Larger LV Research Articles

268 IMPACT OF AORTIC REGURGITATION ON LONG TERM OUTCOME IN HEART FAILURE AND PRESERVED EJECTION FRACTION

Abstract Background Aortic Regurgitation (AR) may aggravate the clinical course in patients with heart failure and preserved ejection fraction (HFpEF) by increasing filling pressures and triggering LV remodelling. Objective To assess AR's prevalence and long-term prognostic implications in patients with HFpEF. Methods The study population consisted of 458 consecutive patients (age 77.5 ± 9.2 y, 57.9% females) hospitalized with de novo or worsened HFpEF. Patients with more than moderate aortic and/or mitral valve disease were excluded. Data on cardiovascular death, HF re-hospitalization and their composite (MACE) were collected. Results Out of 309 (67.5%) patients with any AR, 156 (34.0%) and 153 (33.5%) had mild-AR and moderate-AR, respectively. The remaining 149 (32.5%) individuals had no-AR. Patients with versus without AR were significantly older with larger LV and LA volumes and a higher prevalence of diastolic dysfunction (all p < 0.05). During a median follow-up of 33 ± 25 months, a total of 114 patients (24.9%) died from cardiovascular causes, 126 patients (27.5%) were re-hospitalized for HF, while 272 (59.4%) had the composite endpoint (MACE). In multivariable Cox regression analysis, any AR emerged as an only independent predictor of MACE (HR=1.90, 95%CI 1.26–2.87, p=0.002). Mild-AR and Moderate AR increased the risk of MACE by 77% and 92%, respectively, compared to the No-AR. Conclusions In patients with HFpEF, mild-to-moderate AR is highly prevalent, and it seems to identify individuals with worse long-term outcomes. This suggests that even mild AR should be considered a high-risk prognostic marker in patients with HFpEF.

Impact of aortic regurgitation on long-term outcomes in heart failure with preserved ejection fraction

Abstract Background Aortic Regurgitation (AR) may aggravate the clinical course in patients with heart failure and preserved ejection fraction (HFpEF) by increasing filling pressures and triggering LV remodelling. Objective To assess AR's prevalence and long-term prognostic implications in patients with HFpEF. Methods The study population consisted of 458 consecutive patients (age 77.5±9.2 y, 57.9% females) hospitalized with de novo or worsened HFpEF. Patients with more than moderate aortic and/or mitral valve disease were excluded. Data on cardiovascular death, HF re-hospitalization and their composite (MACE) were collected. Results Out of 309 (67.5%) patients with any AR, 156 (34.0%) and 153 (33.5%) had mild-AR and moderate-AR, respectively. The remaining 149 (32.5%) individuals had no-AR. Patients with versus without AR were significantly older with larger LV and LA volumes and a higher prevalence of diastolic dysfunction (all p<0.05). During a median follow-up of 33±25 months, a total of 114 patients (24.9%) died from cardiovascular causes, 126 patients (27.5%) were re-hospitalized for HF, while 272 (59.4%) had the composite endpoint (MACE). In multivariable Cox regression analysis, any AR emerged as an only independent predictor of MACE (HR=1.90, 95% CI 1.26–2.87, p=0.002). Mild-AR and Moderate AR increased the risk of MACE by 77% and 92%, respectively, compared to the No-AR (Figure). Conclusions In patients with HFpEF, mild-to-moderate AR is highly prevalent, and it seems to identify individuals with worse long-term outcomes. This suggests that even mild AR should be considered a high-risk prognostic marker in patients with HFpEF. Funding Acknowledgement Type of funding sources: None.

Left ventricular thrombus after acute ST-segment elevation myocardial infarction: multi-parametric cardiac magnetic resonance imaging with long-term outcomes.

Left ventricular thrombus (LVT) after acute ST-segment elevation myocardial infarction (STEMI) are generally associated with poorer outcomes for patients at long-term follow-up. We hypothesis that tissue characteristics and strain parameters by cardiac magnetic resonance (CMR) imaging may indicate the interactions of LVT with ventricular myocardium remodeling at both acute stage and chronic stages in STEMI patients. This retrospective study included 111 consecutive STEMI patients (38 with LVT and 73 without LVT). All patients underwent CMR during acute stage (within 7days) and chronic stage (after at least 2months) periods after percutaneous coronary intervention (PCI). Left ventricular native T1, extracellular volume (ECV), radial, circumferential, and longitudinal strain were analyzed in both phases. Major adverse cardiac events (MACE, including cardiovascular death, myocardial reinfarction, and hospitalization for heart failure), thromboembolic and bleeding events, were the clinical endpoints of the study. During the acute stage, left ventricular ejection fraction (LVEF) (OR 0.77, P value = 0.01) and longitudinal strain (OR 1.90, P value < 0.001) were correlated with LVT formation. Strain parameters were reduced, while the native T1 and ECV values of both the infarcted area and remote myocardium were elevated in LVT patients. During the chronic stage, LVT resolved in 29 of 38 patients (76%). LVT remaining patients had lower LVEF, a larger LV, and higher ECV in the acute stage than those of the LVT-resolved patients. In the long-term follow up of 678days, LVT (HR 2.45, P value = 0.02), aneurysm (HR 1.81, P value = 0.04), and native T1 (HR 2.44, P value = 0.01) were identified as three independent predictors of MACE, the incidence of thromboembolic events and bleeding events by a multivariable stepwise Cox proportional hazards regression. STEMI patients developing LVT had worse LV function, myocardial infarction extent, strain, and higher T1 and ECV values than STEMI patients without LVT. The LVT-remaining patients in the chronic stage had poorer functional and mapping parameters beginning in the first week. During the acute stage, LVEF and global longitudinal strain were independent correlated with LVT formation. During the long-term follow up, LVT, aneurysm and elevated myocardial T1 were associated with adverse outcomes in acute STEMI patients.

