Preload Reserve Research Articles

Multifaced risk factors and clinical impact of a deep Y descent in patients with heart failure irrespective of RV-PA coupling

BackgroundA deep Y descent in the jugular venous pulse (JVP) is associated with diseases such as a decrease in right ventricular (RV) preload reserve. The present study investigated the relationship between RV-pulmonary arterial (PA) coupling and a deep Y descent, examined risk factors for a deep Y descent and clarified whether a deep Y descent was an independent risk factor for cardiac events irrespective of RV-PA coupling in patients with heart failure (HF). MethodsWe enrolled 350 patients with HF who underwent echocardiography and JVP examination. A deep Y descent was identified by a deeper ‘Y’ descent than ‘X’ descent in the JVP waveform. We defined cardiac events of HF as follows: sudden death, death from HF, the emergent infusion of loop diuretics, or hospitalization for decompensated HF. Results and ConclusionsA deep Y descent and cardiac events were observed in 129 and 83 patients, respectively. The prevalence of a deep Y descent increased with decreases in the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary arterial pressure (SPAP) ratio. Not only the TAPSE/SPAP ratio (odds ratio,0.756 per0.1 mm/mmHg, 95 %confidence interval [CI], 0.660–0.866, p < 0.001), but also age, atrial fibrillation, and the use of beta-blockers were independent factors for a deep Y descent in multivariate logistic model. Multivariate Cox hazard model demonstrated that a deep Y descent was for cardiac events in patients with HF (Hazard ratio,2.682, 95 %CI, 1.599–4.497, p < 0.001) irrespective of the TAPSE/SPAP ratio. The development of therapeutic strategies based on central venous waveform may be needed for patients with HF.

Right Heart Reserve Function Assessed With Fluid Loading Predicts Late Right Heart Failure After Left Ventricular Assist Device Implantation

BackgroundA left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation that is associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid-loading test with right heart catheterization to evaluate right heart preload reserve function and investigate its impact on LRHF. MethodsPatients aged > 18 years who received a continuous-flow LVAD between November 2007 and December 2022 at our institution, and underwent right heart catheterization with saline loading (10 mL/kg for 15 minutes) 1 month after LVAD implantation, were included. ResultsOverall, 31 cases of LRHF or death (right heart failure [RHF] group) occurred in 149 patients. In the RHF vs the non-RHF groups, the pulmonary artery pulsatility index (PAPi) at rest (1.8 ± 0.89 vs 2.5 ± 1.4, P = 0.02) and the right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96 ± 0.32 vs 1.1 ± 0.20, P = 0.03) were significantly different. The PAPi at rest and the RVSWi change ratio with saline loading were identified as postoperative risks for LRHF and death. The cohort was divided into 3 groups based on whether the PAPi at rest and the RVSWi change ratio were low. The event-free curve differed significantly among the 3 groups (P < 0.001). ConclusionsHemodynamic assessment with saline loading can evaluate the right ventricular preload reserve function of patients with an LVAD. A low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation.

The clinical use of stress echocardiography in chronic coronary syndromes and beyond coronary artery disease: a clinical consensus statement from the European Association of Cardiovascular Imaging of the ESC.

Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.

