Comparison of Arrhythmia Detection by 24-Hour Holter and 14-Day Continuous Electrocardiography Patch Monitoring.

BACKGROUND: Although 24-hour Holter monitoring is routinely used for patients with suspected paroxysmal arrhythmia, its sensitivity in detecting such arrhythmias is insufficient. METHODS: We compared a 14-day electrocardiography (ECG) monitor patch - a single-use, noninvasive, waterproof, continuous monitoring patch - with a 24-hour Holter monitor in 32 consecutive patients with suspected arrhythmia. RESULTS: The 14-day ECG patch was well tolerated, and its rates of detection of relevant arrhythmias on days 1, 3, 7, and 14 were 13%, 28%, 47%, and 66%, respectively. The detection rate of paroxysmal arrhythmias was significantly higher for the 14-day ECG patch than for the 24-hour Holter monitor (66% vs. 9%, p < 0.001). Among the 32 patients, 202 atrial fibrillation or atrial flutter episodes were detected in 6 patients (22%) with the 14-day ECG patch; however, only 1 atrial fibrillation episode was detected in a patient (3%, p < 0.05) with the 24-hour Holter monitor. Other clinically relevant arrhythmias recorded on the 14-day ECG patch included 21 (65.5%) episodes of supraventricular tachycardia, 2 (6.3%) long pause, and 2 (6.3%) ventricular arrhythmias. The mean dermal response score immediately after removal of the 14-day ECG patch from the patients was 0.64, which indicated minimal erythema. CONCLUSIONS: The 14-day ECG patch was well tolerated and allowed for longer continuous monitoring than the 24-hour Holter monitor, thus resulting in improved clinical accuracy in the detection of paroxysmal arrhythmias. Future studies should examine the long-term effectiveness of 14-day ECG patches for managing selected patients.

Antithrombotic Strategies in Patients with Atrial Fibrillation Following Percutaneous Coronary Intervention: A Systemic Review and Network Meta-Analysis of Randomized Controlled Trials.

Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53; 95% credible interval [CrI], 0.35-0.78; I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR: 0.20, 95% CrI: 0.05-0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.

Hyperbaric oxygen activates visfatin expression and angiogenesis via angiotensin II and JNK pathway in hypoxic human coronary artery endothelial cells.

Visfatin is an adipocytokine with important roles in endothelial angiogenesis. Hyperbaric oxygen (HBO) has been widely used to treat various medical illness with enhanced angiogenesis. The molecular effects of HBO on visfatin under hypoxia are poorly understood. This study aimed to investigate the effect of HBO on visfatin in hypoxic human coronary arterial endothelial cells (HCAECs). HCAECs under chemical hypoxia (antimycin A, 0.01 mmol/L) were exposed to HBO (2.5 atmosphere absolute; ATA) for 2-4 hours. Western blot, real-time polymerase chain reaction, electrophoretic mobility shift assay, luciferase promoter activity, migration and tube formation assay, and in vitro glucose uptake were measured. Visfatin protein expression increased in hypoxic HCAECs with earlier angiotensin II (AngII) secretion and c-Jun N-terminal kinase (JNK) phosphorylation, which could be effectively suppressed by the JNK inhibitor (SP600125), AngII antibody or AngII receptor blocker (losartan). In hypoxic HCAECs, HBO further induced earlier expression of visfatin and AngII. Hypoxia significantly increased DNA-protein binding activity of hypoxia-inducible factor-1α (HIF-1α) and visfatin. Hypoxia, hypoxia with HBO and exogenous addition of AngII also increased promoter transcription to visfatin; SP600125 and losartan blocked this activity. In HCAECs, glucose uptake, migration and tube formation were increased in the presence of hypoxia with HBO, but were inhibited by visfatin small interfering RNA, SP600125 and losartan. In conclusion, HBO activates visfatin expression and angiogenesis in hypoxic HCAECs, an effect mediated by AngII, mainly through the JNK pathway.

2018 Guidelines of the Taiwan Society of Cardiology, Taiwan Society of Emergency Medicine and Taiwan Society of Cardiovascular Interventions for the management of non ST-segment elevation acute coronary syndrome.

