Change In End-diastolic Volume Research Articles

Heart failure biomarkers and prediction of early left ventricle remodeling after acute coronary syndromes

IntroductionSeveral biomarkers are characteristically elevated in patients with acute heart failure (AHF). Our hypothesis was they could predict early changes in left ventricular (LV) characteristics in acute coronary syndrome (ACS) patients. The objective of this study was two-fold: a) compare circulating concentrations of NT-pro BNP, CA-125, ST2, galectin-3 and pro-adrenomedullin among 4 groups of individuals (healthy controls; patients with ACS without AHF; patients with ACS and AHF and patients admitted for AHF); and b) evaluate whether these biomarkers predict adverse LV remodeling and ejection fraction changes in ACS. Methods6 biomarkers (NT-pro BNP, CA-125, ST2, galectin-3, pro-adrenomedullin and C-reactive) were measured within the first 48 h of admission. Echocardiograms were performed during admission and at 3 months. Variables associated with LV end-diastolic volume (EDV) and ejection fraction (LVEF) change were assessed by multivariate linear regression. ResultsWe analyzed 51 patients with ACS, 16 with AHF and, 20 healthy controls. NT-pro BNP and ST2 concentrations were elevated at similar values in patients admitted for AHF and ACS complicated with HF but CA-125 concentrations were higher in AHF patients. NT-pro BNP concentrations were positively correlated with CA-125 (rho = 0.58; p < 0.001), ST2 (rho = 0.58; p < 0.001) and galectin-3 (rho = 0.37; p < 0.001)Median change (median days was 83 days after) in EDV and LVEF was 5 %. CA-125 concentrations were positively associated to LV EDV change (β-coefficient 1.56) and negatively with LVEF trend (β-coefficient = −0.86). No other biomarker predicted changes in EDV or LVEF. ConclusionsCA-125 correlates with early LV remodeling and LVEF deterioration in ACS patients.

DETERMINANTS OF PHYSIOLOGICAL RESPONSE TO EXERTIONAL HEAT STRESS IN HUMANS

INTRODUCTION AND AIMS Previous field studies of exercise undertaken in hot conditions reported dissociation between heat-related symptoms and body core temperature (Tc) elevation. This prompted us to examine physiological mechanisms underpinning responses to exertional heat exposure in a controlled laboratory experiment. METHODS Thirty-eight apparently healthy participants had body composition (DEXA) and fitness (V̇O2peak) measured in a preliminary visit. Tc, heart rate (HR), exercise intensity (V̇O2) and echocardiographic measures of end-diastolic volume (EDV), stroke volume (SV) and cardiac output (Q̇) were measured at rest and at 30-minute intervals throughout a two-hour walk (5km/h and 2% gradient) in a climate-controlled chamber (40⸰C and 50% relative-humidity). RESULTS Twenty-seven participants completed the experiment (Completers; Com), 7 were stopped due to Tc exceeding 39⸰C (Hyperthermics; Hyp). Four participants did not complete the protocol due to adverse symptoms and were excluded from this analysis. Hyp had significantly greater Tc at 60-minutes (38.6±0.5⸰C vs. 38.0±0.3⸰C; P=&amp;lt;0.001) and 90-minutes (39.0±0.3⸰C vs. 38.3±0.3⸰C; P=&amp;lt;0.001) than Com. Baseline V̇O2peak (ml.kg-1.min-1) did not differ between Hyp and Com (P=0.248). Whilst body weight and lean body mass did not significantly differ between Hyp and Com, visceral adipose tissue (VAT) volume (463.2±194.3cm3 vs. 259.9±284.4cm3 P=0.014) and mass (437.0±183.1g vs. 245.2±268.2g P=0.013) were significantly greater in Hyp vs Com. In Hyp, HR change from baseline was greater at 60-minutes (Δ57±15bpm vs. Δ36±18bpm; P=0.01) and 90-minutes (Δ63±20bpm vs. Δ42±19bpm; P=0.017), whilst change in EDV (Δ-22.7±11.4ml vs. Δ-6.92±11.2ml; P=0.016) and SV (Δ-19.4±6.1ml vs. Δ-0.7±7.5ml; P=&amp;lt;0.001) were significantly reduced in Hyp compared to Com. CONCLUSION During walking in the heat, subjects who became hyperthermic had significantly higher baseline visceral fat mass and early signs of exaggerated haemodynamic burden during exertional heat exposure. This study has implications for the identification of appropriate variables for establishing safe work limits during heat exposure in military and work-related contexts.

Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia.

Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD. 40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise. Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL versus 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% versus 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% versus 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with versus without BPD (-10±8% versus -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely. In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.

Abstract 18676: Aneurysmectomy or No Aneurysmectomy - An Unknown Heart Failure Terrain

Case Report: A 40-year male with a history of traumatic inferoapical ventricular septal rupture after a motor vehicle accident status post patch repair and left ventricular thrombus on Rivaroxaban presented to the ED with hemoptysis. The patient on arrival was hemodynamically stable. CTA revealed a new 6.9 cm left ventricular pseudoaneurysm and an echocardiogram revealed an EF of 30% with a pseudoaneurysm involving the entire distal septum, lateral wall, and apex and a ventricular septal rupture into the intraventricular septum. Cardiac MRI revealed a pseudoaneurysm from the inferoseptal wall measuring 9.6 x 6.9 x 10.0 cm and a stroke volume of 123 mL. A right heart catheterization revealed no evidence of left-to-right shunting. Given heart failure with reduced ejection fraction in the setting of a pseudoaneurysm and the complexity of aneurysm repair, advanced heart failure and cardiothoracic surgery teams were consulted for conventional surgical and transplant evaluation. Due to social barriers, the patient was declined from transplant and ultimately proceeded with patch repair. Intraoperative echocardiography revealed a post-operative EF of 25%. Discussion: This case highlights the need for further data on pseudoaneurysms that are confounded with concurrent heart failure. For this patient, the concerns were for adequate stroke volume given the extent of the pseudoaneurysm and whether improvement in systolic function could be seen with repair or result in further decline. It was postulated that surgical repair would raise his effective stroke volume, and thus improve cardiac function. Postoperative EF changes could have been further explained by myocardial stunning during anesthesia or rapid changes in end-diastolic volume with aneurysmectomy altering Frank-Starling hemodynamics. With isolated case report data, further aneurysmectomy outcome characterization is thus imperative to guide advanced heart failure treatment and improve patient mortality.

Role of collateral circulation in the recovery of left ventricular function after recanalization of chronic coronary total occlusion

Aim. To obtain extended data on the impact of collateral circulation on the recovery of left ventricular (LV) function after recanalization of chronic coronary total occlusion (CTO), especially in patients with reduced left ventricle ejection fraction (LVEF).Material and methods. This single-center, prospective, non-randomized study included 20 patients with single-vessel CTO with reduced LVEF (&lt;50%), confirmed by magnetic resonance imaging (MRI), who underwent successful recanalization. All patients were divided into 2 groups depending on the severity of collateral circulation. After 1, 3 and 6 months, MRI was repeated to assess LV function recovery.Results. All patients had prior myocardial infarction, while in 70% of cases — in the area of the occluded artery. A previous attempt to recanalize CTO was noted in 30%. The mean baseline LVEF according to echocardiography was 38,80±6,72%. The most common target vessel was the right coronary artery (n=17, 85%), followed by the circumflex and anterior descending arteries — 1 (5%) and 2 (10%) patients, respectively. In the group with high collateral circulation, the initial LVEF according to MRI was higher compared to the group with mild collateral circulation (35,8±7,33% vs 30,7±8,82%, p=0,17). After 6 months, MRI showed significant changes in end-diastolic volume (from 226±71,1 ml to 203±55,2 ml) and LV endsystolic volume (from 153±72,8 ml to 118±57,6 ml), as well as mean increase in LVEF by 3,3%, 4,8% and 5,2% at 1, 3 and 6 months, respectively (p=0,01 compared with baseline). The predictors of LVEF recovery in multivariate regression analysis were the initial LVEF according to MRI, and the filling rate of distal CTO bed on coronary angiography (R2=0,63).Conclusion. Successful percutaneous coronary intervention with CTO improves LV function in patients with ischemic cardiomyopathy, regardless of the degree of collateral circulation. LV function recovery generally occurs within 3 months after revascularization.

