Association of Left Ventricular Remodeling Assessment by Cardiac Magnetic Resonance With Outcomes in Patients With Chronic Aortic Regurgitation.

Importance: Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload, which results in progressive LV remodeling negatively affecting outcomes. Whether cardiac magnetic resonance (CMR) volumetric quantification can provide incremental risk stratification over standard clinical and echocardiographic evaluation in patients with chronic moderate or severe AR is unknown. Objective: To compare LV remodeling measurements by CMR and echocardiography between patients with and without heart failure symptoms and to verify the association of remodeling measurements of patients with chronic moderate or severe AR but no or minimal symptoms with clinical outcomes receiving medical management. Design, Setting, and Participants: This multicenter retrospective cohort study included consecutive patients with at least moderate chronic native AR evaluated by 2-dimensional transthoracic echocardiography and CMR examination within 90 days from each other between January 2012 and February 2020 at Allina Health System. Data were analyzed from June 2021 to January 2022. Exposures: Clinical evaluation and risk stratification by CMR. Main Outcomes and Measures: The end point was a composite of death, heart failure hospitalization, or progression of New York Heart Association functional class while receiving medical management, censoring patients at the time of aortic valve replacement (when performed) or at the end of follow-up. Results: Of the 178 included patients, 119 (66.9%) were male, 158 (88.8%) presented with no or minimal symptoms (New York Heart Association class I or II), and the median (IQR) age was 58 (44-69) years. Compared with patients with no or minimal symptoms, symptomatic patients had greater LV end-systolic volume index (LVESVi) by CMR (median [IQR], 66 [46-85] mL/m2 vs 42 [30-58] mL/m2; P < .001), while there were no significant differences by echocardiography (LVESVi: median [IQR], 38 [30-58] mL/m2 vs 27 [20-42] mL/m2; P = .07; LV end-systolic diameter index: median [IQR], 21 [17-25] mm/m2 vs 18 [15-22] mm/m2; P = .17). During the median (IQR) follow-up of 3.3 (1.6-5.8) years, 50 patients with no or minimal symptoms receiving medical management developed the composite end point, which, in multivariate analysis adjusted for age and EuroSCORE II, was independently associated with LVESVi of 45 mL/m2 or greater and aortic regurgitant fraction of 32% or greater, the latter adding incremental prognostic value to CMR volumetric assessment. Conclusions and Relevance: In patients with chronic moderate or severe AR, patients presenting with heart failure symptoms have greater LVESVi by CMR than those with no or minimal symptoms. In patients with no or minimal symptoms, CMR quantification of LVESVi and AR severity may identify those at risk of death or incident heart failure and therefore should be considered in the clinical evaluation and decision-making of these patients.

Association of baseline and change in global longitudinal strain by computed tomography with post-transcatheter aortic valve replacement outcomes.

AIMS: Transcatheter aortic valve replacement (TAVR) procedural planning requires computed tomography angiography (CTA) which allows for the assessment of left ventricular global longitudinal strain (CTA-LVGLS). There is, however, limited data on the feasibility of CTA-LVGLS, and its prognostic value. This study sought to evaluate the incremental prognostic value of baseline CTA-LVGLS, change in CTA-LVGLS after TAVR, and their association with post-TAVR outcomes. METHODS AND RESULTS: A total of 431 patients who underwent multiphasic gated CTA using dual-source system for TAVR planning at baseline and 1-month follow-up were included [median (interquartile range) age, 83 (77-87) years; 44% female, STS-PROM score: 3.3 (2.3-5.1)%, Echo-left ventricular ejection fraction (LVEF): 60 (55-65)%, CTA-LVGLS: -18.0 (-21.6 to -14.2)%, feasible in 97% of patients]. CTA-LVGLS was measured using dedicated feature-tracking software. Over a median follow-up of 19 (13-27) months, 99 endpoints of all-cause death or heart failure hospitalization occurred. The relative hazard of the endpoint increased as baseline CTA-LVGLS worsened with -18.2% as the threshold for higher events (P = 0.005). After adjustment for baseline characteristics, CTA-LVGLS remained associated with the endpoint [hazard ratio (HR) (95% confidence interval, CI), 1.08 (1.03-1.14); P = 0.005] and incrementally improved prognostication (C-index difference, 0.026). Although CTA-LVGLS improved after TAVR [-18.3 (-21.6 to -14.3)% vs. -18.7 (-21.9 to -15.4)%, P < 0.001], patients without CTA-LVGLS improvement had higher risk of the endpoint than those with improvement or preserved baseline global longitudinal strain [HR (95% CI), 1.92 (1.19-3.12); P = 0.008]. CONCLUSIONS: In this predominantly low-risk TAVR cohort of patients, mostly with normal LVEF, assessment of CTA-LVGLS is highly feasible improving risk stratification by providing independent and incremental prognostic value over clinical and echocardiographic characteristics.

