Harumi Katoh

Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation

BACKGROUND Plasma brain natriuretic polypeptide (BNP) levels have been used as biochemical markers of systolic left ventricular (LV) dysfunction. Although in vitro studies have shown the existence of BNP messenger RNA in the atria, the main production site of BNP is believed to be the ventricle. The hypothesis that the atrium could be a source of BNP was examined in patients with lone atrial fibrillation (AF), the most common type of sustained arrhythmia. METHODS AND RESULTS We studied 16 controls and 21 patients with lone AF. Plasma samples for BNP were selectively and serially obtained from the aorta, anterior interventricular vein (AIV), and coronary sinus (CS). Atrial natriuretic polypeptide (ANP) levels were also measured to determine whether the CS samples contained significant amounts of atrial venous drainage. Of the 3 sample locations, the CS had the greatest ANP levels, confirming transcatheter sampling position accuracy. BNP levels were significantly greater in the CS than AIV in the patients with AF (279 +/- 226 v 126 +/- 97 pg/mL; P < .01). Consequently, plasma BNP levels were also greater in the patients with AF than controls (103 +/- 90 v 5 +/- 2 pg/mL; P < .001). LV ejection fraction was significantly less in patients with AF than control patients. Atrial production of BNP decreased significantly after successful DC cardioversion of AF in the 5 restudied patients (182 +/- 139 v 59 +/- 64 pg/mL; P < .05). CONCLUSION The data suggest that AF is a condition in which BNP is produced in the atrium itself.

Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium-DTPA–enhanced magnetic resonance imaging

BACKGROUND Cardiac involvement is an important prognostic factor in patients with sarcoidosis. In this study, we evaluated the usefulness of gadolinium-DTPA (diethylene triamine pentaacetic acid)-enhanced magnetic resonance imaging (Gd-MRI) for diagnosing cardiac sarcoidosis and evaluating the effects of steroid therapy. METHODS Sixteen patients with sarcoidosis diagnosed by histology or by Japanese Ministry of Health and Welfare criteria for cardiac sarcoidosis underwent Gd-MRI with a 1.5-Tesla superconducting magnet system using a T1-weighted spin-echo sequence. RESULTS Gd-MRI showed localized enhancement of signal intensity, indicating interstitial edema, in the left ventricle in 8 of the 16 patients. Two patients with enhancement also had thinning of the left ventricular septal wall. After 1 month of prednisolone therapy (60 mg every other day or 30 to 40 mg every day), the localized high-intensity signals were markedly diminished in all 8 patients. CONCLUSIONS Images of the heart obtained by Gd-MRI may reflect active inflammation with interstitial edema in patients with sarcoidosis. Gd-MRI may be a useful noninvasive method for early detection of cardiac sarcoidosis and for evaluating the effects of steroid therapy.

Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis.

OBJECTIVES The aim of this study was to investigate the efficacy of a paclitaxel-eluting balloon (PEB) for the treatment of sirolimus-eluting stent (SES) restenosis. BACKGROUND Because drug-eluting stents (DES) are being used in increasingly complicated settings, DES restenosis is no longer an uncommon phenomenon, and its optimal treatment is unknown. METHODS This study was a prospective single-blind randomized trial conducted in 50 patients with SES restenosis. Patients were randomly assigned to a PEB group (n = 25) or a conventional balloon angioplasty (BA) group (n = 25). The primary end point was late lumen loss at 6-month follow-up. Secondary end points included the rate of binary restenosis (in-segment analysis) and major adverse cardiac events (MACE) at 6-month follow-up. RESULTS At 6-month angiographic follow-up (follow-up rate: 94%), in-segment late lumen loss was lower in the PEB group than in the BA group (0.18 ± 0.45 mm vs. 0.72 ± 0.55 mm; p = 0.001). The incidence of recurrent restenosis (8.7% vs. 62.5%; p = 0.0001) and target lesion revascularization (4.3% vs. 41.7%; p = 0.003) was also lower in the PEB group than in the BA group. The cumulative MACE-free survival was significantly better in the PEB group than in the BA group (96% vs. 60%; p = 0.005). CONCLUSIONS In patients with SES restenosis, PEB provided much better clinical, angiographic outcomes than conventional BA.

