Prediction of Acute Response to Cardiac Resynchronization Therapy by Means of the Misbalance in Regional Left Ventricular Myocardial Work.

BACKGROUND: Patients with left ventricular (LV) dyssynchrony have a marked misbalance in LV myocardial work distribution, with wasted work in the septum and increased work in the lateral wall. We hypothesized that a low septum-to-lateral wall (SL) myocardial work ratio at baseline predicts acute LV pump function improvement during cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Twenty patients (age 65 ± 10 y, 15 men) underwent cardiac magnetic resonance (CMR) tagging for regional LV circumferential strain assessment and invasive pressure-volume loop assessment at baseline and during biventricular pacing. Segmental work at baseline was calculated from regional strain rate and LV pressure. Subsequently, the SL work ratio was calculated and related to acute pump function (stroke work [SW]) improvement during CRT. During biventricular pacing, SW increased by 33% (P <.001). SL work ratio at baseline was found to be significantly related to SW improvement by means of CRT (R = -0.54; P = .015). Moreover, it proved to be the only marker that was significantly related to acute response to CRT, whereas QRS duration and other measures of dyssynchrony or dyscoordination were not. CONCLUSIONS: The contribution of the septum to LV work varies widely in CRT candidates with left bundle branch block. The lower the septal contribution to myocardial work at baseline, the higher the acute pump function improvement that can be achieved during CRT.

Prognostic implications of invasive hemodynamics during cardiac resynchronization therapy: Stroke work outperforms dP/dtmax.

Background: Invasive measurements of left ventricular (LV) hemodynamic performance can evaluate acute response to cardiac resynchronization therapy (CRT). Objective: The study sought to determine which metric, maximum rate of LV pressure rise (LV dP/dtmax) or LV stroke work (LVSW), is more strongly associated with long-term prognosis. Methods: CRT patients were prospectively included from 3 academic centers. Invasive pressure-volume loop measurements during implantation were performed, and LV dP/dtmax and LVSW were determined at baseline and during biventricular pacing (BVP) as well as their relative increase (%Δ). Hazard ratios (HRs) for the primary outcome of 8-year all-cause mortality were derived using Cox proportional hazards. The secondary endpoint was echocardiographic response, defined as 6-month LV end-systolic volume reduction ≥15%. Results: Paired data from 82 patients were analyzed (67% male; age 66 ± 9 years; QRS duration 158 ± 22 ms, median survival time 72 months). Survival was better when LVSW during BVP was ≥4400 mL∙mm Hg (HR 0.21, 95% CI 0.08-0.58, P < .003) or when ΔLVSW% was ≥10% (HR 0.22, 95% CI 0.08-0.65, P = .006). In multivariate analysis, following direct comparison of continuous measures of acute ΔLV dP/dtmax% and ΔLVSW%, only ΔLVSW% remained associated with the primary endpoint (HR 0.982 per percentage point, P = .028). In contrast to LV dP/dtmax (all P > .05), significant associations with echocardiographic response were found for stroke work during BVP (area under the receiver-operating characteristic curve 0.745, P = .001) and ΔLVSW% (area under the receiver-operating characteristic curve 0.803, P < .001). Conclusion: Stroke work, but not LV dP/dtmax, is consistently associated with long-term prognosis and response after CRT. Our results therefore favor the use of stroke work as the hemodynamic parameter to predict long-term outcome after CRT.

Loss of opposite left ventricular basal and apical rotation predicts acute response to cardiac resynchronization therapy and is associated with long-term reversed remodeling.

BACKGROUND: Normal left ventricular (LV) torsion is caused by opposite basal and apical rotation. Opposite rotation can be lost in heart failure, but might be restored by pacing; therefore, the predictive value of the loss of opposite base-apex rotation in heart failure patients for the response to cardiac resynchronization therapy (CRT) was studied. METHODS AND RESULTS: In 34 CRT candidates and 12 controls, basal and apical LV rotations were calculated using magnetic resonance image tagging. Loss of opposite rotation was quantified by the correlation between both rotation curves: a negative correlation indicates normal, opposite rotation and a positive correlation indicates that base and apex rotate in the same direction. In patients, LV pressure was measured invasively during biventricular stimulation. Acute response to CRT was defined by >10% increase in dP/dt(max) relative to baseline. LV volume was determined at baseline and 8 months follow-up using echocardiography. The base-apex rotation correlation (BARC) was significantly higher in acute responders (n=22) than in nonresponders (n=12) and controls (0.64+/-0.51, -0.23+/-0.67, and -0.68+/-0.22, respectively; P=.001). The sensitivity and specificity for prediction of acute response were 82% and 83%, respectively, at a cutoff value of 0.5. At follow-up, volumes could be analyzed in 18 patients. In the group with BARC >0.5, end-diastolic volume decreased by 7% (NS), end-systolic volume by 16%, and ejection fraction increased by 28% (both P=.02), whereas in the group with BARC <0.5, no significant changes were observed. CONCLUSIONS: The loss of opposite base-apex rotation in patients eligible for CRT is an excellent predictor of acute response and is associated with LV reverse remodeling.

