Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis.

BACKGROUND AND PURPOSE: Group III pulmonary hypertension (PH) is a highly lethal and widespread lung disorder that is a common complication in idiopathic pulmonary fibrosis (IPF) where it is considered to be the single most significant predictor of mortality. While increased levels of hyaluronan have been observed in IPF patients, hyaluronan-mediated vascular remodelling and the hyaluronan-mediated mechanisms promoting PH associated with IPF are not fully understood. EXPERIMENTAL APPROACH: Explanted lung tissue from patients with IPF with and without a diagnosis of PH was used to identify increased levels of hyaluronan. In addition, an experimental model of lung fibrosis and PH was used to test the capacity of 4-methylumbeliferone (4MU), a hyaluronan synthase inhibitor to attenuate PH. Human pulmonary artery smooth muscle cells (PASMC) were used to identify the hyaluronan-specific mechanisms that lead to the development of PH associated with lung fibrosis. KEY RESULTS: In patients with IPF and PH, increased levels of hyaluronan and expression of hyaluronan synthase genes are present. Interestingly, we also report increased levels of hyaluronidases in patients with IPF and IPF with PH. Remarkably, our data also show that 4MU is able to inhibit PH in our model either prophylactically or therapeutically, without affecting fibrosis. Studies to determine the hyaluronan-specific mechanisms revealed that hyaluronan fragments result in increased PASMC stiffness and proliferation but reduced cell motility in a RhoA-dependent manner. CONCLUSIONS AND IMPLICATIONS: Taken together, our results show evidence of a unique mechanism contributing to PH in the context of lung fibrosis.

Improved Outcomes With the Evolution of a Neoadjuvant Chemotherapy Approach to Right Heart Sarcoma.

BACKGROUND: Right-side heart sarcomas tend to be bulky, infiltrative, and difficult to treat. We have previously examined our outcomes with right heart sarcomas. Surgical resection with R0 margins showed better survival than positive margins but in only one third of cases could R0 status be achieved. The hypothesis for this study was that preoperative neoadjuvant chemotherapy would shrink the tumor margins and allow an increase in R0 resection, and hence, better survival. METHODS: Review of our cardiac tumor database from 1990 to 2015 yielded 133 primary cardiac sarcoma cases. Of these, we identified 44 patients with primary right-side heart sarcomas. Prospective database and retrospective data collection and clinical outcomes were evaluated for all 44 patients. Primary outcomes included 30-day mortality and morbidity and long-term survival. We used univariate and multivariate analyses to identify independent predictors of overall survival. RESULTS: There were 27 male and 17 female patients with a mean age of 41 ± 12.7 years (range, 15 to 67). Seventy-three percent of the patients (32 of 44) received neoadjuvant chemotherapy. The most common tumor histology was angiosarcoma in 30 of 44 (68%). Thirty-day mortality was 4.5%, and statistically similar between the two groups. The median survival of patients who had R0 resection was 53.5 months compared with 9.5 months for R1. Neoadjuvant chemotherapy led to a doubling of survival (20 versus 9.5 months). CONCLUSIONS: Neoadjuvant chemotherapy followed by radical surgery is a safe and effective strategy in patients with primary right-side heart sarcoma. This multimodality treatment enhances resectability (R0 resection) that translates into improved patient survival.

Case Report: Cardiac Tumor Resection And Repair With Porcine Xenograft.

Primary cardiac sarcomas are rare and carry a grave prognosis. Improved survival requires a complete margin negative resection of the tumor. These surgical resections are often large and complex, requiring extensive reconstructive procedures. The appropriate material for cardiac reconstruction is not known. We have used glutaraldehyde-fixed bovine pericardium in our early series but have recently employed the MatriStem(®) Surgical Matrix PSMX membrane (ACell(®), Inc.; Columbia, MD), a unique proprietary urinary bladder matrix derived from porcine urinary bladder with the potential for viability and tissue ingrowth. In our study of six patients at this institution, all six underwent successful surgical resection and repair with the MatriStem acellular porcine urinary bladder membrane (ACell). The postoperative course was uncomplicated in all patients, and they are still alive at this time. An aggressive surgical approach to cardiac tumors can possibly lead to complete resection but often requires reconstruction of the cardiac tissue with a membrane. We were able to achieve acceptable results in our cardiac reconstruction by using the ACell extracellular matrix to reconstruct the defect following tumor resection. Longer-term follow-up in these patients, including imaging studies, will be necessary to demonstrate the durability and integrity of the reconstruction.

