Optimal Atrioventricular Research Articles

Multicenter Randomized Controlled Crossover Trial Comparing Hemodynamic Optimization Against Echocardiographic Optimization of AV and VV Delay of Cardiac Resynchronization Therapy: The BRAVO Trial

ObjectivesBRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method. BackgroundCardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform. MethodsThis study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro–B-type natriuretic peptide. ResultsA total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro–B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms. ConclusionsOptimization of cardiac resynchronization therapy devices by using noninvasive blood pressure is noninferior to echocardiographic optimization. Therefore, noninvasive hemodynamic optimization is an acceptable alternative that has the potential to be automated and thus more easily implemented. (British Randomized Controlled Trial of AV and VV Optimization [BRAVO]; NCT01258829)

Prediction of optimal cardiac resynchronization by vectors extracted from electrograms in dyssynchronous canine hearts.

Proper optimization of atrioventricular (AV) and interventricular (VV) intervals can improve the response to cardiac resynchronization therapy (CRT). It has been demonstrated that the area of the QRS complex (QRSarea) extracted from the vectorcardiogram can be used as a predictor of optimal CRT-device settings. We explored the possibility of extracting vectors from the electrograms (EGMs) obtained from pacing electrodes and of using these EGM-based vectors (EGMVs) to individually optimize acute hemodynamic CRT response. Biventricular pacing was performed in 13 dogs with left bundle branch block (LBBB) of which five also had myocardial infarction (MI), using 100 randomized AV- and VV-settings. Settings providing an acute increase in LV dP/dtmax ≥ 90% of the highest achieved value were defined as optimal. The prediction capability of QRSarea derived from the EGMV (EGMV-QRSarea) was compared with that of QRS duration. EGMV-QRSarea strongly correlated to the change in LV dP/dtmax (R = -0.73 ± 0.19 [LBBB] and -0.66 ± 0.14 [LBBB + MI]), while QRS duration was more poorly related to LV dP/dtmax changes (R = -0.33 ± 0.25 [LBBB] and -0.47 ± 0.39 [LBBB + MI]). This resulted in a better prediction of optimal CRT-device settings by EGMV-QRSarea than by QRS duration (LBBB: AUC = 0.89 [0.86-0.93] vs. 0.76 [0.69-0.83], P < 0.01; LBBB + MI: AUC = 0.91 [0.84-0.99] vs. 0.82 [0.59-1.00], P = 0.20, respectively). In canine hearts with chronic LBBB with or without MI, the EGMV-QRSarea predicts acute hemodynamic CRT response and identifies optimal AV and VV settings accurately. These data support the potency of EGM-based vectors as a noninvasive, easy and patient-tailored tool to optimize CRT-device settings.

Atrioventricular dyssynchrony from empiric device settings is common in cardiac resynchronization therapy and adversely impacts left ventricular morphology and function.

Echocardiographic atrioventricular (AV) optimization after cardiac resynchronization therapy (CRT) is uncommon due to time constraints and the use of vendor-specific device algorithms. It remains unclear whether optimization of mitral inflow velocities can still be useful. We aimed to investigate post implantation left ventricular (LV) inflow patterns to determine the incidence of AV dyssynchrony from empirically set devices. This was a retrospective study of patients undergoing CRT using empiric device settings. Forty-eight patients with clinical, echocardiographic, and pacemaker follow-up were grouped by their post implantation LV filling pattern. Baseline characteristics and echocardiographic measurements were compared with post implantation findings at median 6.3months (interquartile range [IQR], 3.9-17.0). Twenty-four patients demonstrated AV dyssynchrony (Group 1) after CRT, and 24 patients did not (Group 2). Group 1 patients had less LV reverse remodeling compared to Group 2 patients (ΔLV end-diastolic volume: -3.6mL vs -49.5mL, P<.05; ΔLV end-systolic volume: -16.9mL vs -53.5mL, P<.05) and did not experience significant improvements in LV outflow tract velocity time integral, stroke volume, or LV ejection fraction. There were no differences in new-onset atrial fibrillation, heart failure readmissions, or mortality between groups. Our study suggests that up to 50% of patients with empiric device settings have AV dyssynchrony at 6months despite atrioventricular delay optimization (AVO) algorithms. As AV dyssynchrony is common and has proven to be modifiable, a strategic approach to Doppler echocardiography-guided AVO after CRT is warranted, particularly in nonresponders where the LV filling pattern is fused or truncated.

