Israel M. Barbash

Real-time MRI-guided right heart catheterization in adults using passive catheters

AIMSnReal-time MRI creates images with superb tissue contrast that may enable radiation-free catheterization. Simple procedures are the first step towards novel interventional procedures. We aim to perform comprehensive transfemoral diagnostic right heart catheterization in an unselected cohort of patients entirely using MRI guidance.nnnMETHODS AND RESULTSnWe performed X-ray and MRI-guided transfemoral right heart catheterization in consecutive patients undergoing clinical cardiac catheterization. We sampled both cavae and both pulmonary arteries. We compared success rate, time to perform key steps, and catheter visibility among X-ray and MRI procedures using air-filled or gadolinium-filled balloon-tipped catheters. Sixteen subjects (four with shunt, nine with coronary artery disease, three with other) underwent paired X-ray and MRI catheterization. Complete guidewire-free catheterization was possible in 15 of 16 under both. MRI using gadolinium-filled balloons was at least as successful as X-ray in all procedure steps, more successful than MRI using air-filled balloons, and better than both in entering the left pulmonary artery. Total catheterization time and individual procedure steps required approximately the same amount of time irrespective of image guidance modality. Catheter conspicuity was best under X-ray and next-best using gadolinium-filled MRI balloons.nnnCONCLUSIONnIn this early experience, comprehensive transfemoral right heart catheterization appears feasible using only MRI for imaging guidance. Gadolinium-filled balloon catheters were more conspicuous than air-filled ones. Further workflow and device enhancement are necessary for clinical adoption.

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Adaptive noise cancellation to suppress electrocardiography artifacts during real-time interventional MRI.

To develop a system for artifact suppression in electrocardiogram (ECG) recordings obtained during interventional real‐time magnetic resonance imaging (MRI).

Closed-Chest Transthoracic Magnetic Resonance Imaging-Guided Ventricular Septal Defect Closure in Swine

OBJECTIVESnThe aim of this study was to close ventricular septal defects (VSDs) directly through the chest wall using magnetic resonance imaging (MRI) guidance, without cardiopulmonary bypass, sternotomy, or radiation exposure.nnnBACKGROUNDnSurgical, percutaneous, and hybrid management of VSD each have limitations and known morbidity.nnnMETHODSnPercutaneous muscular VSDs were created in 10 naive Yorkshire swine using a transjugular laser catheter. Under real-time MRI guidance, a direct transthoracic vascular access sheath was introduced through the chest into the heart along a trajectory suitable for VSD access and closure. Through this transthoracic sheath, muscular VSDs were occluded using a commercial nitinol device. Finally, the right ventricular free wall was closed using a commercial collagen plug intended for arterial closure.nnnRESULTSnAnterior, posterior, and mid-muscular VSDs (6.8 ± 1.8 mm) were created. VSDs were closed successfully in all animals. The transthoracic access sheath was displaced in 2, both fatal. Thereafter, we tested an intracameral retention sheath to prevent this complication. Right ventricular access ports were closed successfully in all, and after as many as 30 days, healed successfully.nnnCONCLUSIONSnReal-time MRI guidance allowed closed-chest transthoracic perventricular muscular VSD closure in a clinically meaningful animal model. Once applied to patients, this approach may avoid traditional surgical, percutaneous, or open-chest transcatheter (hybrid) risks.

Direct Percutaneous Left Ventricular Access and Port Closure: Pre-Clinical Feasibility

OBJECTIVESnThis study sought to evaluate feasibility of nonsurgical transthoracic catheter-based left ventricular (LV) access and closure.nnnBACKGROUNDnImplanting large devices, such as mitral or aortic valve prostheses, into the heart requires surgical exposure and repair. Reliable percutaneous direct transthoracic LV access and closure would allow new nonsurgical therapeutic procedures.nnnMETHODSnPercutaneous direct LV access was performed in 19 swine using real-time magnetic resonance imaging (MRI) and an active MRI needle antenna to deliver an 18-F introducer sheath. The LV access ports were closed percutaneously using a commercial ventricular septal defect occluder and an active MRI delivery cable for enhanced visibility. We used permissive pericardial tamponade (temporary fluid instillation to separate the 2 pericardial layers) to avoid pericardial entrapment by the epicardial disk. Techniques were developed in 8 animals, and 11 more were followed up to 3 months by MRI and histopathology.nnnRESULTSnImaging guidance allowed 18-F sheath access and closure with appropriate positioning of the occluder inside the transmyocardial tunnel. Of the survival cohort, immediate hemostasis was achieved in 8 of 11 patients. Failure modes included pericardial entrapment by the epicardial occluder disk (n = 2) and a true-apex entry site that prevented hemostatic apposition of the endocardial disk (n = 1). Reactive pericardial effusion (192 ± 118 ml) accumulated 5 ± 1 days after the procedure, requiring 1-time drainage. At 3 months, LV function was preserved, and the device was endothelialized.nnnCONCLUSIONSnDirect percutaneous LV access and closure is feasible using real-time MRI. A commercial occluder achieved hemostasis without evident deleterious effects on the LV. Having established the concept, further clinical development of this approach appears realistic.

MRI-Guided Vascular Access with an Active Visualization Needle

To develop an approach to vascular access under magnetic resonance imaging (MRI), as a component of comprehensive MRI‐guided cardiovascular catheterization and intervention.

