Prognostic value of left atrial mechanics in cardiac light-chain amyloidosis with preserved ejection fraction: a cohort study.

BACKGROUND: Light-chain amyloidosis is a plasma cell disorder associated with poor outcomes, especially when the heart is involved. The characteristics of left atrial (LA) function and its prognostic implications in cardiac amyloidosis (CA) have not been fully investigated. METHODS: Between April 2014 and June 2019, 93 patients with a diagnosis of CA, normal left ventricular ejection fraction (LVEF) and sinus rhythm were included. Their clinical, baseline echocardiographic and follow-up data were investigated. LA function, including LA strain and strain rate, was assessed using 2D speckle tracking echocardiography in different LA functional phases. RESULTS: Among all patients, 38 (40.9%) died. Multivariate Cox regression analyses showed that LA mechanics regarding LA reservoir and booster pump functions were independent predictors for overall survival. Traditional echocardiographic parameters for LA structure like LA volume index and LA width were not associated with mortality. Moreover, LA strain and strain rate in reservoir and contractile phases improved the discrimination and goodness of fit of the conventional prognostic model, the Mayo criteria 2004 and 2012, in our study population. Decreased LA mechanics were associated with impaired left ventricular (LV) systolic and diastolic function, and LA reservoir and contractile functions were associated with LA structure. CONCLUSIONS: Assessment of LA reservoir and contractile functions via 2D speckle tracking echocardiographic LA mechanical indices provide clinical and prognostic insights into cardiac light-chain amyloidosis patients, especially those with preserved EF and sinus rhythm. Emphasizing the monitoring of LA function may be beneficial for the prognosis prediction of CA.

Electrophysiological, structural, and functional disorders in patients with inflammatory cardiomyopathy secondary to inflammatory myopathy.

BACKGROUND: Inflammatory cardiomyopathy (IC) is a syndrome with chronic myocarditis and cardiac remodeling. This study aimed to explore predicting factors of adverse outcomes in patients with IC secondary to idiopathic inflammatory myopathy (IIM-IC). METHODS: By means of a single-center retrospective study, 52 patients with IIM-IC at Peking Union Medical College Hospital were identified from January 1999 to June 2019. Electrocardiogram and echocardiography data were analyzed for the primary outcome (defined as all-cause death) and secondary outcomes (defined as re-hospitalization of heart failure and all-cause death), using regression and survival analysis. RESULTS: The prevalence of atrial fibrillation, ventricular tachycardia, Q-wave abnormality, left ventricular conduction abnormalities, and reduced left ventricular ejection fraction (LVEF) (≤40%) were 65.4%, 67.3%, 67.3%, 61.6%, and 50.5%. After a median follow-up of 2 years (IQR 0.8-3.0), 26 cases were readmitted due to heart failure. Twenty-two deaths were recorded, including 20 cardiogenic deaths. Among the patients with adverse events, the incidence of poor R-wave progression, low-voltage of the limb leads, Q-wave abnormality, QRS duration >130 ms, left ventricular enlargement, and impaired systolic function were higher. Kaplan-Meier analysis showed that Q-wave abnormality, limb leads low-voltage, LVEF ≤40%, and left ventricular end-diastolic dimension >60 mm were correlated with shorter survival. However, multivariate Cox regression analysis revealed that only Q-wave abnormality (HR = 12.315) and LVEF ≤40% (HR = 5.616) were independent risk factors for all-cause death. CONCLUSION: Q-wave abnormality and reduced LVEF are predictive of poor prognosis in patients with IIM-IC.

