Early LV Research Articles

Estimated total amyloid burden from 18F-florbetaben PET predicts all-cause mortality in light-chain cardiac amyloidosis.

The positron emission tomography (PET) tracer 18F-florbetaben is a promising diagnostic tool for light-chain cardiac amyloidosis (AL-CA). A greater cardiac uptake might signal more amyloid burden and a worse outcome. We aimed to assess the prognostic significance of 18F-florbetaben uptake in AL-CA. Consecutive patients with AL-CA underwent 18F-florbetaben PET scans. Total amyloid burden (TAB; calculated as mean standardized uptake value multiplied by molecular volume) was assessed in the left and right ventricles (LV/RV) in early (5-15') and late (50-60') acquisitions. The endpoint was all-cause mortality. Forty patients (median age 69 years, 73% males, Mayo 2004 stage III in 80%) underwent 18F-florbetaben PET with a median time from tissue biopsy of 21 days (interquartile range, IQR 7-83). Late LV TAB, but not early LV TAB, correlated with N-terminal pro-BNP (NT-proBNP) and hs troponin T. Over 13 months after the PET scan (IQR 5-21), 65% of patients died. A late LV TAB ≥273 cm3 (cut-off derived from spline curve analysis) predicted 18- and 24-month all-cause mortality independently from baseline variables, including NT-proBNP, hs-troponin T, and Mayo 2004 stage. Late RV TAB ≥135 cm3 independently predicted 18- and 24-month all-cause mortality. Patients with both late LV and RV TAB ≥cut-offs had a shorter survival than those with only LV TAB ≥cut-off and those with TAB in both ventricles <cut-offs (Log-rank 16.52, p<0.001). 18F-florbetaben PET imaging offers valuable prognostic information in AL-CA. Values of late TAB measured in the LV and RV are strong predictors of all-cause mortality.

Differences in cardiac mechanics assessed by left ventricular hemodynamic forces in athletes and patients with hypertension

We sought to assess cardiac magnetic resonance derived left ventricular hemodynamic forces (HDF) in athletes compared to patients with hypertension. Sixty athletes and 48 hypertensive patients were studied. HDF were measured during the entire cardiac cycle, the systolic phase, suction, early LV filling, and atrial thrust. Statistical comparisons were made between athletes and hypertensive patients, and between endurance and strength athletes. The slope of the systolic ejection was higher in athletes compared to hypertensive patients (541.5 vs. 435 1/sec; p = 0.033). Athletes showed higher HDF during the first phase of systole (4.53 vs. 3.86; p = 0.047) and the systolic impulse (11.26 vs. 8.76; p = 0.045). Compared to hypertensive patients, the AUC of the elastic rebound in athletes was lower (-0.31 vs. -0.44; p = 0.011). Moreover, hypertensive patients had an abnormal suction as revealed by a divergent direction (apex-to-base) of the HDF. The atrial thrust was higher in hypertensive patients than in athletes (-0.31 vs. -0.05; p < 0.001). Compared to endurance athletes, strength athletes had a shorter duration of the systolic impulse (250 vs. 280 ms; p = 0.019) and higher AUC during the early LV filling (1.65 vs. 0.97; p = 0.016). We conclude that HDF allows distinction between the hemodynamic patterns of athletes and patients with hypertension.

No Difference in Systolic Dysfunction from Left Ventricular Pressure-Volume Loop’s Area and Stroke Work Between Chronic Late Load vs. Early Systolic LV Load in Porcine Model

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;in increased LV afterload as in hypertension, early systolic LV dysfunction (SD) in late compares to early peak systolic LV load for P-V area, stroke work, potential energy with effective LV work (EW) is not being defined (aortic stenosis, arterial hypertension or coarctation of the aorta) in LVH remodeling. &amp;lt;i&amp;gt;Objectives:&amp;lt;/i&amp;gt; to assess in porcine model how LV stroke work, PVA and EW are related to LVH remodeling in developing early SD with HF, between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week in chronic LL compares to EL. It is suggested that reduced proximal thoracic or asc. aortic compliance results with myocardial ischemia. However, difference for LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand and effective LV work in different LV afterload is not understood in early development systolic HF. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; in fourteen domestic male pigs (28±3 kg) with moderate descending aortic banding having chronic late LV load (LL=8) or ascending aortic stenosis with early systolic LV load (EL=6) SD was assessed, from PVA, in invasive LV pressure-volume loops’ measurements, at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week, to assess LV maximal ESPVR, with Millar 5Fr P-V pig-tailed conductance catheter. LV stroke work, and pressure-volume area PVA, reflecting the maximal LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand were assessed in chronic LL compares to EL from nonlinear regression analysis of maximal LV end-systolic stiffness, in special software. For variance analysis, two-way repeated measures ANOVA was performed, with normality assessment. Results are means±(SEM) or medians for significant p&amp;lt;0.05. &amp;lt;i&amp;gt;Results: &amp;lt;/i&amp;gt;LV PVA was not different, in LL compared to EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. LV stroke work with effective works were not different and potential energy, neither were changed between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. No difference was found in different LV afterload, in both indexed and absolute LVO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand, in LL vs. EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; or 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. Indexed PVA parameters with LV stroke work, effective work and potential energy were not different or changed in LL compares to EL between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; weeks, normalized per body surface-area (in m&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;). &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Both absolute and indexed LV stroke work, potential LV energy, PVA with EW and maximum LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand are not different in LL compares to EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week of LVH remodeling, indicating no difference in early SD development in increased late vs. early LV afterload.

