A strong association exists between left atrial (LA) structural remodeling and the development of atrial fibrillation (AF). The role of LA function in AF prediction remains unclear. We studied the relationship between LA function and incident AF using cardiac CT. We retrospectively analyzed patients who underwent multiphasic cardiac CT. LA volumes and parameters of LA global, reservoir and booster function were calculated. The association between measures of LA function and incident AF was analyzed using multivariable Cox regression adjusting for clinical variables, LA volume and left ventricular function. 1025 patients (age 64 years ± 14) were evaluated. Over a median of 3.9 years, 90 patients developed AF. There was a significant association between LA total emptying fraction (adjusted hazard ratio (HR) 1.05; 95

INTRODUCTION:Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibro-fatty replacement of cardiomyocytes, leading to life-threatening ventricular arrhythmia and heart failure. Pathogenic variants of desmoglein2 gene (DSG2) have been reported as genetic etiologies of AC. In contrast, many reported DSG2 variants are benign or variants of uncertain significance. Correct genetic variant classification is crucial for determining the best medical therapy for the patient and family members.METHODS:Pathogenicity of the DSG2 Ser194Leu variant that was identified by whole exome sequencing in a patient, who presented with ventricular tachycardia and was diagnosed with AC, was investigated by electron microscopy and immunohistochemical staining of endomyocardial biopsy sample.RESULTS:Electron microscopy demonstrated a widened gap in the adhering junction and a less well-organized intercalated disk region in the mutated cardiomyocytes compared to the control. Immunohistochemical staining in the proband diagnosed with AC showed reduced expression of desmoglein 2 and connexin 43 and intercalated disc distortion. Reduced expression of DSG2 and Connexin 43 were observed in cellular cytoplasm and gap junctions. Additionally, we detected perinuclear accumulation of DSG2 and Connexin 43 in the proband sample.CONCLUSION:Ser194Leu is a missense pathogenic mutation of DSG2 gene associated with arrhythmogenic left ventricular cardiomyopathy.

BACKGROUND: Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction. METHODS: We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110). RESULTS: The early passive filling progressively decreased with worsening diastolic function (P<0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation (P=0.021) and declines with more advanced diastolic function (P<0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively (P<0.001), accounting for 75% of stroke volume (interquartile range, 63-81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71; P<0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow. CONCLUSIONS: An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure.

Introduction Third generation LVAD, HeartMate3 (HM3) are associated with favorable prognosis. A rare life-threatening adverse event is a sudden outflow graft obstruction due to a rotational twist. There is limited data regarding the natural history of this complication. Case Report A 70-year-old male with dilated cardiomyopathy was implanted with an HM3 LVAD on September 2019. Echocardiography and cardiac CT immediately following the implantation showed appropriate left ventricular (LV) unloading and normal outflow cannula flows and patency. On April 2021 the patient complained of weakness. Clinical examination was normal, but LVAD interrogation identified decline of LVAD flow. Laboratory tests revealed INR in therapeutic range and normal LDH. An echocardiography revealed impaired unloading of the LV and opening of the aortic valve. A CTA showed a large irregular filling defect sized 7cm at the proximal outflow cannula. Differential diagnosis included outflow cannula twist or thrombosis. Three-dimensional CT volume rendering demonstrated a full rotational twist of the outflow cannula. An untwist operation using a lateral thoracotomy approach identified a >270º twist of the outflow graft. The cannula was untwisted and using a fixation device, the cannula was fixed, resulting in immediate improvement of the flow rate. Repeated transient low flow events at the end of the procedure mandated a repeat CTA to confirm the adequacy of cannula untwisting. Four months following the untwist procedure, the patient is well with stable LVAD flows. Summary This is the first case of an outflow graft twist obstruction with comprehensive CTA imaging at 3 critical time points: immediately after LVAD implantation, at twist occurrence and after surgical repair. We believe that it is very important to maintain a high degree of active awareness that a sudden drop in pump flow without signs of pump thrombosis may indicate outflow graft obstruction due to a twist, which is best recognized by three-dimensional CT reconstruction of the outflow graft.

