ABSTRACT
Since variants of uncertain significance (VUS) reported in genetic testing cannot be acted upon clinically, this classification may delay or prohibit precise diagnosis and genetic counseling in adult genetic disorders patients. Large-scale analyses about qualitatively distinct lines of evidence used for VUS can make them re-classification more accurately. We analyzed 458 Chinese adult patients WES data, within 15 pathogenic evidence PS1, PS2, PM1, PM6 and PP4 were not used for VUS pathogenic classification, meanwhile the PP3, BP4, PP2 were used much more frequently. The PM2_Supporting was used most widely for all reported variants. There were also 31 null variants (nonsense, frameshift, canonical ±1 or 2 splice sites) which were probably the disease-causing variants of the patients were classified as VUS. By analyzed the evidence used for all VUS we recommend that appropriate genetic counseling, reliable releasing of in-house data, allele frequency comparison between case and control, expanded verification in patient family, co-segregation analysis and functional assays were urgent need to gather more evidence to reclassify VUS. We also found adult patients with nervous system disease were reported the most phenotype-associated VUS and the lower the phenotypic specificity, the more reported VUS. This result emphasized the importance of pretest genetic counseling which would make less reporting of VUS. Our result revealed the characteristics of the pathogenic classification evidence used for VUS in adult genetic disorders patients for the first time, recommend a rules-based process to evaluate the pathogenicity of VUS which could provide a strong basis for accurately evaluating the pathogenicity and clinical grade information of VUS. Meanwhile, we further expanded the genetic spectrum and improve the diagnostic rate of adult genetic disorders.
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BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.
Subject(s)
Cardiotoxicity , Ventricular Dysfunction, Left , Humans , Cardiotoxicity/diagnostic imaging , Cardiotoxicity/etiology , Ventricular Function, Left , Anthracyclines/adverse effects , Global Longitudinal Strain , Stroke Volume , Antibiotics, Antineoplastic/adverse effects , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/drug therapyABSTRACT
BACKGROUND: The application value of myocardial work (MW) in evaluating myocardial function and predicting major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients has not been fully explored. PURPOSE: Comparing noninvasive MW parameters between MHD patients and healthy controls, and further determining its value in predicting MACE in MHD patients. METHODS: A prospective single-institution study included 92 MHD patients without prior cardiovascular disease and 40 age- and sex-matched healthy controls. Conventional echocardiographic data, global longitudinal strain (GLS), and MW parameters (global work index [GWI], global constructive work [GCW], global work efficiency [GWE], global wasted work [GWW]) were derived and compared between MHD and the control. Logistic regression was used to determine the predictive value of these parameters for MACE. The receiver operating characteristic curve was utilized to compare the predictive differences of MACE between GWE and GLS. RESULTS: Compared with healthy individuals, MHD patients had significantly reduced GWE, GLS and elevated LVMI, GWW (all p < 0.001), while there was no significant difference in left ventricular ejection fraction. Twenty eight (30%) MHD patients experienced MACE. Two nested models adding GWE and GLS, respectively, showed that age (p < 0.005), GWE (p = 0.034), and GLS (p = 0.014) were independent predictors of MACE. The AUC derived from GWE for predicting MACE was significantly higher than that derived from GLS (0.836 vs. 0.743, p = 0.039). CONCLUSIONS: Myocardial work is a novel tool for assessing left ventricular myocardial performance in MHD patients. GWE is an independent predictor of MACE.
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Carrier screening can identify people at risk of conceiving pregnancies affected with inherited genetic disorders or who have a genetic disorder with late or variable onset. Carrier screening based on whole exome sequencing (WES) data can offer more comprehensive assessment than on-target carrier screening tests. A total of 224 Chinese adult patients WES data was analyzed, except positive variants associated with the patients' major complaint, 378 pathogenic (P) and "likely pathogenic" (LP) variants from 175 adult patients were identified. Whole exome-wide frequency of carriers for Mendelian disorders in Chinese adult patients was about 78.13% in this study, which was lower than the previously reported carrier frequency in healthy population. Contrary to expectations, the number of P or LP variants did not increase with larger chromosome size or decrease with smaller chromosome size. Totally 83 novel P or LP variants were identified which could further expand the carrier variants spectrum of the Chinese population. GJB2: NM_004004.6:c.299_300delAT:p.His100fs*14 and C6:NM_000065.4:c.654T>A:p.Cys218* were found in two or more patients, which might be two underestimated carrier variants in Chinese population. We also found 9 late-onset or atypical symptoms autosomal/X-linked dominant Mendelian disorders causative genes, which were easily overlooked during pathogenicity analysis. These results can provide a strong basis for preventing and avoiding the prevalence rates of birth defects and reducing social and family burdens. By comparing with three different expanded carrier screening gene panels, we further confirmed carrier screening based on WES could offer more comprehensive assessment and WES was applicable for carrier screening.
