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Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China’s practical experience, the adoption of the “life support-based comprehensive treatment regimen” (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (β= 0.041, p= 0.01) and lower levels of serum creatinine (β= −0.068, p= 0.001) and serum uric acid (β= −0.047, p= 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p= 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.

The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood.

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ObjectiveElevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.MethodsThe study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell’s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson’s staining was analysed.ResultsDuring follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson’s trichrome staining in the myocardium (r=0.198, p<0.05).ConclusionNT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

Aims The predictive value of white blood cells in triple-vessel coronary artery disease (TVD) remains unclear. This study aimed to examine the relationship between WBC counts and long-term prognosis of TVD.Methods A total of 8943 consecutive patients with triple-vessel coronary artery disease were enrolled from April 2004 to February 2011. The primary endpoint was all-cause death and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs; a composite of all-cause death, myocardial infarction or stroke).Results After a median of 7.5 years of follow-up, 7678 patients were included in the final analysis. Multivariable analysis showed that the white blood cell count was an independent predictor of death (hazard ratio: 1.04, p< 0.01) and MACCE (hazard ratio: 1.03, p= 0.02). In white blood cell differential analysis, increased monocytes (hazard ratio: 1.93, p= 0.001) and eosinophils (hazard ratio: 1.82, p< 0.01), and decreased lymphocytes (hazard ratio: 0.89, p= 0.02) were independent predictors of death. Increased monocytes (hazard ratio: 1.62, P= 0.002) and eosinophils (hazard ratio: 1.55, p< 0.01) were independent predictors of MACCE. A combination of monocyte, lymphocyte and eosinophil counts with the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score improved the predictive value for mortality (area under the curve from 0.569 to 0.611; integrated discrimination improvement = 0.012; net reclassification improvement = 0.299) and improved slightly with SYNTAX score II (all p< 0.05).Conclusion Total and differential white blood cell counts are independent prognostic factors of long-term mortality and MACCE in triple-vessel coronary artery disease. A combination of monocyte, lymphocyte and eosinophil counts improved the predictive value for mortality with the SYNTAX score, and improved it slightly with SYNTAX score II.

Fulminant myocarditis (FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen (LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR (81 cases), which includes (i) mechanical life support (positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation), (ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and (iii) application of neuraminidase inhibitors, and those receiving conventional treatment (88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients (26.0%) died in hospitals. In-hospital mortality was 3.7% (3/81) for LSBCTR group and 46.6% (41/88) for traditional treatment (P<0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces in-hospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is needed. This study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.

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BackgroundBuilding effective and efficient stroke care systems is a key step in improving prevention, treatment and rehabilitation of stroke. The aim of this study was to evaluate the effectiveness of this stroke system of care on stroke management during a 2-year follow-up.MethodsA stroke system of care was developed from November 2009 to November 2010 in three townships in Ganyu County. Additional three matched townships were invited as controls. We first investigated the stroke incidence of these populations. Subsequently, this stroke system of care and an educational campaign in the three intervention townships were implemented and the effectiveness of the system was evaluated in the next 2 years.ResultsAt postintervention, more patients in the intervention communities obtained stroke knowledge and then the proportion of patients with stroke who were admitted within 3 hours of onset markedly increased in 2012 (12.0% vs 8.1%, p=0.044) and in 2013 (15.2% vs 9.7%, p=0.008) compared with those in the control communities. In the intervention communities, this proportion of patients with acute ischaemic stroke who received thrombolytic treatment was markedly raised from 2.1% in 2012 to 3.0% in 2013. More importantly, the fatality rate substantially decreased in 2013 in the intervention communities compared with that in the control communities (6.1% vs 9.7%, p=0.032). Similarly, the disability rate significantly decreased in 2013 (45.3% vs 51.5%, p=0.045).ConclusionsThe community-based stroke system of care was effective and practical for optimising stroke treatments and improving patient outcomes.Trial registration numberChiCTR-RCH-13003408, Post-results.

Titin-truncating variants (TTNtv) have been detected in a variety of cardiomyopathies and represent the most common cause of dilated cardiomyopathy. However, their significance in hypertrophic cardiomyopathy (HCM) is still unclear.

