Echocardiographic Evaluation of LV Function in Patients with Tachyarrhythmia and Reduced Left Ventricular Function in Response to Rhythm Restoration

Aims: Tachyarrhythmia due to atrial fibrillation (AF) is often associated with reduced left ventricular (LV) function and has been proposed to cause arrhythmia-induced cardiomyopathy (AIC). However, the precise diagnostics of AIC and reversibility after rhythm restoration are poorly understood. Our aim was to investigate systolic LV function in tachycardic AF and to evaluate the direct effect of rhythm restoration. Methods: We prospectively studied 24 patients (71% male, age 65 ± 9 years) with tachycardic AF and newly diagnosed reduced left ventricular ejection fraction (LVEF). Just before and immediately after electrical cardioversion (ECV), transthoracic echocardiography was performed. Geometric as well as functional data were assessed. Results: Patients presented with a heart rate (HR) of 117.4 ± 21.6/min and a 2D-/3D-LVEF of 32 ± 9/31 ± 8%. ECV to sinus rhythm normalized HR to 77 ± 11/min with an increase of 2D-/3D-LVEF to 37 ± 9/37 ± 10% (p < 0.01 vs. baseline, each). Left ventricular geometry changed with an increase of end-diastolic volume (LVEDV) while end-systolic volume (LVESV) remained unchanged. Parameters concerning myocardial deformation (global longitudinal strain (GLS), strain rate (SR)) decreased whereas the RR interval-corrected GLS (GLSc) remained unchanged. In a simple linear regression model, GLS correlated with 2D- and 3D-LVEF not only before (pre) ECV, but also after (post) ECV. We demonstrate that the increase of LVEF and GLS (ratios pre/post) correlates with the change of HR (ΔHR; R2 = 0.20, 0.33 and 0.32, p < 0.05 each), whereas ratios of GLSc and SR do not significantly correlate with HR (R2 = 0.03 and 0.01, p = n.s. each). Conclusion: In patients with tachyarrhythmia and reduced ejection fraction, ECV leads to immediate improvement in EF and GLS while HR-corrected LV contractility remains unchanged. This suggests that the immediate effects of rhythm restoration are mostly related to changes in left ventricular volume, but not to an acute improvement of heart-rate independent contractility

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

Aims Glucocorticoid (GC) stimulation has been shown to increase cardiac contractility by elevated intracellular [Ca] but the sources for Ca entry are unclear. This study aims to determine the role of store-operated Ca entry (SOCE) for GC-mediated inotropy. Methods and results Dexamethasone (Dex) pretreatment significantly increased cardiac contractile force ex vivo in Langendorff-perfused Sprague-Dawley rat hearts (2 mg/kg BW i.p. Dex 24 h prior to experiment). Moreover, Ca transient amplitude as well as fractional shortening were significantly enhanced in Fura-2-loaded isolated rat ventricular myocytes exposed to Dex (1 mg/mL Dex, 24 h). Interestingly, these Dex-dependent effects could be abolished in the presence of SOCE-inhibitors SKF-96356 (SKF, 2 μM) and BTP2 (5 μM). Ca transient kinetics (time to peak, decay time) were not affected by SOCE stimulation. Direct SOCE measurements revealed a negligible magnitude in untreated myocytes but a dramatic increase in SOCE upon Dex-pretreatment. Importantly, the Dex-dependent stimulation of SOCE could be blocked by inhibition of serum and glucocorticoid-regulated kinase 1 (SGK1) using EMD638683 (EMD, 50 μM). Dex preincubation also resulted in increased mRNA expression of proteins involved in SOCE (stromal interaction molecule 2, STIM2, and transient receptor potential cation channels 3/6, TRPC 3/6), which were also prevented in the presence of EMD. Conclusion Short-term GC-stimulation with Dex improves cardiac contractility by a SOCE-dependent mechanism, which appears to involve increased SGK1-dependent expression of the SOCE-related proteins. Since Ca transient kinetics were unaffected, SOCE appears to influence Ca cycling more by an integrated response across multiple cardiac cycles but not on a beat-to-beat basis

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content. Conclusion Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling

Reduction of radiation exposure during transcatheter edge‐to‐edge mitral valve repair

