Search

Atherosclerosis has been shown to develop preferentially at sites of coronary bifurcation, yet culprit lesions resulting in ST-elevation myocardial infarction do not occur more frequently at these sites. We hypothesized that these findings can be explained by similarities in intracoronary lipid and that lipid and lipid core plaque would be found with similar frequency in coronary bifurcation and nonbifurcation segments. One hundred seventy bifurcations were identified, 156 of which had comparative nonbifurcation segments proximal and/or distal to the bifurcation. We compared lipid deposition at bifurcation and nonbifurcation segments in coronary arteries using near-infrared spectroscopy (NIRS), a novel method for the in vivo detection of coronary lipid. Any NIRS signal for the presence of lipid was found with similar frequency in bifurcation and nonbifurcation segments (79% vs 74%, p = NS). Lipid core burden index, a measure of total lipid quantity indexed to segment length, was similar across bifurcation segments as well as their proximal and distal controls (lipid core burden index 66.3 ± 106, 67.1 ± 116, and 66.6 ± 104, p = NS). Lipid core plaque, identified as a high-intensity focal NIRS signal, was found in 21% of bifurcation segments, and 20% of distal nonbifurcation segments (p = NS). In conclusion, coronary bifurcations do not appear to have higher levels of intracoronary lipid or lipid core plaque than their comparative nonbifurcation regions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fractional flow reserve (FFR), the hyperemic ratio of distal (Pd) to proximal (Pa) coronary pressure, is used to identify the need for coronary revascularization. Changes in left ventricular end-diastolic pressure (LVEDP) might affect measurements of FFR. Methods and Materials: LVEDP was recorded simultaneously with Pd and Pa during conventional FFR measurement as well as during additional infusion of nitroprusside. The relationship between LVEDP, Pa, and FFR was assessed using linear mixed models. Results: Prospectively collected data for 528 cardiac cycles from 20 coronary arteries in 17 patients were analyzed. Baseline median Pa, Pd, FFR, and LVEDP were 73mmHg, 49mmHg, 0.69, and 18mmHg, respectively. FFR<0.80 was present in 14 arteries (70%). With nitroprusside median Pa, Pd, FFR, and LVEDP were 61mmHg, 42mmHg, 0.68, and 12mmHg, respectively. In a multivariable model for the entire population LVEDP was positively associated with FFR such that FFR increased by 0.008 for every 1-mmHg increase in LVEDP (beta=0.008; P<0.001), an association that was greater in obstructed arteries with FFR<0.80 (beta=0.01; P<0.001). Pa did not directly affect FFR in the multivariable model, but an interaction between LVEDP and Pa determined that LVEDP’s effect on FFR is greater at lower Pa. Conclusions: LVEDP was positively associated with FFR. The association was greater in obstructive disease (FFR<0.80) and at lower Pa. These findings have implications for the use of FFR to guide revascularization in patients with heart failure. Summary for Annotated Table of Contents: The impact of left ventricular diastolic pressure on measurement of fractional flow reserve (FFR) is not well described. We present a hemodynamic study of the issue, concluding that increasing left ventricular diastolic pressure can increase measurements of FFR, particularly in patients with FFR<0.80 and lower blood pressure. [Copyright &y& Elsevier]

