Left Ventricular Pressure Research Articles

TCT-578 Impact of Left Ventricular End-Diastolic Pressure on Outcomes Following Percutaneous Coronary Intervention

TCT-578 Impact of Left Ventricular End-Diastolic Pressure on Outcomes Following Percutaneous Coronary Intervention

Do collaterals to infarct bed in STE-ACS patients undergoing emergent percutaneous coronary revascularization matter? An assessment of a prospective pool for in-hospital course

BackgroundLimited data exist on the role of coronary collaterals circulation (CCC) in patients with ST-elevation acute coronary syndrome (STE-ACS). This study aimed to assess CCC and the in-hospital course of patients with CCC undergoing primary percutaneous coronary intervention (pPCI). MethodsThe study included consecutive STE-ACS patients undergoing pPCI. Good CCC was defined as Rentrop collateral score (RCS) of 2–3. Patients with good and poor CCC were compared regarding clinical characteristics, angiographic patterns, and hospital course. ResultsIn the sample of 4683 patients, mean age was 55.6 ± 11 years, and 78.8 % were male. Good CCC was observed in 499 (10.7 %) patients. The rate of intra-procedure slow-flow/no-reflow (SF/NR) was 29.9 % vs. 20.5 % (p < 0.001), and the rate of composite adverse clinical outcomes (CACO) was 21.2 % vs. 19 % (p = 0.225) for patients with good and poor CCC, respectively. Multivariable analysis identified left ventricular end-diastolic pressure (LVEDP), multi-vessel disease (MVD), and thrombus grade ≥4 as independent predictors of good CCC, with adjusted odds ratios of 0.98 [0.97–0.99], 1.69 [1.35–2.10], and 3.45 [2.64–4.52], respectively. In propensity-matched cohorts, the intra-procedure SF/NR rate was 29.9 % vs. 26.9 % (p = 0.292), and the rate of CACO was 21.2 % vs. 23.4 % (p = 0.403) for patients with good and poor CCC, respectively. ConclusionAngiographic evidence of good CCC in STE-ACS patients was limited. Good CCC was associated with a higher prevalence of MVD, high thrombus burden, and low pre-procedure LVEDP, resulting in a higher incidence of intra-procedure SF/NR. However, the CACO did not differ significantly between patients with good and poor CCC.

Cardioprotective Action of the JNK Inhibitor Tryptanthrin Oxime in the Late Period after Myocardial Infarction.

In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function. Four months after myocardial infarction, significant improvement in systemic hemodynamics and cardiohemodynamics parameters was observed in the group treated with TR-Ox: stroke volume, cardiac output, left ventricular systolic pressure, maximum rates of left ventricle pressure rise and fall significantly increased and the left ventricle end-diastolic pressure decreased in comparison with the corresponding parameters in the control group.

Discrepancy between pulmonary arterial wedge pressure and left ventricular end diastolic pressure in patients with interstitial lung disease

BackgroundRight heart catheterization (RHC) is the gold standard for diagnosing pulmonary hypertension (PH) in patients with interstitial lung disease (ILD). However, discrepancies between pulmonary arterial wedge pressure (PAWP) and left ventricular end-diastolic pressure (LVEDP) remain understudied in this population. MethodsWe conducted a retrospective analysis of data from ILD patients who underwent RHC and had concomitant LVEDP measurements. Pulmonary vascular resistance (PVR) was calculated using both PAWP and LVEDP. Patients were categorized based on PAWP and LVEDP values using a threshold of 15 mmHg and PVR values using a threshold of 2 or 3 Wood Units. After that patients were categorized as concordant or discordant if both values were on the same or opposite sides of these thresholds, respectively. A discordantly higher PAWP group (left atrial dysfunction, LAD) was defined as patients with a PAWP-LVEDP difference of more than 3mmHg. ResultsAmong 87 ILD patients, 9 patients (10.3%) showed discordance between PAWP and LVEDP. LAD was observed in 12 patients (13.8%) and was associated with lower forced vital capacity (Odd ratio [OR]: 0.956, p = 0.049) and a larger left atrium diameter (OR: 3.205, p = 0.033). Discordance in PVR values was also noted, with potential treatment targets for PH-specific therapy differing in 9 patients (22.0%) depending on whether PAWP or LVEDP was used. ConclusionsThis study highlights the clinical significance of PAWP-LVEDP discrepancies in suspected PH-ILD patients, emphasizing the need for comprehensive assessments incorporating LVEDP and clinical context for accurate diagnosis, risk stratification, and treatment decisions.

