ARTICLE IN PRESS Journal of Cardiac Failure Vol. ■■ No. ■■ 2017
Clinical Investigation
Diaphragm Muscle Dysfunction in Patients With Heart Failure MARI MIYAGI, MS, YOSHIHARU KINUGASA, MD, PhD, TAKESHI SOTA, PT, KENSAKU YAMADA, MD, TAKUYA ISHISUGI, MS, MASAYUKI HIRAI, MD, PhD, KIYOTAKA YANAGIHARA, MD, PhD, NOBUHIKO HARUKI, MD, PhD, KOICHI MATSUBARA, MD, PhD, MASAHIKO KATO, MD, PhD, AND KAZUHIRO YAMAMOTO, MD, PhD Yonago, Japan
ABSTRACT Background: Inspiratory muscle weakness is associated with the development of exercise intolerance in patients with heart failure (HF). Ultrasound assessment of the diaphragm is used to evaluate respiratory muscle function, but its application in patients with HF remains undefined. We examined the relationship of diaphragm function as assessed by ultrasonography with inspiratory muscle strength and exercise tolerance in HF. Methods and Results: Seventy-seven patients hospitalized with HF were enrolled. Impaired diaphragm muscle function was defined as a diaphragm thickness at end-inspiration of less than the median value of 4.0 mm, which represents diaphragm muscle loss and reduced contraction. Compared with patients with preserved diaphragm muscle function, those with impaired diaphragm muscle function were older; had significantly lower vital capacity, handgrip strength, and inspiratory muscle strength as assessed by the maximum inspiratory pressure; and had a significantly shorter 6-minute walk distance (6MWD; P < .05). Although low handgrip strength was also associated with a short 6MWD, the relationship between impaired diaphragm muscle function and short 6MWD was independent from age, vital capacity, and handgrip strength. Conclusion: Diaphragm dysfunction as assessed by ultrasonography represents inspiratory muscle weakness and predicts exercise intolerance independently from comorbid pulmonary dysfunction and dynapenia in patients with HF. (J Cardiac Fail 2017;■■:■■–■■) Key Words: Diaphragm ultrasound, frailty, inspiratory muscle weakness.
sured by spirometry is the standard parameter used to evaluate inspiratory muscle strength in patients with HF.6–8 Ultrasound assessment of the diaphragm, which plays a pivotal role in inspiration, is an alternate technique used to evaluate respiratory muscle function and has the advantage of allowing for direct assessment of the diaphragm muscle mass and contraction.9 In addition, data can be obtained during the echocardiographic examination, and it is relatively easy to perform at the bedside compared with spirometry. However, the clinical significance of ultrasound assessment of diaphragm function in patients with HF remains undefined. We hypothesized that diaphragm muscle function as assessed by ultrasonography was related to inspiratory muscle strength and exercise performance in patients with HF, and the present study was performed to describe the clinical significance of diaphragm muscle function in these patients.
