Radioprotective strategies for interventional echocardiographers during structural heart interventions.

OBJECTIVE: We investigated radioprotective strategies for the interventional echocardiographer (IE) during structural heart interventions in comparison with the interventional cardiologist (IC). BACKGROUND: Structural heart interventions are expanding in complexity with increased reliance on IE. Recent reports have demonstrated concerning exposure and higher radiation to the IE. METHODS: We monitored 32 structural interventions - 19 transcatheter aortic valve replacements (TAVR), 6 transcatheter mitral valve repairs, 5 paravalvular leak closures, and 2 atrial septal defect closures. Seventeen utilized transesophageal echocardiography (TEE) while 15 used transthoracic echocardiography (TTE). Members of the IC and IE teams wore multiple dosimeters on different sites of the body to measure radiation dose to the total body, lens of the eye, and hand. During each case, IE utilized dedicated radiation shielding. RESULTS: Mean doses were higher for the primary IC than the primary IE: IC#1-99, 222, 378; IE#1-48, 52, 416 (body, lens, and hand doses in µSv). IE radioprotective strategies were able to reduce body and lens doses compared to IC during both TTE and TEE-guided procedures. Hand equivalent dose remained higher for the IE driven by exposure during TEE-guided procedures (IC#1 294 vs. IE#1 676 µSv). In a subgroup using radioprotective drapes during TTE-guided TAVR, IC dose was reduced without effect on the IE. CONCLUSIONS: Radiation exposure during structural heart interventions is concerning. With dedicated shielding, IE received lower doses to the body and lens than IC. Further optimization of structural suite design and shielding is needed.

Exploring putative genetic determinants of inter-individual phenotypic heterogeneity in sickle cell disease: A cross-sectional Jamaican cohort-based study.

Patients with sickle cell disease (SCD) display puzzling inter-individual phenotypic heterogeneity, conceivably related to inherent differences in antioxidant protection, hemoglobin binding, bilirubin catabolism and methyl group handling. Therefore, we explored putative associations between clinically important phenotypic measures and functional polymorphisms within specific candidate genes encoding glutathione S-transferase, haptoglobin, uridine 5'-diphospho-glucuronosyltransferase 1A1, methyl tetrahydrofolate reductase, 5-methyltetrahydrofolate-homocysteine methyltransferase, and cystathionine beta-synthase. Two-hundred and thirty SCD participants (mean age 25.1 ±â€¯2.8) were recruited from Jamaica's Annual Sickle Cell Unit Cohort Review - two-hundred and five had homozygous hemoglobin SS (HbSS) disease, twenty-five had hemoglobin SC (HbSC) disease. Regression analyses revealed some novel genotype-phenotype associations. HbSC participants had significantly lower mean lactate dehydrogenase (p = 0.01) and glutathione (p < 0.001) values than HbSS participants. Glutathione S-transferase P1 (GSTP1) was significantly associated with mean corpuscular hemoglobin concentration using univariate (p = 0.044) and multivariable regression (p = 0.012). 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) was significantly associated with hemoglobin F % using univariate (p = 0.010) and multivariable regression (p = 0.009). In conclusion, this exploratory cross-sectional study generated novel, useable, and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants are related to inter-individual phenotypic variability in SCD.

A cross-sectional clinic-based study exploring whether variants within the glutathione S-transferase, haptoglobin and uridine 5'-diphospho-glucuronosyltransferase 1A1 genes are associated with interindividual phenotypic variation in sickle cell anaemia in Jamaica.

OBJECTIVES: To explore putative associations between specific variants in either the glutathione S-transferase (GST), haptoglobin (HP) or uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) genes and clinically important phenotypes in sickle cell anaemia (HbSS). METHODS: 371 HbSS participants were recruited from the Sickle Cell Clinic of the Sickle Cell Unit at the University of the West Indies, Kingston, Jamaica. Markers within four GST superfamily genes, the HP gene and the UGT1A1 gene were analysed using PCR-based assays. RESULTS: Multivariable regression revealed statistically significant associations between the GSTP1 Ile105Val heterozygote and HbA2 levels (P = .016), HbF percentage (P = .001), MCH concentration (P = .028) and reticulocyte count (P = .032), while the GSTM3 D/D homozygote was significantly associated with HbA2 levels (P = .032). The UGT1A1 (TA)6 /(TA)8 heterozygote showed statistically significant associations with HbA2 levels (P = .019), HbF percentage (P < .001), haemoglobin levels (P = .008), PCV values (P = .007) and RBC counts (P = .041). CONCLUSION: This exploratory cross-sectional study has generated novel and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants within the GST, UGT1A1 and HP genes are related to interindividual phenotypic variability in HbSS.