Clinical benefit of atrio-ventricular delay optimization in patients with a dual-chamber pacemaker: a pilot study. The CBRAVO trial (NCT01998256)

Objective Outcome data on exercise capacity following atrio-ventricular (AV) optimization of dual-chamber pacing are sparse. Pacemaker settings are often left at manufacturers’ nominal values upon implantation. We studied the short-term effect of AV optimization on exercise capacity in patients with a dual-chamber pacemaker.Methods and results Twenty-eight patients (mean age 73 ± 14 y) with a dual-chamber pacemaker, were randomized towards either nominal AV settings (group 1) or echo-guided AV optimization using the iterative mitral inflow VTI (velocity time integral) method (group 2) at baseline. At 4 weeks, patients were crossed-over to AV optimization in group 1 and returned to nominal AV settings in group 2 for another period of 4 weeks.Oxygen uptake efficiency slope improved significantly after AV optimization (by 126.7 mL/logL ± 190.7 mL/logL; P= 0.003).Conclusions AV optimization in dual-chamber pacing significantly improved functional capacity after 4 weeks. These data provide the background for further validation studies.

179-02: First-degree atrioventricular Block, Atrioventricular (Dys)synchrony and Dual-chamber pacing. A long PR interval or a wide QRS? That is the dilemma

Background: In modern DDD pacemakers, strategies to minimize artificial right ventricular activation seek to avoid the potential but well-studied deleterious effects of cardiac pacing. While these mechanisms maintain electrical atrioventricular (AV) sequence, if significant 1st. degree AV block (1st.AVB) coexists, paradoxically AV mechanical dyssynchrony could be promoted. Apparently, atrioventricular sequence differs from atrioventricular synchrony. The purpose of this study was to elucidate clinical and hemodynamic results of long AV delays - narrow intrinsic QRS against DDD pacing with optimized AV interval - paced wide QRS. Methods: Prospectively included 32 adult patients with DDD pacemakers implanted for sick sinus node disease (SSND) and 1st.AVB. Study protocol demanded septal right ventricular lead, demonstrated <5% of ventricular pacing overall since implantation, normal QRS duration, preserved left ventricular ejection fraction (LVEF), no prosthetic valves and no history of atrial fibrillation (AF). Using Doppler echocardiography diastolic and systolic performances were verified in AAI pacing 10 beats/min faster than sinus rhythm, intrinsic long AV delay and native QRS (Ap-Vs), against the hemodynamic results (VTi, LVEF and Mitral regurgitation obtained by iteratively shortening the programmed AV delay (DDD pacing - Ap-Vp) at same cardiac rate. By Mitral valve inflow analysis (E/A waves measurements) optimal diastolic function (AV synchrony) was verified. Best left ventricular contractility and function was assessed by means of higher aortic flow time velocity integral (VTi) and LVEF. Optimal AV delay was defined by maximal separation of E/A waves, higher VTi and best LVEF with less Mitral valve regurgitation. AV dyssinchrony was determined by fused E + A waves, or E + A duration <40% of cardiac cycle. This patients were kept to ventricular pacing at the optimal AV interval (optimized AV – OAV group) for further comparison. The non-optimized AV (NOAV) group was formed by those whose best cardiac function was found at the intrinsic PR interval-native QRS. This group was kept to minimal ventricular pacing at the baseline PR interval. Follow-up included clinical evaluation and cardiac structure and function assessment at 3 and 6 months for both groups of patients. Results: Our cohort so far (mean= 73,6 + /-11,8 years) confirmed the existence of 2 separate groups from the diastolic function point of view: those showing AV dyssynchrony requiring AV optimization (OAV group: 18/32) and those with no AV dyssynchrony (no need for AV optimization - NOAV group: 14/32); p= 0.003. No other statistical differences were found in age, gender, symptoms, NYHA functional class, medication use, and structural heart disease, baseline PR interval or LVEF between groups. AAI pacing rate for echo measurements was 65 + /-9bpm for the OAV group vs. 67,5 + /-6,7bpm of their counterparts (p= NS). Remarkably, the AV interval when exceeded 263ms in the OAV group was 72% sensitive and 73% specific to demonstrate AV dyssynchrony. Moreover, in the OAV group, under optimized AV delay and artificial ventricular pacing, after 6 months of follow-up, LVEF is noticed to significantly decline (p= 0.002) and detrimental changes of cardiac structure with significant increase in left ventricular systolic (p= 0.04) and diastolic (p= 0.02) dimensions are noticed. No other statistical differences at follow-up were found in clinical outcomes (incidence of new AF episodes, electronic arrhythmias, pacemaker syndrome-like symptoms, NYHA functional class or hospitalizations) between groups. Conclusion: Our results preliminarily suggest that 1st.AVB with non-physiologically prolonged AV conduction (when ≥263ms) is highly associated with disturbed AV synchrony. However, this AV dyssynchrony when corrected by echocardiographycally optimized AV delays and forced ventricular pacing is negatively affected by the detrimental consequences of continual right ventricular artificial activation. Alternative-pacing strategies such as biventricular-pacing in this scenario merit further investigation.

