Feasibility and Utility of Anatomical and Physiological Evaluation of Coronary Disease With Cardiac CT in Severe Aortic Stenosis (FUTURE-AS Registry): Rationale and Design.

Background: Coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is common and may be associated with worse outcomes. Computed tomography coronary angiography (CTCA) and fractional flow reserve derived from computed tomography (FFRCT) are tools for comprehensive coronary assessment. The utility and safety of CTCA and FFRCT in the work-up for transcatheter aortic valve replacement (TAVR) is not established, especially in an evolving landscape that involves younger TAVR patients. The FUTURE-AS Registry will assess the utility and safety of cardiac-optimized CTCA and FFRCT to evaluate CAD and guide referral for downstream invasive coronary angiography (ICA) in patients with severe AS being considered for TAVR. Methods: FUTURE-AS is an international, prospective, multicenter registry of patients with severe AS referred for TAVR being assessed for CAD with CTCA and FFRCT. The primary end point is the per-patient sensitivity and negative predictive value of CTCA and FFRCT for identifying anatomical and physiologically significant CAD compared to ICA and invasive FFR. The safety end point is the incidence of symptomatic hypotension or bradycardia requiring intervention following the administration of nitroglycerin or ß-blocker medications. Feasibility end points include the incidence of noninterpretable CTCA scans and CTCA scans not adequate for FFR analysis. Other utility end points include specificity, positive predictive value, and accuracy of CTCA and FFRCT. Lastly, the potential of a CTCA and FFRCT guided strategy to defer pre-TAVR ICA will be assessed. Conclusions: FUTURE-AS will characterize the utility, safety, and feasibility of CTCA and FFRCT for coronary assessment pre-TAVR.

A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder.

BACKGROUND: Advanced neuroscientific insights surrounding post-traumatic stress disorder (PTSD) and its associated symptomatology should beget psychotherapeutic treatments that integrate these insights into practice. Deep Brain Reorienting (DBR) is a neuroscientifically-guided psychotherapeutic intervention that targets the brainstem-level neurophysiological sequence that transpired during a traumatic event. Given that contemporary treatments have non-response rates of up to 50% and high drop-out rates of >18%, DBR is investigated as a putative candidate for effective treatment of some individuals with PTSD. OBJECTIVE: To conduct an interim evaluation of the effectiveness of an eight-session clinical trial of videoconference-based DBR versus waitlist (WL) control for individuals with PTSD. METHOD: Fifty-four individuals with PTSD were randomly assigned to DBR (N = 29) or WL (N = 25). At baseline, post-treatment, and three-month follow-up, participants' PTSD symptom severity was assessed using the Clinician Administered PTSD Scale (CAPS-5). This is an interim analysis of a clinical trial registered with the U. S. National Institute of Health (NCT04317820). RESULTS: Significant between-group differences in CAPS-total and all subscale scores (re-experiencing, avoidance, negative alterations in cognitions/mood, alterations in arousal/reactivity) were found at post-treatment (CAPS-total: Cohen's d = 1.17) and 3-month-follow-up (3MFU) (CAPS-total: Cohen's d = 1.18). Significant decreases in CAPS-total and all subscale scores were observed within the DBR group pre - to post-treatment (36.6% CAPS-total reduction) and pre-treatment to 3MFU (48.6% CAPS-total reduction), whereas no significant decreases occurred in the WL group. After DBR, 48.3% at post-treatment and 52.0% at 3MFU no longer met PTSD criteria. Attrition was minimal with one participant not completing treatment; eight participants were lost to 3MFU. CONCLUSIONS: These findings provide emerging evidence for the effectiveness of DBR as a well-tolerated treatment that is based on theoretical advances highlighting alterations to subcortical mechanisms in PTSD and associated symptomatology. Additional research utilizing larger sample sizes, neuroimaging data, and comparisons or adjacencies with other psychotherapeutic approaches is warranted.Trial registration: ClinicalTrials.gov identifier: NCT04317820..

First study to evaluate the effects of Deep Brain Reorienting (DBR) therapy on PTSD symptoms.Eight internet-based DBR sessions resulted in significant decreases in PTSD symptoms post-treatment and at 3-month follow-up in comparison to a waitlist group.Large effect sizes and a low drop-out rate suggest that DBR may be an effective, well-tolerated neuroscientifically guided treatment for PTSD.

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.

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.

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.

Shame as an evolved basic affect - Approaches to it within the Comprehensive Resource Model (CRM).

