Left Ventricular Stroke Work Index Research Articles

Echocardiographic surrogate of left ventricular stroke work in a model of brain stem death donors

AbstractBackgroundThe commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload‐independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non‐invasive echocardiographic parameter, Pressure‐Strain Product (PSP), as a potential surrogate of catheter‐based LVSWI. This study aimed to investigate if PSP could correlate with catheter‐based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post‐transplant hearts was also evaluated.MethodsThirty‐one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter‐based LVSWI were simultaneously measured at 8‐timepoints during 24‐h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6‐h observation after heart transplantation.ResultsIn BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut‐off point; mean value of complex 1,2 O2 Flux) in post‐transplant hearts, which was greater than other echocardiographic parameters.ConclusionsPSPcirc could be used as a surrogate of catheter‐based LVSWI reflecting mitochondrial function.

Optimizing resuscitation of the donation after circulatory death heart by mitochondrial protection in a female porcine model.

Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death, DCD). Using a translational porcine DCD model, we developed and evaluated a protocol based on cardioprotection by multi-drug postconditioning to optimize resuscitation of DCD hearts by ex situ heart perfusion (ESHP). Hearts of female pigs (45.0±4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N=5) or presence (treated, N=5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for additional 300 min in working mode for a total perfusion time of 6 hrs. Oxidative capacity and detailed left ventricular (LV) mechanical function under increasing workload (left atrial pressure 6-12 mmHg) were assessed hourly. LV tissue was snap-frozen at the end of ESHP and used for molecular analyses. LV inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax= 440 mmHg/s, p=0.009). Treated DCD hearts exhibited persistently higher LV stroke work index (LVSWI) during the 6-hr period of ESHP, whereas untreated DCD hearts displayed a significant decline (ΔLVSWI=-3.10 mL*mmHg/g, p(time within untreated group)<0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2=3.11 mL O2/min/100g; p=0.004), and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, while untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates, reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

Changes in the indicators of hemodynamics and oxygen transport in patients with idiopathic pulmonary arterial hypertension depending on their survival

Background. Idiopathic pulmonary arterial hypertension (IPAH) is a severe disease that affects the vessels of the pulmonary circulation and leads to right ventricular failure and death of patients. Indicators of hemodynamics and oxygen transport play central role in the progression and development of the disease. Objective: to evaluate indicators of hemodynamics, oxygen transport. Materials and methods. The study included 124 patients with IPAH. They were divided into two groups: alive patients (group 1) and those who died (group 2). All of them underwent general clinical examinations, a 6-minute walk test, transthoracic and speckle tracking echocardiography, right heart catheterization, blood gas analysis and calculation of hemodynamic parameters. Results. We calculated and compared the right (RVSWI) (19.93 ± 7.84 vs. 16.47 ± 4.67 g·m·m–2, p = 0.009) and left ventricular stroke work index (LVSWI) (39.47 ± 10.53 vs. 35.92 ± 11.19 g·m·m–2, p = 0.036) and their ratio (RVSWI/LVSWI) (0.59 ± 0.16 vs. 0.46 ± ± 0.13, p = 0.008), right (RVPC) (97.00 ± 2.16 vs. 1.82 ± 1.04 g·m, p = 0.001) and left ventricular pump coefficient (LVPC) (5.36 ± 4.84 vs. 4.41 ± 2.15 g·m, p = 0.04) and their ratio (RVPC/LVPC) (0.54 ± 0.19 vs. 0.44 ± 0.11, p = 0.05) in both groups of patients. Also, we found differences in partial pressure of carbon dioxide (PaCO2) of venous blood (34.5 ± 5.1 vs. 40.2 ± 6.9 mm Hg, p = 0.02), partial pressure of oxygen (PaO2) of arterial blood (90.2 ± 15.1 vs. 78.9 ± 11.2 mm Hg; p = 0.01), arteriovenous oxygen difference (A-vO2) (4.5 ± 1.2 vs. 5.0 ± 0.8 ml/dL, p = 0.02) between both groups. Conclusions. RVSWI, LVSWI, RVSWI/LVSWI, RVPC, LVPC, RVPC/LVPC were significantly different between the groups. The use of the above hemodynamic parameters can help in a deeper understanding of the prognosis in IPAH patients. Performance of oxygen transport indicators (PaCO2, PaO2) and A-vO2 in IPAH patients provides a broader understanding of the status and prognosis of this disease.

