Relative Impact of Surgical Mitral Repair and MitraClip on Annular Remodeling-A Potential Mechanism for Therapeutic Response to Mitral Repair for Degenerative Mitral Regurgitation.

OBJECTIVES: Three-dimensional transesophageal echocardiography (TEE) is widely used to guide decision-making for mitral repair. The relative impact of surgical mitral valve repair (MVr) and MitraClip on annular remodeling is unknown. The aim was to determine the impact of both mitral repair strategies on annular geometry, including the primary outcome of annular circumference and area. DESIGN: This was a retrospective observational study of patients who underwent mitral intervention between 2016 and 2020. SETTING: Weill Cornell Medicine, a single, large, academic medical center. PARTICIPANTS: The population comprised 50 patients with degenerative mitral regurgitation (MR) undergoing MVr. INTERVENTIONS: Elective MVr and TEE. MEASUREMENTS AND MAIN RESULTS: Patients undergoing MitraClip or surgical MVr were matched (1:1) for sex and coronary artery disease. Mitral annular geometry indices were quantified on intraprocedural three-dimensional TEE. Mild or less MR on follow-up transthoracic echocardiography defined optimal response. Patients undergoing MitraClip were older (80 ± eight v 66 ± six years; p < 0.001) but were otherwise similar to surgical patients. Patients undergoing MitraClip had larger baseline left atrial and ventricular sizes, increased tenting height, and volume (p < 0.01), with a trend toward increased annular area (p = 0.23). MitraClip and surgery both induced immediate mitral annular remodeling, including decreased area, circumference, and tenting height (p < 0.001), with greater remodeling with surgical repair. At follow-up (4.1 ± 9.0 months) optimal response (≤ mild MR) was ∼twofold more common with surgery than MitraClip (81% v 46%; p = 0.02). The relative reduction in annular circumference (odds ratio [OR] 1.05 [1.00-1.09] per cm; p = 0.04) and area (OR 1.03 [1.00-1.05] per cm2; p = 0.049) were both associated with optimal response. CONCLUSIONS: Surgical MVr and MitraClip both reduce annular size, but repair-induced remodeling is greater with surgery and associated with an increased likelihood of optimal response.

Differential Effects of Aortic Valve Replacement on Aortic Circumferential Strain in Aortic Stenosis and Aortic Insufficiency.

OBJECTIVES: Aortic valve replacement (AVR) potentially can modify pulse-wave propagation to the distal aorta. Echo-derived global circumferential strain (GCS) was used to test whether AVR for aortic stenosis (AS) or aortic insufficiency (AI) resulted in differential aortic biomechanics in the descending thoracic aorta. DESIGN: This was a prospective observational study of patients who underwent cardiac surgery between 2016 and 2019. SETTING: Weill Cornell Medicine, a single large academic medical center. PARTICIPANTS: The population comprised 48 patients undergoing AVR (62 ± 15 y/o, 79% male; 22 with AI and 26 with AS) and 11 patients undergoing coronary bypass surgery as controls. INTERVENTIONS: Elective cardiac surgery, transesophageal echocardiography (TEE), pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Pre- and postprocedural TEEs were collected. Descending aorta short-axis images were analyzed for GCS, time-to-peak strain, aortic end-diastolic, end-systolic area, and fractional area changes. Pulse pressure (PP) and stroke volume were quantified. Preprocedural GCS significantly differed between patients with AI and AS, with AI patients having greater GCS (median/interquartile range, 9.6 95.3,13.6) than patients with AS (4.3 [3.4-5.1]). After AVR, in AI patients, strain significantly decreased (5.5 [3.8,8.2], p = 0.001), along with PP (mean ± standard deviation) (66.4 ± 0.8 to 54.1 ± 13.7, p < 0.001), and PP corrected strain did not (GCS/PP = 14.8 [6.9-19.9] v 12.7[8.2-18.6], p = 0.34). In AS patients, GCS significantly increased after AVR to (5.45 [4.2-6.8], p = 0.003), as did PP-corrected strain (6.9 [5.8-9.2] v 9.7 [6.5-13.4], p = 0.016). Surgical AVR produced decrements in time-to-peak strain in AI and AS groups (both p < 0.001). CONCLUSIONS: After AVR for AI and AS, the direction of change in distal aortic strain from baseline depends on valve pathology. This finding may have important clinical implications in terms of indication for surgery and postoperative surveillance, especially in patients with aortopathies.

