P3332Epicardial fat, left ventricular contractility and myocardial fibrosis in obese subjects: the utility of cardiac magnetic resonance in the context of obesity-related heart failure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PN-III-P1-1-TE-2016-0669, within PNCDI III Background Left ventricular non-compaction (LVNC) is associated with an increased risk of heart failure (HF). The presence of a real LVNC with HF with preserved ejection fraction (HFpEF), is still controverted. Methods We evaluated prospectively 42 patients with HFpEF, 21 with LVNC (61 ± 9 years) and 21 without LVNC (LVC), aged and risk factor matched, by cardiac magnetic resonance (CMR) 1.5T. LVNC diagnosis was confirmed by Petersen and Jacquier criteria (NC/C ratio and the percentage of NC myocardium). We performed myocardial T1 mapping (normal value of 950 ± 21ms). We calculated a mean value of all native T1 (T1mean), and also for apical (apicalT1) and basal segments (basalT1). We also calculated ECV mean, basal and apical. All patients had NTproBNP and biomarkers for systemic inflammation (hsCRP, IL6, cystatin C and sST2), endothelial dysfunction: VCAM, von Willebrand factor (vWf), vWF metalloproteinase-ADAMTS13, and myocardial fibrosis: vascular peroxidase (VPO), and Galectin-3. Results In the LVNC, mean NC/C ratio was 2.9 ± 0.5 mm and the percentage of NC myocardium was 24.41 ± 8.8%. LVNC patients had significantly higher T1apical, higher ECVmean, ECV basal and apical (Table) by comparison with LVC group, suggesting an extensive fibrosis in LVNC group with significantly higher apical fibrosis. Inflammatory markers were similar between groups, LVNC patients had lower values of ADAMTS13, suggesting endothelial dysfunction, and higher values of Galectin-3, suggesting increased myocardial fibrosis (Table). Galectin-3 correlated positively only with apicalT1 (R = 0.49, p = 0.04). NTproBNP significantly correlated with VPO, a promotor of fibrosis (r = 0.61, p = 0.009) in LVNC group, whereas in LVC group correlated with cystatin C (r = 0.62, p = 0003) and VCAM (r = 0.4, p = 0.05). Native apical T1 cut off >1021 ms provided the highest sensibility and specificity to differentiate segments with and without NC in HFpEF (p = 0.002) (Figure). Conclusion HFpEF patients with LVNC have significant higher NTproBNP, higher fibrosis than patients without LVNC, more extensive in non-compacted apical segments. Galectin-3 level correlates only with apical fibrosis on CMR, expressed by apicalT1 time. Moreover, endothelial dysfunction seems to play an important role in HFpEF generation in LVNC. All findings suggests that LVNC is a stand alone condition, not an adaptive hyper-trabeculation in HFpEF. Table.Comparison between groups NTproBNP (pg/ml) Galectin3 (ng/ml) ADAMTS13 (ng/ml) T1mean (ms) basalT1 (ms) apicalT1 (ms) ECV mean (%) ECV basal (%) ECV apical (%) LVNC 294 ± 282 8.44 ± 3.45 767.35 ± 335.56 1013.8 ± 31.8 1002.8 ± 27.2 1059 ± 73 27.2 ± 2.9 26.2 ± 2.9 29.6 ± 3.9 LVC 163 ± 71 6.67 ± 2.88 962.33 ± 253.78 1003.2 ± 28.1 1004.3 ± 29.5 1007 ± 40 24.3 ± 2.5 24.2 ± 2.7 25.2 ± 2.8 P value 0.031 0.048 0.049 0.26 0.865 0.007 0.002 0.033 <0.001 Abstract Figure

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Synergy between sacubitril and valsartan leads to hemodynamic, antifibrotic, and exercise tolerance benefits in rats with preexisting heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00579.2018 ◽

2019 ◽

Vol 316 (2) ◽

pp. H289-H297 ◽

Cited By ~ 8

Author(s):

Mikhail Y. Maslov ◽

Stephan Foianini ◽

Dita Mayer ◽

Michael V. Orlov ◽

Mark A. Lovich

Keyword(s):

