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Activation of soluble epoxide hydrolase (sEH) is associated with endothelial dysfunction in hypertension, though the underlying mechanisms are inadequately understood and the role of endoplasmic reticulum (ER) stress is yet to be studied in detail. Tetramethylpyrazine (TMP), a major bioactive ingredient of Chinese herb Chuanxiong, is well-known for its cardiovascular benefits. Nevertheless, whether TMP may protect vascular endothelium from ER stress and whether regulation of sEH is involved remain unknown. This study aimed at investigating the role of ER stress in angiotensin-II (Ang-II)-induced sEH dysregulation and elucidating the significance of ER stress regulation in the vasoprotective effect of TMP. Porcine primary coronary artery endothelial cells (PCECs) were used for western blot, ELISA, and reverse-transcription PCR analysis. Porcine coronary arteries were assessed in a myograph for endothelial dilator function. Ang-II induced expression of ER stress molecules in PCECs meanwhile enhanced sEH expression and decreased 11,12-EET. Exposure of PCECs to the chemical ER stress inducer tunicamycin also increased sEH expression. Inhibition of ER stress suppressed sEH upregulation, resulting in an increase of 11,12-EET. The impairment of endothelium-dependent vasorelaxation induced by Ang-II or tunicamycin was ameliorated by inhibitors of ER stress or sEH. TMP showed comparable inhibitory effect to ER stress inhibitors on the expression of ER stress molecules, the dysregulation of sEH/EET, and the impairment of endothelial dilator function. We demonstrated that ER stress mediates Ang-II-induced sEH upregulation in coronary endothelium. TMP has potent anti-ER stress capacity through which TMP normalizes sEH expression and confers protective effect against Ang-II on endothelial function of coronary arteries. [ABSTRACT FROM AUTHOR]

Aims: We report the results of long-term follow-up of the Pacing to Avoid Cardiac Enlargement (PACE) trial, a prospective, double-blinded, randomized, multicentre study that confirmed the superiority of biventricular (BiV) pacing compared with right ventricular apical (RVA) pacing in prevention of LV adverse remodelling and deterioration of systolic function at 1 and 2 years. Methods and Results: Patients with bradycardia and preserved LVEF were randomized to receive RVA (n = 88) or BiV pacing (n = 89). Co-primary endpoints were LV end-systolic volume (LVESV) and LVEF measured by echocardiography. There were 149 patients who had extended follow-up, with a mean duration of 4.8 ± 1.5 years (2.5-7.8 years). The primary endpoint analyses were performed in 146 patients (74 in the RVA group and 72 in the BiV group). In the RVA pacing group, the LVEF decreased while the LVESV increased progressively at follow-up, but remained unchanged in the BiV pacing group. The differences in LVEF between the RVA and BiV groups were -6.3, -9.2, and -10.7% at 1-year, 2-year, and long-term follow-up, respectively (all P < 0.001). The corresponding differences in LVESV were +7.4, +9.9, and +13.1 mL, respectively (all P < 0.001). The deleterious effects of RVA pacing consistently occurred in all the pre-defined subgroups. Furthermore, patients with RVA pacing had a significantly higher prevalence of heart failure hospitalization than the BiV group (23.9% vs. 14.6%, log-rank χ²  = 7.55, P  = 0.006). Conclusion: Left ventricular adverse remodelling and deterioration of systolic function continued at long-term follow-up in patients with RVA pacing; this deterioration was prevented by the use of BiV pacing. Also, heart failure hospitalization was more prevalent in the RVA pacing group. [ABSTRACT FROM AUTHOR]

Aims We report the results of long-term follow-up of the Pacing to Avoid Cardiac Enlargement ( PACE) trial, a prospective, double-blinded, randomized, multicentre study that confirmed the superiority of biventricular ( BiV) pacing compared with right ventricular apical ( RVA) pacing in prevention of LV adverse remodelling and deterioration of systolic function at 1 and 2 years. Methods and results Patients with bradycardia and preserved LVEF were randomized to receive RVA ( n = 88) or BiV pacing ( n = 89). Co-primary endpoints were LV end-systolic volume ( LVESV) and LVEF measured by echocardiography. There were 149 patients who had extended follow-up, with a mean duration of 4.8 ± 1.5 years (2.5-7.8 years). The primary endpoint analyses were performed in 146 patients (74 in the RVA group and 72 in the BiV group). In the RVA pacing group, the LVEF decreased while the LVESV increased progressively at follow-up, but remained unchanged in the BiV pacing group. The differences in LVEF between the RVA and BiV groups were -6.3, -9.2, and -10.7% at 1-year, 2-year, and long-term follow-up, respectively (all P < 0.001). The corresponding differences in LVESV were +7.4, +9.9, and +13.1 mL, respectively (all P < 0.001). The deleterious effects of RVA pacing consistently occurred in all the pre-defined subgroups. Furthermore, patients with RVA pacing had a significantly higher prevalence of heart failure hospitalization than the BiV group (23.9% vs. 14.6%, log-rank χ2 = 7.55, P = 0.006). Conclusion Left ventricular adverse remodelling and deterioration of systolic function continued at long-term follow-up in patients with RVA pacing; this deterioration was prevented by the use of BiV pacing. Also, heart failure hospitalization was more prevalent in the RVA pacing group. Trial registration CUHK_CCT00037. [ABSTRACT FROM AUTHOR]

Abstract: Background: Current clinical guidelines recommend ultrafiltration (UF) for patients with acute decompensated heart failure (ADHF) who are unresponsive or resistant to diuretics. We systematically reviewed the latest randomized evidence on the efficacy and safety of UF in ADHF. Methods: MEDLINE, EMBASE and the Cochrane database were searched in January 2013 for eligible randomized controlled trials (RCTs) evaluating UF in patients with ADHF. A Mantel–Haenszel random-effects model was used to calculate mean differences (MDs) and odds ratios (ORs) for continuous and dichotomous data, respectively, with 95% confidence intervals (CIs). Results: Data of 12 studies (n=659) were meta-analyzed; follow-up duration ranged from 36h to 12months. Compared to control, treatment of UF was associated with significant fluid removal (MD 1.28, 95% CI 0.43 to 2.12, P=0.003) and weight loss (MD 1.23, 95% CI 0.03 to 2.44, P=0.04), with no significant effects on all-cause mortality (OR 1.08, 95% CI 0.63 to 1.86, P=0.77) or all-cause rehospitalization (OR 0.89, 95% CI 0.39 to 2.00, P=0.77). No significant differences were observed in the analyses of change in serum creatinine or unscheduled medical care; analysis of adverse effects was inconclusive since only one study provided usable data. Conclusions: For patients with ADHF, UF is effective in reducing fluid retention and body weight, with no significant benefits in mortality or rehospitalization. The current limited randomized evidence highlights the need for further well-conducted randomized studies of adequate power to establish the role of UF in ADHF patients for whom conventional HF treatment is unsuccessful or contraindicated. [Copyright &y& Elsevier]