Hemodynamic Optimization in Cardiac Resynchronization Therapy: Should We Aim for dP/dtmax or Stroke Work?

OBJECTIVES: This study evaluated the acute effect of dP/dtmax- versus stroke work (SW)-guided cardiac resynchronization therapy (CRT) optimization and the related acute hemodynamic changes to long-term CRT response. BACKGROUND: Hemodynamic optimization may increase benefit from CRT. Typically, maximal left ventricular (LV) pressure rise dP/dtmax is used as an index of ventricular performance. Alternatively, SW can be derived from pressure-volume (PV) loops. METHODS: Forty-one patients underwent CRT implantation followed by invasive PV loop measurements. The stimulation protocol included 16 LV pacing configurations using each individual electrode of the quadripolar lead with 4 atrioventricular (AV) delays. Conventional CRT was defined as pacing from the distal electrode with an AV delay of approximately 120 ms. RESULTS: Compared with conventional CRT, dP/dtmax-guided optimization resulted in a one-third additional dP/dtmax increase (17 ± 11% vs. 12 ± 9%; p < 0.001). Similarly, SW-guided optimization resulted in a one-third additional SW increase (80 ± 55% vs. 53 ± 48%; p < 0.001). Comparing both optimization strategies, dP/dtmax favored contractility (8 ± 12% vs. 5 ± 10%; p = 0.015), whereas SW optimization improved ventricular-arterial (VA) coupling (45% vs. 32%; p < 0.001). After 6 months, mean LV ejection fraction (LVEF) change was 10 ± 9% with 23 (56%) patients becoming super-responders to CRT (≥10% LVEF improvement). Although acute changes in SW were predictive for long-term CRT response (area under the curve: 0.78; p = 0.002), changes in dP/dtmax were not (area under the curve: 0.65; p = 0.112). CONCLUSIONS: PV-guided hemodynamic optimization in CRT results in approximately one-third SW improvement on top of conventional CRT, caused by a mechanism of enhanced VA coupling. In contrast, dP/dtmax optimization favored LV contractility. Ultimately, acute changes in SW showed larger predictive value for long-term CRT response compared with dP/dtmax.

Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements.

AIMS: Invasive assessment of acute haemodynamic response to biventricular pacing has been proposed as a tool to determine individual response and to optimize the effects of CRT. However, the long-term results of this approach have been poorly studied. The present study relates acute haemodynamic effects of CRT to long-term outcome. METHODS AND RESULTS: Forty-one patients were analysed in the present study. During temporary biventricular pacing before implantation, acute changes in LV pump function were assessed by pressure-volume loop measurements and related to long-term response after CRT. In the study population [30 (71%) men, NYHA class 2.9 ± 0.4, EF 28 ± 7%, QRS 150 ± 25 ms], baseline mean stroke work (SW) and dP/dt(max) were 4.6 ± 2.6 L × mmHg and 874 ± 259 mmHg/s, respectively. During biventricular pacing, mean SW and dP/dt(max) increased significantly by 43 ± 39% (+ 2.2 ± 2.4 L × mmHg, P < 0.001) and 13 ± 18% (+ 96 ± 136 mmHg/s, P < 0.001), respectively. In long-term responders (n = 29, 71%) compared with non-responders (n = 12, 29%), the acute increase in SW was significantly higher (+57 ± 33% vs. + 10 ± 30%, P < 0.001), whereas the acute increase in dP/dt(max) was not significantly different between responders and non-responders (+ 15 ± 18% vs. 6 ± 15%, P = 0.139). Receiver operating characteristic (ROC) curve analysis indicated that SW was superior to dP/dt(max), QRS duration and LV dyssynchrony in prediction of response to CRT. A cut-off value for SW of 20% yielded a sensitivity of 90% and specificity of 75% to predict reverse remodelling at 6 months. CONCLUSION: Invasive assessment of acute haemodynamics is a reliable tool to determine individual response to CRT. An acute increase in SW predicts long-term response to CRT with a higher accuracy than an acute increase in dP/dt(max), baseline QRS duration, and degree of LV mechanical dyssynchrony.

