Percentage Of Left Ventricular Mass Research Articles

Prevalence and clinical significance of late gadolinium enhancement in children and adolescents with hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death among the paediatric population. The aim of this study is to investigate the prevalence and clinical significance of late gadolinium enhancement, as assessed by cardiac MRI, in paediatric hypertrophic cardiomyopathy. A systematic literature search was conducted in PubMed, SCOPUS, and Ovid SP to identify relevant studies. Pooled estimates with a 95% confidence interval were calculated using the random-effects generic inverse variance model. Statistical analysis was performed using Review Manager v5.4 and R programming. Seventeen studies were included in this meta-analysis, encompassing a total of 778 patients. Late gadolinium enhancement was highly prevalent in paediatric hypertrophic cardiomyopathy, with a pooled prevalence of 51% (95% confidence interval, 40-62%). The estimated extent of focal fibrosis expressed as a percentage of left ventricular mass was 4.70% (95% confidence interval, 2.11-7.30%). The presence of late gadolinium enhancement was associated with an increased risk of adverse cardiac events (pooled odds ratio 3.49, 95% confidence interval 1.10-11.09). The left ventricular mass index of late gadolinium enhancement-positive group was higher than the negative group, with a standardised mean difference of 0.91 (95% confidence interval, 0.42-1.41). This meta-analysis demonstrates that prevalence of late gadolinium enhancement in paediatric hypertrophic cardiomyopathy is similar to that in the adult population. The presence and extent of late gadolinium enhancement are independent predictors of adverse cardiac events, underscoring their prognostic significance among the paediatric population.

Effects of colchicine treatment after myocardial infarction on top of standard therapy: evidence from a preclinical study

Abstract Background An intense inflammatory and fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Colchicine is an anti-inflammatory drug that has been reported to improve the outcome of patients with MI; its effects on LV remodeling have not been specifically investigated. We aimed to characterize the effects of the anti-inflammatory drug colchicine in an animal model of reperfused MI. Methods In 4-month-old pigs, MI was induced by occluding the LAD artery through an angioplasty balloon for 90 minutes. Pigs surviving MI induction were randomized in a 1:1 fashion to 2 arms: - control group (n=13): MI induction and reperfusion, standard treatment (the same therapies as in the rat study), - colchicine group (n=13): MI induction and reperfusion, standard treatment plus colchicine. The pigs underwent a first CMR scan 72 hours after MI induction, and another CMR at day 30. The pigs were then sacrificed the day after the second CMR. The primary efficacy endpoint was LGE mass (as a percentage of LV mass). Results The infarcted area at 72 hours (expressed as absolute mass or as a percentage of the LV mass) and the changes over 1 month did not differ significantly between pigs on colchicine plus standard therapy vs. those on standard therapy alone. When assessing the extent of fibrosis on the explanted hearts (as a percentage of the tissue sample areas) there was a trend toward a lower extent of myocardial fibrosis in pigs on colchicine plus standard therapy (p=0.091). The percent differences in LV volumes, ejection fraction and mass across the two CMR scans did not reach statistical difference. Conclusions The results from a pig model of reperfused MI suggest that colchicine has no additional effects to standard MI therapy on MI size and LV remodeling.

Effects of pirfenidone on scar size and ventricular remodeling after myocardial infarction: a preclinical study

Abstract Background An intense fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Pirfenidone is a drug currently approved for the treatment of idiopathic pulmonary fibrosis, and reduces LV fibrosis in patients with heart failure and preserved ejection fraction. We aimed to characterize the different profiles or protein expression in the infarct zone in rats receiving or not receiving pirfenidone on top of standard therapy for MI. Methods Male Wistar rats were randomized to: sham procedure (group 1; n=13), reperfused MI induced by surgical ligation of the left anterior descending artery (LAD) for 45 minutes (group 2; n=17), reperfused MI plus standard therapy (aspirin, angiotensin-converting enzyme inhibitor, beta-blocker, and also mineralocorticoid receptor antagonist [MRA]) (group 3; n=17), reperfused MI plus pirfenidone alone (group 4; n=17), reperfused MI plus standard therapy and pirfenidone (group 5; n=17). Rats surviving LAD ligation and reperfusion underwent cardiac magnetic resonance (CMR) after 72 hours and 30 days from MI, and were sacrificed the day after the second CMR exam. The primary endpoint was the change in late gadolinium enhancement (LGE) mass as a percentage of LV mass. Results Forty-six rats survived until the second CMR. Percent changes in LV end-diastolic and end-systolic volume (p=0.370 and 0.423, respectively), ejection fraction (p=0.236) and mass (p=0.815) did not differ significantly between rats on pirfenidone plus standard therapy compared with those receiving standard therapy alone. The decrease in LGE mass was significantly greater in rats on pirfenidone plus standard therapy vs. those on standard therapy alone: -22.0% (interquartile range, -37.1 to -5.7, range -51.1 to +37.5) vs. +1.9% (-7.7 to +12.5, range -19.8 to +56.5), p=0.029. Conclusions Pirfenidone had additive effects to standard therapy for MI (including an MRA) in reducing LV fibrosis in a rat model of reperfused MI, while it did not further improve LV function, volumes or mass.

Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction

In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. Percutaneous coronary intervention in addition to optimal medical therapy. Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. ClinicalTrials.gov Identifier: NCT01920048.

Long-Term Monitoring of Cardiac Involvement under Migalastat Treatment Using Magnetic Resonance Tomography in Fabry Disease.

Background: Fabry cardiomyopathy is characterized by left ventricular hypertrophy, myocardial fibrosis, arrhythmia, and premature death. Treatment with migalastat, an oral pharmacological chaperone, was associated with a stabilization of cardiac biomarkers and a reduction in left ventricular mass index, as measured by echocardiography. A recent study, using cardiac magnetic resonance (CMR) as the gold standard, found a stable course of myocardial involvement after 18 months of treatment with migalastat. Our study aimed to provide long-term CMR data for the treatment with migalastat. Methods: A total of 11 females and four males with pathogenic amenable GLA mutations were treated with migalastat and underwent 1.5T CMR imaging for routine treatment effect monitoring. The main outcome was a long-term myocardial structural change, reflected by CMR. Results: After migalastat treatment initiation, left ventricular mass index, end diastolic volume, interventricular septal thickness, posterior wall thickness, estimated glomerular filtration rate, and plasma lyso-Gb3 remained stable during the median follow-up time of 34 months (min.: 25; max.: 47). The T1 relaxation times, reflecting glycosphingolipid accumulation and subsequent processes up to fibrosis, fluctuated over the time without a clear trend. No new onset of late gadolinium enhancement (LGE) areas, reflecting local fibrosis or scar formation of the myocardium, could be detected. However, patients with initially present LGE showed an increase in LGE as a percentage of left ventricular mass. The median α-galactosidase A enzymatic activity increased from 37.3% (IQR 5.88-89.3) to 105% (IQR 37.2-177) of the lower limit of the respective reference level (p = 0.005). Conclusion: Our study confirms an overall stable course of LVMi in patients with FD, treated with migalastat. However, individual patients may experience disease progression, especially those who present with fibrosis of the myocardium already at the time of therapy initiation. Thus, a regular treatment re-evaluation including CMR is needed to provide the optimal management for each patient.

P253 EFFECTS OF COLCHICINE TREATMENT AFTER MYOCARDIAL INFARCTION ON TOP OF STANDARD THERAPY: EVIDENCE FROM A PRECLINICAL STUDY

Abstract Background An intense inflammatory and fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Colchicine is an anti–inflammatory drug that has been reported to improve the outcome of patients with MI; its effects on LV remodeling have not been specifically investigated. We aimed to characterize the effects of the anti–inflammatory drug colchicine in an animal model of reperfused MI. Methods In 4–month–old pigs, MI was induced by occluding the LAD artery through an angioplasty balloon for 90 minutes. Pigs surviving MI induction were randomized in a 1:1 fashion to 2 arms: – control group (n=13): MI induction and reperfusion, standard treatment (the same therapies as in the rat study), – colchicine group (n=13): MI induction and reperfusion, standard treatment plus colchicine. The pigs underwent a first CMR scan 72 hours after MI induction, and another CMR at day 30. The pigs were then sacrificed the day after the second CMR. The primary efficacy endpoint was LGE mass (as a percentage of LV mass). Results The infarcted area at 72 hours (expressed as absolute mass or as a percentage of the LV mass) and the changes over 1 month did not differ significantly between pigs on colchicine plus standard therapy vs. those on standard therapy alone. When assessing the extent of fibrosis on the explanted hearts (as a percentage of the tissue sample areas) there was a trend toward a lower extent of myocardial fibrosis in pigs on colchicine plus standard therapy (p=0.091). The percent differences in LV volumes, ejection fraction and mass across the two CMR scans did not reach statistical difference. Conclusions The results from a pig model of reperfused MI suggest that colchicine has no additional effects to standard MI therapy on MI size and LV remodeling.

