Long-term effects of lowering postprandial glucose level on cardiovascular outcomes in early-stage diabetic patients with coronary artery disease: 10-year post-trial follow-up analysis of the DIANA study.

AIMS: To elucidate the long-term cardiovascular benefit of lowering postprandial hyperglycemia (PPG) in early-stage T2DM patients. METHODS: This 10-year post-trial follow-up study included 243 patients from the DIANA (DIAbetes and diffuse coronary Narrowing) study, a multi-center randomized controlled trial which compared the efficacy of one-year life-style and pharmacological (voglibose/nateglinide) intervention lowering PPG on coronary atherosclerosis in 302 early-stage T2DM subjects [impaired glucose tolerance (IGT) or newly-diagnosed T2DM] (UMIN-CTRID#0000107). MACE (all-cause death, non-fatal MI or unplanned coronary revascularization) were compared in (1) three assigned therapies (life-style intervention/vogliose/nateglinide) and (2) patients with and without improvement of PPG (reversion from IGT to NGT or from DM to IGT/NGT on 75 g oral glucose tolerance test). RESULTS: During the 10-year post-trial observational period, voglibose (HR = 1.07, 95%CI: 0.69-1.66, p = 0.74) or nateglinide (HR = 0.99, 95%CI: 0.64-1.55, p = 0.99) did not reduce MACE. Similarly, achieving the improvement of PPG was not associated with a reduction of MACE (HR = 0.78, 95%CI: 0.51-1.18, p = 0.25). However, in IGT subjects (n = 143), this glycemic management significantly reduced the occurrence of MACE (HR = 0.44, 95%CI: 0.23-0.86, p = 0.01), especially unplanned coronary revascularization (HR = 0.46, 95%CI: 0.22-0.94, p = 0.03). CONCLUSIONS: The early improvement of PPG significantly reduced MACE and unplanned coronary revascularization in IGT subjects during the post-trial 10-year period.

Development of an amino acid sequence-dependent analytical method for peptides using near-infrared spectroscopy.

We aimed to develop an amino acid sequence-dependent analytical method using near-infrared (NIR) spectroscopy. The detailed analysis of the NIR spectra of eight different amino acid aqueous solutions (glycine, alanine, serine, glutamine, lysine, phenylalanine, tyrosine, and proline) revealed different spectral patterns characteristic of different amino acid residues in the 6200-5700 and 5000-4200 cm-1 regions, and the amino acids were identified based on the patterns. The spectra in the region of 5000-4500 cm-1 for tripeptide organic solutions that were composed of the aforementioned eight amino acids clearly showed the spectral differences depending on the amino acid species and amino acid sequences. Namely, tripeptide species were clearly differentiated from each other based on the spectral pattern of NIR bands due to the combinations of N-H stretching and amide II/III modes and those derived from the first overtones of amide II and amide I. The quantitative evaluation of changes in the concentrations of dipeptides and tripeptides composed of two different amino acids, glycine and proline was performed using partial least squares regression (PLSR) analysis and a combination of bands for amide modes. The calibration and validation results with high determination coefficients (R2 ≥ 0.99) were successfully obtained based on the amino acid sequences. The results not only revealed the usefulness of NIR spectroscopy as a process analytical technology (PAT) tool for synthesizing peptides in a micro flow reactor but also proposed a general method for quantitatively analyzing NIR spectra obtained in the course of chemical synthesis.

Diagnostic utility of fusion 18F-fluorodeoxyglucose positron emission tomography/cardiac magnetic resonance imaging in cardiac sarcoidosis.

