Kenneth M. Kent

Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy

Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialisation of the stent struts. We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimus-eluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.

Patterns and Mechanisms of In-Stent Restenosis A Serial Intravascular Ultrasound Study

BACKGROUND Studies have suggested that restenosis within Palmaz-Schatz stents results from neointimal hyperplasia or chronic stent recoil and occurs more frequently at the articulation. METHODS AND RESULTS Serial intravascular ultrasound (IVUS) was performed after intervention and at follow-up in 142 stents in 115 lesions. IVUS measurements (external elastic membrane [EEM], stent, and lumen cross-sectional areas [CSAs] and diameters) were performed, and plaque CSA (EEM lumen in reference segments and stent lumen in stented segments), late lumen loss (delta lumen), remodeling (delta EEM in reference segments and delta stent in stented segments), and tissue growth (delta plaque) were calculated. After intervention, the lumen tended to be smallest at the articulation because of tissue prolapse. At follow-up, tissue growth was uniformly distributed throughout the stent; the tendency for greater neointimal tissue accumulation at the central articulation reached statistical significance only when normalized for the smaller postintervention lumen CSA. In stented segments, late lumen area loss correlated strongly with tissue growth but only weakly with remodeling. Stents affected adjacent vessel segments; remodeling progressively increased and tissue growth progressively decreased at distances from the edge of the stent. These findings were similar in native arteries and saphenous vein grafts and in lesions treated with one or two stents. There was no difference in the postintervention or follow-up lumen (at the junction of the two stents) when overlapped were compared with nonoverlapped stents. CONCLUSIONS Late lumen loss and in-stent restenosis were the result of neointimal tissue proliferation, which tended to be uniformly distributed over the length of the stent.

Angiographic Patterns of In-Stent Restenosis Classification and Implications for Long-Term Outcome

BACKGROUND The angiographic presentation of in-stent restenosis (ISR) may convey prognostic information on subsequent target vessel revascularizations (TLR). METHODS AND RESULTS We developed an angiographic classification of ISR according to the geographic distribution of intimal hyperplasia in reference to the implanted stent. Pattern I includes focal (< or =10 mm in length) lesions, pattern II is ISR>10 mm within the stent, pattern III includes ISR>10 mm extending outside the stent, and pattern IV is totally occluded ISR. We classified a total of 288 ISR lesions in 245 patients and verified the angiographic accuracy of the classification by intravascular ultrasound. Pattern I was found in 42% of patients, pattern II in 21%, pattern III in 30%, and pattern IV in 7%. Previously recurrent ISR was more frequent with increasing grades of classification (9%, 20%, 34%, and 50% for classes I to IV, respectively; P=0.0001), as was diabetes (28%, 32%, 39%, and 48% in classes I to IV, respectively; P<0.01). Angioplasty and stenting were used predominantly in classes I and II, whereas classes III and IV were treated with atheroablation. Final diameter stenosis ranged between 21% and 28% (P=NS among ISR patterns). TLR increased with increasing ISR class; it was 19%, 35%, 50%, and 83% in classes I to IV, respectively (P<0.001). Multivariate analysis showed that diabetes (odds ratio, 2.8), previously recurrent ISR (odds ratio, 2. 7), and ISR class (odds ratio, 1.7) were independent predictors of TLR. CONCLUSIONS The introduced angiographic classification is prognostically important, and it may be used for appropriate and early patient triage for clinical and investigational purposes.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA): A report from the PTCA registry of the national heart, lung, and blood institute

The results of follow-up angiography in patients from 27 clinical centers enrolled in the PTCA Registry were analyzed to evaluate restenosis after PTCA. Of 665 patients with successful PTCA, 557 (84%) had follow-up angiography (median follow-up 188 days). Restenosis, defined as an increase of at least 30% from the immediate post-PTCA stenosis to the follow-up stenosis or a loss of at least 50% of the gain achieved at PTCA, was seen in 187 patients (33.6%). The incidence of restenosis in patients who underwent follow-up angiography was highest within the first 5 months after PTCA. Restenosis was found in 56% of patients with definite or probable angina after PTCA and in 14% of patients without angina after PTCA. Twenty-four percent of patients with restenosis did not have either definite or probable angina. Multivariate analysis selected 4 factors associated with increased rate of restenosis: male sex, PTCA of bypass graft stenosis, severity of angina before PTCA and no history of MI before PTCA.