In Taiwan, the incidence of non-ST segment elevation acute coronary syndrome (NSTE-ACS) continues to increase in recent years. The purpose of this guideline is to help health care professionals in Taiwan to use adequate tests and treatments for management of NSTE-ACS. For rapid diagnosis, in addition to history and physical examination, 0/3 h rapid diagnosis protocol with high sensitivity cardiac troponin assay is recommended in this guideline. Dual antiplatelet and anticoagulation therapies are important parts in the initial treatment. Risk stratification should be performed to identify high risk patients for early coronary angiography. Through evaluation of the coronary anatomy and other clinical factors, the decision for coronary revascularization, either by percutaneous coronary intervention or coronary artery bypass grafting, should be decided by the heart team. The duration of dual antiplatelet therapy should be given for at least 12 months after discharge. Other secondary preventive medications are also recommended for long term use.

2018 Expert Consensus on the Management of Adverse Effects of Antiplatelet Therapy for Acute Coronary Syndrome in Taiwan.

Antiplatelet therapy is a key component in the treatment of acute coronary syndrome (ACS). The management of ACS has evolved considerably over recent years with the development of new and more potent antiplatelet agents. Clinical trials on ACS have demonstrated that potent antiplatelet agents can more effectively reduce cardiovascular events. However, there is a tipping point between safety and efficacy, beyond which the risk of bleeding and other adverse effects can outweigh the benefits of antiplatelet therapy. Striking a balance between safety and efficacy remains a major challenge. A consensus meeting of an expert panel composed of Taiwanese experts was held to provide recommendations for the management of adverse effects in patients with ACS receiving antiplatelet therapy. The common adverse effects of antiplatelet therapy include upper gastrointestinal bleeding, ecchymosis, hematuria, epistaxis and ticagrelor-related dyspnea. In this study, a literature review of these adverse events was performed and recommendations for the management were made.

Can osteoporosis increase the incidence of heart failure in adults?

BACKGROUND: Recent studies have suggested shared comorbidities between heart failure and osteoporosis. In addition, patients with osteoporosis are associated with increased risks of developing cardiovascular disease. METHODS: A retrospective cohort analysis was conducted to determine the association between osteoporosis and heart failure. Data was from the Longitudinal Health Insurance Database 2000 (LHID 2000), Taiwan. Patients with newly diagnosed osteoporosis were identified, and osteoporosis-free controls were randomly selected from the general population and frequency matched according to age, sex, and index year using the LHID 2000. We analyzed the risks of heart failure using Cox proportional-hazards regression models. RESULTS: During the mean follow-up of 7.1 ± 3.5 years, the cumulative incidence of heart failure was 2.24% higher in the osteoporosis cohort than in the comparison cohort (p < .001). The overall incidence of heart failure was 10.3 versus 7.62 per 1000 person-years in osteoporosis patients and controls, respectively, with an adjusted HR of 1.13 (95% CI = 1.06-1.21). CONCLUSION: We observed a higher incidence of developing heart failure in Taiwanese adults with osteoporosis, especially in those with chronic comorbidities. There might be linking pathophysiology and mechanisms from osteoporosis to heart failure.

Correction: Mechanical Stretch Inhibits MicroRNA499 via p53 to Regulate Calcineurin-A Expression in Rat Cardiomyocytes.

[This corrects the article DOI: 10.1371/journal.pone.0148683.].

Diabetes and Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome - Data from Taiwan's Acute Coronary Syndrome Full Spectrum Data Registry.