Use of three-dimensional models to assist in the resection of malignant cardiac tumors.

The application of three-dimensional (3D) printing enables the creation of material objects from digital images by depositing layers of plastic material into 3D structures and can be used for training, education, and surgical planning. We report two patients with large complex cardiac tumors where 3D technology was utilized to analyze the tumor size, location, and extension more precisely, allowing better preoperative planning and decision making.

Total Artificial Heart Implantation after Excision of Right Ventricular Angiosarcoma.

Primary cardiac sarcomas, although rare, are aggressive and lethal, requiring thorough surgical resection and adjuvant chemotherapy for the best possible outcome. We report the case of a 32-year-old woman who underwent total artificial heart implantation for right-sided heart failure caused by right ventricular angiosarcoma. For the first several weeks in intensive care, the patient recovered uneventfully. However, a postoperative liver biopsy indicated hepatocellular injury consistent with preoperative chemotherapy. She developed continuing liver failure, from which she died despite good cardiac function.

Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. The development of pulmonary hypertension (PH) is considered the single most significant predictor of mortality in patients with chronic lung diseases. The processes that govern the progression and development of fibroproliferative and vascular lesions in IPF are not fully understood. Using human lung explant samples from patients with IPF with or without a diagnosis of PH as well as normal control tissue, we report reduced BMPR2 expression in patients with IPF or IPF+PH. These changes were consistent with dampened P-SMAD 1/5/8 and elevated P-SMAD 2/3, demonstrating reduced BMPR2 signaling and elevated TGF-ß activity in IPF. In the bleomycin (BLM) model of lung fibrosis and PH, we also report decreased BMPR2 expression compared with control animals that correlated with vascular remodeling and PH. We show that genetic abrogation or pharmacological inhibition of interleukin-6 leads to diminished markers of fibrosis and PH consistent with elevated levels of BMPR2 and reduced levels of a collection of microRNAs (miRs) that are able to degrade BMPR2. We also demonstrate that isolated bone marrow-derived macrophages from BLM-exposed mice show reduced BMPR2 levels upon exposure with IL6 or the IL6+IL6R complex that are consistent with immunohistochemistry showing reduced BMPR2 in CD206 expressing macrophages from lung sections from IPF and IPF+PH patients. In conclusion, our data suggest that depletion of BMPR2 mediated by a collection of miRs induced by IL6 and subsequent STAT3 phosphorylation as a novel mechanism participating to fibroproliferative and vascular injuries in IPF.

Minimally Invasive Repair of Left Ventricular Pseudoaneurysm after Transapical Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement is becoming a routine procedure to treat severe symptomatic aortic stenosis. At most transcatheter aortic valve replacement centers, transapical access is a frequent alternative for use in patients whose ileofemoral access is inadequate. Transapical access is increasingly applied to a variety of other structural heart and aortic procedures as well. There is a caveat, however. When performed in elderly patients with friable myocardium, transapical access is associated with such serious sequelae as bleeding and left ventricular apical pseudoaneurysmal formation. Here, we describe the case of a 70-year-old woman who developed a left ventricular apical pseudoaneurysm 3 weeks after transapical transcatheter aortic valve replacement. Our successful repair took a minimally invasive left lateral approach that involved peripheral cardiopulmonary bypass cannulation, Foley catheter occlusion and primary defect closure, and BioGlue reinforcement.

Cardiac Papillary Fibroelastoma: Single-Institution Experience with 14 Surgical Patients.

