Takayoshi Yamaki

Impact of adaptive servo‐ventilation on cardiovascular function and prognosis in heart failure patients with preserved left ventricular ejection fraction and sleep‐disordered breathing

Effective pharmacotherapy for heart failure with preserved left ventricular ejection fraction (HFpEF) is still unclear. Sleep‐disordered breathing (SDB) causes cardiovascular dysfunction, giving rise to factors involved in HFpEF. However, it remains unclear whether adaptive servo‐ventilation (ASV) improves cardiovascular function and long‐term prognosis of patients with HFpEF and SDB.

Acute heart failure volume control multicenter randomized (AVCMA) trial: comparison of tolvaptan and carperitide.

Acute decompensated heart failure (ADHF) is a common and highly morbid cardiovascular disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide.

Soluble Amyloid Precursor Protein 770 Is Released from Inflamed Endothelial Cells and Activated Platelets: A NOVEL BIOMARKER FOR ACUTE CORONARY SYNDROME*

Background: Separate monitoring of the cleavage products of different amyloid β precursor protein (APP) variants may provide useful information. Results: We found that soluble APP770 (sAPP770) is released from inflamed endothelial cells and activated platelets as judged by ELISA. Conclusion: sAPP770 is an indicator for endothelial and platelet dysfunctions. Significance: How sAPP770 is released in vivo has been shown. Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product, sAPP, is considered to be a possible marker for AD diagnosis, sAPP has been widely measured as a mixture of these variants. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable discrimination between endothelial and neurological dysfunctions. Using our newly developed ELISA system for sAPP770, we observed that inflammatory cytokines significantly enhanced sAPP770 secretion by endothelial cells. Furthermore, we unexpectedly found that sAPP770 was rapidly released from activated platelets. We also found that cerebrospinal fluid mainly contained sAPP695, while serum mostly contained sAPP770. Finally, to test our hypothesis that sAPP770 could be an indicator for endothelial dysfunction, we applied our APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial injury and platelet activation lead to fibrous plaque disruption and thrombus formation. Development of a biomarker is essential to facilitate ACS diagnosis in clinical practice. The results revealed that ACS patients had significantly higher plasma sAPP770 levels. Furthermore, in myocardial infarction model rats, an increase in plasma sAPP preceded the release of cardiac enzymes, currently used markers for acute myocardial infarction. These findings raise the possibility that sAPP770 can be a useful biomarker for ACS.

Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy

BACKGROUND Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. METHODS AND RESULTS Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. CONCLUSIONS ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV.

Liver Dysfunction Assessed by Model for End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System Predicts Adverse Prognosis in Heart Failure

Aims Liver dysfunction due to heart failure (HF) is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. Methods and Results We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289) and Group H (MELD-XI ≥10, n = 273). We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days), 104 deaths (62 cardiac deaths and 42 non-cardiac deaths) were observed. The event (cardiac death, non-cardiac death, all-cause death)-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively). In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively). Conclusions The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF.

Clinical features of patients with decompensated heart failure after the Great East Japan Earthquake.

The occurrence of heart failure (HF) and its clinical features after a great disaster have not been rigorously examined. We retrospectively examined the effect of the Great East Japan Earthquake on the occurrence of decompensated HF. The number of patients admitted for treatment of decompensated HF and their clinical features were compared between 2 periods, March 11, 2011 to September 10, 2011 (after the earthquake) and the same period in the previous year. The number of admissions increased from 55 in 2010 to 84 in 2011. A comparison of the clinical features showed that the patients admitted after the earthquake had (1) older age (p = 0.031), (2) greater systolic blood pressure (p = 0.039), (3) a greater incidence of new-onset HF due to valvular heart disease (p = 0.040), (4) interruption of drugs (p = 0.001), (5) a greater incidence of infection (p = 0.019), (6) greater B-type natriuretic peptide (p = 0.005) and C-reactive protein (p = 0.003) levels, (7) a lower estimated glomerular filtration rate (p = 0.048) and lower albumin levels (p = 0.021), and (8) a larger diameter of the inferior vena cava (p = 0.008). In conclusion, these results suggest that the earthquake increased the incidence of HF in association with high blood pressure, interruption of drugs, inflammation, malnutrition, and fluid retention. Taking appropriate measures to control blood pressure, nutritional status, and hygiene environment might decrease the occurrence of HF in future disasters.

Simultaneous cardiac imaging to detect inflammation and scar tissue with (18)F-fluorodeoxyglucose PET/MRI in cardiac sarcoidosis.

A 50-year-old female was referred to our hospital for complete right bundle branch block, which was detected by annual health check-up. Although she had no symptoms, echocardiography demonstrated left ventricular wall thinning and aneurysm at basal inter-ventricular septum and apex of the left ventricle (Figure 1, arrows). Thus, we suspected cardiac sarcoidosis and performed F-fluorodeoxyglucose (FDG) PET/MRI. After low carbohydrate diet for 24 hour before imaging and fasting for more than 18 hour, the patient was administered heparin 50 IU/kg intravenously to suppress physiological FDG uptake on the myocardium. Image acquisition was initiated 60 minutes after FDG administration.Maximum intensity projection revealed FDG uptake on bilateral hilar lymph nodes and mediastinal lymph nodes (Figure 2, arrows). Intense FDG uptake and late gadolinium enhancement (LGE) were observed in the left ventricle and in the right ventricle (Figure 3). T2-weighted images (T2WI) also showed high signal intensity indicating myocardial edema (Figure 3, arrows). Fusion images showed concordance of myocardial FDG uptake and LGE in most regions, but it should be noted that there was a discrepancy among the areas of FDG uptake, LGE, and high-intensity region on T2WI. This discrepancy revealed by simultaneous PET/MRI reminds us differential aspects of myocardial FDG uptake (active inflammation), LGE (fibrotic scar), and high-intensity region on T2WI (myocardial edema). PET/MRI is a useful imaging technology to provide helpful diagnostic information and guide a therapeutic strategy of cardiac sarcoidosis.

