Response to Letters Regarding Article, “Tissue Doppler Imaging in the Estimation of Intracardiac Filling Pressure in Decompensated Patients With Advanced Systolic Heart Failure”
We thank all the authors for their interest and insightful comments about our article1 and the tremendous contributions of the American Society of Echocardiography/European Association of Echocardiography Diastology Writing Group.2 We believe the many issues raised about the potential inaccuracies of our findings are precisely the factors that may directly influence the reliability of the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/Ea) to act as the single surrogate estimate of left ventricular filling pressures. In particular, the confounding factors that they addressed (such as the degree of ventricular remodeling, prevalence of mitral regurgitation, presence of dyssynchrony, or previous cardiac resynchronization therapy) are commonly observed in patients presenting with advanced decompensated heart failure. These are the exact patients in whom assessing intracardiac filling pressures may have a major impact on treatment decisions (such as initiation of diuretic therapy to relieve congestion). In essence, their salient points about the limitations of our findings are concordant with our observations on the limitations of E/Ea in this largest reported series of patients with advanced decompensated heart failure. Taken together, their comments are supportive of the conclusion that more careful interpretation of E/Ea alone as a surrogate for left ventricular filling pressures is warranted when confounding factors may affect its accuracy and reliability.
Several comments have been made with regard to the technical limitations of our measurements. In other words, what was once hailed as a broadly applicable, technically simple measurement now becomes a challenge in acquisition and patient selection when the data do not fit prior assumptions. Although the accuracy of our measurements has been questioned, we firmly believe that our article represents the best-case scenario of data acquisition in the clinical setting, assessed in a dedicated heart failure unit by experienced heart failure physicians and research sonographers. To clarify, pulmonary capillary wedge pressure (PCWP) was assessed simultaneously at the time of echocardiographic evaluation as the midpoint between the top of the a-wave and the nadir of the x-descent at end-expiration. The position of PCWP was verified by fluoroscopy, and the E/Ea data were always averaged from at least 3 heart beats in the septum and lateral wall to minimize potential effects of regional wall-motion abnormalities. We have discussed at length the potential challenges of measuring Ea in paced ventricles and in those with extensive left ventricular remodeling, which may have in part contributed to our findings.
Concerns were expressed that some of our PCWP measurements seemed low for patients with decompensated heart failure, but lowering intracardiac and intravascular pressures and reducing mitral regurgitation within 12 hours is clearly possible despite ongoing overall congestion when vasodilatation and aggressive diuresis are employed.3 As a reminder, patients with restrictive filling patterns may still demonstrate echocardiographic evidence of diastolic dysfunction despite being aggressively optimized with intravenous medications, which may explain why a lack of correlation exists between changes in E/Ea and PCWP in some patients.
Even when patients with more than moderate mitral regurgitation (22%) or atrial fibrillation (7%) were excluded from the analysis, the predictive value of E/Ea to detect elevated PCWP remained lower than previously reported. In addition, sensitivity and specificity to detect elevated PCWP with E/Ea remained low even when the PCWP threshold was lowered from 18 mm Hg to 15 mm Hg. Indeed, PCWP was similar in patient groups with mitral E/Ea ratios <8, 8 to 15, and >15, and the correlation coefficients for E/Ea assessed using the medial or lateral annulus data or their average were all low (<0.2), indicating that E/Ea did not accurately predict PCWP in our population of patients with advanced heart failure.
Our primary goal is to explain the potential contributing factors that may have affected prior assumptions about this association that was once considered robust between E/Ea and PCWP. Rather than simply contradicting existing data, we believe our findings provide an important refinement to our understanding of echocardiographic indices to estimate left ventricular filling pressures, specifically in this important population. Throughout the article, no assertion has been made that combining several echocardiographic measures and clinical assessment as outlined by the American Society of Echocardiography/European Association of Echocardiography recommendations cannot yield a reliable estimate of left ventricular filling pressure in this patient population. However, the bigger challenge is to understand how to best use these measurements (or changes of these measurements) to help with therapeutic decisions because false action on a presumption of elevated filling pressures due to any single measurement may lead to unwanted clinical consequences. Despite the relatively neutral findings in recent prospective randomized trials comparing routine invasive hemodynamic-guided therapy or natriuretic peptide–guided therapy with standard clinical assessment,4,5 both measurements have established their relative safety profiles in guiding therapeutic decisions. We hope our article draws attention to the need for further prospective investigations to better clarify the appropriate interpretation of echocardiographic measures in the clinical context, especially with regard to safety and efficacy of therapeutic decisions mostly aimed at reducing congestion and guided by these measurements.
Mullens W, Borowski A, Curtin R, Thomas J, Tang WH. Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation. 2009; 119: 62–70.
Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW, ESCAPE Investigators, ESCAPE Study Coordinators. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005; 294: 1625–1633.
Pfisterer M, Buser P, Rickli H, Gutmann M, Erne P, Rickenbacher P, Vuillomenet A, Jeker U, Dubach P, Beer H, Yoon SI, Suter T, Osterhues HH, Schieber MM, Hilti P, Schindler R, Brunner-La Rocca HP, TIME-CHF Investigators. BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-CHF) randomized trial. JAMA. 2009; 301: 383–392.