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This study sought to investigate whether elevated liver stiffness (LS) values at discharge reflect residual liver congestion and are associated with worse outcomes in patients with heart failure (HF).Transient elastography is a newly developed, noninvasive method for assessing LS, which can be highly reflective of right-sided filling pressure associated with passive liver congestion in patients with HF.LS values were determined for 171 hospitalized patients with HF before discharge using a Fibroscan device.The median LS value was 5.6 kPa (interquartile range: 4.4 to 8.1 kPa; range 2.4 to 39.7 kPa) and that of right-sided filling pressure, which was estimated based on LS, was 5.7 mm Hg (interquartile range: 4.1 to 8.2 mm Hg; range 0.1 to 18.9 mm Hg). The patients in the highest LS tertile (6.9 kPa, corresponding to an estimated right-sided filling pressure of7.1 mm Hg) had advanced New York Heart Association functional class, high prevalence of jugular venous distention and moderate/severe tricuspid regurgitation, large inferior vena cava (IVC) diameter, low hemoglobin and hematocrit levels, high serum direct bilirubin level, and a similar left ventricular ejection fraction compared with the lower tertiles. During follow-up periods (median: 203 days), 8 (5%) deaths and 33 (19%) hospitalizations for HF were observed. The patients in the highest LS group had a significantly higher mortality rate and HF rehospitalization (hazard ratio: 3.57; 95% confidence interval: 1.93 to 6.83; p 0.001) compared with the other tertiles. Although LS correlated with IVC diameter and serum direct bilirubin and brain natriuretic peptide levels, LS values were predictive of worse outcomes, even after adjustment for these indices.These data suggest that LS is a useful index for assessing systemic volume status and predicting the severity of HF, and that the presence of liver congestion at discharge is associated with worse outcomes in patients with HF.

Background: Left ventricular reverse remodeling (LVRR) is a favorable response in non-ischemic, non-valvular cardiomyopathy (NICM) patients. Recently, 18-lead body surface electrocardiography (ECG), the standard 12-lead ECG with synthesized right-sided/posterior chest leads, has been developed, but its predictive value for LVRR has not been evaluated. Methods and Results: Of 216 consecutive hospitalized NICM patients with LV ejection fraction (LVEF) ≤35%, we studied 125 who received optimization of their heart failure treatment and had 18-lead ECG and echocardiography data available for evaluating LVRR, defined as an absolute increase in LVEF ≥10% concomitant with LVEF ≥35% after 1-year optimized treatment. Most 18-lead ECG parameters in the NICM patients differed from those in 312 age- and body mass index-matched subjects with normal echocardiography. LVRR occurred in 59 NICM patients and they had a larger QRS amplitude in the limb leads (I, II, aVR, and aVF), precordial leads (V3–V6), and synthesized leads (syn-V4R–5R), decreased QRS axis and duration, and lower prevalence of fragmented QRS than those without LVRR. The ECG score using 3 selected parameters (QRS amplitude in aVR ≥675 µV; QRS duration

BACKGROUND Treatment decisions in dilated cardiomyopathy (DCM) patients with severe heart failure (HF) and short clinical history are challenging because of the difficulty of determining HF stage or prognosis in the acute HF phase. We hypothesized that persistent decreased systemic or increased pulmonary arterial pressure , including in the sub-clinical phase, might affect the main pulmonary artery diameter (PAD), ascending aortic diameter (AoD), and their ratio (PAD/AoD). This study assessed AoD, PAD, and PAD/AoD by non-contrast computed tomography scans in DCM patients in the acute phase of HF and examined the association of these parameters with their clinical course. METHODS Of 261 screened individuals, we studied 110 consecutive hospitalized patients with DCM suspected of being in advanced stage of HF and 45 age-matched controls, assessing clinical data and later events (cardiac death or left ventricular assist device implantation). RESULTS Compared with controls, DCM patients had smaller AoD (26.6 ± 4.4 vs 30.6 ± 2.7 mm) and larger PAD (27.7 ± 3.5 vs 25.4 ± 2.8 mm) and PAD/AoD (1.05 ± 0.14 vs 0.83 ± 0.08; all p 1.05) had more frequent past HF hospitalizations, lower blood pressure, stroke volume, and ejection fraction , higher brain natriuretic peptide levels, smaller AoD, and similar PAD compared with patients with a low PAD/AoD. A higher PAD/AoD was associated with poorer outcomes even after adjusting for age, blood pressure, ejection fraction, or number of hospitalizations. CONCLUSION Assessment of AoD and PAD may have important clinical implications in determining whether DCM patients are in an advanced stage of HF with a poorer prognosis.