Descending aortic strain quantification by intra-operative transesophageal echocardiography: Multimodality validation via cardiovascular magnetic resonance.

BACKGROUND: Whereas cardiac magnetic resonance (CMR) imaging provides high temporal resolution imaging of aortic distensibility (strain), transesophageal echocardiography (TEE) is widely used for intra-operative aortic imaging and provides a clinical alternative for aortic assessment. We tested intra-operative global circumferential aortic strain (GCS) measured on TEE in relation to the reference of CMR-derived strain among patients undergoing surgical graft repair of ascending aortic aneurysms. METHODS: CMR (3T) was prospectively performed in patients scheduled for aortic repair. TEE was performed intra-operatively; images were co-localized with MRI. GCS on CMR and TEE was quantified independently, blinded to results of the other modality. RESULTS: 25 patients (54 ± 10 year-old, 88% male) were studied, inclusive of 13 genetically mediated and 12 degenerative aneurysms: CMR and TEE were performed within 12 ± 9 days. Pulse pressure (PP)-adjusted descending aortic TEE-derived GCS strongly correlated with cine-CMR-derived GCS (r = .75, P = .002) though absolute GCS and PP-adjusted values were slightly lower (5.40 ± 1.11 vs 6.49 ± 1.43% and 11.55 ± 3.04 vs 13.99 ± 4.53%, respectively). Similarly, TEE yielded slightly lower end-diastolic area (EDA [5.1 ± 1.7 cm2 vs 5.8 ± 1.3 cm2 , P = .004]) and end-systolic area (ESA [6.1 ± 1.9 cm2 vs 6.5 ± 1.7 cm2 , P = .10]), with significant correlations between the two modalities (r = .73, .76, P < .05 for all). CONCLUSIONS: This exploratory study supports feasibility of TEE for assessing aortic GCS in a surgical at-risk population, as well as magnitude of agreement between intra-operative TEE and preoperative CMR. We found that there is a significant correlation between GCS and EDA and ESA aortic areas, but that TEE-derived parameters underestimated CMR values by a small but significant amount.

Immediate Impact of Prosthetic Graft Replacement of the Ascending Aorta on Circumferential Strain in the Descending Aorta.

OBJECTIVES: Prosthetic replacement of the ascending aorta (AA) can potentially modify energy propagation to the distal aorta and contribute to adverse aortic remodelling. This preliminary study employed intra-operative transoesophageal echocardiography (TOE) to assess the immediate impact of prosthetic graft replacement of the AA on circumferential strain in the descending aorta. METHODS: Intra-operative TOEs in patients undergoing AA graft replacement were analysed for circumferential strain, fractional area change (FAC), dimensions (end diastolic area [EDA], and end systolic area [ESA]) in the descending aorta immediately before and after graft replacement. Deformation was assessed via global peak circumferential aortic strain (CAS), together with pulse pressure corrected strain, time to peak strain (TTP), and aortic distensibility. RESULTS: Forty-five patients undergoing AA replacement with prosthetic graft (91% elective) were studied. Following grafting, descending thoracic aortic circumferential strain increased (6.3 ± 2.8% vs. 8.9 ± 3.4%, p = .001) paralleling distensibility (5.7 [3.7-8.6] 10-3 mmHg vs. 8.5 [6.4-12.4] 10-3 mmHg, p < .001). Despite slight increments in post graft left ventricular ejection fraction (LVEF) (52.3 ± 10.8% vs. 55.0 ± 11.9, p < .001), stroke volume was similar (p = .41), and magnitude of increased strain did not correlate with change in stroke volume (r = -.03, p = .86), LVEF (r = .18, p = .28), or pulse pressure (r = .28, p = .06). Descending aortic size (EDA 4 [2.7-4.6] cm2vs. 3.7 [2.5-5] cm2, p = .89; ESA 4.3 [3.2-5.3] cm2vs. 4.5 [3.3-5.8] cm2, p = .14) was similar pre- and post graft. In subgroup analysis, patients with cystic medial necrosis had a significantly higher post procedure CAS than patients with atherosclerotic aneurysms (9.7 ± 3.5% vs. 7.0 ± 2.3%, p = .03). CONCLUSIONS: Prosthetic graft replacement of the AA increases immediate aortic circumferential strain of the descending aorta, particularly in patients with cystic medial necrosis. Our findings suggest that grafts augment energy transfer to the distal aorta, a potential mechanism for progressive distal aortic dilation and/or dissection.

