Iwao Okai

Long-term prognosis and clinical characteristics of young adults (≤40 years old) who underwent percutaneous coronary intervention.

BACKGROUND Limited data exist regarding the long-term prognosis of percutaneous coronary intervention (PCI) in young adults. The aim of this study was to retrospectively assess the long-term clinical outcomes in young patients who underwent PCI. METHODS AND RESULTS Between 1985 and 2011, 7649 consecutive patients underwent PCI, and data from 69 young adults (age ≤40 years) and 4255 old adults (age ≧65 years) were analyzed. A Cox proportional hazards regression analysis was used to determine the independent predictors of a composite endpoint that included all-cause death and acute coronary syndrome (ACS) during the follow-up period. The mean age of the 69 young patients was 36.1±4.9 years, and 96% of them were men. Approximately 30% were current smokers, and their body mass index (BMI) was 26.7±5.0kg/m(2). The prevalence of diabetes and hypertension was 33% and 48%, respectively. All patients had ≥1 conventional cardiovascular risk factor. At a median follow-up of 9.8 years, the overall death rate was 5.8%, and new-onset ACS occurred in 8.7%. Current smoking was an independent predictor of the composite endpoint (hazard ratio 4.46, confidence interval 1.08-19.1, p=0.04) for young adults. CONCLUSION Current smoking and obesity (high BMI) are the important clinical characteristics in young Japanese coronary heart disease patients who undergo PCI. The long-term prognosis in young patients is acceptable, but current smoking is a significant independent predictor of death and the recurrence of ACS in young Japanese coronary heart disease patients who are obese.

Impact of Lipoprotein(a) as Residual Risk on Long-Term Outcomes in Patients After Percutaneous Coronary Intervention

Cardiovascular risk remains uncertain in patients with cardiovascular disease despite achieving target lipid levels. Serum levels of lipoprotein(a) [Lp(a)] can be risk factors for adverse events. The aim of this study was to determine the role of Lp(a) as a residual risk factor in patients who achieve target lipid levels by the time of treatment by percutaneous coronary intervention (PCI). A total of 3,508 patients were treated by PCI from 1997 to 2011 at our institution. Among them, we analyzed consecutive 569 patients who achieved target lipid levels of low-density lipoprotein cholesterol <100 mg/dl, high-density lipoprotein cholesterol ≥40 mg/dl, and triglycerides <150 mg/dl at PCI. A total of 411 eligible patients were assigned to groups according to Lp(a) levels of ≥30 mg/dl (high Lp(a); n = 119) or <30 mg/dl (low Lp(a); n = 292). The primary outcome was a composite of all-cause death and acute coronary syndrome. The median follow-up period was 4.7 years. Cumulative event-free survival was significantly worse for the group with high Lp(a) than with low Lp(a) group (p = 0.04). Multivariate analysis selected a high Lp(a) level as an independent predictor of primary outcomes (hazard ratio 1.68, 95% confidence interval 1.03 to 2.70, p = 0.04). In conclusion, a high Lp(a) value (≥30 mg/dl) could be associated with a poor prognosis after PCI even for patients who achieved target lipid levels.

Comparison of Clinical and Angiographic Outcomes After Bare Metal Stents and Drug-Eluting Stents Following Rotational Atherectomy.

Few studies have investigated the clinical outcomes of rotational atherectomy (RA) prior to and during the drugeluting stent (DES) era. The goal of this study was to assess the long-term outcome after RA followed by DES and bare metal stent (BMS) implantation in complex calcified coronary lesions and to compare the outcomes among various DESs.This was a single center retrospective observational study. Consecutive 406 patients who underwent elective RA followed by BMS or DES implantation at our institution from 2001 to 2011 were included. This study compared the long-term outcomes after treatment with RA among BMS and 3 different DESs (sirolimus-eluting stent, paclitaxel-eluting stent, and everolimus-eluting stent) implantation.The mean follow-up period was 4.6 years. Patients with DES were older and exhibited more vessel disease, longer lesion length, and smaller vessel size. Patients with BMS had a significantly higher rate of target lesion revascularization, restenosis, and larger late lumen loss than those with DES. Composite events including mortality, ACS, and target vessel revascularization were significantly higher in the BMS-RA group than in the DES-RA group. After adjustment, BMS remained an independent predictor of MACE and ACS plus death in patients treated with RA. However, there were no significant differences in late lumen loss, restenosis rate, and MACE among the 3 DES.The combination of DES-RA has a favorable effect in both the angiographic and clinical outcomes compared with BMS-RA. However, no significant differences in late loss and events rates were observed among the 3 DES groups.