Effect of recreational exercise and fitness on left ventricular torsion and wall mechanics study (FIT-TWIST/Health)

Abstract Background Left ventricular (LV) remodeling is associated with elite athletics. This study aimed to assess the effects of recreational exercise on LV remodeling and mechanics in healthy adults. Methods A prospective cross-sectional study evaluated 38 healthy adult recreational exercise participants with a Bruce protocol treadmill exercise stress test, and 2D and speckle-tracking echocardiography. Fitness level was stratified by the achieved age- and sex-predicted metabolic equivalents (METS) as average/good (group A, N=20; METS=13.9) and high (group B, N=18; METS=18.2) groups. Results Mean age was 33 years, and 58% were female. Participants in Group B used more multi-modality (67 vs 20%; p=0.008) or running (50% vs 15%; p=0.04) exercise regimens, and had larger LV mass (66 vs 56 g/m2; p=0.05) and left atrial volume indices (28 vs 22 ml/m2; p=0.02), when compared with group A. However, all LV strain and torsion mechanics were similar between groups (Figure). Multivariate linear regression analysis revealed independent associations between global longitudinal strain (GLS) and transmitral E-wave (β=−0.57), maximum systolic blood pressure (β=0.32), and LV end-diastolic volume index (β=0.32) (model r=0.72; p&amp;lt;0.001). No correlation between METS achieved and LV parameters was observed. Conclusion Recreational exercise and fitness are associated with healthy LV geometry and mechanics in adults. Early diastolic LV filling, LV chamber size, and peak exercise blood pressure are correlated with GLS. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Florida Heart Research Foundation

Left atrial function in heart failure with preserved ejection fraction vs. aortic stenosis: evidence for atrial myopathy?

Abstract Funding Acknowledgements Type of funding sources: None. Background and Aim Left atrial (LA) enlargement and impaired LA function are frequently found in patients with heart failure with preserved ejection fraction (HFpEF). Whether these structural and functional LA abnormalities are a consequence of increased LA pressure or whether HFpEF patients have an intrinsic LA myopathy is unknown. We compared LA pressure, size and function between patients with HFpEF and aortic stenosis, as a comparator with LA pressure overload, as well as community-dwelling control subjects. Methods Extensive echocardiographic assessments were performed in 219 patients with HFpEF (age 68 ± 11, 48% female), 173 patients with moderate to severe AS (age 69 ± 11, 55% female, aortic valve area index 0.55 ± 0.15 cm2/m2), and 219 controls (age 65 ± 9, 48% female, 42.2% hypertensive) Results Compared to controls, both patients with HFpEF and AS had larger LV and LA size and worse LV systolic, diastolic and LA function. Compared with AS patients, HFpEF patients had smaller LA volume index (40.2 ± 19.4 vs. 44.5 ± 11.9 ml/m2 p = 0.01) but similar LV filling pressure estimated by E/e’ (13.4 ± 4.8 13.4 ± 4.8 , p = 0.12). Despite smaller LA volume index and similar LV filling pressure, HFpEF patients had remarkably poorer LA function compared to AS [reservoir GLS, 22.6 ± 10% vs 31.4 ± 10.1 (p &amp;lt; 0.001); contractile GLS, 15.8 ± 6.1% vs 17.5 ± 6.9 (p &amp;lt; 0.05); LASrs, 0.92 ± 0.35% vs 1.27 ± 0.41 (p &amp;lt; 0.001); LASre, -1.49 ± 0.65 vs -1.86 ± 0.67 (p &amp;lt; 0.001)]. The differences in LA reservoir GLS and LASrs remained significant after adjustment for atrial fibrillation, diabetes, coronary artery disease, LV ejection fraction and LV mass index. Conclusion Patients with HFpEF had significantly worse LA function than patients with AS, despite similar LA pressure overload. These findings support the concept of an intrinsic LA myopathy in patients with HFpEF, beyond LA pressure overload. Abstract Figure.

Risk stratification on echocardiography and outcome in ischaemic mitral regurgitation

