Prognostic Importance of Pulmonary Artery Pulsatility Index and Right Ventricular Stroke Work Index in End-Stage Heart Failure Patients

Background: Right ventricular (RV) failure is an important cause of morbidity and mortality in patients with left ventricular (LV) end-stage heart failure (ESHF). Pulmonary artery pulsatility index (PAPi) and right ventricular stroke work index (RVSWI) are invasive parameters related to RV function. This study aimed to investigate the prognostic impact of PAPi and RVSWI in these patients. Methods and Results: In this study, 416 patients with ESHF were included. The adverse cardiac event (ACE) was defined as left ventricular assist device (LVAD) implantation, urgent heart transplantation, or cardiac mortality. There were 218 ACE cases and 198 non-ACE cases over a median follow-up of 503.50 days. Patients with ACE had lower PAPi and similar RVSWI compared to those without ACE (3.1±1.9 vs. 3.7±2.3, P=0.003 and 7.3±4.9 vs. 6.9±4.4, P=0.422, respectively). According to the results of multivariate analysis, while PAPi (from 2 to 5.65) was associated with ACE, RVSWI (from 3.62 to 9.75) was not associated with ACE (HR: 0.75, 95% CI (0.55-0.95), P=0.031; HR: 0.79, 95% CI: (0.58-1.09), P=0.081, , respectively). Survival analysis revealed that PAPi ≤2.56 was associated with a higher ACE risk compared to PAPi >2.56 (HR: 1.46, 95% CI: 1.11-1.92, P=0.006). PAPi ≤2.56 could predict ACE with 56.7% sensitivity and 51.3% specificity at one year. Furthermore, the association between RVSWI and ACE was nonlinear (J-curve pattern). Low and high values seem to be associated with higher ACE risk compared to intermediate values. Conclusion: The low PAPi was an independent risk for ACE and it had a linear association with it. However, RVSWI seems to be have a nonlinear association with ACE (J-curve pattern).

Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited

Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion.Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN.Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p < 0.001), left ventricular (LV) stroke work (7,708 ± 2,782 vs. 6,071 ± 2,660 ml mmHg, p < 0.001), and rate pressure product (7,214 ± 1,051 vs. 6,929 ± 976 mmHg bpm, p = 0.06) all fell. LV ejection fraction increased (61 ± 3 vs. 66 ± 4%, p < 0.001), with cardiac output remaining constant (6.2 ± 1.5 vs. 6.5 ± 1.4 l/min, p = 0.37). Myocardial PCr/ATP fell during GTN infusion (2.17 ± 0.2 vs. 1.99 ± 0.22, p = 0.03) with an increase in both CK kf (0.16 ± 0.07 vs. 0.25 ± 0.1 s−1, p = 0.006) and CK flux (1.8 ± 0.8 vs. 2.6 ± 1.1 μmol/g/s, p = 0.03).Conclusion: During GTN infusion, despite reduced LV stroke work and maintained cardiac output, there was a 44% increase in myocardial ATP delivery through CK. As PCr/ATP fell, this increase in ATP demand coincided with GTN-induced impairment of mitochondrial oxidative phosphorylation. Overall, this suggests that while GTN reduces cardiac work, it does so at the expense of increasing ATP demand beyond the capacity to increase ATP production.

Electro-energetics of Biventricular, Septal and Conduction System Pacing

Abnormal electrical activation of the ventricles creates abnormalities in cardiac mechanics. Local contraction patterns, as reflected by strain, are not only out of phase, but also show opposing length changes in early and late activated regions. Consequently, the efficiency of cardiac pump function (the amount of stroke work generated by a unit of oxygen consumed), is approximately 30% lower in dyssynchronous than in synchronous hearts. Maintaining good cardiac efficiency appears important for long-term outcomes. Biventricular, left ventricular septal, His bundle and left bundle branch pacing may minimise the amount of pacing-induced dyssynchrony and efficiency loss when compared to conventional right ventricular pacing. An extensive animal study indicates maintenance of mechanical synchrony and efficiency during left ventricular septal pacing and data from a few clinical studies support the idea that this is also the case for left bundle branch pacing and His bundle pacing. This review discusses electro-mechanics and mechano-energetics under the various paced conditions and provides suggestions for future research.

