Background ST-segment elevation myocardial infarction (STEMI) is a fatal cardiovascular emergency requiring rapid reperfusion treatment. During the coronavirus disease-2019 (COVID-19) pandemic, medical professionals need to strike a balance between providing timely treatment for STEMI patients and implementing infection control procedures to prevent nosocomial spread of COVID-19 among health care workers and other vulnerable cardiovascular patients. Objectives This study evaluates the impact of the COVID-19 outbreak and China Chest Pain Center’s modified STEMI protocol on the treatment and prognosis of STEMI patients in China. Methods Based on the data of 28,189 STEMI patients admitted to 1,372 Chest Pain Centers in China between December 27, 2019 and February 20, 2020, the study analyzed how the COVID-19 outbreak and China Chest Pain Center’s modified STEMI protocol influenced the number of admitted STEMI cases, reperfusion strategy, key treatment time points, and in-hospital mortality and heart failure for STEMI patients. Results The COVID-19 outbreak reduced the number of STEMI cases reported to China Chest Pain Centers. Consistent with China Chest Pain Center’s modified STEMI protocol, the percentage of patients undergoing primary percutaneous coronary intervention declined while the percentage of patients undergoing thrombolysis increased. With an average delay of approximately 20 min for reperfusion therapy, the rate of in-hospital mortality and in-hospital heart failure increased during the outbreak, but the rate of in-hospital hemorrhage remained stable. Conclusions There were reductions in STEMI patients’ access to care, delays in treatment timelines, changes in reperfusion strategies, and an increase of in-hospital mortality and heart failure during the COVID-19 pandemic in China.

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia worldwide. Here, we investigate the molecular and cellular mechanisms of lone AF-linked germline mutations in the connexin40 (Cx40) gene, GJA5. The entire coding region of GJA5 was sequenced in 68 unrelated patients with lone AF. A novel germline heterozygous missense mutation in Cx40 (p.I75F) was identified in one index patient. The mutation was also present in the proband's father with lone AF but was not found in the unaffected family members who were examined and 200 unrelated healthy control individuals. Electrophysiological studies revealed no electrical coupling of the cell pairs expressing the mutant alone and a significant reduction in gap junction coupling conductance when the mutant was coexpressed with wild-type (wt) Cx40 or Cx43. Interestingly, another lone AF-linked Cx40 mutant p.L229M did not show any apparent coupling defect when expressed alone or together with wt Cx40 but specifically reduced the gap junction coupling when coexpressed with wt Cx43. This study is the first to demonstrate that the germline familial mutations in Cx40 impair the gap junctions through different mechanisms, which may predispose the mutant carriers to AF.

Background: Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality of acute coronary syndrome (ACS); however, the associations of sub-daily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated. Methods: We conducted a time-stratified case-crossover study among 1,292,880 ACS patients from 2,239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM 2.5 ), coarse particulate matter (PM 2.5-10 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), carbon monoxide (CO), and ozone (O 3 ) were collected. Hourly onset data of ACS and its subtypes, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, were also obtained. Conditional logistic regressions combined with polynomial distributed lag models were applied. Results: Acute exposures to PM 2.5 , NO 2 , SO 2 , and CO were each associated with the onset of ACS and its subtype. These associations were strongest in the concurrent hour of exposure and were attenuated thereafter, with the weakest effects observed after 15-29 hours. There were no apparent thresholds in the concentration-response curves. An interquartile range increase in concentrations of PM 2.5 (36.0 μg/m 3 ), NO 2 (29.0 μg/m 3 ), SO 2 (9.0 μg/m 3 ), and CO (0.6 mg/m 3 ) over the 0-24 hours preceding onset was significantly associated with 1.32%, 3.89%, 0.67%, and 1.55% higher risks of ACS onset, respectively. For a given pollutant, the associations were comparable in magnitude across different subtypes of ACS. Generally, NO 2 showed the strongest associations with all three subtypes, followed by PM 2.5 , CO, and SO 2 . Greater magnitude of associations was observed among patients older than 65, without a history of smoking or chronic cardiorespiratory diseases, and in the cold season. Null associations of exposure to either PM 2.5-10 or O 3 with ACS onset were observed. Conclusions: The results suggest that transient exposure to the air pollutants of PM 2.5 , NO 2 , SO 2 , CO, but not PM 2.5-10 or O 3 , may trigger the onset of ACS, even at concentrations below the World Health Organization air-quality guidelines.