Evaluation of left ventricular systolic function in patients with iron deficiency anemia based on non-invasive left ventricular pressure–strain loops

BackgroundIron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press–strain loop (LV-PSL).MethodsSixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL < Hb < 9 g/dL. Thirty-three healthy individuals were used as the control (Group A). The global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global waste work (GWW), global work efficiency (GWE) were derived using LV-PSL analysis. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal left ventricular systolic function in IDA patients.ResultsCompared to group A, GWI and GCW were reduced in group B (both P < 0.01). Compared with groups B and A, GLS, GWI, GCW and GWE, and E/A were all diminished, and GWW, LVEDV, LVESV, and E/mean e’ were all increased in group C (all P < 0.01). GLS was positively correlated with GWI, GCW, and GWE (r = 0.679, 0.681, and 0.447, all P < 0.01), and negatively associated with GWW (r = − 0.411, all P < 0.01). For GWI, area under the ROC curve (AUROC) was 0.783. The optimal GWI threshold for detecting abnormal LV systolic function in IDA was1763 mmHg%, with sensitivity of 0.71 and specificity of 0.78.ConclusionsLV-PSL allows noninvasive quantitative assessment of early impaired LV systolic function in IDA patients with preserved LV ejection fraction, and GWI has high sensitivity and specificity compared with other parameters.

Abstract We094: Acute Administration of The Novel Cardiac Sarcomere Modulator EDG-7500, Improves Ventricular Filling While Preserving LVEF In Dogs with Pacing Induced Left-Ventricular Systolic Dysfunction

Introduction: EDG-7500 is a cardiac sarcomere modulator that has been shown to slow early LV contraction and to improve diastolic filling, without directly inhibiting cardiac myosin. To assess the acute hemodynamic effects of EDG-7500 in a model of depressed systolic and diastolic LV function, we studied dogs with pacing-induced LV dysfunction before and after EDG-7500 administration. Methods: Beagle dogs (n = 7) underwent chronic RV pacing (180 to 240 ppm), and were studied, in sinus rhythm, at two levels of induced-dysfunction: mid-range EF (mEF, targeting 50%), and reduced EF (rEF, targeting 40%). At each level, animals were evaluated by echocardiography before and after administration of 0.3 mg/kg IV EDG-7500. Healthy beagle dogs served as disease controls (n = 7). Results: Post-pacing (Paced) dogs had depressed EF (mEF: 50 ± 4 and rEF: 40 ± 4 vs. 74 ± 1%, P &lt; 0.05) and short-axis global circumferential strain (mEF: -23 ± 2 and rEF: -14 ± 2 vs. -33 ± 1%, P &lt; 0.05), and elevated NT-proBNPs (mEF: 1,049 ± 319 and rEF: 4,236 ± 722 vs. 302 ± 27 pmol/L, P &lt; 0.05) when compared vs. healthy dogs. Paced dogs had slower early diastolic mitral annular velocity (mean e’, mEF: 11.0 ± 0.9 and rEF: 8.4 ± 0.8 vs. 14.2 ± 0.7 cm/s, P &lt; 0.05) and elevated E/e’ (mEF: 7.4 ± 0.7 and rEF: 8.4 ± 0.9 vs. 6.0 ± 0.2 n/u, P &lt; 0.05), at similar heart rates. Acute EDG-7500 increased e’ (mean e’, mEF: +9 ± 2 and rEF: +12 ± 3%, P&lt;0.05) and decreased E/e’ (mEF: -7 ± 2% and rEF: -9 ± 2%, P&lt;0.05), with no detectable effects on EF (mEF: +3 ± 6% and rEF: -5 ± 3%, P=NS). There were no adverse clinical observations. Conclusions: Treatment with EDG-7500 was well tolerated in dogs with tachycardia-induced mid-range (mEF) and reduced LV systolic function (rEF). In both cases, EDG-7500 improved echocardiographic indices of early ventricular filling and filling pressures, without observable effect on systolic performance. This data supports exploration of the effects of EDG-7500 in patient populations with LV diastolic dysfunction and mild to moderately reduced cardiac systolic performance.

