Khaled M. Ziada

Extent and Direction of Arterial Remodeling in Stable Versus Unstable Coronary Syndromes An Intravascular Ultrasound Study

BACKGROUNDnThe morphological characteristics of coronary plaques in patients with stable versus unstable coronary syndromes have been described in vivo with intravascular ultrasound, but the relationship between arterial remodeling and clinical presentation is not well known.nnnMETHODS AND RESULTSnWe studied 85 patients with unstable and 46 patients with stable coronary syndromes using intravascular ultrasound before coronary intervention. The lesion site and a proximal reference site were analyzed. The remodeling ratio (RR) was defined as the ratio of the external elastic membrane (EEM) area at the lesion to that at the proximal reference site. Positive remodeling was defined as an RR >1.05 and negative remodeling as an RR <0.95. Plaque area (13.9+/-5.5 versus 11.1+/-4.8 mm(2); P=0.005), EEM area (16.1+/-6.2 versus 13.0+/-4.8 mm(2); P=0. 004), and the RR (1.06+/-0.2 versus 0.94+/-0.2; P=0.008) were significantly greater at target lesions in patients with unstable syndromes than in patients with stable syndromes. Positive remodeling was more frequent in unstable than in stable lesions (51. 8% versus 19.6%), whereas negative remodeling was more frequent in stable lesions (56.5% versus 31.8%) (P=0.001).nnnCONCLUSIONSnPositive remodeling and larger plaque areas were associated with unstable clinical presentation, whereas negative remodeling was more common in patients with stable clinical presentation. This association between the extent of remodeling and clinical presentation may reflect a greater tendency of plaques with positive remodeling to cause unstable coronary syndromes.

High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults Evidence From Intravascular Ultrasound

Background—Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. Methods and Results—Intravascular ultrasound was performed in 262 heart transplant recipients 30.9±13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4±13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness ≥0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals <20 years old to 85% in subjects ≥50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08±0.48 mm and 32.7±15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). Conclusions—This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.

Arterial remodeling and coronary artery disease: the concept of “dilated” versus “obstructive” coronary atherosclerosis

Traditionally, the development of coronary artery disease (CAD) was described as a gradual growth of plaques within the intima of the vessel. The outer boundaries of the intima, the media and the external elastic membrane (EEM), were thought to be fixed in size. In this model plaque growth would always lead to luminal narrowing and the number and severity of angiographic stenoses would reflect the extent of coronary disease. However, histologic studies demonstrated that certain plaques do not reduce luminal size, presumably because of expansion of the media and EEM during atheroma development. This phenomenon of arterial remodeling was confirmed in necropsy specimens of human coronary arteries. More recently, the development of contemporary imaging technology, particularly intravascular ultrasound, has allowed the study of arterial remodeling in vivo. These new imaging modalities have confirmed that plaque progression and regression are not closely related to luminal size. In this review, we will analyze the role of remodeling in the progression and regression of native CAD, as well as its impact on restenosis after coronary intervention.

Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials.

Background—Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. Methods and Results—A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P =0.006) and 6 months (4.7% versus 2.0%, P <0.001). Revascularization of a graft was identified as an independent predictor of death, myocardial infarction, or revascularization at 6 months (hazard ratio, 1.42; 95% CI, 1.24 to 1.63;P <0.001). Among patients undergoing graft PCI, the incidence of the triple end point at 30 days was 16.5% in the platelet GP IIb/IIIa inhibitor group and 12.6% in the placebo group (odds ratio, 1.38; 95% CI, 0.85 to 2.24;P =0.18). At 6 months, 39.4% of patients randomized to GP IIb/IIIa inhibitors and 32.7% of patients allocated to placebo had an ischemic event (hazard ratio, 1.29; 95% CI, 0.97 to 1.72;P =0.07). Conclusions—Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.

Delayed Lead Perforation: A Disturbing Trend

Background: Delayed lead perforation (occurring more than 1 month after implantation) is a rare complication. Its pathophysiology and optimal management are currently unclear.

Plasma B-Type Natriuretic Peptide Levels Predict Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery

Background—Postoperative (postop) atrial fibrillation (AF) occurs in up to 60% of patients after cardiac surgery, leading to longer hospital stays and increased healthcare costs. Recently, B-type natriuretic peptide (BNP) has been reported to predict occurrence of nonpostoperative AF. This study evaluates whether elevated preoperative (preop) plasma BNP levels predict the occurrence of postop AF. Methods and Results—One hundred eighty-seven patients with no history of atrial arrhythmia who had a preoperative BNP level and had undergone cardiac surgery were identified. Their records were reviewed, and postoperative ECG and telemetry strips were analyzed for AF until the time of discharge. Postop AF was documented in 80 patients (42.8%). AF patients were older (68±11 versus 64±14 years, P =0.04), but there was no difference in sex distribution, hypertension, left ventricular (LV) function, LV hypertrophy (LVH), left atrial size, history of coronary artery disease (CAD), or β-blocker use. Preop plasma BNP levels were higher in the postop AF patients (615 versus 444 pg/mL, P =0.005). After adjustment for age, sex, type of surgery, hypertension, LV function, LVH, left atrial size, CAD, and β-blocker use, the odds ratios of postop AF according to increasing quartiles, compared with patients with lowest quartile, were 1.8, 2.5, and 3.7 (Ptrend=0.03). Conclusions—An elevated preop plasma BNP level is a strong and independent predictor of postop AF. This finding has important implications for identifying patients at higher risk of postop AF who could be considered for prophylactic antiarrhythmic or β-blocker therapy.