Transcatheter Left Ventricular Restoration in Patients With Heart Failure

BackgroundLeft ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in patients with heart failure with reduced ejection fraction. The AccuCinch Transcatheter Left Ventricular Restoration system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to the basal free wall radius. We evaluated the echocardiographic and clinical outcomes following transcatheter left ventricular restoration. Methods and ResultsWe analyzed 51 heart failure patients with a left ventricular ejection fraction between 20% and 40%, with no more than 2+ mitral regurgitation treated with optimal medical therapy, who subsequently underwent transcatheter left ventricular restoration. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire scores, and 6-minute walk test distances were measured at baseline through 12 months. Primary analysis end point was change in end-diastolic volume at 12 months compared with baseline. Patients (n = 51) were predominantly male (86%) with a mean age of 56.3 ± 13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% decrease in the free wall arc length. At 12 months, the LV end-diastolic volume decreased by 33.6 ± 34.8 mL (P < .01), with comparable decreases in the LV end-systolic volume. These decreases were associated with significant improvements in the overall Kansas City Cardiomyopathy Questionnaire score (16.4 ± 18.7 points; P < .01) and 6-minute hall walk test distance (45.9 ± 83.9 m; P < .01). There were no periprocedural deaths; through the 1-year follow-up, 1 patient died (day 280) and 1 patient received a left ventricular assist device (day 13). ConclusionsIn patients with heart failure with reduced ejection fraction without significant mitral regurgitation receiving optimal medical therapy, the AccuCinch System resulted in decreases of LV volume, as well as improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).

Serial measurements of myocardial efficiency in patients with aortic valve stenosis: pathophysiological insights and prognostic information

Abstract Background In patients with aortic valve stenosis (AS), the pathophysiological abnormalities involved in the transition to symptomatic heart failure are unclear. During progression of chronic heart failure, the coupling between myocardial stroke work and myocardial oxygen consumption, i.e. myocardial external efficiency (MEE), deteriorates. However, in AS patients it is unknown whether changes in MEE over time are involved in disease progression and whether MEE has prognostic information. Purpose In patients with AS, we 1) investigated changes in MEE over time and 2) studied if MEE was associated with long-term prognosis. Methods In a prospective design, we studied 10 healthy controls and 38 patients with moderate-severe, asymptomatic AS (aortic valve area 0.5±0.1 cm2/m2, mean gradient 31±12 mmHg) and left ventricular ejection fraction ≥50%. The patient group was evaluated by serial 11C-acetate positron emission tomography, cardiovascular magnetic resonance imaging and echocardiography with a median follow-up period of 2.8 years. Furthermore, we conducted an extended follow-up of patients for a median of 5.2 years to detect clinical events (defined as symptoms due to AS, aortic valve replacement, hospitalization due to heart failure or cardiovascular death) and related them to MEE changes. Results During follow-up AS patients mean aortic valve pressure gradients increased by 13 mmHg (9 to 17; p&amp;lt;0.001) (mean (95% confidence interval)) and aortic valve opening area declined by −0.15 cm2 (−0.20 to −0.09; p&amp;lt;0.001). Global longitudinal strain worsened by 2.6% (1.8 to 3.5; p&amp;lt;0.001) and N-terminal pro-B-type natriuretic peptide increased by 162 ng/L (28 to 296; p=0.02) whereas left ventricular ejection fraction and cardiac index did not change significantly. MEE increased during follow-up by 4.3% (1.9 to 6.8; p=0.001) from 25.2% (24.0 to 26.5) to 29.5% (27.3 to 31.8) and was higher compared to healthy volunteers 19.9% (18.1 to 21.8; p&amp;lt;0.001). The changes in MEE were positively correlated to changes in end-diastolic volume (r=0.58, p=0.005) and wall stress (r=0.54, p=0.01). There were no changes in MVO2 0.0 mL/min/100g (−0.8 to 0.8; p=0.98) during follow-up. As compared to event-free patients, patients who experienced a clinical event during long-term follow-up (n=24, 63%) had higher baseline MEE 26.5% (24.3 to 28.6) vs 23.8% (22.6 to 25.1) (p=0.04) and did not increase MEE during follow-up 1.9% (−1.8 to 5.6; p=0.28) vs 5.9% (2.6 to 9.2; p=0.002). Conclusion In asymptomatic AS patients, MEE increased over time in tandem with increasing transvalvular gradients and wall stress. Thus, the myocardium displayed an inherent capacity to improve the coupling between oxidative metabolism and contractile function in response to pressure overload. High baseline MEE and blunted MEE increase predicted a poor prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Lundbeck FoundationArvid Nilssons Foundation

Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy

BackgroundThe relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood. ObjectivesThis study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM. MethodsThis randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest. ResultsNo treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008). ConclusionsIn patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802)

Infarct size and long-term left ventricular remodelling in acute myocardial infarction patients subjected to transcoronary delivery of progenitor cells.