Abstract 17527: Plasma Proteomic Representations of Central Hemodynamics Over Time in Heart Failure

Introduction: Perturbation of central hemodynamic parameters are defining features in heart failure (HF) and strong prognostic factors, including increased filling pressures, reduced cardiac output (CI), extended blood circulation times and increased peripheral oxygen extraction (ΔAVO2). Invasive catheterization is used for precise assessment of central hemodynamics. Hypothesis: We postulated that plasma proteins may serve as non-invasive representations of central hemodynamics in HF patients. Methods: Affinity-based plasma proteomic profiling of 1305 proteins was applied to a cohort of patients with advanced HF undergoing invasive cardiac catheterization before and 6 months after heart transplantation. A total of 30 central hemodynamic parameters were measured and calculated. Protein profiles associated with central hemodynamics over time were identified from repeated-measures models. Results: We identified 1304 associations for 201 unique proteins meeting our Bonferroni-adjusted significance threshold (p&lt;1x10-6) for at least one hemodynamic parameter. Most of the 201 proteins were associated with more than one parameter. Most proteins (70%) associated with parameters in more than one of five domains (filling pressures, left ventricular (LV) function, right ventricular (RV) function, systemic arterial function, pulmonary arterial function). No proteins were associated with 6 of the 30 hemodynamic parameters, which changed little after transplantation and related to arterial function or RV function. The largest number of protein associations were observed for RAP, cardiac power index, left ventricular stroke work index, and ΔAVO2 followed by systolic blood pressure, CI, and PAWP (&gt;80). These include expected associations of natriuretic peptides, ST2 with LV function, filling pressures and of angiotensinogen with vascular function parameters. We further describe the discriminatory ability of identified proteins for clinically relevant differences in key hemodynamic parameters. Conclusions: We have identified circulating biomarkers to non-invasively monitor central hemodynamics in HF over time. Our findings may also inform understanding of pathways involved in HF pathophysiology and circulatory regulation.

Normothermic ex vivo heart and lung autoperfusion: assessment of functional status and metabolism

Objective: to carry out a comparative study of the efficacy of a 6-hour normothermic ex vivo heart and lung autoperfusion and cold cardioplegia using Bretschneider’s solution (Custodiol®, Germany).Materials and methods. Landrace pigs weighing 50 ± 5 kg at the age of 4–5 months (n = 10) were used as a model for a series of acute experiments. In the experimental group (n = 5), the cardiopulmonary complex was conditioned by autoperfusion for 6 hours. In the control group, the heart pumping function was restored after 6-hour cold cardioplegia using Bretschneider’s solution. The efficiency of graft preservation was assessed by measuring hemodynamic parameters, myocardial contractile function, and myocardial oxygen consumption.Results. After reperfusion and repeated isolation of the working cardiopulmonary complex, cardiac output was 0.63 [0.37; 0.8] L/min and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (p &lt; 0.05). Indicators – global left ventricular stroke work index and preload recruitable stroke work – were significantly higher in the experimental group (p &lt; 0.05).Conclusion. Normothermic autoperfusion is significantly more effective in preserving the morphofunctional status of a donor heart than static cold storage with Bretschneider solution for 6 hours.

Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy.

Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.

Association of Shock Index with Echocardiographic Parameters in Cardiac Intensive Care Unit

BackgroundA high shock index (SI), the ratio of heart rate (HR) to systolic blood pressure (SBP), has been associated with unfavorable outcomes. We sought to determine the hemodynamic underpinnings of an elevated SI using 2-D and doppler Transthoracic Echocardiography (TTE) in unselected cardiac intensive care unit (CICU) patients. MethodsWe included Mayo Clinic CICU admissions from 2007 to 2018 who were in sinus rhythm at the time of TTE. The SI was calculated using HR and SBP at the time of TTE. Patients were grouped according to SI: <0.7, 4012 (64%); 0.7–0.99, 1764 (28%); and ≥ 1.0, 513 (8%). Pearson's correlation coefficient was used to assess associations between continuous variables. ResultsWe included 6289 unique CICU patients, 58% of whom had acute coronary syndrome. The median age was 67.9 years old and 37.8% were females. The mean SI was 0.67 BPM/mmHg. As the SI increased, markers of left ventricular (LV) systolic function and forward flow decreased, including left ventricular ejection fraction (LVEF), fractional shortening, left ventricular outflow tract (LVOT) velocity time integral (VTI), stroke volume, LV stroke work index, and cardiac power output. Biventricular filling pressures increased, and markers of right ventricular function worsened with rising SI. Most TTE measurements reflecting LV function and forward flow were inversely correlated with SI, including LV stroke work index (r = −0.59) and LVOT VTI (r = −0.41), as were both systemic vascular resistance index (r = −0.43) and LVEF (r = −0.23). ConclusionCICU patients with elevated SI have worse biventricular function and systemic hemodynamics, particularly decreased stroke volume and related calculated TTE parameters. The SI is an easily available marker that can be used to identify CICU patients with unfavorable hemodynamics who may require further assessment.

