Left Ventricular Scar Research Articles

Left atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.

Low lead one ratio predicts clinical outcomes in left bundle branch block.

We evaluated the association between a novel electrocardiographic (ECG) marker of late, rightward electrocardiographic forces (termed the lead one ratio [LOR]), and left ventricular ejection fraction (LVEF), myocardial scar, and clinical outcomes in patients with left bundle branch block (LBBB). LOR was calculated in patients with LBBB from a derivation cohort (n = 240) and receiver operator characteristic curves identified optimal threshold values for predicting myocardial scar and LVEF less than 35%. An independent validation cohort of patients with LBBB (n = 196) was used to test the association of LOR with the myocardial scar, LVEF, and the likelihood of death, heart transplant or left ventricular assist device (LVAD) implantation. The optimal thresholds in the derivation cohort were LOR less than 13.7 for identification of scar (sensitivity 55%, specificity 80%), and LOR less than 12.1 for LVEF less than 35% (sensitivity 49%, specificity 80%). In the validation cohort, LOR less than 13.7 was not associated with scar size or presence (P > 0.05 for both). LOR less than 12.1 was associated with lower LVEF (30 [20-40] versus 40 [25-55]%; P = 0.002) and predicted LVEF less than 35% in univariable (odds ratio [OR], 2.2 [1.2-4.1]; P = 0.01) and multivariable analysis (OR, 2.2 [1.2-4.3]; P = 0.02). LOR less than 12.1 was associated with scar presence when patients with nonischemic cardiomyopathy were excluded (OR = 7.2 [1.5-33.2]; P = 0.002). LOR less than 12.1 had an adjusted hazard ratio of 1.53 ([1.05-2.21]; P = 0.03) for death, transplant or LVAD implantation. In conclusion, ECG LOR less than 12.1 predicts reduced-LV systolic function and poorer prognosis in patients with LBBB.

Mechanism of Abnormal Septal Motion in Left Bundle Branch Block: Role of Left Ventricular Wall Interactions and Myocardial Scar

ObjectivesThis study sought to investigate how regional left ventricular (LV) function modifies septal motion in left bundle branch block (LBBB). BackgroundIn LBBB, the interventricular septum often has marked pre-ejection shortening, followed by immediate relengthening (rebound stretch). This motion, often referred to as septal flash, is associated with positive response to cardiac resynchronization therapy (CRT). MethodsIn 10 anesthetized dogs, we induced LBBB by radiofrequency ablation and occluded the circumflex (CX) (n = 10) and left anterior descending (LAD) (n = 6) coronary arteries, respectively. Myocardial dimensions were measured by sonomicrometry and myocardial work by pressure-segment length analysis. In 40 heart failure patients with LBBB, including 20 with post-infarct scar and 20 with nonischemic cardiomyopathy, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Scar was assessed by cardiac magnetic resonance imaging with late gadolinium enhancement. ResultsDuring LBBB, each animal showed typical septal flash with pre-ejection shortening and rebound stretch, followed by reduced septal systolic shortening (p < 0.01). CX occlusion caused LV lateral wall dysfunction and abolished septal flash due to loss of rebound stretch (p < 0.0001). Furthermore, CX occlusion restored septal systolic shortening to a similar level as before induction of LBBB and substantially improved septal work (p < 0.001). LAD occlusion, however, accentuated septal flash by increasing rebound stretch (p < 0.05). Consistent with the experimental findings, septal flash was absent in patients with LV lateral wall scar due to lack of rebound stretch (p < 0.001), and septal systolic shortening and septal work far exceeded values in nonischemic cardiomyopathy (p < 0.0001). Septal flash was present in most patients with anteroseptal scar. ConclusionsLV lateral wall dysfunction and scar abolished septal flash and markedly improved septal function in LBBB. Therefore, function and scar in the LV lateral wall should be taken into account when septal motion is used to evaluate dyssynchrony.

