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Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6Clo macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6Clo macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

International audience; The dynamical property of the heart bioelectrical system is closely associated with cardiac diseases. There is thus a growing interest in the development of system analysis for studying the cardiac signaling network. In this article, the electrical potentials of cardiac muscle cells have been measured on an array of microelectrodes using the Thin-Film-Transistor (TFT) technology, and electrophysiological data were analyzed. This study shows the possibility of obtaining and accurately analyzing extracellular signals measured on TFT arrays.

Background His-bundle pacing is an emerging routine technique that avoids pacing-dependent side effects. However, the success rate of His-bundle pacing is not 100%.Methods and Results:Left bundle pacing or peri-left bundle pacing (LBP/peri-LBP) are recently developed techniques that directly capture the left bundle or ventricular tissue near the left bundle. We evaluated the success rate of LBP/peri-LBP in patients whose treatment with His-bundle pacing failed. In addition, we evaluated left ventricular contraction and desynchrony after LBP/peri-LBP. Conclusions LBP/peri-LBP is an alternative ventricular pacing method in atrioventricular block in patients with failure of His-bundle pacing.

Di Carlo et al . comment that our original results were insufficient to prove that the ghost cytometry technique is performing a morphologic analysis of cells in flow. We emphasize that the technique is primarily intended to acquire and classify morphological information of cells in a computationally efficient manner without reconstructing images. We provide additional supporting information, including images reconstructed from the compressive waveforms and a discussion of current and future throughput potentials.

A 41-year-old man developed cardiac arrest. A resting 12-lead electrocardiogram showed a delta wave, suggestive of preexcitation syndrome. An electrophysiological test revealed the existence of inducible atrial fibrillation and a fasciculoventricular accessory pathway (FVAP). After these examinations, idiopathic ventricular arrhythmia was suspected. For evaluating concealed Brugada syndrome, pilsicainide was administered, which diminished the delta wave and no Brugada-like electrocardiogram was observed. Ventricular double extra-stimulation from the RV apex easily induced VF, which could not be defibrillated by an external defibrillator, and later stopped spontaneously. These results established the diagnosis of FVAP and idiopathic VF, and not pre-excited atrial fibrillation or Brugada syndrome.

Cardiac involvement in systemic sarcoidosis sometimes provokes life-threatening ventricular tachyarrhythmia. Steroid administration is one of the fundamental anti-arrhythmia therapies. For an indication of steroid therapy, a definitive diagnosis of sarcoidosis is required.1) However, cases that are clearly suspected of cardiac sarcoidosis based on their clinical courses sometimes do not meet the current diagnostic criteria and result in the loss of an appropriate opportunity to perform steroid therapy.Here we report a case that was diagnosed as sarcoidosis by incidental biopsy of an inguinal lymph node during cardiac resuscitation for cardiac tamponade.2) While the inguinal lymph node was not swollen on computed tomography, a specimen obtained from an incidental biopsy during the exposure of a femoral vessel for the establishment of extracorporeal cardio-pulmonary resuscitation showed a non-caseating granuloma.This findings suggest a non-swelling lymph node biopsy might be an alternative strategy for the diagnosis for sarcoidosis if other standard strategies do not result in a diagnosis of sarcoidosis.

Ebstein's anomaly is a rare congenital heart disease characterized by apical displacement of the septal and posterior tricuspid valve leaflets. It is often complicated with left ventricular (LV) dysfunction as well as right-sided abnormalities. On the other hand, in the presence of LV dysfunction, right ventricular pacing is likely to aggravate the diseased LV function, which is termed pacemaker-induced cardiomyopathy. Thus, deteriorating effects of RV pacing on cardiac function might be enhanced and result in pacemaker-induced cardiomyopathy in patients with Ebstein's anomaly, even if they have preserved LVEF. Cardiac resynchronization therapy (CRT) is effective for the treatment of pacemaker-induced cardiomyopathy, and we present the first case of effect of CRT on pacemaker-induced cardiomyopathy associated with Ebstein's anomaly.

Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Kruppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5PostnKO: Klf5flox/flox; PostnCre/-) and wild-type mice (WT: Klf5flox/flox; Postn-/-). We implanted a DOCA pellet and provided drinking water containing 0.9% NaCl for 8 weeks. The DOCA-salt treatment induced hypertension in both genotypes, as observed by increases in systolic blood pressure. In WT animals, DOCA-salt treatment increased the aortic medial area compared with the non-treated controls. Similarly, Tgfb1 was overexpressed in the aortas of the DOCA-salt treated WT mice compared with the controls. Immunofluorescence staining revealed that fibroblast-specific protein 1 (FSP1)+-α smooth muscle actin (αSMA)+ myofibroblasts exist in the medial area of the WT aortas after DOCA-salt intervention. Importantly, these changes were not observed in the Klf5PostnKO animals. In conclusion, the results of this study suggest that the presence of KLF5 in postn-positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.

Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed after cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using a mouse model of lymphedema, we show here that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. We found that CD4 + T cells interact with macrophages to promote lymphangiogenesis, and that both lymphangiogenesis and edema were greatly reduced in macrophage-depleted mice, lymphocyte-deficient Rag2 −/− mice or CD4 + T-cell–deficient mice. Mechanistically, T helper type 1 and T helper type 17 cells activate lesional macrophages to produce vascular endothelial growth factor-C, which promotes lymphangiogenesis, and inhibition of this mechanism suppressed not only early lymphangiogenesis, but also later development of lymphedema. Finally, we show that atorvastatin suppresses excessive lymphangiogenesis and lymphedema by inhibiting T helper type 1 and T helper type 17 cell activation. These results demonstrate that the interaction between CD4 + T cells and macrophages is a potential therapeutic target for prevention of lymphedema after surgery.

Malignant melanoma is one of the untreatable cancers in which conventional therapeutic strategies, including chemotherapy, are hardly effective. Therefore, identification of novel therapeutic targets involved in melanoma progression is urgently needed for developing effective therapeutic methods. Overexpression of interleukin-13 receptor α2 (IL13Rα2) is observed in several cancer types including glioma and pancreatic cancer. Although IL13Rα2 is implicated in the progression of various types of cancer, its expression and roles in the malignant melanoma have not yet been elucidated. In the present study, we showed that IL13Rα2 was expressed in approximately 7.5% melanoma patients. While IL13Rα2 expression in human melanoma cells decreased their proliferation in vitro, it promoted in vivo tumour growth and angiogenesis in melanoma xenograft mouse model. We also found that the expression of amphiregulin, a member of the epidermal growth factor (EGF) family, was correlated with IL13Rα2 expression in cultured melanoma cells, xenograft tumour tissues and melanoma clinical samples. Furthermore, expression of amphiregulin promoted tumour growth, implicating causal relationship between the expression of IL13Rα2 and amphiregulin. These results suggest that IL13Rα2 enhances tumorigenicity by inducing angiogenesis in malignant melanoma, and serves as a potential therapeutic target of malignant melanoma.

A cardiac resynchronization therapy defibrillator (CRT-D) (Medtronic Inc. Protecta XT) was implanted in a 67-year-old man who had cardiac sarcoidosis with extremely low cardiac function. He had ventricular tachycardia which was controlled by catheter ablation, medication and pacing. The programmed mode was DDI, lower rate was 90 beats/minute, paced AV delay was 150 ms, and the noncompetitive atrial pacing (NCAP) function was programmed as 300 ms.After his admission for pneumonia and heart failure, we changed his DDI mode to a DDD mode because he had atrial tachycardia, which led to inadequate bi-ventricular pacing. After a while, there were cycle lengths which were longer than his device setting and alternately varied. We were able to avoid this phenomenon with AV delay of 120 ms and NCAP of 200 ms.NCAP is an algorithm which creates a gap above a certain period after the detection of an atrial signal during the postventricular atrial refractory period of the pacemaker. This is to prevent atrial tachycardia and repetitive non-reentrant ventriculoatrial (VA) synchrony in the presence of retrograde VA conduction. But in this case, NCAP algorithm induced much lower rate than the programmed basic lower rate. This situation produced some arrhythmias and exacerbated symptoms of heart failure. This had to be paid attention to, especially when the device was programmed at high basic heart rate.