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Background: Predicting outcomes of surgical aortic valve replacement (AVR) in patients with chronic severe aortic regurgitation (AR) and markedly reduced left ventricular (LV) function remains a challenge. This study aimed to explore the preoperative echocardiographic index that could predict the recovery of LV systolic function after surgery in patients with chronic severe AR and reduced left ventricular ejection fraction (LVEF). Methods: The study group consisted of 50 patients diagnosed with chronic severe AR ( > 6 months) and significantly reduced LVEF (18~35%, average 26.2 ± 5.3%). Low-dose dobutamine stress echocardiography (DSE) was performed before surgery. Only patients with an absolute increase in LVEF ≥ 8% during DSE were referred for surgical AVR. During following up (over six months to one year after surgery), the patients were divided into two groups by postoperative LVEF ( > or ≤ 40%). DSE- and speckle tracking echocardiography (STE)-derived LV functional parameters were compared between groups to identify predictors of post-operative improvement in LVEF. Results: A total of 38 patients underwent AVR. One patient died before discharge. Post-surgical LV size and LVEF improved markedly after surgery in all patients (n = 37). Pre-surgical LV end-systolic diameter, baseline global longitudinal strain (GLS) and peak GLS were better in the group with LVEF > 40% (n = 18; p < 0.05, t test). Baseline GLS and peak GLS correlated moderately with post-surgery LVEF (R = -0.581, p < 0.001; R = -0.596, p < 0.001; respectively). Logistic regression analysis demonstrated baseline GLS and peak GLS were the independent predictors of post-surgery improvement of LVEF. Peak GLS had the highest prediction value (area under the curve = 0.895, sensitivity and specificity: 89.5% and 77.8%, respectively), with a cutoff value of -9.4%. Conclusions: This study shows that STE combined with DSE can provide sensitive quantitative indices for predicting improvement of LV systolic function after AVR in patients with chronic severe AR and significantly decreased LVEF.
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OBJECTIVES: To investigate the prognostic value of coronary CT angiography (CCTA) in heart failure patients with preserved ejection fraction (HFpEF). METHODS: Between January 2009 and December 2013, 6497 participants (mean age 63 ± 9.4 [range 32-86] years; 4111 men) who underwent CCTA and echocardiography were prospectively included. Participants were divided into HFpEF group and without HFpEF group. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal myocardial infarction (MI), or hospitalization for heart failure (HF). RESULTS: Among those participants, 3096 were identified with HFpEF and 3401 were without HFpEF. Higher prevalence of coronary atherosclerosis was observed in HFpEF group than those without (78.3% vs. 64.9%, p < 0.001). During a median of 11.0 [IQR: 9.0-12.0] years follow-up, participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS = 1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001), while CAD-RADS ≥ 3 conferred 3.9-fold and 3.1-fold higher risk for cardiovascular mortality (adjusted HR: 3.9, 95% CI: 2.2 to 7.1, p < 0.001) and hospitalization due to HF (adjusted HR: 3.1, 95% CI: 1.9 to 5.3, p < 0.001) with reference to CAD-RADS = 0 respectively. CONCLUSIONS: Coronary artery disease is common in participants with HFpEF and associated with MACEs. Among those participants, the presence of CAD-RADS = 1-2 increased the risk of nonfatal MI, while CAD-RADS ≥ 3 were correlated with cardiovascular mortality and hospitalization due to HF. KEY POINTS: ⢠Higher median of CACS and higher CAD-RADS categories were observed in the HFpEF group than those without (p < 0.001 for both). ⢠Participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). ⢠In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS =1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001) with reference to CAD-RADS = 0 respectively.