This study sought to examine the safety of percutaneous coronary intervention (PCI) before and during de novo establishment of a transradial (TR) program at a teaching hospital. TR access remains underused in the United States, where cardiology fellowship programs continue to produce cardiologists with little TR experience. Establishment of TR programs at teaching hospitals may affect PCI safety. Starting in July 2009 a TR program was established at a teaching hospital. PCI-related data for academic years 2008 to 2009 (Y1) and 2009 to 2010 (Y2) were prospectively collected and retrospectively analyzed. Of 1,366 PCIs performed over 2 years, 0.1% in Y1 and 28.7% in Y2 were performed by TR access. No major complications were identified in 194 consecutive patients undergoing TR PCI, and combined bleeding and vascular complication rates were lower in Y2 versus Y1 (0.7% vs 2.0%, p = 0.05). Patients treated in Y2 versus Y1 and by TR versus transfemoral approach required slightly more fluoroscopy but similar contrast volumes and had similar procedural durations, lengths of stay, and predischarge mortality rates. PCI success rates were 97% in Y1, 97% in Y2, and 98% in TR cases. TR PCIs were performed by 13 cardiology fellows and 9 attending physicians, none of whom routinely performed TR PCI previously. In conclusion, de novo establishment of a TR program improved PCI safety at a teaching hospital. TR programs are likely to improve PCI safety at other teaching hospitals and should be established in all cardiology fellowship training programs. [Copyright &y& Elsevier]

We hypothesized that myocardial perfusion imaging (MPI) would fail to identify all vascular zones with the potential for myocardial ischemia in patients with multivessel coronary disease (MVD). MPI is based on the concept of relative flow reserve. The ability of these techniques to determine the significance of a particular stenosis in the setting of MVD is questionable. Fractional flow reserve (FFR) can determine the significance of individual stenoses. Thirty-six patients with disease involving 88 arteries underwent angiography, FFR, and MPI. FFR was performed using a pressure wire with hyperemia from intracoronary adenosine. Myocardial perfusion images were analyzed quantitatively and segments assigned to a specific coronary artery. The relation between FFR and perfusion was determined for each vascular zone. Of the 88 vessels, the artery was occluded (n = 20) or had an abnormal FFR ≤0.75 (n = 34) in 54 of 88 (61%). MPI showed no defect in 51 zones (58%). Concordance between angiography, FFR, and MPI was seen in 61 of 88 zones (69%). Discordance was seen in the remaining 27 zones (31%) and was predominantly from the finding of a FFR <0.75 or total occlusion despite no defect on MPI. In conclusion, many patients with MVD show no perfusion defect in zones supplied by arteries with total occlusion or a FFR <0.75. Thus, MPI underestimates ischemic burden and FFR may be better at guiding revascularization decisions than perfusion imaging in patients with MVD. [Copyright &y& Elsevier]

The aim of this study was to use myocardial contrast echocardiography to evaluate the effect of intravenous adenosine on microvascular reflow in patients with acute myocardial infarction who underwent primary coronary stenting (PCS). Thirty patients who underwent primary PCS for acute myocardial infarction were randomized to intravenous adenosine (50 to 70 μg/kg/min) or vehicle for 3 hours. Myocardial contrast echocardiography was performed before and sequentially after PCS to determine the risk area during coronary occlusion and infarct size. The risk area was similar in the adenosine- and placebo-treated patients. The infarct size as a ratio to the risk area was smaller in patients treated with adenosine when measured at 3 to 5 days (0.37 ± 0.29 vs 0.68 ± 0.25, p <0.01) and at 4 weeks (0.34 ± 0.26 vs 0.60 ± 0.21, p <0.01) after PCS. This effect was greatest when patency was achieved <4 hours after symptom onset (0.18 ± 0.18 vs 0.74 ± 0.31, p <0.05), with little effect after 4 hours. The relative microvascular blood volume in the risk area at 4 weeks was higher in patients receiving adenosine than in those receiving placebo (0.73 ± 0.22 vs 0.57 ± 0.20, p <0.01), and was highest when patency was achieved in <4 hours. In conclusion, the adjunctive use of intravenous adenosine after PCS reduces the infarct size relative to the risk area. This beneficial effect occurs primarily in those undergoing early intervention. [Copyright &y& Elsevier]

