Ventricular-arterial Interaction Research Articles

Relationship between 3-dimensional aortic geometry and the risk of new-onset heart failure

Abstract Introduction Aortic geometric assessments to date have typically involved cross-sectional imaging of discrete aortic segments. However, the complex 3D geometry of the thoracic aorta, and its relationship to the risk of cardiovascular disease has not been assessed in large studies. Methods We segmented the thoracic aorta in SSFP axial MRI images from 49,282 UK Biobank participants using a deep convolutional neural network (U-Net). We then computed geometric measurements (centerline length, arch height, arch width, arch height-width ratio, arch unfolding index [inverse of tortuosity], curvature and mean, minimum and maximum diameters) in the overall thoracic aorta as well as in 6 subsegments. We quantified their relationship to the risk of cardiomyopathy and heart failure (HF) using multivariable Cox-proportional hazards models. All hazard ratios are standardized. Centerline length was allometrically indexed to body height. Results In models adjusted for age, sex, BMI kg/m2, low-density lipoprotein mg/dl, high-density lipoprotein mg/dl, triglycerides mg/dl, systolic blood pressure and diastolic blood pressure, the curvature of the aorta (HR=0.63; 95% CI=0.39, 0.99; P<0.05), particularly the aortic arch (HR=0.54; 95% CI= 0.35, 0.87; P<0.05) was strongly related to a lower risk of incident cardiomyopathy. A higher arch unfolding index (HR=1.46; 95% CI=1.03, 2.07; P<0.05), higher width-to-height ratio (HR=1.10; 95% CI= 1.02, 1.19; P<0.05) and lower aorta tortuosity (HR=1.20; 95% CI= 1.09, 1.32; P<0.05) were all associated with a higher risk of cardiomyopathy. This aortic geometric pattern was also associated with a greater risk of a new HF diagnosis (arch unfolding [HR=1.23; 95% CI= 1.07, 1.42; P<0.05], width to heigh ratio [HR=1.06; 95% CI= 1.01, 1.11; P0.05]). Conclusion We demonstrate that 3-D thoracic aortic geometric indices are strongly associated with incident cardiomyopathy and HF, independent of classic risk factors. This is likely related to abnormal afterload and ventricular-arterial interactions since adverse geometric remodeling affects left ventricular pulsatile load.Cardiomyopathy & Heart Failure Hazards

Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction.

Sacubitril/valsartan improves outcome in chronic heart failure (HF) with reduced ejection fraction (EF). The underlying mechanisms on left ventricular (LV) myocardial function are incompletely understood. In this study, 117 patients with symptomatic HF and LV-EF ≤ 40% were enrolled prospectively. Non-invasive pressure-volume analysis was calculated from transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements. Primary outcome parameters were LV end-systolic elastance (Ees; a measure of LV contractility), effective arterial elastance (Ea; a measure of afterload), and the ventricular-arterial coupling ratio (Ea/Ees). Mean age was 65±13 years, 30% were female, and 54.7% had ischemic heart disease. During six months of follow-up, eight patients died, three withdrew their consent, and four were lost to follow-up. 102 patients were included in pressure-volume analyses. After six months of sacubitril/valsartan treatment, Ees increased (0.66mmHg/ml [IQR 0.45-0.94] vs. 0.78mmHg/ml [IQR 0.57-1.10], p=0.001), Ea decreased (1.76mmHg/ml [IQR 1.48-2.13] vs. 1.62mmHg/ml [IQR 1.36-1.96], p=0.014), and the Ea/Ees ratio improved (2.52 [IQR 1.88-4.05] vs. 1.93 [IQR 1.50-2.63], p<0.001). LV end-diastolic pressure and LV volumes were reduced, and LVEF increased from 33% to 43% (both p<0.001). Clinical improvement occurred in NYHA functional class, NT-proBNP level, and 6-minute walking distance. Change in LVEF correlated with change in Ees (r=0.33, p=0.0008), while change in NT-proBNP was associated with change in LVEDP (r=0.42, p<0.0001). In conclusion, sacubitril/valsartan is associated with improved ventricular-arterial coupling by enhancing LV contractility and reducing afterload. Beyond LV reverse remodeling, optimized ventricular-arterial interaction may contribute to the favorable outcome of sacubitril/valsartan treatment in HF with reduced EF.