Background Transcatheter mitral valve repair is an increasingly used therapy for mitral regurgitation which requires fluoroscopic guidance. Limiting radiation exposure during lengthy procedures is important for both patient and operator safety. This study aimed to investigate radiation dose during contemporary use of MitraClip implantation and the effects of a dose reduction program. Methods A total of 115 patients who underwent MitraClip implantation were prospectively enrolled in a single-center observational study. During the inclusion period, our institution adopted a radiation dose reduction program, comprising lowering of fluoroscopy pulse rate and image target dose. The first 58 patients were treated with conventional fluoroscopy settings, while the following 57 patients underwent the procedure with the newly implemented low dose protocol. Results Radiation dose area product significantly decreased after introduction of the low dose protocol (693 [366–1231] vs. 2265 [1517–3914] cGy·cm2, p < 0.001). After correcting for fluoroscopy time, gender and body mass index, the low dose protocol emerged as a strong negative predictor of radiation dose (p < 0.001), reducing dose area product by 64% (95% confidence interval [57–70]). Device time, device success, and procedural safety did not differ between the normal dose and low dose group. Furthermore, the low dose protocol was not associated with an increased incidence of a combined endpoint consisting of death, repeat intervention, or heart surgery during 12 months follow-up. Conclusion Reduction of radiation exposure during transcatheter mitral valve repair by 64% is feasible without affecting procedural success or safety

A Pilot Trial to Compare the Long-Term Efficacy of Pulmonary Vein Isolation with High-Power Short-Duration Radiofrequency Versus Laser Energy with Rapid Ablation Mode

Background: Pulmonary vein (PV) reconnection is the major cause of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). The probability of reconnection is higher if the primary lesion is not sufficiently effective, which can be unmasked with an adenosine provocation test (APT). High-power short-duration radiofrequency energy (HPSD) guided with ablation index (AI) and the third generation of the visually guided laser balloon (VGLB) are new methods for PVI. Methods: A total of 70 participants (35 in each group) who underwent a PVI with either AI-guided HPSD (50 W; AI 500 for the anterior and 400 for the posterior wall, respectively) or VGLB ablation were included in this observational pilot trial. Twenty minutes after each PVI, an APT was performed. The primary endpoint was the event-free survival from AF after three years. Results: A total of 137 (100%) PVs in the HPSD arm and 131 PVs (98.5%) in the VGLB arm were initially successfully isolated (p = 0.24). The overall procedure duration was similar in both arms (155 ± 39 in HPSD vs. 175 ± 58 min in VGLB, p = 0.191). Fluoroscopy time, left atrial dwelling time and duration from the first to the last ablation were longer in the VGLB arm (23 ± 8 vs. 12 ± 3 min, p < 0.001; 157 (111–185) vs. 134 (104–154) min, p = 0.049; 92(59–108) vs. 72 (43–85) min, p = 0.010). A total of 127 (93%) in the HPSD arm and 126 (95%) PVs in the VGLB arm remained isolated after APT (p = 0.34). The primary endpoint was met 1107 ± 68 days after ablation in 71% vs. 66% in the VGLB and HPSD arms, respectively (p = 0.65). Conclusions: HPSD and VGLB did not differ with respect to long-term outcome of PVI. A large, randomized study should be conducted to compare clinical outcomes with respect to these new ablation techniques

Vascular Alterations in a Murine Model of Acute Graft-Versus-Host Disease Are Associated With Decreased Serum Levels of Adiponectin and an Increased Activity and Vascular Expression of Indoleamine 2,3-Dioxygenase

