Serial Cardiovascular Magnetic Resonance Strain Measurements to Identify Cardiotoxicity in Breast Cancer: Comparison With Echocardiography

ObjectivesThis study sought to compare the prognostic value of cardiovascular magnetic resonance (CMR) and 2-dimensional echocardiography (2DE) derived left ventricular (LV) strain, volumes, and ejection fraction for cancer therapy–related cardiac dysfunction (CTRCD) in women with early stage breast cancer.BackgroundThere are limited comparative data on the association of CMR and 2DE derived strain, volumes, and LVEF with CTRCD.MethodsA total of 125 prospectively recruited women with HER2+ early stage breast cancer receiving sequential anthracycline/trastuzumab underwent 5 serial CMR and 6 of 2DE studies before and during treatment. CMR LV volumes, left ventricular ejection fraction tagged-CMR, and feature-tracking (FT) derived global systolic longitudinal (GLS) and global circumferential strain (GCS) and 2DE-based LV volumes, function, GLS, and GCS were measured. CTRCD was defined by the cardiac review and evaluation committee criteria.ResultsTwenty-eight percent of patients developed CTRCD by CMR and 22% by 2DE. A 15% relative reduction in 2DE-GLS increased the CTRCD odds by 133% at subsequent follow-up, compared with 47%/50% by tagged-CMR GLS/GCS and 87% by FT-GCS. CMR and 2DE-LVEF and indexed left ventricular end-systolic volume (LVESVi) were also associated with subsequent CTRCD. The prognostic threshold change in CMR-left ventricular ejection fraction and FT strain for subsequent CTRCD was similar to the known minimum-detectable difference for these measures, whereas for tagged-CMR strain it was lower than the minimum-detectable difference; for 2DE, only the prognostic threshold for GLS was greater than the minimum-detectable difference. Of all strain methods, 2DE-GLS provided the highest increase in discriminatory value over baseline clinical risk factors for subsequent CTRCD. The combination of 2DE-left ventricular ejection fraction or LVESVi and strain provided greater increase in the area under the curve for subsequent CTRCD over clinical risk factors than CMR left ventricular ejection fraction or LVESVi and strain (18% to 22% vs. 9% to 14%).ConclusionsIn women with HER2+ early stage breast cancer, changes in CMR and 2DE strain, left ventricular ejection fraction, and LVESVi were prognostic for subsequent CTRCD. When LVEF can be measured precisely by CMR, FT strain may function as an additional confirmatory prognostic measure, but with 2DE, GLS is the optimal prognostic measure. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)     

The effects of long- and short-term interdisciplinary treatment approaches in women with fibromyalgia: a randomized controlled trial

We investigated the effects of long- and short-term interdisciplinary treatment approaches for reducing symptoms and improving health-related quality of life (HRQoL) and physical functions of patients with fibromyalgia and compared the effects of two different interdisciplinary treatment approaches. We conducted a prospective, randomized, controlled trial involving 66 women with fibromyalgia eligible for the study at a university hospital setting. The patients were randomized into three groups (allocation ratio 1:1:1) using a computer-generated random numbers: a long-term interdisciplinary treatment group (LG, n = 22) that participated in 10 sessions (3-h once-weekly session for 10 weeks) of cognitive behavioral therapy (CBT) together with exercise training and other fibromyalgia related educational programs (two full days); a short-term interdisciplinary treatment group (SG, n = 22) that received two full days of educational, exercise, and CBT programs; and a control group (CG, n = 22). The patients were evaluated at baseline and 6 months after treatment using the visual analog scale (pain, fatigue, and sleep), Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Short Form-36, tender point numbers, and pressure algometry as primary outcomes. The statistical analysis was confined to the ‘per-protocol’ set. No blinding was performed. The number of patients analyzed was 21 in the LG, 19 in the SG, and 19 in the CG. The intensity of pain (p < 0.001), severity of fatigue (p = 0.048), number of tender points (p = 0.002), and pressure pain threshold (p = 0.012) decreased significantly in both the LG and SG groups compared with controls. Moreover, physical functions (p = 0.017) and physical components of the HRQoL (p = 0.036) improved significantly in the intervention groups compared with the controls. However, there was no significant difference between intervention groups and the control group at the end of study in terms of quality of sleep (p = 0.055), severity of depressive symptoms (p = 0.696), and mental components of the HRQoL (p = 0.229). Finally, with the exception of the severity of fatigue and physical components of the HRQoL, there was no obvious significant difference between the efficacies of the two treatment approaches when compared with controls; the long-term treatment was found more effective in reducing pain than the short-term. Both, long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia particularly in relation to pain and health status as measured using FIQ; however, a long-term program may be beneficial in reducing fatigue and improving physical function to a higher extent.     

