Predicting Outcomes Following CRT: The Quest Continues

Cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in symptomatic patients with heart failure and systolic dysfunction.1-7 The benefits are most convincing in patients in sinus rhythm, with left bundle branch block (LBBB) morphology, and a broad QRS complex on optimal medical therapy.8-10 There is a persistent rumour in the cardiology community that up to one-third of patients do not respond to CRT therapy—so called ‘non responders’. This can partly be explained by the fact that clinicians exploring new indications have implanted CRT devices on relatively weak indications.11 As more evidence emerges on CRT, it is becoming increasingly clear that patient response can be considerably improved by appropriate patient selection, improved CRT implantation technique and by diligent follow-up after implantation. In a bid to improve response, several attempts have been made to target patients most likely to benefit from CRT by defining demographic variables that can be used to identify these patients. Gasparini et al.12 have joined this quest by designing a risk score, VALID-CRT, that can be used to identify patients likely to have higher mortality after CRT implantation. The score has been formulated and validated using data from 5153 patients in 72 European centres post-CRT implantation with left ventricular ejection fraction (LVEF) ≤35, QRS ≥120 ms and New York Heart Association (NYHA) class II–IV. The primary endpoint was total mortality. The Kaplan–Meier survival curves demonstrate clear and convincing separation according to quartiles in both the derivation and validation cohorts. The clinical variables used in VALID-CRT include age, gender, LVEF, NYHA class, and the presence or absence of atrial fibrillation, atrioventricular junction ablation, coronary heart disease, diabetes, and a CRT-D (defibrillator). There are some salient points regarding this new scoring system that require emphasis. First, clinicians will consider the major limitation of this score to be the fact that no measure of renal function or natriuretic peptide levels are included. This is most unfortunate. The authors excluded these variables because they were unable to obtain them in >25% of the population studied. This raises questions about the quality of the overall database. The lack of inclusion of these variables into VALID-CRT limits its applicability as such important parameters are conventional when constructing a prognostic index and would have strengthened the validity of their scoring system. In contrast, in the recently published EAARN (EF, Age, AF, Renal dysfunction, NYHA class IV) score,13 a similar scoring system designed to predict survival following CRT implantation, impaired renal dysfunction was shown to be a powerful determinant. Interestingly, two of the most powerful known determinants of outcome QRS width and morphology emerged in this study as non-significant predictors on univariable analyses. This is because of the nature of analysis, as these are the original criteria that have been used to select the patient for CRT implantation. The most recent European Society of Cardiology Guidelines on CRT deliver their guidance based on QRS morphology and duration.14, 15 Furthermore, the only endpoints reported are all-cause and cardiovascular mortality. There are no data provided concerning morbidity as expressed by cardiovascular hospitalizations. One must keep in mind that death is an extreme event and does not necessarily reflect disease procession, and that only a limited number of patients contribute to this outcome. Another extremely important point that the reader must grasp is the purpose for which the score is intended. This is not patient selection. One of the variables, device type CRT-P (pacemaker)/CRT-D, can only be obtained post-implantation. So the VALID-CRT score cannot be used to optimally select patients for this procedure. The role that Gasparini et al.12 envisaged for their score is for risk stratification after successful implantation to identify patients that require more intensive follow-up. VALID-CRT is a scoring system post-CRT implantation that may be helpful in tailoring patient follow-up by defining patients with the highest mortality risk. It does not provide us with any information regarding the implantation process itself; neither does it provide us with guidance on how patients will respond to their CRT device regarding improvement of symptoms, improved quality of life, or decreased cardiovascular hospitalizations. It would have been interesting to include a measure of morbidity such as hospitalization in order to provide information regarding the patient's clinical response. CRT implantation is an invasive procedure with a certain risk of periprocedural associated morbidity and mortality. It is very different from a pharmacological therapy, in which a drug can be easily withdrawn and reinstated, or dose adjusted, depending on patient response. In addition, the degree of the placebo/nocebo effect is highly variable with devices in the individual patient. All health-care providers have limited budgets, and it is imperative that we invest these resources wisely and restrict implantation of devices to patients likely to have favourable clinical outcomes. Such a favourable response depends on three essential aspects of the procedure. First, appropriate patient selection and device type are crucial. Motivated symptomatic patients with heart failure on evidence-based medical therapy in sinus rhythm, LBBB, and a wide QRS have the greatest likelihood of a good clinical response. Major co-morbidities should also be identified and taken into consideration. Second, in contrast to drug therapy for heart failure, it matters who delivers the therapy. The expertise of the implanter is paramount to success: optimal left ventricular lead placement is time consuming, technically challenging and ‘requires a certain passion’ from the implanter (A. Auricchio, Lisbon, Portugal, 2013, Personal communication). Third, there are aspects of follow-up that may be decisive in determining a successful course following CRT. Rigorous attention to detail in the optimal programming of the device and management of the patient with a multidisciplinary approach are essential following implantation as we make a long-term commitment when offering such a device to a patient. There was no funding provided for this editorial.