William J. van Gaal

Plaque Volume and Occurrence and Location of Periprocedural Myocardial Necrosis After Percutaneous Coronary Intervention Insights From Delayed-Enhancement Magnetic Resonance Imaging, Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade Analysis, and Intravascular Ultrasound

Background— Myocardial necrosis can occur during percutaneous coronary intervention (PCI) despite optimal adjunctive pharmacology and careful technique. We investigated the mechanisms of procedural infarction using angiographic analysis, intravascular ultrasound, and delayed-enhancement magnetic resonance imaging. Methods and Results— Fifty-two patients (64 vessels) who underwent complex PCI were studied. All patients were preloaded with clopidogrel and received glycoprotein IIb/IIIa inhibitors. “Adjacent” myonecrosis was defined as the presence of an area of new gadolinium hyperenhancement close to the stent. “Distal” myonecrosis was defined as situated at least 10 mm downstream from the stent. Fifteen vessels (23%) had evidence of new hyperenhancement after PCI. Of these, 8 (12%) had the distal type, and 7 (11%) had the adjacent type. Intravascular ultrasound showed a significantly greater reduction in plaque volume (91.6±51.5 versus 8±14 versus 20±35 mm3; P<0.001) in the group with distal hyperenhancement compared with patients without new hyperenhancement or adjacent hyperenhancement. In the entire sample, a significant correlation was seen between changes in plaque volume (&rgr;=0.58, P<0.001) after PCI and the mass of new necrosis measured by magnetic resonance imaging. Thrombolysis in Myocardial Infarction perfusion grade assessment of a closed microvasculature after PCI carried an odds ratio of 8.0 (95% confidence interval, 1.4 to 46.1; P=0.02) for the occurrence of hyperenhancement, whereas side-branch occlusion was associated with an odds ratio of 16.2 (95% confidence interval, 2.6 to 102.5; P=0.03). However, a closed microvasculature was associated with distal hyperenhancement (P=0.02), and side-branch occlusion was associated with adjacent hyperenhancement (P<0.001). Conclusions— These data suggest that distal embolization of plaque material occurs in contemporary PCI of native coronary arteries. Efforts to minimize procedural necrosis may require careful review of side branch anatomy and/or use of distal protection during extensive coronary stenting.

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: A systematic review and individual patient data meta-analysis

OBJECTIVES The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

The Syntax score predicts peri-procedural myocardial necrosis during percutaneous coronary intervention.

BACKGROUND Peri-procedural myocardial injury (PPI) during percutaneous coronary intervention (PCI) is common and associated with a poor outcome. No reliable angiographic or clinical predictors of PPI exist. We evaluated the ability of the SYNTAX score (SXscore), Gensini score, American Heart Association/American College of Cardiology (AHA/ACC) and Society for Cardiovascular Angiography and Intervention (SCAI) classifications to predict PPI. METHODS Consecutive patients were included from two existing databases of PCI. Patients with coronary bypass grafts or instent restenosis were excluded. PPI was defined as troponin I elevation (>1.0 microg/L) at 6-24 h post-PCI. Delayed enhancement magnetic resonance imaging distinguished PPI territory in patients undergoing multi-vessel PCI. Quantitative coronary angiography was performed blinded to PPI. In total, 100 patients underwent PCI to 122 vessels. PPI occurred in 20/100 (20.0%) patients. RESULTS Mean patient SXscore was higher in patients with PPI (20.6 vs. 12.4, p = 0.0001), however Gensini score was not significantly different (34.2 vs. 27.3, p = 0.15). Mean vessel SXscore was higher in vessels associated with PPI (12.1 vs. 7.6, p = 0.002), but not different for vessel Gensini score (16.2 vs. 13.6, p = 0.42). No vessels with AHA type A or B1 lesions were associated with PPI. Higher AHA scores (B2 and C) were associated with PPI (chi2 for trend 11.6, p = 0.0007). SCAI scores were not predictive of PPI (chi2 for trend 3.6, p = 0.06). By ROC analysis, a patient SXscore of > or = 17 predicted PPI with a sensitivity of 75.0% and specificity of 70.0%. CONCLUSION Higher SXscores are predictive of myocardial injury, whilst AHA type A and B1 lesions have a high negative predictive value for PPI.