Association of ventricular-arterial interaction with left ventricular remodelling after acute myocardial infarction: a 2-year follow-up study

Abstract Background/Introduction Adverse left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) is associated with heart failure. Purpose We aimed to investigated the association of ventricular-arterial interaction with LV remodelling in patients with STEMI. Methods In 109 patients within 48 hours of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (1) pulse wave velocity (PWV-Complior), (2) LV global longitudinal strain (GLS) and left atrial strain, (3) PWV/GLS ratio as a marker of ventricular-arterial interaction, and (4) LV end-diastolic and end-systolic volumes. A &amp;gt;15% decrease in LV end-systolic volume at 2-years follow-up was considered as a criterion of reverse LV remodelling. Results Compared with baseline, all patients had reduced PWV, PWV/GLS, LV end-diastolic and end-systolic volumes, while GLS and reservoir left atrial strain were increased (p&amp;lt;0.05) after 2 years. Both baseline and percentage change of PWV/GLS ratio were associated with LV end-systolic volume percentage change at 2 years (r=0.43, p=0.012 and r=0.35, p=0.038, respectively). Patients with LV end-systolic volume reduction &amp;gt;15% had lower baseline PWV and PWV/GLS and higher GLS and left atrial strain than patients with LV end-systolic volume reduction &amp;lt;15% (p&amp;lt;0.05). Multivariable analysis revealed that PWV and PWV/GLS were independently associated with LV remodelling. A baseline value of PWV of 8.1m/s and PWV/GLS of -0.52m/s% had a sensitivity of 84% and 82% and a specificity of 80% and 77% respectively for prediction of LV remodelling (area under the curve: 0.751, p=0.001 and 0.779, p&amp;lt;0.001). Conclusion Ventricular-arterial interaction is an independent predictor of LV remodelling after 2 years of the ischemic event.

Association of aortic stiffness early post myocardial infarction with left ventricular remodelling.

Adverse left ventricular (LV) remodelling after myocardial infarction is associated with heart failure. We investigated whether aortic stiffness during acute ST-segment elevation myocardial infarction is associated with LV remodelling at long-term follow-up. In 109 patients within 48 h of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (a) carotid to femoral pulse wave velocity (PWV), (b) LV global longitudinal strain (GLS) and left atrial strain using speckle-tracking echocardiography, (c) PWV/GLS ratio as a surrogate marker of ventricular-arterial interaction, and (d) LV end-diastolic and end-systolic volumes. A > 15% decrease from the baseline in LV end-systolic volume at 2-year follow-up was considered as a criterion of reverse LV remodelling. Compared with baseline, all patients had reduced PWV, LV end-diastolic and end-systolic volumes while PWV/GLS, GLS and reservoir left atrial strain were improved (p < .05) after 2 years. Baseline values of PWV, GLS, PWV/GLS ratio and reservoir left atrial strain were associated with percentage change of LV end-systolic volume at 2 years (p < .05). Multivariable analysis revealed that lower baseline values of PWV and a less impaired GLS and PWV/GLS were independently associated with reverse LV remodelling at 2 years with a C-statistic of .748, .711 and .787, respectively. Aortic stiffness early post-infarction determines LV remodelling after 2 years of the ischemic event despite post successful revascularization. http://www. gov. Unique identifier: NCT03984123, 30/04/2020.

Abstract P230: Central Artery Pulsatile Hemodynamics Are Associated With Cerebral Total, Periventricular, And Deep White Matter Lesions: Role Of Reservoir-excess Pressure Components.