A novel speckle-tracking echocardiography parameter assessing left ventricular afterload.

Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.

Invasive Phenoprofiling of Acute-Myocardial-Infarction-Related Cardiogenic Shock.

Studies had previously identified three cardiogenic shock (CS) phenotypes (cardiac-only, cardiorenal, and cardiometabolic). Therefore, we aimed to understand better the hemodynamic profiles of these phenotypes in acute myocardial infarction-CS (AMI-CS) using pulmonary artery catheter (PAC) data to better understand the AMI-CS heterogeneity. We analyzed the PAC data of 309 patients with AMI-CS. The patients were classified by SCAI shock stage, congestion profile, and phenotype. In addition, 24 h hemodynamic PAC data were obtained. We identified three AMI-CS phenotypes: cardiac-only (43.7%), cardiorenal (32.0%), and cardiometabolic (24.3%). The cardiometabolic phenotype had the highest mortality rate (70.7%), followed by the cardiorenal (52.5%) and cardiac-only (33.3%) phenotypes, with significant differences (p < 0.001). Right atrial pressure (p = 0.001) and pulmonary capillary wedge pressure (p = 0.01) were higher in the cardiometabolic and cardiorenal phenotypes. Cardiac output, index, power, power index, and cardiac power index normalized by right atrial pressure and left-ventricular stroke work index were lower in the cardiorenal and cardiometabolic than in the cardiac-only phenotypes. We found a hazard ratio (HR) of 2.1 for the cardiorenal and 3.3 for cardiometabolic versus the cardiac-only phenotypes (p < 0.001). Also, multi-organ failure, acute kidney injury, and ventricular tachycardia/fibrillation had a significant HR. Multivariate analysis revealed that CS phenotypes retained significance (p < 0.001) when adjusted for the Society for Cardiovascular Angiography & Interventions score (p = 0.011) and ∆congestion (p = 0.028). These scores independently predicted mortality. Accurate patient prognosis and treatment strategies are crucial, and phenotyping in AMI-CS can aid in this effort. PAC profiling can provide valuable prognostic information and help design new trials involving AMI-CS.

Prognostic significance of the biomarker NT-proBNP in the surgical treatment of aortic stenosis (pilot study)

The objective was to study the relationship between the preoperative blood levels of the N-terminal segment of B-type natriuretic peptide precursor (NT-proBNP) and ultrasound and thermodilution indicators of cardiac function before and after on-pump surgery for aortic stenosis, as well as to evaluate the prognostic significance of the biomarker in relation to postoperative myocardial dysfunction.Materials and methods. The study involved 27 patients aged 57.7±2.5 years who underwent aortic valve replacement. NT-proBNP level was determined before surgery. The indicators of invasive hemodynamics and transesophageal echocardiography were analyzed at stages: I – after anesthesia induction, II – at the end of surgery. Correlation analysis, logistic regression and ROC analysis were used.Results. The preoperative NT-proBNP level was 2002.0 [540.8–4001.5] pg/ml. At I stage, NT-proBNP correlated with mean pulmonary artery pressure (rho = 0.468; p = 0.014), indices of left ventricular function (rho = –0.509; p = 0.007), end-diastolic and end-systolic volumes (rho = 0.737–0.757; p &lt; 0.0001), as well as ejection fraction (rho = –0.556; p = 0.004) and area contraction fraction (rho = –0.783; p &lt; 0.0001). At II stage, the level of NT-proBNP &gt; 2000 pg/ml was a predictor of the left ventricular area contraction fraction &lt; 50% (OR 1.0011, 95% CI 1.0002–1.0020, p = 0.028, AUC 0.799) , the left ventricular end-systolic area index &gt; 9 cm2/m2 (OR 1.0007, 95% CI 1.0001–1.0013, p = 0.027, AUC 0.886), vasoactive-inotropic score &gt; 10 (OR 1.0006, 95% CI 1.0001–1.0012, p = 0.032, AUC 0.876), duration of sympathomimetic therapy &gt; 24 h (OR 1.0001, 95% CI 1.0000–1.0003, p = 0.049, AUC 0.889).Conclusions. NT-proBNP blood level was increased in 66.7% of patients with aortic stenosis before surgery. Moreover, the biomarker level directly correlates with the mean pulmonary artery pressure, the indices of end-diastolic and end-systolic volumes, end-diastolic and end-systolic areas of the left ventricle, and it inversely correlates with the left ventricular stroke work index, ejection fraction and left ventricular area contraction fraction. The preoperative NT-proBNP level was a predictor of the postoperative decrease to the pathological level of the ejection fractions and left ventricular area contraction, an increase in the left ventricular end-systolic area index, intensive and prolonged sympathomimetic therapy. Myocardial dysfunctions were most pronounced in patients with biomarker levels above 2000 pg/ml.