Percutaneous Treatment of Chronic Total Coronary Occlusions Improves Regional Hyperemic Myocardial Blood Flow and Contractility: Insights From Quantitative Cardiovascular Magnetic Resonance Imaging

OBJECTIVES We sought to investigate temporal changes in contractility and hyperemic and resting myocardial blood flow (MBF) in dependent and remote myocardium after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) by using cardiovascular magnetic resonance (CMR) imaging. BACKGROUND Data about the physiological consequences of revascularization of CTOs are limited. The use of CMR allows investigation of the regional effects of revascularization on MBF and left ventricular contractility. METHODS We prospectively recruited 3 patient groups: 17 patients scheduled for CTO PCI, 17 scheduled for PCI of a stenosed but nonoccluded coronary artery (non-CTO), and 6 patients with CTO who were not scheduled for revascularization. All patients undergoing PCI underwent CMR imaging <24 h before PCI, with repeat CMR imaging 24 h and 6 months after PCI. Each CMR scan consisted of cine, perfusion, and delayed enhancement imaging. Regional hyperemic and resting MBF, wall thickening, and transmural extent of infarction were calculated. RESULTS In both intervention groups, hyperemic MBF in treated segments increased 24 h after PCI compared with baseline: CTO group, 2.1 +/- 0.2 ml/min/g versus 1.4 +/- 0.2 ml/min/g (p < 0.01); non-CTO group, 2.5 +/- 0.2 ml/min/g versus 1.6 +/- 0.2 ml/min/g (p < 0.01). This improvement persisted 6 months after PCI (p < 0.01 for both groups). Contractility in treated segments was improved at 24 h and 6 months after CTO PCI but only at 6 months after non-CTO PCI. In both intervention groups, treated segments no longer had reduced MBF or contractility compared with remote segments. In patients with untreated CTO segments, MBF and wall thickening did not improve at follow-up. CONCLUSIONS Successful CTO PCI increases hyperemic MBF as early as 24 h after the procedure, with a greater and earlier improvement in regional contractility than after non-CTO PCI, despite a greater likelihood of irreversible injury in CTO segments.

Effect of distal embolization on myocardial perfusion reserve after percutaneous coronary intervention: a quantitative magnetic resonance perfusion study.

Background— Studies have shown that a subset of patients demonstrate persistent impairment in microcirculatory function after percutaneous coronary intervention (PCI). Distal embolization of plaque contents has been postulated as the main mechanism for this. We sought to investigate this further by evaluating PCI-induced changes in myocardial perfusion reserve index (MPRI) over time in segments with “distal-type” procedure-related myonecrosis using high-resolution quantitative cardiovascular magnetic resonance imaging. Methods and Results— Forty patients undergoing PCI were studied with pre-PCI and 24-hour post-PCI delayed-enhancement magnetic resonance imaging and first-pass perfusion magnetic resonance imaging at rest and stress. Twenty patients underwent a third magnetic resonance imaging scan at 6 months. For perfusion imaging, 3 short-axis images were acquired during every heartbeat with a T1-weighted turboFLASH sequence. MPRI was calculated as the ratio of hyperemic to resting myocardial blood flow and subdivided according to the presence and location of new delayed hyperenhancement. Twenty-one patients demonstrated new distal hyperenhancement after PCI. Mean MPRI in revascularized myocardial segments not demonstrating new HE was significantly increased after the procedure (2.06 [95% CI, 1.99 to 2.13] before PCI and 2.52 [95% CI, 2.42 to 2.62] after PCI; P<0.001). In contrast, MPRI in segments with distal hyperenhancement was reduced after PCI (2.16 [95% CI, 1.95 to 2.37] before PCI; 2.00 [95% CI, 1.82 to 2.19] after PCI; mixed-model z=−4.82; P<0.001). Changes in mean MPRI 24 hours after PCI in segments upstream to new injury were not significantly different compared with perfusion changes in remote myocardium (z=−0.68; P=0.50). At 6 months after the procedure, mean MPRI in segments with new injury improved significantly compared with MPRI measured in these segments at 24 hours after PCI. Conclusions— MPRI is reduced in myocardial segments that demonstrate new distal irreversible injury at 24 hours after PCI. These reductions are confined to the segments with injury and do not affect the entire supply territory of the culprit vessel.