Heart Failure ◽

Myocardial Fibrosis ◽

Exercise Tolerance ◽

Left Ventricular ◽

Potential Contribution ◽

Angiotensin Receptor ◽

Ventricular Contractility ◽

Left Ventricular Contractility ◽

Therapeutic Benefits ◽

Relaxation Exercise

Simultaneous neprilysin inhibition (NEPi) and angiotensin receptor blockade (ARB) with sacubitril/valsartan improves cardiac function and exercise tolerance in patients with heart failure. However, it is not known whether these therapeutic benefits are primarily due to NEPi with sacubitril or ARB with valsartan or their combination. Therefore, the aim of the present study was to investigate the potential contribution of sacubitril and valsartan to the benefits of the combination therapy on left ventricular (LV) function and exercise tolerance. Heart failure was induced by volume overload via partial disruption of the aortic valve in rats. Therapy began 4 wk after valve disruption and lasted through 8 wk. Drugs were administered daily via oral gavage [sacubitril/valsartan (68 mg/kg), valsartan (31 mg/kg), and sacubitril (31 mg/kg)]. Hemodynamic assessments were conducted using Millar technology, and an exercise tolerance test was conducted using a rodent treadmill. Therapy with sacubitril/valsartan improved load-dependent indexes of LV contractility (dP/d tmax) and relaxation (dP/d tmin), exercise tolerance, and mitigated myocardial fibrosis, whereas monotherapies with valsartan, or sacubitril did not. Both sacubitril/valsartan and valsartan similarly improved a load-independent index of contractility [slope of the end-systolic pressure-volume relationship ( Ees)]. Sacubitril did not improve Ees. First, synergy of NEPi with sacubitril and ARB with valsartan leads to the improvement of load-dependent LV contractility and relaxation, exercise tolerance, and reduction of myocardial collagen content. Second, the improvement in load-independent LV contractility with sacubitril/valsartan appears to be solely due to ARB with valsartan constituent. NEW & NOTEWORTHY Our data suggest the following explanation for the effects of sacubitril/valsartan: 1) synergy of sacubitril and valsartan leads to the improvement of load-dependent left ventricular contractility and relaxation, exercise tolerance, and reduction of myocardial fibrosis and 2) improvement in load-independent left ventricular contractility is solely due to the valsartan constituent. The findings offer a better understanding of the outcomes observed in clinical studies and might facilitate the continuing development of the next generations of angiotensin receptor neprilysin inhibitors.

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Prognostic significance of cardiac magnetic resonance-based markers in patients with hypertrophic cardiomyopathy

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02165-8 ◽

2021 ◽

Author(s):

Zsofia Dohy ◽

Liliana Szabo ◽

Attila Toth ◽

Csilla Czimbalmos ◽

Rebeka Horvath ◽

...

Keyword(s):

Cardiac Magnetic Resonance ◽

Hypertrophic Cardiomyopathy ◽

Magnetic Resonance ◽

Myocardial Fibrosis ◽

Ventricular Arrhythmias ◽

Prognostic Significance ◽

Strain Analysis ◽

Left Ventricular ◽

Icd Therapy ◽

Lv Mass

AbstractThe prognosis of patients with hypertrophic cardiomyopathy (HCM) varies greatly. Cardiac magnetic resonance (CMR) is the gold standard method for assessing left ventricular (LV) mass and volumes. Myocardial fibrosis can be noninvasively detected using CMR. Moreover, feature-tracking (FT) strain analysis provides information about LV deformation. We aimed to investigate the prognostic significance of standard CMR parameters, myocardial fibrosis, and LV strain parameters in HCM patients. We investigated 187 HCM patients who underwent CMR with late gadolinium enhancement and were followed up. LV mass (LVM) was evaluated with the exclusion and inclusion of the trabeculae and papillary muscles (TPM). Global LV strain parameters and mechanical dispersion (MD) were calculated. Myocardial fibrosis was quantified. The combined endpoint of our study was all-cause mortality, heart transplantation, malignant ventricular arrhythmias and appropriate implantable cardioverter defibrillator (ICD) therapy. The arrhythmia endpoint was malignant ventricular arrhythmias and appropriate ICD therapy. The LVM index (LVMi) was an independent CMR predictor of the combined endpoint independent of the quantification method (p < 0.01). The univariate predictors of the combined endpoint were LVMi, global longitudinal (GLS) and radial strain and longitudinal MD (MDL). The univariate predictors of arrhythmia events included LVMi and myocardial fibrosis. More pronounced LV hypertrophy was associated with impaired GLS and increased MDL. More extensive myocardial fibrosis correlated with impaired GLS (p < 0.001). LVMi was an independent CMR predictor of major events, and myocardial fibrosis predicted arrhythmia events in HCM patients. FT strain analysis provided additional information for risk stratification in HCM patients.