854 SODIUM NITROPRUSSIDE IN ACUTE HEART FAILURE: EFFECTS ON LV AFTERLOAD AND VENTRICULO-ARTERIAL COUPLING

Abstract Background Acute heart failure (AHF) with left ventricle (LV) dysfunction is characterized by a condition of afterload mismatch without preload reserve. LV ejection fraction (LVEF) and stroke volume (SV) become thus dependent on the afterload. Owing to its arteriolar vasodilator properties, sodium nitroprusside (SNP) may reduce LV afterload and result particularly beneficial in this setting, improving LV ejection and ventriculo-arterial coupling (VAC). Hypothesis We aimed to assess the effect of SNP on LV afterload (arterial elastance, Ea), LV contractility (end-systolic elastance, Ees) and VAC (Ea/Ees ratio) in AHF patients. Methods Patients with AHF receiving SNP were prospectively enrolled and underwent Ea and Ees estimation with a single-beat echocardiographic method, before and after SNP infusion. The method was described by Chen et al (J Am Coll Cardiol, 2001) and Kelly et al (Circulation, 1992). Echocardiography was analyzed by a physician blinded to the images timing. Results A total of 36 AHF patients [69% male, age 70 (68, 76) years] received SNP infusion and were enrolled. Patients were admitted for acute coronary syndrome (47%) and for worsening heart failure (53%). SNP median dose was low: 0.30 (0.21-0.57) mcg/kg/min. SNP led to a trend to SBP reduction [140 (131-150) vs 158 (140-168) mmHg; p=0.002]. Heart rate did not change: 84 (75, 92) vs 83 (72, 94) bpm; p=0.800. Afterload (Ea) was reduced following SNP infusion: 2.2 (1.9, 2.7) vs 2.8 (2.4, 3.4) mmHg/mL; p&amp;lt;0.001. LV contractility (Ees) was unchanged: 1.3 (0.8, 2.2) vs 1.5 (0.9, 3.4) mmHg/mL; p=0.13. End-diastolic volume did not change: 148 (110, 205) vs 146 (108, 213) mL; p=0.880. These effects led to an increased SV: 56 (47, 67) vs 50 (38, 56) mL; p&amp;lt;0.001; p&amp;lt;0.001 and, subsequently to an increased EF [40 (30, 50) vs 30 (20, 40)%; p&amp;lt;0.001]. The VAC did not significantly change after SNP infusion: 1.5 (0.9-2.8) vs 1.6 (0.9-2.7); p=0.64. Conclusion In this report on consecutive AHF, low-dose SNP did not significantly affect VAC but led to a significant reduction in LV afterload and to a significant increase in SV and LVEF.

Abstract 12774: Detecting Change in Cardiopulmonary Bypass Blood Flow Rate With a Novel, Wireless, Wearable Doppler Ultrasound Patch: A Pilot Study

Introduction: Assessing preload reserve (PR) is important when managing cardiac surgery patients. Typically, a 10% change in cardiac output is used as a reference standard to gauge PR; how this change in cardiac output translates to common carotid artery (CCA) velocity is unknown. In this pilot study, we compared known changes in cardiopulmonary bypass (CPB) flow rate to those measured by a novel wireless, wearable Doppler ultrasound placed over the CCA. Methods: A sample of 14 adult patients undergoing elective CABG was studied. While on CPB, at least two changes in blood flow (one negative, one positive) were made. The corresponding change in CCA velocity was measured by a wearable continuous wave (CW) Doppler ultrasound patch. For each subject, CPB flow changes were determined from the displayed spectrogram by the peristaltic pulsation frequency and CCA velocity changes were calculated from the automated maximum velocity trace. 5-10s windows pre- and post-CPB speed changes were selected, with sufficient signal quality to determine both relative CPB flow and CCA velocity. A “dose-response” curve was fitted to the relative changes in flow and velocity for each subject, as shown in Fig. 1, and the CCA velocity change corresponding to a 10% change in CPB flow was calculated. Results: CPB flows ranged from 0.5-6.3L/min. Mean relative flow changes were -58 and 179%, corresponding to mean CCA velocity changes of -43 and 107%. A mean CCA velocity change of 14% was found to correspond to 10% CPB flow change, ranging from 1.5-27.8%. Conclusions: CCA velocity measured with the Doppler patch successfully tracked changes in CPB flow. A CCA velocity change of &gt;14% suggests a &gt;10% change in cardiac output. Although preliminary, these results provide another important parameter for predicting the response to preload using a novel, easy-to-use, wireless Doppler device.

