Evaluation of left ventricular relaxation and filling pressures in obstructive hypertrophic cardiomyopathy: comparison between invasive hemodynamics and two-dimensional speckle tracking.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is usually associated with marked diastolic dysfunction, characterized by impaired myocardial relaxation and increased myocardial stiffness. The noninvasive evaluation of diastolic function in these patients remains a challenge since usual methods have shown a modest correlation with invasive measurements of left ventricular (LV) relaxation and filling pressures. METHODS AND RESULTS: We retrospectively analyzed 44 patients with obstructive HCM who underwent cardiac catheterization and echocardiography performed within 48 hours. Standard echocardiographic diastolic parameters and systolic and diastolic myocardial mechanics (including longitudinal and circumferential strain [S] and strain rate [Sr]), LV rotation, and early reverse rotation rate (fraction of early apical reverse rotation [FEARR]) were correlated with diastolic hemodynamic indices. Estimated LA pressure by echo and the LV end-diastolic pressure (LVEDP) or the LV pre-A pressure did not correlate. Longitudinal strain was low and circumferential strain was abnormally higher than normal. FEARR and negative dp/dt inversely correlated (R =-0.57, P = 0.0001), and early diastolic Sr to systolic Sr ratio (SrE/SrS) correlated with the LVEDP (r = 0.61, P < 0.0001). Furthermore, a SrE to SrS ratio ≥ 0.79 had a sensitivity of 87% and a specificity of 75% for predicting elevated LVEDP (≥ 15 mmHg). Average circumferential strain rate during atrial contraction and LV pre-A pressure (r =-0.62, P < 0.001) inversely correlated. CONCLUSIONS: FEARR is decreased in HCM and appears to be a good measure of diastolic dysfunction. Myocardial mechanics can be used to assess LV relaxation and filling pressures in patients with obstructive HCM.

Selective use of embolic protection devices during saphenous vein grafts interventions: a single-center experience.

OBJECTIVES: To report on outcomes with selective use of embolic protection devices (EPD) during percutaneous coronary intervention (PCI) to saphenous vein grafts (SVG). BACKGROUND: PCI to SVG is associated with increased risk and the use of EPD is recommended in this setting. METHODS: Angiographic and clinical outcomes were prospectively obtained from 534 consecutive patients who underwent PCI to SVG with or without EPD at a tertiary cardiac centre. Long-term outcomes were obtained by linkage to a provincial registry. RESULTS: EPD, deployed in 198 of 373 SVGs (53%) suitable for deployment of a distal EPD, were used more often in ectatic (33% vs. 19%, P = 0.003), ulcerated (17% vs. 9%, P = 0.03), thrombotic (26% vs. 10%, P < 0.0001) vein grafts, with longer degenerated segments (P = 0.002), and in lesions involving the body of the graft (85% vs. 66%, P < 0.0001), and less with lesions involving the graft ostium (29% vs. 44%, P = 0.003). Patients suitable for but not receiving EPD tended to be more likely to have a periprocedural myocardial infarction. During 3 years of follow-up, 49% of the patients had a cardiovascular event. Cumulative mortality was 8.4%, 18.8% and 14.7% in patients unsuitable for distal EPD, suitable but without EPD, and with EPD (p = 0.11). Nonuse of EPD was an independent predictor of MACE at 3 years. (P = 0.02). CONCLUSIONS: Selective use of EPD is associated with low in-hospital cardiovascular event rates. Long-term outcomes are manifested by a high rate of events, especially in patients with SVG's suitable for but not receiving EPD. This suggests that routine use of distal EPD may be warranted in unselected patients with suitable SVG anatomy.

Early Structural Deterioration of a Sutureless Bioprosthetic Aortic Valve.