Background Preoperative and intraoperative use of a contrast medium is unavoidable in catheter ablation for atrial fibrillation, which can become a particularly significant issue for patients suffering from renal impairment. Objective The purpose of this study is to investigate the feasibility and safety of a technique for atrial fibrillation ablation without a contrast medium via intra-cardiac ultrasound imaging only. Methods We prepared the geometry of the pulmonary vein and left atrium via a SOUNDSTAR catheter from inside the left atrium, without preoperative and intraoperative investigations using contrast mediums, for computed tomography or magnetic resonance imaging and pulmonary venography. This was followed by retrospective investigation of the success rate and complications observed in 200 successive paroxysmal and persistent atrial fibrillation cases that underwent catheter ablation from January 2011 to November 2012. The outcomes were assessed after the one-year follow-up. Results Inserting a SOUNDSTAR catheter into the left atrium was successful in all cases, wherein rendering of all pulmonary veins and the left atrium was possible, and extensive encircling pulmonary vein isolation was successful in all cases. The sinus rhythm maintenance rate one year after the procedure was 90.4% for paroxysmal atrial fibrillation and 76.0% for persistent atrial fibrillation. The major complication rate was 0.5% (cardiac tamponade), with no cases presenting aggravation of renal function. Conclusion Atrial fibrillation ablation using an intra-cardiac ultrasound from the left atrium without employing a contrast medium was safe, with no adverse effects on renal function.

BackgroundThe circadian autonomic fluctuation in chronic kidney disease (CKD) patients has not yet been fully elucidated. The aim of this study was to compare the autonomic fluctuation using heart rate variability between patients with and without CKD.MethodsThe study population consisted of consecutive 101 non-diabetic CKD patients (Stages 3–5, 54 males, 70±10years) and 129 age- and sex-matched controls without CKD (65 males, 68±10years) who underwent 24-hour Holter monitoring. The proportion of successive normal sinus NN intervals that differ >50ms (pNN50) and the high-frequency component (HF) were adopted as vagal parameters. The low- to high-frequency ratio (LF/HF ratio) was evaluated as a sympatho-vagal balance parameter. To evaluate the direct contribution of CKD and other comorbidities to the autonomic variation, the regression analysis was performed after we arbitrarily divided 24h into night-time (10PM–8AM) and day-time (8AM–10PM).ResultsThe CKD patients had higher prevalence of hypertension, hyperuricemia, and low hemoglobin as compared to controls (P0.05), but to low Hb (P

The heart is composed of several cell types including cardiomyocytes, cardiac fibroblasts, endothelial, and smooth muscle cells. In addition to these major cell types, cardiac macrophages are also present in small numbers under physiological conditions. Recently, the resident macrophage is considered to have vital functions in the maintenance of tissues and homeostasis in many organs, including brain, liver, adipose tissue, lymphatic tissue, and intestinal tract. However, detailed functions of the cardiac resident macrophage are not fully understood. Although the removal of debris arising from damaged cardiomyocytes and pro-inflammatory effects after heart injuries are conventional tasks of cardiac macrophages (classically activated macrophage or M1 macrophage), novel functions like anti-inflammatory roles, adaptive response, and tissue maintenance have also been reported in recent years. Macrophages that possess these novel functions are generally so-called M2 macrophages, which are alternatively activated and show anti-inflammatory phenotype under pathological conditions. In this review, we focus on the cardioprotective function of the cardiac macrophage and discuss in light of unveiled fundamental functions of macrophages that have been also found in other organs.

YPERTROPHIC CARDIOMYOPATHY (HCM) often includes asymmetric (or nonphysiologic) massive left ventricular hypertrophy, which can be diagnosed by electrocardiography and echocardiography. In patients with HCM, hypertrophy is more common in the ventricular septum below the aortic valve, leading to left ventricular outflow tract (LVOT) obstruction. 1-3 There have been many reports of anesthetic management for noncardiac surgery of patients with ischemic heart disease. However, there have been only a few reports concerning the anesthetic management of patients with HCM undergoing noncardiac surgery. 4-7 Hreybe et al reported that the presence of HCM significantly increased the risk of death and myocardial infarction associated with noncardiac surgery. 8 Patients with HCM undergoing elective procedures may require more careful preoperative assessment and perioperative monitoring. However, it is not known exactly what factors associated with HCM have harmful effects on the perioperative condition of a patient. Left ventricular hypertrophy and LVOT, which induce left ventricular diastolic dysfunction and a pressure gradient, may be involved. In addition, better ways for decreasing the risks have not yet been established. Permanent dual-chamber pacing has been proposed as an adjunct treatment to lessen symptoms in markedly symptomatic patients with obstructive HCM refractory to drugs. 9 This approach is based on the concept that pre-excitation of the interventricular septum by right ventricular pacing would cause the septum to move away from the left ventricular wall during systole and artificially make dyssynchrony, resulting in an increase in LVOT dimensions and, hence, a decrease in LVOT blood velocities. This would, in turn, decrease the systolic anterior motion of the mitral valve, resulting in further relief of the LVOT obstruction and less severe mitral regurgitation. However, the application of this procedure in perioperative management has been rare. Here, the authors describe a case of noncardiac surgery with left ventricular hypertrophy and LVOT obstruction. The surgery included resection of a catecholamine-secreting endocrine tumor that was having a harmful effect on the patient’s hypertrophic heart. After assessing the effect with temporary pacing, the authors performed temporary dual-chamber pacing to decrease the perioperative risks. Noncardiac surgery then was performed successfully without any adverse cardiac events. The clinical course of left ventricular hypertrophy and LVOT obstruction complicated with a catecholamine-secreting tumor involves significant implications in clinical practice.