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Myocardial work index: a marker of left ventricular contractility in pressure‐induced or volume overload‐induced heart failure

ESC Heart Failure ◽

10.1002/ehf2.13314 ◽

2021 ◽

Author(s):

Bálint Károly Lakatos ◽

Mihály Ruppert ◽

Márton Tokodi ◽

Attila Oláh ◽

Szilveszter Braun ◽

...

Keyword(s):

Heart Failure ◽

Volume Overload ◽

Left Ventricular ◽

Ventricular Contractility ◽

Left Ventricular Contractility ◽

Work Index

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Left ventricular noncompaction—a rare cause of triad: heart failure, ventricular arrhythmias, and systemic embolic events: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02862-x ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Despina Toader ◽

Alina Paraschiv ◽

Petrișor Tudorașcu ◽

Diana Tudorașcu ◽

Constantin Bataiosu ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Left Ventricle ◽

Ventricular Arrhythmias ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

The Right

Abstract Background Left ventricular noncompaction is a rare cardiomyopathy characterized by a thin, compacted epicardial layer and a noncompacted endocardial layer, with trabeculations and recesses that communicate with the left ventricular cavity. In the advanced stage of the disease, the classical triad of heart failure, ventricular arrhythmia, and systemic embolization is common. Segments involved are the apex and mid inferior and lateral walls. The right ventricular apex may be affected as well. Case presentation A 29-year-old Caucasian male was hospitalized with dyspnea and fatigue at minimal exertion during the last months before admission. He also described a history of edema of the legs and abdominal pain in the last weeks. Physical examination revealed dyspnea, pulmonary rales, cardiomegaly, hepatomegaly, and splenomegaly. Electrocardiography showed sinus rhythm with nonspecific repolarization changes. Twenty-four-hour Holter monitoring identified ventricular tachycardia episodes with right bundle branch block morphology. Transthoracic echocardiography at admission revealed dilated left ventricle with trabeculations located predominantly at the apex but also in the apical and mid portion of lateral and inferior wall; end-systolic ratio of noncompacted to compacted layers > 2; moderate mitral regurgitation; and reduced left ventricular ejection fraction. Between apical trabeculations, multiple thrombi were found. The right ventricle had normal morphology and function. Speckle-tracking echocardiography also revealed systolic left ventricle dysfunction and solid body rotation. Abdominal echocardiography showed hepatomegaly and splenomegaly. Abdominal computed tomography was suggestive for hepatic and renal infarctions. Laboratory tests revealed high levels of N-terminal pro-brain natriuretic peptide and liver enzymes. Cardiac magnetic resonance evaluation at 1 month after discharge confirmed the diagnosis. The patient received anticoagulants, antiarrhythmics, and heart failure treatment. After 2 months, before device implantation, he presented clinical improvement, and echocardiographic evaluation did not detect thrombi in the left ventricle. Coronary angiography was within normal range. A cardioverter defibrillator was implanted for prevention of sudden cardiac death. Conclusions Left ventricular noncompaction is rare cardiomyopathy, but it should always be considered as a possible diagnosis in a patient hospitalized with heart failure, ventricular arrhythmias, and systemic embolic events. Echocardiography and cardiac magnetic resonance are essential imaging tools for diagnosis and follow-up.

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Abstract MP31: Left Ventricular Hypertrophy by Electrocardiogram versus Cardiac Magnetic Resonance Imaging as a Predictor for Heart Failure: The MESA Study

Circulation ◽

10.1161/circ.133.suppl_1.mp31 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Abdullahi O Oseni ◽

Waqas T Qureshi ◽

Mohammed F Almahmoud ◽

Alain Bertoni ◽

David A Bluemke ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Heart Failure ◽

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Left Ventricular Hypertrophy ◽

