Masataka Nakano

Elevated Levels of High-Sensitivity C-Reactive Protein and Serum Amyloid-A Late After Kawasaki Disease: Association Between Inflammation and Late Coronary Sequelae in Kawasaki Disease

Background—Coronary sequelae that persist after Kawasaki disease (KD) have been associated with obstructive changes of the lesions and coronary vascular events in adolescents and young adults. However, little is known about the association between sequelae late after KD and inflammatory markers, which are potential mediators and markers for atherogenesis. Methods and Results—Cross-sectional study was performed to test the hypothesis that coronary sequelae are associated with elevated levels of inflammatory markers in patients late after KD (mean time interval after the onset, 10 years, 10 months). Levels of high-sensitivity C-reactive protein (CRP), serum amyloid-A (SAA), interleukin-6, and soluble intercellular adhesion molecule-1 were measured in the 4 groups (n=80): the referent group (n=15) and KD subgroups with normal coronary arteries from the onset (n=27); with regressed aneurysms (n=18); and with coronary artery lesions, such as persistent aneurysms, stenosis, and occlusion (n=20). CRP levels were significantly elevated in a KD subgroup with coronary artery lesions compared with the referent or other KD subgroups, as analyzed by ANOVA and ANCOVA after adjustment for a confounding factor body mass index. Levels of CRP, SAA, and interleukin-6 were positively correlated. Stepwise regression and logistic regression analyses support the association between the persistence of coronary artery lesions and the levels of CRP and SAA. Conclusions—Results demonstrate that the persistence of coronary lesions late after KD was independently associated with levels of CRP and SAA, suggesting that inflammation may be a novel functional aspect of coronary artery diseases late after KD.

Impact of transport pathways on the time from symptom onset of ST-segment elevation myocardial infarction to door of coronary intervention facility

BACKGROUNDnReducing total ischemic time is important in achieving better outcome in ST-segment elevation myocardial infarction (STEMI). Although the onset-to-door (OTD) time accounts for a large portion of the total ischemic time, factors affecting prolongation of the OTD time are not established.nnnPURPOSEnThe purpose of this study was to determine the impact of transport pathways on OTD time in patients with STEMI.nnnMETHODS AND SUBJECTSnWe retrospectively studied 416 STEMI patients who were divided into 4 groups according to their transport pathways; Group 1 (n = 41): self-transportation to percutaneous coronary intervention (PCI) facility; Group 2 (n = 215): emergency medical service (EMS) transportation to PCI facility; Group 3 (n = 103): self-transportation to non-PCI facility; and Group 4 (n = 57): EMS transportation to non-PCI facility. OTD time was compared among the 4 groups.nnnESSENTIAL RESULTSnMedian OTD time for all groups combined was 113 (63-228.8)min [Group 1, 145 (70-256.5); Group 2, 71 (49-108); Group 3, 260 (142-433); and Group 4, 184 (130-256)min]. OTD time for EMS users (Groups 2 and 4) was 138 min shorter than non-EMS users (Groups 1 and 3). Inter-hospital transportation (Groups 3 and 4) prolonged OTD by a median of 132 min compared with direct transportation to PCI facility (Groups 1 and 2). Older age, history of myocardial infarction, prior PCI, shock at onset, high Killip classification, and high GRACE Risk Score were significantly more frequent in EMS users.nnnPRINCIPAL CONCLUSIONSnSelf-transportation without EMS and inter-hospital transportation were significant factors causing prolongation of the OTD time. Approximately 35% of STEMI patients did not use EMS and 21% of patients were transported to non-PCI facilities even though they called EMS. Awareness in the community as well as among medical professionals to reduce total ischemic time of STEMI is necessary; this involves educating the general public and EMS crews.

Impact of a single universal guiding catheter on door-to-balloon time in primary transradial coronary intervention for ST segment elevation myocardial infarction