Cardiovascular Function during First 24 Hours after Off-Pump and On-Pump CABG—A Prospective Observational Comparative Study

Purpose: Myocardial revascularization by coronary artery bypass grafting (CABG) in ischemic heart disease patients has direct impact on hemodynamic parameters in the immediate post-operative period. The peri-operative cardiovascular functioning is an important determinant for outcome of surgery. In On-Pump CABG (ONCAB), the cardiopulmonary bypass has a negative effect on myocardium. Off-Pump CABG (OPCAB) avoids the effect of CPB but complete revascularization with difficult positioning of heart is technically demanding. This study is aimed to compare the cardiovascular functioning in the immediate post-operative period after OPCAB and ONCAB. Methods: Total 106 patients were operated for CABG from January 2015 to June 2016, of which 75 patients were operated for OPCAB and 31 patients were operated for ONCAB. For the comparison, hemodynamic parameters were measured during anesthesia before surgery, postoperatively after 1 and 4 hours (h) in the ICU, and in the morning after surgery, approximately after 20 h. Results: The time-dependent rise of hemodynamic parameters like Cardiac Output (CO), Cardiac Index (CI), Stroke volume (SV) and Left Ventricular Stroke Work Index (LVSWI) in the immediate post-operative hours (1 h and 4 h) are more predominant in OPCAB group than ONCAB group although the difference is eliminated mostly at 20 h. The better peripheral vasodilation after OPCAB causes immediate fall of Systemic Vascular Resistance Index (SVRI) after OPCAB. Conclusion: Better cardiovascular functioning immediately after OPCAB than ONCAB may be important for better hemodynamic stability. The difference is however eliminated after 24 hours indicating little significance in long term outcome.

The prognostic role of advanced hemodynamic variables in patients with left ventricular assist devices.

Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure (HF). However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs. Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality. Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02-5.74, p=0.045) in univariate analysis and Kaplan-Meier analysis (p=0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09-4.17, p=0.03) in univariate analysis and Kaplan-Meier analysis (p=0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions. Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs.

Abstract 15000: Advanced Hemodynamics in the Assessment of Waitlist Mortality

Introduction: Our analysis seeks to determine whether it or advanced hemodynamic variables, including aortic pulsatility index (API), pulmonary artery pulsatility index (PAPI), left ventricular stroke work index (LVSWI), or right ventricular stroke work index (RVSWI), correlated more strongly than traditional metrics with waitlist mortality for heart transplant. Hypothesis: Advanced hemodynamic markers of cardiac function, including API and PAPI, correlate more strongly with waitlist mortality than traditional hemodynamic criteria, including SBP and PCWP. Methods: This retrospective analysis of the Scientific Registry of Transplant Candidates (SRTR) included adults listed at all Statuses after the new heart allocation system in 2018. Hemodynamic data was obtained for patients listed after the 2018 policy change. Kaplan-Meier survival analysis was completed, with API, PAPI, LVSWI, and RVSWI as the independent variable stratified into quintiles. Results: There were 9,418 patients listed for heart transplant since the new policy implementation, with 8,636 patients with complete hemodynamic data at listing. Kaplan-Meier survival analysis revealed that API and LVSWI were best at stratifying patients appropriately in terms of waitlist survival with homogeneity of dispersion between groups (Figure 1), (lowest API quintile to highest: HR 2.04, 95%CI 1.94 - 2.15; HR 1.70, 1.59 - 1.81; HR 1.40, 1.29-1.51; HR 1.19, 1.08 - 1.30). The traditional parameters of PCWP, CO and systolic blood pressure had considerable dispersion of risk between quintiles while the right-sided parameters of PAPI and RVSWI did not. Conclusions: Advanced left-sided hemodynamic parameters better risk strategy waitlist mortality and the urgent need for heart transplantation than traditional metrics or right-sided advanced parameters.