BACKGROUND: Although each 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been used to diagnose cardiac sarcoidosis (CS), active CS is still misdiagnosed. METHODS: Active CS, diagnosed by PET alone, was defined as focal or focal on diffuse FDG uptake pattern. In fusion PET/CMR imaging, using a regional analysis with AHA 17-segment model, the patients were categorized into four groups: (1) PET-/LGE-, (2) PET+/LGE-, (3) PET+/LGE+, and (4) PET-/LGE+. PET+/LGE+ was defined as active CS. RESULTS: 74 Patients with suspected CS were enrolled. Between PET alone and fusion PET/CMR imaging, 20 cases had mismatch evaluations of active CS, and most had diffuse or focal on diffuse FDG uptake pattern on PET alone imaging. 40 Patients fulfilled the 2016 the Japanese Circulation Society diagnostic criteria for CS. The interobserver diagnostic agreement was excellent (κ statistics 0.89) and the overall accuracy for diagnosing CS was 87.8% in fusion PET/CMR imaging, which were superior to those in PET alone imaging (0.57 and 82.4%, respectively). In a sub-analysis of diffuse and focal on diffuse patterns, the agreement (κ statistics 0.86) and overall accuracy (81.8%) in fusion PET/CMR imaging were still better. CONCLUSIONS: Fusion PET/CMR imaging with regional analysis offered reliable and accurate diagnosis of CS, covering low diagnostic area by FDG-PET alone.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- A Report From the CURRENT AS Registry.

BACKGROUND: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22). CONCLUSIONS: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

Sex difference in pulmonary hypertension in the evaluation by exercise echocardiography.

Male patients with pulmonary hypertension have poor survival than their female counterparts. Poor right ventricular function in men may be one of the major determinants of poor prognosis. This study aimed to investigate the difference in hemodynamics during exercise between men and women by exercise echocardiography. Consecutive patients with pulmonary hypertension who underwent right heart catheterization were enrolled, and survival was analyzed. In patients who underwent exercise echocardiography, the change in tricuspid regurgitation pressure gradient during exercise was calculated at multiple stages (low-, moderate-, and high-load exercise), and the mortality was also recorded. In a total of 93 patients, although there were no differences in pulmonary artery pressure and vascular resistance between sexes, male patients showed poor survival. In patients with exercise echocardiography, change in tricuspid regurgitation pressure gradient at low-load (25 W) exercise was significantly lower in men, although that at maximum-load exercise was not different between men and women. In the Kaplan-Meier analysis, in a median follow-up duration of 1760 days, male patients and those with lower change in tricuspid regurgitation pressure gradient at low-load exercise showed poorer survival (P = 0.002 and 0.026, respectively). In the Cox proportional hazards analysis, the change in tricuspid regurgitation pressure gradient at low-load exercise was independently associated with poor survival after adjustment for age and sex. In conclusion, a lower change in tricuspid regurgitation pressure gradient at low-load exercise was observed in male patients and was a prognostic marker, which may be associated, at least in part, with poorer prognosis in male patients with pulmonary hypertension.

Predictive value of the coronary artery calcium score and advanced plaque characteristics: Post hoc analysis of the PREDICT registry.

BACKGROUND: Whether coronary plaque characteristics assessed in coronary computed tomography angiography (CCTA) in association with the coronary artery calcium score (CACS) have predictive value for coronary events is unclear. We aimed to examine the predictive value of the CACS and plaque characteristics for the occurrence of coronary events. METHODS: Among 2802 patients who were analyzed in the PREDICT registry, 2083 with suspected coronary artery disease (CAD) were studied using post hoc analysis. High-risk plaques were defined as having ≥2 adverse characteristics, such as low computed tomographic attenuation, positive remodeling, spotty calcification, and napkin-ring sign. An adjudicative composite of coronary events (cardiac death, nonfatal acute coronary syndrome, and coronary revascularization ≥3 months after indexed CCTA) were analyzed. RESULTS: Seventy-three (3.5%) patients had coronary events and 313 (15.0%) had high-risk plaques. Multivariate Cox proportional hazard analysis showed that high-risk plaques remained an independent predictor of coronary events (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.13-3.34, P â€‹= â€‹0.0154), as well as the log-transformed CACS (adjusted HR 1.24, 95% CI 1.11-1.39, P â€‹= â€‹0.0002) and the presence of obstructive stenosis (adjusted HR 5.63, 95% CI 3.22-10.12, P 0.0001). In subgroup analyses, high-risk plaques were independently predictive only in the low CACS class (<100). CONCLUSION: This study shows that assessment of adverse features by coronary plaque imaging independently predicts coronary events in patients with suspected CAD and a low CACS. Our findings suggest that the clinical value of high-risk plaques to CACS and stenosis assessment appears marginal.