Sacubitril/Valsartan Averts Adverse Post-Infarction Ventricular Remodeling and Preserves Systolic Function in Rabbits

BackgroundSacubitril/valsartan (SAC/VAL) is approved by the U.S. Food and Drug Administration for heart failure with reduced ejection fraction (HFrEF). ObjectivesThis study investigated the effects of SAC/VAL on acute myocardial infarction (MI) and cardiac remodeling in a translational rabbit model of MI. MethodsNew Zealand White rabbits were sedated and underwent conscious MI (45-min ischemia) by balloon inflation (previously implanted surgically) followed by 72 h (acute protocol) or 10 weeks (chronic protocols) of reperfusion. “Infarct-sparing” protocol: SAC/VAL, VAL, or placebo were randomly allocated and administered at reperfusion. “HFrEF-treatment” protocol: rabbits were randomized, and treatment commenced after echocardiography-confirmed left ventricular ejection fraction (LVEF) ≤40%. “HFrEF-prevention” protocol: treatment started at reperfusion and continued daily throughout the study. ResultsCompared with placebo, SAC/VAL and VAL significantly reduced infarct size (TTC staining) and plasma troponin levels; however, only SAC/VAL preserved LVEF at 72 h post-MI. In the HFrEF-treatment protocol, LVEF improvement was observed with SAC/VAL compared with both placebo and VAL starting 2 weeks post-treatment, a benefit that persisted throughout study duration. In the HFrEF-prevention protocol, SAC/VAL and VAL attenuated the decline in LVEF post-MI, although SAC/VAL offered better functional protection. The functional improvement observed in both treatment protocols was paralleled by significant reduction in left ventricular (LV) scar size (Picrosirius red staining) in the SAC/VAL groups. ConclusionsReperfusion therapy with SAC/VAL or VAL offers robust acute infarct-sparing benefits; however, SAC/VAL treatment offered superior short-term and long-term benefits in preventing MI-induced LV dysfunction compared with VAL. SAC/VAL also significantly attenuated LV scar size following MI compared with placebo, whereas VAL did not reach statistical significance in scar reduction.

Myocardial Scar and Mortality in Severe Aortic Stenosis.

Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

A CASE OF MASSIVE PULMONARY EMBOLISM CAUSING VENTRICULAR FIBRILLATION AND CARDIAC ARREST

SESSION TITLE: Critical Care 1 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Massive Pulmonary Embolism (PE) is a known noncardiac cause of circulatory arrest, it is associated with very poor outcomes and high mortality. We herein report a unique case of cardiac arrest due to massive PE that presented with a dominant rhythm of Ventricular Fibrillation (VF). CASE PRESENTATION: A 42-year-old male with past medical history of morbid obesity and chronic back pain; presented to our hospital with acute on chronic low back pain and inability to ambulate. On admission, vital signs were normal. Physical examination showed signs of left lower extremity radiculopathy. Often times and because of the pain severity, patient used to refuse to participate in physical therapy and assisted ambulation. Given that, patient was on appropriate pharmacological deep venous thrombosis prophylaxis. During hospitalization, the patient was found unresponsive and pulseless, code blue was activated and cardiopulmonary resuscitation was started. Upon connecting it, the cardiac monitor showed VF rhythm (Image 1) for which a shock was delivered. After few minutes, return of spontaneous circulation achieved. A 12-lead electrocardiogram demonstrated sinus tachycardia and new right bundle branch block (Image 2) and that triggered the suspicion of PE. A stat bedside echocardiogram revealed dilatation of the right ventricle. Computed Tomography of chest with intravenous contrast (PE protocol) confirmed the diagnosis of PE in the left and right main pulmonary arteries(Image 3). As a result, systemic thrombolytic therapy was initiated. Few hours later, the patient went into three successive episodes of cardiac arrest in which VF was the recurrent rhythm and multiple shocks were delivered. DISCUSSION: PE is the third most common cause of hospital-related death[1]. The vast majority of VF cases are strongly linked to cardiac events; mainly coronary artery disease due to ischemia[2]. On the other hand, PE with circulatory arrest is highly associated with pulseless electric activity (PEA) followed by asystole[3]. For VF to be the dominant rhythm in the setting of cardiac arrest due to massive PE and without any evidence of myocardial ischemia is unreported. This case highlights the importance of considering PE in the differential diagnosis of cardiac arrest causes when the presenting and the dominant rhythm is VF particularly in the absence of myocardial ischemia. CONCLUSIONS: To our knowledge, this is the first case in the literature to provide a direct link between PE and VF in the context of circulatory arrest. It is crucial to recognize the initial rhythm that is associated with the cardiac arrest as it may guide toward the etiology of the arrest. While, PEA and asystole are by far the most common rhythms in massive PE with cardiac arrest, our case should encourage physicians to also consider PE as a possible cause of cardiac arrest when VF is the main rhythm and no signs of cardiac ischemia exist. Reference #1: Lindblad B, Eriksson A, Bergqvist D. Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. Br J Surg. 1991;78:849–852. [PubMed] Reference #2: Warnes CA, Roberts WC. Sudden coronary death: relation of amount and distribution of coronary narrowing at necropsy to previous symptoms of myocardial ischemia, left ventricular scarring and heart weight. Am J Cardiol. 1984 Jul 1. 54(1):65-73. Reference #3: Kürkciyan I, Meron G, Sterz F, Janata K, Domanovits H, Holzer M, Berzlanovich A, Bankl HC, Laggner AN. Pulmonary Embolism as Cause of Cardiac ArrestPresentation and Outcome. Arch Intern Med.2000;160(10):1529–1535. https://doi.org/10.1001/archinte.160.10.1529 DISCLOSURES: No relevant relationships by Michel Chalhoub, source=Web Response No relevant relationships by halim el hage, source=Web Response No relevant relationships by Cheikh Talal El Imad, source=Web Response No relevant relationships by Ahmad Itani, source=Web Response No relevant relationships by boutros karam, source=Web Response No relevant relationships by Ahmed Mahgoub, source=Web Response No relevant relationships by chadi salmane, source=Web Response No relevant relationships by Jay Solanki, source=Web Response

