Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.

OBJECTIVES Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction

Direct comparison of whole heart quantifications between different retrospective and prospective gated 4D flow CMR acquisitions.

INTRODUCTION 4D flow cardiovascular magnetic resonance (CMR) is a versatile technique to non-invasively assess cardiovascular hemodynamics. With developing technology, choice in sequences and acquisition parameters is expanding and it is important to assess if data acquired with these different variants can be directly compared, especially when combining datasets within research studies. For example, sequences may allow a choice in gating techniques or be limited to one method, yet there is not a direct comparison investigating how gating selection impacts quantifications of the great vessels, semilunar and atrioventricular valves and ventricles. Thus, this study investigated if quantifications across the heart from contemporary 4D flow sequences are comparable between two commonly used 4D flow sequences reliant on different ECG gating techniques. METHODS Forty participants (33 healthy controls, seven patients with coronary artery disease and abnormal diastolic function) were prospectively recruited into a single-centre observational study to undergo a 3T-CMR exam. Two acquisitions, a k-t GRAPPA 4D flow with prospective gating (4Dprosp) and a modern compressed sensing 4D flow with retrospective gating (4Dretro), were acquired in each participant. Images were analyzed for volumes, flow rates and velocities in the vessels and four valves, and for biventricular kinetic energy and flow components. Data was compared for group differences with paired t-tests and for agreement with Bland-Altman and intraclass correlation (ICC). RESULTS Measurements primarily occurring during systole of the great vessels, semilunar valves and both left and right ventricles did not differ between acquisition types (p > 0.05 from t-test) and yielded good to excellent agreement (ICC: 0.75-0.99). Similar findings were observed for the majority of parameters dependent on early diastole. However, measurements occurring in late diastole or those reliant on the entire-cardiac cycle such as flow component volumes along with diastolic kinetic energy values were not similar between 4Dprosp and 4Dretro acquisitions resulting in poor agreement (ICC < 0.50). DISCUSSION Direct comparison of measurements between two different 4D flow acquisitions reliant on different gating methods demonstrated systolic and early diastolic markers across the heart should be compatible when comparing these two 4D flow sequences. On the other hand, late diastolic and intraventricular parameters should be compared with caution

Feasibility of Azacitidine Added to Standard Chemotherapy in Older Patients with Acute Myeloid Leukemia — A Randomised SAL Pilot Study

Introduction: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML. Trial Design: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size. Patients and Methods: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of ,20,000/ml at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint. Results: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days. Conclusions: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm. Trial Registration: This trial is registered at clinical trials.gov (identifier: NCT00915252)

Direct comparison of whole heart quantifications between different retrospective and prospective gated 4D flow CMR acquisitions

Introduction4D flow cardiovascular magnetic resonance (CMR) is a versatile technique to non-invasively assess cardiovascular hemodynamics. With developing technology, choice in sequences and acquisition parameters is expanding and it is important to assess if data acquired with these different variants can be directly compared, especially when combining datasets within research studies. For example, sequences may allow a choice in gating techniques or be limited to one method, yet there is not a direct comparison investigating how gating selection impacts quantifications of the great vessels, semilunar and atrioventricular valves and ventricles. Thus, this study investigated if quantifications across the heart from contemporary 4D flow sequences are comparable between two commonly used 4D flow sequences reliant on different ECG gating techniques.MethodsForty participants (33 healthy controls, seven patients with coronary artery disease and abnormal diastolic function) were prospectively recruited into a single-centre observational study to undergo a 3T-CMR exam. Two acquisitions, a k-t GRAPPA 4D flow with prospective gating (4Dprosp) and a modern compressed sensing 4D flow with retrospective gating (4Dretro), were acquired in each participant. Images were analyzed for volumes, flow rates and velocities in the vessels and four valves, and for biventricular kinetic energy and flow components. Data was compared for group differences with paired t-tests and for agreement with Bland-Altman and intraclass correlation (ICC).ResultsMeasurements primarily occurring during systole of the great vessels, semilunar valves and both left and right ventricles did not differ between acquisition types (p &gt; 0.05 from t-test) and yielded good to excellent agreement (ICC: 0.75–0.99). Similar findings were observed for the majority of parameters dependent on early diastole. However, measurements occurring in late diastole or those reliant on the entire-cardiac cycle such as flow component volumes along with diastolic kinetic energy values were not similar between 4Dprosp and 4Dretro acquisitions resulting in poor agreement (ICC &lt; 0.50).DiscussionDirect comparison of measurements between two different 4D flow acquisitions reliant on different gating methods demonstrated systolic and early diastolic markers across the heart should be compatible when comparing these two 4D flow sequences. On the other hand, late diastolic and intraventricular parameters should be compared with caution

Prognostic impact of <i>CEBPA </i>mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIP InDel), frameshift InDel or nonsense mutations inducing translational stop (bZIP STOP) or single base-pair missense alterations (bZIP ms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIP InDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIP InDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIP InDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIP InDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIP ms). (Figure presented.)</p

Quality of out-of-hospital palliative emergency care depends on the expertise of the emergency medical team—a prospective multi-centre analysis

The number of palliative care patients who live at home and have non-curable life-threatening diseases is increasing. This is largely a result of modern palliative care techniques (e.g. specialised out-of-hospital palliative medical care services), changes in healthcare policy and the availability of home care services. Accordingly, pre-hospital emergency physicians today are more likely to be involved in out-of-hospital emergency treatment of palliative care patients with advanced disease. In a prospective multi-centre study, we analysed all palliative emergency care calls during a 24-month period across four emergency services in Germany. Participating pre-hospital emergency physicians were rated according to their expertise in emergency and palliative care as follows-group 1: pre-hospital emergency physicians with high experience in emergency and palliative medical care, group 2: pre-hospital emergency physicians with high experience in emergency medical care but less experience in palliative medical care and group 3: pre-hospital emergency physicians with low experience in palliative and emergency medical care. During the period of interest, the centres received 361 emergency calls requiring a response to palliative care patients (2.8% of all 12,996 emergency calls). Ten percent of all patients were treated by group 1; 42% were treated by group 2 and 47% were treated by group 3. There was a statistically significant difference in the treatment of palliative care patients (e.g. transfer to hospital, symptom control, end-of-life decision) as a result of the level of expertise of the investigated pre-hospital emergency physicians (p < 0.01). In Germany, out-of-hospital emergency medical treatment of palliative care patients depends on the expertise in palliative medical care of the pre-hospital emergency physicians who respond to the call. In our investigation, best out-of-hospital palliative medical care was given by pre-hospital emergency physicians who had significant expertise in palliative and emergency medical care. Our results suggest that it may be necessary to take the core principles of palliative care into consideration when conducting out-of-hospital emergency medical treatment of palliative care patients

Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation

Background The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K). Methods Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal–Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate. Results Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002). Conclusion In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making