Assessment of Cardiac Function and Ventricular Mechanical Synchronization in Left Bundle Branch Area Pacing by Speckle Tracking and Three-Dimensional Echocardiography.

Real-time 3-dimensional echocardiography combined with speckle tracking was used in this study. A total of 90 patients with normal left ventricular ejection fraction were divided into 3 groups according to the pacing site: left bundle branch area pacing (LBBAP), right ventricular septal pacing (RVSP) or right ventricular apical pacing (RVAP). Procedure duration (90 ± 18 vs 61 ± 6.6 vs 58 ± 5.6 minutes, p = 0.015), Fluoroscopy duration (15.5 ± 5.4 vs 4.8 ± 2.2 vs 4 ± 1.9 minutes, p = 0.004), and ventricular capture threshold at implantation (0.8 ± 0.3 vs 0.6 ± 0.2 vs 0.6 ± 0.1 V, p = 0.002) were significantly increased in patients that received LBBAP compared with RVSP or RVAP. At 4 weeks of follow-up, brain natriuretic peptide levels were significantly lower (22 [12 to 59] vs 135 [86 to 231] vs 235 [147 to 428] pg/ml, p = 0.04), paced QRS duration was significantly shorter (115 ± 26 vs 134 ± 28 vs 157 ± 29 ms, p = 0.012), and global longitudinal strain (-19.4 ± 2.4 vs -19.3 ± 3.4 vs -17.3 ± 3.5%, p = 0.026) and systolic dyssynchrony index (2.5 ± 0.3 vs 5.9 ± 0.9 vs 7.7 ± 1.2, p = 0.001), longitudinal absolute maximum difference of time to peak strain (17 [6 to 68] vs 117 [71 to 173] vs 126 [79 to 178] ms, p <0.0001), and circumferential absolute maximum difference of time to peak strain (76 [32 to 129] vs 148 [117 to 208] vs 161 [118 to 266] ms, p = 0.005) were significantly lower in patients that received LBBAP compared with RVSP or RVAP. In conclusion, LBBAP can provide a more physiological ventricular activation pattern than RVSP or RVAP and results in good left ventricular electrical and mechanical synchronization.

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study.

BACKGROUND: There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia. OBJECTIVE: To define the characteristics of phenotypic and genetic HoFH probands from mainland China. METHODS: We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test. RESULTS: A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH. CONCLUSIONS: This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.

Change and impact of left ventricular global longitudinal strain during transcatheter aortic valve implantation.

BACKGROUND: Although transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for aortic stenosis, it still carries some risks, such as valve leaks, stroke, and even death. The left ventricular global longitudinal strain (LVGLS) measurement may be useful for the prediction of adverse events during this operation. AIM: To explore the change of LVGLS during TAVI procedure and the relationship between LVGLS and perioperative adverse events. METHODS: In this study, 61 patients who had undergone percutaneous transfemoral TAVI were evaluated by transthoracic echocardiography. Before surgery, data on left ventricular ejection fraction (LVEF) and LVGLS were collected separately following balloon expansion and stent implantation. Difference in values of LVGLS and LVEF during preoperative balloon expansion (pre-ex), preoperative stent implantation (pre-im) and balloon expansion-stent implantation (ex-im) were also examined. Adverse events were defined as perioperative death, cardiac rupture, heart arrest, moderate or severe perivalvular leakage, significant mitral regurgitation during TAVI, perioperative moderate or severe mitral regurgitation, perioperative left ventricular outflow tract obstruction, reoperation, and acute heart failure. RESULTS: The occurrence of perioperative adverse events was associated with differences in pre-ex LVGLS, but not with difference in pre-ex LVEF. There were significant differences between pre-LVGLS and ex-LVGLS, and between pre-LVGLS and im-LVGLS (P = 0.037 and P = 0.020, respectively). However, differences in LVEF were not significant (P = 0.358, P = 0.254); however differences in pre-ex LVGLS were associated with pre-LVGLS (P = 0.045). Compared to LVEF, LVGLS is more sensitive as a measure of left heart function during TAVI and the perioperative period. Moreover, the differences in LVGLS were associated with the occurrence of perioperative adverse events, and changes in LVGLS were apparent in patients with undesirable LVGLS before the surgery. Furthermore, LVGLS is useful to predict changes in cardiac function during TAVI. CONCLUSION: Greater attention should be paid to the patients who plan to undergo TAVI with normal LVEF but poor LVGLS.