The role of Intravascular Ultrasound in the management of spontaneous coronary artery dissection

Primary or spontaneous coronary artery dissection (SCAD) is an unusual but increasingly recognized cause of acute myocardial ischemia and sudden cardiac death. Typically, SCAD presents in younger patients without conventional risk factors for coronary artery disease. It occurs more commonly in women than in men, and frequently during pregnancy or the postpartum period. Its pathophysiology is poorly understood, and there is considerable controversy regarding the optimal management of patients with SCAD-related myocardial ischemia. Therapeutic approaches include conservative medical therapy, coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). We present four cases of SCAD to illustrate specific aspects of the presentation and management of this condition, with particular reference to the importance of intravascular ultrasound (IVUS) to aid diagnosis and guide subsequent PCI.

The direct thrombin inhibitor ximelagatran/melagatran: a systematic review on clinical applications and an evidence based assessment of risk benefit profile

The direct thrombin inhibitor, ximelagatran, and its active form, melagatran (X/M), have been compared against conventional anticoagulant therapy (CAT) in many clinical settings. Their risk–benefit profile drove large debate until withdrawal by the manufacturer. A systematic review of all published randomized trials has been performed and a meta-analysis of randomised controlled trial (RCT) of X/M versus CAT. Major medical databases were searched for RCTs. Major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, pulmonary embolism), major bleeds (MB), minor bleeds and the rate of hepatotoxicity (HT) were compared. In terms of efficacy, X/M was at least as effective as, or even superior to, CAT. In terms of safety, the overall risk of MAE, MB, minor bleeds and HT was not significantly different for X/M compared with CAT. According to individual clinical settings, X/M was associated with a lower risk of MB but a prohibitive higher risk of HT in those clinical settings requiring prolonged treatment.

Early Diagnosis of Perioperative Myocardial Infarction After Coronary Bypass Grafting: A Study Using Biomarkers and Cardiac Magnetic Resonance Imaging

BACKGROUND Myocardial injury related to coronary artery bypass grafting (CABG) is poorly characterized, and understanding the characteristic release of biomarkers associated with revascularization injury might provide novel therapeutic opportunities. This study characterized early changes in biomarkers after revascularization injury during on-pump CABG. METHODS This prospective study comprised 28 patients undergoing on-pump CABG and late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMRI) who underwent measurements of cardiac troponin I (cTnI), creatine kinase-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, interleukin 6, tumor necrosis factor-α, matrix metalloproteinase 9a, monocyte chemotactic protein-1, plasminogen activator inhibitor-1a) at baseline, at 1, 6, 12, and 24 hours, and at 1 week (inflammatory markers only) post-CABG. Biomarker results at 1 hour were studied for a relationship to new myocardial infarction as defined by CMRI-LGE, and the diagnostic utility of combining positive biomarkers was assessed. RESULTS All patients had an uneventful recovery, but 9 showed a new myocardial infarction demonstrated by new areas of hyperenhancement on CMR. Peak cTnI at 24 hours (ρ = 0.66, p < 0.001) and CK-MB (ρ = 0.66, p < 0.001) correlated with the amount of new LGE. At 1 hour, 3 biomarkers--cTnI, interleukin 6, and tumor necrosis factor-α--were significantly elevated in patients with vs those without new LGE. Receiver operating curve analysis showed cTnI was the most accurate at detecting new LGE at 1 hour: a cutoff of cTnI exceeding 5 μg/L at 1 hour had 67% sensitivity and 79% specificity for detecting new LGE. CONCLUSIONS Unexpected CABG-related myocardial injury occurs in a significant proportion of patients. A cTnI test at 1 hour after CABG could potentially differentiate patients with significant revascularization injury.

