Annette M. Stine

Imipramine in patients with chest pain despite normal coronary angiograms

BACKGROUND Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients. METHODS Sixty consecutive patients underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then participated in a randomized, double-blind, placebo-controlled three-week trial of clonidine at a dose of 0.1 mg twice daily (20 patients), imipramine at a dose of 50 mg nightly with a morning placebo (20 patients), or placebo twice daily (20 patients); this treatment phase was compared with an identical period of twice-daily placebo for all patients (placebo phase). RESULTS Thirteen (22 percent) of the 60 patients had ischemic-appearing electrocardiographic responses to exercise, 22 of the 54 tested (41 percent) had abnormal esophageal motility, 38 of 60 (63 percent) had one or more psychiatric disorders, and 52 of 60 (87 percent) had their characteristic chest pain provoked by right ventricular electrical stimulation or intracoronary infusion of adenosine. During the treatment phase, the imipramine group had a mean (+/- SD) reduction of 52 +/- 25 percent in episodes of chest pain, the clonidine group had a reduction of 39 +/- 51 percent, and the placebo group a reduction of 1 +/- 86 percent, all as compared with the placebo phase of the trial. Only the improvement with imipramine was statistically significant (P = 0.03). Repeat assessment of sensitivity to cardiac pain while the patients were receiving treatment showed significant improvement only in the imipramine group (P = 0.01). The response to imipramine did not depend on the results of cardiac, esophageal, or psychiatric testing at base line, or on the change in the psychiatric profile during the course of the study, which generally improved in all three study groups. CONCLUSIONS Imipramine improved the symptoms of patients with chest pain and normal coronary angiograms, possibly through a visceral analgesic effect.

Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial

OBJECTIVES This phase I study was designed to evaluate the safety, tolerability and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) and intermittent claudication. We also assessed the effects of basic fibroblast growth factor (bFGF) on calf blood flow as a measure of biologic activity. BACKGROUND Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind limb ischemia. The safety and efficacy of bFGF in patients is unknown, and early clinical trials are underway in coronary and peripheral arterial disease. METHODS A double-blind, placebo-controlled, dose-escalation trial was conducted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 microg/kg of bFGF (n = 4), 30 microg/kg of bFGF once (n = 5) and 30 microg/kg of bFGF on two consecutive days (n = 4). Study drug was infused into the femoral artery of the ischemic leg. Detailed safety information including retinal photography for neovascularization were obtained through one year. Calf blood flow was measured with strain gauge plethysmography in the two higher dose treatment groups and in four placebo patients at baseline, one month and three to seven months after treatment. RESULTS Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean +/- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS In this initial randomized, double-blind, placebo-controlled trial in patients with atherosclerotic PVD and claudication, bFGF was well-tolerated. The data suggest a salutary biologic effect, and initiation of phase 2 trials is warranted.

Invasive Human Magnetic Resonance Imaging: Feasibility During Revascularization in a Combined XMR Suite

We tested the feasibility and safety of invasive magnetic resonance imaging (MRI) during peripheral angioplasty. Real‐time MRI can image soft tissue and may potentially guide therapeutic procedures without ionizing radiation or nephrotoxic contrast. MRI‐guided diagnostic catheterization has been described recently, but safe and conspicuous catheter devices are not widely available. An active guidewire, which serves as an MRI receiver antenna, might be useful to guide catheterization or even to image atheroma. We describe a combined interventional suite offering both X‐ray fluoroscopy and real‐time MRI. We used a 0.030″ active guidewire receiver coil for invasive MRI after X‐ray lesion traversal in patients undergoing percutaneous iliofemoral artery revascularization. Intravascular MRI was compared with noninvasive MRI, X‐ray angiography, and intravascular ultrasound (IVUS). Seven eligible patients consented to participate, but three were excluded because of lengthy revascularization procedures. Four remaining patients safely underwent combined X‐ray fluoroscopy and real‐time magnetic resonance imaging (XMR) transport, continuous monitoring, and all imaging modalities. There was no device dislodgment, contamination or evidence of heating. The intravascular MRI coil was well visualized except at the tip, but did not provide superior mural imaging compared with IVUS. Therefore, because an adequate safety and workflow experience was obtained, enrollment was terminated after only four subjects. Invasive MRI is feasible and apparently safe during peripheral angioplasty. Patients can safely be transported and monitored in an XMR interventional suite. An active quarter‐wavelength guidewire coil does not provide superior imaging compared with IVUS, but provides satisfactory guidewire visualization. These tools may prove useful for advanced therapeutic procedures in the future. Catheter Cardiovasc Interv 2005;64:265–274. Published 2005 Wiley‐Liss, Inc.

