Author + information
- Stephen F. Crawley, MBChB,
- Martin K. Johnson, MD,
- Henry J. Dargie, MD and
- Andrew J. Peacock, MD∗ ()
- ↵∗Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Beardmore Street, Clydebank, Glasgow, United Kingdom, G81 4HX.
There has been increasing recognition of pulmonary hypertension (PH), which develops as a direct consequence of impaired left ventricular distensibility and relaxation, described as PH due to heart failure with preserved ejection fraction (PH-HFpEF) (1). Current guidelines emphasize the importance of distinguishing PH-HFpEF from idiopathic pulmonary arterial hypertension (IPAH), a rare disease caused by progressive luminal obliteration of small pulmonary arteries (2). At present, right heart catheterization (RHC) is the definitive investigation to confirm the diagnosis. In this prospective study, we explored the use of cardiac magnetic resonance (CMR)–derived left atrial volume (LAV) as a simple, noninvasive method for distinguishing IPAH from PH-HFpEF, without the need for additional variables or derived equations.
Consecutive treatment-naive patients with a suspected new diagnosis of pulmonary hypertension underwent diagnostic assessment between January 2009 and March 2011. Patients with clear evidence of an underlying cause of pulmonary hypertension such as chronic thromboembolic disease, connective-tissue disease, left ventricular (LV) systolic dysfunction, or significant valvular heart disease on echocardiography were excluded.
CMR imaging was performed in the supine position on a 1.5-T magnetic resonance imaging scanner and images were analyzed using the Argus analysis software (Houston, Texas). CMR images were fully analyzed prior to RHC, but the analyzer was blinded to the catheterization results. LAV was determined using standard 2- and 4-chamber views and the biplane area-length method. Measurements were made in accordance with previously published methods (3).
RHC was performed within 72 h of CMR, with the patient in a supine position breathing room air. Cardiac output was determined using thermodilution. Following RHC, the diagnosis of IPAH or PH-HFpEF was made according to current guidelines (2).
After RHC, 37 patients were diagnosed with IPAH, 21 patients with PH-HFpEF, and 23 patients were found not to have pulmonary hypertension. The IPAH group was younger, had lower systemic blood pressure, and a lower incidence of diabetes mellitus and atrial fibrillation than the PH-HFpEF group did.
At CMR, in comparison to PH-HFpEF, IPAH patients had increased right ventricular dilation, reduced right ventricular function, impaired LV filling, and lower left atrial volume (24 ± 9 ml/m2 vs. 67 ± 20 ml/m2, p < 0.0001) (Fig. 1).
Receiver-operating characteristic analysis of CMR-derived variables that differed between IPAH and PF-HFpEF demonstrated that LAV was the most sensitive and specific variable to discriminate between the two conditions. Using a threshold LAV of <43 ml/m2, IPAH could be distinguished from PH-HFpEF with 97% sensitivity and 100% specificity, with area under the receiver-operating characteristic curve of 0.990.
With the global increase in hypertension, coronary artery disease, and diabetes, PH-HFpEF is becoming more prevalent. One of the most important diagnostic challenges for a pulmonary vascular center is to distinguish IPAH from PH-HFpEF, particularly since the emergence of PAH-specific therapies. These treatments are expensive, potentially dangerous, and current guidelines recommend their use in IPAH, but not in PH-HFpEF, where they are harmful (2).
In HFpEF, there is preserved LV systolic function, but impaired diastolic function with abnormal LV relaxation and increased LV filling pressure. Sustained elevations of LV diastolic filling pressures will result in enlargement of the thin-walled left atrium, allowing LAV to be used as a marker of the severity and chronicity of diastolic dysfunction (4). Thenappan et al. (1) noted echocardiographic left atrial enlargement in 64% of their PH-HFpEF group and only 18% of the PAH group, but they used multiple variables requiring clinical, hemodynamic, and echocardiographic data to distinguish between these conditions.
We acknowledge that echocardiography will give a measure of LAV, but note the following limitations: 1) echocardiography underestimates CMR-derived LAV, in both healthy subjects and patients with cardiovascular disease; and 2) CMR can be used when acoustic windows are poor (3). We have shown that a single, noninvasive, CMR-derived variable, LAV of <43 ml/m2, will distinguish IPAH from PH-HFpEF, which is attractive for busy pulmonary vascular centers.
Please note: Dr. Johnson has received research and travel grants and speaking honoraria from Actelion, Pfizer Inc., and GlaxoSmithKline. Dr. Peacock has received speaking honoraria and travel expenses from Actelion, Bayer HealthCare, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc., and United Therapeutics; received research grants from Actelion and Bayer HealthCare; and has served on the advisory boards of Actelion, Bayer HealthCare, Eli Lilly, GlaxoSmithKline, Novartis, and Pfizer Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Thenappan T.,
- Shah S.J.,
- Gomberg-Maitland M.,
- et al.
- Galie N.,
- Hoeper M.M.,
- Humbert M.,
- et al.,
- for the Task Force for Diagnosis and Treatment of Pulmonary Hypertension of ESC, ERS, ISHLT