Introduction: Accumulating evidence suggests that increased central, rather than peripheral, blood pressure (BP) may be a better predictor of cardiovascular risk. The shape of the central BP waveform is determined by ventricular-arterial interactions that can be quantified via novel hemodynamic analyses, from which some parameters have been implicated in the development of cardiac, vascular, and renal dysfunction. Comparatively, the potential effect of central pulsatile hemodynamics on brain structure has been understudied. Thus, we sought to determine the association of novel central hemodynamic parameters with cerebral white matter lesions. Methods: Central BP waveforms were measured in 130 healthy adults (age 63±6y; 58% female) via non-invasive carotid tonometry and modeled using reservoir-excess pressure analysis to separate the central BP waveform into a reservoir (Rp TI ) and excess (Ep TI ) pressure component. Systolic (Sk) and diastolic (Dk) rate constants were estimated from the rate of increase and decrease of the Rp TI component, respectively. Total, periventricular, and deep cerebral white matter lesion volumes (WMLV) were estimated from T2 weighted and FLAIR MRI and adjusted for total intracranial volume. Results: Both Sk and Ep TI were correlated with total (Sk: r = -0.19, p = 0.033; Ep TI : r = 0.21, p = 0.016), periventricular (Sk: r = -0.18, p = 0.037; Ep TI : r = 0.23, p = 0.009), and deep (Sk: r = -0.28, p = 0.002; Ep TI : r = 0.20, p = 0.027) WMLV. The association of Sk with total ( B = -0.032; 95% confidence interval [CI] = -0.054, -0.010; p = 0.0056), periventricular ( B = -0.030; 95%CI = -0.051, -0.009; p = 0.0063), and deep ( B = -0.064; 95%CI = -0.101, -0.028; p &lt;0.001) WMLV remained significant in multivariable analyses adjusting for age, sex, BMI, peripheral pulse pressure, carotid-femoral pulse wave velocity, heart rate, and non-HDL cholesterol. Additionally, the association between Ep TI and deep WMLV persisted in multivariable analysis ( B = 0.158; 95%CI = 0.045, 0.271; p = 0.007). Conclusion: Pulsatile components of central artery hemodynamics are associated with cerebral WMLV independent of traditional cardiovascular risk factors. In particular, Sk may represent a novel biomarker of early central BP-related cerebral white matter damage.

IMPACT OF DIABETES MELLITUS ON ARTERIAL STIFFNESS, AND PULSATILE HEMODYNAMICS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

Objective: The aim of the current study was to characterize different parameters of arterial stiffness and pulsatile hemodynamics in patients with arterial hypertension and metabolic syndrome according the presence of diabetes mellitus and diastolic dysfunction. Design and method: 121 consecutive patients with left ventricular ejection fraction &gt; 40% were included in the study. LV diastolic function was assessed using pulsed wave Doppler on transthoracic echocardiography. Brachial-ankle pulse wave velocity (baPWV) and the cardio-ankle vascular index (CAVI) was measured using a VaSera VS-1500® device (Fukuda Denshi). Ambulatory BP monitoring over 24 hours was performed using the Mobilograph device (IEM, Stolberg, Germany) which measures brachial and central (aortic) BP, as well as time-resolved waveforms, allowing for ambulatory pulse wave analysis (including wave separation into forward and backward waves and reflection magnitude) Results: Among 121 patients included, diabetes mellitus was present in 55 (54.5%) and diastolic dysfunction in 54 (45.4%). The presence of impaired myocardial relaxation on echocardiography was associated with markedly increase of arterial stiffness parameters – CAVI (8.7 vs 8.1, p = 0.03), PWV (8.8 vs 7.9, p = 0.001), central hemodynamics - central SBP (129.4 vs 114 mmHg, p&lt;0.001), cardiac output and total peripheral resistance (1.34 vs 1.25, p = 0.001) and pulsatile hemodynamics - with reduced reflection magnitude (60.7 vs 63, p = 0.04). Diabetic subjects with HFpEF exhibited a markedly greater left ventricular wall thickness and left atrium size on echocardiography. Pronounced aortic stiffening was also observed in the diabetic group (pulse wave velocity, 8.7 vs 7.9, p, 0.001; cardio-ankle vascular index, 9.1 vs 7.8, p&lt;0.001), with an adverse pulsatile hemodynamic profile characterized by increased forward and backward wave amplitude and reduced reflection magnitude (61 vs 64.8, p = 0.05). Conclusions: The presence of diastolic dysfunction is associated with changes of arterial stiffness and pulsatile hemodynamics. Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile hemodynamics, and ventricular-arterial interactions in HFpEF.