Sutureless bioprosthetic valves such as the Sorin Perceval S valve (SPV) have been used in patients with aortic stenosis that require surgical aortic valve replacement (SAVR). These prostheses have been marketed on the basis of their rapid implantation techniques with avoidance of sutures and reduced aortic cross-clamp times. We report a case of an early failure of a SPV nearly 4 years after implantation in a 58-year-old woman who was low-risk. While the patient's symptoms initially improved with SAVR with a sutureless bioprosthetic valve, they progressively worsened as the valve degraded, and the leaflets became increasingly calcified and stenotic ultimately, requiring reoperative SAVR with a St. Jude mechanical valve. This case raises the issue of the lack of much-needed data describing the long-term durability and hemodynamic performance of these valves, particularly in a low-risk patient with excellent functional status. We hope to shed further insight into the lack of long-term studies on patients with SPV to assess their longevity and long-term effectiveness, as well as elucidation of possible prevention and monitoring of these potential complications. The use of newer generation prostheses, although attractive for their ease of implantation, potentially carries higher long-term risk due to shorter durability leading to reintervention to address valve deterioration. This is especially true in low-risk patients who are young and active. Cardiology and cardiothoracic surgery societies need to develop a universal registry with follow-up of all valves in order to track and study the durability of these valves, and to evaluate for incidence of known and potential complications.

The impact of diabetic status on coronary artery bypass graft patency: insights from the radial artery patency study.

BACKGROUND: Despite worse outcomes in diabetics after coronary artery bypass grafting surgery, studies have not examined graft patency in this high-risk group. This study examined the impact of diabetes on graft patency, 1-year postcoronary artery bypass grafting, using data from a multicenter randomized trial. METHODS AND RESULTS: The Radial Artery Patency Study enrolled 561 patients undergoing coronary artery bypass grafting, comparing graft patency of the saphenous vein (SV) versus radial artery 1-year postcoronary artery bypass grafting. Angiographic follow-up was acquired for 440 patients (115 diabetics, 325 nondiabetics), each with a study radial artery and a control SV graft. Preoperative characteristics were similar. The proportion of small-sized target vessels was greater in diabetics (P=0.04). At 1 year, 33 of 230 study grafts (14.4%) were occluded in the diabetics versus 63 of 650 (9.7%) in the nondiabetics (P=0.052). Multivariable regression found diabetes to be a significant independent predictor of 1-year graft occlusion (relative risk, 1.45; 95% CI, 1.03 to 2.05; P=0.03) along with female gender, SV conduit, and small target-vessel size. A significantly higher proportion of SV grafts were occluded in the diabetics (19% versus 12%, P=0.04). Radial artery grafting was protective in the diabetic cohort (radial artery: 11 of 115 occluded [9.5%] versus SV: 22 of 115 occluded [19.1%], McNemar corrected P=0.05; relative risk, 0.42; 95% CI, 0.16 to 1.01) and nondiabetics (radial artery: 25 of 325 occluded [7.7%] versus SV: 38 of 325 occluded [11.7%], McNemar corrected P=0.11; relative risk, 0.63; 95% CI, 0.35 to 1.10). CONCLUSIONS: Coronary artery bypass grafting occlusions were more common among diabetics versus nondiabetics at 1-year angiography, mainly because of more frequent SV graft failure in diabetics. Radial artery, compared with SV grafting, is protective in both diabetic and nondiabetic patients.

Contemporary management of pregnancy-related coronary artery dissection: A single-centre experience and literature review.

Spontaneous coronary artery dissection (SCAD) is an infrequent event that is most commonly associated with pregnant women or those in the postpartum period. Because of its rarity, the literature describing this condition is confined to sporadic case reports, with few reporting long-term follow-up, and no clear consensus exists on the optimal treatment strategy for these patients. The present article reports a single-centre experience with SCAD, highlighting the issues surrounding its management with a brief description of five cases of pregnancy-associated coronary dissection. The treatment used in these cases ranged from a conservative medical approach to surgical and percutaneous intervention, with one patient proceeding to transplantation. Four of the cases have long-term angiographic follow-up.In addition, a comprehensive review of all previously published cases is presented, and temporal trends in the management strategy are highlighted. Possible pathophysiological mechanisms pertaining to this condition, and the complex diagnostic and therapeutic issues involved, which may affect both patient and fetus, are discussed. Finally, an optimal approach to patients with SCAD, informed by our experience and literature review, is described.