PROGNOSTIC VALUE OF ECHO-DOPPLER GUIDED AV DELAY OPTIMIZATION FOLLOWING CARDIAC RESYNCHRONIZATION THERAPY

The utility of Atrio-Ventricular (AV) delay optimization following Cardiac Resynchronization Therapy (CRT) remains unclear. We aimed to determine the utility and outcome of interrogating and selectively optimizing AV synchrony using Echo-Doppler-Guided (EDG) AV optimization following CRT. All

0329 : Automatic AV delay adaptation to exercise in CRT-D patients according to underlying heart disease

Several studies have shown the benefit of optimizing inter-ventricular (VV) and atrio-ventricular (AV) delays in improving the response to CRT. We evaluated AV delay automatic adaptation at rest and during exercise according to underlying heart disease in patients implanted with a SonR CRT-D device (Sorin CRM, Clamart, France). This device is connected to the atrial SonRTip™ lead with a hemodynamic SonR sensor allowing automatic weekly AV and VV delays optimization, at rest and exercise. This prospective study evaluated patients implanted with a SonR CRT-D device in our center between November 2011 and November 2014. Only patients in sinus rhythm with a CRT optimization function programmed “on” were included. Optimization success was evaluated according to the percentage of weeks where the device succeeded AV delay optimization. Twenty-nine patients (67.8±9 years; 75.9% M) were included: 14 (48.2%) had an ischemic cardiomyopathy (ICM) and 15 (51.8%) a dilated cardiomyopathy (DCM). QRS duration was 165 ±19 msec. LVEF was 28±5%. AV delay at rest was 87±14 msec. and at exercise 54±7 msec. No difference was found between both groups (ICM and DCM). In ICM group, 11 (78,6%) patients were responders (optimization success 99%) and non-responders (optimization success 66%). In the DCM group, 4 (26,7%) patients were hyper-responders, 6 (40%) responders and 5 (33,3%) non-responders with respectively 99, 97 and 60% of optimization success. no difference was found in AV delay mean values in responders and nonresponders in both groups. AV delay automatic adaptation at exercise in patients implanted with the SonR CRT-D device was not different between ICM and DCM patients. The author hereby declares no conflict of interest

