Selected Abstracts > Cardiovascular Disease

Title: Carotid Artery Revascularization in High-Surgical-Risk Patients Using the Carotid WALLSTENT and FilterWire EX/EZ

(J Am Coll Cardiol Jan 2008;51:427-34)

Objectives :The multicenter, single-arm BEACH (Boston Scientific EPI: A Carotid Stenting Trial for High-Risk Surgical Patients) evaluated outcomes in high-surgical-risk patients with carotid artery stenosis treated with the Carotid WALLSTENT plus FilterWire EX/EZ Emboli Protection System (Boston Scientific, Natick, Massachusetts).

Background :Carotid artery stent (CAS) placement offers a less invasive alternative for high-risk surgical carotid endarterectomy (CEA) patients.

 Methods: The trial enrolled 480 pivotal patients who were candidates for carotid revascularization but considered high surgical risk due to pre-specified anatomic criteria and/or medical comorbidities. The primary end point (all stroke, death, or Q-wave myocardial infarction [MI] through 30 days; non-Q-wave MI through 24 h; and ipsilateral stroke or neurologic death through 1 year) was compared with a proportionally weighted objective performance criterion (OPC) of 12.6% for published surgical endarterectomy results in similar patients, plus a pre-specified noninferiority margin of 4%.

Results :Among pivotal patients, 41.2% were at high surgical risk due to comorbid risk factors, and 58.8% due to anatomic risk factors; 76.7% were asymptomatic with flow-limiting carotid stenosis
80%. At 1 year, the composite primary end point occurred in 8.9% (40 of 447), with a repeat revascularization rate of 4.7%. With an upper 95% confidence limit of 11.5% for the primary composite end point, the BEACH trial results met the prespecified criteria for noninferiority relative to the calculated OPC plus noninferiority margin (16.6%) for historical surgical CEA outcomes in similar patients (p  0.0001 for noninferiority).

Conclusions: The BEACH trial results demonstrate that CAS with the WALLSTENT plus FilterWire embolic protection is noninferior (equivalent or better than) to CEA at 1-year in high-surgical-risk patients (Boston Scientific Embolic Protection, Inc. [EPI]: A Carotid Stenting Trial for High-Risk Surgical Patients [BEACH]; http://clinicaltrials.gov/ct2/ show/NCT00316108?termNCT00316108&rank1; NCT00316108).

Title: Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling

J Am Coll Cardiol jan 2008;51:476-86

Objectives We examined whether mitral regurgitation (MR) augments post-myocardial infarction (MI) remodeling.

Background MR doubles mortality after MI, but its additive contribution to left ventricular (LV) remodeling is debated and has not been addressed in a controlled fashion.

Methods Apical MIs were created in 12 sheep, and 6 had an LV-to-left atrial shunt implanted, consistently producing regurgitant fractions of 30%.the groups were compared at baseline,1 and 3 months.  .

Results Left ventricular end-systolic volume progressively increased by 190% with MR versus 90% without MR (p 0.02). Pre-load-recruitable stroke work declined by 82  13% versus 25  16% (p 0.01) with MR, with decreased remote-zone sarcoplasmic reticulum Ca2-ATPase levels (0.56  0.03 vs. 0.76  0.02, p 0.001), and decreased isolated myocyte contractility. In remote zones, pro-hypertrophic Akt and gp130 were upregulated in both groups at 1 month, but significantly lower and below baseline in the MR group at 3 months. Pro-apoptotic caspase 3 remained high in both groups. Matrix metalloproteinase (MMP)-13 and membrane-type MMP-1 were increased in remote zones of MR versus infarct-only animals at 1 month, then fell below baseline. The MMP tissue inhibitors rose from baseline to 3 months in all animals, rising higher in the MI  MR-group border zone.

Conclusions In this controlled model, moderate MR worsens post-MI remodeling, with reduced contractility. Pro-hypertrophic pathways are initially upregulated but subsequently fall below infarct-only levels and baseline; with sustained caspase 3 elevation, transformation to a failure phenotype occurs. Extracellular matrix turnover increases in MR animals. Therefore, MR can precipitate an earlier onset of dilated heart failure.