Comparison between three-dimensional speckle-tracking echocardiography and cardiac magnetic resonance imaging for quantification of left ventricular volumes and function.

AIMS: We evaluated the accuracy of three-dimensional speckle-tracking echocardiography (3DSTE) to evaluate left ventricular (LV) volumes, ejection fraction (EF), and global circumferential strain (CS) in comparison with cardiac magnetic resonance imaging (MRI) in a healthy population. METHODS AND RESULTS: A total of 45 out of 50 consecutive healthy subjects (38 males, age 45 ± 15 years) successfully underwent both 3DSTE and MRI on the same day. Three-dimensional echocardiography data sets were analysed using speckle tracking to measure LV end-diastolic and end-systolic volumes, EF, and global CS. With MRI, the method of discs approximation was used to obtain volumes and the EF, whereas CS was acquired using myocardial tissue tagging. Inter-technique comparisons included regression and the Bland-Altman analysis. For quantification of LV volumes, 3DSTE correlated well with MRI (r: 0.75-0.81), but volumes were significantly underestimated with relatively large biases (13-34 mL) and wide limits of agreement (SD: 11-25 mL). However, excellent accuracy was revealed for measurement of EF by 3DSTE with a good correlation (r: 0.91), minimal bias, and narrow limits of agreement (0.6 ± 1.7%) compared with MRI. For measurement of CS, a large mean bias was found between techniques (10.0%), despite narrow limits of agreement (SD: 1.7%) and a good correlation between techniques (r: 0.80). CONCLUSION: Although 3DSTE-derived LV volumes are underestimated in most patients compared with MRI, measurement of the LVEF revealed excellent accuracy. Measurements of CS were systematically greater (i.e. more negative) with 3DSTE than MRI, which likely reflects various inter-technique differences that preclude direct comparability of their measurements.

Effects of QRS duration and pacing location on pressure-volume loop evaluation of cardiac resynchronization therapy in end-stage heart failure.

Cardiac resynchronization therapy (CRT) decreases the morbidity and mortality in patients with end-stage heart failure. However, patient selection remains challenging, because a considerable 30% to 50% do not respond. Controversy exists on the cutoff values for the QRS duration and the optimal lead location. The present study relates these parameters on an individual basis to acute pump function improvement using invasively obtained pressure-volume loops. Fifty-seven patients with symptomatic end-stage heart failure were included in our temporary biventricular stimulation study and were grouped according to the QRS duration (QRS <20 ms, QRS ≥120 ms but <150 ms, and QRS ≥150 ms). All patients underwent pressure-volume loop assessment of the response to biventricular pacing, comparing the baseline measurements to both right ventricular apex pacing combined with a left ventricular lead in the posterolateral and anterolateral region of the LV. Group analysis during conventional (posterolateral and right ventricular apex) CRT did not show improvement in stroke work and dP/dt(max) (-2%, p = NS; and -7%; p <0.001) in the narrow QRS group but a significant increase in the intermediate (+27%, p = 0.020, and +5%, p = 0.044) and wide (+48%, p = 0.002, and +18%, p <0.001) QRS groups. CRT using the anterolateral and right ventricular apex configuration evoked a consistently lower response compared to posterolateral and right ventricular apex, resulting in a significant hemodynamic deterioration in the narrow QRS group. However, analysis on an individual basis identified 25% of patients with narrow QRS duration showing possible hemodynamic benefit from CRT compared to 83% of patients with intermediate and wide QRS combined. In contrast, 15% of patients had deterioration by conventional (posterolateral right ventricular apex) CRT in the intermediate and wide QRS groups compared to 31% in the narrow QRS group; 19% of patients could be improved by lead placement in the anterolateral rather than the posterolateral region. In conclusion, the acute hemodynamic response to CRT is generally in line with the long-term results from large randomized trials; however, the individual variation is large. The temporary biventricular stimulation protocol might aid in individual patient selection and in research aiming at a reduction of nonresponders and improvement in lead positioning.