P251 EFFECTS OF PIRFENIDONE ON SCAR SIZE AND VENTRICULAR REMODELING AFTER MYOCARDIAL INFARCTION: A PRECLINICAL STUDY

Abstract Background An intense fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Pirfenidone is a drug currently approved for the treatment of idiopathic pulmonary fibrosis, and reduces LV fibrosis in patients with heart failure and preserved ejection fraction. We aimed to characterize the different profiles or protein expression in the infarct zone in rats receiving or not receiving pirfenidone on top of standard therapy for MI. Methods Male Wistar rats were randomized to: sham procedure (group 1; n=13), reperfused MI induced by surgical ligation of the left anterior descending artery (LAD) for 45 minutes (group 2; n=17), reperfused MI plus standard therapy (aspirin, angiotensin–converting enzyme inhibitor, beta–blocker, and also mineralocorticoid receptor antagonist [MRA]) (group 3; n=17), reperfused MI plus pirfenidone alone (group 4; n=17), reperfused MI plus standard therapy and pirfenidone (group 5; n=17). Rats surviving LAD ligation and reperfusion underwent cardiac magnetic resonance (CMR) after 72 hours and 30 days from MI, and were sacrificed the day after the second CMR exam. The primary endpoint was the change in late gadolinium enhancement (LGE) mass as a percentage of LV mass. Results Forty–six rats survived until the second CMR. Percent changes in LV end–diastolic and end–systolic volume (p=0.370 and 0.423, respectively), ejection fraction (p=0.236) and mass (p=0.815) did not differ significantly between rats on pirfenidone plus standard therapy compared with those receiving standard therapy alone. The decrease in LGE mass was significantly greater in rats on pirfenidone plus standard therapy vs. those on standard therapy alone: –22.0% (interquartile range, –37.1 to –5.7, range –51.1 to +37.5) vs. +1.9% (–7.7 to +12.5, range –19.8 to +56.5), p=0.029. Conclusions Pirfenidone had additive effects to standard therapy for MI (including an MRA) in reducing LV fibrosis in a rat model of reperfused MI, while it did not further improve LV function, volumes or mass.

269 EFFECTS OF COLCHICINE TREATMENT AFTER MYOCARDIAL INFARCTION ON TOP OF STANDARD THERAPY: EVIDENCE FROM A PRECLINICAL STUDY

Abstract Background An intense inflammatory and fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Colchicine is an anti-inflammatory drug that has been reported to improve the outcome of patients with MI; its effects on LV remodeling have not been specifically investigated. We aimed to characterize the effects of the anti-inflammatory drug colchicine in an animal model of reperfused MI. Methods In 4-month-old pigs, MI was induced by occluding the LAD artery through an angioplasty balloon for 90 minutes. Pigs surviving MI induction were randomized in a 1:1 fashion to 2 arms: The pigs underwent a first CMR scan 72 hours after MI induction, and another CMR at day 30. The pigs were then sacrificed the day after the second CMR. The primary efficacy endpoint was LGE mass (as a percentage of LV mass). Results The infarcted area at 72 hours (expressed as absolute mass or as a percentage of the LV mass) and the changes over 1 month did not differ significantly between pigs on colchicine plus standard therapy vs. those on standard therapy alone. When assessing the extent of fibrosis on the explanted hearts (as a percentage of the tissue sample areas) there was a trend toward a lower extent of myocardial fibrosis in pigs on colchicine plus standard therapy (p=0.091). The percent differences in LV volumes, ejection fraction and mass across the two CMR scans did not reach statistical difference. Conclusions The results from a pig model of reperfused MI suggest that colchicine has no additional effects to standard MI therapy on MI size and LV remodeling.

267 EFFECTS OF PIRFENIDONE ON SCAR SIZE AND VENTRICULAR REMODELING AFTER MYOCARDIAL INFARCTION: A PRECLINICAL STUDY

Abstract Background An intense fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Pirfenidone is a drug currently approved for the treatment of idiopathic pulmonary fibrosis, and reduces LV fibrosis in patients with heart failure and preserved ejection fraction. We aimed to characterize the different profiles or protein expression in the infarct zone in rats receiving or not receiving pirfenidone on top of standard therapy for MI. Methods Male Wistar rats were randomized to: sham procedure (group 1; n=13), reperfused MI induced by surgical ligation of the left anterior descending artery (LAD) for 45 minutes (group 2; n=17), reperfused MI plus standard therapy (aspirin, angiotensin-converting enzyme inhibitor, beta-blocker, and also mineralocorticoid receptor antagonist [MRA]) (group 3; n=17), reperfused MI plus pirfenidone alone (group 4; n=17), reperfused MI plus standard therapy and pirfenidone (group 5; n=17). Rats surviving LAD ligation and reperfusion underwent cardiac magnetic resonance (CMR) after 72 hours and 30 days from MI, and were sacrificed the day after the second CMR exam. The primary endpoint was the change in late gadolinium enhancement (LGE) mass as a percentage of LV mass. Results Forty-six rats survived until the second CMR. Percent changes in LV end-diastolic and end-systolic volume (p=0.370 and 0.423, respectively), ejection fraction (p=0.236) and mass (p=0.815) did not differ significantly between rats on pirfenidone plus standard therapy compared with those receiving standard therapy alone. The decrease in LGE mass was significantly greater in rats on pirfenidone plus standard therapy vs. those on standard therapy alone: -22.0% (interquartile range, -37.1 to -5.7, range -51.1 to +37.5) vs. +1.9% (-7.7 to +12.5, range -19.8 to +56.5), p=0.029. Conclusions Pirfenidone had additive effects to standard therapy for MI (including an MRA) in reducing LV fibrosis in a rat model of reperfused MI, while it did not further improve LV function, volumes or mass.

