Kotaro Arai

Cardiomyocyte triglyceride accumulation and reduced ventricular function in mice with obesity reflect increased long chain Fatty Acid uptake and de novo Fatty Acid synthesis.

A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients. Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression in male C57BL/6J control mice and three obesity groups: similar mice fed a high-fat diet (HFD) and db/db and ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights and fatty livers. By echocardiography, ejection fraction (EF) and fractional shortening (FS) of left ventricular diameter during systole were significantly reduced. The Vmax for saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations. Vmax also correlated with expression of genes for the cardiac fatty acid transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn, Scd1) were also upregulated. Ten oxidative phosphorylation pathway genes were downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might explain the decreased contractile function in obese hearts.

Correlation between left atrial appendage morphology and flow velocity in patients with paroxysmal atrial fibrillation

AIMS Reduction of left atrial appendage (LAA) flow velocity (FV) is a risk factor for thrombus formation and increases the risk of stroke in patients with atrial fibrillation (AF). Furthermore, LAA morphology is correlated with stroke in patients with AF. The aim of this study was to correlate LAAFV with LAA morphology in patients with AF. METHODS AND RESULTS We studied 96 patients (age 59.0 ± 10.2 years, 75% male) referred for radiofrequency catheter ablation for paroxysmal AF. All patients underwent computed tomography (CT) and transthoracic and transoesophageal echocardiography during sinus rhythm. LAA morphology was classified as one of the four types (chicken wing, windsock, cactus, and cauliflower) on CT images. There were significant differences in LAAFV among LAA morphologies (chicken wing 73.7 ± 21.9 cm/s, windsock 61.9 ± 19.6 cm/s, cactus 55.3 ± 14.1 cm/s, cauliflower 52.7 ± 18.1 cm/s, P = 0.008). Post hoc multiple comparisons showed that LAAFV was higher in patients with chicken wing than in those with cactus (P = 0.006, vs. chicken wing) and cauliflower (P = 0.006, vs. chicken wing), but not with windsock (P = 0.102). After adjustment for clinical and LAA anatomical covariates (orifice area, volume, and trabeculation), multiple linear regression analyses revealed that LAA morphology was an independent determinant of LAAFV [chickens wing: standardized partial regression coefficients (β) = 0.317, P = 0.0014; windsock: β = 0.303, P = 0.038]. CONCLUSION LAA morphology is a significant determinant of LAAFV, suggesting an underlying mechanism for the association between LAA morphology and embolic events.

Single administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve: a transthoracic Doppler echocardiography study

HMG-CoA reductase inhibitors (statins) have been shown to improve the endothelial function by lowering lipids. Recent studies also suggest a direct impact of statins on the vascular wall. We assessed the rapid effect of cerivastatin on the coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). The coronary flow velocity from the distal left anterior descending artery was measured in 16 healthy subjects (all male, age 24–38 years) using a 5-MHz transducer, on the day before, just before, and 3 h after administering 0.3 mg of cerivastatin. Hyperemia was achieved by the intravenous administration of adenosine, and the CFVR was calculated as the radio of the mean diastolic hyperemic coronary flow velocity to the basal flow velocity. The serum lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured. The CFVR following the single administration of cerivastatin increased from 2.93 ± 0.58 to 3.91 ± 0.86, P = 0.003, and was significantly higher than the CFVR measured at the same time on the previous day (3.91 ± 0.86 vs 3.37 ± 0.48, P = 0.009). Neither the serum lipid profile nor hsCRP exhibited a remarkable change after cerivastatin administration. We concluded that a single-dose administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve without modifying the serum lipid profile.

Long-term outcome and preprocedural predictors of atrial tachyarrhythmia recurrence following pulmonary vein antrum isolation-based catheter ablation in patients with non-paroxysmal atrial fibrillation

