Left atrial remodeling and the prognostic value of feature tracking derived left atrial strain in patients with light-chain amyloidosis: a cardiovascular magnetic resonance study.

Systemic light-chain (AL) amyloidosis is characterized by the aggregation of misfolded immunoglobulin light chain, predominantly infiltrating in the heart, including left atrium (LA). LA remodeling, such as increased interatrial septal thickness and enlarged size, has been observed. However, LA strain assessed by cardiac magnetic resonance feature tracking (CMR-FT) and its prognostic role remains to be further determined. Using CMR, the current study sought to investigate the characteristic of LA remodeling and the prognostic value of LA strain in patients with AL. Eighty-seven consecutive patients who underwent CMR with histologically confirmed systemic light-chain amyloidosis were retrospectively enrolled. LA strain parameters were analyzed based on CMR-FT algorithm. Amyloid infiltration and burden loads were assessed with CMR late gadolinium enhancement (LGE) and extracellular volume (ECV). Patients were categorized according to the extent of amyloid infiltration in cardiac myocardium. The primary endpoint was defined as all-cause mortality. The prognosis value of LA strain indices was evaluated using Cox proportional hazards regression and Kaplan-Meier curves. Interatrial septal thickness (3 [2-5] vs. 4 [3-5] mm, p = 0.007) and indexed LA volume (34.6 [26.9-44.6] vs. 50.5 [36.1-58.5] ml/m2, p = 0.001) were significantly higher in patients with atrial involvement (LA-LGE). Compared with patients with low amyloid burden loads (ECV group I), those at moderate and high (ECV group II and III) show progressive impairment in LA reservoir, conduit, and booster strains and strain rates. A total of 44 patients died during a median follow-up of 12 months. In multivariate analysis, LA reservoir strain, New York Heart Association (NYHA), and ECV remained independently associated with survival. On Kaplan-Meier analyses, low LA reservoir strain (< 8.6%) increased the risk of mortality. In moderate amyloid burden loads patients, low LA reservoir strain provides additive prognosis value. Progress left atrial remodeling and dysfunction are common findings in AL cardiac amyloidosis. The CMR-FT-derived LA reservoir strain provides independent and additive prognostic value for all-cause mortality in patients with AL cardiac amyloidosis.

Assessing mental stress on myocardial perfusion and myocardial blood flow in women without obstructive coronary disease: protocol for a mechanistic clinical trial.

INTRODUCTION: Two-thirds of women with symptoms of angina have 'angina with no obstructive coronary artery disease' (ANOCA). Growing evidence supports the use of coronary artery function testing for the diagnosis of ANOCA. Research into the prevalence of mental stress-induced myocardial ischaemia (MSIMI) among women with ANOCA is lacking. MSIMI is common in clinically stable patients with coronary artery disease. It is not associated coronary stenosis but is a prognostic risk factor. Here, we describe the rationale and protocol for a mechanistic clinical trial to test the following hypotheses: (1) that MSIMI is more common in women with ANOCA women than in age-matched and sex-matched controls, and (2) MSIMI is associated with mental stress-induced myocardial blood flow (MBF) change but not with adenosine vasodilator stress-induced MBF change. METHODS AND ANALYSIS: This is a mechanistic clinical trial. 84 women with confirmed ANOCA and 42 aged-matched healthy women (neither angina symptoms nor coronary stenosis) are to be recruited for mental and adenosine vasodilator stress tests. Positron emission tomography CT with ammonia N-13 will be used to evaluate the myocardial perfusion and MBF changes between stress and rest. MSIMI is defined as a summed difference score (SDS) of ≥3 and adenosine stress-induced myocardial ischaemia is defined as an SDS of ≥4. Other assessments include Reactive Hyperemia Index for microvascular endothelial function, peripheral arterial tonometry or digital vasomotor response, and a series of blood and psychometric tests. ETHICS AND DISSEMINATION: This mechanistic clinical trial was approved by the Ethics Committee of Guangdong Provincial People's Hospital. Findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03982901; Pre-results.