Abstract Background Ischaemic mitral regurgitation (IMR) confers a poor prognosis. Transcatheter intervention may improve survival but benefit is likely to depend on severity of IMR relative to LV remodelling following myocardial infarction (MI). In theory, those with “discordant” IMR (significant regurgitant volume without severe LV dilatation or impairment), are expected to benefit most from mitral intervention. While subcategorization may help to inform treatment, there are no data on post-MI patients in this respect. Purpose To determine the incidence of discordant &amp; concordant IMR categorised on echocardiography post-MI and impact on outcomes. Methods 1000 consecutive patients admitted to our hospital with myocardial infarction who underwent coronary angioplasty were included. Early inpatient TTE was performed by accredited echocardiographers using standard multiparametric quantification. Using TTE parameters, 4 subgroups were identified (figure) according to the degree of MR relative to LV remodelling. Thresholds were based on European guidelines (± 2SD from normal) and median value among survivors for vena contracta (VC): – LVEF: 52% (♂), 54% (♀) – Indexed LV end diastolic volume (LVEDVi): 74ml/m2 (♂), 61ml/m2 (♀) – Effective regurgitant orifice area (EROA) ≥0.2cm2 – Regurgitant volume (RVol) ≥30ml – VC ≥0.5cm Results MR was seen in 294/1000 patients (29.4%) with a severity of mild (76%), moderate (21%) and severe (3%). Concordant and discordant IMR were each seen in 16/294 (5%) of IMR patients post-MI. After a mean follow up of 3.2 years, IMR patients had a 3% rate of heart failure (HF) within 1 year and 19% mortality. Non-survivors had significantly worse IMR (PISA 0.65±0.25cm vs 0.54±0.19cm; p=0.033; VC 0.63±0.25cm vs 0.49±0.18cm; p=0.014), worse LV function (LVEF 44±17% vs 51±13%; p&amp;lt;0.001), larger LV (LVEDVi 67±23ml/m2 vs 60±22ml/m2; p=0.032) and larger indexed LA volume (LAVi) (44±22ml vs 35±15ml; p&amp;lt;0.001). Those with concordant IMR had the worst survival (50%) although almost 1 in 5 of those with discordant MR died within the follow up period (19%). Using multivariable Cox regression, significant predictors of mortality included LVEF (p&amp;lt;0.001; HR 0.96, 0.94–0.98) and LAVi (p&amp;lt;0.001; HR 1.02, 1.01–1.03) but not LVEDVi. Conclusion 1) Significant predictors of mortality in IMR include LA dilatation and decline in LVEF, but not LV dilatation. 2) Although discordant severe IMR is uncommon following MI, mortality if left untreated remains high. Attention should be paid to early selection of this cohort for intervention. Funding Acknowledgement Type of funding source: None

Prognostic value of global myocardial constructive work in patients with secondary mitral regurgitation

Abstract Background Left ventricular (LV) myocardial contractility evaluation is of crucial importance in patients with secondary mitral regurgitation (SMR). The most widespread echocardiographic tool, left ventricular ejection fraction (LVEF), might overestimate LV function, since it calculates the volume changes regardless of the flow direction. Global myocardial constructive work (GMCW) might be a more suitable tool, as LV myocardial work derived from pressure-strain loops obtained with speckle tracking echocardiography incorporates non-invasive blood pressure measurements. Purpose To evaluate the prognostic value of LV GMCW in patients with SMR. Methods 378 patients (72% men, median age 68 [range 60 to 74 years]) with various grades of SMR were retrospectively analysed. LV global myocardial constructive work, wasted work and work efficiency were measured with speckle tracking echocardiography. Results There were 145 patients with mild SMR, 130 with moderate SMR and 103 with severe SMR. Patients with severe SMR had larger LV volumes, lower LVEF and more impaired LV GLS. GMCW was more impaired in patients with severe SMR, compared with mild MR (678 mmHg% vs. 845 mmHg% p&amp;lt;0.001 respectively). After a mean follow-up of 59±37 months, 162 patients died. When dividing the population according to prognostically relevant cut offs derived by spline curve analysis, patients with a GMCW≤700 mmHg% had a worse prognosis, compared with their counterparts (Figure 1). Conclusion Global myocardial constructive work ≤700 mmHg% is associated with worse long-term survival in patients with SMR. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: None

Time, magnitude and patterns of left ventricular remodeling after MitraClip implantation: clinical implications

Abstract Background The reverse left ventricular remodeling (LV-R) is well known phenomenon that may occurs in a wide spectrum of heart disease, generally associated with an improvement of prognosis. Recently, conflicting data are reported from two randomized trials assessing prognosis after MitraClip implantation. Purpose To assess time, magnitude and pattern of LV-R and its relationship with outcome, and to assess the role of ejection fraction (EF) in selection of patients for MitraClip procedure. Methods and results Among 47 patients treated with MitraClip for severe mitral regurgitation (MR), 2 switched to surgical intervention. All patients underwent echo before, at discharge, 1 and 6-month after procedure (age 78.2±8.3 years, NYHA 3.74±0.44, LV EF 36.5±12.8%, logistic EuroSCORE I 22.41±8.4, STS-PROM 4.6±1.9, functional MR 82%). From baseline to 6-month reverse LV-R was defined as a ≥15% decrease in LV end-systolic volume (LVESV) and an adverse LV-R as a increase of ≥10% in LVESV, respectively. At 6-month, sustained reduction of MR ≤2 was observed in all patients, but 2; reverse LV-R occurred in 51% (23), adverse LV-R in 18% (8) and no LV-R in 31% (14) patients. In a multivariate regression model, baseline LVEDV were a strong independent predictor of reverse LV remodeling [β −0.564, 95% CI: −0.363 to −0.074; P=0.004], whereas baseline LVEF was not (P=0.126). Furthermore, an LVEDV ≤130 mL was strongly associated with reverse remodeling with an OR: 0.796 (CI: 0.052–0.792, P=0.022). During follow-up (17.5±9.3 months), in adverse/no LV-R patients mortality for any cause and hospitalization for heart failure (HF) occurred in 50% vs. 95.7% (log-rank, P value= 0.006). By Cox analysis, adverse LV-R was strongly associated with mortality for any cause and hospitalization for HF with adjusted OR of 5.6 (95% CI: 1.65–19.00, P=0.006). Finally, combining adverse/no LV-R together the risk of mortality for any cause and hospitalization for HF increased with adjusted OR of 10.08 (95% CI: 1.29–78.6, P=0.027). Conclusion The half of real-world patients undergoing percutaneous mitral valve repair for severe MR showed reverse remodeling. However, there was a half of patients in whom afterload mismatch resulted in early and sustained adverse and no remodeling associated with subsequently high mortality and recurrence of HF. Baseline larger LV volumes rather than EF may help us to refine selection patients for MitraClip procedure, avoiding futility. Funding Acknowledgement Type of funding source: None

