A Robust Cardiac MRI Assessment for the Characterization of an Ovine Ischemic Cardiomyopathy Model Creation Protocol Demonstrates Rapid Heart Failure Progression With Minimized Mortality

AbstractThe mitochondrial pyruvate carrier (MPC) is the entry point for the glycolytic end-product pyruvate to the mitochondria. MPC activity, which is controlled by its abundance and post-translational regulation, determines whether pyruvate is oxidised in the mitochondria or metabolised in the cytosol. MPC serves as a crucial metabolic branch point that determines the fate of pyruvate in the cell, enabling metabolic adaptations during health, such as exercise, or as a result of disease. Decreased MPC expression in several cancers limits the mitochondrial oxidation of pyruvate and contributes to lactate accumulation in the cytosol, highlighting its role as a contributing, causal mediator of the Warburg effect. Pyruvate is handled similarly in the failing heart where a large proportion of it is reduced to lactate in the cytosol instead of being fully oxidised in the mitochondria. Several recent studies have found that the MPC abundance was also reduced in failing human and mouse hearts that were characterised by maladaptive hypertrophic growth, emulating the anabolic scenario observed in some cancer cells. In this review we discuss the evidence implicating the MPC as an important, perhaps causal, mediator of heart failure progression.

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Implications of multiple late gadolinium enhancement lesions on the frequency of left ventricular reverse remodeling and prognosis in patients with non‐ischemic cardiomyopathy

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/s12968-021-00734-3 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Shingo Ota ◽

Makoto Orii ◽

Tsuyoshi Nishiguchi ◽

Mao Yokoyama ◽

Ryoko Matsushita ◽

...

Keyword(s):

Heart Failure ◽

Late Gadolinium Enhancement ◽

Ischemic Cardiomyopathy ◽

Left Ventricular ◽

Reverse Remodeling ◽

Cardiac Events ◽

Gadolinium Enhancement ◽

Systolic Volume ◽

Linear Pattern ◽

Multiple Lesions

Abstract Background Non-ischemic cardiomyopathy (NICM) is a heterogeneous disease, and its prognosis varies. Although late gadolinium enhancement (LGE)-cardiovascular magnetic resonance (CMR) demonstrates a linear pattern in the mid-wall of the septum or multiple LGE lesions in patients with NICM, the therapeutic response and prognosis of multiple LGE lesions have not been elucidated. This study aimed to investigate the frequency of left ventricular (LV) reverse remodeling (LVRR) and prognosis in patients with NICM who have multiple LGE lesions. Methods This single-center retrospective study included 101 consecutive patients with NICM who were divided into 3 groups according to LGE-CMR results: patients without LGE (no LGE group = 48 patients), patients with a typical mid-wall LGE pattern (n = 29 patients), and patients with multiple LGE lesions (n = 24 patients). LVRR was defined as an increase in LV ejection fraction (LVEF) ≥ 10 % and a final value of LVEF > 35 %, which was accompanied by a decrease in LV end-systolic volume ≥ 15 % at 12-month follow-up using echocardiography. The frequency of composite cardiac events, defined as sudden cardiac death (SCD), aborted SCD (non-fatal ventricular fibrillation, sustained ventricular tachycardia, or adequate implantable cardioverter-defibrillator therapies), and heart failure death or hospitalization for worsening heart failure, were summarized and compared between the groups. Results Among the 3 groups, the frequency of LVRR was significantly lower in the multiple lesions group than in the no LGE and mid-wall groups (no LGE vs. mid-wall vs. multiple lesions: 49 % vs. 52 % vs. 19 %, p = 0.03). There were 24 composite cardiac events among the patients: 2 in patients without LGE (hospitalization for worsening heart failure; 2), 7 in patients of the mid-wall group (SCD; 1, aborted SCD; 1 and hospitalization for worsening heart failure; 5), and 15 in patients of the multiple lesions group (SCD; 1, aborted SCD; 8 and hospitalization for worsening heart failure; 6). The multiple LGE lesions was an independent predictor of composite cardiac events (hazard ratio: 11.40 [95 % confidence intervals: 1.49−92.01], p = 0.020). Conclusions Patients with multiple LGE lesions have a higher risk of cardiac events and poorer LVRR. The LGE pattern may be useful for an improved risk stratification in patients with NICM.