Contribution of Endogenous Nitric Oxide to Basal Vasomotor Tone of Peripheral Vessels and Plasma B-Type Natriuretic Peptide Levels in Patients With Congestive Heart Failure

OBJECTIVES We examined whether a relationship exists between the vasoconstrictive response to endogenous nitric oxide (NO) synthesis inhibition and the severity of heart failure in patients with congestive heart failure (CHF). BACKGROUND Controversy exists as to whether the vasoconstrictive response to NO synthesis inhibition in patients with CHF is comparable to that in normal subjects or is enhanced. METHODS Forearm blood flow (FBF) and calculated forearm vascular conductance (FVC) were obtained using plethysmography before and after administration of the NO synthesis inhibitor L-NMMA (NG-monomethyl-L-arginine) in 40 patients with CHF due to dilated cardiomyopathy and in 16 normal control subjects. Basal plasma B-type natriuretic peptide (BNP) and nitric oxide concentrations were measured in all subjects. RESULTS Plasma BNP and nitrite/nitrate (NOx) levels in the patients group were significantly greater and baseline FBF was significantly less. Administration of L-NMMA significantly decreased FBF and FVC in both groups. The percent changes in FBF (%FBF) and FVC (%FVC) from the baseline after L-NMMA correlated significantly with plasma BNP level (%FBF: r = 0.72; %FVC: r = 0.76; both p < 0.001). Percent changes in both FBF and FVC were greater in patients with BNP > or = 100 pg/ml than in normal subjects; however, in patients with BNP < 100 pg/ml they were comparable to those in normal subjects. CONCLUSIONS Vasoconstrictive response to L-NMMA in patients with CHF was preserved or enhanced in proportion to the basal plasma BNP level, indicating a close relationship between the contribution of endogenous NO to basal vasomotor tone and the severity of heart failure.

Vascular Involvement in a Patient with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes

A 26-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) was admitted to our hospital for further cardiovascular examination. A muscle biopsy demonstrated strongly succinate dehydrogenase-reactive blood vessels. Pulse wave contour analysis revealed that both capacitive and oscillatory compliance were markedly reduced in this patient compared with 45 normal age-matched control subjects. Hepatocyte growth factor was remarkably elevated in this patient over that of 10 normal control subjects. These findings suggest that a MELAS patient has not only pathologic but also functional vascular involvement. If so, patients with MELAS need systemic vascular assessment.

An inhibitor of inducible nitric oxide synthase decreases forearm blood flow in patients with congestive heart failure

OBJECTIVES The functional activation of inducible nitric oxide synthase (iNOS) was evaluated as a source of nitric oxide (NO) in the forearm of patients with heart failure. BACKGROUND Although endogenous NO is normally produced by constitutive NO synthase (cNOS) in patients with congestive heart failure (CHF), expression of iNOS provides an additional source of NO. However, there are no in vivo studies showing functional activation of iNOS in humans. METHODS A nonselective NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), and a selective inhibitor of iNOS, aminoguanidine, were administered intra-arterially in graded doses into the brachial arteries of 13 patients with CHF and 10 normal control subjects. Forearm blood flow (FBF) was measured simultaneously in the infused and noninfused arms by plethysmography. Arterial and venous plasma concentrations of nitrite/nitrate (NOx) were measured at baseline and at the highest dose of each drug. RESULTS L-NMMA significantly reduced the FBF ratio between the infused and noninfused arms in both the control and patient groups (35 +/- 12% and 34 +/- 10%, respectively; both p < 0.001). Aminoguanidine at the same concentration significantly reduced the ratio in the patient group (15 +/- 9%, p < 0.01), with no change in the control group. The arterial NOx concentration was not affected by either drug; however, venous NOx concentrations were significantly decreased in both the control and patient groups by L-NMMA (18 +/- 5% and 18 +/- 17%, respectively; both p < 0.05) and in the patient group only by aminoguanidine (7 +/- 6%, p < 0.05). CONCLUSIONS These findings suggest that NO production in the forearms of patients with CHF is induced partly by iNOS activation, whereas in normal subjects, it can be ascribed to cNOS activation.

Association between tissue characteristics assessed with optical coherence tomography and mid-term results after percutaneous coronary intervention for in-stent restenosis lesions: a comparison between balloon angioplasty, paclitaxel-coated balloon dilatation, and drug-eluting stent implantation