Subject(s)
Coronary Artery Disease , Heart Failure , Myocardial Infarction , Male , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Prognosis , Heart Failure/complications , Computed Tomography Angiography , Stroke Volume , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Risk FactorsABSTRACT
BACKGROUND: The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. METHODS: We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi) > .7 mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. RESULTS: Of the 94 patients with MVP and significant MR, 31 patients showed a TVi > .7 mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. CONCLUSIONS: Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.
Subject(s)
Echocardiography, Three-Dimensional , Mitral Valve Insufficiency , Mitral Valve Prolapse , Humans , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/diagnostic imaging , Echocardiography, Transesophageal/methods , Echocardiography, Three-Dimensional/methods , Mitral Valve Prolapse/complications , Mitral Valve/diagnostic imagingABSTRACT
OBJECTIVE: Occult atrial fibrillation (AF) is a significant risk factor for occult stroke but is difficult to detect. Myocardial strain, based on speckle tracking echocardiography (STE), can detect subclinical changes in left atrial (LA) function. This study aimed to investigate the diagnostic value of LA strain in identifying asymptomatic AF patients with normal electrocardiograms and healthy volunteers. METHODS: A total of 354 subjects were retrospectively enrolled. Patients were divided into two groups based on whether they had AF during echocardiography. Patients with sinus rhythm during echocardiography were further divided into healthy control group and occult AF group. Patients with AF during echocardiography were further divided into paroxysmal AF group and persistent AF group. LA mechanical function measured by STE was compared between patients with asymptomatic AF and volunteers. Conventional echocardiographic indicators were measured. The diagnostic value of LA strain for identifying asymptomatic AF was assessed by univariate and multivariate regression analysis and receiver operating characteristic (ROC) curves. RESULTS: Occult AF patients had higher NT-proBNP levels, larger RA area, larger LAVmax and decreased LAEF than control group. However, occult AF patients had lower NT-proBNP levels, RA area and LAVmax and higher LAEF than paroxysmal and persistent AF. The measured LA reservoir strain (LASr), LA conduit strain (LAScd), LA contraction strain (LASct) of occult AF group was significantly lower than that of control group. However, occult AF patients had preserved LAScd and LASct than paroxysmal and persistent AF. RA area, LAEF and LASr were remarkable correlation with occult AF after adjustment for NT-proBNP, LAVmax, and LAScd. The area under curve of ROC for LASr was the greatest among RA area, LAEF and LASr, with a cut-off value of 34.1% (sensitivity: 75.4%, specificity: 87.6%). CONCLUSION: LASr can identify occult AF in the asymptomatic population. Patients with LASr values ≤34.1% have a higher incidence of occult cardiac dysfunction. These findings help identify patients with occult AF and further risk stratification for the AF population.
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BACKGROUND: PRKAG2 syndrome is a rare disease characterized as left ventricular hypertrophy (LVH), ventricular preexcitation syndrome, and sudden cardiac death. Its natural course, treatment, and prognosis were significantly different from sarcomeric hypertrophic cardiomyopathy (HCM). However, it is often clinically misdiagnosed as sarcomeric HCM. PRKAG2 patients tend to experience delayed treatment. The delay may lead to adverse outcomes. This study aimed to identify the echocardiographic parameters which can differentiate PRKAG2 syndrome from sarcomeric HCM. METHODS: Nine PRKAG2 patients with LVH, 41 HCM patients with sarcomere gene mutations, and 202 healthy volunteers were enrolled. Clinical characteristics, conventional echocardiography, and three-dimensional images were recorded, and reviewed by an attending cardiologist. We evaluated the parameters of left ventricular strains from three-dimensional speckle tracking echocardiography (3D STE) by TomTec software. Receiver operating characteristic (ROC) curves analysis was used to assess clinical and echocardiographic parameters' differential diagnosis potential. RESULTS: The heart rate (HR) of the PRKAG2 group was significantly lower than both the healthy group (53.11 ± 10.14 vs. 69.22 ± 10.48 bpm, P < 0.001) and the sarcomeric HCM group (53.11 ± 10.14 vs. 67.23 ± 10.32 bpm, P = 0.001). The PRKAG2 group had similar interventricular septal thickness (IVS), posterior wall thickness (PWT), and maximum wall thickness (MWT) to the HCM group (P > 0.05). The absolute value of GLS in the PRKAG2 group was significantly higher than HCM patients (-18.92 ± 4.98 vs. -13.43 ± 4.30%, P = 0.004). SV calculated from EDV and ESV in PRKAG2 syndrome showed a higher value than sarcomeric HCM (61.83 ± 13.52 vs. 44.96 ± 17.53%, P = 0.020). The area under the ROC curve (AUC) for HR + GLS was 0.911 (0.803 -1). For HR + GLS, the sensitivity and specificity of the best cut-off value (0.114) were 69.0% and 100%, respectively. CONCLUSIONS: PRKAG2 patients present deteriorated LV diastolic function and preserved LV systolic function. Bradycardia and preserved GLS are useful to identify PRKAG2 syndrome from sarcomeric HCM, which may be beneficial for clinical decision-making.
