Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril.

Enalapril is effective in the suppression of left ventricular remodeling after acute myocardial infarction (AMI), but the effect of telmisartan is unclear. The consecutive 163 AMI patients underwent primary percutaneous coronary intervention and were randomized to telmisartan (n = 82) or enalapril (n = 81). Left ventriculography was performed in the acute and chronic (6 months) phases. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured by zymography in the acute (days 1, 7, and 14) and chronic (6 months) phases. Plasma pentraxin3 (PTX3), a marker of vascular inflammation, was also measured. There were no adverse effects in the telmisartan group. The analysis of the left ventriculograms in the acute and chronic phases revealed no difference between the two groups. MMP-9 activities at days 7 and 14 and in the chronic phase were decreased compared to that at day 1 in both groups. MMP-2 activity was also decreased in the acute phase, but increased in the chronic phase in both groups. There was no difference in the plasma PTX3 level in the acute phase, but in the chronic phase, PTX3 was significantly lower in telmisartan than in enalapril group (2.6 ± 1.4 vs. 3.2 ± 1.6 ng/ml, p = 0.04). Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalapril in AMI patients. Telmisartan can be an alternative to angiotensin converting enzyme inhibitor in patients with AMI.

Increased serum anandamide level at ruptured plaque site in patients with acute myocardial infarction.

Inflammation caused by activated macrophages and T lymphocytes may trigger plaque rapture in acute coronary syndrome (ACS). Anandamide and 2-arachidonylglycerol (2-AG) are macrophage-derived signal lipids and may be involved in the pathogenesis of ACS, but no clinical relevant data have been reported. In 43 acute myocardial infarction (AMI) patients (66 +/- 2 years), blood samples were obtained from the aortic root and the infarct-related coronary artery (IRA) using a PercuSurge system during primary percutaneous coronary intervention (PCI). In six patients with stable effort angina (SEA) (56 +/- 6 years), blood samples were obtained from the site of stenosis during elective PCI. In 25 of the 43 AMI patients, anandamide was detected in the serum. Serum anandamide level was 35 +/- 20 pmol/mL in the aorta and was significantly increased to 401 +/- 134 pmol/mL in the IRA (P < 0.01). 2-AG was undetectable in most of the patients. In patients with SEA, neither anandamide nor 2-AG was detected in the serum at the plaque site. In AMI patients with anandamide detected, left ventricular ejection fraction at 2 weeks after PCI was increased by 3.7 +/- 2.1% compared with that at the acute phase, while it was decreased by 3.0 +/- 1.8% in those without anandamide detected (P < 0.05). The serum anandamide level at the culprit lesion was elevated compared with the systemic level in a significant number of AMI patients, indicating the synthesis of anandamide at the IRA. Anandamide was suggested to be derived from ruptured plaque and may exert beneficial effects in humans.

Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril.

OBJECTIVE: To determine whether telmisartan reduces in-stent restenosis (ISR) after coronary angioplasty using bare metal stent (BMS) in patients with acute myocardial infarction (AMI) compared with an angiotensin converting enzyme (ACE) inhibitor. BACKGROUND: The efficacy of inhibition of renin-angiotensin-aldosterone system in patients with AMI has been established, and the prescription of ACE inhibitor is recommended as class I indication for all AMI patients, whereas that of angiotensin II receptor blocker (ARB) as class IIa. Telmisartan is a unique ARB since it has a peroxisome proliferator-activated receptor (PPAR) gamma activating effect which is known to reduce neointimal tissue proliferation after coronary stenting. METHODS: In 64 patients, telmisartan (20-40 mg per day) was orally administered for 6 months after stenting (telmisartan group). The incidence of ISR after stenting in these patients was retrospectively compared with those in the other 60 patients administrated enalapril (2.5-5 mg per day) (enalapril group). RESULTS: There were no adverse events such as death, re-infarction and emergency bypass surgery in telmisartan group during a follow-up period for 6 months. The ISR rate was lower in telmisartan group (18.8%) than in enalapril group (33.3%) (p=0.06). However, percent diameter stenosis (%DS) at follow-up in telmisartan group was significantly smaller than in enalapril group (26.7+/-18.6% vs 38.0+/-23.9%, p=0.004). Late lumen loss was also significantly smaller in telmisartan group than in enalapril group (0.97+/-0.48 mm vs 1.19+/-0.68 mm, p=0.039). CONCLUSIONS: Telmisartan not only is tolerable in patients with AMI but has a potential to reduce neointimal tissue proliferation after AMI treated with coronary angioplasty using BMS compared with enalapril.

