Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol.

BACKGROUND: Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group. CONCLUSIONS: Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

Echocardiography-based pressure-volume loop assessment in the evaluation for the effects of indoxyl sulfate on cardiovascular function.

BACKGROUND: Indoxyl sulfate (IS), a uremic toxin, has been reported to have hypertrophic effects on the heart. Previous studies, however, have shown no association between elevated IS levels and cardiovascular outcomes in hemodialysis patients. We hypothesized that, despite left ventricular (LV) hypertrophy, myocardial contractility and ventricular-arterial coupling would remain preserved, and that this would explain the reason for the absence of prognostic impact of IS. METHODS: We evaluated the association of IS with LV structure, contractility, vascular function, and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) in 154 patients on hemodialysis, using echocardiography-based pressure-volume loop assessment. RESULTS: As expected, subjects in the high IS group (IS ≥ 33.8 µg/mL) had greater LV mass index and end-diastolic volume index compared to subjects in the low IS group (IS < 33.8 µg/mL). These differences remained significant after adjusting for age, sex, body mass index, diabetic nephropathy, duration of hemodialysis, and NT-proBNP levels, suggesting a potential role of elevated IS levels in LV remodeling. However, no differences in LV contractility (preload recruitable stroke work, peak power index, and systolic mitral annular velocity) and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) were observed between the groups. CONCLUSIONS: Deleterious effects of IS on LV remodeling are not accompanied by impaired LV contractility or mechanical efficiency, which could contribute to the absence of cardiovascular prognostic impact observed in previous studies performed on hemodialysis patients.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity and cardiac events in patients with ischemic cardiomyopathy and mild to moderate heart failure.

INTRODUCTION: We determined whether statin therapy improved cardiac sympathetic nerve activity as evaluated using iodine-123-metaiodobenzylguanidine (I-MIBG) scintigraphy, and whether this therapy affects prognosis in patients with ischemic cardiomyopathy. PATIENTS AND METHODS: This study was a subanalysis of our previous report of the result that the serial I-MIBG scintigraphic studies were the most useful prognostic indicator in patients with heart failure. Patients with heart failure [left ventricular ejection fraction (LVEF) <45%] but no cardiac events for at least 5 months before the study were identified according to their history of decompensated acute heart failure requiring hospitalization. The patients underwent I-MIBG scintigraphy and echocardiography immediately before hospital discharge and after 6 months. The % denervation, heart/mediastinum count ratio, and washout rate were determined from the I-MIBG scintigraphy, and the left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF were also determined from echocardiography. We selected 76 patients with old myocardial infarction without active ischemia and used propensity score matching to compare patients who received oral statin (n=38) with those who did not (n=38). The patients were followed up for a median of 4.74 years, with the primary and secondary study end points defined as incidences of fatal cardiac events and major adverse cardiac events (MACEs), respectively. RESULTS: After treatment, the I-MIBG scintigraphic and echocardiographic parameters were improved in the statin and nonstatin groups. However, the extent of change in the % denervation was -12.3±10.3 and -6.2±9.6 (P<0.01), whereas that in the heart/mediastinum count ratio was 0.19±0.14 and 0.08±0.15 (P<0.01), and that in washout rate was -8.1±7.2 and -0.5±9.2% (P<0.01). The extent of change in left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF in the statin group tended to exceed than in the nonstatin group, but these changes were not statistically significant. Of the 76 patients, 18 experienced fatal cardiac events and 32 experienced MACEs during the study. Multivariate Cox regression analyses revealed that the nonstatin therapy was a significant predictor of both cardiac death and MACEs in our patients. On Kaplan-Meier analysis, the rates of freedom from cardiac death or MACEs were significantly higher in the statin group than those in the nonstatin group (all, P<0.05). CONCLUSION: Statin therapy improved cardiac sympathetic nerve activity in patients with ischemic cardiomyopathy and mild to moderate heart failure. Furthermore, statin is potentially effective for reducing cardiac events in these patients.

Relationships of high cardiac output with ventricular morphology, myocardial energetics, and energy costs in hemodialysis patients with preserved ejection fraction.

Hemodialysis patients have conditions that increase cardiac output (CO), including arteriovenous fistula, fluid retention, vasodilator use, and anemia. We sought to determine the relationships between these factors and CO and to evaluate the effects of the high-output states on ventricular morphology, function, and myocardial energetics in hemodialysis patients, using noninvasive load-insensitive indices. Cardiovascular function was assessed in hemodialysis patients with high output [ejection fraction ≥ 50%, cardiac index (CI) > 3.5 L/min/m2, n = 30], those with normal output (CI < 3.0 L/min/m2, n = 161), and control subjects without hemodialysis (n = 155). As compared to control subjects and hemodialysis patients with normal CI, patients with elevated CI were anemic and displayed decreased systemic vascular resistance index (SVRI), excessive left ventricular (LV) contractility, larger LV volume, and tachycardia. Lower hemoglobin levels were correlated with decreased SVRI, excessive LV contractility, and higher heart rate, while estimated plasma volume and interdialytic weight gain were associated with larger LV volume, thus increasing CO. High output patients displayed markedly increased pressure-volume area (PVA) and PVA/stroke volume ratio, which were correlated directly with CO. The use of combination vasodilator therapy (angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker and calcium channel blocker) was not associated with high-output states. In conclusion, anemia and fluid retention are correlated with increased CO in hemodialysis patients. The high-output state is also associated with excessive myocardial work and energy cost.

Effect of Sex Differences on the Association Between Stroke Risk and Left Atrial Anatomy or Mechanics in Patients With Atrial Fibrillation.

