Relationship of Different Left Bundle Branch Pacing Sites and Clinical Outcomes in Heart Failure Patients.

BACKGROUD: Left bundle branch pacing (LBBP) is a novel physiological pacing modality. However, whether it delivers comparable efficacy with different capture sites in heart failure (HF) patients remains unclear. OBJECTIVE: This study aims to assess the association between different pacing sites and the response of LBBP . METHODS: Forty-three consecutive HF patients , referred for successful LBBP implantation, were prospectively recruited in this study. Patients were assigned to 3 subgroups according to the paced QRS complex morphology (left bundle branch trunk pacing (LBTP), left posterior fascicular pacing (LPFP) or left anterior fascicular pacing (LAFP) groups). Echocardiograms, electrocardiograms were recorded and analyzed at baseline and 6-month follow-up. RESULTS: The response rate was 95.0%, 88.2%, 83.3% in LBTP, LPFP and LAFP groups, respectively. All subgroups were efficient in narrowing QRS complex(ΔQRS: 62.4±10.4 ms, 54.7±14.2ms, 58.2±14.5ms) and improving cardiac function (ΔLVEF: 25.7±8.1%, 15.3±8.1%, 18.8±4.4%). Compared with left fascicle pacing(LFP), LBTP resulted in longer LVAT (76.5±10.2ms vs 82.3±6.5ms; P=0.037) , shorter QRSid (128.0±6.0ms vs 113.3±5.2ms; P＜0.0001),along with better improvement in septal systolic longitudinal strain(P=0.007) and lateral-septal myocardial loading inhomogeneity (P=0.036). Linear regression analysis further revealed LBB capture sites was strongly associated with the improvement of peak strain dispersion (PSD) (model R2 = 0.586, P =0.042) and LVEF (model R2 = 0.425, P <0.0001). CONCLUSIONS: Different LBB capture sites led to subtle difference in mechanical synchrony , which may in-turn affect LVEF improvement in HF patients.

Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice.

Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.

Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study.

BACKGROUND: The effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. OBJECTIVES: The study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. METHODS: Sixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. RESULTS: Patients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography-derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro-brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. CONCLUSION: LBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

Three-dimensional echocardiography reveals early mitral valve alterations in hypertrophic cardiomyopathy genetic mutation carriers.

BACKGROUND: The mitral valve undergoes structural modifications in response to cardiac functional changes, often predating cardiac decompensation and overt clinical signs. Our study assessed the potential of mitral valve morphological changes as early indicators for detecting carriers of hypertrophic cardiomyopathy (HCM)-associated gene mutations. METHODS: We studied 505 participants: 189 without the pathogenic gene mutations and left ventricular hypertrophy (G-/LVH-), 149 carriers without LV hypertrophy (G+/LVH-), and 167 manifest HCM patients (G+/LVH+). We juxtaposed the mitral valve morphology and associated metrics across these groups, emphasizing those carrying MYH7 and MYBPC3 mutations. RESULTS: We discerned pronounced disparities in the mitral annulus and leaflet structures across the groups. The mitral valve apparatus in mutation carriers exhibited a tendency towards a flattened profile. Detailed analysis spotlighted MYBPC3 mutation carriers, whose mitral valves were notably flatter (with notably lower AHCWR values than non-carriers); this contrast was not evident in MYH7 mutation carriers. This mitral valve flattening, manifest in the mutation carriers, suggests it might be an adaptive response to incipient cardiac dysfunction in HCM's nascent stages. CONCLUSIONS: Three-dimensional echocardiography illuminates the initial mitral valve structural changes in HCM patients bearing pathogenic gene mutations. These morphological signatures hold promise as sensitive imaging markers, especially for asymptomatic carriers of the MYBPC3 mutation.

ESCRT-III Component CHMP4C Attenuates Cardiac Hypertrophy by Targeting the Endo-Lysosomal Degradation of EGFR.

