The concept of triple wavefront fusion during biventricular pacing: Using the EGM to produce the best acute hemodynamic improvement in CRT.

BACKGROUND: Previous reports suggest that biventricular pacing (BiVp) fused with intrinsic conduction (BiVp-fusion, triple wavefront fusion) is associated with improved resynchronization compared to pure-BiVp in cardiac resynchronization therapy (CRT). This study aimed to assess the association between acute hemodynamic benefit of CRT and signs of BiVp-fusion by using a novel electrogram (EGM)-based method. METHODS: In 17 patients undergoing CRT implantation, 28 combinations of atrioventricular (AV) and interventricular (VV) delays were applied while invasively measuring acute hemodynamic response based on maximum rate of left ventricular (LV) pressure rise (LV dP/dtmax ) to assess optimal BiVp settings. BiVp-fusion was noted if farfield signal (caused by first intrinsic ventricular depolarization) was seen prior to right ventricular (RV) pacing (RVp) artifact on integrated bipolar RV EGM, or QRS morphology changed compared to pure-BiVp (short AV-delay) as seen on electrocardiogram (ECG). RESULTS: Mean optimal RVp timing was at 98 ± 17% of intrinsic right atrial (RA)-RVfarfield (interval from right atrial pace or sense to RV farfield signal) interval, while preactivating the LV at 50 ± 11% of RA-RVsense (interval from right atrial pace or sense to RV sense interval) interval. BiVp-fusion was noted in 16 of 17 (94%) patients on ECG during optimal BiVp. Eight of these patients showed intrinsic farfield signal prior to RVp artifact on RV EGM. In the remaining eight, the RVp was paced just within the RA-RVfarfield interval with a mean of 25 ± 14 ms prior to the onset; therefore, the intrinsic farfield was masked. CONCLUSION: Optimal hemodynamic BiVp facilitates triple wavefront fusion, by pacing the RV around the onset of intrinsic farfield signal on RV EGM, while preactivating the LV. Aiming at BiVp-fusion could be a target for noninvasive EGM-based CRT device setting optimization.

Cardiac resynchronisation therapy optimisation strategies: systematic classification, detailed analysis, minimum standards and a roadmap for development and testing.

In this article an international group of CRT specialists presents a comprehensive classification system for present and future schemes for optimising CRT. This system is neutral to the measurement technology used, but focuses on little-discussed quantitative physiological requirements. We then present a rational roadmap for reliable cost-effective development and evaluation of schemes. A widely recommended approach for AV optimisation is to visually select the ideal pattern of transmitral Doppler flow. Alternatively, one could measure a variable (such as Doppler velocity time integral) and "pick the highest". More complex would be to make measurements across a range of settings and "fit a curve". In this report we provide clinicians with a critical approach to address any recommendations presented to them, as they may be many, indistinct and conflicting. We present a neutral scientific analysis of each scheme, and equip the reader with simple tools for critical evaluation. Optimisation protocols should deliver: (a) singularity, with only one region of optimality rather than several; (b) blinded test-retest reproducibility; (c) plausibility; (d) concordance between independent methods; and (e) transparency, with all steps open to scrutiny. This simple information is still not available for many optimisation schemes. Clinicians developing the habit of asking about each property in turn will find it easier to win now down the broad range of protocols currently promoted. Expectation of a sophisticated enquiry from the clinical community will encourage optimisation protocol-designers to focus on testing early (and cheaply) the basic properties that are vital for any chance of long term efficacy.

Programmed versus effective VV delay during CRT optimization: when what you see is not what you get.