Development of Transplantation Vasculopathy and Progression of Donor-Transmitted Atherosclerosis Comparison by Serial Intravascular Ultrasound Imaging

BACKGROUNDnTransplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy. We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound.nnnMETHODS AND RESULTSnIntravascular ultrasound examination was performed in 93 patients at 27.2+/-15.0 and 369. 7+/-23.9 days after transplantation. The maximally and minimally diseased sites were selected in each segment as defined by Coronary Artery Surgery Study classification. For each matched site, maximal plaque thickness was measured. Lesions (maximum plaque thickness >/=0.5 mm) present at baseline examination were defined as donor lesions. On follow-up, lesions that developed at previously normal sites were defined as de novo lesions. The distribution and severity of donor and de novo lesions were similar in proximal, mid, and distal segments. The de novo lesions were less focal (43% vs 74%) and more circumferential (69% vs 45%) compared with the donor lesions, but there was significant morphological heterogeneity. Similar numbers of patients with and those without donor lesions developed de novo lesions. Moreover, progression of donor lesions was not associated with the presence or absence of de novo lesions.nnnCONCLUSIONSnDifferentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult. Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction. This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other.

Coronary Plaque Morphology and Frequency of Ulceration Distant From Culprit Lesions in Patients With Unstable and Stable Presentation

Objective—Intravascular ultrasound studies describe ruptured coronary plaques at sites remote from the culprit lesion in patients with acute myocardial infarction (MI), suggesting multifocal plaque vulnerability. However, the role of intravascular ultrasound in the diagnosis of lesion vulnerability before rupture is unclear. Methods and Results—We compared morphology and frequency of ulceration of additional plaques proximal to the culprit lesion in 105 patients treated with emergent stenting during an evolving, acute MI in the CADILLAC study and 92 patients with stable/subacute presentation who underwent elective stenting. Additional plaques proximal to the culprit lesion were found in 52 (50%) and 54 (59%) patients in the acute MI and stable/subacute group, respectively. The prevalence of ulceration was significantly higher in the acute MI than in the stable/subacute group (19% versus 4%; P =0.014). However, there was no significant difference in other morphological lesion characteristics. Conclusions—Additional plaques are frequently found adjacent to the culprit lesions in patients undergoing percutaneous coronary intervention independent of clinical presentation. The increased prevalence of plaque ulceration but otherwise similar morphology of additional lesions in patients with acute MI versus stable/subacute presentation demonstrates the limitations of imaging in the assessment of plaque vulnerability.

Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study

OBJECTIVESnWe sought to determine the role of conventional atherosclerosis risk factors in the development and progression of transplant coronary artery disease (CAD) using serial intravascular ultrasound imaging.nnnBACKGROUNDnTransplant artery disease is a combination of allograft vasculopathy and donor atherosclerosis. The clinical determinants for each of these disease processes are not well characterized. Intravascular ultrasound imaging is the most sensitive tool to serially study these processes.nnnMETHODSnBaseline intravascular ultrasound imaging was performed 0.9 +/- 0.5 months after transplantation to identify donor atherosclerosis. Follow-up imaging was performed at 1.0 +/- 0.07 year to evaluate progression of donor atherosclerosis and development of transplant vasculopathy. Conventional risk factors for CAD included recipient age, gender, smoking history, diabetes mellitus, hypertension and hypercholesterolemia.nnnRESULTSnDonor-transmitted atherosclerosis was present in 36 patients (39%). At follow-up, progression of donor lesions was seen in 15 patients (42%) and 42 patients (45%) developed transplant vasculopathy, leaving 35 patients (38%) without any disease. There was no difference in any conventional risk factors in patients with and without allograft vasculopathy. However, the severity of allograft vasculopathy was associated with a larger increase in low density lipoprotein (LDL) cholesterol from baseline (p = 0.02). High one-year posttransplant serum triglyceride level and pretransplant body mass index were the only significant predictors (p = 0.03) for progression of donor atherosclerosis.nnnCONCLUSIONSnConventional atherosclerosis risk factors do not predict development of allograft vasculopathy, but greater change in serum LDL cholesterol level during the first year after transplant is associated with more severe vasculopathy. Therefore, maintenance of LDL cholesterol as close to pretransplant values as possible may help to limit the rate of progression of acquired allograft vasculopathy.

Intravascular ultrasound imaging after cardiac transplantation: advantage of multi-vessel imaging

BACKGROUNDnIntravascular ultrasound is a sensitive tool to study transplant vasculopathy. However, there is no consensus regarding the methodology for imaging protocol. The impact of single versus multiple epicardial vessel imaging in determining the prevalence of transplant vasculopathy has not been determined. This study examines the benefit of three-vessel imaging versus one-vessel imaging in detecting transplant vasculopathy.nnnMETHODS AND RESULTSnOne hundred eleven transplant recipients with intravascular ultrasound imaging at baseline (within 2 months of transplantation) were studied: 107 at 1-year, 53 at 2-year and 41 at 3-year follow-up. A total of 222 arteries, 519 segments and 772 sites were analyzed (94 LAD, 65 LCX and 65 RCA). The prevalence of transplant vasculopathy lesions was 27%, 41% and 58% at 1 year, 39%, 55% and 71% at 2 years and 39%, 55% and 74% at 3 years for patients with one-, two- and three-vessel imaging, respectively. Single- or two-vessel disease was present in 23% (7) and 32% (10) patients with three-vessel imaging, leading to the potential mislabeling of these 17 (55%) patients as disease free if they underwent only single-vessel imaging.nnnCONCLUSIONSnMultivessel imaging is more sensitive in detecting the transplant vasculopathy lesions compared to single-vessel imaging. This important variable should be considered when designing and interpreting trials utilizing intravascular imaging derived end-point.