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We assessed the left atrial-left ventricular (LA-LV) long axis angulation value as a new measure of LA remodeling, and studied its predictors, its effect on two-dimensional LA volume (2D LAVol) estimation, and optimization techniques for 2D LAVol values. Retrospective electrocardiogram-gated coronary computed tomographic angiograms of 164 consecutive patients were reviewed. The LA–LV angle was measured in reconstructed 3-chamber views, and its predictors were determined. The LAVol measured by the area-length method after image optimization along the LV long axis (AL) and the LA long axis (AC–AL), was compared with that measured by the three-dimensional (3D)-volumetric method. LAVol calculation was modified to minimize differences from the 3D values. LA–LV angles ranged from 0° to 63°. In the univariate analysis, decreasing angulation was significantly associated with increasing LV end-diastolic volume (LVEDV), mitral regurgitation grade, LV and LA anteroposterior dimensions, and decreasing LV ejection fraction (LVEF). On multivariate analysis, increasing LVEDV, MR, and LA anteroposterior dimension inversely correlated with angulation; LVEF was positively correlated. The AL and 3D methods significantly differed only for patients with angles ≤ 29.9°. Conversely, LAVol was overestimated for all angules by AC–AL. Modification of AL LAVol using a regression equation, or by substituting the shortest with the longest and average LA lengths in patients with angles ≤ 29.9° and 30–39.9°, respectively neutralized the difference. The LA–LV angle is a new measure of LA and LV remodeling predicted by LV size and function, MR, and LA-anteroposterior dimension. AL formula modifications based on angulation in LV-optimized views better correlate with the 3D method than LA-view modification.

BACKGROUND Hypertension (HTN) has the greatest population-attributable risk for aortic dissection and is highly prevalent among patients with thoracic aortic aneurysms (TAAs). Although HTN is diagnosed based on brachial blood pressure (bBP), central HTN (central systolic blood pressure [cSBP] ≥130 mm Hg) is of interest as it better reflects blood pressure (BP) in the aorta. We aimed to (i) evaluate the prevalence of central HTN among TAA patients without a diagnosis of HTN, and (ii) assess associations of bBP vs. central blood pressure (cBP) with aneurysm size and growth. METHODS One hundred and five unoperated subjects with TAAs were recruited. With validated methodology, cBP was assessed with applanation tonometry. Aneurysm size was assessed at baseline and follow-up using imaging modalities. Aneurysm growth rate was calculated in mm/year. Multivariable linear regression adjusted for potential confounders assessed associations of bBP and cBP with aneurysm size and growth. RESULTS Seventy-seven percent of participants were men and 49% carried a diagnosis of HTN. Among participants without diagnosis of HTN, 15% had central HTN despite normal bBP (“occult central HTN”). In these patients, higher central systolic BP (cSBP) and central pulse pressure (cPP) were independently associated with larger aneurysm size (β ± SE = 0.28 ± 0.11, P = 0.014 and cPP = 0.30 ± 0.11, P = 0.010, respectively) and future aneurysm growth (β ± SE = 0.022 ± 0.008, P = 0.013 and 0.024 ± 0.009, P = 0.008, respectively) while bBP was not (P > 0.05). CONCLUSIONS In patients with TAAs without a diagnosis of HTN, central HTN is prevalent, and higher cBP is associated with larger aneurysms and faster aneurysm growth.

AimsPurpose of this study is to compare the clinical course and outcome of patients with recurrent versus first-episode infective endocarditis (IE).MethodsPatients with recurrent and first-episode IE enrolled in the EUROpean ENDOcarditis (EURO-ENDO) registry including 156 centres were identified and compared using propensity score matching. Recurrent IE was classified as relapse when IE occurred ≤6 months after a previous episode or reinfection when IE occurred >6 months after the prior episode.Results3106 patients were enrolled: 2839 (91.4%) patients with first-episode IE (mean age 59.4 (±18.1); 68.3% male) and 267 (8.6%) patients with recurrent IE (mean age 58.1 (±17.7); 74.9% male). Among patients with recurrent IE, 13.2% were intravenous drug users (IVDUs), 66.4% had a repaired or replaced valve with the tricuspid valve being more frequently involved compared with patients with first-episode IE (20.3% vs 14.1%; p=0.012). In patients with a first episode of IE, the aortic valve was more frequently involved (45.6% vs 39.5%; p=0.061). Recurrent relapse and reinfection were 20.6% and 79.4%, respectively.Staphylococcus aureuswas the microorganism most frequently observed in both groups (p=0.207). There were no differences in in-hospital and post-hospitalisation mortality between recurrent and first-episode IE. In patients with recurrent IE, in-hospital mortality was higher in IVDU patients. Independent predictors of poorer in-hospital and 1-year outcome, including the occurrence of cardiogenic and septic shock, valvular disease severity and failure to undertake surgery when indicated, were similar for recurrent and first-episode IE.ConclusionsIn-hospital and 1-year mortality was similar in patients with recurrent and first-episode IE who shared similar predictors of poor outcome.

