Jaemin Shim

Coronary Artery Calcium Scoring Does Not Add Prognostic Value to Standard 64-Section CT Angiography Protocol in Low-Risk Patients Suspected of Having Coronary Artery Disease

PURPOSE To evaluate the prognostic outcome of cardiac computed tomography (CT) for prediction of major adverse cardiac events (MACEs) in low-risk patients suspected of having coronary artery disease (CAD) and to explore the differential prognostic values of coronary artery calcium (CAC) scoring and coronary CT angiography. MATERIALS AND METHODS Institutional review committee approval and informed consent were obtained. In 4338 patients who underwent 64-section CT for evaluation of suspected CAD, both CAC scoring and CT angiography were concurrently performed by using standard scanning protocols. Follow-up clinical outcome data regarding composite MACEs were procured. Multivariable Cox proportional hazards models were developed to predict MACEs. Risk-adjusted models incorporated traditional risk factors for CAC scoring and coronary CT angiography. RESULTS During the mean follow-up of 828 days ± 380, there were 105 MACEs, for an event rate of 3%. The presence of obstructive CAD at coronary CT angiography had independent prognostic value, which escalated according to the number of stenosed vessels (P < .001). In the receiver operating characteristic curve (ROC) analysis, the superiority of coronary CT angiography to CAC scoring was demonstrated by a significantly greater area under the ROC curve (AUC) (0.892 vs 0.810, P < .001), whereas no significant incremental value for the addition of CAC scoring to coronary CT angiography was established (AUC = 0.892 for coronary CT angiography alone vs 0.902 with addition of CAC scoring, P = .198). CONCLUSION Coronary CT angiography is better than CAC scoring in predicting MACEs in low-risk patients suspected of having CAD. Furthermore, the current standard multisection CT protocol (coronary CT angiography combined with CAC scoring) has no incremental prognostic value compared with coronary CT angiography alone. Therefore, in terms of determining prognosis, CAC scoring may no longer need to be incorporated in the cardiac CT protocol in this population.

First-degree atrioventricular block is associated with advanced atrioventricular block, atrial fibrillation and left ventricular dysfunction in patients with hypertension.