Shorten τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; in Chronic Early vs. Late Systolic LV Load for Systolic Dysfunction in Ascending vs. Descending Thoracic Aortic Stenosis

&amp;lt;i&amp;gt;Background:&amp;lt;/i&amp;gt; Arterial hypertension (HTA) results with diastolic LV dysfunction (DD), important to develop systolic LV dysfunction and exercise intolerance with HF. Separating between chronic late (LL) to early LV load (EL) during systole, impaired LV relaxation is present earlier in chronic LL vs. EL, having early HF, as result of myocardial ischemia and systolic LV dysfunction in HTA. &amp;lt;i&amp;gt;Objective and Methods:&amp;lt;/i&amp;gt; to assess early systolic in diastolic LV dysfunction from biexponential τ regression assessment, using single beat and mono-exponential regression analysis, with nonzero asymptote with special software in LL and EL, between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; and 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week in a porcine model. This assesses early HF and systolic LV pump dysfunction, from fast_τ (τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt;), for early systolic LV dysfunction, in LVH remodeling in moderate LV afterload increase. Fourteen domestic male pigs, underwent LV pressure measurements with conductance Millar 5F catheter having moderate ascending aortic banding (EL=6), and in descending thoracic aortic stenosis, as in hypertension (LL=8). τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; (τ_fast) and τ&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; (for τ_slow) component of bi-exponential τ analyzed LV dysfunction at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. Under reduced LV load (m3), during ventilation preserved (m1) or suspended transitionally (m2), fast τ assess early systolic dysfunction in LL vs. EL. Associated murmurs were assessed to detect LV valves dysfunction. Data was compared statistically, using two-way repeated measurement ANOVA, after Leven normality test. Results are means±SEM or medians (quartiles), for significant p&amp;lt;0.05. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; mono-exponential τ was not different, neither changed in LL vs. EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; and 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week in m1, m2 or m3, that reduced in both groups with mechanical LV load reduction at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; and 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week (p&amp;lt;0.05). Prolonged bi-exponential asynchronous τ&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;/τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; ratio in EL was different from LL at 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week, resulted from LV afterload (τ&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; interaction p&amp;lt;0.05). τ_fast was different, being shorten in EL vs. LL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; and 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. Reduced bi-exponential τ&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; ratio in EL and increased in LL, with mechanical load reduction, improved LV ischemia with DD in EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; and 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week of moderate LV afterload increase, but did not respond in LL. There was predominant systolic murmur in EL and diastolic murmur in LL, pronounced with load reduction. &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Prolonged bi-exponential τ&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; in LL shows early systolic LV dysfunction within DD. LV ischemia and systolic with diastolic LV pump dysfunction in EL presents shorten fast_τ, being unresponsive to mechanical LV load reduction in LL.