Key Teaching Points • In most patients, the His bundle pacing (HBP) lead is positioned on the atrial side of the His bundle; in others, it is positioned in the tricuspid valve or on the ventricular side of the His bundle. • Echocardiography showed no worsening of tricuspid regurgitation severity in any patient with a permanent HBP, even in those whose leads were located on or under the tricuspid valve. • The HBP lead tip can be positioned in a commissural position in the right ventricle without impinging on leaflet mobility.

We report on a 64-year-old female patient who underwent cardiac surgery for left atrial myxoma, using the superior septal approach with large atrial septal wall resection and patch closure. The superior septal approach is reported to be a relatively safe method for preventing the development of sinus node dysfunction after cardiac surgery. However, this patient developed sinus node dysfunction after surgery and required the implantation of a permanent pacemaker. Moreover, in this case, determining the appropriate positions of the pacemaker leads was difficult because of the presence of a large conduction delay in the interatrium. Selecting the appropriate atrioventricular delay settings was important in order to achieve proper sequential contractions between the left atrium and the left ventricle.

Use of short interfering RNA (siRNA) is a promising new approach thought to have a strong potential to lead to rapid development of gene-oriented therapies. Here, we describe a newly developed, systemically injectable siRNA vehicle, the “wrapsome” (WS), which contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer and hydrophilic polymers. WS protected siRNA from enzymatic digestion, providing a long half-life in the systemic circulation. Moreover, siRNA/WS leaked from blood vessels within tumors into the tumor tissue, where it accumulated and was subsequently transfected into the tumor cells. Because the transcription factor KLF5 is known to play a role in tumor angiogenesis, we designed KLF5-siRNA to test the antitumor activity of siRNA/WS. KLF5-siRNA/WS exhibited significant antitumor activity, although neither WS containing control scrambled-siRNA nor saline containing KLF5-siRNA affected tumor growth. KLF5-siRNA/WS inhibited Klf5 expression within tumors at both mRNA and protein levels, significantly reducing angiogenesis, and we detected no significant acute or long-term toxicity. Our findings support the idea that siRNA/WS can be used to knock down specific genes within tumors and thereby exert therapeutic effects against cancers. [Cancer Res 2009;69(16):6531–8]

Supraventricular tachycardia (SVT) was observed in a 13-year-old male patient with complex clinical features that included univentricular heart with single atrium, pulmonary atresia, and polysplenia syndrome. During electrophysiologic study, atrial burst stimuli reproducibly induced and terminated the SVT, while the occurrence of ventriculoatrial block did not interrupt the SVT. His bundle electrograms (HBEs) were recognized both in the anterior and posterior regions on the common atrioventricular (AV) valve annulus. The posterior His bundle activation was progressively delayed along with the shortening of atrial pacing cycle length until it finally lagged behind local ventricular activation. Thus, antegrade AV conduction was solely via the anterior AV node. In contrast, during the SVT, the earliest activation was observed in the posterior HBE. These observations suggested that the posterior AV node serves as an origin of the SVT and that two AV nodes were linked together possibly through a sling at the infra-Hisian level. Radiofrequency catheter ablation applied to the posterior HBE eliminated the SVT.

