Jeff L. Conger

Myocardial Revascularization With Laser Preliminary Findings

BACKGROUND We assessed the transmyocardial laser revascularization (TMLR) as sole therapy in patients with symptomatic coronary artery disease refractory to interventional or medical treatment. METHODS AND RESULTS Thirty-one patients were evaluated with positron emission tomography (PET), dobutamine echocardiography, 201Tl single-photon emission computed tomography (201Tl-SPECT), and multigated acquisition radionuclide ventriculography (MUGA). TMLR was performed in 21 patients who had demonstrable ischemia in viable myocardium. The mean Canadian Cardiovascular Society (CCS) angina class was 3.70 +/- 0.7 (4 patients with unstable angina). Untreated septal segments were used as controls. At 3 months, (n = 15 patients), the mean CCS angina class was to 2.43 +/- 0.9 (P < .05). On dobutamine echocardiography, the mean resting wall motion score index was improved by 16% in lased segments (P < .03 vs control), and mean LVEF at peak stress increased by 19% (P = NS vs baseline). On 201Tl-SPECT, perfusion of lased and nonlased segments did not change. On PET, the mean ratio of subendocardial to subepicardial perfusion (SEn/SEp) increased 14% over baseline (P < .001 vs control). At 6 months (n = 15 patients), the mean CCS angina class was 1.7 +/- 0.8 (P < .05). The mean resting wall motion score index was up by 13% in lased segments (P < .05 vs control). Resting LVEF was unchanged. Stress LVEF increased 21% (P = NS vs baseline). Myocardial perfusion remained unchanged by 201Tl-SPECT. On PET, 36% of the lased segments were better, and 25% were worse compared with baseline. The resting SEn/SEp by PET was up 21% (P < .001 vs control). All deaths (two perioperative and three late) occurred in patients with preoperative congestive heart failure. Two patients required repeat revascularization of new coronary lesions. CONCLUSIONS These results suggest that TMLR improves anginal status, relative endocardial perfusion, and cardiac function in patients who do not have preoperative congestive heart failure.

Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart

Advances in technology and increased clinical need have led to the development of a new type of blood pump. The Jarvik 2000 Heart is an electrically powered, axial-flow left ventricular assist device that has been developed during the past 13 years. Unlike first-generation left ventricular assist devices, which were developed in the 1970s and were designed to totally capture the cardiac output, the Jarvik 2000 is designed to normalize the cardiac output by augmenting the function of the chronically failed heart for extended periods. Design iterations have been tested in 67 animals, and clinical trials have recently begun. Three patients have received the Jarvik 2000 as a bridge to transplantation, and 1 patient is being supported permanently outside the hospital. All 4 patients have improved from New York Heart Association functional class IV to class I, and 2 of them have been discharged from the hospital after heart transplantation. The experimental and clinical results indicate that the Jarvik 2000 can provide physiologic support with minimal complications and is reliable, biocompatible, and easy to implant.

Long- and short-term effects of transmyocardial laser revascularization in acute myocardial ischemia

This study examined the effect of transmyocardial laser revascularization (TMLR) on infarct size and global and regional left ventricular (LV) function.

Progress in the development of a transcutaneously powered axial flow blood pump ventricular assist system.

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 ± 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (∼1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.

Biventricular support with the Jarvik 2000 ventricular assist device in a calf model of pulmonary hypertension.

