Impact of drug-eluting stent selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the sirolimus vs paclitaxel drug-eluting stent for left main registry (SP-DELFT).

AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.

Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome.

OBJECTIVE: To determine the differences in the inflammatory status between diabetic and non-diabetic patients and to evaluate the usefulness of C reactive protein, fibrinogen, and leucocyte count as predictors of death in diabetic patients with unstable coronary disease. DESIGN: Nested case-control comparisons of the inflammatory status between diabetic and non-diabetic patients. Prospective cohort analysis of C reactive protein concentration, fibrinogen concentration, and leucocyte count as predictors of cardiovascular death in diabetic patients. SETTING: Coronary care unit in Spain. PARTICIPANTS: 83 diabetic patients with non-ST elevation acute coronary syndrome and 83 sex and aged matched patients selected from 361 non-diabetic patients with non-ST elevation acute coronary syndrome. MAIN OUTCOME MEASURES: Plasma concentrations of C reactive protein and fibrinogen, and leucocyte count. Investigators contacted patients to assess clinical events. RESULTS: Concentrations of C reactive protein and fibrinogen, and leucocyte count on admission were higher in diabetic than in non-diabetic patients (7 mg/l v 5 mg/l, p = 0.020; 3.34 g/l v 2.90 g/l, p = 0.013; and 8.8 x 10(9)/l v 7.8 x 10(9)/l, p = 0.040). Among diabetic patients, these values were also higher in those who died during the 22 month follow up (13 mg/l v 6 mg/l, p = 0.001; 3.95 g/l v 3.05 g/l, p < 0.001; and 11.4 x 10(9)/l v 8.4 x 10(9)/l, p = 0.005). After adjustment for confounding factors, diabetic patients in the highest tertile of C reactive protein had a hazard ratio for cardiovascular death of 4.51 (95% confidence interval (CI) 1.62 to 12.55). Similar hazard ratios were for fibrinogen 3.74 (95% CI 1.32 to 10.62) and for leucocyte count 3.64 (95% CI 1.37 to 9.68). CONCLUSIONS: Inflammation appears more evident in diabetic than in non-diabetic patients with acute coronary syndrome. C reactive protein concentration, fibrinogen concentration, and leucocyte count constitute independent predictors of cardiovascular death in diabetics with unstable coronary disease.

Contrast M-mode power Doppler ultrasound in the detection of right-to-left shunts: utility of submandibular internal carotid artery recording.

Cardiac right-to-left shunts (RLSs) can be detected by echocardiography and transcranial Doppler ultrasound (TCD). In patients without adequate transtemporal bone windows, results may be obtained by insonating extracranial arteries; however, the sensitivity and practicality of this approach is unknown. In 34 patients evaluated with echocardiography for RLSs, 73 studies were performed with unilateral, simultaneous contrast TCD (cTCD) of the middle cerebral artery (MCA) and anterior cerebral artery (ACA) and submandibular power M-mode Doppler (PMD) ultrasound of the extracranial internal carotid artery (ecICA). The number of microbubble (MB) signals and their times of first appearance were determined. RLS volume was graded on 6 levels (I = trace, II = small, III = medium, IVa = large, IVb = shower, IVc = curtain) and compared between MCA and ecICA recordings. In 2 of 24 cTCD studies in 15 patients without evidence of RLSs on single-gated MCA monitoring, low-volume RLSs (grades I and II) were detected via ecICA insonation; in both, MB signatures were tracked in the ecICA, passing into the ipsilateral ACA. In 40 of 49 studies (26 patients) in which RLSs were demonstrated with single-gated MCA monitoring, more MBs were detected in the ecICA than the MCA, with either single-gated or M-mode images, with increases of 76.9% and 66.1%, respectively (P = .027). Compared to single-gated studies, M-mode technology detected nonsignificant increases in MB number in both the MCA and the ecICA (by 20.2% and 14.0%, respectively). Contrast PMD with cervical ICA recording is at least as sensitive and specific as the traditional MCA method in detecting RLSs; furthermore, this method seems to be more sensitive for low-volume RLSs (grades I-III) because of air MB decay (9.2%) and entry into the ipsilateral ACA (34.2%). This is in concordance with the increase of detected RLS grades observed in 32.7% of patients with echocardiography-documented RLSs. The authors therefore suggest the incorporation of ecICA PMD not only in patients with poor ultrasonic bone windows but also in every patient being evaluated for suspected RLSs.

Coronary stenting versus coronary bypass surgery in patients with multiple vessel disease and significant proximal LAD stenosis: results from the ERACI II study.