Ejection fraction in left bundle branch block is disproportionately reduced in relation to amount of myocardial scar

IntroductionThe relationship between left ventricular (LV) ejection fraction (EF) and LV myocardial scar can identify potentially reversible causes of LV dysfunction. Left bundle branch block (LBBB) alters the electrical and mechanical activation of the LV. We hypothesized that the relationship between LVEF and scar extent is different in LBBB compared to controls. MethodsWe compared the relationship between LVEF and scar burden between patients with LBBB and scar (n = 83), and patients with chronic ischemic heart disease and scar but no electrocardiographic conduction abnormality (controls, n = 90), who had undergone cardiovascular magnetic resonance (CMR) imaging at one of three centers. LVEF (%) was measured in CMR cine images. Scar burden was quantified by CMR late gadolinium enhancement (LGE) and expressed as % of LV mass (%LVM). Maximum possible LVEF (LVEFmax) was defined as the function describing the hypotenuse in the LVEF versus myocardial scar extent scatter plot. Dysfunction index was defined as LVEFmax derived from the control cohort minus the measured LVEF. ResultsCompared to controls with scar, LBBB with scar had a lower LVEF (median [interquartile range] 27 [19–38] vs 36 [25–50] %, p < 0.001), smaller scar (4 [1–9] vs 11 [6–20] %LVM, p < 0.001), and greater dysfunction index (39 [30–52] vs 21 [12–35] % points, p < 0.001). ConclusionsAmong LBBB patients referred for CMR, LVEF is disproportionately reduced in relation to the amount of scar. Dyssynchrony in LBBB may thus impair compensation for loss of contractile myocardium.

Reduction in mortality from implantable cardioverter-defibrillators in non-ischaemic cardiomyopathy patients is dependent on the presence of left ventricular scar.

