Transradial percutaneous coronary intervention (PCI), which is less invasive than transfemoral PCI, may facilitate early rehabilitation of patients with acute myocardial infarction (AMI). The aim of our study was to investigate whether transradial PCI is associated with a shorter coronary care unit (CCU) stay in very elderly AMI patients (≥ 80 years old). We enrolled 116 AMI patients aged ≥ 80 years. There were 39 patients in the transradial group and 77 patients in the non-transradial group. The length of CCU stay, the length of hospital stay, in-hospital mortality, the day of the monitored sitting and standing test, and the occurrence of delirium were compared between the two groups. The duration of CCU stay in the transradial and non-transradial groups was 3.6 ± 1.5 days and 5.0 ± 3.2 days, respectively (P = 0.001). The duration of hospital stay in the transradial and non-transradial groups was 13.3 ± 7.4 days and 19.2 ± 11.1 days, respectively (P = 0.001). In-hospital mortality was not different between the two groups (7.7% versus 2.6%, P = 0.20). The day of the monitored standing test in the transradial and non-transradial groups was 3.2 ± 0.7 and 4.6 ± 2.3, respectively (P < 0.0001). Multivariate logistic regression analysis identified a transradial approach as an independent predictor of short (≤ 3 days) CCU stay (OR: 3.01, 95%CI: 1.16-7.83, P = 0.02). In conclusion, transradial PCI was associated with a shorter CCU stay in AMI patients ≥ 80 years old. Furthermore, transradial PCI facilitated early rehabilitation in this high risk population.

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Few studies have assessed the incremental usefulness of multimarkers as predictors of cardiovascular events in patients with mild to moderate coronary artery lesions.
We examined 9 plasma inflammatory cytokines (cathepsin S, CXCL16, sopluble CD40 ligand, interleukin-10, placental growth factor, GDF15, matrix metalloproteinase 9, monocyte chemoattractant protein-1, and high-sensitivity C-reactive protein) in 964 patients showing mild to moderate lesions and assessed their association with risk of cardiovascular events during 3 years of follow-up (median 17 months).
In a backward Cox regression procedure, Cystatin S (hazard ratio [HR]: 1.788, 95% CI:1.233 to 2.593, P = 0.02), soluble CD40 ligand (HR: 1.255, 95% CI:1.054 to 1.494, P = 0.011), placental growth factor (HR: 1.194, 95% CI:0.976 to 1.461, P = 0.035), and GDF15 (HR: 0.725, 95% CI:0.550 to 0.956, P = 0.023) were significantly related to cardiovascular events. Compared with multimarker score (according to regression coefficients of significant biomarkers) in the lowest two quintiles, patients in the highest quintile had a higher risk of cardiovascular events after adjustment for traditional risk factors (HR: 2.77, 95% CI:1.30 to 5.87, P = 0.008). Adding the multimarker score to traditional risk factors contributed significantly to the prediction of cardiovascular events (AUC increased from 0.67 to 0.72).
A multimarker approach added to the predictive information obtained from traditional risk factors in patients with mild to moderate coronary artery lesions.

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Clopidogrel in combination with aspirin has been widely used in patients who have undergone coronary stent implantation. However, the benefit to Japanese patients with stable angina (SA) or old myocardial infarction (OMI) undergoing percutaneous coronary intervention (PCI) still remains unclear.
The aim of this multicenter, randomized, double-blind, clinical study was to evaluate the safety of a clopidogrel 300 mg loading dose followed by a 75 mg maintenance dose compared to ticlopidine 100 mg twice daily in patients with SA or OMI undergoing PCI who were on aspirin (81 to 100 mg once daily). The primary endpoint was the composite of safety events comprising clinically significant bleeding, blood disorders, elevated liver function values, and study drug discontinuation up to week 12. The key secondary endpoints were major adverse cardiac events (MACE), major adverse cardiac and cerebrovascular events (MACCE), and bleeding events.
A total of 1003 patients were randomly allocated to receive either clopidogrel or ticlopidine and 931 patients underwent PCI. The cumulative incidence of the composite safety endpoint in the clopidogrel group was statistically lower than that of ticlopidine (P < 0.0001, hazard ratio; 0.259; 95%CI; 0.187 to 0.359). There were no statistically significant differences between treatments with respect to MACE at week 12 (P = 0.7899) nor to the bleeding events (P = 0.5292, stratified log-rank test).
Clopidogrel was found to have a better benefit/risk profile than ticlopidine in Japanese patients with SA or OMI undergoing PCI.

