Ventricular-arterial Coupling Research Articles

Association between lung ultrasound B-lines and exercise-induced pulmonary hypertension in patients with connective tissue disease.

Identification of elevation in pulmonary pressures during exercise may provide prognostic and therapeutic implications in patients with connective tissue disease (CTD). Interstitial lung disease (ILD) is common in CTD patients and subtle interstitial abnormalities detected by lung ultrasound could predict exercise-induced pulmonary hypertension (PH). Echocardiography and lung ultrasound were performed at rest and bicycle exercise in CTD patients (n=41) and control subjects without CTD (n=24). Ultrasound B-lines were quantified by scanning four intercostal spaces in the right hemithorax. We examined the association between total B-lines at rest and the development of exercise-induced PH during ergometry exercise. Compared to controls, the number of total B-lines at rest was higher in CTD patients (0 [0, 0] vs 2 [0, 9], P<.0001) and was correlated with radiological severity of ILD assessed by computed tomography (fibrosis score, r=.70, P<.0001). Pulmonary artery systolic pressure (PASP) was increased with ergometry exercise in CTD compared to controls (48 ± 14vs 35 ± 13mm Hg, P=.0006). The number of total B-lines at rest was highly correlated with higher PASP (r=.52, P<.0001) and poor right ventricular pulmonary artery coupling (tricuspid annular plane systolic excursion/PASP ratio, r=-.31, P=.01) during peak exercise. The number of resting B-lines predicted the development of exercise-induced PH with an area under the curve .79 (P=.0003). These data may suggest the value of a simple resting assessment of lung ultrasound as a potential tool for assessing the risk of exercise-induced PH in CTD patients.

Echocardiographic Hemodynamic Heterogeneity of Advanced Heart Failure Patients as Compared to Patients with „Pre-Heart Failure”

Abstract Background Advanced heart failure (HF) represents a clinical entity encompassing severely symptomatic HF with severely dysfunctional left ventricles (LV). The single most important parameter for defining severe LV dysfunction and indicating the prescription of evidence-based therapies is LV ejection fraction (EF). We sought to investigate the hemodynamics by echocardiography in a cohort of advanced HF patients during a hospitalization for HF decompensation and assess the relevant differences when compared to a control cohort of asymptomatic patients with minor structural/functional cardiac abnormalities. Methods and results In this prospective study we selected 18 advanced HF patients and 12 asymptomatic pre-HF patients with only minor structural/functional abnormalities. The 2 groups were clearly delineated by size parameters (end -systolic and -diastolic diameters and volumes respectively, with very low p values p&lt;0.0001). Hemodynamic parameters were significantly different as well in the advanced HF group vs the ‘pre-HF’ group, including: ventricular-arterial coupling 1.745 vs. 0.895, p=0.0007; cardiac power output 0.762 vs. 0.932, p=0.044, systolic times ratio 0.406 vs. 0.200, p=0.0001. There were no significant differences for neither effective arterial elastance (Ea) and nor for cardiac index. Inside the advanced HF group, no correlation between LVEF and other parameters were found and none of these parameters could predict outcome. We observed a highly skewed variation of Ea in advanced HF patients. Conclusion Among the most severe HF patients, the hemodynamic interaction between the dysfunctional LV and the compensatory response of the peripheral system is heterogenous and cannot predict outcome by single parameters. In these patients, assessment of cardiac performance should no longer rely on LEVF alone.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure–volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure–volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end‐systolic pressure–volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end‐systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular‐arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow‐limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST‐segment depression on exercise); five patients without flow‐limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow‐limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

INTERRELATION OF INDICATORS OF LEFT VENTRICULAR-ARTERIAL COUPLING AND PARAMETERS OF LOCAL ARTERIAL STIFFNESS IN THE POSTINFARCTION PERIOD