Subject(s)
Cardiomyopathy, Hypertrophic , Echocardiography, Three-Dimensional , AMP-Activated Protein Kinases , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Echocardiography , Heart Ventricles/diagnostic imaging , Humans , Hypertrophy, Left Ventricular , Sarcomeres/genetics , Ventricular Function, LeftABSTRACT
Sinus of Valsalva aneurysm (SVA) is a rare cardiovascular disease with male predominance. Recently, an association with aortic aneurysm and SVA has been revealed in periventricular nodular heterotopia patients with loss-of-function Filamin A (FLNA) mutations, which were located on chromosome X and almost exclusively affect females.Among patients hospitalized for aortic surgery with aortic root diameter over 4.0 cm, next-generation sequencing was performed to investigate 30 candidate genes related to inherited aortic aneurysm syndromes and familial thoracic aortic aneurysm and dissection. The present report reviewed an electronic case database and identified two female cases of unruptured SVA with heterozygous FLNA truncating mutations.Case 1 displaying a rare SVA phenotype involving left and noncoronary sinus harbored a nonsense variant p.Tyr1720Ter/c.5160C > G. Case 2 displayed right and noncoronary SVA with predominantly enlarged right coronary sinus, posterior mitral valve prolapse, and harbored a frameshift variant p.Val1724fs*68/c.5171_5172delTG. Both novel mutations resulted in the premature termination of filamin A with the loss of functional Rod 2 and dimerization region.The present report raised the possibility of the presence of a cardiovascular onset form in the spectrum of FLNA hereditary diseases. The association between SVA and loss-of-function FLNA mutations indicates a unique etiology and pathogenesis among female patients, which requires further investigation to establish the linkage between FLNA variants and a wide spectrum of phenotypes.
Subject(s)
Aortic Aneurysm, Thoracic , Aortic Aneurysm , Sinus of Valsalva , Male , Female , Humans , Filamins/genetics , Aortic Aneurysm/complications , Phenotype , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/genetics , Aortic Aneurysm, Thoracic/complicationsABSTRACT
OBJECTIVES: We sought to assess the acute intraprocedural effects of the ValveClamp system in DMR patients on the mitral valve (MV) three-dimensional (3D) geometry and the association of these effects with mitral regurgitation (MR) reduction. BACKGROUND: Few data are available about the specific impact of transcatheter edge-to-edge repair in patients with degenerative mitral regurgitation (DMR). METHODS: Thirty-five symptomatic patients (age 74.26 ± 6.61 years) with Grade 3 to 4+ degenerative MR underwent 3D transoesophageal echocardiography (TEE) during ValveClamp implantation. Volumetric data sets were retrospectively analyzed using mitral valve quantitative 3D modeling software. RESULTS: Mitral valve annular anterior-posterior (AP) diameter decreased from 33.24 ± 4.03 to 31.12 ± 3.66 mm (p < .001), and prolapse height from 4.78 ± 2.19 to 2.32 ± 1.92 mm (p < .001), and total exposed leaflet area from 1,110.29 ± 224.21 mm2 to 1,013.44 ± 228.71 mm (p = .004). Accordingly, we observed a significant reduction of MR severity after ValveClamp implantation. Multivariable analysis revealed postprocedural MR reduction was associated with shortening in anterior-posterior diameter (coefficient 0.427, p = .008) and reduction in prolapse height (coefficient 0.369, p = .021). CONCLUSIONS: ValveClamp implantation exerts an acute effect on the 3D MV geometry. Postprocedural reduction in AP diameter and reduction in prolapse height correlates with MR downgrading in patients with degenerative MR.