The flow of thin liquid layers on circular cylinders.

The time evolution of a coating layer of liquid on an inclined circular cylindrical substrate is studied experimentally and theoretically. For small-diameter cylinders, the motion of Newtonian liquids, driven by the combined influences of surface tension and gravity, is analyzed using the long-wave or "lubrication" approximation. Computed time-dependent solutions of the lubrication model are in general agreement with our experimental observations. Starting from a slightly-perturbed uniform coating, the full family of evolving flows is shown to depend only on three dimensionless parameters: the inclination angle of the cylinder from the vertical direction, the Bond number representing the ratio of gravity to surface tension effects, and a nondimensional measure of the initial coating thickness. Typically flow is initiated by the well-known Rayleigh-Plateau instability followed by drainage, and also wave propagation if the cylinder is not horizontal. Steady propagation of ring-like structures can occur as well as eventual overtaking, merging and reformation of the rings. We demonstrate that volumetric transport is maximized if the cylinder axis is inclined to, rather than aligned with, the direction of gravity. Results are relevant to the understanding, and potential optimization, of small-scale liquid transport. Such problems arise in the natural and industrial worlds.

Impact of patient and target-vessel characteristics on arterial and venous bypass graft patency: insight from a randomized trial.

BACKGROUND: The purpose of this investigation was to determine optimal patient and target-vessel characteristics to maximize arterial and venous graft patency on the basis of data from a large clinical trial. METHODS AND RESULTS: Angiographic data on 440 radial artery grafts and 440 saphenous vein grafts were analyzed with methodology to account for within-patient clustering. Multivariable models that incorporated patient demographic, operative, anatomic, and postdischarge medical management were constructed to determine predictors of graft occlusion. Radial artery use was strongly protective against graft occlusion at 1 year after adjustment for all covariates, with a larger protective effect seen in women (P=0.05 for a subgroup-by-treatment interaction). Among all grafts, diabetes and small target-vessel diameter were associated with an increased risk of graft occlusion, and grafting to a target vessel with more severe proximal stenosis was associated with a decreased risk of graft occlusion. With regard to gender, radial artery graft occlusion at 1 year occurred in similar proportions of men (8.6%) and women (5.3%, P=0.6), whereas, for saphenous vein grafts the comparable occlusion rates were 12.0% and 23.3% respectively (P=0.02). A history of peripheral vascular disease was associated with an elevated risk of radial artery occlusion but was not associated with early vein graft occlusion (P=0.02 for a subgroup-by-treatment interaction). CONCLUSIONS: Patients benefit from radial artery-coronary artery bypass conduits as opposed to saphenous vein conduits, and this effect is especially strong in women. Small target-vessel size adversely affected graft patency, and grafting to a target vessel with more severe proximal stenosis improved graft patency.

Decreased complication rates using the transradial compared to the transfemoral approach in percutaneous coronary intervention in the era of routine stenting and glycoprotein platelet IIb/IIIa inhibitor use: a large single-center experience.

BACKGROUND: Studies evaluating the efficacy and safety of the transradial approach for percutaneous coronary intervention (PCI) were carried out mainly before the widespread use of stents and glycoprotein (GP) IIb/IIIa inhibitors. We sought to determine the association between the choice of the vascular access site and procedural complications after PCI performed with routine stenting and GP IIb/IIIa inhibition. METHODS: The data source was a prospective registry of 13,499 consecutive cases of PCI at the University Health Network, Toronto, Canada, from April 2000 to September 2006. Logistic regression was used to calculate the probability of selection to the radial access group. Using propensity score methodology, 3,198 patients with femoral access were randomly matched to 3,198 patients with radial access based on clinical, angiographic, and procedural characteristics. Multivariable logistic regression analysis was used to identify the independent predictors of access site-related complications. Major adverse cardiac event was defined as death, myocardial infarction, abrupt vessel closure, or coronary artery bypass surgery. RESULTS: Use of the transradial approach was associated with fewer vascular access complications (1.5% vs 0.6%, P<.001) and a shorter length of hospital stay. Multivariable analysis revealed transradial access (OR 0.39, 95% CI 0.2-0.7) to be an independent predictor of lower risk, whereas primary PCI (OR 4.36, 95% CI 1.4, 13), recent myocardial infarction (OR 2.0 95% CI 1.2, 3.4), age (per 10 years increase: OR 1.37, 95% CI 1.1-1.7) and female gender (0R 2.78 95% CI 1.7, 4.6) were independent predictors of a higher risk of access site complications. CONCLUSIONS: Use of transradial access for PCI is safe and is independently associated with a reduced rate of in-hospital access site complications and reduced length of hospital stay.