Infarct size (IS) is a fundamental determinant of left-ventricular (LV) remodelling (end-systolic and end-diastolic volume change, ΔESV, ΔEDV) and adverse clinical outcomes after myocardial infarction (MI). Our prior work found that myocardial uptake of transcoronary-delivered progenitor cells is governed by IS. To evaluate the relationship between IS, stem cell uptake, and the magnitude of LV remodelling in patients receiving transcoronary administration of progenitor cells shortly after MI. Thirty-one subjects (age 36-69 years) with primary percutaneous coronary intervention (pPCI)-treated anterior ST-elevation MI (peak CK-MB 584 [181-962] U/l, median [range]) and sustained left ventricle ejection fraction (LVEF) ≤ 45% were studied. On day 10 (median) 4.3 × 106 (median) autologous CD34+ cells (50% labelled with 99mTc-extametazime) were administered via the infarct-related artery (left anterior descending). ΔESV, ΔEDV, and mid circumferential myocardial strain (mCS) were evaluated at 24 months. Infarct mass (cMRI) was 57 [11-112] g. Cell label myocardial uptake (whole-body γ-scans) was proportional to IS (r = 0.62), with a median 2.9% uptake in IS 1st tercile (≤ 45 g), 5.2% in 2nd (46-76 g), and 6.7% in 3rd (> 76 g) (p = 0.0006). Cell uptake in proportion to IS attenuated the IS-ΔESV (p = 0.41) and IS-ΔEDV (p = 0.09) relationship. At 24 months, mCS improved in IS 2nd tercile (p = 0.028) while it showed no significant change in smaller (p = 0.87) or larger infarcts (p = 0.58). This largest human study with labelled CD34+ cell transplantation shortly after MI suggests that cell uptake (proportional to IS) may attenuate the effect of IS on LV adverse remodelling. To boost this effect, further strategies should involve cell types and delivery techniques to maximize myocardial uptake.

Abstract 14327: Intramyocardial Delivery of an Imageable Theranostic Hydrogel Post Myocardial Infarction Alters Regional Strain and Reduces Remodeling in Chronic Porcine Model

Introduction: Myocardial infarction (MI) causes acute regional changes in stiffness and strain, resulting in pathological remodeling in the left ventricle (LV). Intramyocardial injection of hydrogel (HG) into the MI region may alter deformation and improve LV remodeling. Using high resolution cineCT (CCT) we evaluated changes in regional strain, global function, and geometry in chronic porcine MI model. Methods: Yorkshire pigs (n=12) subjected to 90 min balloon occlusion and reperfusion were randomized 5 days post MI to intramyocardial delivery of MI+HG (n=6) or MI only (n=6). Imageable HG was delivered in a 3x3 grid after assessing MI region with hybrid 201 Tl SPECT/CT. Contrast CCT was performed at baseline, day 5 (post MI before HG delivery), and day 12 (7 days post HG delivery) to assess end diastolic volume (EDV) and ejection fraction (EF). Custom software was used to calculate 3D myocardial Lagrangian strains on 6 HG animals and 3 MI only animals in remote, border (&gt;50% normal) and MI regions (&lt;50% normal). Results: At day 5 in both groups, EDV increased by 13.2% (p=0.016), LVEF decreased by 15.7% (p=0.008), and radial strain (E rr ) decreased in MI region by -0.11 (p=0.007). On day 12, EDV decreased by 8.3% in the MI+HG group but increased by 10.4% in the MI only group (p=0.003). LVEF increased significantly in the MI+HG group by 8.96% and was significantly greater than in MI only group (p=0.027) which had no significant changes. Average change in E rr between baseline and day 12 was not different between groups within the MI (p=0.13) or border region (p=0.67). However, average E rr did not decline in the MI+HG group (+0.029) but significantly declined in MI only group (-0.14, p=0.017) (MI+HG vs MI only; p=0.003), mirroring EDV changes. Conclusions: Intramyocardial delivery of HG 5 days post-MI resulted in greater improvement in E rr in remote region and global LVEF and a decrease in EDV suggesting reduced LV remodeling compared to MI only controls.

Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension.

Although pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy, diastolic dilation is prevented by subsequent resting myocardial stiffening.NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation.

Comparison of impedance cardiography and cardiac magnetic resonance imaging for the evaluation of cardiac function in early-stage breast cancer patients

Objective. Breast cancer treatment can negatively impact cardiac function in some breast cancer patients. Current methods (MUGA, echocardiography) used in clinical practice to detect abnormal cardiac changes as a result of treatment suffer from important limitations. Use of alternative techniques that would offer safe, inexpensive and non-invasive cardiac function assessment in this population would be highly advantageous. The aim of this study was to examine the agreement between impedance cardiography (ICG) and cardiac magnetic resonance imaging (CMR) in quantifying stroke volume (SV), cardiac output (CO) and end-diastolic volume (EDV) in this population. Approach. Sixteen breast cancer patients underwent ICG and CMR assessments at three time-points (before treatment, immediately after chemotherapy, and four months after chemotherapy). Bland–Altman analysis was used to quantify the accuracy and precision of ICG (relative to CMR) in estimating absolute values of SV, CO and EDV. Four methods (concordance rate, polar concordance rate, clinical concordance rate and trend interchangeability rate) were also used to assess ICG performance in tracking changes in these variables. Main results. Bland–Altman analysis showed that the accuracy of ICG relative to CMR was −3.1 ml (SV), 0.2 l·min−1 (CO) and −26.0 ml (EDV) and precision was 13.2 ml (SV), 1.1 l·min−1 (CO) and 20.1 ml (EDV), respectively. Trending ability assessment showed that (1) the concordance rate was 87% (SV), 73% (CO) and 73% (EDV), (2) the polar concordance rate was 67% (SV), 53% (CO) and 33% (EDV), (3) the clinical concordance rate was 33% (SV), 40% (CO) and 20% (EDV) and (4) the trend interchangeability rate was 29% (SV), 43% (CO) and 17% (EDV), respectively. Significance. Our findings show that, although ICG showed good accuracy for absolute SV and CO measurements and for CO and EDV changes, precision was poor for all variables in terms of both absolute measurements and trend tracking performance. This suggests that ICG cannot be used interchangeably with CMR in breast cancer patients.

Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction.

Inflammation is a key factor of myocardial damage in reperfused ST-segment-elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment-elevation myocardial infarction. In this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment-elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes. We enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement-defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16-44] versus 28.4 IQR [14-40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, -8.3% to 11.1%) versus -1.1% (IQR, -8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10-28] versus 18 IQR [10-27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002). In this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03156816.

Inflammation in Remote Myocardium and Left Ventricular Remodeling After Acute Myocardial Infarction: A Pilot Study Using T2 Mapping.

The pathophysiological changes in the remote myocardium after acute myocardial infarction (MI) remains less understood. To assess the inflammation in the remote myocardium post-MI and its association with left ventricular (LV) remodeling using T2 mapping. Prospective. Twelve pigs at 3-day post-MI, 6 pigs at 3-month post-MI, 6 healthy pigs; 54 patients at 3-day and 3-month post-MI, 31 healthy volunteers; FIELD STRENGTH/SEQUENCE: A 3T MRI/ steady-state free-precession sequence for T2 mapping (animals: 0, 30, and 55 msec; human: 0, 25, and 55 msec), phase-sensitive inversion recovery gradient echo for late gadolinium enhancement (LGE), balanced steady free-precession sequence for cine. Infarcted myocardium was defined on LGE, remote T2 was measured on T2 maps. LV remodeling was evaluated as LV end-diastolic volume change index between two scans using cine. CD68 staining was conducted to detect monocyte/macrophage. Student-t test and one-way ANOVA were used to compare remote T2 with normal controls. The association of remote T2 with LV remodeling was assessed using linear regression. P values of <0.05 were used to denote statistical significance. Compared with healthy pigs, remote T2 significantly increased from 3 days to 3months post-MI (31.43 ± 0.67 vs. 33.53 ± 1.15 vs. 36.43 ± 1.07 msec). CD68 staining demonstrated the inflammation in remote myocardium post-MI but not in healthy pigs. Significant remote myocardial alterations in T2 were also observed in human group (40.51 ± 1.79 vs. 41.94 ± 1.14 vs. 42.52 ± 1.71 msec). In patients, the 3-month remote T2 (β=0.432) and remote T2 variation between two scans (β=0.554) were both independently associated with LV remodeling. T2 mapping could characterize the abnormalities in the remote myocardium post-MI, which was potentially caused by the inflammatory response. Moreover, variations in remote T2 were associated with LV remodeling. 1 TECHNICAL EFFICACY: Stage 3.

