Variant Coronary Arterial Collateral Ring.

A 74-year-old man presented with symptoms and noninvasive diagnostic studies suggestive of myocardial infarction. Coronary angiography revealed total occlusion of the distal right coronary artery with a unique accessory coronary ring that provided retrograde collateral flow to the left ventricle, demonstrating the importance of considering non-native vessels when identifying target lesions.

Hysteretic device characteristics indicate cardiac contractile state for guiding mechanical circulatory support device use.

BACKGROUND: Acute heart failure and cardiogenic shock remain highly morbid conditions despite prompt medical therapy in critical care settings. Mechanical circulatory support (MCS) is a promising therapy for these patients, yet remains managed with open-loop control. Continuous measure of cardiac function would support and optimize MCS deployment and weaning. The nature of indwelling MCS provides a platform for attaining this information. This study investigates how hysteresis modeling derived from MCS device signals can be used to assess contractility changes to provide continuous indication of changing cardiac state. Load-dependent MCS devices vary their operation with cardiac state to yield a device-heart hysteretic interaction. Predicting and examining this hysteric relation provides insight into cardiac state and can be separated by cardiac cycle phases. Here, we demonstrate this by predicting hysteresis and using the systolic portion of the hysteresis loop to estimate changes in native contractility. This study quantified this measurement as the enclosed area of the systolic portion of the hysteresis loop and correlated it with other widely accepted contractility metrics in animal studies (n = 4) using acute interventions that alter inotropy, including a heart failure model. Clinical validation was performed in patients (n = 8) undergoing Impella support. RESULTS: Hysteresis is well estimated from device signals alone (r = 0.92, limits of agreement: - 0.18 to 0.18). Quantified systolic area was well correlated in animal studies with end-systolic pressure-volume relationship (r = 0.84), preload recruitable stroke work index (r = 0.77), and maximum slope of left ventricular pressure (dP/dtmax) (r = 0.95) across a range of inotropic conditions. Comparable results were seen in patients with dP/dtmax (r = 0.88). Diagnostic capability from ROC analysis yielded AUC measurements of 0.92 and 0.90 in animal and patients, respectively. CONCLUSIONS: Mechanical circulatory support hysteretic behavior can be well modeled using device signals and used to estimate contractility changes. Contractility estimate is correlated with other accepted metrics, captures temporal trends that elucidate changing cardiac state, and is able to accurately indicate changes in inotropy. Inherently available during MCS deployment, this measure will guide titration and inform need for further intervention.

A Scalable Approach to Determine Intracardiac Pressure From Mechanical Circulatory Support Device Signals.

OBJECTIVE: Effective mechanical circulatory support (MCS) relies on cardiac function measures to guide titration. Left ventricular end diastolic pressure (LVEDP) is a useful measure that is indirectly estimated using pulmonary artery catheters (PACs). PACs require additional intervention and provide intermittent and unreliable estimations. MCS device signals can estimate LVEDP but are prone to inter-device variability and require rigorous specialized characterization. We present a scalable and implementable approach to calculate LVEDP continuously using device signals. METHODS: LVEDP was calculated from MCS device measured aortic pressure and motor current, which approximates the pressure head between the aorta and left ventricle. This motor current-pressure head relationship is device-specific but approximated using existing flow calibration and assumed physiologic relationships. Performance was evaluated with comparison from direct measurement of LVEDP in a series of acute animal models. RESULTS: LVEDP measures (n = 178,279) from 18 animals had good correlation (r = 0.84) and calibration (Bland-Altman limits of agreement -7.77 to 7.63 mmHg; mean bias -0.07 ± 0.02 mmHg). The total mean error prediction interval was -3.42 to 3.32 mmHg and RMS error was 3.85 mmHg. CONCLUSION: LVEDP can be continuously calculated using device signals without specialized characterization. Calculated LVEDP values improved upon PAC estimations and were found using a scalable and manufacturer-accessible method. SIGNIFICANCE: This method improves upon existing LVEDP measures without the need for rigorous characterization, external calibration, or additional intervention; this allows widescale deployment of continuous LVEDP measurement for patients on MCS and demonstrates key considerations necessary to translate research-grade technologies.

Dynamic Modulation of Device-Arterial Coupling to Determine Cardiac Output and Vascular Resistance.

Clinical adoption of mechanical circulatory support for shock is rapidly expanding. Achieving optimal therapeutic benefit requires metrics of state to guide titration and weaning of support. Using the transvalvular positioning of a percutaneous ventricular assist device (pVAD), device:heart interactions are leveraged to determine cardiac output (CO) and systemic vascular resistance (SVR) near-continuously without disrupting therapeutic function. An automated algorithm rapidly alternates between device support levels to dynamically modulate physiological response. Employing a two-element lumped parameter model of the vasculature, SVR and CO are quantified directly from measurements obtained by the pVAD without external calibration or invasive catheters. The approach was validated in an acute porcine model across a range of cardiac (CO = 3-10.6 L/min) and vascular (SVR = 501-1897 dyn s/cm5) states. Cardiac output calculations closely correlated (r = 0.82) to measurements obtained by the pulmonary artery catheter-based thermodilution method with a mean bias of 0.109 L/min and limits of agreement from - 1.67 to 1.89 L/min. SVR was also closely correlated (r = 0.86) to traditional catheter-based measurements with a mean bias of 62.1 dyn s/cm5 and limits of agreement from - 260 to 384 dyn s/cm5. Use of diagnostics integrated into therapeutic device function enables the potential for optimizing support to improve outcomes for cardiogenic shock.

Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock.

BACKGROUND: Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). OBJECTIVE: To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. METHODS: CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 µg/kg/min), epinephrine (0.10 µg/kg/min), or dopamine (10 µg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 µg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. RESULTS: All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002). CONCLUSION: Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.

Dual Carbon Dioxide Capture to Achieve Highly Efficient Ultra-Low Blood Flow Extracorporeal Carbon Dioxide Removal.

Extracorporeal CO2 removal is a highly promising support therapy for patients with hypercapnic respiratory failure but whose clinical implementation and patient benefit is hampered by high cost and highly specialized expertise required for safe use. Current approaches target removal of the gaseous CO2 dissolved in blood which limits their ease of clinical use as high blood flow rates are required to achieve physiologically significant CO2 clearance. Here, a novel hybrid approach in which a zero-bicarbonate dialysis is used to target removal of bicarbonate ion coupled to a gas exchange device to clear dissolved CO2, achieves highly efficiently total CO2 capture while maintaining systemic acid-base balance. In a porcine model of acute hypercapnic respiratory failure, a CO2-reduction of 61.4 ± 14.4 mL/min was achieved at a blood flow rate of 248 mL/min using pediatric-scale priming volumes. The dialyzer accounted for 81% of total CO2 capture with an efficiency of 33% with a minimal pH change across the entire circuit. This study demonstrates the feasibility of a novel hybrid CO2 capture approach capable of achieving physiologically significant CO2 removal at ultralow blood flow rates with low priming volumes while leveraging widely available dialysis platforms to enable clinical adoption.

Leveraging Device-Arterial Coupling to Determine Cardiac and Vascular State.

OBJECTIVE: Limitations in available diagnostic metrics restrict the efficacy of managing therapies for cardiogenic shock. In current clinical practice, cardiovascular state is inferred through measurement of pulmonary capillary wedge pressure and reliance on linear approximations between pressure and flow to estimate peripheral vascular resistance. Mechanical circulatory support devices residing within the left ventricle and aorta provide an opportunity for both determining cardiac and vascular state and offering therapeutic benefit. We leverage the controllable mode of operation and transvalvular position of an indwelling percutaneous ventricular assist device to assess vascular and, in turn, cardiac state through the effects of device-arterial coupling across different levels of device support. METHODS: Vascular state is determined by measuring changes in the pressure waveforms induced through intentional variation in the device generated blood flow. We evaluate this impact by applying a lumped parameter model to quantify state-specific vascular resistance and compliance and calculate beat-to-beat stroke volume and cardiac output in both animal models and retrospective patient data without external calibration. RESULTS: Vascular state was accurately predicted in patients and animals in both baseline and experimental conditions. In the animal, stroke volume was predicted within a total root mean square error of 3.71 mL (n = 482). CONCLUSION: We demonstrate that device-arterial coupling is a powerful tool for evaluating patient and state specific parameters of cardiovascular function. SIGNIFICANCE: These insights may yield improved clinical care and support the development of next generation mechanical circulatory support devices that determine and operate in tandem with the supported organ.

Mechanical circulatory support device-heart hysteretic interaction can predict left ventricular end diastolic pressure.

The full potential of mechanical circulatory systems in the treatment of cardiogenic shock is impeded by the lack of accurate measures of cardiac function to guide clinicians in determining when to initiate and how to optimally titrate support. The left ventricular end diastolic pressure (LVEDP) is an established metric of cardiac function that refers to the pressure in the left ventricle at the end of ventricular filling and immediately before ventricular contraction. In clinical practice, LVEDP is typically only inferred from, and poorly correlates with, the pulmonary capillary wedge pressure (PCWP). We leveraged the position of an indwelling percutaneous ventricular assist device and advanced data analysis methods to obtain LVEDP from the hysteretic operating metrics of the device. We validated our hysteresis-derived LVEDP measurement using mock flow loops, an animal model of cardiac dysfunction, and data from a patient in cardiogenic shock to show greater measurement precision and correlation with actual pressures than traditional inferences via PCWP. Delineation of the nonlinear relationship between device and heart adds insight into the interaction between ventricular support devices and the native heart, paving the way for continuous assessment of underlying cardiac state, metrics of cardiac function, potential closed-loop automated control, and rational design of future innovations in mechanical circulatory support systems.