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The antioxidant N-2-mercaptopropionyl glycine attenuates left ventricular hypertrophy in in vivo murine pressure-overload model.

OBJECTIVES In order to identify the role of reactive oxygen species (ROS) in cardiac hypertrophy, we examined the effect of N-2-mercaptopropionyl glycine (MPG) on cardiac hypertrophy. BACKGROUND Recent in vitro studies have suggested that ROS play an important role as a second messenger in cardiac hypertrophy. It was therefore thought to be of particular value to examine the relevance of studies using in vitro models for cardiac hypertrophy in an in vivo setting. METHODS The transverse thoracic aorta in mice was constricted, and MPG (100 mg/kg) was infused intraperitoneally twice daily. The animals were assessed seven days after the operation for hemodynamic functions, oxidative stress and antioxidative enzyme activities. RESULTS Banding of the transverse aorta in mice resulted in an increase in the ratio of heart weight to tibia length and the appearance of an endogenous atrial natriuretic factor messenger ribonucleic acid (mRNA) seven days postoperatively. Administration of MPG significantly attenuated the hypertrophic responses induced by pressure overload. Cardiac hypertrophy was accompanied by increases in heme oxygenase-1 mRNA expression and lipid peroxidation, which was eliminated by the treatment with MPG. Pressure overload led to increases in antioxidant enzyme activities, such as superoxide dismutase and glutathione peroxidase, but not catalase, activity. CONCLUSIONS Our results indicated that oxidative stress was increased in our model and that it plays an important role in the development of cardiac hypertrophy.

Cardiac-specific overexpression of a high Ca2+ affinity mutant of SERCA2a attenuates in vivo pressure overload cardiac hypertrophy

In cardiomyocytes, calcium plays important roles as a signal in cardiac hypertrophy and contraction‐relaxation cycling. Elevation of Ca2+ concentration in myoplasm is associated with the onset and progression of hypertrophy as well as the enhancement of contractility. The cardiac Ca2+ ATPase (SERCA2a) of the sarcoplasmic reticulum plays a dominant role in lowering cytoplasmic calcium levels during relaxation and is regulated by phospholamban (PLN). To examine whether the modulation of SERCA2a activity results in the attenuation of cardiac hypertrophy and enhancement of contractility, we generated transgenic mice (TG) overexpressing a high calcium affinity SERCA2a mutant (K397/400E), lacking a functional association with PLN. In the TG hearts, the apparent affinity of SERCA2a for Ca2+ significantly increased compared with their nontransgenic littermate controls. The TG showed increased contraction and relaxation, with increases in the amplitude of Ca2+ transient and rapid Ca2+ decay. Upon induction of pressure overload by transverse aortic constriction, the TG developed less cardiac hypertrophy than littermate controls did. The activation of Ca2+‐sensitive protein kinase C by pressure overload was significantly attenuated in the TG hearts. Our findings indicate an association of SERCA2a activity with cardiac hypertrophy and thus a new therapeutic target for the prevention and treatment of cardiac hypertrophy.

Marshall vein as arrhythmogenic source in patients with atrial fibrillation : Correlation between its anatomy and electrophysiological findings

Background: Atrial fibrillation (AF) may originate from catecholamine‐sensitive vein of Marshall (VOM) or its ligament in addition to pulmonary veins (PVs). The anatomy of VOM and its relation to arrhythmogenic foci in the left atrium are unknown. We studied the anatomy of VOM and its relation to foci in patients with AF.

Clinical Implications of Distal Embolization During Coronary Interventional Procedures in Patients With Acute Myocardial Infarction: Quantitative Study With Doppler Guidewire

