Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes.

BACKGROUND: Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial. The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus (DM). METHODS: In a double-blind, placebo-controlled trial, we randomized 100 type 2 DM patients to vitamin D supplement (5000 IU/day, n = 50) or placebo (controls, n = 50) for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilatation (FMD), circulating levels of endothelial progenitor cells (EPCs) and brachial-ankle pulse wave velocity, and metabolic parameter, high-sensitivity C-reactive protein (hsCRP) and oxidative stress markers were performed before and after the supplementation. RESULTS: After 12 weeks, vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [25(OH)D] concentration (treatment effect 34.7 ng/mL, 95% CI 26.4-42.9, P < 0.001) and serum ionized calcium (treatment effect 0.037 mmol/L, 95% CI 0.007-0.067, P = 0.018); decreased serum parathyroid hormone concentration (treatment effect -0.55 pmol/L, 95% CI -1.08 to -0.02, P = 0.042) compared to patients who received placebo. Nevertheless, vitamin D supplementation did not improve vascular function as determined by FMD, circulating EPC count or baPWV (all P > 0.05). Furthermore, hsCRP, oxidative stress markers, low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups (all P > 0.05). CONCLUSION: In patients with type 2 DM, 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress. CLINICAL TRIAL NUMBER: HKCTR-867, www.hkclinicaltrials.com.

Relevance of electrical remodeling in human atrial fibrillation: results of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial mechanisms of atrial fibrillation study.

BACKGROUND: In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. METHODS AND RESULTS: The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial enrolled 2580 patients receiving a dual-chamber pacemaker, who were older than the age of 65 and had a history of hypertension, but no history of AF. Serial noninvasive electrophysiological testing was performed over 2 years in a subgroup of 485 patients. There were no differences in the clinical characteristics between patients with and those without device-detected atrial tachyarrhythmias during the first year. Patients with atrial tachyarrhythmias had longer paced (153±29 versus 145±28 ms; P=0.046) and sensed (128±46 versus 118±25 ms; P=0.06) P-wave durations and were more likely to have AF induced during electrophysiological testing (23.5% versus 13.6%; P=0.03). They had similar corrected sinus node recovery times at 90 bpm (388±554 versus 376 ± 466 ms; P=0.86), atrial effective refractory periods at 90 bpm (250±32 versus 248±36 ms; P=0.70), and rate-adaptive shortening of the atrial effective refractory periods (14±13 versus 12±14 ms; P=0.11). There were no significant differences in the change in electrophysiological properties over 2 years between patients with and those without atrial tachyarrhythmias. CONCLUSIONS: Prolonged P-wave duration, but not differences in atrial effective refractory periods, was associated with the development of atrial tachyarrhythmias in pacemaker patients.

Effect of herbal consumption on time in therapeutic range of warfarin therapy in patients with atrial fibrillation.

It has been established that herbal intake affects the anticoagulation effects of warfarin, but the long-term impact on anticoagulation control is unclear. We sought to investigate the effect of concomitant herbal intake on anticoagulation control in patients with nonvalvular atrial fibrillation (AF) treated with warfarin. The effects of common herbs were determined by monitoring the international normalized ratio in 250 patients with AF (69 ± 10 years, 50% male). All the patients had been prescribed warfarin therapy for at least 6 months before enrollment, and their dietary intake, including the type and the frequency of common herbs, was recorded using a standardized questionnaire. Up to 50% of the patients reported consumption of foods with herbal ingredients, including garlic (80.4%), ginger (74.8%), green tea (50.4%), and papaya (55.2%) but rarely herbal drugs such as danshen (1.2%), dong guai (0.8%), fenugreek (1.2%), psyllium seed (0.4%), and ginseng (4%). Infrequent users (1 kind of herb for <4 times per week and nonusers) were more likely to have an international normalized ratio within the optimal therapeutic range (2.0-3.0) than frequent users (>1 kind of herb for ≥4 times per week) (58.1% vs 51.1%, P = 0.046). In conclusion, the patients with AF treated with warfarin had little knowledge about the potential interaction of herbal substances in foods with warfarin. The patients who consumed common herbs at least 4 times per week had suboptimal anticoagulation control with warfarin.

