Platypnea-Orthodeoxia: An Effective Diagnostic Tool for Hepatopulmonary Syndrome With Chronic Obstructive Pulmonary Disease.

Hepatopulmonary syndrome (HPS) shows progressive dyspnea resulting from intrapulmonary atrioventricular shunts in liver cirrhosis. The comorbidity of chronic lung disease often hampers the diagnosis of progressive dyspnea in patients with HPS. Therefore, a comprehensive approach to the determination of dyspnea is required. Here, this case report shows that a patient with chronic obstructive pulmonary disease (COPD) and alcoholic liver cirrhosis was diagnosed with HPS after admission due to worsening dyspnea. Although COPD exacerbation was initially suspected because of the long history of smoking, physical examinations, laboratory findings, and imaging data, dyspnea remained after recovery from worsening respiratory failure. HPS was suspected due to the absence of increased CO2 levels and the presence of platypnea-orthodeoxia. We diagnosed the intrapulmonary arteriovenous shunt with microbubble-contrast echocardiography and technetium-99m macroaggregated albumin scintigraphy. Therefore, this case highlighted that HPS rather than COPD was suspected of hypoxemia associated with repositioning for the differential diagnosis of dyspnea.

Communicating Coronary and Ventricular Pseudoaneurysms Complicating Coronary Artery Perforation.

We present the case of a 75-year-old man who experienced rebleeding after surgical treatment of grade III coronary perforation, resulting in intertwined complications including communicating coronary and ventricular pseudoaneurysms. The percutaneous intervention of sealing the rebleeding site with a covered stent implantation managed this rare pseudoaneurysm successfully. (Level of Difficulty: Advanced.).

Questionnaire in patients with aborted sudden cardiac death due to coronary spasm in Japan.

OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.

Impact of out-stent plaque characteristics on vascular response after second generation drug-eluting stent implantation: iMAP-intravascular ultrasound and angioscopic study.

PURPOSE: The purpose of this study is to elucidate the impact of out-stent plaque characteristics on vascular response after implantation of second generation drug-eluting stent (G2-DES). METHODS: Enrolled were 37 patients with 39 coronary artery lesions into which three types of G2-DES were successfully implanted (9 Nobori biolimus-, BES; 15 Xience everolimus-, EES; 15 Resolute zotarolimus-eluting stents; R-ZES). Immediately after (baseline) and one year after the implantation (follow-up), iMAP-intravascular ultrasound (IVUS) was performed to measure out-stent plaque volume (OSPV) and its components. Percent OSPV and vulnerable plaque index (VPI) were defined as percentile of OSPV to vessel volume and as percentile of lipidic plus necrotic volume to OSPV. Coronary angioscopy at follow-up rated the degree of arterial repair by neointimal stent coverage (NSC). RESULTS: Poor NSC was found in approximately 60% of each G2-DES. In BES, % OSPV at baseline was significantly greater in poor NSC than in good NSC (36.2 ±â€¯3.9 vs. 27.3 ±â€¯4.0%, P = 0.01). In EES, %OSPV was significantly greater in poor NSC than in good NSC (41.0 ±â€¯4.1 vs. 32.6 ±â€¯2.7%, P < 0.01). In R-ZES implantation, there was no significant difference with regards to %OSPV between poor and good NSC. In BES, VPI at baseline was significantly greater in poor NSC than good NSC (54.0 ±â€¯5.8 vs. 42.2 ±â€¯5.1%, P = 0.02). There was no significant difference with regards to VPI between poor and good NCS in EES and R-ZES. CONCLUSIONS: Impact of out-stent plaque characteristics on vascular response was different among the three types of G2-DES.

Angioscopic observation of extremely late arterial repair after intracoronary implantation of the first-generation sirolimus-eluting stents.