Method of Monitoring the Number of Amide Bonds in Peptides Using Near-Infrared Spectroscopy.

Using near-infrared (NIR) spectroscopy, we aimed to develop a method of monitoring the increasing number of amide bonds with the elongation of the chain length of peptides. Because peptide synthesis can be monitored by evaluating the increasing number of amide bonds with dehydration occurring between amino acids, polyglycine, which has the simplest structure among polyamino acids, was studied, and the key bands whose absorption intensities increased with the elongation of the chain length, such as the bands attributed to glycine, diglycine, triglycine, and tetraglycine, were searched. The bands due to the combinations of the amide A and amide II/III modes in the region of 5000-4500 cm-1 were revealed to be good candidates for key bands, their second derivative intensities increased as the number of amide bonds increased, regardless of pH, solvent species, and the presence of protecting groups. The number of amide bonds was evaluated by a partial least square regression using the abovementioned combination bands, and a calibration model with a high determination coefficient (≥0.99) was constructed. These results not only have demonstrated the usefulness of NIR spectroscopy as a process analytical technology tool for the process of synthesizing the peptide in a microflow reactor but also have provided basic knowledge for analyzing amide bonds in the NIR spectra of proteins, polyamino acids, polypeptides, and polyamides.

Impact of Neointimal Condition and Platelet Reactivity on Intrastent Thrombus at Long-Term Follow-up After 2nd- and 3rd-Generation Drug-Eluting Stent Implantation　- Insights From a Coronary Angioscopy and Pharmacodynamic Study.

BACKGROUND: Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. CONCLUSIONS: Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry.

BACKGROUND: There is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer. METHODS: In the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer. RESULTS: Among 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer. IVC filters were placed and not retrieved in 455 patients (17%) in the entire cohort, in 150 patients (24.8%) in the active cancer stratum, and in 305 patients (15.1%) in the non-cancer stratum. In the entire cohort, non-retrieved IVC filter placement was not associated with a lower adjusted risk for PE recurrence (HR 0.59, 95% CI 0.30-1.15, P = 0.122), but with an increased adjusted risk for DVT recurrence (HR 2.27, 95% CI 1.43-3.60, P<0.001). In the non-cancer stratum, the non-retrieved IVC filter placement was associated with a decreased risk for PE (HR 0.29, 95% CI 0.09-0.93, P = 0.037), but not with an increased risk for DVT (HR 1.73, 95% CI 0.89-3.38, P = 0.108), while in the active cancer stratum, it was associated with an increased risk for DVT (HR 2.47, 95% CI 1.24-4.91, P = 0.010), but not with a decreased risk for PE (HR 0.82, 95% CI 0.34--1.96, P = 0.650). CONCLUSIONS: There were some differences in the risk-benefit balance between VTE patients with and without active cancer.

Determinants and prognostic implications of instantaneous wave-free ratio in patients with mild to intermediate coronary stenosis: Comparison with those of fractional flow reserve.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

Increased Left Ventricular Trabeculation Is Associated With Increased B-Type Natriuretic Peptide Levels and Impaired Outcomes in Nonischemic Cardiomyopathy.

BACKGROUND: The clinical significance of left ventricular (LV) trabeculation remains unknown in cardiomyopathies. B-Type natriuretic peptide (BNP) strongly reflects LV end-diastolic wall stress and is a useful prognostic marker of cardiovascular diseases. The enhanced identification of LV trabeculae (T) with the use of cardiac magnetic resonance and the evaluation of its relationship with BNP may elucidate the biologic significance and clinical impact of trabeculation in patients with nonischemic cardiomyopathy (NICM). METHODS: The LV volume and mass of 515 patients with NICM and 36 control subjects were analyzed with the use of a steady-state free precession sequence, and individual T mass was planimetred. Major adverse cardiac events (MACE) were assessed. RESULTS: T mass index correlated with LV end-diastolic volume index (EDVI), LV mass index, and papillary muscle mass index (all P < 0.001). Also, T mass index was positively correlated with BNP level (R = 0.381; P < 0.001) and was an independent determinant of BNP after adjusting for age, sex, body mass index (BMI), etiology, LV ejection fraction, and LV EDVI (P < 0.001). Kaplan-Meier analysis during a median follow-up of 17.3 months showed that higher T mass index and increased BNP level correlated with MACE. On multivariate analysis, T mass index (P = 0.031) and BNP (P < 0.001) remained associated with poor outcomes when combined with age, sex, BMI, and etiology. CONCLUSIONS: Increased LV trabeculation was associated with LV dysfunction/remodelling and impaired outcomes in NICM of various etiologies. This may support the biologic significance of LV trabeculation and could be attributed to its association with BNP through LV wall stress.