Dietary intake of phytoestrogen is associated with increased circulating endothelial progenitor cells in patients with cardiovascular disease.

Endogenous estrogen is known to positively influence the level and functionality of endothelial progenitor cells (EPC). However, the effect of phytoestrogen on EPC is unknown. Isoflavone is a major component of phytoestrogen. This study aims to investigate if the intake of isoflavone has any impact on the circulating level of EPC. We studied 102 consecutive patients (mean age: 66.5 ± 9.5 years, 78% male, all female post-menopausal) with cardiovascular disease (atherothrombotic stroke 62%, coronary artery disease 38%). Circulating levels of CD133(+) EPC were determined by flow cytometry. Non-invasive pulse wave velocity (PWV) was measured. Long-term intake of isoflavone was determined by a validated food frequency questionnaire. Isoflavone intake was positively associated with circulating CD133(+) EPC (r = 0.31, p = 0.001). Patients with circulating CD133(+) EPC <10th percentile had significantly lower isoflavone intake than patients with CD133(+)EPC ≥10th percentile (4.6 ± 3.7 mg/day versus 19.3 ± 30.2 mg/day, p < 0.001). A significant overall linear trend of circulating EPC across increasing tertiles of isoflavone intake was observed (p = 0.004). Adjusted for potential confounders, increased isoflavone intake from the 1st to the 3rd tertile independently predicted increased circulating CD133(+) EPC level by 221 cells/µl (95%CI: 71.4 to 369.8, relative increase 160%, p = 0.004). Gender was not a significant factor (p > 0.05). Furthermore, circulating CD133(+) EPC <10th percentile was independently predictive of increased PWV by 261.7 cm/s (95% CI: 37.1 to 486.2, p = 0.024). The study demonstrated that circulating EPC increased by more than one fold in patients with cardiovascular disease who had higher intake of isoflavone, suggesting that isoflavone may confer vascular protection through enhanced endothelial repair.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

AIMS: Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 µg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). CONCLUSION: In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD.

Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium.

BACKGROUND: Cellular replacement strategies using embryonic stem cells (ESCs) and their cardiac derivatives are emerging as novel experimental therapeutic paradigms for the treatment of post-myocardial infarction (MI) left ventricular (LV) dysfunction; however, their potential proarrhythmic risk remains unclear. OBJECTIVE: The purpose of this study was to investigate the functional effect and proarrhythmic risk of ESC transplantation in a mouse model of MI. METHODS: We compared the functional effects and proarrhythmic risk of direct intramyocardial transplantation of 3 × 10(5) undifferentiated mouse ESCs (MI+ESC group, n = 33) and mouse ESC-derived cardiomyocytes (MI+ESC-CM group, n = 40) versus culture medium (MI group, n = 33) at the infarct border zone in a mouse model of acute MI. LV performance was assessed with serial cardiac magnetic resonance imaging (MRI) at 1 and 3 week(s) post-MI, and invasive LV pressure measurement was assessed (dP/dt) at 4 weeks before sacrifice for histological examination. Furthermore, electrophysiological study was also performed in another set of animals in each group (n = 24) to assess for proarrhythmias after transplantation. RESULTS: In vitro cellular electrophysiological study demonstrated that ESC-CMs exhibit arrhythmogenesis including automaticity, lengthened action potential duration, and depolarized resting membrane potential. At 4 weeks, the MI+ESC-CM group (21/40, 53%) had a higher mortality rate compared with those in the MI group (10/33, 30%, P = .08) and in the MI+ESC group (7/33, 21%, P = .012). Electrophysiological study showed a significantly higher incidence of inducible ventricular tachyarrhythmias in the MI+ESC-CM group (13/24, 54%) compared with in the MI group (6/24, 21%, P = .039) and in the MI+ESC group (5/24, 21%, P = .017). Cardiac MRI showed similar improvement in LV ejection fraction in the MI+ESC and MI+ESC-CM groups compared with in the MI group at 1 week (27.5% ± 3.8%; 30.3% ± 5.2% vs. 12.4% ± 1.4%; P < .05) and 3 weeks (29.8% ± 3.9%; 27.0% ± 4.8% vs. 10.6% ± 2.8%; P < .05) post-MI, respectively. Furthermore, invasive hemodynamic assessment at 4 weeks showed significant similar improvement in LV +dP/dt in the MI+ESC (2,644 ± 391 mmHg/s, P < .05) and MI+ESC-CM groups (2,539 ± 389 mmHg/s; P < .05) compared with in the MI group (2,042 ± 406 mmHg/s). CONCLUSIONS: Our results demonstrate that transplantation of undifferentiated ESCs and ESC-CMs provides similar improvement in cardiac function post-MI. However, transplantation of ESC-CMs is associated with a significantly higher prevalence of inducible ventricular tachyarrhythmias and early mortality than transplantations with ESCs.