BACKGROUND: Embolic stroke in atrial fibrillation is more prevalent in women than in men, yet the basis for this difference remains unclear. This study seeks to elucidate whether there are any sex differences in the relationships between stroke risk (CHADS2 score, CHA2DS2-VASc score without a sex category, and estimated stroke rate) and left atrial (LA) anatomy or mechanics in patients with atrial fibrillation. METHODS AND RESULTS: LA emptying fraction and global peak atrial longitudinal strain were assessed in 414 subjects with paroxysmal or persistent atrial fibrillation (156 women and 258 men). Linear regression models with an interaction term were performed to test the effect of sex difference on associations between the embolic risk and LA function or anatomy. Sensitivity analyses were performed in 228 age, heart rate, and rhythm-matched subjects (114 women and men). Women were older and had larger LA volumes and lower LA mechanics than men. Significant negative association between the CHADS2 score and LA emptying fraction was only demonstrated in women with a significant interaction between sexes. Similar significant interactions were found in global peak atrial longitudinal strain but not in LA volume. These findings were corroborated in the comparisons against CHA2DS2-VASc score without a sex category and the estimated stroke rate. Sensitivity analyses in the matched subgroup also confirmed the robustness of these sex differences in LA emptying fraction, but less so in global peak atrial longitudinal strain. CONCLUSIONS: Significant sex interactions on the association between global LA function and risk stratification schemes exist, which may be a reason for the higher prevalence of embolic stroke in women.

Hypoxia-inducible factor-1α mediates TGF-ß-induced PAI-1 production in alveolar macrophages in pulmonary fibrosis.

Hypoxia-inducible factor-1α (HIF-1α), a transcription factor that functions as a master regulator of oxygen homeostasis, has been implicated in fibrinogenesis. Here, we explore the role of HIF-1α in transforming growth factor-ß (TGF-ß) signaling by examining the effects of TGF-ß(1) on the expression of plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of lung tissue from a mouse bleomycin (BLM)-induced pulmonary fibrosis model revealed that expression of HIF-1α and PAI-1 was predominantly induced in alveolar macrophages. Real-time RT-PCR and ELISA analysis showed that PAI-1 mRNA and activated PAI-1 protein level were strongly induced 7 days after BLM instillation. Stimulation of cultured mouse alveolar macrophages (MH-S cells) with TGF-ß(1) induced PAI-1 production, which was associated with HIF-1α protein accumulation. This accumulation of HIF-1α protein was inhibited by SB431542 (type I TGF-ß receptor/ALK receptor inhibitor) but not by PD98059 (MEK1 inhibitor) and SB203580 (p38 MAP kinase inhibitor). Expression of prolyl-hydroxylase domain (PHD)-2, which is essential for HIF-1α degradation, was inhibited by TGF-ß(1), and this decrease was abolished by SB431542. TGF-ß(1) induction of PAI-1 mRNA and its protein expression were significantly attenuated by HIF-1α silencing. Transcriptome analysis by cDNA microarray of MH-S cells after HIF-1α silencing uncovered several pro-fibrotic genes whose regulation by TGF-ß(1) required HIF-1α, including platelet-derived growth factor-A. Taken together, these findings expand our concept of the role of HIF-1α in pulmonary fibrosis in mediating the effects of TGF-ß(1) on the expression of the pro-fibrotic genes in activated alveolar macrophages.

Practical assessment of myocardial viability with a positron coincidence gamma camera using 18F-fluorodeoxyglucose in acute myocardial infarction: comparison with dedicated positron emission tomography and 201Tl single photon emission computed tomography.

OBJECTIVE: 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) began to be supplied commercially to our hospital, which does not have a cyclotron, in autumn of 2005. The purpose of this study was to compare the utility of a dual-head positron coincidence detection (PCD) gamma camera in the detection of myocardial viability using (18)F-FDG with that of dedicated positron emission tomography (PET) and with that of thallium-201 ((201)Tl) single photon emission computed tomography (SPECT). METHODS: A total of 15 patients (14 men and 1 woman, mean age: 60+/-7 years, range: 46-73) with a large acute myocardial infarction (AMI) underwent (18)F-FDG PET, (18)F-FDG PCD imaging after oral glucose loading (75 g) and (201)Tl SPECT imaging. We divided the SPECT and PET images into a total of 20 segments, and semiquantitative visual analysis was performed by assessing regional tracer activities on a 4-point scoring system (DS): 0=normal uptake, 1=mildly reduced uptake, 2=severely reduced uptake, and 3=no uptake. We summed the DS in each patient as the total DS (TDS). RESULTS: The TDS of the (18)F-FDG PET image was 14.4+/-7.7. The TDS of the (18)F-FDG PCD image was 18.7+/-7.7. The TDS of the (201)Tl SPECT image was 24.1+/-11.5. The TDS of the (18)F-FDG PET image was significantly smaller than that of the (18)F-FDG PCD image. The TDS of the (18)F-FDG PET image was significantly smaller than that of the (201)Tl SPECT image. The TDS of the (18)F-FDG PCD image was significantly smaller than that of the (201)Tl SPECT image. CONCLUSION: The findings of the project suggest that (18)F-FDG PCD is a good modality based on its accuracy, convenience, and cost-performance for detecting myocardial viability in hospitals that do not have a PET system.

Usefulness of insulin resistance measured by homeostasis model assessment in predicting restenosis after coronary stent placement in nondiabetic patients.

The homeostasis model assessment enabled us to evaluate insulin resistance easily and accurately in the clinical setting. The restenosis rate of coronary stenting was significantly higher among patients with high values for the homeostasis model assessment. Our findings suggest that insulin resistance measured by the homeostasis model assessment predicts restenosis after coronary stent placement in nondiabetic patients.