In early age-related macular degeneration (AMD), complement component C3 can be observed in drusen, which is the accumulation of material beneath the retinal pigment epithelium. The complement pathways, via the activation of C3, can upregulate the expression of cytokines and their receptors and the recruitment of inflammatory leukocytes, both of which play an important role in the development of choroidal neovascularization (CNV) in exudative AMD. Laser-induced CNV lesions were found to be significantly smaller in C3−/− mice than in wild-type mice. By using flow cytometry, we demonstrated that the proportions of intraocular granulocytes, CD11b+F4/80+Ly6Chi and CD11b+F4/80+Ly6Clo cells, were lower in C3−/− mice than in wild-type mice as early as day 1 after laser injury and the proportions of granulocytes and three macrophage/monocyte subsets were significantly lower on day 3. In contrast, C3−/− mice had more granulocytes and CD11b+F4/80+Ly6Chi cells in peripheral blood than wild-type mice after injury. Further, the expression levels of Vegfa164 were upregulated in intraocular Ly6Chi macrophages/monocytes of C3−/− mice, but not as much as in wild-type mice. Collectively, our data demonstrate that despite a more pronounced induction of systemic inflammation, inhibition of complement factor C3 suppresses CNV by decreasing the recruitment of inflammatory cells to the lesion.

An asymptomatic 35 year-old man was referred to our hospital because of abnormal ECG findings. The ECG showed complete right bundle branch block and left anterior hemiblock. Echocardiography revealed a moderately enlarged right ventricle (RV) and an apical aneurysm. RV wall motion showed diffusely moderate impairment, while the systolic function of the left ventricle (LV) was slightly decreased. The ejection fractions (EF) of the RV and LV were calculated as 28.1% and 41.9% by Simpson's method using multiple cardiac computed tomography (CT) scans. A 24 hour ambulatory ECG showed only 372 single premature ventricular contractions (PVC). Cardiac catheterizaion revealed that the RV was enlarged with prominent trabeculation and decreased motion. In an electrophysiologic study, neither electrical stimulation of the RV nor electrical stimulation plus isoproterenol infusion could induce ventricular tachycardia. Pathological examination of a biopsy from the interventricular septum of the RV revealed fibrofatty change in the myocardium. Based on these results, we made a diagnosis of arrhythmogenic right ventriclular cardiomyopathy (ARVC) and administered 5 mg of carvedilol. Sixty days after the initiation of carvedilol therapy, we performed repeat cardiac CT. The EF of the LV was markedly improved from 41.9% to 62.0%, although the EF of the RV was not changed. The number of PVCs showed no change. This case suggests that carvedilol is not only useful for controlling arrhythmia but also for improving left ventriclular function in some patients with ARVC. Sympathetic overactivity is reported to cause sudden death, so carvedilol may be a first-line drug for some patients with ARVC.

Background: Diet and fluid restrictions that need continuous self-management are among the most difficult aspects of dialysis treatment. Smartphone applications may be useful for supporting self-management. Objective: Our objective is to investigate the feasibility and usability of a novel smartphone-based self-management support system for dialysis patients. Methods: We developed the Self-Management and Recording System for Dialysis (SMART-D), which supports self-monitoring of three mortality-related factors that can be modified by lifestyle: interdialytic weight gain and predialysis serum potassium and phosphorus concentrations. Data is displayed graphically, with all data evaluated automatically to determine whether they achieve the values suggested by the Japanese Society for Dialysis Therapy guidelines. In a pilot study, 9 dialysis patients used SMART-D system for 2 weeks. A total of 7 of them completed questionnaires rating their assessment of SMART-D’s usability and their satisfaction with the system. In addition, the Kidney Disease Quality of Life scale was compared before and after the study period. Results: All 9 participants were able to use SMART-D with no major problems. Completion rates for body weight, pre- and postdialysis weight, and serum potassium and phosphorus concentrations were, respectively, 89% (SD 23), 95% (SD 7), and 78% (SD 44). Of the 7 participants who completed the usability survey, all were motivated by the sense of security derived from using the system, and 6 of the 7 (86%) reported that using SMART-D helped improve their lifestyle and self-management. Conclusions: Using SMART-D was feasible, and the system was well regarded by patients. Further study with larger scale cohorts and longer study and follow-up periods is needed to evaluate the effects of SMART-D on clinical outcomes and quality of life. [JMIR Res Protoc 2017;6(4):e63]

Procedure-related coronary dissection is associated with an increased risk of major adverse cardiovascular events after percutaneous coronary intervention (PCI). In most patients with such an iatrogenic complication, further PCI or bypass surgery aimed at complete revascularization is performed. Moreover, conventional coronary angiography has been used as a standard modality in the follow-up of such patients. The present report describes a 70 year old female patient who was complicated by catheter-related extensive coronary dissection in the right coronary artery (RCA) when treated for an acute myocardial infarction. Although RCA flow was insufficient, we decided against revascularization and followed her medically without additional revascularization procedures. Her clinical course had been uneventful for 4 years. However, symptoms of effort angina developed and re-examinations were performed at approximately 5 years after the myocardial infarction. Although conventional coronary angiography failed to show the culprit lesion responsible for the angina symptoms, the superior spatial resolution of the coronary CT angiography clearly identified significant progression of the stenotic lesion in the true lumen of the dissected RCA. Thus, coronary CT angiography might be considered as a possible first-line follow-up modality in patients with procedure-related coronary dissection.