Stroke in patients with atrial fibrillation (AF) is often associated with substantial morbidity and mortality. Oral anticoagulation remains the first-line approach to stroke prevention in such individuals; however, for a considerable proportion of patients, traditional treatment using warfarin is limited by a number of factors, such as the inconvenience of frequent therapeutic monitoring and the risk of haemorrhage. The development of new oral anticoagulants with improved efficacy and safety profiles has provided viable options for oral anticoagulation therapy in patients with nonvalvular (nonrheumatic AF). Nonetheless, in patients who have an increased risk of major haemorrhage, a nonpharmacological approach to antithrombotic therapy remains an attractive alternative. The left atrial appendage (LAA) has been found to be the source of >90% of thrombi in patients with nonvalvular AF; thus, prevention of thrombus formation via transcatheter mechanical LAA occlusion is a novel therapeutic target for stroke prevention in this patient population. In this Review, we present the rationale for LAA occlusion in patients with AF, the available occlusion devices and their clinical evidence to date. We also discuss the roles of various imaging techniques in device implantation and the management strategy for associated procedural complications. [ABSTRACT FROM AUTHOR]

Abstract: Background: Drug-eluting balloons (DEB) are attractive new alternatives to drug-eluting stents (DES) for percutaneous coronary interventions. We aimed to systematically review the efficacy and safety of DEB in the treatment of coronary artery disease (CAD). Methods: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in December 2011 for eligible randomized controlled trials. Primary outcomes were target lesion revascularization (TLR), major adverse cardiac events (MACE) and mortality. Secondary outcomes were late lumen loss, minimal lumen diameter and binary restenosis. Results: Five studies involving 349 patients were included. Compared to controls, DEB improved angiographic measures with no significant effect on clinical outcomes in the overall CAD population. There is clear superiority of DEB in patients with in-stent restenosis in TLR (OR 0.17, 95% CI 0.07 to 0.38, p<0.0001, I2 =0%), MACE (OR 0.22, 95% CI 0.10 to 0.51, p=0.0005, I2 =13%), late lumen loss (in-stent: MD −0.51, 95% CI −0.73 to −0.28, p<0.00001, I2 =60%; in-segment: MD −0.51, 95% CI −0.77 to −0.24, p=0.0002, I2 =72%;), minimal lumen diameter (in-stent: MD 0.49, 95% CI 0.05 to 0.93, p=0.03, I2 =85%; in-segment: MD 0.49, 95% CI 0.13 to 0.86, p=0.008, I2 =79%) and binary restenosis (in-stent: OR 0.15, 95% CI 0.05 to 0.47, p=0.001, I2 =37%; in-segment: OR 0.11, 95% CI 0.05 to 0.27, p<0.00001, I2 =17%). Conclusions: Our findings support the current recommendation of using DEB in in-stent restenosis. Large, well-conducted trials are essential in determining the application of DEB in other lesion types as well as exploring device-specific efficacy and safety profiles. [Copyright &y& Elsevier]

Abstract: Objective: We aimed to evaluate the effectiveness of transthoracic saline contrast echocardiography (TSCE) in detecting patent foramen ovale (PFO). Background: Transesophageal echocardiography (TEE) is semi-invasive and not ideal for PFO screening. Methods: 112 patients (48 males, 46±14years) with suspected PFO received intravenous agitated-saline contrast at rest and stress (strain and release phases of Valsalva maneuver and coughing). The presence of interatrial shunting was defined as >5 bubbles appearing in the left heart within 3 cardiac cycles. The stage of the maneuver at which interatrial shunting occurred was recorded. The TSCE findings were validated by TEE. Results: TEE identified PFO in 45% of patients. The sensitivities of TSCE in detecting PFO at rest, during strain and release of Valsalva maneuver, and coughing were 12.0%, 38.0%, 80.0% and 94.0% respectively (each p<0.05 when compared to previous stage). Specificities were similar and >95% for all stages. Moreover, the release phase of the maneuver improved the diagnostic accuracy [defined as (number of true positives+true negatives) divided by total in sample] with incremental value over the preceding strain phase (89.2 vs. 70.5%, p<0.001). Conclusions: Patent foramen ovale can be identified confidently with proper conduct of the Valsalva maneuver during the transthoracic saline contrast echocardiography. [Copyright &y& Elsevier]

Whether the relief of chronic right atrial (RA) volume load by device closure of an atrial septal defect (ASD) normalizes RA size is unknown. The present study evaluated the prevalence and determinants of incomplete RA reverse remodeling (RAR) after ASD closure in adults. Transthoracic echocardiography was performed in 44 consecutive patients with secundum ASD (age 43 ± 17 years, 10 men) without a history of atrial arrhythmia shortly before and at 3 months after device closure of ASD. The pulmonary/systemic flow ratio was derived using invasive oximetry. The RA size had significantly decreased at 3 months of follow-up (RA volume index [RAVI] 52 ± 29 to 27 ± 17 ml/m2, p <0.001). Incomplete RAR (defined as a RAVI of ≥21 ml/m2) was detected in 25 patients (57%) after closure. They were older, had a larger pulmonary/systemic flow ratio, a higher pulmonary arterial systolic pressure, more tricuspid regurgitation, and larger RA, left atrial, and right ventricular sizes before closure than those with a normalized right atrium. Before closure, RAVI was the only independent determinant for incomplete RAR (odds ratio 1.115, 95% confidence interval 1.019 to 1.220; p = 0.018). A cutoff value of RAVI of ≥40 ml/m2 has a sensitivity of 84% and specificity of 72% in the receiver operating characteristic curve. The preclosure RAVI correlated moderately with the shunt-duration index, calculated by multiplying the age to pulmonary/systemic flow ratio (r = 0.64, p <0.01). In conclusion, incomplete RAR occurred in >1/2 of the adult patients at 3 months after ASD device closure and was related to excessive preclosure RA dilation. [ABSTRACT FROM AUTHOR]

The assessment of systolic dyssynchrony by echocardiography is useful in predicting a favorable response to cardiac resynchronization therapy (CRT). Tissue Doppler velocity and tissue Doppler longitudinal strain have been suggested for this purpose. This study compared parameters of systolic dyssynchrony derived from these 2 imaging modalities for their predictive values of CRT response. Two hundred fifty-six patients from 3 different centers who received CRT were followed for 6 ± 3 months. Parameters of systolic dyssynchrony based on tissue Doppler velocity and strain imaging were assessed for the prediction of left ventricular (LV) reverse remodeling (reduction of LV end-systolic volume ≥15%). These included time to peak systolic velocity (or peak strain) of 12 LV segments to calculate the SD (Ts-SD or Tε-SD), maximal difference in delay (Ts-Diff or Tε-Diff), and opposite wall delay (Ts-OW or Tε-OW). The septal-to-lateral delay (Ts-Sep-Lat or Tε-Sep-Lat) was also measured. LV reverse remodeling, defined as improvement in end-systolic volume ≥15%, was observed in 141 patients (55%). All 4 tissue velocity parameters predicted LV reverse remodeling, and the areas under the receiver-operating characteristic curves were 0.86, 0.85, 0.84, and 0.79 for Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat, respectively (all p <0.001). The cut-off values derived from receiver-operating characteristic curve analysis were 33 ms for Ts-SD, 100 ms for Ts-Diff, 90 ms for Ts-OW, and 60 ms for Ts-Sep-Lat, and their sensitivities were 93%, 92%, 81%, and 70%, with specificities of 78%, 68%, 80%, and 76%, respectively. In contrast, none of the longitudinal strain parameters predicted LV reverse remodeling. The areas under the receiver-operating characteristic curves ranged from 0.49 to 0.53 (all p = NS). The same conclusions were obtained in subgroup analyses of QRS duration (120 to 150 vs >150 ms) and ischemic or nonischemic cause of heart failure. In conclusion, parameters of tissue Doppler longitudinal velocity, but not longitudinal strain, predicted LV reverse remodeling after CRT. [Copyright &y& Elsevier]