BACKGROUND Although various empiric adjunctive ablation techniques are widely performed with pulmonary vein antrum isolation (PVAI) to enhance the procedural efficacy of catheter ablation in non-paroxysmal atrial fibrillation (NPAF) patients, they are not required in all NPAF patients. METHODS AND RESULTS Eighty consecutive NPAF patients refractory to antiarrhythmic drugs underwent a PVAI-based ablation. Structural heart disease was present in 40% of patients and systolic dysfunction in 21%. After 31 ± 16 months of follow-up, 41% of the patients were free of atrial tachyarrhythmia recurrences after a single procedure. Finally, during a mean follow-up of 25 ± 15 months, 63 of 80 (79%) patients remained in sinus rhythm (SR) after the final procedure (two procedures in 48%, and three in 3%). A Cox regression multivariate analysis revealed that left atrial volume (LAV) was the only independent predictor of atrial tachyarrhythmia recurrences not only after single procedures (p = 0.027), but also after the final procedures (p = 0.001). Ten patients (13%) needed ablation for concomitant atrial tachycardias originating from the left atrium and right atrium other than common atrial flutter. Repeat ablation procedures increased the best cut-off value for predicting recurrences analyzed by receiver operating characteristic curves, from 86 mL (sensitivity 70%, specificity 64%) to 92 mL (sensitivity 71%, specificity 78%). CONCLUSIONS PVAI-based ablation strategies could achieve SR maintenance in almost 80% of NPAF patients after multiple procedures during long-term follow-up. The preprocedural LAV was an important predictor of the procedural outcome.

Left Atrial Appendage Flow Velocity and Time from P-Wave Onset to Tissue Doppler–Derived A' Predict Atrial Fibrillation Recurrence after Radiofrequency Catheter Ablation

Atrial fibrillation (AF) is associated with atrial remodeling. We investigate the abilities of preprocedural echocardiographic parameters reflecting atrial remodeling to predict AF recurrence after radiofrequency catheter ablation (RFCA) for paroxysmal AF (PAF).

Impact of an Empiric Isolation of the Superior Vena Cava in Addition to Circumferential Pulmonary Vein Isolation on the Outcome of Paroxysmal Atrial Fibrillation Ablation.

The safety and efficacy of an empiric superior vena cava isolation (SVCI) in addition to circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF) have not been clarified. A total of 186 consecutive patients who underwent catheter ablation of PAF were included. All patients underwent a CPVI. Patients in the first half underwent an additional SVCI only if SVC-triggered AF or rapid SVC activity was observed during the procedure (n = 93, as-needed SVCI, group I), and those in the second half underwent an empirical SVCI after the CPVI (n = 93, empiric SVCI, group II). The CPVI was successfully performed in all patients. An SVCI was performed in 8 of 93 patients (9%) in group I and 81 of the 93 patients (87%) in group II. In the remaining 12 patients in group II, an SVCI was not performed because of the lack of SVC potentials. During a mean follow-up of 27 ± 12 months, the atrial tachyarrhythmia recurrence rate after a single ablation procedure in the patients in group II was lower than that in group I (44% vs 23%, p = 0.035). A Cox regression multivariate analysis demonstrated that an empiric SVCI was an independent predictor of an atrial tachyarrhythmia recurrence after a single ablation procedure (odds ratio: 0.57, 95% confidence interval 0.31 to 0.999; p = 0.049). Neither sinus node injury nor any injury to the phrenic nerve was observed. In conclusion, an empiric SVCI in addition to the CPVI improved the outcome of AF ablation in patients with PAF without any additional adverse effects.

Low-dose dobutamine induces left ventricular mechanical dyssynchrony in patients with dilated cardiomyopathy and a narrow QRS: A study using real-time three-dimensional echocardiography

AIMS The effects of inotropic agents on left ventricular (LV) synchrony in heart failure patients are still unknown. The purpose of this study was to investigate the effects of dobutamine on LV mechanical dyssynchrony and LV systolic performance in patients with dilated cardiomyopathy (DCM) and a narrow QRS using real-time three-dimensional echocardiography (RT3DE). METHODS AND RESULTS Thirty-three patients with idiopathic DCM and a narrow QRS underwent low-dose dobutamine stress echocardiography (LDSE) with RT3DE. A time-global LV volume curve and time-regional LV volume curves were derived from RT3DE. Regional LV stroke volumes were summed in each stage, and the dobutamine-induced increase in the sum of regional LV stroke volumes was considered as the sum of regional contractile reserve. Systolic dyssynchrony index (SDI) was calculated as follows: (standard deviation of time to minimal volume for regional LV segments)×100/RR duration. Among the 33 patients, low-dose dobutamine increased global LV stroke volume (SV) in 28 (85%), but decreased global LVSV in the remainder (15%). The sum of regional contractile reserve was modestly correlated with the dobutamine-induced increase in global LVSV (R=0.57, p<0.001). In contrast, low-dose dobutamine increased SDI in 14 (42%) patients without a significant change in QRS duration, and there was an inverse correlation between the increase in SDI and the increase in global LVSV induced by dobutamine (R=-0.67, p<0.001). CONCLUSIONS Dobutamine may induce LV mechanical dyssynchrony in a substantial proportion of patients with DCM and a narrow QRS. In such cases, regional LV contractile reserve does not fully contribute to an increase in global LVSV.