Subject(s)
Echocardiography, Three-Dimensional , Mitral Valve Insufficiency , Aged , Echocardiography, Transesophageal , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
MitraClip edge-to-edge (E2E) repair system is the only transcatheter device recommended in the current guidelines for treating mitral regurgitation (MR). The percutaneous femoral venous transseptal access of MitraClip requires a complex steerable delivery system and may thus be technically complex to optimally position and deploy the clip onto the mitral valve. A transapical approach for E2E repair has been devised to treat MR for the ease of operation (ValveClamp system, Hanyu Medical Technology, Shanghai). The first-in-human study of ValveClamp has demonstrated its early feasibility and effectiveness for the treatment of patients with degenerative MR. Transesophageal echocardiography (TEE) is the only imaging modality required for intraoperative guidance of ValveClamp implantation. Successful implantation depends on accurate localization and orientation of the clamp and efficient intraoperative communication between the echocardiographer and the intervention team. Thus, the focus of this review is on elaborating how two-dimensional (2D) and three-dimensional (3D) TEE are used in clinical practice to guide ValveClamp implantation and it may facilitate the understanding of simplicity and safety of this novel procedure. We also describe the implementation of several novel advancements in 3D TEE imaging, which improve the confidence of image interpretation for intraoperative guidance and expedite implantation times.
Subject(s)
Echocardiography, Transesophageal/methods , Mitral Valve Insufficiency/surgery , Surgery, Computer-Assisted/methods , Echocardiography, Three-Dimensional/methods , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Humans , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnosisABSTRACT
Bicuspid aortic valve (BAV) is characterized by elevated risk of aortic dilatation and aneurysm. Although genetic susceptibility is suspected to influence on the development of BAV aortopathy, clinical application of genetic markers still needs validation in BAV entities with strictly defined phenotypic features. The 'root phenotype' represents a young, male predominant, and severely aortic regurgitant BAV population prone to aortic root dilatation. The present study launched a two-step genetic survey to evaluate the clinical significance of germline genetic markers in BAV patients. The whole-exome sequencing (WES) cohort consisted of 13 BAV patients with 'root phenotype' under the age of 40 years. We identified 28 different heterozygous missense mutations in 19 genes from the WES cohort, among which six variants (COL1A2 R882C, COL5A1 I1161F, ACVRL1 R218W, NOTCH1 P1227S, MYLK S243W, MYLK D717Y) were identified as pathogenic variants via unanimous agreement of in silico prediction tool analysis, and three variants (C1R I345L, TGFBR2 V216I, FBN2 G475V) were identified as recurrent variants. The panel of nine genetic markers was tested in an independent validation cohort of 154 BAV patients consecutively included from January to May 2018 in our institution. The validation cohort demonstrated 71.4% male predominance and the average age of 57 ± 13 years, among which 26.6% showed aortic root dilatation and 66.9% ascending aortic dilatation. Genetic markers were found in 32 patients, including 18 with C1R I345L, 11 with TGFBR2 V216I, 2 with FBN2 G475V, and 1 with both TGFBR2 V216I and MYLK D717Y. BAV patients carrying these genetic markers demonstrated younger age [(51 ± 12) vs. (58 ± 13) years, P = 0.014], more moderate to severe aortic regurgitation (56.2% vs. 33.6%, P = 0.019), elevated prevalence of mitral valve prolapse (9.4% vs. 0.8%, P = 0.028) and aortic root dilatation (62.5% vs. 17.2%, P < 0.001) but not ascending aortic dilatation than those without these markers. The early-onset 'root phenotype' entities displayed great value for BAV genetic surveys. As one of the promising complements of the current risk stratification system, recurrent germline mutations in TGFBR2, C1R, FBN2 genes could be identified and applied as genetic markers of elevated susceptibility for aortic root but not ascending aortic dilatation among BAV patients.