Clinical and angiographic factors predicting fractional flow reserve and explaining the visual-functional mismatch in patients with intermediate coronary artery stenosis.

BACKGROUND: Visual-functional mismatch between coronary angiography and fractional flow reserve (FFR) has been reported, and the underlying reason remains poorly understood. Therefore, the relationship between angiographic measurements and FFR was evaluated, and predictors for FFR in intermediate coronary artery stenosis were determined. METHODS: Consecutive 314 patients (405 lesions) with a lesion of 30-80% angiographic diameter stenosis who underwent invasive FFR were recruited. The myocardial area supplied by the coronary artery distal to the stenosis was evaluated using a modified version of the Bypass Angioplasty Revascularization Investigation (BARI) score. Participants underwent follow-up, and major cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), and unplanned revascularization were recorded. RESULTS: Although % diameter stenosis was correlated with FFR (R = 0.279, P < 0.001), diameter stenosis-FFR mismatch was observed in 37.8% of the lesions. Although FFR values were not associated with clinical factors, such as age, sex, and comorbidities, it was correlated with minimal lumen diameter (MLD), diffuse lesion, presence of proximal lesion, and BARI score. In addition, the lesions in left anterior descending (LAD) coronary artery showed low FFR values compared with those in the left circumflex coronary artery or right coronary artery. In multivariate logistic analysis, MLD (ß coefficient = 0.330), diffuse lesion (ß coefficient = -0.266), proximal lesion (ß coefficient = -0.144), BARI score (ß coefficient = -0.219), and LAD lesion (ß coefficient = -0.293) were all independent predictors for FFR value. The estimated FFR value based on these factors showed smaller mismatch and higher sensitivity. No difference was observed in the event rates for MACE and MI or revascularization between the FFR-guided and estimated FFR-guided strategies. CONCLUSIONS: MLD, diffuse lesion, proximal lesion, BARI score, and lesion vessel were independent predictors for FFR in intermediate coronary stenosis. Not only the extent of local lesion stenosis but also the amount of myocardial supply and the lesion location may determine the physiological significance and explain the visual-functional mismatch. The estimation of FFR by these factors may be useful in clinical practice.

Right ventricular involvement is an important prognostic factor and risk stratification tool in suspected cardiac sarcoidosis: analysis by cardiac magnetic resonance imaging.

BACKGROUND: Late gadolinium enhancement imaging (LGE) of the left ventricle (LV) by cardiac magnetic resonance (CMR) has prognostic value for patients with cardiac sarcoidosis (CS). Right ventricle (RV) dysfunction is also associated with adverse outcomes in patients with heart failure. Therefore, we sought to determine if RV LGE and dysfunction predicted adverse events in patients with suspected CS. METHODS: In 103 consecutive patients with suspected CS who underwent CMR, functional and remodeling indexes of both the LV and RV were measured and the extent and localization of LGE were also analyzed. Major adverse cardiac events (MACE) were defined as cardiovascular mortality, severe ventricular tachyarrhythmia, hospitalization with heart failure, and advanced atrioventricular block. RESULTS: During a median follow-up of 20.6 months, Kaplan-Meier analysis showed that decreased RV ejection fraction (EF) was associated with MACE (P < 0.001) and receiver operating characteristics curve (ROC) analysis indicated good predictive performance of RV EF for MACE (area under the ROC = 0.834). RV EF operated independently of LV EF or LGE extent for predicting MACE. In addition, the presence of LGE in RV was independently associated with MACE (P = 0.011), and a combined analysis of RV EF and RV LGE showed better risk stratification for MACE (P < 0.001). CONCLUSIONS: Both RV EF and LGE were independently associated with MACE and enhanced risk stratification in patients with suspected CS. CMR may be a useful tool for detecting myocardial function and fibrosis in both the LV and RV.