Usefulness of N-terminal pro-brain natriuretic peptide to predict postoperative cardiac complications and long-term mortality after emergency lower limb orthopedic surgery.

After emergency orthopedic-geriatric surgery, cardiac complications are an important cause of morbidity and mortality. The utility of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for the prediction of cardiac complications and mortality was evaluated. NT-pro-BNP was tested pre- and postoperatively in 89 patients >60 years of age. They were followed for 2 years for cardiac complications (defined as acute myocardial infarction, congestive cardiac failure, atrial fibrillation or major arrhythmia) or death. Receiver operating characteristic curves were constructed to determine the optimal discriminatory level for cardiac events and death using NT-pro-BNP. Twenty-three patients (25.8%) sustained an in-hospital postoperative cardiac complication. Total all-cause mortality was 3 of 89 (3.4%) in hospital, 21 of 89 (23.6%) at 1 year, and 27 of 89 (30.3%) at 2 years. Median preoperative and postoperative NT-pro-BNP levels were higher in patients who had an in-hospital cardiac event compared to those without (387 vs 1,969 pg/ml, p <0.001; and 676 vs 7,052 pg/ml, p <0.001 respectively). The optimal discriminatory level for preoperative NT-pro-BNP was 842 pg/ml and that for postoperative NT-pro-BNP was 1,401 pg/ml for the prediction of in-hospital cardiac events and 1- and 2-year mortality. Preoperative NT-pro-BNP >/=842 pg/ml (odds ratio 11.6, 95% confidence interval 2.1 to 65.0, p = 0.005) was an independent predictor of in-hospital cardiac complications using multivariate analysis and pre- and postoperative NT-pro-BNP levels were independent predictors of 2-year cardiovascular events. Patients who had preoperative NT-pro-BNP >/=842 pg/ml or postoperative NT-pro-BNP >/=1,401 pg/ml had significantly worse survival using log-rank testing (p <0.001) and these variables independently predicted 2-year mortality. In conclusion, increase pre- and postoperative NT-pro-BNP levels are independent predictors of in-hospital cardiac events and 1- and 2-year mortality in older patients undergoing emergency orthopedic surgery.

Drug eluting stents versus bare metal stents in the treatment of saphenous vein graft disease: a systematic review and meta-analysis.

AIMS Treatment of saphenous vein graft (SVG) disease is still a matter of debate given the uncertainty of the available conflicting data. Our aim was to assess, by means of a meta-analytic approach, the risk/benefit profile of drug eluting stents (DES) versus bare metal stents (BMS) in the treatment of SVG disease. METHODS AND RESULTS A search of relevant studies in several databases was performed. The endpoints of interest such as: major adverse events (MAE) (the combination of overall death and non-fatal myocardial infarction [AMI]), target vessel revascularisation (TVR), and target lesion revascularisation (TLR) have been calculated in-hospital and at the longest follow-up. Single endpoints and the rate of stent thrombosis (ST) were also assessed. Three randomised controlled trials and 15 registry studies were appraised, totalling 3,294 patients. During hospitalisation, there was no difference in the risk of MAE, overall death, AMI and TVR. No data were available to calculate the TLR rate. At a mean follow-up of 19.8 months, no significant differences were found in the risk of MAE and AMI. BMS were associated with a trend towards a higher risk of overall death (OR 1.32 [1,00-1.74], p=0.05, number needed to treat [NNT]=55). DES showed superiority in terms of TVR (OR 1.86 [1.33-2.61], p=0.0003, NNT=16), and TLR (OR 1.77 [1.27-2.48], p<0.0001, NNT=25). According to pre-specified subgroup analyses, these effects seem less evident at the long-term follow-up. DES were not associated with an increased risk of ST. CONCLUSIONS Use of DES in SVG substantially reduces both TVR and TLR. These data also demonstrate that using DES in SVG is safe and contradict previous reports of potential risks.