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Exertional dyspnea has been documented in US military personnel after deployment to Iraq and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD). We performed detailed histomorphometry of pulmonary vasculature in 52 Veterans with biopsy-proven post-deployment respiratory syndrome (PDRS) and then recruited five of these same Veterans with continued exertional dyspnea to undergo a follow-up clinical evaluation, including symptom questionnaire, pulmonary function testing, surface echocardiography, and right heart catheterization (RHC). Morphometric evaluation of pulmonary arteries showed significantly increased intima and media thicknesses, along with collagen deposition (fibrosis), in Veterans with PDRS compared to non-diseased (ND) controls. In addition, pulmonary veins in PDRS showed increased intima and adventitia thicknesses with prominent collagen deposition compared to controls. Of the five Veterans involved in our clinical follow-up study, three had borderline or overt right ventricle (RV) enlargement by echocardiography and evidence of pulmonary hypertension (PH) on RHC. Together, our studies suggest that PVD with predominant venular fibrosis is common in PDRS and development of PH may explain exertional dyspnea and exercise limitation in some Veterans with PDRS.

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BACKGROUND: Depression and cognitive dysfunction (CD) are not routinely screened for in patients before transcatheter aortic valve replacement (TAVR) and their association with postprocedural outcomes is poorly understood. The objectives of this study are to determine the prevalence of depression and CD in patients with aortic stenosis undergoing TAVR and evaluate their association with mortality and quality of life. METHODS: We analyzed a prospective, multicenter TAVR registry that systematically screened patients for preexisting depression and CD with the Patient Health Questionnaire-2 and Mini-Cog, respectively. The associations with mortality were assessed with Cox proportional hazard models and quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol visual analogue scale) were evaluated using multivariable ordinal regression models. RESULTS: A total of 884 patients were included; median follow-up was 2.88 years (interquartile range=1.2-3.7). At baseline, depression was observed in 19.6% and CD in 31.8%. In separate models, after adjustment, depression (HR, 1.45 [95% CI, 1.13-1.86]; P<0.01) and CD (HR, 1.27 [95% CI, 1.02-1.59]; P=0.04) were each associated with increased mortality. Combining depression and CD into a single model, mortality was greatest among those with both depression and CD (n=62; HR, 2.06 [CI, 1.44-2.96]; P<0.01). After adjustment, depression was associated with 6.6 (0.3-13.6) points lower on the Kansas City Cardiomyopathy Questionnaire 1-year post-TAVR and 6.7 (0.5-12.7) points lower on the EuroQol visual analogue scale. CD was only associated with lower EuroQol visual analogue scale. CONCLUSIONS: Depression and CD are common in patients that undergo TAVR and are associated with increased mortality and worse quality of life. Depression may be a modifiable therapeutic target to improve outcomes after TAVR.

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Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post-transcatheter aortic valve implantation recovery, rehabilitation, and survival.

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Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (P<0.001 for each). aGLS <15% was associated with increased mortality in univariable analysis (P=0.009), but, in a model with both biomarkers, aGLS, and clinical covariates included, aGLS was not associated with mortality; elevation in each biomarker was associated with an increased hazard of mortality (adjusted hazard ratio, >2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

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Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5 years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P<0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01-1.77, P=0.043). cTnT and NT-proBNP each risk stratified patients with moderate/severe LVH (P<0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45-3.00, P<0.001) and elevated NT-proBNP (aHR, 1.46; 95% CI 1.00-2.11, P=0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not (P=0.15). Conclusions Elevations in circulating cTnT and NT-proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT-proBNP predict post-transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.