Data-driven computational models of ventricular-arterial hemodynamics in pediatric pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a complex disease involving increased resistance in the pulmonary arteries and subsequent right ventricular (RV) remodeling. Ventricular-arterial interactions are fundamental to PAH pathophysiology but are rarely captured in computational models. It is important to identify metrics that capture and quantify these interactions to inform our understanding of this disease as well as potentially facilitate patient stratification. Towards this end, we developed and calibrated two multi-scale high-resolution closed-loop computational models using open-source software: a high-resolution arterial model implemented using CRIMSON, and a high-resolution ventricular model implemented using FEniCS. Models were constructed with clinical data including non-invasive imaging and invasive hemodynamic measurements from a cohort of pediatric PAH patients. A contribution of this work is the discussion of inconsistencies in anatomical and hemodynamic data routinely acquired in PAH patients. We proposed and implemented strategies to mitigate these inconsistencies, and subsequently use this data to inform and calibrate computational models of the ventricles and large arteries. Computational models based on adjusted clinical data were calibrated until the simulated results for the high-resolution arterial models matched within 10% of adjusted data consisting of pressure and flow, whereas the high-resolution ventricular models were calibrated until simulation results matched adjusted data of volume and pressure waveforms within 10%. A statistical analysis was performed to correlate numerous data-derived and model-derived metrics with clinically assessed disease severity. Several model-derived metrics were strongly correlated with clinically assessed disease severity, suggesting that computational models may aid in assessing PAH severity.

AI-Based Estimation of End-Systolic Elastance From Arm-Pressure and Systolic Time Intervals.

Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular-arterial interaction. Previous methods for the Ees estimation require the use of the echocardiographic ejection fraction (EF). However, given that EF expresses the stroke volume as a fraction of end-diastolic volume (EDV), accurate interpretation of EF is attainable only with the additional measurement of EDV. Hence, there is still need for a simple, reliable, noninvasive method to estimate Ees. This study proposes a novel artificial intelligence—based approach to estimate Ees using the information embedded in clinically relevant systolic time intervals, namely the pre-ejection period (PEP) and ejection time (ET). We developed a training/testing scheme using virtual subjects (n = 4,645) from a previously validated in-silico model. Extreme Gradient Boosting regressor was employed to model Ees using as inputs arm cuff pressure, PEP, and ET. Results showed that Ees can be predicted with high accuracy achieving a normalized RMSE equal to 9.15% (r = 0.92) for a wide range of Ees values from 1.2 to 4.5 mmHg/ml. The proposed model was found to be less sensitive to measurement errors (±10–30% of the actual value) in blood pressure, presenting low test errors for the different levels of noise (RMSE did not exceed 0.32 mmHg/ml). In contrast, a high sensitivity was reported for measurements errors in the systolic timing features. It was demonstrated that Ees can be reliably estimated from the traditional arm-pressure and echocardiographic PEP and ET. This approach constitutes a step towards the development of an easy and clinically applicable method for assessing left ventricular systolic function.

Physiological and clinical insights from reservoir-excess pressure analysis.

There is a growing body of evidence indicating that reservoir-excess pressure model parameters provide physiological and clinical insights above and beyond standard blood pressure (BP) and pulse waveform analysis. This information has never been collectively examined and was the aim of this review. Cardiovascular disease is the leading cause of mortality worldwide, with BP as the greatest cardiovascular disease risk factor. However, brachial systolic and diastolic BP provide limited information on the underlying BP waveform, missing important BP-related cardiovascular risk. A comprehensive analysis of the BP waveform is provided by parameters derived via the reservoir-excess pressure model, which include reservoir pressure, excess pressure, and systolic and diastolic rate constants and Pinfinity. These parameters, derived from the arterial BP waveform, provide information on the underlying arterial physiology and ventricular-arterial interactions otherwise missed by conventional BP and waveform indices. Application of the reservoir-excess pressure model in the clinical setting may facilitate a better understanding and earlier identification of cardiovascular dysfunction associated with disease. Indeed, reservoir-excess pressure parameters have been associated with sub-clinical markers of end-organ damage, cardiac and vascular dysfunction, and future cardiovascular events and mortality beyond conventional risk factors. In the future, greater understanding is needed on how the underlying physiology of the reservoir-excess pressure parameters informs cardiovascular disease risk prediction over conventional BP and waveform indices. Additional consideration should be given to the application of the reservoir-excess pressure model in clinical practice using new technologies embedded into conventional BP assessment methods.

