Kenichi Sakakura

CVPath Institute, GAI, Maryland, United States

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Publications (86)295.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombus aspiration is currently the standard strategy for primary PCI. Thrombus can be aspirated via aspiration catheters, restoring coronary blood flow. However, there are a limited number of reports regarding thrombus aspiration toward tumor embolized occlusion. We present a case of 90-year-old male with AMI caused by the metastatic tumor embolism. Emergent coronary angiography revealed total occlusion in three epicardial vessels. Histopathological examination of the aspirated specimen revealed the mixture of thrombus and metastatic tumor cells. Thrombus aspiration was partially effective for restoring coronary blood flow; however, it was very helpful for the final diagnosis of tumor embolism.
    Cardiovascular Intervention and Therapeutics 02/2015;
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    ABSTRACT: The pathology of radiofrequency-derived sympathetic renal denervation has not been studied over time and may provide important understanding of the mechanisms resulting in sustained blood pressure reduction. The purpose of this study was to investigate chronological changes after radiofrequency-renal denervation in the swine model. A total of 49 renal arteries from 28 animals with 4 different time points (7, 30, 60, and 180 days) were examined. Semiquantitative histological assessment of arteries and associated tissue was performed to characterize the chronological progression of the radiofrequency lesions. Arterial medial circumferential injury (%) was greatest at 7 days (38±13%), followed by 30 days (31±6%) and 60 days (31±15%), and least at 180 days (21±12%) (P=0.046). Nerve injury score was significantly greater (P<0.001) at 7 days (3.9±0.4) compared with 30 days (2.5±0.5), 60 days (2.6±0.5), and 180 days (1.9±0.9). Tyrosine hydroxylase score, which assesses functional nerve damage, was significantly less after 7 (1±1) and 30 days (0.7±0.6) compared with 60 (2.7±0.6) and 180 days (2.7±0.6; P=0.01). Focal nerve regeneration at the sites of radiofrequency ablation was observed in 17% of renal arteries at 60 days and 71% of 180 days. Nerve injury after radiofrequency ablation was greatest at 7 days, with maximum functional nerve damage sustained ≤30 days. Focal terminal nerve regeneration was observed only at the sites of ablation as early as 60 days and continued to 180 days. Renal artery and peri-arterial soft tissue injury is greatest in the subacute phase, and least in the chronic phase, suggesting gradual recovery of the renal arterial wall and surrounding tissue. © 2015 American Heart Association, Inc.
    Circulation Cardiovascular Interventions 02/2015; 8(2). · 6.98 Impact Factor
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    ABSTRACT: The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (P<0.001 for circumference; P=0.003 for thinning). Severe collagen damage such as denatured collagen was also significantly less in the irrigated compared with the conventional radiofrequency group (P<0.001). Nerve damage although not statistically different between the irrigated radiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (P<0.001). Saline irrigation significantly reduces arterial and periarterial tissue damage during radiofrequency ablation, and there is a trend toward less nerve damage. © 2014 American Heart Association, Inc.
    Circulation Cardiovascular Interventions 01/2015; 8(1). · 6.98 Impact Factor
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    ABSTRACT: The optimal preoperative therapeutic strategy for patients with coronary artery disease (CAD) is an important concern in the era of drug-eluting stents and antiplatelet therapy. However, there are few studies about the impact of prior percutaneous coronary intervention (PCI) on perioperative major adverse cardiac events (MACEs) and bleeding events associated with oral antiplatelet therapy. The aim of this study was to examine the risks and benefits of performing PCI before non-cardiac surgery (NCS) in patients with CAD. We investigated 130 patients who had angiographically significant and stable CAD and underwent NCS after index coronary angiography. We divided the patients into two groups: patients undergoing PCI with coronary stenting (PCI group), and those not undergoing PCI before NCS (no-PCI group), and compared the MACEs and bleeding events within 30 days from NCS between the groups. There were 53 and 77 patients in the PCI and no-PCI groups, respectively. MACEs were observed in 2 patients (3.8%) in the PCI group and 3 patients (3.9%) in the no-PCI group (p=0.97), whereas bleeding events were observed in 10 (18.9%) and 8 patients (10.4%) in the PCI and no-PCI groups, respectively (p=0.17). There were no significant differences between the two groups in terms of MACEs and bleeding events. The rate of MACEs following NCS was not significantly different between the PCI and no-PCI groups, while the rate of bleeding events was higher in the PCI group without reaching statistical significance. This study suggests that patients with stable CAD may be able to safely undergo NCS without revascularization even in the presence of significant coronary artery stenosis. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
    Journal of cardiology. 01/2015;
  • JACC Cardiovascular Imaging 11/2014; · 6.99 Impact Factor
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    ABSTRACT: Aims: The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Methods and results: Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. Conclusions: The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.
