Acute myocardial infarction with simultaneous total occlusion of the left anterior descending artery and right coronary artery successfully treated with percutaneous coronary intervention.

BACKGROUND: Simultaneous thrombosis in more than one coronary artery is an uncommon angiographic finding in patients with acute ST-segment elevation myocardial infarction. It is difficult to identify using 12-lead electrocardiography and usually leads to cardiogenic shock and fatal outcomes, including sudden cardiac death. Therefore, immediate revascularization and adequate mechanical circulatory support are required. CASE PRESENTATION: We report the case of a 58-year-old man who presented with vomiting and chest pain complicated by cardiogenic shock and complete atrioventricular block. Electrocardiography revealed ST-segment elevation in leads II, III, aVF, and V1-V6. Emergency coronary angiography revealed total occlusion of the proximal left anterior descending artery and right coronary artery. The patient successfully underwent primary percutaneous coronary intervention with ballooning and stenting for both arteries. An Impella CP was inserted during the procedure. Fifty-seven days after admission, he had New York Heart Association class II heart failure and was transferred to a rehabilitation hospital. CONCLUSIONS: Acute double-vessel coronary thrombosis, a serious event with a high mortality rate, requires prompt diagnosis and management to prevent complications such as cardiogenic shock and ventricular arrhythmias. A combination of judicious medical treatment, efficient primary percutaneous coronary intervention, and early mechanical support device insertion is crucial to improve the survival rate of patients with this disease.

Nutri-pharmacogenomics of warfarin anticoagulation therapy: VKORC1 genotype-dependent influence of dietary vitamin K intake.

Warfarin is the most widely prescribed oral anticoagulant, but large interindividual variations exist in the dose required to achieve comparable therapeutic effects. Several clinical and genetic variables have been identified that influence warfarin dosing. However, interactions between genotype and nutrition remain uncertain in terms of dietary vitamin K intake. To investigate genotype-nutrient interactions in warfarin anticoagulation therapy, 202 consecutive outpatients (M/F = 142/60, mean age, 69 years) undergoing treatment with warfarin were enrolled. Prevalent single nucleotide polymorphisms in VKORC1 and CYP2C9 were genotyped, and dietary vitamin K intake during the week preceding the blood sampling was quantitatively estimated by a dietitian-assisted questionnaire. Patients were classified according to low, medium, or high vitamin K intake. The mean daily warfarin dose in subjects with a VKORC1-1639 A/A genotype was significantly smaller than that with a -1639A/G genotype (2.74 vs. 3.91 mg/day, respectively, p < 0.0001). Dose requirements did not differ between subjects with a CYP2C9 *1/*3 genotype versus a CYP2C9 *1/*1 genotype. In subjects with a variant VKORC1-1639 G allele, the mean daily warfarin dose was significantly attenuated by low vitamin K intake compared with medium and high intake after adjustment for covariates (3.4 vs. 5.0 vs. 4.0 mg/day, respectively, p = 0.028). No such genotype effects were observed in homozygous patients for the VKORC1-1639 A allele. The results of the present study suggest that the capacity of dietary vitamin K intake to influence warfarin dose requirements during anticoagulation therapy is VKORC1 genotype-dependent, at least in part.

Serious takotsubo cardiomyopathy: an autopsy case presenting severe irreversible myocardial damage after frequent episodes of recurrence.