Abstract 16138: Validation of a Non-invasive Approach for the Assessment of Left Ventricular-arterial Coupling Following Transcatheter Aortic Valve Replacement

Introduction: Transcatheter aortic valve replacement (TAVR) is an established treatment for patients with severe, symptomatic aortic stenosis (AS). Ventriculoarterial (LV-arterial) coupling defined as the ratio of total arterial elastance (Ea) to left ventricular end-systolic elastance (Ees) reflects effective cardiac energetics and is a well-accepted index for quantification of LV-arterial coupling. Despite its usefulness, estimating Ees/Ea has technical difficulties. Intrinsic Frequency (IF) method is a noninvasive and single waveform system-based approach for quantification of LV-arterial coupling. The objective of this study was to compare IF variables with Ea/Ees in predicting optimum LV-arterial energetics following TAVR. Method: Twenty-eight patients with severe AS, undergoing TAVR were included. Mean age was 85±4, 53% male with mean ejection fraction 59±6.4. IFs during systole (ω1), diastole (ω2), and total IF variation (Δω=ω1-ω2) were computed from the ascending aortic pressure waveforms at baseline and following TAVR. Ea/Ees was computed using single-beat technique proposed by Takeuchi et al. ( Circulation . 1991;83(1):202-212). Results: There was a significant decrease in Ea/Ees (p&lt;0.001) toward optimum coupling immediately after TAVR (Figure 1a). There was a statistically significant correlation between Ea/Ees and Δω (r= 0.68, p&lt;0.01) (Figure 1b). Conclusion: IF appears to be an accurate and reliable index for quantification of LV-arterial coupling given significant concordance with Ea/Ees. The management of patients with acutely altered hemodynamic states post TAVR can benefit from the assessment of LV-arterial coupling. Since IFs can be measured noninvasively using hand-held devices (e.g. an iPhone), this approach should broaden the clinical applicability of this useful parameter for assessing systolic function, therapeutic response and ventricular-arterial interaction post TAVR.

Long-term antihypertensive treatment improves ventricular-arterial interaction in hypertensive patients: a 3-year follow-up study

Abstract Background We investigated the effects of antihypertensive treatment on vascular function, longitudinal deformation and ventricular-arterial interaction in hypertensives. Methods In 200 untreated patients with arterial hypertension (age 52.5±11.6 years, 56% females), we measured at baseline and after a 3-year of antihypertensive treatment (160 received ACEi± diuretics and 40 CCBs± diuretics): a) 24h ambulatory blood pressure b) Carotid-femoral pulse wave velocity (PWV) b) Coronary flow reserve (CFR), LV mass index (LVMI), the global longitudinal strain (GLS). We calculated the ratio of PWV/GLS (-m/sec%) reflecting the ventricular-arterial interaction. Results Compared to baseline, there was an improvement of GLS (−19.9±3.4 vs. −18.7±3.1%), post-treatment. In parallel, there were improvement in CFR (2.72±0.61 vs. 2.55±0.64), PWV (10.3±1.9 vs. 11.2±2.1 m/s), LVMI and PWV/GLS (−0.539±0.146 vs. −0.618±0.178 -m/sec%) (p&amp;lt;0.01 for all comparisons). By multivariate analysis, the reduction of 24h meanBP as well as PWV independently determined the respective improvement of GLS (b=0.478, b=0.248, respectively, p&amp;lt;0.001). By ANOVA, the interaction term between changes of all the above parameters and antihypertensive treatment (ACE inhibitors vs calcium channel blockers) was not significant (p&amp;gt;0.05). Conclusions Long-term optimal blood pressure control with ACE inhibitors and CCBs improves LV longitudinal deformation along with reduction of arterial stiffness, leading to improved ventricular-arterial interaction in hypertensives. Funding Acknowledgement Type of funding source: None

Increased arterial stiffness during acute myocardial infarction results in adverse cardiac remodelling: a two year follow-up study

