Left Ventricular Stroke Work Research Articles

Abstract P2011: Reduced Activity Of Activin Like Kinase 1 (ALK1) Increases Mortality And Myocardial Rupture After Acute Myocardial Infarction

Introduction: Acute myocardial infarction (AMI) is a primary cause of heart failure (HF). Transforming growth factor beta (TGFβ) plays a central role in cardiac remodeling after AMI. Reduced activity of the TGFβ Type I receptor, activin like kinase (ALK)-1 promotes cardiac fibrosis in murine models of heart failure. A functional role for ALK1 in post-infarct cardiac remodeling remains poorly understood. We hypothesize that reduced ALK1 activity reduces survival and promotes cardiac fibrosis after AMI. Methods: AMI was induced by left coronary ligation in wild type (WT), and ALK+/- mice. After 14 days, LV function was assessed using conductance catheters and myocardial ALK1 signaling was quantified. Using siRNAs targeting ALK1 in in human cardiac fibroblasts (H-CFs), we further tested the role of ALK1 in cardiac fibrosis. Results: Reduced ALK1 activity significantly reduced survival compared to WT (p= 0.008 respectively) after AMI. ALK1 mice demonstrated a higher rate of cardiac rupture compared to WT after AMI (0% vs 85.7%). Both WT ad ALK1+/- mice demonstrated reduced LV ejection fraction and stroke work compared to sham controls (p=0.001 and p=0.0001 respectively). Profibrotic SMAD3 signaling was increased and antifibrotic SMAD1 signaling decreased in ALK1-/+ (pSMAD3, p=0.03, pSMAD1, p=0.003) mice 14 days after AMI. Reduced SMAD1 signaling was directly associated with increased myocardial Type 1 collagen protein levels in ALK1-/+ (R2=0.42, p=0.01) mice compared to WT. Myocardial levels of the TGFb1 co-receptor, endoglin, were increased significantly in ALK+/- as compared to WT (p=0.001) after AMI. Activity of MMP9 was increased in ALK1+/- mice, but protein levels were not affected 2 weeks after MI. Conclusion: We identify for the first time that loss of ALK1 activity increases cardiac rupture and mortality after AMI. These findings identify a novel functional role for ALK1 as a determinant of post-infarct survival and cardiac remodeling and implicate ALK1 as a potential therapeutic target to improve survival after AMI.

Non-invasive pressure-volume analysis by 3-dimensional echocardiography: a novel method for left ventricular stroke work estimation

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Institute for Surgical Research, Oslo University Hospital. Introduction Left ventricular pressure-volume analysis is a powerful method to quantify left ventricular function. A major limitation of its clinical utility, however, is the need for invasive pressure and volume measurements. We hypothesized that accurate non-invasive left ventricular (LV) stroke work analysis is feasible by combining continuous 3-dimensional (3D) echocardiographic LV volume measurements with non-invasive LV pressure curve estimation. Purpose To investigate if LV stroke work can be estimated non-invasively by combining 3D echocardiographic volume measurements with non-invasive pressure curve estimation. Methods In 21 open-chest anesthetized canines, piezoelectric crystals were placed in the LV subendocardium for volume measurements and a micromanometer catheter was placed in the LV cavity for pressure measurements. Echocardiography was performed directly on the heart to acquire 3D LV volumes and timings of mitral and aortic valve events. The estimated LV pressure curve was obtained by adjusting the cardiac phases of an LV reference pressure curve to these valve events and adjusting its amplitude to measured peak LV pressure. Stroke work was calculated as the area under the pressure-volume curve from mitral valve closure to mitral valve opening. Non-invasively estimated and invasively measured stroke work were compared. Recordings were done during baseline, aortic constriction, dobutamine infusion and after induction of left bundle branch block by ablation. Results Panel A in the Figure illustrates non-invasive (left) and invasive (right) pressure-volume loops from a representative experiment. Baseline and the different interventions are colour-coded allowing visual comparison of the similar non-invasive and invasive stroke work. Panel B shows the pooled data from all experiments. There was a strong correlation (r=0.98, p<0.0001) and good agreement between the non-invasive and invasive stroke work. Furthermore, the non-invasive method captured similar changes in stroke work during interventions as compared to the invasive method (Panel C). Conclusions Non-invasive pressure-volume analysis by combining 3D echocardiography and estimated pressure for stroke work evaluation, is feasible and accurate.