Shame is an evolved emotional response which requires relational evaluation at a prefrontal cortical level but which has the visceral sensation and defence response impulse of a basic affect. We argue that the severe forms of shame, those residual from traumatic interpersonal experiences, have midbrain and diencephalic components mediating experiences of painful withdrawal while anhedonia is derived from a negatively valenced state of the mesolimbic dopamine system. This specific form of separation distress, with a characteristic sense of exclusion and unworthiness, benefits in treatment from the presence of attachment resources which allow secure access to the core distress. We discuss the use of the Comprehensive Resource Model (CRM) in the psychotherapy of post-traumatic states in which shame is prominent.

Comparison of Clinical and Echocardiographic Outcomes After Surgical Redo Mitral Valve Replacement and Transcatheter Mitral Valve-in-Valve Therapy.

OBJECTIVES: There are minimal data regarding clinical outcomes and echocardiographic findings after transcatheter mitral valve-in-valve replacement (TMVR) compared with redo surgical mitral valve replacement (SMVR). BACKGROUND: TMVR therapy has emerged as therapy for a degenerated bioprosthetic valve failure. METHODS: The authors retrospectively identified patients with degenerated mitral bioprostheses who underwent redo SMVR or TMVR at 3 U.S. institutions. The authors compared clinical and echocardiographic outcomes of patients who had TMVR with those of patients who underwent redo SMVR. RESULTS: Sixty-two patients underwent TMVR and 59 patients underwent SMVR during the study period. Mean age and the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) scores were significantly higher in patients with TMVR than in those with SMVR (age 74.9 ± 9.4 years vs. 63.7 ± 14.9 years; p < 0.001; STS PROM 12.7 ± 8.0% vs. 8.7 ± 10.1%; p < 0.0001). Total procedure time, intensive care unit hours, and post-procedure length of stay were all significantly shorter in the TMVR group. There was no difference in mortality at 1 year between the 2 groups (TMVR 11.3% vs. SMVR 11.9%; p = 0.92). Mean mitral valve pressure gradient and the grade of mitral regurgitation (MR) were similar between the TMVR group and the SMVR group (mitral valve pressure gradient 7.1 ± 2.5 mm Hg vs. 6.5 ± 2.5 mm Hg; p = 0.42; MR [≥moderate] 3.8% vs. 5.6%; p = 1.00) at 30 days. At 1 year, the mitral valve pressure gradient was higher in the TMVR group (TMVR 7.2 ± 2.7 vs. SMVR 5.5 ± 1.8; p = 0.01), although there was no difference in the grade of MR. CONCLUSIONS: Despite the higher STS PROM in TMVR patients, there was no difference in 1-year mortality between the TMVR and SMVR groups. Echocardiographic findings after TMVR were similar to SMVR at 30 days. There was a statistically significant difference in mitral gradient at 1 year, though this is likely not clinically important. TMVR may be an alternative to SMVR in patients with previous mitral bioprosthetic valves.

Coronary and Peripheral Vasomotor Responses to Mental Stress.

BACKGROUND: Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation. METHODS AND RESULTS: In 38 patients aged 59±8 years undergoing coronary angiography, endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate-pressure product by 22% (±23%) and constricted epicardial coronary arteries by -5.9% (-10.5%, -2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [-10.9%, 8.2%], P=not significant). The MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand-adjusted change in CBF during MS (r=-0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation. CONCLUSIONS: The coronary microvascular response to MS is determined by endothelium-dependent, but not endothelium-independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation.

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.

Supra-annular valve strategy for an early degenerated transcatheter balloon-expandable heart valve.

Currently, there are no recommendations regarding the selection of valve type for a transcatheter heart valve (THV)-in-THV procedure. A supra-annular valve design may be superior in that it results in a larger effective orifice area and may have a lower chance of valve thrombosis after THV-in-THV. In this report, we describe the use of a supra-annular valve strategy for an early degenerated THV.