BACKGROUND: Takotsubo cardiomyopathy is characterized by transient dysfunction of the medial to apical segment of the left ventricle. Recurrence within a few months or years has been reported and serious complications, including arrhythmia, acute cardiac shock and cardiac rupture, can arise; however, recurrence is rare and takotsubo cardiomyopathy is typically a reversible functional disorder. CASE PRESENTATION: A 91-year-old Japanese woman with a past medical history of angina pectoris, hypertension and uterine carcinoma noted bilateral axillary pain and presented herself to an emergency room. Although the pain improved and she went home, there were several subsequent episodes of recurrent chest pain. At approximately 1 week after the onset, she was hospitalized as her symptom worsened. Electrocardiography showed low voltage in limb and chest leads, and ST-segment elevation in leads II, III, aVF and V3 to V6. Echocardiography revealed medial to apical dyskinesia and basal hypercontractility of the left ventricle, and cardiac tamponade. Pericardiocentesis improved the symptom, but not her cardiac dysfunction. At 3 days after her admission, cardiopulmonary resuscitation was performed due to ventricular fibrillation. She died on the 5th day of admission (2 weeks after the onset). At autopsy, the left ventricle was dilatated and the apical ventricular wall was thin. On microscopy, remarkable wavy change and thinning of myocardium were diffusely observed, especially at the apex and the anterior to lateral wall of the left ventricle, interventricular septum and right ventricle, intermingled with interstitial fibrosis, hemorrhage and neutrophil infiltration. Contraction band necrosis was mainly observed on the posterior to inferior wall of the left ventricle. CONCLUSION: Our case showed severe morphological myocardial change after several chest pain episodes that were considered to be takotsubo cardiomyopathy. This notable case suggests that the frequent recurrence of serious takotsubo cardiomyopathy is life threatening and can lead to irreversible serious myocardial degeneration.

[Marked PT-INR prolongation associated with appetite loss due to urinary tract infection in a late elderly case with chronic atrial fibrillation].

An 80-year old woman presented with macroscopic hematuria on June 4(th), 2008. She had been suffering from general malaise and appetite loss since about 10 days previously. She had received anticoagulant therapy with warfarin due to chronic atrial fibrillation and PT-INR was well controlled between 1.6-2.2. When she presented, PT-INR was 12.88, and urinary tract infection (UTI) and hypoalbuminemia (2.2 g/dl) were observed. Therefore, warfarin therapy was discontinued, and antibiotics and vitamin K were administered. Normalization of PT-INR resulted in the disappearance of hematuria and UTI improved as a result of antibiotics administration. As the appetite loss improved, for serum albumin level increased. The previous dose of warfarin achieved PT-INR around 1.8. Her drug compliance had been good, and she took no drug nor food which could interact with warfarin. We also found no liver dysfunction, acute renal failure, malignancy, nor hyper- or hypo-thyroidism. Hypoalbuminemia caused by appetite loss due to UTI seems very likely to increase concentration of circulating free warfarin resulting in extreme prolongation of PT-INR. Our findings in the present case may suggest that we should pay more attention on changes of drug pharmacokinetics in elderly patients because of their poor adaptation to their circumstances such as infection or dehydration.

Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) as a novel predictor of clinical outcome after endovascular therapy in patients with peripheral artery disease (PAD).

BACKGROUND AND AIMS: Despite advances in the treatment of peripheral artery disease (PAD), cardiovascular events and death rates remain high. This study aimed at identifying markers of outcome in patients with PAD undergoing endovascular therapy (EVT). METHODS: Consecutive patients undergoing EVT were recruited. Markers of oxidative stress (malondialdehyde-modified low-density lipoprotein [MDA-LDL]), inflammation (IL-6; high-sensitivity C-reactive protein [hsCRP]) and fibrinolysis (D-dimer) were measured pre-EVT and at post-EVT time-points to 36 h. Clinical follow-up assessed major cardiovascular and/or limb events. RESULTS: In the 35 patients enrolled, mean MDA-LDL levels decreased from a baseline level of 106.2 U/L to 72.6 U/L immediately post-EVT (p<0.0001); levels remained significantly reduced at all time-points. IL-6, hsCRP and D-dimer increased and were significantly higher at the 36 h time-point. A significant, negative association was seen between decreased MDA-LDL and pre-EVT hsCRP levels (r = -0.42, p=0.012). Clinical follow-up data were obtained for a mean period of 16 months. MDA-LDL ratios (obtained by comparison of post- and pre-EVT values) allowed assessment of high (≥0.495) and low (<0.495) ratio groups. A significantly higher rate of major adverse events, including limb-related events or death, was seen in the low ratio group (p<0.001). Cox proportional hazard analysis including traditional risk factors indicated that this ratio is a significant predictor of clinical endpoints (HR = 0.4210, p=0.0154). An association with clinical outcome was not observed with the other candidate biomarkers. CONCLUSIONS: Assessment of pre- and post-EVT MDA-LDL levels is a promising marker of clinical outcome in patients with PAD.