Abstract Increased arterial stiffness is associated with adverse cardiac events. However, it not clear whether increased arterial stiffness at the early phase of acute myocardial infraction (AMI) is associated with adverse left ventricular remodelling. Methods We examined 80 patients with STEMI (53±16 years, 80% male, 42% anterior AMI, LVEF=49±15%) after successful revascularisation by echocardiography 48h after admission and 2 years after the index event. We measured a) left-ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) using the Simpson Method b) global longitundinal strain (GLS) by speckle tracking imaging c) carotid-femoral pulse wave velocity (PWV, augmentation index and central Aortic pressures by Complior apparatus d) The ratio of PWV/GLS as a marker of ventricular-arterial interaction. Results LVEDV and LVESV were decreased while GLS was improved after the 2-year follow-up period (from 103.3±30 to 89.1±37ml, p=0.004, 58.3±25 to 57.6±25, p=0.05, −16.1±4.7 to 17.5±3.2%, p=0.03 respectively). Baseline PWV, GLS and the ratio PWV/GLS were associated with the percent change of LVESV at 2 years (p=0.033, p=0.04 and p=0.035 respectively) after adjustment for type of MI (anterior vs other location), baseline troponin blood pressure and medication. Patients with PWV &amp;gt;10.6 m/s (upper tercile) had similar baseline LVESV (56.5±18 to 57.2±24 ml, p=0.8) but higher LVESV at 2 years follow-up (74.4±35 to 55.9±24 ml, p=0.03) resulting in a greater percent increase of LVESV compared to patients with baseline PWV &amp;lt;10.6m/s (+26% vs −5% p=0.012). Conclusion Increased arterial stiffness in the early phase of AMI impairs ventricular-arterial coupling resulting in adverse LV remodeling despite successful revascularization. Funding Acknowledgement Type of funding source: None

Effects of glucagon like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on vascular function and myocardial work index in patient with type-2 diabetes

Abstract Background/Introduction Type-2 diabetes mellitus (T2DM) is associated with endothelial and myocardial dysfunction. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on vascular and cardiac function of T2DM patients. Methods A hundred-sixty T2DM patients were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (marker of glycocalyx thickness), b) pulse wave velocity (PWV), central systolic blood pressure (cSBP), c) global LV longitudinal (GLS), circumferential (GCS) and radial (GRS) strain, d) the ratio PWV/GLS, as an index of ventricular-arterial interaction, e) myocardial work index (GWI) using speckle tracking imaging. Results Twelve months post-treatment, all patients improved PBR, PWV, GLS, GCS and GRS (p&amp;lt;0.05). GLP-1RA, SGLT-2i and their combination showed a greater reduction of PBR, PWV and cSBP than insulin, despite a similar HbA1c reduction (p&amp;lt;0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater decrease of PWV/GLS (28.1% and 31% vs. 11.1% and 14.5%) and a greater increase of GWI (12.7% and 17.4% vs. 3.1% and 2%) compared with insulin or SGLT-2i. SGLT-2i or GLP-1RA+SGLT-2i showed a greater decrease of PWV (10.1% and 13%), cSBP than insulin or GLP-1RA (PWV: 3.6% and 8.6%) (p&amp;lt;0.05 for all comparisons) (Table 1). The dual therapy showed the greatest effect on measured markers in patients with LVEF &amp;lt;55% (p&amp;lt;0.05). Conclusions Twelve-month treatment with GLP-1RA, SGLT-2i and their combination showed a greater improvement of vascular markers and effective cardiac work than insulin in T2DM. The combined therapy was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

On the severity of aortic stenosis in ascending aortic aneurysm: A computational tool to examine ventricular-arterial interaction and aortic wall stress

An ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular consequence of vessel dilatation that portends adverse events and death. From a clinical perspective, ATAA should not be treated as an isolated disease, and surgery is often carried out in the presence of AS, aortic insufficiency or a calcified valve leaflet. Aortic stenosis (AS) is common in ATAAs and leads to both vessel rigidity and left ventricular (LV) impairment. In this study, lumped-parameter modeling and computational analysis were used to assess the change in the wall shear stress (WSS) and intramural wall stress of patient-specific ATAA models with different degrees of AS (i.e., mild to severe). The ATAAs of four patients were reconstructed from imaging data and AS was simulated virtually using the lumped-based CircAdapt tool using clinical and echocardiographic data. Results show that LV work derived from pressure-volume loops increased with the severity of AS. Post-stenotic hemodynamic and structural variables markedly increased with AS severity, with WSS showing a 10-fold increase for the most severe AS model as compared to the baseline model with a well-functioning aortic valve. Most importantly, the increase in WSS and aortic wall stress was associated with pronounced values of valvulo-arterial impedance as an indicator of LV dysfunction. This study provides novel insights into progression of AS in patients with ATAAs at high risk of adverse events, and the potential value of valvulo-arterial impedance to predict changes in hemodynamic and structural parameters with the severity of AS.