Transthoracic echocardiography features of adult-type anomalous left coronary artery from the pulmonary artery before and after surgery: highlights from observational study in a single center of China.

To review the imaging characteristics of adult-type anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and evaluate the post-operative echocardiographic features. The transthoracic echocardiography (TTE) records and invasive coronary angiography (ICA), coronary computed tomography angiography (CTA) or operative findings of thirty adult patients with final diagnosis of ALCAPA were reviewed at our center. The diagnostic reliability of TTE was determined by comparing its results with that of ICA/CTA, and the echocardiographic features of the patients during early visit and post-operative follow-up were summarized. The coincidence rate of TTE and ICA/CTA diagnosing ALCAPA was 96.3% (26/27), and one case was misdiagnosed as coronary artery fistula. All patients showed abnormal left coronary ostium arising from the pulmonary trunk with retrograde coronary artery flow, 20 patients had enlarged right coronary artery (RCA), and 20 showed abundant inter-coronary septal coronary collaterals. Left ventricle (LV) abnormalities such as wall thinning, abnormal wall motion, papillary muscle fibrosis, mitral valve (MV) prolapse and moderate-severe mitral regurgitation (MR) were respectively observed in 4, 7, 10, 8 and 10 patients. Three patients showed ventricular septal defect, patent foramen ovale and tetralogy of Fallot respectively. Post-operative data was available for 12 patients, and showed that the diameter of RCA, size of left atrium (LA) and LV were decreased after surgery compared to the respective pre-operative values. Furthermore, inter-coronary septal coronary collaterals lessened in 8 of these patients. Although 6 patients showed residual mild MR, moderate or severe MR was not observed, and the ejection fraction (EF) also showed no obvious changes before and after surgery. TTE is a non-invasive diagnostic tool for adult-type ALCAPA, and can indicate abnormal coronary origin, collateral arteries and other associated malformations. Some of the structural and hemodynamic parameters of adult-type ALCAPA were improved after surgery.

Compound and heterozygous mutations of DSG2 identified by Whole Exome Sequencing in arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular tachycardia.

BACKGROUNDS: This study was designed to identify the pathogenic mutations in two Chinese families of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) using the Whole Exome Sequencing (WES). METHODS AND RESULTS: The proband 1 (Family 1, II:1) and proband 2 (Family 2, II:1) underwent the WES of DNA from peripheral blood. The genes susceptible to arrhythmias and cardiomyopathies were analyzed and both the probands carried the same exonic mutation of DSG2 p.F531C (NM_001943, exon 11: c.T1592G). The proband 1 also carried the splicing mutation of DSG2 (NM_001943: exon 4:c.217-1G>T), and proband 2 carried the intronic mutation of DSG2 (NM_001943: exon 6: c.524-3C>G) that potentially influenced the splicing function predicted by Human Splicing Finder. The compound heterozygous mutations of the two probands inherited from their paternal and maternal side, respectively. The carriers with DSG2 p.F531C showed early abnormal electrocardiograms, characterized as the subclinical phenotype of ARVC/D. CONCLUSIONS: The DSG2 p.F531C was the main reason for ARVC/D. More severe phenotypes of ARVC/D occurred when coexisting with 217-1G>T or 524-3C>G mutation that potentially affecting the splicing function, as a compound heterozygous recessive inheritance.

Case report of familial sudden cardiac death caused by a DSG2 p.F531C mutation as genetic background when carrying with heterozygous KCNE5 p.D92E/E93X mutation.