Transthoracic delivery of large devices into the left ventricle through the right ventricle and interventricular septum: preclinical feasibility

BackgroundWe aim to deliver large appliances into the left ventricle through the right ventricle and across the interventricular septum. This transthoracic access route exploits immediate recoil of the septum, and lower transmyocardial pressure gradient across the right versus left ventricular free wall. The route may enhance safety and allow subxiphoid rather than intercostal traversal.MethodsThe entire procedure was performed under real-time CMR guidance. An “active” CMR needle crossed the chest, right ventricular free wall, and then the interventricular septum to deliver a guidewire then used to deliver an 18Fr introducer. Afterwards, the right ventricular free wall was closed with a nitinol occluder. Immediate closure and late healing of the unrepaired septum and free wall were assessed by oximetry, angiography, CMR, and necropsy up to four weeks afterwards.ResultsThe procedure was successful in 9 of 11 pigs. One failed because of refractory ventricular fibrillation upon needle entry, and the other because of inadequate guidewire support. In all ten attempts, the right ventricular free wall was closed without hemopericardium. There was neither immediate nor late shunt on oximetry, X-ray angiography, or CMR. The interventricular septal tract fibrosed completely. Transventricular trajectories planned on human CT scans suggest comparable intracavitary working space and less acute entry angles than a conventional atrial transseptal approach.ConclusionLarge closed-chest access ports can be introduced across the right ventricular free wall and interventricular septum into the left ventricle. The septum recoils immediately and heals completely without repair. A nitinol occluder immediately seals the right ventricular wall. The entry angle is more favorable to introduce, for example, prosthetic mitral valves than a conventional atrial transseptal approach.

Limitations of Closing Percutaneous Transthoracic Ventricular Access Ports Using a Commercial Collagen Vascular Closure Device

Introduction: Closed‐chest access and closure of direct cardiac punctures may enable a range of therapeutic procedures. We evaluate the safety and feasibility of closing percutaneous direct ventricular access sites using a commercial collagen‐based femoral artery closure device. Methods: Yorkshire swine underwent percutaneous transthoracic left ventricular access (n = 13). The access port was closed using a commercial collagen‐based vascular closure device (Angio‐Seal, St. Jude Medical) with or without prior separation of the pericardial layers by instillation of fluid into the pericardial space (“permissive pericardial tamponade”). After initial nonsurvival feasibility experiments (n = 6); animals underwent 1‐week (n = 3) or 6‐week follow‐up (n = 4). Results: In naïve animals, the collagen plug tended to deploy outside the parietal pericardium, where it failed to accomplish hemostasis. “Permissive pericardial tamponade” was created under MRI, and accomplished early hemostasis by allowing the collagen sponge to seat on the epicardial surface inside the pericardium. After successful closure, six of seven animals accumulated a large pericardial effusion 5 ± 1 days after closure. Despite percutaneous drainage during 6‐week follow‐up, the large pericardial effusion recurred in half, and was lethal in one. Conclusions: A commercial collagen‐based vascular closure device may achieve temporary but not durable hemostasis when closing a direct left ventricular puncture port, but only after intentional pericardial separation. These insights may contribute to development of a superior device solution. Elective clinical application of this device to close apical access ports should be avoided.

Experimental Model of Large Pulmonary Embolism Employing Controlled Release of Subacute Caval Thrombus in Swine

PURPOSEnTo develop a catheter-based model of large pulmonary embolism (PE) in swine based on in situ venous thrombus formation.nnnMATERIALS AND METHODSnTen Yorkshire swine underwent transjugular implantation of a retrievable inferior vena cava (IVC) filter. A thrombin and collagen mixture was injected into a confined space created by two balloons inflated proximal and distal to the IVC filter. Animals were left to survive for 7 days ± 3 to allow thrombus to organize in situ. The caval thrombus was released on transcatheter retrieval of the IVC filter and embolized into the main and branch pulmonary arteries. The severity of PE was scored based on digital subtraction angiography with the Miller index. At necropsy, thrombi were recovered and analyzed histopathologically.nnnRESULTSnLarge PE was induced in all animals (Miller index score of 15 ± 5). Two animals developed saddle embolus with bilateral pulmonary artery occlusion, and five developed proximal occlusion of the left or right pulmonary artery. Nevertheless, no animal exhibited significant hemodynamic compromise. Large tubular thrombi were explanted in the size range of 5-10 cm long and 0.5-1 cm wide. Histologic analysis indicated an organized thrombus with infiltration of white blood cells and fibrin deposition.nnnCONCLUSIONSnLarge caval thrombi can be formed in vivo and released at a predetermined time to induce large PE in a large animal model. This may help in the development and testing of new therapeutic approaches for PE.

Real-time MRI guided percutaneous transthoracic left ventricular access and closure

Introduction and objective Percutaneous transthoracic left ventricular (LV) access and closure would be an enabling technology for a wide range of structural heart, electrophysiologic and proximal aorta procedures. We propose a real-time MRI guided approach to access and close the LV using novel active devices. Methods Sixteen Yorkshire swine underwent percutaneous transthoracic LV access and followed up to three months (n=8). All procedures were guided by real-time bSSFP MRI (Espree, Siemens) using two slices along the needle trajectory and a short-axis slice for cardiac monitoring. Transthoracic ventricular puncture was performed using a customized 18G active needle with integrated loop coil. Puncture trajectory was planned using realtime MRI to identify optimal LV puncture target and trajectory with respect to intraventricular and valvular structures (Figure 1A). After needle entry, an 18-French sheath was inserted and anticoagulation begun.