Triiodothyronine promotes cardiac differentiation and maturation of embryonic stem cells via the classical genomic pathway.

Embryonic stem cells (ESCs) can differentiate into functional cardiomyocytes and thus represent a promising cell source for cardiac regenerative therapy. Nevertheless, the therapeutic application of ESC-derived cardiomyocytes is limited by the low efficacy of the current protocol for cardiac differentiation and their immature phenotypes. Although thyroid hormone is essential for normal cardiac development and function, its role in the cardiac differentiation of ESCs, as well as the maturation of ESC-derived cardiomyocytes, remains unclear. In this study, we examined the cardiac differentiation of murine ESCs in the presence of T(3) for 7 d using flow cytometry, RT-PCR, cellular electrophysiology study, and confocal calcium imaging. Compared with control conditions, T(3) supplementation increased the number of ESC-derived cardiomyocytes and was accompanied by up-regulation of a panel of cardiac markers, including Nkx2.5, myosin light chain-2V, as well as alpha- and beta-myosin heavy chain. More importantly, electrophysiological study revealed that ESC-derived cardiomyocytes exhibited more adult-like phenotypes after T(3) supplementation based on action potential characteristics. They also exhibited more adult-like calcium homeostasis properties. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase-2a and ryanodine receptor-2 expression. In addition, the classical (genomic) pathway was shown to be involved in T(3)-induced cardiac differentiation of ESCs. Our results show that T(3) supplementation promotes cardiac differentiation of ESCs and enhances maturation of electrophysiological, as well as calcium homeostasis, properties of ESC-derived cardiomyocytes.

Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke.

AIMS: To investigate the effect of oral isoflavone supplement on vascular endothelial function in patients with established cardiovascular disease. METHODS AND RESULTS: A randomized, double-blinded, placebo-controlled trial was performed to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence interval (95% CI) 0.1-2.0, P = 0.035]. Adjusted for baseline differences in FMD, isoflavone treatment was independently associated with significantly less impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13-0.80, P = 0.014). The absolute treatment effect of isoflavone on brachial FMD was inversely related to baseline FMD (r = -0.51, P < 0.001), suggesting that vasoprotective effect of isoflavone was more pronounced in patients with more severe endothelial dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a significant decrease in serum high-sensitivity (hs)-C-reactive protein level (treatment effect -1.7 mg/L, 95% CI -3.3 to -0.1, P = 0.033). Nevertheless, isoflavone did not have any significant treatment effects on nitroglycerin-mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose and insulin, haemoglobin A1c, and oxidative stress as determined by serum superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05). CONCLUSION: This study demonstrated that 12 week isoflavone treatment reduced serum hs-C-reactive protein and improved brachial FMD in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status. These findings may have important implication for the use of isoflavone for secondary prevention in patients with cardiovascular disease, on top of conventional interventions.

Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs.