Cardiac Work: A New Parameter to Asses the Ventricular Arterial Interaction in Patients with Repaired Congenital Heart Disease

BACKGROUND: The left ventricle (LV) systolic function is usually assessed by the cardiac output (CO) parameters such as ejection fraction and shortening fraction. However, these parameters do not take into consideration the role of afterload on LV contractility. Cardiac work (CW) is a parameter which combines the afterload and LV cardiac output to assess the cardiac contractility and the ventricular arterial interaction. CW is measured as the product of CO and mean arterial pressure (MAP). In adult patients with chronic heart failure, low resting CW has been associated with poorer outcomes and higher mortality. However, the role of CW in patients with …

Cardiac Work: A New Parameter to Asses the Ventricular Arterial Interaction in Patients with Repaired Congenital Heart Disease

Cardiac Work: A New Parameter to Asses the Ventricular Arterial Interaction in Patients with Repaired Congenital Heart Disease

Optimal Blood Pressure Control Improves Left Ventricular Torsional Deformation and Vascular Function in Newly Diagnosed Hypertensives: a 3-Year Follow-up Study.

We investigated the effects of optimizing blood pressure control on cardiac deformation and vascular function. For this purpose, in 200 untreated patients with essential hypertension, we assessed at baseline as well as after 3years of optimal blood pressure control: arterial stiffness and coronary microcirculatory function as well as longitudinal and torsional deformation parameters. Compared to baseline, after 3years of optimal blood pressure control, there was an improvement of longitudinal strain, twisting as well as untwisting parameters of the left ventricle. In parallel, there was an improvement in coronary microcirculatory function, arterial stiffness, left ventricular mass, and ventricular-arterial interaction. The reduction of arterial stiffness was independently associated with the respective improvement of cardiac deformation markers and coronary flow reserve after adjusting for blood pressure improvement. Blood pressure optimization improves LV longitudinal and torsional mechanics in hypertensives in parallel with arterial stiffness, resulting in improved ventricular-arterial interaction and coronary flow reserve. Trial registration: ClinicalTrials.gov Identifier: NCT02346695.

414 Ventricular-arterial interaction predicts response to cardiac resynchronization therapy: a link with improvement of endothelial function and arterial elastic properties

Abstract Background Endothelial dysfunction (ED) is a hall mark of chronic heart failure and has been linked to disease progression, hospitalizations and mortality. Purpose to evaluate the impact of cardiac resynchronization therapy (CRT) in ED and to determine predictors of response to CRT Methods CRT recipients from 19/07/2016 until 19/10/2018 were studied at baseline and 3 months after. In each visit we evaluated a 12 lead ECG, carotid to femoral pulse wave velocity (cfPWV), flow-mediated dilatation of the brachial artery (FMD), left ventricle ejection fraction (LVEF) and left ventricle (LV) global longitudinal strain (GLS). We evaluated arterial elastance (Ea) to ventricular elastance (Ees) ratio (Ea/Ees) by echocardiography and the ratio of cfPWV to GLS, as valid markers of ventricular-arterial interaction. We also assessed the layer of endothelial glycocalyx by measurement of Perfused Boundary Region (PBR) of the sublingual microvessel range:5-25 microns. Results 32 patients with a mean age 65.5 (±10.9) years and severe LV systolic dysfunction were enrolled. During follow-up, LVEF, GLS, LVESV and all ED markers exhibited significant improvement (table 1). 23 patients were responders. Among the baseline vascular function markers, only the ratio cfPWV/GLS predicted response to CRT (OR: 0.245, 95%CI: 0.042-0.759, p = 0.044).Threshold analysis showed that the best threshold of cfPWV/GLS for response to CRT was 2.75 (specificity: 0.67%, sensitivity: 0.94%). Conclusions After 3 months of CRT, endothelial function, arterial elasticity and ventricular arterial interaction are improved. The baseline ratio cfPWV/GLS, a novel marker of ventricular arterial interaction, can be applied to predict response to CRT. table 1 Baseline Follow-up Change Measurement mean (sd) mean (sd) mean (sd) p-value SBP (mmHg) 126 (19) 128 (16) 2.18 (11.98) 0,465 DBP (mmHg) 79 (9) 80 (9) 1.06 (8.58) 0,618 LVEF (%) 27 (7) 35 (9) 7.50 (4.77) &amp;lt;0.001 LVESV (mL) 151 (42) 120 (46) -26.91 (17.20) &amp;lt;0.001 GLS (%) 6.47 (2.89) 9.33 (4.18) 2.85 (2.28) &amp;lt;0.001 FMD (%) 5.88 (2.79) 10.25 (3.67) 4.37 (3.34) &amp;lt;0.001 Ea/Ees 2.81 (1.10) 2.04 (0.99) -0.77 (0.47) &amp;lt;0.001 cfPWV 11.11 (2.61) 10.01 (2.45) -1.10 (1.56) 0,003 PBR 5-25(microns) 2.26 (0.20) 2.14 (0.24) -0.13 (0.25) 0,028 cfPWV/GLS 2.18 (1.46) 1.45 (1.11) -0.73 (0.55) &amp;lt;0.001 Measurements at baseline, follow-up and their change during study Abstract 414 Figure. picture 1

