Trends and Outcomes of Pulmonary Arterial Hypertension–Related Hospitalizations in the United States

Anand, Vidhu; Roy, Samit S.; Archer, Stephen L.; Weir, Ε. Kenneth; Garg, Sushil Kumar; Duval, Sue; Thenappan, Thenappan

doi:10.1001/jamacardio.2016.3591

Cited by 76 publications

(82 citation statements)

References 28 publications

(55 reference statements)

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“…Thus, coronary arteries in PAH are remodeled independently of their localization within the heart. Interestingly, when investigating the clinical characteristics of our patients with PAH (Table I in the online-only Data Supplement), we observed that 23% of our patients with PAH received a diagnostic of CAD, which corresponds to what was observed in the study by Anand et al 30 and that close to half of them also exhibited risk factors for developing the disease. Furthermore, when looking at the autopsy reports, an additional 23% of the patients with PAH had CAD and these numbers do not include coronary MVDs.…”

Section: Patients With Pah Exhibit Increased Coronary Wall Thicknesssupporting

confidence: 84%

“…Furthermore, a recent study analyzed trends and outcomes in PAH-related hospitalization in the United States and observed an increase in associated comorbid conditions in patients with PAH between the years 2001 and 2012, such as diabetes mellitus, hypertension, and CAD. 30 During that decade, CAD in patients with PAH increased from 15.6% to 22.3%, in addition to an increase in diseases considered as risk factors for coronary diseases. This concept is not surprising because PAH is now recognized not to be restricted to the lungs.…”

Section: P Ulmonary Arterial Hypertension (Pah) Is a Vascularmentioning

confidence: 99%

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Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension

Meloche

Lampron

Nadeau

et al. 2017

ATVB

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P ulmonary arterial hypertension (PAH) is a vascularremodeling disease (VRD) first described as an obstructive pathology affecting the distal pulmonary arteries. It is characterized by enhanced inflammation, vasoconstriction, and proliferation/apoptosis imbalance within the arterial wall, leading to increased pulmonary vascular resistance and right ventricular (RV) failure and death. 1 The smooth muscle cells (SMCs) within the pulmonary arterial wall exhibit exaggerated proliferation and resistance to apoptosis. Many groups have studied the underlying mechanisms of this "cancer-like" phenotype to find better ways to treat this deadly disease. The similarities in histological features between PAH and other VRDs suggest common pathogenic mechanisms. We and others have described the implication of the receptor of advanced glycation endproducts, 2-4 the oncoprotein kinase Pim-1 3, 5 and the transcription factor nuclear factor of activated T cells 6,7 in promoting proliferation in remodeling processes occurring in both VRD and PAH. In PAH patients' lung vasculature, these molecular actors are, at least in part, regulated by proinflammatory cytokines, alterations in the miR-223/DNA damage/ Poly[ADP-ribose] polymerase 1/miR-204 axis 8-11 and subsequent overexpression of the epigenetic reader bromodomain protein 4 (BRD4). 12 BRD4 functions as a scaffold for transcription factors at promoters and superenhancers, modulating the chromatin landscape and facilitating transcriptional activation of target genes. 13 Interestingly, BRD4 is also implicated in systemic VRD by triggering proinflammatory endothelial © 2017 American Heart Association, Inc. Objective-Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance in other vascular remodeling diseases, such as coronary artery disease (CAD). Intriguingly, CAD is 4× more prevalent in PAH compared with the global population, suggesting a link between these 2 diseases. Both PAH and CAD are associated with sustained inflammation and smooth muscle cell proliferation/ apoptosis imbalance and we demonstrated in PAH that this phenotype is, in part, because of the miR-223/DNA damage/ Poly[ADP-ribose] polymerase 1/miR-204 axis activation and subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 is also a trigger for calcification and remodeling processes, both of which are important in CAD. Thus, we hypothesize that BRD4 activation in PAH influences the development of CAD. Approach and Results-PAH was associated with significant remodeling of the coronary arteries in both human and experimental models of the disease. As observed in PAH distal pulmonary arteries, coronary arteries of patients with PAH also exhibited increased DNA damage, inflammation, and BRD4 overexpression. In vitro, using human coronary artery smooth muscle cells from PAH, CAD and non-PAH-non-CAD patients, we showed that both PAH and CAD smooth muscle cells exhibited increased proliferation and suppres...