    10/2014;
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    ABSTRACT: Transcatheter ablation of renal autonomic nerves is a viable option for the treatment of resistent arterial hypertension; however, structured pre-clinical evaluation with standardization of analytical procedures remains a clear gap in this field. Here we discuss the topics relevant to the pre-clinical model for the evaluation of renal denervation (RDN) devices and report methodologies and criteria toward standardization of the safety and efficacy assessment, including histopathological evaluations of the renal artery, periarterial nerves, and associated periadventitial tissues. The pre-clinical swine renal artery model can be used effectively to assess both the safety and efficacy of RDN technologies. Assessment of the efficacy of RDN modalities primarily focuses on the determination of the depth of penetration of treatment-related injury (e.g., necrosis) of the periarterial tissues and its relationship (i.e., location and distance) and the effect on the associated renal nerves and the correlation thereof with proxy biomarkers including renal norepinephrine concentrations and nerve-specific immunohistochemical stains (e.g., tyrosine hydroxylase). The safety evaluation of RDN technologies involves assessing for adverse effects on tissues local to the site of treatment (i.e., on the arterial wall) as well as tissues at a distance (e.g., soft tissue, veins, arterial branches, skeletal muscle, adrenal gland, ureters). Increasing experience will help to create a standardized means of examining all arterial beds subject to ablative energy and in doing so enable us to proceed to optimize the development and assessment of these emerging technologies.
    JACC Cardiovascular Interventions 09/2014; · 7.44 Impact Factor
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    ABSTRACT: Background Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri-arterial renal nerves is poorly understood. Objectives The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries. Methods Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti–tyrosine hydroxylase and anti–calcitonin gene–related peptide. Results A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 ± 16.7 per section and 39.9 ± 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 ± 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 ± 0.78 mm), followed by middle segments (3.10 ± 0.69 mm), and least in distal segments (2.60 ± 0.77 mm) (p < 0.001). The mean number of nerves in the ventral region (11.0 ± 3.5 per section) was greater compared with the dorsal region (6.2 ± 3.0 per section) (p < 0.001). Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene–related peptide ratio 25.1 ± 33.4; p < 0.0001). Nerve anatomy in hypertensive patients was not considerably different compared with nonhypertensive patients. Conclusions The density of peri-arterial renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures.
    Journal of the American College of Cardiology 08/2014; 64(7):635–643. · 15.34 Impact Factor
  • Kenichi Sakakura, Michael Joner, Renu Virmani
    JACC. Cardiovascular imaging. 08/2014; 7(8):796-8.
  • Kenichi Sakakura, Michael Joner
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 06/2014; 10(2):178-80. · 3.76 Impact Factor
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    ABSTRACT: The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb) has shown promising clinical results; however, only limited preclinical data have been published. We sought to investigate detailed pathological responses to the Absorb versus XIENCE V (XV) in a porcine coronary model with duration of implant extending from 1 to 42 months.
    Circulation Cardiovascular Interventions 06/2014; · 6.54 Impact Factor
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    ABSTRACT: Peripheral artery disease (PAD) is an emerging problem especially with aging population and increase in the incidence of diabetes and metabolic syndrome. The disease is histologically characterized by the presence of moderate to severe calcification and fibrous plaques as compared to coronary and carotid atherosclerotic disease, which are richer in necrotic core. Endovascular therapy for the superficial femoral artery (SFA), at least in the United States, has been largely limited to balloon angioplasty and stenting and these are considered safe and relatively effective therapies. However, the patency rates remain low even at one year and restenosis is a growing and challenging problem. Recently the development of newer devices, i.e., drug-eluting stent, and drug coated balloon are showing greater efficacy and are being adopted into daily practice. In this review, we will present the morphologic characteristics of the underlying SFA atherosclerotic disease and discuss in-stent restenosis and the mechanisms that may be involved in the induction of excessive smooth muscle cell proliferation and deposition of proteoglycans and collagen, that lead to restenosis.