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD). Previous studies analyzing 1α-hydroxylase or vitamin D receptor (Vdr) knockout mice revealed active vitamin D as a promising agent inhibiting LVH progression. Paricalcitol, an active vitamin D analog, failed to suppress the progression of LV mass index (LVMI) in pre-dialysis patients with CKD. As target genes of activated VDR differ depending on its agonists, we examined the effects of maxacalcitol (22-oxacalcitriol: OCT), a less calcemic active vitamin D analog, on LVH in hemodialysis patients and animal LVH models with renal insufficiency. In retrospective cohort study, patients treated with OCT who underwent hemodialysis were enrolled. Using cardiac echocardiography, LV mass was evaluated by the area-length method. In animal study, angiotensin II (Ang II)-infused Wister rats with heminephrectomy or Ang II-stimulated neonatal rat ventricular myocytes (NRVM) were treated with OCT. OCT significantly inhibited the progression of LVMI in hemodialysis patients. In Ang II-infused heminephrectomized rats, OCT suppressed the progression of LVH in a blood pressure-independent manner. OCT also suppressed the activity of calcineurin in the left ventricle of model rats. Specifically, OCT reduced the protein levels of calcineurin A, but not the mRNA levels of Ppp3ca (calcineurin Aα). Luciferase assays showed that OCT increased the promoter activity of Fbxo32 (atrogin1), an E3 ubiquitin ligase targeting calcineurin A. Finally, OCT promoted ubiquitination and degradation of calcineurin A. Our works indicated that OCT retards progression of LVH through calcineurin-NFAT pathway, which reveal a novel aspect of OCT in attenuating pathological LVH.

A 34-year-old man underwent heart transplantation because of ischemic cardiomyopathy. Coronary angiography after the transplantation showed no significant stenosis in his coronary trees except for mild stenosis in the proximal left anterior descending (LAD) artery. However, 6 years later, coronary

A 49-year-old woman was admitted with suspicion of acute myocarditis. On the next day after admission, her serum troponin I level continued to rise, indicating progression of myocardial damage. Moreover, her symptoms persisted, and left ventricular ejection fraction did not improve. Because of a predominant infiltration of lymphocytes in the myocardial specimens, lymphocytic myocarditis was diagnosed. However, a close observation of the specimens revealed eosinophil degranulation. Based on this finding, intravenous steroid therapy was initiated. High-dose methylprednisolone led to rapid and appreciable improvements in symptoms and left ventricular function within 12 hours after the first administration, which was followed by normalization of serum troponin I level. Steroid therapy was switched to oral administration and tapered carefully. There was no recurrence of left ventricular dysfunction or elevation of serum troponin I level. In eosinophilic myocarditis, eosinophil degranulation has been recognized as an important finding associated with progression of inflammation and myocardial damage. However, no attention has been paid to the presence and clinical implications of eosinophil degranulation in lymphocytic myocarditis. This case indicates that eosinophil degranulation in lymphocytic myocarditis may be an important finding associated with a high therapeutic response to steroid therapy.

Objective The authors examined the effect of prolonged support with continuous-flow ventricular assist devices (CF-VADs) and other related factors on the severity of infections within 30 days of heart transplantation (HTx). Design A retrospective analysis of consecutive HTx procedures. Setting University hospital, between 2010 and 2016. Participants A cohort of 53 heart transplantation recipients (median age, 38.5 yr; interquartile range [IQR], 30.3-49.2 yr; women, 34%). Interventions Forty-nine patients required CF-VAD support (median duration, 946 d; IQR, 600-1,132 d). Measurements and Main Results Severity of postoperative infections was categorized as follows: no infection, minor infection (resolved within 14 days), major infection (resolved after >14 days), and severe infection (septic shock). Results were expressed as number (frequency) and median with IQR. Potential risk factors for increased infection severity were expressed as odds ratio (OR) with 95% confidence interval (CI). Postoperatively, no infection, minor infection, major infection, and severe infection occurred in 32 (60.4%), 8 (15.1%), 8 (15.1%), and 5 patients (9.4%), respectively. Active ventricular assist device (VAD)-specific infections at the time of HTx occurred in 37.7% of patients. Moderate-to-severe primary graft dysfunction occurred in 26.4% of the patients. Multivariable analysis indicated that risk factors for increased infection severity included active VAD-specific infection (OR 4.8; 95% CI 2.3-11.2) and moderate-to-severe primary graft dysfunction (OR 8.8; 95% CI 2.1-42.5) but not duration of CF-VAD support (OR 1.0; 95% CI 1.0-1.0). Conclusion Active VAD-specific infection and poor graft function likely contribute to the severity of early postoperative infections after HTx.

