Li-Tang Kuo

Late-Outgrowth Endothelial Cells Attenuate Intimal Hyperplasia Contributed by Mesenchymal Stem Cells After Vascular Injury

Objectives—Mesenchymal stem cells (MSCs) are one of a number of cell types undergoing extensive investigation for cardiac regeneration therapy. It has not yet been determined whether this cell therapy also substantially contributes to vascular remodeling of diseased vessels. Methods and Results—Human MSCs and a variety of progenitor and vascular cells were used for in vitro and in vivo experiments. Wire-induced vascular injury mobilized MSCs into the circulation. Compared with human aortic smooth muscle cells, MSCs exhibited a 2.8-fold increase in the adhesion capacity in vitro (P<0.001) and a 6.3-fold increase in vivo (P<0.001). In all animal models, a significant amount of MSCs contributed to intimal hyperplasia after vascular injury. MSCs were able to differentiate into cells of endothelial or smooth muscle lineage. Coculture experiments demonstrated that late-outgrowth endothelial cells (OECs) guided MSCs to differentiate toward an endothelial lineage through a paracrine effects. In vivo, cell therapy with OECs significantly attenuated the thickness of the neointima contributed by MSCs (intima/media ratio, from 3.2±0.4 to 0.4±0.1, P<0.001). Conclusions—Tissue regeneration therapy with MSCs or cell populations containing MSCs requires a strategy to attenuate the high potential of MSCs to develop intimal hyperplasia on diseased vessels.

Interaction between cigarette smoking and high-sensitivity C-reactive protein in the development of coronary vasospasm in patients without hemodynamically significant coronary artery disease

Background:Interaction between 2 major risk factors, cigarette smoking and high-sensitivity C-reactive protein (hs-CRP), has not been evaluated in patients with coronary vasospasm (CV) without hemodynamically significant coronary artery disease. Methods:From 1999 to 2005, patients undergoing diagnostic coronary angiography with or without proven CV and without coronary stenosis >50% were evaluated. A total of 621 subjects (335 and 286 with and without CV, respectively) were enrolled in the study. The levels of hs-CRP, measured immediately before coronary angiography, were examined in a subset of 314 patients. Results:Subjects with CV were likely to be older, men, current smokers, and have high hs-CRP levels. The most significant factors for CV were smoking and hs-CRP. In the nonsmoker group, elevated risk of developing CV was only demonstrated in patients with the highest hs-CRP tertile (>5.01 mg/L, P = 0.012). In the smoker group, however, a positively monotonic trend of association was demonstrated between hs-CRP tertile and CV risk, with multivariate-adjusted odds ratios of 1.11, 3.09 (P = 0.012), and 4.12 by the hs-CRP tertiles, suggesting that smokers developed CV at a lower hs-CRP level than nonsmokers and there was a positive interaction between smoking and hs-CRP. Conclusions:The smokers developed CV at a lower hs-CRP level compared with the nonsmokers. A positive interaction between smoking and hs-CRP was demonstrated for this disease in our study population.

Cardiopulmonary resuscitation during coronary vasospasm induced by tilt table testing.

A 65‐year‐old man presented to our institution with recurrent episodes of early morning chest discomfort and near syncope. An ergonovine provocation test documented a diagnosis of coronary va‐sospastic angina. During our investigation of the syncope, a head‐up tilt table test provoked a severe episode of coronary vasospasm that resulted in a life‐threatening cardiac event. The present case reminds us that an elevation of ST segments on the electrocardiogram during tilt testing should be promptly managed as an attack of coronary vasospasm.

Effects of verapamil in normal elderly individuals with left ventricular diastolic dysfunction.

Treatment with oral verapamil for 3 to 4 days has been found to enhance left ventricular (LV) diastolic filling in elderly subjects as assessed by radionuclide angiography. However, there are no Doppler echocardiographic studies to assess the long‐term effect of verapamil in normal elderly subjects. Thirteen healthy elderly subjects (mean age, 64 ± 7 years; 8 men and 5 women) with LV diastolic dysfunction underwent this placebo‐controlled cross‐over trial. The effect of verapamil on LV diastolic function was assessed by treadmill exercise test and Doppler echocardiography at baseline, and after each 3‐month treatment period (placebo or verapamil 120 mg once daily), separated by a 1‐week washout period before cross‐over. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. The exercise time was similar at baseline (11.4 ± 2.4 min) and after placebo treatment (11.4 ± 2.3 min) but significantly increased (P < 0.05) after verapamil treatment (12.3 ± 2.0 min). The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil treatment (1.12 ± 0.08) compared to placebo (0.93 ± 0.06, P < 0.05) and baseline (0.89 ± 0.09), which had similar durations. The isovolumic relaxation time (IVRT) was significantly decreased (P < 0.05) from 85 ± 13 msec at baseline and 87 ± 13 msec with placebo to 73 ± 9 msec with verapamil. The results of this study suggest that in normal elderly patients with Doppler evidence of diastolic dysfunction, 3 months treatment with verapamil can increase exercise tolerance and improve LV diastolic function.