Disturbed ventricular-arterial coupling and increased left atrial stiffness in a patient with heart failure with preserved ejection fraction and hyperaldosteronism: a case report

BackgroundAldosterone is involved in almost all parts of the cardiovascular system. Hyperaldosteronism causes arterial hypertension and might predispose to stroke, atrial fibrillation, and heart failure.Case summaryA 60-year-old obese woman with long-standing hypertension, hypokalaemia, and shortness of breath was admitted to our hospital. Hypertension was caused by primary hyperaldosteronism due to an adenoma of the adrenal gland. Detailed transthoracic echocardiography revealed diastolic dysfunction, disturbed ventricular–arterial interaction, and atrial compliance resulting in heart failure with preserved ejection fraction (HFPEF). Three months of aldosterone antagonist treatment improved ventricular–arterial coupling, while left ventricular diastolic and atrial dysfunction remained unchanged.DiscussionPresumably, hyperaldosteronism is the reason for HFPEF in this case. Standard criteria to diagnose HFPEF include clinical symptoms of heart failure and an ejection fraction (EF) >50% as well as echocardiographically or invasively assessed elevated filling pressures. Single beat pressure-volume analysis gives insights on the pathophysiology of increased filling pressures, showing in our case diastolic dysfunction as well as disturbed ventricular–arterial interaction. Three months of aldosterone antagonist treatment reduced blood pressure with concomitant improvement of ventricular–arterial interaction, thereby reducing stroke work while stroke volume remained nearly unchanged. Diastolic dysfunction and increased atrial stiffness were unaltered.

Influence of concomitant chronic obstructive pulmonary disease on left ventricular-arterial interaction in patients with ischemic cardiomyopathy

Aim. To assess the influence of concomitant chronic obstructive pulmonary disease (COPD) on the parameters of left ventricular-arterial interaction in patients with ischemic cardiomyopathy (ICMP).Material and methods. We examined 130 patients with ICMP and 42 patients with ICMP and COPD. All patients underwent transthoracic echocardiography using the MyLab 70 (Italy) according standard method, followed by calculation of the left ventricular-arterial interaction and left ventricular (LV) energy. Statistical data processing was performed using the program “Statistica 12.0” (Stat Soft, Inc., USA).Results. We found that patients with isolated ICMP and in combination with COPD often have a functional imbalance between the activity of LV and arterial system, as evidenced by an increase in the left ventricular-arterial interaction ratio. The increase in the left ventricular-arterial interaction ratio is due to an insufficient increase in left ventricular stiffness, but not a change in the elastic properties of the arterial system. This is indicated by a pronounced decrease in left ventricular elasticity against the background of the relative constancy of arterial elasticity. At the same time, in patients with ICMP and COPD we detected significantly more severe impairment in the parameters of left ventricular-arterial interaction and LV energy than in isolated pathology.Conclusion. The presence of COPD in patients with ICMP allows us to consider it as a significant negatively modifying factor that has a negative impact on the functionality of LV and parameters of left ventricular-arterial interaction.