OBJECTIVES: Clinical significance of first-degree atrioventricular block (AVB) have not been known in patients with hypertension. This study was performed to elucidate long-term prognosis of first-degree AVB in patients with hypertension. METHODS: We included 3816 patients (mean age, 61.0 ± 10.6 years; men, 47.2%) with hypertension. We reviewed their ECGs and measured the PR interval. The patients were divided into two groups: normal PR interval (120 ms ≤ PR ≤200 ms) and first-degree AVB (PR >200 ms). We compared the incidence, cumulative incidence and hazard ratios of advanced AVB, sick sinus syndrome, atrial fibrillation and left ventricular dysfunction between the two groups during the follow-up period. RESULTS: The prevalence of first-degree AVB in patients with hypertension was 14.3%. The patients were followed up for 9.4 ± 2.4 years. Incidence and cumulative incidence of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with first-degree AVB were significantly higher than in patients with normal PR interval. By multivariate Coxs regression, patients with first-degree AVB had an increased risk of advanced AVB [hazard ratio 2.77; 95% confidence interval (95% CI) 1.38-5.59; P = 0.004], atrial fibrillation (hazard ratio 2.33; 95% CI 1.84-2.94; P < 0.001) and left ventricular dysfunction (hazard ratio 1.49; 95% CI 1.11-2.00; P = 0.009). However, sick sinus syndrome was not associated with first-degree AVB. CONCLUSION: First-degree AVB is an independent risk factor for future development of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with hypertension.Background: Chronic kidney disease (CKD) is characterized by aortic stiffness and increased cardiovascular mortality. In end-stage renal disease, aortic stiffness predicts mortality, whereas this role remains uncertain in mild-to-moderate CKD. We aimed to investigate whether aortic pulse wave velocity (aPWV) predicts mortality and renal disease progression in CKD patients. Methods: We enrolled 135 CKD patients stages 2–4 [estimated glomerular filtration rate (eGFR): 41.1 (28.5–61.6) ml/min per 1.73 m2] in the study and assessed aPWV. The combined renal end-point was defined as at least 50% decline in renal function and/or start of renal replacement therapy. Results: During the observational period of 42 (30–50) months six patients were lost of follow-up, 13 patients died and 16 patients reached the combined renal end-point. Stratification according to the mean of aPWV (10 m/s), Kaplan–Meier analysis revealed increased mortality with aPWV ≥10 m/s (log-rank P < 0.05). Stepwise logistic regression analysis confirmed aPWV as an independent predictor for mortality in CKD stage 2–4. The hazard ratio of mortality in the cohort with an aPWV at least 10 m/s was 5.1 (1.1–22.9). By contrast, Kaplan–Meier analysis revealed no effect of aPWV on the combined renal end-point (log-rank P = 0.90). Discussion: These results provide the first direct evidence that in patients with CKD stage 2–4, increased aortic stiffness determined by aPWV is a strong independent predictor of all-cause mortality.OBJECTIVES Clinical significance of first-degree atrioventricular block (AVB) have not been known in patients with hypertension. This study was performed to elucidate long-term prognosis of first-degree AVB in patients with hypertension. METHODS We included 3816 patients (mean age, 61.0 ± 10.6 years; men, 47.2%) with hypertension. We reviewed their ECGs and measured the PR interval. The patients were divided into two groups: normal PR interval (120 ms ≤ PR ≤200 ms) and first-degree AVB (PR >200 ms). We compared the incidence, cumulative incidence and hazard ratios of advanced AVB, sick sinus syndrome, atrial fibrillation and left ventricular dysfunction between the two groups during the follow-up period. RESULTS The prevalence of first-degree AVB in patients with hypertension was 14.3%. The patients were followed up for 9.4 ± 2.4 years. Incidence and cumulative incidence of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with first-degree AVB were significantly higher than in patients with normal PR interval. By multivariate Coxs regression, patients with first-degree AVB had an increased risk of advanced AVB [hazard ratio 2.77; 95% confidence interval (95% CI) 1.38-5.59; P = 0.004], atrial fibrillation (hazard ratio 2.33; 95% CI 1.84-2.94; P < 0.001) and left ventricular dysfunction (hazard ratio 1.49; 95% CI 1.11-2.00; P = 0.009). However, sick sinus syndrome was not associated with first-degree AVB. CONCLUSION First-degree AVB is an independent risk factor for future development of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with hypertension.

Intracoronary thrombus formation after drug-eluting stents implantation: Optical coherence tomographic study

BACKGROUND Intracoronary thrombus formation after drug-eluting stent (DES) implantation is not sufficiently evaluated. METHODS Optical coherence tomography (OCT) was performed in 226 patients (total DES n = 244, sirolimus-eluting stent [SES] n = 95, paclitaxel-eluting stent [PES] n = 62, zotarolimus-eluting stent [ZES] n = 87) after implantation (mean 11 months, range 3-66 months). Using OCT, we investigated the incidence and determinants of intracoronary thrombus. RESULTS Intracoronary thrombus was detected in 35 (14%) cases (27 SES [28%], 7 PES [11%], and 1 ZES [1%], P < .001) and was associated with longer stent, smaller stent diameter, and stents at bifurcation lesions. More uncovered stent struts (26 +/- 23 vs 8 +/- 17, P < .001) and malapposed stent struts (6 +/- 14 vs 2 +/- 6, P < .001) were also associated with intracoronary thrombus. Multiple logistic regression analysis found the following determinants of intracoronary thrombus: stent length > or =28 mm (odds ratio [OR] 7.31, 95% CI 1.79-29.86, P = .01), stent diameter <3.0 mm (OR 4.38, 95% CI 1.38-13.97, P = .01), and > or =8 uncovered struts in each stent (OR 3.29, 95% CI 1.07-10.17, P = .04). CONCLUSIONS Length, size, and types of DES may be more important than clinical factors in intracoronary thrombus formation after DES implantations.