Recurrent cerebral embolism and impending detachment of a previous nonmobile left atrial thrombus following initiation of anticoagulant therapy in a patient with nonvalvular atrial fibrillation.

A 65‐year‐old female with nonvalvular atrial fibrillation who presented with a transient ischemic attack was admitted to our hospital. Transesophageal echocardiography (TEE) revealed a nonmobile thrombus attached to the wall of the left atrial appendage. She suffered from a new episode of syncope on the 8th day following initiation of anticoagulant therapy. Follow‐up TEE indicated not only that the left atrial (LA) thrombus decreased in size but also that the previous nonmobile thrombus became mobile and showed impending detachment. Urgent surgery was subsequently performed to remove the LA thrombus, and the patient recovered uneventfully. In conclusion, anticoagulant therapy may precipitate partial fragmentation or partial detachment of LA thrombus.

Large Right Atrial Thrombus with Pulmonary Embolism

We present the cases of two patients, aged 67 and 77 years, who were admitted for the evaluation of rapidly progressive dyspnea and syncope, respectively. Both patients developed large right atrial thrombi with pulmonary embolism. The first patient received recombinant tissue plasminogen activator and survived with an uneventful result, whereas the second patient received operative thrombectomy followed by intravenous heparin and died 15 days later of pulmonary infarction with pulseless electrical activity. Data from these limited experiences suggest that thrombolytic therapy might be considered in patients withright heart thrombi with pulmonary embolism.

Levels of blood periostin decrease after acute myocardial infarction and are negatively associated with ventricular function after 3 months.

Background A recent study showed that periostin (PN) induced reentry of differentiated cardiomyocytes into the cell cycle and improved heart function after acute myocardial infarction (AMI). This study sought to investigate whether PN levels increase after AMI and whether they provide prognostic value. Methods and Results We recruited 123 patients: 45 with AMI, 45 with stable coronary artery disease (CAD), and 33 healthy controls (CON). Blood PN and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were measured. Echocardiography was repeated 3 months after AMI. In the AMI group, the PN levels 1.3 ± 1.2 days after AMI were significantly lower than those in the CAD and CON groups (175 ± 60, 245 ± 68, and 232 ± 63 ng/mL, respectively, P = 0.001). The NT-pro-BNP levels were significantly higher in the AMI group, compared to the CON and CAD groups (10.07 ± 28.2 [median, 0.70] vs 0.08 ± 0.06 [median, 0.05] and 1.1 ± 4.2 [median, 0.09] ng/mL, respectively; P = 0.02). The PN levels further decreased 8 ± 2 days after AMI (from 175 ± 60 to 143 ± 57 ng/mL; P = 0.003). However, NT-pro-BNP levels did not significantly change. With respect to the echocardiographic parameters 3 months after AMI, the PN levels measured before discharge were negatively associated with the left ventricular ejection fraction (r s = −0.50; P = 0.001), end diastolic (r s = 0.42; P = 0.009) and systolic (r s = 0.46; P = 0.004) diameters. The NT-pro-BNP levels were not significantly correlated with these parameters. Conclusion Acute myocardial infarction is associated with a decrease in blood PN levels, and PN concentrations predict cardiac function 3 months after AMI.