Long-term outcomes after percutaneous coronary intervention of bifurcation narrowings.

The optimal approach to percutaneous coronary intervention (PCI) of bifurcation lesions remains unclear, reflecting lack of long-term follow-up and heterogeneity of lesions encountered. We evaluated the long-term outcome of patients undergoing bifurcation PCI followed in the prospective bifurcation registry at the University Health Network, Toronto, Ontario, Canada. Of 526 patients undergoing bifurcation PCI between November 2003 and March 2005, most (n = 406) were treated by main vessel stenting only (n = 266) or crush/culotte stenting (n = 140). After median follow-up of 26.5 months, major adverse cardiac events (MACEs) and Canadian Cardiovascular Society class > or =2 angina occurred in 28.5% and 22.3% of patients in these groups, respectively (p = 0.190), whereas MACE rates were 20.8% for main vessel stenting and 18.7% for crush/culotte stenting (p = 0.670). A low bifurcation angle was associated with better outcomes in the crush/culotte group but had no effect on outcome of patients treated with main vessel stenting only. Use of crush/culotte techniques independently predicted freedom from MACEs or Canadian Cardiovascular Society class > or =2 angina compared with main vessel stenting only (odds ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.029). In conclusion, the use of crush/culotte stenting is safe, with efficacy and MACE rates being similar to main vessel stenting alone. Our observations regarding the effect of lesion characteristics such as bifurcation angle and extent of side branch disease on outcome underscore the need for randomized trials that are inclusive of patients with complex side branch disease.

Impact of renal insufficiency on angiographic, procedural, and in-hospital outcomes following percutaneous coronary intervention.

Patients with chronic renal insufficiency (RI) have higher in-hospital mortality and major adverse cardiac event (MACE) rates after percutaneous coronary intervention (PCI). The mechanisms of this adverse course are not well understood. It was hypothesized that this worse outcome may be caused by inadequate PCI results secondary to more complex coronary anatomy in patients with RI. Baseline, procedural, and outcome variables of all PCI cases at the University Health Network are entered prospectively in the PCI Registry. All PCI cases between April 1, 2000, and October 31, 2005, excluding patients in shock, who had preprocedural creatinine clearance (CrCl) measured were included in this study (n = 10,821 of 11,023 patients). Moderate RI (CrCl <60 ml/min) was evaluated as an independent predictor of procedural outcomes, death, and MACE (defined as death, myocardial infarction, abrupt closure, or coronary artery bypass grafting). Moderate RI (CrCl <60 ml/min) independently predicted the procedural outcomes of worse residual stenosis >20% (p = 0.03), number of undeliverable stents (p = 0.003), and smallest stent diameter (p <0.001). Worst residual stenosis >20% and any undeliverable stent were significantly associated with in-hospital MACEs (odds ratio [OR] 3.97, 95% confidence interval [CI] 3.0 to 5.3, p <0.001 and OR 1.89, 95% CI 1.2 to 2.9, p = 0.002) and mortality (OR 3.82, 95% CI 2.2 to 6.7, p <0.001 and OR 3.0, 95% CI 1.6 to 5.9, p = 0.002). These risks were independent of all other measured variables. In conclusion, moderate to severe RI was a strong predictor of worse procedural results during PCI, which, in turn, were independent predictors of in-hospital MACE and mortality and independent contributors to the higher risk of in-hospital adverse events observed after PCI in patients with RI.