Right ventricular dysfunction by computed tomography associates with outcomes in severe aortic stenosis patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Although cardiac computed tomography angiography (CCTA) assessment of right ventricular dysfunction (RVD) is feasible, the incremental prognostic value remains uncertain in patients undergoing transcatheter aortic valve replacement (TAVR) evaluation. This study sought to determine the incremental clinical utility of RVD identification by CCTA while accounting for clinical and echocardiographic parameters. METHODS: Patients who underwent multiphasic ECG-gated functional CCTA using dual-source system for routine TAVR planning were evaluated. Biphasic contrast protocol injection allowed for biventricular contrast enhancement. CCTA-based RVD was defined as right ventricular ejection fraction (RVEF) â€‹< â€‹50%. The association of CCTA-RVD with all-cause mortality and the composite outcome of death or heart failure hospitalization after TAVR was evaluated and examined for its incremental utility beyond clinical risk assessment and echocardiographic parameters. RESULTS: A total of 502 patients were included (median [IQR] age, 82 [77 to 87] years; 56% men) with a median follow-up of 22 [16 to 32] months. Importantly, 126 (25%) patients were identified as having RVD by CCTA that was not identified by echocardiography. CCTA-defined RVD predicted death and the composite outcome in both univariate analyses (HR for mortality, 2.15; 95% CI, 1.44-3.22; p â€‹< â€‹0.001; HR for composite outcome, 2.11; 95% CI, 1.48-3.01; p â€‹< â€‹0.001) and in multivariate models that included clinical risk factors and echocardiographic findings (HR for mortality, 1.74; 95% CI, 1.11-2.74; p â€‹= â€‹0.02; HR for composite outcome, 1.63; 95% CI, 1.09-2.44; p â€‹= â€‹0.02). CONCLUSIONS: Functional CCTA assessment pre-TAVR correctly identified 25% of patients with RVD that was not evident on 2D echocardiography. The presence of RVD on CCTA independently associates with clinical outcomes post-TAVR.

Cardiac Computed Tomography and Magnetic Resonance Imaging of the Tricuspid Valve: Preprocedural Planning and Postprocedural Follow-up.

Transcatheter tricuspid valve interventions (TTVIs) are rapidly growing as a less invasive treatment of high surgical risk patients with advanced TR. A comprehensive anatomic and functional assessment of the tricuspid valve and right-sided chambers is essential for candidate selection and procedural planning. Advanced imaging with cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) can provide accurate anatomic and functional assessment of the tricuspid valve, its apparatus, and the right-sided chambers. In this review, we provide an updated overview of the emerging role of CCT and CMR for TR patient evaluation, TTVI planning, and follow-up.

Computed Tomography Planning for Transcatheter Mitral Valve Replacement.

Transcatheter mitral valve replacement (TMVR) is a rapidly evolving treatment for mitral regurgitation. As with transcatheter aortic valve replacement, multidetector computed tomography analysis plays a central role in defining the candidacy, device selection and safety for TMVR procedures. This contemporary review will describe in detail the multidetector computed tomography data collection, analysis, and planning for TMVR procedures in patients with native mitral regurgitation as well as in those with failed surgical prosthetic mitral valve replacement or surgical mitral valve repair.

Prosthesis-patient mismatch defined by cardiac computed tomography versus echocardiography after transcatheter aortic valve replacement.

