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Biomedical subjects

D R Holmes

Publications and source records attributed to D R Holmes.

At least 19 recordsLinked to original sources
PubMed1992

The restenosis paradigm revisited: an alternative proposal for cellular mechanisms.

Coronary restenosis is a reparative response to arterial injury during angioplasty, and remains a major clinical problem. The reasons for treatment failures likely stem from our incomplete understanding of the cellular mechanisms in restenotic neointimal formation. Restenosis is thought to result from migration and replication of medial smooth muscle cells to form an obstructive neointima, a concept neither observed nor demonstrated in humans. An alternative hypothesis for restenosis is based on observations in the porcine coronary injury model. In this model, there are three cellular stages in neointimal formation: thrombotic (stage I), cellular recruitment (stage II) and proliferative (stage III). The thrombotic stage occurs early and consists of platelets, fibrin and red blood cells accumulating at the vessel injury site. In the recruitment stage, the mural thrombus itself develops an endothelium, followed by a mononuclear leukocytic infiltrate beginning on the lumen side of the vessel. In the proliferative stage, a "cap" of actin-positive cells forms on the lumen surface and progressively thickens. These cells do not arise from media at the injury site. Extracellular matrix secretion and additional recruitment likely add to neointimal volume during this phase. Thrombus assumes a major role in restonosis by providing an absorbable matrix into which smooth muscle cells proliferate. Further studies are needed to validate or modify this hypothesis.

Animals↗
PubMed1992

Results of directional atherectomy of primary atheromatous and restenosis lesions in coronary arteries and saphenous vein grafts.

Directional coronary atherectomy (DCA) was performed in 158 patients over a 2-year period at the Mayo Clinic. Primary atheromatous lesions were treated in 92 patients (group 1) and restenosis lesions were treated in 66 (group 2). Technical success (recovery of tissue and greater than or equal to 40% luminal enlargement with a residual stenosis of less than 50%) was achieved in 152 lesions (92%); clinical success (technical success and no in-hospital death, Q-wave myocardial infarction or coronary bypass surgery) was achieved in 143 patients (91%). Adjunctive balloon angioplasty was used in 41 patients. DCA was successful less often in group 1 than in group 2 (86 vs 97%; p = 0.038). A major complication occurred in 7% of patients; in-hospital death, Q-wave myocardial infarction and emergency coronary bypass surgery occurred in 3, 1 and 4% of patients, respectively. Major complications were more frequent in group 1 than in group 2 (10 vs 1; p = 0.02). During a follow-up period of 14 +/- 8 months, no difference between the groups was found in the incidence of late death (4%), Q-wave myocardial infarction (1%), recurrent severe angina (29%), bypass surgery (15%) or repeat interventional procedure of the same vascular segment (24%). Vein graft and restenosis lesions tended to have greater success and fewer complications. Angiographic restenosis (increase of greater than or equal to 30% in stenosis severity by visual assessment) occurred in 62% of patients and 58% of lesions with successful DCA, and was similar in the 2 groups; a tendency toward higher restenosis rates was seen in patients with vein graft DCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Methodologic issues in clinical evaluation of stenosis severity in adults undergoing aortic or mitral balloon valvuloplasty. The NHLBI Balloon Valvuloplasty Registry.

Although both catheterization and Doppler measures of valvular stenosis severity have been validated, each has specific advantages and limitations, particularly in the setting of balloon valvuloplasty. Invasive valve area and mean pressure gradient recorded immediately before and after aortic (n = 589) or mitral (n = 608) catheter balloon valvuloplasty were compared with Doppler valve area and mean pressure gradient recorded less than 30 days before and 24 to 72 hours after the procedure. For aortic stenosis, Doppler valve area ranged from 0.1 to 1.4 cm2 before and 0.2 to 2.3 cm2 after catheter balloon valvuloplasty. Doppler and invasive aortic valve areas differed by less than or equal to 0.5 cm2 in 99% and by less than 0.2 cm2 in 92% of patients. Linear correlation was higher before versus after catheter balloon valvuloplasty, for both valve area (r = 0.49 vs r = 0.35, p = 0.01) and mean pressure gradient (r = 0.64 vs r = 0.50, p = 0.01). Group mean invasive valve area was slightly smaller before (0.50 vs 0.59 cm2, p less than 0.0001) but was not different after (0.80 vs 0.78 cm2, p = 0.16) catheter balloon valvuloplasty. Variables affecting the valve area differences were cardiac output, aortic regurgitation, heart rate and blood pressure. Mean pressure gradient differences were related to echo quality, blood pressure and mitral regurgitation. For mitral stenosis, 2-dimensional echocardiographic valve area ranged from 0.4 to 2.8 cm2 before and 0.7 to 3.8 cm2 after catheter balloon valvuloplasty. Two-dimensional echocardiography and invasive mitral valve areas differed by less than or equal to 0.5 cm2 in 96% and by less than 0.2 cm2 in 81% of cases. Linear correlation was not different before versus after catheter balloon valvuloplasty for two-dimensional echocardiographic valve area (r = 0.40 vs 0.36), pressure halftime valve area (r = 0.31 vs 0.32) or mean pressure gradient (r = 0.55 vs r = 0.46). Group mean 2-dimensional echocardiography and pressure halftime valve areas were larger than invasive valve areas before (1.09 vs 1.02 cm2, p = 0.001) and smaller after (1.71 vs 2.02 cm2, p less than 0.0001) catheter balloon valvuloplasty. Important variables affecting the differences were mitral regurgitation, interatrial shunt, cardiac output and heart rate. Nonsimultaneous studies, differing volume flow measurements, and the underlying accuracy of each technique largely account for discrepancies between these methods. The clinical use of each will depend on its ability to predict long-term patient outcome.