Decreased plasma and cardiac matrix metalloproteinase activities in patients with coronary artery disease and treated with pravastatin.

Matrix metalloproteinase (MMP), which is activated by oxidative stress, plays an important role in the development of ventricular remodeling in coronary artery disease. Pravastatin is shown to reduce oxidative stress. We tested the hypothesis that cardiac oxidative stress and MMP activity are reduced in patients with coronary artery disease and treated with pravastatin. Forty-eight patients who underwent coronary artery bypass graft surgery (CABG) were studied. Twenty-four patients had the serum low-density lipoprotein (LDL) cholesterol level >2.59 mM, and were treated with pravastatin (10 mg/day) for 2 months before CABG (pravastatin group). The other 24 had LDL cholesterol< or =2.59 mM, and were untreated (control group). The plasma and pericardial MMP-2 and MMP-9 activities were measured by gelatin zymography, and MMP-2 and MMP-9 levels, and pericardial 8-iso-prostagrandin F2alpha (8-iso-PGF2alpha) level, a maker of oxidative stress, by enzyme-linked immunosorbent assay. The plasma and pericardial MMP-2 and MMP-9 activities and levels were all lower by 20-30% in pravastatin than in control group (all P<0.05). The pericardial 8-iso-PGF2alpha level was lower in pravastatin than in control group (38+/-4 vs 64+/-7 pg/ml, P<0.05). The pericardial MMP-2 and MMP-9 activities were positively correlated with the pericardial 8-iso-PGF2alpha level (r=0.57 and 0.47, respectively, both P<0.01). Thus, cardiac oxidative stress and MMP activities are reduced in patients with coronary artery disease and treated with pravastatin, which may be beneficial in preventing and reducing ventricular remodeling.

Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction.

Nicorandil, a hybrid KATP channel opener and nicotinamide nitrate, reduces no-reflow phenomenon and improves cardiac function in patients with acute myocardial infarction (AMI). We reported that nicorandil suppresses radical formation in patients with AMI undergoing primary percutaneous coronary intervention (PCI). In the present study, we tested the hypothesis that nicorandil treatment suppresses MMP activities and predicts ventricular remodeling in AMI. Sixty-two patients with AMI were randomized into nicorandil pretreatment (n = 31) and control (n = 31) groups after admission and underwent primary PCI. Nicorandil was administered as a bolus injection (4 mg) followed by constant infusion (8 mg/h) for 24 h just after admission. On days 1, 2, and 14 after the onset of AMI, the plasma levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by enzyme-linked immunosorbent assay and the activities by gelatin zymography. There were no differences in the baseline clinical characteristics between the two groups. On day 1, there were no differences in both MMP-2 and MMP-9 levels and their activities between the two groups. However, both MMP-2 and MMP-9 levels and their activities were significantly lower in nicorandil than in control group on day 2 (MMP-2 level, 1 014 +/- 39 vs 1 174 +/- 44 ng/ml; MMP-9 level, 17 +/- 1 vs 23 +/- 2 ng/ml; both P < 005) and on day l4 (MMP-2 level, 970 +/- 38 vs 1 221 +/- 44 ng/ml; MMP-9 level, 17 +/- 1 vs 23 +/- 1 ng/ml; both P < 0.05). Left ventricular end-diastolic volume index (LVEDVI) at acute phase was not different between the two groups. At 6 months after AMI, LVEDVI was significantly smaller in nicorandil than in the control group (83 +/- 4 vs 96 +/- 4 ml/m2, P < 0.05). The change in LVEDVI from acute phase to 6 months was positively correlated with MMP-2 and MMP-9 levels and activities. Nicorandil suppresses the increases in MMP levels and activities and prevents the development of ventricular remodeling in AMI.

Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty with the use of bare metal stent in patients with acute myocardial infarction and with type 2 diabetes mellitus or impaired glucose tolerance.

Thiazolidinediones (TZDs) have beneficial effects on markers of cardiovascular risk in patients with type 2 diabetes mellitus (DM). This study aimed to investigate the efficacy and safety of low-dose pioglitazone (15 mg per day) in patients with acute myocardial infarction (AMI) and type 2 DM or impaired glucose tolerance (IGT) treated with coronary angioplasty using bare metal stent (BMS). In 56 patients, pioglitazone was orally administered for 6 months after stenting (pioglitazone group). The incidence of in-stent restenosis (ISR) and left ventricular end-diastolic volume index (LVEDVI) at acute phase and 6 months after stenting in these patients were retrospectively compared with those in the other 37 patients (control group) treated without pioglitazone. No adverse events including death, emergency bypass surgery, and reinfarction, occurred in any patients in the hospital. There was no congestive heart failure (CHF) during a follow-up period in the pioglitazone group. At 6 months after stenting, the overall angiographic ISR rate was significantly lower in the pioglitazone group than in the control group (28.6% vs 48.6%, P = 0.049). In patients with hemoglobin A1c (HbA1c) <7.0% at follow-up, the ISR rate was also significantly lower in the pioglitazone group than in controls (21.3% vs 44.8%, P = 0.03). Delta-LVEDVI (defined as follow-up LVEDVI minus acute LVEDVI) was similar between the pioglitazone group and control group (0.13 vs 5.16 ml/m(2), P = 0.482). Low-dose pioglitazone seems to have a potential to reduce ISR and does not adversely affect LV remodeling after AMI treated with coronary angioplasty using BMS in patients with type 2 DM or IGT.

