Two-dimensional speckle-tracking strain detects subclinical cardiotoxicity in older patients treated for acute myeloid leukemia.

BACKGROUND: Patients with acute myeloid leukemia (AML) are surviving longer. There are no data on changes in myocardial mechanics from standard of care low-dose anthracycline-based induction chemotherapy in older patients with AML. The aim of this study was to demonstrate the potential utility of strain imaging in detecting early changes in left ventricular function in this patient population after induction chemotherapy. METHODS: Thirty two patients enrolled in the ECOG-ACRIN E2906 study (cytarabine and daunorubicin vs clofarabine [Genzyme/Sanofi]) from 2011 to 2014 were evaluated retrospectively. Two-dimensional transthoracic echocardiography (TTE) imaging with Doppler and two-dimensional speckle-tracking echocardiography (2DSTE) using EchoInsight software (Epsilon imaging) were performed before and after induction chemotherapy. RESULTS: Eighteen patients received cytarabine and daunorubicin (7 + 3) and 14 received clofarabine. The clofarabine group was older than the 7 + 3 cohort (67.8 ± 4.0 vs 63.7 ± 3.8, P = .007). There were no other significant differences in cardiac risk factors between groups. The 7 + 3 group had a decrease in average peak systolic global longitudinal (-19.1 ± 2.8 to -17.2 ± 3.0, P = .01) and circumferential strain (-29.4 ± 6.3 to -23.9 ± 4.3, P = .011). These changes were not demonstrated in the clofarabine group and were not associated with a decline in left ventricular ejection fraction (LVEF). CONCLUSIONS: In older AML patients, standard cytarabine and daunorubicin chemotherapy causes early changes in global longitudinal and circumferential strain not seen with clofarabine therapy. These findings demonstrate subclinical left ventricular dysfunction after exposure to low cumulative doses of anthracycline-based induction chemotherapy and may help us better identify those patients at risk for adverse long-term cardiovascular outcomes.

Immunosuppression and adult heart transplantation: emerging therapies and opportunities.

INTRODUCTION: Immunosuppression following heart transplantation has improved graft longevity through the reduction of cellular and antibody mediated rejection. The attempt to limit the unintended consequences of immunosuppressive therapies and address sensitized patients has led to a revolution in immunosuppression. Areas covered: This review will focus on the current emerging immunosuppressive therapies in heart transplantation while reviewing the effective contemporary treatments, and explore the potential development of new immunomodulatory therapies. An exhaustive review of the PubMed database and abstract data from national meetings was performed to compile the data for the manuscript. Expert commentary: The timing and targets of immunosuppressive therapies are evolving to provide adjunctive therapies to the established treatments. Recent advances will allow for further tailoring of immunomodulatory therapies to the individual patient.

Left Atrial and Left Atrial Appendage 4D Blood Flow Dynamics in Atrial Fibrillation.

BACKGROUND: Atrial 4D flow magnetic resonance imaging was used for the characterization of left atrial (LA) and left atrial appendage (LAA) flow dynamics in patients with atrial fibrillation (AF). METHODS AND RESULTS: 4D flow magnetic resonance imaging measured in vivo 3D blood flow velocities in 60 AF patients and 15 controls. Anatomic maps of LA and LAA stasis and velocity were calculated to quantify atrial peak velocity, mean velocity, and stasis (velocities <0.1 m/s). In a substudy with 30 AF patients, 4D flow metrics were compared with Doppler transesophageal echocardiography. For all 15 controls, LAA mean and peak velocities were consistently lower (by 21%/12%; P<0.001) while LAA stasis was higher (by 58%; P<0.001) compared with the LA. In contrast, lower LAA velocity and increased LAA stasis were only found in a fraction (38 of 60) of AF patients. In AF patients, increased CHA2DS2-VASc score was associated with significantly (P<0.043) reduced LA velocities and elevated stasis. There was a heterogeneous expression of atrial flow dynamics, and 25% to 68% of AF patients demonstrated flow in the normal range: 25%/68% for LA/LAA stasis and 38%/60% for LA/LAA peak velocities. Transesophageal echocardiography velocities modestly but significantly (P<0.05) correlated with 4D flow-based LA velocities (r=0.41) and stasis (r=-0.39). CONCLUSIONS: AF resulted in overall impaired but individually variable flow dynamics in both the LA and LAA. AF patients demonstrated atrial flow in the normal range, despite elevated CHA2DS2-VASc score.

Effects of septal myectomy on left ventricular diastolic function and left atrial volume in patients with hypertrophic cardiomyopathy.

Ventricular septal myectomy in patients with obstructive hypertrophic cardiomyopathy (HC) has been shown to reduce left ventricular (LV) outflow tract (LVOT) gradient and improve symptoms, although little data exist regarding changes in left atrial (LA) volume and LV diastolic function after myectomy. We investigated changes in LA size and LV diastolic function in patients with HC after septal myectomy from 2004 to 2011. We studied 25 patients (age 49.2 ± 13.1 years, 48% women) followed for a mean of 527 days after surgery who had serial echocardiography at baseline and at most recent follow-up, at least 6 months after myectomy. In addition to myectomy, 3 patients (12%) underwent Maze surgery and 13 (52%) underwent mitral valve surgery, of whom 5 had a mitral valve replacement or mitral annuloplasty. Patients with mitral valve replacement or mitral annuloplasty were excluded from LV diastolic function analysis. LA volume index decreased (from 47.2 ± 17.6 to 35.9 ± 17.0 ml/m(2), p = 0.001) and LV diastolic function improved with an increase in lateral e' velocity (from 7.3 ± 2.9 to 9.8 ± 3.1 cm/sec, p = 0.01) and a decrease in E/e' (from 14.8 ± 6.3 to 11.7 ± 5.5, p = 0.051). Ventricular septal thickness and LVOT gradient decreased, and symptoms of dyspnea and heart failure improved, with reduction in the New York Heart Association functional class III/IV symptoms from 21 (84%) to 1 (4%). In conclusion, relief of LVOT obstruction in HC by septal myectomy results in improved LV diastolic function and reduction in LA volume with improved symptoms.

