Search

Background The association between diastolic abnormality and postexercise contractile decompensation is uncertain in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF). Hypothesis The higher mitral E/annular early diastolic velocity (E/e′) is relevant to postexercise regional myocardial contractile maladaptation. Methods Seventy HF patients with LVEF 65 ms (OR: 64, 95% CI: = 6–651, P < 0.001) in HF patients with reduced LVEF in multivariate analysis. Conclusions The higher mitral E/e′-related postexercise maladaptation of myocardial contractile motion and synchronicity suggests the involvement of systolic abnormality in exercise pathophysiology in HF patients with reduced LVEF.

Chang S-N, Tsai C-T, Wu C-K, Lee J-K, Lai L-P, Huang S-W, Huang L-Y, Tseng C-D, Lin J-L, Chiang F-T, Hwang J-J (National Taiwan University Hospital Yun-Lin Branch, Yun-Lin; National Taiwan University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305–315. Objectives. In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. Methods. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. Results. Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The −390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. Conclusion. A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Background Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor δ (PPARδ) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). Methods The HEK cells and HMC were separated into the following groups: 100 µg/mL AGE alone for 18 h; AGE treated with 1 µM L-165041 or 10 µM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-κB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. Results AGE significantly increased tumour necrosis factor-α (TNF-α), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-κB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. Conclusions This study demonstrated that PPARδ agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARδ agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy. Copyright © 2010 John Wiley & Sons, Ltd.

Background and purpose: Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic-reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts. Experimental approach: Action potentials and membrane currents were recorded by the whole-cell patch clamp techniques. Fluo-3 fluorimetry was used to measure cellular Ca2+ transients. Antiarrhythmic activity was examined from isolated Langendorff-perfused rat hearts. Key results: In rat ventricular cells, piceatannol (3–30 µmol·L−1) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (Vmax) without altering Ca2+ transients. Piceatannol decreased peak INa and slowed INa inactivation, rather than induced a persistent non-inactivating current, which could be reverted by lidocaine. Resveratrol (100 µmol·L−1) decreased peak INa without slowing INa inactivation. The inhibition of peak INa or Vmax was associated with a negative shift of the voltage-dependent steady-state INa inactivation curve without altering the activation threshold. At the concentrations more than 30 µmol·L−1, piceatannol could inhibit ICa,L, Ito, IKr, Ca2+ transients and Na+-Ca2+ exchange except IK1. Piceatannol (1–10 µmol·L−1) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury. Conclusions and implications: The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in INa inhibition and uniquely slowing INa inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 µmol·L−1.

Background Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. Materials and methods A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene were genotyped. Results In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT1R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT1R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. Conclusions Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

Up-Regulation of MLC-2V in Atrial Fibrillation. Introduction: Functional and structural changes of atrial tissue occur during the natural course of atrial fibrillation (AF), and these changes may contribute to further AF. We investigated the changes in AF tissue using cDNA microarray and two-dimensional protein electrophoresis techniques. Methods and Results: We established a porcine model of AF by rapid right atrial appendage pacing at a rate of 600/min. Atrial tissue was obtained after rapid atrial depolarization for 6 weeks. Microarrays containing 6,035 cDNA clones were used to evaluate the alterations of mRNA. Two-dimensional protein electrophoresis was performed to compare protein patterns. In cDNA microarray studies, we identified 387 genes with significant change in the left atrium and 81 genes in the right atrium. Among the genes, the ventricular isoform of the myosin regulatory light chain (MLC-2V) showed the greatest fold of change (9.4 and 7.3 in the left and right atrium, respectively). In protein electrophoresis, the expression levels of three protein spots spanning from 18 to 20 kDa in the acidic region (PI 4.5‐5.0) were specifically elevated in the AF group. Interestingly, through tandem mass spectrometric analysis, these three spots were identified as MLC-2V. Thus, MLC-2V expression at the mRNA and protein levels corresponded well, and both indicated a significant increase in AF. Conclusion: Both cDNA microarray and two-dimensional polyacrylamide protein electrophoresis studies revealed characteristic changes in AF tissue. We demonstrated the reprogramming of myosin regulatory light chain isoform composition, with a significant increase of its ventricular isoform (MLC-2V). (J Cardio

Bioimpedance During Radiofrequency Catheter Ablation. Introduction: Efficiency of heating (defined as the average temperature divided by the average power) during radiofrequency (RF) catheter ablation (RFCA) can be predicted by the electrode-tissue contact pressure before RFCA. To predict the efficiency of heating during RFCA, we prospectively measured bioimpedance and correlated the bioimpedance with the efficiency of heating in patients undergoing RFCA for supraventricular tachycardias. Method and Results: Of 239 RF applications in 55 patients, bioimpedance was measured from the distal pair of the electrodes of the ablation catheter using an extremely low current (10 μ A at 45 kHz). Tip electrode temperature was measured with a closed-loop RF generator. Efficiency of heating and the difference (Δbioimpedance) between preablation bioimpedance (measured from the target ablation site) and baseline bioimpedance (measured in the right atrium without tissue contact) were calculated. There was significant positive correlation between preablation bioimpedance and efficiency of heating (regression coefficient = 0.053; P = 0.003) and between Δbioimpedance and efficiency of heating (regression coefficient = 0.067; P = 0.003). The highest degree of correlation was found during RFCA of the accessory pathways in the left free wall (regression coefficient = 0.14; P 21.5 Ω, applications targeted at the left free-wall, left posteroseptal, or right septal accessory pathways had a greater likelihood of achieving effective tissue heating (defined as maximal temperature achieved > 55°C). Conclusion: Both preablation bioimpedance and Δ bioimpedance have positive correlation with efficiency of heating during RFCA of supraventricular tachycardia. Measuring preablation bioimpedance appears to be a useful tool for predicting the efficiency of heating during RFCA.