Objectives: We sought to examine whether cardiac resynchronization therapy (CRT) improves atrial function and induces atrial reverse remodeling. Background: Cardiac resynchronization therapy is an established therapy for advanced heart failure with prolonged QRS duration, which improves left ventricle (LV) function and is associated with LV reverse remodeling. Methods: A total of 107 heart failure patients (66 ± 11 years) who received CRT and were followed up for 3 months were studied. Atrial function was assessed by M-mode, 2-dimensional echocardiography, transmitral Doppler, tissue Doppler velocity, and strain (ε) imaging. Left atrial (LA) emptying fraction based on the change in areas (LAA-EF) and volumes (LAV-EF) were calculated. The LV reverse remodeling was defined by a reduction of LV end-systolic volume >10%. Results: In the responders of LV reverse remodeling (n = 62), LAA-EF and LAV-EF were significantly increased (p < 0.001). Responders also had significant decrease in LA size area and volumetric measurements, both before (p < 0.05) and after atrial systole (p < 0.001). However, these parameters were unchanged in the nonresponders (n = 45, p = NS). In the responders, tissue Doppler velocity analysis showed improvement of contraction velocity in both left (p = 0.005) and right atria (p = 0.018), whereas ε in both atria were increased in all the phases of cardiac cycle, namely ventricular end-systole (p < 0.001), early diastole (p < 0.001), and late diastole (p = 0.007). Conclusions: Cardiac resynchronization therapy improves both left and right atrial pump function. The increase in atrial ε throughout the cardiac cycle is likely reflecting the improvement of atrial compliance. These changes lead to LA reverse remodeling with reduction of LA size before and after atrial systole. [Copyright &y& Elsevier]

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is ≥15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score. [Copyright &y& Elsevier]

Objectives: The present study aimed to examine whether diastolic and systolic asynchrony exist in diastolic heart failure (DHF) and their prevalence and relationship to systolic heart failure (SHF) patients. Background: Few data exist on mechanical asynchrony in DHF. Methods: Tissue Doppler echocardiography was performed in 373 heart failure patients (281 with SHF and 92 with DHF) and 100 normal subjects. Diastolic and systolic asynchrony was determined by measuring the standard deviation of time to peak myocardial systolic (Ts-SD) and peak early diastolic (Te-SD) velocity using a 6-basal, 6-mid-segmental model, respectively. Results: Both heart failure groups had prolonged Te-SD (DHF vs. SHF vs. controls subjects: 32.2 ± 18.0 ms vs. 38.0 ± 25.2 ms vs. 19.5 ± 7.1 ms) and Ts-SD (31.8 ± 17.0 ms vs. 36.7 ± 15.2 ms vs. 17.6 ± 7.9 ms) compared with the control group (all p < 0.001 vs. control subjects). Based on normal values, the DHF group had comparable diastolic (35.9% vs. 43.1%; chi-square = 1.48, p = NS), but less systolic asynchrony than the SHF group (39.1% vs. 56.9%; chi-square = 8.82, p = 0.003). Normal synchrony, isolated systolic, isolated diastolic, and combined asynchrony were observed in 39.1%, 25.0%, 21.7%, and 14.1% of DHF patients, respectively, and these were 25.6%, 31.3%, 17.4%, and 25.6%, correspondingly, in SHF (chi-square = 10.01, p = 0.019). The correlation between systolic and diastolic asynchrony, and between the myocardial velocities and corresponding mechanical asynchrony appeared weak. A wide QRS duration (>120 ms) was rare in DHF (10.9% vs. 37.7% in SHF) (chi-square = 16.69, p < 0.001). Conclusions: Diastolic and/or systolic asynchrony was common in 61% of DHF patients despite narrow QRS complex. The presence of asynchrony was not related to myocardial systolic or diastolic function. Systolic and diastolic asynchrony were not tightly coupled, implying distinct mechanisms. [Copyright &y& Elsevier]

Objectives: This study was designed to evaluate the role of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with narrow QRS complexes (<120 ms) and echocardiographic evidence of mechanical asynchrony. Background: Cardiac resynchronization therapy is currently recommended to advanced HF patients with prolonged QRS duration. Echocardiographic assessment of systolic mechanical asynchrony has been proven useful to predict a favorable response after CRT. Methods: A total of 102 HF patients with New York Heart Association (NYHA) functional class III or IV were enrolled. Among them, 51 had wide QRS (>120 ms) and 51 had narrow QRS (<120 ms). Tissue Doppler imaging (TDI) was employed to select patients with systolic asynchrony (increased asynchrony index) in the narrow-QRS group. Clinical and echocardiographic assessments were performed at baseline and 3 months after CRT. Results: There was a significant reduction of left ventricular (LV) end-systolic volume in both narrow (122 ± 42 cc vs. 103 ± 47 cc, p < 0.001) and wide (148 ± 74 cc vs. 112 ± 64 cc, p < 0.001) QRS groups. Improvement of NYHA functional class (both p < 0.001), maximal exercise capacity (both p < 0.05), 6-min hall-walk distance (both p < 0.01), ejection fraction (both p < 0.001), and mitral regurgitation (both p < 0.005) was also observed. In both groups, the degree of baseline mechanical asynchrony determined LV reverse remodeling to a similar extent, as shown by the superimposed regression lines. Withholding CRT for 4 weeks resulted in loss of echocardiographic benefits. Conclusions: Cardiac resynchronization therapy for HF patients with narrow QRS complexes and coexisting mechanical asynchrony by TDI results in LV reverse remodeling and improvement of clinical status. The amplitude of benefit is similar to the wide-QRS group provided that similar extent of systolic asynchrony is selected. [Copyright &y& Elsevier]

Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and reverse left ventricular (LV) remodeling. It is not known, however, whether diastolic function will improve after CRT and diastolic asynchrony will predict LV reverse remodeling. Seventy-six patients (mean age 65 ± 12 years, 74% men) who received CRT were studied at baseline and after 3 months. Diastolic function was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and diastolic asynchrony were assessed by the time to peak myocardial contraction (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental model. There were 42 responders (55%) with LV reverse remodeling (defined as a reduction of LV end-systolic volume ≥15%). Parameters of systolic function were significantly improved only in the responders. For diastolic function, there were reductions of transmitral E velocity in the 2 groups, without any change in atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial early diastolic velocity was unchanged in responders but was significantly worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV segments) correlated significantly with LV reverse remodeling (r = −0.64, p <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments) (r = −0.10, p = NS). The systolic asynchrony index was the only independent predictor of reverse remodeling (β = −0.99, 95% confidence interval −1.41 to −0.58, p <0.001). In conclusion, CRT improves systolic function and systolic asynchrony but has a neutral effect on diastolic function and diastolic asynchrony. LV reverse remodeling response is determined by the severity of prepacing systolic asynchrony but not diastolic asynchrony or the diastolic filling pattern. [Copyright &y& Elsevier]