PURPOSE: To compare percutaneous coronary intervention (PCI) using stent implantation versus coronary artery bypass graft (CABG) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery (LAD). METHODS: 230 patients with multiple vessel disease and severe stenosis of the proximal LAD (113 with PCI, 117 with CABG). They were a cohort of patients from the randomised ERACI (Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease) II study. RESULTS: Both groups had similar baseline characteristics. There were no significant differences in 30 day major adverse cardiac events (death, myocardial infarction, stroke, and repeat procedures) between the strategies (PCI 2.7% v CABG 7.6%, p = 0.18). There were no significant differences in survival (PCI 96.4% v CABG 95%, p = 0.98) and survival with freedom from myocardial infarction (PCI 92% v CABG 89%, p = 0.94) at 41.5 (6) months' follow up. However, freedom from new revascularisation procedures (CABG 96.6% v PCI 73%, p = 0.0002) and frequency of angina (CABG 9.4% v PCI 22%, p = 0.025) were superior in the CABG group. CONCLUSION: Patients with multivessel disease and significant disease of the proximal LAD randomly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infarction at long term follow up. Repeat revascularisation procedures were higher in the PCI group.

Histopathology of coronary in-stent restenosis following gamma brachytherapy.

The histopathology of in-stent restenosis (ISR) following gamma brachytherapy is described. Such histology has not been reported previously. An 82 year old man presented with recurrent ISR three months after gamma brachytherapy to an area of ISR within a native circumflex vessel. The recurrent ISR was treated with directional coronary atherectomy; the histopathology of this directional coronary atherectomy specimen is discussed. These histopathological examinations showed abundant extracellular matrix material. Surprisingly, there was a relatively small cellular (myofibroblastic) component, with an absence of endothelial cells and little evidence of active proliferation. ISR after gamma brachytherapy may be a pathologically distinct entity.

Significant atheromatous debris following uncomplicated vein graft direct stenting: evidence supporting routine use of distal protection devices.

We present the case of an angiographically uncomplicated direct stent vein graft intervention in which the Percusurge embolization containment device was used. We performed histological examination of the resulting debris and observed massive particulate atheromatous material. This case illustrates the severity of distal embolization that can go clinically unnoticed after direct stenting and also supports the routine use of distal protection devices for vein graft intervention.

Adjunctive pharmacotherapy for coronary stenting.

The use of coronary stents improves the outcomes of percutaneous coronary intervention (PCI). This has led to a rapid increase in their use. Coronary stenting is not without problems and is complicated by both early ischemic events and late restenosis. The combination of anticoagulation with unfractionated heparin (UFH) and the use of antiplatelet agents including aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors has led to a major reduction in early ischemic events after stenting. Low molecular weight heparin (LMWH) and direct thrombin inhibitors have a number of theoretical advantages over UFH. Their role as an adjunct to coronary stenting is still under investigation. Trials of systemic pharmacotherapy aimed at reducing in-stent restenosis have been consistently disappointing. Preliminary results of stents coated with agents that inhibit neointimal proliferation are extremely promising. The results of ongoing phase III trials of these coated stents are eagerly awaited.

The use of mechanical devices as adjuncts to intracoronary stenting.

A number of mechanical adjuncts to intracoronary stenting are now available to the interventional cardiologist. These devices have assisted in the development of a safer and more effective stenting practice. Intravascular ultrasound-guided stenting has been shown to reduce the rate of subacute thrombosis and subsequent restenosis. It allows a greater appreciation of lesion structure and severity so that an appropriate intervention strategy can be devised. Debulking techniques may allow the optimal deployment of stents so that restenosis is reduced; however, the results of large randomized studies are still awaited. The use of thrombectomy and distal embolization protection devices is emerging as a safer alternate to stenting alone in difficult patient subsets, such as those with thrombus-laden lesions and degenerated vein grafts. Doppler and pressure wires may be useful in determining optimal stent deployment and predict subsequent patient outcomes. An understanding of the indications and limitations of these devices is of increasing importance to the interventional cardiologist as the coming decade threatens to yield an impressive array of high-tech innovations.

Learning curve of the Inoue technique of percutaneous mitral balloon valvuloplasty.