297 Echocardiographic biventricular coupling index to predict pre-capillary pulmonary hypertension

Aims Pulmonary hypertension (PH) affects millions of people worldwide. Right heart catheterization (RHC) is the gold standard to correctly classify the subtype of PH. Biventricular coupling index (BCI) is a new echocardiographic index defined as the ratio between non-invasive right ventricular stroke work index (RVSWI) and E/E′ ratio. Due to his comprehensive functional characterization of the right heart physiology, we hypothesized it might correctly identify pre-capillary PH. Methods and results BCI was derived in a cohort of 334 patients from the University Hospital of Trieste (Italy) and Karolinska University Hospital (Sweden) who underwent transthoracic echocardiography and RHC for all indications (<6 h between the exams). The accuracy of BCI to identify pre-capillary PH was high in the derivation cohort (AUC: 0.82, P < 0.001, CI: 0.78–0.88). Subsequently BCI was tested in a large validation cohort of 1349 patients with available transthoracic echocardiography and RHC from the Fondazione Toscana G. Monasterio of Pisa (Italy). Among patients with PH, BCI showed a high accuracy to correctly identify pre-capillary PH (AUC = 0.91, 95% CI: 0.89–0.93, P < 0.001), with an optimal cut-off of 1.9 providing a sensitivity of 82% and a specificity of 89%, PPV 77%, and a NPV 92%. BCI outperformed previous indexes, such as the D’Alto score (Z coefficient 3.56, difference between areas 0.05 95% CI: 0.02–0.07, P < 0.001) and the echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) index (Z coefficient 2.88, difference between areas 0.02 95% CI: 0.01–0.04, P < 0.004). Conclusions BCI is a new non-invasive index based on standard echocardiographic parameters that allows, with high accuracy, the identification of patients with pre-capillary PH, outperforming previously proposed indexes. Routine use of BCI index could be implemented in the screening work-up of pre-capillary PH.

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.

48 Correlation of left ventricular myocardial work indices and invasive measurement of stroke work

Aims A novel echocardiographic method allows to non-invasively assess myocardial work using pressure–strain loops. Even though left ventricular myocardial work has already emerged as a promising prognostic tool for various pathological conditions, its relationship with invasively-derived corresponding indices has not been assessed in humans yet. This study aimed to explore the correlation between left ventricular myocardial work (LVMW) indices and invasively derived left ventricular stroke work index (LVSWI) in a cohort of patients with advanced heart failure (HF) considered for heart transplantation. Methods and results All consecutive patients with advanced heart failure considered for heart transplantation from 2016 to 2021 that had already performed right heart catheterization (RHC) as part of the workup and with an available echocardiographic exam were included (n = 91). Myocardial work analysis was performed in 44 patients, according to exclusion criteria. Conventional LV functional parameters and LVMW indices, including LV global work index (LVGWI), LV global constructive work (LVGCW), LV global wasted work (LVGWW), LV global work efficiency (LVGWE), and other were calculated and compared with invasively measured LV stroke work index (LVSWI). Median age was 60 years [interquartile range (IQR): 54–63]. Median time between RHC and echocardiography was 0 months (IQR: 0–1). For the most part, etiology of HF was non-ischaemic (61.4%) and all patients were either on class NYHA II (61.4%) or III (27.3%). Median left ventricular ejection fraction was 25% (IQR: 22.3–32.3), median NT-proBNP 1377 pg/ml (IQR: 646–2570). Among conventional parameters of LV function, LVEF did not significantly correlate with LVSWI (r = 0.308; P = 0.050) whereas LV global longitudinal strain (LVGLS) did (r = −0.337; P = 0.031). With regard to LVMW indices, some of them demonstrated correlation with LVSWI, particularly LVGWI (r = 0.425; P = 0.006), LVGCW (r = 0.506; P = 0.001), LV global positive work (LVGPW; r = 0.464; P = 0.003), and LV global systolic constructive work (LVGSCW; r = 0.471; P = 0.002). Conclusions Among left ventricular myocardial work indices, LVGCW correlated better with invasively derived stroke work, thus representing a powerful and reliable tool for a more comprehensive evaluation of myocardial function.

The Cardiovascular Implications of Thoracic Endovascular Aortic Repair: how aortic stenting impacts LV function and coronary artery flow

Aortic stents are known to have harmful effects on the cardiovascular system. They augment left ventricular function by decreasing aortic compliance. How these cardiovascular parameters change during and immediately after deployment of aortic stents has not been rigorously quantified, despite the development of heart failure in as many as 40% of post-TEVAR survivors within one-year. Without a comprehensive understanding of how the cardiovascular system changes in response to aortic stenting, surgical or medical strategies to augment prevent these changes cannot be developed. The goal of this study is to evaluate alterations in cardiovascular physiology that develop during and after total aortic endografting in a swine model. We will employ left ventricular (LV) pressure-volume (PV) loop analysis, which provides comprehensive pump mechanical information about LV function including stroke work and cardiac output, coupled with direct coronary flow measurements to understand how these parameters change when an aortic stent is placed. Our hypotheses are that aortic stenting: 1) is associated with decreased aortic compliance and increased LV afterload, 2) augments the LV end systolic pressure relationship (i.e., stroke work and end systolic pressure increase) and 3) increases coronary blood flow but decreases the coronary flow/cardiac output ratio.