Background: Endocardial lead in the right ventricle is recognized as a cause for tricuspid regurgitation (TR), but the mechanism remains elusive. We sought to evaluate lead-specific features on the development of TR after endocardial lead implantation. Methods: This was a prospective single-center study. The patients underwent 2-dimensional echocardiograms before endocardial lead implantation and at follow-up visits at 4 to 6 weeks, 6 months, and 12 months. We assessed the position of the endocardial lead at the tricuspid annulus by 3-dimensional echocardiography, the tricuspid leaflet interference by the endocardial lead by both 2- and 3-dimensional echocardiography, and the degree of lead slack radiologically. Patient characteristics and lead-related factors were evaluated in the prediction of new or worse TR by univariable and multivariable analyses. Results: New or increased TR was detected in 38 of 128 patients at the 12-month follow-up. The postero-septal commissure was the most common lead position, and tricuspid leaflet interference detected in 21 patients was associated with a noncommissural lead position. The implantation of an implantable cardioverter defibrillator lead was not associated with new TR compared with the implantation of a pacemaker lead. Tricuspid leaflet interference (P < 0.0001), but not lead position or lead slack, was the only lead-specific factor associated with the development of TR. Conclusion: After right ventricle endocardial lead implantation, leaflet interference determined by echocardiography, but not the nature of the lead, the lead position at the tricuspid annulus, and the radiological lead slack, predicted TR development at 1 year postimplantation. Résumé: Contexte: Il est établi que la présence d’une sonde endocavitaire dans le ventricule droit est une cause de régurgitation tricuspide (RT), mais le mécanisme en cause n’est pas encore bien compris. Nous avons tenté d’évaluer la corrélation entre certaines caractéristiques des sondes et l’apparition d’une RT secondaire à l’implantation d’une sonde endocavitaire. Méthodologie: Il s’agit d’une étude prospective menée dans un seul centre. Une échocardiographie bidimensionnelle a été réalisée avant la mise en place d’une sonde endocavitaire, ainsi qu’aux visites de suivi menées 4 à 6 semaines, 6 mois et 12 mois après l’intervention. Nous avons évalué la position de la sonde endocavitaire par rapport à l’anneau tricuspidien par échocardiographie tridimensionnelle, l’interférence de la sonde avec la valve tricuspide par échocardiographie bidimensionnelle et tridimensionnelle, et le degré de liberté de mouvement de la sonde par radiographie. Les caractéristiques des patients et les facteurs liés à la sonde ont été pris en compte dans la prédiction du risque de RT nouvelle ou d’aggravation d’une RT existante au moyen d’analyses univariées et multivariées. Résultats: Une RT nouvelle ou aggravée a été détectée au suivi à 12 mois chez 38 des 128 patients. Dans la plupart des cas, la sonde se trouvait à la commissure postéroseptale; chez 21 patients, une interférence avec la valve tricuspide a été détectée alors que la sonde ne se trouvait pas à la commissure. La mise en place d'une sonde de défibrillateur implantable n’a pas été associée à l’apparition d’une RT, comparativement à l’implantation d'une sonde de stimulateur cardiaque. L’interférence avec la valve tricuspide (p < 0,0001) était le seul facteur lié à la sonde associé à l’apparition d’une RT; aucun lien n’a été établi avec la position et le degré de liberté de mouvement de la sonde. Conclusion: Après la mise en place d’une sonde endocavitaire dans le ventricule droit, l’interférence avec la valve tricuspide établie par échocardiographie permettait de prédire l’apparition d’une RT dans l’année suivant la mise en place de la sonde sans égard au type de sonde, à sa position par rapport à l’anneau tricuspidien ou à la liberté de mouvement détectée par radiographie.

Aortic valve stenosis (AS) is the most common valvular heart disease in the Western world, affecting about 3% of the population over 75 years of age and after onset of symptoms is associated with adverse events including death.1 With the ageing of the population, AS likely will become an increasingly important health issue. Despite this grim prospect, a therapeutic strategy to slow the progression of AS has not been developed and the only effective treatment is aortic valve replacement. Furthermore, AS is a progressive condition, but the rate of progression is quite variable from individual to individual. The predilection of AS in the older individuals has led to the belief that AS was an inevitable result of a degenerative process, but research has shown that it is an active process involving multiple metabolic pathways, raising the possibility that the process can potentially be modified or interrupted.2 Epidemiological studies have shown that AS is associated with traditional atherosclerotic risk factors such as hypertension, smoking, diabetes and increased cholesterol. At the molecular level, AS also shares common features with atherosclerosis including lipid infiltration, inflammation, fibrosis and calcification in the subendothelial space and lamina fibrosa. Since lipoproteins are involved in several putative pathways in the development of AS, lipid-lowering agents such as statins would be expected to …

Thoracic aortic aneurysm (TAA) is a highly morbid disease. We have previously shown that baseline hemodynamic measures reflecting aortic function are associated with future TAA expansion. However, whether serial arterial hemodynamic assessment further improves TAA growth assessment remains unknown. Therefore, we aimed to compare single vs serial arterial hemodynamic assessments in the evaluation of future TAA growth.Eighty-six unoperated participants with TAA underwent noninvasive arterial hemodynamic assessment using arterial tonometry and echocardiography at baseline and after 1 year. Aortic diameter was measured serially with the use of standard imaging modalities. Stepwise multivariable linear regression was used to assess associations of baseline and 1-year change (Δ) in arterial hemodynamic measures with TAA growth.Mean age was 62.7 ± 11.0 years; 79% were male. Mean aneurysm growth was 0.48 ± 0.54 mm/year after a follow-up of 2.96 ± 1.03 years. Yearly changes in arterial hemodynamic measures ranged from -3.2% to +4.2%. Linear regression results showed that while baseline arterial hemodynamic measures were independently associated with aneurysm growth (carotid-femoral pulse wave velocity: β ± SE = 0.038 ± 0.013; aortic characteristic impedance: β ± SE = 0.002 ± 0.001; proximal aortic compliance: β ± SE = -0.011 ± 0.006; forward pressure wave amplitude: β ± SE 0.009 ± 0.002; reflected pressure wave amplitude: β ± SE = 0.017 ± 0.006; P0.05 for each), the 1-year Δ in these measures did not incrementally add to aneurysm growth assessment (P0.05 for each Δ).Although baseline measures of aortic function independently predict TAA expansion, 1-year changes in these measures do not improve this prediction. Thus, for TAA risk assessment purposes, a baseline assessment of aortic function may suffice, which simplifies its use for potential predictive algorithms.