Abstract: Background: Atrial function is an integral part of cardiac function which is often neglected. The presence of coronary artery disease (CAD) may impair atrial function. This study investigated if atrial mechanical dysfunction was present in patients with CAD by tissue Doppler echocardiography (TDI). Methods: Echocardiography with TDI was performed in 118 patients with CAD, and compared with 100 normal controls with comparable age and heart rate. Regional atrial function was assessed at the left (LA) and right (RA) atrial free wall and inter-atrial septum (IAS). The peak regional atrial contraction velocity of (V A) and the timing of mechanical events were compared. Results: The V A in the LA (5.0±2.6 Vs 7.7±2.6 cm/s), IAS (4.8±1.7 Vs 5.7±1.5 cm/s) and RA (6.8±3.1 Vs 9.2±2.9 cm/s) were significantly decreased in patients with CAD when compared with controls (all p <0.001). Patients with impaired systolic function (ejection fraction≤50%) had significantly lower V A in the LA and IAS than those with ejection fraction>50% (both p <0.001); and were lower in those with restrictive filling pattern (RFP) than non-RFP of diastolic dysfunction (both p <0.05). The V A in all the subgroups was lower than controls. In contrast, transmitral atrial velocity was unable to reveal any abnormality except in the subgroup with a RFP. The LA dimension, area and volume were increased in the disease groups, but were largely unchanged in the RA despite abnormal V A. The physiological inter-atrial delay for the onset and peak atrial contraction between the RA and LA were unaffected by CAD. Conclusions: The atrial contractile function in both atria was impaired in the presence of CAD, especially in the LA. This was detected even in patients with preserved systolic function or mild diastolic dysfunction such as non-RFP. Direct assessment of atrial velocity by TDI may better reflect atrial mechanical function than transmitral atrial velocity. [Copyright &y& Elsevier]

Introduction: Cardiac resynchronization therapy (CRT) is now an established nonpharmacologic therapy for advanced heart failure with electromechanical delay. Despite compelling evidence of the benefits of CRT, one troubling issue is the lack of a favorable response in about one-third of patients. Methods and Results: Currently, there is no unifying definition of responders, and published data were based on acute hemodynamic changes, chronic left ventricular reverse remodeling, as well as the intermediate or long-term clinical response. The lack of improvement with CRT can be due to many factors including the placement of the left ventricular pacing lead in an inappropriate location, the absence of electrical conduction delay or mechanical dyssynchrony despite wide QRS complexes, and possibly failure to optimize the CRT settings after device implantation. In acute hemodynamic studies, placing the left ventricular leads at the free wall region has been suggested to generate the best pulse pressure and positive dp/dt. The degree of mechanical dyssynchrony has recently been assessed noninvasively in CRT patients by echocardiography and in particular by tissue Doppler imaging. These studies suggested that responders of left ventricular reverse remodeling or systolic function had more severe systolic dyssynchrony. However, further studies are needed to examine the clinical utility of these parameters when applied to the standardized anatomic or functional endpoints. Optimization of atrioventricular and interventricular pacing intervals may also reduce the number of nonresponders, though newer methods, especially interventricular pacing intervals, are still under clinical investigation. Conclusion: With the adjunctive use of imaging technology, physicians are able to characterize the response to CRT objectively, and cardiac imaging is an important clinical tool for determining more precisely the presence and degree of mechanical dyssynchrony. [ABSTRACT FROM AUTHOR]

Although the beneficial role of cardiac resynchronization therapy (CRT) in selected patients with heart failure is well proven, its effect on the incidence of atrial fibrillation (AF) is unclear. The present study compared the incidence of AF in 36 consecutive patients with chronic heart failure receiving CRT with its incidence in controls matched for age, gender, and left ventricular ejection fraction but not receiving CRT. The findings suggest that patients with CRT had a significantly lower incidence of AF than controls. Further studies to establish the role of CRT in preventing AF and its mechanisms are warranted. [Copyright &y& Elsevier]

Objectives: This study was designed to investigate if tissue synchronization imaging (TSI) is useful to identify regional wall delay and predict left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). Background: Echocardiographic assessment of systolic asynchrony is helpful to predict a positive response to CRT. Tissue synchronization imaging is a new imaging technique that allows quick evaluation of regional systolic delay. Methods: Tissue synchronization imaging was performed in 56 heart failure patients at baseline and three months after CRT. Regional wall delay was identified on TSI images and the time to regional peak systolic velocity (Ts) in LV was measured by the six-basal-six-mid-segmental model. Eight TSI parameters of systolic asynchrony were computed when Ts was measured in ejection phase or also included postsystolic shortening. Results: Severe lateral wall delay occurred in 17 patients, which predicted LV reverse remodeling (chi-square = 8.13, p = 0.004). Among the eight quantitative parameters of asynchrony, the predictive values were higher for parameters that measured Ts in ejection phase than in postsystolic shortening. The standard deviation of Ts of 12 LV segments in ejection phase (Ts-SD-12-ejection) was most powerful to predict reverse remodeling (r = −0.61, p < 0.001) and gain in ejection fraction (r = 0.53, p < 0.001). The area of the receiver-operating characteristic (ROC) curve was the largest for Ts-SD-12-ejection (0.90, p < 0.001), with a sensitivity of 87% and specificity of 81% at a cutoff of 34.4 ms. The combination of lateral wall delay with Ts-SD-12-ejection gave a sensitivity and specificity of 82% and 87%. Conclusions: Tissue synchronization imaging allows quick evaluation of regional wall delay, and combined with Ts-SD-12-ejection provides a reliable way of predicting reverse remodeling after CRT. [Copyright &y& Elsevier]

A new echocardiographic technology, the timing of regional volumetric changes by 3-dimensional echocardiography, was applied to assess intraventricular mechanical synchronicity in 13 patients who had received cardiac resynchronization therapy (CRT). When biventricular pacing was withheld, left ventricular (LV) asynchrony occurred as reflected by these echocardiographic parameters, whereas LV volume increased and the ejection fraction decreased. Further studies are needed to explore whether this novel method can be used to select suitable candidates for CRT and to predict a favorable response. [Copyright &y& Elsevier]