Pulmonary congestion during Exercise stress Echocardiography in Hypertrophic Cardiomyopathy

BackgroundB-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in patients with hypertrophic cardiomyopathy (HCM).AimTo assess the clinical, anatomical and functional correlates of pulmonary congestion elicited by exercise in HCM.MethodsWe enrolled 128 HCM patients (age 52 ± 15 years, 72 males) consecutively referred for ESE (treadmill in 46, bicycle in 82 patients) in 10 quality-controlled centers from 7 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Serbia, Spain). ESE assessment at rest and peak stress included: mitral regurgitation (MR, score from 0 to 3); E/e’; systolic pulmonary arterial pressure (SPAP) and end-diastolic volume (EDV). Change from rest to stress was calculated for each variable. Reduced preload reserve was defined by a decrease in EDV during exercise. B-lines at rest and at peak exercise were assessed by lung ultrasound with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was ≥ 2.ResultsLUS was feasible in all subjects. B-lines were present in 13 patients at rest and in 38 during stress (10 vs 30%, p < 0.0001). When compared to patients without stress B-lines (n = 90), patients with B-lines (n = 38) had higher resting E/e’ (14 ± 6 vs. 11 ± 4, p = 0.016) and SPAP (33 ± 10 vs. 27 ± 7 mm Hg p = 0.002). At peak exercise, patients with B-lines had higher peak E/e’ (17 ± 6 vs. 13 ± 5 p = 0.003) and stress SPAP (55 ± 18 vs. 40 ± 12 mm Hg p < 0.0001), reduced preload reserve (68 vs. 30%, p = 0.001) and an increase in MR (42 vs. 17%, p = 0.013) compared to patients without congestion. Among baseline parameters, the number of B-lines and SPAP were the only independent predictors of exercise pulmonary congestion.ConclusionsTwo-thirds of HCM patients who develop pulmonary congestion on exercise had no evidence of B-lines at rest. Diastolic impairment and mitral regurgitation were key determinants of pulmonary congestion during ESE. These findings underscore the importance of evaluating hemodynamic stability by physiological stress in HCM, particularly in the presence of unexplained symptoms and functional limitation.

Hemodynamic Aberrancies in Left Ventricular Assist Device–Associated Heart Failure Syndromes

Hemodynamic Aberrancies in Left Ventricular Assist Device–Associated Heart Failure Syndromes

Changes of left ventricular remodeling due to increased afterload in patients with essential hypertension

BackgroundIt is unclear whether afterload mismatch occurs during the initial stage of essential hypertension (EHT). Additionally, critical left ventricular hypertrophy (LVH) between preserved and reduced systolic functions in hypertension is also unclear. Thus, we aimed to clarify these points. MethodsForty-five normal control subjects (NCS) and 140 EHT patients participated. EHT patients were subdivided into three groups: group I, without LVH (n = 37); group II, with LVH (n = 80); and group III, with LVH and LV heart failure (LVHF) (n = 23). Routine electrocardiographic and echocardiographic parameters, V5R/V6R ratio, relative wall thickness (RWT), LV mass (LVM) index, and peak systolic wall stress (PSWS) were measured. ResultsIn group I, LV systolic functions were preserved despite the increase of PSWS. In group II, LVH advanced, but LV systolic functions remained normal. A negative T-wave was observed in 69% of group II and 100% of group III. A significant correlation between RWT and LVM index was seen in NCS and groups I and II (r2 = 0.545, P < 0.0001) but not in group III. Afterload mismatch occurred in group III due to the decrease in V5R/V6R ratio, the increase of LV end-diastolic dimension, and the LV systolic dysfunctions, which are caused by exhaustion of preload reserve. The boundary of the LVM index between groups II and III was approximately 180 g/m2. ConclusionAfterload mismatch did not occur in group I, but it was observed in group III due to the exhaustion of preload reserve.

Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction.

Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described. This prospective, single-center study analyzed consecutive symptomatic patients with HFpEF diagnosed according to the 2016 European Society of Cardiology heart failure guidelines. Patients were grouped into LVEF 50% to 60% and LVEF >60% cohorts. All patients underwent cardiac magnetic resonance imaging. Transfemoral cardiac catheterization was performed to derive load-dependent and load-independent left ventricular (LV) properties on pressure-volume loop analyses. Fifty-six patients with HFpEF were enrolled and divided into LVEF 50% to 60% (n=21) and LVEF >60% (n=35) cohorts. On cardiac magnetic resonance imaging, the LVEF >60% cohort showed lower LV end-diastolic volumes (P=0.019) and end-systolic volumes (P=0.001) than the LVEF 50% to 60% cohort; stroke volume (P=0.821) did not differ between the cohorts. Extracellular volume fraction was higher in the LVEF 50% to 60% cohort than in the LVEF >60% cohort (0.332 versus 0.309; P=0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL; P<0.001) and passive diastolic stiffness (β constant, 0.032 versus 0.018; P=0.004) in the LVEF >60% cohort. Ventriculo-arterial coupling (end-systolic elastance/arterial elastance) at rest was in the range of optimized stroke work in the LVEF >60% cohort but was impaired in the LVEF 50% to 60% cohort (1.01 versus 0.80; P=0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL; P=0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²; P<0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg; P=0.023). LV stroke volume decreased in the LVEF >60% cohort (P=0.007) under exertion. Patients with HFpEF in whom LVEF ranged from 50% to 60% demonstrated reduced contractility, impaired ventriculo-arterial coupling, and higher extracellular volume fraction. In contrast, patients with HFpEF and a LVEF >60% demonstrated a hypercontractile state with excessive LV afterload and diminished preload reserve. A LVEF-based stratification of patients with HFpEF identified distinct morphologic and pathophysiologic subphenotypes.

Ability of Left Atrial Distensibility After Radiofrequency Catheter Ablation to Predict Recurrence of Atrial Fibrillation

This study sought to assess the left atrial (LA) functional recovery after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) and to evaluate the determining factor of procedural success of RFCA, using a novel preload stress echocardiography. A total of 111 patients with AF were prospectively recruited. The echocardiographic parameters were obtained during the leg-positive pressure (LPP) maneuver, both at baseline and midterm after RFCA. As an index of LA distensibility, the LA expansion index was calculated as (LAVmax - LAVmin)×100 / LAVmin. During a median follow-up period of 14.2 months, AF recurrence was observed in 23 patients (20.7%). In LA functional parameters at baseline, only the Δ LA expansion index was significantly larger in the success group (16 ± 11% vs 4 ± 9%, p <0.05). At midterm follow-up, the Δ LA expansion index significantly increased to 32 ± 19% (p <0.05), together with structural LA reverse remodeling only in the success group. Moreover, the Δ stroke volume index during the LPP stress test significantly increased only in the success group (from 2.3 ± 1.3 ml/m2 to 3.1 ± 4.8 ml/m2, p <0.05). In a multivariate analysis, left ventricular ejection fraction (hazard ratio 0.911, p <0.05) and baseline Δ LA expansion index (hazard ratio 0.827, p <0.001) were independent predictors of AF recurrence. In conclusion, the baseline Δ LA expansion index during LPP stress is a reliable marker for predicting procedural success after RFCA. Moreover, maintenance of sinus rhythm resulted in an improvement of the preload reserve after RFCA.

Feasibility and value of two-dimensional volumetric stress echocardiography.

Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Role of conduit volume as a compensatory mechanism to left atrial dysfunction in severe aortic stenosis

Abstract Background Left atrial (LA) function has a central role in maintaining optimal cardiac output despite impaired left ventricular (LV) diastolic function through atrial reservoir, conduit and contractile functions. In normal subjects, the contribution of LA volume (conduit and contractile) to LV filling volume is approximately 60–70% and the rest is completed by the conduit volume (CV) defined as the blood flow from pulmonary veins to LV during passive emptying that does not produce change in atrial volume. As LV filling pressures progressively increase, the limits of preload reserve are reached and LA serves predominantly as a conduit with increase in CV. Severe aortic stenosis is characterized by diastolic dysfunction (DD) in early stages of the disease and LA dysfunction in more advanced stages. Purpose The aim of the study was to analyze the role of CV as a compensatory mechanism to complete LV filling volume in presence of atrial dysfunction. Methods 210 patients (p) (age 69±11 years, 48% female) with severe aortic stenosis (aortic valve area index 0.37±0.12 cm2/m2) were studied with Doppler echocardiography. LA function were evaluated by LA (total) emptying fraction (LAEF) as the difference between maximum (Mx) (include conduit and contractile phases) and minimum (Mn) volumes/Mx volume x 100 and peak LA strain. The contribution of CV to SV was estimated as a percentage of SV (CV%): SV − (LA Mx − Mn volume)/SV x 100. LA volumes, SV and left ventricular ejection fraction (LVEF) were calculated by Simpson method. Grade of DD was classified according to ASE/EACVI recommendation and p were divided in 3 groups: DD grade I (98 p), DD grade II (74 p) and DD grade III (38 p). Results CV% were negatively related to LAEF (r=−0.57, p&amp;lt;0.0001) and peak LA strain (r=−0.38, p&amp;lt;0.001) and directly to the grade of DD (r=0.35, p&amp;lt;0.001). LVEF correlated with LAEF (r=0.57, p&amp;lt;0.0001) and CV% (r=−033, p&amp;lt;0.001). In group DD grade III SV was maintained by increase in CV% despite significant decrease in LAEF and peak LA strain. Conclusion LA dysfunction expressed as a decreased in LAEF and LA strain correlated with an increase in contribution of CV to SV (CV%). In patients with AS, as the DD progress, SV is maintained by increase in CV as a compensatory mechanism to LA dysfunction. Funding Acknowledgement Type of funding sources: None. Table

Clinical Application of the Fluid Challenge Approach in Goal-Directed Fluid Therapy: What Can We Learn From Human Studies?

Resuscitative fluid therapy aims to increase stroke volume (SV) and cardiac output (CO) and restore/improve tissue oxygen delivery in patients with circulatory failure. In individualized goal-directed fluid therapy (GDFT), fluids are titrated based on the assessment of responsiveness status (i.e., the ability of an individual to increase SV and CO in response to volume expansion). Fluid administration may increase venous return, SV and CO, but these effects may not be predictable in the clinical setting. The fluid challenge (FC) approach, which consists on the intravenous administration of small aliquots of fluids, over a relatively short period of time, to test if a patient has a preload reserve (i.e., the relative position on the Frank-Starling curve), has been used to guide fluid administration in critically ill humans. In responders to volume expansion (defined as individuals where SV or CO increases ≥10–15% from pre FC values), FC administration is repeated until the individual no longer presents a preload reserve (i.e., until increases in SV or CO are <10–15% from values preceding each FC) or until other signs of shock are resolved (e.g., hypotension). Even with the most recent technological developments, reliable and practical measurement of the response variable (SV or CO changes induced by a FC) has posed a challenge in GDFT. Among the methods used to evaluate fluid responsiveness in the human medical field, measurement of aortic flow velocity time integral by point-of-care echocardiography has been implemented as a surrogate of SV changes induced by a FC and seems a promising non-invasive tool to guide FC administration in animals with signs of circulatory failure. This narrative review discusses the development of GDFT based on the FC approach and the response variables used to assess fluid responsiveness status in humans and animals, aiming to open new perspectives on the application of this concept to the veterinary field.

Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40years), middle aged (n = 25, 40-65years), and elderly (n = 25, > 65years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14mL/m2, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Easy-to-use preload stress echocardiography by using combined dynamic postural stress can identify high-risk patients with heart failure with reduced ejection fraction.