Clinical Significance of Increased Cardiac Troponin T in Patients with Chronic Hemodialysis and Cardiovascular Disease: Comparison to B-Type Natriuretic Peptide and A-Type Natriuretic Peptide Increase.

BACKGROUND: An increased cardiac troponin T (cTnT) level identifies a high-risk group in patients with end-stage renal disease; however, the mechanism of cTnT elevation remains unclear in such patients without acute coronary syndrome (ACS). Therefore, we explored the relationship between cTnT levels and the hemodynamic parameters and the prognostic potential of cTnT in stable patients with chronic hemodialysis (HD). METHODS: We included consecutive 174 patients with HD who were referred for coronary angiography due to stable coronary artery disease (CAD), peripheral artery disease (PAD), or heart failure (HF). Hemodynamic measurement was performed, and plasma cTnT, B-type natriuretic peptide (BNP), and A-type natriuretic peptide (ANP) were measured at the same time. The potential of 3 biomarkers to predict all-cause mortality, cardiac death or hospitalized HF, and vascular event was assessed. RESULTS: Increased log cTnT levels were correlated with increased log BNP and log ANP levels (r = 0.531, p < 0.001 and r = 0.411, p < 0.001, respectively). Not increased log cTnT, but increased log BNP and log ANP were associated with the presence of CAD and the extent of CAD. In contrast, they were all associated with the New York Heart Association functional classification and the presence of PAD and significantly correlated with left ventricular end-diastolic pressure (LVEDP) in an independent manner. Increased cTnT and BNP levels were associated with the mortality and hospitalized HF. However, increased cTnT was not associated with vascular events, unlike increased BNP. CONCLUSIONS: In patients with chronic HD without ACS, increased cTnT reflected increased LVEDP and the presence of HF or PAD independently, and it did not reflect the presence of CAD in contrast to increased BNP. cTnT and BNP were significant prognostic predictors; however, increased cTnT was associated with HF-related events, not with arteriosclerotic events.

Early transient recurrence of ventricular fibrillation after catheter ablation of premature ventricular contraction from Purkinje fibers in two patients with myocardial infarction.

Catheter ablation (CA) targeting premature ventricular contraction (PVC) from Purkinje fibers can be an effective therapy for refractory ventricular fibrillation (VF) after myocardial infarction (MI). We experienced two cases in which catheter ablation targeting PVC initiating VF after percutaneous coronary intervention (PCI) in post-MI patients was effective despite transient early recurrences of VF. The first patient (a 68-year-old woman with MI) developed drug-refractory VF 3 days after PCI to the left anterior descending artery (LAD) and left circumflex artery. CA targeting Purkinje potential preceding PVC at the infarcted area eliminated both the PVCs and VF. Three days after the procedure, the VF attacks relapsed by a different type of PVC. However, the VF responded to conventional treatments and disappeared thereafter. In the second patient (an 83-year-old woman with old MI), refractory VF attacks occurred after PCI to the LAD. CA targeting Purkinje potential preceding two distinct types of PVC successfully suppressed the VF. Although the VF relapsed 2 days after CA, it was suppressed by conventional treatment and disappeared the next day. .

Early and later studies on action potential and fertilization potential of echinoderm oocytes and Ca2+ response of mammalian oocytes.

This is a personal essay starting from the early study on fertilization signals in echinoderm and mammalian oocytes. It presents actual examples showing that a unexpected discovery leads to unimaginable development of the research in diverse directions in later years and yields a common concept after long years' effort and accumulation. Those outcomes are the happiest gift for researchers. We also learn many precepts in our own research life.

Acute effects of intravenous carvedilol versus metoprolol on baroreflex-mediated sympathetic circulatory regulation in rats.

