and/or LV dysfunction (8–15). Left ventricular dilation (i.e., eccentric hypertrophy) and concentric hypertrophy are both associated with a greater prevalence of cardiovascular events and death, and both are captured by measuring LV mass (10,16–18). In fact, in multiple studies, LV mass consistently appears as a strong independent predictor of outcome. In a cohort of 1,172 patients enrolled in the SOLVD (Studies Of Left Ventricular Dysfunction) trials (n = 577) and registry (n = 595), LV mass, LA size, and EF were independent predictors of 1-year mortality and the rate of cardiovascular hospitalizations (10). Left ventricular mass was a strong predictor, and at lower ranges, had a protective effect irrespective of EF. The fact that close to 98% of the participants in this study had preserved EF explains why this measurement lost power as an independent predictor of HF hospitalization.

Although each of the 5 echocardiographic parameters in this study predicted outcome, when combined into an HFRI, the prediction of risk was superior to that provided by any single parameter. This is a good example of "the whole is greater than the sum of its parts." There are several examples in medicine in which individual parameters are combined into a risk stratification score; perhaps the most commonly known in cardiology is the Framingham Risk Score, which combines sex, age, blood pressure, cholesterol levels, diabetes, and smoking to predict a 10-year risk of developing CAD (19). Therefore, this concept makes clinical sense and has a strong statistical basis.

Although the components of the HFRI are commonly used by clinical echocardiographers, measurement techniques vary between laboratories, and this could influence the cut-off values used to determine the HFRI. The authors measured LA volume with the biplane method of disc, but other laboratories use the area-length method; both are endorsed by the American Society of Echocardiography (20). However, normal ranges vary slightly between these methods. Similarly, LV mass was measured with the truncated ellipsoid equation, but other laboratories use the American Society of Echocardiography modification of the cube formula, which has slightly different normal ranges. The authors defined pseudonormal diastolic dysfunction as a peak mitral early diastolic to atrial contraction velocity (E/A) ratio between 0.76 and 1.4, with diastolic-dominant pulmonary vein flow, and a restrictive pattern as an E/A 1.5, with diastolic dominant pulmonary vein flow. These patterns are markers for elevated LV filling pressures and were initially described in patients with depressed LV function using the E/A ratio and deceleration time (9). However, they are known to lose accuracy in patients with preserved EF (21). Consequently, most laboratories currently use the ratio of transmitral E-velocity to early diastolic annular velocity by tissue Doppler (E/E') to better define these patterns, particularly in patients with normal EF; an E/E' 15 detects a mean left atrial pressure >15 mm Hg and is a marker of advanced diastolic dysfunction (15,22). This ratio has also been shown to predict HF events in populations at risk (14,15). Using E/E' to define diastolic dysfunction could have important influence on the HFRI, perhaps by improving its predictive accuracy. It may be worthwhile to investigate this hypothesis prospectively.

Ultimately, the value of any risk stratification method is to identify patients who benefit from more aggressive preventive measures. All of the study participants were in stage A or B heart failure and would benefit from aggressive management of their risk factors (2). Consequently, it is not clear how much more is gained by restratifying them with an echocardiographic HFRI. Perhaps patients in stage A with an HFRI >5 would benefit from receiving therapy recommended for stages B or C, particularly if they have evidence of diastolic dysfunction (i.e., elevated filling pressures). The only answer to this question would come from a randomized clinical trial in which 1 group is treated based on an HFRI, while the other is managed according to the ACC/AHA guidelines. Until then, we should adhere to the ACC/AHA recommendations. Nevertheless, the echocardiographic HFRI represents an important step in simplifying data from a routine transthoracic echocardiogram and using it to enhance our assessment of risk for heart failure hospitalization in selected patients.

	Footnotes

 
^_* Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.

^_* Reprint requests and correspondence: Dr. Miguel A. Quinones, Department of Cardiology, Methodist Hospital, Cardiology, 6550 Fannin, Suite 1901, Houston, Texas 77030 (Email: maquinones{at}tmhs.org).

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