IRAK-M deletion aggravates acute inflammatory response and mitochondrial respiratory dysfunction following myocardial infarction: A bioinformatics analysis.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Interleukin-1 receptor associated kinase (IRAK)-M is a regulator of Toll-like receptor mediated inflammatory responses and plays an important role in the pathophysiologic processes of acute MI. We aimed to explore the effect of IRAK-M on regulating biological function and molecular interactions post-MI through bioinformatics analysis. Datasets from the Gene Expression Omnibus database were used to identify characteristics of IRAK-M expression in MI patients. The expression of IRAK-M was upregulated in MI patients and altered in a time-dependent manner during MI progression. Enrichment analysis showed that biological processes related to inflammatory response and leukocyte activation were markedly activated in MI patients with upregulated IRAK-M. Furthermore, we constructed MI model using wildtype and IRAK-M-/- mice and performed proteomics analysis of infarcted hearts. Functional enrichment of proteomics data indicated that IRAK-M deletion aggravated a series of pathophysiologic functions, such as acute inflammatory response, macrophage activation and mitochondrial dysfunction. S100A8/A9 acted as the central molecule in the above functions based on the protein-protein interaction network and was significantly elevated in IRAK-M-/- infarcted hearts at both the protein and mRNA levels. In conclusion, IRAK-M functioned as an essential regulator in pathophysiologic processes post-MI, exerting effects not only on controlling acute inflammatory responses but also on mediating mitochondrial respiratory function based on integrated bioinformatics analysis. SIGNIFICANCE: In this study, we combined microarray datasets and a proteomics approach to explore the effect of IRAK-M on mediating biological processes and systemic molecular interactions following MI. Our data firstly showed that IRAK-M is involved in ATP synthesis and mitochondrial respiratory chain complex during MI progression. S100A8/A9 acted as the central molecule in above regulatory network and displayed a tight connection with IRAK-M. The findings provide novel evidence and clues for understanding the complex roles and molecular mechanisms of IRAK-M in the development of MI.

Prognostic Value of Left Atrial Strain in Heart Failure: A Systematic Review and Meta-Analysis.

Background: Heart failure (HF) is a global health problem with high morbidity and mortality. Recently, the association between peak atrial longitudinal strain (PALS) and clinical outcomes of HF has gained increasing attention. Our aim was to systematically assess the prognostic value of PALS for adverse events in HF. Methods: PubMed, Embase, and Scopus databases were systematically searched from inception to 30 April 2022. Studies in which PALS was assessed to predict adverse outcomes in adult patients with HF were included. Study selection, quality assessment, and data extraction were performed independently by two authors. The primary endpoints were all-cause death and cardiac hospitalization. Results: Among 7,787 patients in 17 included studies, 3,029 (38.9%) experienced the primary endpoint. Patients with events had lower PALS than those without events [weighted mean difference (WMD) 6.17, 95% confidence interval (CI) 3.09-9.26, p < 0.001]. Each unit increment of PALS was independently associated with decreased risk for the primary endpoint [hazard ratio (HR) 0.96, 95% CI 0.94-0.98, p < 0.001]. The addition of PALS significantly improved the predictive power of conventional risk models [net reclassification index (NRI) 0.22, 95% CI 0.06-0.39, p = 0.008]. Conclusion: Peak atrial longitudinal strain was an independent predictor for all-cause mortality and cardiac hospitalization in patients with HF, highlighting the clinical importance of left atrial (LA) deformation in the prognosis of HF. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42020185034].

Predictive Value of Echocardiographic Strain for Myocardial Fibrosis and Adverse Outcomes in Autoimmune Diseases.