Efficacy of CRT for Mildly Prolonged QRS.. Introduction:Cardiac resynchronization therapy (CRT) has been shown to reverse left ventricular (LV) remodeling and improve symptoms in heart failure patients with wide QRS complexes; however, its role in patients with mildly prolonged QRS complexes is unclear. This study investigated if CRT benefited patients with mildly prolonged QRS complexes>120 to 150 ms and explored if the severity of systolic asynchrony determined such a response.Methods and Results:Fifty-eight patients (age 66± 11 years, 66% male) who had undergone CRT were studied prospectively. Of these patients, 27 had QRS duration between 120 and 150 ms (group A), and 31 had QRS duration>150 ms (group B). Tissue Doppler echocardiography and clinical assessment were performed at baseline and 3 months after CRT. Both groups had significant reduction of LV volume and increased ejection fraction,+dP/dt, and sphericity index (all P<0.05). These improvements were greater in group B and were explained by the higher prevalence of systolic intraventricular asynchrony. Significant reverse remodeling (reduction of LV end-systolic volume>15%) was evident in 46% of group A patients and 68% of group B patients. Improvement in clinical endpoints was observed in both groups (all P<0.01), although the changes in metabolic equivalent and New York Heart Association functional class were greater in group B. In both groups, systolic asynchrony index (TS-SD) was the most important predictor of reverse remodeling (r=−0.78, P<0.001) and was the only independent predictor in the multivariate model (β=−1.80, confidence interval=−2.18 to−1.42, P<0.001); QRS duration was not. A predefined TS-SD value>32.6 ms had a sensitivity of 94% and specificity of 83% to predict reverse remodeling. Improvement of intraventricular asynchrony after CRT was evident only in responders (P= 0.01).Conclusion:Improvement of LV remodeling and clinical status is evident after CRT in heart failure patients with QRS duration>120 to 150 ms. These responders are closely predicted by the severity of prepacing intraventricular asynchrony but not QRS duration.(J Cardiovasc Electrophysiol, Vol. 15, pp. 1-8, September 2004) [ABSTRACT FROM AUTHOR]

This study investigated the effect of fosinopril (Fos), valsartan (Val), and combination of both drugs (Fos + Val) on the cardiac and renal expression of aquaporin-1 (AQP1) and aquaporin-2 (AQP2) in congestive heart failure (CHF). A rat model of CHF was created by ligating the left anterior descending coronary artery to induce acute myocardial infarction (AMI). Rats were treated by Fos, Val, or Fos + Val for 4 weeks. In renal medulla and cortex, AMI was associated with 2.2- and 1.8-fold increase in AQP2 mRNA expression when compared with Sham-operated rats (medulla: 23.6 ± 2.8 vs. 52.3 ± 8.7%; P < 0.001; cortex: 19.4 ± 3.9 vs. 35.5 ± 7.1%; P < 0.05). All the treatment regimens were able to normalize AQP2 transcription in the renal medulla (Fos, 19.9 ± 4.9%; Val, 22.8 ± 4.9%; Fos + Val, 20.1 ± 5.1%; P = NS vs. Sham) and in the cortex (Fos, 21.2 ± 6.7%; Val, 20.4 ± 6.0%; Fos + Val, 18.9 ± 7.5%; P = NS vs. Sham). Similarly, the AQP2 protein expression increased by 2.1-fold after CHF (P < 0.05), and was normalized by the treatment regimens (Sham, 0.57 ± 0.19%; CHF, 1.22 ± 0.45%; Fos, 0.39 ± 0.36%; Val, 0.46 ± 0.34%; Fos + Val, 0.36 ± 0.15%; all P < 0.05 vs. CHF). These treatment regimens also prevented the increase in body weight as found in untreated CHF rats (analysis of variance P < 0.05). The renal and cardiac AQP1 gene and protein expressions were unaltered in CHF or by medical therapy. There was no observed cardiac AQP2 expression in all the study groups. Treatment with Fos, Val, or combination therapy was effective in preventing the upregulation of renal AQP2 gene and protein expressions in CHF rats caused by AMI. [Copyright &y& Elsevier]

Biventricular pacing results in left ventricular (LV) reverse remodeling in heart failure patients with wide QRS complexes. This study examines potential predictors of reverse remodeling. Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients (21 men and 9 women, mean age 62 ± 14 years). There were 17 responders to reverse remodeling (defined as a reduction in LV end-systolic volume by >15%) and 13 nonresponders. Responders had significant improvement in 6-minute hall-walking distance (p = 0.006), metabolic equivalents (p = 0.02), peak oxygen uptake (p = 0.02), New York Heart Association functional class (p <0.001), and quality of life (p <0.001); an increase in the sphericity index (p = 0.007), ejection fraction (p <0.001), and diastolic filling time (p = 0.03); a decrease in myocardial performance index (p = 0.02), isovolumic relaxation time (p = 0.004), and mitral regurgitation (p = 0.007); and an improvement in systolic dyssynchrony (SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index) (45.0 ± 8.3 vs 32.5 ± 14.5 ms, p = 0.003). In contrast, nonresponders only had a small degree of clinical improvement in New York Heart Association class (p = 0.03) and quality-of-life scores (p = 0.03), without any change in cardiac function, and worsening of systolic dyssynchrony (24.8 ± 4.5 vs 34.1 ± 13.5 ms, p = 0.02). When all the above factors were put into univariate and multivariate analyses models, systolic dyssynchrony was the only independent predictor of reverse remodeling (r = −0.76, p <0.001) (β = −1.54, p = 0.007). A preimplant dyssynchrony index of 32.6 ms (+2 SDs from mean of 88 normal controls) was able to totally segregate responders from nonresponders of biventricular pacing. Thus, responders of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity. Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy. [Copyright &y& Elsevier]

YU, C.‐M., et al.: Regional Left Ventricle Mechanical Asynchrony in Patients with Heart Disease and Normal QRS Duration: Implications for Biventricular Pacing Therapy.LV electromechanical delay results in asynchronized contraction. However, it is not known if the presence of cardiac diseases without QRS prolongation may result in inter‐ or intraventricular asynchrony. This study investigated the occurrence of systolic mechanical delay in different regions of the LV in patients with underlying heart diseases and normal QRS duration. Tissue Doppler imaging (TDI) was performed in 141 patients(age 63.7 ± 11.5 years)with underlying heart diseases (82% had ischemic heart disease) and 92 normal healthy volunteers(age 63.9 ± 9.8 years)based on the four‐basal and four‐mid‐segment model by apical views. Of these, 124 patients had normal QRS duration(≤120 ms)while 17 were prolonged due to LBBB or intraventricular conduction defect. Patients with normal QRS duration had significantly lower peak myocardial isovolumic contraction velocity(IVCM), sustained systolic velocity(SM), and prolonged time to peakIVCMandSMin almost all myocardial segments when compared to controls. The time to peakIVCM(basal lateral vs basal septal segment:61.0 ± 29.4 vs 53.3 ± 24.1 ms, P < 0.005) andSM(basal lateral vs basal septal segment:174 ± 44vs154 ± 36 ms, P < 0.001) was further delayed in the LV free‐wall segments. Mechanical delay was also evident in the LV free‐wall segments in patients with preserved or impaired systolic function, in patients with or without previous myocardial infarction, and in patients with prolonged QRS duration. Patients with prolonged QRS had a higher prevalence of LV free‐wall delay of >50ms (47 vs 24%, chi‐square = 4.6, P < 0.05). In conclusion, the presence of cardiac diseases was characterized by LV global mechanical delay; and, intraventricular asynchronized contraction characterized mostly by further mechanical delay in the free‐wall region. These changes occur even in those with normal QRS duration. (PACE 2003; 26[Pt. I]:562–570) [ABSTRACT FROM AUTHOR]

The authors reflect on right ventricular pacing and on the article "Long Term Mechanical Consequences of Permanent Right Ventricular Pacing: Effect of Pacing Site," by D. Leong, A. M. Mitchell, I. Salna, A. G. Brooks, G. Sharma, H. S. Lim, M. Alasady, M. Barlow, J. Leitch, P. Sanders and G. D. Young. They suggest that right ventricular pacing is safe and feasible. They argue that additional research is needed to determine the benefits of right ventricular pacing.