SYNTAX Score and Long-Term Outcomes: The BARI-2D Trial.

BACKGROUND: The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. OBJECTIVES: This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. METHODS: Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. RESULTS: A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p < 0.001). Among patients with low SYNTAX scores (≤22), major cardiovascular events did not differ significantly between revascularization and medical therapy, either in the CABG stratum (26.1% vs. 29.9%, p = 0.41) or in the PCI stratum (17.8% vs. 19.2%, p = 0.84). Among patients with mid/high SYNTAX scores, however, major cardiovascular events were lower after revascularization than with medical therapy in the CABG stratum (15.3% vs. 30.3%, p = 0.02), but not in the PCI stratum (35.6% vs. 26.5%, p = 0.12). CONCLUSIONS: Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305).

Predictors of long-term outcome after crush stenting of coronary bifurcation lesions: importance of the bifurcation angle.

OBJECTIVES: We hypothesized that the bifurcation angle (BA) may affect the outcome of crush stenting (CS) of bifurcation lesions and thus set out to determine the effect of the BA on outcome of patients undergoing coronary bifurcation CS. METHODS: Of 538 bifurcation PCI cases performed between November 2003 and March 2005, 133 were performed using CS (n = 56), balloon CS (n = 71), or reverse CS (n = 6). Patients were divided into low-angle and high-angle groups using the median BA as the cut point. RESULTS: The median BA was 50 degrees. High-angle patients were more likely to be women (33% vs 15%, P = .02), with a prior percutaneous coronary intervention (26% vs 12%. P = .05) and coronary artery bypass grafting (15% vs 5%, P = .05). Procedural success was 98.5% in the low-angle and 95.4% in the high-angle group (P = nonsignificant). Two high-angle patients had acute stent thrombosis, and 1 died in hospital. Four additional high-angle patients (6.1%) and 1 low-angle patient (1.5%) died (P = nonsignificant) during follow-up. Major adverse cardiac events (MACE) occurred more frequently in the high-angle group (22.7% vs 6.2%, P = .007). Bifurcation angle > or = 50 degrees (P = .004), no final kissing balloon inflation (P = .012), and creatinine clearance < 40 mL/min (P = .031) independently predicted MACE. CONCLUSIONS: Bifurcation angle > or = 50 degrees is an independent predictor of MACE after bifurcation CS, in addition to no final kissing balloon inflation and severe renal dysfunction. A high BA confers a setting of increased turbulent flow that is further exacerbated by suboptimal treatment of the crushed side-branch stent. Further study to improve outcome in this subset of patients is warranted.

Comparison of Radial Artery and Saphenous Vein Graft Stenosis More Than 5 Years After Coronary Artery Bypass Grafting.

BACKGROUND: Graft stenosis may be associated with future graft failure. The purpose of this investigation was to compare graft stenosis between radial artery (RA) grafts and saphenous vein grafts (SVGs) at least 5 years postoperatively using the multicenter Radial Artery Patency Study (RAPS) data. METHODS: Two hundred thirty-four patients underwent late invasive angiography after coronary artery bypass operations. The study population consists of 163 patients with thrombolysis in myocardial infarction (TIMI) 3 flow of both the RA graft and study SVGs. Angiograms were reviewed centrally and in a blinded fashion. Graft stenosis was recorded for the proximal anastomosis, graft body, and distal anastomosis; significant stenosis was defined as greater than or equal to 50%. Major adverse cardiac events (MACE) were reported in patients with and those without significant graft stenosis. RESULTS: There was no difference in significant graft stenosis of the patent RA grafts and SVGs (14 of 163 [8.6%] versus 19 of 163 [11.7%]) or in the proximal anastomosis (5 of 163 [3.1%] versus 5 of 163 [3.1%]), graft body (6 of 163 [3.7%] versus 13 of 163 [8.0%]), or distal anastomosis (4 of 163 [2.5%] versus 5 of 163 [3.1%]) considered separately. However, the overall burden of graft body disease was higher in SVGs (p = 0.03). MACE was higher in patients with significant graft stenosis than in patients without stenosis (10 of 28 [35.7%] versus 7 of 135 [5.2%]; p < 0.0001). CONCLUSIONS: There was no significant difference in the rates of significant stenosis of patent RA grafts and SVGs more than 5 years postoperatively. However, the burden of graft body stenosis was less in RA grafts compared with SVGs, suggesting that the RA grafts will continue to outperform the SVGs late after operation.