Adult↗
PubMed1992

Percutaneous transluminal coronary angioplasty in patients with cardiogenic shock.

In cardiogenic shock complicating acute myocardial infarction, percutaneous transluminal coronary angioplasty has been reported to significantly improve the modest survival benefits afforded by emergency surgical revascularization and thrombolytic therapy. The records of all patients who underwent angioplasty for acute myocardial infarction complicated by cardiogenic shock were retrospectively reviewed to determine whether coronary angioplasty improves survival. Of the 45 patients, 28 (group 1, 62%) had successful dilation of the infarct-related artery and 17 (group 2, 38%) had unsuccessful angioplasty. The groups were similar in extent of coronary artery disease, infarct location, incidence of multivessel disease and hemodynamic variables. The overall hospital survival rate was 56% (71% in group 1 and 29% in group 2). Group 1 patients had more left main coronary artery disease, and group 2 patients were older and had a higher incidence of prior myocardial infarction. Multivariate analysis showed that the survival advantage in patients with successful angioplasty was statistically significant (p = 0.014) when these factors were taken into account. At a mean follow-up interval of 2.3 years (range 1 month to 5.6 years), there were five deaths (four cardiac and one noncardiac), for a 2.3-year survival rate of 80% in patients surviving to hospital discharge. During the follow-up period, 36% of hospital survivors had repeat hospitalization for cardiac evaluation, 8% had myocardial infarction, 8% had coronary artery bypass surgery and 24% had angina.

Actuarial Analysis↗
PubMed1992

Clinical angiographic and histologic correlates of ectasia after directional coronary atherectomy.

Directional coronary atherectomy can cause ectasia (final area stenosis less than 0%), presumably due to an excision deeper than the angiographically "normal" arterial lumen. In a multicenter series in which quantitative coronary arteriography was performed after directional atherectomy in 382 lesions (372 patients), ectasia after atherectomy occurred in 50 (13%) lesions. By univariate analysis, ectasia was seen more often within the circumflex coronary artery (p = 0.008), in complex, probably thrombus-containing lesions (p = 0.015), and with higher device:artery ratios (p less than 0.001). Ectasia occurred less often in lesions within the right coronary artery (p = 0.008). Histologic analysis demonstrated adventitia or media, or both, in all patients with angiographic ectasia. Repeat angiography was performed in 188 of 271 eligible patients (69%) 6.1 +/- 2.4 months after atherectomy. Restenosis, defined as a follow-up area stenosis greater than or equal to 75%, was present in 50% of patients without procedural ectasia and in 70% of patients with marked ectasia (residual area stenosis less than -20%; p = 0.12). It is concluded that excision beyond the normal arterial lumen may occur after directional coronary atherectomy, related, in part, to angiographic and procedural features noted at the time of atherectomy. Restenosis tends to occur more often in patients with marked ectasia after coronary atherectomy.

Aged↗
PubMed1992

Balloon angioplasty of chronic total coronary artery occlusions: what does it cost in radiation exposure, time, and materials?