BACKGROUND Advanced left heart failure (HF) often accompanies post-capillary pulmonary hypertension related to RV afterload. Although pulmonary arterial capacitance (PAC), a measure of pulmonary artery compliance, reflects right ventricular (RV) afterload, the clinical utility of PAC obtained by echocardiography (echo-PAC) is not well established in advanced HF.Methods and Results:We performed right heart catheterization in advanced HF patients (n=30), calculating echo-PAC as stroke volume/(tricuspid regurgitation pressure gradient-pulmonary regurgitation pressure gradient). The difference between the echo-PAC and catheter-measured PAC values was insignificant (0.21±0.17 mL/mmHg, P=0.23). Echo-PAC values predicted both pulmonary arterial wedge pressure (PAWP) ≥18 mmHg and pulmonary vascular resistance ≥3 Wood units (P=0.02, area under the curve: 0.88, cutoff value: 1.94 mL/mmHg). Next, we conducted an outcome study with advanced HF patients (n=72). Patients with echo-PAC

Fulminant myocarditis is one of the most challenging diseases. We sought to examine the outcomes of our multidisciplinary treatment strategy for fulminant myocarditis. A retrospective review of consecutive 30 patients with fulminant myocarditis was conducted. Of the 30 patients, 25 required mechanical circulatory support (MCS). Percutaneous extracorporeal membrane oxygenation (ECMO) was the first-line therapy to rescue the patients and inserted in 23 of them. The other 2 were implanted with temporary ventricular assist device (t-VAD) with extracorporeal centrifugal pump(s). Sixteen of the ECMO-supported patients were later transitioned to t-VAD. Of the 18 patients who underwent t-VAD support, heart function recovered and the VAD was explanted in 10. Four patients were bridged to long-term VAD and the other 4 died on t-VAD. Two patients were directly bridged to long-term VAD by ECMO. Heart function recovered only with ECMO in 4 patients and 1 died on ECMO. Overall survival rate was 83.3%. The duration of ECMO support significantly correlated with total bilirubin level, which was a significant risk factor for mortality. Pathologically, 7 patients (23.3%) had eosinophilic myocarditis and 1 (3.3%) had giant-cell myocarditis, and all the 8 patients underwent immunosuppressive therapy including steroids. Heart function recovered to normal level in 7 of them (87.5%). Timely conversion from the percutaneous ECMO to the temporary VAD before elevation of total bilirubin level is crucial for improving the clinical outcomes. Endomyocardial biopsy is needed to be done as soon as possible, because immunosuppressive therapy carries promising outcomes in certain etiologies.

Background The prevalence of atrial fibrillation (AF) is high in elder subjects. Our previous observational study suggested that vitamin K antagonist (VKA) promotes aortic valve degeneration, a principal cause of aortic stenosis in the elderly, and that angiotensin receptor blocker (ARB) attenuates its progression. This study aimed to prospectively investigate these observations in non-valvular AF patients. Methods Of enrolled 430 patients with calcification on no or one aortic valve leaflet, all of the planned 4-year follow-up data were obtained in 122 non-valvular AF patients treated with warfarin (warfarin group) and 101 patients with cardiovascular diseases and without AF and prescription of warfarin (non-warfarin group). Results Despite higher atherosclerotic risks in the non-warfarin group, 2 or 3 newly calcified leaflets emerged during 4 years in 18.0% of patients in the warfarin group and in 6.9% in the non-warfarin group (p = 0.014). Aortic valve area (AVA) did not significantly change in the non-warfarin group during the follow-up, but tended to decrease in the warfarin group (p = 0.057). Non-vitamin K antagonist oral anticoagulant got available in Japan after this study started, and warfarin was discontinued in 15 patients of the warfarin group. The reduction of AVA was significant in the remaining 107 patients on the continuous warfarin treatment (p = 0.002). The effects of ARB on AVA were obscure. Conclusion Major bleeding associated with VKA is well recognized. This study suggests that the development of aortic valve degeneration is another risk of long-term use of VKA in non-valvular AF patients with no or mild aortic valve degeneration.