Coronary bypass graft patency in patients with diabetes in the Bypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: Few studies have compared long-term status of bypass grafts between patients with and without diabetes, and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG. METHODS AND RESULTS: Among 1526 patients in BARI who underwent CABG as initial revascularization, 99 of 292 (34%) with treated diabetes mellitus (TDM) (those on insulin or oral hypoglycemic agents) and 469 of 1234 (38%) without TDM had follow-up angiography. Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention (mean 3.9 years) were reviewed. An average of 3.0 grafts were placed at initial CABG for patients with TDM (n=297; internal mammary artery [IMA], 33%) and 2.9 grafts for patients without TDM (n=1347; IMA, 34%). Patients with TDM were more likely than those without to have small (<1.5 mm) grafted distal vessels (29% versus 22%) and vessels of poor quality (9% versus 6%). On follow-up angiography, 89% of IMA grafts were free of stenoses > or =50% among patients with TDM versus 85% among patients without TDM (P=0.23). For vein grafts, the corresponding percentages were 71% versus 75% (P=0.40). After statistical adjustment, TDM was unrelated to having a graft stenosis > or =50% (adjusted odds ratio, 0.87; 95% CI, 0.58 to 1.32). CONCLUSIONS: Despite diabetic patients' having smaller distal vessels and vessels judged to be of poorer quality, diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up. Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes.

Differential influence of diabetes mellitus on increased jeopardized myocardium after initial angioplasty or bypass surgery: bypass angioplasty revascularization investigation.

BACKGROUND: Data are absent that compare midterm angiographic outcome between patients with and without diabetes after initial percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG). Importantly, diabetes mellitus may differentially influence long-term survival after PTCA or CABG. METHODS AND RESULTS: Patients with multivessel coronary disease who were previously enrolled in the Bypass Angiopathy Revascularization Investigation to compare initial PTCA versus CABG (n=1829) and who had a reduction in jeopardized myocardium after initial revascularization and at least 1 angiogram during 5-year follow-up were analyzed (n=897). This included 369 CABG-treated patients (16% with diabetes) and 528 PTCA-treated patients (18% with diabetes). The influence of diabetes on angiographic increase in percentage of jeopardized myocardium after initial revascularization with either PTCA or CABG was investigated. Among PTCA patients, the mean percentage increase in total jeopardized myocardium was significantly greater in those with diabetes than in those without at 1-year protocol-directed angiography (42% versus 24%, P=0.05) and on the first clinically performed (unscheduled) angiogram within 30 months (63% versus 50%, P=0.01) but not at 5-year protocol-directed angiography (34% versus 26%, P=0.33). This excess midterm risk associated with diabetes persisted after statistical adjustment. In contrast, among CABG patients, diabetes was not associated with percentage increase in jeopardized myocardium at any angiographic follow-up interval. CONCLUSIONS: Presence of diabetes differentially influences worsening of jeopardized myocardium after initial PTCA compared with CABG. This differential effect occurs irrespective of whether follow-up angiography is undertaken for clinical or nonclinical purposes.

Effects of AGI-1067 and probucol after percutaneous coronary interventions.