AimsHaemodynamic assessment during stress testing is not commonly performed in patients with heart failure with reduced ejection fraction (HFrEF) because of its invasiveness, lower feasibility, and safety concerns. This study aimed to assess the haemodynamic characteristics of patients with HFrEF in response to non‐invasive preload stress during dynamic postural alterations achieved by combining both semi‐sitting position and passive leg‐lifting and to evaluate whether combined postural stress could be used for risk stratification in these patients.Methods and resultsFor this study, 101 patients with HFrEF and 35 age‐matched and sex‐matched healthy controls were prospectively recruited. After all standard echocardiographic measurements were obtained in the left decubitus position, all subjects underwent postural stress testing, which consisted of changing from semi‐sitting position to passive leg‐lifting. During a median follow‐up period of 12.2 months, 21 (21%) patients developed adverse cardiovascular events. In patients without adverse cardiovascular events, the stroke volume index (SVi) significantly changed from 28 ± 8 to 35 ± 10 mL/m2 (P < 0.001) during combined postural stress. By contrast, ΔSVi during combined dynamic postural stress was significantly smaller in patients with cardiovascular events than in those without events (ΔSVi 3.4 ± 4.0 vs. 6.4 ± 3.8 mL/m2, P = 0.002), which indicated severely diseased heart operated on a relatively flat portion of the Frank–Starling curve. In a multivariate Cox proportional hazard analysis, ΔSVi (hazard ratio 0.81, P = 0.02) was an independent predictor of future adverse cardiovascular events.ConclusionsThe combined assessment of dynamic postural stress is a non‐invasive, simple, quick, and easy‐to‐use clinical tool for assessing preload reserve and risk stratification in HFrEF patients.

Preload stress echocardiography by using dynamic postural alteration can identify high risk patients with heart failure with reduced ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Haemodynamic assessment during stress testing is not commonly performed for patients with heart failure with reduced ejection fraction (HFrEF) due to its invasiveness, less feasibility, and safety concerns. Passive leg-lifting (PLL) manoeuvres have been introduced as a simple alternative for non-invasive preload stress testing; however, the haemodynamic load imposed on the cardiovascular system is unsatisfactory, which precludes the accurate assessment of the preload reserve for patients with HF. Purpose The purpose of this study was to assess the haemodynamic characteristics of patients with HFrEF in response to a preload stress during dynamic postural alterations by combining the semi-sitting position (SSP) and PLL. We also evaluated whether combined postural stress could be used for risk stratification for these patients. Methods For this study, 101 patients with HFrEF and 35 age- and sex-matched normal controls were prospectively recruited. At each postural position (i.e., baseline, SSP, and PLL), all standard echocardiographic and Doppler variables were obtained. Adverse cardiac events were prespecified as the combined endpoints of death from or hospitalisation for deteriorated HF, or sudden cardiac death. Clinical follow-up was conducted for a median of 7 months. Results During PLL stress, the stroke volume index (SVi) significantly increased in both controls (from 40 ± 6 to 43 ± 6 mL/m², P = 0.03) and HFrEF patients (from 31 ± 9 to 34 ± 10 mL/m², P = 0.03). Conversely, during SSP stress, the SVi significantly decreased for both controls (from 40 ± 6 to 37 ± 6 mL/m², P = 0.03) and HFrEF patients (31 ± 9 to 28 ± 8 mL/m², P = 0.03). During the follow-up period, 16 patients developed cardiac events. In patients without events, the Frank-Starling mechanism was well preserved (Fig. A). Namely, the SVi significantly increased from 31 ± 9 to 35 ± 10 mL/m² (P = 0.02) during PLL stress, while the SVi significantly decreased from 31 ± 8 to 28 ± 8 mL/m² (P = 0.02) during SSP stress. In contrast, for patients with cardiac events, the SVi did not change during postural alterations (n.s), which indicated that the failing heart operates on the flat portion of the Frank-Starling curve (Fig. A). When patients were divided into three equal sub-groups based on the total difference in the SVi during dynamic postural stress, patients with impaired preload reserve (third trimester, ΔSVi ≤ 3.0 mL/m²) showed significantly worse event-free survival than the other two sub-groups (Fig. B; P &amp;lt; 0.001). In a Cox proportional-hazard analysis, baseline LVEF (hazard ratio 0.93; P = 0.04), and ΔSVi during postural stress (hazard ratio 0.76; P = 0.004) were predictors of future cardiac events. Conclusions The combined assessment of dynamic postural stress during PLL and SPP is a simple, time-saving, and easy-to-use clinical tool for the assessment of preload reserve for patients with HFrEF. Moreover, postural stress echocardiography proved to contribute to the risk stratification for these patients. Abstract Figure.

