Influence of omeprazole and famotidine on the antiplatelet effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes: a prospective, randomized, multicenter study.

BACKGROUND: It remains unclear whether concomitant use of omeprazole attenuates platelet function as compared with that of famotidine in patients with acute coronary syndromes (ACS) who receive clopidogrel. METHODS AND RESULTS: In this prospective study, 130 ACS patients treated with aspirin and clopidogrel who underwent stent implantation were randomly assigned to receive a Japanese standard dose of omeprazole 10mg daily or famotidine 20mg daily for at least 4 weeks. Between 14 and 28 days after enrollment, there was no significant difference in the platelet reactivity index (PRI) measured with vasodilator-stimulated phosphoprotein phosphorylation assay between the omeprazole group (n=65) and famotidine group (n=65) (55±17% vs. 51±19%; P=0.26). The cumulative rate of adverse cardiovascular events at 12 months was similar in the groups (13% vs. 17%; P=0.81). The PRI was similar (54.9±17.9% vs. 54.0±17.8%; P=0.83) in the omeprazole group (n=33) and the famotidine group (n=39) among patients with ST-elevation myocardial infarction (STEMI). However, there was a trend toward a higher PRI (55.2±15.9% vs. 46.4±19.4%; P=0.06) in the omeprazole group (n=32) as compared with the famotidine group (n=26) among patients without persistent ST-segment elevation ACS. CONCLUSIONS: As compared with famotidine, concomitant use of low-dose omeprazole does not significantly attenuate the antiplatelet effects of clopidogrel in patients with ACS, especially in those with STEMI.

Effects of valsartan, an angiotensin II receptor blocker, on coronary atherosclerosis in patients with acute myocardial infarction who receive an angiotensin-converting enzyme inhibitor.

BACKGROUND: The aim of the present study was to assess the effects of angiotensin II receptor blocker (ARB) on coronary plaque progression in patients with acute myocardial infarction (AMI) who received an angiotensin-converting enzyme inhibitor (ACEI). METHODS AND RESULTS: After local ethics committee approval and obtaining of informed consent, 116 patients with AMI were randomly assigned to receive a combination of valsartan and captopril or captopril alone. Non-culprit intermediate coronary atherosclerosis was assessed on intravascular ultrasound. The primary and secondary endpoints were the nominal change in percent atheroma volume (PAV) and percent change in lumen volume (%ΔLV), respectively. The combination group had a significantly lower systolic blood pressure (117 vs. 125 mmHg; P=0.02) and a lower plasma aldosterone level (56 vs. 75 pg/ml; P=0.02) at follow-up. The nominal change in PAV was slightly lower in the combination group than in the ACEI group (-1.9 vs. -0.68%, P=0.06). %ΔLV was -0.3% in the ACEI group and was 4.3% in the combination group (P=0.03). Logistic regression analysis showed that additional ARB therapy was independently associated with LV enlargement (odds ratio, 2.144; 95% confidence interval: 1.818-5.618; P=0.03). CONCLUSIONS: In this study of patients with AMI, additional ARB therapy had minimal impact on the progression of coronary atherosclerosis as compared with an ACEI alone. The combination of these 2 drugs, however, induces coronary artery enlargement.

Consensus document on the standard of coronary angioscopy examination and assessment from the Japanese Association of Cardiovascular Intervention and Therapeutics.

Coronary angioscopy (CAS) is a unique diagnostic device that allows direct visualization of the vascular luminal surface in living patients. CAS contributes to elucidate the pathology of coronary artery disease. This consensus document provides a standard for CAS examination and assessment.

Optimal Anticoagulant Strategy for Periprocedural Management of Atrial Fibrillation Ablation: A Systematic Review and Network Meta-Analysis.