NOVEL INTEGRATED IMAGING PARAMETERS FOR RISK STRATIFICATION OF ATRIAL FIBRILLATION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Abstract Background Atrial fibrillation (AF) impacts prognosis of hypertrophic cardiomyopathy (HCM) by promoting progressive heart failure (HF) and increasing risk of stroke. Over the past years, several indexes and methods to predict AF among HCM patients have been proposed. However, they are limited by a lack of accuracy. Aims of our study was to evaluate the role of new echocardiographic parameters in predicting new onset of AF and to validate them by cardiac magnetic resonance (CMR). Methods and Results We analyzed clinical and imaging data of 141 HCM patients in sinus rhythm who underwent first evaluation at our center (51.2 ± 17.3 years, mean follow up 5.3 ± 3 years). Main parameters analyzed were left atrium (LA) end–diastolic volume (LAV min), end–systolic volume (LAVmax), LA ejection fraction (LAEF), left atrioventricular coupling index (LACI), and LA diameter (LAD). LACI was defined by the LAVmin divided by the LV end–diastolic volume (LVEDV); this parameter was assessed in previous studies as a good detector of early atrial remodeling and impaired LV compliance. 35 patients developed new–onset AF (after a mean period of 4 ± 3.2 years). At the baseline evaluation, LACI, LAD, and LAVmin showed to be significantly greater in patients who developed AF compared to patients who did not. At CMR, LACI &amp;gt;44% accurately predicted new–onset AF (sensitivity 85%, specificity 70%; AUC 0.81). LACI by ETT showed similar accuracy (AUC 0.75) and was superior to that shown by LAD (AUC 0.71) (Figure 1). Patients who did not develop AF had significantly higher LAEF at ETT (49.3 ± 11% vs 37 ± 9.6%; p &amp;lt; 0.0001). CMR analysis confirmed this result. LAEF &amp;gt;43% was a good predictor of AF free survival (log rank&amp;lt;0.001). Conversely, at a multivariate analysis, LAFE &amp;lt;43% by ETT was independently associated with AF occurrence (OR 4.5, 95% CI 1.4–13.7) (Figure 2). 11 patients experienced death or heart transplant (HTx). Higher values of LACI and LAVmin and lower values of LAEF were found to be associated the composite outcome of death or HTx. LACI&amp;gt;60% predicted the composite of death or HTx with good accuracy (AUC 0.74) (Figure 3). Conclusions LACI and LAEF showed to improve accuracy in predicting the new onset of AF in HCM patients without severe LA dilatation (LAD&amp;gt;45mm). Higher LACI and Lower LAEF (namely &amp;lt;43%) identify patients at higher risk of new onset AF, and, therefore, worthy of a more strict follow–up.

THE COMPLEX WORLD OF NON CRITICAL CORONARY ARTERIES DISEASE

Abstract Background and Aim Acute coronary syndrome (ACS) with non–critical coronary arteries represents a major diagnostic, therapeutic and prognostic challenge for clinicians. The aim was to compare clinical–anamnestic characteristics and assess the prognosis of three cohorts with ACS with non–critical coronary arteries i.e. Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA), type 2 myocardial infarction (MI) and Takotsubo syndrome (TTS). Methods In this single center observational study, 18223 patients who underwent coronary angiography between 2005 and 2022 were retrospectively analyzed. The final cohort included 676 patients with initial presentation as NSTEMI (301 MINOCA, 237 type 2 MI and 138 TTS). Results The median age was 68±11, with the TTS population being the oldest (72±10, p&amp;lt;0.01), presenting greater hypotension (p&amp;lt;0.01), tachycardia (p&amp;lt;0.01), and fewer cardiovascular risk factors, such as diabetes (p&amp;lt;0.01) and hypertension (p&amp;lt;0.01). The TTS cohort had worse LVEF on admission (p&amp;lt;0.01) and on discharge (p&amp;lt;0.01) (Fig. 1). At Kaplan–Meier analysis, patients with type 2 MI were more prone to the composite endpoint, while the TTS group was less likely (p&amp;lt;0.01) (Fig. 2). In the overall cohort, ACEi/ARB therapy on admission was an independent predictor of the composite endpoint (HR: 1.58;p=0.01), while dual antiplatelet therapy (DAPT) (HR: 0.59;p=0.01) and statin (HR: 0.71;p=0.03) at discharge were protective. After stratification according to diagnosis, ACEi/ARB therapy remained a negative predictor only in the type 2 MI cohort (HR: 2.03;p=0.01) as well as beta–blocker therapy at admission in TTS (HR: 2.97;p=0.03), while statin therapy remained protective in the MINOCA (HR: 0.51;p=0.01) and DAPT therapy in the TTS group (HR: 0.21;p=0.04) at discharge. Although a substantial number of patients with all three diagnoses achieved the endpoint, the multivariable Cox regression analysis indicated that type 2 MI, in addition to older age, male gender, worse LVEF, and anemia, is an independent factor for worse outcomes (Fig. 3). Conclusions Among all cohorts, T2 MI were associated with worse outcome. The use of DAPT in TTS and Statins in the MINOCA group showed a protective role. Since the TTS population was more compromised, BB use in the ADHF phase of TTS could predict a poorer outcome as much as ACEI/ARB use at admission could be a marker of greater early LV impairment of the T2 MI cohort, which was an independent predictor for worst outcome.

Determining The Risk of Atrial Fibrillation Paroxysm in Patients With Chronic Heart Failure With Intact and Reduced Ejection Fraction.