This study was designed to evaluate several electromechanical mapping parameters for assessment of myocardial viability and inducible ischemia as defined by dipyridamole single-photon emission computed tomographic (SPECT) imaging at rest in patients with severe ischemic cardiomyopathy. Unipolar voltage, normalized unipolar voltage, bipolar voltage, and fragmentation were compared with tracer uptake at rest and reversibility on stress or rest quantitative technetium-99m sestamibi SPECT imaging in 32 patients with severe ischemic cardiomyopathy (left ventricular ejection fraction 0.24 ± 0.08). In dysfunctional myocardial segments, logistic regression showed unipolar voltage, normalized unipolar voltage, and bipolar voltage to be predictive of viable myocardium (≥60% tracer uptake at rest) and was significantly higher in viable than in nonviable segments (p <0.01). A unipolar voltage of ≥7.1 mV was the best predictor of viable myocardium. In dysfunctional viable segments, unipolar voltage was significantly higher in reversible than in fixed segments (p <0.001), and a unipolar voltage of ≥8.5 mV had optimal power for identifying reversibility on dipyridamole SPECT imaging. We conclude that in patients with severe ischemic cardiomyopathy, unipolar voltage can identify viable from nonviable myocardium and reversible from fixed viable defects as defined by dipyridamole technetium-99m sestamibi SPECT imaging. [Copyright &y& Elsevier]

We tested the hypothesis that experienced interventional cardiologists can identify patients with fractional flow reserve (FFR) <0.75 either by visual assessment of the angiogram or by quantitative coronary angiography (QCA). Estimation of the significance of moderate lesions is difficult. FFR can determine the physiologic significance of a stenosis. Data comparing visual assessment and QCA of moderate lesions with FFR are limited. FFR was measured in 83 moderate lesions defined as having a 40% to 70% stenosis by visual inspection. An FFR <0.75 was considered “significant.” Lesions were visually assessed by 3 experienced interventional cardiologists and their significance estimated. QCA was performed. Both analyses were compared with FFR. FFR averaged 0.82 ± 0.11 and was <0.75 in 15 of 83 lesions (18%). The reviewers’ classification was concordant with the FFR in about half the lesions. Concordance between reviewers was poor (Spearman’s rho = 0.36). Visual assessment resulted in good sensitivity (80%) and negative predictive value (91%), but poor specificity (47%) and positive predictive value (25%) compared with FFR. By QCA, no patient with stenosis <60% or minimal luminal diameter >1.4 mm had FFR <0.75. QCA did not discriminate the significance of lesions outside of these parameters. Thus, neither visual assessment of an angiogram by experienced interventional cardiologists nor QCA can accurately predict the significance of most moderate narrowings. [Copyright &y& Elsevier]

Recent studies demonstrate increased cellular adhesion molecule expression by neointimal endothelium overlying primary and restenotic atherosclerotic plaque. In this study, we developed an atherosclerotic mouse model of arterial injury and characterized adhesion molecule expression after injury. Sixteen apolipoprotein-E-(ApoE)-deficient mice fed a Western-type diet for 4 weeks underwent carotid artery wire denudation at week 2. For each segment, the extent of neointima formation and medial thickening, or adhesion molecule expression, were scored separately on a scale from 0 (no plaque/thickening or expression) to 3 (extensive plaque/thickening or expression) using Movat staining (n = 3) or immunohistochemical analysis (n = 13). Histology revealed significant medial thickening (1.8 ± 0.9 vs. 0.3 ± 0.5, p < 0.001) versus controls and pronounced staining for monocytes/macrophages in the wall of injured vessels. Immunohistochemical analysis showed more robust expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the luminal surface of injured arteries versus controls (2.2 ± 0.6 vs. 1.4 ± 0.7, p < 0.01, and 2.5 ± 0.5 vs. 1.2 ± 0.6, p < 0.001, respectively). Injury increased adventitial ICAM-1 expression (2.6 ± 0.5 vs. 1.6 ± 0.5, p < 0.002) and medial VCAM-1 expression (2.2 ± 0.6 vs. 1.2 ± 0.7, p < 0.004). Thus, carotid injury results in significant medial thickening and increases adhesion molecule expression beyond that induced in ApoE-deficient mice fed a Western diet alone. The observation of macrophage infiltration into the media at sites of increased ICAM-1 and VCAM-1 expression suggests that these molecules may mediate monocyte/macrophage trafficking into the wall of injured arteries.Copyright © 1999 S.Karger AG, Basel [ABSTRACT FROM AUTHOR]