Antiarrhythmic Potential of Mesenchymal Stem Cell Is Modulated by Hypoxic Environment

OBJECTIVES The purpose of this study was to evaluate the antiarrhythmic potential of mesenchymal stem cells (MSC) under a different environment. BACKGROUND Little is known about how environmental status affects antiarrhythmic potential of MSCs. METHODS To investigate the effect of paracrine factors secreted from MSCs under different circumstances on arrhythmogenicity in rats with myocardial infarction, we injected paracrine media (PM) secreted under hypoxic, normoxic conditions (hypoxic PM and normoxic PM), and MSC into the border zone of infarcted myocardium in rats. RESULTS We found that the injection of hypoxic PM, but not normoxic PM, markedly restored conduction velocities, suppressed focal activity, and prevented sudden arrhythmic deaths in rats. Underlying this electrophysiological alteration was a decrease in fibrosis, restoration of connexin 43, alleviation of Ca(2+) overload, and recovery of Ca(2+)-regulatory ion channels and proteins, all of which is supported by proteomic data showing that several paracrine factors including basic fibroblast growth factor, insulinlike growth factor 1, hepatocyte growth factor, and EF-hand domain-containing 2 are potential mediators. When compared with PM, MSC injection did not reduce or prevent arrhythmogenicity, suggesting that the antiarrhythmic or proarrhythmic potential of MSC is mainly dependent on paracrine factors. CONCLUSIONS A hypoxic or normoxic environment surrounding MSC affects the type and properties of the growth factors or cytokines, and these secreted molecules determine the characteristics of the electro-anatomical substrate of the surrounding myocardium.

Does additional linear ablation after circumferential pulmonary vein isolation improve clinical outcome in patients with paroxysmal atrial fibrillation? Prospective randomised study

Objective Circumferential pulmonary vein isolation (CPVI) has been considered the cornerstone of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, it is unclear whether linear ablation in addition to CPVI improves clinical outcome. Design Prospective randomised study to compare the efficacy of CPVI and CPVI with additional linear ablation in patients with paroxysmal AF (PAF). Setting University hospital. Patients This study enrolled 156 patients (male 76.3%, 55.8±11.5 years old (mean±SD)) who underwent RFCA for PAF. Interventions CPVI (n=52), CPVI+roof line (CPVI+RL; n=52) and CPVI+RL+posterior inferior line (CPVI+PostBox; n=52). Main outcome measures Procedure time, ablation time and clinical outcome. Results (1) The CPVI group showed shorter total procedure time (180.4±39.5 min vs 189.6±29.0 min and 201.7±51.7 min, respectively (mean±SD); p=0.035) and ablation time (4085.5±1384.1 s vs 5253.5±1010.9 s and 5495.0±1316.0 s, respectively; p<0.001) than the CPVI+RL and CPVI+PostBox groups. (2) During 15.6±5.0 months of follow-up, the recurrence rates 3 months after RFCA were 11.5% in CPVI, 21.2% in CPVI+RL and 19.2% in CPVI+PostBox (p=0.440). (3) The achievement rate of CPVI was 100.0%, and bidirectional block rate was 80.8% in CPVI+RL and 59.6% in CPVI+PostBox. The clinical recurrence rates with or without achieving bidirectional block were not significantly different from each other (p=0.386). Conclusion In patients with PAF, linear ablation in addition to CPVI did not improve clinical outcome, regardless of bidirectional block achievement, while it prolonged the total procedure and ablation time.

Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation.