BACKGROUND: The development of atrium-selective antiarrhythmic agents is a current strategy for inhibiting atrial fibrillation (AF). The present study investigated whether the natural flavone acacetin from the traditional Chinese medicine Xuelianhua would be an atrium-selective anti-AF agent. METHODS AND RESULTS: The effects of acacetin on human atrial ultrarapid delayed rectifier K(+) current (I(Kur)) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed I(Kur) and the transient outward K(+) current (IC(50) 3.2 and 9.2 mumol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine-activated K(+) current; however, it had no effect on the Na(+) current, L-type Ca(2+) current, or inward-rectifier K(+) current in guinea pig cardiac myocytes. Although acacetin caused a weak reduction in the hERG and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, it did not prolong the corrected QT interval in rabbit hearts. In anesthetized dogs, acacetin (5 mg/kg) prolonged the atrial effective refractory period in both the right and left atria 1 to 4 hours after intraduodenal administration without prolongation of the corrected QT interval, whereas sotalol at 5 mg/kg prolonged both the atrial effective refractory period and the corrected QT interval. Acacetin prevented AF induction at doses of 2.5 mg/kg (50%), 5 mg/kg (85.7%), and 10 mg/kg (85.7%). Sotalol 5 mg/kg also prevented AF induction (60%). CONCLUSIONS: The present study demonstrates that the natural compound acacetin is an atrium-selective agent that prolongs the atrial effective refractory period without prolonging the corrected QT interval and effectively prevents AF in anesthetized dogs after intraduodenal administration. These results indicate that oral acacetin is a promising atrium-selective agent for the treatment of AF.

First human demonstration of cardiac stimulation with transcutaneous ultrasound energy delivery: implications for wireless pacing with implantable devices.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of a novel technology that uses energy transfer from an ultrasound transmitter to achieve cardiac stimulation without the use of a pacing lead in humans. BACKGROUND: To overcome the limitations of pacemaker leads, a new technology enabling stimulation without the use of a lead is desirable. METHODS: A steerable bipolar electrophysiology catheter incorporating a receiver electrode into the tip and circuitry to convert ultrasound energy to electrical energy was inserted transvenously into the heart. An ultrasound transmitting transducer was placed on the chest wall with ultrasound gel. Ultrasound energy was amplitude-adjusted and transmitted at 313 to 385 kHz. The output waveform of the receiver electrode was monitored while the transmitter was moved on the chest wall to target the receiver. The ultrasound transmission amplitude was limited to a mechanical index of 1.9, the maximum allowed for ultrasound imaging systems. Ultrasound-mediated pacing with minimum voltage but consistent capture was obtained for 12 s. RESULTS: Twenty-four patients (48 +/- 12 years) were tested during or after completion of clinical electrophysiology procedures. A total of 80 pacing sites were tested (mean 3.3 sites/patient): 12 right atrial, 35 right ventricular, and 33 left ventricular (31 endocardial) sites. The transmit-to-receive distance was 11.3 +/- 3.2 cm (range 5.3 to 22.5 cm). Ultrasound-mediated pacing was achieved at all 80 test sites, with consistent capture at 77 sites. The mechanical index during pacing was 0.5 +/- 0.3 (range 0.1 to 1.5). The mean ultrasound-mediated capture threshold was 1.01 +/- 0.64 V. There was no adverse event related to ultrasound pacing. No patient experienced discomfort during pacing. CONCLUSIONS: The feasibility and safety of pacing usng ultrasound energy has been shown acutely.

Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium.