In general, treatment for symptomatic and asymptomatic cardiac papillary fibroelastoma is surgical resection-particularly of left-sided lesions, because of the risk of systemic embolization. However, few institutions have enough experience with these tumors to validate this approach. We present our institutional experience with papillary fibroelastoma and discuss our current approach. We searched our institution's cardiac tumor database, identified all patients diagnosed with cardiac papillary fibroelastoma from 1992 through 2014, and recorded the clinical and pathologic characteristics of each case. We found 14 patients (mean age, 60.5 ± 12.3 yr) who had 18 lesions. Eleven patients (79%) were symptomatic; however, we could not always definitively associate their symptoms with a cardiac tumor. Most lesions were solitary and ≤1.5 cm in diameter; half involved the left side of the heart. All 18 lesions were surgically excised. There were no operative or 30-day deaths, and no patient needed valve replacement postoperatively. There was one late death; at one year, another 3 patients were lost to follow-up, and the others were alive without tumor recurrence. Because of the embolic risk inherent to intracardiac masses and our relatively good postoperative outcomes, we recommend the surgical resection of all left-sided papillary fibroelastomas in surgical candidates, and we discuss with patients the advisability of resecting right-sided lesions.

Right Atrial Tumor Resection and Reconstruction with Use of an Acellular Porcine Bladder Membrane.

Malignant cardiac tumors typically have a grave prognosis; their resection with negative margins is optimal. We present the case of a 21-year-old woman in whom we surgically resected a primary cardiac sarcoma and reconstructed the right atrium with use of a porcine urinary bladder membrane-the MatriStem(®) Surgical Matrix PSMX. The patient recovered uneventfully. Six months postoperatively, the right atrial wall had retained its integrity. In addition to our patient's case, we discuss the benefits of using the MatriStem membrane in cardiac reconstruction.

Cannulation Strategies and Pitfalls in Minimally Invasive Cardiac Surgery.

For any given cardiac surgery, there are two invasive components: the surgical approach and the cardiopulmonary bypass circuit. The standard approach for cardiac surgery is the median sternotomy, which offers unrestricted access to the thoracic organs-the heart, lung, and major vessels. However, it carries a long list of potential complications such as wound infection, brachial plexus palsies, respiratory dysfunction, and an unpleasant-looking scar. The cardiopulmonary bypass component also carries potential complications such as end-organ dysfunction, coagulopathy, hemodilution, bleeding, and blood transfusion requirement. Furthermore, the aortic manipulation during cannulation and cross clamping increases the risk of dissection, arterial embolization, and stroke. Minimally invasive cardiac surgery is an iconic event in the history of cardiothoracic medicine and has become a widely adapted approach as it minimizes many of the inconvenient side effects associated with the median sternotomy and bypass circuit placement. This type of surgery requires the use of novel perfusion strategies, especially in patients who hold the highest potential for postoperative morbidity. Cannulation techniques are a fundamental element in minimally invasive cardiac surgery, and there are numerous cannulation procedures for each type of minimally invasive operation. In this review, we will highlight the strategies and pitfalls associated with a minimally invasive cannulation.

Case Report: Chronic Recurrent Unilateral Pulmonary Infection: Result of Congenital Unilateral Agenesis of Pulmonary Artery.

Unilateral agenesis of the pulmonary artery (UAPA) is a rare congenital anomaly. This report describes a 52-year-old female who gave a long history of chronic, recurrent, left-sided pulmonary infections related to UAPA. For many years, she was managed medically but the infection continued to recur. She eventually underwent left pneumonectomy and made a good recovery.

Case Report: A Rare Case of Left Atrial Hemangioma: Surgical Resection and Reconstruction.

Hemangioma of the heart presenting as a primary cardiac tumor is extremely rare, accounting for approximately 2% of all primary resected heart tumors. Only a few cases of cardiac hemangiomas have been reported to arise from the left atrial wall. In this case report we share our experience in the diagnosis and surgical resection of a large (9 × 7 cm) left atrial hemangioma and reconstruction of the heart using porcine urinary bladder membrane.

Case Report: Delayed Type A Aortic Dissection Following Complete Debranching of the Aortic Arch and Stent Graft Placement.

Treatment options for aortic arch disease in high-risk patients includes supra-aortic debranching and thoracic endovascular aortic repair (TEVAR). Acute ascending aortic dissection is a concerning complication of this approach and has been reported to occur in a retrograde fashion. We report a case of a 60-year-old gentleman who had undergone thoracic endovascular aortic repair with debranching and presented 31 months later with acute isolated ascending aortic dissection. The patient underwent successful total replacement of the ascending aorta with a 30-mm gelwave Valsalva(™) graft using cardiopulmonary bypass.

