Pluripotent Stem Cell-Based Platforms in Cardiac Disease Modeling and Drug Testing.

The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing.

Online myocardial viability assessment in the catheterization laboratory via NOGA electroanatomic mapping: Quantitative comparison with thallium-201 uptake.

BACKGROUND: The aim of this prospective study was to investigate the concordance between quantitative resting (201)Tl uptake as an established myocardial viability index and the electrical activity of the heart, determined by NOGA nonfluoroscopic electroanatomic mapping. METHODS AND RESULTS: The myocardial resting and late resting thallium uptakes of 384 myocardial segments from 32 patients (27 males aged 65+/-8 years) with previous myocardial infarction and chronic stable angina were compared with unipolar voltage potentials and local shortening of the left ventricle as assessed by electroanatomic mapping. The quantitative thallium uptake data were analyzed by polar map analysis by division into 12 comparable myocardial segments, as represented in electroanatomic mapping images. Unipolar voltage potentials exhibited a significant logarithmic correlation with both resting and late resting thallium uptake (attenuation corrected: r=0.660 and r=0.744; non-attenuation corrected: r=0.623 and r=0.721). Receiver operator characteristic analyses revealed unipolar voltage cutoff points of 12.0 mV (predictive accuracy 0.853, P< 0.001; sensitivity/specificity 81%) for normal myocardium and 6.4 mV (predictive accuracy 0.901, P< 0.001; sensitivity/specificity 82%) for nonviable myocardium assessed by attenuation-corrected (201)Tl late resting images and of 12.7 mV (predictive accuracy 0.822, P<0.001; sensitivity/specificity 75%) and 6.5 mV (predictive accuracy 0.808, P<0.001; sensitivity/specificity 73%) for non-attenuation-corrected late resting (201)Tl images. CONCLUSIONS: These results indicate that the unipolar voltage potentials obtained by electroanatomic mapping correlate well with standard quantitative late resting (201)Tl imaging for the evaluation of myocardial viability; thus, NOGA endocardial mapping provides useful "online" data at the time of catheterization, especially when information from other methods for viability assessment is unavailable.

Detailed endocardial mapping accurately predicts the transmural extent of myocardial infarction.

OBJECTIVES: This study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping. BACKGROUND: The degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue. METHODS: Electromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data. RESULTS: From the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 +/- 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7 mV, 0.8 +/- 0.4 mV in the three groups respectively, p < 0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (<30%) and second transmurality subgroups. CONCLUSIONS: The degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.