Validation of the obesity paradox by body mass index and waist circumference in patients undergoing percutaneous coronary intervention.

BACKGROUND: The paradoxical association of obesity with mortality, named the "obesity paradox", has been inconsistent, possibly due to a difference between body mass index (BMI) and central obesity, estimated by waist circumference (WC) as patterns of adiposity. SUBJECTS/METHODS: We enrolled 8513 participants from the Kumamoto Intervention Conference Study, a multicenter registry that included consecutive patients undergoing percutaneous coronary intervention (PCI) at 18 centers between 2008 and 2017 in Japan. Patients were divided into quartiles in ascending order of the BMI or WC. The primary endpoints were all-cause mortality and cardiovascular death within a year. RESULTS: There were 186 deaths (case fatality rate, 22.1/1000 person-years) during the follow-up period. The lowest group (1st quartile) of BMI or WC had the worst prognosis among the quartiles (1st quartile, 4.2%; 2nd quartile, 1.9%; 3rd quartile, 1.5%; 4th quartile, 1.1%; P < 0.001 (χ2) and 1st quartile, 4.1%; 2nd quartile, 2.3%; 3rd quartile, 1.2%; 4th quartile, 1.5%; P < 0.001 (χ2), respectively). Similar results were obtained for cardiovascular death. In a multivariable analysis adjusted by nine conventional factors, the lowest group (1st quartile) of BMI (hazards ratio, 2.748; 95% confidence interval [CI], 1.712-4.411) and WC (hazards ratio, 2.340; 95% CI, 1.525-3.589) were independent prognostic factors for all-cause mortality. By dividing the participants into two groups according to either the BMI or WC based on the National Cholesterol Education Program Adult Treatment Panel III and World Health Organization classification, the highest mortality was observed in the lower group. However, the C-statistic after adding BMI (quartile) to conventional factors was found to be slightly higher than BMI (two categories) and WC (two categories) (0.735 vs. 0.734). CONCLUSIONS: The obesity paradox was observed in patients after PCI, and single-use of BMI (or WC) was sufficient to predict the prognosis of patients after PCI.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

256-Slice coronary computed tomographic angiography in patients with atrial fibrillation: optimal reconstruction phase and image quality.

OBJECTIVES: To assess the optimal reconstruction phase and the image quality of coronary computed tomographic angiography (CCTA) in patients with atrial fibrillation (AF). METHODS: We performed CCTA in 60 patients with AF and 60 controls with sinus rhythm. The images were reconstructed in multiple phases in all parts of the cardiac cycle, and the optimal reconstruction phase with the fewest motion artefacts was identified. The coronary artery segments were visually evaluated to investigate their assessability. RESULTS: In 46 (76.7 %) patients, the optimal reconstruction phase was end-diastole, whereas in 6 (10.0 %) patients it was end-systole or mid-diastole, and in 2 (3.3 %) patients it was another cardiac phase. In 53 (88.3 %) of the controls, the optimal reconstruction phase was mid-diastole, whereas it was end-systole in 4 (6.7 %), and in 3 (5.0 %) it was another cardiac phase. There was a significant difference between patients with AF and the controls in the optimal phase (p < 0.01) but not in the visual image quality score (p = 0.06). CONCLUSIONS: The optimal reconstruction phase in most patients with AF was the end-diastolic phase. The end-systolic phase tended to be optimal in AF patients with higher average heart rates. KEY POINTS: The optimal reconstruction phase in 76.7 % of patients with atrial fibrillation (AF) was end-diastole. The end-systolic phase was optimal in AF patients with higher heart rates. ECG and heart-rate control are necessary to obtain end-diastolic images with fewer motion artefacts.

Clinical Impact of Telemedicine Network System at Rural Hospitals Without On-Site Cardiac Surgery Backup.

BACKGROUND: In Japan, catheterization laboratories are available in each medical service area. However, cardiovascular centers capable of surgical procedures are concentrated in urban areas. Critically ill patients with complex coronary lesions must be transferred to receive advanced medical care. Interhospital conferencing is necessary for an optimal patient transfer. We investigated the benefit and utility of a Digital Imaging and Communications in Medicine (DICOM) telemedicine network at a rural hospital without on-site cardiac surgery backup in Japan. MATERIALS AND METHODS AND RESULTS: The Kumamoto telemedicine network consists of 2 high-volume centers and 12 rural low-volume hospitals without on-site cardiac surgery. Between January 2010 and December 2014, 293 teleconferences were conducted. At the Aso Medical Center, a low-volume hospital, teleconferences were carried out in 48 cases (30 coronary artery disease, 6 peripheral artery disease, 3 aortic aneurysm, 3 deep vein thrombosis, 2 inflammatory aortitis, 1 annuloaortic ectasia, 1 cardiac tamponade, 1 myocarditis, and 1 heart failure). After the conferences were initiated, 10 cases (20.8%) were transferred to the high-volume center. We investigated the prevalence of patient transfer before and after network system deployment. Telemedicine-based collaborative care significantly decreased the frequency of patient transfers from the Aso area. CONCLUSIONS: The Kumamoto telemedicine network enabled open communication between distant hospitals. This collaboration has the potential to improve cardiac care in rural areas.

