Page 169 - Simplicity is Key in CRT

to CRT (MARC) observational study in the Netherlands investigated a large range of potential biomarkers of CRT response in a group of 230 patients. This study found that QRS area was the strongest marker of echocardiographic response to CRT, out of all tested predictors [21].
The analysis in chapter 7 shows that QRS area has added value in differentiating between responders and non- responders in the category of patients with an LBBB morphology and a QRS duration above 150ms (class I indication), although this category is already recommended for CRT by current guidelines. An even larger additive value of QRS area is achieved in the non-class I patients. Chapter 7 shows that non-class I patients with a QRS area ≥109ųVs have a similar clinical and echocardiographic outcome in CRT as class I patients. Moreover, in multivariable analysis of the ECG markers, QRS area proved to be the only marker independently associated with clinical outcome.
While the strength of this study is the large number of (real-world) patients included, the true “CRT benefit” can only be quantified by analysis in a randomized trial. This is currently being performed for data from the RAFT study [14]. Furthermore, while class I patients are already recommended for CRT implantation, adding QRS area to the selection for CRT would reduce the number of non-responders. However, use of QRS area in non-class I patients could uncover potential responders who are currently not selected for CRT. For the latter purpose, our group is currently starting a prospective observational multimarker study (MARC-2 study), like the aforementioned MARC-study, now focussing on non-LBBB patients.
For the analyses presented in this thesis, QRS area was calculated using custom-made software to converge vectorcardiographic data and the QRS area algorhythm from the original digital 12-lead ECG signals. An important step towards a wider clinical use of QRS area is to program the algorithm for its calculation into ECG machines. When, indeed QRS area can be calculated automatically and its value will be further established in substudies of randomized trials, it may be possible that QRS area replaces LBBB morphology and QRS duration as ECG markers for patient selection in CRT. Such use would avoid the subjectivity and variability involved in defining LBBB morphology, ‘simplifying’ patient selection and increasing prediction of outcomes to CRT.
Patient management
The aim of the research presented in part II of this thesis is to introduce a solution for the complex care for HF patients treated with CRT. As the reasons for non-response or diminished benefit from CRT are numerous, complexity of management of these patients is high, needing both HF and electrophysiological evaluation and treatment. This often leads to a large burden on the outpatient clinic, with many consultations and additive investigations. Moreover, as these patients are by definition limited because of their disease and frequent comorbidities, the burden of visits and examinations for these patients is high.
In this part of the thesis we show how we benchmark and implement a structured CRT patient management program, including evidence and experience-based process and medical management recommendations for care of HF patients treated with CRT. The consensus CRT care pathway paper presented in chapter 8 differs from guidelines [2, 22] and consensus papers [23] already available in such a way that it offers the reader an ready-to-use blueprint including tools (checklists) to compare and improve their current practice. Guidelines scantly address the topic of management of the HF patient with CRT, apart from the patient selection and implantation phase. Moreover, most of the recommendations on patient management have a level of evidence C (expert consensus) and are of little help to introduce and implement a CRT patient management program in clinical practice [1, 2].
169