In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM. We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

Abstract 113: Steering Fibroblast Phenotype to Promote Left Ventricular Scar Maturation and Function Post-MI

The prevalence for myocardial infarction (MI) in the US is ~7.9 million. Although current therapies have significantly improved survival rate, adverse left ventricular (LV) remodeling still occurs in nearly 40% of MI patients. The size, composition, and mechanical properties of the scar that forms post-MI determines patient outcomes. Scar formation is mostly driven by inflammatory factors and fibroblast differentiation into myofibroblast. Suppression of inflammation and fibrosis, however, have led to unexpected results, including infarct expansion and LV wall thinning. Recently our lab uncovered that extracellular matrix (ECM) degradation post-MI releases collagen derived fragments that are biologically active. Using a synthesized peptide mimetic of one such fragment - p1158/59 - we found that p1158/59 dynamically interacts with fibroblasts regulating cell migration and the type and amount of collagen deposited post-MI. We hypothesize that p1158/59 binds to fibroblasts to delay or prevent myofibroblast differentiation, which promotes scar stabilization by controlled secretion of ECM and scar maturation. Fibroblasts were isolated from mice LV and incubated with vehicle or p1158/59 in serum free media. Complete media (10% FBS) and TGFb were used as positive controls respectively for migration and myofibroblast activation. We assessed fibroblast phenotype and ECM secretion. Mice were treated with p1158/59 post-MI and mid- and long-term LV remodeling and function assessed. p1158/59 promoted fibroblast migration to levels similar to positive control. Surprisingly, this was not accompanied by increased alpha smooth muscle actin (i.e. myofibroblast activation). Mice treated with p1158/59 for 7 days (D7) post-MI presented less collagen deposition with decreased LV dilation compared to controls. At D14 post-MI, p1158/59 repressed expression of pro-angiogenic factors and promoted fiber alignment and cellular apoptosis, which resulted in improved cardiac function, providing proof-of-concept that p1158/59 reduces adverse LV remodeling. These data suggest that p1158/59 modulates scar formation and remodeling post-MI by delaying or partially inhibiting fibroblast phenotype transition and promoting scar stabilization and maturation.

P269Reduction in mortality from implantable cardioverter-defibrillators in non-ischemic cardiomyopathy patients is dependent on the presence of left ventricular scar

P269Reduction in mortality from implantable cardioverter-defibrillators in non-ischemic cardiomyopathy patients is dependent on the presence of left ventricular scar

Impact of right ventricular volume and function evaluated using cardiovascular magnetic resonance imaging on outcomes after surgical ventricular reconstruction.

This study aimed to evaluate whether cardiac magnetic resonance imaging (MRI)-derived right ventricular (RV) assessment can facilitate risk stratification among patients with ischaemic cardiomyopathy who underwent surgical ventricular reconstruction (SVR). We retrospectively analysed 53 patients who underwent SVR. The patients were preoperatively evaluated using cardiac MRI. Cine-MRI was acquired for left ventricular (LV) and RV volume. Gadolinium-enhanced MRI was performed to evaluate LV scarring. The mid-term (median, 58 months) risk factors of all-cause mortality and major adverse cardiac events were analysed. A significant reduction in LV end-diastolic and end-systolic volume index and an increase in LV ejection fraction were observed early after SVR. RV end-diastolic volume index (RVEDVI) and RV end-systolic volume index (RVESVI) decreased after SVR (preoperative versus postoperative: RVEDVI, 71 ± 24 vs 62 ± 17 ml/m2, P = 0.006; RVESVI, 44 ± 26 vs 37 ± 16 ml/m2, P = 0.033), but RV ejection fraction did not change (preoperative versus postoperative: RV ejection fraction 40.8±14.6 vs 42.0±11.0%, P = 0.067). At follow-up, 25 deaths and 31 major adverse cardiac events occurred. After adjustment for age, creatinine level and preoperative mitral regurgitation grade, the Cox-hazard model indicated that RVEDVI [P = 0.006, hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05] and RVESVI [P = 0.007, HR 1.02, 95% CI 1.01-1.04] were significant predictors for all-cause mortality. As for major adverse cardiac events, RVEDVI (P = 0.007, HR 1.03, 95% CI 1.01-1.05), RVESVI (P = 0.002, HR 1.03, 95% CI 1.01-1.04) and RV ejection fraction (P = 0.018, HR 0.97, 95% CI 0.94-0.99) were significant. RV parameters were more sensitive than LV parameters for predicting worse outcomes following SVR. Preoperative assessment of RV volume and function using cardiac MRI may improve the risk stratification of SVR.