HomeCirculation: Cardiovascular ImagingVol. 15, No. 4Three-Dimensional Computed Tomography Reconstruction for Diagnosis of Left Ventricular Assist Device Outflow Graft Twist Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessCase ReportPDF/EPUBThree-Dimensional Computed Tomography Reconstruction for Diagnosis of Left Ventricular Assist Device Outflow Graft Twist Boaz Elad, Jonathan Lessick, Zvi Adler and Oren Caspi Boaz EladBoaz Elad Department of Cardiology (B.E., J.L., O.C.), Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. , Jonathan LessickJonathan Lessick Department of Cardiology (B.E., J.L., O.C.), Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. , Zvi AdlerZvi Adler Cardiovascular Surgery (Z.A.), Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. and Oren CaspiOren Caspi Correspondence to: Oren Caspi, MD, PhD, Department of Cardiology, Rambam Health Care Campus and, the B. Rappaport Faculty of Medicine, Technion, Haifa, Israel, POB 9602, Haifa 31096, Israel. Email E-mail Address: [email protected] https://orcid.org/0000-0002-2464-7357 Department of Cardiology (B.E., J.L., O.C.), Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. Originally published29 Mar 2022https://doi.org/10.1161/CIRCIMAGING.121.013714Circulation: Cardiovascular Imaging. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 29, 2022: Ahead of Print A 70-year-old male with dilated cardiomyopathy, having an ejection fraction of 10%, and INTERMACS 4, was implanted with a left ventricular assist device (LVAD) HeartMate 3 (Abbott, Abbott Park, IL) without major complications, on the ninth of September 2019. Echocardiography and cardiac computed tomography (CT) following device implantation showed appropriate left ventricle (LV) unloading and normal outflow cannula flows and patency (Figure 1 and Figure S1A). In April 2021, the patient complained of general weakness. Clinical examination was normal, but LVAD interrogation identified a gradual decline of LVAD flow (from 3.4 to 2.6 L/min) without a significant change in pulsatility index or power consumption (Figure 2). Laboratory evaluation revealed worsening of renal function (creatinine increased from 1 to 1.5 mg/dL), therapeutic INR (2.3), normal lactate dehydrogenase, and stable hemoglobin levels. He was hospitalized for further evaluation.Download figureDownload PowerPointFigure 1. Three-dimensional (3D) computed tomography (CT) reconstruction of the left ventricular assist device (LVAD) outflow cannula. A 3D volume rendering (upper), longitudinal (middle), and cross-sectional CT images (lower) at 3 time-points: immediately after LVAD implantation (A), at twist occurrence (B), and after surgical repair (C). Red Arrow: outflow graft twist obstruction.Download figureDownload PowerPointFigure 2. Left ventricular assist device (LVAD) parameters before, at twist, and after twist repair. A gradual flow decrease is noted before the identification of the LVAD outflow graft twist. Flow decrease was accompanied by a simultaneous decrease in Pulsatility index (PI) while power was relatively stable. Immediately following twist repair surgery (dashed line), a substantial improvement in flow rate occurred and PI values returned to normal. RPM indicates revolutions per minute.Trans-esophageal echocardiography examination identified impaired unloading of the LV, manifesting as a shift of the septum toward the right ventricle, mild mitral regurgitation, and systolic opening of the aortic valve (permanently closed in prior exams) at 5100 revolutions per minute. Speed ramping, up to 5500 revolutions per minute, did not elicit an improvement in LV unloading. A CT angiography showed a large irregular filling defect sized 7 centimeters at the proximal outflow cannula. The initial differential diagnosis included outflow cannula twist and outflow cannula thrombosis. Three-dimensional CT volume rendering of the outflow cannula demonstrated a full rotational twist of the outflow cannula (Figure 1 and Figure S1B marked by a red arrow) and compromised LV unloading (Figure S2B). Treatment options included a minimally invasive surgery with an untwist operation or a more extensive surgery with an optional outflow cannula or total device replacement. Based on the clear diagnostic image from the CT and the clinical information, the initial intent of the planned surgery was to conduct an untwist operation without outflow graft or device replacement.Using a lateral thoracotomy approach, a >270º twist of the Dacron outflow graft was identified, leading to severe outflow cannula compression. The outflow cannula was untwisted and using the Abbot fixation device, the cannula was fixed, resulting in immediate improvement of the flow rate (Figure 2) and LV unloading (Figure S2C).Repeated transient low flow events at the end of the procedure mandated a repeat CT angiography after surgery to confirm the adequacy of the untwisting procedure (Figure 1 and Figure S1C). A week after surgery, the patient was discharged in good condition and with an LVAD flow of 3.8 to 4 L/min.Four months following the untwist procedure, the patient is well with stable LVAD flows.HeartMate 3 is a fully magnetically levitated centrifugal-flow pump reported recently to be associated with a favorable prognosis including low rates of stroke and low rates of pump thrombosis, and pump replacement in a 2-year follow-up.1 A rare, but life-threatening, adverse event associated with HeartMate 3 is the development of sudden outflow graft obstruction due to rotational twist.1 This complication is unique to HeartMate 3. There is only limited data illustrating the diagnostic criteria, optimal surgical repair, and postrepair follow-up.2 This phenomenon may occur due to repeated rotation of the outflow's swivel joint associated with HeartMate 3 artificial pulse, cardiac and respiratory frictional forces, turbulent flow, and migration of the LVAD during cardiac remodeling.2An important question is whether anatomic or technical considerations evident immediately after implantation may predispose patients to outflow graft twists. In this current case, we found no evidence of a predisposing factor after the implantation. The purpose of this report is to describe the first case of an outflow graft twist obstruction with comprehensive CT angiography imaging at 3 critical time points: immediately after LVAD implantation, at twist occurrence, and after surgical repair.CT angiography is considered the gold standard in obtaining the diagnosis and etiology of outflow graft obstruction.3,4 Three-dimensional reconstruction of the proximal outflow graft, as demonstrated in Figure 1, is crucial for assuring the diagnosis of twist and ruling out other etiologies of mechanical obstruction, such as outflow graft thrombosis or external kink. It has been recently recommended to implant HeartMate 3 LVADs with Abbott's outflow graft clip or a revised outflow graft swivel joint fixture.In conclusion, we believe that it is very important to maintain a high degree of active awareness that a drop in pump flow without signs of pump thrombosis may indicate outflow graft obstruction due to twist, which is best recognized by 3-dimensional CT reconstruction of the outflow graft.Article InformationSources of FundingNone.Supplemental MaterialsFigures S1 and S2Disclosures None.FootnotesSupplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.121.013714.For Sources of Funding and Disclosures, see page 282.Correspondence to: Oren Caspi, MD, PhD, Department of Cardiology, Rambam Health Care Campus and, the B. Rappaport Faculty of Medicine, Technion, Haifa, Israel, POB 9602, Haifa 31096, Israel. Email [email protected]gov.ilReferences1. Mehra MR, Goldstein DJ, Uriel N, Cleveland JC, Yuzefpolskaya M, Salerno C, Walsh MN, Milano CA, Patel CB, Ewald GA, et al. Two-year outcomes with a magnetically levitated cardiac pump in heart failure.N Engl J Med. 2018; 378:1386–1395. https://doi.org/10.1056/NEJMoa1800866CrossrefMedlineGoogle Scholar2. Potapov EV, Netuka I, Kaufmann F, Falk V, Mehra MR. Strategy for surgical correction and mitigation of outflow graft twist with a centrifugal-flow left ventricular assist system.J Heart Lung Transplant. 2018; 37:670–673. doi: 10.1016/j.healun.2018.03.014CrossrefMedlineGoogle Scholar3. Kagan V, Mehta C, Michel E, Ward A, Jivan A, Ricciardi M, Anderson A, Pham DT, Rich J. Approaches to repairing outflow graft stenosis in left ventricular assist devices.J Heart Lung Transplant. 2019; 38:S367. https://doi.org/10.1016/j.healun.2019.01.933CrossrefGoogle Scholar4. Wamala I, Kneissler S, Kaufmann F, Eulert-Grehn JJ, Potapov E, Dreysse S, Starck C, Falk V, Solowjowa N. Computed tomography and fluoroscopic angiography in management of left ventricular assist device outflow graft obstruction.JACC Cardiovasc Imaging. 2020; 13:2036–2042. doi: 10.1016/j.jcmg.2019.11.018CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails April 2022Vol 15, Issue 4 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.121.013714PMID: 35348000 Originally publishedMarch 29, 2022 Keywordsechocardiographyleft ventricular outflow obstructionheart assist devicecomputed tomography angiographythrombosisPDF download Advertisement SubjectsCardiovascular SurgeryHeart FailureImaging

