Assessment of prognosis in immunoglobulin light chain amyloidosis patients with severe heart failure: a predictive value of right ventricular function

Nagano, Nobutaka; Yano, Toshiyuki; Fujita, Yugo; Kouzu, Hidemichi; Koyama, Masayuki; Ikeda, Hiroshi; Yasui, Kohichiroh; Muranaka, Atsuko; Nishikawa, Ryo; Takahashi, Ryo; Kishiue, Naohiro; Yuda, Satoshi; Miura, Tetsuji

doi:10.1007/s00380-019-01513-y

Cited by 6 publications

(2 citation statements)

References 34 publications

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“…Transthoracic echocardiography and tissue Doppler echocardiography (TDE) were performed using Vivid 7 or Vivid E9 (GE Healthcare, Tokyo, Japan) as previously reported. 24 Two‐dimensional echocardiography was performed using standard echocardiographic views including parasternal long‐axis and apical four‐chamber, three‐chamber, and two‐chamber views from a left lateral decubitus position. The left ventricular (LV) ejection fraction (LVEF, %) was calculated using the biplane modified Simpson's method.…”

Section: Methodsmentioning

confidence: 99%

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy

et al. 2022

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Aims The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain‐like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. Methods and results Patients with DCM (n = 56, 56 ± 15 years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p‐MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p‐MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r = −0.327, P = 0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r = 0.339, P = 0.023), while p‐MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r = −0.360, P = 0.014). During a median follow‐up period of 3.5 years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p‐MLKL expression levels, patients were divided into two groups by using the median value of nuclear p‐MLKL or intercalated disc p‐MLKL. A group with high nuclear p‐MLKL level (H‐nucMLKL group) had a higher adverse event rate than did a group with low nuclear p‐MLKL level (L‐nucMLKL group) (32% vs. 4%, P = 0.012), and Kaplan–Meier survival curves showed that the adverse event‐free survival rate was lower in the H‐nucMLKL group than in the L‐nucMLKL group (P = 0.019 by the log‐rank test). Such differences were not detected between groups divided by a median value of intercalated disc p‐MLKL. In δ‐sarcoglycan‐deficient (Sgcd−/−) mice, a model of DCM, total p‐MLKL and nuclear p‐MLKL levels were higher than in wild‐type mice. Conclusion The results suggest that increased localization of nuclear p‐MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.

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Section: Methodsmentioning

confidence: 99%

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy

et al. 2022

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“…A large number of cardiovascular parameters have been investigated for prognostic relevance with regards to AL amyloidosis and are summarized in Table 1 . 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 For those thought to have isolated renal amyloidosis, a PR interval over 160 msec and a QTc interval over 417 msec were both independently associated with all-cause mortality ( P values of .005 and .004, respectively) 49 and could therefore serve as a simple way to screen for patients who warrant a more intensive look at their cardiac function prior to initiation of therapy.…”

Section: Pretreatment Variablesmentioning

confidence: 99%

Light Chain Amyloidosis: Epidemiology, Staging, and Prognostication

Baker

2022

Methodist DeBakey Cardiovascular Journal

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Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually death. Out of the 60-plus heterogeneous amyloidogenic proteins that have been identified, approximately 30 are associated with human disease. The unifying feature of these proteins is their tendency to form beta-pleated sheets aligned in an antiparallel fashion. These sheets then form rigid, nonbranching fibrils that resist proteolysis, causing mechanical disruption and local oxidative stress in affected organs such as the heart, liver, kidneys, nervous system, and gastrointestinal tract. Here we review the epidemiology of light chain amyloidosis, the staging, and the concomitant prognostication that is critical in determining the appropriate treatment.

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Echocardiographic phenotype for refined risk stratification and treatment selection in light chain amyloidosis with heart failure

Yang

et al. 2023

J Cancer Res Clin Oncol

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Assessment of prognosis in immunoglobulin light chain amyloidosis patients with severe heart failure: a predictive value of right ventricular function

Cited by 6 publications

References 34 publications

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy

Light Chain Amyloidosis: Epidemiology, Staging, and Prognostication

Echocardiographic phenotype for refined risk stratification and treatment selection in light chain amyloidosis with heart failure

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