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BACKGROUND: Nonchicken wing left atrial appendage (LAA) morphology is associated with higher risk for stroke in patients with atrial fibrillation (AF) than chicken wing (CW) morphology. OBJECTIVE: Assess whether LAA morphology predicts the formation of LAA thrombus independent of age, sex, presenting rhythm, left ventricular ejection fraction (LVEF), or anticoagulant use. METHODS: A cross-sectional analysis was performed on patients prospectively enrolled in the Vanderbilt LAA Registry or presenting for transesophageal echocardiogram (TEE) between January 1, 2015, and November 1, 2017 (n = 306). Two physicians independently reviewed TEEs interpreted as having LAA thrombus. Determination of LAA morphology, ejection velocity, and presence of thrombus (n = 102) were based on 0°, 45°, 90°, and 135° TEE views. The control cohort (n = 204) included consecutive AF patients undergoing TEE without LAA thrombus. RESULTS: LAA morphology in patients with LAA thrombus was: 35% windsock, 47% broccoli, and 12% CW. Windsock (odds ratio [OR], 4.0; 95% confidence interval [CI]: 1.7-9.3, p = .001) and broccoli (OR, 6.6; 95% CI: 2.6-16.6; p < .001) morphology were higher risk for thrombus compared to CW. Female sex predicted higher-odds for LAA thrombus (OR, 2.6; 95% CI: 1.4-4.8; p = .002) as did LAA-EV < 20 cm/s (OR, 11.12; 95% CI: 5.6-22.1). Anticoagulation use (OR, 0.5; 95% CI: 0.3-0.9; p = .03) and higher LVEF (OR, 0.95; 95% CI: 0.93-0.98; p < .001) were associated with lower risk. In patients with a CW morphology who had LAA thrombus, 4 of the 7 had an LAA-EV < 20 cm/s and acute systolic heart failure with LVEF < 30% or active malignancy. In multivariable linear regression analysis controlling for presenting rhythm, anticoagulant use, age, sex, and LVEF, CW morphology appears relatively protective from LAA thrombus (p = .001). CONCLUSION: CW LAA morphology appears relatively protective against the formation of LAA thrombus.

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BACKGROUND: Incomplete surgical left atrial appendage occlusion (S-LAAO) with a narrow neck has been shown to predict an increased rate of embolic stroke. Patients with a previously attempted S-LAAO were systematically excluded from all clinical trials of LAA closure devices. OBJECTIVE: The purpose of this study was to evaluate the feasibility of Watchman LAA device closure for patients referred with chronically incomplete S-LAAO. METHODS: A prospective single-arm feasibility cohort evaluated only subjects undergoing Watchman LAA closure following incomplete S-LAAO. Patients referred and implanted were followed in the Vanderbilt LAA Registry. Preprocedure computed tomographic angiography and transesophageal echocardiography (TEE) were performed to evaluate suitability for closure, with 45-day follow-up TEE postimplant. RESULTS: All attempted LAA closures after incomplete S-LAAO were successful (n = 6). Mean age was 76.3 ± 7 years. Mean CHADS2Vasc score was 3.8 ± 0.8, and HAS-BLED score was 3.5 ± 0.5. At 45-day follow up, all subjects had complete device seal with no thrombus on device and had transitioned to clopidogrel plus aspirin. Three subjects had narrow ostial necks with a maximum diameter ≤9 mm. In all cases, the 4.7-mm Watchman access sheath was able to cross the ostial stricture. Mean occluder size implanted was 28 ± 4 mm. Mean LAA dimension by TEE in the 45° and 135° views for depth was 31 mm and ostial diameter was 11 × 16 mm, below the minimum Watchman indication for use of 17 mm. No major intraoperative complications occurred. CONCLUSION: Watchman LAA closure seems to be feasible in patients with chronically incomplete S-LAAO, including subjects with a narrow neck ≤9 mm in width.

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The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

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The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.