The use of mixed reality for the treatment planning of unruptured intracranial aneurysms.

BACKGROUND: A thorough comprehension of topographic neuroanatomy is paramount in neurosurgery. In recent years, great attention has been raised towards extended reality, which comprises virtual, augmented, and mixed reality (MR) as an aid for surgery. In this paper, we describe our preliminary experience with the use of a new MR platform, aiming to assess its reliability and usefulness in the planning of surgical treatment of unruptured intracranial aneurysms. METHODS: We prospectively enrolled 5 patients, harboring a total of 8 intracranial unruptured aneurysms, undergoing elective surgical clipping. A wearable mixed-reality device (HoloLens; Microsoft Corp., Redmond, WA, USA) was used to display and interact with a holographic model during surgical planning. Afterward, a total of 10 among surgeons and residents filled in a 5-point Likert-Scale evaluation questionnaire. RESULTS: According to the participants' feedback, the main MR platform advantages were considered the educational value, its utility during patients positioning and craniotomy planning, as well as the anatomical and imaging interpretation during surgery. The graphic performance was also deemed very satisfactory. On the other hand, the device was evaluated as not easy to use and pretty uncomfortable when worn for a long time. CONCLUSIONS: We demonstrated that MR could play important role in planning the surgical treatment of intracranial aneurysms by enhancing the visualization and understanding of the patient-specific anatomy.

Distal aortic biomechanics after transcatheter versus surgical aortic valve replacement: a hypothesis generating study.

BACKGROUND: Biomechanical effects of transcatheter (TAVR) versus surgical (SAVR) aortic valve interventions on the distal aorta have not been studied. This study utilized global circumferential strain (GCS) to assess post-procedural biomechanics changes in the descending aorta after TAVR versus SAVR. METHODS: Patients undergoing TAVR or SAVR for aortic stenosis were included. Transesophageal (TEE) and transthoracic (TTE) echocardiography short-axis images of the aorta were used to image the descending aorta immediately before and after interventions. Image analysis was performed with two-dimensional speckle tracking echocardiography and dedicated software. Delta GCS was calculated as: post-procedural GCS-pre-procedural GCS. Percentage delta GCS was calculated as: (delta GCS/pre-procedural GCS) × 100. RESULTS: Eighty patients, 40 TAVR (median age 81 y/o, 40% female) and 40 SAVR (median 72 y/o, 30% female) were included. The post-procedure GCS was significantly higher than the pre-procedural GCS in the TAVR (median 10.7 [interquartile range IQR 4.5, 14.6] vs. 17.0 [IQR 6.1, 20.9], p = 0.009) but not in the SAVR group (4.4 [IQR 3.3, 5.3] vs. 4.7 [IQR 3.9, 5.6], p = 0.3). The delta GCS and the percentage delta GCS were both significantly higher in the TAVR versus SAVR group (2.8% [IQR 1.4, 6] vs. 0.15% [IQR - 0.6, 1.5], p < 0.001; and 28.8% [IQR 14.6%, 64.6%] vs. 4.4% [IQR - 10.6%, 5.6%], p = 0.006). Results were consistent after multivariable adjustment for key clinical and hemodynamic characteristics. CONCLUSIONS: After TAVR, there was a significantly larger increase in GCS in the distal aorta compared to SAVR. This may impact descending aortic remodeling and long-term risk of aortic events.

Impact of ascending aortic prosthetic grafts on early postoperative descending aortic biomechanics on cardiac magnetic resonance imaging.