Thoracic aortic aneurysm is a disease associated with high morbidity and mortality. Clinically useful strategies for medical management of thoracic aortic aneurysm are critically needed. To address this need, we sought to determine the role of aortic stiffness and pulsatile arterial load on future aneurysm expansion. One hundred five consecutive, unoperated subjects with thoracic aortic aneurysm were recruited and prospectively followed. By combining arterial tonometry with echocardiography, we estimated measures of aortic stiffness, central blood pressure, steady, and pulsatile arterial load at baseline. Aneurysm size was measured at baseline and follow-up with imaging; growth was calculated in mm/y. Stepwise multivariable linear regression assessed associations of arterial stiffness and load measures with aneurysm growth after adjusting for potential confounders. Mean±SD age, baseline aneurysm size, and follow-up time were 62.6±11.4 years, 46.24±3.84 mm, and 2.92±1.01 years, respectively. Aneurysm growth rate was 0.43±0.37 mm/y. After correcting for multiple comparisons, higher central systolic (β±SE: 0.026±0.009, P =0.007), and pulse pressures (β±SE: 0.032±0.009, P =0.0002), carotid-femoral pulse wave velocity (β±SE: 0.032±0.011, P =0.005), amplitudes of the forward (β±SE: 0.044±0.012, P =0.0003) and reflected (β±SE: 0.060±0.020, P =0.003) pressure waves, and lower total arterial compliance (β±SE: −0.086±0.032, P =0.009) were independently associated with future aneurysm growth. Measures of aortic stiffness and pulsatile hemodynamics are independently associated with future thoracic aortic aneurysm growth and provide novel insights into disease activity. Our findings highlight the role of central hemodynamic assessment to tailor novel risk assessment and therapeutic strategies to patients with thoracic aortic aneurysm.

Background: Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF); however, there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Our primary hypothesis was that routine use of CMR will yield more specific diagnoses in nonischemic HF. Our secondary hypothesis was that routine use of CMR will improve patient outcomes. Methods: Patients with nonischemic HF were randomized to routine versus selective CMR. Patients in the routine strategy underwent echocardiography and CMR, whereas those assigned to selective use underwent echocardiography with or without CMR according to the clinical presentation. HF causes was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months. Results: A total of 500 patients (344 male) with mean age 59±13 years were randomized. The routine and selective CMR strategies had similar rates of specific HF causes at 3 months clinical follow-up (44% versus 50%, respectively; P =0.22). At image interpretation, rates of specific HF causes were also not different between routine and selective CMR (34% versus 30%, respectively; P =0.34). However, 24% of patients in the selective group underwent a nonprotocol CMR. Patients with specific HF causes had more clinical events than those with nonspecific caused on the basis of imaging classification (19% versus 12%, respectively; P =0.02), but not on clinical assessment (15% versus 14%, respectively; P =0.49). Conclusions: In patients with nonischemic HF, routine CMR does not yield more specific HF causes on clinical assessment. Patients with specific HF causes from imaging had worse outcomes, whereas HF causes defined clinically did not. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01281384.

Endocardial lead in the right ventricle (RV) is recognized as a cause for tricuspid regurgitation (TR), but the prevalence and significance are not well defined [(1)][1]. The objectives of the study were to prospectively assess the prevalence of TR in this clinical setting, evaluate the functional

Background The development of mitral stenosis (MS) is not uncommon after mitral valve (MV) repair for degenerative mitral regurgitation (MR), but the significance of MS in this setting has not been defined. Methods We prospectively studied 110 such patients who underwent supine bicycle exercise testing to assess intracardiac hemodynamics at rest and at peak exercise. B-type natriuretic peptide (BNP) levels were measured at rest and after the exercise test. The patients also performed the 6-minute walk test and completed the 36-Item Short Form Survey (SF-36). Follow-up was performed by a review of the medical record and telephone interview. Results Of 110 patients, 22 had MS defined by a mitral valve area (MVA) ≤ 1.5 cm 2 . The resting and peak exercise mitral gradients and pulmonary artery systolic pressure were significantly higher in patients with MS compared with patients with an MVA > 1.5 cm 2 . BNP levels at rest and after exercise were also higher in the patients with MS, who also had lower exercise capacity and worse perception of well-being in 3 domains (physical function, vitality, and social function) on the SF-36. MVA had higher specificity and positive predictive value in predicting outcome events compared with a mean gradient of 3 or 5 mm Hg. Conclusions In patients who had MV repair for degenerative MR, an MVA ≤ 1.5 cm 2 occurs in about one-fifth of patients and is associated with adverse intracardiac hemodynamics, lower exercise capacity, and adverse outcomes.

