Jun Kwan

A Randomized, Open-Label, Multicenter Trial for the Safety and Efficacy of Adult Mesenchymal Stem Cells after Acute Myocardial Infarction

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%±8.5% vs 1.6%±7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)

Assessment of left ventricular asynchrony using volume—time curves of 16 segments by real‐time 3 dimensional echocardiography: Comparison with tissue Doppler imaging

Recent technical developments with high‐resolution real‐time 3 dimensional echocardiography (RT3DE) facilitate the acquisition of high quality images and the analysis of segmental volume—time curves (VTCs).

Dynamic change of mitral apparatus as potential cause of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

AIMS the geometry of the mitral apparatus changes dynamically throughout systole and diastole. We investigated how geometric dynamics of the mitral apparatus could affect the haemodynamics of the outflow tract in patients with hypertrophic cardiomyopathy presenting with systolic anterior motion (HCM(SAM)) using three-dimensional (3D) echocardiography. METHODS AND RESULTS we obtained transthoracic volumetric images in 21 patients with HCM(SAM) with differing trans-left ventricular (LV) outflow tract pressure gradient (PG(LVOT)) and in 23 controls. Original software was used to crop the 3D data into 18 radial planes; the mitral annulus, leaflets, coaptation point, protruding septum, and papillary muscles (PMs) tips were traced in each plane. The data were then reconstructed for 3D distance measurements and volumetric assessment. Shorter coaptation-septal distance (12 ± 4 vs. 21 ± 3 mm, P < 0.001), shorter inter-PM distance (13 ± 5 vs. 18 ± 4 mm, P = 0.02), and larger mitral tenting volume/body surface area (TVindex) (2.1 ± 1 vs. 0.5 ± 0.3 mL/m(2), P < 0.001) were associated with HCM(SAM) vs. control. PG(LVOT) increased with TVindex (r = 0.51, P = 0.01), and decreased with coaptation-septal distance(r = -0.83, P < 0.001) and the inter-PM distance (r = -0.69, P < 0.001) at mid-systole but not at mid-diastole (all P> 0.05). In addition, the coaptation-septal distance, TVindex, and inter-PM distance correlated each other (all P < 0.05). After adjustment for measures of mitral geometric change, the coaptation-septal distance was closely associated with PG(LVOT) (β = -0.73, P < 0.001). CONCLUSION these findings suggest that dynamic geometric changes by interaction of PMs, mitral tenting, and the coaptation point at mid-systole may be important contributors to outflow obstruction in HCM(SAM).

The relationship between the left atrial volume and the maximum P-wave and P-wave dispersion in patients with congestive heart failure.

Purpose A maximum P-wave duration (Pmax) of ≥ 110 msec and a P-wave dispersion (PWD) ≥ 40 msec are accepted indicators of a disturbance in interatrial conduction and an inhomogeneous propagation of the sinus impulse, respectively. The left atrial (LA) volume has been reported to be strongly associated with a systolic and diastolic dysfunction and is considered to be an index of atrial remodeling. We aimed to investigate the relationship between LA volume and Pmax or PWD in patients with congestive heart failure (CHF). Patients and Methods Sixty-one patients with CHF were enrolled in this study. The study population was classified into four groups: two groups were divided according to the Pmax (≥ 110 msec or < 110 ms), and the other two groups were formed based on the PWD (≥ 40 msec or < 40 msec). The left atrial volume index (LAVi) was measured by three-dimensional (3-D) transthoracic echocardiography. The Pmax and PWD were measured from a 12-lead electrocardiogram. Results There were significant differences in the ejection fraction (EF), diastolic function, and LAVi between patients with a Pmax ≥ 110 ms or a PWD ≥ 40 ms and those with a Pmax < 110 ms or a PWD < 40 ms. The LAVi was independently associated with a disturbance in interatrial conduction and an inhomogeneous propagation of the sinus impulse. The LAVi can be used to identify patients with a disturbance in interatrial conduction and an inhomogeneous propagation of the sinus impulse with reasonably good accuracy. Conclusion We concluded that a disturbance in interatrial conduction and an inhomogenous propagation of the sinus impulse in patients with CHF is associated with an increase in the LA volume and a deleterious systolic and diastolic dysfunction.

SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR): A Multi-Center, Retrospective, Observational Study

Background Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea. Method and Results The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction <45%) admitted to 23 university hospitals. The guideline adherence indicator (GAI) was defined as a performance measure on the basis of 3 pharmacological classes: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta-blocker (BB), and aldosterone antagonist (AA). Based on the overall adherence percentage, subjects were divided into 2 groups: those with good guideline adherence (GAI ≥50%) and poor guideline adherence (GAI <50%). We included 1319 regional participants as representatives of the standard population from the Korean national census in 2008. Adherence to drugs at discharge was as follows: ACEI or ARB, 89.7%; BB, 69.2%; and AA, 65.9%. Overall, 82.7% of the patients had good guideline adherence. Overall mortality and re-hospitalization rates at 1 year were 6.2% and 37.4%, respectively. Survival analysis by log-rank test showed a significant difference in event-free survival rate of mortality (94.7% vs. 89.8%, p = 0.003) and re-hospitalization (62.3% vs. 56.4%, p = 0.041) between the good and poor guideline-adherence groups. Conclusions Among patients with systolic HF in Korea, adherence to pharmacologic treatment guidelines as determined by performance measures, including prescription of ACEI/ARB and BB at discharge, was associated with improved clinical outcomes.

Huge sinus of Valsalva aneurysm causing mitral valve incompetence

We describe a case of a large sinus of Valsalva aneurysm originating from the noncoronary sinus. The aneurysm compressed the roof of the left atrium rendering the annulus and the anterior leaflet of the mitral valve severely distorted and, as a result, incompetent. The neck of the aneurysm was closed with a patch from the side of the aortic sinus, but we had to replace the mitral valve as the distorted structure did not resume its original shape even though we opened the aneurysm and debrided all thrombotic material inside the aneurysm.

Early dipyridamole stress myocardial SPECT to detect residual stenosis of infarct related artery: comparison with coronary angiography and fractional flow reserve.

Background The detection of residual stenosis of infarct related artery (IRA) at early stage after acute myocardial infarction (AMI) is crucial in clinical decision making for interventional revascularization. The aim of this study was to evaluate the relevancy of early dipyridamole stress myocardial SPECT to detect functionally and luminologically significant residual stenosis of IRA after AMI. Methods Twenty five consecutive patients (M:F=19:6, age: 56±13yrs) with AMI underwent SPECT and coronary angiography within 5 days of the attack. Infarct related arteries with FFR < 0.75 and diameter stenosis (DST) >70% were regarded to have functionally and morphologically significant residual stenosis. Reversible perfusion defect was defined if there was improvement of the perfusion score more than one grade in infarct segments on rest images of SPECT compared with stress images. Results Mean FFR and DST were 0.76±0.14 and 74±15%. SPECT showed no significant correlation with both FFR and DST with Kendall’s coefficiency of 0.28 (p=0.05) and 0.13 (p=0.35). The sensitivity and specificity of SPECT to detect functionally and morphologically significant residual stenosis were 92%, 31% and 83%, 29%. Conclusion The early dipyridamole stress myocardial SPECT after AMI does not seem to be a useful non-invasive test for the detection of functionally and luminologically significant residual stenosis of IRA.

Randomised trial to compare a protective effect of Clopidogrel Versus TIcagrelor on coronary Microvascular injury in ST-segment Elevation myocardial infarction (CV-TIME trial).