Technology Preview: X-Ray Fused With Magnetic Resonance During Invasive Cardiovascular Procedures

We have developed and validated a system for real‐time X‐ray fused with magnetic resonance imaging, MRI (XFM), to guide catheter procedures with high spatial precision. Our implementation overlays roadmaps—MRI‐derived soft‐tissue features of interest—onto conventional X‐ray fluoroscopy. We report our initial clinical experience applying XFM, using external fiducial markers, electrocardiogram (ECG)‐ gating, and automated real‐time correction for gantry and table movement.

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

AIMS Real-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. METHODS AND RESULTS We 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. CONCLUSION In 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.

An efficient, free-breathing protocol for MR right heart catheterization

Methods The baseline MR examination begins with cardiac localizers. At this stage it is important to verify isocenter because if the patient is too deep in the bore then femoral vascular access sheaths are inaccessible to the operator. Through-plane phase contrast (PC) scans in the ascending aorta and main pulmonary artery follow for quantification of Qp and Qs. To avoid the need to repeat long PC scans (3 averages), we first perform brief PC ‘localizer’ scans with a single average to confirm the selected velocityencoding factor is correct. For cardiac volumetric analysis, long and short axis views are obtained using a real-time SSFP sequence that sacrifices some spatial resolution for increased temporal resolution. Data is collected over one and a half heartbeats to ensure the entire cardiac cycle is captured. Because of the delay in image reconstruction, the short axis stack is acquired last while the operator prepares for catheterization. A dedicated user interface (Interactive Front End, Siemens; Erlangen, Germany) is used for real-time imaging during catheterization. This interface permits interactive manipulation of imaging planes, slice thickness, saturation pre-pulse, and cine loop recordings. To minimize catheterization time, reference images

MR guided right heart catheterization - the NIH experience

Background Realtime MR enables radiation free guidance for right heart catheterization (RHC). In addition to catheter navigation for sampling of invasive pressures and blood oxygen saturations, MR permits concomitant assessment of cardiac chamber volumes and cardiac output with phase contrast flow measurements. By performing repeat measurements under different physiological provocations (e.g. saline volume challenge, inhaled nitric oxide, or exercise), diagnostic yield increases by revealing symptoms and pathologic findings not apparent at rest. Herein we present the NIH experience of MR RHC to date.

Technologist primer for MRI right heart catheterization: the NIH and CNMC experience

Background We have begun to perform routine and research MRI right heart catheterization in adults and research MRI catheterization in children. We report our technologist workflow. Methods Scanner preparation: The scanner facade and bore are covered with adhesive clear sterile drapes and surface coils enveloped in sterile plastic bags. A MR catheterization pack contains only non-ferromagnetic supplies. Sterile

Provocative MRI catheterization

Background Invasive right heart catheterization plays a central role in the investigation of patients with cardiac and pulmonary vascular disease. Physiological provocations during invasive heart catheterization augment the diagnostic yield and can provide useful prognostic information. MRI catheterization combines invasive hemodynamic measurements with MRI structural and functional evaluations thus providing superior diagnostic information than either test alone. An additional benefit to both patient and operator is no ionizing radiation, which is of particular value in pediatric patients.