BACKGROUND: Sudden cardiac death (SCD) induced by malignant ventricular tachycardia (MVT) among young adults with right ventricular cardiomyopathy/dysplasia (ARVC/D) is a devastating event. Parts of ARVC/D patients have a mutation in genes encoding components of cardiac desmosomes, such as desmoglein-2 (DSG2), plakophilin-2 and desmoplakin. CASE PRESENTATION: Here we report a potentially pathogenic mutation in the DSG2 gene, which was identified in a family with ARVC/D using Whole Exome Sequencing (WES) and Sanger Sequencing. In all, Patient III:1 with ARVC/D carried the compound heterozygous mutations of DSG2 p.F531C and KCNE5 p.D92E/E93X, which were both inherited from her mother (II:2), who died of SCD. Carriers of DSG2p.F531C showed various phenotypes, such as ARVC/D, SCD, MVT and dilated cardiomyopathy. For III:1, there were significant low-voltage regions in the inferior-apical, inferior-lateral wall of the right ventricular epicardium and outflow tracts of the right ventricle. Under the guidance of a three-dimensional mapping system, MVT was successfully ablated with an epicardial-endocardial approach targeting for late, double or fragmental potentials after implantable cardioverter-defibrillator (ICD) electrical storms. No VT recurrence was observed during the one year of follow-up. CONCLUSIONS: When coexisting with heterozygous KCNE5 p.D92E/E93X, heterozygous DSG2 p.F531C as a genetic background was found to predispose to ARVC/D, SCD and MVT, which were successfully ablated using an epicardial-endocardial approach.

Activation of miR-34a-5p/Sirt1/p66shc pathway contributes to doxorubicin-induced cardiotoxicity.

The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells. MiR-34a-5p could augment Bax expression, but inhibited Bcl-2 expression, along with the increases of the activated caspase-3 and mitochondrial potentials in H9C2 cells. MiR-34a-5p was verified to modulate Sirt1 expression post-transcriptionally. In parallel to Sirt1 siRNA, miR-34a-5p could enhance p66shc expression, accompanied by increases of Bax and the activated caspase-3 and a decrease of Bcl-2 in H9c2 cells. Moreover, enforced expression of Sirt1 alleviated Dox-induced apoptosis of H9c2 cells, with suppressing levels of p66shc, Bax, the activated caspase-3 and miR-34a-5p, and enhancing Bcl-2 expression. Therefore, miR-34a-5p enhances cardiomyocyte apoptosis by targeting Sirt1, activation of miR-34a-5p/Sirt1/p66shc pathway contributes to Dox-induced cardiotoxicity, and blockage of this pathway represents a potential cardioprotective effect against anthracyclines.

Myocardial Strain Is Associated with Adverse Clinical Cardiac Events in Patients Treated with Anthracyclines.

BACKGROUND: Anthracycline-induced symptomatic heart failure is often irreversible, underlining the usefulness of pretreatment risk assessment. Global longitudinal strain (GLS) before or after chemotherapy is associated with a later decrease in left ventricular ejection fraction (LVEF); however, whether prechemotherapy GLS is associated with symptomatic heart failure and cardiac death in patients treated with anthracyclines is unknown. METHODS: Patients with hematologic cancers treated with anthracyclines who underwent prechemotherapy echocardiography between November 2006 and June 2011 were retrospectively recruited. Basic demographic data, end-diastolic and end-systolic left ventricular volumes, LVEF, and GLS were measured. Clinical cardiac events (CEs) were defined as cardiac death or symptomatic heart failure. The association of prechemotherapy parameters with CEs was analyzed using proportional hazard analysis. RESULTS: Over a median follow-up period of 1,593 days (range, 13-2,891 days) after the start of chemotherapy, 28 of 450 patients (6%) experienced CEs. Prechemotherapy LVEF and GLS were lower in patients with CEs compared with those without CEs (58 ± 10% vs 62 ± 7% [P = .005] and -15.0 ± 2.8% vs -19.7 ± 2.7% [P < .0001], respectively). Diabetes (hazard ratio [HR], 7.06; P < .0001), hypertension (HR, 2.22; P = .04), LVEF (HR, 0.93; P = .005), and GLS (HR, 1.47; P < .0001) were associated with CEs. After controlling for clinical variables, prechemotherapy GLS remained independently associated with CEs (P < .0001). GLS less than the absolute value of -17.5% was found in 105 patients (23%) and was associated with a sixfold increase in CEs (P < .0001). CONCLUSIONS: Prechemotherapy GLS is an effective tool to stratify patients at high risk for CEs after anthracycline therapy and may help tailor treatments to decrease anthracycline-induced cardiotoxicity.