The Jarvik 2000 ventricular assist device (VAD) is clinically efficacious for treating end-stage left ventricular failure. Because simultaneous right ventricular support is also occasionally necessary, we developed a biventricular Jarvik 2000 technique and tested it in a calf model. One VAD was implanted in the left ventricle with outflow-graft anastomosis to the descending aorta. The other VAD was implanted in the right ventricle with outflow-graft anastomosis to the pulmonary artery. Throughout the 30 day study, hemodynamic values were continuously monitored. On day 30, both pumps were evaluated at different speeds, under various hemodynamic conditions. By gradually occluding the pulmonary artery proximally or distally, we simulated varying degrees of high pulmonary vascular resistance, right ventricular hypertension, global heart failure, or ventricular fibrillation. The two VADs maintained biventricular support even during pulmonary artery occlusion and ventricular fibrillation, yielding a cardiac output of 3–11 L/min, left ventricular end-diastolic pressure of 11–24 mm Hg, and central venous pressure of 9–25 mm Hg. End-organ function was unimpaired, and no major adverse events occurred. The dual VADs offered safe, effective biventricular assistance in the calf. Additional studies are needed to assess the effects of lowered pulse pressure upon the pulmonary circulation and to develop a single pump speed controller.

Intraoperative arrhythmias and tissue damage during transmyocardial laser revascularization

BACKGROUND Transmyocardial laser revascularization creates transmural channels to improve myocardial perfusion. Different laser sources and ablation modalities have been proposed for transmyocardial laser revascularization. We investigated the incidence of cardiac arrhythmias and laser-tissue interactions during transmyocardial laser revascularization of normal porcine myocardium with three different lasers. METHODS We used a continuous-wave, chopped CO2 laser (20 J/pulse, 15 ms/pulse) synchronized with the R wave; a holmium:yttrium aluminum garnet (Ho:YAG) laser (2 J/pulse, 250 micros/pulse, 5 Hz); and a xenon-chloride (excimer, Xe:Cl) laser (35 mJ/pulse, 20 ns/pulse, 30 Hz). Each laser was used 30 times as the sole modality in four consecutive pigs, yielding 120 channels. RESULTS The average number of pulses needed to create a channel was 1, 11 +/- 4, and 37 +/- 8 for the CO2, Ho:YAG, and Xe:Cl lasers, respectively. All Ho:YAG and Xe:Cl channels had premature ventricular contractions. Ventricular tachycardia occurred in 70% of the Xe:Cl and 60% of the Ho:YAG channels. Only 36% of the CO2 channels had premature ventricular contractions, and only 3% of the CO2 channels had ventricular tachycardia (p < 0.001 versus Ho:YAG and Xe:Cl). Ho:YAG channels were highly irregular: each had a 0.6-mm-wide central zone surrounded by a ring of coagulation necrosis (diameter, 1.84 +/- 0.67 mm) with effaced cellular architecture in a thin hemorrhagic zone. The Xe:Cl sections exhibited the same patterns on a smaller scale (diameter, 0.74 +/- 0.18 mm). The CO2 channels were straight and well demarcated. The zone of structural and thermal damage extended over half the channels diameter, measuring 0.52 +/- 0.25 mm. CONCLUSIONS During transmyocardial laser revascularization, the CO2 laser synchronized with the R wave is significantly less arrhythmogenic than the Ho:YAG and Xe:Cl lasers not synchronized with the R wave. In addition, the interaction of the CO2 laser with porcine cardiac tissue is significantly less traumatic than that of the Ho:YAG and the Xe:Cl lasers.

Ninety-day survival of a calf implanted with a continuous-flow total artificial heart.

We evaluated the effects of steady state flow and perfusion on end-organ function in a long-term calf model. The animal received a continuous-flow total artificial heart (CFTAH) that we created from two axial-flow ventricular assist devices. Pump flow, blood pressure, and other pump parameters were monitored throughout the study, as were arterial blood gas and hematologic values, including neurohormone levels. Some hematologic values were mildly abnormal transiently after surgery but returned to acceptable levels within the first week. During the 90-day study, the calf showed no signs of hemolysis or thrombosis. Its mental function remained normal, as evidenced by the animal’s interest in its surroundings and response to stimuli. End-organ and vasomotor function was not adversely affected by 90 days of steady state flow. This was the first study in which CFTAH support of an animal model was maintained for this duration.

