Algorithms for CRT device AV and VV delay optimisation

As technology has progressed, CRT leads and generators have become more sophisticated with potential ability to offer remote monitoring, intra-thoracic impedance measurement and measures of volume status. In conjunction with these, all major manufacturers have

considered whether a dedicated device incorporated algorithm would improve the process of optimisation. The rationale being that due to constant beat to beat monitoring via atrial and ventricular leads, the CRT device would be able to use intrinsic and paced delays to self- adjust AV and VV delays to improve a preset cardiac haemodynamic variable.

These algorithms have been tested in large randomised studies which thus far have not shown any significant superiority over other methods of optimisation.

The SMART-AV (The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy) Study was the first

algorithmic based clinical trial to publish in 2010.(126) The study recruited a cohort of 1014 patients and randomised them to one of three arms following implantation with a CRT-D device. The population fulfilled modern criteria for CRT implantation and were randomised to either a fixed AV delay of 120 ms, SMART-AV™ delay optimisation or an

echocardiographic guided optimisation using the iterative technique and transmitral Doppler flows. The SMART AV delay was a programme based on detection of paced and intrinsic AV delays and resulting self-adjustment. The primary end point was a change in left ventricular end systolic volume. The usual collection of secondary endpoints comprising NYHA class, quality of life scores and 6MWT test distance were used within the study. The findings demonstrated no statistical significance between any of the three arms (SMART AV delay as compared to echocardiography P=0.52 and fixed delay P=0.66) in terms of left ventricular volume changes. The follow up period ran for six months following enrolment into the study. There was also no positive effect on any of the secondary endpoints.

Alternative studies have been performed or are underway from rival manufacturers and different algorithms to investigate the area, further. The FREEDOM (Frequent Optimization Study Using the QuickOpt Method) study was performed using the Quick Opt algorithm from St Jude.(127) Again a large number of patients (n=1580 patients) were recruited into the study and randomised either to a one off echocardiographic optimisation following CRT

implantation or algorithmic optimisation 'QuickOpt™'. Further attempts at echocardiography guided optimisation could be considered but were completely up to the investigator on site. If the patient whilst in this arm had symptomatic deterioration the trial structure encouraged a review and further attempt at optimisation of the AV and VV intervals. The other group were subjected to algorithm guided frequent optimisation of AV and VV intervals. The primary and secondary endpoints were clinical and focussed on clinical response, all-cause mortality and hospitalisation with heart failure. The trial completed recruitment in 2010 but thus far there has been no publication of data. Both Quick Opt and Smart AV relied on intra-cardiac electrocardiograms to calculate the optimal AV and VV delays.

Sorin had a different algorithm, the SonR™ algorithm which works by calculating myocardial contractility from VV delay and then finding the ideal AV delay from the figures derived

in the pilot randomised trial, the CLEAR (Clinical evaluation on advanced resynchronisation) study which evaluated its performance as compared to traditional echocardiographic guided optimisation.(128) Slightly differently as compared to other modern CRT trials, the steering group decided on inclusion criteria which replicated those of CARE-HF.(6) This was a more severe group of patients with NYHA III/IV heart failure with QRS durations above 120 ms (and evidence of mechanical dyssynchrony if in the 120-149 ms bracket - using echo

measures as per CARE-HF protocol). The primary endpoint was a clinical composite made up of improvement in NYHA class, quality of life, HF hospitalisations and all-cause mortality. A total of 238 patients were recruited and randomised to frequent device based optimisation or conventional echocardiographic measurement on a 1:1 basis. Each patient was followed up for one year and the SonR optimised group had significant improvement in functional class (P=0.002) and which drove a significant improvement in the primary endpoint as compared to those with conventional optimisation. (P=0.03)

The most recent data was published from the Adaptive-CRT study in 2012.(129) This was a study designed to evaluate the Medtronic Adaptive™ algorithm which offered dynamic ambulatory optimisation of AV and VV intervals. The trial was designed as a non-inferiority trial. A total of 522 patients were randomised in a 2:1 fashion to the Adaptive optimisation versus conventional echocardiographic optimisation. Patients were reviewed at one, three and six months following enrolment. The study successfully proved on the non-inferiority basis that the proportion of clinical improvement between the two arms was the same. (73.6 per cent vs 72.5 percent, with a non-inferiority margin of 12 percent; P = .0007). Evaluating the haemodynamic profiles using measured aortic velocity time integral between the two groups demonstrated high rates of correlation. (Concordance correlation coefficient = 0.93; 95 percent confidence interval 0.91-0.94) and at 6-month post randomisation (Concordance correlation coefficient = 0.90; 95 percent confidence interval 0.87-0.92). There were no significant differences between the arms with respect to heart failure events or ventricular arrhythmia episodes.

The DECREASE-HF (The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure) study was a study focused on VV optimisation via a device based algorithm.(130) The Expert-Ease™ algorithm was based on the measurement of intrinsic VV interval with data derived from the PATH-CHF studies.(92) The trial randomised 306 patients in a 1:1:1 fashion to sequential and simultaneous

biventricular pacing and left ventricular pacing only. Echocardiography was performed at baseline, 3 and 6 months. There were uniform reductions in LV end systolic and diastolic dimensions. (P<0.001). The simultaneous VV pacing group had the greatest reduction in LV end systolic dimensions (P<0.007). Stroke volume and ejection fraction improved in all three groups. (P<0.001).