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 < 0.0001), as well as ejection fraction (rho = –0.556; p = 0.004) and area contraction fraction (rho = –0.783; p < 0.0001). At II stage, the level of NT-proBNP > 2000 pg/ml was a predictor of the left ventricular area contraction fraction < 50% (OR 1.0011, 95% CI 1.0002–1.0020, p = 0.028, AUC 0.799) , the left ventricular end-systolic area index > 9 cm2/m2 (OR 1.0007, 95% CI 1.0001–1.0013, p = 0.027, AUC 0.886), vasoactive-inotropic score > 10 (OR 1.0006, 95% CI 1.0001–1.0012, p = 0.032, AUC 0.876), duration of sympathomimetic therapy > 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.

Estimation of Left Ventricular Stroke Work for Rotary Left Ventricular Assist Devices.

Continuous monitoring of left ventricular stroke work (LVSW) may improve the medical management of patients with rotary left ventricular assist devices (LVAD). However, implantable pressure-volume sensors are limited by measurement drift and hemocompatibility. Instead, estimator algorithms derived from rotary LVAD signals may be a suitable alternative. An LVSW estimator algorithm was developed and evaluated in a range of in vitro and ex vivo cardiovascular conditions during full assist (closed aortic valve [AoV]) and partial assist (opening AoV) mode. For full assist, the LVSW estimator algorithm was based on LVAD flow, speed, and pump pressure head, whereas for partial assist, the LVSW estimator combined the full assist algorithm with an estimate of AoV flow. During full assist, the LVSW estimator demonstrated a good fit in vitro and ex vivo (R 2 : 0.97 and 0.86, respectively) with errors of ± 0.07 J. However, LVSW estimator performance was reduced during partial assist, with in vitro : R 2 : 0.88 and an error of ± 0.16 J and ex vivo : R 2 : 0.48 with errors of ± 0.11 J. Further investigations are required to improve the LVSW estimate with partial assist; however, this study demonstrated promising results for a continuous estimate of LVSW for rotary LVADs.

Extracorporeal Life Support in Critical Care Medicine

Veno-arterial extracorporeal life support (ECLS) may be indicated in patients with refractory heart failure. The list of conditions in which ECLS is successfully used is growing and includes cardiogenic shock following myocardial infarction, refractory cardiac arrest, septic shock with low cardiac output and severe intoxication. Femoral ECLS is the most common and often preferred ECLS-configuration in the emergency setting. Although femoral access is usually quick and easy to establish, it is also associated with specific adverse haemodynamic effects due to the direction of blood flow and access-site complications are inherent. Femoral ECLS provides adequate oxygen delivery and compensates for impaired cardiac output. However, retrograde blood flow into the aorta increases left ventricular afterload and may worsen left ventricular stroke work. Therefore, femoral ECLS is not equivalent to left ventricular unloading. Daily haemodynamic assessments are crucial and should include echocardiography and laboratory tests determining tissue oxygenation. Common complications include the harlequin-phenomenon, lower limb ischaemia or cerebral events and cannula site or intracranial bleeding. Despite a high incidence of complications and high mortality, ECLS is associated with survival benefits and better neurological outcomes in selected patient groups.