Background: Myocardial fibrosis is an important pathophysiologic mechanism of cardiac involvement that leads to increased mortality in patients with autoimmune diseases (AIDs). The aim of this study was to evaluate the association between myocardial strain from speckle-tracking echocardiography (STE) and fibrosis on cardiovascular magnetic resonance (CMR) and to further explore their prognostic implications in patients with AIDs. Methods: We prospectively included 102 AIDs patients with clinically suspected cardiac involvement and 102 age- and sex-matched healthy individuals. Patients underwent CMR for evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) and T1 mapping. A semiquantitative evaluation based on the extent of LGE was used to calculate the total (tLGEs) and segmental (sLGEs) LGE score. Global longitudinal strain (GLS) was evaluated by STE in all subjects. All patients were regularly followed up every 6 months. The primary endpoint was the composite incidence of all-cause death and cardiovascular hospitalization. Results: Compared to healthy controls, AIDs patients had impaired GLS (-17.9 ± 5.1% vs. -21.2 ± 2.5%, p < 0.001). LGE was detected in 70% of patients. Patients with LGE presented worse GLS (-17.1 ± 5.3% vs. -19.6 ± 4.1%, p = 0.018) than those without LGE. On multivariate logistic analysis, GLS ≥ -15% was an independent predictor of LGE presence (OR = 4.98, 95%CI 1.35-18.33, p = 0.016). Moreover, a marked and stepwise impairment of segmental longitudinal strain (-19.3 ± 6.6 vs. -14.9 ± 6.5 vs. -8.9 ± 6.3, p < 0.001) was observed as sLGEs increased. During a median follow-up time of 25 months, 6 patients died, and 14 patients were hospitalized for cardiovascular reasons. Both GLS ≥ -15% (HR 3.56, 95%CI 1.28-9.86, p = 0.015) and tLGEs ≥ 6 (HR 4.13, 95%CI 1.43-11.92, p = 0.009) were independently associated with the primary endpoint. Conclusions: In AIDs patients, impaired myocardial strain on STE could reflect the presence and extent of myocardial fibrosis and provide incremental prognostic value in addition to LGE in the prediction of adverse outcomes.

The quest for diagnostic approaches of cardiac involvement in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases characterized by inflammation of skeletal muscle, primarily manifesting as chronic muscle weakness. Extramuscular organs can also be affected. Cardiac involvement is one of the visceral organ damages whose prevalence is underestimated and is a marker of poor prognosis leading to irreversible dysfunction or even death. Although early and accurate recognition of cardiac involvement remains a key barrier to improving survival in PM/ DM patients, considerable progress has been made, and an overview will be provided in this review. The new concept of multimodality imaging, which involves an integrated approach of echocardiography (Echo), cardiac magnetic resonance and sometimes positron emission tomography (PET), can facilitate diagnosis. The development of ultrasound technology, including strain analysis, stress Echo and contrast-enhanced Echo, helps disclose early cardiac dysfunction more sensitively than conventional Echo. Cardiac magnetic resonance unveils silent, acute or chronic myocarditis in PM/DM and is used to monitor treatment efficacy due to its excellent tissue characterization. PET can be useful thanks to the appearance of new tracers that can eliminate the effects of glucose uptake by normal cardiomyocytes. The sensitivity of endomyocardial biopsy may be increased by targeted sampling with the guidance of cardiac imaging. Troponin I is specific to cardiac injury, and investigations into antibodies against cardiac tissue are being carried out. Disease-specific mechanisms and therapies are also discussed to give more insights into cardiac involvement in PM and DM.

Usefulness of Myocardial Strain and Twist for Early Detection of Myocardial Dysfunction in Patients With Autoimmune Diseases.

Cardiac involvement in autoimmune diseases (AD) is common but underdiagnosed due to a lack of sensitive imaging methods. We aim to evaluate the characteristics of left ventricular (LV) systolic dysfunction in patients with AD using deformational parameters from 2-dimensional speckle-tracking echocardiography (STE). We retrospectively enrolled 86 AD patients and 71 healthy controls. All subjects underwent transthoracic echocardiography and STE to analyze LV strain and twist. A twist-radial displacement loop was constructed to investigate the relation between LV contractility and dimension. In AD patients, 68 had preserved LV ejection fraction (EF ≥ 50%), and 18 had reduced LVEF (EF < 50%). The patients with preserved LVEF exhibited significantly lower values of global longitudinal, circumferential, and radial strain than controls (-19.11 ± 4.18 vs -21.49 ± 2.53%, -25.17 ± 5.04% vs -27.37 ± 2.87%, 17.68 ± 5.69% vs 21.17 ± 6.44%, respectively; all p <0.01) and a marked attenuation in peak twist (14.24 ± 5.57 vs 18.10 ± 5.97, p <0.01) attributed to impaired apical rotation (9.03 ± 5.17 vs 12.79 ± 5.99, p <0.01). AD patients were more likely to present with abnormal loop types with flat ascending slope and delayed peak twist time. In conclusion, abnormal strain and twist precede deterioration in LVEF, suggesting early myocardial involvement in AD. STE can be used as a good alternative for early detection of myocardial dysfunction in AD patients.