To determine predictors for the development of atrial fibrillation (AF) in patients with chronic heart failure (CHF) with preserved and reduced ejection fraction by echocardiography (EchoCG) according to an extended protocol with determination of diastolic function and left atrial global strain. Data of 168 patients with stage I-III CHF without a history of AF were analyzed. All patients underwent echocardiography according to an extended protocol with the determination of diastolic dysfunction (DD), left atrial ejection fraction (LA EF), and left atrial global strain (LA GS). Tissue Doppler imaging (TDI) was used to evaluate the early (E) and late (A) LV filling velocity and the early (E') and late (A') diastolic mitral annular velocity. In all patients, Holter ECG monitoring (HM ECG) of heart rhythm was performed for 3 days, and ECG monitoring with telemedicine technologies was performed for 7 days, 3 times a day for 3 minutes. The follow-up period was 3 months or until an AF episode. During the study, paroxysmal AF (pAF) was detected in 41 (24.4%) patients using various methods of heart rhythm monitoring. Complaints of palpitations were noted for 10 (24.4%) patients during pAF, which was recorded using a CardioQVARK® device, HM ECG or a 12-lead ECG. In 5 (12.2%) patients, daily ECG monitoring revealed pAF without associated complaints. HM ECG detected 8, 2, 4 (19.5%, 4.8%, and 9.7%) cases during 24, 48 and 72 hours, respectively; a single-channel CardioQVARK® detected 30 (73.2%) cases when used 3 times a day for 7 days. These results showed that AF frequently develops in CHF without accompanying symptoms. The method for detecting pAF with CardioQVARK® showed good results: it was twice more effective than HM ECG and three times more effective than 12-lead ECG. Also, according to ultrasound data, significant changes in the following parameters were noted in patients with AF: LA EF &lt;36% (OR 1.04, 95% CI: 1.02-1.08), p=0.003; LA GS &lt;9.9% (OR 1.16, 95% CI: 1.02-1.38), p&lt;0.001; TDI E med &lt;5.7 cm/s (OR 0.97, 95% CI: 0.94-1.00), p=0.026. Grade 2 DD did not show statistically significant results (OR 1.1, 95% CI: 0.7-1.5, p=0.54). However, it was detected more frequently in patients with AF, in 34% of cases, compared to 29% of cases in patients without AF, which requires further study on a larger patient sample. Patients with CHF have a high risk of developing pAF (24.4%). 75% of patients with AF do not feel the development of paroxysm. All CHF patients should undergo EchoCG with assessment of LA EF, TDI E med and LA GS to identify a group at risk for the development of AF. Heart rhythm remote monitoring with CardioQVARK® devices can be considered a reliable method for early detection of pAF and timely initiation of anticoagulant therapy in patients with CHF.

Impact of a 16-week strength training program on physical performance, body composition and cardiac remodeling in previously untrained women and men.

Even if more and more women are involved in strength-training (ST) programs in fitness centers, studies on strength gain, body composition, and cardiac remodeling were mainly conducted in men and whether they are similar in women remains to be explored. In this context, the aim of our study was to assess the effect of a supervised ST program on strength gains, body composition, and cardiac remodeling in previously untrained women and men. 17 healthy and previously untrained young women and 17 young men participated in a supervised 16-week ST program built according to the recommendation of the American College of Sports Medicine in terms of intensity, and strictly using similar volume and intensity in both groups. Strength performance, body composition, and cardiac remodeling were evaluated every 4weeks. Cardiac adaptations were assessed using resting echocardiography, including regional 2D-Strain analysis of the left atrium and ventricle (LA and LV, respectively). Despite lower values at baseline, women exhibited similar or even higher strength gains compared to men. ST induced a decrease of body and abdominal fat mass and an increase of lean body mass in both groups. Similar cardiac remodeling was observed in women, and women, including an early and progressive LV and LA enlargement throughout the ST program, without any alteration of LV diastolic and systolic functions. These findings underlie that ST programs are highly suitable for women to enhance their strength performance and their cardiovascular health.

Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of β-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.

Incremental prognostic value of speckle tracking echocardiography and early follow-up echo assessment in predicting left ventricular recovery after reperfusion for ST-segment elevation myocardial infarction (STEMI).