Background: Endovascular aortic repair (EVAR) is performed in patients with thoracic or abdominal aortic aneurysm because it is less invasive than conventional open repair. However, the effects of EVAR on vascular and cardiac function remain to be clarified. Methods and Results: We studied the effects of EVAR on several outcome variables in 40 consecutive patients undergoing EVAR for abdominal and/or thoracic aneurysm with preserved ejection fraction. Echocardiography and brachial–ankle pulse wave velocity (baPWV) data were collected before, 1 week, and 1 year after EVAR. Although no changes in blood pressure were found, baPWV, left ventricular mass index (LVMI), and left atrial volume index were significantly elevated at both post-op time periods after EVAR compared with baseline data. The changes in LVMI correlated with those in baPWV (R=0.32, P

Although the mouse heart failure (HF) model of hypertensive heart disease (HHD) is useful to investigate the pathophysiology and new therapeutic targets for HHD, the model using simple experimental procedures and stable phenotypes has not been established. This study aimed to develop a novel mouse HF model of HHD by combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion, uninephrectomy, and salt loading (ANS). Systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was found in AT, AN, AS, and ANS mice, and there were no significant differences in those parameters between the four groups. At 6 wk after the procedures, only ANS mice showed significant decreases in LV fractional shortening and increases in lung weight with a high incidence. This phenotype was reproducible, and there were few perioperative or early deaths in the experimental procedures. Severe LV fibrosis was found in ANS mice. Oxidative stress was enhanced and small GTPase Rac1 activity was upregulated in the hearts of ANS mice. After the addition of salt loading and uninephrectomy to the ANG II infusion mouse model, cardiac function was significantly impaired, and mice developed HF. This might be a novel and useful mouse HF model to study the transition from compensated LV hypertrophy to HF in HHD.

Objectives Prognosis of heart failure with preserved ejection fraction (HFpEF) remains poor because of unknown pathophysiology and unestablished therapeutic strategy. This study aimed to identify a potential therapeutic intervention for HFpEF through metabolomics-based analysis. Methods and results Metabolomics with capillary electrophoresis time-of-flight mass spectrometry was performed using plasma of Dahl salt-sensitive rats fed high-salt diet, a model of hypertensive HFpEF, and showed decreased free-carnitine levels. Reassessment with enzymatic cycling method revealed the decreased plasma and left-ventricular free-carnitine levels in the HFpEF model. Urinary free-carnitine excretion was increased, and the expression of organic cation/carnitine transporter 2, which transports free-carnitine into cells, was down-regulated in the left ventricle (LV) and kidney in the HFpEF model. L-Carnitine was administered to the hypertensive HFpEF model. L-Carnitine treatment restored left-ventricular free-carnitine levels, attenuated left-ventricular fibrosis and stiffening, prevented pulmonary congestion, and improved survival in the HFpEF model independent of the antihypertensive effects, accompanied with increased expression of fatty acid desaturase (FADS) 1/2, rate-limiting enzymes in forming arachidonic acid, and enhanced production of arachidonic acid, a precursor of prostacyclin, and prostacyclin in the LV. In cultured cardiac fibroblasts, L-carnitine attenuated the angiotensin II-induced collagen production with increased FADS1/2 expression and enhanced production of arachidonic acid and prostacyclin. L-Carnitine-induced increase of arachidonic acid was canceled by knock-down of FADS1 or FADS2 in cultured cardiac fibroblasts. Serum free-carnitine levels were decreased in HFpEF patients. Conclusions L-carnitine supplementation attenuates cardiac fibrosis by increasing prostacyclin production through arachidonic acid pathway, and may be a promising therapeutic option for HFpEF.