[Echocardiographic manifestation and analysis of TGFBR1 gene variant in a Chinese patient with Loeys-Dietz syndrome].

OBJECTIVE: To explore the genetic basis for a patient with aortic root aneurysm and valve insufficiency. METHODS: The patient was subjected to whole exome sequencing (WES) with a focus on the analysis of genes related to aortic aneurysm and other genetic diseases involving the cardiovascular system. Suspected pathogenic site was validated by Sanger sequencing of the patient and his family members. RESULTS: WES has revealed a heterozygous c.830T>C variant (NM_001130916.3) in the patient, which was not detected among healthy members of his family. SIFT, PolyPhen2 and Mutation Taster predicted the variant to be disease causing, resulting in destruction of the structure and function of the TGFBR1 protein. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM1+PM2+PM6+PP3+PP4). CONCLUSION: The c.830T>C variant of the TGFBR1 gene probably underlay the disease in the proband. Above finding has enriched the spectrum of TGFBR1 gene variants in Chinese population.

Prognostic value of coronary flow velocity reserve in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Coronary flow velocity reserve (CFVR) can provide useful quantitative information on the functional status of coronary artery circulation, and an impaired CFVR (< 2.0) was associated with a significant increase in the occurrence of cardiac events. Coronary artery disease (CAD) is the leading cause of death in homozygous familial hypercholesterolemia (HoFH), but the relationship between impaired CFVR and outcome in HoFH has never been discussed before METHODS: To explore the long-term prognostic value of CFVR in patients with HoFH, 39 HoFH patients with CFVR data (mean age with 16.7 years) were enrolled from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. All patients were divided into impaired CFVR (CFVR < 2.0, n = 17) and preserved CFVR (CFVR≥2.0, n = 22) group. Follow-up was performed until a major adverse cardiac event (MACE) occurred or up to June 30, 2020 RESULTS: During a median follow-up of 89 months, 16 events were registered, 12 of which were occurred in the impaired CFVR group and four occurred in the preserved CFVR group. The event-free survival rate of impaired CFVR group was significantly lower than that in the preserved CFVR group (29.4% vs 81.8%, P < .001), and CFVR < 2.0 was independently associated with prognosis before and after adjustment for related risk factors (HR 5.197, 95% CI 1.669 to 16.178, P = .004 and HR 5.488, 95% CI 1.470 to 20.496, P = .011, respectively) CONCLUSIONS: an impaired CFVR predicts a worse outcome in HoFH. CFVR shows an independent value in the prediction of long-term outcome in HoFH.

Speckle-Tracking Echocardiography for Detecting Subclinical Left Ventricular Dysfunction in Patients With Familial Hypercholesterolemia.

Myocardial ischemia and left ventricular dysfunction have been documented in young adults with familial hypercholesterolemia. We investigated whether speckle-tracking echocardiography can be used to detect subclinically impaired global and regional myocardial function in patients with this lipid disorder. This single-center study included 47 patients with familial hypercholesterolemia and 37 healthy control subjects who underwent transthoracic Doppler echocardiography and speckle-tracking echocardiography from January 2003 through December 2016. Conventional echocardiographic and strain parameters in the 2 groups were analyzed and compared. Left ventricular dimensions were significantly larger at end-diastole (P=0.02) and end-systole (P=0.013), left ventricular walls were significantly thicker (P <0.0001), and the early transmitral/early diastolic mitral annular velocity ratio was significantly higher (P=0.006) in the patient group than in the control group. In the patient group, global longitudinal and circumferential strain values were significantly lower (P <0.0001) and global radial strain values significantly higher (P=0.006); all segmental longitudinal strain (P <0.04) and most segmental circumferential strain values (P ≤0.01) were significantly lower; and some segmental radial strains, especially at the apex, were significantly higher (P ≤0.04). However, average longitudinal, circumferential, and radial strains in the different segments of the 3 main coronary artery territories were significantly lower in the patient group (P <0.01). Global longitudinal strain (r=0.561; P=0.001) and global circumferential strain (r=0.565; P <0.0001) were inversely correlated with low-density-lipoprotein cholesterol levels. We conclude that speckle-tracking echocardiography can be used to detect subclinical global and regional systolic abnormalities in patients with familial hypercholesterolemia.

Supravalvular Aortic Stenosis and the Risk of Premature Death Among Patients With Homozygous Familial Hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL_C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate.

Features of Sitosterolemia in Children.