Transbrachial intra-aortic balloon pumping for a patient with fulminant myocarditis

A 57-year-old man with acute myocarditis was transferred to our hospital from a local clinic. The patient experienced unexpected sudden cardiac arrest 16 h after admission. Mechanical cardiopulmonary support was started using percutaneous cardiopulmonary support, intra-aortic balloon pumping (IABP), continuous hemodialysis filtration, and temporary cardiac pacing with percutaneous cannulation of the femoral vessels. Hematoma developed at the IABP insertion site on the 5th day after admission. The IABP was removed, and another IABP system was inserted via the left brachial artery. The patient’s condition improved, and the IABP was removed on the 9th day after admission. The remainder of the patient’s in-hospital treatment was uneventful, and he showed near-normal left ventricular systolic function 1 year after discharge.

Simultaneous subacute coronary artery stent thrombosis in a carrier of two CYP2C19 loss–of function polymorphisms (*2/*3)

Clopidogrel, a second generation thienopyridine and a selective inhibitor of the platelet adenosine diphosphate (ADP) P2Y12 receptor, is the historical standard anti-platelet treatment added to aspirin following percutaneous coronary intervention (PCI) in order to reduce the risk of stent thrombotic complications. Clopidogrel is an inactive pro-drug that requires hepatic metabolism by cytochrome P450 2C19 (CYP2C19) into its active form in order to inhibit platelet aggregation. Recently, substantial subpopulations have been recognized that exhibit an inadequate response to clopidogrel leading to insufficient antiplatelet effects [1]. Individuals carrying at least one loss-of function allele (either *2 or *3) of the CYP2C19 gene demonstrate reduced active clopidogrel metabolites and suppressed antiplatelet activity [2]. Such patients have been identified to carry a significantly higher risk of stent thrombosis, a major adverse event that is associated with >60% risk of death or myocardial [3]. Of note, the stent thrombosis risk in patients carrying a CYP2C19 loss-of function allele appears to be similarly elevated across stable and unstable patient populations, regardless of elective or urgent PCI, or treatment with bare metal or drug-eluting stents [4,5]. A 61-year-old dyslipidemic, non-diabetic male with stable angina presented for elective cardiac catheterization. Coronary angiography showed complex multivessel disease consisting of a proximal RCA chronic total occlusion (CTO) with collateral flow from conus branch of RCA and a diagonal branch (Fig. 1a, white arrow), and severe proximal LAD stenosis (Fig. 1d, white arrow). Based on the angiographic results, we first treated the RCA-CTO lesion by deploying three overlapping drug eluting stents (DES) (Promus Premier, Boston Scientific)with proximal to distal sizes of 3.5 × 24 mm, 3.0 × 24 mm and 2.5 × 28 mm. The mid stent and proximal stent were then post-dilated with 3.0 mm and 3.75 mm diameter non-compliant balloons, respectively. Post-PCI intravascular ultrasound (IVUS) imaging confirmed good stent apposition with a sufficient stent/lumen diameter ratio in comparison to the proximal and distal reference vessel segments (Fig. 2, upper left panel). Four days later, staged PCI of the proximal LAD lesion was performed with implantation of a 3.0 × 23 mm DES (Xience Alpine, Abott Vascular) with post-dilatation using a 3.0 mm diameter noncompliant balloon. Similar to the RCA results, good stent apposition was shown by IVUS (Fig. 2, upper right panel). Both procedures were successful with no complications (Fig. 1b and e, white arrows). The patient was continued uninterrupted on treatment with dual-antiplatelet therapy consisting of aspirin 100 mg and clopidogrel 75 mg daily, which had been started 30 days prior to the index PCI without adverse effects. He was discharged to home without angina and in stable condition. Fig. 1 Coronary angiography at initial presentation for elective coronary stent placement, and following representation with ST elevation myocardial infarction due to subacute stent thrombosis. Before (a and d) and after (b and e) initial percutaneous coronary ... Fig. 2 Intravascular ultrasound (IVUS) after initial PCI and intracoronary optical coherence tomography (OCT) imaging of multivessel stent thrombosis. Upper panels: IVUS demonstrated good stent expansion and apposition to the vessel wall. Lower panels: Massive ... The day following discharge, the patient developed sudden-onset severe chest pain and diaphoresis at rest. He presented within 2 hours of symptom onset in hemodynamically stable condition (blood pressure 157/92 mmHg, heart rate 83 beats per minute). The electrocardiogram revealed new ST elevations (>2 mm) with inverted T waves in V1 through V3, and stat echocardiography