Accuracy and Prognostic Value of Physiologist-Led Stress Echocardiography for Coronary Disease.

BACKGROUND: We demonstrated that physiologist-led stress echocardiography (PLSE) is feasible for coronary artery disease (CAD) assessment. We sought to extend our work by assessing its accuracy and prognostic value. METHODS: Retrospective study of 898 subjects undergoing PLSE (n=393) or cardiologist-led stress echocardiography (CLSE) (n=505) for CAD assessment using exercise or dobutamine. For accuracy assessment, the primary outcome was the ability of stress echocardiography to identify significant CAD on invasive coronary angiography (ICA). Incidence of 24-month non-fatal MI, total and cardiac mortality, revascularisation and combined major adverse cardiac events (MACE) were assessed. RESULTS: Demographics, comorbidities, CAD predictors, CAD pre-test probability and cardiac medications were matched between the PLSE and CLSE groups. PLSE had high sensitivity, specificity, positive and negative predictive value and accuracy (85%, 74%, 69%, 88%, 78% respectively). PLSE accuracy measures were similar and non-inferior to CLSE. There was a similar incidence of individual and combined outcomes in PLSE and CLSE subjects. Negative stress echocardiography conferred a comparably low incidence of non-fatal MI (PLSE 1.4% vs. CLSE 0.9%, p=0.464), cardiac mortality (0.6% vs. 0.0%, p=0.277) and MACE (6.8% vs. 3.1%, p=0.404). CONCLUSION: This is the first study of the accuracy compared with gold standard of ICA, and prognostic value of PLSE CAD assessment. PLSE demonstrates high and non-inferior accuracy compared with CLSE for CAD assessment. Negative PLSE and CLSE confer a similarly very low incidence of cardiac outcomes, confirming for the first time the important prognostic value of PLSE.

Novel genetic therapeutic approaches for modulating the severity of ß-thalassemia (Review).

Thalassemia is a genetic haematological disorder that arises due to defects in the α and ß-globin genes. Worldwide, 0.3-0.4 million children are born with haemoglobinopathies per year. Thalassemic patients, as well as their families, face various serious clinical, socio-economic, and psychosocial challenges throughout their life. Different therapies are available in clinical practice to minimize the suffering of thalassemic patients to some extent and potentially cure the disease. Predominantly, patients undergo transfusion therapy to maintain their haemoglobin levels. Due to multiple transfusions, the iron levels in their bodies are elevated. Iron overload results in damage to body organs, resulting in heart failure, liver function failure or endocrine failure, all of which are commonly observed. Certain drugs have been developed to enhance the expression of the γ-gene, which ultimately results in augmentation of fetal haemoglobin (HbF) levels and total haemoglobin levels in the body. However, its effectiveness is dependent on the genetic makeup of the individual patient. At present, allogeneic haematopoietic Stem Cell Transplantation (HSCT) is the only practically available option with a high curative rate. However, the outcome of HSCT is strongly influenced by factors such as age at transplantation, irregular iron chelation history before transplantation, histocompatibility, and source of stem cells. Gene therapy using the lentiglobin vector is the most recent method for cure without any mortality, graft rejection and clonal dominance issues. However, delayed platelet engraftment is being reported in some patients. Genome editing is a novel approach which may be used to treat patients with thalassemia; it makes use of targeted nucleases to correct the mutations in specific DNA sequences and modify the sequence to the normal wild-type sequence. To edit the genome at the required sites, CRISPR/Cas9 is an efficient and accurate tool that is used in various genetic engineering programs. Genome editing mediated by CRISPR/Cas9 has the ability to restore the normal ß-globin function with minimal side effects. Using CRISPR/Cas9, expression of BCL11A can be downregulated along with increased production of HbF. However, these genome editing tools are still under in-vitro trials. CRISPR/Cas9 has can be used for precise transcriptional regulation, genome modification and epigenetic editing. Additional research is required in this regard, as CRISPR/Cas9 may potentially exhibit off-target activity and there are legal and ethical considerations regarding its use.

Early Readmissions After Acute Myocardial Infarction.

This study aims to evaluate the rate, predictors, and causes of 30-day readmissions in a single tertiary hospital in the United Kingdom. We conducted a retrospective study of all patients admitted between 2012 and 2014 with a diagnosis of acute myocardial infarction, who were in the Myocardial Infarction National Audit Project register. Data on patient demographics, comorbidities, care received, and in-hospital mortality were collected. Rates of 30-day readmission and causes of readmission were evaluated. Univariate and multiple logistic regressions were used to identify predictors of all-cause, cardiac, and noncardiac readmission. A total of 1,869 patients were included in the analysis and 171 had an unplanned readmission with 30 days (9%). Noncardiac problems represented half of all readmissions with the dominant cause noncardiac chest pain (50%). A variety of other noncardiac causes for readmission were identified and the most common were lower respiratory tract infection (4.3%), gastrointestinal problems (4.9%), bleeding (3.7%), dizziness, syncope, or fall (3.0%), and pulmonary embolus (2.4%). For cardiac causes of readmissions, common causes included acute coronary syndrome (17.1%), stable angina (11.6%), and heart failure (9.8%). Readmitted patients were more likely to be older, anemic, and less likely to receive coronary angiogram and percutaneous coronary intervention. After adjustment, the only predictor of all-cause readmission was older age. For noncardiac readmission, previous myocardial infarction was associated with significantly fewer readmissions. Our results suggest that early readmission after discharge with diagnosis of acute myocardial infarction is common. Chest pain is the most frequent cause of readmission, and interventions to reduce noncardiac chest pain admissions are needed.

Feasibility of physiologist-led stress echocardiography for the assessment of coronary artery disease.

BACKGROUND: Physiologist-led stress echocardiography (PLSE) services provide potential for expansion of SE services and increased productivity for cardiologists. There are however no published data on the feasibility of PLSE. We sought to assess the feasibility, safety and robustness of PLSE and cardiologist-led stress echocardiography (CLSE) for coronary artery disease (CAD) assessment. METHODS: Retrospective analysis of 898 patients undergoing PLSE or CLSE for CAD assessment using exercise or dobutamine stress over 24 months. PLSE involved 2 cardiac physiologists (exercise) or 1 physiologist plus 1 cardiac nurse (dobutamine). A cardiology registrar was present in the echocardiography department during PLSE in case of medical complications. CLSE involved 1 physiologist and 1 trainee cardiologist who analysed the study and reviewed findings with an imaging cardiologist. Sixteen-segment wall motion scoring (WMS, WMSI) analysis was performed. Feasibility (stressor, image quality, proportion of completed studies, agreement with imaging cardiologist analysis) and safety (complication rate) were compared for PLSE and CLSE. RESULTS: The majority of studies were CLSE (56.2%) and used dobutamine (68.7%). PLSE more commonly used exercise (69.2%). Overall, 96% of studies were successfully completed (>14 diagnostic segments in 98%, P = 0.899 PLSE vs CLSE). Commencement of PLSE was associated with an increase in annual SE's performed for CAD assessment. Complication rates were comparably very low for PLSE and CLSE (0.8% vs 1.8%, P = 0.187). There was excellent agreement between PLSE and CLSE WMS interpretation of 480 myocardial segments at rest (κ = 0.87) and stress (κ = 0.70) and WMSI (ICCs and Pearson's r >0.90, zero Bland-Altman mean bias). CONCLUSION: This to our knowledge is the first study of the feasibility of PLSE. PLSE performed by well-trained physiologists is feasible and safe in contemporary practice. PLSE and CLSE interpretation of stress echocardiography for CAD agree very closely.