Relationship between left ventricular dyssynchrony and scar burden in the genesis of ventricular tachyarrhythmia

BackgroundLeft ventricular (LV) ejection fraction (EF) has poor predictive value for ventricular tachyarrhythmia (VT). Other parameters such as LV dyssynchrony (LVD), and LV scar burden have also been individually associated with VT, but the interplay of these factors in the genesis of VT has not been explored. This retrospective study sought to evaluate the relationship between LVD and imaging characteristics of the myocardial substrate in predicting VT. MethodsWe identified 183 patients (150 men; mean age: 64 ± 14 years and mean LVEF: 23% ± 7%), who received an implantable cardioverter defibrillator (ICD) for primary prevention and who underwent a gated single-photon emission computed tomography (GSPECT) myocardial perfusion scan prior to ICD implantation. LVD was determined by phase analysis of the GSPECT images. Occurrence of VTs was established through routine ICD interrogations and review of electronic medical records. ResultsLVD was present in 136 (74%) patients. VT occurred in 48 (26%) patients. Ninety-eight percent of patient who experienced VT had LVD. Patients without LVD had a significantly better survival free of both sustained and non-sustained VT (HR, 95% CI 4.90, 2.12-11.20; P < 0.0001). The combination of LVD and myocardial scar occupying > 6% of LV myocardium accounted for 83% of all VT events. ConclusionsLVD assessment by GSPECT is strongly associated with incident VT in patients with low LVEF. The combination of LVD and scar burden predicted the majority of VT events.

Utility of dual-source computed tomography in cardiac resynchronization therapy—DIRECT study

Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT). We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time. In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE). There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both). Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT.

Reduction in Mortality from Implantable Cardioverter Defibrillators in Non-Ischaemic Cardiomyopathy Patients is Dependent on the Presence of Left Ventricular Scar

Reduction in Mortality from Implantable Cardioverter Defibrillators in Non-Ischaemic Cardiomyopathy Patients is Dependent on the Presence of Left Ventricular Scar

Abstract 24021: Sacubitril/Valsartan Attenuates Fibrosis and Improves Left Ventricular Function in a Rabbit Model of HFrEF

Background: Sacubitril/Valsartan (SAC/VAL), a drug combining a neprilysin inhibitor and an angiotensin receptor blocker, was shown to reduce myocardial infarct size and left ventricular (LV) dysfunction in preclinical models of myocardial infarction (MI). In the PARADIGM-HF trial, SAC/VAL prevented the clinical progression of patients with heart failure (HF) more effectively than enalapril. Whether SAC/VAL attenuates cardiac fibrosis and improves LV function in a rabbit model of MI-induced HF with reduced ejection fraction (rEF) is unknown. Methods: Anesthetized adult male NZW rabbits (~2.5kg) underwent left thoracotomy and the left anterior descending (LAD) coronary artery was identified and occluded for 45 min followed by reperfusion. Weekly echocardiography was performed to confirm reduced EF (~40%), which was uniformly achieved at 5 weeks post MI. Subsequently, rabbits were randomized to orally receive placebo (volume-matched water, BID), SAC/VAL (10 mg/kg, BID) or VAL (9.1mg/kg/day) starting on week 6. At 10 weeks post MI, rabbits were sacrificed and hearts were harvested, fixed with 10% formalin and embedded in paraffin to assess myocardial fibrosis (Picrosirius red staining). Operators performing echocardiography, Picrosirius red staining and analysis were blinded to treatment allocation. Results: Two weeks after treatment initiation, a significant improvement in LVEF was observed in the SAC/VAL group compared to both placebo and VAL, a benefit that lasted throughout the entire study (Fig. A). The functional improvement observed was associated with a significant reduction in LV scar size compared to placebo at week 10 (Fig. B). However, when compared to VAL, the decrease in scar size did not reach statistical significance despite a clear trend. Conclusion: Our results suggest that SAC/VAL may offer superior benefits compared to equivalent dose of stand-alone VAL in attenuating LV scar size and improving LVEF in a rabbit model of ischemic HFrEF.

Predictors of Mortality in Patients With Severe Ischemic Cardiomyopathy Undergoing Surgical Mitral Valve Intervention.