P1292 Prevalence and mechanisms of mitral regurgitation and its association with advanced heart failure in patients with a systemic right ventricle

Abstract Background Although tricuspid regurgitation in patients with cardiac diseases is an established predictor of adverse outcomes, prevalence, mechanisms and clinical/prognostic value of non-systemic mitral regurgitation (MR) in patients with congenitally corrected transposition of great arteries (ccTGA) or simple transposition after Mustard or Senning procedures (TGA) are still poorly understood. Purpose To assess prevalence, mechanisms of MR and its association with severity of heart failure in patients with a systemic right ventricle (SRV). Methods From our digital echocardiographic database, we have identified all patients with a SRV who underwent echocardiography between 2014 and 2018. Severity of MR, size and function of SRV and subpulmonary LV were assessed from the latest echocardiographic studies. Results 157 patients fulfilled inclusion criteria (89 post-Mustard/Senning, 68 ccTGA), median age 40.6 (33.1; 46.8) years, 57% male, median BNP 79.5 [38.3; 173.3] ng/l. More than trivial MR was present in 44 (28.0%), further classified as mild, moderate and severe in 26 (16.6%), 15 (9.6%) and 3 (1.9%), respectively. Principal mechanisms of MR included (i) device lead interference with the leaflet(s) in 26, (ii) organic pathology of mitral valve in 5 (2 prolapse, 2 cleft and 1 parachute mitral valve) and (iii) systolic leaflet(s) tethering ± annular dilatation in 4; no obvious cause of MR was identified in 10 patients. Presence of more than trivial MR was significantly associated with NYHA class 3-4 (Chi-square 25.74, p &amp;lt; 0.0001). Patients with MR also had higher BNP levels, larger LV with poorer systolic function and were more likely to have pulmonary stenosis (Table). MR was less common in patients post-Mustard/Senning procedures compared to ccTGA (p &amp;lt; 0.0001, Table); however, patients from the former group were more likely to have severe heart failure (Figure). Conclusions Non-systemic MR in patients with a SRV is relatively uncommon, but when present is associated with LV dilatation and systolic dysfunction, raised BNP levels, and heart failure symptoms. Predominant underlying mechanisms were device leads, organic pathology, and valve tethering. MR should be routinely assessed in SRV patients, particularly those with previous Mustard/Senning procedures, and be taken into account in decision making and timing interventions. Characteristics of 157 patients with SRV Parameter No/trivial MR (N = 113) Mild-severe MR (N = 44) P value Age, years Mustard/Senning ccTGA Pulmonary stenosis NYHA class 3-4 ICD/Pacemaker lead 39.5 (33.1; 45.7) 75 (66%) 38 (34%) 13 (12%) 7 (6%) 31 (27%) 44.4 (32.7; 52) 14 (32%) 30 (68%) 12 (27%) 17 (39%) 32 (73%) 0.105 &amp;lt;0.0001 &amp;lt;0.0001 0.022 &amp;lt;0.0001 &amp;lt;0.0001 LV EDDi, cm/m2 LV FAC, % MAPSE, mm SRV EDAi, cm2/m&amp;sup2; TAPSE, mm 2.11 (1.9; 2.45) 48 (42; 52.5) 18 (14; 22) 17.6 (15.0; 20.2) 12 (9; 15) 2.5 (2.0; 2.9) 40 (34; 48.8) 14.6 (11.5; 16.5) 17.5 (14.4; 22.2) 10.5 (9; 13) 0.0007 0.0011 0.0005 0.754 0.435 BNP 68 (35.3; 104.3) 177 (62.5; 345.3) &amp;lt;0.0001 Values are reported as median (25th; 75th percentile) or n(%) Abstract P1292 Figure. SRV patients with more than trivial MR

P4659Left ventricular thrombus and arterial embolism in patients with noncompaction cardiomyopathy - Prognostic value of cardiac magnetic resonance imaging