Right ventricular function in adult patients with Eisenmenger physiology: insights from quantitative echocardiography.

BACKGROUND: The favorable outcomes of Eisenmenger syndrome (ES) relative to other forms of pulmonary arterial hypertension (PAH) have been partially attributed to a unique adaptation of the right ventricle (RV). However, conventional measures of RV function may not adequately express this adaptation. METHODS: We studied 23 patients with ES (age 43 ± 17 years, 16 women, pulmonary artery systolic pressure [PASP] 93 ± 26 mmHg), 25 patients with PAH (age 44 ± 13 years, 17 women, PASP 92 ± 19 mmHg), and 25 subjects without known structural disease (age 45 ± 16 years, 17 women). We evaluated long- and short-axis function of the RV with two-dimensional strain and anatomical M-mode echocardiography, respectively. RESULTS: Long-axis function of the RV was comparable between patients with ES and PAH although depressed relative to controls (global strain, -15.6 ± 4.7, -14.9 ± 4.3, and -22.4 ± 2.8%, respectively, P < 0.001; global RV systolic strain rate, -0.77 ± 0.26, -0.84 ± 0.24, and -1.11 ± 0.21 1/sec, respectively, P < 0.001). However, short-axis RV function was significantly better in patients with ES versus those with PAH and preserved relative to controls (RV fractional shortening by anatomical M-mode, median [interquartile range], 21%[14-33%], 14%[10-16%], and 26%[22-36%], respectively, P = 0.002 for ES vs. PAH, P = 0.09 for ES vs. controls). This differential was not reflected in conventional measures of RV function (fractional area change, 32 ± 10 vs. 29 ± 8% in ES and PAH, respectively, P = 0.26). CONCLUSION: In patients with ES, the RV is characterized by preserved short-axis function, despite a depressed long-axis function. Thus, conventional assessment of RV function might not be suitable for patients with ES.

Imaging for Predicting, Detecting, and Managing Complications After Transcatheter Aortic Valve Replacement.

The management of patients with valvular heart disease is increasingly reliant on multimodal cardiac imaging. In patients with severe aortic stenosis considered for transcatheter aortic valve replacement, careful pre-procedural planning with multimodal imaging is necessary to avoid and prevent complications during the procedure. During or immediately after the procedure, rapid echocardiographic assessment is important to assess the new valve's function and manage major complications. Echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging all share important roles in the post-procedural evaluation of abnormal transcatheter valve function. This review discusses the use of multimodal imaging for predicting, detecting, and managing complications after TAVR.

Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.

Pulmonary Venous Waveforms Predict Rehospitalization and Mortality After Percutaneous Mitral Valve Repair.

OBJECTIVES: In this study, the authors hypothesized that intraprocedural improvement of pulmonary venous (PV) waveforms are predictive of improved outcomes. In this report, they analyzed intraprocedural invasive and echocardiographic changes with respect to rehospitalization and mortality. BACKGROUND: The effects of hemodynamic changes during percutaneous mitral valve repair (PMVR) with MitraClip (Abbott Vascular, Santa Clara, California) are incompletely characterized. METHODS: The authors retrospectively reviewed records and intraprocedural transesophageal echocardiograms of 115 consecutive patients (age 76 ± 12 years) who underwent PMVR for mitral regurgitation (MR) from May 2013 to January 2017 at Emory University Hospital. They assessed intraprocedural PV waveforms for improvement in morphology, measured change in MR grade by semiquantitative methods, evaluated invasive changes in left atrial pressure (LAP) and V-wave, and compared with 30-day and 1-year rehospitalization and all-cause mortality. RESULTS: Ninety-three cases (80%) had PV waveforms before and after clip placement sufficient for analysis, of which 67 (73%) demonstrated intraprocedural improvement in PV morphology and 25 (27%) did not. At 24 months, 57 (85%) of those with PV improvement were living, compared with only 10 (40%) of those without improvement. Proportional hazards models demonstrated a significant survival advantage in those with PV improvement (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.08 to 0.93, p = 0.038). By multivariable analysis, PV improvement predicted reduced 1-year cardiac rehospitalization (odds ratio [OR]: 0.18, p = 0.044). Intraprocedural assessment of MR grade and invasive hemodynamics did not consistently predict mortality and rehospitalization. CONCLUSIONS: PV waveforms are important markers of procedural success after PMVR. Our data show intraprocedural PV waveforms may predict rehospitalization and mortality after PMVR. A larger, multicenter cohort will be important to clarify this relationship.