Recent data indicate that left atrial (LA) function assessment by cardiac computed tomography (CT) is closely related to diastolic dysfunction (DD). Therefore, we aimed to perform a direct comparison between CT and echocardiography for diagnosis of advanced DD and prediction of future heart failure or cardiovascular death. We identified 340 patients who had both spiral cardiac CT and a proximate echocardiogram. LA total emptying fraction (LATEF), a measure of global LA function, was automatically calculated from CT data, as a surrogate for diastolic function and was compared with echocardiographic grades of diastolic function. The area under the receiver operating characteristic curve for LATEF to differentiate between advanced DD (grades 2 and 3) and all other grades was 0.84 (0.79 to 0.88). Over a median of 4 years, 69 events (admissions for heart failure and cardiovascular deaths) occurred. By multivariate Cox analysis, LATEF < 40% provided incremental prognostic information after adjustments for advanced DD by echocardiography (hazard ratio 2.15, 95% confidence interval 1.13 to 3.94). There was a significant interaction (p = 0.03) between LATEF and echocardiography-based diastolic grades. Stratified analyses within the diastolic function groups revealed that LATEF <40% was equivalent to echocardiography in predicting events in the subgroup with advanced DD by echocardiography (p = 0.20) but was associated with a significantly higher event rates in patients with normal filling pressures (p = 0.0001) or indeterminate diastolic function (p = 0.04) by echocardiography. In conclusion, LA function derived from CT can accurately detect advanced DD diagnosed by echocardiography and has additive value to echocardiography-derived DD. (c) 2022 Elsevier Inc. All rights reserved. (Am J Cardiol 2022;181:71-78)