Abstract Background Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by an increased number of LV trabeculations with deep intertrabecular recesses. This abnormality is associated with heart failure, arrhythmias and arterial embolic events (AE). At present, it is unknown if AE is mainly due to blood stasis within the intertrabecular recesses, reduced LV ejection fraction or concomitant atrial fibrillation. LVNC is usually diagnosed by echocardiography but cardiac magnetic resonance imaging (CMRI) has evolved as an alternative method. This study assessed the prognostic value of CMRI for arterial embolic events in patients (pts) with LVNC. Methods 34 consecutive pts (19m, 15f, age 53±16) with LVNC underwent cine and contrast-enhanced CMRI with a 1.5 T scanner. LV diameter, volume, ejection fraction, and ratio of noncompacted to compacted myocardium (NC/C) were determined, and in 32 pts presence and localization of late gadolinium enhancement (LGE) was assessed. Clinical and CMRI findings were compared in pts with and without LV thrombus and/or AE. Results Overall, 20 pts (59%) were in heart failure NYHA III or IV, 14 (41%) had left bundle branch block (LBBB), 7 (21%) paroxysmal atrial fibrillation and 6 (19%) ventricular tachycardia (VT). By CMRI, LV diameter in end-diastole (66±8 mm), end-systole (53±10 mm), end-diastolic (229±69 ml) and end-systolic volume (150±68 ml) were enlarged and ejection fraction (36±14%) was reduced. The NC/C ratio was 3.2±1.4 in end-diastole and 2.6±1.4 in end-systole. One pt had right ventricular involvement with a thrombus. LGE was seen in 9/32 pts (28%) in the compacted myocardial layer (n=6), in the noncompacted trabecular layer (n=6) and within the papillary muscles (n=3). LGE was present in 3 areas in 1 and in 2 areas in 4 pts. In 3 pts (9%) a thrombus was seen within the trabecular layer which resolved under anticoagulation, and 6 additional pts (18%) without detectable thrombus experienced AE (transient ischemic attack n=1, stroke n=5). Thrombus and/or AE were not associated with age, sex, NYHA class, larger left atrial or LV diameter, LV volume, LBBB or documented VT. Atrial fibrillation (2/9 vs 5/25 pts, p=ns), LV ejection fraction (33±13% vs 38±15%, p=ns) and the NC/C ratio in end-diastole (median 3.2 vs 3) or end-systole (both median 2.6, p=ns) were similar. Thrombus and/or AE occurred mainly in pts with LGE (6/9 vs 2/23 pts, p=0.002). Conclusion In LVNC, evaluation by CMRI and demonstration of LGE in the compacted or noncompacted myocardium identifies patients at high risk for thrombus formation and/or arterial embolic events, warranting anticoagulation.

P3095Left ventricular thrombus formation after ST-elevation myocardial infarction: a prospective observational CMR study

Abstract Background Left ventricular (LV) thrombus formation is a severe complication after acute ST-segment elevation myocardial infarction (STEMI). The incidence and determinants of LV thrombus formation are still a matter of controversy. Purpose We aimed to assess the incidence as detected by cardiac magnetic resonance (CMR) imaging as well as the determinants of LV thrombus formation in contemporary reperfused STEMI patients. Methods This prospective observational study included 530 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Comprehensive CMR was performed at a median of 3 days (interquartile range 2–4 days) after symptom onset for the evaluation of LV thrombus formation as well as LV function and infarct severity. Results LV thrombi were detected in 17 patients (3.2% of the overall cohort). The incidence of LV thrombi in anterior STEMI patients (n=247) was 6.9%. In all patients presenting with LV thrombus left anterior descending artery (LAD) was identified as culprit lesion. The occurrence of thrombi was significantly associated with reduced LV ejection fraction (LVEF) (p&lt;0.001), larger LV end-diastolic volume (p&lt;0.001) and LV end-systolic volume (p&lt;0.001), larger areas of microvascular obstruction (MVO) (p=0.003) and larger infarct size (IS) (p&lt;0.001). Furthermore, increased levels of peak high sensitivity cardiac Troponin T (p&lt;0.001) and hyperlipidaemia (p=0.038) were significantly related to LV thrombi. In multivariable analysis including IS, LVEF and MVO, only LVEF (odds ratio: 0.91 (95% confidence interval: 0.87–0.96); p=0.001) emerged as independent predictor of LV thrombus formation. Conclusion The risk of LV thrombus formation remains considerable in contemporary treated STEMI patients, especially in those with LAD as culprit lesion. Among CMR parameters of LV dysfunction and infarct severity, only baseline LVEF, but not IS or MVO, independently predicted LV thrombus formation after STEMI.

P629Voluntary exercise associated with myokine production ameliorates cardiac remodeling and inflammation in a myocardial infarction mouse model

Abstract Background Left ventricular (LV) remodeling, through excessive inflammation, leads to heart failure. Exercise (Ex) training is associated with a risk reduction in heart failure through direct and indirect mechanisms by which Ex contributes an anti-inflammatory effect. During Ex, contracting muscle fibers release myokines, including interleukins (ILs), tumor necrosis factor α (TNF-α), follistatin-like protein 1 (FSTL-1), and fibroblast growth factor 21 (FGF-21), into the bloodstream. These myokines may have beneficial effects on other damaged organs, such as an infarcted myocardium, through anti-inflammatory effects. However, the exact mechanisms of the anti-inflammatory effects of voluntary Ex in myocardial infarction (MI) are poorly understood. Therefore, we investigated the effect of voluntary Ex on cardiac remodeling and inflammation, the relationship between cardiac remodeling and skeletal muscle (SKM) response, and circulating myokine levels in a mouse model of MI. Methods Twelve-week-old male C57BL/6J mice were used and divided into the following 4 groups: sham operation (Sham), MI, Sham+Ex, and MI+Ex. MI was induced by ligation of the left anterior descending coronary artery. Ex groups began voluntary wheel running for 4 weeks after the operation. An echocardiography was performed at baseline and 4 weeks after the operation. The mRNA levels in the LV infarcted area and SKM were measured with RT-PCR and western blot analysis. Plasma levels of myokines were also measured with immunoassays. Results Four weeks after MI induction, echocardiographic evaluation showed that the MI mice had a larger LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) than the Sham mice. The MI mice also showed higher mRNA levels of TNF-α, IL-1β, IL-6, and IL-10 in the LV tissue when compared to the Sham mice. These changes were significantly ameliorated in the MI+Ex mice. Interestingly, in the MI+Ex mice, mRNA levels of IL-6, IL-1β, FSTL-1, and FGF-21 in the SKM were significantly higher than in the MI mice, while there were no significant differences in TNF-α and IL-10 levels in all groups. Similarly, protein expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, sirtuin-1, and mitochondrial transcriptional factor A of mitochondrial function markers in SKM were also significantly higher in the MI+Ex mice than in the MI mice. Furthermore, there were significant correlations between plasma levels of IL-1β, but not other myokines, and LVEDD, and LVESD. In addition, there was also a significant correlation between the SKM IL-1β level and LVESD in the Sham+Ex mice (all, P&lt;0.05). Conclusions Amelioration of cardiac remodeling and inflammation by voluntary Ex is associated with increased myokines, especially IL-1β, in a MI mouse model. These results suggest that increased myokine levels, through voluntary exercise, may play an important role in the prevention of cardiac remodeling after MI.

