Left atrial appendage morphology predicts the formation of left atrial appendage thrombus.

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.

Underestimation of Aortic Stenosis Severity by Doppler Mean Gradient during Atrial Fibrillation: Insights from Aortic Valve Weight.

BACKGROUND: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity when obtained during atrial fibrillation (AF) compared with sinus rhythm (SR). Aortic valve weight (AVW) is a flow-independent measure of AS severity. The objective of this study was to determine whether AVW or AVW/MG ratio was increased in AF versus SR in patients with AS. METHODS: Excised native aortic valves from 495 consecutive patients (median age, 77 years; interquartile range [IQR], 71-82 years; 40% women), with left ventricular ejection fractions ≥50% who underwent surgical aortic valve replacement for native valve severe AS (aortic valve area ≤ 1 cm2 or indexed aortic valve area ≤ 0.6 cm2/m2) were weighed. Excised AVW/MG ratios were compared in AF versus SR in patients with high-gradient AS (aortic peak velocity ≥ 4 m/sec or MG ≥ 40 mm Hg) and low-gradient AS (aortic peak velocity < 4 m/sec and MG < 40 mm Hg) in sex-specific analyses. RESULTS: AF was present in 51 patients (10%; 11 of 51 [22%] had low-gradient AS) and SR in 444 (90%; 23 of 444 [5%] had low-gradient AS). There was no difference in sex distribution between AF and SR. Aortic valve area was not different, but forward stroke volume index and transaortic valve flow rate were lower in AF (P ≤ .002 for all); MG was lower in AF versus SR (median, 46 mm Hg [IQR, 37-50 mm Hg] vs 50 mm Hg [IQR, 44-61 mm Hg]; P < .0001). Overall AVW was not different (median, 2,290 mg [IQR, 1,830-3,063 mg] vs 2,140 mg [IQR, 1,530-2,958 mg]; P = .31), but overall AVW/MG ratio was higher in AF (median, 55 [IQR, 41-67] vs 42 [IQR, 30-55]; P = .001). In sex- and MG-specific analyses, the AVW/MG ratio was higher in AF compared with SR in men with high-gradient AS (median, 58 [IQR, 41-75] vs 51 [IQR, 39-61]; P = .03), but the differences were not statistically significant between AF and SR in other groups. CONCLUSIONS: AVW was discordant to Doppler MG in AF compared with SR in men with high-gradient AS. Additional studies of the relationship of MG to other measures of AS severity, such as leaflet fibrosis, are needed.

Remodeling of intrinsic cardiac neurons: effects of ß-adrenergic receptor blockade in guinea pig models of chronic heart disease.

Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (∼20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg·kg(-1)·day(-1)) or vehicle, for a total of 6-7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that ß-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the ß-receptors were more influential on remodeling during dynamic disease progression.

Caval Valve Implantation for Tricuspid Regurgitation: Insights From the United States Caval Valve Registry.

BACKGROUND: We sought to describe the outcomes of patients who underwent caval valve implantation (CAVI) for treatment of severe tricuspid regurgitation (TR) in the United States. Previous studies on CAVI have used a variety of techniques and transcatheter valves. We present our findings from CAVI with inferior vena cava (IVC) implant only using a single valve. METHODS: Patients who were determined to be poor candidates for tricuspid valve surgery and underwent CAVI in the United States from March 1, 2013 through March 1, 2018 were included in this study. Data during hospitalizations and interim outpatient follow-up from each individual site were collected and entered into a central password-protected database. RESULTS: A total of 24 patients were treated. The median age was 79.5 years, 63% were women, and 96% were white. Twenty-three of 24 patients underwent valve implantation with a 29 mm Sapien 3 valve (Edwards Lifesciences). There was a 100% rate of successful valve implantation. There were no cases requiring emergency surgery. Thirty-day mortality rate was 25%. The median survival as of last follow-up of all patients was 350 days. Pre- and postprocedure New York Heart Association (NYHA) class data were available in 11 of 24 patients; of these 11 patients, 72.7% improved at least 1 NYHA class from baseline. CONCLUSION: CAVI may be performed safely in a high surgical risk population with severe tricuspid regurgitation. Dedicated studies with longer-term follow-up are needed.

Spontaneous coronary artery dissection and its association with heritable connective tissue disorders.

OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. METHODS: We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. RESULTS: Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. CONCLUSIONS: Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD.

Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

BACKGROUND: Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. OBJECTIVES: This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. METHODS: We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). RESULTS: Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). CONCLUSIONS: SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.

Platypnea-Orthodeoxia Syndrome: Diagnostic Challenge and the Importance of Heightened Clinical Suspicion.

Platypnea-orthodeoxia syndrome is an uncommon condition of positional dyspnea and hypoxemia; symptoms occur when the patient is upright and resolve with recumbency. Causes can be broadly categorized into 4 groups: intracardiac shunting, pulmonary shunting, ventilation-perfusion mismatch, or a combination of these. Platypnea-orthodeoxia syndrome should be suspected when normal arterial oxygen saturations are recorded while an individual is supine, followed by abrupt declines in those saturations when upright. Further investigations with use of imaging and cardiac catheterization aid in the evaluation. When platypnea-orthodeoxia syndrome is due to intracardiac shunting without pulmonary hypertension, intracardiac shunt closure can be curative. In this article, we report a case of platypnea-orthodeoxia syndrome in an 83-year-old woman who was successfully treated by means of percutaneous transcatheter closure of an atrial septal defect.