Sphingosine-1-phosphate levels are inversely associated with left ventricular and atrial chamber volume and cardiac mass in men

AimsSphingosine-1-phosphate (S1P) is a signaling lipid, which is involved in several cellular processes including cell growth, proliferation, migration and apoptosis. The associations of serum S1P levels with cardiac geometry and function are still not clear. We investigated the associations of S1P with cardiac structure and systolic function in a population-based sample.Methods and resultsWe performed cross-sectional analyses of 858 subjects (467 men; 54.4%), aged 22 to 81 years, from a sub-sample of the population-based Study of Health in Pomerania (SHIP-TREND-0). We analyzed the associations of serum S1P with structural and systolic function left ventricular (LV) and left atrial (LA) parameters as determined by magnetic resonance imaging (MRI) using sex-stratified multivariable-adjusted linear regression models. In men, MRI data showed that a 1 µmol/L lower S1P concentration was associated with an 18.1 mL (95% confidence interval [CI] 3.66–32.6; p = 0.014) larger LV end-diastolic volume (LVEDV), a 0.46 mm (95% CI 0.04–0.89; p = 0.034) greater LV wall thickness (LVWT) and a 16.3 g (95% CI 6.55–26.1; p = 0.001) higher LV mass (LVM). S1P was also associated with a 13.3 mL/beat (95% CI 4.49–22.1; p = 0.003) greater LV stroke volume (LVSV), an 18.7 cJ (95% CI 6.43–30.9; p = 0.003) greater LV stroke work (LVSW) and a 12.6 mL (95% CI 1.03–24.3; p = 0.033) larger LA end-diastolic volume (LAEDV). We did not find any significant associations in women.ConclusionsIn this population-based sample, lower levels of S1P were associated with higher LV wall thickness and mass, larger LV and LA chamber sizes and greater stroke volume and work of the LV in men, but not in women. Our results indicate that lower levels of S1P were associated with parameters related with cardiac geometry and systolic function in men, but not in women.Graphical abstract

Long-term changes in coronary physiology after aortic valve replacement.

The detrimental effects of long-standing severe aortic stenosis (AS) often include left ventricular hypertrophy (LVH) and exhaustion of coronary flow reserve (CFR), the reversibility of which is unclear after valve replacement. Our aims were to 1) investigate whether CFR in the left anterior descending artery (LAD) would improve following valve replacement, and if the change was related to changes in hyperaemic coronary flow (QLAD) and minimal microvascular resistance (Rμ,LAD); and 2) investigate the relationship between changes in CFR and changes in left ventricular mass (LVM) and stroke work (LVSW). We measured intracoronary bolus thermodilution-derived CFR, and continuous thermodilution-derived QLAD and Rμ,LAD before and 6 months after aortic valve replacement. Cardiac magnetic resonance imaging was used to quantify left ventricular anatomy and function for the calculation of LVM and LVSW. Results: Thirty-four patients were included (17 patients had transcatheter aortic valve implantation; 14 had surgical valve replacement with a bioprosthesis and 3 with a mechanical prosthesis) who underwent invasive assessment in the LAD. CFR increased from 2.5 (interquartile range [IQR] 1.5-3.3) at baseline to 3.1 (IQR 2.2-5.1) at follow-up (p=0.005), despite no significant change in QLAD (230±106 mL/min to 250±101 mL/min; p=0.26) or Rμ,LAD (347 [IQR 247-463] to 287 [IQR 230-456]; p=0.20). When indexed for LVM, QLAD was 39% (IQR 8-98%) higher at follow-up compared with baseline (p<0.001). The improvement in CFR was correlated with ΔLVSW, r= -0.39; p=0.047. Conclusions: CFR in the LAD increased significantly at follow-up although global hyperaemic flow and minimal microvascular resistance remained unchanged. Thus, a decrease in resting flow was the cause of CFR improvement. CFR improvement was associated with reduction in LVSW.

Sex differences in left ventricular stroke work and cardiac power output per unit myocardium relate to blood pressure in apparently healthy adults.