Development of a Severe Mitral Valve Stenosis Secondary to the Treatment of Mitral Regurgitation with a Single MitraClip.

We report a patient with class III heart failure symptoms due to mitral regurgitation (MR) subsequent to nonischemic cardiomyopathy. The patient underwent percutaneous transcatheter mitral valve repair using a single MitraClip, which reduced the MR; however it created mild-to-moderate mitral stenosis, which progressed to severe mitral stenosis. Subsequently the patient underwent mitral valve replacement surgery.

Open Removal of Penetrating Inferior Vena Cava Filter with Repair of Secondary Aortic Dissection: Case Report.

Inferior vena cava (IVC) filters are indicated for the management of venous thromboembolism in patients who are not candidates for anticoagulation, have a contraindication to anticoagulation or who have recurrent thromboembolism despite anticoagulation. As IVC filter usage has increased, there has been a corresponding increase in presentation of filter-related complications. Filter leg penetration is commonly seen although is infrequently associated with complications. But in a small percentage of patients, penetration can result in damage to adjacent structures: duodenum, lumbar spine, and rarely the aorta. We report the case of a 77-year-old man with a chronic aortoiliac dissection secondary to aortic IVC filter penetration who underwent open filter retrieval and aortic repair.

Surgical Treatment of Primary Cardiac Sarcomas: Review of a Single-Institution Experience.

BACKGROUND: Primary cardiac sarcomas are rare, aggressive, and usually lethal. Surgical management protocols are not defined because of the lack of extensive experience in treating these patients. In this study, we reviewed our outcomes with primary cardiac sarcoma, and we make recommendations regarding management. METHODS: Review of the Houston Methodist Hospital cardiac tumor database from 1990 to 2015 (25 years) yielded 131 primary cardiac evaluations of possible cardiac sarcoma. From these we identified 95 patients who underwent surgical excision. A computer search of cardiac sarcomas yielded 131 tumors that were coded as primary cardiac sarcoma or possible primary cardiac sarcoma. Retrospective data collection and clinical outcomes were evaluated for all 95 patients. Medical records and follow-up material were requested for all patients through clinic visits and contacting the physician of the patient, the hospital record department, and the cardiac tumor board after previous approval. The procedures were performed using an institutional review board-approved cardiac tumor protocol, and the patients gave full consent. RESULTS: All 95 patients were diagnosed as having primary cardiac sarcoma by histologic appearance. Age ranged from 15 to 84 years at the time of presentation (mean, 44 years). Male patients made up 57% of the sample. The most common site for the cardiac sarcoma was the right atrium (37 patients) followed by the left atrium (31 patients). Postoperative 1-year mortality was 35% (33 patients). The most common tumor histologic type was angiosarcoma (40%) followed by spindle cell sarcoma (11%). CONCLUSIONS: Primary cardiac sarcoma is a rare but lethal disease. Surgical intervention is associated with acceptable surgical mortality in this high-risk group of patients.

Value of C-Arm Cone Beam Computed Tomography Image Fusion in Maximizing the Versatility of Endovascular Robotics.

