Left heart disease is accountable for about two thirds of pulmonary hypertension (PH) and PH in patients with congestive heart failure has negative impact on the survival (1). Pulmonary hypertension due to left heart disease (PH-LHD) is defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest and a pulmonary arterial wedge pressure (PAWP) >15 mmHg measured by right heart catheterization (RHC), which is essential for the evaluation of PH (2). A new clinical classification of PH-LHD was established on the 5th World Symposium on PH in Nice 2013 and was defined as isolated post-capillary PH (IpcPH) and combined post-capillary and precapillary PH (CpcPH) (3). CpcPH is hemodynamically defined as a mPAP >15 mmHg with a diastolic pressure difference (DPD = diastolic PAP – PAWP) ≥7 mmHg.
The pathophysiology of PH-LHD is not yet fully understood, but considering its negative impact on patient prognosis and the current lack of an optimal treatment protocol, new and more effective treatment modalities are required. Over the past years, specific agents targeting pulmonary arterial hypertension (PAH) have been developed, and several clinical trials have been conducted to measure the effect of PAH targeting agents on PH-LHD, but the results have been conflicting.
A 31-year-old Asian man was referred to our center with hemoptysis and biventricular failure. He reported having some hemoptysis over a 2-year period previously and recently experienced two episodes of hemoptysis. He denied having symptoms such as dyspnea on exertion, fatigue, dizziness, or syncope, but confirmed having epilepsy for 23 years, which was well controlled with anti-epileptic medications, and had no history of alcohol abuse or illicit drug use, or family members or relatives with heart failure. His blood pressure was 126/88 mmHg and it remained within the normal range throughout the admission period. Cardiac enzymes and thyroid function tests were normal. Anti-nuclear antibody, rheumatoid factor, and anti-neutrophil cytoplasmic antibody tests were negative.
A chest CT scan showed bilateral enlargement of the main pulmonary arteries and diffuse ground glass opacities on both lungs, possibly resulting from aspirated blood. There was no evidence of thromboembolism or pulmonary vascular malformation. Echocardiography showed an enlarged left ventricle (LV) with decreased LV systolic function and the LV ejection fraction (EF) was 26%. The E/e’ ratio was 18, indicating high LV filling pressure. The right ventricle (RV) was also dilated and systolic dysfunction was observed (Table 1). The heart valves were normal with respect to morphology and function. He experienced massive hemoptysis after admission and underwent bilateral bronchial arterial embolization.
RHC showed elevated mPAP and PAWP values, with a DPD of 45 mmHg (Table 2). A lung perfusion scan did not show any perfusion defects in either lung. We diagnosed him as PH-LHD, specifically CpcPH, which we consider to have been caused by a dilated cardiomyopathy. He was treated with spironolactone 12.5 mg, bisoprolol 2.5 mg which was gradually increased to 10 mg, and losartan 50 mg which was increased later to 100 mg. Sildenafil, 25 mg 3 times a day, was also used to manage CpcPH because DPD was markedly elevated.
After 2 years of treatment, follow-up echocardiography revealed complete restoration of LV systolic function and the near restoration of RV systolic function, but PH remained elevated. Repeated RHC revealed an elevated mPAP with a normalized PAWP (Table 2). The diagnosis was subsequently changed from CpcPH to idiopathic pulmonary arterial hypertension (IPAH).
Cardiac catheterization is the gold standard for the evaluation of PH, despite advances in echocardiographic methods used to estimate PH (4). We initially diagnosed the patient as having CpcPH with a markedly elevated DPD, but we later changed the diagnosis to IPAH after treatment for heart failure and repeated RHC. It is important for CpcPH patients to undergo repeated RHC after restoration of LV dysfunction to eliminate other possible causes of PH, such as IPAH. Repeated RHC is recommended in heart transplant candidates (5), but the value of repeated RHC in CpcPH patients is underappreciated.
Our case report has some limitations. At the time of diagnosis, our RHC protocol did not included measurement of left ventricle end-diastolic pressure (LVEDP), the value could not be provided. Although the patient’s RHC results meets the diagnostic criteria of IPAH, the diagnosis of IPAH relying solely on the PAWP may lead to misclassification of PH because there is a discrepancy between the PAWP and LV EDP (6). In this case, a left heart catheterization and additional imaging such as cardiac magnetic resonance (MR) would have provided better grasp of underlying pathology (7).
We added sildenafil to the treatment regimen to treat CpcPH in the current case, but the role of PAH targeting agents on PH-LHD is uncertain. Several studies showed that sildenafil improves exercise capacity and the quality of life in patients with heart failure (8,9). Other PAH targeting agents, such as bosentan, have also been shown to improve exercise capacity and functional status, but have failed to improve mortality (10,11). Another problem is that the optimal cut-off value of DPD for the initiation of therapy with these agents has not been properly studied. In conclusion, the use of PAH targeting agents in CpcPH patients requires further investigations.
Conflicts of Interest: The authors have no conflicts of interest to declare.
- Strange G, Playford D, Stewart S, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart 2012;98:1805-11. [PubMed]
- Hansdottir S, Groskreutz DJ, Gehlbach BK. WHO’s in second?: A practical review of World Health Organization group 2 pulmonary hypertension. Chest 2013;144:638-50. [PubMed]
- Vachiéry JL, Adir Y, Barberà JA, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol 2013;62:D100-8. [PubMed]
- Fisher MR, Forfia PR, Chamera E, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med 2009;179:615-21. [PubMed]
- Fang JC, DeMarco T, Givertz MM, et al. World Health Organization Pulmonary Hypertension group 2: pulmonary hypertension due to left heart disease in the adult--a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2012;31:913-33. [PubMed]
- Bitar A, Selej M, Bolad I, et al. Poor agreement between pulmonary capillary wedge pressure and left ventricular end-diastolic pressure in a veteran population. PLoS One 2014;9:e87304. [PubMed]
- Swift AJ, Rajaram S, Hurdman J, et al. Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry. JACC Cardiovasc Imaging 2013;6:1036-47. [PubMed]
- Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007;116:1555-62. [PubMed]
- Guazzi M, Vicenzi M, Arena R, et al. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail 2011;4:8-17. [PubMed]
- Packer M, McMurray J, Massie BM, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. J Card Fail 2005;11:12-20. [PubMed]
- Liu C, Chen J, Gao Y, et al. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst Rev 2013;2:CD004434. [PubMed]