The purpose of this study was to investigate the atrioventricular AV nodal physiology and the inducibility of AV nodal reentrant tachycardia (AVNRT) under pharmacological autonomic blockade (AB). Seventeen consecutive patients (6 men and 11 women, mean age 39 +/- 17 years) with clinical recurrent slow-fast AVNRT received electrophysiological study before and after pharmacological AB with atropine (0.04 mg/kg) and propranolol (0.2 mg/kg). In baseline, all 17 patients could be induced with AVNRT, 5 were isoproterenol-dependent. After pharmacological AB, 12 (71%) of 17 patients still demonstrated AV nodal duality. AVNRT became noninducible in 7 of 12 nonisoproterenol dependent patients and remained noninducible in all 5 isoproterenol dependent patients. The sinus cycle length (801 +/- 105 ms vs 630 +/- 80 ms, P < 0.005) and AV blocking cycle length (365 +/- 64 ms vs 338 +/- 61 ms, P < 0.005) became shorter after AB. The antegrade effective refractory period and functional refractory period of the fast pathway (369 +/- 67 ms vs 305 +/- 73 ms, P < 0.005; 408 +/- 56 ms vs 350 +/- 62 ms, P < 0.005) and the slow pathway (271 +/- 30 ms vs 258 +/- 27 ms, P < 0.01; 344 +/- 60 ms vs 295 +/- 50 ms, P < 0.005) likewise became significantly shortened. However, the ventriculoatrial blocking cycle length (349 +/- 94 ms vs 326 +/- 89 ms, NS) and effective refractory period of retrograde fast pathway (228 +/- 38 ms vs 240 +/- 80 ms, NS) remained unchanged after autonomic blockade. Pharmacological AB unveiling the intrinsic AV nodal physiology could result in the masking of AV nodal duality and the decreased inducibility of clinical AVNRT.

Atrial tachycardia, with its focus near the apex of Koch's triangle, may carry a potential risk of atrioventricular block during radiofrequency catheter ablation. The efficacy and safety of this procedure have never been addressed. The characteristics and catheter ablation results are reported for six patients with atrial tachycardia near the apex of Koch's triangle. All six patients were female aged 49.6 +/- 9.3 years (range 39-63). Organic heart disease was present in 3 (50%) of the 6 patients. The P wave in surface ECG had a mean axis of -28 degrees (range -90 degrees - +30 degrees) in the frontal plane. The catheter ablation was guided by activation sequence mapping. The energy was titrated from low power level. Atrial overdrive pacing was used to monitor the atrioventricular conduction should accelerated junctional rhythm occur. At the final successful ablation site, the local atrial activation was 41.8 +/- 9.1 ms before the P wave and His-bundle potential was present in 5 of the 6 patients. All patients had their atrial tachycardia eliminated without recurrence or heart block during a follow-up period of 17.7 +/- 8.5 months (range 6-30). In conclusion, atrial tachycardia near the apex of Koch's triangle has distinct clinical and electrophysiological features. Radiofrequency catheter ablation can be performed effectively. However, extreme care must be taken to prevent inadvertent atrioventricular block. Titrated energy application and continuous monitoring of atrioventricular conduction are mandatory.

The entrance site of the slow conduction zone was identified by entrainment study in an 18 year-old woman with verapamil-sensitive idiopathic left ventricular tachycardia. Radiofrequency catheter ablation at this site eliminated the tachycardia. The entrance site was at a mid-septal location and was more than 2 cm away from the exit site. Electrophysiologic findings suggested macroreentry in the Purkinje system as the mechanism of idiopathic left ventricular tachycardia.

Background: A recent genome-wide association study in individuals of European ancestry demonstrated a significant association of the single nucleotide polymorphism (SNP) rs13376333 in KCNN3 on chromosome 1q21 with lone AF, indicating a common genetic basis for AF. Objectives: We sought to replicate the association between SNP rs13376333 in KCNN3 and AF in the Taiwanese population. Methods: We conducted a case-control association study and genotyped SNP rs13376333 in 214 lone AF patients (58.3±11.4 years) versus 214 controls (57.7±13.2 years), and 322 structural AF patients (69.6±13.7 years) versus 322 controls (68.4±14.2 years). Results: The associations between SNP rs13376333 and structural or lone AF were significant. In lone AF group, the frequency of the minor allele of SNP rs13376333 was 8.6% compared with 3.0% in controls (allelic p