Objective: To study the correlations between the parameters of the left ventricular-arterial coupling (LVAC) and the parameters of local arterial stiffness in patients after STEMI 6 months after revascularization. Design and method: 125 patients (mean age 51.2 ± 8.8 years) after STEMI were included in the study. The diagnosis was confirmed by biomarkers of myocardial necrosis, ECG, coronary angiography. Echocardiography was performed at the 7–9th day and 6 months after STEMI (MyLab, Esaote, Italy), followed by calculation of LVAC indices: arterial elastance (Ea), left ventricular elastance (Ees), LVAC index (Ea/Ees). The study of the right and left common carotid arteries (CCA) was carried out on a MyLab ultrasound scanner (Esaote, Italy) using high-frequency RF signal technology. The following parameters were recorded: QIMT - intima-media thickness, DC - lateral distensibility coefficient, stiffness index β, loc Psys - local SBP, locPdia - local DBP, locPWV - local pulse wave velocity, AP - amplification pressure. Results: In the study of the correlation of LVAC indices with the CCA rigidity parameters recorded on 7–9th day from the STEMI, a relationship was revealed only between Ees and LocPsys (r = 0.40; p = 0.01), Ees and LocPdia (r = 0, 26; p = 0.004). After 6 months of follow-up, a closer relationship between the LVAC and the parameters of the local CCA stiffness was diagnosed. The Ea indicator correlated with DC (r = -0.23; p = 0.009), PWV (r = 0.21; p = 0.02), LocPsys (r = 0.33; p = 0.0002), LocPdia (r = 0.26; p = 0.004) and AP (r = 0.19; p = 0.03). The Ees indicator was found to be associated with LocPsys (r = 0.38; p = 0.00001), LocPdia (r = 0.27; p = 0.002), AP (r = 0.22; p = 0.01). Conclusions: After 6 months, there was a closer correlation between the LVAC indices and the parameters of local pressure and rigidity. This is probably partly due to the remodeling of the cardiovascular system in the postinfarction period and the inclusion of compensatory-adaptive mechanisms that ensure the contractile function of the heart.

DYNAMICS OF INDICES OF LEFT VENTRICULAR-ARTERIAL COUPLING IN PATIENTS WITH HYPERTENSION AFTER ACUTE MYOCARDIAL INFARCTION

Objective: To study the dynamics of left ventricular-arterial coupling (LVAC) indices in patients with arterial hypertension (AH) after STEMI, depending on the presence or absence of rapidly progressing left ventricular (LV) remodeling. Design and method: The study included 71 patients (mean age 51.4 ± 8.4 years) with hypertension after STEMI. Echocardiography was performed at the 7–9th day and 24th, 48th weeks after STEMI (MyLab, Esaote, Italy) with the determination of EDV, its index (EDVi) and calculation of LVAC indices: arterial elastance (Ea), LV elastance (Ees), LVAC index (Ea/Ees). All patients received STEMI treatment for 48 weeks. Results: According to the EDVi dynamic during the 24 weeks, the patients were divided into two groups: group 1 - 30 people with rapidly progressive LV remodeling (increase in the EDVi &gt; 20%); group 2 - 41 people without LV remodeling (EDVi dynamics &lt; 20%). The following dynamics of LVAC indices was revealed: in group 1 Ea initialy was 2.0[95%CI 1.8;2.2], after 24 weeks - 1.6 [95%CI 1.4;1.8] (p = 0.0003), 48 weeks - 1.8[95%CI 1.5;2.0] (p = 0.0007); in group 2, respectively, 1.9[95%CI 1.7;2.1], 1.9[95%CI 1.7;2.0] (p = 0.46), 1.8[95%CI 1.7;1.9] (p = 0.27). Ees in the 1st group initially 1.8[95%CI 1.4;2.3], after 24 weeks - 1.2[95%CI 0.9;1.6] (p = 0.0002), 48 weeks - 1.3[95%CI 1.1;1.6] (p = 0.0001); in group 2 - 2.0[95%CI 1.9;2.2], 2.2[95%CI 2.0;2.4] (p = 0.08), 2.3[95%CI 2.1;2.5] (p = 0.009). In the 1st group the Ea/Ees index initially corresponded to normal values: 1.2[95 CI 1.0;1.4], followed by an increase after 24 weeks to 1.4 [95% CI 1.1; 1.6] (p = 0.007) and after 48 weeks - 1.4[95%CI 1.2;1.7] (p = 0.002). In the 2nd group, a decrease of Ea/Ees was revealed: initially - 1.0[95%CI 0.9;1.1], after 24 weeks - 0.9[95%CI 0.8;0.9] (p = 0.02), 48 weeks - 0.8[95%CI 0.7;0.9] (p = 0.002). Conclusions: In the group of patients, against the background of the development of rapidly progressive LV remodeling after STEMI in combination with hypertension, a pathological increase in the LVAC index was revealed due to a more pronounced decrease in left ventricular elastance, which reflects impaired homeostasis of the cardiovascular system.

Aerobic Versus Resistance Training Effects on Ventricular-Arterial Coupling and Vascular Function in the STRRIDE-AT/RT Trial.