The "athletic heart" is characterized by hypertrophy and dilation of the heart, in addition to functional and electrical remodeling. The aim of this study was to provide reference 2-dimensional (2DE) and 3-dimensional (3DE) echocardiographic measurements in a large database on draft-eligible elite ice hockey players and to determine the frequency of occult cardiac anomalies in this cohort of athletes. In this prospective cohort study, we performed a comprehensive cardiac assessment of the 100 top draft picks selected by the National Hockey League. Complete 2DE and 3DE examinations were performed to obtain comprehensive measurements of cardiac structure and function at rest, which were compared with nonathlete controls. A total of 592 athletes were evaluated (mean age 18 ± 0.5 years) from 2009 to 2014 at the National Hockey League combine. 2DE and 3DE ventricular, atrial dimensions, and left ventricular mass were significantly greater in the athletes compared with controls. Abnormalities were identified in 15 hockey players (2.5%) consisting of a bicuspid aortic valve in 10 (1.7%), patent ductus arteriosus in 1 (0.2%), low normal left ventricular systolic function in 2 (0.3%), an idiopathic pericardial effusion in 1 (0.2%), and posterior mitral valve prolapse in 1 (0.2%). In conclusion, intense ice hockey training is associated with typical myocardial adaptations and the frequency of cardiac anomalies found in this cohort of young elite hockey players is low and does not differ significantly from the reported incidences in the general population.

ObjectiveThis study assessed whether apolipoprotein CIII-lipoprotein(a) complexes (ApoCIII-Lp(a)) associate with progression of calcific aortic valve stenosis (AS).MethodsImmunostaining for ApoC-III was performed in explanted aortic valve leaflets in 68 patients with leaflet pathological grades of 1–4. Assays measuring circulating levels of ApoCIII-Lp(a) complexes were measured in 218 patients with mild–moderate AS from the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. The progression rate of AS, measured as annualised changes in peak aortic jet velocity (Vpeak), and combined rates of aortic valve replacement (AVR) and cardiac death were determined. For further confirmation of the assay data, a proteomic analysis of purified Lp(a) was performed to confirm the presence of apoC-III on Lp(a).ResultsImmunohistochemically detected ApoC-III was prominent in all grades of leaflet lesion severity. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), oxidised phospholipids on apolipoprotein B-100 (OxPL-apoB) or on apolipoprotein (a) (OxPL-apo(a)) with annualised Vpeak(all ppeak(pConclusionApoC-III is present on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild–moderate AS who display rapid progression of AS and higher rates of AVR/cardiac death.Trial registrationNCT00800800.

Background Bicuspid aortic valve ( BAV ) is the most common congenital cardiac abnormality. A thoracic aortic aneurysm ( TAA ) is present in ≈50% of BAV patients, who also have an 8‐fold higher risk of aortic dissection than the general population. Because the health of the aorta is directly reflected in its stiffness and pulsatile hemodynamics, we hypothesized that measures of aortic stiffness and arterial load would be associated with TAA growth in BAV . Methods and Results Twenty‐nine unoperated participants with TAA due to BAV who had serial imaging were recruited. Aortic stiffness and steady and pulsatile arterial load were evaluated with validated methods that integrate arterial tonometry with echocardiography. TAA growth was assessed retrospectively based on available imaging, blinded to hemodynamic status. Multivariable linear regression assessed associations of aortic stiffness and hemodynamic variables with TAA growth, adjusting for potential confounders. Overall, 66% of participants were men. Mean±SD for age, baseline aneurysm size, growth rate, and follow‐up time were 57.2±8.3 years, 46.9±3.6 mm, 0.75±0.81 mm/y, and 2.9±3.3 years, respectively. We found that greater aortic stiffness (β± SE for carotid‐femoral pulse wave velocity: 0.30±0.13. P =0.03) and aortic characteristic impedance (β± SE : 0.46±0.18, P =0.02), as well as lower total arterial and proximal aortic compliance (β± SE : −0.44±0.21, P =0.05, and −0.63±0.16, P =0.001, respectively) were independently associated with faster aneurysm growth. Conclusions In patients with TAA due to BAV , measures of greater aortic stiffness and pulsatile arterial load indicate an association with accelerated aneurysm expansion. Assessing arterial hemodynamics may be useful for risk stratification and disease monitoring in TAA patients with BAV .

