Seung-Jae Joo

Application of veno-arterial-venous extracorporeal membrane oxygenation in differential hypoxia

Veno-arterial extracorporeal membrane oxygenation (ECMO) through the femoral vein and artery may cause differential hypoxia, i.e., lower PaO2 in the upper body than in the lower body, because of normal cardiac output with severe impairment of pulmonary function. Hereby, we report the diagnosis and the treatment of differential hypoxia caused by veno-arterial ECMO. A 39-year-old man received cardiopulmonary resuscitation from a cardiac arrest due to acute myocardial infarction. Even after more than 30 min of resuscitation, spontaneous circulation had not resumed. Next, we performed veno-arterial ECMO through the femoral artery and vein, and the patient recovered consciousness on the second day of ECMO. On day 5 of ECMO, he lost consciousness again and presented a generalized tonic-clonic seizure, and an electroencephalogram showed delta waves suggesting diffuse cerebral cortical dysfunction. While an echocardiogram revealed improvements in myocardial function, a follow up chest radiograph showed increasing massive parenchymal infiltrations, and gas analysis of blood from the right radial artery revealed severe hypoxemia. These findings indicated a definite diagnosis of differential hypoxia, and therefore, we inserted a 17-Fr cannula into the left subclavian vein as a return cannula. The patient’s consciousness and pulmonary infiltrations were improved 2 days after veno-arterial-venous ECMO, and the electroencephalogram showed normal findings. To our knowledge, this is the first report of successful clinical management of differential hypoxia. We suggest that veno-arterial-venous ECMO could be the treatment of choice for differential hypoxia resulting from veno-arterial ECMO.

Mechanisms of Platelet Activation and Integrin αIIβ3

Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A2 activate platelet integrin αIIbβ3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by Gq, G12/G13 or Gi, include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.

Determining the necessity for right heart catheterization in pulmonary hypertension associated with connective tissue diseases assessed by echocardiography

The prognosis of pulmonary hypertension (PH) in systemic sclerosis (SSC) and in systemic lupus erythematosus (SLE) is different. According to the guidelines, right heart catheterization (RHC) is necessary in pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD). However, there is little supporting evidence. Therefore, we attempted to determine the necessity for RHC and the causes of differences in prognosis of PH by comparing SSC to SLE.

An Assay of Measuring Platelet Reactivity Using Monoclonal Antibody against Activated Platelet Glycoprotein IIb/IIIa in Patients Taking Clopidogrel

Background and Objectives Residual platelet reactivity in patients who are taking clopidogrel is commonly measured with VerifyNow assay, which is based on the principle of light transmission aggregometry. However, to evaluate the residual platelet reactivity, it would be more accurate if the reactivity of platelet glycoprotein (GP) IIb/IIIa is directly monitored. In this study, PAC1, a monoclonal antibody against activated platelet GP IIb/IIIa, was used to measure the residual platelet reactivity. Subjects and Methods Twenty seven patients with coronary artery disease taking clopidogrel were enrolled. Platelets in whole blood were stained with fluorescein isothiocyanate (FITC)-conjugated PAC1. Mean fluorescence intensity (MFI) and % positive platelets (PP) were measured with flow cytometry, and the binding index (BI; MFI × %PP/100) was calculated. P2Y12 reaction unit (PRU) and % inhibition of VerifyNow assay were also measured in the usual manner. Results PRU of VerifyNow assay correlated significantly with MFI, %PP, and BI at 10 µM (r=0.59, 0.73, and 0.60, respectively, all p<0.005) and 20 µM of adenosine diphosphate (ADP; r=0.61, 0.75, and 0.63, respectively, all p<0.005). The % inhibition also correlated significantly with MFI, %PP, and BI at 10 µM (r=-0.60, -0.69, and -0.59, respectively, all p<0.005) and 20 µM of ADP (r=-0.63, -0.71, and -0.62, respectively, all p<0.005). Conclusion Direct measurements of the reactivity of platelet GP IIb/IIIa were feasible using PAC1 and flow cytometry in patients taking clopidogrel. Further clinical studies are required to determine the cut-off values which would define high residual platelet reactivity in patients on this treatment protocol.