Graft-versus-host disease (GVHD) is the limiting complication after bone marrow transplantation (BMT), and its pathophysiology seems to be highly influenced by vascular factors. Our study aimed at elucidating possible mechanisms involved in vascular GVHD. For this purpose, we used a fully MHC-mismatched model of BALB/c mice conditioned according to two different intensity protocols with total body irradiation and transplantation of allogeneic (C57BL/6) or syngeneic bone marrow cells and splenocytes. Mesenteric resistance arteries were studied in a pressurized myograph. We also quantified the expression of indoleamine 2,3-dioxygenase (IDO), endothelial (eNOS), and inducible NO synthase (iNOS), as well as several pro-and anti-inflammatory cytokines. We measured the serum levels of tryptophan (trp) and kynurenine (kyn), the kyn/trp ratio (KTR) as a marker of IDO activity, and adiponectin (APN). The myographic study showed a correlation of GVHD severity after allogeneic BMT with functional vessel alterations that started with increased vessel stress and ended in eccentric vessel remodeling, increased vessel strain, and endothelial dysfunction. These alterations were accompanied by increasing IDO activity and decreasing APN levels in the serum of allogeneic animals. The mRNA expression showed significantly elevated IDO, decreased eNOS, and elevation of most studied pro-and anti-inflammatory cytokines. Our study provides further data supporting the importance of vessel alterations in GVHD and is the first to show an association of vascular GVHD with hypoadiponectinemia and an increased activity and vascular expression of IDO. Whether there is also a causative involvement of these two factors in the development of GVHD needs to be further investigated

Complement Regulator FHR-3 Is Elevated either Locally or Systemically in a Selection of Autoimmune Diseases

Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets of graft-versus-host disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols. Syngeneically transplanted and untreated animals served as controls. Four weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (tumor necrosis factor alpha, interferon-gamma, interleukin 1 alpha [IL-1 alpha], IL-2, IL-6, and IL-10), and adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cellmediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal impairment

Predictors of functional improvement in the short term after MitraClip implantation in patients with secondary mitral regurgitation

Background and objectives MitraClip implantation is an established therapy for secondary mitral regurgitation (MR) in high-risk patients and has shown to improve several important outcome parameters such as functional capacity. Patient selection is both challenging and crucial for achieving therapeutic success. This study investigated baseline predictors of functional improvement as it was quantified by the six-minute walk distance (6MWD) after transcatheter mitral valve repair. Methods and results We retrospectively analyzed 79 patients with secondary MR treated with MitraClip implantation at an academic tertiary care center. Before and four weeks after the procedure, all patients underwent comprehensive clinical assessment, six-minute walk tests and echocardiography. 6MWD significantly improved after MitraClip therapy (295 m vs. 265 m, p < 0.001). A linear regression model including seven clinical baseline variables significantly predicted the change in 6MWD (p = 0.002, R-2 = 0.387). Female gender, diabetes mellitus and arterial hypertension were found to be significant negative predictors of 6MWD improvement. At baseline, female patients had significant higher left ventricular ejection fraction (49% vs. 42%, p = 0.019) and lower 6MWD (240 m vs. 288 m, p = 0.034) than male patients. Conclusion MitraClip implantation in secondary MR significantly improves functional capacity in high risk patients even in the short term of four weeks after the procedure. Female gender, diabetes mellitus and arterial hypertension are baseline predictors of a less favourable functional outcome. While further validation in a larger cohort is recommended, these parameters may improve patient selection for MitraClip therapy

Infective Endocarditis: Predictive Factors for Diagnosis and Mortality in Surgically Treated Patients

Background: Diagnosis of infective endocarditis (IE) often is challenging, and mortality is high in such patients. Our goal was to characterize common diagnostic tools to enable a rapid and accurate diagnosis and to correlate these tools with mortality outcomes. Methods: Because of the possibility of including perioperative diagnostics, only surgically treated patients with suspected left-sided IE were included in this retrospective, monocentric study. A clinical committee confirmed the diagnosis of IE. Results: 201 consecutive patients (age 64 ± 13 years, 74% male) were finally diagnosed with IE, and 14 patients turned out IE-negative. Preoperative tests with the highest sensitivity for IE were positive blood cultures (89.0%) and transesophageal echocardiography (87.5%). In receiver operating characteristics, vegetation size revealed high predictive power for IE (AUC 0.800, p < 0.001) with an optimal cut-off value of 11.5 mm. Systemic embolism was associated with mortality, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) had predictive power for mortality. Conclusion: If diagnostic standard tools remain inconclusive, we suggest employing novel cut-off values to increase diagnostic accuracy and accelerate diagnosis. Patients with embolism or elevated NT-proBNP deserve a closer follow-up