Up to 50% of patients do not achieve significant left ventricular ejection fraction (LVEF) recovery after primary percutaneous intervention (PPCI) for STEMI. We aimed to identify the echocardiographic predictors for LVEF recovery and assess the value of early follow-up echocardiography (Echo) in risk assessment of post-myocardial infarction (MI) patients. One hundred one STEMI patients undergoing PPCI were enrolled provided EF below 50%. Baseline echocardiography assessed LVEF, volumes, wall motion score index (WMSI), global longitudinal strain (GLS), global circumferential strain (GCS), and E/e'. Follow-up echocardiography after 6weeks reassessed left ventricular volumes, LVEF and GLS.GCS was not assessed at follow up. Patients were classified into recovery and non-recovery groups. Predictors of LVEF recovery and major adverse cardiovascular events (MACE) at 6 months were analysed. The mean change of EF was 8.04±3.32% in group I versus -.39±5.09 % in group II (p<.001). Recovered patients had better baseline GLS, baseline GCS, E/e', and follow-up GLS. Multivariate regression analysis revealed E/e', GCS, and follow-up GLS after 6weeks to be strong independent predictors for LVEF recovery. Composite MACE was considerably higher in group II (32.7% vs. 4.1%, p<.001) mainly driven by higher heart failure hospitalisation Multivariate regression analysis revealed baseline GLS, E/e', and ejection fraction (EF) percentage recovery as strong independent predictors for MACE. Multiparametric echocardiographic approach incorporating LVEF, strain parameters, and diastolic function could allow early optimal risk stratification after STEMI treated with PPCI. Follow-up GLS and LVEF percentage change are the strongest predictors for early LV recovery and long term clinical outcome, respectively.

Abstract 15612: EDG-7500, a Novel Cardiac Sarcomere Regulator That Preserves Intrinsic Myosin-Motor Function, Improves Cardiac Function and Reserve in a Minipig Model of Hypertrophic Cardiomyopathy

Introduction: Hypertrophic Cardiomyopathy (HCM) is a myocardial disease characterized by LV hypertrophy, hyperdynamic contraction, and diastolic dysfunction that results in impaired exercise capacity. In HCM, excess acto-myosin crossbridge formation during diastole increases myocardial stiffness leading to hindered ventricular filling and limited cardiac reserve. EDG-7500, a novel sarcomere regulator that slows the rate of contraction but does not directly inhibit the myosin motor head, may offer salutary effects in HCM with minimal reduction in systolic performance. Here, this hypothesis was tested in the setting of the pathological HCM beta-myosin heavy chain (MYH7) R403Q mutation. Methods: In vitro, force dynamics were evaluated in human IPSC-derived engineered heart tissues (EHT) with the MYH7 R403Q mutation compared to isogenic controls (WT). The biomechanical effects of EDG-7500 were evaluated in permeabilized fibers from tissues isolated from minipigs carrying the MYH7 R403Q mutation. The in vivo cardiac responses to EDG-7500 were studied via echocardiography and invasive hemodynamics in the R403Q minipigs. In a subset of pigs, β-adrenergic receptor (β-AR) dependent cardiac output reserve was studied. Results: R403Q mutant EHT preserved peak force (PF) relative to WT but impaired relaxation kinetics (RT90: +19±4 ms, 171±4 vs. 152±2 ms in WT, P&lt;0.05). EDG-7500 (0.3uM) accelerated relaxation kinetics in R403Q EHTs (RT90: -8±3ms, 180±4 to 172±2 ms, P&lt;0.05) without affecting PF. RT90 improvement occurred at 6-fold lower concentrations than systolic inhibition (PF IC20: 1.95 ± 0.70 μM). In vivo, EDG-7500 improved early LV filling, accelerating e’ (6.9 ± 0.8 to 8.6 ± 0.6 cm/s, P &lt; 0.05) and decreased atrial volume (-22%, P &lt; 0.05) while enhancing β-AR dependent cardiac output recruitment; in R403Q pigs, EDG-7500 plus dobutamine led to higher cardiac outputs relative to only dobutamine (3.1±0.3 vs. 2.6±0.3 L/min, P&lt;0.05). Conclusions: EDG-7500, a novel cardiac sarcomere regulator, improved diastolic function in EHT and animals with the HCM-pathogenic MYH7 R403Q mutation, improving β-AR dependent cardiac output reserve. This novel profile could be valuable for the treatment of patients with HCM and diseases of diastolic dysfunction.

Clinical study of left ventricular structure and function in patients with Anderson-Fabry disease before and after enzyme replacement therapy.

Cardiac left ventricular hypertrophy (LVH) is the most common manifestation of heart involvement in Anderson-Fabry disease (AFD). Conventional cardiac imaging is not sensitive enough to detect early signs of LVH in AFD. It remains uncertain whether enzyme replacement therapy (ERT) can prevent LVH progression and improve myocardial function. This study aimed to assess the effectiveness of two-dimensional speckle tracking echocardiography (2D-STE) in early detection of cardiac involvement in AFD and monitoring the efficacy of agalsidase alfa and agalsidase beta therapy. Thirteen consecutive AFD patients and 12 healthy controls underwent standard transthoracic 2D, color Doppler, tissue Doppler echocardiography, and 2D strain analysis. Global longitudinal strain (GLS) and global circumferential strain (GCS) were measured. Diastolic strain rate (SR) was extracted. Compared to healthy subjects, AFD patients without LVH showed lower levels of GLS (p < 0.001) and SR (p = 0.01), while there was no difference in GCS (p = 0.82). Following treatment, apical circumferential strain (ACS) showed improvement (p = 0.01). In AFD patients without LVH, there was a decrease in global and segmental LS. Higher plasma Lyso-GL-3 concentrations were associated with elevated ACS values after ERT, indicating that ACS in AFD patients without LVH, albeit normal, is involved in early LV dysfunction.