Prevalence of atrial myopathy among hypertrophic cardiomyopathy patients without atrial fibrillation

Abstract Background Atrial myopathy (AM) is an entity reflecting left atrial (LA) structural and electrical remodeling, connected to atrial fibrillation (AF) development and heart failure progression in various substrates. In hypertrophic cardiomyopathy (HCM), prevalence of AM beyond AF and its correlations are not fully investigated. Purpose Aim of this study was to estimate the prevalence of AM in a cohort of HCM patients without AF history through assessment of LA volume index (LAVI), LA reservoir strain (LARS) and total atrial conduction time (TACT) (estimated by tissue Doppler imaging). Additionally, to investigate AM indices' correlation with other phenotypic and functional characteristics of HCM. Methods We included 50 HCM patients (60±16 years, 80% male, maximum wall thickness 18.6±4.1mm) without history of AF who have consecutively undergone 2D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). TACT and LARS measurement is shown on left panel. Burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Cut-off points for TACT, LAVI and LARS were adopted by literature (≥115 msec, ≥34 mL/m2 and <21.3% respectively). Results All HCM patients had preserved EF (61.8±8%), while 13 (26%) presented outflow tract obstruction and 4 (8%) diastolic dysfunction stage≥2. LGE was observed in 32 patients (64%) occupying 7.2±5% of left ventricular (LV) mass. Mean TACT was 139.9±22 msec, with LAVI being 30.8±16.1 mL/m2 and LARS 27.6±13.9%. After assessing prevalence of AM parameters, 41 patients (82%) presented a prolonged (≥115 msec) TACT with only 13 of them having also a significantly dilated LA (≥34 mL/m2) and 16 an impaired LARS. Among HCM demographic, phenotypic and functional characteristics tested, age and LV mass index were found to be the only independent regressors of TACT (r=0.54, p<0.0005 and r=0.44, p=0.002 respectively, right panels), while E/E' (r=−0.44, p=0.003) and fibrosis extent (r=0.36, p=0.02) were the strongest predictors of LARS and LAVI values respectively. Conclusions Atrial electro-mechanical delay assessed through TDI based TACT, is the most frequent AM parameter among HCM patients irrespective of AF and even before LA dilatation and LA strain impairment. AM parameters seem to correlate with various morphological and functional characteristics of HCM, their significance, however, in predicting progression towards AF development or HF presentation remains to be elucidated. Funding Acknowledgement Type of funding sources: None.

Total atrial conduction time and its relationship with morphological & functional characteristics in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Total atrial conduction time (TACT), estimated by tissue Doppler imaging (TDI), is an index reflecting left atrial (LA) structural and electrical remodeling, connected to atrial fibrillation (AF) development and heart failure progression in various substrates. In hypertrophic cardiomyopathy (HCM), the significance of TACT beyond AF and its determinants are not fully investigated. Purpose Aim of this study was to estimate TACT in a cohort of HCM patients without AF history and to examine its relationship with other parameters of atrial myopathy, such as LA volume index (LAVI) or LA reservoir strain (LARS). Additionally, to investigate TACT correlation with other phenotypic and functional characteristics of HCM. Methods We included 50 HCM patients (60 ± 16 years, 80% male, maximum wall thickness 18.6 ± 4.1mm) without history of AF who have consecutively undergone 2D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). TACT was measured from the onset P wave on electrocardiogram to the peak A’ wave of the lateral LA wall using TDI (left panel). Burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Cut-off points for TACT, LAVI and LARS were adopted by literature (≥115 msec, ≥34 mL/m2 and <21.3 % respectively). Results All HCM patients had preserved EF (61.8 ± 8%), while 13 (26%) presented outflow tract obstruction and 4 (8%) diastolic dysfunction stage≥2. LGE was observed in 32 patients (64%) occupying 7.2 ± 5% of left ventricular (LV) mass. Mean TACT was 139.9 ± 22 msec, with LAVI being 30.8 ± 16.1 mL/m2 and LARS 27.6 ± 13.9%. After assessing prevalence of atrial myopathy parameters, 41 patients (82%) presented a prolonged (≥115 msec) TACT with only 13 of them having also a significantly dilated LA (≥34 mL/m2) and 16 an impaired LARS. Among HCM demographic, phenotypic and functional characteristics tested, age and LV mass index were found to be the only independent regressors of TACT (r = 0.54, p < 0.0005 and r = 0.44, p = 0.002 respectively, right panels). On the contrary, no significant correlation was established between TACT and traditional diastolic dysfunction indices such as E/E’ or fibrosis extent. Conclusions Atrial electro-mechanical delay assessed through TDI based TACT, is very frequent among HCM patients irrespective of AF and even before LA dilatation and LA strain impairment. Age and hypertrophy magnitude are the main determinants of TACT, the prognostic significance of which remains to be further elucidated. Abstract Figure.