Atrioventricular Optimized Direct His Bundle Pacing Improves Acute Hemodynamic Function in Patients With Heart Failure and PR Interval Prolongation Without Left Bundle Branch Block

ObjectivesThe purpose of this study was to investigate whether heart failure patients with narrow QRS duration (or right bundle branch block) but with long PR interval gain acute hemodynamic benefit from atrioventricular (AV) optimization. We tested this with biventricular pacing and (to deliver pure AV shortening) direct His bundle pacing. BackgroundBenefits of pacing for heart failure have previously been indicated by acute hemodynamic studies and verified in outcome studies. A new target for pacing in heart failure may be PR interval prolongation, which is associated with 58% higher mortality regardless of QRS duration. MethodsWe enrolled 16 consecutive patients with systolic heart failure, PR interval prolongation (mean, 254 ± 62 ms) and narrow QRS duration (n = 13; mean QRS duration: 119 ± 17 ms) or right bundle branch block (n = 3; mean, QRS duration: 156 ± 18 ms). We successfully delivered temporary direct His bundle pacing in 14 patients and temporary biventricular pacing in 14 participants. We performed AV optimization using invasive systolic blood pressure obtaining parabolic responses (mean R2: 0.90 for His, and 0.85 for biventricular pacing). ResultsThe mean increment in systolic BP compared with intrinsic ventricular conduction was 4.1 mm Hg (95% confidence interval [CI]: +1.9 to +6.2 mm Hg for His and 4.3 mm Hg [95% CI: +2.0 to +6.5 mm Hg] for biventricular pacing. QRS duration lengthened with biventricular pacing (change = +22 ms [95% CI: +18 to +25 ms]) but not with His pacing (change = +0.5 ms [95% CI: −2.6 to +3.6 ms). ConclusionsAV-optimized pacing improves acute hemodynamic function in patients with heart failure and long PR interval without left bundle branch block. That it can be achieved by single-site His pacing shows that its mechanism is AV shortening. The improvement is ∼60% of the effect size previously reported for biventricular pacing in left bundle branch block. Randomized, blinded trials are warranted to test for long-term beneficial effects.

A novel curve fitting method for AV optimisation of biventricular pacemakers

In this study, we designed and tested a new algorithm, which we call the ‘restricted parabola’, to identify the optimum atrioventricular (AV) delay in patients with biventricular pacemakers. This algorithm automatically restricts the hemodynamic data used for curve fitting to the parabolic zone in order to avoid inadvertently selecting an AV optimum that is too long.We used R, a programming language and software environment for statistical computing, to create an algorithm which applies multiple different cut-offs to partition curve fitting of a dataset into a parabolic and a plateau region and then selects the best cut-off using a least squares method. In 82 patients, AV delay was adjusted and beat-to-beat systolic blood pressure (SBP) was measured non-invasively using our multiple-repetition protocol. The novel algorithm was compared to fitting a parabola across the whole dataset to identify how many patients had a plateau region, and whether a higher hemodynamic response was achieved with one method.In 9/82 patients, the restricted parabola algorithm detected that the pattern was not parabolic at longer AV delays. For these patients, the optimal AV delay predicted by the restricted parabola algorithm increased SBP by 1.36 mmHg above that predicted by the conventional parabolic algorithm (95% confidence interval: 0.65 to 2.07 mmHg, p-value = 0.002).AV optima selected using our novel restricted parabola algorithm give a greater improvement in acute hemodynamics than fitting a parabola across all tested AV delays. Such an algorithm may assist the development of automated methods for biventricular pacemaker optimisation.