IMPROVEMENT IN LV END-DIASTOLIC PRESSURE AFTER PRIMARY PCI AND ITS IMPACT ON PATIENTS’ RECOVERY

Left ventricular end-diastolic pressure (LVEDP) is a crucial indicator of cardiac function, particularly in patients with acute ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) is the standard of care for STEMI, but its impact on LVEDP and patient recovery remains to be thoroughly studied. Objective: This study aimed to evaluate the improvement in LVEDP following primary PCI in patients with acute STEMI and to assess its impact on recovery and clinical outcomes. Methods: This prospective study included 100 patients with acute STEMI treated by primary PCI. LVEDP was recorded at four-time points: before PCI, and at one week, one month, and three months post-PCI. Demographic and clinical characteristics were also collected. Statistical analysis was performed to compare LVEDP values at different time intervals using paired t-tests and repeated measures ANOVA to assess significant changes over time. Results: The mean LVEDP significantly decreased from 18 ± 4 mmHg before PCI to 12 ± 3 mmHg at one week, 10 ± 2 mmHg at one month, and 9 ± 2 mmHg at three months post-PCI (p &lt; 0.001). This demonstrated a consistent improvement in left ventricular function and hemodynamic status, suggesting favorable patient recovery post-intervention. Conclusion: Primary PCI significantly reduces LVEDP in patients with acute STEMI, leading to improved cardiac function and patient recovery. Monitoring LVEDP post-PCI can serve as a valuable predictor of patient prognosis and long-term outcomes. Further studies are warranted to explore additional therapies that may further enhance recovery and improve the quality of life in STEMI patients.

Dynamics of Blood Flows in the Cardiocirculatory System

Models and simulations of blood flow in vascular networks are useful to deepen knowledge of cardiovascular diseases. This paper considers a model based on partial differential equations that mimic the dynamics of vascular networks in terms of flow velocities and arterial pressures. Such quantities are found by using ad hoc numerical schemes to examine variations in the pressure and homeostatic conditions of a whole organism. Two different case studies are examined. The former uses 15 arteries—a network that shows the real oscillations in pressures and velocities due to variations in artery volume. The latter focuses on the 55 principal arteries, and blood flows are studied by using a model of a heart valve that opens and closes via the differences in the aortic and left ventricle pressures. This last case confirms the possibility of autonomously regulating blood pressure and velocity in arteries in general and when tilt tests are applied to patients.

Left ventricular end-diastolic pressure response to spinal anaesthesia in euvolaemic vascular surgery patients

Left ventricular end-diastolic pressure response to spinal anaesthesia in euvolaemic vascular surgery patients

Physiological control for left ventricular assist devices based on deep reinforcement learning.

The improvement of controllers of left ventricular assist device (LVAD) technology supporting heart failure (HF) patients has enormous impact, given the high prevalence and mortality of HF in the population. The use of reinforcement learning for control applications in LVAD remains minimally explored. This work introduces a preload-based deep reinforcement learning control for LVAD based on the proximal policy optimization algorithm. The deep reinforcement learning control is built upon data derived from a deterministic high-fidelity cardiorespiratory simulator exposed to variations of total blood volume, heart rate, systemic vascular resistance, pulmonary vascular resistance, right ventricular end-systolic elastance, and left ventricular end-systolic elastance, to replicate realistic inter- and intra-patient variability of patients with a severe HF supported by LVAD. The deep reinforcement learning control obtained in this work is trained to avoid ventricular suction and allow aortic valve opening by using left ventricular pressure signals: end-diastolic pressure, maximum pressure in the left ventricle (LV), and maximum pressure in the aorta. The results show controller obtained in this work, compared to the constant speed LVAD alternative, assures a more stable end-diastolic volume (EDV), with a standard deviation of 5 mL and 9 mL, respectively, and a higher degree of aortic flow, with an average flow of 1.1 L/min and 0.9 L/min, respectively. This work implements a deep reinforcement learning controller in a high-fidelity cardiorespiratory simulator, resulting in increases of flow through the aortic valve and increases of EDV stability, when compared to a constant speed LVAD strategy.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension.

Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation. However, the impact of LVH and LAE and their regression following antihypertensive therapy on atrial fibrillation incidence remains unclear. This retrospective analysis included consecutive patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6-18 months between 2006 and 2021 at tertiary care centres in Korea. LVH was defined as LV mass index greater than 115 g/m2 (men) and greater than 95 g/m2 (women), and LAE was defined as LA volume index greater than 42 ml/m2. The occurrence of new-onset atrial fibrillation (NOAF) was assessed in relation to changes in LVH and LAE status. Among the 1464 patients included, 163 (11.1%) developed NOAF during a median 63.8 [interquartile range (IQR) 35.9-128.5] months of surveillance period. New-onset LVH [adjusted hazard ratio (aHR) 1.88, 95% confidence interval (CI) 1.20-2.94, P = 0.006] and LAE (aHR 1.89, 95% CI 1.05-3.40, P = 0.034) were significant predictors of NOAF. Conversely, regression of LVH (aHR 0.51, 95% CI 0.28-0.91, P = 0.022) or LAE (aHR 0.30, 95% CI 0.15-0.63, P = 0.001) was associated with a reduced risk for developing NOAF. Patients with both LVH and LAE at follow-up echocardiography had a higher risk for NOAF (aHR 4.30, 95% CI 2.81-6.56, P < 0.001) than those with either LVH or LAE or those with neither. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

β-Adrenergic receptor signalling pathway mediated antiarrhythmic activity of s-limonene in the rat heart.

S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of β-adrenoceptor (β-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the β-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 μM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 μM and reduced heart rate at the concentrations of 30 (12.4%) and 50 μM (16.6%). s-Lim (10 μM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 μM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker β1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists β1-AR), presenting a similar effect to propranolol (a non-selective blocker β-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 μM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of β-AR in the heart.

The protective effect of Ghrelin peptide on doxorubicin hydrochloride induced heart failure in rats

BackgroundTo investigate the protective effect and mechanism of Ghrelin on Doxorubicin (Dox) hydrochloride induced heart failure (HF) and myocardial injury in rats.Methods45 rats were randomly divided into control group, HF group and Ghrelin group. Dox hydrochloride was injected intraperitoneally to establish the model of HF in rats of HF group and Ghrelin group. Rats in the Ghrelin group were given intraperitoneal injection of Ghrelin twice a day, and rats in the HF group and control group were given equal volume of normal saline for a total of 6 weeks. The changes of echocardiography, cardiac hemodynamics, myocardial histology and plasma inflammatory factors were observed.ResultsAfter the Ghrelin intervention, compared with the HF group, the left ventricular end-diastolic diameter (LVDD) and left ventricular end-systolic diameter (LVSD) in the Ghrelin group was markedly reduced (P < 0.05), and left ventricular ejection fraction (LVEF) was significantly increased (P < 0.05). Compared with HF group, the left ventricular systolic pressure (LVSP), maximum rate of increase in left ventricular pressure (+ dP/dtmax) and maximum rate of decrease in left ventricular pressure (− dP/dtmax) of Ghrelin group was remarkedly increased (P < 0.05), left ventricular diastolic pressure (LVDP) decreased (P < 0.05). In the Ghrelin group, the degree and extent of cardiomyocyte degeneration and necrosis were remarkedly reduced compared with the HF group. The levels of TNF-α and iNOS in Ghrelin group were notably lower than those in HF group (P < 0.05), the IL-10 level increased markedly (P < 0.05).ConclusionGhrelin may reduce Dox-induced myocardial injury and improve cardiac function in rats by regulating inflammation and oxidative stress.

