Association between stress hyperglycemia on admission and unfavorable neurological outcome in OHCA patients receiving ECPR.

BACKGROUND: Stress hyperglycemia is a normal response to stress and has been associated with outcomes in out-of-hospital cardiac arrest (OHCA) patients. However, this association remained unknown in OHCA patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). This study aimed to examine the association between degree of stress hyperglycemia on admission and neurological outcomes at discharge in OHCA patients receiving ECPR. PATIENTS AND METHODS: This was a retrospective cohort study of adult OHCA patients receiving ECPR between 2011 and 2021. Patients were classified into three groups: absence of stress hyperglycemia (blood glucose level on admission < 200 mg/dL), moderate stress hyperglycemia (200-299 mg/dL), and severe stress hyperglycemia (≥ 300 mg/dL). The primary outcome was unfavorable neurological outcome (Cerebral Performance Category: 3-5) at discharge. RESULTS: This study included 160 patients; unfavorable neurological outcomes totaled 79.4% (n = 127). There were 23, 52, and 85 patients in the absence, moderate, and severe stress hyperglycemia groups, respectively. Of each group, unfavorable neurological outcomes constituted 91.3%, 71.2%, and 81.2%, respectively. Multivariable analysis showed that, compared with moderate stress hyperglycemia, absence of stress hyperglycemia on admission was significantly associated with unfavorable neurological outcome at discharge (odds ratio [OR], 4.70; 95% confidence interval [CI], 1.07-33.35; p = 0.039). CONCLUSION: Compared with moderate stress hyperglycemia on admission, absence of stress hyperglycemia showed significant association with unfavorable neurological outcome at discharge in OHCA patients receiving ECPR.

Potent effect of prasugrel on acute phase resolution of intra-stent athero-thrombotic burden after percutaneous intervention to acute coronary syndrome.

BACKGROUND: Recent studies suggested protruding thrombus and atheroma after stent placement could be a substrate for subsequent adverse ischemic events. Although protruded atherothrombotic burden can be assessed as intra-stent tissue (IST) by optical coherence tomography (OCT), the effects of potent antiplatelet therapy on the acute phase resolution of IST in patients with acute coronary syndrome (ACS) was unknown. METHODS: Ninety-six consecutive ACS patients with multi-vessel disease were enrolled in this prospective registry. In combination with aspirin, either clopidogrel or prasugrel was selected according to the date of enrolment. OCT examination was done immediately after percutaneous coronary intervention (post-PCI) and 10 days after index PCI (follow-up acute phase) to calculate averaged IST score as semi-quantitative measures of IST. High residual platelet reactivity (HRPR) was defined as platelet reactivity units (PRU)≥240 by VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA). RESULTS: Thirty two patients (38 stents) were enrolled in the prasugrel group and sixty four patients (72 stents) in the clopidogrel group. Averaged IST scores post-PCI were similar between the two groups (0.68±0.41 vs. 0.68±0.40, p=0.99), which decreased in all of the prasugrel group and in 87.5% of the clopidogrel group (p=0.02). Consequently, changes in averaged IST score (delta averaged IST score) were significantly greater in the prasugrel group compared to those in the clopidogrel group (-0.411±0.288 vs. -0.299±0.270, p=0.045). The frequency of HRPR was significantly lower in the prasugrel group (10.0% vs 32.4%, p=0.028). CONCLUSIONS: Prasugrel plus aspirin achieved greater acute phase reduction of IST than clopidogrel plus aspirin, which might underlie the clinical benefit of potent antiplatelet therapy in ACS. (UMIN000018751).

The importance of catheter stability evaluated by Visitag(TM) during pulmonary vein isolation.

BACKGROUND: The recurrence rates of atrial fibrillation (Af) after ablation are still high, and repeat procedures are required in these patients. The main reason for Af recurrence is the recovery of the conduction between the pulmonary veins and left atrium. The importance of catheter stability during the pulmonary vein isolation (PVI) is not well studied. PURPOSE: The purpose of this study was to evaluate the contact force (CF), stable ablation time, and power during conduction blocking lesion formation for PVI. METHODS: Thirty-two consecutive drug-refractory Af patients who underwent an initial PVI using CARTO 3 and Visitag were included. The CF, ablation time, force time integral (FTI), and ablation power were recorded by Visitag. Residual conduction gap points requiring touch-up ablation after an encircling linear ablation (R point), spontaneous reconnection points (S point), and dormant conduction points (D point) were considered as non-conduction blocking lesion points. Each ablation parameter for the non-conduction blocking lesion points was compared with the other lesion points. RESULTS: Twenty-one points in 16 patients were considered non-conduction blocking lesions. Ten were R, eight were S, and three were D points. The CF, ablation time, FTI, and power at the non-conduction blocking lesion points and other points were 12.0 g (7.0-21.5) and 12.0 g (9.0-16.0) (P = 0.9), 7.7 s (5.6-10.1) and 12.5 s (9.4-16.8) (P < 0.05), 103.0 g*s (62.0-174.5) and 149.0 g*s (104.0-213.0) (P < 0.05), and 30.0 W (22.5-30.0) and 30.0 W (30.0-30.0) (P = 0.06), respectively. CONCLUSIONS: Shorter ablation time recorded in Visitag lead to non-conduction blocking lesion.

Optical coherence tomography study of chronic-phase vessel healing after implantation of bare metal and paclitaxel-eluting self-expanding nitinol stents in the superficial femoral artery.