BACKGROUND: Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated degradation of membrane proteins, is associated with cardiac hypertrophy progression. CHMP4C (charged multivesicular body protein 4C), a critical constituent of multivesicular bodies, is involved in cellular trafficking and signaling. However, the specific role of CHMP4C in the progression of cardiac hypertrophy remains largely unknown. METHODS: Mouse models with CHMP4C knockout or cardiadc-specific overexpression were subjected to transverse aortic constriction surgery for 4 weeks. Cardiac morphology and function were assessed through histological staining and echocardiography. Confocal imaging and coimmunoprecipitation assays were performed to identify the direct target of CHMP4C. An EGFR (epidermal growth factor receptor) inhibitor was administrated to determine whether effects of CHMP4C on cardiac hypertrophy were EGFR dependent. RESULTS: CHMP4C was significantly upregulated in both pressure-overloaded mice and spontaneously hypertensive rats. Compared with wild-type mice, CHMP4C deficiency exacerbated transverse aortic constriction-induced cardiac hypertrophy, whereas CHMP4C overexpression in cardiomyocytes attenuated cardiac dysfunction. Mechanistically, the effect of CHMP4C on cardiac hypertrophy relied on the EGFR signaling pathway. Fluorescent staining and coimmunoprecipitation assays confirmed that CHMP4C interacts directly with EGFR and promotes lysosome-mediated degradation of activated EGFR, thus attenuating cardiac hypertrophy. Notably, an EGFR inhibitor canertinib counteracted the exacerbation of cardiac hypertrophy induced by CHMP4C knockdown in vitro and in vivo. CONCLUSIONS: CHMP4C represses cardiac hypertrophy by modulating lysosomal degradation of EGFR and is a potential therapeutic candidate for cardiac hypertrophy.

Gene-echocardiography: refining genotype-phenotype correlations in hypertrophic cardiomyopathy.

AIMS: This study aims to clarify the association between hypertrophic patterns and genetic variants in hypertrophic cardiomyopathy (HCM) patients, contributing to the advancement of personalized management strategies for HCM. METHODS AND RESULTS: A comprehensive evaluation of genetic mutations was conducted in 392 HCM-affected families using Whole Exome Sequencing. Concurrently, relevant echocardiographic data from these individuals were collected. Our study revealed an increased susceptibility to enhanced septal and interventricular septal thickness in HCM patients harbouring gene mutations compared with those without. Mid-septal hypertrophy was found to be associated predominantly with myosin binding protein C3 (MYBPC3) variants, while a higher septum-to-posterior wall ratio correlated with myosin heavy chain 7 (MYH7) variants. Mutations in MYH7, MYBPC3, and other sarcomeric or myofilament genes (troponin I3 [TNNI3], tropomyosin 1 [TPM1], and troponin T2 [TNNT2]) showed a relationship with increased hypertrophy in the anterior wall, interventricular septum, and lateral wall of the left ventricle. In contrast, alpha kinase 3 (ALPK3)-associated hypertrophy chiefly presented in the apical region, while hypertrophy related to titin (TTN) and obscurin (OBSCN) mutations exhibited a uniform distribution across the myocardium. Hypertrophic patterns varied with the type and category of gene mutations, offering valuable diagnostic insights. CONCLUSION: Our findings underscore a strong link between hypertrophic patterns and genetic variants in HCM, providing a foundation for more accurate genetic testing and personalized management of HCM patients. The novel concept of 'gene-echocardiography' may enhance the precision and efficiency of genetic counselling and testing in HCM.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

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.

Evaluation of Right Ventricular Myocardial Mechanics by 2- and 3-Dimensional Speckle-Tracking Echocardiography in Patients With an Ischemic or Non-ischemic Etiology of End-Stage Heart Failure.

Background: The aims of our study were (1) to assess the right ventricular (RV) myocardial mechanics by two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) in patients with an ischemic or non-ischemic etiology of end-stage heart failure (HF) and (2) to explore which RV index evaluated by 2D- and 3D-STE was the most powerful indicator for identifying the ischemic and non-ischemic etiologies of end-stage HF. Methods: A total of 96 patients with left ventricular ejection fraction (LVEF) < 30% were enrolled in our study: 42 patients (mean age, 52 ± 10 years; 9.5% female) with ischemic cardiomyopathy and 54 patients (mean age, 46 ± 14 years; 16.7% female) with non-ischemic cardiomyopathy. A total of 45 healthy subjects (mean age, 46 ± 13 years; 24.4% female) served as controls. The longitudinal strain of the RV free wall (RVFWLS) was determined by both 2D- and 3D-STE. Results: Compared to controls, patients with an ischemic or non-ischemic etiology of end-stage HF had lower 2D-RVFWLS, 3D-RVFWLS and RV ejection fraction (RVEF) values (P < 0.05). Patients with non-ischemic cardiomyopathies (NICMs) had significantly lower 3D-RVFWLS and RVEF values than in those with ischemic cardiomyopathies (ICMs), whereas 2D-RVFWLS and conventional RV function parameters did not differ between the two subgroups. RVEF was highly related to 3D-RVFWLS (r = 0.72, P < 0.001), modestly related to 2D-RVFWLS (r = 0.51, P < 0.001), and weakly related to conventional RV function indices (r = -0.26 to 0.46, P < 0.05). Receiver operating characteristic curve analysis revealed that the optimal 3D-RVFWLS cut-off value to distinguish NICM from ICM patients was -14.78% (area under the curve: 0.73, P < 0.001), while 2D-RVFWLS and conventional RV echocardiographic parameters did not. Conclusion: Our study demonstrated the superiority of 3D-RVFWLS over 2D-RVFWLS and conventional RV function indices in identifying the ischemic and non-ischemic etiologies of end-stage HF. These findings support the idea that 3D-RVFWLS may be a promising non-invasive imaging marker for distinguishing NICM from ICM.