We sought to evaluate cardiac CT angiography (CCTA)–based assessment of left atrial (LA) function as a predictor of hospitalizations for heart failure (HF) and cardiovascular (CV) mortality. LA function was evaluated using automatic derivation of LA volumes to calculate LA total emptying fraction (LATEF) in 788 consecutive patients with normal sinus rhythm who had undergone spiral CT scans. The relationship between LATEF evaluated by CCTA and the composite endpoint of admission for HF or CV mortality was analyzed using Cox models. During a median follow-up of 4 years, there were 100 events, 62 HF hospitalizations, and 38 cardiovascular deaths. Mean LATEF was 30.7 ± 10.7% and 40.5 ± 11.2% in patients with and without events, respectively (p < 0.0001). A high LATEF (upper tertile > 46%) was associated with a very low event rate (3.5% at 6 years [95% CI 1.7–7.1%]). The adjusted HR for HF or CV mortality was 4.37 (95% CI 1.99–9.60) in the lowest LATEF tertile, and 2.29 (95% CI 1.03–5.14) in the middle tertile, relative to the highest tertile. For the endpoint of HF alone, adjusted HR for the lowest LATEF tertile was 5.93 (95% CI 2.23–15.82) and for the middle tertile 2.89 (95% CI 1.06–7.86). The association of LATEF with outcome was similar for patients with both reduced and preserved left ventricular (LV) ejection fraction (Pinteraction = 0.724). Reduced LATEF was associated with a high event rate, even when coupled with normal LA volume. CCTA-derived LA function is a predictor of HF hospitalization or CV death, independent of clinical risk factors, LA volume, and LV systolic function. • Left atrial function can be automatically derived from cardiac CTA scans. • Cardiac CTA-derived left atrial function is a predictor of hospitalization for heart failure and cardiovascular death. • Evaluation of left atrial function could be useful in identifying patients at risk of heart failure.

Objectives We aimed to assess the agreement between cardiac computed tomography (CT) and echo for diagnosing advanced diastolic dysfunction (DD) and to assess the prognostic value of CT-based parameters. Methods One hundred one consecutive patients who had both CT and echo-Doppler within 1 month were included. Diastolic function was assessed by CT using a previously validated method, based on left atrial volume changes, and compared with echocardiography grades 0 to 3. Patients were followed up for a combined outcome of cardiac death and hospitalization for heart failure. Results By operating characteristic curve analysis, the best CT-based parameter for predicting advanced DD based on echo was left atrial total emptying fraction. Left atrial total emptying fraction <36% had sensitivity/specificity of 76%/86%. Agreement between echo and CT for detecting advanced (grades 2/3) DD was substantial (κ = 0.62, P < 0.0001). By Cox multivariate analysis, left atrial total emptying fraction was a powerful independent predictor of outcome at 3 years (hazard ratio, 8.0 [2.2–28.4]; P < 0.0001). Conclusions Computed tomography–based assessment of DD has a good agreement with echo-Doppler–based results. Left atrial total emptying fraction seems to have a strong prognostic value.