Arterial Remodeling After Coronary Angioplasty A Serial Intravascular Ultrasound Study

BACKGROUND Restenosis occurs after 30% to 50% of transcatheter coronary procedures; however, the natural history and pathophysiology of restenosis are still incompletely understood. METHODS AND RESULTS Serial (postintervention and follow-up) intravascular ultrasound imaging was used to study 212 native coronary lesions in 209 patients after percutaneous transluminal coronary angioplasty, directional coronary atherectomy, rotational atherectomy, or excimer laser angioplasty. The external elastic membrane (EEM) and lumen cross-sectional areas (CSA) were measured; plaque plus media (P+M) CSA was calculated as EEM minus lumen CSA. The anatomic slice selected for serial analysis had an axial location within the target lesion at the smallest follow-up lumen CSA. At follow-up, 73% of the decrease in lumen (from 6.6+/-2.5 to 4.0+/-3.7 mm2, P<.0001) was due to a decrease in EEM (from 20.1+/-6.4 to 18.2+/-6.4 mm2, P<.0001); 27% was due to an increase in P+M (from 13.5+/-5.5 to 14.2+/-5.4 mm2, P<.0001). Delta Lumen CSA correlated more strongly with delta EEM CSA (r=.751, P<.0001) than with delta P+M CSA (r=.284, P<.0001). Delta EEM was bidirectional; 47 lesions (22%) showed an increase in EEM. Despite a greater increase in P+M (1.5+/-2.5 versus 0.5+/-2.0 mm2, P=.0009), lesions exhibiting an increase in EEM had (1) no change in lumen (-0.1+/-3.3 versus 3.6+/-2.3 mm2, P<.0001), (2) a reduced restenosis rate (26% versus 62%, P<.0001), and (3) a 49% frequency of late lumen gain (versus 1%, P<.0001) compared with lesions with no increase in EEM. CONCLUSIONS Restenosis appears to be determined primarily by the direction and magnitude of vessel wall remodeling (delta EEM). An increase in EEM is adaptive, whereas a decrease in EEM contributes to restenosis.

Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.

Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease.

Although coronary angiography defines regions of potential ischemia in patients with coronary-artery disease, accurate assessment of the presence and functional importance of ischemia requires appraisal of regional and global left ventricular function during stress. To perform such assessment, we developed a noninvasive real-time radionuclide cineangiographic procedure permitting continuous monitoring and analysis of left ventricular function during exercise. In 11 patients with coronary disease who had normal regional and global ventricular function at rest, new regions of dysfunction developed during exercise (P less than 0.001), and in 10, global ejection fraction dropped 7 to 47 per cent. Fourteen age-matched normal subjects were studied; during exercise none had regional dysfunction, and each increased global ejection fraction (average increase, 23 +/- 3 per cent [+/-S.E.], P less than 0.001 as compared with patients with coronary disease). Radionuclide cineangiography during exercise permits accurate assessment of the presence and functional severity of ischemic heart disease.

Correlates and Long-Term Outcomes of Angiographically Proven Stent Thrombosis With Sirolimus- and Paclitaxel-Eluting Stents

