Improving cardiac resynchronisation therapy

Jagmeet Singh

Jagmeet Singh is the founding director of the Resynchronisation and Advanced Cardiac Therapeutics Program. Singh is the principal investigator for the Personalised CRT-MPP Post-Approval Study and a paid consultant for Medtronic. In this commentary he discusses his research on cardiac resynchronisation.

Cardiac resynchronisation therapy (CRT) is an effective tool for treating select heart failure patients. Numerous randomised clinical trials have shown CRT can favourably remodel the heart, thereby enhancing quality of life, reducing hospitalisations of patients with New York Heart Association (NYHA) Class II, III and IV heart failure, and improving overall survival. Yet, it is estimated that as many as one-third of heart failure patients do not improve following CRT.

Several factors may contribute to ineffective or suboptimal CRT delivery, including patient selection, suboptimal atria-to-ventricle (AV) timing, the presence of atrial fibrillation (AF), and left ventricular (LV) lead placement. However, recent advances in technology and techniques that allow for a more personalised CRT delivery can help improve patient response rates to the therapy.

CRT response

For example, a proprietary devicebased pacing algorithm has demonstrated a 12% absolute higher response rate to CRT compared to historical trials. This algorithm automatically optimises the CRT pacing method and A-V/V-V timing to meet the constantly changing needs of the patient. By providing LV-only pacing or biventricular (Bi-V) pacing, the algorithm can help minimise unnecessary right ventricular (RV) pacing and improve CRT efficacy.

Several factors can cause ineffective CRT pacing, such as the presence of AT/AF, prolonged AV intervals, inadequate LV pacing output, delayed LV activation, LV/RV electrode proximity, or atrial or right ventricular undersensing. Optimal CRT delivery requires a high percentage of effective LV-only or Bi-V pacing, but device counters that indicate only the percentage of ventricular pacing are inadequate, as they give no indication of successfully capturing the heart muscle. The use of a diagnostic algorithm, such as the EffectivCRT Diagnostic (Medtronic), to verify effective capture and quality of pacing enables improved CRT delivery.

Furthermore, all heart failure patients have diverse anatomies and some patients do not respond to CRT due to lead placement and dislodgement. Two options that may help improve the response to CRT are multiple point pacing, which allows pacing from two LV electrodes, and newer active fixation left heart leads, which are currently being evaluated in clinical studies.

Management of heart failure patients with AF

A large percentage of heart failure patients also have AF. However, the irregular conduction to the ventricles that occurs during AF often prevents the delivery of effective CRT therapy.

While managing these patients has been challenging, new algorithms have been shown to reduce the risk of AF compared with echo-optimised CRT. Additionally, one such technological advancement allows for pacing configurations that automatically adjust the pacing rate during AF without adversely affecting the average heart rate, which was shown to increase effective CRT delivery during AF by up to 15%.

Reducing repeat hospitalisations

As therapies for heart failure have evolved, hospital length of stay, and in-hospital and 30-day mortality have decreased, but readmission rates have not proportionally decreased. Among Medicare patients hospitalised for heart failure from 2008 to 2010, 67.4% experienced a readmission within one year of discharge.

Repeated heart failure hospitalisations are not only burdensome for patients, they are one of the costliest diagnoses among Medicare patients. Algorithms that allow for personalised CRT have been shown effective in reducing hospital readmissions. Notably, the AdaptivCRT algorithm (Medtronic) reduces a patient’s odds of a 30-day heart failure readmission by 59%.

Obtaining real-world evidence of CRT delivery

To evaluate how heart failure patients respond to CRT and its technological features in various combinations not previously studied in randomised clinical trials, a real-world prospective, observational, multicenter cohort study is underway. The Personalised CRT-Multiple Point Pacing (MPP) Post-Approval Study is expected to enroll patients at 50 sites in the USA and 25 sites in other countries. Study participants will be followed prospectively for three years in alignment with routine clinical care practices. The study will determine specific approaches for patients at a higher risk of non-response (i.e., non- LBBB and narrower QRS).

As clinicians, we have an obligation to aggressively treat our patients with heart failure and seek out treatment options that allow for optimal CRT delivery. Results from the Personalised CRT study should provide useful insight into which patients do not respond to CRT and why, and help clinicians significantly improve response rates by using new technologies to personalise the therapy for each individual heart failure patient.

Jagmeet Singh is the associate chief of the Cardiology Division at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School.

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