Sitosterolemia is a rare lipid metabolism disease with heterogeneous manifestations. Atherosclerosis can occur in children, and therefore, early detection, diagnosis, and treatment of this disease are important. We studied 18 pediatric patients with sitosterolemia who showed a significant increase in plasma lipid levels and analyzed their clinical, biochemical, and genetic characteristics. We recorded the initial serum lipid results and clinical manifestations of the patients. Lipid and plant sterol levels were measured after homozygous or compound heterozygous mutations of ABCG5 or ABCG8 were identified by genetic testing. Plasma plant sterol levels were analyzed by gas chromatography. Fourteen cases of sitosterolemia were examined by ultrasound and echocardiography. The initial total cholesterol and low-density lipoprotein levels of the children were significantly increased, but then markedly decreased after diet control or drug treatment, and even reached normal levels. Carotid atherosclerosis and aortic valve regurgitation were present in three of 14 patients. Serum lipid levels of children with sitosterolemia and xanthomas were notably higher than those without xanthomas. There were no significant differences in clinical manifestations between patients with different genotypes. In conclusion, sitosterolemia should be considered in children with hyperlipidemia who do not present with xanthomas, especially with a significant increase in total cholesterol and low-density lipoprotein levels. There does not appear to be a correlation between clinical phenotype and genotype.

Association between ideal cardiovascular health score trajectories and arterial stiffness: the Kailuan Study.

Some studies have shown that a higher ideal cardiovascular health score (CVHS) predicts a lower incidence of arterial stiffness. Few studies have used multiple measurements of CVHS to examine the impact of CVHS on arterial stiffness. The current study aimed to identify the long-term patterns in CVHS trajectory and to explore the association between CVHS trajectory and arterial stiffness. The study cohort consisted of 18,854 participants from the Kailuan Study who were followed up for five physical examinations over 8.10 years. Five discrete CVHS trajectories were identified among the participants: low-stable (8.10%), low-moderate (6.84%), moderate-low (23.46%), moderate-stable (39.83%), and elevated-stable (21.77%). After adjustment for confounding factors, generalized linear model analysis showed that CVHS trajectory group correlated negatively with brachial-ankle pulse wave velocity (baPWV). Compared with the low-stable group, the low-moderate group, moderate-low group, moderate-stable group, and elevated-stable group had B values of -41.81, -24.11, -86.79, and -169.54, respectively. We also used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for CVHS trajectory groups and arterial stiffness. In fully adjusted models, ORs were 0.76 (95% CI: 0.62-0.94) for the low-moderate group, 0.80 (95% CI: 0.67-0.97) for the moderate-low group, 0.51 (95% CI: 0.42-0.62) for the moderate-stable group, and 0.23 (95% CI: 0.18-0.29) for the elevated-stable group compared with the low-stable group. The results were consistent across a number of sensitivity analyses. In conclusion, the higher long-term attainment and the improvement of CVHS were negatively associated with baPWV and could reduce the risk of arterial stiffness. Our study emphasizes the importance of optimizing CVH throughout life to prevent the incidence of arterial stiffness.

Combined transthoracic echocardiography and contrast-enhanced ultrasonography to trace intravenous leiomyomatosis with intracardiac extension.

Intravenous leiomyomatosis (IVL) with intracardiac extension is a rare condition, which the benign tumor invades into the right heart through inferior vena cava. We described the findings of ultrasonography in eight patients with this disease. Transthoracic echocardiography (TTE) can reveal the intracardiac lesion burden and associated compromise. Contrast-enhanced ultrasonography (CEUS) can trace the origin of the lesion and extension. Therefore, combining TTE with CEUS is used to better characterize this complex lesion and plays a crucial role in guidance of surgical decision.

Effects of a protective agent on freeze-dried platelet-rich plasma.

: Freeze-drying is an effective means of storing platelets. In this study, we investigated the effects of a protective agent on freeze-dried platelet-rich plasma (FD-PRP) after a 12-week preservation period. Platelet structure was measured by transmission electron microscopy (TEM), and the expression levels of procaspase activating compound (PAC)-1 and CD62P were measured by flow cytometry. The levels of transforming growth factor-beta (TGF-ß), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) were determined by ELISA. The effect of FD-PRP on cell proliferation was measured by cell counting. TEM revealed that most platelets were intact, and their internal structure was evident. The expression levels of the platelet activation marker CD62P in FD-PRP and fresh PRP were 36.83% ±â€Š8.21 and 35.47% ±â€Š4.11, respectively, without a significant difference (P > 0.05). The expression levels of PAC-1 in FD-PRP and fresh PRP were 3.23% ±â€Š0.49 and 2.83% ±â€Š0.44, respectively, without a significant difference (P > 0.05). Upon activation of FD-PRP and fresh PRP by thrombin, the levels of TGF-ß, PDGF and VEGF were not significantly decreased in FD-PRP. Moreover, FD-PRP promoted cell proliferation in a manner similar to that of fresh PRP. The protective agent maintained the biological activity of FD-PRP after a 12-week preservation period.