OBJECTIVE: To determine the optimal bone marrow (BM) cell types, and their potential mechanisms of action for neovascularization in chronic ischaemic myocardium. METHODS AND RESULTS: The functional effects, angiogenic potential and cytokine expression of direct intramyocardial implantation of autologous BM CD31-positive endothelial progenitor cells (EPC, n=9), BM mononuclear cells (MNCs, n=9), and saline (n=9) were compared in a swine model of chronic ischaemic myocardium. Autologous BM cells were harvested and catheter-based electromechanical mapping-guided direct intramyocardial injection was performed to target ischaemic myocardium. After 12 weeks, injection of BM-MNC resulted in significant improvements in left ventricular dP/dt (+21+/-8%, P=0.032), left ventricular pressure (+17+/-4%, P=0.048) and regional microsphere myocardial perfusion over ischaemic endocardium (+74+/-28%, P<0.05) and epicardium (+73+/-29%, P<0.05). No significant effects were observed following injection of BM-EPC or saline. Capillary density (1132+/-69 versus 903+/-44 per mm(2), P=0.047) and expression of mRNA of vascular endothelial growth factor (VEGF, 32.3+/-5.6 versus 13.1+/-3.7, P<0.05,) and angiopoietin-2 (23.9+/-3.6 versus 13.7+/-3.1, P<0.05) in ischaemic myocardium was significantly greater in the BM-MNC group than the saline group. The capillary density in ischaemic myocardium demonstrated a significant positive correlation with VEGF expression (r=0.61, P<0.001). CONCLUSION: Catheter-based direct intramyocardial injection of BM-MNC enhanced angiogenesis more effectively than BM-EPC or saline, possibly via a paracrine effect, with increased expression of VEGF that subsequently improved cardiac performance of ischaemic myocardium.

Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes.

Voltage-gated cardiac fast sodium channel current (I(Na)) plays a critical role in the initiation and propagation of the myocardial action potential, and regulation of cardiac I(Na) by protein tyrosine kinases (PTKs) is not well documented, though it is known that ion channels are among the targets of PTKs. The present study was therefore designed to investigate whether/how cardiac I(Na) was modulated by PTKs in guinea pig ventricular myocytes using whole-cell patch clamp and immunoprecipitation and Western blotting approaches. It was found that cardiac I(Na) was enhanced by epidermal growth factor (EGF), and the effect was antagonized by the selective epidermal growth factor receptor (EGFR) kinase inhibitor tyrphostin AG556 while potentiated by orthovanadate (a protein tyrosine phosphatase (PTP) inhibitor). In addition, AG556 inhibited, while orthovanadate increased I(Na), and the inhibition of I(Na) by AG556 was antagonized by orthovanadate. Immunoprecipitation and Western blotting analysis demonstrated that tyrosine phosphorylation level of cardiac sodium channels was enhanced by EGF or orthovanadate, and reduced by AG556. The AG556-induced reduction of phosphorylation level was significantly reversed by orthovanadate. Our results demonstrate the novel information that EGFR kinase enhances, and PTPs reduce native cardiac I(Na) in guinea pig ventricular myocytes.

Prevalence, awareness, treatment, and control of hypertension: United States National Health and Nutrition Examination Survey 2001-2002.

The prevalence, awareness, treatment, and control of hypertension in the United States are analyzed using the National Health and Nutrition Examination Survey (NHANES) database covering the period 1988-2002. Mean body mass index was 26.1+/-0.1 kg/m2 in 1988-1991 and 27.9+/-0.2 kg/m2 in 2001-2002 (p < 0.001). In the same period, the prevalence of diabetes mellitus increased from 5.0% to 6.5% (p = 0.03). Diastolic blood pressure was 73.3+/-0.2 mm Hg in 1988-1991 and 71.6+/-0.4 mm Hg in 2001-2002 (p < 0.001). Among the 18-39 years and 60 years and older age groups, the prevalence of hypertension increased significantly since 1988-1991. Multiple regression shows age, body mass index, and being non-Hispanic black were significantly associated with hypertension. In the period 1988-2002, the percentage receiving treatment and the percentage with blood pressure controlled increased significantly. In 2001-2002, significantly more people with hypertension and diabetes reached a blood pressure target of <130/85 mm Hg. Overall, the control rates were low, especially among middle-aged Mexican-American men (8%).

Transvenous cryoablation reduces platelet activation during pulmonary vein ablation compared with radiofrequency energy in patients with atrial fibrillation.