Noninvasive assessment of myocardial damage after acute anterior myocardial infarction: myocardial blush grade in conjunction with analysis of coronary flow pattern

In patients with acute myocardial infarction (AMI), both myocardial blush grade (MBG) and coronary flow pattern obtained by transthoracic Doppler echocardiography (TTDE) have limitations in assessing myocardial viability. Accordingly, we assessed the usefulness of combination of MBG and TTDE in predicting myocardial damage following AMI. A total of 45 patients with anterior AMI were enrolled. Myocardial blush grade and coronary flow velocity (CFV), diastolic deceleration time (DDT), and coronary flow velocity reserve (CFVR) were measured immediately after reperfusion. The regional wall motion score index (RWMSI) was measured at 14 days after onset. The MBG was normal in 12 patients. The RWMSI was significantly better in the patients with normal than with abnormal MBG (1.65 ± 0.29 vs 2.03 ± 0.46, P < 0.05). Among the coronary flow indices, only DDT showed the significant correlation with RWMSI (P < 0.05, r = −0.44). To predict RWMSI ≥2, sensitivity and positive predictive value (PPV) were 86.3% and 65.5% in DDT alone, 90.9% and 65.5% in MBG alone, respectively. Predictable value was enhanced by the combination with DDT and MBG, with sensitivity of 100% and PPV of 70.8% in 31 patients whose results of both corresponded. MBG in conjunction with TTDE was useful in predicting myocardial damage after anterior AMI.

Prevalence, clinical characteristics, and outcome of atrial functional mitral regurgitation in hospitalized heart failure patients with atrial fibrillation

BACKGROUND Functional mitral regurgitation (MR) caused by reduced left ventricular ejection fraction (EF) and tethering, termed ventricular functional MR (VFMR), is associated with worse outcomes. Atrial functional MR (AFMR) caused by left atrial enlargement and annular dilatation was also recently described in patients with atrial fibrillation (AF). However, the clinical profiles of AFMR in hospitalized heart failure (HF) patients are unclear. We investigated the prevalence, clinical characteristics, and prognosis of AFMR in hospitalized HF patients with AF. METHODS We analyzed 189 hospitalized HF patients with AF. The prevalence, clinical characteristics, and prognosis were compared between 4 groups: patients with EF ≥50% and no/mild MR (pEFnoMR), patients with EF <50% and no/mild MR (rEFnoMR), patients with EF ≥50% and moderate/severe MR (AFMR), and patients with EF <50% and moderate/severe MR (VFMR). RESULTS The prevalence of AFMR was 15.9% in hospitalized HF patients with AF. AFMR patients were older and more likely to have an enlarged left atrium, lower tenting height, and moderate/severe tricuspid regurgitation than VFMR patients. There were no differences in all-cause death after discharge among pEFnoMR, rEFnoMR, and AFMR patients. AFMR patients were associated with a higher rate of a composite of cardiac death and readmission for HF compared with pEFnoMR and rEFnoMR patients (log-rank p=0.046 and p=0.004). There were no differences in composite endpoints between AFMR and VFMR patients (log-rank p=0.507). CONCLUSIONS AFMR was present in a proportion of elderly hospitalized HF patients with AF, and was a condition requiring attention because of readmission for HF in a hospitalized HF cohort.

Narrowing filtered QRS duration on signal-averaged electrocardiogram predicts outcomes in cardiac resynchronization therapy patients with nonischemic heart failure

To evaluate the impact of changes in the filtered QRS duration (fQRS) on signal‐averaged electrocardiograms (SAECGs) from pre‐ to postimplantation on the clinical outcomes in nonischemic heart failure (HF) patients under cardiac resynchronization therapy (CRT).