Impaired preload reserve is an important haemodynamic characteristics that discriminates between physiological ageing and overt heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood. Purpose The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography. Methods A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, &amp;gt;65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.). Results The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P &amp;lt; 0.001, respectively). Although baseline LV ejection fraction and cardiac output were quite comparable between groups, E/e’ ratio significantly increased with with ageing (ANOVA P &amp;lt; 0.001, Fig.). During LPP stress, E/e’ ratio significantly increased in the middle-aged and elderly groups (from 8.8 ± 2.7 to 9.7 ± 3.3, and from 11.4 ± 2.4 to 13.0 ± 2.2, P &amp;lt; 0.05, respectively), which was further deteriorated in HFpEF (from 16.8 ± 5.8 to 18.0 ± 7.6, P &amp;lt; 0.05). On the other hand, stroke volume index (SVi) significantly increased in each healthy group during LPP stress (young; from 45 ± 10 to 50 ± 11 mL/m², middle-age; from 39 ± 7 to 44 ± 6 mL/m² and elderly; from 37 ± 7 to 43 ± 8 mL/m², all P &amp;lt; 0.001), while SVi failed to increase in the HFpEF group (from 45 ± 13 to 45 ± 14 mL/m², P = 0.60). In a multivariate logistic regression analysis, LVMI (hazard ratio; HR 1.055, P &amp;lt; 0.05), baseline E/e’ (HR 1.444; P &amp;lt; 0.05), and ΔSVi (HR 0.755; P &amp;lt; 0.05) during LPP stress were the independent parameters that characterised overt HFpEF. Conclusions Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF. Abstract Figure.

Extracardiac Abnormalities of Preload Reserve: Mechanisms Underlying Exercise Limitation in Heart Failure with Preserved Ejection Fraction, Autonomic Dysfunction, and Liver Disease.

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.

Changes in left ventricular size, geometry, pump function and left heart pressures during healthy aging.

There are cross-sectional and longitudinal imaging studies using echocardiography and cardiac magnetic resonance in healthy adult subjects which have demonstrated associations of left ventricular (LV) structure and pump function with age. There are also cross-sectional data regarding the relationships of age with invasively measured left heart chamber pressures. Increasing age is associated with decreases in LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic length (LVEDL), stroke volume (SV) and cardiac output (CO), and increases in relative wall thickness (RWT), LV mass/LVEDV ratio (LVMVR) and ejection fraction (LVEF). Older age is not accompanied by a change in mean left atrial (LA) pressure, but there is both direct and indirect evidence which suggests that LV end-diastolic pressure (LVEDP) increases with age. LVEDV remains lower in older than younger subjects during fluid infusion and the resulting increases in LA pressure. The combination of an increase in LVEF with reductions of both SV and CO demonstrates an age-related increase in divergence between LVEF and LV pump function. A lower LVEDV in older compared to younger subjects can be characterized as an aging-related decrease in LV capacity, with the higher LVEDP in older subjects also indicating a reduction of preload reserve.