Prolonged QRS duration as a predictor of right ventricular dysfunction after balloon pulmonary angioplasty

https://doi.org/10.1016/j.ijcard.2018.11.026Get rights and content

Highlights

  • Residual right ventricular dysfunction after balloon pulmonary angioplasty was studied.

  • CMR image was obtained at baseline, and 3-month and 12-month follow up after BPA.

  • High percentage of residual RV dysfunction with worse WHO-functional class was observed.

  • Male sex and prolonged QRS duration were associated with residual RV dysfunction.

  • In 11 CTEPH autopsy cases, QRS duration was correlated with RV fibrosis area.

Abstract

Background

Balloon pulmonary angioplasty (BPA) has shown beneficial effects for chronic thromboembolic pulmonary hypertension (CTEPH). However, previous studies have shown less cardiac output improvement and symptoms remaining after BPA, implying poor right ventricular (RV) function recovery. Therefore, we investigated the residual RV dysfunction after BPA to reveal risk factors, clinical effects, and possible underlying histopathological mechanisms.

Methods and results

We investigated 61 consecutive CTEPH patients who underwent cardiovascular magnetic resonance before and 3 and 12 months after BPA series. Residual dysfunction (RD) of RV was defined as RV end-diastolic volume index >100 ml/m2 or RV ejection fraction (EF) <45% at 12-month follow-up. Patients were divided into RD (44%) and normalized dysfunction (ND) (56%) groups.

Compared with the ND group, the RD group had significantly worse World Health Organization (WHO) functional class at follow-up. No significant hemodynamic differences were observed between the groups. On multivariable logistic regression analysis, male sex (odds ratio [OR] 12.5, p = 0.004) and prolonged QRS duration (OR 1.08, p = 0.029) were independently associated with residual RV dysfunction. Additionally, RV histopathology in 11 CTEPH autopsy cases showed that QRS duration was correlated with RV fibrosis area.

Conclusions

Relatively high percentage (44%) of residual RV dysfunction with worse WHO functional class was observed in CTEPH patients even after BPA. Prolonged QRS duration may predict poor recovery in RV function after BPA.

Introduction

Right ventricular (RV) function is a major determinant of symptoms, functional capacity, and prognosis in pulmonary hypertension (PH) [1,2]. Chronic pressure and volume overload of RV in PH induce RV remodeling and dysfunction, resulting in exercise limitations, renal and liver dysfunction, arrhythmias, acute heart failure, and sudden cardiac death. Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease characterized by high pulmonary vascular resistance due to organized thrombi and leads to progressive right heart failure and death if untreated [3].

Pulmonary endarterectomy (PEA) is the gold standard for the treatment of CTEPH [4,5]. While PEA improves CTEPH prognosis, previous studies have indicated that RV dysfunction is improved but not normalized after PEA [6,7]. In the United Kingdom national PEA cohort (n = 880), 82 of the patients who survived surgery died during the follow-up period (4.3 ± 3.6 years) and 29 of these deaths were caused by RV failure [8]. Residual RV dysfunction after PEA might be multifactorial, resulting not only from afterload burden, but also from myocardial injury caused by deep hypothermic circulatory arrest during surgery.

Recently, we and others reported that balloon pulmonary angioplasty (BPA) could improve symptoms, hemodynamics, exercise capacity, and prognosis of patients with CTEPH in a less invasive manner than PEA [[9], [10], [11]]. Our previous pilot study, which composed of small number of patients and short-term follow-up, revealed that BPA induced RV reverse remodeling by ameliorating hemodynamics in patients with inoperable CTEPH [12]. However, the extent of RV reversibility varied among individuals. Moreover, previous studies showed limited improvement in cardiac output and symptoms remaining in long-term after BPA [13]. Thus, the present study focused on the variability of RV response, and we aimed to clarify the frequency, clinical characteristics, and predictors of residual RV dysfunction following BPA in patients with CTEPH in larger and longer follow-up cohort using cardiovascular magnetic resonance (CMR) imaging.

Section snippets

Study design and subjects

We retrospectively investigated 61 consecutive patients for whom quantitative cardiovascular magnetic resonance (CMR) imaging was obtained before and 3 and 12 months after the final BPA between August 2012 and January 2017 to evaluate the prevalence, clinical characteristics, and predictors of residual RV dysfunction. All patients complained of dyspnea on effort that was more severe than World Health Organization functional class (WHO-FC) II. CTEPH was diagnosed according to the WHO guideline

Baseline clinical characteristics

The baseline clinical characteristics of the patients are summarized in Table 1. In the cohort, 44 patients were female, the median age was 69 (interquartile range 61–77) years, and the mean BNP level was 133 ± 154 pg/ml. WHO-FC II, III, and IV were observed in 23%, 72%, and 5% of the patients, respectively. PH-specific drugs were used in 72% of the patients.

BPA effects on clinical, hemodynamic, and CMR parameters

A series of BPA (mean 4.9 ± 1.8 sessions per patients) was performed, with a median duration of 25 (interquartile range 15–67) months from

Discussion

The major findings of the present study are that in patients with CTEPH, 1) RV dysfunction remained in 44% of the patients despite hemodynamic improvement at 12 months after the final BPA, 2) male sex and prolonged QRS complex were independent risk factors for residual RV dysfunction after BPA, and 3) additional histopathological analysis revealed that QRS duration was correlated with RV fibrosis area.

Conclusions

The present findings indicate that RV dysfunction remained with worse symptoms in nearly half of CTEPH patients following BPA and was associated with male sex and prolonged QRS duration at baseline. QRS duration was correlated with the extent of RV fibrosis in histopathological analysis and could be a useful marker to predict poor RV function recovery after BPA.

Acknowledgements

We express our appreciation to Koko Asakura, PhD, for her expert assistance with the statistical analysis.

Funding

The work was supported by the Intramural Research Fund (28-6-4) for Cardiovascular Disease of the National Cerebral and Cardiovascular Center.

Disclosures

T. Ogo has received lecture fees from GlaxoSmithKline K.K., Actelion Pharmaceuticals Japan Ltd., Nippon Shinyaku Co., Pfizer Japan Inc., and Bayer Yakuhin Ltd., and a research grant from Pfizer Japan Inc. and Mochida Pharmaceutical Co. T. Ogo belongs to a department endowed by Actelion Pharmaceuticals Japan Ltd.

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    Grant support: The work was supported by the Intramural Research Fund (28-6-4) for Cardiovascular Disease of the National Cerebral and Cardiovascular Center.

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