Electromagnetic field and cardiovascular diseases: A state-of-the-art review of diagnostic, therapeutic, and predictive values.

Despite encouraging advances in early diagnosis and treatment, cardiovascular diseases (CVDs) remained a leading cause of morbidity and mortality worldwide. Increasing evidence has shown that the electromagnetic field (EMF) influences many biological processes, which has attracted much attention for its potential therapeutic and diagnostic modalities in multiple diseases, such as musculoskeletal disorders and neurodegenerative diseases. Nonionizing EMF has been studied as a therapeutic or diagnostic tool in CVDs. In this review, we summarize the current literature ranging from in vitro to clinical studies focusing on the therapeutic potential (external EMF) and diagnostic potential (internal EMF generated from the heart) of EMF in CVDs. First, we provided an overview of the therapeutic potential of EMF and associated mechanisms in the context of CVDs, including cardiac arrhythmia, myocardial ischemia, atherosclerosis, and hypertension. Furthermore, we investigated the diagnostic and predictive value of magnetocardiography in CVDs. Finally, we discussed the critical steps necessary to translate this promising approach into clinical practice.

Correlations between geomagnetic field and global occurrence of cardiovascular diseases: evidence from 204 territories in different latitude.

BACKGROUND: The correlation between stable geomagnetic fields and unstable geomagnetic activities with mortality, incidence, and prevalence of cardiovascular diseases (CVDs) remains ambiguous. METHOD: To investigate the correlations between geomagnetic field (GMF) intensity and geomagnetic disturbance (GMD) and CVDs events in global, long-period scale, global and 204 countries and territories were included on the base of 2019 Global Burden of Disease study (GBD 2019). Data of GMF intensity, GMD frequency, CVDs events, weather and health economic indicators from 1996 to 2019 of included locations were collected. Linear regression and panel data modelling were conducted to identify the correlations between GMF intensity and CVDs events, multi-factor panel data analysis was also generated to adjust the effect of confounding factors. RESULTS: For the average data during 1996-2019, linear regression model revealed consistent positive correlations between total GMF (tGMF) intensity and mortality of total CVDs [coef = 0.009, (0.006,0.011 95%CI)], whereas negative correlations were found between horizonal GMF (hGMF) intensity and total CVD mortality [coef = -0.010 (-0.013, -0.007 95%CI)]. When considering the time trend, panel data analysis still demonstrated positive correlation between tGMF and total CVDs mortality [coef = 0.009, (0.008,0.009 95%CI)]. Concurrently, the hGMF negatively correlated with total CVDs mortality [coef = -0.008, (-0.009, -0.007 95%CI)]. When the panel models were adjusted for confounding factors, no reverse of correlation tendency was found between tGMF, hGMF and CVDs events. In high-income territories, positive correlation was found between geomagnetic storm (GMS) frequency and mortality of total CVDs [coef = 14.007,(2.785, 25.229 95%CI)], however, this positive trend faded away gradually with the latitude decreasing from polar to equator. CONCLUSIONS: Stable and long-term horizontal component of GMF may be beneficial to cardiac health. Unstable and short-term GMF called GMD could be a hazard to cardiac health. Our results suggest the importance of regular GMF in maintaining cardio-health state and the adverse impacts of GMD on cardiac health.

Treating patients with excessively large annuli with self-expanding transcatheter aortic valves: insights into supra-annular structures that anchor the prosthesis.