The structural and functional characteristics of left atrial appendage (LAA) in patients with atrial fibrillation (AF) with previous stroke remain incompletely elucidated. This study investigated whether a larger LAA orifice is related to decreased LAA flow velocity and stroke in nonvalvular AF. The dimension, morphology, and flow velocity of LAA were compared in patients with nonvalvular AF with (stroke group, n = 67, mean age 66 ± 9 years) and without ischemic stroke (no-stroke group, n = 151, mean age 56 ± 10 years). Compared with no-stroke group, the stroke group had larger LA dimension (4.7 ± 0.8 vs 4.2 ± 0.6 cm, p <0.001), larger LAA orifice area (4.5 ± 1.5 vs 3.0 ± 1.1 cm(2), p <0.001), and slower LAA flow velocity (36 ± 19 vs 55 ± 20 cm/s, p <0.001). LAA flow velocity was negatively correlated with LAA orifice size (R = -0.48, p <0.001). After adjustment for multiple potential confounding factors including CHA2DS2-VASc score, persistent AF, and LA dimension, large LAA orifice area (odds ratio 6.16, 95% confidence interval 2.67 to 14.18, p <0.001) and slow LAA velocity (odds ratio 3.59, 95% confidence interval 1.42 to 9.08, p = 0.007) were found to be significant risk factors of stroke. In patients with LAA flow velocity <37.0 cm/s, patients with large LAA orifice (>3.5 cm(2)) had greater incidence of stroke than those with LAA orifice of ≤3.5 cm(2) (75% vs 23%, p <0.001). In conclusion, LAA orifice enlargement was related to stroke risk in patients with nonvalvular AF even after adjustment for other risk factors, and it could be the cause of decreased flow velocity in LAA.

Prognostic value of multidetector coronary computed tomography angiography in relation to exercise electrocardiogram in patients with suspected coronary artery disease

OBJECTIVES This study was designed to determine the prognostic value of multidetector coronary computed tomography angiography (CTA) in relation to exercise electrocardiography (XECG) findings. BACKGROUND The prognostic usefulness of coronary CTA findings of coronary artery disease in relation to XECG findings has not been explored systematically. METHODS Patients with suspected coronary artery disease who had undergone both coronary CTA and XECG (<90 days between tests) from 2003 through 2009 were enrolled retrospectively. Coronary CTA results were classified according to the severity of maximal stenosis (normal, mild: <40% of luminal stenosis, moderate: 40% to 69%, severe: ≥70%), XECG results were categorized as positive and negative, and Duke XECG score was calculated. Clinical follow-up data were collected for major adverse cardiac events (MACE): cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and revascularization after 90 days from index coronary CTA. C-statistics were calculated to compare discriminatory values of each test. RESULTS Among the 2,977 (58 ± 10 years) study patients, 12% demonstrated positive XECG results. By coronary CTA, patients were categorized as normal (56%) or having mild (26%), moderate (13%), or severe (5%) disease. During a median follow-up of 3.3 years (interquartile range: 2.3 to 4.6), 97 MACE were observed and the 5-year cumulative event rate was 3.6% (95% confidence interval: 3.0 to 4.3). Although both XECG (C-statistic: 0.790) and coronary CTA (C-statistic: 0.908) improved risk stratification beyond clinical risk factors (C-statistic: 0.746, p < 0.05 for all), XECG in addition to coronary CTA (C-statistic: 0.907) did not provide better discrimination than coronary CTA alone (p = 0.389). In subgroup analyses, coronary CTA stratified risk of MACE in groups with both positive and negative XECG results (all p < 0.001 for trend). However, positive XECG results predicted risk of MACE on coronary CTA only in the moderate stenosis group (hazard ratio: 2.58, 95% confidence interval: 1.29 to 5.19, p = 0.008) and severe stenosis group (hazard ratio: 2.28, 95% confidence interval: 1.19 to 4.38, p = 0.013). CONCLUSIONS In patients with suspected coronary artery disease, coronary CTA discriminates future risk of MACE in patients independent of XECG results. Compared with coronary CTA, XECG has an additive prognostic value only in patients with moderate to severe stenosis on coronary CTA.