CMR analysis of the cardioprotective effects of chronic statin therapy prior to first STEMI: a propensity score analysis

Abstract Background In addition to their lipid-lowering properties, statins possess cardioprotective effects. However, the impact of the latter on acute cardioprotection and adverse left ventricular (LV) remodelling following ST-elevation myocardial infarction (STEMI) have not been investigated through cardiac magnetic resonance (CMR) analysis to date. Purpose To investigate the cardioprotective effects of chronic oral statin treatment prior to first STEMI. Methods The study included 1236 patients with a first STEMI and a CMR performed during the index admission. Among them, 923 underwent a second CMR at 6 months follow-up. The effects of chronic oral statin treatment prior to STEMI on acute infarct size (IS) as a percentage of LV mass, LV ejection fraction (LVEF), microvascular obstruction (MVO), and changes in LV end-diastolic volume (EDVi) and end-systolic volume indexes (ESVi)] at 6 months were evaluated. A propensity score to receive treatment prior to STEMI with statins was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age on admission, sex, smoking status, type 2 diabetes, hypertension, family history of coronary artery disease, current co-treatments (ACEis/ARBs and/or beta-blockers), heart rate (HR), blood pressure (BP) and creatinine levels on admission, and pre-PCI TIMI flow in the culprit artery. Results were stratified according to a symptom-to-balloon time (S2Bt) ≤ or >3 hours. Results The study population's median age was 59 years (IQR 50–68), 16.3% were women; 18.9% were receiving treatment with statins prior to STEMI (table 1). Despite no effect on MVO occurrence (OR: 0.81 [0.60; 1.09], p=0.166), prior treatment with statins was associated with a reduction in IS (18.43% [16.67; 20.19] vs 21.50% [20.67; 22.34], p=0.002), particularly among subjects with ≤3 hours of S2Bt. Accordingly, prior treatment with statins conferred a benefit in mean baseline LVEF (50.23% [48.73; 51.73] vs 48.15% [47.43; 48.87], p=0.014). At 6 months, treatment with statins prior to STEMI blunted the changes in EDVi and ESVi, but only among patients with ≤3 hours of S2Bt (table 2). In addition, a reduction in the probability of adverse LV remodelling, defined as an increase in ESVi >10%, was observed in statin pre-treated patients (OR: 0.67 [0.45; 0.99], p=0.043). Conclusion Treatment with statins before STEMI is associated with improved indexes of cardioprotection as assessed by CMR, particularly among subjects with S2Bt ≤3 hours. Those effects seem to have an impact in limiting adverse LV remodelling as early as 6 months follow-up, and a greater than 10% change in ESVi. These findings warrant further and prospective evaluation of the potential cardioprotective effects of chronic oral statin treatment prior to STEMI. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This study was partially funded by several grants from Fundaciό La Marato TV3 (2015 30 31 32), Instituto de Salud Carlos III (FIS15/00531) and La Caixa Banking Foundation (HR17-00527).

Impact of blood pressure on the extent of microvascular damage in the setting of reperfusion injury in STEMI asessed with magnetic resonance imaging

Abstract Hypertension is a poor prognostic factor following STEMI, however the impact of blood pressure (BP) on the extent of microvascular damage in the setting of acute ischemia -reperfusion injury has not yet been fully evaluated and this evaluation is the purpose of the present study. Methods A cohort of patients with acute STEMI referred to primary percutaneus intervention were prospectively included. Angiographic analysis were performed according to standard clinical practice and decision regarding type of stent and antiplatelet drugs was left to the discretion of cardiologist. Information about high blood pressure needing drug therapy before acute event and also BP levels at catheterization laboratory during reperfusion procedures were assessed. All patients underwent cardiac MRI during the first week post reperfusion with a standardized protocol including 8–10 short axis slices in order to asses: area of myocardium at risk (AR) as an area of signal hyperintensity >2sd with respect to the remote one in TSE-T2 sequences, necrosis size (NS) as signal hyperintensity >5 SDs relative to the remote in IR-FGE sequences, microvascular obstruction (MVO) as signal hypointensity in the infarct core in IR-FGE sequences and intra-infarct haemorrhage (IIH) as an area with T2*<20msec in T2* mapping sequences. The extent was quantified using a semi-automatic approach and expressed as a percentage of left ventricular mass. Results 94 patients,mean age 62,SD 13, 67% males were included. Hypertensive patients were more likely to have diabetes mellitus 43 vs 28% (p<0.05) while smoking was more frequent in non-hypertensive patients 41% vs 80%. (p<0.05). No differencies were found in extent of AR o rmyocardial salvage between groups, nevertheless hypertensive patients had significantly lower extent of NS, MVO and IIH. Regarding microvascular damage, hypertension showed a protective effect and presence of IIH was observed in 35% of hypertensive patients vs. 65% of non-hypertensive patients (p=0.019 OR: 0.9, p=0.04, CI: 0.1–0.9) and MVO in 40% vs 70% (OR: 0.2, p=0.02, CI: 0.1–0.6). Furthermore patients with BP levels below 120mmhg at cathetherization laboratory showed higher percentage of MVO (62% vs 36%, p<0.05) and IIH (36 vs 15%, p>0.05). Conclusions 1. Hypertension is associated with lower extent of necrosis and microvascular damage without differences in myocardial salvage and area of myocardium at risk. 2. Low BP levels at catheterization laboratory were associated with a significantly higher extent of microvascular damage, so maintaining systolic blood pressure over 120mmhg during reperfusion procedures should be advised. Funding Acknowledgement Type of funding sources: None. Typical CMR sequences: T2w, T2*, IR-FGRCMR segmental analysis with T2* mapping