3-Dimensional Versus 2-Dimensional STE for Right Ventricular Myocardial Fibrosis in Patients With End-Stage Heart Failure.

BACKGROUND: Longitudinal strain of the right ventricular (RV) free wall (RVFWLS) assessed by 2-dimensional (2D) speckle-tracking echocardiography (STE) has been recently demonstrated to correlate with the extent of RV myocardial fibrosis (MF). However, the value of 3-dimensional (3D) STE-derived strain parameters in predicting RV MF has not been investigated in patients with end-stage heart failure (HF). OBJECTIVES: This study aimed to determine which RV strain parameter assessed by 2D-STE and 3D-STE was the most reliable parameter for predicting RV MF in patients with end-stage HF against histological confirmation of MF. METHODS: A total of 105 consecutive patients with end-stage HF undergoing heart transplantation were enrolled in our study. The conventional RV function parameters, 2D-RVFWLS, and 3D-RVFWLS were obtained in these patients. The degree of MF was quantified by Masson trichrome staining in RV myocardial samples. The study population was divided into 3 groups according to the degree of MF on histology. RESULTS: Patients with severe MF had lower 3D-RVFWLS, 2D-RVFWLS, and conventional parameters of RV function compared with those with mild and moderate MF. RV MF strongly correlated with 3D-RVFWLS (r = -0.72; p < 0.001), modestly with 2D-RVFWLS (r = -0.53; p < 0.001), and weakly with conventional RV function parameters (r = -0.21 to -0.49; p < 0.01). 3D-RVFWLS correlated best with the degree of MF (r = -0.72 vs. -0.21 to -0.53; p < 0.05) compared with 2D-RVFWLS and conventional RV function parameters. 3D-RVFWLS had the highest accuracy for detecting severe MF (area under the receiver-operating characteristic curve: 0.90 vs. 0.24-0.80; p < 0.05) compared with 2D-RVFWLS and conventional RV parameters. The model with 3D-RVFWLS (R2 = 0.63; p < 0.001) was better in predicting the degree of RV MF than that with 2D-RVFWLS (R2 = 0.54; p < 0.001). CONCLUSIONS: 3D-RVFWLS may be the most robust echocardiographic measure for predicting the extent of RV MF in patients with end-stage HF.

Impaired left atrial function in clinically well heart transplant patients.

Left atrial (LA) enlargement is present in the majority of adult heart transplant (HT) recipients. We used speckle-tracking echocardiography to investigate whether LA phasic function in HT patients is altered and explored its relationship to HT-related clinical variables. This study evaluated LA function in 112 clinically well HT patients and 40 healthy controls. Clinical data included recipient age at HT, donor age, ischemia time, left ventricular function, and biochemical indicators. Atrial deformation and volume indices were measured with two-dimensional and three-dimensional speckle-tracking echocardiography, respectively. Components of phasic atrial function were calculated and correlations to clinical variables were explored. Compared with controls, HT patients had worse LA reservoir, conduit, and pump function. LA reservoir function of the bicaval group was better than the biatrial group, but differences did not persist after adjustment for potential confounders. Among patients with HT, those with lower LAS-peak had an older recipient age, larger LA volume, as well as worse left ventricular systolic function than those patients with higher LAS-peak. However, E/e', biochemical indicators and donor-related information were similar across the quartiles of LA function. In HT cohort, we observed impairment in all phases of LA function, and LA reservoir function was decreased independent of surgical technique. LAS-peak was associated with worse left ventricular systolic function, which suggested that LA function may play an important role in HT patients.

Assessment of Myocardial Fibrosis Using Two-Dimensional and Three-Dimensional Speckle Tracking Echocardiography in Dilated Cardiomyopathy With Advanced Heart Failure.