showed severe hypokinesis of the mid-distal-apical anterior wall. Blood tests returned with leukocytosis (12,500 cells/µl). Emergent coronary angiography for acute anterior ST elevation myocardial infarction (STEMI) was performed after administration of unfractionated heparin 5000 units, supported by an intra-aortic balloon pump (IABP), that showed thrombotic occlusion of both the RCA (Fig. 1c, black arrowhead) and LAD stents (Fig. 1f, black arrowhead). Given the clopidogrel failure, a loading dose of prasugrel (20 mg) was orally administered. GPIIb/IIIa inhibitor was not used. We then proceeded to restore flow in the LAD by passing a coronary guidewire through the stent and performing manual aspiration thrombectomy followed by subsequent percutaneous transluminal angioplasty (PTCA) with a 3.0 mm diameter balloon within the stent. Intracoronary optical coherence tomography demonstrated massive thrombus within the LAD stent despite excellent stent strut apposition throughout (Fig. 2, lower right panel). After achieving TIMI3 flow in the LAD (Fig. 1f, right bottom corner), we moved to treat the RCA with aspiration and PTCA in similar fashion resulting in return of TIMI3 flow in RCA (Fig. 1c, right bottom corner). Intracoronary OCT imaging in the RCA also showed massive thrombus in the distal stent (Fig. 2, lower left panel). The patient was discharged day 16 post-PCI on a medical regimen of an αβ-blocker (carvedilol, 5 mg once daily), an angiotensin converting enzyme inhibitor (Perindopril erbumine, 2 mg once daily) and dual anti-platelet therapy with prasugrel 3.75 mg and aspirin 100 mg once daily. At four months follow-up, the patient has been doing well without any evidence of recurrent myocardial ischemia. Genotyping of CYP2C19 gene polymorphyrisms revealed that the patient carries two reduced-function alleles (*2/*3) of the CYP2C19 gene, and he was thus defined as a poor clopidogrel metabolizer. In this case, the patient carried two non-functioning polymorphisms (*2/*3) of the CYP2C19 gene, a deficit known to result in critically reduced clopidogrel antiplatelet activity, that precipitated simultaneous subacute stent thrombosis of two major epicardial coronary arteries. The frequency for the most common loss-of-function variant CYP2C19*2 is <15% in Caucasians and Africans, but affects up to 35% of those of Asian descent; in comparison, CYP2C19*3 is the second-most common genetic mutation, occurring in fewer than 10% of Asians [1]. Therefore, especially in Asian population, the number of patients defined as a “poor clopdigrel metabolizer” carrying the CYP2C19*2/*2 or *2/*3 polymorphisms may be higher than previously postulated. To date, cardiovascular society guidelines recommend against routine gene testing for CYP2C19 polymorphisms for patients treated with clopidogrel after PCI [6,7], primarily because a priori knowledge of CYP2C19 genetic mutations or the results of platelet function testing have not demonstrated an improvement in outcomes [8]. However, while clinical trials may be equivocal, in certain high-risk individual patients, as presented in this case of an Asian patient undergoing elective complex PCI and suffering simultaneous subacute stent thromobisis, it might be reasonable to perform risk estimation using genetic screening or platelet reactivity testing before coronary stenting. In carriers of *2 and/or *3 alleles of CYP2C19 that have less or no CYP2C19 enzymatic activity (intermediate and poor metabolizers) on standard doses of clopidogrel (75 mg daily), two alternative strategies have been considered: 1) increasing the clopidogrel dose by two- to four-fold [9], which more potently decreases platelet activity but has not been proven to reduce cardiovascular events [10], or 2) the preferred approach of switching to alternative P2Y12 inhibitors, such as the third generation thienopyridines prasugrel and ticagrelor that are less influenced by polymorphisms of the CYP2C19 gene. For prasugrel, carriers of the CYP2C19*2 allele are known to produce equivalent concentrations of active prasugrel metabolite and achieve a similar antiplatelet effect to those that do not carry this allele [5]. In this patient, clopidogrel was replaced by prasugrel with no clinical or adverse events observed in early follow up. Based on the clinical course of this case and related evidence, we suggest that when elective PCI is planned in certain patients at high risk for CYP2C19 polymorphisms, such as those of Asian decent, that are also at high risk for critical stent thrombosis due to complex multivessel or left main coronary artery disease, that physicians consider performing genetic testing for CYP2C19 polymorphisms or platelet function testing to evaluate the potential risk of using clopidogrel, or to simply use a third generation thienopyridine primarily.