Background: The goal was studying the differential effects of aerobic training (AT) vs. resistance training (RT) on cardiac and peripheral arterial capacity on cardiopulmonary (CP) and peripheral vascular (PV) function in sedentary and obese adults.Methods: In a prospective randomized controlled trial, we studied the effects of 6 months of AT vs. RT in 21 subjects. Testing included cardiac and vascular ultrasoundography and serial CP for ventricular-arterial coupling (Ees/Ea), strain-based variables, brachial artery flow-mediated dilation (BAFMD), and peak VO2 (pVO2; mL/kg/min) and peak O2-pulse (O2p; mL/beat).Results: Within the AT group (n = 11), there were significant increases in rVO2 of 4.2 mL/kg/min (SD 0.93) (p = 0.001); O2p of 1.9 mL/beat (SD 1.3) (p = 0.008) and the brachial artery post-hyperemia peak diameter 0.18 mm (SD 0.08) (p = 0.05). Within the RT group (n = 10) there was a significant increase in left ventricular end diastolic volume 7.0 mL (SD 9.8; p = 0.05) and percent flow-mediated dilation (1.8%) (SD 0.47) (p = 0.004). Comparing the AT and RT groups, post exercise, rVO2 2.97, (SD 1.22), (p = 0.03), O2p 0.01 (SD 1.3), (p = 0.01), peak hyperemic blood flow volume (1.77 mL) (SD 140.69) (p = 0.009), were higher in AT, but LVEDP 115 mL (SD 7.0) (p = 0.05) and Ees/Ea 0.68 mmHg/ml (SD 0.60) p = 0.03 were higher in RT.Discussion: The differential effects of AT and RT in this hypothesis generating study have important implications for exercise modality and clinical endpoints.

ASSESSMENT OF ANGIOTENSIN RECEPTOR BLOCKERS THERAPY WHEN ASSOCIATED TO MINERALOCORTICOID RECEPTOR ANTAGONISTS OR TO HYDROCHLOROTHIAZIDE ACCORDING CENTRAL HAEMODYNAMIC PARAMETERS

Objective: OBJECTIVE: The goal of antihypertensive therapy is to prevent complications. The harmful effects of aldosterone are innumerable: induced cardiac/renal fibrosis, sodium and water retention, inflammation, oxidative stress, among others, that are involved in arterial/myocardium stiffness, remodelling, heart failure and new onset atrial fibrillation. Thiazide diuretics can activate the neurohormonal system, impair glucose metabolism, increase new-onset diabetes, and are potentially arrhythmogenic. Protective effect of Angiotensin Receptor Blockers (ARBs) on major cardiovascular events might be partly independent of the degree of blood pressure reduction. Mineralocorticoid Receptor Antagonists (MRAs) therapy reduce arterial stiffness, plasma volume, collagen/elastin ratio and vascular/myocardial fibrosis. The objective is to assess the levels reached in central haemodynamic parameters (CHPs) when thiazide is replaced by MRA, and associated with ARBs, during the treatment of hypertensive patients with normal kidney function. Design and method: DESIGN AND METHOD: For this cross-sectional retrospective study, data were registered from 70 hypertensive patients, female/male: 39/31 (average age: 66/62), while being treated with hydrochlorothiazide (Hctz) combined to ARBs, and after changing to MRAs+ARBs therapy in the same patients. The average dose of Hctz among female/male were 14/15 mg and the duration of the Hctz+ARB therapy were 35/34 months, while the MRA+ARB therapy were 13/14 months. The CHPs (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure, Augmentation Index) were measured by the SphygmoCor System PVX (AtCor-Medical, Australia), according system's standard methods. Also was measured the difference between the normal levels, and the observed values of Augmentation Index (Diff-AIx) according age. Results: RESULTS: The results of CHPs, Diff-AIx, systolic and diastolic blood pressure during association of ARBs+MRAs therapy compared to ARBs+Hctz, both genders, showed the lowest values with a highly statistically significant difference, except augmentation pressure and pulse pressure among male. No hyperkalaemia was observed in this sample. Conclusions: CONCLUSIONS: These findings suggest that the dual block with MRA+ARB therapy giving better central haemodynamic parameters, reducing the stress to arterial-ventricular coupling, it could be helpful to prevent, in the short- and long-term, the harmful effects of angiotensin-aldosterone system such as the development of heart failure and atrial fibrillation.

Right Ventricular Pulmonary Artery Coupling and Mortality in Cardiac Intensive Care Unit Patients.