In vivo testing of an intra-annular aortic valve annuloplasty ring in a chronic calf model

OBJECTIVE To increase applicability and stability of aortic valve repair, a three-dimensional aortic annuloplasty ring has been developed for intra-annular placement. The goal of this study was to test the safety of this device with in vivo implantation in the calf model. METHODS In 10 chronic calves, the HAART annuloplasty ring was sutured to the aortic valve annulus using cardiopulmonary bypass. The animals were recovered and followed for 1-2 months. Serial echocardiography was used to evaluate valve competence, and contrast aortograms and CT angiograms were obtained in selected animals. After completion of follow-up, each animal was euthanized, and aortic endoscopy was performed under water distension in five. Full autopsies with histologic examinations were performed. RESULTS All animals survived surgery. Two were euthanized in the first week for complications, and the remaining eight calves were followed uneventfully for the 1-2 months. Serial echocardiography showed completely competent valves in all but one animal, in which the ring was intentionally up-sized to test the sizing strategy. Contrast aortographic and CT angiographic findings were similar to the echocardiograms. Postmortem examination showed proper seating of all rings with endothelialization at 1-2 months. All valves demonstrated good leaflet coaptation and no abnormalities. CONCLUSIONS In vivo testing of a three-dimensional aortic annuloplasty ring in a chronic calf model proved to be very successful and safe. Using the sizing and implant strategies developed, human trials seem indicated.

Baseline hemodynamic and echocardiographic indices in anesthetized calves.

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 ± 87.0 days; mean body weight, 106.9 ± 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 ± 12 beats per minute), mean aortic pressure (113.5 ± 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 ± 38.9 mm Hg), and mean pulmonary artery pressure (21.7 ± 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 ± 0.7 cm), left ventricular diastolic dimension (5.6 ± 0.8 cm), end-systolic intraventricular septal thickness (1.7 ± 0.2 cm), end-diastolic intraventricular septal thickness (1.2 ± 0.2 cm), ejection fraction (63 ± 10%), and fractional shortening (37 ± 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 ± 0.5 m/s and a cardiac index of 3.7 ± 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.

In vivo evaluation of a trileaflet mechanical heart valve

Design goals for a mechanical heart valve include duplicating the hemodynamic performance of the natural valve, eliminating the need for anticoagulants, and maintaining safety. The Lapeyre-Dassault (Dassault-Aviation, Paris, France) prosthetic valve, undergoing development, addresses these goals. The unique trileaflet design consists of a solid titanium ring and three leaflets. Prototypes of the valve fabricated with Delrin leaflets were implanted in the mitral position in six calves (70-90 kg). Four calves (Studies 1, 2, 3, 5) had long-term survival of 165, 158, 219, and 281 days, respectively. Two calves were killed, one on Day 37 and one on Day 39, after complications unrelated to the valve developed. In all calves heparin was given intravenously to maintain partial thromboplastin time at 1.5 to 2.0 x baseline for approximately 1 week. In Studies 1 and 2 full anticoagulation and antiplatelet therapy was given (orally administered sodium warfarin to maintain prothrombin time at 1.5 to 2.0 x baseline, along with aspirin (1 g/day) and dipyridamole 400 mg/day). In Study 3, all anticoagulation and antiplatelet therapy was discontinued at 1 month after implant. In Study 5, no anticoagulation therapy was given after the initial week of intravenous heparin; however, antiplatelet therapy was started on the fifth postoperative month and maintained until the studys end at 9 months. At 1, 2, 3, and 5 months, the mean plasma free hemoglobin level in the four long-term animals was 5.0 +/- 2.16, 6.0 +/- 3.83, 8.5 +/- 4.93, and 11.3 +/- 6.74 mg/dl, respectively. Hemolysis was not a problem. Valve performance during normal activity was excellent in all the calves, as evidenced by echocardiography and the overall appearance of good health. In the four completed long-term studies, left heart catheterization showed a mean valve pressure gradient of 11.57 +/- 1.26 mmHg and no apparent valvular regurgitation. Histopathologic examination of major organs showed no evidence of thromboembolic events. This study shows that the innovative design of this trileaflet valve performed well in initial in vivo testing, justifying further development.