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Biomedical subjects

P D Kligfield

Publications and source records attributed to P D Kligfield.

8 recordsLinked to original sources

Transmyocardial laser revascularization with excimer laser: clinical results at 1 year.

BACKGROUND: Transmyocardial laser revascularization, a new strategy for the treatment of diffuse ischemic heart disease, uses laser technology for the theoretical purpose of forming transmyocardial channels in the heart to increase perfusion to ischemic zones. This report summarizes our initial clinical experience with the procedure. METHODS: Excimer transmyocardial laser revascularization was performed in a reversibly ischemic region of the heart in 15 patients. Ischemia and myocardial viability were evaluated by assessment of symptoms and of results of radionuclide single photon emission computed tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring. RESULTS: No adverse events occurred as a result of the laser revascularization, although 1 patient with preoperative ventricular arrhythmias died 48 hours postoperatively as a result of refractory ventricular tachycardia. Angina class decreased significantly from base line values in patients who had undergone the procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months, 1.8+/-0.8 at 12 months; p<0.002), and nitroglycerin requirements were similarly decreased in patients who had undergone laser revascularization (mean g/wk of sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3 months, 4+/-2 at 6 months, 2+/-1 at 12 months; p<0.02). Exercise tolerance testing demonstrated increase in exercise duration compared with base line values (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3 months, and 9.0+/-3.9 at 12 months; p>0.05); those increases were not large enough to be statistically significant, however. CONCLUSIONS: Our data are consistent with the concept that excimer transmyocardial laser revascularization in individuals with significant ischemic heart disease appears to be well tolerated, can be performed safely, and may lead to a reduction in ischemic symptomatology.

Adult↗

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Adenoviridae↗

Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA.

OBJECTIVE: To summarize the 6-month follow-up of a cohort of patients with clinically significant coronary artery disease who received direct myocardial injection of an E1-E3- adenovirus (Ad) gene transfer vector (Ad(GV)VEGF121.10) expressing the human vascular endothelial growth factor (VEGF) 121 cDNA to induce therapeutic angiogenesis. BACKGROUND: Therapeutic angiogenesis describes a novel approach to the treatment of vascular occlusive disease that uses the administration of growth factors known to induce neovascularization of ischemic tissues. METHODS: Direct myocardial injection of Ad(GV)VEGF121.10 into an area of reversible ischemia was carried out in 21 patients as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy using a minithoracotomy (group B, n = 6). RESULTS: No evidence of systemic or cardiac-related adverse events related to vector administration was observed up to 6 months after therapy. Trends toward improvement in angina class and exercise treadmill testing at 6-month follow-up in the sole therapy group suggest the effects of this therapy are persistent for > or =6 months. CONCLUSIONS: This study suggests that direct myocardial administration of Ad(GV)VEGF121.10 appears to be well tolerated in patients with clinically significant coronary artery disease. Initiation of phase II evaluation of this therapy appears warranted.

Adenoviridae↗

Electrocardiographic recognition of left atrial enlargement.

The ECG is widely used as a screening test for left atrial enlargement (LAE). Surprisingly, the most widely used criterion of LAE, the P-terminal force in lead V1 (PTF-V1) has not been systematically evaluated to determine the optimal level of PTF-V1 for detection of LAE in clinical populations. Accordingly, we examined the relationship between PTF-V1 and left atrial size by echocardiogram in 361 patients and performed a Bayesian analysis of test performance in populations with a varying prevalence of LAE. As PTF-V1 increased from greater than or equal to 0.03 to greater than or equal to 0.08, sensitivity in the 82 patients with LAE (LA dimension greater than 40 mm) fell from 51% to 23%, and specificity rose from 70% to 93%. In our study population (LAE prevalence = 23%), diagnostic performance of criteria was: PTF-V1 greater than or equal to 0.03 greater than or equal to 0.04 greater than or equal to 0.05 greater than or equal to 0.06 greater than or equal to 0.08 Positive Predictive Accuracy 33 46 52 58 50 Negative Predictive Accuracy 83 83 84 83 80 Per Cent Correct Diagnosis 66 76 78 80 77 Positive predictive accuracy and per cent correct diagnosis improved progressively as PTF-V1 rose from greater than or equal to 0.03 to greater than or equal to 0.06, but fell at greater than or equal to 0.08. Applying our sensitivity and specificity data to Bayesian analysis, PTF-V1 greater than or equal to 0.06 performed best in all populations with prevalence of LAE less than or equal to 50%. We conclude that use of PTF-V1 greater than or equal to 0.06 is superior to the standard criterion of PTF-V1 greater than or equal to 0.04 for all purposes ranging from screening of a general population to evaluation of diseased individuals whose likelihood of LAE ranges up to 50%.

Adolescent↗

A method for understanding three-dimensional coronary anatomy.

A simple method for interpreting and reviewing the anatomy of the coronary arteries as seen on angiograms uses the concept of two imaginary circles around the interventricular and atrioventricular grooves, respectively. The hands and fingers of the viewer are used to res in various angiographic projections may be properly understood.

Angiography↗

Human tecg changes during prolonged hyperbaric exposures breathing N2-O2 mixtures.

In an effort to determine whether hyperbaric exposures while breathing N2-O2 mixtures have an effect on cardiac depolarization and repolarization, electrocardiograms of 10 divers participating in four N2-O2 saturation dives were analyzed. In all cases, a decline in heart rate was observed upon compression to saturation depth (20-30%); a slow adaptation and return of heart rate toward normal was observed in those dives where the depth and environmental parameters remained constant. twhenever excursion dives were performed, the heart rate responded by decreasing on deeper excursions and increasing on upward excursions. Hyperbaric bradycardia disappeared after 8 days at pressure during the saturation dives at 50 and 60 feet seawater gauge (fswg), but was still present at this time at 200 fswg. The magnitude of the hyperbaric bradycardia produced by excursion dives following saturation at depth was influenced by the state of adaptation of heart rate. Decompression was uniformly accompanied by a rapid increase in heart rate resulting in a significant elevation in the postdive period. Alterations in myocardial repolarization as evidenced by Q-T interval, ST, and T wave changes were observed. Development of slight right ventricular conduction delay compatible with right ventricular strain was noted in four of the divers during the two deepest dives to 100 and 198 fswg. During the latter dive, progressive decrease in P wave amplitudes and eventual loss of P waves resulting in an apparent nodal rhythm was observed in one diver. Multiple premature ventricular contractions occurred in another diver. These observations, along with the reports by other authors, suggest that the different variables associated with the hyperbaric environment--gas density, pressure, inert gas--have a definite effect on the pacemaker activity of the heart and myocardial depolarization and repolarization.

Adaptation, Physiological↗