BackgroundImpaired right ventricular (RV) pulmonary artery coupling has been associated with higher mortality in patients with chronic heart disease, but few studies have examined this metric in critically ill patients. We sought to evaluate the association between RV pulmonary artery coupling, defined by the ratio of tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP), and mortality in cardiac intensive care unit patients.Methods and ResultsUsing a database of unique cardiac intensive care unit admissions from 2007 to 2018, we included patients with TASV/RVSP ratio measured within 1 day of hospitalization. Hospital mortality was analyzed using multivariable logistic regression, and 1‐year mortality was analyzed using multivariable Cox proportional‐hazards analysis. We included 4259 patients with a mean age of 69±15 years (40.1% women). Admission diagnoses included acute coronary syndrome in 56%, heart failure in 52%, respiratory failure in 24%, and cardiogenic shock in 12%. The mean TASV/RVSP ratio was 0.31±0.14, and in‐hospital mortality occurred in 7% of patients. Higher TASV/RVSP ratio was associated with lower in‐hospital mortality (adjusted unit odds ratio, 0.68 per each 0.1‐unit higher ratio; 95% CI, 0.58–0.79; P<0.001) and lower 1‐year mortality among hospital survivors (adjusted unit hazard ratio, 0.83 per each 0.1‐unit higher ratio; 95% CI, 0.77–0.90; P<0.001). Stepwise decreases in hospital and 1‐year mortality were observed in each higher TASV/RVSP quintile. The TASV/RVSP ratio remained associated with mortality after adjusting for left ventricular systolic and diastolic function.ConclusionsA low TASV/RVSP ratio is associated with increased short‐term and long‐term mortality among cardiac intensive care unit patients, emphasizing importance of impaired RV pulmonary artery coupling as a determinant of poor prognosis. Further study is required to determine whether interventions to optimize RV pulmonary artery coupling can improve outcomes.

Influence of chest conformation on ventricular-arterial coupling during normal pregnancy.

There is still controversy regarding the changes of ventricular-arterial coupling (VAC) during normal pregnancy. The possible influence of chest shape on VAC during normal pregnancy has never been investigated. Between October 2019 and June 2020, 59 healthy pregnant women (33.7± 4.4 years/old) were consecutively included. They underwent obstetric visit, modified Haller index (MHI) assessment, and complete echocardiographic evaluation with blood pressure measurement to assess arterial elastance (Ea), end-systolic elastance (Ees), and Ea/Ees as an index of VAC, at 12-14 weeks and 36-38 weeks gestation, then 6-9 weeks after delivery. VAC progressively increased from the first to the third trimester of pregnancy, then decreased in the postpartum (P< 0.0001) in the whole study population. Women with concave-shaped chest wall (MHI >2.5, n=31) but not women with normal chest shape (MHI ≤2.5, n=28) showed a progressive increase in VAC during normal pregnancy. Women with MHI >2.5 showed a significantly less pronounced increase in stroke volume index (SVi) from the first to the third trimester of pregnancy. There was a strong linear correlation between third trimester MHI and VAC (r=0.93). Anatomical and/or extrinsic mechanical factors rather than impaired arterial elastance or reduced left ventricular contractility may contribute to changes in VAC during normal pregnancy in women with concave-shaped chest wall.

Longitudinal uncoupling of the heart and arteries with aging in a community-dwelling population.

Although mechanical energy transfer between the heart and arterial system, referred to as arterial-ventricular (AV) coupling, is an important determinant of cardiovascular performance, how AV coupling changes over time within and among individuals as they age has not been fully explored. We studied 129 participants (baseline age 21-96) of the Baltimore Longitudinal Study of Aging, free of clinical CVD. Participants underwent repeated multigated cardiac blood pool scans to estimate left ventricular (LV) volumes (SV, EDV, and ESV). Total systemic vascular resistance (TSVR), total arterial compliance (TAC), effective arterial elastance (Ea), and end-systolic LV elastance (Elv) were calculated using LV volumes and brachial BP measurements; calculated Ea/Elv was the measure of AV coupling. Linear mixed-effects models were used to estimate person-specific rates of change (Change) for each variable. The rate at which Ea increased over time was faster than the rate at which Elv increased, resulting in AV uncoupling (increased Ea/Elv) over time that was significantly greater in women than in men. Loss of arterial compliance was the main determinant of (Ea/Elv)Change, which was negatively associated with changes in SV and EDV but positively with changes in ESV. Progressive AV uncoupling occurred with aging and was more pronounced in women than men. While Ea change did not differ by sex, Elv increased at a slower rate in women than in men. AV uncoupling was inversely associated with EDV and SV rates of change and a directly associated with an increase in ESV rate of change. Additional studies are needed to explore the functional consequences of AV uncoupling in healthy individuals with respect to the emergence of age-associated clinical cardiovascular diseases, such as heart failure with preserved ejection fraction.