Protein Kinase A (PKA) is a major effector of cyclic-AMP (cAMP) signaling and has recently been appreciated to play a role in multiple malignancies. Mutations of its catalytic subunit (PRKACA) have been identified in a substantial proportion of adrenocortical tumors, and are also detected in a wide spectrum of tumor types in the TCGA dataset, although at a low frequency. A unique fusion protein of PRKACA and DNAJB1 is seen in the majority of fibrolamellar liver cancers (FLC), a rare malignancy of young adults, where it is suspected to be the primary oncogenic driver. However, the key effectors of oncogenic signaling in FLC and other PRKACA driven cancers remain unknown. To understand PKA's downstream targets, we generated genetic cell models with doxycycline-inducible PRKACA or its dominant negative counterpart, a mutant form of the PRKAR1A regulatory subunit. These cell models were then subjected to mass spectrometry for kinome profiling in order to detect kinases with significant altered activity following PKA modulation. This was integrated with small molecule inhibition and siRNA knockdown to identify PKA-regulated kinases that impact cell proliferation. Our analysis revealed activation of the aurora-family kinase AURKA, with preferential sensitivity to the confirmation-disrupting AURKA inhibitor (CD-AURKAi) CD532 compared to other AURKA inhibitors. CD-AURKAi not only selectively inhibit AURKA's kinase activity, but also disrupt its interaction with MYC-family transcription factors. These key oncogenic mediators are necessary to drive the proliferation of multiple tumor types, although they have not yet been connected with oncogenic PKA signaling. Our follow up quantitative PCR experiments confirm that CD-532 treatment results in reduced expression of MYC family members and their transcriptional targets. We next confirmed that MYC family members support the proliferation of PKA-driven cell models with live cell imaging. Finally, we have begun to investigate other kinases identified in our siRNA screen for potential effects on MYC, and have identified several potential combination partners to augment the activity of CD-532 and other CD-AURKAi. These data suggest that CD-AURKAi, either alone or in combination, have the potential to serve as therapeutic agents for PKA-driven cancers. Citation Format: Gary Kwan Leung Chan, Samantha M. Maisel, Y. Christina Hwang, Rebecca Wolber, Danielle L. Swaney, Nabeel Bardeesy, John D. Gordan. Mapping oncogenic signal transduction in PKA-driven cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 309.

Background Thoracic aortic aneurysm ( TAA ) outcomes are worse in women than men, although reasons for sex differences are unknown. Because faster TAA growth is a risk factor for acute aortic syndromes, we sought to determine the role of sex and aneurysm etiology on TAA growth. Methods and Results Eighty‐two consecutive unoperated subjects with TAA who had serial aneurysm measurements were recruited. In multivariable linear regression the association of female sex with aneurysm growth rate was assessed after adjustment for potential confounders. We also tested the interaction term sex×aneurysm etiology in the prediction of TAA growth. Seventy‐four percent of subjects were men; mean± SD age was 62.4±11.9 years in men and 67.7±10.7 years in women ( P =0.06). Forty‐seven (57%) subjects had degenerative TAA s, and the remainder had heritable TAA s. Absolute baseline aneurysm size and follow‐up time were not different between men and women. Aneurysm growth rate was 1.19±1.15 mm/y in women and 0.59±0.66 mm/y in men ( P =0.02). Female sex remained significantly associated with greater aneurysm growth in multivariable analyses (β± SE : 0.35±0.12, P =0.005). In addition, female sex was associated with faster TAA growth only among those with degenerative TAA (β± SE : 0.33±0.08, P =0.0002) and not among those with heritable TAA ( P =0.79), with a significant sex×etiology interaction ( P =0.001). Conclusions TAA growth rates are greater in women than men, and this difference is specific to women with degenerative TAA s. Our findings may explain sex differences in TAA outcomes and provide a foundation for future investigations of this topic.

Background Matrix γ-carboxyglutamate protein is an inhibitor of cardiovascular calcification. The objective of this substudy of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial was to examine the relationship between total (ie, carboxylated [active] form + uncarboxylated [inactive] form) circulating desphosphorylated matrix γ-carboxyglutamate protein (dpMGP) level and the progression rate of aortic stenosis (AS). Methods Among the patients included in the ASTRONOMER trial, 215 patients had measures of baseline circulating total dpMGP level and an echocardiographic follow-up (mean follow-up: 3.5 ± 1.3 years). Progression of AS was assessed according to the measurement of the annualized increase in peak aortic jet velocity. Results In the whole cohort, baseline dpMGP level was associated with faster progression rate of peak aortic jet velocity ( r = 0.16; P = 0.02) in individual analysis but not in multivariable analysis ( P = 0.40). However, there was a significant interaction ( P = 0.03) between dpMGP level and age, with respect to the effect on AS progression. After dichotomization according to median value of age (ie, 57 years old), total dpMGP level was associated with faster AS progression rate ( r = 0.24; P = 0.008) in the younger patients, and this association remained significant in multivariable analysis ( P = 0.04), but not in the older ones. The independent correlates of dpMGP level were fasting glucose ( P = 0.009) and oxidized low-density lipoprotein ( P = 0.01). Conclusions This is the first prospective study to demonstrate a relationship between increased circulating levels of total dpMGP and faster progression rate of AS in younger individuals. Future studies are needed to determine if dpMGP is simply a marker or a contributing factor to ectopic mineralization of aortic valve.

Hypertension (HTN) has the highest population-attributable risk for acute aortic syndromes and is highly prevalent among patients with thoracic aortic aneurysm (TAA). Although HTN is diagnosed based on brachial blood pressure (BP), this does not accurately correspond to central BP, which is of

Background— We have observed that elevated mitral gradients can develop in some patients after mitral valve repair for degenerative mitral regurgitation. Methods and Results— We screened 275 patients who had mitral valve repair involving >1 leaflet scallop between October 2001 and July 2010. Mitral valve hemodynamics were assessed at rest and at peak exercise using the cycle ergometer. B-type natriuretic peptide levels were measured at rest and after exercise. The patients also performed a 6-minute walk test and short-form 36-Item Health Survey questionnaire. We enrolled 110 patients, with resting mean mitral diastolic gradient of ≤3 mm Hg in 35 patients (group 1) and >3 mm Hg indicative of elevated mitral gradients in 75 patients (group 2). Posterior mitral leaflet plication ( P =0.04) and the use of a complete mitral annuloplasty ring ( P P =0.02), higher mitral gradients at peak exercise and higher pulmonary artery systolic pressure at rest and at peak exercise, and lower exercise capacity (101±40 versus 122±51 W; P =0.02). Group 2 patients also had higher B-type natriuretic peptide levels and lower scores in 3 short-form 36-Item Health Survey health concepts. Multivariate regression analyses showed that mitral valve area was an independent predictor of maximum exercise capacity ( P =0.003). Conclusions— After mitral valve repair for degenerative mitral regurgitation, elevated mitral gradients is not uncommon and is associated with worse intracardiac hemodynamics, higher B-type natriuretic peptide levels, lower exercise capacity, and poorer quality of life. Further refinement in the surgical technique may reduce the incidence of this complication.