BACKGROUND: Radiofrequency (RF) ablation procedures for atrial fibrillation (AF) are associated with potential risks of thromboembolism, which may be minimized by the use of cryoablation that preserves the integrity of endocardium. The objective of this study was to compare the thrombogenic potential of transvenous cryoablation versus RF ablation during pulmonary vein (PV) isolation. METHODS AND RESULTS: Thirty consecutive patients with paroxysmal AF were randomized to undergo segmental PV isolation procedure using 4-mm tip RF ablation (n = 15) or cryoablation (CryoCor, San Diego, CA, USA) (n = 15). Blood samples were drawn after sheath insertion (baseline), after transseptal puncture, before ablation (after heparin administration), and after isolation of a superior PV. Activation of coagulation was measured with plasma levels of prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), and platelets by plasma level of beta-thromboglobulin (beta-TG) and flow cytometric enumerating of P-selectin (CD62)-positive platelets. In both groups, the plasma level of beta-TG, F1 + 2, and TAT were elevated after sheath insertion. The percentage changes in plasma level of beta-TG, F1 + 2, and TAT and CD41/62-positive platelets from baseline after transseptal puncture and before ablation were similar (P > 0.05). However, the percentage changes in CD62-positive platelets from baseline were significantly higher in patients treated with RF ablation (82 +/- 20%) than with cryoablation (22 +/- 14%, P = 0.02), although their plasma levels of beta-TG, F1 + 2, and TAT were not different (P > 0.05). CONCLUSIONS: Significant platelet and coagulation activations were observed during PV ablation procedures, and heparin administration only prevented activation of coagulation but not platelets. Persistent platelets activation was observed during RF energy application, but not during cryoablation.

Inappropriate implantable cardioverter defibrillator shock from a transcutaneous muscle stimulation device therapy.

Inappropriate shock from implantable cardioverter defibrillator (ICD) may result from external electromagnetic interference (EMI), especially for unipolar ventricle sensing. Previous case reports and small in-vitro safety study suggested that endocardial bipolar lead system may be immune from EMI resulting from transcutaneous electrical neuromuscle stimulation (TENS) therapy. This report presents an unusual case of inappropriate discharge in a patient with ICD of endocardial bipolar lead system, receiving TENS from a commercially available device.

Methods for testing automatic mode switching in patients implanted with DDD(R) pacemakers.

The assessment of automatic mode switching (AMS) algorithms is impossible in vivo, due to a low chance of seeing the patient at the onset of a spontaneous episode of atrial fibrillation (AF). As the induction of AF to test AMS has clinical concerns, three alternative and non-invasive techniques may be proposed for this purpose: myopotentials, chest wall stimulation, and an external supraventricular arrhythmia simulator. The first method is simple and does not require additional equipment, even though in some patients adequate signals cannot be generated with a soft effort such as handgrip or hand compression. The main advantage of the chest wall stimulation method is the possibility that it be performed in every implanting center, since it is based on the use of standard devices for cardiac stimulation. The method based on the external supraventricular arrhythmia simulator allows the most detailed of the ECG traces, but it needs a dedicated electronic device.

Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles.

OBJECTIVES: This study was designed to determine whether ionic currents in right ventricular myocytes from explanted human transplant recipient hearts are related to right ventricular histopathology and function. BACKGROUND: Cardiac action potential duration (APD) is prolonged in ventricular tissues/cells from patients with heart failure, but the ionic mechanisms are not well documented. METHODS: Membrane currents and transmembrane action potentials in myocytes from right ventricular epicardium of explanted human hearts were recorded using whole-cell patch clamp technique. Data from cells from right ventricles with severe histologic and functional abnormalities (abnormal histology group [AH]) and from right ventricles with preserved histology and function (relatively normal histology group [RNH]) were compared. RESULTS: We found that APD at 50% (APD(50)) and 90% repolarization (APD(90)) were significantly longer in AH cells than in RNH cells. Early afterdepolarizations (EADs) were observed in 20% of AH cells and none of the RNH cells. Inwardly rectifying K(+) current (I(K1)) was decreased (both inward and outward components). Both transient outward K(+) current (I(to1)) and slowly delayed rectifier K(+) current (I(Ks)) were down-regulated in AH cells. L-type Ca(2+) (I(Ca.L)) was not altered in AH cells. CONCLUSIONS: I(K1), I(to1), and I(Ks) are down-regulated in AH cells of human heart failure. This down-regulation contributes to APD prolongation that favors the occurrence of arrhythmogenic EADs and suggests a link between human cardiac histopathologic/functional abnormalities and arrhythmogenic ionic remodeling.