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Parameters obtained from cardiopulmonary exercise testing (CPX) are recognized for their high prognostic value in predicting future cardiac events in cardiac patients. Our group compared the prognostic value of CPX parameters between patients with sinus rhythm (SR) and patients with atrial fibrillation (AF).
Peak O2 uptake (VO2), the ratio of the increase in VO2 to the increase in work rate (ΔVO2/ΔWR), and the slope of the increase in ventilation to the increase in CO2 output (VE-VCO2 slope) were obtained from CPX in 72 AF patients and 478 SR patients. The prognostic values of these indices were compared between the two groups.
Six cardiac deaths and 25 cardiac events were observed in the AF group and 9 cardiac deaths and 96 cardiac events were observed in the SR group, over a prospective follow-up period of 1,192 days. The percentages of cardiac deaths and cardiac events were higher in the AF group than in the SR group. In a multivariate Cox proportional hazards analysis, peak VO2 was identified as a sole significant predictor of cardiac death and cardiac events in SR patients and VE-VCO2 slope was identified as a sole significant predictor of cardiac death and cardiac events in AF patients.
Our results suggest that the VE-VCO2 slope is strongly predictive of future cardiac events in patients with AF and that peak VO2 is strongly predictive of future cardiac events in SR patients.

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Although the pacing threshold of steroid-eluting active-fixation leads remains stable over the long term, it changes rapidly after screw-in. We compared the pacing threshold in the acute phase between retractable and Sweet-Tip active-fixation leads. We studied 132 patients who were implanted with active-fixation leads for new pacemaker implantation or additional leads required due to disconnected/leaking leads. Pacing threshold was measured at 4 time points: before screw-in, immediately, and 5 and 10 minutes after screw-in. If the pacing threshold was > 1.5 volts (V) at 5 minutes, we changed the pacing site so that it became ≤ 1.5 V. A total of 169 retractable leads (Medtronic: 107 leads, St. Jude Medical: 62 leads) and 33 Sweet-Tip leads (Boston: 33 leads) were implanted. Eighty-nine leads were implanted in the atrium and 113 leads in the ventricle. Seventy patients were implanted with both atrial and ventricular leads. The pacing threshold of Sweet-Tip leads increased immediately after screw-in, while that of retractable leads decreased (Sweet-Tip: 0.20 ± 0.57 V, Retractable: -0.15 ± 0.53 V, P < 0.05). The pacing threshold of both types of leads decreased similarly from immediately to 5 minutes after screw-in (Sweet Tip: -0.29 ± 0.43 V, Retractable: -0.25 ± 0.36 V, P = NS). Few changes in the threshold were detected between 5 and 10 minutes. Because the pacing threshold of Sweet-Tip active-fixation leads increased immediately after screw-in and that of both type leads decreased from immediately to 5 minutes, we should measure the pacing threshold from 5 minutes after screw-in.

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Pacing from the right ventricular (RV) apex is associated with adverse effects such as heart failure and atrial fibrillation. We attempted pacing from the RV mid-septum, which is theoretically a more physiological pacing site. A total of 172 consecutive patients with indications for permanent pacemaker implantation were studied. A screw-in lead and a curved stylet were used for lead positioning on the RV mid-septum. Pacemaker indices were evaluated at implantation and one year later. As an electrocardiographic parameter, QRS duration was measured in lead II. These data were compared to those of 66 patients subjected to conventional RV apical pacing. Lead placement was successful in all patients of RV mid-septal pacing. There were no technical problems during or after the procedure. The cumulative percentage of ventricular pacing at one year postimplantation was 85 ± 24 % in the SSP group. Sensing, pacing threshold, and lead impedance in the SSP group remained clinically stable over one year. When these measurements were compared between the SSP and AP groups, the pacing threshold and the lead impedance at one year postimplantation in the SSP group were higher (P < 0.05) and lower (P < 0.01), respectively, than those of the AP group. The mean QRS duration was markedly shorter (123 ± 16 versus 150 ± 18 msec, P < 0.0001). Selective site pacing from the RV mid-septum is feasible and results in less conduction delay compared to conventional RV apical pacing, and its procedure seems to be more physiological in permanent pacemaker implantation.

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It is notoriously difficult to classify patients with acute heart failure (AHF) because of variations in clinical presentation, different etiologies, the impact of comorbidities, and variable prognoses. In this study, we used DNA whole-genome microarrays to classify 24 patients with AHF based on the transcriptome of their peripheral blood nuclear cells. The main purpose was to verify whether any transcriptomic sub-clusters had clinical correlations. We identified two distinct groups of transcriptomic profiles that correlated with normal (1.125 mg/dL) and increased (1.783 mg/dL) mean blood creatinine concentrations. These two subgroups of patients (n = 12) differed in the expression of more than 6000 genes and 108 signaling pathways. The most significant regulated signaling pathway was the aldosterone-regulated sodium reabsorption pathway and the most significant regulated genes included the angiotensin-converting enzyme gene. This suggests that kidney impairment in patients with AHF is related to dysregulation of the renin-angiotensin-aldosterone system. The interesting findings of our study were the significant differences in expression of genes belonging to the aldosterone-regulated signaling pathway: Na⁺/K⁺ transporting ATPase and NEDD4L (neuronal precursor cell expressed developmentally down-regulated 4-like) between patients with and without renal dysfunction. Future studies of blood-cell transcriptomic profiles in patients with AHF will provide further insights into the molecular pathogenesis of this cardiorenal disorder.