Predictors and Clinical Outcomes of Next-Day Discharge After Minimalist Transfemoral Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to investigate predictors and safety of next-day discharge (NDD) after transcatheter aortic valve replacement (TAVR). BACKGROUND: Information about predictors and safety of NDD after TAVR is limited. METHODS: The study reviewed 663 consecutive patients who underwent elective balloon-expandable TAVR (from July 2014 to July 2016) at our institution. We first determined predictors of NDD in patients who underwent minimalist transfemoral TAVR. After excluding cases with complications, we compared 30-day and 1-year outcomes between NDD patients and those with longer hospital stay using Cox regression adjusting for the Predicted Risk of Mortality provided by the Society of Thoracic Surgeons. The primary endpoint was the composite of mortality and readmission at 1 year. RESULTS: A total of 150 patients had NDD after TAVR and 210 patients had non-NDD. Mean age and the Society of Thoracic Surgeons Predicted Risk of Mortality were 80.7 ± 8.8 years and 6.6 ± 3.7%, respectively. Predictors of NDD were male sex (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.28 to 3.18), absence of atrial fibrillation (OR: 1.62; 95% CI: 1.02 to 2.57), serum creatinine (OR: 0.71; 95% CI: 0.55 to 0.92), and age (OR: 0.95; 95% CI: 0.93 to 0.98). As expected, 84% of patients with complications had non-NDD. After excluding cases with complications, there was no difference in hazard rates of the 30-day composite outcome between NDD and non-NDD (hazard ratio: 0.62; 95% CI: 0.20 to 1.91), but the hazard of the composite outcome at 1 year was significantly lower in the NDD group (hazard ratio: 0.47; 95% CI: 0.27 to 0.81). This difference in the composite outcome can be explained by the lower hazard of noncardiovascular related readmission in the NDD group. CONCLUSIONS: Factors predicting NDD include male sex, absence of atrial fibrillation, lower serum creatinine, and younger age. When compared with patients without complications with a longer hospital stay, NDD appears to be safe, achieving similar 30-day and superior 1-year clinical outcomes.

Ostial right coronary chronic total occlusion: Transesophageal echocardiographic guidance for retrograde aortic re-entry.

As antegrade options are limited, intervention upon the ostial right coronary artery (RCA) chronic total occlusion (CTO) warrants a retrograde approach. Landmarks for an aggressive approach are concerning as passage of stiff guidewires or electrocautery near the RCA ostium may result in wire passage into structures other than the aorta. We report the first use of transesophageal echocardiography (TEE) to assist retrograde passage of a guidewire into the aorta. For the ostial RCA CTO, TEE guidance may be considered to assist retrograde passage of aggressive guidewires into the aorta.

Relation of Changes in Body Fat Distribution to Oxidative Stress.

Android fat is a surrogate measure of visceral obesity in the truncal region. Both visceral adiposity and oxidative stress (OS) are linked to cardiometabolic risk factors and clinical cardiovascular disease. However, whether body fat distribution (android vs gynoid) is associated with OS remains unknown. We hypothesized that increased android fat will be associated with greater OS. Body fat distribution and markers of OS, including plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulfide) aminothiols, were estimated in 711 volunteers (67% female, 23% black, mean age 48 ± 11) enrolled in the Emory Georgia Tech Predictive Health study. At 1 year, 498 subjects had repeat testing. At baseline, anthropometric and fat distribution indexes, including body mass index, waist circumference, weight/hip ratio, and android and gynoid fat mass correlated with lower plasma concentrations of glutathione and higher cystine levels indicative of higher OS. At 1 year, the change in android but not gynoid fat mass or body mass index negatively correlated with the change in the plasma glutathione level after adjustment for cardiovascular risk factors. Increased body fat, specifically android fat mass, is an independent determinant of systemic OS, and its change is associated with a simultaneous change in OS, measured as plasma glutathione. In conclusion, our findings suggest that excess android or visceral fat contributes to the development of cardiovascular disease through modulating OS.

Changes in truncal obesity and fat distribution predict arterial health.

BACKGROUND: Truncal obesity is associated with metabolic syndrome and cardiovascular risk. Although vascular health is influenced by weight, it is not known whether changes in fat distribution modulate arterial function. OBJECTIVE: We assessed how changes in truncal (android) fat at 1 year affect arterial stiffness and endothelial function. METHODS: We recruited 711 healthy volunteers (235 males, age 48 ± 11 years) into the Emory Predictive Health Study; 498 returned at 1 year. Measurements included anthropometric and chemistry panels, fat mass using dual-energy X-ray absorptiometry, arterial stiffness indices (pulse wave velocity [PWV], augmentation index [AIx], and subendocardial viability ratio [SEVR]; Sphygmocor), flow-mediated dilation (FMD), and reactive hyperemia index (Endo-PAT). RESULTS: At baseline, measures of body mass correlated with PWV, AIx, SEVR, and FMD. In a multivariable analysis including body mass index (BMI) and traditional risk factors, BMI remained an independent predictor of PWV, AIx, SEVR, and FMD. In a model including BMI and measures of fat distribution, android fat remained an independent predictor of PWV (ß = 0.31, P = .004), AIx (ß = 0.24, P = .008), and SEVR (ß = -0.41, P < .001). The 1-year change in android fat correlated negatively with change in SEVR (ß = -0.13, P = .005) and FMD (ß = -0.13, P = .006) after adjustment for change in gynoid fat. CONCLUSION: In addition to BMI, android fat is a determinant of arterial stiffness, independent of traditional risk factors. Changes in android fat over time are associated with simultaneous changes in vascular function, indicating fat distribution's effect on vascular health.