Comparison of ventricular tachyarrhythmia recurrence between ischemic cardiomyopathy and dilated cardiomyopathy: a retrospective study.

BackgroundThe use of an implantable cardioverter-defibrillator (ICD) has been established as an effective secondary prevention strategy for ventricular tachycardia (VT)/ventricular fibrillation (VF). However, few reports discuss the difference in clinical predictors for recurrent VT/VF between patients with ischemic cardiomyopathy (ICM) and patients with dilated cardiomyopathy (DCM).MethodsFrom May 2004 to December 2015, 132 consecutive patients who had ICM (n = 94) or DCM (n = 38) and had received ICD implantation for secondary prevention were enrolled in this study. All anti-tachycardia events during follow-up were validated. The clinical characteristics and echocardiographic parameters were obtained for comparison. The incidence of recurrence of VT/VF, cardiovascular mortality, all-cause mortality, the change of left ventricular ejection fraction (LVEF) and LV volume were analyzed.ResultsAt a mean follow-up of 3.62 ± 2.93 years, 34 patients (36.2%) in the ICM group and 22 patients (57.9%) in the DCM group had a recurrence of VT/VF episodes (p = 0.032). The DCM group had a lower LVEF (p = 0.019), a larger LV end-diastolic volume (LVEDV) (p = 0.001), a higher prevalence of LVEDV >158 mL (p = 0.010), and a larger LV end-systolic volume (p = 0.010) than the ICM group. LVEDV >158 mL and no use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker were independent predictors of recurrences of VT/VF in ICM patients but not in DCM patients. There were no difference in cardiovascular mortality and all-cause mortality between the ICM and DCM patients.ConclusionThe DCM patients had a higher recurrence rate of VT/VF than did the ICM patients during long-term follow-up. An enlarged LV is an independent predictor of the recurrence of VT/VF in ICM patients receiving ICD for secondary prevention.

Abstract WP202: Cardiac and Brain Structure and Function Associations: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Heart failure (HF) is a disease that impacts many organs, but the effect on the brain remains poorly understood. To explore associations with subclinical disease, in the Atherosclerosis Risk in Communities (ARIC) study, we evaluated the relationship between cardiac dysfunction on echocardiography and vascular lesions on brain MRI. Methods: A cross-sectional analysis between subclinical cardiac and brain markers was performed using echo and brain MRI data from the 5 th visit of the ARIC study (n=1974), a community-based biracial cohort study. LV structure was assessed using wall thickness (mm) and mass index (g/m 2 ), while diastolic function was assessed as LA volume index (g/m2). MRI was evaluated for presence/size/location/number of infarcts and white matter hyperintensities (WMH). Demographic and vascular risk factors (including hypertension) were considered as covariates in statistical models. Results: In adjusted models, worse LV structure was significantly associated with the presence of WMH as well as infarction. WMH was 0.66 cm 3 greater (95%CI [0.11, 1.21]) for every 1 mm increase in wall thickness, and 0.65 cm 3 greater (95%CI [0.27, 1.03]) for every 10g/m 2 increase in LV mass index. Odds of infarction increased (OR 1.11, 95%CI [1.02, 1.21]), per 1 mm thicker LV wall increase as well as with larger LV mass (per 10 g/m 2 ) (OR 1.08, 95%CI [1.02, 1.14]). The rate of accumulating additional cortical infarcts was increased by 2.4% (95%CI 1.01, 1.04) per ml/m 2 increase in LA volume index, a marker of LV diastolic function. The rate of accumulation of lacunar infarcts was increased by 1.5% per ml/m2 increase in LA volume index (95% CI [1.00, 1.03]). No significant interactions were detected by race. Conclusions: Among participants in a large cohort study, subclinical changes in markers of LV structure were associated with increased odds of infarction and volume of WMH even when controlling for hypertension. Our findings could suggest that the brain represents another end-organ at risk among patients with even early stages of heart failure.