BACKGROUND: AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control. METHODS AND RESULTS: Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66+/-1.58 mm2 for placebo, 3.69+/-2.69 mm2 for probucol, 2.75+/-1.76 mm2 for AGI-1067 70 mg, 3.17+/-2.26 mm2 for AGI-1067 140 mg, and 3.36+/-2.12 mm2 for AGI-1067 280 mg (P=0.02 for the dose-response relationship; P< or =0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm3 of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P=0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P=0.02). CONCLUSIONS: AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.

Native coronary disease progression exceeds failed revascularization as cause of angina after five years in the Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: Coronary angiograms obtained five years following revascularization were examined to assess the extent of compromise in myocardial perfusion due to failure of revascularization versus progression of native disease. BACKGROUND: The Bypass Angioplasty Revascularization Investigation (BARI) randomized revascularization candidates between bypass surgery and angioplasty. Entry and five-year angiograms from 407 of 519 (78%) patients at four centers were analyzed. METHODS: Analysis of the distribution of coronary vessels and stenoses provided a measure of myocardial jeopardy that correlates with presence of angina. The extent to which initial benefits of revascularization were undone by failed revascularization versus native disease progression was assessed. RESULTS: Myocardial jeopardy fell following initial revascularization, from 60% to 17% for percutaneous coronary intervention (PCI)-treated patients compared with 60% to 7% for coronary artery bypass graft (CABG) surgery patients (p < 0.001), rebounding at five years to 25% for PCI and 20% for surgery patients (p = 0.01). Correspondingly, angina prevalence was higher at five years in PCI-treated patients than in surgery-treated patients (28% vs. 18%; p = 0.03). However, myocardial jeopardy at five years, and not initial treatment (PCI vs. surgery), was independently associated with late angina. Increased myocardial jeopardy from entry to five-year angiogram occurred in 42% of PCI-treated patients and 51% of CABG-treated patients (p = 0.06). Among the increases in myocardial jeopardy, two-thirds occurred in previously untreated arteries. CONCLUSIONS: Native coronary disease progression occurred more often than failed revascularization in both PCI- and CABG-treated patients as a cause of jeopardized myocardium and angina recurrence. These results support intensive postrevascularization risk-factor modification.

Hypertrophic obstructive cardiomyopathy: comparison of outcomes after myectomy or alcohol ablation adjusted by propensity score.

OBJECTIVE: In November 1998, our center began offering alcohol ablation as an alternative to surgical myectomy for patients with hypertrophic obstructive cardiomyopathy. Patients with concomitant lesions were referred for surgical intervention, and the others were offered either treatment option. We sought to review the early outcomes for both protocols. METHODS: One hundred fifty patients had intervention for hypertrophic obstructive cardiomyopathy to June 30, 2003. Sixty patients elected to have alcohol ablation, and 5 crossed over to surgical intervention. A total of 95 patients had a myectomy. Patients having an isolated myectomy (n = 48) are compared with those who had an ablation. Hospital records were reviewed, and follow-up contact (mean, 2.2 years) with the patient or referring cardiologist and recent echocardiographic reports were obtained. Differences in clinical and hemodynamic outcomes between achieved treatment groups were compared after adjustment for differing baseline patient characteristics, including use of a propensity score, to adjust for the non-randomization. RESULTS: The patients undergoing alcohol ablation (n = 60) were older (58 vs 48 years) and had fewer associated lesions (1 vs 39 patients), lower pressure gradients (67 vs 73 mm Hg), and similar symptomatic status and degrees of mitral regurgitation compared with those in the myectomy group. Alcohol ablation was abandoned in 6 patients, 5 of whom underwent myectomy. Among the completed alcohol ablations, there were 5 late deaths, and 1 other patient was referred for myectomy. One late death occurred after myectomy. At latest follow-up, 3-year survival is 97%, and 92% of the patients are in New York Heart Association class II or I. Adjusted comparisons showed significantly lower postintervention left ventricular outflow gradients at rest in the myectomy group (5 vs 15 mm Hg), with provocation (14 vs 42 mm Hg), mitral systolic anterior motion (67% vs 29%), and New York Heart Association class. No significant difference was present in postintervention septal thickness or freedom from postintervention pacing, although in time-related analysis, the 3-year freedom from pacing is 88% versus 59% (P = .02), favoring myectomy. CONCLUSION: Either alcohol ablation or myectomy offers substantial clinical improvement for patients with hypertrophic obstructive cardiomyopathy. Hemodynamic resolution of the obstruction and its sequelae is more complete with myectomy. Residual lesions after alcohol ablation might affect longer-term outcomes.