Echocardiographic findings of cardiovascular involvement in Behçet's disease and post-operative complications after cardiac surgery.

OBJECTIVES: The aim of this study was to analyse the spectrum of echocardiographic findings in patients with cardiovascular involvement in Behçet's disease (BD) and followed up the post-operative complications. METHODS: We enrolled 26 BD patients who underwent first cardiac surgery in Anzhen Hospital, Beijing, China. Medical records and echocardiographic findings were retrospectively analysed. RESULTS: The 26 patients consisted of 4 women and 22 men. 22 (84.6%) of the patients were diagnosed with moderate/severe aortic regurgitation (AR). Some distinctive echocardiographic features with AR were observed, including prolapse of aortic cusps, vegetation-like mobile lesions, an echo-free space mimicking aortic root abscess and aortic aneurysm formation. 3 (11.5%) of the patients were diagnosed with isolated descending aortic aneurysm. 1(3.8%) of the patients was diagnosed with pulmonary artery aneurysm. BD was preoperatively diagnosed by clinicians in 20 patients. And 6 patients were diagnosed post-operatively by clinicians. In a total of 26 patients, post-operative complications occurred in 8 (30.7%) patients. The complications occurred in the 6 patients diagnosed post-operatively and 2 patients diagnosed pre-operatively. The post-operative complications of these patientsincluded aortic paravalvular leakage, coronary-graft anastmotic leakage and mitral paravalvular leakage. CONCLUSIONS: The most common echocardiographic feature of cardiovascular involvement in BD is severe aortic regurgitation with prolapse of aortic cusps, vegetation-like mobile lesions, an echo-free space mimicking aortic root abscess or aortic aneurysm formation. Accurate preoperative diagnosis of BD is beneficial to the choice of immunosuppressive therapy before and after surgery, which is likely to reduce postoperative complications especially for patients with severe lesions.

Identification of Novel Causal FBN1 Mutations in Pedigrees of Marfan Syndrome.

Marfan syndrome (MFS) is an autosomal dominant genetic disorder of the connective tissue, typically characteristic of cardiovascular manifestations, valve prolapse, left ventricle enlargement, and cardiac failure. Fibrillin-1 (FBN1) is the causative gene in the pathogenesis of MFS. Patients with different FBN1 mutations often present more considerable phenotypic variation. In the present study, three affected MFS pedigrees were collected for genetic analysis. Using next-generation sequencing (NGS) technologies, 3 novel frameshift pathogenic mutations which are cosegregated with affected subjects in 3 pedigrees were identified. These novel mutations provide important diagnostic and therapeutic insights for precision medicine in MFS, especially regarding the lethal cardiovascular events.

Characteristic Echocardiographic Manifestations of Behçet's Disease.

The objective of this study was to determine the characteristic echocardiographic manifestations of Behçet's disease. Ninety-seven Behçet's patients admitted to our hospital from January 2002 to December 2016 were retrospectively analyzed. There were 63 patients (64.9%) with cardiac involvement; these included 47 men (74.6%) and 16 women (25.4%). Of these 63 patients, most (74.6%) exhibited valvular lesions, especially aortic regurgitation. The primary characteristic manifestations of valves were cusp prolapse with aneurysmal changes, vegetation-like lesions and echo-free spaces within the annulus. Second (30.0%) were aortic lesions, including aortic dilation or aneurysm formation, aortic pseudoaneurysm and coronary sinus aneurysm. Other manifestations, such as cardiac thrombosis, coronary arterial pseudoaneurysm, pulmonary aneurysm and pericardial effusion, were rare. Cardiac involvement is not uncommon in Behçet's patients, especially in males, and it is characterized by valvular disease, especially aortic regurgitation. The diagnosis of Behçet's disease should be considered when evaluating patients with these characteristic echocardiographic manifestations.