BACKGROUND: In cardiac resynchronization therapy (CRT) devices, the interventricular (VV) delay denotes the time interval between left (LV) and right ventricular (RV) pacing. This study aimed to determine the proportion of patients in whom the effective VV delay (VVeff , delay between LV and RV depolarization, being induced either by pacing or intrinsic conduction) is different from the programmed VV delay during a standard VV delay optimization procedure. METHODS: Thirty-three patients with heart failure and left bundle branch block configuration without total atrioventricular (AV) block receiving CRT were prospectively included. VVeff was calculated from intrinsic AV intervals, programmed optimal AV delay, and programming system. Intrinsic AV intervals were measured on intracardiac electrograms. The optimal AV and VV delays were determined by highest increase in maximum rate of LV pressure rise (dP/dtmax ). VV delays of 20-80 ms LV and RV preactivation were tested. RESULTS: Calculated maximum possible VVeff was shorter than 80 ms LV preactivation in up to 46% of patients and shorter than 40 ms LV preactivation in up to 3% of the patients. These proportions were 6% and 0% during 80 and 40 ms RV preactivation, respectively. CONCLUSIONS: In CRT patients with left bundle branch block without total AV block, the effective VV delay is shorter than the programmed VV delay during a standard optimization procedure in approximately half of the patients and this phenomenon is encountered predominantly during LV preactivation by 40 ms or more. Calculation of the individual maximum VVeff in advance can shorten the VV delay optimization procedure.

Cardiac resynchronization therapy beyond nominal settings: who needs individual programming of the atrioventricular and interventricular delay?

AIMS: This study aimed to determine the additional acute haemodynamic effect of atrioventricular (AV) and interventricular (VV) delay optimization compared with current nominal cardiac resynchronization therapy (CRT) device settings, and to explore whether clinical characteristics correlate to the effect of optimization. METHODS AND RESULTS: Fifty CRT patients were prospectively enrolled. The optimal AV and VV delays were guided by relative improvement in maximum rate of left ventricular (LV) pressure rise (%dP/dt(max)). A significant improvement in %dP/dt(max) was obtained by optimization in 23-33% (sensed AV delay), 32-57% (paced AV delay), and 45% of patients (VV delay). Adjustment of the device nominal VV delay from 0 to 40 ms LV pre-activation would diminish the proportion of patients with additional effect of individual optimization from 45 to 15%. Heart failure aetiology [ischaemic 2 ± 2 vs. non-ischaemic 1 ± 1 percentage points (PP) %dP/dt(max), P= 0.013], gender (men 2 ± 2 vs. women 1 ± 1 PP %dP/dt(max), P= 0.012) and intrinsic PR interval (R= 0.49, P= 0.002) correlated to the degree of effect of AV delay optimization. Women yielded more effect of VV delay optimization (4 ± 3 vs. 2 ± 1 PP %dP/dt(max), P= 0.026). CONCLUSION: Compared with the best of the currently available device nominal AV and VV delays, 23-45% of CRT patients can yield additional acute haemodynamic effect by individual optimization of the delays. A new nominal VV delay of 40 ms LV pre-activation is recommended. Male gender, ischaemic aetiology, and longer PR interval are associated with a larger effect of individual optimization.

The ECG in cardiac resynchronization therapy: influence of left and right ventricular preactivation and relation to acute response.

INTRODUCTION: The aims of this study were to compare ECG signs of biventricular electrical resynchronization during cardiac resynchronization therapy (CRT) with various interventricular (VV) delays and to correlate these and other ECG characteristics with the acute hemodynamic benefit of CRT. METHODS AND RESULTS: Thirty-four patients with heart failure and a left bundle branch block (LBBB) pattern were prospectively enrolled. A 12-lead surface ECG and the relative improvement in left ventricular (LV) dP/dt(max) (the maximum rate of pressure rise) were recorded at baseline and during CRT with VV delays varying from 80 ms LV preactivation to 40 ms right ventricular (RV) preactivation. Rightward QRS-axis shift occurred in 71-80% among all VV delays. Activation reversal to dominant negative in leads I/aVL was progressively observed at increasing LV preactivation (53-65%) and less (18-22%) during RV preactivation. Activation reversal to dominant positive in leads V1/V2 was observed in 21-27% during LV preactivation and in 6-15% during RV preactivation. Higher acute response to CRT was independently predicted by a complete LBBB at baseline (regression coefficient B = 7.7 [0.3-15.0], P = 0.042), later timing of LV depolarization within the QRS at baseline (Q-LVsense: B = 0.2 [0.1-0.3], P = 0.002), and biventricular electrical resynchronization during CRT as evidenced by activation reversal in leads I/aVL (B = 9.9 [3.2-16.6], P = 0.005). CONCLUSION: ECG signs of biventricular electrical resynchronization are present over a wide range of LV preactivated VV delays but to a lesser extent during RV preactivation. The presence of complete LBBB and longer Q-LVsense at baseline and signs of biventricular electrical resynchronization during CRT predict higher acute hemodynamic response.

