Nobuhiro Kodani

Activation of Inducible NOS in Peripheral Vessels and Outcomes in Heart Failure Patients

BACKGROUND Activation of inducible nitric oxide synthase (iNOS) has been reported in congestive heart failure (CHF) conditions. However, it is unknown whether activation of iNOS affects prognosis of CHF patients. We prospectively studied the influence of activation of iNOS in the forearm on the outcome of CHF patients. METHODS AND RESULTS Forearm blood flow (FBF) responses to 3 doses of acetylcholine (ACh) and nitroglycerin (NTG), and 4 doses of a selective iNOS inhibitor (aminoguanidine: Amn) and a nonselective NOS inhibitor (L-NMMA) were examined using plethysmography in 68 patients with CHF from idiopathic dilated cardiomyopathy. Plasma brain natriuretic peptide (BNP) and tumor necrosis factor-alpha (TNF-alpha) were also measured in all patients. During the mean follow-up period of 3.8 years, 25 patients were hospitalized for worsening heart failure and 9 of these patients died. Patients with adverse events had a diminished vasodilator response to ACh (P < .001) compared to patients without adverse events. Amn significantly decreased FBF (P < .001) in patients with adverse events, but not in patients without adverse events. FBF responses to NTG and L-NMMA were not significantly different between the 2 groups. When grouped by maximum FBF responses to each drug above and below the median value, multivariate Cox proportional hazards model analyses for cardiac event showed a significance in the FBF response to Amn (adjusted hazard ratio 5.89, P < .001). FBF responses to maximum dose of Amn significantly correlated with BNP and TNF-alpha levels (both P < .001). CONCLUSIONS CHF patients with vascular iNOS activation, as demonstrated by a greater vasoconstrictor response to Amn, had poor outcomes. Activation of iNOS in peripheral vessels, associated with proinflammatory cytokines in accordance to the severity of heart failure, is a marker for, or contributes to, adverse events in patients with CHF.

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.

Factors influencing left atrial volume in treated hypertension

BACKGROUND Left atrial (LA) enlargement has been documented to occur in hypertension (HT), and has been an index for evaluating the diastolic function of the left ventricle. Enlargement of the LA is one of the vital factors that induce heart failure and atrial fibrillation (AF) in patients with HT. METHODS AND SUBJECTS 130 treated hypertensive patients were enrolled. All recruits participated in an echocardiogram, electrocardiogram, a routine blood examination including brain natriuretic peptide (BNP), and physical examinations. RESULTS Left ventricular mass (LVM) indexed to height(2.7) had a significant positive correlation with left atrial volume index (LAVI) (p<0.0001), as well as natural logarithm BNP (p<0.001). Blood pressure levels were not associated with LAVI, neither body mass index nor age. LAVI had a positive correlation with factors involving the left ventricle volume, LVM, and right ventricle systolic pressure (RVSP) (r=0.687, p<0.0001). The parameters of LV diastolic function were positively but weakly associated with LA size. In the subgroup of LAVI, the evidence of paroxysmal atrial fibrillation (PAF): LAVI<32 ml/m(2) had no PAF, whereas the incidence of PAF was 7.5%, 11.4%, and 15.2%, respectively in the LAVI>32 ml/m(2) group. Of anti-hypertension drugs, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers had a tendency to reduce LAVI; however, there was no statistical significance within the groups. CONCLUSIONS Left ventricular volume and mass are independent factors affecting LAVI in treated HT. The incidence of PAF is associated with LA size. In patients with treated HT, LA size may be a useful surrogate marker for monitoring the effectiveness of medical therapy and occurrence of AF.

Left Atrial Remodeling and Recurrence of Congestive Heart Failure in Patients Initially Diagnosed with Heart Failure

Left atrial volumes (LAVs) have been suggested to represent long‐term exposure to elevated pressures. This study examined the recurrence of heart failure (HF) based on LAV in patients initially diagnosed with congestive HF (CHF).

A case of long QT syndrome having compound mutations of KCNH2 and SCN5A

Long QT syndrome (LQTS) is a hereditary ion channelopathy resulting in prolonged cardiac repolarization and abnormal prolongation of the QT interval on the electrocardiogram (ECG). The patients are likely to develop ventricular arrhythmias and sudden cardiac death. Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. A 16-year-old-woman with QT prolongation on ECG had frequent syncopal episodes and an attack of ventricular tachycardia followed by ventricular fibrillation. The SCN5A mutation (intravene sequence 4-1 c/t) in addition to the KCNH2 mutation (Arg56Gln) was identified. Her mother and older sister were also diagnosed as having LQTS, but had only a single mutation (KCNH2). Her older sister had an episode of syncope, but her mother did not. Genetic analysis sometimes reveals 2 or more mutations in LQTS patients with clinical phenotypes of the Romano-Ward syndrome. Compound mutations in different LQTS-related genes are likely to modify clinical characteristics. In addition, comprehensive screening of LQTS-related genes might be needed when facing family members with different clinical manifestations. <Learning objective: Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. We described a case of LQTS having compound mutations of KCNH2 and SCN5A who had frequent syncopal episodes and an attack of ventricular fibrillation. The mutations of 2 different genes were associated with a severe phenotype of LQTS. Comprehensive screening of LQTS-related genes might be needed for estimating the severity of LQTS.>.