AIMS Morphological assessment of neointimal tissue using optical coherence tomography (OCT) is important for clarifying the pathophysiology of in-stent restenosis (ISR) lesions. The aim of this study was to determine the impact of OCT findings on recurrence of ISR after various types of percutaneous coronary intervention (PCI) including plain old balloon angioplasty (POBA), paclitaxel-coated balloon (PCB) dilatation, and drug-eluting stent (DES) implantation. METHODS AND RESULTS Between June 2008 and August 2013, we performed PCI for 428 ISR lesions in 379 patients using POBA (78 lesions, POBA group), PCB dilatation (202 lesions, PCB group), and DES implantation (148 lesions, DES group). Morphological assessment of neointimal tissue at the minimum lumen area site to determine restenotic tissue structure (homogeneous, heterogeneous, or layered type) using OCT was performed. We examined the association between tissue structure and midterm results including ISR and target lesion revascularization (TLR) rates. The patients were 308 men and 71 women with a mean age of 68.9 ± 9.4 years. The mean follow-up period was 211 ± 40 days. ISR and TLR rates of lesions with a homogeneous structure were significantly higher in the POBA group than in the PCB group (ISR: 54.8 vs. 19.1%, P < 0.001; TLR: 38.7 vs. 10.6%, P < 0.001) and DES group (ISR: 54.8 vs. 19.6%, P = 0.002; TLR: 38.7 vs. 10.7%, P = 0.005), whereas there were no differences in ISR and TLR rates between the three groups in lesions with a heterogeneous structure. CONCLUSION Morphological assessment of ISR tissue using OCT might suggest favourable types of PCI for ISR lesions.

Everolimus-eluting stent implantation versus repeat paclitaxel-coated balloon angioplasty for recurrent in-stent restenosis lesion caused by paclitaxel-coated balloon failure.

AIMS Although paclitaxel-coated balloon (PCB) angioplasty has been reported to be effective for in-stent restenosis (ISR) lesions, the optimal treatment for recurrent ISR lesions caused by PCB failure remains unclear. This study compared clinical and angiographic outcomes after everolimus-eluting stent (EES) implantation and repeat PCB angioplasty for PCB failure. METHODS AND RESULTS From November 2008 to October 2011, we performed PCB angioplasty for 599 ISR lesions, of which 93 recurrent ISR lesions underwent EES implantation (53 lesions, 52 patients) or repeat PCB angioplasty (40 lesions, 37 patients). The choice of treatment strategy was decided at the operatorÕs discretion. Angiographic outcomes were evaluated by follow-up angiography at six to eight months after procedure. The baseline characteristics were similar between the two groups. At follow-up angiography (93.5% of all lesions), minimum lumen diameter was significantly larger and the binary restenosis rate was significantly lower after EES implantation than after repeat PCB angioplasty (2.08±0.79 mm vs. 1.45±0.68 mm, p<0.001; 20.0% vs. 54.1%, p=0.001; respectively), whereas late lumen loss was not different between the two groups (0.49±0.62 mm vs. 0.59±0.74 mm, p=0.47). At two years, the incidences of both target lesion revascularisation (TLR) and clinically driven TLR were significantly lower after EES implantation than after repeat PCB angioplasty (17.9% vs. 57.5%, p=0.001; 5.9% vs. 18.1%, p=0.01; respectively). CONCLUSIONS EES implantation was more effective for PCB failure in preventing subsequent TLR than repeat PCB angioplasty because of better angiographic results.

Stent Fracture After Sirolimus-Eluting Stent Implantation 8-Year Clinical Outcomes

Background—Stent fracture (SF) after sirolimus-eluting stent implantation is reported to be associated with target lesion revascularization (TLR) and stent thrombosis. We aimed to assess the clinical impact of SF at 8 years. Methods and Results—Between 2002 and 2005, 972 patients (1795 lesions) underwent sirolimus-eluting stent implantation and follow-up angiography within 1 year after index procedure. SF, defined as the complete separation of stent segments or stent struts at follow-up angiography, was observed in 105 lesions (5.8%). The study sample comprised 954 patients (1630 lesions), excluding 147 lesions undergoing TLR and 18 patients (18 lesions) who died or in whom stent thrombosis developed within 1 year after sirolimus-eluting stent implantation. The median follow-up duration was 9.1 years (the first and third quarters, 8.7 and 9.4 years). The primary end point was defined as any TLR. The 8-year cumulative rates of adverse events were estimated by Kaplan–Meier methods with P values from log-rank tests. Between patients with and without SF, there were no significant differences in the cumulative rates of all-cause death (23.5% versus 27.6%, P=0.35) and cardiac death (4.7% versus 9.1%, P=0.14), whereas patients with SF had significantly higher cumulative rates in myocardial infarction (10.1% versus 3.3%, P=0.001), very late stent thrombosis (6.8% versus 0.7%, P<0.001), any TLR (38.1% versus 10.8%, P<0.001), and clinically driven TLR (26.2% versus 6.6%, P<0.001). Conclusions—SF after sirolimus-eluting stent implantation was consistently associated with higher rates of adverse cardiac events during the 8-year follow-up.

Nitric oxide-mediated vasodilatory effect of atrial natriuretic peptide in forearm vessels of healthy humans.

1. The aim of the present study was to determine whether the vasorelaxant effect of atrial natriuretic peptide (ANP) is, in part, endothelium dependent in humans.