BACKGROUND: Diabetes mellitus (DM) is a major public health problem in Taiwan and is associated with poor outcomes in patients with coronary artery disease. However, the role of DM in outcomes for patients with acute coronary syndrome (ACS) has not been clearly defined in Taiwan. This study utilized the Taiwan ACS registry, and characterized the clinical features, risk factors, hospital therapies, hospital outcomes, and events within one year post-discharge to identify the effect of DM on adverse cardiovascular outcomes in ACS patients. METHODS: A total of 3183 patients were enrolled from a Taiwan nationwide registry, from October 2008 to January 2010. We compared these ACS patients with and without DM in terms of baseline demographics, clinical presentation, risk factors, medical treatment, intervention, and outcomes in the following 12 months. The primary endpoint was a composite outcome that included death, re-myocardial infarction and stroke within a 12-month period. The secondary endpoint consisted of the combined results of death, re-myocardial infarction, stroke, re-vascularization, and re-hospitalization over 12 months. RESULTS: Overall, 2766 (86.8%) ACS patients were analyzed in this study. Of that total, 1000 (36%) of them were diabetes patients. Over the course of one year of follow-up, the DM patients had higher probabilities of all-cause death (10.1% vs. 6.06%, p < 0.05), for both primary outcomes (15.7% vs. 10.93%, p < 0.05) and secondary outcomes (51.6% vs. 42.41%, p < 0.05). Logistic regression analysis showed that patients in the DM group were at a higher risk of all-cause death and the primary outcomes, after adjusting the confounding variables (odds ratio was 1.9 and 1.6 respectively, p < 0.01). For those patients suffering from primary outcomes, the mean survival time was 34.7 ± 10.4 days in the Non-DM group and 33.3 ± 11.8 days in the DM group (p < 0.05). The log rank test showed the two survival curves were significantly distinctive (p < 0.05). Cox regression analysis showed the odds ratio for all-cause death and the primary outcomes were 1.66 and 1.5, respectively (p < 0.05). CONCLUSIONS: Compared to patients without DM, ACS patients with diabetes had significantly worse outcomes in terms of all-cause death and the combined results for death, re-infarction and stroke.

The Relation between the Timing of Percutaneous Coronary Intervention and Outcomes in Patients with Acute Coronary Syndrome with Routine Invasive Strategy - Data from Taiwan Acute Coronary Syndrome Full Spectrum Data Registry.

BACKGROUND: Several large trials have indicated that a routine invasive strategy was favored for high-risk patients with non-ST-elevation acute coronary syndromes. However, the optimal timing for this intervention is unclear. METHODS: We included patients with unstable angina or non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI) from the Taiwan acute coronary syndrome registry. Thrombolysis in Myocardial Infarction (TIMI) score was used to stratify our patients into three groups: low (TIMI 0-2), intermediate (TIMI 3-4) and high risk (TIMI 5-7).We analyzed outcomes according to the timing of PCI. RESULTS: Overall, 984 patients were included in this study. For primary outcomes including cardiac death and recurrent myocardial infarction, early PCI within 24 hours did not show benefits over late PCI (24-72 or > 72 hours) (p > 0.05) in the low and intermediate risk groups. However, in the high risk group, patients who underwent PCI after 72 hours had significantly worse primary outcomes than those who underwent PCI within 24-72 hours. For secondary outcomes including non-cardiac death, unplanned revascularization, and major bleeding, the events rate was significantly higher for early or delayed PCI in low-risk patients when compared with patients who underwent PCI within 24-72 hours. CONCLUSIONS: In our study, for high-risk NSTE-ACS patients, PCI within 24-72 hours from symptom onset is demonstrably the optimum time for PCI. Delayed PCI over 72 hours is associated with the worst outcomes and should be avoided. For patients with low risks, routine early PCI < 24 hours after PCI is not beneficial. KEY WORDS: Acute coronary syndrome; Early invasive strategy.

Mechanical Stretch Inhibits MicroRNA499 via p53 to Regulate Calcineurin-A Expression in Rat Cardiomyocytes.

BACKGROUND: MicroRNAs play an important role in cardiac remodeling. MicroRNA 499 (miR499) is highly enriched in cardiomyocytes and targets the gene for Calcineurin A (CnA), which is associated with mitochondrial fission and apoptosis. The mechanism regulating miR499 in stretched cardiomyocytes and in volume overloaded heart is unclear. We sought to investigate the mechanism regulating miR499 and CnA in stretched cardiomyocytes and in volume overload-induced heart failure. METHODS & RESULTS: Rat cardiomyocytes grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of volume overload with aorta-caval shunt in adult rats was used to study miR499 expression. Mechanical stretch downregulated miR499 expression, and enhanced the expression of CnA protein and mRNA after 12 hours of stretch. Expression of CnA and calcineurin activity was suppressed with miR499 overexpression; whereas, expression of dephosphorylated dynamin-related protein 1 (Drp1) was suppressed with miR499 overexpression and CnA siRNA. Adding p53 siRNA reversed the downregulation of miR499 when stretched. A gel shift assay and promoter-activity assay demonstrated that stretch increased p53 DNA binding activity but decreased miR499 promoter activity. When the miR499 promoter p53-binding site was mutated, the inhibition of miR499 promoter activity with stretch was reversed. The in vivo aorta-caval shunt also showed downregulated myocardial miR499 and overexpression of miR499 suppressed CnA and cellular apoptosis. CONCLUSION: The miR499-controlled apoptotic pathway involving CnA and Drp1 in stretched cardiomyocytes may be regulated by p53 through the transcriptional regulation of miR499.