There is controversy as to whether the double-balloon or the Inoue technique of percutaneous mitral balloon valvuloplasty (PMBV) provides superior immediate and long-term results. This study was undertaken to analyze the effect of the learning curve of the Inoue technique of PMBV in the immediate and long-term outcome of PMBV. The learning curve of Inoue PMBV was analyzed in 233 Inoue PMBVs divided into 2 groups: "early experience" (n = 100) and "late experience" (n = 133). The results of the overall Inoue technique were compared with those of 659 PMBVs performed with the double-balloon technique. Baseline clinical and morphologic characteristics between early and late experience Inoue groups were similar. Post-PMBV mitral valve area (1.89 +/- 0.56 vs 1.69 +/- 0.57 cm(2); p = 0.008) and success rate (60% vs 75.9%; p = 0.009) were significantly higher in the late experience Inoue group. Furthermore, there was a trend for less incidence of severe post-PMBV mitral regurgitation > or = 3+ in the late experience group (6.8% vs 12%; p = 0.16). Although the post-PMBV mitral valve area was larger with the double-balloon technique (1.94 +/- 0.72 vs 1.81 +/- 0.58 cm(2); p = 0.01), the success rate (71.3% vs 69.1%; p = NS), incidence of > or = 3+ mitral regurgitation (9% vs 9%), in-hospital complications, and long-term and event-free survival were similar with both techniques. In conclusion, there is a significant learning curve of the Inoue technique of PMBV. Both the Inoue and the double-balloon techniques are equally effective techniques of PMBV because they resulted in similar immediate success, in-hospital adverse events, and long-term and event-free survival.

Platypnea-orthodeoxia: management by transcatheter buttoned device implantation.

Dyspnea and arterial desaturation on upright position in elderly subjects is described as platypnea-orthodeoxia syndrome (POS) and in some patients it is due to right-to-left shunt across the atrial septal defect (ASD)/patent foramen ovale (PFO). Surgical closure of ASD/PFO has been the only available treatment option. Buttoned device has been used for occlusion of ostium secundum ASD, PFO associated with presumed paradoxical embolism and cerebrovascular accidents and ASD/PFO in association with other congenital heart defects causing right-to-left shunt. The objective of this article is to describe the use of buttoned device in effectively occluding ASD/PFO to relieve hypoxemia of POS. During a 4-year period ending January 2000, 10 patients, ages 71 +/- 9 (range 60-83) years with POS underwent buttoned device closure of their ASD/PFO. Echocardiographic and balloon-stretched atrial defect sizes were 8 +/- 3 mm and 12 +/- 3 mm, respectively. The ASD/PFO were occluded with devices ranging in size from 25 to 40 mm delivered via 9 French, long, blue Cook sheaths; eight had an additional 25- or 35-mm occluder placed on the right atrial side. The oxygen saturation increased (P < 0.001) from 76 +/- 7% (range 69-86%) to 95 +/- 2% (range 92-98%). No complications were encountered. Relief of symptoms was seen in all patients. Follow-up of 1-36 months (median 12 months) revealed persistent improvement of symptoms. Buttoned device occlusion of ASD/PFO to relieve hypoxemia of POS is feasible, safe, and effective and is an excellent alternative to surgery. Cathet Cardiovasc Intervent 2001;54:77-82.

Comparison of self-expanding and balloon-expandable stents for the reduction of restenosis.

To compare the efficacy of self-expanding (SE) and balloon-expandable (BE) stents in native coronary arteries, we randomly assigned 1,096 patients with new and restenotic lesions to receive either device. Baseline demographics and coronary angiographic characteristics were similar in the 2 groups. The incidence of major adverse cardiac events including death, myocardial infarction, bypass surgery, and repeat intervention was similar for both groups at 1 month (2.9% vs 3.1% for SE vs BE, respectively) and at 9 months (19.3% vs 20.1%, SE vs BE respectively). In a subgroup of patients who underwent follow-up angiography (n = 250), the binary restenosis rates (24.2% vs 18.7%, p = 0.30), late loss (0.98 vs 94 mm, p = 0.60), and loss index (0.55 vs 55, p = 0.95) were not significantly different for both groups. In 62 patients who underwent intravascular ultrasound examination (IVUS), there was a trend toward a lower incidence of edge tears in the SE group (6% vs 23%, p = 0.06). Follow-up IVUS analysis showed that the minimum stent area of the SE stent increased by 33% at 6 months, whereas no change occurred in the BE stents; this was accompanied by a greater degree of intimal proliferation in the SE stents compared with BE stents (3.1 +/- 2.0 vs 1.7 +/- 1.7 mm(2)). Thus, the SE stents had similar clinical and angiographic outcomes in patients with lesions in native coronary arteries.

Stroke as a complication of cardiac catheterization: risk factors and clinical features.

