Myocardial perfusion grade after late infarct artery recanalization is associated with global and regional left ventricular function at one year: analysis from the Total Occlusion Study of Canada-2.

BACKGROUND: Whether myocardial perfusion grade (MPG) following late recanalization of infarct-related arteries (IRAs) predicts left ventricular (LV) function recovery beyond the acute phase of myocardial infarction (MI) is unknown. METHODS AND RESULTS: The Total Occlusion Study of Canada-2 enrolled stable patients with a persistently occluded IRA beyond 24 hours and up to 28 days post-MI. We studied the relationship between the initial MPG and changes in LV function and volume as well as the change in MPG from immediate post-percutaneous coronary intervention (PCI) to 1 year in 139 PCI patients with thrombolysis in myocardial infarction grade 3 epicardial flow post-PCI and with paired values grouped into impaired or good MPG groups (MPG 0/1 or MPG 2/3). MPG 0/1 patients were more likely to have received thrombolytic therapy and to have a left anterior descending IRA. They had lower blood pressure and LV ejection fraction (LVEF) and a higher heart rate and systolic sphericity index at baseline. Changes in the MPG 0/1 and MPG 2/3 groups from baseline to 1 year were LVEF, 3.3±9.0% and 4.8±8.9% (P=0.42); LV end-systolic volume index (LVESVI), -1.1±9.2 and -4.7±12.3 mL/m(2) (P=0.25); LV end-diastolic volume index (LVEDVI), 0.08±19.1 and -2.4±22.2 mL/m(2) (P=0.67); and SDs/chord for infarct zone wall motion index (WMI), 0.38±0.70 and 0.84±1.11 (P=0.01). By covariate-adjusted analysis, post-PCI MPG 0/1 predicted lower WMI (P<0.001), lower LVEF (P<0.001), and higher LVESVI (P<0.01) but not LVEDVI at 1 year. Of the MPG 0/1 patients, 60% were MPG 2 or 3 at 1 year. CONCLUSIONS: Preserved MPG is present in a high proportion of patients following late PCI of occluded IRAs post-MI. Poor MPG post-PCI frequently improves MPG over 1 year. MPG graded after IRA recanalization undertaken days to weeks post MI is associated with LV recovery, indicating that MPG determined in the subacute post-MI period remains a marker of viability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00025766.

Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function: the Total Occlusion Study of Canada (TOSCA)-2 trial.

BACKGROUND: In the present study, we sought to determine whether opening a persistently occluded infarct-related artery (IRA) by percutaneous coronary intervention (PCI) in patients beyond the acute phase of myocardial infarction (MI) improves patency and indices of left ventricular (LV) size and function. METHODS AND RESULTS: Between May 2000 and July 2005, 381 patients with an occluded native IRA 3 to 28 days after MI (median 10 days) were randomized to PCI with stenting (PCI) or optimal medical therapy alone. Repeat coronary and LV angiography was performed 1 year after randomization (n=332, 87%). Coprimary end points were IRA patency and change in LV ejection fraction. Secondary end points included change in LV end-systolic and end-diastolic volume indices and wall motion. PCI was successful in 92%. At 1 year, 83% of PCI versus 25% of medical therapy-only patients had a patent IRA (P<0.001). LV ejection fraction increased significantly (P<0.001) in both groups, with no between-group difference: PCI 4.2+/-8.9 (n=150) versus medical therapy 3.5+/-8.2 (n=136; P=0.47). Median change (interquartile range) in LV end-systolic volume index was -0.5 (-9.3 to 5.0) versus 1.0 (-5.7 to 7.3) mL/m2 (P=0.10), whereas median change (interquartile range) in LV end-diastolic volume index was 3.2 (-8.2 to 13.3) versus 5.3 (-4.6 to 23.2) mL/m2 (P=0.07) in the PCI (n=86) and medical therapy-only (n=76) groups, respectively. CONCLUSIONS: PCI with stenting of a persistently occluded IRA in the subacute phase after MI effectively maintains long-term patency but has no effect on LV ejection fraction. On the basis of these findings and the lack of clinical benefit in the main Occluded Artery Trial, routine PCI is not recommended for stable patients with a persistently occluded IRA after MI.

Vagal heart rate responses to chronic beta-blockade in human heart failure relate to cardiac norepinephrine spillover.

We have documented a pre-junctional beta-2 adrenoceptor mediated reduction in cardiac norepinephrine spillover (CNES) in heart failure patients receiving chronic beta-blockade. Our present objective was to ascertain the consequence of this decrease for vagal heart rate (HR) regulation by determining CNES, arterial baroreflex sensitivity for HR (BRS) and arterial baroreflex modulation of muscle sympathetic nerve activity (MSNA) before and upon 4 months of beta-blockade with either carvedilol or metoprolol. In 19 heart failure patients in sinus rhythm (age: 55+/-2 [mean+/-S.E.]; ejection fraction: 20+/-2%), beta-blockade increased BRS from 4.8+/-0.9 to 7.9+/-1.3 ms/mm Hg (P<0.005) but had no effect on arterial baroreflex modulation of MSNA. Changes in CNES and BRS were inversely related (r=-0.52; n=16, P<0.05). Chronic beta-blockade in heart failure augments reflex vagal control of HR at an efferent site of interaction involving blockade of cardiac sympathetic pre-junctional beta-2 adrenoceptors that facilitate NE release.

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.