Cardiac Magnetic Resonance Imaging ◽

Ventricular Hypertrophy ◽

Predictive Ability ◽

Left Ventricular ◽

Resonance Imaging

Background: Left ventricular hypertrophy (LVH) is an established risk factor for heart failure (HF). However, it is unknown whether LVH detected by electrocardiogram (ECG-LVH) is equivalent to LVH ascertained by cardiac magnetic resonance imaging (MRI-LVH) in terms of prediction of incident HF using risk prediction models like the Framingham Heart Failure Risk Score (FHFRS). Methods: This analysis included 4745 (mean age 61+10 years, 53.5% women, 61.7% non-whites) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at the time of enrollment. ECG-LVH was defined using Cornell’s criteria while MRI-LVH was derived from left ventricular (LV) mass measured by cardiac MRI. Cox proportional hazard regression was used to examine the association between ECG-LVH and MRI-LVH with incident HF. Harrell’s concordance C-index was used to estimate the predictive ability of the FHFRS when either ECG-LVH or MRI-LVH were included as one of its components. The added predictive ability of ECG-LVH and MRI-LVH were investigated using integrated discrimination improvement (IDI) index and relative IDI. Results: ECG-LVH was present in 291(6.1%) while MRI-LVH was present in 499 (10.5%) of the participants. Over a median follow up of 10.4 years, 140 participants developed HF. Both ECG-LVH [HR (95% CI): 2.25(1.38-3.69)] and MRI-LVH [HR (95% CI): 3.80(1.56-5.63)] were associated with an increased risk of HF in multivariable adjusted models (Table 1). The ability of FHFRS to predict HF was improved with MRI-LVH (C-index 0.871, 95% CI: 0.842-0.899) when compared with ECG-LVH (C-index 0.860, 95% CI: 0.833-0.888) (p < 0.0001). To assess the potential clinical utility of using LVH-MRI instead of ECG-LVH, we calculated several measures of reclassification (Table 1), which were consistent with the statistically significantly improved C-statistic with MRI-LVH. Conclusion: Both ECG-LVH and MRI-LVH are predictive of HF when used in the FHFRS. Substituting MRI-LVH for ECG-LVH improves the predictive ability of the FHFRS.

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Abstract 10378: Characterization of Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance Imaging

Circulation ◽

10.1161/circ.132.suppl_3.10378 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Pedro V Staziaki ◽

Hoshang Farhad ◽

Otávio Coelho-Filho ◽

Ravi V Shah ◽

Richard N Mitchell ◽

...

Keyword(s):

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Myocardial Fibrosis ◽

Myocardial Edema ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Post Contrast ◽

Cardiac Edema ◽

Early Increase ◽

Acute Increase

Introduction: Anthracyclines are a standard chemotherapeutic agent. However, the anthracyclines are associated with a late reduction in left ventricular ejection fraction (LVEF) and heart failure. Pathologically, anthracycline-induced cardiotoxicity (AIC) is characterized by the development of cardiac edema and fibrosis and cardiac magnetic resonance (CMR) is the gold-standard imaging technique for edema and fibrosis. Hypothesis: We hypothesized that a) cardiac edema and fibrosis would be detected by CMR after anthracyclines and b) edema and fibrosis would provide prognostic information. Methods: We performed a longitudinal CMR and histological study of 45 wild-type mice randomized to doxorubicin (DOX, n=30, 5 mg/kg/week for 5 weeks) or placebo (n=15). Measurements were performed at baseline, 5, 10, and 20 weeks after DOX or placebo. Measures of interest were LVEF, myocardial edema and fibrosis. Edema was assessed by T2 mapping, fibrosis by calculating the extracellular volume (ECV) from pre- and post-contrast T1 measurements. Results: In DOX-treated mice vs. placebo, myocardial edema at 5 weeks was increased (T2 values of 32±4 vs. 21±3 ms, P<0.05, Fig. A), while LVEF was unchanged. At 10 weeks, there was a reduction in LVEF (54±6 vs. 63±5% μL, P<0.05) and an increase in myocardial fibrosis (ECV of 0.34±0.03 vs. 0.27±0.03, P<0.05, Fig. B). There was a correlation between T2 measures and cardiac water weight (r=0.79, P=0.007, Fig. C) and between the ECV and histological myocardial fibrosis (r=0.90, P<0.001; Fig. D). Both the early increase in edema and the sub-acute increase in fibrosis predicted the late DOX-induced mortality (P<0.001, Fig. E and F). Conclusions: Our data suggest that, in mice, CMR can detect the early increase in edema and sub-acute increase in fibrosis after anthracyclines, that an increase in edema precedes a reduction in LVEF, that the increase in edema and fibrosis are linked and both are predictive of late animal mortality.

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