BACKGROUND: Some patients referred for transcatheter aortic valve replacement (TAVR) have excessively large annuli (ELA) without device options according to current sizing charts. This retrospective study aims to summarize the presentation and outcomes of ELA patients receiving first-generation self-expanding valves. METHODS: The TAVR database was reviewed in search for cases of self-expanding valves. Patients who had annuli exceeding the perimeter limit on the device sizing chart were referred to as the ELA group. Patients who had annuli within the range covered by the two largest sizes and received the corresponding valve size served as the control group (CG). Baseline, procedures, outcomes, and imaging characteristics on multislice computed tomography (MSCT), such as native anatomy and postimplant stent geometry, were compared. RESULTS: A total of 28 patients were included in the ELA group and 82 in the CG. The patients in the ELA group were younger than those in the CG (72.5 ± 6.2 vs. 75.4 ± 5.8 years, P = 0.03). The median intended perimeter oversizing in relation to the annulus in the ELA group was much smaller than in the CG (-0.4 [-4.6, 4.1] % vs. 16.1 [11.7, 20.8] %, P < 0.01). The calcium burden in the aortic root was around 1.3-fold greater in the ELA group than the CG (756.0 [534.5, 1670.9] vs. 582.1 [310.3, 870.9] mm3, P = 0.01). The need for second valve implantation was higher in ELA (21.4% vs. 12.2%, P = 0.23) but no valve embolization was encountered. The 1­year follow-up was comparable, including >mild paravalvular leak. CONCLUSION: Under cautious patient selection using MSCT, TAVR with self-expanding valves in patients with ELA appears feasible. Supra-annular structures likely provide the extra anchoring.

Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

OBJECTIVES: We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis. BACKGROUND: TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies. METHODS: Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon. RESULTS: A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days. CONCLUSIONS: Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

Differences in metabolic profiles between bicuspid and tricuspid aortic stenosis in the setting of transcatheter aortic valve replacement.

BACKGROUND: To explore why bicuspid aortic stenosis has certain clinical differences from the tricuspid morphology, we evaluated the metabolomics profile involved in bicuspid aortic valve (BAV) aortic stenosis prior to and after transcatheter aortic valve replacement (TAVR) in comparison with tricuspid aortic valve (TAV). METHODS: In this TAVR cohort with prospectively collected data, blood samples were obtained before TAVR valve deployment and at the 7th day after TAVR, which were then sent for liquid and gas chromatography-mass spectrometry detection. Besides comparisons between BAV and TAV, BAV patients were also divided in subgroups according to baseline hemodynamics (i.e. maximal transaortic velocity, Vmax) and post-procedural reverse left ventricular (LV) remodeling (i.e. the change in LV mass index from baseline, ∆LVMI) for further analysis. Metabolic differences between groups were identified by integrating univariate test, multivariate analysis and weighted correlation network analysis algorithm. RESULTS: A total of 57 patients were enrolled including 33 BAV patients. The BAV group showed lower arginine and proline metabolism both before and post TAVR than TAV represented by decreased expression of L-Glutamine. In BAV subgroup analysis, patients with baseline Vmax > 5 m/s (n = 11) or the 4th quartile of change in ∆LVMI at one-year follow-up (i.e. poorly-recovered LV, n = 8) showed elevated arachidonic acid metabolism compared with Vmax < 4.5 m/s (n = 12) or the 1st quartile of ∆LVMI (i.e. well-recovered LV, n = 8) respectively. CONCLUSIONS: Difference in arginine and proline metabolism was identified between BAV and TAV in TAVR recipients. Elevated arachidonic acid metabolism may reflect more severe baseline hemodynamics and worse LV reserve remodeling after TAVR in BAV.

The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis Having Coronary Cusp Fusion versus Mixed Cusp Fusion Nonraphe Bicuspid Aortic Valve.