The authors aimed to delineate the risk factors and radiologic pattern of stroke complicating cardiac catheterization. Twenty-two cases were matched with three control subjects. Stroke was significantly associated with severity of coronary artery disease and length of fluoroscopy time (OR 1.96 and 1.65). The use of MRI with diffusion weighting allowed the identification of multiple asymptomatic lesions and a subset of lacunar-type infarcts (23%), which most likely occurred on an atheroembolic basis.

Effectiveness of and adverse events after percutaneous coronary intervention in patients with mild versus severe renal failure.

Patients with renal failure undergoing percutaneous coronary intervention (PCI) experience reduced procedural success rates and increased in-hospital and long-term follow-up major adverse cardiac events. This study was designed to determine whether the severity of preprocedural renal failure influences the outcomes of patients with renal failure undergoing PCI. We compared the immediate and long-term outcomes of 192 patients with mild renal failure (creatinine 1.6 to 2.0 mg/dl, mean 1.76) with those of 131 patients with severe renal failure (creatinine >2.0 mg/dl, mean 2.90), selected from 3,334 consecutive patients undergoing PCI between 1994 and 1997. Although the overall population with renal failure represents a high-risk group, the severe renal failure cohort had a higher incidence of hypertension, multivessel disease, prior coronary bypass surgery, vascular disease, and congestive heart failure (all p values <0.05), yet had similar angiographic characteristics. Procedural success was higher in the group with severe renal failure (93.7% vs 87.7%, p = 0.04). There were no statistically significant differences in in-hospital mortality (11.5% vs 9.9%, p = 0.7), Q-wave myocardial infarction (0.5% vs 0%, p = 0.4), emergent bypass surgery (0% vs 0%, p = 1.0), and in-hospital major adverse cardiac events (11.5% vs 9.9%, p = 0.7) between the mild and severe renal groups, respectively. Kaplan-Meier analyses showed no statistically significant difference in long-term survival (log rank test, p = 0.1) or event-free survival (log rank test, p = 0.3) between the 2 groups. Finally, creatinine was not identified as an independent predictor of in-hospital or long-term follow-up major adverse cardiac events. In our high-risk population, patients with mild renal insufficiency undergoing PCI experience major adverse outcomes in the hospital and at long-term follow-up similar to those of patients with severe renal failure.

Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus.

BACKGROUND: Lipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis, which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus. METHODS AND RESULTS: A total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger in specimens from patients with diabetes (7+/-2%) than in specimens from patients without diabetes (2+/-1%; P:=0.01), and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22+/-3%) than in specimens from patients without diabetes (12+/-1%; P:=0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%; P:=0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet. CONCLUSIONS: Coronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus.

Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement.

OBJECTIVES: We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND: Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS: Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. RESULTS: There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance (one patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological event following device placement was 3.2% per year for all patients. CONCLUSION: Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention.

Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era?

BACKGROUND: Patients with end-stage renal disease undergoing conventional balloon angioplasty have reduced procedural success and increased complication rates. This study was designed to determine the immediate and long-term outcomes of patients with varying degrees of renal failure undergoing percutaneous coronary intervention in the current device era. METHODS AND RESULTS: We compared the immediate and long-term outcomes of 362 renal failure patients (creatinine >1.5 mg/dL) with those of 2972 patients with normal renal function who underwent percutaneous coronary intervention between 1994 and 1997. Patients with renal failure were older and had more associated comorbidities. They had reduced procedural success (89.5% versus 92.9%, P:=0.007) and greater in-hospital combined major event (death, Q-wave myocardial infarction, emergent CABG; 10.8% versus 1.8%; P:<0.0001) rates. Renal failure was an independent predictor of major adverse cardiac events (MACEs) (OR, 3.41; 95% CI, 1.84 to 6.22; P:<0.00001). Logistic regression analysis identified shock, peripheral vascular disease, balloon angioplasty strategy, and unstable angina as independent predictors of in-hospital MACEs in the renal group. Compared with 362 age- and sex-matched patients selected from the control group, patients with renal failure had a lower survival rate (27.7% versus 6.1%, P:<0.0001) and a greater MACE rate (51% versus 33%, P:<0.001) at long-term follow-up. Cox regression analysis identified age and PTCA strategy as independent predictors of long-term MACEs in the renal group. Finally, within the renal failure population, the dialysis and nondialysis patients experienced remarkably similar immediate and long-term outcomes. CONCLUSIONS: Although patients with renal failure can be treated with a high procedural success rate in the new device era, they have an increased rate of major events both in hospital and at long-term follow-up. Nevertheless, utilization of stenting and debulking techniques improves immediate and long-term outcomes.