Left ventricular-arterial coupling as a predictor of stroke volume response to norepinephrine in septic shock \u2013 a prospective cohort study

BackgroundLeft ventricular-arterial coupling (VAC), defined as the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), is a key determinant of cardiovascular performance. This study aims to evaluate whether left VAC can predict stroke volume (SV) response to norepinephrine (NE) in septic shock patients.MethodsThis was a prospective cohort study conducted in an intensive care unit of a tertiary teaching hospital in China. We recruited septic shock patients who had persistent hypotension despite fluid resuscitation and required NE to maintain mean arterial pressure (MAP) > 65 mmHg. Those patients in whom the target MAP was not reached after NE infusion were ineligible. Echocardiographic variables were measured before (baseline) and after NE infusion. SV responder was defined by a ≥ 15% increase in SV after NE infusion.ResultsOf 34 septic shock patients included, 19 (56%) were SV responders. Before NE infusion, SV responders had a lower Ees (1.13 ± 0.24 mmHg/mL versus 1.50 ± 0.46 mmHg/mL, P = 0.005) and a higher Ea/Ees ratio (1.47 ± 0.40 versus 1.02 ± 0.30, P = 0.001) than non-responders, and Ea in SV responders was comparable to that in non-responders (1.62 ± 0.36 mmHg/mL versus 1.43 ± 0.28 mmHg/mL, P = 0.092). NE significantly increased Ea and Ees in both groups. The Ea/Ees ratio was normalized by NE administration in SV responders but unchanged in non-responders. The baseline Ea/Ees ratio was positively correlated with NE-induced SV increases (r = 0.688, P < 0.001). Logistic regression analysis indicated that the baseline Ea/Ees ratio was a predictor of SV increases induced by NE (odd ratio 0.008, 95% confidence interval (CI): 0.000 to 0.293), with an area under the receiver operating characteristic curve of 0.816 (95% CI: 0.646 to 0.927).ConclusionsThe left VAC has the ability to predict SV response to NE infusion in septic shock patients.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024031, Registered 23 June 2019 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=40359&htm=4.

Intermittent outpatient administration of levosimendan improves right ventricular-pulmonary arterial coupling in ambulatory patients with advanced heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Intermittent infusions of levosimendan in an outpatient setting have been associated with improved symptoms and reduced hospitalizations in patients with advanced heart failure (HF). Little is known on the potential effect of intermittent levosimendan infusions on right ventricle (RV)-pulmonary arterial (PA) coupling in ambulatory patients with advanced HF. Purpose Aim of the present study was to explore the effects of intermittent levosimendan infusions on the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PAPs), an echocardiographic measure of RV/PA coupling, in ambulatory patients with advanced HF, and on left ventricular arterial coupling (VAC), expressed as the relationship between arterial elastance (Ea) and ventricular elastance (Ees). Methods 17 ambulatory patients with advanced HF treated with intermittent levosimendan (6-hour intravenous infusion, 0.2 ug/kg/min without bolus) received baseline clinical, biochemical and echocardiographic evaluation and changes in TAPSE/PAPs ratio were assessed from baseline to 48 hours after the infusion, based on the pharmacokinetic profile of levosimendan. VAC, expressed as Ea/Ees ratio, was obtained by a calculator (iElastance) designed for non-invasive single beat measure of end-systolic Ees and Ea according to Chen"s method. Results After 48 hours from levosimendan infusion, there was a significant improvement of TAPSE/PAPs ratio (p = 0.04), stroke voume (SV) (p = 0.05) and cardiac output (CO)(p = 0.04). We observed a significant reduction of Ea (p = 0.007) and of Ees (p = 0.01) and a non significant improvement of VAC (p = 0.4)(Tab.1). Conclusion. Our results show that an intermittent 6-hour levosimendan infusion at 0.2 ug/kg/min improves after 48 hours RV-PA coupling, SV, CO, Ea and Ees in ambulatory patients with advanced HF. Further studies including more patients are necessary to confirm these preliminary findings. Tab.1 Baseline 48h afterlevosimendan infusion p value NT-proBNP (pg/mL) 5607 ± 4300 3868 ± 3856 &amp;lt;0.001 LVEF (%) 24.1 ± 7.7 25.7 ± 7.3 0.5 SV (mL) 36.8 ± 12.4 46.1 ± 14.8 0.05 CO (L/min)36.8 ± 12.4 2.6 ± 0.7 3.2 ± 0.9 0.05 TAPSE/PAPs (mm/mmHg) 0.38 ± 0.13 0.49 ± 0.16 0.04 Ea (mmHg/mL/m2) 2.9 ± 0.9 2.1 ± 0.6 0.007 Ees (mmHg/mL/m2) 1.3 ± 0.4 1.0 ± 0.2 0.01 VAC 2.2 ± 0.6 2.0 ± 0.4 0.4