Comparison of Left Ventricular Torsion and Strain With Biventricular Pacing in Patients With Underlying Right Bundle Branch Block Versus Those With Left Bundle Branch Block

The benefits of biventricular pacing in patients with cardiac resynchronization therapy (CRT) remain poorly understood in those with right bundle branch block (RBBB). The aim of this study was to examine the differences in several speckle tracking-derived parameters, including left ventricular torsion and longitudinal strain with CRT on and off for patients with underlying left bundle branch block (LBBB) and RBBB. Twelve patients with CRT and RBBB were compared with a similar group of patients with underlying LBBB who were sent for evaluation and atrioventricular optimization. Echocardiographic images were acquired with biventricular pacing on and off. The 2 groups had similar baseline characteristics, including age, the ejection fraction, and QRS duration. During intrinsic conduction (CRT off), patients with LBBB had lower torsion angles than those with RBBB (2.3 ± 1.0° in those with LBBB vs 6.3 ± 1.0° in those with RBBB, p = 0.03) but trended toward improvements in torsional parameters, including torsional angle and peak untwisting velocity with CRT on, whereas these parameters worsened in patients with RBBB. Compared with CRT off, analyses of septal and lateral strain curves showed significant improvements in septal strain during 100% and 200% of systole with CRT on in patients with LBBB, whereas biventricular pacing resulted in a trend toward worsening of septal strain in patients with RBBB. Negligible changes were noted in lateral strain values. In conclusion, CRT favorably improves regional mechanics in patients with LBBB primarily involving the ventricular septum, with a negligible positive impact on cardiac function in patients with underlying RBBB.

Feasibility of a novel atrioventricular delay optimization method using transmitral and pulmonary venous flow in patients with sequential ventricular pacing or cardiac resynchronization therapy.

BackgroundAlthough several echo-Doppler methods were proposed to optimize atrioventricular (AV) delay in patients with sequential ventricular pacing, “echo-guided” AV optimization has not been widely adopted clinically. A combination of trasmitral flow (TMF) and pulmonary venous flow (PVF) measurements may be beneficial to further optimize AV delay to achieve better cardiac function. The aim of this study was to assess the feasibility and usefulness of AV delay optimization by combined use of TMF and PVF.MethodsA total of 32 patients after sequential ventricular pacemaker implantation were enrolled and studied. The optimal AV delay was defined as the timing to minimize the duration between PVF reversal (a) wave and the duration of the “A” wave of TMF. Stroke volume was measured at the “optimized” AV delay (AVDOPT) and was compared with that obtained at shorter (AVDOPT − 50 ms) and longer (AVDOPT + 50 ms) AV delays.ResultsAV optimization was feasible in 27 of 32 patients (87 %). Stroke volume at AVDOPT was significantly higher than that at shorter or longer AV delay (63 ± 18 ml vs. 57 ± 15 ml vs. 56 ± 16 ml, P = 0.001).ConclusionsAV delay optimization using TMF and PV flow was feasible. Usefulness of this method requires further investigation with a larger study population.

A simplified method for determination of the optimal atrioventricular delay in cardiac resynchronization therapy

We read with great interest the paper of Raphael et al. [1] regarding the evaluation of the iterative method of optimal atrioventricular (AV) delay for cardiac resynchronization therapy (CRT). The paper addressed an important issue that iterative AV optimization is not executed reliably by experts. Such optimization is essentially important in CRT, which could reduce morbidity and mortality in patients with severe heart failure if the value is settled appropriately [2]. However, despite the fact that several methods have been proposed, AV delay is often programmed via an empirical method or left to a predefined value.

British randomised controlled trial of AV and VV optimization (“BRAVO”) study: rationale, design, and endpoints

BackgroundEchocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources.Methods/DesignBRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014.DiscussionIf exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented.Trial registrationClinicaltrials.gov NCT01258829

Continuously adjusting CRT therapy: clinical impact of adaptive cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce morbidity and mortality in patients with moderate and severe symptomatic congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic right ventricular (RV) conduction results in similar or even better cardiac performance compared to biventricular (Biv) pacing. Optimal programming of the atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV performance since suboptimal programming of AV and VV delays affect LV filling as well as cardiac output. CRT optimization using echocardiogram is resource-dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic, automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing) and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for CRT-indicated patients without permanent atrial fibrillation. It has been shown to improve CRT response and reduce morbidity and mortality for patients with normal AV conduction.