Purpose: Nonsense mutation readthrough is used as a gene-specific treatment in some genetic diseases. The response to readthrough treatment is determined by the readthrough efficiency of various nonsense mutations. In this manuscript, we aimed to explore the harmful effects of nonsense mutation suppression. Methods: HEK293 cells were transfected with two SCN5A (encode cardiac Na+ channel) nonsense mutations, p.R1623X and p.S1812X. We applied two readthrough-enhancing methods (either aminoglycosides or a siRNA-targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1)) to suppress these SCN5A nonsense mutations. When either of readthrough methods was used, the sodium channel proteins were examined by western blot and immunoblotting and recorded by whole cell patch-clamp to observe the functional characterization of the restored channels. Results: Upon readthrough treatment, the sodium currents were restored to the mutant cDNAs. These mutations reduced full-length sodium channel protein levels, and the sodium currents were reduced to 3% of wild-type. The mutant cDNA sodium currents were increased to 30% of wild-type, and the fulllength proteins also increased. However, the functional characterization of these channels from cDNAs carrying p.R1623X and p.S1812X exhibited abnormal biophysical properties, including a negative shift in steady-state sodium channel inactivation, a positive shift in sodium channel activation and robust late sodium currents. The ramp test showed prolonged QT intervals. Conclusion: These results demonstrated that readthrough-enhancing methods effectively suppressed nonsense mutations in SCN5A and restored the expression of full-length channels. However, the restored channels may increase the risk of arrhythmia.

Uric acid (UA) has been shown to be an independent risk factor for various cardiovascular diseases. However, its significance in hypertrophic cardiomyopathy (HCM) has not yet been evaluated. The objective of the present study was to evaluate clinical implications of plasma UA levels on the prognosis of patients with HCM.

Objective.To describe the clinical features and longterm outcomes of patients with Takayasu arteritis (TA) in China who experienced neurological symptoms.Methods.A retrospective study was undertaken of patients with TA who attended a single study center from 2002 to 2013, who also exhibited neurological symptoms (n = 274). Clinical and imaging features were analyzed, as well as longterm outcomes.Results.The mean age at disease onset was 28.2 ± 11.2 years, with a female-to-male ratio of 4.3:1. The most common neurological manifestation was dizziness (214, 78.1%), the most frequent type of TA was type III (112, 40.9%), and the most common affected artery was the left subclavian (147, 53.6%). Involvement of 3 or 4 branches of the aortic arch was observed in 28% of patients. Among 30 patients experiencing a stroke (10.9%), steno-occlusive lesions of the subclavian artery and common carotid artery were frequently observed in patients with ischemic stroke, while steno-occlusive lesions of the descending aorta, abdominal aorta, and/or renal arteries were more frequently observed with hemorrhagic stroke. Heart failure was the most common cardiovascular event in those who died (n = 6) and in surviving cohorts.Conclusion.Neurological features in patients with TA were variable, and correlated with the number of arteries and the site of artery involvement. Resistant hypertension was one of the most important risk factors for hemorrhagic stroke in patients with TA.

Intracranial aneurysms (IAs) are acquired lesions in the brain and can pose potential risk of rupture leading to subarachnoid hemorrhage. Endoglin plays a pivotal role in the vascular development and disease. Variations of endoglin gene have been shown to be risk factors for IAs in different racial population. In the present study, we investigated the correlation between polymorphism in the endoglin gene with IAs in Chinese Han population. The association of endoglin D366H variant (rs1800956) with sporadic IAs was tested in 313 patients with intracranial aneurysms, and 450 controls. The difference in allelic frequency between patients and control group was evaluated with the chi-square test. The frequency of the GG+CG genotype of rs1800956 was significantly higher in patients with IAs than in controls [22.0% vs 15.3%, P = .018; crude OR(odds ratio), 1.56; 95% CI(confidence interval), 1.08-2.26]. Multivariate analysis showed that rs1800956G conferred a risk to IAs [adjusted OR, 1.56 [95% CI, 1.08-2.26]; P=.019], independent of conventional factors, including age, sex, blood pressure, smoking, and alcohol consumption. The variant rs1800956 of endoglin might raise the risk of sporadic IAs among individuals of Chinese Han ethnicity.