BACKGROUND: Arterial repair delays after intracoronary implantation of Cypher sirolimus-eluting stents (SES), a representative first-generation drug-eluting stent. It remains unclear whether this delay would catch up with bare metal stents (BMS) during extremely long observation. The aim of this study was angioscopic observation of extremely late arterial repair after Cypher SES implantation. METHODS: Thirty-seven SES and 17 BMS were implanted into 22 and 9 patients with angina pectoris, respectively. Duration after implantation (DAI) ranged from 3 to 10.5years in both stents. Coronary angioscopy revealed neointimal stent coverage (NSC), presence of in-stent yellow plaque (YP), and mural thrombi (MT). NSC was semi-quantified into 4 grades (grade 0, no coverage; grade 1, thin coverage; grade 2, thick coverage; grade 3, fully embedded into neointima). RESULTS: In the BMS-implanted lesions (BMSL), NSC was either grade 1 (24%) or grade 3 (74%), with rare YP and no MT. In the SES-implanted lesions (SESL), NSC was various, i.e. grade 0 (5%), grade 1 (59%), grade 2 (22%), and grade 3 (14%). YP and MT were observed in 27 and 24% of in SESL, respectively. In SESL with DAI>8years (n=5), NSC was either grade 1 (40%) or grade 3 (60%), although YP and MT were more frequently observed (60 and 40%, respectively). CONCLUSIONS: Arterial repair after SES implantation caught up with BMS at around 8years with regards to NSC, although prevalence of YP and MT remained still greater in SESL than BMSL at extremely late phase.

Angioscopic comparison of arterial repair after second-generation drug-eluting stent implantation into vulnerable and stable coronary plaques.

BACKGROUND: Arterial repair after intracoronary stenting depends on stent types and plaque vulnerability. The aim of this study was angioscopic comparison of arterial repair after implantation of the second-generation drug-eluting stents (G2-DES) between the stable and vulnerable plaques. METHODS: Four types of G2-DES were successfully implanted into stable plaques (n=41) and vulnerable plaques (n=34): 13 and 9 Xience-everolimus-, 7 and 6 Endeavor-zotarolimus-, 15 and 9 Resolute-zotarolimus-, and 6 and 10 Nobori-biolimus-eluting stents (EES, E-ZES, R-ZES, and BES), respectively. Coronary angioscopy at 1-year follow-up revealed in-stent appearance, such as neointimal stent coverage (NSC), presence of yellow plaques (YP), and in-stent mural thrombus (MT). NSC was graded into poor and good coverage. RESULTS: Yellow plaques and mural thrombi were found more frequently in the vulnerable plaques than in the stable plaques (29% vs. 12%, P=0.06; 12 vs. 0%, P=0.02; respectively). In EES, poor NSC was observed more frequently in the vulnerable plaques than in the stable plaques (54% vs. 11%, P=0.04). In BES, YP was observed more frequently in the vulnerable plaques than in the stable plaques (80% vs. 17%, P=0.01). In E-ZES and R-ZES, there were no significant differences with regards to angioscopic parameters between the stable and vulnerable plaques. CONCLUSIONS: Arterial repair after EES and BES implantation into the vulnerable plaques remained vulnerable even at 1-year follow-up.

Oral direct renin inhibitor aliskiren reduces in vivo oxidative stress and serum matrix metalloproteinase-2 levels in patients with permanent atrial fibrillation.

We aimed to determine the effects of the oral direct renin inhibitor aliskiren on in vivo oxidative stress in atrial fibrillation (AF) patients. In this study, 150 mg oral direct renin inhibitor aliskiren was administered once daily to 12 permanent AF patients. Aliskiren significantly reduced urinary excretion of the oxidative stress biomarker 8-iso-prostglandin F2α and serum levels of matrix metalloproteinase-2(MMP-2). We concluded that aliskiren reduces in vivo oxidative stress and serum MMP-2 levels in patients with permanent AF.

Characterization of patients with angioscopically-detected in-stent mural thrombi ­ genetics of clopidogrel responsiveness and generations of drug-eluting stents.