Differential Effects of Strong and Regular Statins on the Clinical Outcome of Patients With Chronic Kidney Disease Following Coronary Stent Implantation　- The Kumamoto Intervention Conference Study (KICS) Registry.

BACKGROUND: The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants. METHODS AND RESULTS: This study included 5,801 consecutive patients (males, 4,160; age, 69.7±11.1 years, mean±SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mild-to-moderate CKD (30≤eGFR<60, n=1,956) and severe CKD (eGFR <30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31-0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively). CONCLUSIONS: In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events.

Improved image quality at 256-slice coronary CT angiography in patients with a high heart rate and coronary artery disease: comparison with 64-slice CT imaging.

BACKGROUND: The 256-slice computed tomography (CT) scanners with wider detector coverage and faster gantry rotation speed are now available. The performance of scanners that feature a rotation speed of 270 ms at coronary CT angiography (CCTA) has not been evaluated in patients with a higher heart rate. PURPOSE: To evaluate the image quality of 256-slice CT with faster gantry rotation speed in patients undergoing CCTA. MATERIAL AND METHODS: We enrolled 886 patients; 357(40.3%) underwent study on a 64-slice CT at a rotation speed of 420 ms, the other 529 (59.7%) were examined using a 256-slice CT scanner at 270 ms. Two observers judged the image quality of 2658 imaged coronary arteries on a 4-point scale. RESULTS: The mean image quality score was significantly higher for the 256 - than the 64-slice CT scans (3.94 ± 0.28 vs. 3.73 ± 0.61; P < 0.01). There was no significant difference in the image quality scores between 64 - and 256-slice scans in patients whose heart rate (HR) was <60 bpm. However, in patients whose HR exceeded 60 bpm these scores were significantly higher for 256-slice CT images (P < 0.01). CONCLUSION: CCTA performed on the 256-slice CT scanner yielded significantly better image quality in patients with an HR exceeding 60 bpm.

A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Several susceptibility genes for ALS have been reported; however, ALS etiology and pathogenesis remain largely unknown. To identify further ALS-susceptibility genes, we conducted a large-scale case-control association study using gene-based tag single-nucleotide polymorphisms (SNPs). A functional SNP (rs2275294) was found to be significantly associated with ALS through a stepwise screening approach (combined P= 9.3 × 10(-10), odds ratio = 1.32). The SNP was located in an enhancer region of ZNF512B, a transcription factor of unknown biological function, and the susceptibility allele showed decreased activity and decreased binding to nuclear proteins. ZNF512B over-expression increased transforming growth factor-ß (TGF-ß) signaling, while knockdown had the opposite effect. ZNF512B expression was increased in the anterior horn motor neurons of the spinal cord of ALS patients when compared with controls.  Our results strongly suggest that ZNF512B is an important positive regulator of TGF-ß signaling and that decreased ZNF512B expression increases susceptibility to ALS.

Clinical outcomes following coronary stenting in Japanese patients treated with and without proton pump inhibitor.

BACKGROUND: The aim of this study was to examine the effect of proton-pump inhibitor (PPI) on clinical outcomes in Japanese patients who undergo coronary stent implantation. METHODS AND RESULTS: A total of 1,270 patients (males 915, 69 years) were enrolled and dual antiplatelet therapy of aspirin and a thienopyridine derivative was prescribed (clopidogrel 630, ticlopidine 640). Patients were divided into 2 groups treated with or without PPI. PPI was administered in 331 cases (26%), and non-PPI in 939 (74%). There were no significant differences in cardiovascular death (PPI vs. non-PPI: 5 vs. 11 cases), nonfatal myocardial infarction (3 vs. 5), and stroke (3 vs. 16) between PPI and non-PPI groups, but the ratio of gastrointestinal events had a higher tendency in non-PPI group compared with PPI group (1 vs. 17, P=0.08). In subgroup analysis of patients taking clopidogrel, or patients with acute coronary syndrome, there was no significant difference in the ratio of cardiovascular events (7 vs. 16, 6 vs. 17, NS). The non-PPI group had a tendency of an increased risk of gastrointestinal events compared with the PPI group (0 vs. 9, P=0.06; 1 vs. 7, P=0.14). CONCLUSIONS: In contrast to the negative drug interaction of PPI reported elsewhere, in the present study the intake of PPI was not associated with an increased risk for adverse clinical outcomes in patients treated with stents.