BackgroundIschemic mitral regurgitation is associated with substantial risk of death. Although surgical mitral valve intervention (MVi) may improve symptoms, it has not been shown to improve survival. The aim of this study was to identify predictors of mortality in patients with ischemic mitral regurgitation and MVi.Methods and ResultsWe evaluated 117 consecutive patients (age, 65±10 years) with advanced ischemic cardiomyopathy who underwent cardiac magnetic resonance and subsequent MVi between January 1, 2002 and January 1, 2012. Cardiac magnetic resonance was used to assess left ventricular remodeling and myocardial scarring. The effective regurgitant orifice area was calculated from the proximal isovelocity surface area by echocardiography. There were 43 deaths (37%) during follow‐up (median, 62 months). On multivariable analysis, age ≥70 years (P=0.013), diabetes mellitus (P=0.001), dyslipidemia (P=0.012), papillary muscle scar (P=0.010), incomplete revascularization (P=0.001), and total scar %×effective regurgitant orifice area ≥0.20 cm2 (P=0.005) were each independently associated with all‐cause mortality. Although patients with effective regurgitant orifice area <0.2 cm2 at baseline demonstrated an increased hazard ratio of 3.3 for every 10% increase in scar, the hazard ratio increased to 9 for every 10% increase in scar in those with baseline effective regurgitant orifice area ≥0.20 cm2. Mortality also was significantly higher in patients with incomplete revascularization compared with those with vascularized viable myocardium (61% versus 28%; P<0.001).ConclusionsIncreased total scar burden and the presence of incomplete revascularization are powerful predictors of mortality in patients with advanced ischemic cardiomyopathy undergoing MVi. Viability assessment with cardiac magnetic resonance imaging can identify which patients with ischemic mitral regurgitation are at highest risk for mortality after surgical MVi.

Transplantation of Isl1+ cardiac progenitor cells in small intestinal submucosa improves infarcted heart function

BackgroundApplication of cardiac stem cells combined with biomaterial scaffold is a promising therapeutic strategy for heart repair after myocardial infarction. However, the optimal cell types and biomaterials remain elusive.MethodsIn this study, we seeded Isl1+ embryonic cardiac progenitor cells (CPCs) into decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) to assess the therapeutic potential of Isl1+ CPCs and the biocompatibility of SIS-ECM with these cells.ResultsWe observed that SIS-ECM supported the viability and attachment of Isl1+ CPCs. Importantly, Isl1+ CPCs differentiated into cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. In addition, SIS-ECM with CPC-derived cardiomyocytes showed spontaneous contraction and responded to β-adrenergic stimulation. Next, patches of SIS-ECM seeded with CPCs for 7 days were transplanted onto the outer surface of infarcted myocardium in mice. Four weeks after transplantation, the patches were tightly attached to the surface of the host myocardium and remained viable. Transplantation of patches improved cardiac function, decreased the left ventricular myocardial scarring area, and reduced fibrosis and heart failure.ConclusionsTransplantation of Isl1+ CPCs seeded in SIS-ECM represents an effective approach for cell-based heart therapy.

Electrocardiographic Strain Pattern Is Associated With Left Ventricular Concentric Remodeling, Scar, and Mortality Over 10Years: The Multi-Ethnic Study of Atherosclerosis.

