Background: Development of aortic regurgitation (AR) following left ventricular assist device (LVAD) implantation is common, and it is associated with a poor prognosis. Transcatheter aortic valve replacement (TAVR) has become a mainstay therapy for patients with severe aortic stenosis, with an off-label use for severe AR. The aim of this study was to assess the feasibility and durability of TAVR in LVAD patients with significant AR. Methods: We evaluated all LVAD patients within our database that underwent TAVR for AR. Clinical and echocardiographic data were collected before and after TAVR procedure. Aortic regurgitant fraction (RF) was calculated using outflow graft Doppler echocardiography. Results: Seven patients underwent nine attempted TAVR procedures. Median age was 69 (IQR 63–73) and 43% were female. Median time from LVAD to TAVR was 23 (IQR 17–52) months. One procedure was aborted due to vascular complications, and one patient underwent two separate procedures 22 months apart. Five patients (71%) survived over median follow-up of 9 (IQR 6–23) months. Two patients died of paravalvular complications following device deployment. Procedural success was achieved in 67% of attempts, with significant improvement in RF from 44.8% (IQR 37.6–63.6) pre-procedurally to 28.1% (IQR 0.30–29.6) at six-month follow-up. Qualitatively, mild or moderate paravalvular leak was noted on all surviving patients at one- and six-month follow-up. There was significant improvement in right ventricular function at 6-month follow-up. Conclusion: TAVR is a reasonable option for treating LVAD-induced AR. Longer follow-up and larger cohorts are needed to assess the durability and long-term efficacy of this procedure. Abbreviations: AR: Aortic regurgitation; AV: Aortic valve; LV: Left ventricle; LVAD: Left ventricular assist device; LVIDd: Left ventricular internal dimension at end-diastole; LVIDs: Left ventricular internal dimension at end-systole; PAPi: Pulmonary artery pulsatility index; RA: Right atrial; RF: Regurgitant fraction; RV: Right ventricle; RVEDA: Right ventricular end-diastolic area; RVFAC: Right ventricular fractional area change; RVSP: Right ventricular systolic pressure; TAPSE: tricuspid annular plane systolic excursion; TAVR: Transcatheter aortic valve replacement; TV: Tricuspid valve
Bronchial arteriovenous malformation is a rare disease in which there is an abnormal communication between a bronchial artery and pulmonary artery or vein. We present a case of a 73-year-old woman who was referred for further evaluation and management of a right middle lobe endobronchial mass. After biopsy of the lesion, there was significant bleeding that required urgent right middle lobectomy. A bronchial artery arteriovenous malformation was identified during the surgery.
Objective: Structural alterations of cardiac extracellular matrix occur as a result of pathological processes in the heart, e.g. dilated cardiomyopathy or myocardial infarction. Matrix metalloproteinases (MMPs) are proteolytic enzymes which play a pivotal role in stress induced matrix remodeling. FOXO transcription factors are important stress-activated regulators of cell cycle and size. Therefore, we hypothesized that FOXO3a, a member of the FOXO family known to be expressed in myocardium, modulates the expression of MMPs. Methods: Cardiac myocytes and fibroblasts were transduced with adenoviral vectors encoding either wild-type FOXO3a (WT-FOXO3a), constitutive-active FOXO3a (TM-FOXO3a) or GFP as control. Effects on potential target genes were assessed by QRT-PCR, Western blot/IHC, specific Collagenase assay, CHIP or luciferase promoter assay. Effects of viral myocarditis were studied in WT and FOXO3a-/- mice. Results: Cardiac myocytes and fibroblasts transduced with FOXO3a did not show differences in MMP1, -2, -3, -9 as well as TIMP 1,-2,-4 gene or protein expression when compared with control vector. However, WT-FOXO3a or TM-FOXO3a gene transfer dose-dependently upregulated MMP13 mRNA expression (3.5 ± 1.2 and 22.0 ± 11.0 fold; p < 0.001, WT and TM-FOXO3a vs. GFP, respectively). Furthermore, MMP13 protein levels were also significantly upregulated under these conditions (p < 0.01). Moreover, FOXO3a transduction led to significantly increased Collagenase activity (p < 0.01). Accordingly, FOXO3a-/- mice showed diminished MMP13 mRNA and protein expression. CHIP and luciferase promoter assays revealed binding of FOXO3a to the MMP13 promoter and its transcriptional activation. Finally, viral myocarditis led to FOXO3a activation associated with increased MMP13 mRNA expression that was significantly diminished in FOXO3a-/- mice which demonstrated increased Collagen 1 and 3 protein expression in IHC (p < 0.05). Conclusion: In conclusion our results implicate FOXO3a directly in the regulation of MMP13 expression. FOXO3a might play an important role in controlling extracellular matrix remodeling processes under cardiovascular stress and injury such as inflammation. Thus, targeting FOXO3a might have therapeutic potential.
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