Reevaluation of cardiac risk scores and multiple biomarkers for the prediction of first major cardiovascular events and death in the drug-eluting stent era

BACKGROUND Risk scores and cardiac biomarker tests allow clinicians to accurately diagnose acute coronary syndrome (ACS) and perform early risk stratification. However, few investigations have evaluated the use of these risk scores and biomarkers for predicting risk of cardiovascular events in drug-eluting stent (DES) era. METHODS This prospective cohort study included 861 patients with ACS. Three risk scores-Global Registry of Acute Coronary Events (GRACEs), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin, and Thrombolysis In Myocardial Infarction-and levels of four biomarkers-N-terminal pro-B-type natriuretic peptide (NT pro-BNP), high-sensitivity troponin T, heart-fatty acid binding protein, and high-sensitivity C-reactive protein-were recorded on admission. Major adverse cardiac events (MACE) (death, cardiovascular events) were evaluated at 30-day and 1-year follow-up. RESULTS At 30-day follow-up, there were 23 (3.1%) deaths from cardiovascular events and 4 (0.5%) cerebral accidents. NT pro-BNP levels and GRACE score were strong MACE predictors, with adjusted odds ratios (ORs) (95% CI) of 2.90 (1.63-5.20) and 1.01 (1.00-1.02), respectively, in logistic model. The C-statistic of NT pro-BNP (0.77; 95% CI, 0.67-0.86) was similar to that of GRACE score (0.76; 95% CI, 0.66-0.87); however, the combined C-statistic was higher (0.81), yielding a net reclassification improvement of 13% (p<0.01). At 1-year follow-up, there were 51 (6.8%) deaths and 10 (1.3%) cerebral accidents. CONCLUSION In the DES era, GRACE score and biomarkers can still predict major cardiac events in patients with ACS for both acute and long-term prognoses.

The use of serum bepridil concentration as a safe rhythm control strategy in patients with atrial tachyarrhythmias

The aim of this study was to evaluate the clinical significance of serum bepridil (Bep) concentration (SBC) for safely managing patients with atrial tachyarrhythmias (AT).