P227 MACROPHAGE TO MYOFIBROBLAST TRANSITION IN THE DEVELOPMENT OF DIASTOLIC DYSFUNCTION

Diastolic dysfunction (DD) and heart failure (HF) ravage a significant portion of the world's population. These end-stage diseases are most often precluded by hypertension (HTN). Cardiac fibrosis is one of the major factors in the degradation of cardiac function. There are multiple cellular players involved in fibrosis—including, macrophages. Indeed, in the past decade these cells have been shown to differentiate into professional fibrotic cells, myofibroblasts, a process termed macrophage to myofibroblast transition (MMT), in models of kidney injury. Despite this, the role of MMT in fibrotic remodeling in HTN and DD remains unknown. As such, we seek to investigate this phenomenon in the HTN heart and determine the role it plays in the pathological progression of HTN to DD. We utilized cardiac ultrasound and direct left ventricular (LV) pressure catheterization to gauge diastolic function. These gold-standard methods allowed us to assess cardiac function during HTN and investigate the heart at the transition to DD. Furthermore, flow cytometry was utilized to identify MMT cells (α-SMA+, CD68+) in the heart. These methods gave insight into the role that MMT plays in the degradation of heart function during HTN that inevitably leads to DD and HF. Cardiac ultrasound revealed that E/A and deceleration time (DcT) were greatly decreased in DOCA mice 10 days after the start of HTN. Further, LV pressure catheterization revealed decreased cardiac function, as shown by decreased -dp/dt. Finally, HTN and normal hearts were harvested and leukocytes isolated. Indeed α-SMA and CD68 staining showed a significant increase in MMT cells in the HTN heart. This study has shown a rapid onset of DD inside of DOCA + salt HTN mice. In addition, there was a significant increase of MMT cells in these same hearts, elucidating a novel mechanism of cardiac fibrosis. Future studies will aim to parse out the gravity of MMT in HTN to find new pharmaceutical targets against this debilitating disease.

Abstract P335: An innate immune component in hypertension-induced cardiac dysfunction Christoph Mora, Katherine Deck, Yunmeng Liu, Lance Benson, Tonya Rafferty, &amp; Shengyu Mu

Hypertension affects nearly half of American adults, inevitably leading to cardiac dysfunction and heart failure. Cardiac fibrosis is a major factor contributing to cardiac dysfunction during hypertension progression. However, the mechanisms involved in cardio-fibrogenesis remain to be elucidated. In the past decade, studies revealed that macrophages could differentiate into professional fibrotic cells, myofibroblasts, through a process termed macrophage to myofibroblast transition (MMT), helping maintain the integrity of major organs, such as the kidney. However, it is unknown whether MMT contributes to fibrotic remodeling in hypertensive hearts. Here, we aim to identify this phenomenon in the hearts of hypertensive animals and determine the role it plays in the pathological progression from hypertension to cardiac diastolic dysfunction. In this study we adopt the classic DOCA + Salt model of hypertension and utilized cardiac ultrasound and direct left ventricular (LV) pressure catheterization to gauge diastolic function. Heart sections from hypertensive and sham mice were stained with Masson’s trichrome to assess the extent of cardiac fibrosis. Furthermore, flow cytometry was utilized to identify MMT cells, which express both CD68 (monocytes) and α-SMA (myofibroblast) markers. These methods gave insight into the role that MMT plays in the degradation of heart function during hypertension. Direct left ventricle pressure catheter revealed that DOCA + salt mice exhibited impaired diastolic function. This result is supported by cardiac ultrasound showing that the compliance of the heart had significantly decreased, as evidenced by the lowering of the efferent/atrial (E/A) ratio and deceleration time (DcT). In addition to this evidence of mechanical cardiac degradation, leukocytes isolated from the heart and stained with macrophage and myofibroblast markers revealed a significant increase in CD68+ &amp; αSMA+ cells—a result reflected by increased fibrotic remodeling via Masson’s trichrome stain, in the hypertensive animals. This study demonstrated an onset of diastolic dysfunction in the heart of DOCA + salt hypertensive mice. Moreover, we found a positive association between MMT cells and fibrosis in the hearts of hypertensive animals. Future studies will aim to parse out both the gravity of MMT in hypertensive heart dysfunction and the mechanism by which macrophages undergo this transition to find new targets against this debilitating disease.