Intravascular delivery of an E1/E3 deleted adenovirus encoding the hirudin protein reduces neointimal formation in the rat arterial injury model. Given the interspecies variability in response to adenoviral vectors, we tested this same construct in the hirudin-sensitive cholesterol-fed rabbit arterial balloon injury model. We hypothesized that local delivery of an E1/E3-deleted adenovirus encoding hirudin (Ad-Hir) in addition to early hirudin infusion would limit neointimal formation compared to early hirudin alone. Methods and Results: Local delivery of Ad-Hir, 2.5 × 10[sup 10] PFU/ml, using a double balloon catheter [n = 6 vessels (v)] produced a 79% reduction in vessel wall thrombin activity at 48 h after balloon angioplasty (BA) compared with vehicle (Veh, n = 6v; p = 0.05). In chronic experiments, hypercholesterolemic rabbits underwent femoral BA, and received either early hirudin alone (n = 9v) or early hirudin plus locally delivered Ad-Hir (early hirudin + Ad-Hir; n = 9v), an E1/E3-deleted adenovirus encoding β-galactosidase (early hirudin + AdGal; n = 7v), or Veh (early hirudin + Veh; n = 10v). Early hirudin + Ad-Hir did not limit the arterial response to injury versus the other groups at 4 weeks after BA. Plaque area, cross-sectional luminal area narrowing by plaque, and T cell infiltration were significantly increased in the adenovirus- versus non-adenovirus-treated arteries. Plaque area correlated with T cell density. Conclusion: Following BA in cholesterol-fed rabbits, local transduction with A-Hir produced a marked reduction in vessel wall-associated thrombin activity. However, this strategy increased rather than decreased the arterial response to BA injury. Our results suggest that the lack of therapeutic effect resulted from adenovirus-stimulated plaque formation, possibly resulting from a T cell-mediated inflammatory response.Copyright © 1999 S.Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab. Methods: Using a double-blind, double-dummy design at 149 hospitals in 18 countries, we randomly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting. The primary end point was a composite of death, nonfatal myocardial infarction, or urgent target-vessel revascularization at 30 days. The trial was designed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab. Results: The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group (7.6 percent vs. 6.0 percent; hazard ratio, 1.26; one-sided 95 percent confidence interval of 1.51, demonstrating lack of equivalence, and two-sided 95 percent confidence interval of 1.01 to 1.57, demonstrating the superiority of abciximab over tirofiban; P=0.038). The magnitude and the direction of the effect were similar for each component of the composite end point (hazard ratio for death, 1.21; hazard ratio for myocardial infarction, 1.27; and hazard ratio for urgent target-vessel revascularization, 1.26), and the difference in the incidence of myocardial infarction between the tirofiban group and the abciximab group was significant (6.9 percent and 5.4 percent, respectively; P=0.04). The relative benefit of abciximab was consistent regardless of age, sex, the presence or absence of diabetes, or the presence or absence of pretreatment with clopidogrel. There were no significant differences in the rates of major bleeding complications or transfusions, but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia. Conclusions: Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab, the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab. (N Engl J Med 2001;344:1888-94.) [ABSTRACT FROM AUTHOR]

