Pulmonary Hypertension in Myeloproliferative Neoplasms

Analysis of Montani et al. (2023) Study Findings

Author

Ashwin Kishtagari

Published

today

4.1 Introduction

Myeloproliferative neoplasms (MPNs) are disorders of clonal hematopoiesis that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF). Pulmonary hypertension (PH) has been associated with MPNs and classified by the World Health Organization in group 5 (unclear and/or multifactorial mechanisms). This analysis examines the findings from Montani et al. (2023) published in the American Journal of Respiratory and Critical Care Medicine, which investigated the prevalence, hemodynamic characteristics, etiologies, and prognostic implications of PH in MPNs.

4.2 Study Population

The study identified 90 patients with MPNs with precapillary or combined pre-/postcapillary PH from a national PH registry. The distribution of MPN types among these patients is shown below:

Distribution of MPN Types
MPN Type	Count	Percentage (%)
Polycythemia vera	42	46.7
Essential thrombocythemia	35	38.9
Primary myelofibrosis	13	14.4

4.3 PH Etiology by MPN Type

The study found different patterns of PH etiology depending on the MPN type:

Pulmonary Hypertension Etiology by MPN Type
MPN Type	PH Etiology	Percentage (%)
PV or ET	CTEPH	64.5
PV or ET	WHO Group 5	35.5
MF (primary or secondary)	CTEPH	18.0
MF (primary or secondary)	WHO Group 5	82.0

Key findings:

Among patients with PV or ET, CTEPH (Chronic Thromboembolic Pulmonary Hypertension) was the most common etiology (64.5%)
Among patients with MF (primary or secondary), WHO Group 5 PH was the most common etiology (82%)

4.4 Secondary Myelofibrosis and PH Type

The study found a significant difference in PH types among patients with secondary MF:

Significantly more patients with secondary MF had Group 5 PH than CTEPH (29% vs. 4%, p<0.01).

4.5 Time Between MPN and PH Diagnoses

Patients with Group 5 PH had a longer interval between MPN and PH diagnoses (median, 93 vs. 22 months; p<0.01).

4.6 Combined Visualization

4.7 Clinical Implications

The study by Montani et al. (2023) suggests two predominant phenotypes of precapillary PH in patients with MPNs:

A thrombotic phenotype (CTEPH) - more common in PV and ET
A nonthrombotic phenotype (WHO Group 5) - more common in MF and potentially related to disease progression and extramedullary hematopoiesis

The association between Group 5 PH and MF, along with the finding that PH was associated with progression to MF among patients with ET and PV in prior studies, suggests that:

PH screening may be beneficial in patients with MPNs for disease progression surveillance
Clinicians caring for patients with MPNs who experience dyspnea should consider workup for PH

4.8 Limitations and Future Directions

Several questions remain unanswered by this study:

The prevalence and phenotype of PH meeting the newer criteria (mean pulmonary artery pressure >20 mm Hg instead of >25 mm Hg) among patients with MPNs is unclear
Echocardiography characteristics were not reported in this study
The true prevalence and etiologies of PH among asymptomatic patients with MPNs remain to be elucidated
The role of driver and non-driver mutations in PH development needs further investigation

4.9 References

Montani D, Thore P, Mignard X, et al. Clinical phenotype and outcomes of pulmonary hypertension associated with myeloproliferative neoplasms: a population-based study. Am J Respir Crit Care Med. 2023;208:600-612.

Leiva O, Ren S, Neuberg D, et al. Pulmonary hypertension is associated with poor cardiovascular and hematologic outcomes in patients with myeloproliferative neoplasms and cardiovascular disease. Int J Hematol. 2023;117:90-99.

Leiva O, Hobbs G, Ravid K, Libby P. Cardiovascular disease in myeloproliferative neoplasms: JACC: CardioOncology state-of-the-art review. JACC CardioOncol. 2022;4:166-182.