Long-Term Outcomes of Patients With Apical Hypertrophic Cardiomyopathy Utilizing a New Risk Score

BackgroundApical hypertrophic cardiomyopathy (aHCM) is a distinct variant characterized by predominant hypertrophy of the left ventricle apex. ObjectivesThis study sought to describe aHCM patients' characteristics and develop a risk score for aHCM patients. MethodsA total of 462 patients (age 58 ± 15 years, 68% male) diagnosed with aHCM were included. The primary endpoint was death, appropriate defibrillator discharge, or need for cardiac transplantation. Variables showing potential association with the composite endpoint were considered to develop an aHCM-specific risk score. ResultsAt baseline, 67% patients were asymptomatic and 69% had no risk factors for sudden death. On echocardiography, the mean left ventricle ejection fraction, left atrial volume index, and right ventricular systolic pressure were 64% ± 8%, 36 ± 15 ml/m2, and 32 ± 10 mm Hg, respectively, with 51(11%) demonstrating an apical aneurysm. Baseline cardiac magnetic resonance, performed in 246 (53%) patients, demonstrated delayed gadolinium enhancement in 170 (71%) patients (mean percentage of 4.9% ± 6.6%). At age 6.3 ± 4.8 years, the composite events occurred in 80 (17%, death in 62 [13%]) patients. The aHCM-specific risk score, incorporating age, apical aneurysm, left atrial volume index, serum creatinine, and right ventricular systolic pressure, demonstrated good discrimination (C-statistic = 0.75) with an expected to observed ratio of 1.02 and a calibration slope of 0.91. The risk score ranged between 0 and 8 points, with a higher score associated with higher composite events. ConclusionsaHCM constituted 6.8% of our overall HCM cohort with a composite event rate of 2.8%/year. The aHCM risk score provided good discrimination in predicting the composite primary endpoint, with a higher score associated with a higher rate of events.

P195 CARDIOVASCULAR OUTCOMES IN PATIENTS WITH AORTIC STENOSIS AND HYPERTENSION UNDERGOING AORTIC VALVE REPLACEMENT

Background and Objective: Aortic valve stenosis (AS) is most common valvular heart disease and in its severe form requires aortic valve replacement (AVR). The prevalence of both AS and arterial hypertension (HTN) increases with age and the conditions therefore often co-exist. Co-existence of AS and HTN is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Management of HTN in AS has historically been associated with prudence and concerns, mainly related to drug-induced potential adverse consequences. We evaluated the cardiovascular outcomes of patients with AS and HTN undergoing to AVR Methods: A retrospective cohort study where all the patients who underwent AVR between 2019- 2024, in a 4-level center in Bogotá, Colombia. A descriptive analysis was performed. Continuous variables were expressed as mean or median with their respective measure of dispersion, standard deviation or interquartile range (ICR), the categorical variables were expressed in proportions and absolute numbers. Results: We analyzed 1043 Patients with moderate/severe AS undergoing AVR, 64.3% (671 with HTN), median age for all of 69.8 years ICR (61.7-77.4) Hypertensive patient being older (72 years p&lt;0.0001). In the HTN group 57.8% were men, and more frequently they had diabetes and dyslipidemia comorbidities (p&lt;0.001) as well as greater baseline renal involvement (p&lt;0.001) comparatively with NO-HTN. In addition, hypertensive patient had better LVEF and were treated with ARA II/IECA (55,6% vs 19.4% p&lt;0.001), beta blockers (60.4% vs 47.3% p&lt; 0.001) and anti-calcium medication (13,1% vs 19,5% p&lt;0.001).Table 1. Cardiovascular outcomes showed greater tendency towards worsening of renal function. There were no statistically significant differences in mortality. Conclusions: AVR is presented as a safe procedure in patients with AS and HTN in developing countries. The institutional results show a safe technique, associated with low mortality rates. Hypertensive patients had more acute kidney injury in the post-surgical period, which leads us to propose kidney protection strategies in this group.

Torsemide in the Management of Pulmonary Edema.

Pulmonary edema, either cardiogenic or noncardiogenic, is caused by fluid accumulation in the alveolar spaces. Cardiogenic pulmonary edema (CPE), one of the causes of congestive heart failure (CHF), is treated with loop diuretics. Torsemide and furosemide were found to be useful in the treatment of CHF-associated pulmonary edema due to their ability to lower pulmonary capillary pressure and left ventricular end-diastolic pressure, respectively. Pharmacological features of torsemide, such as greater bioavailability, higher absorption rate, and efficacy, make it a better alternative for treating pulmonary edema than the regularly used loop diuretic, furosemide. Torsemide administered intravenously was found to be both efficacious and well tolerated in CPE. However, more research is needed to determine its usefulness in non-CPE.