Role of Tissue Doppler and Strain/Strain Rate Imaging in the Assessment of the Effects of Obesity on Left Ventricular Structure and Myocardial Systolic Function

Aim: Obesity is a major contributor to the global burden of disease and disability. Objectives: Assessment of subclinical effects of obesity on left ventricular structure and systolic function by strain and strain rate tissue Doppler imaging. Patients and methods: Fifty obese patients with body mass index >30 kg/m² and without cardiovascular disease were included. Twenty five patients of this group were severely obese (BMI>35 kg/ m²) and another 25 were mildly obese (BMI 30-35 kg/m²). Another 50 age-and sex-matched healthy volunteers (BMI <25 kg/m²) were included as a control group. Conventional echodopplercardiography and tissue Doppler strain/strain rate imaging were done. Results: Obese persons have a larger LV mass and LV mass index and a significant direct correlation was found between body mass index and left ventricular mass index there was significant reduction in the mean systolic myocardial velocity in the obese group versus non obese groups. Mean systolic strain was significantly lower in the obese group versus non obese. Mean systolic strain rate was significantly lower in obese group versus non obese groups. Global longitudinal strain & average peak systolic strain rate was lower in obese versus non obese groups and a significant inverse relation was found between body mass index and the peak systolic velocity of strain and strain rate. Conclusions: strain and strain/rate tissue Doppler imaging can predict sub-clinical cardiac functional and structural changes in obesity.

Usefulness of speckle myocardial imaging modalities for differential diagnosis of left ventricular non-compaction of the myocardium

Background/objectivesCurrent diagnostic criteria for left ventricular non-compaction (LVNC) may result in over-diagnosis of the disease. We evaluate the role of speckle imaging in differential diagnosis of LVNC. Methods and resultsWe included all patients who, between January 2012 and May 2015, fulfilled currently accepted criteria for LVNC (28 patients). A control group of 28 healthy individuals and a third group of 13 patients with dilated cardiomyopathy (DCM) were created. Speckle-tracking echocardiography was performed in all groups. Thirteen patients with LVNC had an ejection fraction (EF) <50% (33.5%, SD 10). When compared to controls, patients with LVNC and EF<50% had a larger LV, larger left atrial diameter (LA), reduced e′, and reduced global longitudinal strain (GLS). All but one patient with LVNC and EF<50% showed an abnormal LV rotation. This abnormal pattern was observed in 4 LVNC patients (27%) with EF≥50% and in none of the controls. In patients with LVNC, EF ≥50%, and abnormal rotation, GLS was lower than in controls, (−17 (SD 3) vs −21 (SD 3)). Rigid body rotation (RBR) was also observed in 2 DCM patients, with significant differences in EF, GLS, LV diameters relative to the rest of the DCM group. ConclusionsIn patients who fulfil the morphologic criteria for LVNC, speckle myocardial imaging techniques could be useful in differentiating between healthy individuals (functionally normal LV) and patients with LVNC (with functional abnormalities in the myocardium in spite of a preserved EF).

Abstract 31: Impact of Acculturation on Cardiac Structure and Function Among Latinos in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): The ECHO-SOL Ancillary Study

Background: Abnormalities of cardiac structure and function are part of the spectrum of heart failure risk and progression. Acculturation is the process whereby an individual adopts the beliefs and practices of a host culture. Increasing acculturation has been associated with increased psychosocial stress and the adoption of deleterious health behaviors. The extent to which acculturation contributes to cardiovascular disease among Latinos is not well defined, and its association with cardiac structure and function in particular has not been studied among Latinos. Hypothesis: We hypothesized that higher acculturation is associated with worse left ventricular structure and function. Methods: The HCHS/SOL cohort included 16,415 Latino adults age 18-74 years from Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American backgrounds. A random subsample of 1350 also underwent detailed echocardiographic assessment for the following primary outcome measures: left atrial volume index (LAVI), left ventricular mass index (LVMI) and LV ejection fraction (LVEF), LV end diastolic volume (LVEDV) and diastolic dysfunction (Grade 0 vs. Grade 1-3). Acculturation was measured by length of residence in the US categorized as (&lt; 5 years, 5-10 years, &gt;10 years). Chi-square and ANOVA were used to assess differences across acculturation level and dependent variables. Separate linear and logistic regression analyses were used with sequential modeling for age and sex followed by models including diabetes, hypertension, body mass index, tobacco use, and estimated glomerular filtration rate. Results: The mean age of the Echocardiographic Cohort was 56 years (S.D. ±0.5). Length of residence among first generation immigrants (n=1239) was as follows: 9.7% ≤ 5 years; 14.8% 5-10 years; and 75.5% ≥10 years. Fully adjusted models demonstrated abnormal cardiac structure was significantly higher with increasing years of US residence: increasing LAVI (1.6 ml/m 2 higher ≥10 years vs. ≤ 5 years), increasing LVEDV (5.6 ml higher ≥10 years vs. ≤ 5 years), and LVMI (4.9g/m 2 higher ≥10 years vs. ≤ 5 years) (p&lt;0.01 each). Increasing length of residence in the US was also associated with higher prevalence of diastolic dysfunction in models adjusted for age and gender (54.2% ≤ 5 years vs. 63.7% ≥10 years; p=0.04), though this became marginally non-significant in our fully adjustment models (p=0.07). There were no significant differences in systolic cardiac function as measured by LVEF. Conclusions: Among a diverse Latino population, higher acculturation defined as greater length of residence in the US, a proxy measure for acculturation, was associated with larger LA volume, larger LV cavity, higher LV mass and a tendency to higher prevalence of diastolic dysfunction independent of traditional risk factors. Acculturation may be a significant process that impacts cardiac structure and function among Latinos.