OBJECTIVES: We aimed to assess the procedural and clinical results of transcatheter aortic valve replacement (TAVR) for nonraphe bicuspid aortic stenosis (AS) with coronary vs mixed cusp fusion. BACKGROUND: It remains unclear whether cusp fusion morphology affects TAVR outcomes in patients with nonraphe bicuspid AS. METHODS: This retrospective study enrolled consecutive patients with severe symptomatic AS and type-0 bicuspid aortic valve, who underwent TAVR at our institution between 2012 and 2017. TAVR outcomes were defined based on the Valve Academic Research Consortium-2 recommendations. RESULTS: Compared to patients with mixed cusp fusion (44/71), those with coronary cusp fusion (27/71) had a larger ellipticity index for the aortic annulus (21.9% ± 9.0% vs 15.6% ± 9.3%, p=0.007) and increased left ventricular outflow tract obstruction (31.1% ± 9.4% vs 26.9% ± 7.5%, p=0.04) but comparable rates of second valve implantation (15.9% vs 14.8%), mild paravalvular leakage (PVL, 38.5% vs 30.2%), permanent pacemaker implantation (PPM, 25.9% vs 15.9%), and 30-day mortality (7.4% vs 6.8%). Use of a first-generation transcatheter heart valve was associated with higher risk for mild PVL (odds ratio (OR) = 4.37; 95% confidence interval (95% CI) = 1.14-16.75; p=0.03) but not PPM (OR = 0.77; 95% CI = 0.22-2.62; p=0.67), whereas a larger oversizing ratio tended to be associated with a higher PPM rate (OR = 1.49; 95% CI = 0.46-4.86; p=0.51) but lower incidence of mild PVL (OR = 0.51; 95% CI = 0.19-1.35; p=0.17). CONCLUSIONS: In AS patients with type-0 bicuspid valves, cusp fusion morphology does not affect the procedural or clinical results of TAVR. Use of second-generation transcatheter heart valves may provide more favorable results in such patients. This trial is registered with NCT01683474.

The triglyceride paradox in the mortality of coronary artery disease.

BACKGROUND: The role of triglyceride (TG) in secondary prevention of patients with coronary artery disease (CAD) was debated. In the present study, we assessed the association between admission TG levels and long-term mortality risk in CAD patients. METHODS: A retrospective analysis was conducted from a single registered database. 3061 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission serum TG levels. The primary end point in this study was all-cause mortality and the secondary end point was cardiovascular mortality. RESULTS: The mean follow-up time was 26.9 ± 13.6 months and death events occurred in 258 cases and cardiovascular death events occurred in 146 cases. Cumulative survival curves indicated that the risk of all-cause death decreased with increasing TG level (Tertile 1 vs. Tertile 2 vs. Tertile 3 = 10.3% vs. 8.6% vs. 6.3%, log rank test for overall p = 0.001). Cox regression analysis showed an independent correlation between TG level and risk of all-cause mortality [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.86] and cardiovascular mortality (HR 0.67, 95% CI 0.51-0.89) in total patients with CAD. Subgroup analysis found the similar results in patients with acute coronary syndrome and acute myocardial infarction. CONCLUSIONS: This study found an inverse association between TG levels and mortality risk in CAD patients, which suggests that the "TG paradox" may exist in CAD patients. TRIAL REGISTRATION: ChiCTR, ChiCTR-OOC-17010433 . Registered 17 February 2017 - Retrospectively registered.

Permanent pacemaker implantation after transcatheter aortic valve replacement in bicuspid aortic valve patients.

BACKGROUND: Studies of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) specifically for bicuspid aortic valve (BAV) patients are lacking. We aim to delineate possible aspects that might affect the incidence of PPI in a retrospective cohort of BAV patients treated with early-generation self-expanding devices. METHODS: A total of 80 patients with bicuspid morphology who successfully underwent TAVR by self-expanding devices without prior PPI were included. Baseline clinical, echocardiographic, and angiographic characteristics, procedural and post-procedural details were collected. RESULTS: The incidence of PPI after early-generation self-expanding valves in this BAV cohort was 26.3%. Baseline characteristics were comparable between patients requiring PPI post-TAVR or not. Perimeter oversizing greater than 20% significantly increased the risk of PPI compared with an oversizing of 10-20% (OR 5.08 [1.22, 21.07], P = 0.03). The proportion of patients with a depth of implantation greater than 6 mm was significantly higher in those who required PPI (82.4% vs 54.3%, P = 0.04). When testing the impact of depth of implantation >6 mm and oversizing in different morphologies, only in type 1 bicuspid patients and by oversizing>20% increased the risk of PPI (OR 12.00 [1.25, 115.36], P = 0.03) compared with an oversizing of 10-20%. CONCLUSIONS: Excessive perimeter oversizing in relation to aortic annulus and depth of implantation greater than 6 mm should be avoided to improve PPI post-TAVR for BAV patients receiving self-expanding devices, especially for type 1 BAV.

Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement.

The imaging finding of hypo-attenuated leaflet thickening (HALT) on bioprosthesis after transcatheter aortic valve replacement (TAVR) has been reported. The underlying mechanism is not clear, but leaflet thrombosis is speculated to be the cause. Heterogeneous antiplatelet responses may play a role in the process. This is a prospective, single-center pilot study in patients who received successful TAVR from June 2012 to November 2016. HALT on post-procedural multi-detector computed tomography. We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01). We found that rs4244285 G>A polymorphism of the CYP2C19 gene was associated with the risk of HALT in the overdominant model (OR 4.00 [1.15-13.97], P = 0.02 for GA vs. GG+AA) adjusted by sex and the presence of pre-TAVR AF. Antiplatelet drug resistance is a reasonable possibility involved in HALT. Potential directions were suggested in polymorphisms of the CYP2C19 gene.

Transcatheter aortic valve implantation with the self-expandable venus A-Valve and CoreValve devices: Preliminary Experiences in China.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been demonstrated to be an effective alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis who are deemed high risk or inoperable. Currently, TAVI procedures in China mostly make use of the domestic Venus A-Valve and the CoreValve; however, there is no data on their comparative performance. METHODS: Consecutive patients undergoing TAVI with the aforementioned devices were included. The outcomes were reported according to the Valve Academic Research Consortium-2 (VARC) definitions. RESULTS: A total of 54 TAVI procedures were performed, 27 with the CoreValve and the other 27 with the Venus A-Valve. An additional valve was required in 4 (14.8%) and 3 (11.1%) patients, and the VARC-2 device success rates were 81.5 and 85.2%, respectively. The incidences of common complications were similar, except for the significantly less frequent pacemaker insertion in the Venus A-Valve group (7.4 vs. 37.0%, P = 0.03). Within 30 days, 2 (3.7%) patients died, 1 in each group, and both had a bicuspid aortic valve (BAV). No other serious complications, such as annular rupture, coronary obstruction and aortic dissection, occurred in the 32 BAV patients treated with the Venus A-Valve (14) or the CoreValve (18). After 2-years of follow-up, there was no significant difference between CoreValve group and Venus-A group (11.1 vs. 7.4%, P = 0.64). CONCLUSION: TAVI with the domestic Venus A-Valve is feasible, safe, and can produce favorable short-term outcomes comparable to those with the CoreValve in inoperable or high-risk patients with tricuspid and bicuspid aortic valve stenosis. © 2017 Wiley Periodicals, Inc.

The relationship between chronic obstructive pulmonary disease and transcatheter aortic valve implantation--A systematic review and meta-analysis.

OBJECTIVE: The present study was performed to investigate the relationship between chronic obstructive pulmonary disease (COPD) and transcatheter aortic valve implantation (TAVI). BACKGROUND: Controversies regarding the relationship between COPD and TAVI have intensified. METHODS: A literature review of the PubMed online database was performed, and articles published between January 1, 2002 and March 20, 2015 were analyzed. Random-effect and fixed-effect models were used, depending on the between-study heterogeneity. RESULTS: A total of 28 studies, involving 51,530 patients, were identified in our review. The burden of COPD ranged from 12.5% to 43.4%, and COPD negatively impacted both short-term and long-term all-cause survival (30 days: odds ratio [OR], 1.43, 95% CI, 1.14-1.79; >2 years: hazard ratio [HR], 1.34, 95% CI, 1.12-1.61). COPD was also associated with increased short-term and mid-term cardiac-cause mortality (30 days: OR, 1.29, 95% CI, 1.02-1.64; 1 year: HR: 1.09, 1.02-1.17). Moreover, COPD (OR, 1.97, 95% CI, 1.29-3.0) predicted post-TAVI acute kidney disease. Importantly, chronic kidney disease (CKD) (HR, 1.2, 95% CI, 1.1-1.32) and the distance of the 6 minute walk test (6MWT) (HR, 1.16, 1.06-1.27) predicted TAVI futility in patients with COPD. CONCLUSION: COPD is common among patients undergoing TAVI, and COPD impacts both short- and long-term survival. COPD patients, who had a lower BMI, shorter distance of 6MWT and CKD, were at higher risk for TAVI futility.