--- title: "Pulmonary Hypertension in MPNs" --- --- title: "Pulmonary Hypertension in Myeloproliferative Neoplasms" subtitle: "Analysis of Montani et al. (2023) Study Findings" author: "Ashwin Kishtagari" date: today format: html: theme: journal toc: true code-fold: true fig-width: 8 fig-height: 6 bibliography: references.bib --- ```{r setup, include=FALSE} knitr::opts_chunk$set(echo = FALSE, warning = FALSE, message = FALSE, fig.align = "center") library(tidyverse) library(knitr) library(ggplot2) library(patchwork) library(kableExtra) ``` ## Introduction Myeloproliferative neoplasms (MPNs) are disorders of clonal hematopoiesis that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF). Pulmonary hypertension (PH) has been associated with MPNs and classified by the World Health Organization in group 5 (unclear and/or multifactorial mechanisms). This analysis examines the findings from Montani et al. (2023) published in the American Journal of Respiratory and Critical Care Medicine, which investigated the prevalence, hemodynamic characteristics, etiologies, and prognostic implications of PH in MPNs. ## Study Population ```{r data-prep} # Create dataset from the paper findings mpn_data <- tibble( MPN_Type = c("Polycythemia vera", "Essential thrombocythemia", "Primary myelofibrosis"), Count = c(42, 35, 13), Percentage = c(42/90*100, 35/90*100, 13/90*100) ) # Create PH etiology data ph_etiology <- tibble( MPN_Type = c("PV or ET", "PV or ET", "MF (primary or secondary)", "MF (primary or secondary)"), Etiology = c("CTEPH", "WHO Group 5", "CTEPH", "WHO Group 5"), Percentage = c(64.5, 35.5, 18, 82) ) # Create secondary MF data sec_mf_data <- tibble( PH_Type = c("Group 5 PH", "CTEPH"), Percentage = c(29, 4) ) # Create diagnosis interval data interval_data <- tibble( PH_Type = c("Group 5 PH", "CTEPH"), Interval_Months = c(93, 22) ) ``` The study identified 90 patients with MPNs with precapillary or combined pre-/postcapillary PH from a national PH registry. The distribution of MPN types among these patients is shown below: ```{r mpn-distribution} mpn_data %>% mutate(Percentage = round(Percentage, 1)) %>% kable(col.names = c("MPN Type", "Count", "Percentage (%)"), caption = "Distribution of MPN Types") %>% kable_styling(bootstrap_options = c("striped", "hover")) ``` ```{r mpn-plot} ggplot(mpn_data, aes(x = "", y = Count, fill = MPN_Type)) + geom_bar(stat = "identity", width = 1) + coord_polar("y", start = 0) + theme_minimal() + labs(title = "Distribution of MPN Types in Patients with PH", fill = "MPN Type") + theme(legend.position = "bottom") ``` ## PH Etiology by MPN Type The study found different patterns of PH etiology depending on the MPN type: ```{r etiology-table} ph_etiology %>% kable(col.names = c("MPN Type", "PH Etiology", "Percentage (%)"), caption = "Pulmonary Hypertension Etiology by MPN Type") %>% kable_styling(bootstrap_options = c("striped", "hover")) ``` ```{r etiology-plot} ggplot(ph_etiology, aes(x = MPN_Type, y = Percentage, fill = Etiology)) + geom_bar(stat = "identity", position = "stack") + theme_minimal() + labs(title = "Pulmonary Hypertension Etiology by MPN Type", y = "Percentage (%)", x = "") + theme(legend.position = "bottom") ``` Key findings: - Among patients with PV or ET, CTEPH (Chronic Thromboembolic Pulmonary Hypertension) was the most common etiology (64.5%) - Among patients with MF (primary or secondary), WHO Group 5 PH was the most common etiology (82%) ## Secondary Myelofibrosis and PH Type The study found a significant difference in PH types among patients with secondary MF: ```{r sec-mf-plot} ggplot(sec_mf_data, aes(x = PH_Type, y = Percentage, fill = PH_Type)) + geom_bar(stat = "identity") + theme_minimal() + labs(title = "Percentage of Secondary MF Patients by PH Type", y = "Percentage (%)", x = "") + theme(legend.position = "none") + geom_text(aes(label = paste0(Percentage, "%")), vjust = -0.5) ``` Significantly more patients with secondary MF had Group 5 PH than CTEPH (29% vs. 4%, p\<0.01). ## Time Between MPN and PH Diagnoses ```{r interval-plot} ggplot(interval_data, aes(x = PH_Type, y = Interval_Months, fill = PH_Type)) + geom_bar(stat = "identity") + theme_minimal() + labs(title = "Median Interval Between MPN and PH Diagnoses", y = "Months", x = "") + theme(legend.position = "none") + geom_text(aes(label = paste0(Interval_Months, " months")), vjust = -0.5) ``` Patients with Group 5 PH had a longer interval between MPN and PH diagnoses (median, 93 vs. 22 months; p\<0.01). ## Combined Visualization ```{r combined-plot} # Display combined figures with patchwork (ggplot(ph_etiology, aes(x = MPN_Type, y = Percentage, fill = Etiology)) + geom_bar(stat = "identity", position = "stack") + theme_minimal() + labs(title = "PH Etiology by MPN Type", y = "Percentage (%)", x = "") + theme(legend.position = "bottom")) | (ggplot(sec_mf_data, aes(x = PH_Type, y = Percentage, fill = PH_Type)) + geom_bar(stat = "identity") + theme_minimal() + labs(title = "Secondary MF by PH Type", y = "Percentage (%)", x = "") + theme(legend.position = "none") + geom_text(aes(label = paste0(Percentage, "%")), vjust = -0.5)) / (ggplot(interval_data, aes(x = PH_Type, y = Interval_Months, fill = PH_Type)) + geom_bar(stat = "identity") + theme_minimal() + labs(title = "Time Between MPN and PH Diagnoses", y = "Months", x = "") + theme(legend.position = "none") + geom_text(aes(label = paste0(Interval_Months, " months")), vjust = -0.5)) + plot_annotation(title = 'Key Findings: PH in Myeloproliferative Neoplasms', theme = theme(plot.title = element_text(size = 16, hjust = 0.5))) ``` ## Clinical Implications The study by Montani et al. (2023) suggests two predominant phenotypes of precapillary PH in patients with MPNs: 1. A **thrombotic phenotype** (CTEPH) - more common in PV and ET 2. A **nonthrombotic phenotype** (WHO Group 5) - more common in MF and potentially related to disease progression and extramedullary hematopoiesis The association between Group 5 PH and MF, along with the finding that PH was associated with progression to MF among patients with ET and PV in prior studies, suggests that: - PH screening may be beneficial in patients with MPNs for disease progression surveillance - Clinicians caring for patients with MPNs who experience dyspnea should consider workup for PH ## Limitations and Future Directions Several questions remain unanswered by this study: 1. The prevalence and phenotype of PH meeting the newer criteria (mean pulmonary artery pressure \>20 mm Hg instead of \>25 mm Hg) among patients with MPNs is unclear 2. Echocardiography characteristics were not reported in this study 3. The true prevalence and etiologies of PH among asymptomatic patients with MPNs remain to be elucidated 4. The role of driver and non-driver mutations in PH development needs further investigation ## References Montani D, Thore P, Mignard X, et al. Clinical phenotype and outcomes of pulmonary hypertension associated with myeloproliferative neoplasms: a population-based study. Am J Respir Crit Care Med. 2023;208:600-612. Leiva O, Ren S, Neuberg D, et al. Pulmonary hypertension is associated with poor cardiovascular and hematologic outcomes in patients with myeloproliferative neoplasms and cardiovascular disease. Int J Hematol. 2023;117:90-99. Leiva O, Hobbs G, Ravid K, Libby P. Cardiovascular disease in myeloproliferative neoplasms: JACC: CardioOncology state-of-the-art review. JACC CardioOncol. 2022;4:166-182.