Coronary angioplasty of chronic total occlusions is known to have a lower success rate and higher frequency of restenosis than angioplasty of subtotal stenoses, but there are no data describing the additional time, resources, and radiation exposure associated with this procedure. The purpose of this study was to compare these features in 90 consecutive patients who underwent angioplasty of a total occlusion (group 1) to those of 100 consecutive patients who underwent angioplasty of a subtotal stenosis (group 2). Angioplasty was successful in 60% of group 1 and in 94% of group 2 patients. Procedures were longer in group 1 and significantly more guide catheters, angioplasty balloon catheters, and guide wires were required per patient compared to group 2. The volume of contrast media used in each group was similar. Estimates of radiation entry exposure, calculated from fluoroscopy exposure times and using data from phantom studies, were 53 R (roentgen) per patient in group 1 vs. 34 R in group 2. These procedures were performed using pulsed progressive fluoroscopy; radiation exposure would be considerably higher using conventional fluoroscopic systems. Cineangiographic radiation exposures were similar for each group and accounted for an average additional exposure of 14-22 R for each procedure. Total radiation exposure was reduced in both groups when the angioplasty procedure was combined with the diagnostic angiogram. These observations should be considered when dilation of a total occlusion is planned. Efforts to reduce the amount of radiation exposure should remain a priority in interventional catheterization laboratories.

Aged↗
PubMed1992

Excimer laser coronary angioplasty: results in restenosis versus de novo coronary lesions. Excimer Laser Coronary Angioplasty Investigators.

There is limited information regarding the use of excimer laser coronary angioplasty (ELCA) in patients with restenotic lesions. The purpose of this investigation was to compare the results of ELCA in patients with restenosis following prior PTCA with results obtained in de novo (no restenosis) patients. A retrospective review was obtained of all patients undergoing attempted ELCA at each of the 12 participating clinical investigative centers. There were 620 patients in the prior restenosis group and 949 in the de novo group. Both laser success (88% vs 78%) and procedural success (92% vs 88%) were higher in restenosis lesions compared with de novo lesions (P less than 0.001). Six-month follow-up was available in 40% of patients. Restenosis occurred in 49% of the prior restenosis group vs 44% of the de novo group (P nonsignificant) but death was more common in the de novo group (2.2 vs 0.4%, P = 0.01). ELCA can be performed with a high success rate in patients with restenosis following prior balloon angioplasty but recurrent restenosis following laser procedure remains a significant problem.

Adult↗
PubMed1992

Ventricular relaxation and myocardial ischemia: a comparison of different models of tau during coronary angioplasty.

This study compares the sensitivity and variability of four models of tau, the time constant of ventricular relaxation, to detect the presence of myocardial ischemia. High fidelity left ventricular pressure recordings were obtained in ten patients undergoing coronary angioplasty at baseline, during balloon inflation, and at recovery. Four models of tau were considered: 1) a semilogarithmic, zero asymptote model (TL), 2) a semilogarithmic model using data from the first 40 ms of isovolumic relaxation (T40), 3) an exponential non-zero asymptote model (TE), and 4) a derivative non-zero asymptote model (TD). TL, T40, and TE increased significantly during inflation and returned to near baseline values at recovery. TD showed no change during inflation. Comparisons of TL, T40, and TE using the derived relaxation half-time (T1/2), failed to reveal significant differences between the models at baseline, during inflation, or at recovery. The non-zero asymptote models were associated with a greater beat-to-beat variability than the semilogarithmic models. Thus, T1/2 using the semilogarithmic zero asymptote models (TL and T40) may be more useful and consistent when measuring the rate of isovolumic relaxation during myocardial ischemia.

Angioplasty, Balloon, Coronary↗
PubMed1992

The Tracker catheter: a new vascular access system.

Technologic advances in dilation equipment have been important in improving angioplasty success rates and in expanding the indications of dilation. Despite these improvements, approximately 7% to 10% of attempted dilations may ultimately fail because of inability to cross the culprit lesion. As angioplasty techniques are applied to an increasingly complex cohort of patients, the ultimate success of a given procedure depends more and more on the ability of the operator to select the appropriate equipment for a given procedure. We report the unique application of a commercially available perfusion catheter which may improve patient outcome during complex angioplasty.

Aged↗
PubMed1992

Recurrence of symptoms after percutaneous aortic balloon valvuloplasty: relationship to Doppler diastolic filling values.

Short-term follow-up after percutaneous aortic balloon valvuloplasty shows a high incidence of restenosis. Yet a high percentage of patients with restenosis continue to show symptomatic improvement. Those with decreased left ventricular function originally tend to have a recurrence of symptoms. In this study Doppler-derived diastolic filling values at follow-up were most highly associated with symptom status, suggesting that change in diastolic filling after percutaneous aortic balloon valvuloplasty is one of the factors related to symptoms.

Aged↗
PubMed1992

Long-term follow-up of patients undergoing closed transventricular mitral commissurotomy: a useful surrogate for percutaneous balloon mitral valvuloplasty?