BackgroundBoth ECG strain pattern and QRS measured left ventricular (LV) hypertrophy criteria are associated with LV hypertrophy and have been used for risk stratification. However, the independent predictive value of ECG strain in apparently healthy individuals in predicting mortality and adverse cardiovascular events is unclear.Methods and ResultsMESA (Multi‐Ethnic Study of Atherosclerosis) is a multicenter, prospective cohort of 6441 participants (mean age, 62 years; 54% women). In 2847 of these participants, cardiac magnetic resonance imaging was repeated ≈10 years later (Year‐10). At Year‐10, 1759 participants underwent cardiac magnetic resonance imaging with gadolinium to detect myocardial scar. During a median follow‐up of 11.7 years, ECG strain (n=168, 2.6%) was significantly associated with all‐cause death (adjusted hazard ratio, 1.33; 95% confidence interval, 1.01–1.77; P=0.045), heart failure (2.62; 1.73–3.97; P<0.001), myocardial infarction (1.86; 1.09–3.18; P=0.024), and incident cardiovascular disease (1.45; 1.06–2.00; P=0.022). ECG strain was also associated with an increase in LV mass (β=9.29 g; P<0.001) and LV mass‐to‐volume ratio (β=0.07 g/mL; P=0.007) and a decline in LV ejection fraction (β=−3.30%; P<0.001). Moreover, ECG strain either at baseline and Year‐10 was associated with LV scar (odds ratio, 4.93 and 5.22; P=0.002 and <0.001, respectively), whereas these associations were not observed in ECG LV hypertrophy.ConclusionsECG strain is independently associated with all‐cause mortality, adverse cardiovascular events, development of LV concentric remodeling and systolic dysfunction, and myocardial scar over 10 years in multiethnic participants without past cardiovascular disease. ECG strain may be an early marker of LV structural remodeling that contributes to development of adverse cardiovascular events.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT00005487.

Integrated Noninvasive Physiological Assessment of Coronary Circulatory Function and Impact on Cardiovascular Mortality in Patients With Stable Coronary Artery Disease.

It is suggested that the integration of maximal myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows for comprehensive evaluation of patients with known or suspected stable coronary artery disease. Because management decisions are predicated on clinical risk, we sought to determine the independent and integrated value of maximal MBF and CFR for predicting cardiovascular death. MBF and CFR were quantified in 4029 consecutive patients (median age 66 years, 50.5% women) referred for rest/stress myocardial perfusion positron emission tomography scans from January 2006 to December 2013. The primary outcome was cardiovascular mortality. Maximal MBF <1.8 mL·g-1·min-1 and CFR<2 were considered impaired. Four patient groups were identified based on the concordant or discordant impairment of maximal MBF or CFR. Association of maximal MBF and CFR with cardiovascular death was assessed using Cox and Poisson regression analyses. A total of 392 (9.7%) cardiovascular deaths occurred over a median follow-up of 5.6 years. CFR was a stronger predictor of cardiovascular mortality than maximal MBF beyond traditional cardiovascular risk factors, left ventricular ejection fraction, myocardial scar and ischemia, rate-pressure product, type of radiotracer or stress agent used, and revascularization after scan (adjusted hazard ratio, 1.79; 95% confidence interval [CI], 1.38-2.31; P<0.001 per unit decrease in CFR after adjustment for maximal MBF and clinical covariates; and adjusted hazard ratio, 1.03; 95% CI, 0.84-1.27; P=0.8 per unit decrease in maximal MBF after adjustment for CFR and clinical covariates). In univariable analyses, patients with concordant impairment of CFR and maximal MBF had high cardiovascular mortality of 3.3% (95% CI, 2.9-3.7) per year. Patients with impaired CFR but preserved maximal MBF had an intermediate cardiovascular mortality of 1.7% (95% CI, 1.3-2.1) per year. These patients were predominantly women (70%). Patients with preserved CFR but impaired maximal MBF had low cardiovascular mortality of 0.9% (95% CI, 0.6-1.6) per year. Patients with concordantly preserved CFR and maximal MBF had the lowest cardiovascular mortality of 0.4% (95 CI, 0.3-0.6) per year. In multivariable analysis, the cardiovascular mortality risk gradient across the 4 concordant or discordant categories was independently driven by impaired CFR irrespective of impairment in maximal MBF. CFR is a stronger predictor of cardiovascular mortality than maximal MBF. Concordant and discordant categories based on integrating CFR and maximal MBF identify unique prognostic phenotypes of patients with known or suspected coronary artery disease.

Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy

BackgroundRecent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. ObjectivesThe aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (−) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. MethodsClinical events were quantified in patients with NICM who were +MWF (n = 68) or −MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. ResultsIn the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for −MWF). In separate analyses of +MWF and −MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in −MWF. ConclusionsIn patients with NICM, CRT-D was superior to CRT-P in +MWF but not −MWF. These findings have implications for the choice of device therapy in patients with NICM.