Subject(s)
Aortic Aneurysm, Thoracic/genetics , Aortic Valve/diagnostic imaging , Bicuspid Aortic Valve Disease/genetics , DNA/genetics , Genetic Markers/genetics , Germ-Line Mutation , Adult , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/etiology , Bicuspid Aortic Valve Disease/complications , Bicuspid Aortic Valve Disease/metabolism , DNA Mutational Analysis , Female , Humans , Male , Retrospective StudiesABSTRACT
BACKGROUND: To evaluate the detailed dynamic change of left ventricular diastolic function (LVDF) by echocardiography in aortic stenosis (AS) patients receiving transcatheter aortic valve implantation (TAVI) and compare LVDF classification according to 2009 ASE/EAE and 2016 ASE/EACVI recommendations. METHODS: Thirty-five AS patients receiving TAVI underwent echocardiography the day before operation (PRE), on the third day (3D), in the first-month (1 M) and the six-month (6 M) after TAVI. LVDF was analyzed using 2D and doppler imaging to get parameters including E/A, E/e', isovolumic relaxation time (IVRT), deceleration time, LA area, LA volume index (LAVI) and systolic tricuspid regurgitation velocity (TR). LVDF classification was evaluated four times for each patient according to 2009 and 2016 recommendations respectively and the results were compared. RESULTS: The decrease of IVRT and TR occurred immediately post surgery up to 1-month. Improvement of E/e' occurred late from 3-day to 1-month. LA area and LAVI decreased continuously shortly after operation till 6-month. Forty-four percent (62/140) by 2009 recommendations were reclassified with different grades when using 2016 guidelines. Comparing PRE and 6 M, with 2009 guidelines, 19 patients improved 1 grade, 8 patients improved 2 grades; with 2016 guidelines, 9 patients improved 1 grade, 13 patients improved 2 grades, 1 patient improved 3 grades. CONCLUSIONS: The conventional 2D echocardiography could effectively reflect variation process of LVDF in AS patients after TAVI. For LVDD classification, obvious differences resulted by the 2009 and updated recommendations were found, and more patients can be regarded as benefiting from TAVI by 2016.
Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Echocardiography/standards , Guidelines as Topic , Transcatheter Aortic Valve Replacement/methods , Ventricular Function, Left/physiology , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/physiopathology , Diastole , Female , Humans , Male , Retrospective StudiesABSTRACT
BACKGROUND: The quantification of tricuspid regurgitation(TR) using three-dimensional(3D) proximal isovelocity surface area (PISA) derived effective regurgitant orifice area (EROA) is feasible in functional TR. The aim of our study was to explore the diagnostic accuracy and utility of 3D PISA EROA in a larger population of different etiologies. METHODS: One hundred and seven patients with confirmed TR underwent 2D and 3D transthoracic echocardiography (TTE). 3D PISA EROA was calculated and EROA derived from 3D regurgitant volume (Rvol) was used as the reference. RESULTS: 3D PISA EROA showed better correlation in primary TR than in functional TR(r = 0.897, P < 0.01). 3D PISA EROA differentiated severe TR with comparable accuracy in patients with primary and functional etiology (Z-value 16.506 vs 21.202), but with different cut-offs (0.49cm2 vs. 0.41 cm2). The chi-square value for incorporated clinical symptoms, positive echocardiographic results and 3D PISA EROA to grade severe TR was higher than only included clinical symptoms or incorporated clinical symptoms and positive echocardiographic results (chi-square value 137.233, P < 0.01). CONCLUSION: TR quantification using 3D PISA EROA is feasible and accurate under different etiologies. It has incremental diagnostic value for evaluating severe TR.