Pulmonary haemodynamic response to exercise in highlandersversuslowlanders

The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders.This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living <800 m), assessing cardiac function, including tricuspid regurgitation pressure gradient (TRPG), cardiac index and tricuspid annular plane systolic excursion (TAPSE) by echocardiography combined with heart rate and oxygen saturation measured by pulse oximetry (SpO2) during submaximal stepwise cycle exercise (10 W increase per 3 min) at their altitude of residence (at 760 m or 3250 m, respectively).52 highlanders (26 females; aged 47.9±10.7 years; body mass index (BMI) 26.7±4.6 kg·m−2; heart rate 75±11 beats·min−1; SpO2 91±5%;) and 22 lowlanders (eight females; age 42.3±8.0 years; BMI 26.9±4.1 kg·m−2; heart rate 68±7 beats·min−1; SpO2 96±1%) were studied. Highlanders had a lower resting SpO2 compared to lowlanders but change during exercise was similar between groups (highlanders versus lowlanders −1.4±2.9% versus −0.4±1.1%, respectively, p=0.133). Highlanders had a significantly elevated TRPG and exercise-induced increase was significantly higher (13.6±10.5 mmHg versus 6.1±4.8 mmHg, difference 7.5 (2.8 to 12.2) mmHg; p=0.002), whereas cardiac index increase was slightly lower in highlanders (2.02±0.89 L·min−1 versus 1.78±0.61 L·min−1, difference 0.24 (−0.13 to 0.61) L·min−1; p=0.206) resulting in a significantly steeper pressure–flow ratio (ΔTRPG/Δcardiac index) in highlanders 9.4±11.4 WU and lowlanders 3.0±2.4 WU (difference 6.4 (1.4 to 11.3) WU; p=0.012). Right ventricular-arterial coupling (TAPSE/TRPG) was significantly lower in highlanders but no significant difference in change with exercise in between groups was detected (−0.01 (−0.20 to 0.18); p=0.901).In highlanders, chronic exposure to hypoxia leads to higher pulmonary artery pressure and a steeper pressure–flow relation during exercise.

Exploring the mechanisms of action of gliflozines in heart failure and possible implications in pulmonary hypertension

Although results from two major trials trials have shown a clear benefit of gliflozines in the management of heart failure (HF) irrespective of diabetes status, the mechanism of cardiac benefits remains incompletely understood. Gliflozines have an osmotic diuretic effect that differs from that of other diuretic classes, resulting in greater electrolyte-free water clearance, and clinical studies have shown that intravascular volume depletion is rare and occurs at similar frequency in the gliflozines and placebo groups. As a consequence of the negligible effects on the blood volume and body's fluid balance compared to diuretics, gliflozines may limit the reflex neurohumoral stimulation and activation of renin-angiotensin-aldosterone system (RAAS). Since neurohormonal and RAAS activation in patients with HF reduced or ejection fraction (HFrEF and HFpEF) also leads to systemic and pulmonary arterial stiffening, pulmonary hypertension (PH) and PH-related right ventricular failure, gliflozines may lead to a mitigation of systemic and pulmonary arterial stiffening, which in turn can reduce the degree of PH associated with HFrEF or HFpEF, can improve the ventricular arterial coupling and can reduce the overload of the left and right ventricle, improving their function. The current review discusses the latest findings regarding the effects of SGLT2 inhibitors on heart failure with focus also on pulmonary hypertension, discussing the molecular mechanisms involved.

Physiological compensatory mechanisms of improved left heart function in response to simulated acute weightlessness: A human echocardiographic study by speckle tracking strain imaging

<p indent="0mm">The gravity-induced hydrostatic pressure gradient in the cardiovascular system is altered under the aerospace condition of weightlessness, leading to the increase of returned blood volume, and thus changes in cardiac structure and function. However, the characteristics and compensatory mechanisms are still unclear. The present study was to investigate the characteristics and compensatory mechanisms of cardiac preload and function in simulated acute aviation negative gravity and space microgravity using two-dimensional echocardiographic speckle-tracking strain imaging, and to provide theoretical evidence for aerospace heart protection. A total of 27 healthy young male volunteers were recruited. The tilting table was used to simulate acute microgravity (0.87~0 G) and negative gravity (0~−0.87 G). The left heart volumes, strain and functional parameters were collected and analyzed by both conventional and speckle tracking echocardiography. The systemic vascular resistance, compliance and ventricular-arterial coupling were calculated. The results showed that, the left heart volume and strain, left atrial emptying fraction and left ventricular ejecting fraction were all increased as gravity decreased. The arterial compliance was increased and the ventricular-arterial coupling index was decreased within the normal range. Of note, the reservoir, conduit and contraction function of left atrial strain were elevated proportionally; the flow velocity of left ventricular filling during early and late diastolic phases were both increased at the constant ratio. That is, the compensatory pattern was characterized by proportional improvement of cardiac motion in different phases and directions, which is different from that in aging and diseases. The present study demonstrated that the heart of healthy young men can effectively compensate the increase of preload caused by simulated acute microgravity and negative gravity. The major compensatory mechanism is the proportional improvement of myocardial motion of left atrium and ventricle during different phases (early and late diastole, systole) and along different directions (longitudinal and circumferential). The findings suggest that the aviators or astronauts generally have enough cardiac systolic/diastolic reserve to counter the acute change of cardiac preload induced by weightlessness (−0.87~1 G).

