Ultrasound molecular imaging of atherosclerosis

Recent advances in our understanding of the pathophysiological mechanisms of atherosclerosis have created the need for better non-invasive imaging of vascular phenotype. Ultrasound is widely available, inexpensive, and well suited for high-throughput screening in populations that are at risk for atherosclerosis. Novel ultrasonic approaches for the diagnosis of vascular changes in atherosclerosis include (1) assessment of plaque composition by evaluation of the backscattering properties of tissue, (2) assessment of the changes in arterial wall biomechanics, (3) assessment of plaque neovascularization, and (4) molecular imaging of vascular phenotype changes on a subcellular level. It is thought that such new imaging methodologies will lead to earlier detection of atherosclerosis, and better assessment of the risk for aggressive disease progression. Novel therapies for atherosclerosis will undoubtedly become available within the next decades, and non-invasive imaging techniques will be needed for cost-efficient application of existing and new drug

Non-invasive nuclear myocardial perfusion imaging improves the diagnostic yield of invasive coronary angiography

Aims Several studies reported on the moderate diagnostic yield of elective invasive coronary angiography (ICA) regarding the presence of coronary artery disease (CAD), but limited data are available on how prior testing for ischaemia may contribute to improve the diagnostic yield in an every-day clinical setting. This study aimed to assess the value and use of cardiac myocardial perfusion single photon emission computed tomography (MPS) in patient selection prior to elective ICA. Methods and results The rate of MPS within 90 days prior to elective ICA was assessed and the non-invasive test results were correlated with the presence of obstructive CAD on ICA (defined as stenosis of ≥50% of a major epicardial coronary vessel). Multivariate logistic regression analysis was performed to identify predictors of obstructive CAD. A total of 7530 consecutive patients were included. At catheterization, 3819 (50.7%) were diagnosed as having obstructive CAD. Patients with a positive result on MPS (performed in 23.5% of patients) were significantly more likely to have obstructive CAD as assessed by ICA than those who did not undergo non-invasive testing (74.4 vs. 45.6%, P < 0.001). Furthermore, a pathological MPS result was a strong, independent predictor for CAD findings among traditional risk factors and symptoms. Conclusion In an every-day clinical setting, the use of MPS substantially increases the diagnostic yield of elective ICA and provides incremental value over clinical risk factors and symptoms in predicting obstructive CAD, thus emphasizing its importance in the decision-making process leading to the use of diagnostic catheterizatio

Isolated double-orifice mitral valve: a case report

BACKGROUND: Double-orifice mitral valve is an extremely rare cardiac anomaly possibly originating from insufficient endocardial fusion in embryogenesis. Severe concomitant cardiac anomalies and malfunction of the valve usually lead to an early diagnosis in childhood. Therefore the prevalence of isolated double-orifice mitral valve in adulthood is not known. CASE PRESENTATION: We present the case of a 63 years old, female Caucasian patient with isolated double-orifice mitral valve diagnosed in routine echocardiographic evaluation after chemotherapy presenting without clinical symptoms. CONCLUSION: Trans-thoracic echocardiography is a suitable modality to diagnose and further assess anatomical and functional properties of the anomaly. In the presence of double-orifice mitral valve concomitant cardiac anomalies and valvular stenosis or regurgitation must be excluded. If an isolated double-orifice mitral valve with no functional abnormalities is present, no further follow-up is necessary

Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy

Mammalian target of rapamycin (mTOR), a central regulator of growth and metabolism, has tissue-specific functions depending on whether it is part of mTOR complex 1 (mTORC1) or mTORC2. We have previously shown that mTORC1 is required for adaptive cardiac hypertrophy and maintenance of function under basal and pressure-overload conditions. In the present study, we aimed to identify functions of mTORC2 in the heart.; Using tamoxifen-inducible cardiomyocyte-specific gene deletion, we generated mice deficient for cardiac rapamycin-insensitive companion of mTOR (rictor), an essential and specific component of mTORC2. Under basal conditions, rictor deficiency did not affect cardiac growth and function in young mice and also had no effects in adult mice. However, transverse aortic constriction caused dysfunction in the rictor-deficient hearts, whereas function was maintained in controls after 1 week of pressure overload. Adaptive increases in cardiac weight and cardiomyocyte cross-sectional area, fibrosis, and hypertrophic and metabolic gene expression were not different between the rictor-deficient and control mice. In control mice, maintained function was associated with increased protein levels of rictor, protein kinase C (PKC)βII, and PKCδ, whereas rictor ablation abolished these increases. Rictor deletion also significantly decreased PKCε at baseline and after pressure overload. Our data suggest that reduced PKCε and the inability to increase PKCβII and PKCδ abundance are, in accordance with their known function, responsible for decreased contractile performance of the rictor-deficient hearts.; Our study demonstrates that mTORC2 is implicated in maintaining contractile function of the pressure-overloaded male mouse heart

Renal dysfunction and outcome in left ventricular non-compaction

Background: While renal function has been observed to inversely correlate with clinical outcome in other cardiomyopathies, its prognostic significance in patients with left ventricular non-compaction cardiomyopathy (LVNC) has not been investigated. The aim of this study was to determine the prognostic value of renal function in LVNC patients. Methods: Patients with isolated LVNC as diagnosed by echocardiography and/or magnetic resonance imaging in 4 Swiss centers were retrospectively analyzed for this study. Values for creatinine, urea, and estimated glomerular filtration rate (eGFR) as assessed by the CKD-EPI 2009 formula were collected and analyzed by a Cox regression model for the occurrence of a composite endpoint (death or heart transplantation). Results: During the median observation period of 7.4 years 23 patients reached the endpoint. The age- and gender-corrected hazard ratios (HR) for death or heart transplantation were: 1.9 (95% confidence interval [CI] 1.4–2.6) for each increase over baseline creatinine level of 30 µmol/L (p &lt; 0.001), 1.6 (95% CI 1.2–2.2) for each increase over baseline urea level of 5 mmol/L (p = 0.004), and 3.6 (95% CI 1.9–6.9) for each decrease below baseline eGFR level of 30 mL/min (p ≤ 0.001). The HR (log2) for every doubling of creatinine was 7.7 (95% CI 3–19.8; p &lt; 0.001), for every doubling of urea 2.5 (95% CI 1.5–4.3; p &lt; 0.001), and for every bisection of eGFR 5.3 (95% CI 2.4–11.6; p &lt; 0.001). Conclusions: This study provides evidence that in patients with LVNC impairment in renal function is associated with an increased risk of death and heart transplantation suggesting that kidney function assessment should be standard in risk assessment of LVNC patients

Cardiovascular imaging following perioperative myocardial infarction/injury

Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532

Interpreting breast international group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer

The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments

Ultrasound molecular imaging of atherosclerosis

Recent advances in our understanding of the pathophysiological mechanisms of atherosclerosis have created the need for better non-invasive imaging of vascular phenotype. Ultrasound is widely available, inexpensive, and well suited for high-throughput screening in populations that are at risk for atherosclerosis. Novel ultrasonic approaches for the diagnosis of vascular changes in atherosclerosis include (1) assessment of plaque composition by evaluation of the backscattering properties of tissue, (2) assessment of the changes in arterial wall biomechanics, (3) assessment of plaque neovascularization, and (4) molecular imaging of vascular phenotype changes on a subcellular level. It is thought that such new imaging methodologies will lead to earlier detection of atherosclerosis, and better assessment of the risk for aggressive disease progression. Novel therapies for atherosclerosis will undoubtedly become available within the next decades, and non-invasive imaging techniques will be needed for cost-efficient application of existing and new drugs