Non-invasive Systemic Hemodynamic Index in Vascular Risk Stratification Tailored for Hypertensives

Vascular dysfunction is a key hallmark of hypertension and related cardiovascular outcomes. As a well-known hemodynamic disease, hypertension is characterized by abnormal ventricular-vascular interactions. Complementing non-invasive systemic hemodynamics in hypertensive vascular risk assessment is of promising significance. We aimed to investigate the effects of abnormal hemodynamic states other than elevated blood pressure on vascular damage and establish a united index of systemic hemodynamics for generalized vascular risk evaluation. Non-invasive systemic hemodynamics, assessed by impedance cardiography, was compared among blood pressure stages. Vascular function was evaluated by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV). Systemic hemodynamics was obtained from a total of 88 enrollees with a mean (±SD) systolic blood pressure 140 (±17) mm Hg, and aged 17 to 91 years. Both stroke systemic vascular resistance index and left stroke work index exhibited a significant alteration among blood pressure stages (p < 0.001; p = 0.01, respectively), whereas heterogeneous hemodynamic and vascular function subsets existed within similar blood pressure. In addition, blood pressure categories failed to recognize between-group differences in endothelial dysfunction (p = 0.88) and arterial stiffness (p = 0.26). An increase in myocardial contractility and a parallel decrease in afterload was associated with the decline of vascular dysfunction. Systemic Hemodynamic Index (SHI), as a surrogate marker, demonstrated a significantly negative correlation with vascular damage index (VDI, r = −0.49, p < 0.001). These findings illustrate that systemic hemodynamics underlying hypertensives provides more vascular information. The SHI/VDI score may be a feasible tool for cardiovascular function assessment.

Abstract 9439: Invasive Evaluation of Left Ventricular Hemodynamics with Veno-Arterial Extracorporeal Membrane Oxygenation

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a frequently used hemodynamic support strategy, but considerable debate exists about its hemodynamic effects. We evaluated changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. Methods: In this case series, patients underwent evaluation due to persistent vasoplegia or poor LV function despite treatment with VA-ECMO. Hemodynamic parameters were reported as medians with interquartile ranges. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. Results: Six patients aged 53.5 (41.8, 57.8) years were included. Three patients received VA-ECMO for refractory cardiogenic shock and three patients for extracorporeal cardiopulmonary resuscitation. The baseline LV ejection fraction was 22.1% (19.0%, 24.7%). The baseline and lowest VA-ECMO flows were 4.0 (4.0, 4.0) L/min and 1.0 (1.0, 1.5) L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [116 (90, 153) versus 94 (58, 119) mL, p=0.03], LV end-diastolic pressure [16 (12, 24) versus 14 (9,15) mmHg, p=0.03], LV stroke work [2640 (1800, 4275) versus 1953 (759, 2179) mL*mmHg, p=0.03], and pressure-volume area [6864 (4038, 7715) versus 4575 (3142, 5888) mL*mmHg; p=0.046], respectively. The pressure-volume curves at the highest and lowest VA-ECMO flows are represented in blue and red, respectively ( Figure ). Mean arterial pressure and heart rate were similar at the lowest and highest flows (p=0.17 and p=0.60, respectively). All patients were decannulated from VA-ECMO. Four survived the index hospitalization. Conclusion: High flow VA-ECMO support significantly reduced LV end-diastolic volume, end-diastolic pressure, stroke work, and pressure-volume area compared to low flow.

Right atrial function is associated with RV diastolic stiffness: RA-RV interaction in pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study assessed the impact of RV diastolic stiffness on RA-RV interaction.MethodsLow or high end-diastolic elastance (Eed) PAH patients (n=94) were compared to controls (n=31). Treatment response was evaluated in n=62 patients. RV and RA longitudinal strain, RA emptying and RV filling were determined and diastole was divided in a passive and active phase. Vena cava backflow was calculated as RV active filling-RA active emptying; RA stroke work as RA active emptying*RV end-diastolic pressure.ResultsWith increased Eed, RA and RV passive strain were reduced while active strain was preserved. In comparison to controls, patients had lower RV passive filling, but higher RA active emptying and RA stroke work. RV active filling was lower in high Eed patients, resulting in higher vena cava backflow. Upon treatment, Eed reduced in half of high Eedpatients, which coincided with larger reductions in afterload, RV mass and vena cava backflow and greater improvements in RV active filling and stroke volume in comparison to patients in whom Eed remained high.ConclusionsIn PAH, RA function is associated with changes in RV function. Despite increased RA stroke work, severe RV diastolic stiffness is associated with reduced RV active filling and increased vena cava backflow. In 50% of high baseline Eed patients, diastolic stiffness remains high, despite treatment. Eed reduction coincided with a large reduction in afterload, increased RV active filling and decreased vena cava backflow.