Background Cardiac conduction disease (CCD) is a common cardiovascular disease which can lead to life‐threatening conditions. The importance of heredity in CCD has been realized in recent years. Several causal genes have been found to be implicated in CCD such as SCN5A, TRPM4, SCN1B, TNNI3K, LMNA, and NKX2.5. To date, only four genetic mutations in TNNI3K have been identified related to CCD. Methods Whole‐exome sequencing (WES) was carried out in order to identify the underlying disease‐causing mutation in a Chinese family with CCD. The potential mutations were confirmed by Sanger sequencing. Real‐time qPCR was used to detect the level of TNNI3K mRNA expression. Results A nonsense mutation in TNNI3K (NM_015978.2: g.170891C > T, c.1441C > T) was identified in this family and validated by Sanger sequencing. Real‐time qPCR confirmed that the level of TNNI3K mRNA expression was decreased compared with the controls. Conclusions This study found the first nonsense TNNI3K mutation associated with CCD in a Chinese family. TNNI3K harboring the mutation (c.1441C > T) implicated a loss‐of‐function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum of TNNI3K mutations, casting a new light upon the genotype‐phenotype correlations between TNNI3K mutations and CCD and indicating the importance of TNNI3K screening in CCD patients.

Background Cardiac conduction disease(CCD) and dilated cardiomyopathy(DCM) are two common cardiovascular diseases which can lead to life-threatening conditions. The importance of heredity in these two diseases has been realized in recent years. Several casual genes have been found to be implicated in CCD and DCM such as LMNA,SCN5A,TTN,TNNI3K and so on. Rare genetic mutations in TNNI3K have been identified to be in connection with CCD and DCM.Methods Next generation sequencing(NGS) was carried out in order to identify the underlying disease-causing mutation in a Chinese family with CCD and DCM. The mutations were validated by Sanger sequencing.Results A nonsense mutation in TNNI3K(NM_015978.2: g.170891C>T,c.1441C>T) was identified in this family and validated by Sanger sequencing.Conclusions This study described a Chinese family with CCD and DCM caused by a nonsense TNNI3K mutation.TNNI3K harboring the mutation(c.1441C>T) possibly implicated a loss-of-function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum of TNNI3K mutations, casting a new light upon the genotype-phenotype correlations between TNNI3K mutations and cardiovascular diseases.

Background and Aims: Patients with light-chain cardiac amyloidosis (AL-CA) are characterized by high levels of serum carbohydrate antigen 125 (CA 125). However, studies have not explored the correlation between CA 125 and AL-CA. The aim of this study was to explore the clinical implications of an increase in CA 125 in patients with AL-CA.Methods and Results: A total of 95 patients diagnosed with AL-CA at the Second Xiangya Hospital were enrolled in this study. Out of the 95 patients with AL-CA, 57 (60%) patients had elevated serum CA 125 levels. The mean age was 59.7 ± 10.0 years with 44 (77.2%) men in the high serum CA 125 group, and 61.8 ± 9.6 years with 28 (73.7%) men in the normal group. Patients with high CA 125 showed higher rates of polyserositis (79.3% vs. 60.5%, p = 0.03), higher levels of hemoglobin (117.4 ± 21.9 g/L vs. 106.08 ± 25.1 g/L, p = 0.03), serum potassium (4.11 ± 0.47 mmol/L vs. 3.97 ± 0.40 mmol/L, p = 0.049), low-density lipoprotein-cholesterol (3.0 ± 1.6 mmol/L vs. 2.3 ± 1.10 mmol/L, p = 0.01), and cardiac troponin T (96.0 pg/mL vs. 91.9 pg/mL, p = 0.005). The median overall survival times for patients with high or normal serum CA 125 were 5 and 25 months, respectively (p = 0.045). Multivariate Cox hazard analysis showed that treatment without chemotherapy (HR 1.694, 95% CI 1.121–2.562, p = 0.012) and CA 125 (HR 1.002, 95% CI 1.000–1.004, p = 0.020) was correlated with high all-cause mortality. The time-dependent receiver operating characteristic (t-ROC) curve showed that the prediction accuracy of CA 125 was not inferior to that of cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and lactate dehydrogenase (LDH) based on the area under the curve.Conclusions: CA 125 is a novel prognostic predictor. High serum CA 125 values are correlated with low overall survival, and the accuracy of predicting prognosis is similar to that of traditional biomarkers in AL-CA.

Aims: The level of serum carbohydrate antigen 125 (CA 125) elevated is a common finding in patients with cardiac amyloidosis in clinical practice. It is unclear whether CA 125 is correlated with cardiac amyloidosis. The aim of this study was to systematically evaluate the clinical implications of CA 125 elevation in patients with cardiac amyloidosis.Methods and Results: We enrolled 101 patients diagnosed with cardiac amyloidosis at the Second Xiangya Hospital, 41 patients with acute decompensated heart failure (AHF) and 39 patients with multiple myeloma (MM) who were confirmed to have no cardiac amyloidosis served as control group, respectively. In 101 patients with cardiac amyloidosis, 58 (57%) patients had elevated serum CA 125 levels, which the mean age was 61.2 ± 11.4 years. Patients with high CA 125 were more likely to present with polyserositis ( 79.3% vs 60.5%, p = 0.03) , higher levels of hemoglobin (117.22 ± 21.87 g/L vs. 106.07 ± 25.15 g/L, p = 0.01), serum potassium (4.17 ± 0.49 mmol/L vs. 3.98 ± 0.41 mmol/L, p = 0.05), low density lipoprotein-cholesterol (2.98 ± 1.65 mmol/L vs. 2.22 ± 1.10 mmol/L, p = 0.01), and cardiac troponin T (115 pg/mL vs. 59.52 pg/mL, p = 0.005) . The serum CA 125 levels were significantly higher in cardiac amyloidosis than AHF and MM. The median overall survival for patients with elevated and normal serum CA125 were 5 and 20 months, respectively (p = 0.012). According to multivariate Cox hazard analysis, CA 125 (HR 1.002, 95%CI 1.000-1.004, p = 0.020) contributed to all-cause mortality. The time-dependent receiver operating characteristic was used to reflect the accuracy of different biomarkers in predicting overall survival at various time points by the area under the curve (AUC). CA 125 has no worse prediction accuracy than cardiac troponin T, NT-proBNP and LDH according to the AUC.Conclusions: The prevalence of elevated serum CA 125 levels is more than 50% in patients with cardiac amyloidosis. As an independent prognostic predictor, highly serum CA 125 values indicated the lower overall survival and the accuracy of predicting prognosis was not inferior to the other biomarkers.

We report a case with left ventricular pseudo-aneurysm and ventricular septal perforation after acute myocardial infarction. A 77-year-old man was admitted because of repeated chest distress and chest pain for 1 week, which was diagnosed by an electrocardiogram with acute anteroseptal ST-segment elevation myocardial infarction and troponin T elevation. The transthoracic echocardiography and cardiac magnetic resonance showed the left ventricular apical pseudo-aneurysm and lower segment of ventricular septal perforation, and confirmed by left ventriculography. Surgical treatment was performed, with operation procedure successfully. In this article, we report a rare case in clinical and review the literatures of left ventricular pseudo-aneurysm.