Doppler Echocardiographic Assessment of Pulmonary Prostheses: A Comprehensive Assessment Including Velocity Time Integral Ratio and Prosthesis Effective Orifice Area

Objective. Few reports have been published on the Doppler‐derived echocardiographic data for pulmonary valve prostheses (PVPs). The aim of this study was to provide a comprehensive Doppler echocardiographic assessment of PVPs. Methods. We studied 40 patients (mean age 24.2) with PVPs: 13 (32.5%) mechanical and 27 (67.5%) bioprosthetic valves. After clinical evaluation, all patients underwent complete, two‐dimensional and Doppler studies. Results. In 30 patients with normally functioning PVPs, the mean (SD) peak velocity was 2.33 (0.36) m/s with an average peak pressure gradient of 22.69 (6.7) mm Hg and an average mean pressure gradient of 12.5 (4.1) mm Hg. The mean PVPs velocity time integral (VTI) was 47.49 (12.78) cm with mean right ventricle outflow tract/peak velocity (PV) VTI ratio 0.43 (0.14), mean PVPs effective orifice area was 1.63 (0.36) cm². Metallic PVPs had significantly better hemodynamic Doppler study compared with biologic PVPs. In 9 patients with PVP malfunction, average peak PVPs velocity, average peak pressure gradient, mean pressure gradient, PV VTI, PV/left ventricle outflow tract VTI ratio was significantly increased (P < 0.05). Conclusion. This study contributes to establishing the normal range for Doppler hemodynamics in various PVPs.     

Endogenous competition against binding of [18F]DMFP and [18F]fallypride to dopamine D2/3 receptors in brain of living mouse

Aim . Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D_2/3‐receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and [¹¹C]‐labeled ligands are only available at positron emission tomography (PET) research sites with cyclotron‐radiochemistry facilities, whereas [¹⁸F] can be transported, due to its longer physical half‐life. Therefore, we endeavored to characterize the vulnerabilities of the benzamide antagonist [¹⁸F]desmethoxyfallypride (DMFP) and its high‐affinity congener [¹⁸F]fallypride (FP) to competition from endogenous dopamine in living mouse brain. Methods . Groups of awake mice were pretreated with saline, amphetamine (10 mg/kg), or reserpine (5 mg/kg), followed by i.v. tracer injections. Mice were killed at 2.5–90 min (DMFP) or 2.5–180 min (FP) circulation times. Brains were dissected and regional radioactivity concentration measured by gamma counting. Other groups of mice were anesthetized for dynamic microPET recordings with DMFP or FP. Binding potentials (BP_ND) were calculated using cerebellum as reference region. Results . With 90‐min circulation, DMFP BP_ND in striatum was 2.4 by dissection and 2.2 by microPET, which showed a 62% decrease in response to amphetamine‐evoked dopamine release and a 33% increase after reserpine‐evoked dopamine depletion. With 120‐min circulation, FP BP_ND in striatum was 24.1 by dissection and 9.2 by microPET, which showed a 31% decrease in the amphetamine group, but no effect of reserpine. Dissection showed similar sensitivities for FP binding, but only a 29% amphetamine‐evoked reduction for DMFP. Conclusions . Relative to gold standard ex vivo results, microPET estimates of DMFP BP_ND were unbiased, whereas FP BP_ND in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D_2/3‐receptors in striatum of living mice. Synapse 64:313–322, 2010. © 2009 Wiley‐Liss, Inc.     

Colour M-mode superiority in evaluation of improvement in myocardial performance indices following successful percutaneous coronary intervention (PCI)

Aim

This study aimed at evaluating the early effects of successful elective percutaneous coronary intervention (PCI) on systolic and diastolic function.

Methods

We consecutively studied the systolic and diastolic function in 21 patients with stable coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) > 40% before and 48 hours after successful elective PCI.

Results

Tei index and systolic indices (LVEF, regional wall motion abnormality score, tricuspid annular plane systolic excursion and peak systolic velocity of mitral and tricuspid annulus) did not change significantly. Among the diastolic indices, only velocity propagation (Vp) improved significantly (from 42.9 ± 10.8 to 51.8 ± 10.7, p-value = 0.008) following PCI. Diastolic velocities, E/A ratio, deceleration time (DT), early and late diastolic velocities of mitral annulus in TDI, pulmonary vein systolic (PVs) and diastolic flow velocity (PVd) did not show significant improvement.