This network meta-analysis was performed to rank the safety and efficacy of periprocedural anticoagulant strategies in patients undergoing atrial fibrillation ablation. MEDLINE, EMBASE, CENTRAL, and Web of Science were searched to identify randomized controlled trials comparing anticoagulant regimens in patients undergoing atrial fibrillation ablation up to July 1, 2021. The primary efficacy and safety outcomes were thromboembolic and major bleeding events, respectively, and the net clinical benefit was investigated as the primary-outcome composite. Seventeen studies were included (n = 6950). The mean age ranged from 59 to 70 years; 74% of patients were men and 55% had paroxysmal atrial fibrillation. Compared with the uninterrupted vitamin-K antagonist strategy, the odds ratios for the composite of primary safety and efficacy outcomes were 0.61 (95%CI: 0.31-1.17) with uninterrupted direct oral anticoagulants, 0.63 (95%CI: 0.26-1.54) with interrupted direct oral anticoagulants, and 8.02 (95%CI: 2.35-27.45) with interrupted vitamin-K antagonists. Uninterrupted dabigatran significantly reduced the risk of the composite of primary safety and efficacy outcomes (odds ratio, 0.21; 95%CI, 0.08-0.55). Uninterrupted direct oral anticoagulants are preferred alternatives to uninterrupted vitamin-K antagonists. Interrupted direct oral anticoagulants may be feasible as alternatives. Our results support the use of uninterrupted direct oral anticoagulants as the optimal periprocedural anticoagulant strategy for patients undergoing atrial fibrillation ablation.

Combined prognostic utility of ST segment in lead aVR and troponin T on admission in non-ST-segment elevation acute coronary syndromes.

Many studies have shown that ST-segment depression is a strong predictor of poor outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs); however, lead aVR was not considered in these studies. The present study examined the prognostic usefulness of the 12-lead electrocardiogram in combination with biochemical markers in 333 patients with NSTE-ACS. ST-segment deviation of > or =0.5 mm was considered clinically significant. Coronary angiography was performed a median of 3 days after admission in all patients. The primary end point was the composite of death, myocardial infarction, and urgent revascularization at 90 days. ST-segment elevation in lead aVR (odds ratio 13.8, 95% confidence interval 1.43 to 100.9, p = 0.03) and increased troponin T (odds ratio 7.9, 95% confidence interval 1.22 to 123.8, p = 0.04) were the only independent predictors of restricted events (death or myocardial infarction) at 90 days. ST-segment elevation in lead aVR (odds ratio 12.8, 95% confidence interval 4.80 to 33.9, p < 0.0001) and increased troponin T (odds ratio 2.03, 95% confidence interval 1.20 to 4.29, p = 0.04) were also the only independent predictors of adverse events (death, myocardial infarction, or urgent revascularization) at 90 days. When ST-segment status in lead aVR was combined with troponin T, patients with ST-segment elevation in lead aVR and increased troponin T had the highest rates of left main or 3-vessel coronary disease (62%) and 90-day adverse outcomes (47%). In conclusion, our findings suggest that ST-segment status in lead aVR combined with troponin T on admission is a simple and useful clinical tool for early risk stratification in patients with NSTE-ACS.

Beneficial effect of early infusion of landiolol, a very short-acting beta-1 adrenergic receptor blocker, on reperfusion status in acute myocardial infarction.

BACKGROUND: An early IV beta blocker during primary percutaneous coronary intervention (PCI) has been shown to reduce infarct size in ST-segment elevation acute myocardial infarction (STEMI), although the underlying mechanism is unknown. The aim of this study was to investigate the efficacy of early infusion of landiolol, the short-acting beta-1 adrenergic receptor blocker, on the reperfusion status in a STEMI. METHODS: We conducted a prospective, single-group trial of landiolol during the primary PCI for a STEMI. Landiolol was started intravenously just before reperfusion. The reperfusion status and outcomes in 55 treated patients were compared with those in 60 historical controls treated without landiolol. The optimal reperfusion was assessed by an ST-segment resolution (STR), coronary flow, and myocardial brush grade (MBG) after reperfusion. RESULTS: Patients in the landiolol group achieved a higher rate of an STR (64% vs. 42%, p=0.023) and MBG 2/3 (64% vs. 45%, p=0.045), whereas coronary flow was comparable between the two groups. A multivariate analysis showed that landiolol use was an independent predictor of an STR (odds ratio 2.99, 95% confidence interval 1.25-7.16, p=0.014). The incidence of non-sustained ventricular tachycardia (27% vs. 50%, p=0.014), hypotension (15% vs. 32%, p=0.046), and progression to Killip class grade III or IV (0% vs. 10%, p=0.028) were lower in the landiolol group. CONCLUSION: Early infusion of landiolol during the primary PCI was associated with optimal reperfusion and a lower incidence of adverse events in comparison with the control group.