Prognostic impact of renal dysfunction in patients with acute coronary syndrome-role beyond the CHA2 DS2 -VASc score: Data from Taiwan acute coronary syndrome full spectrum registry.

AIM: CHA2 DS2 -VASc score has been proven to have great prognostic value in patients with acute coronary syndrome (ACS). We aimed to determine whether the addition of renal dysfunction in the CHA2 DS2 -VASc score would improve the prognostic impact of the scoring system to predict prognosis among ACS patients. METHODS: A total of 3031 ACS patients were prospectively enrolled at 39 hospitals and followed for 1 year. The patients were divided into three groups based on estimated glomerular filtration rate (eGFR) (group 1, eGFR>90; group 2, eGFR between 60 and 90; and group 3, eGFR<60 mL/min per 1.73 m(2) ). The occurrence of subsequent myocardial infarction (MI), stroke, or death was recorded. RESULTS: As renal function progressively decreased from group 1 to 3, the patients were, respectively older and had higher incidence of comorbidity, worse Killip classification, and less evidence-based medical therapies. The rate of subsequent MI, stroke or death increased from 3.4% in group 1 to 7.4% in group 2 and 17.2% in group 3 (P < 0.001). Renal dysfunction (eGFR<60 mL/min per 1.73 m(2) ) and CHA2 DS2 -VASc scores were both significant predictors of adverse events in multivariable regression analyses. Renal dysfunction can further stratify patients with CHA2 DS2 -VASc score of 0 or 1 into 3 groups with different adverse event rates (group 1, 3.0%; group 2, 4.1%; and group 3, 9.2%, P < 0.001). A new scoring system (R-CHA2 DS2 -VASc score) derived by assigning one more point for eGFR ≤ 60 mL/min per 1.73 m(2) to the CHA2 DS2 -VASc score could improve its predictive accuracy (area under the receiver operating curve, 0.70 vs. 0.66, P < 0.001). CONCLUSIONS: Renal dysfunction is a significant risk factor of future adverse events in ACS patients and may improve the prognostic impact of the CHA2 DS2 -VASc score.

Renal dysfunction and the risk of postoperative atrial fibrillation after cardiac surgery: role beyond the CHA2DS2-VASc score.

AIMS: To investigate whether renal dysfunction is a useful predictor of postoperative atrial fibrillation (POAF) after cardiac surgery. We also aimed to determine whether the addition of renal dysfunction into the scoring system could improve diagnostic accuracy of the CHA2DS2-VASc score to predict POAF. METHODS AND RESULTS: The study prospectively enrolled 350 consecutive patients who underwent cardiac surgery. Echocardiography was performed before cardiac surgery. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL min(-1) 1.73 m(-2). All patients were monitored with continuous electrocardiographic telemetry for the occurrence of POAF until the day of hospital dismissal. Postoperative atrial fibrillation occurred in 103 of 350 patients (29%). Patients with POAF was associated with longer intensive care unit stay compared with those without POAF (3.7 ± 2.2 vs. 3.1 ± 1.4 days, P = 0.002). Both the CHA2DS2-VASc score and renal dysfunction were independent predictors of POAF in multivariate analysis. Renal dysfunction can further stratify patients with a CHA2DS2-VASc score of 0 or 1 into two groups with different POAF rates (3.1% vs. 68.8%, P < 0.001). A new scoring system (R-CHA2DS2-VASc score) derived by assigning an additional point representing renal dysfunction to the CHA2DS2-VASc score could improve its predictive accuracy. The area under the receiver operating characteristic curve increased from 0.68 to 0.71 (P < 0.001). Furthermore, the rate of left ventricular diastolic dysfunction also increased with increasing renal dysfunction. CONCLUSION: Renal dysfunction, associated with left ventricular diastolic dysfunction, was a significant risk factor for POAF after cardiac surgery and may improve the diagnostic accuracy of the CHA2DS2-VASc score.

Molecular regulation of the expression of leptin by hypoxia in human coronary artery smooth muscle cells.