Left atrial morpho-functional changes in hypertrophic cardiomyopathy and Fabry disease: a CMR-feature tracking study

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular (LV) diastolic dysfunction (DD) is a hallmark of hypertrophic cardiomyopathy (HCM) and its phenocopies, such as Fabry disease (FD). Together with left atrial (LA) size, LA function is emerging as a sensitive marker of the adaptive changes to backward transmission of LV cardiac filling pressure, thus implementing DD assessment. Additionally, both HCM and FD are characterized by a primitive atrial myopathy, but LA morpho-functional changes in HCM and FD have never been directly compared. More recently, LA strain by Cardiovascular Magnetic Resonance Feature Tracking (CMR-FT) has been demonstrated to be a feasible and reproducible tool to explore LA function. Purpose To compare LA morpho-functional changes in HCM and FD and to explore their correlation with tissue alterations. Methods 15 HCM and 15 sex-, age- and LV mass index-matched FD patients underwent CMR (Magnetom Aera 1.5T, Siemens) and Doppler Echocardiography for LV diastolic function assessment (E/e’ and DD grading from 0 to 3). LA phasic function was evaluated by CMR-FT strain (Qstrain Medis). The software output included passive (εe, conduit function), active (εa, booster pump function) and total strain (εs, reservoir function), along with LA volumes and ejection fraction (EF). Late gadolinium enhancement (LGE) was quantified as a percentage of LV mass using the standard deviations (SDs) method (≥ 5 SDs). Interstitial fibrosis was assessed by extracellular volume (ECV) quantification in remote myocardium. All patients were in sinus rhythm. Results In the HCM group, the proportion of patients with DD grade 2-3 was only slightly higher than in FD (p 0.26). Accordingly, no significant difference was found in E/e’ value (p 0.78). Compared to FD, HCM patients showed more severe LA morpho-functional changes, including larger LA end-systolic volume (ESV) (113 ± 35 vs 84 ± 23 ml), lower LA EF (37 ± 7 vs 44 ± 9 %) and a greater reduction of εs (-20 ± 5 vs -25 ± 6 %) and εa (-10 ± 4 vs -15 ± 4 %) (all p < 0.05). LV size and function and the burden of fibrosis (LGE quantification and ECV) were comparable between the two groups. Interestingly, in HCM population, unlike in FD, LA morpho-functional measurements significantly correlated with tissue characterization parameters (LA ESV with LGE, r 0.56, p 0.03; εs and εa with ECV, r -0.51, p 0.05 and r -0.59, p 0.02, respectively). Conclusions LA morpho-functional alterations are much more severe in HCM compared to FD with similar degree of LV hypertrophy. A more severe atrial myopathy or different mechanisms of atrial damage in the two cardiomyopathies may explain these findings. LA CMR-FT analysis may represent a sensitive tool to discriminate between HCM and FD, although larger studies are needed to confirm this finding and the possible correlation with the occurrence of atrial arrhythmias and thromboembolic risk.

Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Myocardial and Microvascular Injury in Acute Myocardial Infarction: Insights From the Randomized MonAMI Trial.

BackgroundIntravenous morphine administration can adversely affect platelet inhibition induced by P2Y12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury.Methods and ResultsPatients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P=0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P=0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P=0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14–0.93 [P=0.035]). There was no significant difference in infarct size (P=0.491) and extent (P=0.753) or presence (P=0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group.ConclusionsIn this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02627950.