B-type natriuretic peptide as a predictor of ischemia/reperfusion injury immediately after myocardial reperfusion in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: In animal models of acute myocardial infarction (AMI), B-type natriuretic peptide (BNP) administered before and during coronary occlusion limits infarct size. However, the relation between plasma BNP levels and ischemia/reperfusion injury remains unclear. METHODS: 302 patients with ST-segment elevation AMI (STEMI) received emergency percutaneous coronary intervention within six hours from the onset. The patients were divided into two groups according to the plasma BNP level before angiography: group L (n=151), BNP ≤ 32.2 pg/ml; group H (n=151), BNP >32.2 pg/ml. The Selvester QRS-scoring system was used to estimate infarct size. RESULTS: The rate of ischemia/reperfusion injury immediately after reperfusion, defined as reperfusion ventricular arrhythmias (26% vs. 11%, p=0.001) and ST-segment re-elevation (44% vs. 22%, p=0.008), was higher in group L than in group H. Group L had a greater increase in the QRS score during percutaneous coronary intervention (3.55 ± 0.17 vs. 2.09 ± 0.17, p<0.001) and a higher QRS score 1 h after percutaneous coronary intervention (5.77 ± 0.28 vs. 4.51 ± 0.28, p=0.002). On multivariate analysis, plasma BNP levels in the lower 50th percentile were an independent predictor of reperfusion injury (odds ratio, 2.620; p<0.001). The odds ratios of reperfusion injury according to decreasing quartiles of BNP level, as compared with the highest quartile, were 1.536, 3.692 and 4.964, respectively (p trend=0.002). CONCLUSIONS: Plasma BNP level before percutaneous coronary intervention may be a predictor of ischemia/reperfusion injury and the resultant extent of myocardial damage. Our findings suggest that high plasma BNP levels might have a clinically important protective effect on ischemic myocardium in patients with STEMI who receive percutaneous coronary intervention.

Predictors of left main or three-vessel disease in patients who have acute coronary syndromes with non-ST-segment elevation.

To identify an early, simple, noninvasive predictor of left main (LM) or 3-vessel disease (3-VD), we retrospectively studied clinical variables on admission in 310 patients with acute coronary syndromes with non-ST-segment elevation. Univariate analysis indicated that many factors were related to LM/3-VD. Multivariate analysis showed that ST-segment elevation in lead aVR of >/=0.5 mm was the strongest predictor of LM/3-VD, followed by positive troponin T (odds ratio 19.7, p <0.001, and odds ratio 3.08, p = 0.048, respectively). ST-segment elevation in lead aVR of >/=0.5 mm and positive troponin T identified LM/3-VD with sensitivities of 78% and 62%, specificities of 86% and 59%, positive predictive values of 57% and 26%, and negative predictive values of 95% and 87%, respectively (p <0.05). Our findings suggest that in patients with non-ST-segment elevation acute coronary syndromes, ST-segment elevation in lead aVR of >/=0.5 mm and positive troponin T on admission (especially the former) are useful predictors of LM/3-VD.

Impact of n-3 polyunsaturated fatty acids in predicting ischemia/reperfusion injury and progression of myocardial damage after reperfusion in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: In animal models of acute myocardial infarction, n-3 polyunsaturated fatty acids (PUFAs) administered before coronary occlusion have been suggested to prevent induction of ventricular arrhythmia and limit infarct size. However, the relation between the serum levels of n-3 PUFAs and ischemia/reperfusion (I/R) injury remains unclear. METHODS: 211 patients with ST-segment elevation acute myocardial infarction received emergency percutaneous coronary intervention (PCI) within 6h from the onset. The patients were divided into two groups according to the sum of serum eicosapentaenoic acid (EPA) levels and docosahexaenoic acid (DHA) levels before PCI: group L (n=106), EPA+DHA <155µg/ml and group H (n=105), EPA+DHA ≥155µg/ml. The Selvester QRS-scoring system was used to estimate the serial change in infarct size. RESULTS: Time to reperfusion was similar between the 2 groups. The QRS score before PCI was higher in group L than in group H (2.42±2.00 vs 1.85±2.01, p=0.015). The proportion of patients with I/R injury immediately after reperfusion, defined as reperfusion ventricular arrhythmias (25% vs 11%, p=0.006) and ST-segment re-elevation (44% vs 22%, p<0.001), was also higher in group L than in group H, followed by a greater increment in the QRS score during PCI (3.51±2.51 vs 2.54±1.91, p=0.006) and higher peak levels of creatinine phosphokinase (3552±241U/L vs 2660±242U/L, p<0.01). On multivariate analysis, serum level of EPA+DHA was an independent predictor of reperfusion injury (odds ratio 0.985, p=0.032). CONCLUSION: Serum level of n-3 PUFAs before PCI may be a predictor of I/R injury and the resultant extent of myocardial damage. These findings suggest a protective effect of serum n-3 PUFAs on ischemic myocardium.