Subject(s)
Echocardiography, Three-Dimensional/methods , Tricuspid Valve Insufficiency/diagnostic imaging , Adult , Aged , Female , Humans , Image Interpretation, Computer-Assisted , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Severity of Illness Index , Tricuspid Valve Insufficiency/physiopathologyABSTRACT
BACKGROUND: The aim of this study was to investigate the utility of perimeter-derived diameter (PDD) measured by three-dimensional (3D) transesophageal echocardiography (TEE) in predicting the size of left atrial appendage (LAA) occluder. METHODS AND RESULTS: Left atrial appendage landing zone diameter (LZD) was measured by two-dimensional (2D) TEE, 3DTEE, and digital subtraction angiography (DSA) as LZD-2Dmax, LZD-2Dmean, LZD-3Dmax, LZD-3Dmean, LZD-PDD, LZD-DSAmax, respectively, before and during transcatheter LAA closure with Watchman devices in 100 patients. A difference of one or more device size intervals between the predicted size and the size actually implanted was defined as mismatching. Seventy-eight patients were followed up by TEE to obtain occluder compression ratio. The correlation between LZD and the final implanted occluder size was 0.559, 0.641, 0.754, 0.760, 0.782, and 0.848 for LZD-2Dmax, LZD-2Dmean, LZD-3Dmax, LZD-3Dmean, LZD-PDD and LZD-DSAmax, respectively (P < .001). Matching ratio between the size predicted by retrospective measurements of LZD and the device size actually implanted was 65%, 57%, 66%, 63%, 70%, and 83% for LZD-2Dmax, LZD-2Dmean, LZD-3Dmax, LZD-3Dmean, LZD-PDD and LZD-DSAmax, respectively. There was no significant difference in LZD value, matching ratio, and compression ratio between the patients with eccentric and noneccentric LAA landing zone (P > .05). Compression ratio of the mismatching subjects was higher than that in the matching subjects when evaluated by LZD-2Dmean, LZD-3Dmean, and LZD-PDD (P < .05). CONCLUSIONS: Landing zone diameter derived from LAA perimeter measured by preprocedure 3DTEE showed reference value for LAA occluder size selection, providing superior correlation and matching ratio with the final implanted size and indicating the adjustment of oversizing.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Echocardiography, Three-Dimensional , Septal Occluder Device , Atrial Appendage/diagnostic imaging , Atrial Appendage/surgery , Cardiac Catheterization , Echocardiography, Transesophageal , Humans , Reference Values , Retrospective Studies , Treatment OutcomeABSTRACT
For its high occurrence and elevated risks for aortic valve dysfunction and vascular complications, bicuspid aortic valve (BAV) represents a great health challenge. However, the prevalence and clinical features of BAV in the Chinese population are inadequately illustrated.From January 2011 to December 2015, 3,673 BAV patients with 69.1% male predominance were identified among 325,910 recipients of transthoracic echocardiography in our institution, demonstrating 58.4% overt aortic valve dysfunction, 52.5% ascending aortic dilatation, and 19.2% aortic root dilatation. The prevalence of pure aortic stenosis and mixed aortic valve dysfunction rose strikingly with age (both P < 0.0001), while pure aortic regurgitation showed significant decrease with age (P < 0.0001). Males showed elevated prevalence of pure aortic regurgitation (OR 3.16, 95% CI 2.55-3.91, P < 0.0001) and mixed aortic valve dysfunction than females (OR 1.63, 95% CI 1.23-2.17, P = 0.0008), but lower prevalence of pure aortic stenosis (OR 0.51, 95% CI 0.43-0.60, P < 0.0001). Aortic root dilatation was associated with male gender (OR 5.02, 95% CI 3.74-6.74, P < 0.0001), pure aortic regurgitation (OR 2.61, 95% CI 2.15-3.17, P < 0.0001), and right-left (RL) cusp fusion type (OR 1.98, 95% CI 1.64-2.40, P < 0.0001). Ascending aortic dilatation was associated with an elder age (OR 1.04, 95% CI 1.04-1.05, P < 0.0001), pure aortic stenosis (OR 1.37, 95% CI 1.16-1.61 P = 0.0002), and mixed aortic valve dysfunction (OR 2.51, 95% CI 1.89-3.33, P < 0.0001).Bicuspid aortic stenosis and ascending aortic dilatation demonstrate a similar pattern of age escalation, while aortic regurgitation is more prevalent in younger BAV patients. Aortic root dilatation intervenes closely with a unique phenotypic subgroup of male BAV patients with pure aortic regurgitation and RL fusion type.
