Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Relative Risk Factors for Cardiac Erosion Following Transcatheter Closure of Atrial Septal Defects: A Case–Control Study
- Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle
- Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort
- Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study
- In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target Slug
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Relative Risk Factors for Cardiac Erosion Following Transcatheter Closure of Atrial Septal Defects: A Case–Control Study
Cardiac erosion is a rare but potentially serious complication of transcatheter atrial septal defect closure using the Amplatzer Septal Occluder. The absolute risk of erosion after Amplatzer Septal Occluder implant has been estimated to range from 0.043% to 0.3%, but little is known about specific mechanisms and risk factors for this complication. Therefore, we undertook the current case-control study, in which all erosion cases that have been reported and entered into the St. Jude Medical database were analyzed against an age- and sex-matched control cohort. A total of 125 erosion events were reported and adjudicated between 2002 and 2014, and were diagnosed a median of 14 days after atrial septal defect closure, with 9 deaths. Deficiency of the aortic rim was an almost universal finding in cases, and deficiency of any rim (ie, aortic, superior vena cava, inferior vena cava) was the predominant risk factor for erosion. There were a number of other differences between cases and controls that implicate device oversizing as an additional contributing factor and support the hypothesis that there are potentially modifiable procedure-related factors associated with this complication. The findings of this study, with regard both to limitations in the available data for the largest cohort of erosion cases and to definition of additional or modifying relative risk factors, support the potential utility and incremental value of the prospective ADVANCE ASO Post Market Surveillance Study. Finally, the general inadequacy of recorded echocardiographic data in both cases and controls, which limited the ability of this study to provide deeper insight into risk factors for erosion, highlights the importance of comprehensive evaluation before and during atrial septal defect closure, as also reflected in the protocol for the ADVANCE trial and recently published guidelines. See p 1738.
Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle
A subset of pulmonary arterial hypertension (PAH) patients has a mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene. Despite increased knowledge of the consequences of the BMPR2 mutation on the pulmonary vasculature, only little is known about the effect of a BMPR2 mutation on right ventricular (RV) function and adaptation in PAH patients. In the present study, we provide evidence that PAH patients carrying a BMPR2 mutation have decreased RV function in comparison with PAH patients without the BMPR2 mutation at presentation, despite a similar afterload. Using a translational approach, we could demonstrate that there are no alterations in transforming growth factor β and bone morphogenetic protein signaling in the cardiomyocytes of PAH patients with or without mutation. Furthermore, our data indicate that RV and left ventricular adaptation is not different between BMPR2 mutation carriers and noncarriers. Our results raise the question whether clinical status and time to death or lung transplantation in BMPR2 mutation carriers could be improved by using the RV as a therapeutic target. Furthermore, our results provide rationale for closely monitoring RV function in BMPR2 mutation carriers in PAH referral centers and subsequently timely referral for lung transplantation. Further therapeutic studies targeting the disturbed transforming growth factor β/bone morphogenetic protein pathway will reveal the clinical implications of this disturbed balance in the RV of PAH patients. See p 1747.
Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort
Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli that become organized into vessel walls. Pulmonary endarterectomy (PEA) is the treatment of choice and, in selected patients, is curative, but residual chronic thromboembolic pulmonary hypertension following surgery is common. Its impact on long-term outcome after PEA is poorly understood. We have analyzed the long-term outcome of 880 patients after PEA from the United Kingdom national PEA cohort. These patients underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months after surgery and annually thereafter in specialist pulmonary hypertension centers. If clinically stable and not requiring pulmonary vasodilator therapy, they were discharged after 3 to 5 years of follow-up. The overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension) despite 51% of patients having a mean pulmonary artery pressure of ≥25 mm Hg at the 3- to 6-month review. At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with pulmonary vasodilator therapy initiation at some point during follow-up, and a mean pulmonary artery pressure ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s–1·cm–5 were correlated with worse survival. Our data allow clinicians to stratify patient follow-up after PEA surgery and to identify those in need of close long-term follow-up because of the increased risk of deterioration or death from chronic thromboembolic pulmonary hypertension. See p 1761.
Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study
This prespecified analysis from the Dual Antiplatelet Therapy (DAPT) Study, the largest randomized trial of dual antiplatelet therapy duration to date, provides rigorous data for the effectiveness and safety of dual antiplatelet therapy (thienopyridine plus aspirin) in a large subgroup of patients with diabetes mellitus (DM; 8198 enrolled, 3391 randomly assigned). This important subgroup, frequently seen in clinical practice, is at high risk for recurrent ischemic events after coronary stenting. DAPT Study results demonstrate that, after coronary stenting with either drug-eluting or bare metal stents, in patients with diabetes mellitus who were adherent with and able to tolerate 12 months of thienopyridine plus aspirin without major ischemic or bleeding events, an additional 18 months of thienopyridine plus aspirin (versus placebo plus aspirin) was associated with reduced risk of myocardial infarction (3.5% versus 4.8%, P=0.058). However, this benefit was attenuated in comparison with patients without DM (rate of myocardial infarction, 4.2% in patients with DM versus 2.6% in patients without DM, P<0.001). Bleeding risk with continued thienopyridine was similar among patients with or without DM. Despite the attenuated benefit of myocardial infarction, this study underscores the importance of continuing dual antiplatelet therapy beyond 12 months in eligible patients with DM, who are at greater risk of cardiovascular events than patients without DM, and who experienced worse outcomes from these events. See p 1772.
In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target Slug
Transition of endothelial cells to take on features of smooth muscle cells, a process called endothelial-to-mesenchymal transition, is increasingly appreciated as a mechanism integral to vascular pathobiologies, including pulmonary arterial hypertension. The transformed endothelial cells may contribute to the expanding neointima either directly or by failing to produce inhibitors of smooth muscle cell proliferation. In this report, we relate endothelial-to-mesenchymal transition to reduced expression of the receptor for bone morphogenetic protein (BMPR2) that occurs either related to a mutation or independent of a mutation in patients with pulmonary arterial hypertension. We show that loss of BMPR2 causes an elevation in a chromatin remodeling and scaffolding protein, High Mobility Group AT-hook 1 (HMGA1), that has been implicated in the transition of cancer cells. Elevated HMGA1 leads to an increase in a transcription factor called Slug that upregulates expression of smooth muscle genes such as smooth muscle actin and SM22α. At the same time, impaired structure and reduced expression of endothelial cell junctional proteins, CD-31 (platelet endothelial cell adhesion molecule 1) and CD-144 (VE-cadherin), respectively, lead to morphological changes that promote the smooth muscle cell phenotype. See p 1783.
- © 2016 American Heart Association, Inc.
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