Levosimendan Plus Dobutamine in Acute Decompensated Heart Failure Refractory to Dobutamine.

Randomized studies showed that Dobutamine and Levosimendan have similar impact on outcome but their combination has never been assessed in acute decompensated heart failure (ADHF) with low cardiac output. This is a retrospective, single-center study that included 89 patients (61 ± 15 years) admitted for ADHF requiring inotropic support. The first group consisted of patients treated with dobutamine alone (n = 42). In the second group, levosimendan was administered on top of dobutamine, when the superior vena cava oxygen saturation (ScVO2) remained <60% after 3 days of dobutamine treatment (n = 47). The primary outcome was the occurrence of major cardiovascular events (MACE) at 6 months, defined as all cause death, heart transplantation or need for mechanical circulatory support. Baseline clinical characteristics were similar in both groups. At day-3, the ScVO2 target (>60%) was reached in 36% and 32% of patients in the dobutamine and dobutamine-levosimendan group, respectively. After adding levosimendan, 72% of the dobutamine-levosimendan-group reached the ScVO2 target value at dobutamine weaning. At six months, 42 (47%) patients experienced MACE (n = 29 for death). MACE was less frequent in the dobutamine-levosimendan (32%) than in the dobutamine-group (64%, p = 0.003). Independent variables associated with outcome were admission systolic blood pressure and dobutamine-levosimendan strategy (OR = 0.44 (0.23-0.84), p = 0.01). In conclusion, levosimendan added to dobutamine may improve the outcome of ADHF refractory to dobutamine alone.

Infective endocarditis without biological inflammatory syndrome: Description of a particular entity.

BACKGROUND: Bacterial infective endocarditis (IE) is rarely suspected in patients with a low C-reactive protein (CRP) concentration. AIMS: To address the incidence, characteristics and outcome of left-sided valvular IE with low CRP concentration. METHODS: This was a retrospective analysis of cases of IE discharged from our institution between January 2009 and May 2017. The 10% lowest CRP concentration (<20mg/L) was used to define low CRP concentration. Right-sided cardiac device-related IE, non-bacterial IE, sequelar IE and IE previously treated by antibiotics were excluded. RESULTS: Of the 469 patients, 13 (2.8%; median age 68 [61-76] years) had definite (n=8) or possible (n=5) left-sided valvular IE with CRP<20mg/L (median 9.3 [4.7-14.2] mg/L). The median white blood cell count was 6.3 (5.3-7.5) G/L. The main presentations were heart failure (n=7; 54%) and stroke (n=3; 23%). Transthoracic echocardiography (TTE) showed vegetations (n=5) or isolated valvular regurgitation (n=4). Overall, eight patients (62%) had severe valvular lesions on transoesophageal echocardiography (TOE), and nine patients (69%) underwent cardiac surgery. All patients survived at 1-year follow-up. Bacterial pathogens were documented in eight patients (streptococci, coagulase-negative Staphylococcus, Corynebacteriumjeikeium, HACEK group, Coxiella burnetii, Bartonella henselae) using blood cultures, serology or valve culture and/or polymerase chain reaction analysis. CONCLUSIONS: Left-sided valvular IE with limited or no biological syndrome is rare, but is often associated with severe valvular and paravalvular lesions. TOE should be performed in presence of unexplained heart failure, new valvular regurgitation or cardioembolic stroke when TTE is insufficient to rule out endocarditis, even in patients with a low CRP concentration.

Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use.

BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. METHODS: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. RESULTS: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P<0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; P<0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell-mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access. CONCLUSIONS: Targeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.

A New Three-Dimensional Echocardiography Method to Quantify Aortic Valve Calcification.