Abstract Background Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS). Purpose This study sought to compare aortic root, aorta and iliofemoral artery anatomy in patients with bicuspid versus tricuspid AS. Methods 172 patients with bicuspid AS and 331 patients with tricuspid AS underwent pre-procedural computed tomography (CT) evaluation before TAVR. Dimensions, calcification, and tortuosity of the iliofemoral arteries were evaluated and the dimensions of aortic root, aorta, and left subclavian arteries were determined. Results Dimensions of aortic root, aorta, left subclavian, and iliofemoral arteries were consistently and significantly larger in bicuspid than in tricuspid AS (P<0.001). Patients with bicuspid AS had significantly lower subclavian, aorta, and iliofemoral arteries calcification, lower tortuosity index and lower maximal tortuosity angle compared to patients with tricuspid AS (P<0.001 for all) even after adjustment for baseline characteristics (Figure). Compared to tricuspid AS the prevalence of porcelain aorta and aneurysm in the descending aorta and iliofemoral arteries were significantly less common in bicuspid valve anatomy. After adjustment for baseline characteristics Bicuspid valve anatomy was associated with lower odds of vascular calcification (odds ratio (OR) 0.82: 95% CI 0.52–0.93; P=0.001). Conclusions Bicuspid AS was associated with larger dimensions of aortic root, aorta, subclavian, and iliofemoral arteries compared with tricuspid AS. Low vascular calcification and decreased tortuosity index of iliofemoral arteries characterized bicuspid anatomy. Further studies are needed to evaluate the impact of bicuspid vascular anatomy on vascular complications after TAVR. Funding Acknowledgement Type of funding sources: None.

There is a growing interest in transcutaneous aortic valve implantation (TAVI) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVI, and new-onset permanent LBBB (NOP-LBBB) post-TAVI may be a marker of worse outcomes. We aimed to evaluate the rate of NOP-LBBB following TAVI among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVI Registry were reviewed and compared with patients with TAV. Patients with previous aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVI. A total of 387 patients (66 with BAV, 321 with TAV), age 80.3 ± 7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV versus TAV (29.2% vs 16.9%, p = 0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs 12.5%; respectively, p = 0.62). In BAV and TAV groups, 1-year mortality (6.1% vs 7.2%; respectively, p = 0.75) and stroke rates (6.1% vs 3.5%; respectively, p = 0.30) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (AdjOR = 2.7, 95%CI 1.3 to 5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (AdjOR = 3.2, 95%CI: 1.5 to 6.7). In conclusion, patients with BAV undergoing TAVI have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies.

Abstract Background Bicuspid aortic valve (BAV) patients represent a significant minority of severe aortic stenosis (AS) patients undergoing transcutaneous aortic valve implantation (TAVI). These patients demonstrate anatomic differences compared to tricuspid aortic valve (TAV). Ethnicity is associated with different valve morphologies characterized by Siever's classification. Purpose We aim to evaluated the prevalence of BAV subtypes and the differences in valve morphology and aortic root dimensions between BAV and TAV in patients undergoing computed tomography (CT) before TAVI. Methods In five Israeli medical centers, 131 patients with BAV and 674 patients with TAV underwent CT angiography. BAV morphology was defined according to the number of commissures and raphe, following Siever's classification. Aortic root dimensions were measured at the level of the aortic annulus, sinus of Valsalva (SOV), and sino-tubular junction (STJ). Finally, Agatston score unit (AU) for valve calcification was evaluated. Results Type 0 accounted for 27% (36/131), Type IA for 63% (82/131), Type IC for 9% (12/131), and Type 2 for 1% (1/131). Calcium score in BAV patients was significantly higher compared to TAV patients, 4000±1897 vs. 2152±1216 AU; respectively (P<0.001). Distance from the annulus to the left main coronary artery was greater in BAV patients compared to TAV (13.8±3.6 mm vs. 12.8±2.8 mm; respectively, P<0.001), similar distance from annulus to right coronary artery was observed in BAV and TAV patients (16.7±3.7 mm vs. 15±3 mm; respectively, P<0.001). Aortic annulus perimeter was greater in BAV than TAV patients (79.3±11mm vs. 73±8.7mm, respectively, P<0.001), as well as SOV perimeter (35.7±4.5mm vs. 32±3.7mm, respectively, P<0.001), and STJ perimeter (32.3±5mm vs. 27±3.3 mm; respectively, P<0.001). Conclusion In Israel, AS patients showed more frequently type 1A BAV. BAV patients have larger aortic root dimensions and higher calcium burden than TAV patients. Funding Acknowledgement Type of funding source: None