Long duration of radiofrequency energy delivery is an independent predictor of clinical recurrence after catheter ablation of atrial fibrillation: Over 500 cases experience

BACKGROUND Although radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) is an effective rhythm control strategy, there is a substantial amount of recurrence. We explored the predictors of AF recurrence after RFCA with consistent ablation strategy. METHODS AND RESULTS This study included 575 patients (77% male, 56 ± 11 years old) with AF (65.7% paroxysmal AF [PAF], 34.3% persistent AF [PeAF]) who underwent RFCA. We evaluated the clinical, serological, and electrophysiological parameters thereof. RESULTS 1. During 15 ± 7 months of follow-up, patients who experienced AF recurrence (21.8%) were older (58 ± 10 vs. 55 ± 11 years old, p=0.019) and more likely to have PeAF (50.4% vs. 29.4%, p<0.001) and greater LA volume (137.3 ± 49.1 vs. 116.6 ± 37.9 mL, p<0.001). 2. In patients with clinical recurrence after RFCA, both ablation time (110.1 ± 43.8 vs. 92.3 ± 30.1 min, p<0.001) and procedure time (222.7 ± 79.6 vs. 205.8 ± 58.8 min, p<0.001) were prolonged, and the early recurrence rate within 3 months of the procedure was higher (63.0% vs. 26.4%, p<0.001) than those without clinical recurrence. 3. In logistic regression analysis, LA volume (OR 1.008, CI 1.001-1.014), ablation time (per quartile, OR 1.380, CI 1.031-1.847), and early recurrence (OR 3.858, CI 2.420-6.150) were independent risk factors for recurrence of AF after RFCA. CONCLUSION In this single center consistent study of over 500 cases of AF ablation, patients with AF recurrence had a larger atrium, longer ablation time, and a higher chance of early recurrence than those remained in sinus rhythm. Inadvertent, long duration of ablation was an independent predictor of worse clinical outcomes after catheter ablation of AF.

New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery bypass graft

BACKGROUND New-onset postoperative atrial fibrillation (POAF) is associated with poor short- and long-term outcomes after isolated coronary artery bypass graft (CABG). This study evaluated whether new-onset POAF is independently associated with long-term (>1 year) atrial fibrillation (AF) and mortality. METHODS Among 1,171 consecutive patients who had undergone CABG, AF and mortality were compared between patients with POAF (POAF group, n = 244) and those without POAF (no-POAF group, n = 927) after propensity score matching. RESULTS During the follow-up period of 41 ± 23 months (range 0-87 months), the POAF group had a higher incidence of total (20/927 [2.2%] vs 46/244 [18.9%], P < .001) and long-term AF recurrence (13/927 [1.4%] vs 25/244 [10.2%], P < .001). Even after propensity score matching, the POAF group still showed a higher incidence of total (7/244 [2.9%] vs 46/224 [18.9%], P < .001) and long-term AF recurrence (4/244 [1.6%] vs 25/224 [10.2%], P < .001). In addition, the POAF group had a lower cumulative survival free of long-term AF than the no-POAF group (P < .001). In competing risk regression, POAF was an independent predictor of long-term newly developed AF (hazard ratio 4.99, 95% CI 1.68-14.84, P = .004). Cumulative survival free of death was worse in patients with POAF (P = .01). CONCLUSIONS New-onset POAF was shown to be a predictor of long-term newly developed AF in CABG patients. The results of this study suggest that patients who develop POAF should undergo strict surveillance and routine screening for AF during follow-up after surgery.

Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance

Statins are potent inhibitors of hydroxyl‐3‐methylglutaryl co‐enzyme A (HMG‐CoA) reductase, and have emerged as potential anti‐cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)‐10, transforming growth factor (TGF)‐β and indoleamine‐2,3‐dioxygenase (IDO) by tumours, which induce a regulatory T cell (Treg) response. In this study, we investigated the effect of simvastatin on the production of IL‐10, TGF‐β and IDO production and the proliferation of Tregs using several cancer cell lines, and Lewis lung cancer (3LL) cells‐inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI‐H292). The production of the immune regulatory markers IL‐10, TGF‐β in 3LL and NCI‐H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin‐treated mice groups. Therefore, while simvastatin had an anti‐proliferative effect, it also exhibited immune tolerance‐promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.