Comparison of acute hemodynamic effect of prioritizing ventricular resynchronization vs left ventricular filling during optimization of cardiac resynchronization therapy

BackgroundTargeting maximal ventricular resynchronization, with the shortest QRS duration (QRSd), is commonly implemented after cardiac resynchronization therapy (CRT). ObjectiveThe purpose of this study was to compare optimization of ventricular resynchronization with optimization of left ventricular (LV) filling during CRT by measuring their acute hemodynamic effects. MethodsPatients with standard CRT indications, recruited from 2 centers, underwent biventricular pacing (BVP) and left bundle branch pacing (LBBP). We performed a within-patient comparison of acute hemodynamic response of systolic blood pressure (SBP) at the atrioventricular delay (AVD) with the shortest QRSd against the AVD with the most efficient LV filling. In a validation substudy, we also performed electrical assessment using QRS area (QRSa) and hemodynamic assessment with the maximum rate of LV pressure rise (dP/dtmax). ResultsThirty patients (age 65 ± 10 years; 53% male) were recruited. The AVD producing maximal ventricular resynchronization was associated with a significantly shorter QRSd (difference 15 ± 12 ms for BVP and 18 ± 13 ms for LBBP, both P <.01) and a significantly smaller improvement in SBP (difference −3 ± 4 mm Hg for BVP and −2 ± 2 mm Hg for LBBP, both P <.01) compared with the AVD that optimized filling. Similar findings were observed in the substudy, with a significantly smaller improvement in dP/dtmax assessed with QRSd and QRSa (difference −9% ± 7% and −6% ± 4% during BVP, and −5% ± 6% and −3% ± 3% during LBBP, all P <.01). ConclusionTargeting the maximal ventricular resynchronization results in suboptimal acute hemodynamic performance with both BVP and LBBP as CRT. These findings support prioritizing LV filling when programming AVD for CRT.

P178 CENTRAL OR PERIPHERAL INJECTION OF A FORMULATION CONTAINING THE ANGIOTENSINERGIC DIPEPTIDE ASP-ARG REDUCES ARTERIAL PRESSURE AND CARDIAC INOTROPY IN HYPERTENSIVE RATS

Background and objective: Acute injection of Angiotensin 1-2 [Ang-(1-2)] reduced arterial pressure and heart rate, and improved coronary perfusion in normotensive and hypertensive rats. Formulations that confer stability and protection against proteolysis are requisites to the feasibility peptides. Next, we evaluated in rats the cardiovascular effects of peripheral or central injections of a complex containing Ang-(1-2) surrounded by a cyclodextrin. Methods: Ethics committee approval by CEUA-FOAr/UNESP 15/2022. We used male Holtzman rats that underwent 2 kidneys, 1 clip (2K1C) hypertension or sham surgery. Six weeks later, rats were separated in different experimental sets (n=4-6 per group) and were instrumented for intracerebroventricular (i.c.v.) and intravenous (i.v.) injections while recording arterial and cardiac left ventricular pressures. The dipeptide was injected i.c.v. (1, 25, 50 and 250pmol/2 μL) or i.v. (25mmol/0.1 mL). Results: dipeptide i.c.v. (25, 50 or 250pmol) reduced arterial pressure of normotensive rats (Δ=-20±3, -20±1 and -18±7mmHg respectively, P&lt;0.05 vs. baseline). In 2K1C, the antihypertensive effect was observed at all doses (Δ=-19±4, -26±5, -19±3 and -17±1mmHg respectively, P&lt;0.05 vs. baseline). I.v. injection of the dipeptide evoked slight increase in arterial pressure (Δ=7±3mmHg; P&lt;0.05 vs. baseline) that was accompanied by a positive inotropic effect (Δ=524±159mmHg/s; P&lt;0.05 vs. baseline). In 2K1C, this same injection reduced arterial and ventricular pressures (Δ=-14±4 and -20±1mmHg respectively, P&lt;0.05 vs. baseline), and caused negative inotropy (ΔLVdP/dtmax=-1140±170mmHg/s; P&lt;0.05 vs. baseline). I.c.v. injection of dipeptide in anesthetized normotensive rats discretely increased arterial and ventricular pressures, while in 2K1C group it reduced arterial and ventricular pressures (Δ=-17±3 and -18±4mmHg respectively, P&lt;0.05 vs. baseline). The ratio between the variations in contractility and mean arterial pressure revealed afterload-independent inotropic effects, i.e, the dipeptide directly affects heart performance of 2K1C. Conclusions: The formulation containing Asp1-Arg2 reduces arterial pressure and modulates cardiac function during hypertension. Whether Ang-(1-2) acts through some antagonism on Angiotensin II receptors or other paths remain to be investigated. Support: CONFAP-FAPESP/FAPEG 2019/24154-3, PROPe-UNESP 13/2022, CNPq-404079/2021-0 and FAPEG-202310267000206.