Abstract 15759: Arrhythmic Risk Stratification in Patients With Idiopathic Dilated Cardiomyopathy and No Conventional Indications for Implantable Cardiac Defibrillator

Background: Primary prevention of major ventricular arrhythmias (MVA) in patients with idiopathic dilated cardiomyopathy (IDCM) is primarily based on left ventricular ejection fraction (LVEF) assessment. Nonetheless, unexpected MVA still affect patients considered at low-risk (LR), attesting the limitation of the current risk stratification. We sought to identify the clinical predictors of MVA in patients with IDCM and no conventional indications for implantable cardioverter defibrillator (ICD). Methods: In this retrospective, case-control study, among 922 patients enrolled in the Heart Muscle Disease Registry of Trieste from 1988 to 2013, we analyzed 414 IDCM patients considered at LR according to the following criteria: LVEF≥36% and no previous episodes of MVA (sustained ventricular tachycardia/non-fatal ventricular fibrillation (SVT/VF), appropriate ICD intervention and sudden cardiac death (SD)). Data were recorded at the last available medical examination before the index event. Patients were optimally treated at the time of index evaluation (87% and 84% of ACE-inhibitors/sartans and beta-blockers, respectively). Results: Over a median follow-up of 43 (IQR 16-116) months, 45 patients (11 % of patients at LR; 31% of the all MVA in whole IDCM population) experienced MVA. The mean age at the time of event was 51±14 years. They were characterized by a previous history of syncope in 10 patients (22%), LVEF of 42±6% with a normal value (&gt;50%) in 10 patients (22%), significant LV dilation (VTDi&gt;90ml/m 2 ) in 16 patients (35%) and left bundle branch block 12 patients (27%). Independent risk factors for MVA in LR subgroup were previous history of syncope (OR 3.41, 1.45-8.03, p=0.004), larger left ventricular dilation (OR 2.62, 1.72-3.99, p&lt;0.0001) and longer duration of disease (OR 1.39, 1.42-2.63, p&lt;0.0001). Conclusions: in a large cohort of IDCM patients nearly one-third of the MVA occurred in a population apparently at LR of events. History of syncope, larger LV dilatation and significant duration of disease emerged as strong predictors of MVA and should be considered in the arrhythmic risk stratification of patients without conventional criteria for SD primary protection.

Determinants of anterior chamber angle narrowing after mydriasis in the patients with cataract

To identify the determinants of anterior chamber angle narrowing after mydriasis by quantitative assessment of the anterior chamber components using anterior segment optical coherence tomography (AS-OCT). In this intervention study, anterior chamber angle analysis was performed using AS-OCT in patients with cataract before pharmacological pupillary dilation and 30min afterwards. Angle narrowing was quantified by the change of angle opening distance 500 after mydriasis (ΔAOD500). Multivariate linear regression and stepwise selection regression were used to identify which parameters in AS-OCT significantly determined ΔAOD500. One hundred and two Japanese patients (age, mean ± standard deviation, 71.9 ± 11.2years) were enrolled. Multivariate analysis indicated that smaller ΔAOD500 were significantly associated with larger lens vault (LV; P < 0.001), larger iris area (IA; P = 0.003), and posterior corneal arch distance (PCAL; P = 0.01). Stepwise linear regression analysis revealed that smaller ΔAOD500 was independently associated with larger LV (partial R (2) = 0.232, P < 0.001), larger IA (partial R (2) = 0.080, P = 0.001), and smaller PCAL (partial R (2) = 0.066, P = 0.002) before mydriasis. These three factors explained 37.7% of the decrease in ΔAOD500. Larger LV, larger IA, and smaller PCAL contribute considerably to anterior chamber angle narrowing after mydriasis in patients with cataract.

Prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging in patients with indications for cardiac resynchronization therapy

Background. The aim of our study was to assess the cardiac 123I-MIBG imaging predictive value on the clinical outcome in HF patients with wide QRS complexes and compare its power in different treatment groups. Materials and methods. We have prospectively investigated 67 heart failure patients with the New York Heart Association (NYHA) functional class II–IV, wide QRS complexes (&gt;120 milliseconds), reduced left ventricular ejection fraction (LV EF) eligible for CRT. 123I-MIBG planar and single photon emission computed tomography (SPECT) scans were performed in a supine position with calculation of early and late heart-to-mediastinum (H/M) ratios, washout ratio (WR), summed defect scores and scores difference from SPECT acquisition. All patients were then divided in two groups according to their clinical status – 36 patients underwent implantation of CRT, and 31 patients were continued with OMT. Initial conventional heart failure markers and NYHA were assessed at the time of 123I-MIBG imaging and 6 months later. Comparisons of two groups were done applying the Student’s t-test, and if samples were small, the Fisher’s exact test was used. NYHA groups were compared applying the ANOVA single factor analysis. ROC curve analysis was performed to establish cut off values for predictors of response. Results. Cardiac 123I-MIBG imaging data differed insignificantly, presenting a similar cardiac adrenergic innervation status in both groups. In the CRT group, NYHA and LV EF indicated more pronounced signs of HF. For all patients, NYHA IV patients had significantly larger LV diameter, smaller EF, larger BNP levels, lower late H/M values and larger denervation score difference. Responders to therapy (both groups) had significantly higher early H/M ratio – 2.35 ± 0.41 than non-responders – 2.00 ± 0.44 (p = 0.004), and late H/M ratio – 2.11 ± 0.44 for responders and 1.72 ± 0.54 for non-responders (p = 0.005). There were no significant differences in regional cardiac 123I-MIBG data for responders and non-responders. Conclusions. Cardiac 123I-MIBG imaging has valuable prognostic power predicting clinical outcomes of HF patients with wide QRS complexes, despite the chosen type of treatment, with better outcomes for patients with early H/M ratio 2.00 and late H/M ratio above 1.77.