Conclusion

Propagation velocity of mitral inflow was the earliest index to recover following successful PCI in patients with stable CAD.     

Echocardiographic evaluation of mitral geometry in functional mitral regurgitation

Background

Given the growing population of cardiac surgery patients with impaired preoperative cardiac function and rapidly expanding surgical techniques, continued efforts to improve myocardial protection strategies are warranted. Prior research is mostly limited to either large animal models or ex vivo preparations. We developed a new in vivo survival model that combines administration of antegrade cardioplegia with endoaortic crossclamping during cardiopulmonary bypass (CPB) in the rat.

Methods

Sprague-Dawley rats were cannulated for CPB (n = 10). With ultrasound guidance, a 3.5 mm balloon angioplasty catheter was positioned via the right common carotid artery with its tip proximal to the aortic valve. To initiate cardioplegic arrest, the balloon was inflated and cardioplegia solution injected. After 30 min of cardioplegic arrest, the balloon was deflated, ventilation resumed, and rats were weaned from CPB and recovered. To rule out any evidence of cerebral ischemia due to right carotid artery ligation, animals were neurologically tested on postoperative day 14, and their brains histologically assessed.

Results

Thirty minutes of cardioplegic arrest was successfully established in all animals. Functional assessment revealed no neurologic deficits, and histology demonstrated no gross neuronal damage.

Conclusion

This novel small animal CPB model with cardioplegic arrest allows for both the study of myocardial ischemia-reperfusion injury as well as new cardioprotective strategies. Major advantages of this model include its overall feasibility and cost effectiveness. In future experiments long-term echocardiographic outcomes as well as enzymatic, genetic, and histologic characterization of myocardial injury can be assessed. In the field of myocardial protection, rodent models will be an important avenue of research.     

The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation

Background and introduction

Without adequate prophylaxis, liver transplantation (LTx) is frequently followed by hepatitis B virus (HBV) reinfection, which results in rapidly progressing liver disease and significantly decreased overall survival. In the last two decades, significant progress has been made in the prophylaxis and treatment of HBV.

Discussion

We present an overview of different protocols and regimens used for prophylaxis of HBV reinfection after LTx and describe the protocol implemented at our center. Following LTx, HBV reinfection can be effectively prevented by administration of anti-hepatitis B immunoglobulin (HBIg) alone or more recently in combination with antiviral nucleoside/nucleotide analogs (NUCs). Several studies reported good results with the use of HBIg alone, but combination treatment with HBIg and NUCs has proven to be a superior prophylactic regimen for HBV recurrence. At present, combination therapy (HBIg and a nucleoside or nucleotide analog) is the gold standard used in many transplantation centers. This preventive regimen reduces the risk of a recurrence of HBV infection and thereby the need for re-transplantation. Future and ongoing studies will show how long HBIg must be given after transplantation, especially when used in combination with potent antivirals, such as entecavir or tenofovir.     

Evaluating the effects of extended cold ischemia on interstitial metabolite in grafts in kidney transplantation using microdialysis

Purpose

During kidney transplantation (KTx), the length of cold ischemia time (CIT) and the subsequent changes in energy metabolism may lead to variations in interstitial metabolites. Using microdialysis (MD), we evaluated the effects of a short and long CIT on changes of these metabolites.

Methods

Sixteen pigs were randomized in two identical groups, one with a short CIT and the other one with a long CIT. Using MD in the transplanted grafts, we evaluated the parenchyma concentrations of glucose, lactate, pyruvate, glutamate and glycerol in different stages.

Results

We noted that during the warm ischemia time (WIT) and in the early post-reperfusion phase glucose levels increased more significantly in the long CIT group and remained high until the end of monitoring. At the end of CIT and during WIT, the long CIT group had a significantly higher glycerol level, but the level dropped gradually in the late post-reperfusion phase and reached a steady state in both groups.

Conclusions

The extended CIT clearly results in considerably impaired graft metabolism. The high interstitial glucose levels within hours after KTx could be considered as a marker of primary delayed function of the graft. Furthermore, the glycerol value could reflect the extent of graft injury during the ischemia time or in case of acute impairment of graft perfusion.