BACKGROUND: This study aimed to assess chronic-phase suppression of neointimal proliferation and arterial healing following paclitaxel-coated (PTX) and bare metal stent (BMS) implantation in the superficial femoral artery using optical coherence tomography (OCT). METHODS: Twenty-five patients with 68 stents underwent an 8-month OCT follow-up. Besides standard OCT variables, neointimal characterization and frequencies of peri-strut low-intensity area (PLIA), macrophage accumulation, and in-stent thrombi were evaluated. RESULTS: The mean neointimal thickness was significantly less with PTX stents (544.9±202.2 µm vs. 865.0±230.6 µm, p<0.0001). The covered and uncovered strut frequencies were significantly smaller and larger, respectively, in the PTX stent group vs. the BMS group (93.7% vs. 99.4%; p<0.0001, 4.0% vs. 0.4%; p<0.0001, respectively). Heterogeneous neointima was only observed in the PTX stent group (12.5% vs. 0%, p=0.017). The frequencies of PLIA and macrophage accumulation were significantly greater in the PTX stent group (87.2% vs. 67.6%, p=0.001 and 46% vs. 9.1%, p=0.003, respectively). CONCLUSION: After 8 months, reduced neointimal proliferation was observed with PTX stent implantation. On the other hand, delayed arterial healing was observed compared with BMS.

Deficiency of nectin-2 leads to cardiac fibrosis and dysfunction under chronic pressure overload.

The intercalated disc, a cell-cell contact site between neighboring cardiac myocytes, plays an important role in maintaining the homeostasis of the heart by transmitting electric and mechanical signals. Changes in the architecture of the intercalated disc have been observed in dilated cardiomyopathy. Among cell-cell junctions in the intercalated disc, adherens junctions are involved in anchoring myofibrils and transmitting force. Nectins are Ca(2+)-independent, immunoglobulin-like cell-cell adhesion molecules that exist in adherens junctions. However, the role of nectins in cardiac homeostasis and integrity of the intercalated disc are unknown. Among the isoforms of nectins, nectin-2 and -4 were expressed at the intercalated disc in the heart. Nectin-2-knockout mice showed normal cardiac structure and function under physiological conditions. Four weeks after banding of the ascending aorta, cardiac function was significantly impaired in nectin-2-knockout mice compared with wild-type mice, although both nectin-2-knockout and wild-type mice developed similar degrees of cardiac hypertrophy. Banded nectin-2-knockout mice displayed cardiac fibrosis more evidently than banded wild-type mice. The disruption of the intercalated discs and disorganized myofibrils were observed in banded nectin-2-knockout mice. Furthermore, the number of apoptotic cardiac myocytes was increased in banded nectin-2-knockout mice. In the hearts of banded nectin-2-knockout mice, Akt remained at lower phosphorylation levels until 2 weeks after banding, whereas c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were highly phosphorylated compared with those of wild-type mice. These results indicate that nectin-2 is required to maintain structure and function of the intercalated disc and protects the heart from pressure-overload-induced cardiac dysfunction.

Plasma tetrahydrobiopterin/dihydrobiopterin ratio: a possible marker of endothelial dysfunction.

BACKGROUND: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. METHODS AND RESULTS: In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients with multiple coronary risk factors. There was a positive relationship between FMD and plasma BH4 levels and a negative relationship between FMD and plasma BH2 levels. Subsequently, a strong positive relationship between FMD and the BH4/BH2 ratio (r=0.585, P<0.0001) was found. Although we did not find any significant relationship between pteridine levels and individual traditional risk factors, the BH4/BH2 ratio in patients with more than 2 risk factors showed significant reductions compared with that in those without risk factors. Statin treatment improved FMD in association with an increase in the plasma BH4/BH2 ratio. CONCLUSIONS: Plasma pteridine levels were associated with endothelial dysfunction in cardiovascular disorders.

Beneficial effects of exogenous tetrahydrobiopterin on left ventricular remodeling after myocardial infarction in rats: the possible role of oxidative stress caused by uncoupled endothelial nitric oxide synthase.

BACKGROUND: Reactive oxygen species (ROS) is deeply involved in the process of ventricular remodeling after myocardial infarction (MI). Under oxidative stress, endothelial nitric oxide synthase (eNOS) can be converted to a ROS generator, because a relative lack of tetrahydrobiopterin (BH4), an essential cofactor for NO synthesis, leads to eNOS uncoupling. The uncoupled eNOS generates superoxide rather than NO. The possible role of ROS generated by eNOS in ventricular remodeling after MI was investigated. METHODS AND RESULTS: Rats were treated with oral BH4 supplementation starting at 3 days before coronary artery ligation. At 4 weeks after MI, there was augmented superoxide production in association with reduced BH4/dihydrobiopterin (BH2) ratio and eNOS dimer/monomer protein ratio in the heart. Treatment with BH4 increased BH4/BH2 ratio and eNOS dimer/monomer ratio, and decreased superoxide production. In BH4-treated MI rats, left ventricular size was smaller, thickness of the non-infarcted posterior wall was thinner, and cardiac function was preserved compared with the control MI rats. CONCLUSIONS: The present study suggested that ventricular remodeling process after MI leads to BH4 oxidation and resulted in uncoupled eNOS-derived superoxide generation, which further augmented the remodeling process and deteriorated cardiac function.