BACKGROUND: The loss-of-function genotype of cytochrome P450 2C19 (CYP2C19) has been proposed as a risk factor for stent thrombosis in patients with drug-eluting stent implantation. The aim of this study was to clarify the clinical features of patients with angioscopically-detected in-stent mural thrombi (ISMT). METHODS AND RESULTS: Enrolled were 100 stented segments in 55 patients with stable angina (20 bare-metal stents; 39 Cypher sirolimus-eluting stents [SES]; 26 Endeavor zotarolimus-eluting stents [ZES]; 13 Xience V everolimus-eluting stents; and 2 Nobori biolimus-eluting stents). Dual antiplatelet therapy (100 mg aspirin+75 mg clopidogrel once daily) had been continued since stenting. A poor metabolizer (PM) of clopidogrel was defined as a homozygote of CYP2C19 loss-of-function alleles. Coronary angioscopy revealed ISMT in 6 patients (5 SES, 1 ZES). Between the ISMT group and control group (n=49), there were no significant differences with regards to the VerifyNow P2Y12platelet function assay or in-stent endothelial coverage grade. Exact logistic regression analyses with stepwise forward selection at a significance level of 0.10 were performed to reveal predictive variables for ISMT (respectively: odds ratio, 95% confidence interval, P value: CYP2C19 PM genotype (3.28, 0.88-24.80, 0.09), SES implantation (3.37, 0.90-28.09, 0.08), and presence of yellow plaque (3.69, 1.14-25.70, 0.02). CONCLUSIONS: Patients with ISMT were characterized by SES implantation, poor clopidogrel metabolism, and in-stent yellow plaque.

Spontaneous resolution of pseudoaneurysm after zotarolimus-eluting stent implantation: imaging evidence at 13 months of follow-up.

Coronary pseudoaneurysm is a rare complication of percutaneous coronary intervention with a drug-eluting stent. Neither precise incidence of the complication has been known, nor there has been any established therapeutic approach for it. A 69-years-old male with effort angina underwent percutaneous coronary intervention to his left main coronary artery (LMCA). After pre-dilatation with a balloon, Endeavor zotarolimus-eluting stent (E-ZES) was successfully implanted into the lesion that extended from his LMCA to left anterior descending artery. At 6 months after stenting, coronary angiography (CAG) and intravascular ultrasound (IVUS) revealed coronary pseudoaneurysm at the stented segment. Follow-up CAG at 13 months after stenting showed the spontaneous and complete resolution of the pseudoaneurysm. Subsequent IVUS, optical coherence tomography, and coronary angioscopy visualized complete neointimal coverage of stent struts. This is the first case report of E-ZES-related pseudoaneurysm with relatively rapid resolution. Our patient suggests that E-ZES might incidentally contribute to this favorable outcome.

Characterization of Patients With Angioscopically-Detected In-Stent Mural Thrombi.

Background:The loss-of-function genotype of cytochrome P450 2C19 (CYP2C19) has been proposed as a risk factor for stent thrombosis in patients with drug-eluting stent implantation. The aim of this study was to clarify the clinical features of patients with angioscopically-detected in-stent mural thrombi (ISMT).Methods and Results:Enrolled were 100 stented segments in 55 patients with stable angina (20 bare-metal stents; 39 Cypher sirolimus-eluting stents [SES]; 26 Endeavor zotarolimus-eluting stents [ZES]; 13 Xience V everolimus-eluting stents; and 2 Nobori biolimus-eluting stents). Dual antiplatelet therapy (100 mg aspirin+75 mg clopidogrel once daily) had been continued since stenting. A poor metabolizer (PM) of clopidogrel was defined as a homozygote of CYP2C19 loss-of-function alleles. Coronary angioscopy revealed ISMT in 6 patients (5 SES, 1 ZES). Between the ISMT group and control group (n=49), there were no significant differences with regards to the VerifyNow P2Y12platelet function assay or in-stent endothelial coverage grade. Exact logistic regression analyses with stepwise forward selection at a significance level of 0.10 were performed to reveal predictive variables for ISMT (respectively: odds ratio, 95% confidence interval, P value: CYP2C19 PM genotype (3.28, 0.88-24.80, 0.09), SES implantation (3.37, 0.90-28.09, 0.08), and presence of yellow plaque (3.69, 1.14-25.70, 0.02).Conclusions:Patients with ISMT were characterized by SES implantation, poor clopidogrel metabolism, and in-stent yellow plaque.