Echocardiographic estimation of left ventricular-arterial coupling in dogs with myxomatous mitral valve disease.

BackgroundThe effective arterial elastance (Ea) to left ventricular (LV) end‐systolic elastance (Ees) ratio (Ea/Ees) is an index of the interaction between LV and systemic arterial systems, left ventricular‐arterial coupling (VAC). The Ea is an index of total arterial load of the LV, whereas Ees is an index of LV systolic function. In humans, inappropriate VAC based on increased Ea/Ees estimated using echocardiography is associated with more advanced heart disease severity.HypothesisLeft ventricular‐arterial coupling assessed by echocardiographic estimation of Ea/Ees is associated with disease severity in dogs with myxomatous mitral valve disease (MMVD).AnimalsNinety MMVD dogs and 61 healthy dogs.MethodsProspective cross‐sectional study. The MMVD dogs were classified into stages B1, B2, or C according to American College of Veterinary Internal Medicine guidelines. Effective arterial elastance was echocardiographically estimated using the formula: mean blood pressure/(forward stroke volume/body weight). End‐systolic elastance was echocardiographically estimated using the formula: mean blood pressure/(LV end‐systolic volume/body weight). The ratio Ea/Ees was calculated.ResultsThe ratio Ea/Ees was higher in stage B2 dogs than in healthy dogs and dogs stage B1 (both P < .0001), and higher in stage C dogs than in healthy dogs and dogs in the other 2 stages (healthy vs C and B1 vs C, P < .0001; B2 vs C, P = .0005). Multivariable logistic regression analysis showed that Ea/Ees and the peak velocity of early diastolic transmitral flow to isovolumic relaxation time ratio were independent predictors of stage C among echocardiographic indices in MMVD dogs.Conclusions and Clinical ImportanceInappropriate VAC assessed by echocardiographically estimated Ea/Ees is associated with advanced disease severity in dogs with MMVD.

Soluble Flt1 levels are associated with cardiac dysfunction in Black women with and without severe preeclampsia

ABSTRACT Background: We evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) levels and cardiac function during pregnancy and postpartum among Black women with and without preeclampsia. Study design: Prospective longitudinal cohort study from 2015 to 2017 of Black women with preterm severe preeclampsia and normotensive pregnant controls.We obtained echocardiograms and sFlt-1 levels during pregnancy and postpartum. Results: 93 Black women were included (43 cases, 50 controls). Higher sFlt1 levels were correlated with worse longitudinal strain, diastolic dysfunction, decreased ventricular-arterial coupling, and increased chamber and arterial elastance at the time of preeclampsia diagnosis and postpartum. Conclusions: Higher sFlt1 levels are associated with cardiovascular dysfunction during pregnancy and postpartum.

Early hemodynamic changes after transcatheter aortic valve implantation in patients with severe aortic stenosis measured by invasive pressure volume loop analysis

Replacement of a stenotic aortic valve reduces immediately the ventricular to aortic gradient and is expected to improve diastolic and systolic left ventricular function over the long term. However, the hemodynamic changes immediately after valve implantation are so far poorly understood. Within this pilot study, we performed an invasive pressure volume loop analysis to describe the early hemodynamic changes after transcatheter aortic valve implantation (TAVI) with self-expandable prostheses. Invasive left ventricular pressure volume loop analysis was performed in 8 patients with aortic stenosis (mean 81.3 years) prior and immediately after transfemoral TAVI with a self-expandable valve system (St. Jude Medical Portico Valve). Parameters for global hemodynamics, afterload, contractility and the interaction of the cardiovascular system were analyzed. Left ventricular ejection fraction, (53.9% vs. 44.8%, p = 0.018), preload recruitable stroke work (68.5 vs. 44.8 mmHg, p = 0.012) and end-systolic elastance (3.55 vs. 2.17, p = 0.036) both marker for myocardial contractility declined significantly compared to baseline. As sign of impaired diastolic function, TAU, a preload-independent measure of isovolumic relaxation (37.3 vs. 41.8 ms, p = 0.018) and end-diastolic pressure (13.1 vs. 16.4 mmHg, p = 0.015) raised after valve implantation. Contrarily, a smaller ratio of end-systolic to arterial elastance (ventricular-arterial coupling) indicates an improvement of global cardiovascular energy efficiency (1.40 vs. 0.97 p = 0.036). Arterial elastance had a strong correlation with the number of conducted rapid ventricular pacings (Pearson correlation coefficient, r = 0.772, p = 0.025). Invasive left ventricular pressure volume loop analysis revealed impaired systolic and diastolic function in the early phase after TAVI with self-expandable valve for the treatment of severe aortic stenosis. Contrarily, we found indications for early improvement of global cardiovascular energy efficiency.