Introduction: Autonomic dysfunction is well known in patients with chronic kidney disease (CKD) and linked with cardiac death. In spite of a high incidence of morning death in CKD patients, circadian fluctuation in parasympathetic activation have not been studied in CKD. Hypothesis: We assessed the hypothesis that the cardiac autonomic circadian fluctuation is impaired in patients with CKD. Methods: The study population consisted of consecutive 101 patients (54 males, 70±10 years old) with CKD who underwent 24-hour Holter monitor. As a control group, 134 age and sex matched cases (66 males, 68±10 years old) without CKD who also underwent Holter monitor were recruited. Patients with diabetes orβ-blocker therapy were excluded. The high frequency component (HF), which reflected parasympathetic activity, and the low frequency to high frequency ratio (L/H ratio), which reflected, in part, sympathetic activity, were evaluated. To evaluate the contribution of CKD and other parameters to the cardiac autonomic fluctuation, the night (6PM-6AM) to day (6AM-6PM) ratio of HF and L/H ratio were analyzed utilizing a regression analysis. Results: The L/H ratio showed no significant difference during the night between the two groups, in contrast to the significant difference during the daytime. Patients with CKD showed significantly lower HF during the night as compared to control cases (P Conclusions: Our findings suggest that cardiac autonomic fluctuation is impaired in CKD patients. Whether a deterioration of autonomic activation might explain the high incidence of morning death in CKD patients needs to be clarified in future studies.

Preclinical studies suggest that neuromodulation with thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function and remodeling in systolic heart failure (HF).The purpose of this study was to evaluate the safety and efficacy of a SCS system for the treatment of systolic HF.We performed a prospective, multicenter pilot trial in patients with New York Heart Association (NYHA) class III HF, left ventricular ejection fraction (LVEF) 20%-35%, and implanted defibrillator device who were prescribed stable optimal medical therapy. Dual thoracic SCS leads were used at the T1-T3 level. The device was programmed to provide SCS for 24 hours per day (50 Hz at pulse width 200 μs).We enrolled 22 patients from 5 centers:17 patients underwent implantation of a SCS device and 4 patients who did not fulfill the study criteria served as nontreated controls. No deaths or device-device interactions were noted during the 6-month period in the 17 SCS-treated patients. Fifteen of 17 completed the efficacy endpoint assessments: composite score improved by 4.2 ± 1.3, and 11 patients (73%) showed improvement in ≥4 of 6 efficacy parameters. There was significant improvement in NYHA class (3.0 vs 2.1, P = .002; 13/17 improved); Minnesota Living with Heart Failure Questionnaire (42 ± 26 vs 27 ± 22, P = .026; 12/17 improved); peak maximum oxygen consumption (14.6 ± 3.3 vs 16.5 ± 3.9 mL/kg/min, P = .013; 10/15 improved); LVEF (25% ± 6% vs 37% ± 8%, P.001; 14/16 improved); and LV end-systolic volume (174 ± 57 vs 137 ± 37 mL, P = .002; 11/16 improved) but not in N-terminal prohormone brain natriuretic peptide. No such improvements were observed in the 4 nontreated patients.The results of this first-in-human trial suggest that high thoracic SCS is safe and feasible and potentially can improve symptoms, functional status, and LV function and remodeling in patients with severe, symptomatic systolic HF.

a University of Tokyo Hospital, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan b Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan c Department of Pain and Palliative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan d Department of Medical Engineering, the University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan e Department of Cardiovascular Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan f Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Research Division Gobancho Building, 7, Gobancho, Chiyodaku, Tokyo 102-0076, Japan g Translational Systems Biology and Medicine Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan h Department of Cardiovascular Surgery, Kinki University School of Medicine, 377-2 Onohigashi, Osakasayama, Osaka 589-8511, Japan