THE CLINICAL BENEFITS OF DEVICE OPTIMIZATION AT LONG-TERM FOLLOW-UP IN CARDIAC RESYNCHRONIZATION THERAPY: RESULTS FROM THE CRT UTILIZATION BY INTERVENTIONAL CARDIOLOGISTS (CUBIC) STUDY

Only a few multicenter trials have provided controversial data on the beneficial effects of atrioventricular (AV) and interventricular (VV) intervals optimization on clinical outcomes in patients with cardiac resynchronization therapy (CRT). The objective of this study is to investigate the impact

Influence of Atrioventricular Optimization on Hemodynamic Parameters and Quality of Life in Patients with Dual Chamber Pacemaker with Ventricular Lead in Right Ventricular Outflow Tract

The aim of this study was to ascertain whether individual atrioventricular delay (AVD) optimization using impedance cardiography (ICG) offers beneficial hemodynamic effects as well as improved exercise tolerance and quality of life in patients with requiring constant right ventricular pacing. There were 37 patients with advanced AV block included in the study. Several examinations were performed at the beginning. Next, the optimization of AVD by ICG was done. The next step of the study patients have been randomized into optimal AVD group (AVDopt) or factory setting group (AVDfab). After 3 months, the follow-up all data were collected again and crossover was performed. After another 3 months, during the final follow-up all these measures were repeated. In 87.5% patients, AVDopt were different than factory value. Cardiac output (CO), cardiac index (CI), and stroke volume (SV) were significantly (P < 0.001) higher in AVDopt group than in AVDfab group (CO: 6.0 ± 1.4 L/minute vs. 5.3 ± 1.2 L/minute; SV: 85.8 ± 25.7 mL vs.76.9 ± 22.5 mL; CI: 3.2 ± 0.7 L/minute/m(2) vs. 2.7 ± 0.6 L/minute/m(2) ). There was a statistical significant (P < 0.05) reduction of proBNP and NYHA class in patients with AVDopt compared to AVDfab (proBNP: 196.4 ± 144.7pg/mL vs. 269.4 ± 235.8 pg/mL; NYHA class: 1.7 ± 0.5 vs. 2.3 ± 0.6). Six-minute walking test was significantly (P < 0.05) higher in AVDopt group (409 ± 90 m) than in AVDfab group (362 ± 93 m). There were no statistically significant differences in echocardiographic parameters between AVDopt and AVDfab settings. Our study results suggest that AVD optimization in patients with DDD pacemaker with ICG improves hemodynamic when compared to the default factory settings. Furthermore, optimally programmed AVD reduces BNP and improves exercise tolerance and functional class.

Effects of AV Delay and VV Delay on Left Atrial Pressure and Waveform in Ambulant Heart Failure Patients: Insights into CRT Optimization

We hypothesized that left atrial pressure (LAP) obtained by a permanent implantable sensor is sensitive to changes in cardiac resynchronization therapy (CRT) settings and could guide CRT optimization to improve the response rate. We investigated the effect of CRT optimization on LAP and its waveform parameters in ambulant heart failure (HF) patients. CRT optimization was performed in eight ambulant HF patients, using echocardiography as reference. LAP waveform was acquired at each of eight atrioventricular (AV) intervals and five inter-ventricular (VV) intervals. Selected waveform parameters were also evaluated for their sensitivity to CRT changes and agreement with echocardiography-guided optimal settings. Optimal AV and VV intervals varied considerably between patients. All patients exhibited significant changes in waveform morphology with AV optimization. Optimal AV delay determined from echocardiography ranged between 140 ms and 225 ms. Mean LAP tended to be lower at optimal setting 14 ± 3 mmHg compared to shorter (<100 ms) or longer (>160 ms) AV settings (P = 0.16). There were clear trends to smaller peak a-wave (P = 0.11) and gentler positive a-slope (P = 0.15) and positive v-slope (P = 0.09) with longer AV delays. Mean LAP and negative v-wave slope correlated well with echo-guided optimal setting, r = 0.91 (P = 0.001) and 0.79 (P = 0.03), respectively. No significant effects on LAP or waveform were seen during VV optimization. LAP and its waveform changes considerably with AV optimization. There is good agreement between echo-guided optimal setting and LAP. LAP could provide an objective guide to CRT optimization. (Clinical Trial Registry information: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00632372).