Skeletal muscle dysfunction is often present in patients with heart failure (HF) and involves abnormal energy metabolism, transition of myofibers from type I to type II, mitochondrial dysfunction, and muscle atrophy.1 These abnormalities can cause physical frailty, reduced quality of life (QOL), and a poor prognosis in patients with HF.2–5 In addition to limb skeletal muscle dysfunction, inspiratory muscle weakness has been implicated in the development of limited exercise tolerance and poor QOL in patients with HF.6–8 The maximum inspiratory pressure (MIP) as meaFrom the Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Yonago, Japan. Manuscript received July 5, 2017; revised manuscript received November 4, 2017; revised manuscript accepted December 21, 2017. Reprint requests: Yoshiharu Kinugasa, MD, PhD, Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University 36-1 Nishicho, Yonago, 683-8504, Japan. Tel: +81-859-38-6517; Fax: +81-859-38-6519. E-mail:
[email protected]. See page ■■ for disclosure information. 1071-9164/$ - see front matter © 2017 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.cardfail.2017.12.004
Methods Patients
For this study, 172 consecutive patients with a primary diagnosis of HF who were hospitalized at Tottori University 1
ARTICLE IN PRESS 2 Journal of Cardiac Failure Vol. ■■ No. ■■ ■■ 2017 Hospital and discharged alive from January 2013 to December 2014 were screened. HF was defined according to the Framingham criteria and the presence of pulmonary congestion on X-rays, with the findings of elevated left atrial pressure and pulmonary hypertension on Doppler echocardiography and/or elevated B-type natriuretic peptide levels. In addition, those abnormalities were improved in all of the study subjects after the treatment for HF during the hospital stay, followed by relief from symptoms. Patients with acute coronary syndrome and acute pulmonary artery embolism were excluded. We also excluded patients who could not undergo physical function tests owing to dementia or poor activity of daily living (ADL) due to physical deconditioning or motor dysfunction caused by cerebrovascular or orthopedic disease (bedridden patients or patients with ADL at the bedside; n = 55), as well as patients with missing data (ultrasound measurement of diaphragm muscle thickness [n = 18], pulmonary function test results [n = 6], or physical performance test results [n = 16]). Finally, the data of 77 patients were analyzed in this study. Following stabilization for HF, the patients underwent cardiac rehabilitation during their hospital stay. In our hospital, home-based inspiratory muscle training is applied in some HF patients as an option of cardiac rehabilitation, and the inspiratory muscle strength measured by means of spirometry and diaphragm muscle ultrasound has been routinely evaluated in the standard rehabilitation program for patients hospitalized with HF. Thus, we could retrospectively analyze these data in the present study. Data Collection
The patients’ medical records during the hospital stay were retrospectively reviewed to obtain information on
demographics, medical history, comorbidities, laboratory data, echocardiographic findings, and physical function test results. The etiologies of HF were defined as follows: 1) ischemic heart disease: the presence of significant coronary artery disease and/or a history of coronary artery intervention; 2) valvular heart disease: moderate to severe valvular disease; 3) heart failure with preserved ejection fraction (HFpEF): left ventricular ejection fraction of ≥50% without severe valvular disease. In the present study subjects, median hospital stay was 33 (range 26–52) days. HF patients in Japan have longer hospital stays than those in Western countries because of the difference in insurance systems and of spending time for the patient’s education and rehabilitation during hospital stay.10 Thus, the present study assessed all measurements within 1 week before discharge, when stable status was confirmed by attending physician. Ultrasound Measurement of Diaphragm Muscle Thickness. Ultrasonography was performed with a 9.0MHz ultrasound probe (iE 33; Philips Medical Systems, Eindhoven, The Netherlands) to evaluate the diaphragm in the zone of apposition, which is the vertical section that lies against the lateral portion of the right ribcage, as previously described.11 The ultrasound transducer was placed in line with the right intercostal space between the anteroaxillary and midaxillary lines (Fig. 1A) and held perpendicular to the chest wall. The diaphragm appeared as a 3-layered structure comprising 2 parallel echogenic lines representing the pleural and peritoneal membranes. Measurements of muscle thickness were obtained at the end of inspiration (at total lung capacity; DTinsp) and at resting expiration (at functional residual capacity; DT-exp), as shown in Fig. 1B. The DT-exp value was available in 70 patients.
Fig. 1. Ultrasonographic measurement of the diaphragm. (A) Ultrasound transducer position. The transducer is placed on the skin at the midaxillary line at the level of the right 8th or 9th intercostal space. (B) Ultrasonographic images of the diaphragm. 1) Diaphragm muscle thickness at end-inspiration (at total lung capacity; DT-insp). 2) Diaphragm muscle thickness at resting expiration (at functional residual capacity; DT-exp).
ARTICLE IN PRESS Diaphragm Muscle Dysfunction in HF
DT-exp reflects the diaphragm muscle mass, whereas DTinsp reflects both the diaphragm muscle mass and contractility.12 Therefore, in the present study, we applied DTinsp as a comprehensive indicator of diaphragm muscle function, and impaired diaphragm function was defined as DT-insp below the median value (ie,
