Unexplained Pulmonary Hypertension in Chronic Myeloproliferative Disorders

doi:10.1378/chest.120.3.801

Chest

Volume 120, Issue 3, September 2001, Pages 801-808

https://doi.org/10.1378/chest.120.3.801 Get rights and content

Abstract

Aim

To investigate the potential association between the chronic myeloid disorders (CMDs), including the chronic myeloproliferative disorders, and pulmonary hypertension (PH).

Methods

Retrospective chart review of patients who had received diagnoses of both CMD and PH. Patients with a known cause of PH were excluded. The diagnosis of a CMD was based on established criteria. The diagnosis of PH was based on echocardiographic data or right heart catheterization data.

Results

Twenty-six patients satisfied the criteria for both a CMD and PH. Twelve patients had myeloid metaplasia with myelofibrosis (MMM), 5 patients had essential thrombocythemia (ET), 6 patients had polycythemia vera, 2 patients had a myelodysplastic syndrome, and 1 patient had chronic myeloid leukemia. Twenty-two patients (92%) received treatment for their CMDs, which included therapy with hydroxyurea (18 patients), anagrelide (7 patients), and busulfan (3 patients). PH was diagnosed a median of 8 years after recognition of the CMD (range, 0 to 26 years). The median right ventricular systolic pressure (RVsys) was 71 mm Hg (range, 32 to 105 mm Hg). RVsys correlated with the platelet count in patients with MMM (r = 0.30) and ET (r = 0.6) and with the hemoglobin levels in patients with PV (r = 0.77). Treatment of CMD did not seem to affect the severity of the pulmonary artery pressures as measured by serial echocardiography. With a median survival time of 18 months after the diagnosis of PH, the cause of death in the majority of the patients was cardiopulmonary.

Conclusions

The current study suggests a higher than expected incidence of PH in patients with MMM, PV, and ET. Prognosis in such a setting is poor and may not be influenced by aggressive treatment of the underlying hematologic disorder.

Section snippets

Materials and Methods

At our institution, all patient visits, whether outpatient or in the hospital, are coded under diagnoses that are pertinent to the patient’s condition. These are listed on a “master sheet” that appears in the patient’s permanent record and also are recorded electronically.⁶ We used this diagnostic index to identify all patients seen who had as a dismissal diagnosis both a CMD and PH listed. The search strategy used the following key words: (chronic) myeloproliferative disorder (not otherwise

Patient Characteristics

The initial search for coexistent diagnoses of CMD and PH produced a list of 124 patients seen at the Mayo Clinic between June 1987 and July 31, 2000. Of these, 98 were excluded either because the diagnosis of a CMD could not be confirmed or because of the presence of an alternative explanation for the PH.

The remaining 26 patients constituted our study population (Table 1). Twelve patients had MMM, and of these 4 had postpolycythemic myeloid metaplasia. Six patients had PV, and five patients

Discussion

We described a cohort of 26 patients with CMDs and unexplained PH. Other authors have reported on similarly affected patients.²³⁴⁵ However, to our knowledge, our cohort is the largest series of patients having both PH and a CMD. Of course, patients with unusual combinations of diseases often are referred to academic medical centers, so the possibility arises that the association is due to chance alone.¹²

However, the annual incidence rate of primary PH is only about 0.2 cases per 100,000