Pseudonormal or Restrictive Filling Pattern of Left Ventricle Predicts Poor Prognosis in Patients with Ischemic Heart Disease Presenting as Acute Heart Failure

BACKGROUND In patients with acute heart failure (AHF), diastolic dysfunction, especially pseudonormal (PN) or restrictive filling pattern (RFP) of left ventricle (LV), is considered to be implicated in a poor prognosis. However, prognostic significance of diastolic dysfunction in patients with ischemic heart disease (IHD) has been rarely investigated in Korea. METHODS We enrolled 138 patients with IHD presenting as AHF and sinus rhythm during echocardiographic study. Diastolic dysfunction of LV was graded as ≥ 2 (group 1) or 1 (group 2) according to usual algorithm using E/A ratio and deceleration time of mitral inflow, E′/A′ ratio of tissue Doppler echocardiography and left atrial size. RESULTS Patients in group 1 showed higher 2-year mortality rate (36.2% ± 6.7%) than those in group 2 (13.6% ± 4.5%; p = 0.008). Two-year mortality rate of patient with LV ejection fraction (LVEF) < 40% (26.8% ± 6.0%) was not different from those with LVEF 40%–49% (28.0% ± 8.0%) or ≥ 50% (13.7% ± 7.4%; p = 0.442). On univariate analysis, PN or RFP of LV, higher stage of chronic kidney disease (CKD) and higher New York Heart Association (NYHA) functional class were poor prognostic factors, but LVEF or older age ≥ 75 years did not predict 2-year mortality. On multivariate analysis, PN or RFP of LV (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.09–5.84; p = 0.031), higher stage of CKD (HR, 1.57; 95% CI, 1.14–2.17; p = 0.006) and higher NYHA functional class (HR, 1.81; 95% CI, 1.11–2.94; p = 0.017) were still significant prognostic factors for 2-year mortality. CONCLUSIONS PN or RFP of LV was a more useful prognostic factor for long-term mortality than LVEF in patients with IHD presenting as AHF.

Arterial Stiffness in Subacute Stroke: Changing Pattern and Relationship with Functional Recovery

BACKGROUND To examine changing patterns in arterial stiffness and functional outcome in patients with subacute stroke, and to determine which parameter shows a strong correlation with the reversal of arterial stiffness, during a 3-month period of comprehensive rehabilitation therapy. METHODS This descriptive, observational cohort study enrolled 60 patients (43 male and 17 female; average age, 62.7 years), and all received conventional rehabilitation therapy, during a 3-month period. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Functional assessments included the 6-minute walk test (6MWT), Fugl-Meyer Assessment of hemiparetic upper and lower limbs, the functional ambulatory category, the Berg balance scale, the Korean Mini-Mental Status Examination, and the Korean-Modified Barthel Index. All measurements were conducted at baseline and 1 and 3 months after stroke onset. RESULTS Rehabilitation therapy resulted in a statistically significant improvement in baPWV since 3 months post stroke. Another functional outcome measure showed statistically significant improvements since 1 month after rehabilitation. Multivariable linear regression analysis revealed that a change in baPWV was significantly correlated with changes in the 6MWT. CONCLUSIONS Three months of comprehensive rehabilitation therapy led to statistically significant improvements in arterial stiffness and functional outcomes during the subacute phase of stroke. Thus, the comprehensive rehabilitation focused on improving gait endurance would be warranted in subacute stroke patients.

Erratum: Psychiatric Characteristics of the Cardiac Outpatients with Chest Pain

[This corrects the article on p. 169 in vol. 46, PMID: 27014347.].