OBJECTIVE: The aim of this study was to determine the long-term outcome and multivariate predictors of late events in patients who underwent transventricular mitral commissurotomy at the Mayo Clinic in the early 1960s. BACKGROUND: Percutaneous balloon mitral valvuloplasty is an important new procedure for which long-term follow-up data are not yet available. However, such data do exist for patients who have undergone transventricular mitral commissurotomy, a similar but older and more invasive procedure. METHODS: Follow-up data (mean duration 13.9 years) for 207 women and 60 men who underwent transventricular mitral commissurotomy were obtained from medical records, referring physicians, questionnaires and telephone interviews. Survival and survival free of repeat commissurotomy or mitral valve surgery were estimated with the Kaplan-Meier method. Cox proportional hazards model was used to determine predictors of survival and repeat mitral valve surgery. RESULTS: Postoperatively, 92% of patients had symptomatic improvement, which was sustained for at least 3 to 4 years in 78%. At 10, 15 and 20 years postoperatively, 79%, 67% and 55%, respectively, of patients were alive and 57%, 36% and 24%, respectively, were alive and free of repeat mitral valve surgery. At 10 years, 90% of all patients were free of transient or fixed cerebrovascular events. In multivariate analyses, atrial fibrillation, age and male gender were independently associated with death, whereas mitral valve calcification, cardiomegaly and mitral regurgitation independently predicted repeat mitral valve surgery. CONCLUSIONS: Long-term results after transventricular mitral commissurotomy are excellent in selected patients with symptomatic mitral stenosis. Because of similarities in patient selection and mechanisms of mitral valve dilation, similar favorable long-term outcomes may be expected after percutaneous balloon mitral valvuloplasty.

Adult↗
PubMed1992

Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury.

Human coronary artery restenosis after percutaneous revascularization is a response to mechanical injury. Smooth muscle cell proliferation is a major component of restenosis, resulting in obstructive neointimal hyperplasia. Because ionizing radiation inhibits cellular proliferation, this study tested in a porcine coronary injury model the hypothesis that the hyperplastic response to coronary artery injury would be attenuated by X-irradiation. Deep arterial injury was produced in 37 porcine left anterior descending coronary artery segments with overexpanded, percutaneously delivered tantalum wire coils. Three groups of pigs were irradiated with 300-kV X-rays after coil injury: Group I (n = 10), 400 cGy at 1 day; Group II (n = 10), 400 cGy at 1 day and 400 cGy at 4 days and Group III (n = 9), 800 cGy at 1 day. Eight pigs in the control group underwent identical injury but received no radiation. Treatment efficacy was histologically assessed by measuring neointimal thickness and percent area stenosis. Mean neointimal thickness in all irradiated groups was significantly higher than in the control groups and thickness was proportional to X-ray dose. X-irradiation delivered at these doses and times did not inhibit proliferative neointima. Rather, it accentuated the neointimal response to acute arterial injury and may have potentiated that injury.

Angioplasty, Balloon, Coronary↗
PubMed1992

Relation of deep arterial resection and coronary artery aneurysms after directional coronary atherectomy.

OBJECTIVES: The aims of this study were to document the frequency of coronary artery aneurysm formation in patients undergoing directional coronary atherectomy and to determine the relation of such aneurysms to the depth of arterial resection. BACKGROUND: Deep arterial injury is relatively frequent with the use of directional coronary atherectomy, but the potential for subsequent coronary artery aneurysm formation is unknown. METHODS: Results in a consecutive series of 64 successfully treated patients (a total of 69 lesions; mean angiographic follow-up at 5 months) treated with directional coronary atherectomy were retrospectively analyzed with use of quantitative angiographic and histologic data. RESULTS: Coronary aneurysms (ratio of dilated vessel segment to the adjacent reference segment > 1.2:1) occurred in seven patients (10%). The only significant clinical correlate of aneurysm formation was a relatively shorter duration of angina. There were no significant preprocedural angiographic predictors of aneurysms, although 6 (86%) of the 7 aneurysmal lesions arose from restenosis lesions compared with 30 (48%) of 62 lesions with no subsequent aneurysm development (p = 0.06). Histopathologic examination of 414 specimens from 68 treated lesions showed no significant difference in the occurrence of subintimal resection (media +/- adventitia) between those with and without subsequent aneurysm (29% vs. 22%). Media alone was found in 14% of specimens from lesions that later became aneurysmal versus 15% of those that did not; adventitial resection was found in 14% and 7% of specimens, respectively (p = 0.08), with relatively more adventitia per specimen from those with aneurysm (55% vs. 30% without aneurysm, p = 0.08). CONCLUSIONS: Aneurysms occur relatively frequently after directional coronary atherectomy. Although there was no statistically significant correlation with the depth of arterial resection, the evidence from this study suggests that the role of adventitial resection in the occurrence of late aneurysm development should be explored further.

Aged↗