Cardiac magnetic resonance T1 mapping allows for predicting adverse left ventricular remodeling post-reperfused st-elevation myocardial infarction

Abstract Background Cardiac magnet resonance (CMR) T1 mapping allows the quantitative characterization of the severity of tissue injury and predict functional recovery in acute myocardial infarction (AMI). Purpose The study aimed to investigate whether native T1 and ECV of infarct myocardium are influenced by microvascular obstruction (MVO) and have predictive value for adverse left ventricular (LV) remodeling post-infarction. Method A cohort of 54 patients with successfully reperfused STEMI underwent CMR imaging at a 3T scanner in AMI and 3 months post-infarction. Native T1 data was acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, and ECV maps were calculated using blood sampled hematocrit. Manual regions-of-interest were drawn within the infarct myocardium to measure native T1 and ECV (native T1infarct and ECVinfarct, respectively). MVO identified as a low-intensity area within the infarct zone on LGE was eliminated. Results MVO was present in 36 patients (66.67%) in AMI. ECVinfarct in patients with MVO was different from those without (58.66±8.71% vs. 49.64±8.82%, P=0.001), while no significant difference in T1infarct was observed between patients with and without MVO (1474.7±63.5ms vs. 1495.4±98.0ms, P=0.352). ECV correlated well with the change in end-diastolic volume (all patients: r=0.564, P&amp;lt;0.001) and predicted LV remodeling in patients with and without MVO (rMVO absent = 0.626, P=0.005; rMVO present = 0.686, P&amp;lt;0.001; all patients: r=0.622, P&amp;lt;0.001); Native T1 was only associated with a 3-month change in LV end-diastolic volume (rMVO absent= 0.483, P=0.042) and predicted LV remodeling in patients without MVO (rMVO absent = 0.659, P=0.003). Furthermore, ECV had an association with LV remodeling (β=0.312, P=0.007) in multivariable logistic analysis. Conclusion Absolute native T1 in infarct myocardium might be affected by MVO but ECV isn't. ECV could predict LV remodeling in MI patients with and without MVO, while native T1 predict it in MI with MVO absent. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University

Role of CMV-serostatus and CX3CR1 on lymphocyte kinetics and left ventricular remodelling in patients with acute myocardial infarction

Abstract Background Patients with latent cytomegalovirus (CMV) infection have higher rates of adverse cardiovascular outcomes, but the reasons for this remain elusive. CMV-induced changes to T-lymphocyte populations, with a proliferation of CMV-specific, CX3CR1+ effector memory cells, may contribute. Effector T-cells are associated with cardiovascular mortality in CMV positive patients, and ischaemia-reperfusion injury after ST-elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (pPCI). Purpose To investigate the effect of CMV status on lymphocyte kinetics and cardiac MRI (cMRI) parameters in 52 STEMI patients receiving pPCI, and examine the prognostic relevance of pre-reperfusion lymphocyte count in a large cohort. Methods We retrospectively analysed the association between pre-reperfusion lymphocyte count, troponin, and long-term survival in 4874 consecutive STEMI patients. Using flow cytometry, we analysed lymphocyte kinetics in 52 STEMI patients, of known CMV status, during and after pPCI. We assessed the impact of CMV status on infarct size, left-ventricular (LV) function and microvascular obstruction with cMRI in the first week after reperfusion in 101 patients. Repeat cMRI at 12 weeks, to assess LV remodelling, was obtained in 48 patients. Results Pre-reperfusion lymphopenia is an independent predictor of mortality over 7.5 years (hazard ratio for lowest vs highest quartile: 2.0; 95% CI 1.7–2.4; p&amp;lt;0.001), and is associated with higher admission troponins (p&amp;lt;0.001 for lowest vs second-lowest quartile), suggesting lymphocyte count falls prior to reperfusion in response to myocardial injury. CMV positive patients had more cytotoxic T-cells, strongly expressing the fractalkine receptor, CX3CR1. In CMV positive patients these cells fell dramatically by 90 minutes post-reperfusion, and dropped more sharply in patients with extensive microvascular obstruction on cMRI (p≤0.05 in all effector subsets). CX3CR1 expression was lower at 90 minutes post-reperfusion than at 24 hours (return to physiological expression) in all effector T-cell subsets. All subsets lost a similar proportion of their 24-hour value, but consistently lost a larger proportion in CMV positive patients (−27% in CMV+, −18% in CMV−; p=0.007). CX3CR1 expression falls in the presence of fractalkine, and we hypothesise that membrane-bound fractalkine is induced more strongly in CMV positive patients, as soluble fractalkine levels were similar. At 12 weeks, LV remodeling was worse in CMV positive patients (change in end-diastolic volume: +10.7ml vs −6.1ml; p=0.02). Conclusions Lymphopenia occurs prior to reperfusion in STEMI, and predicts long-term mortality. Effector T-cells drop substantially after reperfusion only in CMV positive patients, likely mediated by CX3CR1-fractalkine interaction, and this is associated with adverse cMRI findings. Remodeling is worse in CMV positive patients at 12 weeks post-STEMI. Lymphocytes, troponin and survival Funding Acknowledgement Type of funding source: Public Institution(s)