N-acetylcysteine reduces contrast-associated nephropathy but not clinical events during long-term follow-up.

BACKGROUND: Contrast-associated nephropathy (CAN) is associated with increased morbidity and mortality following percutaneous coronary intervention (PCI). N-acetylcysteine (NAC) has been shown to reduce the risk of nephropathy; however, the impact of NAC on long-term clinical outcomes has not been assessed. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 180 patients with moderate renal dysfunction undergoing PCI or coronary angiography with a high likelihood of ad hoc PCI; 171 patients completed the clinical follow-up. Patients received oral NAC (2000 mg/dose, n = 95) or placebo (n = 85) twice a day for 3 doses if randomized the night prior to the procedure, and 2 doses if randomized the day of the procedure. The primary end point was the incidence of a > or =25% increase in serum creatinine level 48 to 72 hours after PCI. Secondary end points were the inhospital incidence of death, nonfatal myocardial infarction, or urgent dialysis, and the 9-month incidence of death, nonfatal myocardial infarction, need for dialysis, or repeat hospitalization for cardiac reasons. RESULTS: CAN occurred in 9.6% of patients assigned to NAC and 22.2% of patients assigned to placebo (P =.04); 1 patient receiving NAC required urgent dialysis. The inhospital composite end point occurred in 7 (7.4%) NAC-treated and 3 (3.5%) placebo-treated patients, P = NS. At 9 months, the composite end point occurred in 23 (24.2%) NAC-treated patients and 18 (21.2%) placebo-treated, P = NS. CONCLUSION: Although high-dose NAC prevented periprocedural CAN, this benefit did not translate into a decrease in adverse outcomes over 9 months. Further studies to determine the clinical utility of this drug are required.

Usefulness of myocardial contrast echocardiographic quantification of risk area for predicting postprocedural complications in patients undergoing septal ethanol ablation for obstructive hypertrophic cardiomyopathy.

Septal ethanol ablation (SEA) is an alternative to surgical myectomy in patients who have drug-refractory obstructive hypertrophic cardiomyopathy. However, permanent atrioventricular conduction block is seen more frequently with SEA. To determine whether septal infarction risk area (SIRA) predicts outcome in patients who have obstructive hypertrophic cardiomyopathy and are undergoing SEA, we evaluated 51 patients (mean age 60 +/- 16, 53% women) who had a successful SEA at Toronto General Hospital (November 1998 to June 2003). Intracoronary myocardial contrast echocardiography that targeted the contact area between the septum and the anterior mitral leaflet was performed before ethanol injection. End-systolic myocardial contrast echocardiographic frames were color coded for better delineation of contrast borders, and myocardial contrast echocardiographic area was calculated by planimetry. Patients were assigned to 1 of 2 groups by median SIRA value (3.51 cm(2), range 0.4 to 7.8). The 2 groups did not differ significantly in age, medication before SEA, electrocardiographic characteristics, left ventricular function, left atrial diameter, volume of intracoronary ethanol injected, peak creatine kinase after ablation, and baseline and follow-up left ventricular outflow tract gradients at rest. Patients in the large SIRA group had greater hypertrophy and a larger septal artery than did patients in the small SIRA group. In the small SIRA group, 3 patients (11.5%) had pacemaker implantation; in the large SIRA group, 12 patients (48.0%) had complications after SEA (pacemaker in 5 patients, implantable defibrillator in 5 patients, death in 2 patients; p = 0.008). We conclude that patients who have hypertrophic cardiomyopathy with a small, well-localized SIRA benefit similarly from SEA as patients who have a larger SIRA but with significantly fewer serious complications.