Left ventricular stroke work per unit myocardium (LVSWM) and cardiac power output per unit myocardium (CPOM) are important measures of myocardial workload. The sex differences in the myocardial workload and its correlation with blood pressure remain largely unclear. The purpose of this study is to investigate the sex differences in LVSWM and CPOM, and to relate them to blood pressure in a cohort of apparently healthy adults. The LVSWM and CPOM were estimated in 596 age- and heart rate-matched apparently healthy adults (298 men) using transthoracic echocardiography combined with cuff-measured brachial blood pressure. The data were compared between sexes, and the sex differences in LVSWM and CPOM were related to blood pressure. After adjustment for the blood pressure, the LVSWM and CPOM were higher in women than in men [75.0 (73.7-76.4) vs 64.9 (63.5-66.2) cJ/100g for LVSWM, and 912.4 (894.1-930.6) vs 780.2 (762.0-798.5) milliwatt/100g for CPOM, respectively; all P<0.001]. After adjustment for the LVSWM and CPOM, the mean systolic and diastolic blood pressure were 7.4 mm Hg and 5.2 mm Hg higher in men than in women, respectively (all P<0.001). For any given blood pressure, the workload per unit myocardium is higher in apparently healthy women than in their male counterparts. A sex-specific definition of normal blood pressure with a relatively lower threshold for women can minimize the sex differences in the myocardial workload, which might reduce the potentially comparatively higher risk of heart failure in women.

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.

Class of hemorrhagic shock is associated with progressive diastolic coronary flow reversal and diminished left ventricular function.

Introduction: The relationship between coronary artery flow and left ventricular (LV) function during hemorrhagic shock remains unknown. The aim of this study was to quantify coronary artery flow directionality alongside left ventricular function through the four classes of hemorrhage shock. Methods: Following baseline data collection, swine were exsanguinated into cardiac arrest via the femoral artery using a logarithmic bleed, taking each animal through the four classes of hemorrhagic shock based on percent bleed (class I: 15%; class II: 15%-30%; class III: 30%-40%; class IV: >40%). Telemetry data, left ventricular pressure-volume loops, and left anterior descending artery flow tracings over numerous cardiac cycles were collected and analyzed for each animal throughout. Results: Five male swine (mean 72 ± 12kg) were successfully exsanguinated into cardiac arrest. Mean left ventricular end-diastolic volume, end-diastolic pressure, and stroke work decreased as the hemorrhagic shock class progressed (p < 0.001). The proportion of diastole spent with retrograde coronary flow was also associated with class of hemorrhagic shock (mean 5.6% of diastole in baseline, to 63.9% of diastole in class IV; p < 0.0001), worsening at each class from baseline through class IV. Preload recruitable stroke work (PRSW) decreased significantly in classes II through IV (p < 0.001). Systemic Vascular Resistance (SVR) is associated with class of hemorrhage shock (p < 0.001). Conclusion: With progressive classes of hemorrhagic shock left ventricular function progressively decreased, and the coronary arteries spent a greater proportion of diastole in retrograde flow, with progressively more negative total coronary flow. Preload recruitable stroke work, a load-independent measure of inotropy, also worsened in severe hemorrhagic shock, indicating the mechanism extends beyond the drop in preload and afterload alone.

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 15415: Left Ventricular Unloading Reduces Right Ventricular Preload and Afterload in Patients With Acute Decompensated Heart Failure and Cardiogenic Shock

Background: Use of the Impella 5.5 trans-valvular axial flow pump is increasing among patients with heart failure and cardiogenic shock (HF-CS) as a bridge to advanced therapies or myocardial recovery. The effect of trans-valvular left ventricular (LV) unloading on biventricular hemodynamics remains poorly understood. Methods: Seven patients with HF-CS underwent Impella 5.5 placement. A conductance catheter was placed first in the right ventricle (RV) then the LV to record pre-support pressure-volume loops. After insertion of the Impella 5.5, LV then RV loops were recorded within 15 minutes of device activation. Pulmonary artery catheter indices were recorded before and after Impella 5.5 activation. Results: Compared to baseline values, Impella 5.5 activation significantly decreased LV systolic and diastolic pressures as well as LV dP/dt(max) (Figure and Table). Impella 5.5 also significantly decreased right atrial, pulmonary (systolic/diastolic/mean) and RV diastolic pressures. Both LV and RV pressure-volume area and stroke work were not significantly changed with acute LV unloading. Conclusions: Trans-valvular unloading with an Impella 5.5 decreases biventricular filling pressures and reduces pulmonary pressures. These findings suggest that percutaneous LV unloading in patients with acute decompensated heart failure and cardiogenic shock may improve RV performance.

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.