Background: Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure. Methods: Patients receiving concomitant therapy with digoxin (87 percent) and an angiotensin-converting-enzyme inhibitor (90 percent) who had ejection fractions of 30 percent or less were randomly assigned to receive double-blinded therapy with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. After 253 patients had been enrolled, randomization to the 120-mg vesnarinone group had to be stopped because of a significant increase in early mortality in this group. Thereafter, patients were randomly assigned only to 60 mg of vesnarinone per day (a total of 239 patients) or placebo (a total of 238 patients). Results: Significantly fewer patients in the group receiving 60 mg of vesnarinone than in the group receiving placebo (26 vs. 50 patients; P = 0.003) died or had worsening heart failure during the six-month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 percent). Similarly, there was a 62 percent reduction (95 percent confidence interval, 28 to 80 percent) in the risk of dying from any cause among the patients receiving vesnarinone. Furthermore, quality of life improved to a greater extent in the vesnarinone group than in the placebo group over 12 weeks (P = 0.008). The principal side effect associated with vesnarinone was reversible neutropenia, which occurred in 2.5 percent of the patients. Conclusions: Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown. (N Engl J Med 1993;329:149-55.) [ABSTRACT FROM AUTHOR]

In semiconductors, exciton or charge carrier diffusivity is typically described as an inherent material property. Here, we show that the transport of excitons among CsPbBr 3 perovskite nanocrystals (NCs) depends markedly on how recently those NCs were occupied by a previous exciton. Using transient photoluminescence microscopy, we observe a striking dependence of the apparent exciton diffusivity on excitation laser power that does not arise from nonlinear exciton-exciton interactions or thermal heating. We interpret our observations with a model in which excitons cause NCs to transition to a long-lived metastable configuration that markedly increases exciton transport. The exciton diffusivity observed here (>0.15 square centimeters per second) is considerably higher than that observed in other NC systems, revealing unusually strong excitonic coupling between NCs. The finding of a persistent enhancement in excitonic coupling may help explain other photophysical behaviors observed in CsPbBr 3 NCs, such as superfluorescence, and inform the design of optoelectronic devices.

Silver phenylselenolate (AgSePh, also known as "mithrene") and silver phenyltellurolate (AgTePh, also known as "tethrene") are two-dimensional (2D) van der Waals semiconductors belonging to an emerging class of hybrid organic-inorganic materials called metal-organic chalcogenolates. Despite having the same crystal structure, AgSePh and AgTePh exhibit a strikingly different excitonic behavior. Whereas AgSePh exhibits narrow, fast luminescence with a minimal Stokes shift, AgTePh exhibits comparatively slow luminescence that is significantly broadened and red-shifted from its absorption minimum. Using time-resolved and temperature-dependent absorption and emission microspectroscopy, combined with subgap photoexcitation studies, we show that exciton dynamics in AgTePh films are dominated by an intrinsic self-trapping behavior, whereas dynamics in AgSePh films are dominated by the interaction of band-edge excitons with a finite number of extrinsic defect/trap states. Density functional theory calculations reveal that AgSePh has simple parabolic band edges with a direct gap at Γ, whereas AgTePh has a saddle point at Γ with a horizontal splitting along the Γ-N 1 direction. The correlation between the unique band structure of AgTePh and exciton self-trapping behavior is unclear, prompting further exploration of excitonic phenomena in this emerging class of hybrid 2D semiconductors.