A giant pseudoaneurysm of coronary artery in a young patient with Behçet's disease.

As an uncommon multisystem inflammatory disease, Behçet's syndrome is characterized by mouth and genital ulcers, skin lesions, and eye inflammation, which may also affect joints, blood vessels, central nervous system, or digestive tract. However, the inflammation of coronary artery is relatively rare. We thereby reported a young male of Behçet's syndrome presenting left anterior descending artery pseudoaneurysm with myocardial infarction. Surgical resection was performed with coronary bypass grafting.

Right coronary artery coronary sinus fistula with coronary sinus ostium stenosis.

Coronary artery fistula (CAF) is a rare anomaly of the coronary artery. The draining site of a right coronary artery (RCA) fistula may usually be the right ventricle, right atrium, or pulmonary artery. Here, we present a patient with right coronary artery to coronary sinus fistula (RCACSF) complicated by aneurysmal dilatation of the coronary sinus (CS) and stenosis of CS ostium.

Myocardial layer-specific analysis in patients with heterozygous familial hypercholesterolemia using speckle tracking echocardiography.

OBJECTIVE: Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism, causing premature coronary heart disease (CHD) due to accelerated atherosclerosis from birth, and the study of left ventricular (LV) function of this disease is seldom. The purpose of this study was to explore the value of layer-specific strain on assessing the early damage of LV function in asymptomatic and left ventricular ejection fraction (LVEF) well-preserved patients with heterozygous FH (HeFH). METHODS: A total of 49 patients aged 38.7±8.7 diagnosed with heterozygous familial hypercholesterolemia and who had undergone transthoracic echocardiography from 2010 to 2016 were included in this study. A total 32 healthy volunteers aged 35.6±10.3 were included as control group. Longitudinal and circumferential strains of the endocardium, myocardium, and epicardium (LSendo, LSmyo, and LSepi and CSendo, CSmyo, and CSepi) were obtained by a software enabling the analysis of strains in three myocardial layers. RESULTS: In longitudinal strain (LS), the LS of endocardium (LSendo) and the LS of myocardium (LSmyo) are significantly reduced in patients with HeFH (P<.001 in both). In circumferential strain (CS), only the CS of endocardium (CSendo) is significantly reduced (P<.001). The degree of reduction in strain is positively correlated with the TC and LDLC. CONCLUSIONS: Layer-specific evaluation of the left ventricle has great value in evaluating early impairment of LV in patients with FH. And this relatively novel technique may made it possible to help us understand the process of LV impairment in patients with FH better, thus preventing further damage.

Layer-specific myocardial strain analysis: investigation of regional deformation in a rabbit model of diabetes mellitus during different stages.

AIM: The purpose of the present study was to determine the characteristics of myocardial damage at different stages of diabetes mellitus (DM) using layer-specific myocardial strain. MATERIAL AND METHODS: Thirty six New Zealand white rabbits were randomly divided into either the control group (n =18) or the DM group (induced with alloxan) (n=18). For the myocardial deformation studies echocardiography and layer-specific strain were performed at baseline and after 3, 6, and 9 months in all of the rabbits. Three-layer longitudinal strain (LS) was calculated in the apical 4-chamber view, and three-layer circumferential strain (CS) in the short-axis view at the level of mitral valve. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium and epicardium. For histomorphological study of the heart structure, the rabbits were sacrificed at 3, 6 and 9 months. Routine hematoxylin and eosin staining was performed. RESULTS: The highest absolute values of left ventricular longitudinal strain (LS) and circumferential strain (CS) were registered in the endocardium and the lowest in the epicardium in both groups. At 3 months, there was no significant difference in three-layer LS and CS (p>0.05), but at 6 months the LS of endocardium (LSendo) and CS of endocardium (CSendo) were lower in the DM group compared with the control group; at 9 months, the rest of the parameters were also decreased (p<0.05). Moreover, in ROC analysis at 6 months LSendo yielded better sensitivity and specificity in the detection of diabetic cardiomyopathy (AUC of LSendo was 0.897 and AUC of CSendo was 0.617). With the progression of untreated diabetes, the histopathological abnormalities intensified gradually beginning at 6 months. CONCLUSION: The progressive impairments in LV myocardial deformation and structure occurs early in diabetic rabbits, the myocardial damage may be nontransmural, and endocardial function is more susceptible to be affected by DM. Layer-specific myocardial strain echocardiography may identify subtle myocardial dysfunction in the early stages of DM.