Mean Aortic pressure gradient and global longitudinal strain recovery after transcatheter aortic valve replacement - A retrospective analysis.

BACKGROUND: Global longitudinal strain (GLS) has incremental value in assessing left ventricular (LV) function in severe aortic stenosis and is related to clinical outcome after transcatheter aortic valve replacement (TAVR). We sought to identify relevant echocardiographic predictors of GLS improvement and myocardial function recovery after TAVR. METHODS: We analyzed baseline and 12-month follow-up echocardiograms for LV strain analysis from 123 patients who underwent at Emory University Hospital with the Edwards SAPIEN valve between 7/2007 and 7/2013. RESULTS: At baseline, 61 had reduced LV ejection fraction (LVEF) ≤50% (rEF), and 80 had preserved LVEF >50% (pEF). Higher baseline mean pressure gradient (MPG) and aortic peak velocity (AV Vmax) predicted myocardial function recovery defined as ≥20% improvement in global longitudinal strain (r = 0.29, p < .001; r = 0.26, p = .002). When analyzing subjects with discordant changes in GLS and LVEF at follow-up, subjects with improved GLS, although reduced LVEF after TAVR, experienced a greater reduction in MPG and AV Vmax (-40 vs. -30, p = 0.015; -2.3 vs. -1.9, p = .021) after the procedure. CONCLUSIONS: In high-risk patients undergoing TAVR for severe aortic stenosis, GLS is impaired and more impaired in patients with reduced EF. Higher baseline MPG predicts myocardial function recovery. GLS improvement after TAVR is related to relief of pressure overload.

Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: Comparing Transthoracic versus Transesophageal Echocardiographic Guidance.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being performed in cardiac catheterization laboratories using transthoracic echocardiography (TTE) to guide valve deployment. The risk of paravalvular regurgitation (PVR) remains a concern. METHODS: We retrospectively reviewed 454 consecutive patients (mean age, 82 ± 8; 58% male) who underwent transfemoral TAVR at Emory Healthcare from 2007 to 2014. Two hundred thirty-four patients underwent TAVR in the cardiac catheterization laboratory with TTE guidance (TTE-TAVR; mean Society of Thoracic Surgeons score, 10%), while 220 patients underwent the procedure in the hybrid operating room with transesophageal echocardiography (TEE) guidance (TEE-TAVR; mean Society of Thoracic Surgeons score, 11%). All patients received an Edwards valve (SAPIEN 55%, SAPIEN-XT 45%). Clinical and procedural characteristics, echocardiographic parameters, and incidence of PVR were compared. RESULTS: The incidence of at least mild PVR at discharge was comparable between TTE-TAVR and TEE-TAVR (33% vs 38%, respectively; P = .326) and did not differ when stratified by valve type. However, in the TTE-TAVR group, there was a higher incidence of second valve implantation (7% vs 2%; P = .026) and postdilation (38% vs 17%; P < .001) during the procedure. Although not independently associated with PVR at discharge (odds ratio = 1.12; 95% CI, 0.69-1.79), TTE-TAVR was associated with PVR-related events: the combined outcome of mild PVR at discharge, intraprocedural postdilation, and second valve insertion (odds ratio = 1.58; 95% CI, 1.01-2.46). There were no significant differences in PVR at 30 days, 6 months, and 1 year between the two groups. CONCLUSIONS: TTE-TAVR in a high-risk group of patients was associated with increased incidence of intraprocedure PVR-related events, although it was not associated with higher rates of PVR at follow-up. Multicenter randomized trials are required to confirm the cost-effectiveness and safety of TTE-TAVR.

The use of echocardiography for the evaluation of dyssynchrony.

Tissue Doppler imaging (TDI), is a new imaging tool that allows measurement of dyssynchrony. In several small studies, TDI predicted clinical response and reverse remodeling after cardiac resynchronization therapy (CRT). Moreover, it allowed detection of mechanical dyssynchrony in heart failure patients with narrow QRS. Using TDI, the selection criteria for CRT might be changed to include heart failure patients with narrow QRS. Furthermore, it will help predict responders to this therapy, hence decreasing the percentage of nonresponders and allowing a more cost-effective use of this new technology.