Evaluation of Response Rate to Resynchronization Therapy: the Super-Responder

Cardiac resynchronization therapy (CRT) emerged as a therapeutic modality for patients with cardiac insuﬃ ciency (CI) refractory to pharmacological treatment. Over the last 20 years, several clinical studies have sought to establish their beneﬁ ts in diff erent populations. The review of the results of these studies has shown that in patients with advanced CI (functional class (FC) I, II, III and IV of the New York Heart Association (NYHA) CRT produces consistent improvements in quality of life, FC and exercise capacity, as well as reducing hospitalizations and mortality rates. Up to 70% of patients submitted to CRT evolve as responders. The criteria adopted in the evaluation of the CRT response rate will be elucidated in this article, in which the main objective is to highlight the concept of the CRT super-responder.


INTRODUCTION
Cardiac insufficiency (CI) represents a major public health problem worldwide. In Europe and the United States, it represents an important cause of hospitalization in patients aged 65 and over 1,2 . This disease has a great social, economic and, above all, human impact, since it imposes important physical limitations on patients, resulting in early retirements, with high governmental costs 3 .
Despite advances in available pharmacological therapies, they do not fully meet the needs of patients with heart failure 4 . Non-pharmacological therapies, such as mechanical left ventricular assist devices and cardiac transplantation, are reserved for a small group of patients with CI 5,6 . In addition to these, cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators appeared as a good option for patients with CI refractory to drug treatment [4][5][6][7] . The CRT response rate historically approaches 70% of cases. With improved patient selection, ie QRS duration> 150 ms and LBBB morphology 10 , absence of fibrosis by magnetic resonance imaging (MRI) in the posterolateral region 11 , as well as total fibrosis load <20% 12 , improvement of the surgical technique, adequate programming of the device, a recent and considerable increase in the response rate to CRT was observed.
The following is the case of a patient considered to be a CRT super-responder. We will also discuss the important variables in the selection of these patients, as well as the criteria to be considered super-responders.

CASE REPORT
MJS, 72 years old, born in the state of Paraíba, a patient with CI since 2010, without other comorbidities.
Admitted in a tertiary hospital in 2015 for optimization and investigation of CI etiology.
In this period, FC III, doses of carvedilol, enalapril, and furosemide were optimized. The patient had a significant improvement in FC, now FC II. All the necessary exams were done to elucidate the etiology of CI (Chagas, echocardiogram, MRI of the heart, myocardial scintigraphy), and, as definitive diagnosis, idiopathic CI.
Because he was an LBBB patient and still symptomatic despite clinical treatment, he was referred to the pacemaker team to decide on CRT. Based on the current evidence, we opted for the implantation of the cardiac resynchronizer, performed 12/13/2015. Five essential steps for success in using CRT as a treatment modality were defined. They were followed strictly.

Patient selection
According to the current evidence, HF with ejection fraction <35% and LBBB with QRS duration> 150 ms may be one of the only indications considered to be FC IA de CRT 8,9 . In the present case, those criteria were satisfied.

Surgical technique
The cardiac dyssynchrony generated by LBBB has the slowest and most delayed region on the conduction in the posterolateral wall of the LV 13 . This should be the implant site of the LV electrode. The cardiac vein of choice should be the one that is directed to the posterolateral region of the LV (Fig. 1). In addition, performing an MRI of the pre-implanted heart discards the presence of fibrosis in this region, thus avoiding possible stimulation in a non-viable region 11 . In the present case, all such care was observed.

X-ray and comparison of electroencephalograms (ECGs) (<one month postoperatively)
The correct position of the electrodes, especially the LV coronary sinus electrode, can be verified in the posterolateral region (Fig. 2). In the case of a dislocation, it should be surgically resubmitted for repositioning.
In the present case, the LV electrode was stable in the postoperative period.
In addition, a considerable reduction in pre and postimplant QRS duration provides good prospects regarding   the chances of responding to CRT (Fig. 3). In the present case, there was an 18.75% reduction in QRS duration.

Proper Resynchronizer Programming
Biventricular pacing should be confirmed (> 90% capture by telemetry, ideally 100%) 14 (Fig. 4), as well as the stimulation thresholds. Special attention is given to other factors that reduce the CRT response, such as the presence of atrial fibrillation and frequent ventricular extrasystoles and others associated with worsening of the quality of life, namely phrenic stimulation (absent in the case reported).
It is suggested that the atrioventricular interval (AVI) be adjusted around 120 ms 15 (Fig. 5). The programming of the pacing interval between the ventricles (VV) should be the one in which the lowest QRS is produced in biventricular pacing on the 12-lead ECG, in general, VV interval programmed between 0 ms or -30 ms LV> RV 5).
In the present case, these concepts were adopted.

Concept of super-responder to CRT
Patients without structural heart disease and with LBBB when compared to those without structural heart disease and without LBBB present, on average, 7% less of the VF, considering both within the range of normality 16

REFERENCES CONCLUSION
An increasing selection of CRT candidates, correct surgical technique, adequate device programming, and regular follow-up have all contributed to the increased CRT response rate. In this context, the super-responder concept stands out. In the case reported here, we elucidate that when the approach to CRT is systematized, it approaches more and more of the super-responders, thus achieving the best results that this modality of treatment can provide.

AUTHORS' CONTRIBUTION
All the authors contributed equally to this article.