Impact of high lipoprotein(a) levels on in-stent restenosis and long-term clinical outcomes of angina pectoris patients undergoing percutaneous coronary intervention with drug-eluting stents in Asian population.

Lipoprotein(a) (Lp(a)) is known to be associated with cardiovascular complications and atherothrombotic properties in general populations. However, it has not been examined whether Lp(a) levels are able to predict adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). A total of 595 consecutive patients with angina pectoris who underwent elective PCI with DES were enrolled from 2004 to 2010. The patients were divided into two groups according to the levels of Lp(a): Lp(a) < 50 mg/dL (n = 485 patients), and Lp(a) ≥ 50 mg/dL (n = 111 patients). The 6-9-month angiographic outcomes and 3-year cumulative major clinical outcomes were compared between the two groups. Binary restenosis occurred in 26 of 133 lesions (19.8%) in the high Lp(a) group and 43 of 550 lesions (7.9%) in the low Lp(a) group (P = 0.001). In multivariate analysis, the reference vessel diameter, low density lipoprotein cholesterol, total lesion length, and Lp(a) ≥ 50 mg/dL were predictors of binary restenosis. In the Cox proportional hazards regression analysis, Lp(a) > 50 mg/dL was significantly associated with the 3-year adverse clinical outcomes including any myocardial infarction, revascularization (target lesion revascularization (TLR) and target vessel revascularization (TVR)), TLR-major adverse cardiac events (MACEs), TVR-MACE, and All-MACEs. In our study, high Lp(a) level ≥ 50 mg/dL in angina pectoris patients undergoing elective PCI with DES was significantly associated with binary restenosis and 3-year adverse clinical outcomes in an Asian population.

Successful management of iatrogenic coronary arteriovenous fistula developed during chronic total occlusion intervention.

There have been some reports of iatrogenic coronary arteriovenous fistula (AVF) developing during percutaneous coronary intervention (PCI). PCI for chronic total occlusion (CTO) is more challenging due to a higher rate of procedural failure and increased risk of periprocedural complications. Recently, the coronary CTO guidewire has made rapid strides and revolutionized the procedure to increase high success rates for CTO revascularization. Simultaneously, as the number of CTO interventions increases, more complicated cases have also been reported. We report a case of huge iatrogenic left circumflex artery-to-posterior vein of left ventricle fistula resulting from unexpected penetration of CTO guidewire into cardiac vein during CTO intervention, which was successfully closed by a covered stent. Although controversies still exist concerning the closure of iatrogenic AVF in asymptomatic patients, especially when it drains into a third space including cardiac chambers or venous system, we decided to perform the closure of iatrogenic AVF by covered stent due to relatively bigger AVF size which was generated immediately following balloon angioplasty.

Peripheral arterial disease is associated with coronary artery spasm as assessed by an intracoronary acetylcholine provocation test.

1. Both peripheral arterial disease (PAD) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS may be expected in patients with PAD. In the present study, we evaluated the incidence and characteristics of CAS in patients with PAD. 2. A total of 78 patients with PAD and 241 age- and gender-matched patients without PAD who had chest pain with normal coronary appearance on coronary angiograms underwent intracoronary acetylcholine (ACh) provocation test. Acetylcholine was injected into the left coronary artery in incremental doses of 20, 50 and 100 microg/min. Significant CAS was defined as a transient > 70% luminal narrowing with concurrent chest pain and/or ST segment changes. 3. Patients with PAD had a significantly higher incidence of ACh-induced significant CAS than those without PAD (60.3 vs 34.0%, respectively P < 0.001), as well as chest pain and ST segment changes during the ACh provocation test. Patients with PAD were more sensitive to lower doses of ACh and had a higher incidence of multivessel spasm than those without PAD. Multivariable logistic analysis showed that age, current smoking, PAD and myocardial bridge were independent predictors of ACh-induced significant CAS. Moreover, of these factors, PAD was the strongest independent predictor (odds ratio 4.25; confidence interval 1.33-13.54; P = 0.014). 4. In patients with chest pain, the presence of arterial disease at another site should still push the clinician towards treating the chest pain as angina, even if the coronary anatomy is normal on a coronary angiogram.

Assessment of arterial stiffness index as a clinical parameter for atherosclerotic coronary artery disease.

BACKGROUND: The aim of the present study was to assess the feasibility and usefulness of the arterial stiffness index (ASI) measured non-invasively by computerized oscillometry and by comparing it with the pulse wave velocity (PWV). METHODS AND RESULTS: The study group comprised 60 consutive patients who underwent coronary angiography and whose aorto-femoral PWV were obtained with a Judkins catheter. The ASI was obtained using Cardio Vision MS-2000 (IMDP, Las Vegas, NV, USA): (i) baseline (ASI-B); (ii) hyperemia induced by compression of the arm with cuff pressure for 5 min (ASI-H); and (iii) sublingual nitroglycerin (ASI-N). In total, 34 patients had significant coronary artery disease (CAD). The PWV and all ASI were higher in patients with CAD than in those without CAD (ASI-B, 85.9+/-57.8 vs 48.2+/-24.5, p=0.001; ASI-H, 98.1+/-49.8 vs 48.1+/-21.3, p<0.01; ASI-N, 66.7+/-55.7 vs 33.2+/-27.9, p=0.002). However, only ASI-B and ASI-H were positively correlated to the PWV (ASI-B, r=0.27, p=0.03; ASI-H, r=0.49, p=0.001; ASI-N, r=0.19, p=0.16). The ASI was increased after hyperemia in patients with CAD (ASI-H, 85.9+/-57.8 to 98.1+/-49.8, p=0.01), but not in patients without CAD (ASI-H, 48.2+/-24.5 to 48.1+/-21.3, p>0.01). After adjusting their age, only ASI-H was correlated to the presence of CAD (r=0.33, p<0.01). CONCLUSIONS: It is feasible and useful to use the ASI for detection of atherosclerotic coronary disease. The findings of ASI-H suggests that in addition to stiffening of the arterial wall itself, the impairment of flow mediated vasodilation, because of endothelial dysfunction, further increases the arterial stiffness.