Background— Stent thrombosis (ST) is a serious complication of drug-eluting stent (DES) implantation regardless of the timing (acute, subacute, or late). The correlates of ST with DES are not yet completely elucidated. Methods and Results— From a total cohort of 2974 consecutive patients treated with DES since April 2003, we identified 38 patients who presented with angiographic evidence of ST (1.27%). The ST occurred acutely in 5 patients, subacutely (≤30 days) in 25 patients, and late (>30 days) in 8 patients. The clinical, angiographic, and procedural variables of these patients were compared with the remaining 2936 consecutive patients who underwent DES implantation and did not experience ST during a follow-up of 12 months. Logistic regression analysis was conducted to determine the correlates of ST. Compared with patients without ST, patients with ST had a higher frequency of diabetes, acute postprocedural renal failure, and chronic renal failure. There were more bifurcation lesions, type C lesions, and a trend for smaller-diameter stents. Discontinuation of clopidogrel was higher in these patients (36.8% versus 10.7%; P<0.0001). The mean duration to ST from the stent implantation was 8.9±8.5 days in subacute and 152.7±100.4 days in late thrombosis cases. Mortality was significantly higher in patients with ST compared with those without ST at 6 months (31% versus 3%; P<0.001). Multivariate analysis detected cessation of clopidogrel therapy, renal failure, bifurcation lesions, and in-stent restenosis as significant correlates of ST (P<0.05). Conclusions— ST continues to be a serious complication of contemporary DES use. Careful management is warranted in patients with renal failure and in those undergoing treatment for in-stent restenosis and bifurcations. Special focus on clopidogrel compliance may minimize the incidence of ST after DES implantation.

The Prognostic Implications of Further Renal Function Deterioration Within 48 h of Interventional Coronary Procedures in Patients With Pre-existent Chronic Renal Insufficiency

BACKGROUND Acute deterioration in renal function is a recognized complication after coronary angiography and intervention. OBJECTIVES The goal of this study was to determine the impact on acute and long-term mortality and morbidity of contrast-induced deterioration in renal function after coronary intervention. METHODS We studied 439 consecutive patients who had a baseline serum creatinine > or = 1.8 mg/dL (159.1 /micromol/L) who were not on dialysis who underwent percutaneous coronary intervention in a tertiary referral center. All patients were hydrated before the procedure, and almost all received ioxaglate meglumine; 161 (37%) patients had an increase in serum creatinine > or = 25% within 48 h or required dialysis and 278 (63%) did not. In-hospital and out-of-hospital clinical events (death, myocardial infarction, repeat revascularization) were assessed by source documentation. RESULTS Independent predictors of renal function deterioration were left ventricular ejection fraction (p = 0.02) and contrast volume (p = 0.01). In-hospital mortality was 14.9% for patients with further renal function deterioration versus 4.9% for patients with no creatinine increase (p = 0.001); other complications were also more frequent. Thirty-one patients required hemodialysis; their in-hospital mortality was 22.6%. Four patients were discharged on chronic dialysis. The cumulative one-year mortality was 45.2% for those who required dialysis, 35.4% for those who did not require dialysis and 19.4% for patients with no creatinine increase (p = 0.001). Independent predictors of one-year mortality were creatinine elevation (p = 0.0001), age (p = 0.03) and vein graft lesion location (p = 0.08). CONCLUSIONS For patients with pre-existing renal insufficiency, renal function deterioration after coronary intervention is a marker for poor outcomes. This is especially true for patients who require dialysis.

Coronary Artery Narrowing in Coronary Heart Disease: Comparison of Cineangiographic and Necropsy Findings

Of 10 patients with fatal coronary heart disease undergoing coronary angiography 0 to 69 d (average, 21) before necropsy, the amount of narrowing in 61 coronary arteries observed angiographically (diameter reduction) during life by three angiographers was compared with that observed histologically (cross-sectional area) at necropsy. No overestimations of the degree of narrowing were made angiographically. Of 11 coronary arteries or their subdivisions narrowed 0 to 50% in cross-sectional area histologically, none were underestimated angiographically; of eight narrowed 51% to 75% histologically, seven had been underestimated, and of 42 narrowed 76% to 100% histologically, 17 were underestimated angiographically. The coronary atherosclerotic plaquing was diffuse (greater than 25% cross-sectional area narrowing) in 90% of 467 five-millimetre segments of coronary artery examined (24 cm per patient), and this diffuseness of the atherosclerotic process seems to be the major reason for angiographic underestimation of coronary narrowings.