Objective It remains incompletely understood how homocysteine impairs endothelial function. Whether mechanisms such as calcium-activated potassium (K Ca ) channels are involved is uncertain and the significance of endoplasmic reticulum (ER) stress in K Ca channel-dependent endothelial function in hyperhomocysteinemia remains unexplored. We investigated the effect of homocysteine on endothelial K Ca channels in coronary vasculature with further exploration of the role of ER stress. Methods Vasorelaxation mediated by intermediate- and small-conductance K Ca (IK Ca and SK Ca ) channels was studied in porcine coronary arteries in a myograph. IK Ca and SK Ca channel currents were recorded by whole-cell patch-clamp in coronary endothelial cells. Protein levels of endothelial IK Ca and SK Ca channels were determined for both whole-cell and surface expressions. Results Homocysteine impaired bradykinin-induced IK Ca and SK Ca -dependent EDHF-type relaxation and attenuated the vasorelaxant response to the channel activator. IK Ca and SK Ca currents were suppressed by homocysteine. Inhibition of ER stress during homocysteine exposure enhanced IK Ca and SK Ca currents, associated with improved EDHF-type response and channel activator-induced relaxation. Homocysteine did not alter whole-cell protein levels of IK Ca and SK Ca whereas lowered surface expressions of these channels, which were restored by ER stress inhibition. Conclusions Homocysteine induces endothelial dysfunction through a mechanism involving ER stress-mediated suppression of IK Ca and SK Ca channels. Inhibition of cell surface expression of these channels by ER stress is, at least partially, responsible for the suppressive effect of homocysteine on the channel function. This study provides new mechanistic insights into homocysteine-induced endothelial dysfunction and advances our knowledge of the significance of ER stress in vascular disorders. [ABSTRACT FROM AUTHOR]

Pulse transit time (PTT) is a cardiovascular parameter of emerging interest due to its potential to estimate blood pressure (BP) continuously and without a cuff. Both linear and nonlinear equations have been used in the estimation of BP based on PTT. This study, however, demonstrates that there is a hysteresis phenomenon between BP and PTT during and after dynamic exercise. A total of 46 subjects including 16 healthy subjects, 13 subjects with one or more cardiovascular risk factors, and 17 patients with cardiovascular disease underwent graded exercise stress test. PTT was measured from electrocardiogram and photoplethysmogram of the left index finger of the subject, i.e., a pathway that includes predominately aorta, brachial, and radial arteries. The results of this study showed that, for the same systolic BP (SBP), PTT measured during exercise was significantly larger than PTT measured during recovery for all subject groups. This hysteresis was further quantified as both normalized area bounded by the SBP–PTT relationship (AreaN) and SBP difference at PTT during peak exercise plus 20 ms (ΔSBP20). Significant attenuation of both AreaN (p < \0.05) and ΔSBP20 ( p < \0.01) is observed in cardiovascular patients compared with healthy subjects, independent of resting BP. Since the SBP–PTT relationship are determined by the mechanical properties of arterial wall, which is predominately mediated by the sympathetic nervous system through altered vascular smooth muscle (VSM) tone during exercise, results of this study are consistent with the previous findings of autonomic nervous dysfunction in cardiovascular patients. We further conclude that VSM tone has a nonnegligible influence on the BP–PTT relationship and thus should be considered in the PTT-based BP estimation. [ABSTRACT FROM PUBLISHER]

Abstract: Background: There is an ongoing debate on the role of percutaneous closure of patent foramen ovale (PFO) in preventing recurrent ischemic events in patients with cryptogenic stroke and PFO. We systematically reviewed the latest randomized data on the efficacy and safety of percutaneous PFO closure in patients with cryptogenic stroke and PFO. Methods: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in April 2013 for eligible randomized controlled trials (RCTs). Primary outcome measures included: (i) stroke; (ii) transient ischemic attack (TIA); and (iii) all-cause mortality. Secondary outcomes were new-onset atrial fibrillation (AF) and bleeding. Results: We included a total of three RCTs randomizing 2303 participants. The intervention groups used either the STARFlex® Septal Closure System (one trial, n=447) or the AMPLATZER™ PFO Occluder (two trials, n=703). Control arms (n=1153) used medical treatment composing of antiplatelet or anticoagulation therapy. There were no significant differences between groups in the analyses of stroke (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.36–1.20, P=0.17), TIA (hazard ratio (HR) 0.77, 95% CI 0.45–1.32, P=0.35), all-cause mortality (OR 0.65, 95% CI 0.23–1.85, P=0.42) or bleeding (OR 1.43, 95% CI 0.47–4.42, P=0.53). Percutaneous PFO closure was associated with a significantly higher incidence of new-onset AF as compared to medical therapy (OR 3.77, 95% CI 1.44–9.87, P=0.007). Conclusions: Currently-available randomized data do not support the use of percutaneous PFO closure for secondary stroke prevention in patients with cryptogenic stroke and PFO. An updated meta-analysis including further data from ongoing RCTs is warranted. [Copyright &y& Elsevier]

Abstract: Background: The intervention timing in atrial septal defect (ASD) or pulmonary valvular stenosis (PVS) is more dependent on symptoms than right ventricular (RV) damage in clinical practice. RV long-axis function is sensitive in revealing RV myocardial dysfunction. We evaluate the impact of different chronic loading conditions on RV long-axis function and its relationship to patients' symptoms in ASD or PVS. Methods: Transthoracic echocardiography was performed in normals (n=39) and patients with isolated secundum ASD (n=45) or PVS (n=38). RV volume- and pressure-overloading were defined as the ratio of RV/left ventricular end-diastolic dimension ≥0.5 and RV systolic pressure ≥40mmHg, respectively. RV long-axis dysfunction was defined as M-mode tricuspid annular plane systolic excursion (TAPSE) <1.6cm. New York Heart Association (NYHA) functional class and other symptoms (decreased exercise tolerance, palpitation and chest pain) were recorded. Results: Thirty-nine (32.0%) had normal loading (Group 1; 39 normals); 24 (19.6%) had isolated volume-overloading (Group 2; all ASDs); 21 (17.2%) had isolated pressure-overloading (Group 3; 21 PVSs) and 38 (31.1%) had both overloading conditions (Group 4; 21 ASDs and 17 PVSs). RV long-axis dysfunction in abnormal loading groups were zero (0%, Group 2), 21 (100%, Group 3) and 22 (57.8%, Group 4) (χ2 =45.9, p<0.001). Group 3 were more symptomatic (NYHA functional class 2.5±0.6 versus 1.6±0.5, p<0.05) and had lower TAPSE (1.6±0.4 versus 3.0±0.7cm, p<0.05) than Group 2. RV long-axis dysfunction was the strongest predictor of the presence of symptoms (odds ratio=9.298, p<0.001). Conclusion: Chronic volume-overloading accentuates while pressure-overloading attenuates RV long-axis excursion and its impairment was associated with the presence of symptoms. [Copyright &y& Elsevier]