Hemodynamic heterogeneity of inadequate cardiac output increase identified by 2-dimensional volumetric exercise echocardiography: slow, stiff or weak heart?

Abstract Background Two-dimensional (2-D) volumetric exercise stress echocardiography (ESE) provides an integrated view of preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose To assess the dependence of stroke volume (SV) and cardiac output (CO) upon LVCR EDV changes and heart rate (HR) during ESE. Methods We prospectively performed semi-supine bicycle or treadmill ESE in 1,344 patients (age 59.8±11.4 years; 550 female; ejection fraction = 62.5±8%) referred for known or suspected coronary artery disease in 20 quality controlled laboratories of 16 countries from 2016 to 2019. SV was calculated at rest and peak stress from raw measurement of LV EDV and ESV by biplane Simpson rule, 2-D echo. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values &amp;lt;2.0 identify a “weak” heart). Preload reserve was defined by an increase in LV EDV. Abnormal values (lack of EDV increase, peak EDV ≤ rest EDV) identify a “stiff” heart. Cardiac output was calculated as SV * HR (measured with standard EKG). HR reserve (stress/rest ratio) &amp;lt;1.85 identifies a “slow” heart with chronotropic incompetence. Results By selection, all patients had negative SE by wall motion criteria. Of the 1,344 patients included in the study, 448 belonged to the lowest tertile of CO increase. Of them 326 (73%) achieved HR reserve &amp;lt;1.85; 220 (49%) had a blunted LVCR and 374 (83%) a reduction of preload reserve, with 348 patients (78%) showing ≥2 abnormalities. The more the abnormal criteria, the worse the CO response, which was lowest in slow, stiff and weak hearts: see figure. Conclusion Patients with normal CO reserve during exercise usually have a fast, compliant and strong heart. Abnormal CO reserve is associated with heterogeneous hemodynamic responses, with slow, stiff and/or weak hearts. The clarification of underlying hemodynamic heterogeneity is the prerequisite for a personalized treatment, and can be easily extracted from a standard 2-D volumetric SE. Hearts with normal CO are all alike; every heart with abnormal CO is abnormal in its own way. CO % changes in subsets (*p&amp;lt;0.001) Funding Acknowledgement Type of funding source: None

A novel porcine model of thrombotic myocardial infarction with cardiac dysfunction sensitive to dual antiplatelet therapy