BACKGROUND: Aortic valve calcification (AVC) quantification is computed from multidetector computed tomography (MDCT). The aim of this study was to test the hypothesis that three-dimensional (3D) transthoracic echocardiography can be used to provide a bedside method to assess AVC. METHODS: The study included 94 patients (mean age, 78 ± 12 years; mean aortic valve [AV] area, 1.0 ± 0.6 cm2) referred for MDCT and echocardiography for AV assessment. Apical 3D full-volume data sets focused on the AV region were acquired during transthoracic echocardiography, and a region-growing algorithm was applied offline to compute 3D transthoracic echocardiographic AVC (AVC-3DEcho). AVC-3DEcho was compared with AVC by MDCT and with calcium weight in the subgroup of patients referred for surgery, with explanted AVs analyzed by a pathologist (n = 22). RESULTS: In the explanted valve group, AVC-3DEcho score exhibited fair correlations with MDCT score (r = 0.85, P < .001), calcium load (r = 0.81, P < .001), and peak AV velocity (r = 0.64, P < .001). In the overall population, AVC-3DEcho score correlated modestly with MDCT score (r = 0.61, P < .001) but had similar accuracy to identify severe aortic stenosis (area under the curve = 0.94). AVC-3DEcho > 1,054 mm3 identified severe aortic stenosis with specificity of 100% and sensitivity of 76%. In addition, AVC-3DEcho was associated with the presence of significant paravalvular regurgitation after transcatheter aortic valve implantation. Finally, intraobserver and interobserver variability for AVC-3DEcho score was 4.2% and 8.9%, respectively. CONCLUSIONS: AVC-3DEcho correlated with calcium weight obtained from pathologic analysis and MDCT. These data suggest that a bedside method for quantifying AV calcification with ultrasound is feasible.

Three-Dimensional Inferior Vena Cava for Assessing Central Venous Pressure in Patients with Cardiogenic Shock.

BACKGROUND: The inferior vena cava (IVC) has a complex three-dimensional (3D) shape, but measurements used to estimate central venous pressure (CVP) remain based on two-dimensional (2D) echocardiographic imaging. The aim of this study was to investigate the accuracy of IVC size and collapsibility index obtained by 3D echocardiography for assessing CVP in patients with cardiogenic shock. METHODS: Eighty consecutive echocardiographic examinations performed in 33 patients (mean age, 72 ± 15 years; mean left ventricular ejection fraction, 19 ± 10%) admitted for cardiogenic shock were prospectively included. Two-dimensional and 3D images of the IVC were acquired simultaneously with invasive measurement of CVP, both at rest and during a sniff test. IVC diameters, 3D IVC area, and IVC collapsibility index (IVCCI) were assessed. The eccentricity index was computed from 3D data as the ratio of maximum to minimum IVC diameter. A cutoff value of 10 mm Hg for CVP defined patients with euvolemic hemodynamic status. RESULTS: At rest, IVC diameter averaged 23 ± 7 mm by 2D imaging and 25 ± 8 × 19 ± 7 mm by 3D imaging. The IVC had an eccentric shape (eccentricity index = 1.3) that increased when CVP was ≤10 mm Hg and during the sniff test (P < .001). IVC measurements by 2D and 3D imaging were correlated with CVP. The best correlation was obtained with IVCCI derived from 2D diameters (R = -0.69) and 3D areas (R = -0.82). Using a cutoff value of 50% for IVCCI, 11 examinations were misclassified by 2D imaging and only one by 3D imaging. Inter- and intraobserver reproducibility for IVC area was 7 ± 6% and 5 ± 3%, respectively. CONCLUSIONS: In patients with cardiogenic shock, IVCCI from area by 3D echocardiography is reproducible and accurate to evaluate CVP.

Left ventricular dyssynchrony and 2D and 3D global longitudinal strain for differentiating physiological and pathological left ventricular hypertrophy.

BACKGROUND: Diagnosis of hypertrophic cardiomyopathy (HCM) in athletes can be challenging. AIMS: To ascertain parameters that differentiate patients with HCM from athletes with moderate left ventricular (LV) hypertrophy (LVH 13-15mm). METHODS: We retrospectively included 100 men: 50 elite rugby players (25 with moderate LVH and 25 with no LVH), 25 patients with HCM and moderate LVH and 25 controls. LV dyssynchrony was defined as the standard deviation of time to peak 2D longitudinal strain (16-segment model) and global strain components were computed from two- (2D) and three-dimensional (3D) speckle tracking. RESULTS: 2D global longitudinal strain (GLS) (18±2% vs. 19±2%) and various 3D strain components were similar in athletes with moderate LVH and controls, while LV volumes and dyssynchrony (39±8 vs. 31±9ms; P<0.001) were greater in athletes with moderate LVH. The accuracy for differentiating patients with HCM from athletes ranged between 0.57 and 0.92 for various markers, with the best obtained for LV dyssynchrony (AUC=0.92;>48ms had sensitivity=83%, specificity=89%). Binary logistic regression showed that accuracy was improved when LV dyssynchrony was combined with 2D GLS. HCM was excluded when 2D GLS was preserved (>18%) and there was no LV dyssynchrony (>48ms) and only patients with HCM had reduced longitudinal strain and LV dyssynchrony. CONCLUSIONS: LV dyssynchrony combined with GLS can be used to differentiate athletes with moderate LVH from patients with HCM.