Aims: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments., Methods and Results: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001)., Conclusion: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment., Competing Interests: Conflict of interest: R.W., C.D.M., H.M.G.-G., and R.T. were Principal Investigator, European Principal Investigator, Responsible Officer Core Laboratory NIRS-IVUS and angiographic analysis, Worldwide Study Coordinator of the Lipid Rich Trial, sponsored by Infraredx-Nipro, Bedford, MA, USA. H.M.G.-G. reports the following institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips, and Corflow. C.D.M. is the recipient of research grants (through the Department of Clinical and Experimental Medicine of the University of Florence) from AMGEN, Behring, Chiesi, Daiichi Sankyo, Edwards, Medtronic, and Shockwave. Z.A.A. reports grants from NIH/NHLBI, Abbott Vascular, and Cardiovascular Systems Inc.; personal fees from Amgen, Astra Zeneca, and Boston Scientific; and equity from Shockwave Medical. G.S.M. reports honoraria from Boston Scientific and Philips. R.W. reports serving on the advisory boards of Abbott Vascular, Amgen, Boston Scientific, Cardioset, Cardiovascular Systems Inc., Medtronic, Philips, and Pi-Cardia Ltd.; being a consultant for Abbott Vascular, Amgen, Biotronik, Boston Scientific, Cardioset, Cardiovascular Systems Inc., Medtronic, Philips, Pi-Cardia Ltd., and Transmural Systems; receiving grant support from AstraZeneca, Biotronik, Boston Scientific, and Chiesi; serving on the speakers bureaus of AstraZeneca and Chiesi, and being an investor in MedAlliance and Transmural Systems. All other authors declared no conflict of interest., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Substitutional metal doping is a powerful strategy for manipulating the emission spectra and excited state dynamics of semiconductor nanomaterials. Here, we demonstrate the synthesis of colloidal manganese (Mn 2+ )-doped organic-inorganic hybrid perovskite nanoplatelets (chemical formula: L 2 [APb 1- x Mn x Br 3 ] n -1 Pb 1- x Mn x Br 4 ; L, butylammonium; A, methylammonium or formamidinium; n (= 1 or 2), number of Pb 1- x Mn x Br 6 4- octahedral layers in thickness) via a ligand-assisted reprecipitation method. Substitutional doping of manganese for lead introduces bright (approaching 100% efficiency) and long-lived (>500 μs) midgap Mn 2+ atomic states, and the doped nanoplatelets exhibit dual emission from both the band edge and the dopant state. Photoluminescence quantum yields and band-edge-to-Mn intensity ratios exhibit strong excitation power dependence, even at a very low incident intensity (<100 μW/cm 2 ). Surprisingly, we find that the saturation of long-lived Mn 2+ dopant sites cannot explain our observation. Instead, we propose an alternative mechanism involving the cross-relaxation of long-lived Mn-site excitations by freely diffusing band-edge excitons. We formulate a kinetic model based on this cross-relaxation mechanism that quantitatively reproduces all of the experimental observations and validate the model using time-resolved absorption and emission spectroscopy. Finally, we extract a concentration-normalized microscopic rate constant for band edge-to-dopant excitation transfer that is ∼10× faster in methylammonium-containing nanoplatelets than in formamidinium-containing nanoplatelets. This work provides fundamental insight into the interaction of mobile band edge excitons with localized dopant sites in 2D semiconductors and expands the toolbox for manipulating light emission in perovskite nanomaterials.