Left Ventricular Global Longitudinal Strain in HER-2 + Breast Cancer Patients Treated with Anthracyclines and Trastuzumab Who Develop Cardiotoxicity Is Associated with Subsequent Recovery of Left Ventricular Ejection Fraction.

AIM: The combination of anthracyclines (AC) and trastuzumab (TRZ) is highly effective in patients with aggressive HER-2 + breast cancer, but has a significant risk of cardiotoxicity (CT). Trastuzumab-induced CT may be reversible. The aim of this study was to identify echocardiographic parameters associated with recovery of left ventricular ejection fraction (LVEF) in patients who developed CT after AC and TRZ treatment. METHODS AND RESULTS: Women with newly diagnosed breast cancer treated with AC followed by TRZ and monitored with serial echocardiograms were retrospectively studied. Left ventricular end-diastolic and systolic volumes, LVEF, and global longitudinal strain (GLS) were examined. Development and reversibility of CT were defined based on changes in LVEF according to the 2014 ASE/EACVI recommendations. Cox analysis was used to determine the association of echocardiographic variables with the subsequent development and reversibility of CT. Ninety-five patients underwent 5 echocardiograms or more in a 17-month (13-28 months) follow-up period. Nineteen patients (20%) developed CT. Left ventricular volumes, LVEF, and GLS measured after AC completion identified the subsequent development of CT. Of the 19 patients with CT, the LVEF partially or fully recovered in 13 (68%). GLS at the time of CT diagnosis was associated with subsequent recovery of LVEF (P = 0.004). CONCLUSION: In patients with breast cancer treated with AC and TRZ who develop CT, GLS at the time of CT diagnosis is associated with subsequent recovery of LVEF and may be useful for risk stratification and to guide treatment.

Tricuspid leaflet resection in an open beating heart for the creation of a canine tricuspid regurgitation model.

OBJECTIVES: Outcomes of tricuspid valve replacement are poor, partly due to right heart remodelling. The research on its underlying mechanisms is hampered by a lack of animal models of tricuspid regurgitation (TR). Our objective was to create a reproducible and clinically compatible TR animal model to study right heart remodelling caused by TR. METHODS: Fourteen juvenile male Beagle dogs were divided randomly into an intervention group (n = 11) and a sham-operated control group (n = 3). The intervention group underwent thoracotomy and right atrial incision following superior and inferior vena caval occlusion. The anterior leaflet, together with the chordae, of the tricuspid valve was resected in eight dogs ('one leaflet' group), whereas both anterior and posterior leaflets, together with the chordae, were resected in three dogs ('two leaflets' group). The right atrium and chest were then closed. The control group underwent the same procedure, except leaflet resection. One dog from the 'two leaflets' group and one control dog were sacrificed and autopsy was performed at 12 months post-surgery. RESULTS: All dogs survived over the 1-year observation period postoperatively. TR grade IV occurred immediately postoperatively in the 'one leaflet' group, and TR grade IV plus in the 'two leaflets' group. The overall procedure lasted 30-40 min, and the mean time of vena caval occlusion was 87 ± 10 s. Central venous pressure increased from 6 ± 1.2 at baseline to 13 ± 1.7 mmHg (P < 0.01). By 12 months after TR creation, both in the 'one leaflet' group and in the 'two leaflets' group, the right atrial area, tricuspid annular diameter and right ventricular index of myocardial performance increased significantly, right ventricular fractional area change and tricuspid annular plane systolic excursion decreased significantly. Autopsy of the intervention dog revealed oedema, ascites and cirrhosis. CONCLUSIONS: Our surgical technique to create a TR animal model was reproducible with high success and survival rates. This animal model would prove suitable to investigate the mechanisms of right heart remodelling.

The diagnostic value of transthoracic echocardiography for eosinophilic myocarditis: A single center experience from China.