Abstract: Background: Connective tissue growth factor (CTGF) and vascular endothelial cell growth factor (VEGF) have been implicated as important effectors during cardiac remodeling. This study tested the hypothesis that norepinephrine (NE) induces CTGF and VEGF gene and protein expression in cardiac fibroblasts (CF) and the CTGF/VEGF complex will have an effect on angiogenesis. Methods and results: Rats CF were cultured in NE (0.01 to 100μM) for 24h. CTGF and VEGF gene expression were measured by quantitative-PCR. CTGF protein and CTGF/VEGF complex were detected by Western blot. The effect of CTGF/VEGF complex on angiogenesis was detected by endothelial cell tube formation assay. VEGF antigen level, reactive oxygen species (ROS) production were measured by ELISA and DCFH-DiOxyQ assay respectively. NE at 0.01μM up-regulated CTGF mRNA and secretory protein expression significantly whereas at 100μM both gene and protein were down-regulated significantly when compared with controls. At 0.01 to 0.1μM of NE, there was no change in VEGF gene and protein level. NE at 100μM increased VEGF gene and antigen level and ROS production significantly when compared with controls. CTGF/VEGF complex was found to inhibit the angiogenesis of endothelial cells. Conclusions: NE regulates CTGF and VEGF expression in a dose-dependent manner and via VEGF can induce angiogenesis. This work suggests NE may have an important role in ventricular remodeling. [Copyright &y& Elsevier]

Background: Cardiac contractility modulation (CCM) emerges as a promising device treatment for heart failure (HF). This meta-analysis aimed to systematically review the latest available randomized evidence on the effectiveness and safety of CCM in HF. Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in November 2011 to identify eligible randomized controlled trials comparing CCM with sham treatment or usual care. Primary outcomes of interest were all-cause mortality, all-cause hospitalizations, and adverse effects. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous data using a random-effects model. Results: Three studies enrolling 641 participants were included. Pooled analysis showed that, compared to control, CCM did not significantly improve all-cause mortality (n = 629, RR 1.19, 95% CI 0.50-2.86, P = 0.69), nor was there a favorable effect in all-cause hospitalizations. No increase in adverse effects with CCM was observed. Conclusions: Meta-analysis of data from small randomized trials suggests that CCM, although with no clear benefits in improving clinical outcomes, is not associated with worsening prognosis. Large, well-designed trials are needed to confirm its role in HF patients for whom cardiac resynchronization therapy is contraindicated or unsuccessful. (PACE 2012; 35:1111-1118) [ABSTRACT FROM AUTHOR]

Abstract: Background: Meta-analyses are increasingly used to summarise observational data however a literature meta-analysis (LMA) may give different results to the corresponding individual patient meta-analysis (IPMA). This study compares the published results of equivalent LMAs and IPMAs, highlighting factors that can affect the results and therefore impact on clinical interpretation of meta-analyses. Method: Univariate results from published meta-analyses of prospective observational outcome data were compared, as were the number of studies, patients and length of follow-up. The absolute difference in survival was calculated. The association between severe diastolic dysfunction (RFP) and death post acute myocardial infarction (AMI) and in chronic heart failure (HF) were used as clinical examples. Results: The IPMA hazard ratio was lower that the LMA odds ratio: AMI hazard ratio 2.67 (95% confidence interval 2.23 to 3.20), odds ratio 4.10 (3.38 to 4.99); HF hazard ratio 2.42 (2.06 to 2.83), odds ratio 4.36 (3.60 to 5.04). The IPMAs contained most of the studies from the LMAs as well as additional unpublished data, and a longer length of follow-up was available in the IPMAs (AMI 3.7 vs 2.6 yr, HF 4.0 vs 1.5yr). Restricting analysis to the same studies in both the LMA and IPMA resulted in a similar difference in effect sizes between methods to those found in the published analyses. Conclusions: The result of a meta-analysis is affected by whether study level or individual patient data have been used, and the variant of analysis that is required. Awareness and consideration of these factors is important for clinical interpretation of meta-analyses. [Copyright &y& Elsevier]

Abstract: Objective: Type D personality predicts poor prognosis in coronary heart disease (CHD) but little is known about Type D in non-Western cultures. We examined the (a) validity of the Type D construct and its assessment with the DS14 scale in the Chinese culture, (b) prevalence of Type D, and (c) gender vs. Type D discrepancies in depression/anxiety, among Chinese patients with CHD. Method: Patients with CHD (N=326) completed the Chinese version of the DS14. The NEO Five Factor Inventory (NEO-FFI), Hospital Anxiety and Depression Scale (HADS), and Stress Symptom Checklist (SSC) were administered to subsamples to establish construct and discriminant validity. Administration of the DS14, HADS, and SSC was repeated at 1 month after hospital discharge in 66 patients, and stability of the DS14 was examined in another subsample of 100 patients. Results: The theoretical structure of the Type D construct in the Chinese culture was supported (χ 2/df=2.89, root mean square error of approximation=0.08, normal fit index=0.91, non-normal fit index=0.91, comparative fit index=0.93). The Negative Affectivity (NA) and Social Inhibition (SI) subscales of the DS14 in the entire sample were internally consistent (Cronbach''s alpha=0.89/0.81), measured stable traits (3-month test–retest ICC=0.76/0.74), and correlated significantly with the neuroticism (NA/neuroticism, r=0.78, P<.001) and extraversion subscales (SI/extraversion, r=−0.64, P<.001) of the NEO-FFI, respectively. The prevalence of Type D personality was 31%. Type D was not related to transient emotional states. However, Chinese patients with a Type D personality were at increased concurrent risk of anxiety (P=.002) and depression (P=.016). Conclusion: Type D personality is a cross-culturally valid construct, is associated with an increased risk of anxiety and depression, and deserves prompt attention in estimating the prognostic risk of Chinese CHD patients. [Copyright &y& Elsevier]