Introduction: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC., Methods: We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Optimal cutoff for prediction of response by TMB was determined by receiver operating characteristic analysis, and area under the curve (AUC) was calculated for all 3 biomarkers and combinations. Cox model was used to assess prognostic factors of overall survival (OS) and time to progression (TTP). Survival cutoffs calculated with Kaplan-Meier survival curves were TMB ≥10 mut/Mb, PD-L1 ≥50%, NLR <5, and combined biomarkers., Results: Data from 88 patients treated were analyzed. The optimal TMB cutoff was 9.24 mut/Mb (AUC, 0.62), improving to 0.74 combining all 3 biomarkers. Adjusted Cox model showed that TMB ≥10 mut/Mb was an independent factor of OS (hazard ratio [HR], 0.31; 95% confidence interval; 0.14-0.69; P = .004) and TTP (HR, 0.46; 95% CI, 0.27-0.77; P = .003). The combination of high TMB with positive PD-L1 and low NLR was significantly associated with OS (P = .038) but not TTP., Conclusions: TMB has modest predictive and prognostic power for clinical outcomes after ICI treatment. The combination of TMB, PD-L1, and NLR status improves this power., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Point-of-care cardiac ultrasound (cardiac POCUS) has potential to become a useful tool for improving cardiovascular care in Tanzania. We conducted a pilot program to train clinicians at peripheral health centers to obtain and interpret focused cardiac POCUS examinations using a hand-held portable device., Methods: Over a 5-day period, didactic and experiential methods were used to train clinicians to conduct a pre-specified scanning protocol and recognize key pathologies. Pre- and post-training knowledge and post-training image acquisition competency were assessed. In their usual clinical practices, trainees then scanned patients with cardiovascular signs/symptoms, recorded a pre-specified set of images for each scan, and documented their interpretation as to presence or absence of key pathologies on a case report form. A cardiologist subsequently reviewed all images, graded them for image quality, and then documented their interpretation of key pathologies in a blinded fashion; the cardiologist interpretation was considered the gold standard., Results: 8 trainees (6 Clinical Officers, 1 Assistant Medical Officer, and 1 Medical Doctor) initiated and completed the training. Trainees subsequently performed a total of 429 cardiac POCUS examinations in their clinical practices over a 9 week period. Stratified by trainee, the median percent of images that were of sufficient quality to be interpretable was 76.7% (range 18.0-94.2%). For five of eight trainees, 75% or more of images were interpretable. For detection of pre-specified key pathologies, kappa statistics for agreement between trainee and cardiologist ranged from - 0.03 (no agreement) for detection of pericardial effusion to 0.42 (moderate agreement) for detection of tricuspid valve regurgitation. Mean kappa values across the key pathologies varied by trainee from 0 (no agreement) to 0.32 (fair agreement)., Conclusions: The 5-day training program was sufficient to train most clinicians to obtain basic cardiac images but not to accurately interpret them. Proficiency in image interpretation may require a more intensive training program.

Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials.

Broadband emission in lead iodide 2D perovskites has been alternately attributed to self-trapped excitons (STEs) or permanent structural defects and/or impurities. Here, we investigate six different multilayered ( n > 1) 2D lead iodide perovskites as a function of sample temperature from 5 to 300 K. We distinguish shallow defect-associated emission from a broad near-infrared (NIR) spectral feature, which we assign to an STE through subgap photoexcitation experiments. When we varied the thickness ( n = 2, 3, 4), A-site cation (methylammonium vs formamidinium), and organic spacer (butylammonium vs hexylammonium vs phenylethylammonium), we found that the temperature dependence of broad NIR emission was strongly correlated with both the strength of electron-phonon coupling and the extent of structural deformation of the ground-state lattice, strongly supporting the assignment of this spectral feature to an STE. However, the extent to which formation of these STEs is intrinsic versus defect-assisted remains open to debate.

