Acute contractile recovery extent during biventricular pacing is not associated with follow-up in patients undergoing resynchronization

Abstract

Background: It has been reported that contractility, as assessed using dobutamine infusion, is independently associated with reverse remodeling after CRT. Controversy, however, exists about the capacity of this approach to predict a long-term clinical response. This study's purpose was to assess whether long-term CRT clinical effects can be predicted according to acute inotropic response induced by biventricular stimulation (CRT on), as compared with AAI-VVI right stimulation pacing mode (CRT off), quantified at the time of implantation.

Methods: In 98 patients (ejection fraction 29 ± 10%), acute changes in left ventricular (LV) elastance (Ees), arterial elastance (Ea), and Ees/Ea, as assessed from slope changes of the force-frequency relation obtained when the heart rate increased, and also assessed while measuring triplane LV volumes and continuous noninvasive blood pressure, were related to death or rehospitalization during a 3-year follow-up. Other covariances tested were age, gender, disease etiology, QRS duration, amount of mitral regurgitation, LV diastolic volume, ejection fraction, and the degree of asynchrony and longitudinal strain at baseline.

Results: There was a marked increment in the Ees slope with CRT (interaction P = 0.004), no Ea change, and modest Ees/Ea increase (interaction P < 0.05). In Cox analysis, however, neither slope changes nor baseline values of Ees, Ea, and Ees/Ea were associated with long-term follow-up. Only ventricular diastolic volume (direct relation P = 0.002) and QRS duration (inverse relation P = 0.009) predicted death/rehospitalization.

Conclusions: Acute contractile recovery in CRT patients is not associated with 3 years prognosis. Instead, death or rehospitalization can be predicted from QRS duration and LV diastolic volume at baseline.

Keywords: CRT, biventricular stimulation; Congestive heart failure; DYS, dyssynchrony; Dyssynchrony; EDV, end-diastolic volume; EF, ejection fraction; Ea, arterial elastance; Ees, ventricular elastance; FFR, force–frequency relation; Force–frequency relation; HR, hazard ratio; LV, left ventricle; MR, mitral regurgitation; Resynchronization; Speckle-tracking echocardiography; TUS, temporal uniformity of strain; r2, adjusted r squared.

Fig. 1

Methodology adopted for the study. Ventricular volumes were obtained using real-time 3 apical simultaneous longitudinal planes and then by manually tracing the endocardial border with in-built software. Calibrated continuous blood pressure, together with ECG signal, was also available on the screen of the echo machine.

Fig. 2

Assessment of FFR during different modes of stimulation, as far as diastolic and ventricular filling volumes, Ees, and Ea are concerned. There is no difference in diastolic volume between AAI/VVI (CRT off) vs. biventricular pacing mode (CRT on) during FFR, although cavity declines significantly with heart rate increments (P < 0.001, A). Such ventricular volumetric decrement during FFR was true for stroke volumes too (P < 0.001 for trend), but with a significant interaction between time-changes in ejected blood during DDD-CRT (− 10 ± 44%) compared to AAI–VVI pacing mode (− 12 ± .45%, P = 0.027 for interaction) (B). This relative smaller reduction in stroke volume with DDD-CRT developed with no difference in Ea between the 2 pacing modes (NS for interaction), although overall Ea increased progressively with increasing heart rates (P < 0.001 for trend, C). As far as inotropic challenge was concerned, Ees increased significantly during heart rate increments in DDD-CRT, whereas it decreased in AAI–VVI pacing mode (D, interaction P < 0.001). For Ea and Ees, data are displayed as absolute changes, normalized to the index (CRT off) baseline value.

Fig. 3

Survival curves were obtained by dividing patients into 3 groups according to values of ventricular diastolic volume (EDV) and QRS duration compared to the related medians. Three groups were thus created: Group 1, n = 27: EDV < 87 ml/m² and QRS ≥ 160 ms; Group 2, n = 51: EDV > 87 ml/m² and QRS ≥ 160 ms or EDV < 87 ml/m² and QRS < 160 ms; Group 3, n = 20: EDV > 87 ml/m² and QRS < 160 ms. Event-free survival curves were significantly different among the 3 groups (log-rank test P = 0.012). Group 3 event-free survival rate was less than 1/3 of the rate of Group 1 at the end of follow-up, and rapidly decreased in the first 1000 days after CRT. In contrast, Group 1 event-free survival was maintained around 90% until the end of the observation period. The difference, based on a post hoc Holm–Sidak test was statistically significant (P = 0.015). Group 2 exhibited an intermediate trend, with improved event-free survival as compared with Group 3, but worse relative to Group 1, although not at a significant level. EDV = end-diastolic volume.

Fig. 4

Plot of regression between 2 Ees slope measurements performed 12 months apart by a different reader (left). There is a significant correlation between the 2 measurements (r = 0.62, P < 0.001). Also, a plot of the average of the 2 measurements against their difference showed good agreement (right), but the dispersion of the data was slightly larger for CRT off as compared with CRT on.

Supplementary figure

Stroke work (mean ± 1 SE) during assessment of force frequency relation (FFR). Stroke work decreases less with CRT on vs. CRT off (P = 0.01 for interaction).