Abstract: Background: Prolonged sympathetic activation is damaging to the heart. Recent findings suggest that norepinephrine (NE) may contribute to the apoptotic cardiac cell loss. This study investigated high doses NE apoptotic effect on cardiac fibroblasts (CF) culture and compared the anti-apoptotic effect of α and β (selective and non-selective) adrenergic receptor antagonists. Methods and results: Rat CF were cultured in the presence of NE (1 to 100 µM) for 48 h. bax and bclXL genes expression were measured by real-time quantitative PCR method. Cell viability percentage, apoptotic cell percentage and caspase 3 activity was measured by MTT assay, flow cytometric method and caspase 3 flurogenic assay kit respectively. NE (100 µM) increased bax gene expression by 1.96±0.96 fold while bclXL gene decreased by 0.53±0.15 fold when compared with the control group (p <0.01). The apoptotic cell percentage increased significantly from 5.09±2.94% in control group to 31.48±6.35% (p <0.01) with NE and the caspase 3 activity increased from 1432.2±658.8 in the control group to 5162±2028.6 (OD/µg protein, p <0.05). Addition of carvedilol (non-selective β blocker with α-blockade activity), doxazosin (α blocker), metoprolol (β1 selective blocker) and propranolol (non-selective β blocker) were not capable of inhibiting the apoptotic effect of high dose NE on CF. Conclusion: High dose NE has cytotoxic and apoptotic effect on CF. The process involved the activation of caspase 3, up-regulation of pro-apoptotic gene bax and down-regulation of anti-apoptotic gene bclXL. Both non-selective and selective adrenergic receptor antagonists tested were not capable of inhibiting the apoptotic effect of high dose NE on CF. [Copyright &y& Elsevier]

Abstract: Objective: To perform a psychometric evaluation of the Myocardial Infarction Dimensional Assessment Scale (MIDAS) in Chinese patients with coronary heart disease. Design and setting: Patients with angina (n =162), MI (n =124) or heart failure (n =95) were recruited from a regional university-affiliated hospital. The Chinese version of the MIDAS (C-MIDAS), the Hospital Anxiety and Depression Scale (HADS) and the Short-Form 36 Health Survey (SF-36) were administered to all patients at baseline and the C-MIDAS was also administered seven day (n =92) and three months (n =363) later. Results: The C-MIDAS conforms to the 7-factor structure as proposed in the original version. It is reliable with Cronbach''s alphas from 0.73 to 0.94 and test–retest reliabilities from 0.76 to 0.92. Four of its subscales (physical activity, insecurity, emotional reaction and dependency) correlated significantly with the SF-36 and the HADS in each diagnostic group and had good discriminative properties in terms of gender, emotional disturbance and perceived health deterioration, with responsiveness supported by medium-high effect sizes (0.43–0.83) and standardize response means (0.46–0.82). The other three subscales measuring treatment-related impacts added little to the validity and responsiveness of the C-MIDAS. Conclusion: To render the C-MIDAS a core health-related quality of life measure for Chinese-speaking patients with coronary heart disease, further studies need to clarify the content adequacy and cultural relevancy of those subscales measuring treatment-related impact. [Copyright &y& Elsevier]

Background: Linear microwave ablation has been shown to be effective for treatment of atrial fibrillation during open-heart surgery by producing transmural lesions in the atrium to isolate the pulmonary veins. However, the safety and efficacy of percutaneous, transcatheter, linear microwave ablation for atrial arrhythmias, while demonstrated in animal models, is unknown in humans. Therefore, we studied the safety and efficacy of linear microwave ablation of the cavotricuspid isthmus (CTI) in humans with typical atrial flutter, utilizing a 2-cm long microwave antenna mounted on a steerable 9-French catheter. Methods and Results: In seven consecutive patients, multielectrode catheters were positioned at the His bundle (quadripolar) and around the TV annulus (duo-decapolar) for pacing and recording atrial activation sequence before and after ablation. The microwave antenna was withdrawn gradually from tricuspid annulus towards inferior vena cava to ablate the CTI. Intracardiac ultrasound was used to ensure adequate endocardial contact of the microwave ablation catheter with the CTI. Microwave energy was applied at a power of 18 to 21 W at each ablation point for 120 seconds. Ablation was repeated until bidirectional CTI block was confirmed by demonstrating a descending activation wavefront in the contralateral atrial wall during pacing from the coronary sinus ostium or low lateral right atrium, respectively. Bidirectional isthmus block was achieved in all patients, after a mean number of 27.4 ± 14.7 energy applications per patients. There were no acute procedural complications. Conclusions: Percutaneous, transcatheter microwave ablation of CTI dependent atrial flutter was demonstrated to be safe and effective in this preliminary feasibility study. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine if strain rate imaging (SRI) correlates with the transmural extent of myocardial infarction (MI) measured by contrast-enhanced magnetic resonance imaging (Ce-MRI). Background: Identification of the transmural extent of myocardial necrosis and degree of non-viability after acute MI is clinically important. Methods: Tissue Doppler echocardiography with SRI and Ce-MRI were performed in 47 consecutive patients with a first acute MI between days 2 and 6 and compared to 60 age-matched healthy volunteers. Peak myocardial velocities and peak myocardial deformation strain rates were measured. Location and size of the infarct zone was confirmed by Ce-MRI using the delayed enhancement technique with a 16-segment model. Results: Contrast-enhanced MRI identified transmural infarction in 21 patients, non-transmural infarction in 15 (mean transmurality of infarct 72.3 ± 10.6%), and another 11 patients with subendocardial infarction (&#60;50% transmural extent of the left ventricular wall). Peak systolic strain rate (SRs) of the transmural infarction segments was significantly lower compared to normal myocardium or with non-transmural infarction segments (both p &#60; 0.0005). A cutoff value of SRs >−0.59 s−1 detected a transmural infarction with high sensitivity (90.9%) and high specificity (96.4%), and −0.98 s−1 >SRs >−1.26 s−1 distinguished subendocardial infarction from normal myocardium with a sensitivity of 81.3% and a specificity of 83.3%. Conclusions: Peak myocardial deformation by SRI can differentiate transmural from non-transmural MI, and it allows noninvasive determination of transmurality of the scar after MI and thereby the extent of non-viable myocardium. [Copyright &y& Elsevier]

Objectives: This study sought to investigate the incremental prognostic value of non-invasive measures of early myocardial relaxation and left ventricular diastolic pressure (LVDP) in patients with impaired left ventricular (LV) systolic function. Background: The early diastolic mitral annulus velocity (Em) reflects myocardial relaxation, and the combined ratio of the early transmitral flow velocity (E) to Em (E/Em) >15 correlates well with elevated mean LVDP. It is unknown if these new indexes will predict poorer survival in patients with LV systolic dysfunction. Methods: Echocardiograms were prospectively obtained in 182 patients with impaired LV systolic function, defined as an LV ejection fraction <0.50. The end point was cardiac mortality. The majority of this patient sample (80%) has been reported on in a previous publication. Results: After a median 48 months'' follow-up, Em emerged as an independent predictor of survival (hazard ratio 0.61, 95% confidence interval 0.45 to 0.82). An Em <3 cm/s was associated with a significantly excess mortality (log-rank statistic 9.36, p = 0.002), and this measurement added incremental prognostic value to standard indexes of systolic or diastolic function, including a deceleration time <140 ms and an E/Em >15 (p = 0.038). Conclusions: Early diastolic mitral annulus velocity is a powerful predictor of cardiac mortality in patients with LV systolic impairment; Em <3 cm/s emerged as the best prognosticator in long-term follow-up, incremental to other clinical or echocardiographic variables, including the ratio E/Em. [Copyright &y& Elsevier]