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BACKGROUND: Pulmonary transit time (PTT) obtained from contrast echocardiography is a marker of global cardiopulmonary function. Pulmonary blood volume (PBV), derived from PTT, may be a noninvasive surrogate for left-sided filling pressures, such as pulmonary artery wedge pressure (PAWP). We sought to assess the relationship between PBV obtained from contrast echocardiography and PAWP. METHODS: Participants were adult survivors of childhood cancer that had contrast echocardiography performed nearly simultaneously with right-heart catheterization. PTT was derived from time-intensity curves of contrast passage through the right ventricle (RV) and left atrium (LA). PBV relative to overall stroke volume (rPBV) was estimated from the product of PTT and heart rate during RV-LA transit. PAWP was obtained during standard right-heart catheterization. The Spearman correlation coefficient was used to assess the relationship between rPBV and PAWP. RESULTS: The study population consisted of 7 individuals who had contrast echocardiography and right-heart catheterization within 3 hours of each other. There was a wide range of right atrial (1-17 mm Hg), mean pulmonary artery (18-42 mm Hg), and PAW pressures (4-26 mm Hg) as well as pulmonary vascular resistance (<1-6 Wood Units). We observed a statistically significant correlation between rPBV and PAWP (r = .85; P = .02). CONCLUSION: Relative PBV derived from contrast echocardiography correlates with PAWP. If validated in larger studies, rPBV could potentially be used as an alternative to invasively determine left-sided filling pressure.

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The American College of Cardiology collaborated with the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons to develop and evaluate Appropriate Use Criteria (AUC) for the treatment of patients with severe aortic stenosis (AS). This is the first AUC to address the topic of AS and its treatment options, including surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). A number of common patient scenarios experienced in daily practice were developed along with assumptions and definitions for those scenarios, which were all created using guidelines, clinical trial data, and expert opinion in the field of AS. The 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(1) and its 2017 focused update paper (2) were used as the primary guiding references in developing these indications. The writing group identified 95 clinical scenarios based on patient symptoms and clinical presentation, and up to 6 potential treatment options for those patients. A separate, independent rating panel was asked to score each indication from 1 to 9, with 1-3 categorized as "Rarely Appropriate," 4-6 as "May Be Appropriate," and 7-9 as "Appropriate." After considering factors such as symptom status, left ventricular (LV) function, surgical risk, and the presence of concomitant coronary or other valve disease, the rating panel determined that either SAVR or TAVR is Appropriate in most patients with symptomatic AS at intermediate or high surgical risk; however, situations commonly arise in clinical practice in which the indications for SAVR or TAVR are less clear, including situations in which 1 form of valve replacement would appear reasonable when the other is less so, as do other circumstances in which neither intervention is the suitable treatment option. The purpose of this AUC is to provide guidance to clinicians in the care of patients with severe AS by identifying the reasonable treatment and intervention options available based on the myriad clinical scenarios with which patients present. This AUC document also serves as an educational and quality improvement tool to identify patterns of care and reduce the number of rarely appropriate interventions in clinical practice.

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Transcatheter aortic valve replacement (TAVR) is an effective, nonsurgical treatment option for patients with severe aortic stenosis. The optimal treatment strategy for treating concomitant coronary artery disease (CAD) has not been tested prospectively in a randomized clinical trial. Nevertheless, it is standard practice in the United States to perform coronary angiography and percutaneous coronary intervention for significant CAD at least 1 month before TAVR. All existing clinical trials were designed using this strategy. Therefore, it is wrong to extrapolate current American College of Cardiology/American Heart Association Appropriate Use Criteria against invasive procedures in asymptomatic patients to the TAVR population when evaluating the quality of care by cardiologists or hospitals. In this statement from the Interventional Section Leadership Council of the ACC, it is recommended that percutaneous coronary intervention should be considered in all patients with significant proximal coronary stenosis in major coronary arteries before TAVR, even though the indication is not covered in current guidelines.