OBJECTIVES: Among patients with ascending thoracic aortic aneurysms, prosthetic graft replacement yields major benefits but risk for recurrent aortic events persists for which mechanism is poorly understood. This pilot study employed cardiac magnetic resonance to test the impact of proximal prosthetic grafts on downstream aortic flow and vascular biomechanics. METHODS: Cardiac magnetic resonance imaging was prospectively performed in patients with thoracic aortic aneurysms undergoing surgical (Dacron) prosthetic graft implantation. Imaging included time resolved (4-dimensional) phase velocity encoded cardiac magnetic resonance for flow quantification and cine-cardiac magnetic resonance for aortic wall distensibility/strain. RESULTS: Twenty-nine patients with thoracic aortic aneurysms undergoing proximal aortic graft replacement were studied; cardiac magnetic resonance was performed pre- [12 (4, 21) days] and postoperatively [6.4 (6.2, 7.2) months]. Postoperatively, flow velocity and wall shear stress increased in the arch and descending aorta (P < 0.05); increases were greatest in hereditary aneurysm patients. Global circumferential strain correlated with wall shear stress (r = 0.60-0.72, P < 0.001); strain increased postoperatively in the native descending and thoraco-abdominal aorta (P < 0.001). Graft-induced changes in biomechanical properties of the distal native ascending aorta were associated with post-surgical changes in descending aortic wall shear stress, as evidenced by correlations (r = -0.39-0.52; P ≤ 0.05) between graft-induced reduction of ascending aortic distensibility and increased distal native aortic wall shear stress following grafting. CONCLUSIONS: Prosthetic graft replacement of the ascending aorta increases downstream aortic wall shear stress and strain. Postoperative increments in descending aortic wall shear stress correlate with reduced ascending aortic distensibility, suggesting that grafts provide a nidus for high energy flow and adverse distal aortic remodelling.

Left Atrial Strain Impairment Precedes Geometric Remodeling as a Marker of Post-Myocardial Infarction Diastolic Dysfunction.

OBJECTIVES: The aims of this study were to test the magnitude of agreement between echocardiography (echo)- and cardiac magnetic resonance (CMR)-derived left atrial (LA) strain and to study their relative diagnostic performance in discriminating diastolic dysfunction (DD) and predicting atrial fibrillation (AF). BACKGROUNDS: Peak atrial longitudinal strain (PALS) is a novel performance index. Utility of echo-quantified LA strain has yet to be prospectively tested in relation to current DD guidelines or compared to CMR. METHODS: The study population comprised 257 post-myocardial infarction (MI) patients undergoing echo and CMR, including prospective derivation (n = 157) and clinical validation (n = 100) cohorts. DD was graded on echo using established consensus guidelines blinded to strain results. RESULTS: PALS on both echo and CMR was nearly 2-fold lower among patients with versus no DD (p < 0.001) and was significantly different in those with mild versus no DD (p < 0.01). In contrast, LA geometric parameters including echo- and CMR-derived volumes were significantly different between advanced versus no DD groups (p < 0.001) but not between groups with mild versus no DD (all p > 0.05). Echo and CMR PALS yielded small differences irrespective of orientation and similar diagnostic performance for DD in the derivation (area under the curve [AUC]: 0.70 to 0.78) and validation (AUC: 0.75 to 0.78) cohorts. Impaired PALS on both modalities was independently associated with MI size (p < 0.001). During 4.4 ± 3.8 years of follow-up in the derivation cohort, 8% developed AF. Both 2-chamber echo- and CMR-derived PALS stratified arrhythmic risk (p = 0.004 and p = 0.02, respectively), including a 4-fold difference among patients in the lowest versus remainder of quartiles of echo-derived PALS (24% vs. 6%). Similarly, echo and CMR PALS were lower (both p < 0.05) among patients with subsequent heart failure hospitalizations. CONCLUSIONS: Echo-derived PALS parallels results of CMR, yields incremental diagnostic utility versus LA geometry for stratifying presence and severity of DD, and improves prediction of AF and congestive heart failure after MI.

Prosthetic aortic graft replacement of the ascending thoracic aorta alters biomechanics of the native descending aorta as assessed by transthoracic echocardiography.