Left ventricular strain is associated with acute postoperative refractory hypotension in patients with constrictive pericarditis and preserved ejection fraction.

BACKGROUND: Pericardiectomy is an effective treatment for constrictive pericarditis (CP). Early postoperative complications such as refractory hypotension and congestive heart failure occur in these patients and are associated with increased morbidity and mortality. We hypothesized that left ventricular (LV) myocardial strain measured by two-dimensional speckle tracking echocardiography (2DSTE) could identify early cardiac dysfunction and relate to acute postoperative adverse events in CP patients. METHODS: Forty-four CP patients with preserved left ventricular ejection fraction (LVpEF, 64%±8%) and 44 age- and sex-matched controls were enrolled. Conventional 2DSTE was performed before pericardiectomy. Global and segmental peak systolic strain values were measured. The primary endpoint was a composite of postoperative refractory hypotension, congestive heart failure and cardiogenic death. Refractory hypotension was defined as hypotension requiring prolonged usage of intravenous inotropic medication (IVIM) (≥2 days). RESULTS: Postoperative refractory hypotension occurred in 26 cases, and no patients experienced congestive heart failure or cardiogenic death. Compared to controls, CP patients had decreased absolute global and segmental circumferential strain (CS), radial strain (RS), and longitudinal strain (LS) except septal LS. Patients with refractory hypotension exhibited lower epicardial CS (P=0.04). Epicardial CS was an independent risk factor correlated with postoperative adverse outcome [P=0.014, OR =1.236 (1.044-1.464)] while LVEF was not. Lower absolute value of epicardial CS was related to higher (P=0.02) and longer usage of intravenous furosemide (P=0.04) to keep negative fluid balance perioperatively. CONCLUSIONS: LV strain value is markedly reduced in patients with CP and LVpEF. Lower preoperative epicardial CS value is associated with greater risk of early refractory hypotension and more aggressive fluid management.

Short-term and 1-year outcomes after MitraClip therapy in functional versus degenerative mitral regurgitation patients: a systematic review and meta-analysis.

BACKGROUND: Differences in short-term and 1-year outcomes of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) remain unclear. We performed a systematic review and meta-analysis to investigate the safety and efficacy of MitraClip (MC) in patients with different MR etiologies. METHODS: This study systematically searched three common databases for studies on MC therapy until November 2017. The studies meeting the standard inclusion criteria were included. The data at baseline, short-term and 1-year clinical and echocardiographic outcomes were obtained and analyzed. All data were checked by another reviewer. RESULTS: Thirteen studies totalling 2,351 patients investigating the short-term and 1-year outcomes of MC in patients with functional MR (FMR) versus degenerative MR (DMR) were included for further analysis. FMR patients presented a higher risk profile at baseline. There was no difference in short-term outcomes between DMR and FMR for post-procedural MR grade 0-2 (76.8% vs. 77.1%; P=0.428), mean trans-mitral gradient (3.92 vs. 3.50 mmHg; P=0.098), 30-day mortality rate (0.05% vs. 0.03%; P=0.118) and 30-day NYHA I-II (85.3% vs. 78.7%; P=0.211). FMR patients had a higher rate of acute procedural success compared to the DMR patient group (91.2% vs. 95.2%; P=0.016). A greater portion of DMR patients implanted two or more MCs than the FMR patients (41.4% vs. 35.7%; P=0.043). For the 1-year outcomes, no difference was found in the mortality rate (13.0% vs. 15.2%; P=0.268) and proportion of patients with post-procedural MR grades 0-2 (75.0% vs. 80.7%; P=0.106). CONCLUSIONS: Despite a higher risk profile in FMR patients, the short-term and 1-year outcomes were not significantly different. We conclude that MC therapy is similar between FMR and DMR patients until 1-year follow-up. Large randomized trials are warranted to fully and further assess the clinical impact of the procedure in these two MR etiologies over a longer period of time.