A consistent association has been observed between leukocyte telomere length (LTL) and atherosclerosis, but the mechanisms underlying these associations are still not well understood. Premature biology aging was evident in atherosclerotic plaques, characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, and telomere attrition. As atherosclerosis is a state of chronic low-grade inflammation and increased oxidative stress, shortened LTL in patients with atherosclerosis might stem from the two sources, one is an accelerated rate in hematopoietic stem cells (HSCs) replication to replace leukocytes consumed in the inflammatory process, and another is the increase in the loss of telomere repeats per replication. Thus, diminished HSC reserves at birth and age-dependent telomere attrition afterward are mirrored in shortened LTL during the adulthood. In addition, the inter-individual variation of LTL in the general population can be partly explained by genetic factors regulating telomere maintenance and the rate of HSCs replication. Atherosclerosis is an aging-related disease, and practically all humans develop atherosclerosis if they live long enough. Here we overview the potential roles of LTL dynamics in the imbalance between injurious oxidative stress/inflammation and endothelial repair during the pathogenesis of age-related atherosclerosis, and discuss the possibility that preventing accelerated cellular senescence is a potential target in prevention of atherosclerosis.

Stroke system of care plays key roles both in providing effective therapies and in improving the overall outcome of patients with stroke. Our purpose was to develop and evaluate the system in Chinese rural areas.

Objective.To describe a large cohort of patients with Takayasu arteritis in China.Methods.We retrospectively analyzed 566 patients hospitalized in Fuwai Hospital between 2002 and 2013. Data collected were clinical characteristics, laboratory findings, angiographic features, treatment, and longterm outcome.Results.The female to male ratio was 3.8 to 1, and the mean age of onset was 28.9 ± 12.0 years. The most common inflammatory symptom, initial symptom, and coexisting disease were fever (52, 9.2%), dizziness (214, 37.8%), and hypertension (HTN; 392, 69.3%), respectively. Pulmonary artery, coronary artery involvement, and aortic regurgitation were found in 83 (14.7%), 66 (11.7%), and 181 (36.7%) patients, respectively. Elevation of the erythrocyte sedimentation rate was observed in 131 patients (23.1%). Treatment included drugs, interventional therapy, autologous blood vessel transplant, artificial blood vessel transplant, and aortic valve replacement. During a mean followup of 5.0 ± 0.2 years, 32 patients died, including 1 patient who died suddenly during coronary angiography. HTN, major complications, and a progressive disease course were significant prognostic markers.Conclusion.HTN, rather than fever, is the leading reason for patients with Takayasu arteritis to see a doctor in China. HTN, major complications, and a progressive disease course are statistically significant predictors of survival. Because of cardiovascular events associated with the disease, early diagnosis and treatment are urgent to improve prognosis.

Although mutations of several genes are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation between genotype and ventricular arrhythmia features remains unclear. This study was aimed to examine the possible association of the 9 known genes of ARVC with clinical and electrophysiological characteristics.

Two endophenotypes of arterial calcification, calcification on arterial wall and calcification in atherosclerotic plaques, are associated with different types of cardiovascular events. Mgp-deficient mice showed matrix Gla protein (MGP) is strongly associated with calcification on arterial wall without atherosclerotic plaques, and MGPvariants were not significantly associated with myocardial infarction. MGP may play different roles in the 2 endophenotypes.

Objective.We investigated the clinical characteristics, potential difficulties in diagnosis, and therapy for coronary artery involvement in patients with Takayasu arteritis (TA).Methods.Of 587 consecutive patients hospitalized with TA from 1998 to 2011, those found to have > 50% reduction of diameter of coronary artery by angiography were recruited. We defined the first finding of coronary involvement as baseline. The clinical features, laboratory data, coronary angiographic findings, treatment, and followup outcomes were summarized retrospectively.Results.A total of 45 (7.7%, 45/587) patients with coronary involvement were identified, including 40 with typical angina, and 15 with myocardial infarction. Some had complications such as peripheral vascular murmur, pulseless disease, and hypertension. The average age at onset of cardiac symptoms was 40.3 ± 12.8 years (range 15–64) and 36 were female. At admission, erythrocyte sedimentation rates were elevated in 27 patients (60%) and C-reactive protein levels in 23 (51.1%). The ostia (37.4%) and proximal segments (33.3%) of coronary artery were most frequently involved. The treatment was stent implantation in 10 patients and coronary artery bypass grafting in 13. One female patient suffered sudden death during the angiography. During a mean followup of 5.8 ± 4.5 years, 8 patients died.Conclusion.Coronary artery involvement in TA that leads to cardiovascular events, especially to cardiovascular death, is not rare. Early diagnosis and therapy should be emphasized.

It has long been known that depression is associated with hypertension but whether depression is a risk factor for hypertension incidence is still inconclusive.

Accumulating evidence suggests that telomere length is a maker for biological aging of the cardiovascular system. Whether stroke is associated with accelerated biological aging as measured by telomere length has not been conclusively demonstrated. Our aim was to determine whether mean leukocyte telomere length is a predictor for the development of stroke.