Background Left atrial volume (LAVol) is an important predictor of cardiovascular outcomes. Different formulas are applied to calculate LAVol using two-dimensional transthoracic echocardiography (2DTTE) with variable reference values. The objective of the study was to evaluate the accuracy of methods to calculate LAVol by 2DTTE or cardiac computed tomography (CT). Methods and Results Overall 177 consecutive patients who underwent both a 2DTTE and retrospective electrocardiogram (ECG)-gated coronary CT angiography (CTA) within 15 days were included for this study. LA volume measurements were calculated by 2DTTE and 2DCT using the biplane area-length, biplane Simpson's, prolate-ellipsoid-1 and prolate-ellipsoid-2 methods. These results were compared with those measured by CT using a volumetric method. There was very good correlation between the CT and echocardiographic measures for LAVol, but significant underestimation of the echocardiographic methods when compared to the reference standard (33.5%, 39.1%, 48.1%, and 53.2% for the biplane area-length, biplane Simpson's, prolate-ellipsoid-1, and prolate-ellipsoid-2 methods, respectively). The biplane area-length method using 2DTTE had the closest volume estimation of all echocardiographic methods to the reference standard (67.6 ± 25.5 mL vs. 106 ± 35.5 mL, r = 0.712). Similarly, the biplane area-length method using CT most accurately predicted LAVol (103.3 ± 36.0 mL, r = 0.965). Conclusions Compared to CT, 2DTTE provides reasonable assessment of LAVol, although all measurement methods underestimate LAVol. For both 2DTTE and CT, the biplane area-length method appears to provide the most accurate 2D estimate of LAVol.

Cardiovascular disease is an important extra-articular manifestation of rheumatologic diseases leading to considerable mortality and morbidity. Echocardiography emerges as a useful non-invasive technique for the screening and evaluation of cardiac involvement in these patients. With the technological advancement in echocardiographic techniques, we have gained a greater appreciation of the prevalence and nature of the cardiac involvement in these patients, as detection of subclinical disease is increasingly feasible. This review discusses cardiac involvement in patients with rheumatoid arthritis, systemic lupus erythematosus, anti-phospholipid antibody syndrome, systemic sclerosis and ankylosing spondylitis, and the role of different echocardiographic modalities in their evaluation.

Endocarditis has protean systemic and cardiac manifestations. The infective vegetation mediates a destructive process which can involve the cardiac valves and/or perivalvular region. Valvular complications can vary from leaflet erosion or perforation to diverticulum formation, while perivalvular involvement includes abscess, perivalvular regurgitation, pseudoaneurysm and fistula. Transesophageal echocardiography is the preferred imaging tool in the diagnosis of both valvular and perivalvular complications. Prompt detection of these complications is crucial to the timing of surgery and the surgical approach.

Systemic embolism remains a vexing problem in patients with infective endocarditis. This complication affects about 30 % of these patients and generally occurs in the early stage of the disease. The size of the vegetation is the best echocardiographic predictor of the embolic risk, but there is considerable overlap in vegetation size between patients with and without embolic events. Early cardiac surgery appears to reduce the risk of embolism in patients with large vegetations and severe valvular dysfunction. Prompt diagnosis and effective antibiotic therapy remain the best way to prevent this serious complication of endocarditis.

Objectives: The aim of this study was to examine the relationship between metabolic syndrome (MetS) and left ventricular (LV) geometry and function in patients with asymptomatic aortic stenosis (AS...

This new edition represents a major departure from previous editions, in that most of the chapters and illustrations are not written by Dr Feigenbaum, but by his two coauthors. The format and writing style are different from previous editions, a result of what Dr Feigenbaum aptly described as ‘a change of guards’. The book is well organized and comprehensive, with chapters ranging from the history of echocardiography to a comprehensive discussion of the role of echocardiography in congenital heart diseases. The writing is clear and easy to follow, complemented by numerous tables summarizing differential diagnoses and echocardiographic features. The references are selective and pertinent. In addition to high-quality illustrations, including both black and white, and colour figures, the book is accompanied by a DVD containing many freeze frames and numerous real-time clips. The comprehensive nature of the moving clips contained in the DVD is, indeed, outstanding, and drastically increases the educational value of the book. All the new innovations such as three-dimensional echocardiography and intracardiac echocardiography are included, and illustrated in the book and in the DVD. This book is also unique in that M-mode tracings continue to be used liberally, and important M-mode features are included in the discussion of many entities. This aspect of the book is surely a reflection of Dr Feigenbaum’s conviction that despite all the new advances, M-mode echocardiography continues to have a place and should be properly learned in the practice of echocardiography. This reviewer strongly shares this sentiment. Several chapters are particularly well-presented. They are the chapters on the history of echocardiography (chapter 1), physics and instrumentation (chapter 2), coronary artery disease (chapter 15) and stress echocardiography (chapter 16). These chapters are clearly written, comprehensive and represent state-of-the-art reviews of these topics. However, the comprehensive nature of the book does not always allow for in-depth discussions, which may be required to provide a better understanding of the context in which some of the echocardiographic findings should be interpreted. For instance, in chapter 8, the discussion on tissue Doppler imaging of mitral annular velocities would benefit from a more detailed discussion, including the systolic velocity and the use of different locations on the mitral annulus. The normal ranges are different depending on the specific locations on the mitral annulus in which the velocities are obtained. Similarly, the inclusion of the concept of atrioventricular compliance in the assessment of mitral stenosis will enhance the understanding of the hemodynamics in this clinical setting. The figure in chapter 8 on pressure recovery is misleading. In discrete stenosis, the energy loss is not recovered downstream, such that the velocity downstream is low. This is a welcomed new addition of the classic text on echocardiography. It is comprehensive, yet highly readable. A small detraction is that details and contextual data are lacking in the discussion of some of the conditions. I strongly recommend this book to all students of echocardiography.