Aims The prevalence of heart failure with preserved ejection fraction (HFpEF) has increased in the past two decades, and diabetes mellitus (DM) is frequently associated with HFpEF. Although it has been demonstrated that left ventricular (LV) diastolic and vascular functional abnormalities are generally observed in HFpEF, it remains to be clinically elucidated how an asymptomatic stage progresses to symptomatic HFpEF in DM patients. We aimed to identify risk factors associated with incident HFpEF in DM patients and to evaluate the contribution of LV relaxation and compliance to the development of HFpEF. Methods and results The study included 544 consecutive Japanese DM patients with ejection fraction ≥50%. Patients with coronary artery disease or serum creatinine ≥2.0 mg/dL were excluded. Multiple logistic regression analysis revealed that obesity, female gender, anaemia, and impaired LV compliance were independently associated with the prevalence of HFpEF, and that age, LV mass index, an index of LV relaxation, estimated glomerular filtration rate, and history of hypertension were not. There was no difference in haemoglobin A1c or brachial-ankle pulse wave velocity between the DM patients with and without HFpEF. Conclusions This study suggests that exacerbation of LV compliance impairment, rather than of relaxation abnormality or vascular stiffening, plays a crucial role in the induction of HFpEF in DM patients regardless of the severity of DM and renal dysfunction. Anaemia and obesity may also contribute to the transition from asymptomatic stage to symptomatic HFpEF even without further progression of LV diastolic dysfunction.

Aims Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of heart failure with preserved ejection fraction (HFPEF). Plasma level of digitalis-like factors (DLFs) is increased in patients with hypertension, a principal underlying cardiovascular disease of HFPEF. Digitalis-like factors inhibit ion-pumping function of Na+/K+-ATPase and activate the Ca2+ entry mode of Na+/Ca2+ exchanger (NCX). Digitalis-like factors are known to promote collagen production in fibroblasts. The aim of this study was to explore whether the pharmacological inhibition of the NCX entry mode is effective in the prevention of LV fibrosis and in the development of HFPEF. Methods and results (i) Dahl salt-sensitive rats fed 8% NaCl diet from age 6 weeks served as hypertensive HFPEF model. In this model, 24 h urine excretion of DLFs was greater than that in the age-matched control at compensatory hypertrophic and heart failure stages. (ii) Continuous administration of ouabain for 14 weeks developed LV fibrosis without affecting blood pressure in Sprague–Dawley rats. (iii) Ouabain elevated intracellular Ca2+ concentration through the entry of extracellular Ca2+, increased the phosphorylation level of p42/44 mitogen-activated protein kinases, and enhanced 3H-proline incorporation in cardiac fibroblast; and SEA0400, the inhibitor of the NCX entry mode, suppressed these effects. (iv) In the HFPEF model, administration of SEA0400 at subdepressor dose improved the survival rate in association with the attenuation of LV fibrosis and stiffening. Conclusion Digitalis-like factors and the subsequently activated NCX entry mode may play an important role in the development of hypertensive HFPEF, and the blockade of the NCX entry mode may be a new therapeutic strategy for this phenotype of heart failure.

Background: Systolic abnormality, as well as diastolic dysfunction, is observed in patients with heart failure with preserved ejection fraction (HFPEF). However, the role of these 2 conditions in the transition from asymptomatic diastolic dysfunction to symptomatic heart failure remains unclear. We recently demonstrated that diastolic wall strain (DWS) inversely correlates to the myocardial stiffness constant. Methods and Results: This study consisted of 127 subjects: 52 consecutive HFPEF patients (HFPEF group), 50 asymptomatic hypertensive patients with ejection fraction ≥50% whose age, gender and left ventricular (LV) mass index matched those of the HFPEF group (HT group) and 25 normal volunteers (Normal group). The tissue Doppler-derived peak systolic and early diastolic velocities of the mitral annulus were significantly decreased in groups HFPEF and HT than in group Normal, but were not significantly different between groups HFPEF and HT. DWS was significantly lower in group HFPEF than in group HT. Conclusions: The transition from asymptomatic diastolic dysfunction stage to HFPEF stage is not attributed to progression of systolic abnormality, and exacerbation of LV distensibility rather than relaxation plays a crucial role in the development of HFPEF. (Circ J 2011; 75: 596-602)

Objectives We prospectively compared the predictive value of cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging for sudden cardiac death (SCD) with that of the signal-averaged electrocardiogram (SAECG), heart rate variability (HRV), and QT dispersion in patients with chronic heart failure (CHF). Background Cardiac MIBG imaging predicts prognosis of CHF patients. However, the long-term predictive value of MIBG imaging for SCD in this population remains to be elucidated. Methods At entry, cardiac MIBG imaging, SAECG, 24-h Holter monitoring, and standard 12-lead electrocardiography (ECG) were performed in 106 consecutive stable CHF outpatients with a radionuclide left ventricular ejection fraction (LVEF) Results During a follow-up period of 65 ± 31 months, 18 of 106 patients died suddenly. A multivariate Cox analysis revealed that WR and LVEF were significantly and independently associated with SCD, whereas the SAECG, HRV parameters, or QT dispersion were not. Patients with an abnormal WR (>27%) had a significantly higher risk of SCD (adjusted hazard ratio: 4.79, 95% confidence interval: 1.55 to 14.76). Even when confined to the patients with LVEF >35%, SCD was significantly more frequently observed in the patients with than without an abnormal WR (p = 0.02). Conclusions Cardiac MIBG WR, but not SAECG, HRV, or QT dispersion, is a powerful predictor of SCD in patients with mild-to-moderate CHF, independently of LVEF.