Abstract P2078: Vasohibin Inhibition Improves Myocardial Relaxation In A Rodent Model Of Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection (HFpEF) is a complex syndrome with few therapies available to patients. Diastolic dysfunction is a common clinical feature among HFpEF patients, and strategies to mitigate impaired relaxation may have a therapeutic benefit. Recognizing that increased stabilization of the microtubule network induced by detyrosination of α-tubulin contributes to increased cardiomyocyte stiffness ex vivo , we explored if inhibition of detyrosination with a small molecule vasohibin inhibitor (VASHi) could improve in vivo diastolic function in obese/hypertensive (ob) ZSF1 rats, compared to lean/hypertensive ZSF1 and non-hypertensive Wistar Kyoto (Wky) rats as controls. Animals received two intravenous injections of VASHi (6.6mg/kg) or vehicle (veh) at 30 weeks old, when ob have a HFpEF phenotype. Echocardiography and invasive hemodynamics were performed after the first and second injection, respectively. Compared to ob veh-treated animals, ob VASHi-treated animals had a significant improvement in invasively measured time constant of early LV relaxation, tau (veh: 14.73ms ± 0.73 vs. VASHi: 11.02ms ± 0.45; P &lt; 0.05) and echo-derived deceleration time of early LV filling, indicative of improved early relaxation (Fig. A, B). VASHi improved early relaxation in cardiomyocytes isolated from non-failing (NF, N=3) and failing (HF, N=4) human hearts (Fig. C), providing the first evidence of small molecule VASHi improving human myocyte function. These studies indicate that excess detyrosination contributes to impaired early myocyte and myocardial relaxation in a clinically relevant HFpEF model and supports a potential therapeutic role for VASHi in HFpEF.

Cardiac T1 mapping enables risk prediction of LV dysfunction after surgery for aortic regurgitation.

To assess whether cardiac T1 mapping for detecting myocardial fibrosis enables preoperative identification of patients at risk for early left ventricular dysfunction after surgery of aortic regurgitation. 1.5 Tesla cardiac magnetic resonance imaging was performed in 40 consecutive aortic regurgitation patients before aortic valve surgery. Native and post-contrast T1 mapping was performed using a modified Look-Locker inversion-recovery sequence. Serial echocardiography was performed at baseline and 8 ± 5 days after aortic valve surgery to quantify LV dysfunction. Receiver operating characteristic analysis was performed to determine the diagnostic accuracy of native T1 mapping and extracellular volume for predicting postoperative LV ejection fraction decrease >-10% after aortic valve surgery. Native T1 was significantly increased in patients with a postoperatively decreased LVEF (n = 15) vs. patients with a preserved postoperative LV ejection fraction (n = 25) (i.e., 1,071 ± 67 ms vs. 1,019 ± 33 ms, p = .001). Extracellular volume was not significantly different between patients with preserved vs. decreased postoperative LV ejection fraction. With a cutoff-of value of 1,053 ms, native T1 yielded an area under the curve (AUC) of .820 (95% CI: .683-.958) for differentiating between patients with preserved vs. reduced LV ejection fraction with 70% sensitivity and 84% specificity. Increased preoperative native T1 is associated with a significantly higher risk of systolic LV dysfunction early after aortic valve surgery in aortic regurgitation patients. Native T1 could be a promising tool to optimize the timing of aortic valve surgery in patients with aortic regurgitation to prevent early postoperative LV dysfunction.