Infective endocarditis associated with acute myocardial infarction caused by septic emboli

A 53-year-old Japanese man presented with severe chest pain. He had suffered from persistent fever, muscle pain, arthralgia, and dyspnea on exertion (New York Heart Association class I) for two and half months prior to admission. He had been treated with several antibiotics for two months and prednisolone for almost one month prior to admission. On the day of admission, he had suffered from chest pain at rest, and had come to our hospital. Electrocardiography showed a normal sinus rhythm with significant ST segment elevation in leads V3-6 and abnormal Q waves in leads V4-6. Transthoracic echocardiography demonstrated left ventricular ejection fraction of 52% with severe mitral regurgitation and an 18-mm vegetation on the anterior mitral valve leaflet. Multiple blood cultures identified Streptococcus sanguis. The diagnosis was acute myocardial infarction and mitral regurgitation associated with infective endocarditis (IE). The incidence of acute coronary syndrome caused by IE is quite low in patients with native valves. After a 6-week course of antibiotics, mitral valve replacement and partial cardiomyotomy were performed. Two years after the surgery, follow-up echocardiography showed almost normal left ventricle function and no mitral regurgitation, and the patient has been living an active life without any complications.

Clinical Characteristics and Long-Term Outcomes of Rotational Atherectomy ― J2T Multicenter Registry ―

BACKGROUND Rotational atherectomy (RA) is an adjunct tool for the management of heavily calcified coronary lesions during percutaneous coronary intervention (PCI), but the long-term clinical outcomes of RA use remain unclear in this drug-eluting stent era.Methods and Results:This multi-center registry assessed the characteristics and outcomes of patients treated by RA for calcified coronary lesions between 2004 and 2015. Among 1,090 registered patients, mean age was 70±10 years and 815 (75%) were male. Sixty percent of patients had diabetes mellitus and 27.7% were receiving hemodialysis. The procedure was successful in 96.2%. In-hospital death occurred in 33 patients (3.0%), and 14 patients (1.3%) developed definite/probable stent thrombosis. During the median follow-up period of 3.8 years, the incidence of major adverse cardiac events (MACE), defined as all-cause death, acute coronary syndrome, stent thrombosis, target vessel revascularization and stroke, was 46.7%. On multivariable Cox hazard analysis, hemodialysis (HR, 2.08; 95% CI: 1.53-2.86; P<0.0001) and age (HR, 1.03; 95% CI: 1.01-1.04; P<0.0001) were strong independent predictors of MACE. Conversely, statin treatment was associated with lower incidence of MACE (P=0.035). CONCLUSIONS This study has provided the largest Japanese dataset for long-term follow-up of RA. Although RA in calcified lesions appears feasible with a high rate of procedural success, a high incidence of MACE was observed.

CPAP effects on atherosclerotic plaques in patients with sleep-disordered breathing and coronary artery disease: The ENTERPRISE trial

BACKGROUND Sleep-disordered breathing (SDB) is a novel cardiovascular risk factor. To date, the effects of continuous positive airway pressure (CPAP) on coronary plaque atheroma in SDB patients with coronary artery disease (CAD) have remained unclear. The CPAP Effects on Atherosclerotic Plaques in Patients with Sleep-Disordered Breathing and Coronary Artery Disease (ENTERPRISE) trial was designed to evaluate the effects of CPAP treatment in addition to optimal medical treatment on coronary plaque regression in SDB patients. METHODS This study is planned as a prospective, randomized, open-label, single-center study. The presence of SDB is defined as a 3% oxygen desaturation index (ODI) of ≥15 events/h as measured by nocturnal pulse oximetry. A total of 100 eligible SDB patients undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention will be randomly assigned to either CPAP as add-on therapy or no CPAP for SDB (1:1 ratio for CPAP vs. no CPAP). The intervention will consist of 12 months of CPAP treatment. The primary endpoint will be percentage changes in plaque atheroma volume of the non-culprit lesion segment as measured by IVUS. A specialist sleep cardiology team will carefully monitor patients receiving CPAP treatment in order to quickly detect and resolve problems, and to motivate patients to continue treatment. CONCLUSION This study will provide novel information on the effects of SDB and its treatment with CPAP on coronary plaque stability with regard to secondary prevention of CAD.