The Structure of Left Ventricular Relaxation in Case of Ventriculography.

To study the relaxation structure of the left ventricle (LV) in patients who underwent ventriculography. LV ventriculography was performed in 37 patients. Before catheterization, echocardiography was performed in each patient. In 6 patients, the LV ejection fraction (EF) was below 40%; these patients with systolic dysfunction were not included in the study. In 31 patients, the LV EF was higher than 50%. In this group, 13 patients had NYHA functional class (FC) 2-3 chronic heart failure (CHF); the rest of the patients had FC 1 CHF. Eighteen of 31 patients had stable ischemic heart disease; 50% of these patients had a history of myocardial infarction; the rest of the patients had hypertension and atrial and ventricular arrhythmias. The dynamics of the LV pressure decrease was analyzed from the moment of the maximum rate of pressure drop, which usually coincides with the closure of the aortic valves. The pressure drop curve was logarithmized with natural logarithms and divided into 4-5 sections with different degrees of curve slope. The relaxation time constant was calculated for each section. Its inverse value characterizes the relaxation time constant (tau). In 31 patients with LV EF 52-60%, three types of the dynamics of the relaxation rate constant were identified during the pressure decrease in the isovolumic phase: in 9 patients, the isovolumic relaxation constant (IRC) steadily increased as the pressure decreased; in 13 patients, it continuously decreased; and in 9 patients, the dynamics of IRC change was intermediate, with an initial increase followed by a decrease. In diastolic dysfunction, one group of patients had an adaptation type associated with an increase in the LV wall elasticity, while the other group had a different type of adaptation associated with its decrease. Each type has advantages and disadvantages. This is probably due to changes in the structure of the sarcomeric protein connectin (titin).

Association of ventricular-arterial coupling with biomarkers involved in heart failure pathophysiology-the STANISLAS cohort.

Impaired left ventricular-arterial coupling (VAC) has been shown to correlate with worse prognosis in cardiac diseases and heart failure (HF). The extent of the relationship between VAC and circulating biomarkers associated with HF has been scarcely documented. We aimed to explore associations of VAC with proteins involved in HF pathophysiology within a large population-based cohort of middle-aged individuals. In the forth visit of the STANISLAS family cohort, involving 1309 participants (mean age 48 ± 14 years; 48% male) from parent and children generations, we analysed the association of 32 HF-related proteins with non-invasively assessed VAC using pulse wave velocity (PWV)/global longitudinal strain (GLS) and arterial elastance (Ea)/ventricular end-systolic elastance (Ees). Among the 32 tested proteins, fatty acid-binding protein adipocyte 4, interleukin-6, growth differentiation factor 15, matrix metalloproteinase (MMP)-1, and MMP-9 and adrenomedullin were positively associated with PWV/GLS whereas transforming growth factor beta receptor type 3, MMP-2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were negatively associated. In multivariable models, only MMP-2 and NT-proBNP were significantly and inversely associated with PWV/GLS in the whole population and in the parent generation. Higher levels of NT-proBNP were also negatively associated with Ea/Ees in the whole cohort but this association did not persist in the parent subgroup. Elevated MMP-2 and NT-proBNP levels correlate with better VAC (lower PWV/GLS), possibly indicating a compensatory cardiovascular response to regulate left ventricular pressure amidst cardiac remodelling and overload.