Optical coherence tomographic and angioscopic assessments of arterial healing in coronary artery perforation after implantation of zotarolimus-eluting stent.

We report the case of a 69-year-old male whose left circumflex coronary artery was perforated immediately after implantation of an Endeavor zotarolimus-eluting stent (E-ZES). Despite successful hemostasis by long balloon inflation, a coronary pseudoaneurysm remained at the E-ZES-implanted segment. Coronary angiography performed one year after the coronary perforation showed the pseudoaneurysm had disappeared. Simultaneous optical coherence tomography and coronary angioscopy revealed that stent struts of the E-ZES were fully covered with thick neointima. This is the first case report of a relatively rapid healing process for an E-ZES-related coronary pseudoaneurysm.

Repetitive angioscopic observations of a sirolimus-eluting stent deployed in a patient with silent chronic thrombotic occlusion.

In the era of the drug-eluting stent, very late stent thrombosis has been the most serious issue in the field of interventional cardiology. A sirolimus-eluting stent (SES) was implanted in an in-stent restenotic lesion in the left circumflex artery of a 69-year-old man. Repetitive coronary angiography and angioscopy revealed that stent struts were covered with yellow neointima at 2 years after the SES deployment. At 4 years after the deployment, coronary angiography revealed the total occlusion of the SES. Angioscopy showed massive mural thrombi and yellow atherosclerotic plaques. Dual anti-platelet therapy (DAPT), ticlopidine and aspirin, had been continued since the SES deployment. Interventional cardiologists should heed the risk of silent chronic thrombotic occlusion even if struts of SES are fully covered with neointima under continued DAPT.

Acute coronary occlusion by injured aortic valve during percutaneous coronary intervention.

We report a rare case of a 58-year-old male with accidental occlusion of left main trunk (LMT) artery by injured aortic valve during percutaneous coronary intervention (PCI). Although we successfully bailed out this complication by urgent LMT stenting, aortic regurgitation developed immediately after PCI. Echocardiography detected a filamentous structure attached to the aortic valve. An elective aortic valve replacement surgery revealed that his right coronary cusp was torn into two filamentous strips. One strip accidentally plunged into LMT and was fixed by the intracoronary stent. Another strip floated in the aortic root and appeared as though vegetation attached to the aortic valve in case of acute infective endocarditis. Guiding catheters probably injured the aortic valve during PCI. This report reminded us of the importance of meticulous manipulation of a guiding catheter.

Differences in the mode of presentation for acute coronary syndrome by pre-hospitalization medication, in relation to coronary risk factors, East-Osaka acute coronary syndrome (EACS) registry.

BACKGROUND: Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. METHODS AND RESULTS: We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. CONCLUSION: Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

Admission with metabolic disorder is a useful predictor of the 1-year prognosis for patients with unstable angina, but not for patients with acute myocardial infarction: east-Osaka acute coronary syndrome registry.

BACKGROUND: For patients with acute myocardial infarction (AMI), several studies have examined the relationship between the metabolic syndrome and prognostic outcome. However, few studies have revealed an association between the metabolic syndrome and clinical outcomes in patients with unstable angina (UA). This study compared the differences in the usefulness of recognizing metabolic disorders for the prediction of a 1-year prognosis in patients with UA and AMI. METHODS: The study cohort consisted of 1173 patients with a mean age of 67 years. The focus was on general prognostic factors and five metabolic disorders (body mass index; hypertension; blood glucose/diabetes mellitus; and, serum concentrations of triglycerides and high-density lipoprotein cholesterol) at the time of admission. RESULTS: According to multivariate logistic regression analysis, metabolic scores on admission positively related to 1-year mortality or major adverse cardiovascular events (MACE) for patients with UA, but not for those with AMI, with an increase in either all-causes mortality or MACE being associated with the degree of metabolic dysfunction. No other general prognostic factors were related to either 1-year mortality or MACE in patients with UA. By contrast, general prognostic factors such as age and the Killip classification had a positive effect on 1-year mortality or on MACE for the patients with AMI. CONCLUSION: Accumulation of the effects of each metabolic disorder may affect mortality and MACE for patients with UA.