OBJECTIVES This study examined the effect of aspirin on the risk of embolic events in infective endocarditis (IE). BACKGROUND Embolism is a major complication of IE, and studies in animal models have shown that platelet inhibition with aspirin can lead to more rapid vegetation resolution and a lower rate of embolic events. METHODS We conducted a randomized, double-blinded, placebo-controlled trial of aspirin treatment (325 mg/day) for four weeks in patients with IE to test the hypothesis that the addition of aspirin would reduce the incidence of clinical systemic embolic events. Patients with perivalvular abscess were excluded. Serial cerebral computed tomograms and transesophageal echocardiograms were obtained in a subset of patients. RESULTS During the four-year study period, 115 patients were enrolled: 60 assigned to aspirin and 55 assigned to placebo. Embolic events occurred in 17 patients (28.3%) on aspirin and 11 patients (20.0%) on placebo, with an odds ratio (OR) of 1.62 (95% confidence interval [CI] 0.68 to 3.86, p = 0.29). There was a trend toward a higher incidence of bleeding in the patients taking aspirin versus placebo (OR 1.92, 95% CI 0.76 to 4.86, p = 0.075). Development of new intracranial lesions was similar in both groups. Aspirin had no effect on vegetation resolution and valvular dysfunction. CONCLUSIONS In endocarditis patients already receiving antibiotic treatment, the addition of aspirin does not appear to reduce the risk of embolic events and is likely associated with an increased risk of bleeding. Aspirin is not indicated in the early management of patients with IE.

Aortic stenosis (AS) is the most common valvular disease requiring valve replacement. Its prevalence increases with age. When the severity of AS is only mild to moderate, it is well tolerated. When it becomes severe, AS confers significant morbidity and mortality. Adverse events can be avoided if it is possible to prevent or retard the progression from mild or moderate AS to severe AS. Progression of AS parallels the progression of sclerotic changes involving the aortic valve, which share histological and immunochemical similarities with the process of atherosclerosis. Far from being just a degenerative process, the development of AS is a complex and highly regulated process with a number of modifiable factors. One of the key factors appears to be lipoproteins, which are intimately involved in several pathways crucial to the development of AS. The importance of lipoproteins is further supported by epidemiological and clinical studies showing a strong association between lipoproteins and AS. The time has come to initiate prospective studies to assess the effect of cholesterol lowering on the progression of AS.

Several variants of aortic pathology must be considered in the differential diagnosis of the patient presenting with an acute aortic syndrome. In addition to aortic dissection, such entities include intramural hematoma, penetrating aortic ulcer, and localized intimal tear without dissection. These lesions, which lack a mobile intimal flap, may be difficult to correctly identify by transesophageal echocardiography or other imaging modalities. We present a case of an acute aortic syndrome with unusual features on transesophageal echocardiography.

Background The gold-standard treatment of severe mitral regurgitation (MR) due to degenerative disease is valve repair, which is surgically performed with either a leaflet resection or leaflet preservation approach. Recent data suggest that functional mitral stenosis (MS) may occur following valve repair using a leaflet resection strategy, which adversely affects patient prognosis. A randomised comparison of these two approaches to mitral repair on functional MS has not been conducted. Methods and analysis This is a prospective, multicentre randomised controlled trial designed to test the hypothesis that leaflet preservation leads to better preservation of mitral valve geometry, and therefore, will be superior to leaflet resection for the primary outcome of functional MS as assessed by 12-month mean mitral valve gradient at peak exercise. Eighty-eight patients with posterior leaflet prolapse will be randomised intraoperatively once deemed by the operating surgeon to feasibly undergo mitral repair using either a leaflet resection or leaflet preservation approach. Secondary end points include comparison of repair strategies with regard to mitral valve orifice area, leaflet coaptation height, 6 min walk test and a composite major adverse event end point consisting of recurrent MR ≥2+, death or hospital readmission for congestive heart failure within 12 months of surgery. Ethics and dissemination Institutional ethics approval has been obtained from all enrolling sites. Overall, there remains clinical equipoise regarding the mitral valve repair strategy that is associated with the least likelihood of functional MS. This trial hopes to introduce high-quality evidence to help surgical decision making in this context. Trial registration number NCT02552771.