The aim of this study is to explore the value of transthoracic echocardiography in the diagnosis of eosinophilic myocarditis. The echocardiographic characteristics of nine patients with eosinophilic myocarditis in our hospital between January 2004 and January 2012 were retrospectively reviewed. In our study, four of the nine patients were diagnosed to have small pericardial effusion. The obliteration of the apical cavity was observed in five of the nine patients. There were six patients with both mitral and tricuspid regurgitation, one patient with only mitral regurgitation, and one patient with only tricuspid regurgitation. Transthoracic echocardiography showed that the diameters of the left and right atria were both increased in eight of the nine patients. The diameter of the left ventricle was increased in five patients, and the right ventricular diameter was increased in four patients. The left ventricular ejection fraction was decreased in two of the nine patients. Five of the nine patients had pulmonary hypertension, and one patient had severe pulmonary hypertension. Transthoracic echocardiography is the primary method for the diagnosis of eosinophilic myocarditis and is also useful in follow-up of the disease.

Major Cardiac Events and the Value of Echocardiographic Evaluation in Patients Receiving Anthracycline-Based Chemotherapy.

Anthracyclines are an important component of cancer treatments; however, their use is limited by the occurrence of cardiotoxicity. There are limited data on the occurrence of heart failure and the value of baseline and follow-up measurements of left ventricular (LV) ejection fraction (EF) in the current era. Therefore, the objectives of the present study were twofold: (1) to characterize the occurrence of and risk factors for major adverse cardiac events (MACEs: symptomatic heart failure and cardiac death) in a large contemporaneous population of adult patients treated with anthracyclines and (2) to test the value of LVEF and LV dimensions obtained using echocardiography in the prediction of MACE. Five thousand fifty-seven patients were studied, of whom 124 (2.4%) developed MACE. Of the total cohort, 2,285 patients had an available echocardiogram pre-chemotherapy. Patients with MACE were older (p <0.0001), predominantly men (p = 0.03), and with a higher incidence of cardiovascular risk factors and cardiac treatments. Patients with hematologic cancers had a higher incidence of cardiac events than patients with breast cancer (4.2% vs 0.7%, p <0.0001). Baseline LVEF, LVEF ≤5 points above the lower limits of normal, and LV internal diameter were predictive of the rate of occurrence of MACE. In conclusion, older patients with hematologic cancers and patients with a baseline LVEF ≤5 points above the lower limit of normal have higher incidence of MACE and should be closely monitored.

Transesophageal echocardiography for coronary sinus imaging in partially unroofed coronary sinus.

BACKGROUND: Partially unroofed coronary sinus (PUCS) is a rare congenital cardiac anomaly and prone to be misdiagnosed. The purpose of this study was to explore the value of transesophageal echocardiography (TEE) in CS imaging for the detection of PUCS and to develop a special two-dimensional TEE-based en face view of CS. METHODS: Twenty adult patients with suspected PUCS, showing a dilated coronary sinus and an enlarged right heart on transthoracic echocardiography (TTE), underwent TEE examination. In the mid-esophageal plane and close to an angle of 120°, the en face view of the CS successfully imaged the roof of the CS, which was beyond the realm of the atrial septum, and the interatrial septum was obtained simultaneously in the same view. Meanwhile, the 3D zoom mode could clearly display the comprehensive volume image and the adjacent structures of the PUCS. The results of TEE were compared with the findings of surgery or catheterization. RESULTS: En face view of the CS was obtained successfully by 2DTEE in 20 patients. In addition, 3DTEE was used for imaging of PUCS in 11 of the 20 patients. PUCS was ultimately confirmed in 13 patients either by surgery or catheterization. The TEE for PUCS diagnosis was consistent with the surgical findings. CONCLUSION: Transesophageal echocardiography can be successfully applied to obtain the comprehensive view of CS and its surrounding structures. The en face view of CS provided by 2DTEE may be helpful in better understanding PUCS and discriminating it from associated atrial septal defects.

[Evaluation of implanted cardioverter-defibrillators for primary prevention of sudden cardiac death].