Mutation analysis of 2009 pandemic influenza A(H1N1) viruses collected in Japan during the peak phase of the pandemic.

BACKGROUND: Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges. METHODOLOGY: A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. RESULTS AND CONCLUSIONS: Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.

Lipocalin-type prostaglandin D synthase is a powerful biomarker for severity of stable coronary artery disease.

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin (PG) D(2), has been found to be present in the atherosclerotic plaque of the human coronary artery and also to be detectable in human serum. This multicenter cooperative study was designed to establish the diagnostic value of measuring serum L-PGDS for coronary artery disease. The study included 1013 consecutive patients suspected of having stable coronary artery disease who underwent diagnostic coronary angiography. Peripheral blood was collected prior to angiography. The serum level of L-PGDS, as determined by a sandwich ELISA, was 58.1 +/- 2.2, 62.0 +/- 1.8 and 80.6 +/- 2.6 microg/dl for patients with no stenotic lesion (N, n=241), single-vessel coronary artery disease (S, n=351), and multi-vessel coronary artery disease (M, n=421), respectively (N vs. S; P<0.001, S vs. M; P<0.01, N vs. M; P<0.001). Multiple regression analysis indicated that the most powerful independent predictor of the coronary severity score (Gensini Score) was the L-PGDS level (R=0.55, P<0.0001). The serum L-PGDS level is suitable to evaluate the severity of coronary artery disease. The measurement of serum L-PGDS can be a strategy for screening of stable coronary artery disease prior to coronary angiography.

Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study.

BACKGROUND: It is unclear whether early initiation of low-dose pravastatin therapy can reduce the occurrence of major adverse cardiac events after acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 353 patients with AMI who had plasma total cholesterol levels of 200-250 mg/dl and triglyceride levels <300 mg/dl. The patients were randomly assigned to either receive pravastatin (10 mg/daily, n=176) or not (n=177). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), unstable angina (UA), stroke, revascularization, and rehospitalization because of other cardiovascular disease. The follow-up period was 9 months. The primary endpoint occurred in 31 patients (17.9%) in the pravastatin group and 55 patients (31.4%) in the non-pravastatin group (relative risk, 0.56; 95% confidence interval, 0.36-0.87). There were no significant differences in the risk of death, nonfatal MI, UA, and stroke between the 2 groups, although the pravastatin group had a lower risk of need for revascularization. CONCLUSION: For patients with AMI, early and low-dose pravastatin therapy (10 mg/daily) reduces recurrent major adverse cardiac events, mostly the requirement for revascularization.

Transient enhancement of oxidant stress and collagen turnover in patients with acute worsening of congestive heart failure.

BACKGROUND: Myocardial remodeling is a crucial step for progression of heart failure (HF). Free radical generation by the failing myocardium has been proposed as linked to myocardial remodeling. The aim of this study was to evaluate the urinary excretion of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable marker for oxidant stress in vivo, and collagen turnover in patients with acute worsening of congestive HF. METHODS AND RESULTS: Enrolled were 43 patients with acute worsening of congestive HF of various etiologies. On admission (acute phase) and after approximately 2 weeks of conventional treatment (chronic phase), the following were measured: (1) immunoreactive urinary 8-iso-PGF2alpha, (2) serum total antioxidant status (TAS); and (3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. From the acute to the chronic phase the parameters changed as follows: 335.1+/-245.4 to 205.3+/-107.4 pg/mg creatinine for urinary 8-iso-PGF2alpha (p<0.0001); 0.92+/-0.16 to 0.98+/-0.13 mmol/L for TAS (p<0.01); 171.4+/-72.5 to 93.7+/-33.9 ng/ml for PIP (p<0.0001); and 7.2+/-3.6 to 12.6+/-8.4 ng/ml for CITP (p<0.0001). CONCLUSIONS: Acute worsening of congestive HF promotes free radical generation and collagen synthesis.