BACKGROUND: Leptin, produced mainly by white adipose tissue, is a hormone that promotes vascular smooth muscle cell (VSMC) migration and proliferation, a process involved in the pathophysiology of atherosclerosis. Leptin expression in human coronary artery smooth cell (HCASMC) is induced by hypoxia. However, our understanding of the process of atherosclerosis in HCASMC is only emerging. Since the mechanisms by which hypoxia regulates leptin in HCASMC are as yet unknown, this study aims to investigate the mechanics of molecular regulation of leptin expression in HCASMC under hypoxia. We subjected cultured HCASMCs to hypoxia for varying periods of time. Through use of different signal pathway inhibitors, we were able to sort out and identify the pathway through which hypoxia-induced leptin expression occurs. RESULTS: Leptin mRNA and protein levels increased after 2.5% hypoxia for 2-to-4 hours, with earlier expression of angiotensin II (AngII) and reactive oxygen species (ROS). The addition before hypoxia of the c-Jun N-terminal kinase (JNK) pathway inhibitor (SP600125), JNK small interfering RNA (siRNA), AngII receptor blockers (ARBs; losartan), or N-acetyl-L-cysteine (NAC, an ROS scavenger), had the effect of inhibiting JNK phosphorylation and leptin expression. Gel shift assay and luciferase promoter study showed that leptin/activator protein 1 (AP-1) binding and transcriptional activity to the leptin promoter increased after hypoxia, and SP600125, JNK siRNA, losartan, and NAC abolished the binding and transcriptional activity induced by hypoxia. The use of SP600125, JNK siRNA, losartan, and NAC effectively inhibited the binding and transcriptional activity induced by hypoxia. Migration and proliferation, ROS generation, and the presence of leptin in the nuclei of HCASMCs also increased under hypoxia. CONCLUSION: Hypoxia in HCASMCs increases leptin expression through the induction of AngII, ROS, and the JNK pathway to enhance atherosclerosis in HCASMCs.

Use of CHADS2 and CHA2DS2-VASc scores to predict subsequent myocardial infarction, stroke, and death in patients with acute coronary syndrome: data from Taiwan acute coronary syndrome full spectrum registry.

BACKGROUND: Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS2 and CHA2DS2-VASc scores were useful tools to assess the risk for adverse events among ACS patients. METHODS: This observational prospective study was conducted at 39 hospitals. Totally 3,183 patients with ACS were enrolled, and CHADS2 and CHA2DS2-VASc scores were calculated. The primary endpoint was occurrence of adverse event, including subsequent myocardial infarction, stroke, or death, within 1 year of discharge. RESULTS: CHADS2 and CHA2DS2-VASc scores were significant predictors of adverse events in separate multivariate regression analyses. A Kaplan-Meier analysis of CHADS2 and CHA2DS2-VASc scores of ≥2 showed a higher rate of adverse events as compared with scores of <2 (P<0.001;log-rank test). CHA2DS2-VASc score was better than CHADS2 score in predicting subsequent adverse events; the area under the receiver operating characteristic curve increased from 0.66 to 0.70 (p<0.001). Patients with CHADS2 scores of 0 or 1 were further classified according to CHA2DS2-VASc score, using a cutoff value of 2. The rate of adverse events significantly differed between those with a score of <2 and those with a score of ≥2 (4.1% vs.10.7%, P<0.001). CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores were useful predictors of subsequent adverse events in ACS patients.

Admission hyperglycemia predicts poorer short- and long-term outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction.

AIMS/INTRODUCTION: Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: The 959 consecutive STEMI patients undergoing primary PCI were divided into five groups based on admission glucose levels of <100, 100-139, 140-189, 190-249 and ≥250 mg/dL. Their short- and long-term outcomes were compared. RESULTS: Higher admission glucose levels were associated with significantly higher in-hospital morbidity and mortality, the overall mortality rate at follow up, and the incidence of reinfarction or heart failure requiring admission or leading to mortality at follow up. The odds ratios (95% confidence interval) for in-hospital morbidity, in-hospital mortality, mortality at follow up and re-infarction or heart failure or mortality at follow up of patients with admission glucose levels ≥190 mg/dL, compared with those with admission glucose levels <190 mg/dL, were 2.12 (1.3-3.4, P = 0.001), 2.74 (1.4-5.5, P = 0.004), 2.52 (1.2-5.1, P = 0.01) and 1.70 (1.03-2.8, P = 0.04), respectively. Previously non-diabetic patients with admission glucose levels ≥250 mg/dL had significantly higher in-hospital morbidity or mortality (44 vs 70%, P = 0.03). Known diabetic patients had higher rates of reinfarction, heart failure or mortality at follow up in the 100-139 mg/dL (8 vs 27%, P = 0.04) and 140-189 mg/dL (11 vs 26%, P = 0.02) groups. CONCLUSIONS: Admission hyperglycemia, especially at glucose levels ≥190 mg/dL, is a predictor of poor prognosis in STEMI patients undergoing primary PCI.

Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes.

Cardiomyocyte hypoxia causes cardiac hypertrophy through cardiac-restricted gene expression. Urotensin II (UII) cooperates with activating protein 1 (AP1) to regulate cardiomyocyte growth in response to myocardial injuries. Angiotensin II (AngII) stimulates UII expression, reactive oxygen species (ROS) production, and cardiac hypertrophy. This study aimed to evaluate the expression of UII, ROS, and AngII as well as their genetic transcription after hypoxia treatment in neonatal cardiomyocytes. Cultured neonatal rat cardiomyocytes were subjected to hypoxia for different time periods. UII (Uts2) protein levels increased after 2.5% hypoxia for 4 h with earlier expression of AngII and ROS. Both hypoxia and exogenously added AngII or Dp44mT under normoxia stimulated UII expression, whereas AngII receptor blockers, JNK inhibitors (SP600125), JNK siRNA, or N-acetyl-l-cysteine (NAC) suppressed UII expression. The gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between UII and AP1. The luciferase assay confirmed an increase in transcription activity of AP1 to the UII promoter under hypoxia. After hypoxia, an increase in (3)H-proline incorporation in the cardiomyocytes and expression of myosin heavy chain protein, indicative of cardiomyocyte hypertrophy, were observed. In addition, hypoxia increased collagen I expression, which was inhibited by SP600125, NAC, and UII siRNA. In summary, hypoxia in cardiomyocytes increases UII and collagen I expression through the induction of AngII, ROS, and the JNK pathway causing cardiomyocyte hypertrophy and fibrosis.

Gender and Age Differences in Short- and Long-Term Outcomes Following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Studies have reported that women with ST elevation myocardial infarction (STEMI) have worse short- and long-term outcomes than men. It has not yet been confirmed whether these differences reflect differences in age between men and women. METHODS: We retrospectively enrolled 1035 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Baseline clinical characteristics, coronary anatomy, and outcome were compared between young (< 65 years old) and older patients (≥ 65 years old) of both sexes. RESULTS: Younger women presented with a lower incidence of typical angina (83% vs. 93%, p = 0.03), single-vessel disease (21% vs. 35%, p = 0.03), and total occlusion of infarct-related artery (65% vs. 83%, p = 0.001) than younger men, with no gender difference noted in the older group. Younger women in the study had a higher incidence of reinfarction, heart failure requiring admission, or mortality (23% vs. 6%, p < 0.001) during follow-up, compared with younger men, with no gender difference in the older group. Using the Kaplan-Meier analysis, younger women had lower rates of event-free survival (p < 0.001 by log-rank test) than younger men, with no gender difference in the older group. In multivariate analysis, age could predict long-term outcome in men (Hazard ratio 4.43, 95% confidence interval: 2.89-6.78, p < 0.001) but not in women. CONCLUSIONS: In STEMI patients receiving primary PCI, sex-related long-term outcome differences were age-dependent, with younger women likely to have a worse long-term outcome when compared with younger men. KEY WORDS: Coronary heart disease; Gender; Myocardial infarction.

Angiotensin II and the ERK pathway mediate the induction of leptin by mechanical cyclic stretch in cultured rat neonatal cardiomyocytes.