OBJECTIVE: To evaluate the clinical effect of implanted cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death. METHODS: According to ACC/AHA Guideline of ICD implantation (2005), 35 patients successfully received ICD/CRT-D implantation for primary prevention of sudden cardiac death in our hospital from January 2006 to December 2009. All the patients were followed up for a mean of 2 years. RESULTS: During the follow up, 11 (31.43%) patients experienced ventricular arrhythmic episodes, for which 16 defibrillation therapies and 75 anti-tachycardia pacing (ATP) therapies were delivered without mistaken shock or death. The incidence rate of NVM was 100%, that of PVT was 66.67%, Brugada syndrome 50%, HCM 25% and DCM 16.67%. Of these episodes, the incidence of VF episodes among PVC patients was 87.5% (14 beats), ventricular tachycardia PVC was 82.28% (65 times), 5 beats in NVM patients, 4 beats in HCM and Brugada syndrome patients, and 1 beat in DCM patients. No ICD implantation-related complication was detected, and no ventricular tachycardia induced syncope occurred in these cases. All patients showed improved quality of life after the implantation. CONCLUSION: ICD implantation can prevent malignant ventricular arrhythmia episodes, especially for PVT, NVM and Brugada syndrome in high risk SCD patients, demonstrating the value of implantation of ICD as a primary prevention in high-risk SCD patients.

Real-time three-dimensional transesophageal echocardiography to predict artificial chordae length for mitral valve repair.

BACKGROUND: Artificial chordae replacement is an effective technique for mitral valve repair, however, it is difficult to accurately determine the length of artificial chordae. This study aimed to assess the reliability and accuracy of real-time three-dimensional transesophageal echocardiography (TEE) to predict the length of artificial chordae preoperatively. METHODS: From December 2008 to December 2010, 48 patients with severe mitral regurgitation successfully underwent mitral valve repair using artificial chordae replacement. The patients were divided into a TEE pre-measurement group (n = 26) and a direct measurement group (n = 22), according to the method used to determine the length of artificial chordae. Cardiopulmonary bypass time, aortic cross-clamp time, and the recurrence rate of moderate or severe mitral regurgitation were compared between the two groups. RESULTS: There were no operative deaths in either group. The mean cardiopulmonary bypass time was 113.0 ± 18.7 min and 127.0 ± 28.9 min (p < 0.05), and the aortic cross-clamp time was 70.0 ± 16.6 min and 86.0 ± 20.7 min (p < 0.05) in the TEE pre-measurement group and direct measurement group, respectively. The difference between the pre-measured artificial chordal length and actual constructed artificial chordal length was not significant in the TEE pre-measurement group (p > 0.05). Although the difference in the incidence of moderate or severe mitral regurgitation between the two groups was not significant (p > 0.05), the incidence in the TEE pre-measurement group (3.8%) was lower than that in the direct measurement group (18.2%). CONCLUSIONS: Real-time three-dimensional transesophageal echocardiography can accurately predict the length of artificial chordae required for mitral valve repair, and shortens cardiopulmonary bypass time and aortic cross-clamp time while improving the results of mitral valve repair.

Feasibility of bone marrow stromal cells autologous transplantation for dilated cardiomyopathy.

The feasibility of bone marrow stromal cells autologous transplantation for rabbit model of dilated cardiomyopathy induced by adriamycin was studied. Twenty rabbits received 2 mg/kg of adriamycin intravenously once a week for 8 weeks (total dose, 16 mg/kg) to induce the cardiomyopathy model with the monitoring of cardiac function by transthoracic echocardiography. Marrow stromal cells were isolated from cell-transplanted group rabbits and were culture-expanded on the 8th week. On the 10th week, cells were labeled with 4,6-diamidino-2-phenylindole (DAPI), and then injected into the myocardium of the same rabbits. The results showed that viable cells labeled with DAPI could be identified in myocardium at 2nd week after transplantation. Histological findings showed the injury of the myocardium around the injection site was relieved with less apoptosis and more expression of bcl-2. The echocardiography found the improvement of local tissue movement from (2.12+/-0.51) cm/s to (3.81+/-0.47) cm/s (P<0.05) around the inject site, but no improvement of heart function as whole. It was concluded bone marrow stromal cells transplantation for dilated cardiomyopathy was feasibe. The management of cells in vitro, the quantity and the pattern of the cells transplantation and the action mechanism still need further research.