Abstract 15817: Hemodynamics of the UNOS Heart Allocation System: Is it Time to Add Objectivity to an Subjective System?

Introduction: In the current United States Organ Sharing heart transplant allocation system, hemodynamic criteria, systolic blood pressure (SBP), cardiac index (CI), and pulmonary capillary wedge pressure (PCWP), are utilized to justify certain listing statuses. Hypothesis: We sought to identify how currently utilized, and advanced, hemodynamics discriminated patients by listing status. Methods: Retrospective analysis of the Scientific Registry of Transplant Candidates including all adults listed for heart transplant since the updated listing criteria went live in October 2018 was completed. In addition to SBP, CI, and PCWP, the mean advanced hemodynamic metrics of aortic pulsatility index (API), cardiac power output (CPO), left ventricular stroke work index (LVSWI), right ventricular stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPI), were calculated for each status. Results: Since October 2018, 9,418 patients were listed for heart transplant, and 8,636 had complete hemodynamic data at time of listing. Currently utilized hemodynamic metrics failed to discriminate lower acuity statuses (3 through 6 for PCWP and CI; 4 through 6 for SBP). For advanced hemodynamic metrics, mean API was lowest for Status 1 patients, and rose consistently with increasing status with a clear stepwise and statistically significant difference for sequential statuses (p &lt; 0.001). CPO and LVSWI were unable to discriminate statuses 3-6. For right-sided hemodynamics, PAPI was unable to discriminate statuses 2 through 6, and there were no significant differences across any status for RVSWI. Conclusions: API is the only hemodynamic metric that is able to differentiate patients on the heart transplant waiting list across all active statuses by increasing in a stepwise fashion. Incorporation of API into future iterations of the UNOS heart allocation system may help better risk stratify patients and minimize waitlist mortality.

Abstract 10899: Excessive Right Ventricular Afterload in Pulmonary Arterial Hypertension: Effects on Diastolic Function and the Left Ventricle

Introduction: Right ventricular (RV) diastolic dysfunction in pulmonary arterial hypertension (PAH) remains poorly understood. In this study, we used RV pressure-volume (PV) loops to assess RV diastology as a function of afterload in PAH. Methods: RV PV loops were prospectively measured in control (n=9) and PAH (n=39) patients at rest and during supine bike exercise. PAH patients were stratified by effective arterial elastance (Ea), a lumped measure of total afterload, into two groups: high afterload (HA, n=20) and severe afterload (SA, n=19). Results: PAH groups were matched with respect to age, sex, and PAH medication usage. Ea at rest and exercise was higher in SA PAH (1.8 vs. 0.6 mmHg/ml, P &lt;0.0001 at rest; 2.3 vs 0.8 mmHg/ml, P &lt; 0.0001 with exercise). In the SA group, RV end-diastolic pressure (RVEDP) was higher at rest (13.3 vs 7.6 mmHg, P = 0.0017) and rose markedly with exertion (23.4 vs 13.1 mmHg, P=0.0001). Because RV volumes changed similarly in both groups, SA patients exhibited stiffer RVs (dP/dV 0.30 vs 0.11 mmHg/mL, P=.024). To understand pericardial-interventricular interactions, we calculated the RVEDP-to-pulmonary capillary wedge pressure (PCWP) ratio and the left ventricular (LV) transmural filling pressure (LVTMFP). RVEDP/PCWP was substantially higher in SA (2.1 vs 1.0, P=.005). Therefore, even though PCWP rose considerably in SA (mean 16 mmHg), exercise LVTMFP was significantly reduced in SA vs HA PAH (-7.5 vs 2.55 mmHg, P=0.002). Along with reduced LV size seen by concomitant echo, we thus revealed blunted LV filling specifically in SA PAH. Accordingly, exercise cardiac index, stroke volume index, and LV stroke work index were all markedly reduced in SA PAH. Conclusions: Severe afterload in PAH results in high RV diastolic pressures and RV stiffening, which in turn blunt LV filling and LV output with exertion. Due to ventricular interactions, exercise PCWP may rise considerably in PAH, thus reducing its ability to differentiate from left heart disease.