Real-time three-dimensional echocardiography provides advanced haemodynamic information associated with intra-dialytic hypotension in patients with autonomic dysfunction

BACKGROUND Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate and effective tool for assessing left ventricular (LV) function, compared to traditional two-dimensional (2D) methods. In this study, we used this new tool to revise the controversial relationship between LV function and intra-dialytic hypotension. METHODS This study enrolled 29 intra-dialytic hypotensive patients (the IDH group) and 34 controls (the CON group) on regular maintenance haemodialysis. The RT3DE- and 2D-derived ejection fraction (EF), stroke volume index (SVI) and ratio of early transmitral inflow velocity to diastolic early tissue velocity were assessed at pre-dialysis and mid-dialysis. The intravascular volume was assessed by the inferior vena cava collapsibility index. RESULTS Pre-dialysis evaluation showed no difference in RT3DE- and 2D-derived parameters between the two groups. At mid-dialysis, the IDH group had a lower 2D EF (54 +/- 9.1 versus 62 +/- 6.8% in the CON group, P < 0.001), RT3DE EF (53 +/- 6 versus 60 +/- 7% in the CON group, P < 0.001) and SVI (24.3 +/- 8 versus 30.6 +/- 12.2 mL in the CON group, P = 0.02). From pre-dialysis to mid-dialysis, the IDH group had greater decrease in the change in 2D EF (-4.8% +/- 12.6% versus 5% +/- 13.7% in the CON group, P = 0.004), RT3DE EF (-11.8 +/- 10.3 versus -3.4 +/- 11.5% in the CON group, P = 0.003) and SVI (-17.3 +/- 18.5 versus -9.2 +/- 19.8% in the CON group, P = 0.004). The calculated cardiac index change also showed a greater decrease in the IDH group (-17.8 +/- 20.2 versus -5.7 +/- 18.5% in the CON group, P = 0.02). No significant difference in the ratio of early transmitral inflow velocity to diastolic early tissue velocity, heart rate, systemic vascular resistance index or inferior vena cava collapsibility index was found between the two groups at the baseline or mid-dialysis. A lack of an increase in heart rate and the systemic vascular resistance index in the IDH group during the hypotensive episodes implies that these patients have autonomic dysfunction. Multivariate analysis showed that the RT3DE EF change of < -9.5% (odds ratio = 6, P = 0.003) and the presence of diabetes (odds ratio = 4.4, P = 0.013) had significant and independent associations with intra-dialytic hypotension. CONCLUSIONS By adopting RT3DE to assess LV performance, our data demonstrated that an inadequate compensation in the LV systolic function is the main mechanism mediating the occurrence of intra-dialytic hypotension in patients with autonomic dysfunction.

Irreversible myocardial damage after coronary air embolism--a case report.

This case report describes the complication of an air embolism in the right coronary artery that developed during coronary angiography in a patient with acute anterior myocardial infarction. Follow-up left ventriculography, 4 months later, showed irreversible inferior wall damage. Incomplete aspiration of the angiographic catheter was the cause of this complication and should be avoided.

Analysis of left atrial volume change rate during left ventricular diastolic phase with M-mode echocardiography for differentiation between normal and pseudonormal mitral inflow

Pseudonormalization of mitral inflow is a diagnostic problem in clinical practice. An excellent correlation exists between the change in the left atrial (LA) angiographic area and posterior aortic wall motion. Therefore, we sought to define the role of LA wall motion, indicating LA volume change rate, in patients with normal and pseudonormal mitral inflow. We performed echocardiography after cardiac catheterization in 62 patients with a velocity ratio of early-to-late mitral inflow (E/A ratio) >1. Study patients were classified into 2 groups according to the response of mitral inflow to phase II of the Valsalva maneuver: patients with E/A >1 after the Valsalva maneuver (n = 31, control group), and patients with <1 after the Valsalva maneuver (n = 31, pseudonormal group). The slopes (slope E and A) of early diastolic and late diastolic motion of the LA wall were derived from M-mode analysis together with the time constant of left ventricular (LV) isovolumic relaxation from cardiac catheterization. The values of slope E (41 plus minus 11 vs 61 plus minus 12 mm/s, p <0.001) and slope E/A (0.69 plus minus 0.13 vs 1.32 plus minus 0.35, p <0.001) were significantly lower in the pseudonormal group and were inversely correlated with the time constant of LV isovolumic relaxation (r = 0.64, p <0.001 and r = 0.73, p <0.001, respectively). Using slope E/A <1 as an indicator of relaxation abnormality, the sensitivity, specificity, positive predictive value, and negative predictive value for the detection of pseudonormalization were 94%, 100%, 100%, and 94%, respectively. The slope of LA wall motion, indicating LA volume change rate, during the LV diastolic phase is useful for evaluating pseudonormal LV diastolic dysfunction in the selected patient population.