INTRODUCTION: In patients with ascending aortic (AA) aneurysms, prosthetic graft replacement yields benefit but risk for complications in the descending aorta persists. Longitudinal impact of AA grafts on native descending aortic physiology is poorly understood. METHODS: Transthoracic echocardiograms (echo) in patients undergoing AA elective surgical grafting were analyzed: Descending aortic deformation indices included global circumferential strain (GCS), time to peak (TTP) strain, and fractional area change (FAC). Computed tomography (CT) was used to assess aortic wall thickness and calcification. RESULTS: 46 patients undergoing AA grafting were studied; 65% had congenital or genetically-associated AA (30% bicuspid valve, 22% Marfan, 13% other): After grafting (6.4±7.5 months), native descending aortic distension increased, irrespective of whether assessed based on circumferential strain or area-based methods (both p<0.001). Increased distensibility paralleled altered kinetics, as evidenced by decreased time to peak strain (p = 0.01) and increased velocity (p = 0.002). Augmented distensibility and flow velocity occurred despite similar pre- and post-graft blood pressure and medications (all p = NS), and was independent of pre-surgical aortic regurgitation or change in left ventricular stroke volume (both p = NS). Magnitude of change in GCS and FAC was 5-10 fold greater among patients with congenital or genetically associated AA vs. degenerative AA (p<0.001), paralleling larger descending aortic size, greater wall thickness, and higher prevalence of calcific atherosclerotic plaque in the degenerative group (all p<0.05). In multivariate analysis, congenital/genetically associated AA etiology conferred a 4-fold increment in magnitude of augmented native descending aortic strain after proximal grafting (B = 4.19 [CI 1.6, 6.8]; p = 0.002) independent of age and descending aortic size. CONCLUSIONS: Prosthetic graft replacement of the ascending aorta increases magnitude and rapidity of distal aortic distension. Graft effects are greatest with congenital or genetically associated AA, providing a potential mechanism for increased energy transmission to the native descending aorta and adverse post-surgical aortic remodeling.

Collective behavior in gene regulation: post-transcriptional regulation and the temporal compartmentalization of cellular cycles.

Self-sustained oscillations are perhaps the most studied objects in science. The accomplishment of such a task reliably and accurately requires the presence of specific control mechanisms to face the presence of variable and largely unpredictable environmental stimuli and noise. Self-sustained oscillations of transcript abundance are, in fact, widespread and are not limited to the reproductive cycle but are also observed during circadian rhythms, metabolic cycles, developmental cycles and so on. To date, much of the literature has focused on the transcriptional machinery underlying control of the basic timing of transcript abundance. However, mRNA abundance is known to be regulated at the post-transcriptional level also and the relative contribution of the two mechanisms to gene-expression programmes is currently a major challenge in molecular biology. Here, we review recent results showing the relevance of the post-transcriptional regulation layer and present a statistical reanalysis of the yeast metabolic cycle using publicly available gene-expression and RNA-binding data. Taken together, the recent theoretical and experimental developments reviewed and the results of our reanalysis strongly indicate that regulation of mRNA stability is a widespread, phase-specific and finely tuned mechanism for the multi-layer control of gene expression needed to achieve high flexibility and adaptability to external and internal signals.

Imaging of Thoracoabdominal Aortic Aneurysms.

Untreated thoracoabdominal aortic aneurysms are associated with an exceedingly high mortality rate, and surgery carries a high complication rate. Crawford's classification system of thoracoabdominal aortic aneurysms describes aneurysm morphology and stratifies patients on the basis of risk of major postoperative complications including mortality, spinal cord injury, and renal failure. Computed tomography and magnetic resonance angiography are essential for classifying thoracoabdominal aortic aneurysms and identifying other important features that impact prognosis and surgical management. Four-dimensional flow-sensitive magnetic resonance imaging is an emerging technique that may help predict complications and further impact timing of intervention.

Gene expression waves. Cell cycle independent collective dynamics in cultured cells.

The ergodic hypothesis, which assumes the independence of each cell of the ensemble from all the others, is a necessary prerequisite to attach single cell based explanations to the grand averages taken from population data. This was the prevailing view about the interpretation of cellular biology experiments that typically are performed on colonies of billions of cells. By analysing gene expression data of different cells going from yeast to mammalian cell cultures, we demonstrate that cell cultures display a sort of "ecology-in-a-plate" giving rise to a rich dynamics of gene expression that are independent from reproductive cycles, hence contradicting simple ergodic assumptions The aspecific character of the observed coordinated gene expression activity inhibits any simple mechanistic hypothesis and highlights the need to consider population effects in the interpretation of data coming from cell cultures.