The findings expand the spectrum of mutations in connexin40 linked to AF and provide new insight into the molecular aetiology involved in the pathogenesis of AF.

The cardiac transcription factor GATA4 is essential for cardiac development, and mutations in this gene have been implicated in a wide variety of congenital heart diseases in both animal models and humans. However, whether mutated GATA4 predisposes to dilated cardiomyopathy (DCM) remains unknown. In this study, the whole coding region and splice junction sites of the GATA4 gene was sequenced in 110 unrelated patients with idiopathic DCM. The available relatives of the index patient harboring an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped. The functional effect of the mutant GATA4 was characterized in contrast to its wild-type counterpart using a luciferase reporter assay system. As a result, a novel heterozygous GATA4 mutation, p.C271S, was identified in a family with DCM inherited as an autosomal dominant trait, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 control chromosomes and the altered amino acid was completely conserved evolutionarily among species. Functional analysis demonstrated that the GATA4 mutant was associated with significantly decreased transcriptional activity and remarkably reduced synergistic activation between GATA4 and NKX2-5, another transcription factor crucial for cardiogenesis. The findings provide novel insight into the molecular mechanisms involved in the pathogenesis of DCM, suggesting the potential implications in the prenatal diagnosis and gene-specific treatment for this common form of myocardial disorder.

Abstract. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantial morbidity and mortality. Genetic variants play important roles in the pathogenesis of AF. However, AF is a genetically heterogeneous disorder, and the genetic determinants in most patients with AF remain to be identified. In this study, the entire coding region of the connexin40 gene, encoding the cardiac gap junction membrane channel protein ·5, was sequenced in 126 unrelated probands with familial AF. A novel heterozygous mutation, c.145C>T, in connexin40, was identified in a proband. The mutation was predicted to introduce a premature stop codon at amino acid position 49 (p.Q49X). This nonsense mutation was present in all the living relatives of the mutation carrier, co-segregating with AF in the family with a penetrance of 100%. However, it was absent in 200 ethnically matched unrelated control individuals. The findings suggest a pathogenic link between the compromised connexin40 function and familial AF, hence providing new insight into the molecular mechanisms involved in AF.

Dilated cardiomyopathy (DCM) is the most prevalent type of primary myocardial disease, which is the third most common cause of heart failure and the most frequent reason for heart transplantation. Aggregating evidence demonstrates that genetic risk factors are involved in the pathogenesis of idiopathic DCM. Nevertheless, DCM is of remarkable genetic heterogeneity and the genetic defects underpinning DCM in an overwhelming majority of patients remain unknown. In the present study, the whole coding exons and splice junction sites of the NKX2-5 gene, which encodes a homeodomain transcription factor crucial for cardiac development and structural remodeling, were sequenced in 130 unrelated patients with idiopathic DCM. The available relatives of the index patient harboring an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped for the NKX2-5 gene. The functional effect of the mutant NKX2-5 was characterized in contrast to its wild-type counterpart using a dual-luciferase reporter assay system. As a result, a novel heterozygous NKX2-5 mutation, p.S146W, was identified in a family with DCM inherited as an autosomal dominant trait, which co-segregated with DCM in the family with complete penetrance. Notably, the mutation carriers also had arrhythmias, such as paroxysmal atrial fibrillation and atrioventricular block. The missense mutation was absent in 400 reference chromosomes and the altered amino acid was completely conserved evolutionarily among species. Functional analysis revealed that the NKX2-5 mutant was associated with a significantly reduced transcriptional activity. The findings expand the mutational spectrum of NKX2-5 linked to DCM and provide novel insight into the molecular mechanisms underlying DCM, contributing to the antenatal prophylaxis and allele-specific management of DCM.

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