Global myocardial ischaemia in severe aortic stenosis reverses early after aortic valve replacement

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Myocardial ischaemia is common in aortic stenosis (AS) and is associated with exercise capacity, onset of symptoms and adverse myocardial remodelling. Positron emission tomography and invasive coronary studies have evaluated myocardial blood flow before and after aortic valve replacement (AVR), but these have been limited by imaging resolution, or by assessment of flow in a single coronary territory rather than the extent of the myocardium. Cardiovascular magnetic resonance (CMR) can determine myocardial function, remodelling and scar burden, and can also quantify pixel-wise stress myocardial blood flow (MBF). Using AI-based segmentation, global and regional stress and rest MBF can be determined inline with high precision and reproducibility. Purpose We aimed to evaluate the early effects of AVR on myocardial ischaemia in patients with severe symptomatic AS without flow limiting coronary disease. Methods Patients with severe symptomatic AS, without flow limiting coronary stenosis (by CT or invasive angiography), undergoing either surgical or transcatheter AVR were prospectively recruited. Patients underwent baseline echocardiography, paired cardiovascular magnetic resonance (CMR) with adenosine stress (140mcg/kg/min for 4 minutes) pre-operatively and a median[IQR] of 62 [40–83] days post-operatively. Results 26 patients (median [IQR] age 71 [66–75], 73% male) were included (3 patients only had rest perfusion due to safety concerns). The median [IQR] peak aortic velocity by echocardiography (Vmax) was 4.3 [4.1–4.5]m/s and AVA 0.8 [0.6–0.9]cm2. At a median 62 days post-AVR [IQR 40–83 days], the Vmax improved to median [IQR] 2.5 [2.0–2.9]m/s and the LV mass by CMR regressed from median [IQR] 83 [76–92]g/m2 to 72 [66–88]g/m2 (13% reduction), p = 0.001. Stress myocardial blood flow (MBF) increased 21% from median [IQR] 1.63 [1.38–2.21]ml/g/min to 1.97 [1.68–2.52]ml/g/min, p&amp;lt;0.001. Resting MBF did not change (0.88 vs 0.84, p = 0.32). Both epicardial and endocardial stress MBF improved after AVR, but the improvement in global stress MBF was mostly driven by a 40% improvement in endocardial MBF from median [IQR] 1.26 [1.18–1.78] to 1.77 [1.62–2.32]ml/g/min. Likewise there was an improvement in the endocardial to epicardial ratio from median [IQR] 0.73 [0.67–0.81] to 0.85 [0.80–0.97], p&amp;lt;0.001. Conclusions Severe AS results in marked subendocardial ischaemia which may be a substrate for myocardial fibrosis and adverse cardiac events, but is highly and rapidly reversible by valve intervention. The improvement in myocardial blood flow is driven by 40% increase in subendocardial blood flow. This effect is seen despite only modest early LV mass regression. Larger studies with histological correlation are required to determine the relative contributions of afterload and structural capillary rarefaction to ischaemia in these patients.

Left Ventricular Strain in Systemic Diseases

Systemic diseases consist of various pathological conditions with a wide range of symptoms, often with progressive clinical worsening. Cardiac involvement is not uncommon in many of these conditions. Subclinical myocardial dysfunction is the common manifestation during the early stages of the disease and recognition of early myocardial dysfunction is very important for diagnosis and future prognosis. Left ventricular ejection fraction (LVEF) is considered less sensitive to detect early LV myocardial dysfunction. Strain imaging, performed using speckle-tracking echocardiography (STE), has emerged as a robust tool for detecting early subclinical myocardial dysfunction. The longitudinal muscle fibres are predominantly found in the sub-endocardium and are more susceptible to damage since the sub-endocardium is comparatively less perfused. Hence, longitudinal strain is impaired early in the course of the disease and helps in detecting subtle cardiac involvement in various systemic diseases. Global longitudinal strain, which is the average longitudinal strain of all the LV myocardial segments, is currently the most useful strain parameter for this purpose.

(967) Use of the SherpaPak Cardiac Transport System Improves Freedom from Requirement for Mechanical Circulatory Support, Reduced Early Acute Cellular Rejection and Preserves Early Lv Function When Compared to Conventional Cold Storage

(967) Use of the SherpaPak Cardiac Transport System Improves Freedom from Requirement for Mechanical Circulatory Support, Reduced Early Acute Cellular Rejection and Preserves Early Lv Function When Compared to Conventional Cold Storage

Left ventricular assessment in patients with significant mitral incompetence: a multi-modality imaging study

Background: Detection of the deleterious effect of MR on LV is crucial in guiding the surgical decision. Aim of the study: Comprehensive assessment of LV with significant primary MR using (2D, 3D echo and CMR). Methods: 40 patients with significant MR have been recruited in a prospective study. Patients underwent 2D and 3D echo and CMR studies. LV volumes, function and GLS were calculated. Results: End diastolic and systolic volumes were significantly larger when measured by CMR (all p &lt; 0.001). EDV measures were strongly correlated with CMR and 3D echocardiography. Conclusion: It’s important to identify early deleterious LV changes.