Dose-Dependent Inhibitory Effect of Rosuvastatin in Japanese Patients with Acute Myocardial Infarction on Serum Concentration of Matrix Metalloproteinases-INVITATION Trial.

AIM: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. METHODS: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. RESULTS: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. CONCLUSIONS: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

Temporal trends in coronary intervention strategies and the impact on one-year clinical events: data from a Japanese multi-center real-world cohort study.

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used.

Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.

AIM: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. METHODS: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL. RESULTS: In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008). CONCLUSIONS: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Imaging-guided PCI for event suppression in Japanese acute coronary syndrome patients: community-based observational cohort registry.

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P < 0.001). Even after propensity-score matching, the event rates still showed significant differences between the two groups (log-rank P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR ( http://www.umin.ac.jp/ctr/ ). Identifier: KICS (UMIN000015397).

Expression levels of Toll-like receptor genes in coronary atherosclerotic lesions of patients with acute coronary syndrome or stable angina pectoris.

BACKGROUND: The differences between acute coronary syndrome (ACS) and stable angina pectoris (SAP) in Toll-like receptor (TLR) expression levels in coronary plaques are not well known. TLR gene expression levels were examined, not only in peripheral blood mononuclear cells (PBMCs), but also in coronary plaques in ACS and SAP patients. METHODS AND RESULTS: TLR gene expression levels were examined in PBMCs using real-time RT-PCR in 27 ACS patients, 45 SAP patients and 28 control subjects. TLR2 and TLR4 expression levels in the PBMCs were significantly higher in the ACS group than in the SAP group. TLR9 expression levels were not significantly different among the 3 groups. TLR gene expression levels were also measured in directional coronary atherectomy (DCA) samples from 9 ACS and 14 SAP patients. The TLR2 expression levels in the DCA samples did not significantly differ between the 2 groups. The TLR4 expression levels were significantly higher in the ACS group than in the SAP group. CONCLUSIONS: The results suggest that TLR4 signaling could be more associated with plaque destabilization than with plaque progression. TLR4 expression control may be a novel target for ACS treatment.

Low contrast material dose coronary computed tomographic angiography using a dual-layer spectral detector system in patients at risk for contrast-induced nephropathy.

OBJECTIVE:: To evaluate the effects of virtual monochromatic imaging (VMI) using dual-layer spectral detector CT on the image quality of coronary CT angiography (CCTA) acquired by using a low contrast material (CM) dose. METHODS:: We used a VMI 50keV protocol with a 50% CM dose (140 mgI kg-1) to scan 30 patients with renal insufficiency and a 120 kVp with the standard CM dose (280 mgI kg-1) to scan 30 controls without renal insufficiency. Quantitative parameters, including CT attenuation, image noise, and contrast-to-noise ratio (CNR), were measured. The visual image quality factors of contrast enhancement, image noise, beam-hardening artefact, vessel sharpness, and overall image quality were scored on a 4-point scale. RESULTS:: The mean CT attenuation of the ascending aorta was significantly higher for 50 keV VMI than for 120 kVp. Image noise was significantly lower under the 50 keV VMI. CNR and the mean visual score for contrast enhancement were significantly higher for 50 keV VMI. There were no significant differences in the other visual image quality parameters between the two protocols. CONCLUSION:: Dual-layer spectral detector CT using 50 keV VMI enabled reducing the CM dose by 50 % without CCAT image quality degradation in patients with renal insufficiency. ADVANCES IN KNOWLEDGE:: The VMI 50 keV protocol using dual-layer spectral detector CT and a CM dose reduced by 50 % (140 mgI kg-1) can improve the diagnostic image quality of CCTA.

Elevated mature macrophage expression of human ABHD2 gene in vulnerable plaque.

We previously reported that the mouse alpha/beta hydrolase domain containing 2 (Abhd2) was expressed in smooth muscle cells (SMCs) which suppressed their migration and inhibited the development of intimal hyperplasia by cuff placement; however, the role of ABHD2 in human remains to be elucidated. In this study, we examined ABHD2 expression in the human coronary atherosclerotic lesions of the patients with unstable angina (UA) and stable angina (SA). Our results showed that the ABHD2 was expressed in atherosclerotic lesions, and that the ABHD2 expression was significantly higher in the patients with UA than with SA. Immunohistochemistry analysis revealed abundant expression of ABHD2 in macrophages, but low expression in SMCs of atherosclerotic lesions. Using human vascular primary culture cell lines, we also demonstrated that the expression of ABHD2 was significantly higher in macrophages than in SMCs, and that the expression of ABHD2 significantly increased proportionally with differentiation from monocyte into macrophage.