Refractory vasospasms of the coronary arteries due to multiple factors: an autopsy case.

A 41-year-old man was admitted with decompensated heart failure. Mechanical ventilation was maintained with a large dose of propofol. On day 4, significant ST elevation with complete atrioventricular block was noted, which subsequently induced cardiopulmonary arrest. Treatment with percutaneous cardiopulmonary support and therapeutic hypothermia was initiated. Emergent cardiac angiography showed simultaneous multivessel coronary spasms. Although nitroglycerin and nicorandil were ineffective, the intracoronary administration of fasudil, a Rho-kinase inhibitor, successfully resolved the vasospasms. However, during rewarming, the coronary vasospasms recurred, and the patient died of cardiogenic shock. In addition to hypertrophy, the autopsied heart demonstrated the accumulation of inflammatory cells in the pericardium and adventitia of the coronary arteries.

Congenital aortopulmonary artery fistulas combined with bilateral coronary artery fistulas.

We describe an extremely rare case of "congenital aorto-pulmonary artery fistulas" combined with bilateral coronary artery fistulas associated with clinically significant left-to-right shunt. A multi-detector row computed tomographic scan revealed that tortuous anomalous vessels arising from the aortic arch, left anterior descending coronary artery, diagonal branch, and right coronary artery were connected to the main pulmonary trunk. After surgical intervention, the systemic-to-pulmonary flow ratio nearly normalized from 2.02 to 1.05. We describe the case and speculate as to the embryological pathogenesis of these unique fistulas.

Serum amyloid A is a better predictor of clinical outcomes than C-reactive protein in non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Elevated C-reactive protein (CRP) is associated with adverse outcomes in non-ST-segment elevation acute coronary syndromes (NSTE-ACS); however, the prognostic significance of serum amyloid A (SAA), also an important inflammatory marker, remains unclear. METHODS AND RESULTS: The ability of SAA, in combination with CRP, to predict clinical outcomes was evaluated in 277 patients with NSTE-ACS. Patients were classified according to the presence or absence of elevated SAA (>0.8 mg/dl) and elevated high-sensitivity CRP (>0.200 mg/dl) on admission: group 1, both SAA and CRP normal (n=133); group 2, SAA normal, but CRP elevated (n=30); group 3, SAA elevated, but CRP normal (n=28); and group 4, both SAA and CRP elevated (n=86). In groups 1, 2, 3, and 4, the rates of combined endpoints including death, (re)infarction, or urgent target-vessel revascularization at 30 days were 8%, 3%, 25%, and 23%, respectively (p=0.002). Multivariate analysis showed that as compared with group 1, the odds ratios for combined endpoints in groups 2, 3, and 4 were 0.50 (p=0.30), 1.95 (p=0.038), and 1.86 (p=0.044), respectively. CONCLUSIONS: Regardless of the level of CRP, elevated SAA is associated with adverse 30-day outcomes in patients with NSTE-ACS, so SAA is a better predictor of clinical outcome than CRP in these patients.

Impact of plaque rupture on infarct size in ST-segment elevation anterior acute myocardial infarction.

OBJECTIVES: We sought to assess whether coronary plaque rupture at culprit lesions is associated with infarct size in patients with anterior acute myocardial infarction (AMI). BACKGROUND: Some patients with AMI have large infarcts despite early reperfusion. Whether culprit plaque morphology impacts infarct size or not remains unknown. METHODS: Patients who had a first anterior AMI with reperfusion within 6 hours after onset were enrolled and divided into 2 groups according to the presence or absence of plaque rupture at the culprit lesion as defined by preintervention intravascular ultrasound (IVUS): patients with rupture (n = 54) and without rupture (n = 37). RESULTS: Patients with plaque rupture had a higher incidence of no-reflow phenomenon (15% vs. 3%; p = 0.08) and a lower myocardial blush grade (1.5 vs. 2.3; p < 0.05) after percutaneous coronary intervention. The IVUS analysis showed that patients with plaque rupture had a higher incidence of soft plaque and positive remodeling. Peak creatine kinase levels were higher (4,707 vs. 2,309 IU/l; p < 0.0001) and left ventricular ejection fraction in the chronic phase was lower (54% vs. 63%; p < 0.01) in patients with plaque rupture. A multivariate logistic regression analysis revealed that plaque rupture and the proximal lesion site correlated with a left ventricular ejection fraction of <50% in the chronic phase (odds ratios 6.5 and 17.5, respectively; p < 0.05). CONCLUSIONS: Plaque rupture is associated with morphologic characteristics of vulnerable lesions, as well as with larger infarcts and a higher incidence of no-reflow phenomenon, suggesting that plaque embolism contributes to the progression of myocardial damage in patients with anterior AMI.