Diurnal glycemic fluctuation is associated with severity of coronary artery disease in prediabetic patients: Possible role of nitrotyrosine and glyceraldehyde-derived advanced glycation end products.

BACKGROUND: Glucose fluctuation (GF) is a risk factor for coronary artery disease (CAD). However, it remains unknown whether specific indices of GF are risk factors for CAD. Therefore, we evaluated the relationship between GF, as determined by a continuous glucose monitoring system (CGMS) or the glucose level at 2h after a 75-g oral glucose tolerance test (75g OGTT 120), and the severity of CAD in prediabetic patients. We also evaluated whether nitrotyrosine (NT) and glyceraldehyde-derived advanced glycation end-products (Glycer-AGE) were induced by GF. METHODS: Twenty-eight prediabetic patients underwent coronary angiography (CAG), and the Gensini score and the SYNTAX score were evaluated as the severity of CAD, while the mean amplitude of glycemic excursions (MAGE) by CGMS and 75g OGTT 120 were evaluated. Serum NT and Glycer-AGE were measured. RESULTS: The MAGE was closely associated with the Gensini score (r=0.742, p<0.001) and the SYNTAX score (r=0.776, p<0.001), respectively. The 75g OGTT 120 was not associated with the Gensini score (r=0.36, p=0.06), but it was significantly associated with the SYNTAX score (r=0.413, p=0.036). Multiple linear regression analysis showed that the MAGE was the only independent determinant for the severity of CAD. The levels of NT and Glycer-AGE were significantly higher in the high MAGE group than in the low MAGE group. CONCLUSIONS: Diurnal GF is associated with the severity of CAD, even in prediabetic patients. GF, NT, and Glycer-AGE may play a pathological role in the progression of CAD.

Chronic total occlusions of the right coronary and left anterior descending coronary arteries in a young adult patient with antiphospholipid syndrome.

A 36-year-old male appeared to have an old myocardial infarction on electrocardiogram, and coronary angiography (CAG) was performed. The CAG showed total occlusions of the right coronary artery and left anterior descending artery. He was successfully treated with drug-eluting stent implantation for both occluded coronary arteries. Such serious coronary lesions are uncommon for his young age. The patient was diagnosed as having antiphospholipid syndrome (APS) based on elevation of anticardiolipin antibody and anti-ß2 glycoprotein I antibody. Two years after stent implantation, the patient was well without ischemia or thrombosis. APS should be considered a potential cause of serious coronary disease in young adults. .

Increased levels of the oxidative stress marker, nitrotyrosine in patients with provocation test-induced coronary vasospasm.

BACKGROUND: Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of coronary vasospasm. However, it is not clear whether circulating biomarkers for oxidative stress are altered after coronary vasospasm. We investigated temporal changes in the levels of oxidative stress biomarkers after coronary vasospasm induced by intracoronary acetylcholine provocation testing, resulting in transient myocardial ischemia. METHODS AND RESULTS: Thirty consecutive patients with suspected vasospastic angina pectoris (VSAP) were enrolled in the study. Patients were categorized into the VSAP-positive group (n=14) and the VSAP-negative group (n=16) on the basis of test results. Serum samples were examined for the levels of the oxidative stress markers 4-hydroxynonenal (HNE) and nitrotyrosine (NT) before, and 15min, 3h, and 12h after the provocation test. The serum HNE levels did not change in either group after the test. The serum NT levels in the VSAP-positive group significantly increased at 3h and 12h after the test (11.3±3.3µg/ml at 3h, p=0.015, and 12.1±5.7µg/ml at 12h, p=0.03), as compared with baseline (8.1±3.2µg/ml). In the VSAP-negative group, the serum NT levels significantly decreased from baseline at each of the 3 time points. CONCLUSIONS: Serum NT significantly increased after coronary vasospasm induced by acetylcholine provocation, suggesting that serum NT could be a biomarker of transient myocardial ischemia and could contribute to the development of VSAP.