The purpose of this study is to determine reduction of door-to-balloon (D2B) time using a single universal guiding catheter (Ikari-Left catheter) in transradial approach. In this procedure, we can skip a total of five steps compared with a conventional procedure (two catheter insertions, two catheter removals, and one catheter engagement). Reducing total ischemic time is important to achieving a better outcome in primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). We retrospectively compared 30 consecutive STEMI patients who underwent transradial primary PCI with a single guiding catheter (IL group) with 30 consecutive patients with conventional transradial primary PCI. Patients with cardiogenic shock, heart failure, or need for intra-aortic balloon pumping support before primary PCI were excluded. Baseline characteristics were not different between the two groups. The D2B time was significantly shorter in the IL group (55xa0±xa016 vs. 63xa0±xa017xa0min, respectively; pxa0=xa00.01). Puncture-to-balloon time was also significantly shorter in the IL group (15xa0±xa011xa0min vs. 25xa0±xa011xa0min, respectively; pxa0=xa00.001). The total number of diagnostic and guiding catheters was significantly less in IL group (1 (IQR 1-1) vs. 3 (IQR 3-3), respectively; pxa0<xa00.0001). Primary PCI with a single universal guiding catheter reduced D2B time by skipping several procedural steps, and reduced the total number of catheters needed. This technique could reduce patient mortality as well as total medical cost.

Impact of the origin of the collateral feeding donor artery on short-term mortality in ST-elevation myocardial infarction with comorbid chronic total occlusion

BACKGROUNDnPatients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD) have higher mortality, especially with comorbid chronic total occlusion (CTO). The origin of collateral flow to the CTO segment has not been studied in regard to short-term mortality. This study examined the impact of collateral feeding donor arteries from an infarct-related artery (IRA) or non-IRA to the comorbid CTO segment in regard to STEMI short-term mortality.nnnMETHODSnData from 760 consecutive STEMI patients who underwent primary percutaneous coronary intervention were obtained retrospectively from medical records. The number of vessels involved and origin of the collateral feeding donor artery were evaluated using angiograms from the primary percutaneous coronary intervention. The study population was divided into patients with: single-vessel disease (SVD) (n=483), MVD without CTO (n=208), and MVD with CTO (n=64). All CTO segments had collateral flow from an IRA (n=23) or non-IRA (n=46). All-cause mortality (30-day) was analyzed.nnnRESULTSnCompared to SVD and MVD without CTO, MVD with comorbid CTO had a higher mortality (5.4% vs. 15.9% vs. 24.6%, P<0.0001, respectively). Of patients with CTO, those with collateral flow from the IRA had significantly higher mortality than the non-IRA group (52.2% vs. 10.9%, P<0.0001). Collateral flow from the IRA was extracted as an independent predictor associated with 30-day all-cause mortality using a multivariate Cox proportional hazards model (hazard ratio 4.71, 95% confidence interval 1.60-14.2, P=0.0005).nnnCONCLUSIONSnThe origin of the collateral donor artery from the IRA had an impact on short-term mortality in STEMI patients with comorbid CTO lesions.

Evaluation of coronary arterial calcification – Ex-vivo assessment by optical frequency domain imaging

AIMSnThe purpose of this study was to determine the diagnostic ability of optical frequency domain imaging (OFDI) to carry out quantitative and qualitative evaluation of coronary calcification in comparing with ex vivo human autopsy heart specimens.nnnMETHODSnAnalysis was carried out in 25 coronary artery specimen obtained from 16 cadavers that were imaged ex-vivo imaging by OFDI and intravascular ultrasound (IVUS). Of 235 cross-sections obtained for histologic evaluation, 149 were classified as showing calcified plaques, and in this group a comparison between histology versus co-registered images by OFDI and IVUS was performed.nnnRESULTSnMaximum thickness of calcification measured by OFDI was well correlated with histology (rs = 0.70, p < 0.0001) whereas IVUS was not useful for quantitative analysis because of the presence of acoustic shadows occurring behind calcifications. Furthermore qualitative evaluation could be carried out using OFDI, for calcifications with vague or invisible outer borders by OFDI had lipid contents (lipid pool or histologic necrotic core) more frequently as compared to those with a clear outer border (79% vs. 24%, p < 0.0001). We also found that calcified nodules, a well-recognized thrombogenic substrate, demonstrated atypical appearance in OFDI, showing irregular surfaces with high attenuation.nnnCONCLUSIONnOFDI demonstrated a greater ability than IVUS to provide quantitative and qualitative evaluation of coronary arterial calcification. Precise recognition of calcified plaque morphology by OFDI may serve to determine the treatment strategy of patients having atherosclerotic coronary disease.

