Evaluation of potential underuse of cardiac resynchronization therapy for heart failure with reduced ejection fraction

Abstract Background The number of patients with chronic heart failure is increasing in Japan. However, the annual number of patients with heart failure who receive cardiac resynchronization therapy (CRT) has been constant in the last few years. In this study, we evaluated patients who did not receive CRT despite being eligible for this treatment to elucidate the clinical impact of CRT administration. Methods We assessed 214 patients with a left ventricular ejection fraction (LVEF) ≤ 50% (excluding patients treated with CRT) who underwent transthoracic echocardiography between January and May 2020 at our institution. The patients were stratified into two groups: Group A (n = 26; patients eligible for CRT) and Group B (n = 188; patients ineligible for CRT); however, all patients only received pharmacological therapy. We retrospectively analyzed the prognosis of these patients with respect to the cumulative number of hospitalizations for heart failure and cardiogenic deaths. Results We observed no significant between‐group differences in age, sex, and severity/diagnosis of organic heart disease. Group A had a significantly higher number of hospitalizations for heart failure and cardiogenic deaths than Group B (log‐rank test, P < .01; hazard ratio, 3.05; 95% confidence interval, 1.31‐7.09; average follow‐up period, 675 days). Conclusions This study shows that 12% of patients were eligible for CRT. However, the implantation rate was low and no one was implanted. CRT is underutilized in patients who have heart failure with reduced LVEF. Therefore, we strongly recommend CRT for patients with indications for CRT.


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TAKANO eT Al. deterioration in the condition and functioning of the heart, which necessitates repeated hospitalizations and eventually leads to death.
The Japanese Circulation Society (JCS)/The Japanese Heart Rhythm Society (JHRS) 2018 practical guidelines classify treatment regimens for progressive heart failure according to the patient's left ventricular ejection fraction (LVEF). 3 The categories are as follows: heart failure with preserved ejection fraction (LVEF ≥ 50%), heart failure with midrange reduced ejection fraction (LVEF ≥ 40% and <50%), and heart failure with reduced ejection fraction (HFrEF) (LVEF < 40%). Treatment may be in the In this study, we attempted to investigate whether nonpharmacological management, specifically CRT, is actually underutilized in patients with HFrEF in order to encourage the appropriate use of CRT according to the guidelines. Furthermore, we evaluated the prognosis of patients who were eligible for CRT but did not receive CRT at our institution.

| Patient selection and study design
Among patients who underwent transthoracic echocardiography between January and the end of May 2020 at our institution, this retrospective study only assessed patients with an LVEF of <50% (242 patients) and excluded patients with an LVEF of ≥50% (2008 patients).
Among the 242 patients whose attending physician was a cardiologist, we excluded those who underwent CRT implantation (10 patients) or those for whom lack relevant data on echocardiography were una-

| Statistical analyses
Statistical analyses were performed using SPSS version 21.0 (IBM).
Categorical comparisons between the groups were performed using a F I G U R E 1 Description of the study protocol. Among patients who underwent transthoracic echocardiography between January and the end of May 2020 at our institution, this retrospective study assessed only patients with LVEF < 50% (242 patients) and excluded patients with LVEF > 50% (2008 patients). The final 214 patients were divided into two groups chi-square test and a Fisher's exact test for independence. Continuous variables were compared using a Wilcoxon rank-sum test and a Mann-Whitney rank-sum test. All continuous parameters are presented as mean ± SD values. Differences were considered statistically significant if the P-value was less than .05. Logit transformations of sensitivity and specificity were assumed by the bivariate approach used in this study. patients who were treated with optimal standard drug therapy, CRT was not implanted.

| RE SULTS
We found no significant between-group differences in terms of age, sex, and severity/diagnosis of organic heart disease. Compared to Group B, Group A had a wider QRS complex (Group A vs Group B: QRS width, 155 ± 23 ms vs 101 ± 11 ms; P < .001), and a lower LVEF (Group A vs Group B: LVEF, 35 ± 9.5% vs 39 ± 8.2%; P = .03). This QRS is the QRS width of the electrocardiogram.
In Group A, 13 patients had typical LBBB and were hospitalized due to heart failure; among these, 2 patients died due to sudden cardiac death as a complication of ventricular fibrillation. The clinical courses of these 13 patients are presented in Table 2.
We retrospectively analyzed the two groups with respect to the number of hospitalizations for heart failure and cardiac deaths. The number of hospitalizations and cardiac deaths were greater in Group A than in Group B (log-rank test, P < .01) ( Figure 2). In Japan, only 10% of patients with HFrEF are treated with CRT, as reported by the Chronic Heart Failure Analysis and Registry in Tohoku

| D ISCUSS I ON
District-2 (CHART-2) study. 5 The CHART-2 study also reported a significantly higher prevalence of fatal arrhythmic events in patients with an LVEF of ≤35% than in patients with an LVEF of >35%. Only 2.6% of patients underwent ICD implantation or CRT in the CHART-2 study. 5 The findings of our study, with reference to the underutilization of CRT, were consistent with those of CHART-2. The progression of heart failure (stage) was greater among under-treated patients with HFrEF who were eligible for CRT than among those not eligible for CRT.
Furthermore, our study revealed that CRT-eligible patients had poorer prognosis compared to those patients who were not eligible for CRT.
Cardiac resynchronization therapy administration and ICD implantation are reportedly low in Western countries. 6 Heart failure is a progressive disease, and there may be some patients whose eligibility for CRT may change during the clinical course.
Additionally, patients in Group A were older than those in Group B, which may be why CRT was not administered to patients in Group A.

| CON CLUS IONS
According to the JCS guidelines, CRT is recommended for patients with HFrEF with an intraventricular conduction disorder. However, only 12% of patients were eligible for CRT, and the implantation rate is low compared to the reality that no one was implanted. CRT is underutilized in patients who have heart failure with reduced LVEF. CRT is recommended for eligible patients with heart failure to improve their prognosis.

ACK N OWLED G M ENTS
We would like to thank Editage (www.edita ge.com) for English language editing. This study was supported by Medtronic External Research Program 2020-12313.

CO N FLI C T O F I NTE R E S T
Authors declare no Conflict of Interests for this article.

DATA AVA I L A B I L I T Y S TAT E M E N T
Not applicable.