Septal rebound stretch is a strong predictor of outcome after cardiac resynchronization therapy.

BACKGROUND: Septal rebound stretch (SRSsept) is a distinctive characteristic of discoordination-related mechanical inefficiency. We assessed how intermediate- and long-term outcome after cardiac resynchronization therapy (CRT) relate to baseline SRSsept. METHODS AND RESULTS: A total of 101 patients (age 65 ± 11 years, 69 men, 18 New York Heart Association (NYHA) class IV, QRS 173 ± 23 ms) scheduled for CRT underwent clinical assessment, echocardiography, and brain-type natriuretic peptide (BNP) measurements before and 6.4 ± 2.3 months after CRT. Baseline SRSsept (all systolic stretch after initial shortening in the septum) was quantified by speckle tracking echocardiography. Primary composite end point was death, urgent cardiac transplantation, or left ventricular assist device implantation at the end of the study. Secondary end points were intermediate-term (6 months) response, quantified as decreases in left ventricular end-systolic volume (ΔLVESV) and BNP (ΔBNP). After a mean clinical follow-up of 15.6 ± 9.0 months; 23 patients had reached the primary end point. Baseline SRSsept (hazard ratio [HR] 0.742; 95% confidence intervals [CI] 0.601-0.916, P < .01]) was independently associated with a better outcome and NYHA class (HR 5.786: 95% CI 2.341-14.299, P < .001) with a worse outcome. Contrary to baseline NYHA class, baseline SRSsept was an independent predictor of both ΔLVESV (beta 0.53; P < .001) and ΔBNP (beta 0.29; P < .01). Intermediate-term ΔLVESV and ΔBNP were associated with a favorable long-term outcome. CONCLUSIONS: SRSsept at baseline is a strong, independent predictor of long-term prognosis after CRT and of improvements in left ventricular remodeling and neurohormonal activation at intermediate term.

Baseline left ventricular dP/dtmax rather than the acute improvement in dP/dtmax predicts clinical outcome in patients with cardiac resynchronization therapy.

AIMS: The maximum rate of left ventricular (LV) pressure rise (dP/dt(max)) has been used to assess the acute haemodynamic effect of cardiac resynchronization therapy (CRT). We tested the hypothesis that LV dP/dt(max) predicts long-term clinical outcome after initiation of CRT. METHODS AND RESULTS: This was a retrospective observational multicentre study in 285 patients in whom dP/dt(max) was measured invasively following implantation of a CRT device. The minimum required follow-up was 1 year. We analysed the relationship between dP/dt(max) and time to the composite endpoint, consisting of all-cause mortality, heart transplantation (HTX), or LV assist device (LVAD) implantation within the first year of CRT. Thirty-four events occurred after a mean follow-up of 160 days (range 21-359). Patients with an event had lower dP/dt(max) than patients without an event both at baseline (705 ± 194 vs. 800 ± 222 mmHg/s, P= 0.018) and during CRT (894 ± 224 vs. 985 ± 244 mmHg/s, P= 0.033), but the acute increase in dP/dt(max) was similar in patients with and without an event (190 ± 133 vs. 185 ± 115 mmHg/s, P= n.s.). Left ventricular dP/dt(max)-level at baseline and during CRT both predicted the clinical outcome after adjustment for gender, aetiology and New York Heart Association class: hazard ratio (HR) 0.791 [95% confidence interval (CI) 0.658-0.950, P= 0.012] and HR 0.846 (95% CI 0.723-0.991, P= 0.038), respectively. CONCLUSION: Left ventricular dP/dt(max) measured at baseline and during CRT are predictors of 1-year survival free from all-cause mortality, HTX, or LVAD implantation, but the acute improvement in dP/dt(max) is not correlated to clinical outcome.

Echocardiographic prediction of outcome after cardiac resynchronization therapy: conventional methods and recent developments.