Impact of statin-ezetimibe combination on coronary atheroma plaque in patients with and without chronic kidney disease - Sub-analysis of PRECISE-IVUS trial.

BACKGROUND: Chronic kidney disease (CKD) deteriorates the prognosis of patients undergoing percutaneous coronary intervention (PCI). Because coronary artery disease (CAD) is the major cause of death in CKD patients, cardiovascular risk reduction has been clinically important in CKD. We hypothesized intensive lipid-lowering with statin/ezetimibe attenuated coronary atherosclerotic development even in patients with CKD. METHODS: In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound (IVUS)-guided PCI were randomly assigned to receive atorvastatin/ezetimibe combination or atorvastatin alone (the dosage of atorvastatin was up-titrated to achieve the level of low-density lipoprotein cholesterol < 70 mg/dL). Serial volumetric IVUS findings obtained at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients were compared stratified by the presence or absence of CKD. RESULTS: CKD was observed in 52 patients (26%) among 202 enrolled patients. Compared with the non-CKD group, the CKD group was significantly older (71.5 ±â€¯8.6 years vs. 64.4 ±â€¯9.6 years, P < 0.001) with similar prevalence of comorbid coronary risk factors and lipid profiles. Similar to the non-CKD group (-1.4 [-2.8 to -0.1]% vs. -0.2 [-1.7 to 1.0]%, P = 0.002), the atorvastatin/ezetimibe combination significantly reduced ∆PAV compared with atorvastatin alone even in the CKD group (-2.6 [-5.6 to -0.4]% vs. -0.9 [-2.4 to 0.2]%, P = 0.04). CONCLUSIONS: As with non-CKD, intensive lipid-lowering therapy with atorvastatin/ezetimibe demonstrated stronger coronary plaque regression effect even in patients with CKD compared with atorvastatin monotherapy. TRIAL REGISTRATION: NCT01043380 (ClinicalTrials.gov).

Dose-dependent INhibitory effect of rosuVastatin In Japanese patienTs with Acute myocardial infarcTION on serum concentration of matrix metalloproteinases - INVITATION trial.

BACKGROUND: Acute myocardial infarction (AMI) is mainly characterized by the rupture of lipid-rich vulnerable atherosclerotic plaque. The matrix metalloproteinases (MMPs) have been shown to play a critical role in inflammatory processes underlying plaque rupture. Some reports suggested statins inhibit the increased MMP levels after AMI. However, there are a few comparison studies between the different dosages of the same statin and circulating levels of MMPs. PURPOSE: This study will preliminarily investigate the potential effects of appropriate or low dose of rosuvastatin on circulating MMPs levels in AMI patients. Moreover, we will also obtain plasma from patients while undergoing diagnostic angiography to determine differences in various cardiac sites and peripheral vessels. METHODS: This study is a multicenter, open-label, randomized, parallel-group study to be conducted to compare the appropriate or low dose of rosuvastatin in the effect on serum levels of inflammatory markers in AMI patients. The eligible patients undergoing percutaneous coronary intervention (PCI) will be randomly assigned to receive either appropriate or low-dose rosuvastatin daily using a web-based randomization software within 24h after PCI. The low-dose group will be treated with rosuvastatin 2.5mg once daily with a follow-up. The appropriate-dose group will begin treatment with rosuvastatin 5mg once daily, and the dose of rosuvastatin will be titrated to 10mg within 4 weeks. During administration of the study treatment, subjects will undergo laboratory testing including MMPs and be monitored for the occurrence of adverse events up to 24 weeks. The primary endpoint will be the change rate of MMPs at 24 weeks after administration. CONCLUSIONS: INVITATION will compare the appropriate or low dose of rosuvastatin in the effects on serum levels of inflammatory markers including MMPs in AMI patients. This study will provide significant information on rosuvastatin as an anti-inflammatory agent for AMI.

Isolated Right Ventricular Stress (Takotsubo) Cardiomyopathy.

A 79-year-old woman was admitted with a left femoral neck fracture and she immediately developed circulatory shock. Echocardiography showed a markedly enlarged right ventricle (RV) with systolic ballooning of the mid-ventricular wall and preserved contractility of the apex. The left ventricular (LV) motion was normal. Multi-detector-row computed tomography showed severe congestion of the contrast media in the right atrium with no forward flow to RV, but no pulmonary embolism. She was successfully treated with percutaneous veno-arterial extracorporeal membrane oxygenation. This case presented with acute, profound, but reversible RV dysfunction triggered by acute stress in a manner similar to that seen in LV stress cardiomyopathy.