Few effective porcine models of myocardial infarction (MI) related to platelet thrombus formation are available. In this study, we established a novel porcine MI model and examined the effect of dual antiplatelet therapy (DAPT) with aspirin and prasugrel, a P2Y12 antagonist, using this MI model. Thrombotic MI was photochemically induced using rose bengal. Male miniature pigs were divided into 3 treatment groups: Sham, MI, and DAPT. In the DAPT group, aspirin (10 mg/kg, p.o.) and prasugrel (1 mg/kg, p.o.) were administered 4 h before photo-irradiation. Platelet aggregation, MI volume, and cardiac function were evaluated 24 h after photo-irradiation. Inhibition of ADP-induced platelet aggregation in the DAPT group was about 45%, similar to the effects of DAPT in a clinical setting. No MI was observed in the Sham group, and MI volume was 12.9 ± 2.9% in the left ventricle (P = 0.0016) in the MI group. Additionally, an increase in end-systolic volume (P = 0.0006), and a decrease in stroke volume (P = 0.0001) and ejection fraction (P < 0.0001) were observed in the MI group compared to the Sham group without any changes in end-diastolic volume. DAPT significantly decreased MI volume (P = 0.0006) and ameliorated cardiac dysfunction compared to the MI group. In conclusion, a novel porcine model of thrombotic MI with cardiac dysfunction was established. In this model, DAPT decreased MI volume and ameliorated of cardiac dysfunction, suggesting that this porcine MI model could be useful for future research on MI and antithrombotic agents.

Exercise cardiac magnetic resonance imaging: a feasibility study and meta-analysis.

Cardiac stress testing improves detection and risk assessment of heart disease. Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing cardiac morphology and function at rest; however, exercise MRI has not been widely adapted for cardiac assessment because of imaging and device limitations. Commercially available magnetic resonance ergometers, together with improved imaging sequences, have overcome many previous limitations, making cardiac stress MRI more feasible. Here, we aimed to demonstrate clinical feasibility and establish the normative, healthy response to supine exercise MRI. Eight young, healthy subjects underwent rest and exercise cinematic imaging to measure left ventricular volumes and ejection fraction. To establish the normative, healthy response to exercise MRI we performed a comprehensive literature review and meta-analysis of existing exercise cardiac MRI studies. Results were pooled using a random effects model to define the left ventricular ejection fraction, end-diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data showed a marked increase in cardiac index with exercise, secondary to an increase in both heart rate and stroke volume. The change in stroke volume was driven by a reduction in end-systolic volume, with no change in end-diastolic volume. These findings were entirely consistent with 17 previous exercise MRI studies (226 individual records), despite differences in imaging approach, ergometer, or exercise type. Taken together, the data herein demonstrate that exercise cardiac MRI is clinically feasible, using commercially available exercise equipment and vendor-provided product sequences and establish the normative, healthy response to exercise MRI.

Effects of Increased Preload on Cardiac Function in Younger vs Older Women

PURPOSE: Limitations in cardiac preload and/or compliance could underlie diminished stroke volume and ventricular remodeling adaptations to endurance exercise in older women. The present study tested the hypothesis that attenuated cardiac function in older women persists during acute increases in preload, both at rest and during exercise. METHODS: Nine younger (Y, 21-28 y) and ten older (O, 61-73 y) healthy, non-endurance trained women were studied 1) at rest in the supine and seated positions, and 2) during graded upright cycle ergometer exercise (20, 40, 60 and 80% of VO2peak), both before and after acute plasma volume (PV) expansion (via IV infusion of 5% albumin; 10ml/kg). Cardiac responses to postural change, exercise, and PV expansion were measured using echocardiography (rest and low intensity exercise) and open circuit C2H2 (exercise). RESULTS: Under resting normovolemic conditions, stroke volume (SV) was augmented in the supine (vs. upright) posture in both Y (61±9 vs. 52±8 ml/beat, P<0.05) and O (55±10 vs. 49±7 ml/beat, P<0.05) women. Hypervolemia augmented supine SV further in Y (68±4 ml/beat, P<0.05 vs. normovolemia), but not in O (55±10 ml/ beat, P>0.05 vs. normovolemia) women. These resting postural and hypervolemic effects were mediated by changes in end diastolic volume, and not secondary to age group differences in the extent of PV expansion (averaged +16% and +13% in Y and O, respectively) or estimated filling pressures (E/E’). E/A ratio during peak resting preload conditions (i.e., supine hypervolemia), moreover, was positively associated with VO2peak in Y, but not in O women. During upright exercise, hypervolemia increased SV an average of 15 ml/beat across all 4 work intensities in Y women (p<0.05 vs. normovolemia). This was in contrast to O women, who exhibited very small increases in SV during hypervolemic exercise (i.e., <5 ml/beat). CONCLUSIONS: Healthy older women appear to have a reduced ability (relative to younger women) to utilize acute increases in preload to raise left ventricular stroke volume, including during large muscle exercise. These findings likely reflect the combined effects of exceptional lusitropic function in younger women, and a less compliant ventricle in the aged female heart.