Echocardiography plays an important role in patient assessment before cardiac resynchronization therapy (CRT) and can monitor many of its mechanical effects in heart failure patients. Encouraged by the highly variable individual response observed in the major CRT trials, echocardiography-based measurements of mechanical dyssynchrony have been extensively investigated with the aim of improving response prediction and CRT delivery. Despite recent setbacks, these techniques have continued to develop in order to overcome some of their initial flaws and limitations. This review discusses the concepts and rationale of the available echocardiographic techniques, highlighting newer quantification methods and discussing some of the unsolved issues that need to be addressed.

Should we optimize cardiac resynchronization therapy during exercise?

Should We Optimize CRT During Exercise? Cardiac resynchronization therapy aims at diminishing cardiac dyssynchrony in patients with heart failure. The effect of cardiac resynchronization therapy can be improved by optimization of the atrioventricular (AV) and interventricular (VV) delays. Currently, optimization of these pacing settings is mainly performed during resting conditions. This paper aims to objectively review the current literature about a rate-adaptive AV and VV delay in cardiac resynchronization therapy. The current evidence for a rate-adaptive AV and VV delay comprises only small nonrandomized studies on acute effects. The effect of exercise on the optimal AV delay was heterogeneous between studies. The optimal VV delay was influenced by exercise conditions in some, but not all patients. Possible explanations lie in the heterogeneous electrical and mechanical responses to exercise in patients with a complex disease such as heart failure with asynchronous contraction. Current evidence is insufficient to show the superiority of a rate-adaptive AV or VV delay in all CRT patients. Individualized exercise programming may be warranted in selected patients.

Can optimization of pacing settings compensate for a non-optimal left ventricular pacing site?

AIMS: Optimal left ventricular (LV) lead position improves the response to cardiac resynchronization therapy (CRT). However, in some patients it is not possible to position the LV lead at an optimal pacing site. The aim of this study was to determine whether optimization of the pacing settings atrioventricular delay (AVD) and interventricular delay (VVD) can compensate for a non-optimal LV pacing site. METHODS AND RESULTS: In 16 patients with heart failure [New York Heart Association class III (13) or IV (3), median QRS duration of 172 ms and median LV ejection fraction of 20%] the acute haemodynamic effect of biventricular pacing was assessed at > or =2 pacing sites by the increase in maximum rate of LV pressure rise (%dP/dt(max)). At each site the AVD and VVD were optimized. Biventricular pacing with nominal settings at a non-optimal LV pacing site improved dP/dt(max) by 12.8% (-0.5 to 23.2%). This could be further improved by 6.5 percentage points (1.2-13.9) by optimization of pacing settings (P = 0.001) and by 9.9 percentage points (3.7-13.3, P = 0.004) by optimization of pacing site. Optimization of the LV pacing site and pacing settings together improved %dP/dt(max) by 16.2 per cent points (10.0-21.8, P < 0.001). CONCLUSION: Optimization of the AVD and VVD can partly compensate for a non-optimal LV pacing site. However, a combination of an optimal LV pacing site and optimized pacing settings gives the best acute haemodynamic response.

The prognostic significance of typical perfusion defects on vasodilator stress myocardial perfusion SPECT in patients with left bundle branch block or right ventricular apical pacing.

PURPOSE: Left bundle branch block (LBBB) and ventricular pacing may induce typical artefacts that appear as perfusion defects in myocardial perfusion single photon emission computed tomography (MPS). We assessed the prognosis of patients with LBBB or right ventricular apical (RVA) pacing who had chest pain and an MPS with only abnormal activation-related defects (AARD). METHODS: All patients with LBBB or ventricular pacing referred for vasodilator stress MPS between April 2002 and January 2006 were analyzed. AARD were defined as small, nontransmural, fixed defects and small reversible defects in well-defined regions always accompanied with concomitant wall motion abnormalities. RESULTS: Ninety-seven patients were included, with a mean follow-up period of 3+/-1.3 years. MPS showed AARD in 57 and it was completely normal in 40 patients. No significant difference in cumulative cardiac event-free follow-up was observed between patients with AARD (93%) and normal MPS (85%). The average annual cardiac event rate was not significantly different between the groups (1.7 and 4.3% per year, respectively). No difference was found between patients with LBBB and RVA pacing. CONCLUSION: Patients with chest pain and LBBB or RVA pacing who show AARD on MPS have a comparable prognosis as patients with abnormal activation and a normal MPS. This justifies MPS for risk stratification of patients with chest pain and LBBB or RVA pacing.