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Section: Patients With Pah Exhibit Increased Coronary Wall Thicknesssupporting

confidence: 84%

Section: P Ulmonary Arterial Hypertension (Pah) Is a Vascularmentioning

confidence: 99%

Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension

Meloche

Lampron

Nadeau

et al. 2017

ATVB

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“…There was a trend towards admission of patients greater than 65 years of age that is in line with all recent studies that found a shift in diagnosis of PH to an older age [13,[18][19][20]. Most patients continued to be women in both 2000 and 2013.…”

Section: Age Characteristics and Payer Statussupporting

confidence: 87%

“…This was in spite of the fact that a recent study reported a decline in the number of hospitalizations associated with PAH (Group 1) alone from 2001 through 2012 [13]. This would indicate that the rise in the number of hospitalizations due to PH can actually be attributed to an increase in admissions due to secondary causes of PH i.e.…”

Section: Discharges and Length Of Staymentioning

confidence: 81%

“…right heart catheterization become available in all healthcare centers the increase in the number of inpatient diagnostic tests could also contribute to the increased length of stay in these patients. Another recent study noted an increased frequency of cardiogenic shock, cardiac dysrhythmias, acute respiratory failure and renal failure in patients with PH [13], which in turn may lead to an increased length of stay.…”

Section: Discharges and Length Of Staymentioning

confidence: 99%

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Nationwide Trends in Inpatient Admissions of Pulmonary Hypertension in the United States from 2000 to 2013

Sikachi

Sahni

Mehta

et al. 2017

Advances in Respiratory Medicine

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Introduction: Pulmonary Hypertension (PH) is a disorder of the pulmonary vasculature with high mortality and bears a large economic burden on the healthcare system. We conducted a review of the largest inpatient database in the United States and analyzed the trends in hospitalizations due to PH from the turn of the century (2000) to 2013 to evaluate the rate of hospitalizations and determine the cost and mortality associated with PH. Conclusion:The number of inpatient discharges related to PH has increased even though the number of inpatient discharges with PAH has been reported to be lower in literature. The mean length of stay has also shown a mild increase. This increase is associated with a significant increase in the mean and aggregate cost. These inpatient costs associated with PH contribute significantly to the total healthcare burden. Further research on cost-effective evaluation and management of PH is required.

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Beast of Pulmonary Arterial Hypertension Burden

Mathai

McLaughlin

2016

JAMA Cardiol

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Pulmonary arterial hypertension (PAH) is an incurable, progressive disease of the pulmonary vasculature that leads to right heart failure and, ultimately, death. Significant advances in our understanding of the pathogenesis and pathobiology of the disease have led to the development of novel therapies that, in turn, have offered improvement in outcomes. However, mortality remains unacceptably high for patients with this disease. In addition, PAH is associated with significant morbidity. Complicated medication delivery and adverse effect profiles, disease progression necessitating hospitalization, and effects on social and emotional functioning all contribute to a high burden of disease. However, while hospitalizations for exacerbations of disease are common and appear to be associated with long-term outcomes in PAH, 1 little is known about the characteristics, effect on short-term outcomes, and costs associated with these hospitalizations.In this issue of JAMA Cardiology, Anand and colleagues 2 make an important first step to answer some of these questions. Using the National Inpatient Sample database, a Healthcare Utilization Project database sponsored by the Agency for Healthcare Research and Quality, the authors examine trends in hospitalization rates for patients with PAH between 2001 and 2012 and note some surprising and expected findings. While the admission rates for PAH decreased by 58% over the study period, the overall cost per hospitalization increased by more than 2-fold, even when adjusting for inflation. The authors speculate that rise in costs is related to the increased acuity of illness in those patients with PAH who are hospitalized; as outpatient care has improved, patients admitted to the hospital are generally more sick. This assertion is supported by the reported increased prevalence of significant comorbidities, such as acute kidney injury (more than 3-fold increase) and acute respiratory failure (more than 4-fold increase), that would potentially increase costs among hospitalized patients with PAH. While this is a reasonable conclusion, other factors that were not considered may also contribute to increased costs. Until November 2001, the only available therapy for PAH was intravenous epoprostenol, a therapy that requires continuous infusion through a centrally placed catheter and necessitates expert medical care, including hospitalization, to initiate. Despite being the only therapy that has demonstrated a survival benefit in a clinical trial, these aforementioned factors likely contribute to its underutilization in the United States. 3 By 2012, 7 additional therapies, including 3 oral agents and 2 inhaled agents, were available. While this represents an advance in the therapeutic armamentarium for PAH, the cost of these agents and the increasing use of combination therapy is considerable, both in the inpatient and outpatient settings. 4

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Trends and Outcomes of Pulmonary Arterial Hypertension–Related Hospitalizations in the United States

Cited by 76 publications

References 28 publications

Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension

Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension

Nationwide Trends in Inpatient Admissions of Pulmonary Hypertension in the United States from 2000 to 2013

Beast of Pulmonary Arterial Hypertension Burden

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