OBJECTIVES: The objective of this study was to determine risk factors for progression to hemodynamically significant tricuspid regurgitation (TR) and the population burden attributable to these risk factors. BACKGROUND: Few data are available with regard to risk factors associated with the development of hemodynamically significant functional TR. METHODS: A total of 1,552 subjects were studied beginning with an index echocardiogram demonstrating trivial or mild TR. Risk factors for progression to moderate or severe TR were determined by using logistic regression and classification trees. Population attributable fractions were calculated for each risk factor. RESULTS: During a median follow-up time of 38 (interquartile range [IQR]: 26 to 63) months, 292 patients (18.8%) developed moderate/severe TR. Independent predictors of TR progression were age, female sex, heart failure, pacemaker electrode, atrial fibrillation (AF), and indicators of left heart disease, including left atrial (LA) enlargement, elevated pulmonary artery pressure (PAP), and left-sided valvular disease. Classification and regression tree analysis demonstrated that the strongest predictors of TR progression were PAP of >= 36 mm Hg, LA enlargement, age >= 60 years, and AF. In the absence of these 4 risk factors, progression to moderate or severe TR occurred in similar to 3% of patients. Age (28.4%) and PAP (20.5%) carried the highest population-attributable fractions for TR progression. In patients with TR progression, there was a marked concomitant increase of incident cases of elevated PAP (40%); mitral and aortic valve intervention (12%); reductions in left ventricular ejection fraction (19%), and new AF (32%) (all p < 0.01). CONCLUSIONS: TR progression is determined mainly by markers of increased left-sided filling pressures (PAP and LA enlargement), AF, and age. At the population level, age and PAP are the most important contributors to the burden of significant TR. TR progression entails a marked parallel increase in the severity of left-sided heart disease. (C) 2020 by the American College of Cardiology Foundation

Abstract Background Significant functional tricuspid regurgitation (TR) has been associated with higher risk for adverse cardiovascular outcomes. Left-sided heart disease (LHD) is a potentially important confounder of this association because it is strongly linked to both TR and to clinical outcome. Methods We studied 5886 patients who were followed for a period of 10-years after the index echocardiographic examination. The relationship between TR severity and the composite endpoint of admission for heart failure or cardiovascular mortality was analyzed using a Cox model. An additional analysis included a propensity-score-matching. To simplify the modeling of the severity of LHD, we calculated an additive score summing the number of LHD components as follows: reduced LVEF, LA enlargement ≥moderate, aortic or mitral valve disease (regurgitation or stenosis ≥moderate) and PASP≥50 mmHg. Results Higher TR grade was associated with markers of LHD including left ventricular systolic dysfunction, valvular heart disease ≥moderate, left atrial enlargement and pulmonary hypertension (All P < 0.001). There was a significant interaction between TR and the presence of LHD with regard to the endpoint of heart failure in the model for admission for heart failure (P = 0.01) and the combined endpoint of heart failure and cardiovascular mortality (P = 0.02). In both models, moderate/severe TR was associated with higher risk for heart failure (hazard ratio [HR] 3.13; 95% CI 2.49–3.93, P < 0.0001) and the combined endpoint of heart failure or cardiovascular mortality (HR 2.61; 95% CI 1.33–5.13, P = 0.005) only in patients without LHD. The interaction plot (Figure) demonstrates that when LHD is present, TR is not a predictor of clinical outcome. Propensity score matching yielded 350 patient pairs, of which 88% had LHD. The HR for heart failure or cardiovascular mortality at 10-years was 0.78 (95% CI 0.56–1.08, P = 0.14) in the moderate/severe TR as compared with the trivial/mild TR. Conclusions Moderate or severe functional TR portends an increased risk for heart failure and cardiovascular mortality only when isolated, without concomitant LHD. Abstract 40 Figure. Interaction plot