A case of coagula tamponade 4 years after Bentall procedure

A 76-year-old man was admitted to hospital because of shortness of breath, and a pericardial clot with left ventricular diastolic collapse was detected by echocardiography. Approximately 4 years earlier, the patient had undertaken the Bentall procedure with a bioprosthesis (Freestyle ) because of aortic regurgitation and dilatation of the aortic root. A transthoracic echocardiogram (TTE) obtained 1 year after the operation showed a mild pericardial effusion and no evidence of tamponade. Six months before admission, the patient noticed increased fatigue and shortness of breath. On physical examination, the patient’s blood pressure was 102/68 mmHg, heart rate 80 beats per min, respiratory rate 14 breaths per min, and his temperature was 36.7 C. The breath sounds were clear. An examination of the heart showed no significant murmurs. The arms and legs were warm, with symmetric pulses and no edema. Because the patient had a bioprosthetic valve, anticoagulant therapy was not performed, and activated partial thromboplastin time and prothrombin time were normal. The transthoracic echocardiographic study on admission showed a large localized pericardial clot mass in the postero-lateral region and the inward motion of the left ventricular posterior wall was noted during diastole (i.e., left ventricular diastolic collapse) (Figs. 1 and 2), which are findings consistent with coagula tamponade [1–3]. There were no classical echocardiographic signs of tamponade (i.e., right ventricular diastolic collapse and right atrial collapse) [4, 5]. The patient underwent elective surgery, and the pericardial clot and bloody fluid were removed. Biopsy specimens were taken from the pericardium, and the pericardial biopsy section showed a lymphocyte-rich inflammatory infiltrate. Idiopathic pericarditis was thought to be the cause of slight but continuous oozing into the pericardium, which may produce a localized clot. An echocardiogram obtained after the re-operation showed no re-accumulation of the pericardial effusion. The patient was discharged 21 days after the operation, and has remained stable at home.

S38-3 Prognostic Impact of Peripheral Endothelial Function in Heart Failure

[N-terminal pro-] B-type natriuretic peptide, and left ventricular ultrasonography). Each test is individually scored as 0 if normal, 1 if borderline and 2 with an abnormal test. The total disease score is the sum of all the test scores. We have evaluated this early cardiovascular disease score in patients attending the Rasmussen Center for Cardiovascular Disease Prevention Center and who have no overt cardiovascular disease. This disease score was more predictive for events than the classical cardiovascular risk assessment. Angiotensin II antagonist has been studied in the reduction of this disease score and its effect on the different components (DETECTIV Study). The DETECT Study is now comparing the effect of ACE-inhibitor lisinopril, carvedilol and their combination vs placebo on the disease score in subjects with no overt disease, but already presence of subclinical disease. Early detection of cardiovascular disease in asymptomatic subjects seems to be a better diagnostic and therapeutic stratification than assessment of cardiovascular risk based on a biostatistical approach of the classical risk factors.

P-126 Diagnosis of Cardiac Amyloidosis with Quantitative Analysis of Myocardial Technetium-99m-Pyrophosphate Scintigraphy

Objective: To determine the correlation of Duke treadmill score with gated SPECT-MPI in patients evaluated for chest pain. Methods: We conducted a retrospective study on 200 consecutive patients referred to our imaging laboratory for evaluation of chest pain by using stress MPI from January to August 2008. DTS was calculated after exercise testing and categorized as low, moderate and high subgroups. Subsequent gated SPECT-MPI was performed and stratified according to severity of perfusion defect. Spearmans rho was applied to determine the correlation. Results: The overall result shows positive linear correlation between DTS and MPI (p 0.001). Out of 200 patients, 136 (68%) had low DTS, 51 (25.5%) had moderate and 13 (6.5%) had high DTS respectively. In low DTS group 129 (95%) patients had low risk MPI and 7 (5%) had intermediate risk MPI. In moderate risk DTS group 25 (49%) had low risk MPI whereas 15 (29.5%) and 11 (21.5%) had intermediate and high risk MPI respectively. In high DTS group all 13 patients had high risk MPI. Conclusion: On the basis of our findings it can be hypothesized that patients with high DTS can be referred for coronary angiography without imaging and patients with low DTS can be followed on medical management. However for definite conclusion diagnostic accuracy need to be determine in further studies.