Subject(s)
Aortic Diseases/etiology , Aortic Valve/abnormalities , Heart Valve Diseases/complications , Adolescent , Adult , Aged , Aortic Diseases/diagnostic imaging , Aortic Diseases/epidemiology , Aortic Valve/diagnostic imaging , Bicuspid Aortic Valve Disease , China/epidemiology , Echocardiography , Female , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: A new technique has been developed for treating mitral regurgitation (MR) via a transapical approach, which encompasses an easy-to-use leaflet clamp and a smaller-sized delivery system (14F-16F). OBJECTIVES: We aimed to evaluate the effectiveness of this device in a porcine model of acute MR. METHODS: Acute MR was induced in 36 anesthetized porcine subjects by severing the chordae supporting the corresponding segment of the leaflet. The ValveClamp system was then transapically implanted on the prolapsing segment under epicardial echocardiographic guidance. Echocardiographic assessments were performed before and after the transapical interventions. All of the animals were killed 30 days after the procedure to verify the proper location of the implanted devices. RESULTS: Epicardial echocardiography revealed severe MR (n = 26) or moderate to severe MR (n = 10) in the pig model of acute MR. Overt MR reduction was observed following the procedure through echocardiography; residual MR was absent in 10 cases, mild in 17 cases, and moderate in 9 cases. There was no evidence of mitral stenosis at the end of the procedure in terms of mitral valve area and mitral valve pressure gradient. Autopsy demonstrated that all ValveClamp devices were precisely placed to clamp the prolapsing segment of the mitral valve. CONCLUSIONS: Transapical implantation of the ValveClamp device under epicardial echocardiographic guidance was effective and safe in reducing acutely induced MR in this pig model. It is potentially applicable as a novel user-friendly transcatheter edge-to-edge mitral valve repair device for the treatment of MR in humans.
ABSTRACT
The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin-related protein-1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8-week rapid atrial pacing or 4-week rapid atrial pacing and 4-week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin-II and angiotensin-II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down-regulating MCU and up-regulating DNM1L/Drp1. Cell stretching reversed the angiotensin-II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down-regulated MCU, up-regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin-II-induced cellular enlargement.
Subject(s)
Calcium Channels/metabolism , Cardiac Resynchronization Therapy , Dynamins/metabolism , Heart Failure/metabolism , Heart Failure/therapy , Mitochondria/metabolism , Myocytes, Cardiac/metabolism , Angiotensins , Animals , Autophagosomes/metabolism , Autophagosomes/ultrastructure , Autophagy/physiology , Cells, Cultured , Disease Models, Animal , Dogs , Down-Regulation , Dynamins/genetics , Echocardiography , Gene Expression Regulation , Heart Failure/pathology , Male , Mitochondria/pathology , Mitochondria/ultrastructure , Mitochondrial Dynamics/physiology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Tissue Array Analysis , Transcriptome/genetics , Up-RegulationABSTRACT
OBJECTIVE: This study aimed to determine whether STE could help detect subclinical myocardial dysfunction in patients with CSFP. METHODS: Sixty patients with CSFP confirmed by CAG and 51 controls with normal coronary flow were prospectively enrolled. Coronary angiographic data and conventional and speckle tracking echocardiographic parameters of the LV and RV were obtained for every subject. RESULTS: Compared with controls, CSFP patients presented with higher BMI and TG levels, but lower HDL-C levels. Conventional echocardiographic parameters of biventricular systolic and diastolic function did not differ between the two groups (all P > 0.05). The GLS of the LV and RV was significantly impaired in CSFP patients compared with that in controls (-19.03% vs -21.42%, P < 0.001 and -19.72% vs -22.96%, P = 0.001, respectively). The myocardial impairment pattern of CSFP patients was homogenous in the RV and heterogeneous in the LV, where only endo- and mid-myocardial layers were affected. LV-GLS and RV-GLS were found to be well correlated with mTFC and HDL-C in CSFP groups (r = 0.463 vs r = 0.439; r = -0.569 vs r = -0.552, all P < 0.05). ROC curve analysis demonstrated that LV-GLS-endo had the highest AUC (0.867, P < 0.001) for predicting subclinical myocardial impairment in CSFP patients. CONCLUSIONS: Subclinical myocardial systolic dysfunction occurs in both ventricles, and GLS could be an effective method to detect early-stage myocardial impairment in patients with CSFP.