Mechanical cyclic stretch of cardiomyocytes causes cardiac hypertrophy through cardiac-restricted gene expression. Leptin induces cardiomyocyte hypertrophy in response to myocardial stress. In the present study, we evaluated the expression of leptin under cyclic stretch and its role in regulating genetic transcription in cardiomyocytes. Cultured rat neonatal cardiomyocytes were subjected to cyclic stretch, and the expression levels of leptin, ROS (reactive oxygen species) and AngII (angiotensin II) were evaluated. Signal transduction inhibitors were used to identify the pathway of leptin expression. EMSAs were used to identify the binding of leptin/STAT3 (signal transducer and activator of transcription 3) and luciferase assays were used to identify the transcription of leptin in cardiomyocytes. The study also used an in vivo model of AV (aortocaval) shunt in rats to investigate leptin, ROS and AngII expression. Leptin and leptin receptor levels increased after cyclic stretch with the earlier expression of AngII and ROS. Leptin expression was suppressed by AngII receptor blockers, an ROS scavenger [NAC (N-acetylcysteine)], an ERK (extracellular-signal-regulated kinase) pathway inhibitor (PD98059) and ERK siRNA. Binding of leptin/STAT3 was identified by EMSAs, and luciferase assays confirmed the transcription of leptin in neonatal cardiomyocytes after cyclic stretch. Increased MHC (myosin heavy chain) expression and [3H]-proline incorporation in cardiomyocytes was detected after cyclic stretch, which were inhibited by leptin siRNA and NAC. The in vivo model of AV shunt also demonstrated increased levels of plasma and myocardial leptin, ROS and AngII expression after cyclic stretch. Mechanical cyclic stretch in cardiomyocytes increased leptin expression mediated by the induction of AngII, ROS and the ERK pathway to cause cardiomyocyte hypertrophy. Myocardial hypertrophy can be identified by increased transcriptional activity and an enhanced hypertrophic phenotype of cardiomyocytes.

Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells.

BACKGROUND: The expression of myocardin, a cardiac-restricted gene, increases during environmental stress. How mechanical stretch affects the regulation of myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We identify the mechanisms and pathways through which mechanical stretch induces myocardin expression in VSMCs. RESULTS: Rat VSMCs grown on a flexible membrane base were stretched to 20% of maximum elongation, at 60 cycles per min. An in vivo model of aorta-caval shunt in adult rats was also used to investigate myocardin expression. Cyclic stretch significantly increased myocardin and angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before stretch inhibited the expression of myocardin protein. Gel shift assay showed that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA and ARB abolished the binding activity induced by stretch. Stretch increased while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity. Protein synthesis by measuring [3H]proline incorporation into the cells increased after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo model of aorta-caval shunt also demonstrated increased myocardin protein expression in the aorta. Confocal microscopy showed increased VSMC size 24 h after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for 3 days. CONCLUSIONS: Cyclic stretch enhanced myocardin expression mediated by AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that myocardin plays a role in stretch-induced VSMC hypertrophy.

Diagnostic Performance of 64- versus 256-Slice Computed Tomography Coronary Angiography Compared with Conventional Coronary Angiography in Patients with Suspected Coronary Artery Disease.

PUPOSE: The newer 256-slice computed tomography coronary angiography (CTCA) has the capability of improving diagnostic performance in the detection of obstructive coronary artery disease (CAD) compared to 64-slice CTCA. The aim of this study was to compare the diagnostic performance of 64- versus 256-slice CTCA in two similar populations. METHODS: Our study included 120 consecutive patients who were referred for CTCA and subsequently underwent conventional coronary angiography (CCA). Sixty patients were studied by 64-slice CTCA, with the other 60 by 256-slice CTCA. We compared the technical characteristics and diagnostic performance of 64- and 256-slice CTCA for the detection of ≥ 50% stenosis of the coronary arteries on CCA. RESULTS: The 256-slice CTCA had a shorter scanning time (4.4 ± 0.6 sec vs. 5.0 ± 0.7 sec, p < 0.001) compared to 64-slice CTCA. The diagnostic accuracy rates of 256-slice CTCA based on patient analysis (97% vs. 83%, p < 0.05), vessel analysis (95% vs. 85%, p < 0.05), and segment analysis (94% vs. 88%, p < 0.05) were significantly superior to those of 64-slice CTCA. The diagnostic accuracy rates of 64- and 256-slice CTCA were affected by the presence of stent (65% vs. 75%, respectively, p > 0.05) and severe calcifications (75% vs. 82%, respectively, p > 0.05). CONCLUSIONS: In two similar populations, 256-slice CTCA displayed superior diagnostic performance than 64-slice CTCA. However, the performance of 256-slide CTCA is affected in those segments that are severely calcified and/or stented. KEY WORDS: Computed tomography coronary angiography (CTCA); Conventional coronary angiography; Diagnostic performance; 64-slice helical CTCA; 256-slice helical CTCA.