ANRILencodes a long antisense noncoding RNA in the INK4locus. Although ANRILhas been proven to be associated with coronary heart disease, its roles in stroke are inconsistent, and sparse data are available regarding hemorrhagic stroke.

OBJECTIVE: Tumor necrosis factor-α (TNF-α) is a multifunctional proinflammatory cytokine that influences the pathogenesis of Takayasu arteritis (TA). There is still no evidence of the relationship between TNF-α gene promoter polymorphisms and TA. We examined whether variations in the TNF-α promoter region may lead to TA susceptibility and disease progression. METHODS: Five TNF-α gene promoter polymorphisms (–238G/A, –308G/A, –857C/T, –863C/A, and –1031C/T) were analyzed in 110 Chinese Han patients with TA, with a control group of 362 unrelated healthy individuals. Genotypes of TNF-α gene promoter polymorphisms were identified by direct sequencing. TNF-α plasma concentrations were determined by ELISA. RESULTS: Our results indicated that the frequency of the –863A allele was significantly lower in the patients with TA than in the controls (18.2% vs 25.7%; p = 0.011), but the significance was lost after Bonferroni correction (pc= 0.055). The frequency of –863CA/AA genotypes was significantly lower in the patients with refractory TA than in those with the 863CC genotype (22.4% vs 44.2%; pc< 0.01). The frequency of the GGCCT haplotype was significantly higher in patients than in the controls, while the frequencies of GGCAT and GGCCC haplotypes were significantly lower in patients than in controls. The plasma TNF-α concentrations were significantly lower in the subjects carrying the –863A allele than in those without. Patients with active TA had a significant increase in plasma levels of TNF-α compared with remission patients and the control group. CONCLUSION: Polymorphisms of the TNF-α promoter are not associated with TA in the Chinese Han population. The A allele of the –863C/A polymorphism is associated with decreased TNF-α expression, which might affect medical treatment.

This study aimed to investigate whether plasma levels of HDL cholesterol (HDL-C) were associated with the risk of intracerebral hemorrhage (ICH). Plasma HDL-C was determined via enzymatic methods, and ICH was ascertained via medical history, physical examination, and brain imaging (computed tomography or magnetic resonance imaging). The multivariable logistic regression model was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of ICH according to levels of plasma cholesterol. A total of 170 patients with ICH were identified from 6,046 participants. After adjustment for conventional cardiovascular risk factors, the OR was 2.06 (95% CI, 1.25-3.12; P< 0.01) for participants in the first tertile of HDL-C levels (<1.38 mmol/l) and 1.13 (95% CI, 0.72-1.78; P= 0.59) for participants in the second tertile (1.38-1.64 mmol/l), compared with participants in the third tertile (∩≥1.65 mmol/l). Subgroup analysis indicated that the detrimental effects of HDL-C were more significant in men and lean participants than in their corresponding controls, independent of hypertension. The results presented herein indicate that low plasma HDL-C (<1.38 mmol/l) may be associated with risk of ICH.

This study aimed to investigate whether plasma levels of HDL cholesterol (HDL-C) were associated with the risk of intracerebral hemorrhage (ICH). Plasma HDL-C was determined via enzymatic methods, and ICH was ascertained via medical history, physical examination, and brain imaging (computed tomography or magnetic resonance imaging). The multivariable logistic regression model was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of ICH according to levels of plasma cholesterol. A total of 170 patients with ICH were identified from 6,046 participants. After adjustment for conventional cardiovascular risk factors, the OR was 2.06 (95% CI, 1.25-3.12; P < 0.01) for participants in the first tertile of HDL-C levels (<1.38 mmol/l) and 1.13 (95% CI, 0.72-1.78; P = 0.59) for participants in the second tertile (1.38-1.64 mmol/l), compared with participants in the third tertile (∩≥1.65 mmol/l). Subgroup analysis indicated that the detrimental effects of HDL-C were more significant in men and lean participants than in their corresponding controls, independent of hypertension. The results presented herein indicate that low plasma HDL-C (<1.38 mmol/l) may be associated with risk of ICH.

20-Hydroxyeicosatetraenoic acid has been shown to play an important role in cerebral vascular function. We hypothesized that polymorphisms in genes encoding 20-Hydroxyeicosatetraenoic acid synthesizing enzymes might confer susceptibility to stroke.