OBJECTIVES This study sought to investigate the timing and amount of embolic particles generation during the percutaneous coronary intervention (PCI) procedure and studied the relationship between embolic burden and coronary blood flow and myocardial damage. BACKGROUND Distal embolization is a major complication of PCI. The Doppler guidewire (DGW) can detect the embolic particles as high-intensity transient signals (HITS) during the PCI procedure. METHODS We prospectively studied 37 patients with acute myocardial infarction (MI). Under monitoring with the DGW, we performed first and second balloon angioplasty, followed by stenting and post-high-pressure dilatation. Left ventricular ejection fraction (LVEF) (%) and regional wall motion (RWM) (standard deviation/chord) were measured on days 1 and 22. RESULTS The HITS were detected in 35 of 37 patients. The number of HITS was the greatest after stenting (16 +/- 18) followed by first balloon inflation (5 +/- 4). There was a significant correlation between the total number of HITS and the corrected Thrombolysis In Myocardial Infarction frame count (r = 0.52, p = 0.003) and a significant weak inverse correlation between the total number of HITS and changes in LVEF and RWM (r = 0.37, p = 0.03 and r = 0.35, p = 0.04, respectively). CONCLUSIONS Distal embolization is common during PCI in patients with acute MI, and the majority of HITS were observed after stenting. An increase in the total number of HITS is associated with reduced coronary blood flow, and is weakly associated with poor recovery of left ventricular function.

Trigger-Based Mechanism of the Persistence of Atrial Fibrillation and Its Impact on the Efficacy of Catheter Ablation

Background— We investigated the possibility that a frequent trigger action might play a role in the development of persistent atrial fibrillation (PeAF) and the presence of a substrate. Methods and Results— In 263 consecutive patients who underwent catheter ablation (CA) for PeAF, electric cardioversion was performed at the beginning of the procedure to determine the presence or absence of an immediate recurrence of AF (IRAF). We defined an IRAF as a reproducible AF recurrence within 90 s after restoration of sinus rhythm by electric cardioversion. We performed a mean±SD of 1.3±0.5 sessions of CA, including pulmonary vein isolation and ablation of the premature atrial contractions that triggered the IRAF (IRAF triggers), and observed the patients for 17 (10–27) months. An IRAF was observed in 70 patients (27%), but we could not ablate the IRAF triggers in 16 (23%) of these IRAF patients. The recurrence rate of PeAF was higher in patients with an unsuccessful IRAF trigger ablation than in those with successful IRAF trigger ablation (63% versus 11%; P<0.001). A multivariable analysis also revealed that an unsuccessful IRAF trigger ablation was 1 of the independent predictors of recurrent PeAF (odds ratio, 10.9; 95% CI, 3.4–36.7). Conclusions— In the PeAF patients with an IRAF, successful elimination of the IRAF triggers, in addition to pulmonary vein isolation, resulted in a successful CA. These results imply that such triggers play a major role in the AF persistence in these PeAF patients.

Nicorandil Treatment in Patients With Acute Myocardial Infarction

BACKGROUND It is controversial as to whether nicorandil would have cardioprotective effects in patients with acute myocardial infarction (AMI) who are undergoing reperfusion therapy. A meta-analysis was performed to study the impacts of nicorandil on functional outcomes after AMI. METHODS AND RESULTS Randomized prospective cohort or retrospective cohort publications were identified up to October 2007 by means of a computer search of MEDLINE and Google Scholar databases. Two reviewers checked the quality of the studies and extracted data regarding patient and disease characteristics, study design, functional parameters such as Thrombolysis In Myocardial Infarction (TIMI) flow grade after reperfusion, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI). Seventeen studies were included for the meta-analysis in this study. Nicorandil treatment reduced the incidence of TIMI flow grade < or =2 in 1,337 patients of 10 studies (risk ratio 0.63; 95% confidence interval (CI) 0.44 to 0.91). While no beneficial effect was observed on the peak creatine kinase value, nicorandil treatment was associated with greater LVEF (by 3.7%, 95%CI 1.8 to 5.7%), and lower LVEDVI (by 8.8 ml/kg, -14.4 to -3.3 ml/kg) in 905 patients of 11 studies. CONCLUSIONS The meta-analysis demonstrated that nicorandil treatment adjunctive to reperfusion therapy has beneficial effects on microvascular function and on functional recovery after AMI.