Comparison of Vascular Responses Following New‐Generation Biodegradable and Durable Polymer‐Based Drug‐Eluting Stent Implantation in an Atherosclerotic Rabbit Iliac Artery Model

BACKGROUNDnIncomplete endothelialization is the primary substrate of late stent thrombosis; however, recent reports have revealed that abnormal vascular responses are also responsible for the occurrence of late stent failure. The aim of the current study was to assess vascular response following deployment of biodegradable polymer-based Synergy (Boston Scientific) and Nobori (Terumo) drug-eluting stents and the durable polymer-based Resolute Integrity stent (Medtronic) in an atherosclerotic rabbit iliac artery model.nnnMETHODS AND RESULTSnA total of 24 rabbits were fed an atherogenic diet, and then a balloon injury was used to induce atheroma formation. Synergy, Nobori, and Resolute Integrity stents were randomly implanted in iliac arteries. Animals were euthanized at 28xa0days for scanning electron microscopic evaluation and at 90xa0days for histological analysis. The percentage of uncovered strut area at 28xa0days was lowest with Synergy, followed by Resolute Integrity, and was significantly higher with Nobori stents (Synergy 1.1±2.2%, Resolute Integrity 2.0±3.9%, Nobori 4.6±3.0%; P<0.001). At 90xa0days, inflammation score was lowest for Synergy (0.27±0.45), followed by Nobori (0.62±0.59), and was highest for Resolute Integrity (0.89±0.46, P<0.001). Foamy macrophage infiltration within neointima (ie, neoatherosclerosis) was significantly less with Synergy (0.62±0.82) compared with Nobori (0.85±0.74) and Resolute Integrity (1.39±1.32; P=0.034).nnnCONCLUSIONSnThe biodegradable polymer-coated thin-strut Synergy drug-eluting stent showed the fastest stent strut neointimal coverage and the lowest incidence of neoatherosclerosis in the current animal model.

Impact of transient or persistent slow flow and adjunctive distal protection on mortality in ST-segment elevation myocardial infarction

Routine use of distal protection for ST-segment elevation myocardial infarction (STEMI) is not recommended. The purpose of this study was to analyze the impact of slow flow on mortality after STEMI, and the efficacy of adjunctive distal protection following primary thrombus aspiration. We retrospectively analyzed 414 STEMI patients who underwent primary PCI. Distal protection was used following primary thrombus aspiration only when the operator judged the patient to be at high risk of slow flow. Patients were divided into 3 groups: those receiving no thrombus aspiration (A− Group), thrombus aspiration without distal protection (A+/D− Group) or a combination of aspiration with distal protection (A+/D+ Group). Slow flow/no reflow was characterized as transient or persistent. The A−, A+/D−, and A+/D+ Groups consisted of 28.5xa0% (nxa0=xa0118), 44.4xa0% (nxa0=xa0184), and 27.1xa0% (nxa0=xa0112) of patients, respectively. All-cause mortality at 180xa0days was 6.8xa0% without slow flow, 14.1xa0% with transient and 44.4xa0% with persistent slow flow (Pxa0<xa00.0001), but was similar whether or not distal protection was used among these groups complicated without slow flow (A−, 8.7xa0%; A+/D−, 6.3xa0%; A+/D+, 4.3xa0%; Pxa0=xa00.5854). However, in cases complicated with transient or persistent slow flow, distal protection reduced all-cause mortality to 38.5xa0% (A−), 23.3xa0% (A+/D−), and 10.8xa0% (A+/D+) at 180xa0days (Pxa0=xa00.0114). Our data confirm that routine distal protection is not to be recommended. However, it is suggested that it could reduce mortality of patients with slow flow. Predicting slow flow accurately before PCI, however, remains a challenge.

Regional wall motion abnormality at the lateral wall disturbs correlations between tissue Doppler E/e′ ratios and left ventricular diastolic performance parameters measured by invasive methods

BackgroundThe impact of regional wall motion abnormality (RWMA) on the accuracy of heart failure with preserved ejection fraction (HFpEF) diagnosis using the E/e′ ratio, which is a non-invasive parameter of left ventricular diastolic performance, is unknown. The purpose of this study was to elucidate the impact of RWMA of the lateral wall (RWMAlat) on the correlation between E/e′ and invasive parameters of left ventricular diastolic performance.MethodsThree hundred and eight consecutive patients undergoing tissue Doppler imaging and catheterization pressure examination were retrospectively analyzed. E/e′ was calculated as the ratio of early diastolic transmitral flow velocity to mitral annular velocity at the lateral wall. Invasive parameters including left ventricular end-diastolic pressure (LVEDP) and isovolumetric relaxation time constant (τ) were assessed based on the left ventricular pressure study. Correlation coefficients between E/e′ and these invasive parameters were analyzed and compared between cases with RWMAlat and without RWMA.ResultsLVEDP and τ correlated well with E/e′ for all 308 patients (rxa0=xa00.51 and rxa0=xa00.65, respectively). Sixty-two patients had RWMA; the remaining 246 did not have RWMAlat. We confirmed that the presence of RWMAlat weakens both the correlations between E/e′ and LVEDP (rxa0=xa00.574 vs. rxa0=xa00.381), and E/e′ and τ (rxa0=xa00.729 vs. rxa0=xa00.461).ConclusionsAlthough E/e′ correlates well with parameters of left ventricular diastolic performance assessed by invasive methods, the presence of RWMAlat worsens this correlation. In cases with RWMAlat, careful assessment is required for HFpEF diagnosis because the diagnostic value of the E/e′ ratio could be decreased compared to patients without RWMAlat.