A new percutaneous porcine coronary model of chronic total occlusion.

OBJECTIVE: Chronic total occlusion (CTO) of coronary arteries represents a challenge for percutaneous treatment. Although ameroid constrictors have been used to create CTOs from extrinsic compression of coronary arteries, this model is not suitable for evaluation of novel angioplasty equipment. Thus, the objective of this study was to create a new percutaneous animal model of CTO. METHODS: To create an animal model of CTO, we implanted copper-plated stents in the left circumflex coronary arteries of 18 pigs, and assigned the pigs to early group (n = 6; sacrifice at approximately 1 week), intermediate group (n = 6; sacrifice at approximately 4 weeks), and late group (n = 6; sacrifice at approximately 8 weeks). RESULTS: Follow-up angiography prior to sacrifice revealed complete occlusion in 14 of 17 animals, with the subtotal occlusive lesions (mean 60% stenosis) only in the early group. Most of the pigs with total occlusions (12 of 14) showed bridging collateral flow greater than or equal to grade 2 (grade 2: 4; grade 3: 8). Histology revealed organizing thrombus in the early group with persistent inflammation, and organized thrombus with fibrosis and calcification in the intermediate and late groups. Interestingly, there were fibrotic components in the proximal and distal edges of the occlusions with softer, organizing thrombus in the middle of the CTO in the late group, suggesting that the major areas of difficulty are at the entrance and exit segments of the CTO with percutaneous recanalization. CONCLUSION: This study shows the feasibility and reproducibility of a new porcine coronary percutaneous CTO model. This model may be useful in improving our percutaneous treatment of CTO.

A potent opiate agonist protects against myocardial stunning during myocardial ischemia and reperfusion in rats.

OBJECTIVE: Opioids have a cardioprotective effect during ischemia. Previously, we showed in an ex-vivo model of myocardial ischemia and reperfusion that 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2, a highly potent and long-acting opioid peptide analgesic with fewer side effects than morphine, provides improved cardioprotection compared with morphine. The purpose of this study was to confirm, in an in-vivo model, the cardioprotective effect of 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2. METHODS: Rats (n=6/group) were randomized to 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 therapy (intravenous 10 nmol bolus 30 min before ligation and 10 nmol/h continuous infusion), morphine (100 nmol bolus and 100 nmol/h infusion), or placebo, and underwent left anterior descending (LAD) ligation for 10 min followed by reperfusion for 30 min. Continuous transesophageal echocardiogram and electrocardiogram were monitored. Fractional shortening and systolic wall thickening of the ischemic area were calculated. Time to recovery of left ventricular function was the duration of time needed for fractional shortening to recover to 90% of baseline following reperfusion. Duration of reperfusion arrhythmia was the time to the cessation of salvo (at least three consecutive premature ventricular contractions (PVCs)) following reperfusion. RESULTS: Time to recovery of left ventricular function was significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (4.4+/-2.2 min) and morphine groups (6.0+/-2.5 min) than in the controls (10.5+/-2.2 min; p<0.01). The 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 group showed significantly higher fractional shortening and systolic wall thickening of the ischemic area than the control group. Duration of reperfusion arrhythmia was also significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (2.8+/-1.7 min) and morphine groups (5.8+/-3.9 min) than in the controls (11.8+/-2.0 min; p<0.05). CONCLUSION: 2',6'-Dimethyltyrosine-D-Arg-Phe-Lys-NH2 provides a cardioprotective effect against myocardial ischemia and reperfusion in vivo.

Feasibility and safety of regional myocardial hypothermia during myocardial ischemia and infarction in pigs.

OBJECTIVE: Mild systemic hypothermia has been shown to be feasible and safe in patients during acute myocardial infarction (AMI). Regional myocardial hypothermia of the ischemic myocardium only may be more effective in myocardial salvage with fewer side effects compared with systemic hypothermia. The purpose of this study was to evaluate the feasibility and safety of regional myocardial hypothermia in pigs. METHODS: Open-chest pigs with (n=5) or without (n=4) myocardial infarction underwent left anterior descending coronary artery (LAD) ligation followed by intracoronary infusion of lactated Ringer's solution (at room temperature and at 15 degrees C between 20-35 ml/min for 3 min) via the central lumen of a specially designed balloon catheter at the time of reperfusion. Intramyocardial temperatures via thermocouples at the ischemic zone (LAD territory) and non-ischemic zone (circumflex territory) as well as systemic temperature were constantly recorded, as were the hemodynamics. Each pig acted as its control regarding the myocardial temperature response to both solutions. In addition, intracoronary versus intramyocardial temperatures were compared with thermocouples in both territories during infusion. RESULTS: There was no hemodynamic compromise or arrhythmia seen during the intracoronary infusion of either temperature solution. There was a linear relationship between the infusion solution temperature and infusion rate versus intramyocardial temperature response, with the cooled solution providing 2 degrees C lower temperature and faster infusion resulting in lower intramyocardial temperature. There was no change in the non-ischemic zone or systemic temperature. On average, 6-8 degrees C reduction in tissue temperature, potential target temperature range for hypothermic therapy, was achieved in all animals. In addition, intracoronary temperature in distal LAD measured by intracoronary thermocouples correlated with the intramyocardial temperature (2 degrees C lower temperature in the coronary artery). CONCLUSION: It is feasible and safe to achieve regional myocardial hypothermia by intracoronary infusion of cooled solution in pigs.