    The Journal of cardiovascular surgery 06/2014; 55(3):307-23. · 1.37 Impact Factor
  • Renu Virmani, Michael Joner, Kenichi Sakakura
    Arteriosclerosis Thrombosis and Vascular Biology 05/2014; · 5.53 Impact Factor
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    ABSTRACT: The perioperative risk of non-cardiac surgery (NCS) in the patients on antiplatelet therapy after percutaneous coronary intervention (PCI) remains unclear. This study was a retrospective and single center study. Between January 2008 and December 2011, 198 patients who had already received PCI underwent NCS in our hospital. Among them, 63 patients underwent surgery on dual antiplatelet therapy (DAPT group) and 88 patients on single antiplatelet therapy (SAPT group). We compared bleeding events and cardiovascular events during perioperative period between the two groups. There was no stent thrombosis in either group. The bleeding events in the DAPT group were significantly higher than that in the SAPT group (9.5% vs 2.3%, p=0.049). There was no difference in events between with or without heparin-bridge in the SAPT group. The frequency of bleeding events was higher in the DAPT group. Both bleeding and cardiovascular events with aspirin alone were low in our study. It may be safe to undergo NCS with SAPT after PCI.
    Journal of Cardiology 05/2014; · 2.57 Impact Factor
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    ABSTRACT: Acute coronary syndrome is the leading cause of death worldwide and plaque rupture is the most common underlying mechanism of coronary thrombosis. During the last 2 decades the understanding of atherosclerotic plaque progression advanced dramatically and pathology studies provided fundamental insights of underlying plaque morphology, which paved the way for invasive imaging modalities, which bring a new area of atherosclerotic plaque characterization in vivo. The development of intravascular ultrasound (IVUS) allowed the field to evaluate the principles of vascular anatomy, which is often underestimated by coronary angiography. Furthermore, IVUS image technologies were developed to obtain improved characterization of plaque composition. However, since spatial resolution of IVUS is insufficient to distinguish details of plaque morphology, a broad adoption of this technology in clinical practice was missing. Optical coherence tomography is a light-based imaging modality with higher spatial resolution compared to IVUS, which enables the assessment of vascular anatomy with great detail.
    Expert Review of Cardiovascular Therapy 04/2014;
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    ABSTRACT: Dipeptidyl peptidase-4 (DPP4) is an integral membrane glycoprotein that modulates the pathological state of diabetes mellitus (DM), and DPP4 inhibitors are a new class of anti-type-2 DM drugs. Recent preclinical studies have associated DPP4 inhibition with improved myocardial systolic and diastolic function. Based on preclinical findings, we investigated associations between the administration of DPP4 inhibitors and cardiac function after acute myocardial infarction (AMI) in a clinical setting. We enrolled 34 patients with diabetes who were treated for acute myocardial infarction at our hospital between January 2010 and December 2012. We retrospectively compared changes in cardiac parameters determined by trans-thoracic echocardiography between patients treated with (DPP4-I group; n = 13) or without (non-DPP4-I group; n = 21) a DPP4 inhibitor during follow-up. The values of E/e' and of e'/a' significantly decreased and increased, respectively, in the DPP4-I, compared with the non-DPP4-I group (-2.53 ± 5.53 vs. 2.58 ± 5.68, p = 0.038 and 0.08 ± 0.23 vs. -0.12 ± 0.21, p = 0.036, respectively). We concluded that DPP4 inhibitors could improve E/e' and e'/a' in patients with DM and AMI and thus might be effective for treating left ventricular diastolic failure.