Three‐Dimensional Echocardiographic Optimization Improves Outcome in Cardiac Resynchronization Therapy Compared to ECG Optimization: A Randomized Comparison

There is little consensus on optimal atrioventricular (AV) and ventricular-to-ventricular (VV) intervals in cardiac resynchronization therapy (CRT). The aim of this study was to examine a novel combination of Doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized AV- and VV-interval optimization compared to conventional electrocardiogram (ECG) optimization. In this double-blind, randomized controlled trial, 77 patients (male: 57, age: 68 ± 10 years) with severely reduced ejection fraction (EF), New York Heart Association (NYHA) class III or IV, and wide QRS complex (>120 ms) have been included. Patients were randomized to either AV- and VV-interval optimization using DE and 3DE (group 1, n = 39) or ECG (group 2, n = 38). 3DE was performed in all patients for the evaluation of left ventricular (LV) dimensions, EF and systolic dyssynchrony index (SDI), and NYHA class obtained before CRT and after 3 months. Primary endpoint of the study was clinical response to CRT, defined as a reduction of NYHA class by ≥1 score. Secondary endpoints were change of EF, LV volumes, and SDI. There were significantly more responders in group 1 (82%) than in group 2 (58%, P = 0.021). Similarly, group 1 showed a larger increase in EF (7.0 ± 6.0% vs 3.4 ± 5.6%, P = 0.015) and a more pronounced reduction of SDI (-4.5 ± 5.9% vs -1.5 ± 5.6%, P = 0.039) than group 2. Compared with conventional ECG optimization, this novel echocardiographic optimization protocol resulted in a significantly higher response rate, improved LV systolic function, and may be used to select the optimal AV and VV intervals in CRT.

Clinical response with adaptive CRT algorithm compared with CRT with echocardiography-optimized atrioventricular delay: a retrospective analysis of multicentre trials

Adaptive cardiac resynchronization therapy (aCRT) is a novel algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular (LV) or bi-ventricular (BiV) pacing and optimization of atrioventricular (AV) and inter-ventricular (VV) delays based on periodic measurement of intrinsic conduction. We aimed to compare the clinical response between aCRT and standard CRT in historical trials. The treatment arm of the aCRT trial was compared with a pooled historical control (HC) derived from the CRT arms of four clinical trials (MIRACLE, MIRACLE ICD, PROSPECT, and InSync III Marquis) with respect to the proportion of patients who had an improved clinical composite score (CCS) at the 6-month follow-up. Patients in the HC underwent echocardiography-guided AV optimization after the implant. A propensity score model was used to adjust for 22 potential baseline confounders of the effect of CRT. Patients were stratified into quintiles according to the propensity score and the adjusted absolute treatment effect was obtained by averaging estimates across these quintiles. The propensity score model included 751 patients (aCRT: 266, historical trials: 485). The adjusted absolute difference in percent improved in CCS between the aCRT and HC arms was 11.9% [95% confidence interval (CI): 2.7-19.2%] favouring aCRT. The patients in the aCRT group were significantly more likely to have an improved CCS than the patients in the HC (odds ratio = 1.65, 95% CI: 1.1-2.5). The aCRT algorithm may be associated with additional improvement in clinical response compared with historical CRT with echocardiographic AV optimization.

The clinical benefits of atrioventricular and interventricular intervals optimization at long-term follow-up in cardiac resynchronization therapy: results from CUBIC study

The clinical benefits of atrioventricular and interventricular intervals optimization at long-term follow-up in cardiac resynchronization therapy: results from CUBIC study