Background: We have shown that functional mitral stenosis (MS) can occur in patients following mitral valve repair for degenerative mitral regurgitation. In these patients both mitral valve gradient and calculated mitral valve area are associated with exercise capacity, intracardiac hemodynamics and

A 38-year-old man presented with a 3-month history of night sweats, nonproductive cough, and weight loss. He denied chest pain or shortness of breath. A transesophageal echocardiogram showed a large mass adjacent to the aortic root likely arising from the pericardium or the left ventricle (Figure 1 and Movie I in the online-only Data Supplement). Invasive coronary angiography revealed a highly vascular mass perfused by the left main artery causing deformity of the aortic root (Figure 2 and Movie II in the online-only Data Supplement). Figure 1. Transesophageal color Doppler echocardiogram demonstrates that the left coronary artery (arrow) was embedded in a large solid mass (M) that was perfused by small branches from the same artery. Figure 2. Selective coronary angiogram of the left coronary artery demonstrates multiple feeding vessels extending into a mass. Various imaging modalities were then performed to further characterize the lesion. Cardiac computed tomography angiography revealed a large heterogeneous, intensely enhancing mass within the pericardial sac, just above the anterior wall of the left ventricle, …

Background Valve sparing root replacement (VSRR) and aortic valve repair (AVr) is an attractive treatment option compared with composite valve and root replacement (Bentall procedure) for patients with aortic root dilatation with or without aortic valve disease. While aortic valve preservation reduces the risk of valve-related complications, little is known about echocardiographic differences at follow-up between these 2 strategies. Methods Consecutive nonemergent patients undergoing VSRR and AVr (n = 68) were compared with contemporary historical controls undergoing the Bentall procedure for aortic root pathology with or without mixed aortic valve disease (insufficiency or stenosis) (n = 96). The VSRR was performed preferentially using the reimplantation technique. Bentall procedure utilized a mechanical valve in 65% of patients, a biologic prosthesis in 22%, and a homograft in 13%. Clinical and echocardiographic data were obtained at baseline and at follow-up (median = 30 months). Results The 2 cohorts were similar with respect to all preoperative characteristics with the exception of disease etiology. The Bentall group had a higher proportion of degenerative valve and root disease (47.8% vs 27.9%) and a lower proportion of bicuspid aortic valve disease (22.8% vs 51.5%) as compared with the VSRR group ( p = 0.007). Postoperative echocardiographic outcomes were comparable between groups with the exception of higher peak (23.37 ± 11.80 vs 18.0 ± 12.04; p =0.02) and mean (13.07 ± 7.53 vs 9.56 ± 6.49; p = 0.01) transvalvular aortic gradients in the Bentall group. Persistence of left ventricular dysfunction (8.4% vs 6.1%; p = 0.61), presence of greater than moderate aortic valve (AV) insufficiency (3% vs 4.6%; p = 0.32), and left ventricular mass (213.24 ± 72.36 vs 207.38 ± 63.07, p = 0.61) were comparable between the Bentall and VSRR group, respectively. Finally, survival ( p = 0.21) and freedom from valve-related events ( p = 0.74) were similar between groups. Conclusions Valve sparing root replacement with AV repair provides similar mid-term echocardiographic and clinical outcomes compared with the Bentall.

Atrial fibrillation is a common arrhythmia, particularly in the older age groups. It confers an increased risk of thromboembolism to these patients, and multiple clinical risk factors have been identified to be useful in predicting the risks of thromboembolic events. Recent studies have evaluated the role of transesophageal echocardiography (TEE) in the evaluation of patients with atrial fibrillation. The purpose of this review is to evaluate the significance of transesophageal echocardiographic findings in the prediction of thromboembolic events, particularly stroke, in patients with nonvalvular atrial fibrillation, with an emphasis on recently reported prospective studies. Aortic plaque and left atrial appendage abnormalities are identified as independent predictors of thromboembolic events. Although they are associated with clinical events, they also have independent incremental prognostic values. Other transesophageal echocardiographic findings, such as patent foramen ovale and atrial septal aneurysm, have not been found to be predictors of thromboembolic events in this patient group. Thus, TEE is a useful tool in stratifying patients with nonvalvular atrial fibrillation into different risk groups in terms of thromboembolic events, and it will likely play an important role in future studies to assess new treatment strategies in high-risk patients with atrial fibrillation.

Background . The management of mild aortic stenosis during coronary artery bypass grafting remains controversial. Methods . We reviewed the medical records of consecutive patients between January 1, 1977, and December 31, 1994, to identify 51 patients with mild aortic stenosis who underwent isolated coronary artery bypass grafting (group A), and 19 patients with mild aortic stenosis who underwent combined coronary artery bypass grafting and aortic valve replacement (group B). Patients with more than moderate aortic regurgitation were excluded. Preoperative angiograms were reviewed to assess the severity of calcification and restricted mobility of the aortic cusps. Results . In group A there were 11 deaths and 8 subsequent aortic valve replacements; in group B there were 5 deaths and 3 prosthetic valve-related complications. There was no difference in event-free survival between the two groups after adjusting for the difference in age. Among group A patients, the initial transvalvular gradient ( p = 0.0005) and aortic valvular calcification ( p = 0.06) identified patients who demonstrated progression to severe aortic stenosis during follow-up. Conclusions . Our data suggest that routine aortic valve replacement during coronary artery bypass grafting in patients with mild aortic stenosis is not indicated, but concomitant aortic valve replacement may be appropriate in patients with higher transvalvular gradients and calcified valves.