PS 02-68 THE RELATIONSHIP BETWEEN VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND CLIMATE IN JEJU

Objective: In Korea, Jeju Island is a region where monthly mean temperature does not drop below 0 degrees Celsius. The purpose of this study is to find out the relationship between visit-to-visit blood pressure variability (BPV) and the warm climate. Design and Method: From Jan. 2013 to Dec. 2015, 596 patients who take antihypertensive medication were analyzed in our hospital. 70 patients were excluded: 24 paid no visit more than 3 times, 31 had no blood pressure records, and 15 had atrial fibrillation. The measurement of the BPV is standard deviation. The high variability group was defined as the increased medication or the more than 15mmHg of standard deviation (more than 75 percentile) without decreased medication. Results: An inverse correlations were observed between the monthly mean BP, monthly mean temperature (r = −0.847, p < 0.001; Figure1). In high variability group, which were significantly different compared to the normal variability group (130.7 ± 8.5 mmHg vs. 136.1 ± 11.8 mmHg, p < 0.001; 16.5 ± 1.4oC vs.16.2 ± 1.4oC, p = 0.008). In multivariable analysis, higher monthly mean systolic blood pressure (B = 0.058, odds ratio [OR] = 1.06, p < 0.001, 95% CI = 1.04 – 1.08) and lower monthly mean temperature (B = -0.214, odds ratio [OR] = 0.81, p = 0.003, 95% CI = 0.70 – 0.93) were associated with the high variability group. Conclusions: Even in Jeju, a relatively warm region, blood pressure changed according to the temperature. Blood pressure variability in patients who are taking antihypertensive medication had an association with monthly high mean systolic blood pressure and monthly mean temperature.

PS 05-67 GENDER DIFFERENCE IN THE CHANGE OF AUGMENTATION INDEX AFTER TREADMILL EXERCISE

Objective: Although augmentation index (AIx), which measures the arterial stiffness, has been shown to be greater in women than men, height may influence AIx, and women is usually shorter than men. This study aimed to investigate the gender difference of AIx before and after treadmill exercise. Design and Method: Forty-six subjects (22 women and 24 men), who underwent treadmill exercise test for the evaluation of chest pain, were enrolled in this study. The waveform of central aortic pressure was recorded before and after treadmill exercise using SphygmoCor®, and pulse rate-adjusted AIx (AIx@75) was measured. Results: Age (W; 52.6 ± 16.1 vs. M; 51.8 ± 14.8 years), prevalence of hypertension, coronary artery disease, diabetes or hyperlipidemia, and medications were not different, but height was shorter in women (156.5 ± 6.3 vs. 168.4 ± 7.0 cm, p < 0.001). Baseline AIx@75 was greater in women (25.7 ± 13.0 vs. 18.0 ± 11.1%, p = 0.036). Total duration of exercise and maximal METs during treadmill test were not different. After exercise, AIx@75 was also greater in women (29.5 ± 10.7 vs. 19.2 ± 7.9%, p = 0.001), but changes of AIx@75 were not different between genders (W; 3.7 ± 9.5 vs. M; 1.2 ± 8.5%). AIx@75 was significantly correlated with height (baseline; r = −0.540, p < 0.001, after exercise; r = −0.550, p < 0.001). On multivariate logistic regression analysis including height, AIx@75 at baseline or after exercise was not significantly different between genders. Conclusions: Gender difference of AIx before and after treadmill exercise was not observed. Height was the major determining factor of AIx.

532 CENTRAL HEMODYNAMIC PARAMETERS OF PATIENTS WITH UNCONTROLLED HYPERTENSION

Objectives: To prevent target organ damage and cardiovascular complications of hypertension, BP should be controlled below 140/90 mmHg (<130/80 mmHg in DM or chronic kidney disease), but some hypertensive patients have still uncontrolled BP despite of two or more drugs combination therapy. We investigated the central hemodynamic parameters of hypertensive patients who came to our cardiovascular outpatient facility during 1 month. Methods: 547 hypertensive subjects with sinus rhythm were enrolled. Radial artery waveforms were recorded with the radial tonometry (HEM 9000-AI). Systolic BP (SBP), diastolic BP (DBP), SBP2 (central BP), &Dgr;SBP-SBP2, central pulse pressure (cPP), peripheral augmentation index (pAI), and pAI corrected at pulse rate 75/min (pAI75) were measured. Results: 35% of total patients have uncontrolled BP. Uncontrolled patients have more diabetes (43.8% vs. 15.6%, p < 0.001), left ventricular hypertrophy on ECG (20.1% vs. 17.3%, p = 0.006), higher body mass index, and taking more anti-hypertensive medications (2.69 ± 1.03 vs. 2.31 ± 1.02, p < 0.001), especially diuretics and calcium channel blockers. SBP, DBP, SBP2, &Dgr;SBP-SBP2, and cPP were higher in uncontrolled patients, but pAI and pAI75 were not significantly different. Conclusions: About one third of hypertensive patients had uncontrolled BP. Although their peripheral BP and central BP were higher, they had similar arterial stiffness index. Table. No title available.