Noninvasive Imaging for the Asymptomatic Patient: How to Use Imaging to Guide Treatment Goals?

Imaging subclinical atherosclerosis identifies individuals at higher risk of cardiovascular disease through direct visualization before events occur so that preventative measures can be taken. Coronary artery calcium (CAC) scans are the most widely used and studied to identify subclinical atherosclerosis and are most useful in men older than 40 years and women older than 50 years. Coronary computed tomography angiography has high prognostic value and might be the best modality for assessing subclinical atherosclerosis with incremental increase in predictive value over CAC. Ankle-brachial indexes are specific markers for cardiovascular risk but are a less sensitive tool for risk assessment.

Targeting Natriuretic Peptide Levels in Heart Failure with Therapy: Does "X" Really Mark the Spot?

PURPOSE OF REVIEW: Explore controversial biomarker-guided management of patients with heart failure (HF) with reduced ejection fraction. RECENT FINDINGS: Natriuretic peptides (e.g., BNP, NT-proBNP) are elevated in HF as a result of end-diastolic stress and are used in the diagnosis and prognosis of heart failure. Natriuretic peptide levels decrease with guideline-directed medical therapy (GDMT). Multiple small studies examined whether the use of biomarker-guided therapy would be beneficial to guide HF care and potentially improve outcomes. Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT), the largest randomized control study seeking to answer that question, did not find biomarker guided therapy to be more effective than usual care in improving the primary endpoints of HF hospitalization or cardiovascular mortality in HF patients. Natriuretic peptides are important for diagnosis and prognosis in HF. GUIDE-IT showed that patients with HF and reduced ejection did not benefit from biomarker-guided strategy in terms of clinical outcomes. Future studies could focus on additional routine clinical care settings and take into account other HF phenotypes including preserved ejection fraction.

Imaging of mitochondrial and non-mitochondrial responses in cultured rat hippocampal neurons exposed to micromolar concentrations of TMRM.

Tetramethylrhodamine methyl ester (TMRM) is a fluorescent dye used to study mitochondrial function in living cells. Previously, we reported that TMRM effectively labeled mitochondria of neurons deep within mouse brain slices. Use of micromolar concentration of dye, which was required to get sufficient staining for two-photon imaging, resulted in typical fluctuations of TMRM. With prolonged exposure, we recorded additional responses in some neurons that included slow oscillations and propagating waves of fluorescence. (Note: We use the terms "fluctuation" to refer to a change in the fluorescent state of an individual mitochondrion, "oscillation" to refer to a localized change in fluorescence in the cytosol, and "wave" to refer to a change in cytosolic fluorescence that propagated within a cell. Use of these terms does not imply any underlying periodicity.) In this report we describe similar results using cultured rat hippocampal neurons. Prolonged exposure of cultures to 2.5 µM TMRM produced a spontaneous increase in fluorescence in some neurons, but not glial cells, after 45-60 minutes that was followed by slow oscillations, waves, and eventually apoptosis. Spontaneous increases in fluorescence were insensitive to high concentrations of FCCP (100 µM) and thapsigargin (10 µM) indicating that they originated, at least in part, from regions outside of mitochondria. The oscillations did not correlate with changes in intracellular Ca(2+), but did correlate with differences in fluorescence lifetime of the dye. Fluorescence lifetime and one-photon ratiometric imaging of TMRM suggested that the spontaneous increase and subsequent oscillations were due to movement of dye between quenched (hydrophobic) and unquenched (hydrophilic) compartments. We propose that these movements may be correlates of intracellular events involved in early stages of apoptosis.