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An 80-year-old woman with myelofibrosis and diffuse mosaic attenuation on chest computed tomography
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An 80-year-old woman with myelofibrosis sought evaluation for progressive dyspnea. Her past medical history included essential thrombocytosis, which transformed to myelofibrosis. Inspiratory computed tomography of chest showed diffuse mosaic attenuation with lymphadenopathy. Flexible bronchoscopy with lymph node and pulmonary parenchymal cryo biopsy revealed nodular deposits of extramedullary hematopoiesis in lung parenchyma and moderate to severe vascular medial and intimal thickening of pulmonary vasculature consistent with pulmonary parenchymal extramedullary hematopoiesis associated with pulmonary hypertension (a rare compensatory mechanism in myeloproliferative disorders). In this report, we explore the manifestations, pathogenesis, treatment, and prognosis of pulmonary extramedullary hematopoiesis reported in the literature.
BCR-ABL1–Negative Chronic Myeloproliferative Neoplasms and Pulmonary Hypertension: A Prospective Long-Term Follow-up Study of the Impact of Pulmonary Hypertension on Survival
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To assess the prevalence of PHT in patients with BCR-ABL1–negative CMPN and to evaluate impact of PHT on survival during long-term follow-up.
A total of 122 patients with BCR-ABL1–negative CMPN underwent transthoracic echocardiographic (TTE) evaluation at the beginning of study. Patients undergoing PHT on TTE examination were also evaluated by a pulmonologist. Patients were divided into 3 groups. Group A comprised patients with CMPN-related PHT; group B, patients with no PHT; and group C, patients with PHT due to secondary causes. Patients were evaluated again every 3 to 6 months.
PHT was detected in 33 (27%) of 122 patients. Eight (6.5%) had CMPN-related PHT and the remaining 25 (20.5%) had non–CMPN-related PHT. Positivity for JAK2 V617F mutation in the study population was 72.9%. Groups were similar with respect to hematologic parameters and gender. Follow-up times were as follows: median (range) time from diagnosis to TTE and study end were 34 (1-158) months and 107 (16-251) months, respectively, and from TTE to study end was 88 (7-110) months. No significant differences found among the groups in terms of median time from diagnosis to TTE, follow-up, and overall survival.
BCR-ABL1–negative CMPN patients had a lower prevalence of PHT compared to earlier studies. There was no statistically significant difference in median overall survival between patients with or without PHT. This may be because patients with PHT were asymptomatic and PHT was mild. The impact of PHT on survival was negligible.
Incremental Utility of Right Ventricular Dysfunction in Patients With Myeloproliferative Neoplasm–Associated Pulmonary Hypertension
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Myeloproliferative neoplasm (MPN) has been associated with pulmonary hypertension (PH) on the basis of small observational studies, but the mechanism and clinical significance of PH in MPN are not well established. The aims of this study were to expand understanding of PH in a well-characterized MPN cohort via study of PH-related symptoms, mortality risk, and cardiac remodeling sequalae of PH using quantitative echocardiographic methods.
The population comprised a retrospective cohort of patients with MPN who underwent transthoracic echocardiography: Doppler-derived pulmonary arterial systolic pressure applied established cutoffs for PH (≥35 mm Hg) and advanced PH (≥50 mm Hg); right ventricular (RV) performance was assessed via conventional indices (tricuspid annular plane systolic excursion [TAPSE], S′) and global longitudinal strain. Symptoms and mortality were discerned via standardized review.
Three hundred one patients were studied; 56% had echocardiography-demonstrated PH (20% advanced) paralleling a high prevalence (67%) among patients with invasively quantified PASP. PH was associated with adverse left ventricular (LV) remodeling indices, including increased myocardial mass and diastolic dysfunction (P ≤ .001 for all): LV mass and filling pressure (P < .01) were associated with PH independent of LV ejection fraction. RV dysfunction by strain and TAPSE and S′ increased in relation to PH (P ≤ .001) and was about threefold greater among patients with advanced PH compared with those without PH. Patients with RV dysfunction were more likely to report dyspnea, as were those with advanced PH (P < .05). During median follow-up of 2.2 years, all-cause mortality was 27%. PH grade (hazard ratio, 1.9; 95% CI, 1.1–3.0; P = .012) and TAPSE- and S′-demonstrated RV dysfunction (hazard ratio, 3.3; 95% CI, 1.3–8.2; P = .01) were independently associated with mortality; substitution of global longitudinal strain for TAPSE and S′ yielded similar associations of RV dysfunction with death (hazard ratio, 3.2; 95% CI, 1.5–6.7; P = .003) independent of PH.
PH is highly prevalent in patients with MPN and is linked to LV diastolic dysfunction; echocardiography-quantified RV dysfunction augments risk for mortality independent of PH.
Pulmonary hypertension in patients with myeloproliferative neoplasms: A large cohort of 183 patients
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Chronic myeloproliferative neoplasms (MPN) are recognized as a cause of pulmonary hypertension (pH). We ought to describe the prevalence and characteristics of PH in a cohort of MPN who were screened using transthoracic echocardiography (TTE).
One hundred eighty-three newly diagnosed consecutive MPN patients were prospectively evaluated using TTE to detect PH.
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Conclusion: In this large cohort of 183 MPN patients, TTE was used to diagnose PH, and 14 patients (7.7%) developed PH. This prevalence was lower than expected based on previously reported data, but it remains higher than in the general population.

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Clinical InvestigationsPulmonary VasculatureUnexplained Pulmonary Hypertension in Chronic Myeloproliferative Disorders

Abstract

Aim

Methods

Results

Conclusions

Section snippets

Materials and Methods

Patient Characteristics

Discussion

Mayo Clin Proc

Chest

Chest

Chest

Am J Med

Toxicol Appl Pharmacol

Blood

J Am Coll Cardiol

Blood

Pulmonary hypertension in polycythemia vera

Am J Hematol

Pulmonary hypertension in patients with myelofibrosis secondary to myeloproliferative diseases

Am J Hematol

The patient record in epidemiology

Sci Am

Myelofibrosis with myeloid metaplasia

N Engl J Med

Clinical Investigations
Pulmonary Vasculature
Unexplained Pulmonary Hypertension in Chronic Myeloproliferative Disorders