BACKGROUNDS: Evaluation of prosthesis-patient mismatch (P-PM) after transcatheter aortic valve replacement (TAVR) by transthoracic echocardiography (TTE) has provided conflicting results regarding its impact on outcomes. Whether post-TAVR computed tomography angiography (CTA) evaluation of P-PM can improve our understanding is unknown. We aimed to evaluate the inter-modality (TTE vs. CTA) agreement, inter-valve platform (balloon-expanding valve [BEV] vs. self-expandable valve [SEV]) differences in P-PM severity, and outcomes related to P-PM after TAVR. METHODS: We analyzed patients with both CTA and TTE before and after TAVR. Indexed effective orifice area was calculated using two methods: TTE-derived left ventricular outflow tract (LVOT) area from measured diameter and post-TAVR CTA-measured area. Body size specific cut-offs for P-PM severity were used: for body mass index (BMI) â€‹< â€‹30 â€‹kg/m2, moderate â€‹= â€‹0.66-0.85 â€‹cm2/m2 and severe≤0.65 â€‹cm2/m2; for BMI ≥30 â€‹kg/m2, moderate â€‹= â€‹0.56-0.70 â€‹cm2/m2 and severe≤0.55 â€‹cm2/m2. RESULTS: A total of 447 patients were included (median age, 83 years; 54% male). The prevalence of P-PM (moderate or severe) was lower with CTA vs. TTE (3.5% vs. 19.5%, p â€‹< â€‹0.001). The prevalence of P-PM measured by TTE was more common in BEV compared to SEV (p â€‹= â€‹0.002), while CTA assessment showed no difference in P-PM incidence and severity between TAVR platforms (p â€‹= â€‹0.40). In multivariable analysis, CTA-defined but not TTE-defined P-PM was associated with mortality after TAVR (HR:3.97; 95%CI,1.55-10.2; p â€‹= â€‹0.004). Both CTA-defined and TTE-defined P-PM were associated with the composite of death and heart failure rehospitalization. CONCLUSION: Although post-TAVR CTA substantially downgraded the prevalence of P-PM compared to TTE, it identified a subset of patients with clinically relevant P-PM which associated with outcomes.

Importance of Myocardial Fibrosis in Functional Mitral Regurgitation: From Outcomes to Decision-Making.

Functional mitral regurgitation (FMR) is a common and complex valve disease, in which severity and risk stratification is still a conundrum. Although risk increases with FMR severity, it is modulated by subjacent left ventricular (LV) disease. The extent of LV remodeling and dysfunction is traditionally evaluated by echocardiography, but a growing body of evidence shows that myocardial fibrosis (MF) assessment by cardiac magnetic resonance (CMR) may complement risk stratification and inform treatment decisions. This review summarizes the current knowledge on the comprehensive evaluation that CMR can provide for patients with FMR, in particular for the assessment of MF and its potential impact in clinical decision-making.

Sonothrombolysis Improves Myocardial Dynamics and Microvascular Obstruction Preventing Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction.

BACKGROUND: It has recently been demonstrated that high-energy diagnostic transthoracic ultrasound and intravenous microbubbles dissolve thrombi (sonothrombolysis) and increase angiographic recanalization rates in patients with ST-segment-elevation myocardial infarction. We aimed to study the effect of sonothrombolysis on the myocardial dynamics and infarct size obtained by real-time myocardial perfusion echocardiography and their value in preventing left ventricular remodeling. METHODS: One hundred patients with ST-segment-elevation myocardial infarction were randomized to therapy (50 patients treated with sonothrombolysis and percutaneous coronary intervention) or control (50 patients treated with percutaneous coronary intervention only). Left ventricular volumes, ejection fraction, risk area (before treatment), myocardial perfusion defect over time (infarct size), and global longitudinal strain were determined by quantitative real-time myocardial perfusion echocardiography and speckle tracking echocardiography imaging. RESULTS: Risk area was similar in the control and therapy groups (19.2±10.1% versus 20.7±8.9%; P=0.56) before treatment. The therapy group presented a behavior significantly different than control group over time (P<0.001). The perfusion defect was smaller in the therapy at 48 to 72 hours even in the subgroup of patients with no recanalization at first angiography (12.9±6.5% therapy versus 18.8±9.9% control; P=0.015). The left ventricular global longitudinal strain was higher in the therapy than control immediately after percutaneous coronary intervention (14.1±4.1% versus 12.0±3.3%; P=0.012), and this difference was maintained until 6 months (17.1±3.5% versus 13.6±3.6%; P<0.001). The only predictor of left ventricular remodeling was treatment with sonothrombolysis: the control group was more likely to exhibit left ventricular remodeling with an odds ratio of 2.79 ([95% CI, 0.13-6.86]; P=0.026). CONCLUSIONS: Sonothrombolysis reduces microvascular obstruction and improves myocardial dynamics in patients with ST-segment-elevation myocardial infarction and is an independent predictor of left ventricular remodeling over time.

Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

BACKGROUND: Preclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: This study tested the clinical effectiveness of sonothrombolysis in patients with STEMI. METHODS: Patients with their first STEMI were prospectively randomized to either diagnostic ultrasound-guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared. RESULTS: ST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045). CONCLUSIONS: Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330).

Six-wave mixing coherent anti-Stokes Raman scattering microscopy.

Acquiring images of biological tissues and cells without the assistance of exogenous labels with a fast repetition rate and chemical specificity is what coherent anti-Stokes Raman Scattering (CARS) imaging offers. Nonresonant background (NRB) is one of the main drawbacks of the CARS microscopy technique because it limits the detection of weak Raman lines and the detection of low-concentration molecules. We show that a six-wave mixing process with two beams, which is a cascade effect of CARS, show better signal/NRB ratio and can be utilized for biological tissues imaging. The cascade CARS (CCARS) depends on chi-3 to the fourth power, instead of chi-3 squared as in the usual CARS signal; therefore, the contrast ratio with NRB is higher for CCARS than for CARS. We present analytic calculations showing that CCARS have better contrast over CARS in any situation. Comparison of the signals of both techniques generated on water-ethanol solutions confirm these results. Finally, we acquired CCARS images of fresh biological tissues, attesting that it is a useful tool for biological studies.

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes.

AIMS/HYPOTHESIS: Diabetic cardiomyopathy is characterised by diastolic dysfunction, oxidative stress, fibrosis, apoptosis and pathological cardiomyocyte hypertrophy. Phosphoinositide 3-kinase (PI3K)(p110α) is a cardioprotective kinase, but its role in the diabetic heart is unknown. The aim of this study was to assess whether PI3K(p110α) plays a critical role in the induction of diabetic cardiomyopathy, and whether increasing PI3K(p110α) activity in the heart can prevent the development of cardiac dysfunction in a setting of diabetes. METHODS: Type 1 diabetes was induced with streptozotocin in adult male cardiac-specific transgenic mice with increased PI3K(p110α) activity (constitutively active PI3K [p110α], caPI3K] or decreased PI3K(p110α) activity (dominant-negative PI3K [p110α], dnPI3K) and non-transgenic (Ntg) mice for 12 weeks. Cardiac function, histological and molecular analyses were performed. RESULTS: Diabetic Ntg mice displayed diastolic dysfunction and increased cardiomyocyte size, expression of atrial and B-type natriuretic peptides (Anp, Bnp), fibrosis and apoptosis, as well as increased superoxide generation and increased protein kinase C ß2 (PKCß2), p22 ( phox ) and apoptosis signal-regulating kinase 1 (Ask1) expression. Diabetic dnPI3K mice displayed an exaggerated cardiomyopathy phenotype compared with diabetic Ntg mice. In contrast, diabetic caPI3K mice were protected against diastolic dysfunction, pathological cardiomyocyte hypertrophy, fibrosis and apoptosis. Protection in diabetic caPI3K mice was associated with attenuation of left ventricular superoxide generation, attenuated Anp, Bnp, PKCß2, Ask1 and p22 ( phox ) expression, and elevated AKT. Further, in cardiomyocyte-like cells, increased PI3K(p110α) activity suppressed high glucose-induced superoxide generation and enhanced mitochondrial function. CONCLUSIONS/INTERPRETATION: These results demonstrate that reduced PI3K activity accelerates the development of diabetic cardiomyopathy, and that enhanced PI3K(p110α) activity can prevent adverse cardiac remodelling and dysfunction in a setting of diabetes.

Near-infrared transillumination of teeth: measurement of a system performance.

Transillumination (TI) of dental enamel with near-infrared light is a promising nonionizing imaging method for detection of early caries lesion. Increased mineral loss (caries lesion) leads to increased scattering and absorption. Caries thus appear as dark regions because less light reaches the detector. The aim of this work was to characterize the performance of a TI system from the resolution of acquired images using the modulation transfer function at two wavelengths, 1.28 and 1.4 mum. Test charts with various values of spatial periods, mimicking a perfect caries lesion, were attached to tooth sections, followed by capture of the transmitted image, using both wavelengths. The sections were then consecutively reduced in thickness, and a sequence of all sizes of the test charts were used for repeatedly imaging procedures. The results show that the TI system can detect feature size of 250 mum with 30% modulation. From the information about how the image degrades as it propagates through enamel, we also examined the possibility of estimating the position of a simulated approximal caries lesion by comparing images obtained from the two sides of a tooth section.