Quantitative Assessment of Fluid Accumulation Using Bioelectrical Impedance Analysis in Patients With Acute Decompensated Heart Failure

BACKGROUND Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF. METHODSANDRESULTS Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge. We also predicted optimal ECW volume using original equations based on data from 60 control subjects without the signs of HF. Measured/predicted (M/P) ratio of ECW in ADHF patients was observed to decrease from 1.26±0.25 to 1.04±0.17 during hospitalization (P<0.001). The amount of ECW volume reduction was significantly correlated with reduction in body weight (r=0.766, P<0.001). On multivariate analysis, higher M/P ratio of ECW at discharge was associated with increased risk of ADHF readmission or cardiac death within 6 months after discharge. CONCLUSIONS Multi-frequency BIA-measured ECW was found to offer valuable information for analyzing the pathophysiology of ADHF, and may be a useful guide in the management of this disease.

Detection and quantification of embolic particles during percutaneous coronary intervention to stable plaque: It correlates to coronary flow dynamics and myocardial damage

Objectives: We detected embolic particles liberated from plaque during percutaneous coronary intervention (PCI) as high‐intensity transient signals (HITS) with a Doppler guidewire and studied their impact on coronary flow dynamics and the myocardium in patients with stable angina pectoris. Background: These embolic particles during PCI may cause myocardial injury. However, this was difficult to confirm because it was impossible to detect embolic particles. Methods: We performed balloon angioplasty followed by stenting in 31 patients while monitoring coronary flow velocity. After PCI, we measured average peak velocity at baseline and after infusion of adenosine 5′‐triphosphate to calculate coronary flow velocity reserve (CFVR) and coronary resistance index (CRI). In patients with PCI to the left coronary artery (n = 21), we calculated relative CFVR as the ratio of CFVR in the target vessel to that in the reference vessel. We measured cardiac troponin T (cTnT) the day after PCI. Results: HITS were detected in 27 (87%) of 31 patients and the majority were observed after stenting. The total number of HITS was correlated with CRI (r = 0.36, P = 0.049) or relative CFVR (r = 0.65, P = 0.0036) but not with CFVR (r = 0.048, P = 0.82). Thirteen patients showed elevated cTnT (range, 0.05–0.31 ng/ml) and the total number of HITS was greater in those with elevated cTnT than in those without elevated cTnT (24 ± 9 vs. 10 ± 7, P = 0.0007). Conclusions: Embolic particles are frequently observed during PCI to stable plaque and the majority are liberated after stenting. There appears to be a quantitative relationship between amounts of HITS and coronary microvessel dysfunction and minor myocardial injury.

Prediction of distal embolization during percutaneous coronary intervention for unstable plaques with grayscale and integrated backscatter intravascular ultrasound

We performed microscopic examination of the debris collected by a distal protection device and investigated the usefulness of grayscale and integrated backscatter intravascular ultrasound (IB‐IVUS) for the prediction of distal embolization during percutaneous coronary intervention (PCI) in cases of unstable angina.

Effect of embolic particles during coronary interventional procedures on regional wall motion in patients with stable angina pectoris.

Microembolization during percutaneous coronary intervention (PCI) causes minor myocardial injury, and a Doppler guidewire can detect embolic particles as high-intensity transient signals (HITS). The present study investigated the effect of microembolization during PCI on regional wall motion using a Doppler guidewire and myocardial strain analysis. We performed PCI to the left anterior descending coronary artery in 25 patients (18 men and 7 women, 68 ± 8 years old) with stable angina pectoris. Coronary flow spectrums were obtained with a Doppler guidewire to count the total number of HITS throughout the PCI procedures. On the days before and after PCI, we recorded echocardiography and measured the longitudinal peak systolic strain, peak strain rate, and early diastolic strain rate in the left anterior descending territory using a 2-dimensional speckle tracking method. PCI was successfully performed, and 10 ± 6 HITS (range 0 to 22, median 9) were recognized during PCI. The echocardiographic study showed no visible wall motion abnormalities in the left anterior descending territory either after or before PCI. In cases in which the total number of HITS was ≥10, the peak systolic strain, peak strain rate, and early diastolic strain rate worsened on the day after PCI compared with those on the day before PCI (p <0.01). The rates of change in peak systolic strain and early diastolic strain rate, defined as the ratios of those parameters after PCI to those before PCI, had modest to strong inverse correlations with the total number of HITS (R(2) = 0.35 and R(2) = 0.46, respectively). In conclusion, periprocedural microembolization during PCI reduces subclinical cardiac function in patients with stable angina pectoris.