Target lesion calcification and risk of adverse outcomes in patients with drug-eluting stents. A meta-analysis.

BACKGROUND: Studies focusing on the relationship between calcified lesions and adverse outcomes in the drug-eluting stent (DES) era have presented inconsistent conclusions. The aim of this study was to assess the association between target lesion calcification and adverse outcomes in patients undergoing DES implantation. METHODS: A systematic search was conducted on Medline (Ovid SP, 1946 to 28 February 2014), Embase (Ovid SP, 1974 to 28 February 2014), and the Chinese Biomedical Literature Database (CBM, 1978 to 28 February 2014). Abstracts from the 2012 and 2013 scientific meetings of the American College of Cardiology and American Heart Association were manually searched. Hazard ratios (HRs) were pooled using a fixed or random effects model in the context of heterogeneity. RESULTS: A total of 13 studies comprising 66,361 patients were included. Target lesion calcification was associated with an increased risk of all-cause mortality (HR = 1.41; 95 % CI = 1.27-1.56), cardiac death (HR = 1.97; 95 % CI = 1.68-2.31), myocardial infarction (HR = 1.33; 95 % CI = 1.13-1.57), target lesion revascularization (TLR; HR 1.47, 95 % CI 1.18-1.83), stent thrombosis (HR 1.63, 95 % CI 1.36-1.96), and major cardiovascular events (HR 1.37, 95 % CI 1.19-1.58). The results proved robust in subgroup analyses for TLR and stent thrombosis. CONCLUSION: Calcified target lesions are risk factors for adverse outcomes in the DES era. Further studies focusing on comprehensive therapy in patients with coronary calcification are urgently needed.

Subclassification of left ventricular hypertrophy based on dilation stratifies coronary artery disease patients with distinct risk.

BACKGROUND: A new 4-tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown. METHODS: All the 2297 patients with CAD included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated, and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort was divided into five groups according to LV geometry: (i) eccentric nondilated LVH (normal LVM/EDV((2/3)) and EDV/BSA) (n = 129); (ii) eccentric dilated LVH (normal LVM/EDV((2/3)) with increased EDV/BSA) (n = 222); (iii) concentric nondilated LVH (increased LVM/EDV((2/3)) with normal EDV/BSA) (n = 441); (iv) concentric dilated LVH (increased LVM/EDV((2/3)) and EDV/BSA) (n = 118); and (v) normal LV mass (n = 1387). RESULTS: Dilated LVH was associated with a higher event rates of all-cause death (eccentric 13·1% vs. 3·1%; concentric 13·6% vs. 8·4%) and composite events (eccentric: 17·6% vs. 5·4%; concentric: 18·6% vs. 12·7%) compared with nondilated LVH. While eccentric nondilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0·68, 95% confidential interval (CI) 0·25-1·85; composite events: RR 0·75, 95% CI 0·36-1·58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2·752 [95% CI 1·749-4·328], P < 0·001) and composite events (aHR 2·462 [95% CI 1·688-3·592], P < 0·001). CONCLUSION: In patients with CAD, dilated LVH and nondilated LVH provide distinct prognostic information. Eccentric nondilated LVH does not predict adverse outcomes.

Short communication: Amino trap column improves the separation of methylimidazoles, 5-hydroxymethyl-2-furaldehyde, and sugars in Maillard reaction.

A simultaneous analysis of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde in the Maillard reaction was improved by use of an amino trap column. Analysis was carried out by using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) coupled with an amino trap column. The amino trap column was a useful tool to improve the separation of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde. This technique is useful for simultaneous analysis of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde in risk assessment for dairy products.