Indicators of haemodynamic instability and left ventricular function in a porcine model of esmolol induced negative inotropy

To investigate if the Hypotension Prediction Index was an early indicator of haemodynamic instability in a negative inotropy porcine model, and to assess the correlation of commonly measured indicators of left ventricular systolic function. Eight anaesthetised pigs were volume resuscitated and then underwent an incremental infusion of esmolol hydrochloride (0-3000 mg/hr), following which it was then reduced in a stepwise manner. Full haemodynamic measurements were taken at each stage and measurements of left ventricular systolic function including left ventricular stroke work index, ejection fraction and peripheral dP/dT were obtained. At an infusion rate of 500 mg/hr of esmolol there were no significant changes in any measured variables. At 1000 mg/hr MAP was on average 11 mmHg lower (95% CI 1 to 11 mmHg, p = 0.027) with a mean of 78 mmHg, HPI increased by 33 units (95% CI 4 to 62, p = 0.026) with a mean value of 63. No other parameters showed significant change from baseline values. Subsequent increases in esmolol showed changes in all parameters except SVV, SVR and PA mean. Correlation between dP/dt and LVSWI was 0.85 (95% CI 0.77 to 0.90, p < 0.001), between LVEF and dP/dt 0.39 (95% CI 0.18 to 0.57, p < 0.001), and between LSWI and LVEF 0.41 (95% CI 0.20 to 0.59, p < 0.001). In this model haemodynamic instability induced by negative inotropy was detected by the HPI algorithm prior to any clinically significant change in commonly measured variables. In addition, the peripheral measure of left ventricular contractility dP/dt correlates well with more established measurements of LV systolic function.

Correlation of left ventricular myocardial work indices with invasive measurement of stroke work in patients with advanced heart failure.

This study aimed to explore the correlation between left ventricular (LV) myocardial work (MW) indices and invasively-derived LV stroke work index (SWI) in a cohort of patients with advanced heart failure (AHF) considered for heart transplantation. Left ventricular MW has emerged as a promising tool for diagnostic and prognostic purposes in heart failure (HF) but its relationship with hemodynamic data derived from right heart catheterization (RHC) has not been assessed in patients with advanced heart failure yet. Consecutive patients with AHF considered for heart transplantation from 2016 to 2021 performing RHC and echocardiography as part of the workup were included. Conventional LV functional parameters and LV MW indices, including LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW), LV global work efficiency (GWE), and other were calculated and compared with invasively-measured LV SWI. The population included 44 patients. Median time between RHC and echocardiography was 0 days (IQR: 0-24). Median age was 60 years (IQR: 54-63). For the most part, etiology of HF was non-ischemic (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 1,377 pg/ml (IQR: 646-2570). LV global longitudinal strain (GLS) significantly correlated with LV SWI (r = -0.337; p = 0.031), whereas, LV ejection fraction (EF) did not (r = 0.308; p = 0.050). With regard to LV MW indices, some of them demonstrated correlation with LV SWI, particularly LV GWI (r = 0.425; p = 0.006), LV GCW (r = 0.506; p = 0.001), LV global positive work (LV GPW; r = 0.464; p = 0.003) and LV global systolic constructive work (GSCW; r = 0.471; p = 0.002). Among LV MW indices, LV GCW correlated better with invasively-derived SWI, potentially representing a powerful tool for a more comprehensive evaluation of myocardial function.

Systemic blood pressure in severe aortic stenosis: Haemodynamic correlates and long-term prognostic impact.