Objective: To evaluate the usefulness of cardiac iodine-123 ( 123 I) metaiodobenzylguanidine (MIBG) imaging as a predictor of sudden death in patients with chronic heart failure (CHF). Design and setting: Prospective cohort study in a tertiary referral centre. Patients: 97 outpatients with CHF with a radionuclide left ventricular ejection fraction Interventions: At study entry, cardiac I-123 MIBG imaging was performed. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. Main outcome measures: Patients were assigned to two groups based upon 27% of WR, which was the mean (2SD) control WR. 48 of 97 patients with CHF had abnormal WR (⩾27%), whereas the remaining 49 patients had normal WR ( Results: During the mean (SD) follow-up period of 65 (29) months, 12 (25%) patients in the abnormal WR group and 2 (4%) patients in the normal WR group died suddenly. Kaplan–Meier analysis revealed that sudden death was more often observed in patients with abnormal WR than those with normal WR (p = 0.001). On Cox regression analysis, MIBG WR, H/M on the delayed image and H/M on the early image were significantly associated with sudden death. Conclusion: Cardiac MIBG imaging would be useful for predicting sudden death in patients with CHF.

In the case of an emergency coronary procedure where the risk of contrast-induced nephropathy is especially high, there are few reliable methods to attenuate renal injury. We examined the efficacy of sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure. We enrolled 59 patients who were scheduled to undergo an emergency coronary angiography or intervention. These patients were randomized to receive a 154-mEq/L infusion of sodium bicarbonate (n = 30) or sodium chloride (n = 29), as a bolus of 3 ml/kg/hour for 1 hour before the administration of contrast, followed by an infusion of 1 ml/kg/hour for 6 hours during and after the procedure. In the sodium bicarbonate group, serum creatinine concentration remained unchanged within 2 days of contrast administration (1.31 +/- 0.52 to 1.31 +/- 0.59 mg/dl), whereas it increased in the sodium chloride group (1.32 +/- 0.65 to 1.52 +/- 0.92 mg/dl, p = 0.01). The incidence of contrast-induced nephropathy (an increase0.5 mg/dl or25% in serum creatinine concentration within 2 days of contrast) was significantly lower in the sodium bicarbonate group than in the sodium chloride group (7% vs 35%, p = 0.01, risk ratio 0.19, 95% confidence interval 0.046 to 0.80). In conclusion, hydration with sodium bicarbonate is more effective than with sodium chloride for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure.

BACKGROUND: Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial factor in HFpEF; however, inflammatory mechanisms and mediators involved in the development of HFpEF remain unclear. Therefore, we sought to identify novel inflammatory mediators involved in this process. METHODS AND RESULTS: An analysis by multiplex-bead array assay revealed that serum interleukin-16 (IL-16) levels were specifically elevated in patients with HFpEF compared with HFrEF and controls. This was confirmed by enzyme-linked immunosorbent assay in HFpEF patients and controls, and serum IL-16 levels showed a significant association with indices of LV diastolic dysfunction. Serum IL-16 levels were also elevated in a rat model of HFpEF and positively correlated with LV end-diastolic pressure, lung weight and LV myocardial stiffness constant. The cardiac expression of IL-16 was upregulated in the HFpEF rat model. Enhanced cardiac expression of IL-16 in transgenic mice induced cardiac fibrosis and LV myocardial stiffening accompanied by increased macrophage infiltration. Treatment with anti-IL-16 neutralizing antibody ameliorated cardiac fibrosis in the mouse model of angiotensin II-induced hypertension. CONCLUSION: Our data indicate that IL-16 is a mediator of LV myocardial fibrosis and stiffening in HFpEF, and that the blockade of IL-16 could be a possible therapeutic option for HFpEF.