CMOS-compatible athermal silicon microring resonators.

We propose a new class of resonant silicon optical devices, consisting of a ring resonator coupled to a Mach-Zehnder interferometer, which is passively temperature compensated by tailoring the optical mode confinement in the waveguides. We demonstrate operation of the device over a wide temperature range of 80 degrees. The fundamental principle behind this work can be extended to other photonic devices based on resonators such as modulators, routers, switches and filters.

Characterization of enamel in primary teeth by optical coherence tomography for assessment of dental caries.

BACKGROUND: Caries is a disease that affects both primary and permanent dentitions, therefore new methods of caries diagnosis need to be tested on primary teeth as well as on permanent teeth. AIM: This study reports the application of optical coherence tomography (OCT) to characterize sound dental structure and detect natural caries of human primary teeth. DESIGN: Six primary teeth were sectioned into thin slices ( approximately 1.5 mm), and analysed perpendicular to the enamel surface by two home-made OCT systems operating around 1280 and 840 nm. The generated images were compared with histology as the gold standard. RESULTS: We demonstrated the efficacy of the OCT technique to measure the depth of the enamel layer, whose result was statistically compared with histology (P = 0.823; P > 0.05) with good agreement. We also determined, through measurement of contrast values, an increase in backscattered intensity of the order of two to three times between sound and caries regions. CONCLUSIONS: We employed OCT generated images to characterize the enamel layer. The technique showed great potential to be used on paediatric dentistry clinical on early caries detection with no pain, as it is a noninvasive method.

Sub-nm resolution cavity enhanced microspectrometer.

A novel on-chip spectrometer device using combined functionalities of a micro-ring resonator and a planar diffraction grating is proposed. We investigate the performance of this architecture by implementing it in a silicon-on-insulator platform. We experimentally demonstrate such a device with 100 channels, 0.1 nm channel spacing and a channel crosstalk less than -10 dB. The entire device occupies an area of less than 2 mm(2). Based on our initial results we envision that this device enables the possibility of the realization of low-cost and high-resolution ultra-compact spectroscopy.

In vitro tomographic image of human pulp-dentin complex: optical coherence tomography and histology.

INTRODUCTION: Optical coherence tomography (OCT), a noninvasive imaging method, was used in this work to image the pulp-dentin complex. Pulp and dentin are integrally connected in the sense that physiologic and pathologic reactions in one of the tissues will also affect the other. METHODS: An OCT system with 6-mum spatial resolution at 800 nm was used to image the pulp-dentin complex of in vitro samples. Five intact human maxillary premolars scheduled for surgical extraction were used in this in vitro study. The occlusal surfaces of teeth were polished with wet 600-, 1,000-, and 1,200-grit aluminum oxide abrasive paper perpendicular to the long axis of teeth, producing a plane on that surface. The images of pulp-dentin complex were taken by scanning the occlusal surface in a mesiodistal direction. The laser penetrated into the teeth structure and a tomographic image of pulp-dentin complex, parallel to the long axis of teeth, was obtained. Histological and OCT images were analyzed and compared. RESULTS: The results showed the capability of the OCT technique to generate images of the boundaries of pulp and its relation to the dentin. It could be clearly seen that the OCT image provided the insight into dentinal substrate about 0.65-mm deep (corrected for the dentin refractive index). CONCLUSION: OCT can be used in the future to prevent iatrogenic exposures of the pulp, complementing other existing methods, and will permit a more predictive prognosis of treatments.

In vitro imaging of remaining dentin and pulp chamber by optical coherence tomography: comparison between 850 and 1280 nm.

We report the application of optical coherence tomography (OCT) to generate images of the remaining dentin and pulp chamber of in vitro human teeth. Bidimensional images of remaining dentin and of the pulp chamber were obtained parallel to the long axis of the teeth, by two OCT systems operating around 1280 and 850 nm, and compared to tomography images using the i-CAT(R) Cone Beam Volumetric Tomography system as the gold standard. The results demonstrated the efficacy of the OCT technique; furthermore, the wavelength close to 1280 nm presented greater penetration depth in the dentine than 850 nm, as expected from scattering and absorption coefficients. The OCT technique has great potential to be used on clinical practice, preventing accidental exposure of the pulp and promoting preventive restoration treatment.