Title: Relation Between Stress-Induced Myocardial Perfusion Defects on Cardiovascular Magnetic Resonance and Coronary Microvascular Dysfunction in Patients With Cardiac Syndrome X

(J Am Coll Cardiol Jan 2008 ;51:466-72)

Objectives: The purpose of this study was to investigate whether a direct relation can be demonstrated between myocardial perfusion defects detected during dobutamine stress test (DST) by cardiovascular magnetic resonance (CMR) and impairment of coronary mcrovascular dilatory function in patients with cardiac syndrome X (CSX).

Background: Despite the fact that coronary microvascular dysfunction has been shown in most patients with CSX, the ischemic origin of CSX remains debated. No previous study assessed whether a strict relation exists between abnormalities in myocardial perfusion and coronary microvascular dysfunction in CSX patients.

Methods: Eighteen CSX patients (mean age 58
7 years, 7 men) and 10 healthy control subjects (mean age 54 years, 4 men) underwent myocardial perfusion study by gadolinium-enhanced CMR at rest and at peak DST (maximal dose 40
g/kg/min). Coronary flow response (CFR) to adenosine (140
g/kg/min in 90 s) in the left anterior descending (LAD) coronary artery was assessed by high-resolution transthoracic echo-Doppler and expressed as the ratio between coronary flow velocity at peak adenosine and at rest.

Results: At peak DST, reversible perfusion defects on CMR were found in 10 CSX patients (56%) but in none of the control subjects (p 0.004). The CFR to adenosine in the LAD coronary artery was lower in CSX patients than in control subjects (2.03
0.63 vs. 3.29
1.0, p 0.0004). The CSX patients with DST-induced myocardial perfusion defects in the LAD territory on CMR had a lower CFR to adenosine compared with those without perfusion defects in the LAD territory (1.69
0.5 vs. 2.31
0.6, p 0.01). A significant correlation was found in CSX patients between CFR to adenosine and a DST perfusion defect score on CMR in the LAD territory (r0.45, p 0.019).

Conclusions: Our data concurrently show DST-induced myocardial perfusion defects on CMR and reduced CFR in the LAD coronary artery territory in CSX patients, thus giving strong evidence that a dysfunction of coronary microcirculation resulting in myocardial perfusion abnormalities is present in these patients.

Title: Secondary Prevention With Bezafibrate Therapy for the Treatment of Dyslipidemia

(J Am Coll Cardiol Jan 2008;51:459-65)

Objectives This study was designed to evaluate the long-term cardiovascular benefit of bezafibrate therapy in coronary heart disease patients enrolled in the BIP (Bezafibrate Infarction Prevention) trial.

Background The BIP trial yielded a nonsignificant 7.3% reduction in the rate of major cardiac events after a mean follow-up period of 6.2 years, possibly owing to an increasing unbalanced usage of nonstudy lipid-lowering drugs (LLDs) during the course of the trial.

Methods The adjusted risk for the combined end point of cardiac death or nonfatal myocardial infarction during an extended mean 8.2-year follow-up period of the BIP trial was assessed in 3,090 patients allocated to the original bezafibrate (n
1,548) and placebo (n
1,542) groups of the trial.

Results During the extended follow-up period, nonstudy LLDs were administered to a significantly greater proportion of placebo-allocated patients (57%) than bezafibrate-allocated patients (53%; p
0.02). Interaction-term analysis demonstrated that the benefit of bezafibrate therapy was pronounced (18% risk reduction; p
0.03) without or before treatment with nonstudy LLDs initiated during follow-up and attenuated (hazard ratio 1.05; p
0.85) after therapy with nonstudy LLDs initiated during the observation period. Consistent with these findings, treatment with bezafibrate was shown to be associated with a significant 17% risk reduction (p
0.03) when study patients were censored from the analysis upon initiation of therapy with nonstudy LLDs.

Conclusions The data demonstrate that bezafibrate therapy in the BIP trial was associated with significant long-term cardiovascular protection that was attenuated by an unbalanced usage of nonstudy LLDs during the course of the trial.