AIMS Ticagrelor has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the superiority of ticagrelor for preventing ischaemic damage in STEMI patients has not been proven. The aim of this trial was to assess whether ticagrelor is superior to clopidogrel in preventing microvascular injury in ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS Patients with STEMI underwent prospective random assignment to receive a loading dose (LD) of clopidogrel 600 mg or ticagrelor 180 mg (1:1 ratio) before primary percutaneous coronary intervention (PCI). As the primary endpoint, the index of microcirculatory resistance (IMR) was measured immediately after primary PCI. The secondary endpoint was the infarct size estimated from the wall motion score index (WMSI). A total of 76 patients were enrolled (clopidogrel group=38, ticagrelor group=38). The IMR in the ticagrelor group was significantly lower than that in the clopidogrel group (22.2±18.0 vs. 34.4±18.8 U, p=0.005). Cardiac enzymes were less elevated in the ticagrelor group than in the clopidogrel group (CK peak; 2,651±1,710 vs. 3,139±2,698 ng/ml, p=0.06). Infarct size, estimated by WMSI, was not different between the ticagrelor and clopidogrel groups at baseline (1.55±0.30 vs. 1.61±0.29, p=0.41) or after three months (1.42±0.33 vs. 1.47±0.33, p=0.57). CONCLUSIONS In patients with STEMI treated by primary PCI, a 180 mg LD of ticagrelor might be more effective in reducing microvascular injury than a 600 mg LD of clopidogrel, as demonstrated by IMR immediately after primary PCI.

Comprehensive assessment of microcirculation after primary percutaneous intervention in ST-segment elevation myocardial infarction: insight from thermodilution-derived index of microcirculatory resistance and coronary flow reserve

ObjectivesA pathophysiological mechanism of microvascular dysfunction in ST-segment elevation myocardial infarction (STEMI) is multifactorial; thus, multiple modalities were needed to precisely evaluate a microcirculation. MethodsWe complementarily assessed microcirculation in STEMI by the index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) immediately after a primary percutaneous intervention in 89 STEMI patients. Cardiovascular and cerebrovascular events (MACCE) including cardiovascular death, target vessel failure, heart failure, and stroke were assessed during a mean follow-up period of 3.0 years. ResultsThe microcirculation of enrolled patients was classified into four groups using cutoff CFR and IMR values (CFR>2 and mean IMR): group-1 (n=23, CFR>2 and IMR⩽27); group-2 (n=31, CFR⩽2 and IMR⩽27); group-3 (n=9, CFR>2 and IMR>27); and group-4 (n=26, CFR<2 and IMR>27). On echocardiography 3 months later, improvement in the wall motion score index was shown in group-1 (P<0.01), group-2 (P<0.01), and group-3 (P=0.04), whereas group-4 did not show improvement in wall motion score index (P=0.06). During clinical follow-up, there were no MACCE in group-1 and the patients in group-2 and group-3 showed significantly lower MACCE compared with group-4 (group-1=0%, group-2, and group-3=10%, group-4=23.1%, P=0.04). ConclusionComplimentary assessment of microcirculation by the IMR and CFR may be useful to evaluate myocardial viability and the long-term prognosis of STEMI patients.

The Relationship Between J Wave on the Surface Electrocardiography and Ventricular Fibrillation during Acute Myocardial Infarction

We investigated whether the presence of J wave on the surface electrocardiography (sECG) could be a potential risk factor for ventricular fibrillation (VF) during acute myocardial infarction (AMI). We performed a retrospective study of 317 patients diagnosed with AMI in a single center from 2009 to 2012. Among the enrolled 296 patients, 22 (13.5%) patients were selected as a VF group. The J wave on the sECG was defined as a J point elevation manifested through QRS notching or slurring at least 1 mm above the baseline in at least two leads. We found that the incidence of J wave on the sECG was significantly higher in the VF group. We also confirmed that several conventional risk factors of VF were significantly related to VF during AMI; time delays from the onset of chest pain, blood concentrations of creatine phosphokinase and incidence of ST-segment elevation. Multiple logistic regression analysis demonstrated that the presence of J wave and the presence of a ST-segment elevation were independent predictors of VF during AMI. This study demonstrated that the presence of J wave on the sECG is significantly related to VF during AMI. Graphical Abstract