Invasive Right Ventricular Pressure-Volume Analysis: Basic Principles, Clinical Applications, and Practical Recommendations

Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.

Measuring the systolic and the diastolic properties of single human pluripotent stem-cell cardiomyocyte for drug testing and disease modeling

Background The advent of human pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) provided exciting tools for cardiovascular physiological studies, disease modeling and drug testing applications. Current platforms for studying the mechanical properties of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as single-cells do not measure forces directly, require numerous assumptions, and cannot study cell mechanics at different loading conditions. Objective To establish a novel platform to assess the active and passive mechanical properties of single-cell hPSC-CMs at different loading conditions and to demonstrate the potential of this approach for drug testing and disease modeling applications. Methods and results To allow morphological maturation, hPSC-CMs were treated with Tri-iodo-thyronine hormone, dexamethasone and Insulin-like growth factor-1. The hPSC-CM were then lifted and attached to a highly sensitive optical-force transducer and a piezoelectric length controller and electrically-stimulated. The attached hPSC-CM remained intact and contractile allowing evaluation of their passive and active mechanical properties. Utilizing this technique, single-cell hPSC-CMs exhibited positive length-tension (Frank-Starling) relationships, and appropriate inotropic, klinotropic, and lusitropic changes in response to treatment with isoproterenol. The unique potential of the approach for drug testing and disease modeling was exemplified by treating the cells with doxorubicin (a potential cardiotoxic anti-cancer agent) and omecamtiv mecarbil (a positive ionotropic drug currently in stage 3 clinical trial). The results of these studies recapitulated the drugs' known actions to suppress (doxorubicin) and augment (omecamtiv mecarbil at low dose) cardiomyocyte contractility. Finally, novel insights were gained regarding the cellular effects of these drugs as doxorubicin treatment led to cellular mechanical alternans and high doses of omecamtiv mecarbil suppressed contractility and worsened the cellular diastolic properties. Conclusion A novel method that allows direct active and passive force measurements from single hPSC-CMs at different loading conditions for the first time was established and validated. Our results highlight the potential implications of this novel approach for pharmacological studies and disease modeling studies. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Research Council

Conduction Abnormalities after Transcatheter Aortic Valve Implantation and Diastolic Dysfunction

Objectives: Transcatheter aortic valve implantation (TAVI) is frequently associated with the development of conduction abnormalities. We assessed the effect of conduction abnormalities on diastolic function following TAVI. Methods: In total, 101 consecutive post-TAVI patients were included, each with echocardiographic follow-up at 1 and 6 months. Diastolic properties were correlated with the occurrence of a long PR interval and wide QRS, and their change from baseline. The measured diastolic parameters included E/A ratio, E wave deceleration time, E wave to e′ ratio, left atrial (LA) volume, and systolic pulmonary artery pressure (SPAP). The clinical outcome was all-cause mortality. Results: Overall, TAVI was associated with a consistent decrease in SPAP at the 1- and 6-month follow-up. LA volumes were increased at 1 month post-TAVI in patients with a wide compared to normal QRS (p = 0.03) and at 6 months in patients with a normal compared to prolonged PR (p = 0.03). PR prolongation above 40 ms was associated with lower SPAP at the 1- but not 6-month follow-up. Survival was not influenced by conduction abnormalities. Conclusions: TAVI is associated with a reduction in SPAP. A postprocedural wide QRS and normal PR interval may unfavorably influence the left-sided filling performance, resulting in an increased LA volume. Other diastolic parameters, as well as survival, are not significantly affected by postprocedural conduction abnormalities.