Patricia A. Takeda

Percutaneous Septal Sinus Shortening A Novel Procedure for the Treatment of Functional Mitral Regurgitation

Background— The septal-to-lateral (SL) mitral annular diameter is increased in functional mitral regurgitation (MR). We describe a novel percutaneous technique (the percutaneous septal sinus shortening system) that ameliorates functional MR in an ovine model. Methods and Results— Sheep underwent rapid right ventricular pacing to obtain moderate to severe functional MR with SL enlargement. The percutaneous septal sinus shortening system was placed via standard interventional techniques consisting of a bridge (suture) element between interatrial septal wall and great cardiac vein anchors. Through progressive tensioning of the bridge element, direct SL shortening was achieved. Sheep underwent short-term (n=19) and long-term (n=4) evaluation after device implantation. In short-term studies, SL diameter decreased an average of 24% (32.5±3.5 to 24.6±2.4 mm; P<0.001), and MR grade significantly improved (2.1±0.6 to 0.4±0.4; P<0.001). Despite continued rapid pacing, chronic device implantation resulted in durable SL shortening (30.4±1.9 mm before implantation to 25.3±0.8 mm at 30 days; P=0.01) and MR reduction (1.8±0.5 before implantation to 0.2±0.1 at 30 days; P=0.01). Increased cardiac output, decreased wedge pressure, and decreased brain natriuretic peptide levels were observed in animals undergoing long-term device implantation. Conclusions— The percutaneous septal sinus shortening system is effective in ameliorating functional MR in an ovine tachycardia model. The procedure, which uses standard catheter techniques, can be deployed largely under fluoroscopic guidance. The unique bridge element appears durable and allows direct and precise SL shortening to a diameter optimal for MR reduction.

Effects of diltiazem-induced calcium blockade upon exercise capacity in effort angina due to chronic coronary artery disease.

Few data are available regarding the effects of calcium blockade upon exercise tolerance in patients with stable effort angina due to coronary artery disease (CAD). Therefore we compared the effects of the calcium blocking agent, diltiazem (D), to placebo (P) in 12 patients with chronic effort angina and catheterization documented fixed CAD. The 8-week total protocol consisted of a 1-week baseline period followed by the double-blind randomized crossover alternate 1-week administration of P and D in doses of 120, 180, and 240 mg. Maximal exercise tests (MET) were performed at the end of each 1-week period, while rest radionuclide ventriculography (RVG) was obtained during 240 mg D and corresponding crossover P. Resting heart rate decreased from baseline and initial P at D doses of 60 and 240 mg, but not from P during crossover period. No changes were observed at any dose of D either at rest or during MET in systolic blood pressure or rate . pressure double product. D at 240 mg, but not lower doses, increased MET duration (437 vs 490 seconds, p less than 0.01) and time to angina (383 vs 441 seconds, p less than 0.01). Ejection fraction by RVG was greater with D than P (0.54 vs 0.50, p less than 0.05). Thus these data indicate that calcium blockade with diltiazem provides antianginal efficacy by reducing myocardial oxygen demand, and increases exercise tolerance without depression of myocardial performance in effort angina patients with fixed chronic CAD.

The QuantumCor device for treating mitral regurgitation: an animal study.

Objectives: The mitral annular contraction achieved could help reduce mitral regurgitation (MR), and with appropriate modifications, be applied to human subjects providing a potentially effective percutaneous method of valve repair. Background: MR is an important source of morbidity and is an independent predictor of mortality. A variety of percutaneous approaches are being developed to address this issue. We introduce a novel potential method utilizing radiofrequency (RF) energy to heat and shrink the mitral valve annulus in an animal model. Methods: In open‐heart procedures in 16 healthy sheep (six with naturally occurring MR), we used a malleable probe (QuantumCor, Lake Forest, CA) that conforms to the annular shape to deliver RF energy via a standard generator to replicate a surgical mitral annular ring. Seven sheep were followed chronically and their mitral annulus dimensions measured serially. Results: All sheep underwent intracardiac echocardiography or direct circumferential measurement of the mitral annulus before and after RF therapy. RF therapy was administered in less than 4 min in each case, and the mean anteroposterior (AP) annular distance was reduced by a mean of 23.8% (AP diameter reduction 5.75 ± 0.86 mm, P < 0.001) acutely. In the six sheep with nonischemic MR, regurgitation was eliminated. Acute histopathology (HP) demonstrated no damage to the leaflets, coronary sinuses, or coronary arteries. At the end of the intended 6‐month period of the chronic part of the study, four of the seven animals survived. The four treatment animals showed significant reductions in mitral A‐P dimension, with a percent diameter reduction of 26.4% (AP diameter reduction 7 ± 2.3 mm). Conclusion: The application of RF directly to heat the mitral annulus has resulted in sustained contraction of the annulus in this limited preclinical animal study. With further study and possible modifications, it holds promise for future application in human subjects with MR.

Long‐term safety and durability of percutaneous septal sinus shortening (The PS3 System™) in an ovine model

Objectives: Chronic implants of the PS3™ system were conducted in an ovine model to assess durability and safety at up to 1 year follow‐up. Background: The long‐term durability and safety of emerging percutaneous devices for functional mitral regurgitation remain largely unknown. Methods: The PS3 system (consisting of interatrial septal and great cardiac vein devices connected by an adjustable suture bridge) was placed in eight healthy adult sheep. The mitral annular septal‐lateral dimension in systole (SLS) was acutely reduced by 15–20%. Animals were sacrificed at up to 12 months postimplant and characterized by intracardiac echocardiography, cardiac computed tomography (CT), and histopathology. In vivo forces exerted on the PS3 bridge were measured by means of a novel load cell catheter. Results: At 3, 6, and 12 months after implantation, intracardiac echocardiographic and CT showed the PS3 systems to be intact without erosion and with overall sustained reductions in the SLS. Histopathologic assessment revealed each component correctly deployed in its respective target site without evidence of erosion, thrombus, or device fracture. The SLS was 26.5 ± 1.7 mm preimplant, 22.0 ± 1.4 mm post‐PS3 (17.0% reduction), and 22.0 ± 2.1 mm at latest follow‐up. Mean forces exerted on the bridge in vivo ranged from 1.16 N to 1.87 N. Conclusions: The PS3 System demonstrated excellent biocompatibility without evidence of erosion, thrombosis, or perforation at up to one‐year follow‐up in this chronic healthy ovine model. Forces exerted in the PS3 system were relatively modest and should contribute to the durability of the device.

Bioprosthetic Leaflet Erosion After Percutaneous Mitral Paravalvular Leak Closure

Transcatheter closure of prosthetic paravalvular leaks is increasingly performed at experienced centers ([1–3][1]). The lack of devices dedicated to paravalvular leak closure has not deterred the off-label use of various occluder devices. These images illustrate the potential complexity of

Collagen Mechanics: A Rationale for Radiofrequency Energy to Treat Mitral Regurgitaton

Despite a variety of pharmacological interventions to limit the regurgitant fraction, mitral regurgitation requires surgical intervention for definitive treatment. New nonsurgical techniques are being applied to treat mitral regurgitation. The mitral and tricuspid annuli are areas of dense collagen. Application of heat, in the form of radiofrequency energy, can be used to shrink mitral valve annuli and offers a promising approach to the treatment of mitral regurgitation.