    Heart and Vessels 04/2014; · 2.13 Impact Factor
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    ABSTRACT: We interrogated our autopsy registry to investigate the histopathologic features of early stent thrombosis (ST) in patients presenting with acute coronary syndrome (ACS). The occurrence of early ST following percutaneous coronary intervention (PCI) for ACS remains a clinical problem despite advances in stent technology in both bare metal and drug-eluting stents. - Sixty-seven stented coronary lesions from 59 patients who presented with ACS and died within 30 days were included. Stented segments were cross-sectioned at 3-4 mm intervals, evaluated by light microscopy, and morphometric analysis was performed. Early ST (<30 days of PCI) was identified in 34 (58%) of the 59 patients. Early ST was dependent on the underlying plaque morphology and underlying thrombus burden: presence of necrotic core prolapse was more frequent in thrombosed lesions compared with patent lesions (70% vs. 43%, p=0.045) and maximum underlying thrombus thickness was significantly greater in thrombosed versus patent lesions. All 3 patients with false lumen stenting had ST. Detailed analysis revealed that the percentage of necrotic core prolapse, medial tear, or incomplete apposition was significantly greater in the early ST compared with patent group (28% vs.11%, p<0.001, 27% vs. 15% p=0.004, and 34% vs. 18% p =0.008, respectively). Multivariate analysis revealed that maximum depth of strut penetration, % strut with medial tear, and % struts with incomplete apposition were the primary indicators of early ST. - The current autopsy study highlights the impact of thrombus burden and suboptimal stent implantation in unstable lesions as a trigger of early ST, suggesting that improvement in implantation technique and refinement of stent design may improve clinical outcomes of ACS patients.
    Journal of the American College of Cardiology 04/2014; 63(23). · 15.34 Impact Factor
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    ABSTRACT: Postprandial hyperglycemia is a risk factor for cardiovascular disease and mortality. Serum 1,5-anhydroglucitol (1,5-AG) level is an useful clinical marker of glucose metabolism which reflects postprandial hyperglycemia more robustly compared to hemoglobin A1c (HbA1c). Relationship between serum 1,5-AG level and cardiovascular disease has been reported; however, comparison between HbA1c and 1,5-AG as markers of cardiovascular disease was not performed. We included 227 consecutive patients who underwent coronary angiography meeting the following inclusion criteria: (1) patients who had no history of coronary artery disease (CAD); (2) patients without acute coronary syndrome; (3) patients without poorly controlled diabetes mellitus; (4) patients without anemia, liver dysfunction, acute, and chronic renal failure and malnutrition; and (5) patients without adhibition of acarbose or Chinese herbal medicine. We measured HbA1c, glycoalbumin, and 1,5-AG. Serum 1,5-AG was significantly lower in patients with CAD (16.6 ± 8.50 vs. 21.1 ± 7.97 μg/ml, P < 0.001). Multivariable logistic regression analysis showed decrease in serum 1,5-AG was independently associated with the presence of denovo CAD (0.93, 95 % CI 0.88-0.98, P = 0.006). Serum 1,5-AG was also independently associated with the presence of denovo CAD in patients without diabetes mellitus (0.94, 95 % CI 0.88-0.99, P = 0.046). In conclusion, lower serum 1,5-AG was associated with the presence of denovo CAD. Serum 1,5-AG may identify high cardiovascular risk patients for denovo CAD in both diabetic and non-diabetic patients.
    Heart and Vessels 04/2014; · 2.13 Impact Factor
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    Heart, Lung and Circulation 04/2014; · 1.17 Impact Factor
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    ABSTRACT: Coronary artery calcification is a well-established predictor of future cardiac events; however, it is not a predictor of unstable plaque. The intimal calcification of the atherosclerotic plaques may begin with smooth muscle cell apoptosis and release of matrix vesicles and is almost always seen microscopically in pathological intimal thickening, which appears as microcalcification (≥0.5 μm, typically <15 μm in diameter). Calcification increases with macrophage infiltration into the lipid pool in early fibroatheroma where they undergo apoptosis and release matrix vesicles. The confluence of calcified areas involves extracellular matrix and the necrotic core, which can be identified by radiography as speckled (≤2 mm) or fragmented (>2, <5 mm) calcification. The calcification in thin-cap fibroatheromas and plaque rupture is generally less than what is observed in stable plaques and is usually speckled or fragmented. Fragmented calcification spreads into the surrounding collagen-rich matrix forming calcified sheets, the hallmarks of fibrocalcific plaques. The calcified sheets may break into nodules with fibrin deposition, and when accompanied by luminal protrusion, it is associated with thrombosis. Calcification is highest in fibrocalcific plaques followed by healed plaque rupture and is the least in erosion and pathological intimal thickening. The extent of calcification is greater in men than in women especially in the premenopausal period and is also greater in whites compared with blacks. The mechanisms of intimal calcification remain poorly understood in man. Calcification often occurs in the presence of apoptosis of smooth muscle cells and macrophages with matrix vesicles accompanied by expression of osteogenic markers within the vessel wall.
    Arteriosclerosis Thrombosis and Vascular Biology 02/2014; · 6.34 Impact Factor