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The prognostic value of myocardial deformational patterns on all-cause mortality is modified by ischemic cardiomyopathy in patients with heart failure

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02291-3 ◽

2021 ◽

Author(s):

Philip Brainin ◽

Anna Engell Holm ◽

Morten Sengeløv ◽

Peter Godsk Jørgensen ◽

Niels Eske Bruun ◽

...

Keyword(s):

Heart Failure ◽

Prognostic Value ◽

Ischemic Cardiomyopathy ◽

Patients With Heart Failure ◽

All Cause Mortality

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Clinical significance of Q waves in ischemic cardiomyopathy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.340 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

E Rodenas Alesina ◽

P Jordan ◽

L Herrador ◽

C Espinet-Coll ◽

N Pizzi ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Cox Regression ◽

Cox Model ◽

Cardiovascular Death ◽

P Value ◽

Heart Failure Hospitalization ◽

Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF < 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF <40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between >10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if >10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR < 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 <0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia > 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

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Twin peaks diversity with sacubitril/valsartan treatment responses in cardiomyopathic heart failure patients of non-ischemic compared to ischemic etiologies

European Heart Journal ◽

10.1093/ehjci/ehaa946.1056 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H.Y Chang ◽

W.R Chiou ◽

P.L Lin ◽

C.Y Hsu ◽

C.T Liao ◽

...

Keyword(s):

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Ventricular Remodeling ◽

Left Ventricular Ejection ◽

Funding Source ◽

Heart Failure Patients ◽

Twin Peaks ◽

All Cause Mortality

Abstract Background Ischemic cardiomyopathy (ICM) has been associated with increased mortality when compared with non-ischemic cardiomyopathy (NICM) from several heart failure (HF) cohorts. Instead, PARADIGM study demonstrated similar event rates of cardiovascular (CV) death, all-cause mortality and HF readmissions between ICM and NICM patients. Although the beneficiary effect of sacubitril/valsartan (SAC/VAL) compared to enalapril on these endpoints was consistent across etiologic categories, PARADIGM study did not analyze the effect of ventricular remodeling of SAC/VAL on patients with different HF etiologies, which may significantly affect treatment outcomes. Purpose We aim to compare alterations of left ventricular ejection fraction (LVEF) following SAC/VAL treatment and its association with clinical outcomes in patients with different HF etiologies. Methods Treatment with angiotensin receptor neprilysin inhibitor for Taiwan heart failure patients (TAROT-HF) study is a multicenter study which enrolled 1552 patients with LVEF <40%, whom had been on SAC/VAL treatment from 9 hospitals between 2017 and 2018. After excluding patients without having follow-up echocardiographic studies, patients were grouped by HF etiologies and by LVEF changes following treatment for 8-month period. LVEF improvement ≥15% was defined as “significant improvement”, 5–15% as “marginal improvement”, and <5% or worse as “lack of improvement”. The primary endpoint was a composite of CV death or a first hospitalization for HF. Mean follow-up period was 726 days. Results A total of 1230 patients were analyzed. Patients with ICM were significantly older, more male, and prone to have associated hypertension and diabetes. On the other hand, patients with NICM had lower LVEF and higher likelihood of atrial fibrillation. LVEF increase was significantly greater in patients with NICM compared to those with ICM (11.2±12.4% vs. 6.9±9.8, p<0.001). The effect of ventricular remodeling of SAC/VAL on patients with NICM showed twin peaks diversity (Significant improvement 37.1%, lack of improvement 42.3%), whereas in patients with ICM the proportions of significant, marginal and lack of improvement groups were 19.4%, 28.2% and 52.4%, respectively. The primary endpoint showed twin peaks diversity also in patients with NICM in line with LVEF changes: adjusted HR for patients with NICM and significant improvement was 0.41 (95% CI 0.29–0.57, p<0.001), for patients with NICM and lack of improvement was 1.54 (95% CI 1.22–1.94, p<0.001). Analyses for CV death, all-cause mortality, and HF readmission demonstrated consistent results. Conclusion Patients with NICM had higher degree of LVEF improvement than those with ICM following SAC/VAL treatment, and significant improvement of LVEF in NICM patients may indicate favorable outcome. NICM patients without response to SAC/VAL treatment should serve as an indicator for poor clinical outcome and warranted meticulous HF management. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Cheng Hsin General Hospital

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