Cardiovascular function and prognosis of patients with heart failure coexistent with chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF), and is considered to be associated with adverse outcomes in HF patients. However, the features of cardiovascular function and the detailed all-cause mortality of HF with COPD remain unclear. METHODS AND RESULTS Consecutive 378 patients admitted for HF who underwent spirometry were divided into three groups: HF without COPD (non-COPD group, n=272), HF with mild COPD (GOLD I group, n=82), and HF with moderate COPD (GOLD II group, n=24). The GOLD II group, as compared to non-COPD group, had (1) higher troponin T (p=0.009); (2) greater cardio-ankle vascular index (p=0.032); and (3) similar cardiac systolic and diastolic function of the right and left ventricle. In addition, rates of cardiac (p=0.049), non-cardiac (p=0.001), and all-cause mortality (p=0.002) were higher in GOLD II group than in non-COPD and GOLD I groups. Importantly, in the Cox proportional hazard analyses, the GOLD stage II was an independent predictor of cardiac (p=0.038), non-cardiac (p=0.036), and all-cause mortality (p=0.015) in HF patients. CONCLUSIONS HF patients with coexistent moderate COPD (GOLD stage II) have greater myocardial damage, greater arterial stiffness, and higher cardiac and non-cardiac mortality.

Cardiopulmonary exercise testing as prognostic indicators: Comparisons among heart failure patients with reduced, mid-range and preserved ejection fraction:

Aims We aimed to determine the differences of impact of cardiopulmonary exercise testing (CPX) parameters on prognosis of heart failure with reduced left ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and mid-range ejection fraction (HFmrEF). Methods We compared clinical characteristics and CPX parameters among the three groups, and the value of each CPX parameter to predict adverse cardiac events (cardiac deaths and re-hospitalizations for heart failure), cardiac deaths and all-cause deaths. Results Of 1190 patients, 41.9% had HFrEF, 36.8% had HFpEF and 21.3% had HFmrEF. The patients in HFrEF group had higher rates of adverse cardiac events, cardiac death and all-cause death than those of HFpEF and HFmrEF groups. In HFrEF, the independent predictors of adverse cardiac events were peak oxygen consumption and oxygen uptake efficiency slope, predictors of cardiac death were peak oxygen consumption and oxygen uptake efficiency slope, and the predictor of all-cause death was peak oxygen consumption. In HFpEF, the predictor of adverse cardiac events was peak oxygen consumption, predictors of cardiac deaths and all-cause deaths were peak oxygen consumption and exertional oscillatory ventilation. In HFmrEF, predictors of adverse cardiac events were peak oxygen consumption and oxygen uptake efficiency slope, and the predictor of cardiac deaths and all-cause deaths was peak oxygen consumption. Conclusion Peak oxygen consumption is the strong predictor for adverse events in all groups. Oxygen uptake efficiency slope predicts adverse prognosis in HFrEF, but not in HFpEF. In contrast, exertional oscillatory ventilation is the predictor only in HFpEF. Thus, different CPX parameters may be able to differentially predict prognosis in HFrEF and HFpEF. Those for predicting prognosis in HFmrEF may be intermediate between HFrEF and HFpEF.

Serum tenascin-C level is associated with coronary plaque rupture in patients with acute coronary syndrome

Tenascin-C, a large oligometric glycoprotein of the extracellular matrix, increases the expression of matrix metalloproteinases that lead to plaque instability and rupture, resulting in acute coronary syndrome (ACS). We hypothesized that a high serum tenascin-C level is associated with plaque rupture in patients with ACS. Fifty-two consecutive ACS patients who underwent emergency percutaneous coronary intervention (PCI) and, as a control, 66 consecutive patients with stable angina pectoris (SAP) were enrolled in this study. Blood samples were obtained from the ascending aorta just prior to the PCI procedures. After coronary guide-wire crossing, intravascular ultrasonography (IVUS) was performed for assessment of plaque characterization. Based on the IVUS findings, ACS patients were assigned to two groups according to whether there was ruptured plaque (ruptured ACS group) or not (nonruptured ACS group). There were 23 patients in the ruptured group and 29 patients in the nonruptured group. Clinical characteristics and IVUS measurements did not differ between the two groups. Tenascin-C levels were significantly higher in the ruptured ACS group than in the SAP group, whereas there was no significant difference between the nonruptured ACS and SAP groups. Importantly, in the ruptured ACS group, tenascin-C levels were significantly higher than in the nonruptured ACS group (71.9 ± 34.9 vs 50.5 ± 20.5 ng/ml, P < 0.005). Our data demonstrate that tenascin-C level is associated with pathologic conditions in ACS, especially the presence of ruptured plaque.