Maternal hemodynamics, arterial stiffness and elastic aortic properties in twin pregnancy

Objective: There is scant information about maternal cardiovascular hemodynamic change during twin pregnancies. Aim of the study is to investigate longitudinal changes in maternal arterial stiffness, elastic aortic properties and ventricular-arterial coupling (VAC) in uncomplicated twin pregnancies compared to singleton ones. Approach: In this prospective longitudinal study, we performed applanation tonometry and transthoracic echocardiography in the first (T1; 10–15 weeks’ gestation (w)), second (T2; 19–26 w) and third trimesters (T3; 30–38 w) in women with uncomplicated twin pregnancies, both monochorionic and dichorionic. Heart-rate-corrected augmentation index (AIx@75) was studied as indicator of arterial stiffness. Aortic diameters and elastic properties were calculated. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular end-systolic elastance (Ees). Finally, stroke volume (SV), cardiac output (CO) and total vascular resistance (TVR) were evaluated. The findings were compared to those of women with uncomplicated singleton pregnancies. Main results: Thirty women with twin gestations (11 monochorionic) and 30 singleton controls were obtained for analysis. Blood pressure and TVR significantly decreased from T1 to T2 and then rose in T3, with higher values in twins than in singletons. AIx@75 showed the same trend in both groups with lower values at T2 in twins. SV and CO linearly increased throughout gestation with no significant intergroup difference. Aortic diameters and elastic properties remained stable throughout gestation, with no significant intergroup differences. Both Ea and Ees were greater (i.e. worse) in twins than in singletons at T1 and T3, showing a significant linear trend towards reduction in the two groups, meaning lower vascular and ventricular loads. Using longitudinal analysis blood pressure, TVR, Ea and Ees depended from both multiple gestation and gestational age. Significance: In twins, maternal hemodynamics does not seem to undergo more significant changes than in singletons being characterized by higher blood pressures and TVR with no differences in CO, SV, aortic dimensions and elastic properties. Despite VAC is maintained within its normal range, total vascular load (i.e., Ea) resulted higher in twin than singleton pregnancies throughout gestation. It is conceivable that these findings may represent one of the underlying cause for the increased risk of adverse obstetric outcomes described in multiple gestations.

275 Role of right ventricle in acute heart failure with preserved ejection fraction: a comparison between hypertensive pulmonary edema and decompensated heart failure

Abstract Aims Limited data are available on the pathophysiological role of the right ventricle (RV) in patients with acute heart failure with preserved ejection fraction (AHF-PEF) and its impact on the main clinical manifestation such as pulmonary oedema or peripheral congestion. Mainly through right-to-left stroke volume mismatch and ventricular-arterial decoupling, right chambers size and function may play a key role leading to fluid overload or maldistributed phenotypes. Methods and results In this monocenter, prospective, observational study 80 consecutive patients with AHF-PEF were enrolled. A complete echocardiographic examination was performed within 6 hours from emergency department admission; multiparametric RV function was carefully evaluated in the very acute phase. Focusing on hypertensive pulmonary oedema (H-AHF) and decompensated AHF without pulmonary oedema (D-AHF) phenotypes, the study aims to analyze the echocardiographic peculiarities of these clinical entities in the early phase of admission and its modification at discharge (D-AHF n = 58, H-AHF n = 22). Baseline clinical characteristics were comparable in both groups, except for coronary artery disease more prevalent in H-AHF and atrial fibrillation more prevalent in D-AHF. D-AHF patients showed dilated and dysfunctional right chambers compared to H-AHF. Regarding systolic function, normal values of fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) were registered in H-AHF at admission and at discharge. D-AHF showed greater systolic pulmonary artery pressure (sPAP) and lower TAPSE/sPAP ratio. Left ventricular dimensions and function were comparable in both groups. Conversely, E/e’ ratio was significantly higher in H-AHF at admission. Data are summarized in the tables and figures below. Conclusion D-AHF and H-AHF represent different phenotypes of AHF-PEF. Right heart structure and function and ventricular-arterial coupling could play a crucial role in their pathophysiology. Non dilated RV with preserved systolic function seems to be crucial to develop pulmonary oedema without signs of peripheral congestion. Further investigations are needed to corroborate the hypothesis of interventricular stroke volume mismatch in the complex AHF-PEF clinical scenario.