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Venous blood draining from the left atrium (LA) flows into the coronary sinus (CS) through the Marshall vein which has no valvular apparatus, thus allowing LA retroperfusion if reflow in the right atrium is hindered. We investigated pharmacologic atrial defibrillation via the CS in dogs with chronic atrial fibrillation (AF). Chronic AF was induced by rapid atrial pacing for 4-16 weeks in 6 mongrel dogs. A 7F occlusion balloon catheter was introduced into the proximal CS. Boluses of low doses of the class Ic antiarrhythmic drug, pilsicainide (2, 4, 6, and 8 mg as needed) or class III antiarrhythmic drug, nifekalant (0.5, 1, 2, and 4 mg) were infused directly within 3-4 seconds at 10 minute intervals into the temporarily balloon occluded CS near its orifice. In 4 of the 5 dogs (balloon catheter could not be placed in the CS in 1 dog), the cumulative dose of 11.5 ± 7.4 mg of pilsicainide was effective in restoring sinus rhythm; the venous concentration of pilsicainide was 1.23 ± 0.79 μg/mL. A cumulative dose of 7.5 mg nifekalant restored sinus rhythm in only 1 of the 6 dogs. Our results in dogs with sustained AF indicate that delivery of a class Ic or III antiarrhythmic drug near the CS ostium via the temporarily occluded CS is feasible and effective for pharmacologic atrial defibrillation; however, the effect may be related to the elevation of the serum concentration of the drug to the therapeutic range rather than to the delivery method itself.

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The stepwise approach to radiofrequency (RF) ablation of atrial fibrillation (AF) can include ablation of the coronary sinus (CS) by RF delivery at the left atrium (LA) and/or within the CS. In both cases, the energy is applied between the tip electrode of a percutaneous catheter and a dispersive electrode on the body surface. We explored the feasibility of using the electrode rings of a diagnostic catheter placed in the CS as dispersive electrode(s) for RF delivery within the LA and compared this technique to an established CS ablation method.
Excised pig hearts were superfused with a pulsatile saline flow. Bipolar ablation was performed between a saline-irrigated (20 mL/minute) 4-mm tip electrode placed in the LA adjacent to the CS and 7 electrode rings of a 6F, septapolar, 4-mm nonirrigated electrode placed within the CS adjacent to the LA endocardial electrode. Unipolar ablation was performed between the endocardial electrode and dispersive electrode. A continuous transmural lesion was produced in 6/8 (75%) attempts with bipolar ablation, but in 0/6 (0%) attempts with unipolar ablation. However, the incidence of steam pop tended to be increased with bipolar ablation.
Bipolar ablation of the CS appears to be highly effective for creating a transmural LA-CS lesion.

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Restenosis after percutaneous coronary intervention (PCI) is still a clinically serious problem. We examined the treatment efficacy of IMD-0354, a novel IKK inhibitor, on arteriopathy. Using C57BL/6J mice, a wire-injury model was prepared and the mice were intraperitoneally injected with IMD-0354 or vehicle twice a day. The vehicle-treated injured arteries showed significantly thickened intima (3.77 ± 0.59, n = 8), however, IMD-0354 suppressed its progression (1.62 ± 0.22, n = 10, P < 0.05) on day 28. While enhanced expression of PCNA and NF-κB was observed in the untreated injured arteries, IMD-0354 significantly suppressed their expressions. Quantitative RT-PCR revealed that the expression of several inflammatory factors was reduced in the arteries from mice which received IMD-0354 treatment compared with the control animals. Thus, this drug may effectively prevent restenosis after coronary intervention and other cardiovascular diseases.

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It has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase). In the acute phase, the control EAM rats exhibited a reduced left ventricular ejection fraction (LVEF) and prolonged monophasic action potential duration (MAPD). Neither drug had an affect on the LVEF or degree of myocarditis, but Mex 25 mg suppressed the MAPD prolongation. In the chronic phase, EAM+Nic and EAM+Mex 25 mg exhibited a higher LVEF than the control EAM. Although the control EAM exhibited sustained MAPD prolongation, the other groups showed recovery of the MAPD in the chronic phase. The mitochondorial redox state was lower in the control EAM than in the sham, and EAM+Nic exhibited a similar level of the redox state as the sham in the chronic phase. Nicorandil exhibited a cardioprotective effect through the protection of mitochondrial function. Mexiletine exhibited a cardioprotective effect possibly through a reduction in the calcium overload by shortening the MAPD in the acute phase.

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A 19-year-old man who underwent bicaval orthotopic heart transplantation for idiopathic dilated cardiomyopathy complained of palpitations 2 weeks after the heart transplantation. An ECG revealed paroxysmal atrial tachycardia (AT) with a cycle length of 260 ms and the P wave morphology of the AT was similar to that during sinus rhythm. Echocardio- graphy showed normal contraction. No rejection, vasculopathy, or infection was observed. An electrophysiologic study and catheter ablation guided by a noncontact mapping system were performed due to drug refractory AT. The AT was induced spontaneously by isoproterenol infusion. The activation sequence of the AT exhibited a focal pattern, and the break- out site of the AT into the donor right atrium was just 12 mm below the breakout site of the donor sinoatrial node. Radiofrequency catheter ablation eliminated this AT and resulted in an improvement in the symptoms.

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