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BACKGROUND: A "classic" response to acute vasodilator testing (drop of >10 mm Hg in mean pulmonary artery pressure [mPAP] to <40 mm Hg) confers an excellent prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH) and identifies candidates for treatment with calcium channel blockers (CCB). Little is known about vasodilator responsiveness (VR) in other types of PAH, or about outcomes in patients with a significant but "non-classic" decrease in mPAP. We hypothesized that VR occurs in non-idiopathic PAH and non-classic VR portends a better prognosis than no VR in PAH. METHODS: Acute VR testing with nitric oxide was performed on 155 consecutive patients referred for PH evaluation. Non-classic response was defined as decrease in mPAP >10 mm Hg to >40 mm Hg with preserved cardiac output. Demographics and functional status were assessed at baseline and the first clinic visit after VR testing, and survival was followed over time. RESULTS: Twenty patients (13%) displayed classic VR. Among classic responders, 12 (60%) had IPAH and 8 (40%) had connective tissue disease-associated PAH (CTD-PAH); however, only responders with IPAH had improved survival compared with non-responders (p = 0.02). Thirteen patients (8%) had a non-classic VR. Non-classic response was not associated with improved survival compared with non-responders (p = 0.86). Acute change in mPAP or pulmonary vascular resistance in the entire cohort did not predict survival. CONCLUSIONS: Classic acute VR occurs in CTD-PAH as well as IPAH; however, only IPAH patients have improved outcomes. A significant but non-classic VR is not associated with improved survival.

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Mild therapeutic hypothermia (TH) is an established therapy to improve survival and reduce neurologic injury after cardiac arrest. Adult patients with congenital heart disease (ACHD) are at increased risk of sudden cardiac death. The use of TH in this population has not been extensively studied. The aim of this study is to report our institutional experience using this treatment modality in patients with ACHD after cardiac arrest. We performed a retrospective observational study of a cohort of 245 consecutive patients treated with TH after cardiac arrest from 2007 to 2013. Five patients were identified as having complex ACHD with a mean age of 28 years. All were treated with TH according to an institutional protocol utilizing active surface cooling to maintain a core body temperature of 32°C to 34°C for 24 hours after cardiac arrest. Congenital lesions in these 5 patients included anomalous left coronary artery from the pulmonary artery; l-transposition of the great arteries; d-transposition of the great arteries status post atrial switch; unoperated tricuspid atresia, atrial septal defect, and ventricular septal defect with Eisenmenger's physiology; and surgically corrected atrial septal defect, cleft mitral valve, and subaortic membrane. All 5 patients suffered cardiac arrest due to ventricular arrhythmia and all survived to discharge without significant neurologic impairment. Therapeutic interventions included anomalous left coronary artery from the pulmonary artery ligation, percutaneous coronary intervention, and defibrillator implantation. In conclusion, in 5 patients with ACHD, the use of TH after cardiac arrest resulted in 100% survival to hospital discharge with good neurologic outcome postresuscitation.

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BACKGROUND: Adoption of transradial percutaneous coronary intervention (TRI) in the United States is low and may be related to challenges learning the technique. We examined the relationships between operator TRI volume and procedural metrics and outcomes. METHODS AND RESULTS: We used CathPCI Registry data from July 2009 to December 2012 to identify new radial operators, defined by an exclusively femoral percutaneous coronary intervention approach for 6 months after their first percutaneous coronary intervention in the database and ≥15 total TRIs thereafter. Primary outcomes of fluoroscopy time, contrast volume, and procedure success were chosen as markers of technical proficiency. Secondary outcomes included in-hospital mortality, bleeding, and vascular complications. Adjusted outcomes were analyzed by using operator TRI experience as a continuous variable with generalized linear mixed models. Among 54 561 TRI procedures performed at 704 sites, 942 operators performed 1 to 10 procedures, 942 operators performed 11 to 50 procedures, 375 operators performed 51 to 100 procedures, and 148 operators performed 101 to 200 procedures. As radial caseload increased, more TRIs were performed in women, in patients presenting with ST-segment elevation myocardial infarction, and for emergency indications. Decreased fluoroscopy time and contrast use were nonlinearly associated with greater operator TRI experience, with faster reductions observed for newer (<30-50 cases) compared with more experienced (>30-50 cases) operators. Procedure success was high, whereas mortality, bleeding, and vascular complications remained low across TRI volumes. CONCLUSIONS: As operator TRI volume increases, higher-risk patients are chosen for TRI. Despite this, operator proficiency improves with greater TRI experience, and safety is maintained. The threshold to overcome the learning curve appears to be approximately 30 to 50 cases.

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