Abstract Background Transcatheter aortic valve implantation (TAVI) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS). Objectives This study sought to compare aortic root and ilio-femoral artery characteristics and clinical outcomes in patients with bicuspid versus tricuspid AS from the Bicuspid AS TAVI multicenter registry. Methods 88 patients with bicuspid AS and 213 matched patients with tricuspid AS were referred for pre-procedural computed tomography (CT) evaluation before TAVI. We performed a detailed assessment of aortic root anatomy: size of the annulus, sinus of Valsalva (SoV), sino-tubular junction (STJ); we also determined the dimensions of aorta, left subclavian, and ilio-femoral arteries. Results Patients with bicuspid AS had significantly larger aortic root dimensions, (annulus mean diameter: 25.5±2.9 mm vs. 23.7±2.4 mm, SoV mean diameter: 35.3±4.7 mm vs. 32±4.4mm, STJ mean diameter: 31.5±4.9 mm vs. 27.6±3.5 mm; respectively) than patients with tricuspid AS (P value for all <0.001), even after adjustment for their larger BSA and height. Dimensions of ascending aorta, left subclavian artery, and ilio-femoral arteries were also consistently larger in bicuspid than in tricuspid AS morphology. Conclusions Patients with bicuspid AS had significantly larger aortic root dimensions, larger ascending aorta, subclavian artery and ilio-femoral arteries even after adjustment for their BSA and height. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Rabin Medical Center

Background: Distinct anatomical features predispose bicuspid AS patients to conduction disturbances after TAVR. This study sought to evaluate whether the incidence of permanent pacemaker implantation (PPMI) and left bundle branch block (LBBB) in patients with bicuspid aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR) is related to an anatomical association between bicuspid AS and short membranous septal (MS) length. Methods: Sixty-seven consecutive patients with bicuspid AS from a Bicuspid AS TAVR multicenter registry and 67 propensity-matched patients with tricuspid AS underwent computed tomography before TAVR. Results: MS length was significantly shorter in bicuspid AS compared with tricuspid AS (6.2 +/- 2.5 mm vs. 8.4 +/- 2.7 mm, respectively; p < 0.001). In patients with bicuspid AS, MS length and aortic valve calcification were the most powerful pre-procedural independent predictors of PPMI or LBBB (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.15 to 1.55, p = 0.003 and OR: 1.92, 95% CI: 1.1 to 3.34, p = 0.022, respectively). When taking into account pre-and post-procedural parameters, aortic valve calcification and the difference between MS length and implantation depth were the most powerful independent predictors of PPMI or LBBB in patients with bicuspid AS (OR: 1.82, 95%: 1.1 to 3.1, p = 0.027; OR: 1.25, 95% CI: 1.10 to 1.38, p = 0.003). Conclusion: MS length, which was significantly shorter in bicuspid AS compared with tricuspid AS, aortic valve calcification, and device implantation deeper than MS length predict PPMI or LBBB in bicuspid AS after TAVR.

Abstract Background Tricuspid regurgitation has been the focus of increasing interest and research in recent years. However, few data are available with regard to risk factors associated with the evolution of TR. purpose The aimed to determine the risk factors for the development of hemodynamically significant functional TR. Methods We studied 1552 subjects with an index echocardiogram demonstrating trivial or mild TR. Risk factors for TR progression to moderate or severe TR during a median follow-up time of 38 months (IQR 26 to 63 months), were determined using logistic regression. Results In the multivariable logistic regression model, older age, female gender, pacemaker electrode and indicators of left heart disease (LA enlargement, increased pulmonary artery pressure (PAP), atrial fibrillation, and left-sided valvular disease) were associated with future development moderate or severe TR (Table). The strongest predictors of TR progression were PAP, LA size, AF, and age. The final echocardiographic examination demonstrated a marked worsening in the severity of left-sided myocardial and valvular disease, that was more prominent in subjects with TR progression (Figure). Compared with subjects in whom TR did not progress, subjects with TR progression demonstrated an increase in PAP and in the severity of mitral and aortic valve disease, larger increases in LA and reductions in LVEF (Figure). Lager proportions of subjects progressing to significant TR developed AF, were implanted with pacemakers or defibrillators or underwent valvular interventions (Figure). The mean PAP change between the baseline and final echocardiographic examination was 16 ± 15 mm Hg and 3 ± 11 mm Hg with and without TR progression, respectively (P < 0.0001). Conclusion Predictors of TR progression are mostly indicators of more advanced left heart disease. In addition, progression to significant TR is associated with a more acceleration course of left hear disease. Independent Predictors of TR Progression Characteristics HR (95% CI) P value Age (per 10 years increase) 1.35 (1.31-1.50) <0.0001 Female sex 1.50 (1.13-1.99) <0.0001 Heart failure 2.76 (1.43-5.32) 0.002 LA enlargement ≥ Moderate 1.86 (1.29-2.67) 0.001 Atrial fibrillation 2.34 (1.57-3.49) <0.0001 Pacemaker/ICD 2.93 (1.48-5.78) 0.002 Pulmonary artery pressure (per 10 mm Hg increase) 1.47 (1.29-1.69) <0.0001 Valvular heart disease≥ Moderate 1.50 (1.11-2.04) 0.009 Abstract 44 Figure. Proportion of new abnormalities