Blood pressure (BP) targets in patients with aortic stenosis (AS) are controversial. This study sought to describe the haemodynamic profile and the clinical outcome of severe AS patients with low versus high central meaarterial pressure (MAP). Patients with severe AS (n=477) underwent right and left heart catheterization prior to aortic valve replacement (AVR). The population was divided into MAP quartiles. The mean systolic BP, diastolic BP, and MAP in the entire population were 149±25, 68±11, and 98±14mmHg. Patients in the lowest MAP quartile had the lowest left ventricular ejection fraction (LVEF), systemic vascular resistance, and valvulo-arterial impedance, whereas there were no significant differences in mean right atrial pressure, mean pulmonary artery wedge pressure, pulmonary vascular resistance, and stroke volume index across MAP quartiles. However, left ventricular stroke work index (LVSWI) was lowest in patients in the lowest and highest in those in the highest MAP quartile. After a median (interquartile range) post-AVR follow-up of 3.7 (2.6-5.2) years, mortality was highest in patients in the lowest MAP quartile [hazard ratio 3.08 (95% confidence interval 1.21-7.83); P=0.02 for lowest versus highest quartile]. In the multivariate analysis, lower MAP [hazard ratio 0.78 (95% confidence interval 0.62-0.99) per 10mmHg increase; P=0.04], higher mean right atrial pressure and lower LVEF were independent predictors of death. In severe AS patients, lower MAP reflects lower systemic vascular resistance and valvulo-arterial impedance, which may help to preserve stroke volume and filling pressures despite reduced left ventricular performance, and lower MAP is a predictor of higher long-term post-AVR mortality.

Elevated plasma WIF-1 levels are associated with worse prognosis in heart failure with pulmonary hypertension.

Heart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF-PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF-PH. Plasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF-PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right heart catheterization. Eleven proteins had elevated plasma levels in LHF-PH compared with controls (P<0.01), which decreased towards the controls' levels after HT (P<0.01). Survival analysis of these proteins showed that elevated plasma levels of growth hormone, programmed cell death 1 ligand 2, tissue factor pathway inhibitor 2, and Wnt inhibitory factor 1 (WIF-1) were associated with worse transplantation-free survival in LHF-PH (P<0.05). When adjusted for age, sex and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels using multivariable cox regressions, only WIF-1 remained prognostic [hazard ratio (95% confidence interval)] [1.013 (1.001-1.024)]. WIF-1 levels in LHF-PH patients also correlated with the mean right atrial pressure (rs =0.42; P<0.01), stroke volume index (rs =0.41; P<0.01), cardiac index (rs =-0.42; P<0.01), left ventricular stroke work index (rs =-0.41; P<0.01), and NT-proBNP (rs =0.63; P<0.01). The present study demonstrated that LHF-PH patients have higher plasma WIF-1 levels than healthy controls, suggesting that plasma WIF-1 may be a potential future prognostic biomarker in LHF-PH. Its prognostic capability could be further refined by including it in a multi-marker panel. Further studies are needed to establish the potential role of WIF-1 in LHF-PH pathophysiology in larger cohorts to determine its clinical applicability.

High-dose adenosine versus saline-induced cardioplegic arrest in coronary artery bypass grafting: A randomized double-blind clinical feasibility trial.

In this clinical trial, we evaluated if a short-acting nucleoside, adenosine, as a high-dose bolus injection with blood cardioplegia induces faster arrest and provides better myocardial performance in patients after bypass surgery for coronary artery disease. Forty-three patients scheduled for elective or urgent coronary artery bypass grafting were prospectively recruited in two-arm 1:1 randomized parallel groups to either receive 20 mg of adenosine (in 21 patients) or saline (in 22 patients) into the aortic root during the first potassium-enriched blood cardioplegia infusion. The main outcomes of the study were ventricular myocardial performance measured with cardiac index, right ventricular stroke work index, and left ventricular stroke work index at predefined time points and time to asystole after a single bolus injection of adenosine. Conventional myocardial biomarkers were compared between the two groups at predefined time points as secondary endpoints. Electrocardiographic data and other ad hoc clinical outcomes were compared between the groups. Compared with saline, adenosine reduced the time to asystole (68 (95% confidence interval (95% CI) = 37-100) versus 150 (95% CI = 100-210) seconds, p = 0.005). With myocardial performance, the results were inconclusive, since right ventricular stroke work index recovered better in the adenosine group (p = 0.008), but there were no significant overall differences in cardiac index and left ventricular stroke work index between the groups. Only the post-cardiopulmonary bypass cardiac index was better in the adenosine group (2.3 (95% CI = 2.2-2.5) versus 2.1 (95% CI = 1.9-2.2) L/min/m2, p = 0.016). There were no significant differences between the groups in cardiac biomarker values. A high dose adenosine bolus at the beginning of the first cardioplegia infusion resulted in significantly faster asystole in coronary artery bypass grafting patients but enhanced only partially the ventricular performance.EudraCT number: 2014-001382-26. https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001382-26/FI.