Although international air transfer of the alien patients to their homelands, i.e. air repatriation, is increasing worldwide, paucity of experience in Japan often prevents us from safe transfer. Here we achieved successful air repatriation of the unusually ill patient for unusually long distance, as a fruit of close collaborations between countries. A 41-year-old Australian male was transferred to our hospital for heart failure and pneumonia during his stay in Japan. His heart was markedly dilated and the ejection fraction was only 11%. On day 9, he suddenly suffered cardiopulmonary arrest due to massive pulmonary embolism. We introduced him with mechanical support including venous-arterial ECMO. Prolonged pulmonary hypertension and cardiac dysfunction despite optimal therapy further required thrombectomy and implantation of ventricular assist device (VAD), which was financially impractical in Japan. We contacted the flagship hospital in Brisbane, and collaborated for repatriation through daily discussion as to his status by e-mail and teleconference. We also asked the insurance company to arrange for air ambulance. On day 22, the repatriation team from Brisbane came to our hospital, changed ECMO circuit to portable one, and retrieved him via Narita Airport without any trouble. Although he needed immediate VAD implantation in Brisbane, later he recovered to discharge with no device support. Accumulation of these successful cases will contribute to establish practical and efficient repatriation system in Japan.

Background Diabetic retinopathy (DR) is an independent predictor of heart failure (HF) in patients with diabetes mellitus (DM). However, it is unclear how DR is related to the development of HF. We hypothesized that DR is associated with left ventricular (LV) diastolic dysfunction, which is well recognized to subsequently result in HF. Methods and Results Data were collected in 63 consecutive patients with DM and LV ejection fraction (EF) ≥50%. Patients were excluded if they had HF diagnosed according to the modified Framingham criteria. Doppler echocardiographic indices including peak early-diastolic mitral annular movement velocity (E′) were obtained in each patient.We also assessed the diastolic index of echocardiographic color kinesis (CK-DI), which proportionally decreases with LV relaxation abnormality independently of LV filling pressure, as recently published. The DM patients were divided into groups without (DM-N; n = 30) and with (DM-DR; n = 33) DR. Age, gender, LV end-diastolic dimension, EF, E/A ratio of the transmitral flow velocity curves, E′, and E/E′ were not different between DM-N and DM-DR. However, CK-DI was significantly lower in DM-DR than DM-N. Conclusions DR is associated with LV diastolic dysfunction, and this may at least in part explain the increased incidence of HF in DM patients with DR.

Background Contrast-induced nephropathy is associated with increased in-hospital and long-term adverse clinical outcomes. Methods and Results To investigate whether hydration with sodium bicarbonate improves long-term clinical outcomes compared with sodium chloride, patients with chronic kidney disease undergoing an emergent coronary procedure were enrolled in a randomized clinical trial with ≥1 year of follow-up. The 59 patients with chronic kidney disease (serum creatinine concentration >1.1 mg/dl or estimated glomerular filtration rate

Statins have pleiotropic effects, such as improvement in endothelial function and antiinflammatory, antiproliferative, and antioxidative effects, that should be beneficial for patients with chronic heart failure (CHF). The aim of this study was to investigate the long-term effect of statins on neurohumoral activation and cardiac function in patients with CHF.We enrolled 38 outpatients with mild to moderate CHF and radionuclide left ventricular ejection fraction (LVEF)40%. These patients were randomly assigned to receive atorvastatin (10 mg/d) or conventional treatment for heart failure and were prospectively followed up for at least 3 years. At entry, we measured plasma concentrations of brain natriuretic peptides (BNPs) and left ventricular end-diastolic dimension and LVEF by echocardiography; thereafter, these measurements were repeated at least every 6 months. The primary end point was defined as the improvement in cardiac function and BNP.There were no significant differences in age, sex, New York Heart Association class, left ventricular end-diastolic dimension, LVEF, and serum cholesterol level at entry between patients with (n = 19) and without atorvastatin (control, n = 19). After a follow-up period of 31 +/- 14 months, BNP (median [25th, 75th percentile]) significantly decreased in the atorvastatin group (84 [36, 186] to 55 [37, 91] pg/mL, P = .02) but not in the control group. Left ventricular end-diastolic dimension significantly decreased (67.1 [59.9, 70.8] to 61.1 [58, 63.9] mm, P = .02), and LVEF also significantly increased in the atorvastatin group (33.3% +/- 7.4% to 39.1% +/- 12.1%, P = .01) but not in the control group.Long-term atorvastatin therapy decreases neurohumoral activation and improves cardiac function in patients with mild to moderate CHF.