Abstract Background Transcatheter aortic valve implantation (TAVI) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of differences in valve morphology and aortic root dimensions in patients with BAV in comparison to patients with tricuspid aortic valve (TAV) is important for the spread of TAVI in patients with BAV. Purpose The present study evaluated the prevalence of BAV subtypes and the differences in valve morphology and aortic root dimensions between BAV and TAV in patients undergoing computed tomography (CT) before TAVI. Methods In five medical centers in Israel, 104 patients (69±13.5 years) with BAV and 105 patients (81±8.22 years) with TAV underwent CT angiography. BAV morphology was defined according to the number of commissures and raphe following Siever's classification. Functional BAV was defined as 3 cusps with focal fusion of 1, 2, or 3 commissures. Aortic root dimensions were measured at the level of the aortic annulus, sinus of Valsalva (SOV), sino-tubular junction (STJ), and ascending aorta (AA). Membranous septum (MS) length was measured in coronal view. The volume and agatston score of aortic valve calcification were evaluated. Results Type 0 account for 22% (23/104), type IA for 58% (60/104), Type IC for 9% (9/104), functional BAV for 11% (12/104). Type IB and II were not found in the studied population. As compared with TAV, patients with BAV have significantly larger aortic annulus area, SOV area, STJ area and AA Area; however, the ellipticity index of aortic annulus, SOV, STJ, and AA were similar. MS length was significantly smaller in patients with BAV compared to patients with TAV (6.4±2.3 mm vs. 8.1±2.7mm; retrospectively; P<0.001) and the volume of aortic valve calcifications was significantly higher in BAV compared to TAV patients: 2.3±1.6 ml3 vs. 1.4±1.2 ml3 retrospectively; P=0.003). Conclusions In Israel, patients with BAV showed more frequently type 1A BAV. BAV patients have larger aortic root dimensions than patients with TAV without difference in regard to the ellipticity index. MS length was smaller and the amount of aortic leaflet calcifications was higher in patients with BAV. These findings may have important impact on procedural outcome.

Background: Significant tricuspid regurgitation (TR) is associated with higher risk for adverse cardiovascular outcomes. Left-sided heart disease (LHD) is a potentially important confounder of this association because it is strongly linked to both TR and clinical outcome. Methods: We studied 5,886 patients who were followed for a period of 10 years after the index echocardiographic examination. The relationship between TR severity and the end point of admission for heart failure or cardiovascular mortality was analyzed using competing risk analysis, Cox model, and propensity score matching. Results: Higher TR grade was associated with markers of LHD including left ventricular systolic dysfunction, valvular heart disease $ moderate, left atrial enlargement, and pulmonary hypertension (all P<.001). There was a significant interaction between TR and the presence of LHD with regard to the end point of heart failure in the competing risks model (P=.01) and the combined end point of heart failure and cardiovascular mortality (P=.02). In both models, moderate/severe TR was associated with higher risk for heart failure (hazard ratio [HR]= 3.10; 95% CI, 1.41-6.84; P=.005) and the combined end point of heart failure or cardiovascular mortality (HR= 2.75; 95% CI, 1.33-5.63, P=.006) only in patients without LHD. Propensity score matching yielded 350 patient pairs, of which 88% had LHD. The HR for heart failure or cardiovascular mortality at 10 years was 0.78 (95% CI, 0.56-1.08; P=.14) in the moderate/severe TR group as compared with the trivial/mild TR. Conclusions: Moderate or severe functional TR portends an increased risk for heart failure and cardiovascular mortality only when isolated, without concomitant LHD.