The impact of facecards on patients' knowledge, satisfaction, trust, and agreement with hospital physicians: a pilot study.

BACKGROUND: Simple interventions such as facecards can improve patients' knowledge of names and roles of hospital physicians, but the effect on other aspects of the patient-physician relationship is not clear. OBJECTIVE: To pilot an intervention to improve familiarity with physicians and assess its potential to improve patients' satisfaction, trust, and agreement with physicians. DESIGN: Cluster randomized controlled trial assessing the impact of physician facecards. Physician facecards included pictures of physicians and descriptions of their roles. We performed structured interviews of randomly selected patients to assess outcomes. SETTING: One of 2 similar hospitalist units and 1 of 2 teaching-service units in a large teaching hospital were randomly selected to implement the intervention. MEASUREMENTS: Satisfaction with physician communication and overall hospital care was assessed using the Hospital Consumer Assessment of Healthcare Providers and Systems. Trust and agreement were each assessed through instruments used in prior research. RESULTS: Overall, 138 patients completed interviews, with no differences in age, sex, or race between those receiving facecards and those not. More patients who received facecards correctly identified ≥1 hospital physician (89.1% vs 51.1%; P < 0.01) and their role (67.4% vs 16.3%; P < 0.01) than patients who had not received facecards. Patients had high baseline levels of satisfaction, trust, and agreement with hospital physicians, and we found no significant differences with the use of facecards. CONCLUSIONS: Physician facecards improved patients' knowledge of the names and roles of hospital physicians. Larger studies are needed to assess the impact on satisfaction, trust, and agreement with physicians.

Retention of critical care skills after simulation-based mastery learning.

BACKGROUND: Whether cognitive and patient care skills attained during simulation-based mastery learning (SBML) are retained is largely unknown. OBJECTIVE: We studied retention of intensive care unit (ICU) clinical skills after an SBML boot camp experience. METHODS: Forty-seven postgraduate year (PGY)-1 residents completed SBML intervention designed to increase procedural, communication, and patient care skills. The intervention included ICU skills such as ventilator and hemodynamic parameter management. Residents were required to meet or exceed a minimum passing score (MPS) on a clinical skills examination before starting actual patient care. Skill retention was assessed in 42 residents who rotated in the medical ICU. Residents received a standardized 15-minute booster teaching session reviewing key concepts during the first week of the rotation. During the fourth week of their rotation, PGY-1 residents completed a clinical skills examination at the bedside of an actual ICU patient. Group mean examination scores and the proportion of subjects who met or exceeded the MPS at each testing occasion were compared. RESULTS: Residents scored a mean 90% (SD  =  6.5%) on the simulated skills examination immediately after training. Residents retained skills obtained through SBML as the mean score at bedside follow-up testing was 89% (SD  =  8.9%, P  =  .36). Thirty-seven of 42 (88%) PGY-1 residents met or exceeded the MPS at follow-up. CONCLUSION: SBML leads to substantial retention of critical care knowledge, and patient care skills PGY-1 boot camp is a highly efficient and effective model that can be administered at the beginning of the academic year.

Conserved properties of HP1(Hsalpha).

Heterochromatin protein 1 Hsalpha (HP1(Hsalpha)) is one of three human proteins that share sequence similarity with Drosophila HP1. HP1 proteins are enriched at centric heterochromatin and play a role in chromatin packaging and gene regulation. In humans, HP1(Hsalpha) is down-regulated in highly invasive/metastatic breast cancer cells, compared to poorly invasive/non-metastatic breast cancer cells. To gain insight into this differential regulation, we have cloned the HP1(Hsalpha) gene and characterized its genomic region. HP1(Hsalpha) is located on human chromosome 12q13.13, 589 bp upstream of the divergently transcribed hnRNPA1 gene. Analysis of the promoter region revealed that differential regulation of HP1(Hsalpha) between the two types of breast cancer cells is lost upon mutation of an USF/c-myc transcription factor binding site located 172 bp upstream of the predicted HP1(Hsalpha) transcription start site. These findings provide insights into the down-regulation of HP1(Hsalpha) in highly invasive/metastatic breast cancer cells. To examine the functional properties of HP1(Hsalpha), experiments were performed using Drosophila melanogaster as a genetic system. When human HP1(Hsalpha) was expressed in transgenic Drosophila, silencing of reporter genes inserted at centric and telomeric locations was enhanced. Furthermore, expression of HP1(Hsalpha) rescued the lethality of homozygous Su(var)2-5 mutants lacking HP1. Taken together, these results demonstrate the participation of HP1(Hsalpha) in silent chromatin formation and that HP1(Hsalpha) is a functional homologue of Drosophila HP1.