Regression of left ventricular hypertrophy after treatment of hypertension: comparison of directed M-echocardiography with magnetic resonance imaging in quantification of serial mass changes.

BACKGROUND: This study sought to validate the reliability of serial echocardiographic measurements in detecting left ventricular (LV) hypertrophy regression by using magnetic resonance imaging (MRI) as a reference standard. METHODS AND RESULTS: We studied a small population (n = 20) of patients enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) trial for evaluating LV hypertrophy regression. LV mass was measured by both echocardiography and MRI at baseline and after 1 year. As compared with baseline, systolic and diastolic blood pressures were significantly decreased after 1 year (all P <.05). Echocardiographic technique showed an overestimation of LV mass by 27.6 g at baseline (P =.005) and by 37.1 g after 1 year (P <.001), and there were wide 95% limits of agreement (+/-36.0 g at baseline; and +/-27.6 g after 1 year) when compared with MRI measurement. Significant changes of LV mass from baseline of -20 +/- 22 g (P<.01) and -29 +/- 19 g (P <.01) were detected by using echocardiography and MRI after 1 year, respectively (P =.02), and there were similarly wide limits of agreement for change in LV mass (+/-24.2 g). CONCLUSIONS: Despite the use of careful methodology, echocardiographic measurement of LV mass at a single time point or for serial studies resulted in significant variation in LV mass estimates from measurement using MRI.

Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology.

INTRODUCTION: Ivabradine is a heart rate-lowering agent that selectively inhibits the pacemaker current, I(f), in the sinoatrial node. The objective of this study was to evaluate the effects of a single intravenous administration of ivabradine on cardiac electrophysiological parameters in patients with normal baseline electrophysiology. The safety profile of ivabradine was also investigated. STUDY DESIGN: This was an open-label, single-dose, non-controlled study conducted at one centre. Patients received a single dose of ivabradine (0.2 mg/kg) intravenously as a slow bolus over 15 seconds. Electrophysiological investigations, after catheter ablation for cardiac dysrhythmia, were performed at baseline and 30 minutes and 1 hour after drug administration. Electrode catheters were introduced and advanced to the right atrium, the bundle of His and the right ventricular apex of the heart. Electrophysiological parameters assessed included heart rate, QT interval, corrected QT interval (QTc), PR interval, sinoatrial conduction time, sinus node recovery time, and right atrial and ventricle refractory periods. Changes in electrophysiological parameters over time were assessed using one-way analysis of variance. In the case of a significant time effect, the Newman-Keuls procedure was used for comparison. PATIENTS: A total of 14 patients, 12 male and 2 female, aged 18-75 years were included in the study. The arrhythmia requiring catheter ablation was atrioventricular (AV) excitation in seven patients, paroxysmal supraventricular tachycardia in five patients, atrial fibrillation and flutter in one patient, and cardiac dysrhythmia in one patient. All patients had normal electrophysiology at baseline. RESULTS: Mean heart rate decreased significantly with ivabradine by 12.9 beats/min at 30 minutes and 14.1 beats/min at 1 hour. The mean QT interval increased but QTc showed no significant change from baseline. The PR and QRS intervals were unchanged. The right atrial and right ventricle refractory periods showed no significant change from baseline. The measured QT interval and the sinus node recovery time were increased. There were no clinically relevant changes in any other major electrophysiological parameters. Ivabradine was well tolerated and no serious adverse events occurred. CONCLUSION: A single intravenous dose of ivabradine had a significant heart rate-lowering effect, observed at 30 minutes and 1 hour after administration. Ivabradine did not prolong QTc or modify conductivity and refractoriness of the atrium, AV node, His-Purkinje system and ventricles, or repolarisation duration. These results confirm the action of ivabradine as a specific heart rate-lowering agent.