BACKGROUND: This study aimed to depict strain parameters derived from 2-dimensional (2D)- and 3-dimensional (3D) speckle tracking echocardiography and to explore which may best reflect myocardial fibrosis (MF) in dilated cardiomyopathy with advanced heart failure by comparing with histologic fibrosis. METHODS AND RESULTS: We analyzed 75 patients with dilated cardiomyopathy with advanced heart failure who underwent echocardiographic examination before heart transplantation. Strain parameters derived from 2D- and 3D speckle tracking echocardiography were as follows: left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and tangential strain (TS). The degree of MF was quantified using Masson's staining in left ventricular myocardial samples obtained from all patients. Seventy-five patients were divided into 3 groups according to the tertiles of histologic MF (mild, moderate, and severe MF groups). Patients with severe MF had lower 3DGLS, 3DGRS, 3DTS, and 2DGLS than those with mild and moderate MF. MF strongly correlated with 3DGLS (r = 0.72, P < .001), weakly with 3DGRS (r = -0.39, P = .001), 3DGCS (r = 0.30, P = .009), 3DTS (r = 0.47, P < .001), and 2DGLS (r = 0.44, P < .001), but did not correlate with 2DGCS and 2DGRS. Receiver operating characteristic analysis revealed that the area under the curve of 3DGLS for detecting severe MF was significantly larger than that of other strain parameters (0.86 vs 0.59-0.70, P < .05 for all). The multivariate linear regression models using 3DGLS (R2 = 0.76; Akaike information criterion = 331) was found to be a more accurate indicator to predict MF than that with 3DTS (R2 = 0.65, Akaike information criterion = 354) and 2DGLS (R2 = 0.66, Akaike information criterion = 352). CONCLUSIONS: Three-dimensional GLS may be an optimal surrogate marker for reflecting MF in patients with dilated cardiomyopathy with advanced heart failure.

Diagnostic value of myocardial strain using two-dimensional speckle-tracking echocardiography in acute cardiac allograft rejection: A systematic review and meta-analysis.

BACKGROUND: Two-dimensional speckle-tracking echocardiography (2D STE) has been demonstrated to have certain diagnostic utility in heart transplantation (HTX) patients with acute cardiac allograft rejection (ACAR). The aim of the systematic review and meta-analysis was to evaluate the diagnostic value of common strain parameters for ACAR in HTX patients. METHODS: After conducting a database search, we selected studies evaluating left ventricular global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and free wall right ventricular longitudinal strain (RV FW) in rejection group vs rejection-free group. RESULTS: After reviewing 886 publications, seven studies were finally included in the meta-analysis, representing the data of 1173 pairs of endomyocardial biopsy and echocardiographic examination. Heart transplantation patients with rejection had significantly lower GLS than rejection-free subjects (weighted mean difference -2.32 (95% CI, -3.41 to -1.23; P < .001). Heart transplantation patients with rejection had significantly lower CS than rejection-free subjects (weighted mean difference -2.49 (95% CI, -4.05 to -0.91; P = .0019). In addition, HTX patients with rejection also had significantly lower RV FW (weighted mean difference -4.90 (95% CI, -6.15 to -3.65; P < .001). CONCLUSIONS: The meta-analysis and systematic review demonstrate that myocardial strain parameters derived from 2D STE may be useful in detecting ACAR in HTX patients. The present results provide encouraging evidence to consider the routine use of GLS, CS, and RV FW as markers of graft function involvement during ACAR.

Multimodality imaging of a left atrial calcified amorphous tumor.

A cardiac calcified amorphous tumor (CAT) is an extremely rare non-neoplastic cardiac mass composed of calcium nodules in an amorphous background of fibrin materials. Herein, we report a case of CAT in the left atrium of an asymptomatic 72-year-old man who underwent multimodality imaging and successful resection of the CAT. Results of the present case suggest that multimodality imaging plays an important role in detecting cardiac CAT, determining the treatment plan and serial follow-ups for the patients after the treatment.

Pseudoaneurysm of the non-coronary sinus of Valsalva: A rare complication of percutaneous coronary intervention.

Pseudoaneurysm of the non-coronary sinus of Valsalva is an exceptionally rare but potentially fatal complication of percutaneous coronary interventions (PCI). Here, we report a case of a 53-year-old man with pseudoaneurysm of the non-coronary sinus of Valsalva following PCI who presented with recurrent chest pain and was treated successfully by closure of the orifice of the pseudoaneurysm and coronary artery bypass grafting.