Low-dose intracoronary alteplase during primary percutaneous coronary intervention in patients with acute myocardial infarction: the T-TIME three-arm RCT

Background Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction and is independently associated with adverse outcomes. Objective To determine whether or not a strategy involving low-dose intracoronary fibrinolytic therapy infused early after coronary reperfusion will reduce microvascular obstruction. Design This was a multicentre, randomised, double-blind, parallel-group, placebo-controlled, dose-ranging trial. Setting The trial took place at 11 hospitals in the UK between 17 March 2016 and 21 December 2017. Participants Patients with acute ST-segment elevation myocardial infarction and a symptom onset to reperfusion time of ≤ 6 hours were eligible for randomisation. Radial artery access was a requirement, and further angiographic criteria included a proximal-to-middle coronary artery occlusion or impaired coronary flow in the presence of a definite thrombus in the culprit coronary artery. Exclusion criteria included a functional coronary collateral supply to the infarct-related artery, any contraindication to fibrinolysis and lack of informed consent. Additional exclusion criteria for safety were (1) requirement for immunosuppressive drug therapy for ≤ 3 months and (2) treatment with an antimicrobial agent. Intervention A total of 440 participants were randomly assigned 1 : 1 : 1 to treatment with placebo (n = 151), 10 mg of alteplase (n = 144) or 20 mg of alteplase (n = 145) administered by manual infusion directly into the infarct-related coronary artery over 5–10 minutes. The intervention was scheduled to happen after reperfusion and before stent implantation. Outcomes The primary outcome was the amount of microvascular obstruction (percentage of left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging at 2–7 days after enrolment. The primary analysis was the comparison between the 20 mg of alteplase group and the placebo group; if this comparison was not significant, the comparison of the 10 mg of alteplase group with the placebo group was considered as a secondary analysis. Sample size A total of 618 patients (minimum of 558 patients). Recruitment was halted on 21 December 2017 given that conditional power for the primary outcome based on a prespecified analysis of the first 267 randomised participants was < 30% in both treatment groups (futility criterion). Methods The primary outcome was compared between groups using a stratified Wilcoxon rank-sum test (van Elteren test), stratified by the location of the myocardial infarction. Results Among the 440 patients (mean age of 60.5 years; 15% women), the primary end point was measured in 396 (90%) patients, 17 (3.9%) withdrew, seven died and all other patients were followed up to 3 months. The amount (mean percentage of left ventricular mass) of microvascular obstruction was 2.3% versus 2.6% versus 3.5% in the placebo, 10 mg of alteplase and 20 mg of alteplase groups, respectively. In the primary analysis, microvascular obstruction did not differ between the 20 mg of alteplase group and the placebo group: 3.5% versus 2.3%, estimated difference 1.16% (95% confidence interval –0.08% to 2.41%; p = 0.32). In the secondary analysis, microvascular obstruction did not differ between the 10 mg of alteplase group and the placebo group: 2.6% versus 2.3%, estimated difference 0.29% (95% confidence interval –0.76% to 1.35%; p = 0.74). By 3 months, major adverse cardiac events (cardiac death, non-fatal myocardial infarction and unplanned hospitalisation for heart failure) had occurred in 15 (10.1%) patients in the placebo group, 18 (12.9%) in the 10 mg of alteplase group and 12 (8.2%) in the 20 mg of alteplase group. Conclusions Adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction compared with placebo. Limitations Premature discontinuation of enrolment limited the power of the secondary and safety analyses. Future work Low-dose intracoronary alteplase or tenecteplase could be compared with placebo at the end of primary percutaneous coronary intervention in patients with an ischaemic time of < 4 hours. Trial registration This trial is registered as ClinicalTrials.gov NCT02257294. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 5. See the NIHR Journals Library website for further project information.

Three-dimensional volume-strain loops may reflect fibrosis in hypertrophic cardiomyopathy

Abstract Background Combined plotting of deformation parameters against other indices [e.g. arterial pressure, left ventricular (LV) volume] might offer additional information about different diseases. Especially in hypertrophic cardiomyopathy (HCM) this approach might offer new insights into the various phenotypic and pathophysiologic features of this entity. Purpose Aim of this study was i) to apply strain-volume loops in HCM based on simultaneous frame-by-frame strain and volume changes' recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to investigate potential correlations between these loops and phenotypic features of HCM (including thickness, obstruction and fibrosis). Methods We included 40 HCM patients (54.1±14.3 years, 82.5% male, maximum wall thickness 19.3±4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume loop. Peak of radial, longitudinal, and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), and strain to end-diastolic volume (EDV) ratio (Rs/V, Ls/V, Cs/V) were computed for the analysis (panel A). Additionally, burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60.5±5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO>30 mm Hg at rest). Mean LV mass index was 78.9±14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2±4.5% of LV mass. Concerning strain-volume loops the following values were recorded for radial (Rsp 30.8±9.8%, RsSl 0.4±0.13 and Rs/V 0.25±0.09), longitudinal (Lsp −9.4±3.7%, LsSl 0.12±0.06 and Ls/V 0.08±0.04) and circumferential deformation (Csp −14.2±3.5%, CsSl 0.18±0.05 and Cs/V 0.11±0.03). Among typical HCM characteristics tested (LV mass, LVOTO and LGE), only LV mass presented significant correlations with LsSl (r=−0.41, p<0.01). Interestingly, HCM patients with smaller LVMI and without LGE presented steeper and narrower (difference between systolic and diastolic strain for the same volume) longitudinal strain-volume loops compared to patients with larger LVMIs and fibrosis (panel B). Conclusions Strain-volume loop is an innovative application of 3D deformation imaging in HCM. According to this new non-invasive method, increase of LVMI in HCM is accompanied by less longitudinal contribution to stroke volume, whereas better systolic-diastolic coupling may exclude the presence of underlying fibrosis. Funding Acknowledgement Type of funding source: None

Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time

BackgroundMicrovascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. ObjectivesThis study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time. MethodsThis study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440). ResultsOverall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018). ConclusionIn patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294)

1181 A novel insight into pathophysiology of hypertrophic cardiomyopathy using simultaneous three-dimensional volume-strain loops

Abstract Funding Acknowledgements Supported with a scholarship by the Greek State Scholarship Foundation (IKY). Background Strain assessment offers a robust evaluation of myocardial mechanics and systolic function, however reporting only peak strain values in hypertrophic cardiomyopathy (HCM) may impose limitations in the conception of its complex remodeling. Therefore, combined plotting of deformation parameters against other indices [e.g. arterial pressure, left ventricular (LV) volume] might offer additional insights into the pathophysiology of the disease. Purpose Aim of this study was i) to apply strain-volume loops in HCM based on simultaneous frame-by-frame strain and volume changes’ recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to take advantage of the previous methodology to gain further insights into HCM pathophysiology. Methods We included 40 HCM patients (54.1 ± 14.3 years, 82.5% male, maximum wall thickness 19.3 ± 4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume loop. Peak of radial, longitudinal, and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), and strain to end-diastolic volume (EDV) ratio (Rs/V, Ls/V, Cs/V) were computed for the analysis (panel A). Additionally, burden of fibrosis (percentage of LV mass) was defined by LGE extent (&amp;gt;5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60.5 ± 5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO &amp;gt; 30 mm Hg at rest). Mean LV mass index was 78.9 ± 14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2 ± 4.5% of LV mass. Concerning strain-volume loops the following values were recorded for radial (Rsp 30.8 ± 9.8%, RsSl 0.4 ± 0.13 and Rs/V 0.25 ± 0.09), longitudinal (Lsp -9.4 ± 3.7%, LsSl 0.12 ± 0.06 and Ls/V 0.08 ± 0.04) and circumferential deformation (Csp -14.2 ± 3.5%, CsSl 0.18 ± 0.05 and Cs/V 0.11 ± 0.03). Among typical HCM characteristics tested (LV mass, LVOTO and LGE), only LV mass presented significant correlations with LsSl (r=-0.41, p &amp;lt; 0.01). Interestingly, HCM patients with smaller LVMI and without LGE presented steeper and narrower (difference between systolic and diastolic strain for the same volume) longitudinal strain-volume loops compared to patients with larger LVMIs and fibrosis (panel B). Conclusions Strain-volume loop is an innovative application of 3D deformation imaging in HCM. According to this new non-invasive method, increase of LVMI in HCM is accompanied by less longitudinal contribution to stroke volume, whereas absence of fibrosis and severe hypertrophy is accompanied by better systolic-diastolic coupling. Abstract 1181 Figure.

P5254Prognostic value and clinical predictors of Intramyocardial Hemorrhage measured by CMR T2* weighted sequences

Abstract In the setting of STEMI, microvascular injury consists of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). We aimed to investigate prognostic value and clinical predictors of MR T2* w analysis of IMH in this setting. Methods A single center observational cohort study was performed in patients with reperfused STEMI with CMR examination after percutaneous revascularization. Infarct related CMR characteristics were analyzed in whole LV short-axis late gadolinium enhancement sequences (LGE) for infarct size and MVO and whole volume T2*w sequences for IMH. Extent of MVO and IMH were derived as percentage of LV mass. Kaplan-Meier was used to analyze the incidence of major adverse cardiovascular events, defined as a composite of cardiac death, myocardial re-infarction, and new congestive heart failure. Results 94 reperfused STEMI patients were included in the study. T2*w IMH was present in 26 (28%) patients and the median size of IMH was 1.1% (IQR: 0.5 to 2.9%). MVO was identified in 49 (52%) patients and the median size of MVO was 3% mass (IQR: 1.5 to 5.4%). T2*w IMH extension was independently associated with anterior myocardial infarction (p=0.022) and thrombectomy (p=0.049). IMH was correlated with MVO (R=0.62, p&lt;0.001), necrosis (R=0.58, p&lt;0.001) and LVEF (R=-0.21, p=0.04). Patients with IMH presented higher incidence of MACE, independently of LVEF (p=0.022). Typical CMR sequences Conclusions Whole LV T2*w proves useful to asses IMH. IMH extension was associated with anterior infarction and thrombectomy. T2*w IMH was associated with higher incidence of MACE regardless preserved or reduced LVEF