AIMS: To compare the effects of metoprolol and carvedilol on baroreflex-mediated sympathetic circulatory regulation. METHODS: In anesthetized Wistar-Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in sympathetic nerve activity (SNA), arterial pressure (AP), heart rate (HR), and aortic flow (AoF) in response to a staircase-wise pressure input were examined before (control) and after intravenous injection of low-dose metoprolol (2 mg/kg), high-dose metoprolol (10 mg/kg), or carvedilol (0.67 mg/kg) (n = 6 each). Peripheral vascular resistance (PVR) was calculated from mean AP divided by mean AoF. RESULTS: Low-dose metoprolol had limited effect on sympathetic AP regulation compared to control [operating-point AP (drug vs. control): 88.7 ±â€¯7.1 vs. 98.3 ±â€¯3.3 mm Hg, not significant] despite a significant bradycardic effect. Although high-dose metoprolol showed central sympathoinhibition, it increased PVR at a given SNA as a peripheral effect. Consequently, high-dose metoprolol decreased the operating-point AP slightly (96.1 ±â€¯2.7 vs. 101.9 ±â€¯2.7 mm Hg, P < 0.01). Carvedilol showed no significant central sympathoinhibition at the dose examined in this study, but significantly reduced PVR at a given SNA, leading to a marked reduction in the operating-point AP (71.9 ±â€¯8.2 vs. 112.6 ±â€¯7.6 mm Hg, P < 0.05). CONCLUSION: Low-dose metoprolol has limited hypotensive effect despite blockade of sympathetic HR regulation. Although high-dose metoprolol induces central sympathoinhibition, it also induces peripheral vasoconstriction that antagonizes the hypotensive effect. In contrast, carvedilol exhibits hypotensive effect mainly through peripheral vasodilation. Although carvedilol is frequently classified as a ß-blocker, its vasodilatory effect via α1-adrenergic blockade plays an important role in AP reduction or heart failure treatment.

Cardiac Magnetic Resonance Identified the Fibrotic Lesion Associated with Syncope Attack Due to Complete Atrioventricular Block in a Patient with Hypertrophic Cardiomyopathy and Aortic Stenosis.

An 84-year-old man presented with syncope. Prior to admission, ambulatory electrocardiogram had demonstrated non-sustained ventricular tachycardia. Echocardiography showed severe aortic stenosis. He was also diagnosed with hypertrophic cardiomyopathy (HCM) by cardiac magnetic resonance (CMR) showing remarkable inhomogeneous left ventricular hypertrophy and extensive late gadolinium enhancement (LGE) in the lesions at the upper border and right-ventricular side of the basal-mid septal wall. Finally, he showed complete atrioventricular (AV) block followed by a long pause and syncope several times after admission. In this case with several possible causes of syncope, the CMR findings suggested a clue concerning the etiology of his syncope: complete AV block in HCM.

Importance of sympathetic nervous system activity during left ventricular functional recovery and its association with in-hospital complications in Takotsubo syndrome.

The relationship between activation of the sympathetic nervous system (SNS) and improvement of left ventricular (LV) function and how this correlates with clinical outcomes are not fully explored in Takotsubo syndrome (TS). The purpose of this study is to evaluate the relationship between activation of the SNS and LV function improvement and how this correlates with clinical outcomes in TS. Patients with TS were retrospectively identified. Patients were divided into two groups according to the timing of LV function improvement: < 1 month (S group) and ≥ 1 month (L group). Activation of the SNS was assessed by plasma catecholamine measurement and Iodine-123 meta-iodobenzylguanidine (I123-MIBG) scintigraphy. In-hospital complications included heart failure, cardiogenic shock, the use of invasive or noninvasive ventilation, life-threatening arrhythmia, cerebrovascular event and all-cause death. A total of 90 patients with TS were enrolled. Of these, 39 patients were in the S group and 51 in the L group. There were no significant differences between the two groups in clinical demographics. The L group was characterized by enhanced SNS activation, including higher levels of catecholamines and lower late heart-mediastinum ratio followed by higher washout rate in I123-MIBG scintigraphy, compared with the S group. In-hospital complications were increased in the L group (56% vs. 33.3%, p = 0.03), including higher rates of heart failure (45% vs. 23%, p = 0.03) and in-hospital death (8.0% vs. 0%, p = 0.03). In patients with TS, high activity of the SNS was observed in patients with delayed LV function recovery, which was associated with in-hospital adverse outcomes.