Differences between men and women in terms of clinical features of ST-segment elevation acute myocardial infarction.

BACKGROUND: Many studies have examined sex-related differences in the clinical features of acute myocardial infarction (AMI). However, prospective studies are scant, and sex-related differences in symptoms of AMI remain unclear. We examined differences between men and women in terms of the clinical features of ST-segment elevation AMI. METHODS AND RESULTS: We studied 457 patients (106 women and 351 men) with ST-segment elevation AMI who were admitted within 24 h after symptom onset. The same cardiologist interviewed all patients within 48 h after admission. Women were older than men (72 vs 62 years, p<0.001) and had higher rates of hypertension (70 vs 56%, p=0.010), diabetes mellitus (36 vs 26%, p=0.047), and hyperlipidemia (51 vs 38%, p=0.019). Women were more likely than men to have non-specific symptoms (45 vs 34%, p=0.033), non-chest pain (pain in the jaw, throat, neck, shoulder, arm, hand, and back), mild pain (20 vs 7%, p<0.001), and nausea (49 vs 36%, p=0.013). On coronary angiography, the severity of coronary-artery lesions was similar in both sexes. In-hospital mortality was significantly higher in women than in men (6.6 vs 1.4%, p=0.003). CONCLUSIONS: Clinical profiles and presentations differ between women and men with AMI. Women have less typical symptoms of AMI than men.

Prognostic significance of inverted T waves in patients with acute pulmonary embolism.

BACKGROUND: The significance of inverted T waves remains unclear in patients with acute pulmonary embolism (PE). METHODS AND RESULTS: The relationship of the number of leads with inverted T waves to the severity of PE in 40 patients with acute PE was studied. Patients were classified into 3 groups according to the number of leads with inverted T waves on the admission electrocardiogram (ECG): 15 patients, or=7 leads (group H). In groups L, M and H, the rates of right ventricular dysfunction on echocardiography were 47%, 92% and 100% (p<0.01), respectively, and the rates of in-hospital complicated events (including death or the need for catecholamine support, cardiopulmonary resuscitation or mechanical cardiovascular support because of hemodynamic instability) were 0%, 8% and 46% (p=0.004), respectively. On multivariate analysis, arterial hypotension at presentation (odds ratio (OR) 8.96, p=0.049) and inverted T waves in >or=7 leads on the admission ECG (OR 16.8, p=0.037) were the only independent predictors of in-hospital complicated events. CONCLUSIONS: The number of leads with inverted T waves may be a useful and simple marker of increased risk for early complications in patients with acute PE.

Acute renal failure due to cholesterol crystal embolism treated with LDL apheresis followed by corticosteroid and candesartan.

Cholesterol crystal embolism (CCE) is caused by the shedding of cholesterol crystals into the bloodstream, and it has been recently recognized as a serious complication after vascular procedures. Our case of CCE, which was diagnosed by skin and renal biopsies, occurred in a patient with hypertension and diabetes mellitus, 3 months after coronary angiography, with the development of renal failure and blue toes. After low-density lipoprotein apheresis (LDL-A), the skin lesions, including livedo reticularis and pain from the acrocyanotic toes, dramatically improved, with partial recovery of renal function. Following the administration of low-dose corticosteroid and candesartan--an angiotensin II type 1 receptor antagonist (ARB)--the eosinophilia disappeared and renal function improved gradually with a decrease in urinary protein excretion. Therefore, a combination therapy of LDL-A, low-dose corticosteroid, and an ARB is a possible treatment for CCE, although the possibility of spontaneous recovery of renal function cannot be eliminated for this patient.