Mutational analysis of Kir6.1 in Japanese patients with coronary spastic angina.

The etiology of coronary spastic angina (CSA) remains uncertain. Mice lacking the gene encoding the inwardly rectifying K(+) channel Kir6.1 were developed as an animal model of CSA. We investigated whether mutation in the coding region of the Kir6.1 gene is detected in Japanese patients with CSA. The study population included 19 Japanese patients with CSA (10 men and 9 women with a mean age of 61+/-14 years). Mutational analysis of the coding region of Kir6.1 was performed by direct sequencing. We found no missense or nonsense mutations in these samples, but we found in one female CSA patient, a single base substitution (C to T) at nucleotide position 111 in exon 2 of the coding region, which was heterozygous and did not cause amino acid substitution (Ile37Ile, silent mutation). In the remaining 18 patients, no base substitution was detected in the coding region of the Kir6.1 gene. No mutation that alters primary structure of Kir6.1 was detected in Japanese patients with CSA. The results indicate that abnormality in the primary structure of Kir6.1 may not be involved in the genetic pathogenesis of CSA in humans.

Feasibility and safety of thrombectomy with TVAC aspiration catheter system for patients with acute myocardial infarction.

Early reperfusion with angioplasty and stenting is established as a central, effective treatment for acute myocardial infarction (AMI). The role of thrombectomy prior to angioplasty remains to be elucidated. To evaluate its feasibility, safety, and efficacy, thrombectomy using a TVAC aspiration catheter system was attempted prior to angioplasty and stenting in 40 consecutive patients with AMI. Fifty consecutive patients with AMI in whom angioplasty and stenting were performed without prior thrombectomy served as controls. Neither distribution of Killip classification nor culprit lesion was different between the two groups. In patients treated with the TVAC system, the procedure was successful in 39/40 patients (98%) and there were no procedure-related complications. In the final coronary angiogram, TIMI-3 (Thrombolysis in Myocardial Infarction) flow was obtained in 37/40 (93%) in patients treated with the TVAC system and 43/50 (86%) in control patients. Electrocardiograms before and after coronary intervention were analyzed in patients with ST elevation AMI (35 patients treated with the TVAC system and 41 control patients). ST elevation recovery >50% of the initial value was observed after coronary intervention in 26/35 (74%) in patients treated with the TVAC system and 26/41 (63%) in control patients (P = 0.33). In the case of anterior AMI, ST elevation recovery >50% of the initial value was observed in 13/17 (76%) in patients treated with the TVAC system and 8/20 (40%) in control patients (P = 0.045). Thus, thrombectomy using a TVAC system is feasible, safe, and may have the potential to enhance ST-segment resolution in patients with anterior AMI.

[Deep vein thrombosis caused by pelvic lymphocyst following radical prostatectomy: a case report].

A 66-year-old man was admitted with distal edema of his right leg. He had undergone radical prostatectomy and pelvic lymphadenectomy for prostatic cancer 23 days previously. Abdominal computed tomography (CT) showed a lymphocyst (4.5 x 3.0 cm) along the right pelvic wall compressing the right external iliac vein. CT with contrast medium showed thrombus formation (about 9 cm) in the distal portion of the right external iliac vein and femoral vein. An inferior vena cava filter was placed to prevent pulmonary embolism, and anticoagulation with warfarin was started. One week later, CT showed shrinkage of the lymphocyst and thrombus in the vein, as well as a large thrombus trapped in the filter. Follow-up CT taken 2 months later revealed marked reduction of the lymphocyst and absence of thrombus in both the vein and filter. A lymphocyst, also known as a lymphocele, is a complication of radical pelvic surgery. Most lymphocysts are asymptomatic and regress spontaneously, but may lead to deep vein thrombosis and pulmonary embolism, usually a few weeks after surgery. Careful observation is needed even after discharge from hospital.