Collateral filling efficiency of comorbid chronic total occlusion segment on short-term mortality in ST-elevation myocardial infarction

BACKGROUNDnCollateral filling of chronic total occlusion (CTO) segments is considered to affect hemodynamic stability in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) with CTO, however its value as a prognostic indicator for mortality is uncertain. The present study examined the relationship between collateral filling of CTO segments and short-term mortality in patients with STEMI with a comorbid CTO lesion.nnnMETHODSnAmong 829 STEMI patients who underwent primary PCI, 74 patients with CTO were identified. Collateral filling of their CTO segment was assessed by Rentrop grade (0; n=10, 1; n=13, 2; n=31, 3; n=20) in their initial angiogram and whether the origin of the feeding collateral donor artery was infarct-related artery (IRA) was evaluated using their final angiogram in primary PCI; IRA (n=26) and non-IRA group (n=48). The relationship between these classifications and 30-day all-cause mortality was examined retrospectively.nnnRESULTSnThe 30-day mortalities were 4.5% in single-vessel disease, 18.3% in multi-vessel disease (MVD) without CTO and 25.7% in MVD with CTO. Mortality of MVD with CTO reduced with increasing Rentrop grade from 0 to 3 (80.0%, 30.8%, 19.4%, and 5.0%, respectively). IRA was associated with a significant higher mortality than those of non-IRA (50.0% vs. 12.5%, P=0.0004). Low Rentrop grade 0 or 1 was extracted as an independent predictor of 30-day death (HR 3.28, 95% CI 1.20-9.96, P=0.0203).nnnCONCLUSIONSnPoor collateral filling of the CTO segment assessed by Rentrop grade was an independent angiographic predictor for 30-day death in patients with STEMI combined with CTO.

Coronary flow improvement following unsuccessful primary percutaneous coronary intervention in ST-elevation myocardial infarction with diffuse ectatic coronary artery:

Background: In ST-elevation myocardial infarction (STEMI) patients with diffuse ectatic coronary artery, extensive thrombi inhibit achievement of final successful revascularization of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after primary percutaneous coronary intervention. However, clinical and angiographic outcomes of such patients are uncertain. The present study examined clinical and angiographic outcomes in STEMI incorporating giant coronary artery with diffuse ectasia. Methods: Seven hundred and forty-four STEMI patients undergoing primary percutaneous coronary intervention were surveyed retrospectively. Culprit lesions in giant coronary artery with diffuse ectasia (Ectatic group, n=39) were investigated. Percutaneous coronary intervention success rate and angiographic or clinical outcomes at 360 days were compared with those of the Non-ectatic group (n=705). Results: Angiographic percutaneous coronary intervention success rate was significantly lower in the Ectatic group due to lower achievement of final TIMI grade 3 flow (53.8% vs. 92.9%, p<0.0001; 53.8% vs. 93.5%, p<0.0001, respectively). In follow-up angiography, 86% of the Ectatic group showed angiographic improvement from TIMI grade 2 or less immediately after percutaneous coronary intervention to TIMI grade 3 flow at follow-up. In contrast, angiographic improvement was observed in only 25% of cases in the Non-ectatic group. All-cause 360-day mortality was significantly lower in the ectatic group (2.6% vs. 14.5%, p=0.0361, respectively). Conclusion: In patients with STEMI in giant coronary artery with diffuse ectasia, achievement of TIMI grade 3 flow was significantly reduced immediately after percutaneous coronary intervention. However, improvement of coronary flow up to TIMI grade 3 was not uncommon at follow-up angiogram. Patients had low mortality despite low TIMI grade 3 achievement immediately after primary percutaneous coronary intervention.