BACKGROUND: To report our initial experience and highlight the value of using intraoperative C-arm cone beam computed tomography (CT; DynaCT(®)) image fusion guidance along with steerable robotic endovascular catheter navigation to optimize vessel cannulation. METHODS: Between May 2013 and January 2015, all patients who underwent endovascular procedures using DynaCT image fusion technique along with Hansen Magellan vascular robotic catheter were included in this study. As a part of preoperative planning, relevant vessel landmarks were electronically marked in contrast-enhanced multi-slice computed tomography images and stored. At the beginning of procedure, an intraoperative noncontrast C-arm cone beam CT (syngo DynaCT(®), Siemens Medical Solutions USA Inc.) was acquired in the hybrid suite. Preoperative images were then coregistered to intraoperative DynaCT images using aortic wall calcifications and bone landmarks. Stored landmarks were then overlaid on 2-dimensional (2D) live fluoroscopic images as virtual markers that are updated in real-time with C-arm, table movements and image zoom. Vascular access and robotic catheter (Magellan(®), Hansen Medical) was setup per standard. Vessel cannulation was performed based on electronic virtual markers on live fluoroscopy using robotic catheter. The impact of 3-dimensional (3D) image fusion guidance on robotic vessel cannulation was evaluated retrospectively, by assessing quantitative parameters like number of angiograms acquired before vessel cannulation and qualitative parameters like accuracy of vessel ostium and centerline markers. RESULTS: All 17 vessels were cannulated successfully in 14 patients' attempted using robotic catheter and image fusion guidance. Median vessel diameter at origin was 5.4 mm (range, 2.3-13 mm), whereas 12 of 17 (70.6%) vessels had either calcified and/or stenosed origin from parent vessel. Nine of 17 vessels (52.9 %) were cannulated without any contrast injection. Median number of angiograms required before cannulation was 0 (range, 0-2). On qualitative assessment, 14 of 15 vessels (93.3%) had grade = 1 accuracy (guidewire inside virtual ostial marker). Fourteen of 14 vessels had grade = 1 accuracy (virtual centerlines that matched with the actual vessel trajectory during cannulation). CONCLUSIONS: In this small series, the experience of using DynaCT image fusion guidance together with a steerable endovascular robotic catheter indicates that such image fusion strategies can enhance intraoperative 2D fluoroscopy by bringing preoperative 3D information about vascular stenosis and/or calcification, angulation, and take off from main vessel thereby facilitating ultimate vessel cannulation.

Transcatheter Treatment of Apicoaortic Conduit Dysfunction.

We report a 77-year-old male patient with a history of aortic valve bypass with an apicoaortic conduit 11 years ago for severe aortic stenosis, presenting with acute decompensated congestive heart failure. Severe conduit valve regurgitation and was successfully treated with transcatheter aortic valve replacement (TAVR) of the native aortic valve using a self-expanding bioprosthesis followed by transcatheter closure of the apicoaortic conduit.

Left Ventricular Assist Device Implantation After Intracardiac Parachute Device Removal.

Left ventricular assist device implantation is a proven and efficient modality for the treatment of end-stage heart failure. Left ventricular assist device versatility as a bridge to heart transplantation or destination therapy has led to improved patient outcomes with a concomitant rise in its overall use. Other less invasive treatment modalities are being developed to improve heart function and morbidity and mortality for the heart failure population. Percutaneous ventricular restoration is a new investigational therapy that deploys an intracardiac parachute to wall off damaged myocardium in patients with dilated left ventricles and ischemic heart failure. Clinical trials are under way to test the efficacy of percutaneous ventricular restoration using the parachute device. This review describes our encounter with the parachute device, its explantation due to refractory heart failure, and surgical replacement with a left ventricular assist device.

Extracellular matrix scaffold as a tubular graft for ascending aorta aneurysm repair.

BACKGROUND: Although extracellular xenograft repair has produced encouraging results when applied to cardiac, valvular, and specific aortic defects, its employment as a tube graft to replace the ascending aorta has not been reported. We describe a patient who underwent resection and replacement of an infected ascending aortic graft with an extracellular matrix conduit. The patient did well, but 14 months later developed a pseudoaneurysm from the staple line used to construct the extracellular matrix conduit. METHODS: The patient underwent a repeat sternotomy and removal of the graft. Because of the increased risk of graft failure, a homograft was felt to be more appropriate in this setting. Ultimately, we were unable to implant the homograft because it was too small for the aortic root; therefore we decided to construct a tubular graft from Cormatrix extracellular matrix (CorMatrix, Roswell, GA, USA). Fourteen months later, he presented with shortness of breath. Computed tomography scan revealed a 3.5 cm pseudoaneurysm of the ascending aorta. It appeared as if there was a disruption of the staple line in the extra cellular matrix graft. The plan was to replace it with a Dacron graft. RESULTS: The Cormatrix graft material was removed and sent for culture and histological analysis. A 28-mm Gel weave graft (Terumo Cardiovascular Systems, Ann Arbor, MI, USA) was implanted. The patient tolerated the procedure well with good hemodynamics. CONCLUSIONS: Our experience suggests that the superior strength, handling characteristics, and resistance to infection make extra cellular matrix scaffold a possible alternative conduit to cryopreserved homografts. Applicability as an aortic conduit merits further investigation to better understand behavior of extra cellular matrix in this situation.