Lymphatic flow is augmented in states of chronic heart failure (cHF). However, the biological mechanism driving increased lymphatic flow capacity (lymphangiogenesis) in cHF is unknown. Recent studies have indicated that vascular endothelial growth factors (VEGF-A, -C, and -D) are involved in lymphangiogenesis. This study examined the association between VEGF-A, -C, and -D levels, invasively measured hemodynamics, and heart failure symptoms. Subjects who underwent clinically indicated right heart catheterization at Medical University of South Carolina between 12/2016 and 7/2018 were eligible for inclusion. These subjects underwent clinical assessment of cHF severity (including 6MWT and KCCQ), hemodynamic assessment with right heart catheterization, laboratory studies including B-type natriuretic peptide, and concomitant measurement of VEGF-A, -C, and -D. Fifty-six patients were included for analysis. Subjects with elevated pulmonary artery wedge pressure (PAWP) had significantly higher VEGF-D levels (263 ± 415 pg/ml vs 65 ± 101 pg/ml; p = 0.02). PAWP was not associated with VEGF-A or VEGF-C levels. When stratified by VEGF-D, subjects with elevated VEGF-D had clinical and hemodynamic characteristics associated with worse HF severity (lower ejection fraction, higher b-type natriuretic peptide, higher PAWP, lower cardiac output), but were not more symptomatic by Kansas City Cardiomyopathy Questionnaire scores and had similar 6-minute walk test distance compared with subjects with lower VEGF-D. Subjects with an elevated VEGF-D were more likely to have a diagnosis of heart failure for >3 years. In conclusion, VEGF-D is associated with elevated PAWP in cHF, and elevated VEGF-D may mitigate cHF symptoms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The care of patients with lymphoma relies heavily on accurate tissue diagnosis and classification. In sub-Saharan Africa, where lymphoma burden is increasing because of population growth, aging, and continued epidemic levels of human immunodeficiency virus infection, diagnostic pathology services are limited. This article summarizes lymphoma epidemiology, current diagnostic capacity, and obstacles and opportunities for improving practice in the region., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Across much of Africa, there is a critical shortage of pathology services necessary for clinical care. Even in settings where specialty-level clinical care, such as medical oncology, is available, access to anatomic pathology services has often lagged behind. Pathology laboratories in the region are challenging to establish and maintain. This article describes the successful implementation of telepathology services in Malawi and reviews other successful programs developed to support diagnostic pathology in resource-limited settings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Extranodal NK/T-cell lymphoma (ENKTCL) reports from sub-Saharan Africa (SSA) are remarkably rare, despite early childhood acquisition and high prevalence of the causative infectious agent, Epstein-Barr virus (EBV), and frequent occurrence of other lymphoproliferative disorders causally associated with EBV., Case Presentations: At a national teaching hospital in Malawi, three patients of African descent were seen with ENKTCL between 2013 and 2014. Patients were aged between 29 and 60 years, two with craniofacial involvement and one with a primary abdominal tumor, and all were HIV-negative. All had systemic B symptoms, and two severely impaired performance status. On histologic review, morphology and immunophenotyping demonstrated classical ENKTCL features in all cases, including diffuse proliferations of intermediate-to-large atypical lymphocytes with high mitotic activity and extensive background necrosis, positivity for CD3 and CD56, and negativity for CD20. By in situ hybridization, all three tumors were positive for EBV-encoded RNA (EBER). Baseline plasma EBV DNA was also markedly elevated for all three patients. Due to radiotherapy and chemotherapy limitations, patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with rapid disease progression. All three patients died from progressive lymphoma within 3 months of initial diagnosis., Conclusions: Our experience with these three patients in Malawi can highlight that ENKTCL does indeed occur in SSA, increase familiarity with ENKTCL among clinicians and pathologists throughout the region, and emphasize the need for better diagnosis and treatment for this neglected population.

The surgical treatment for valvular heart disease is well established with excellent long-term outcomes in appropriately selected patients. For patients at elevated risk for surgical intervention, options have traditionally been limited to medical therapy with disappointing results. The advent of transcatheter techniques of valvular repair or replacement has revolutionized treatment options for these patients at significantly elevated risk for surgery. In both the aortic and mitral realms, landmark clinical trials and real-world registries have begun to define the roles of these therapies, and the development of multidisciplinary heart teams have helped optimize patient treatment pathways and outcomes. Transcatheter treatment of aortic stenosis and mitral regurgitation has emerged as an approved option for properly selected patients, and guidelines have evolved to include these therapies. Further procedural refinement, device development, and clinical trials will continue to evolve this field.

Objectives: We compared the efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) in young, middle-aged, and elderly patients., Background: Intersociety guidelines suggest based on limited evidence that young patients with medically refractory symptoms of obstructive HCM should undergo surgical myectomy while elderly patients may be more appropriate for ASA., Methods: Data for 360 patients undergoing 389 ASAs were prospectively collected and retrospectively analyzed according to age., Results: Young (<45 years), middle-aged (45-64 years), and elderly (≥65 years) patients comprised 28, 40, and 32% of the study population, respectively. Young patients had thicker left ventricular septal walls at baseline, and elderly patients had more comorbidity and dyspnea. Resting, mean left ventricular outflow tract gradients (LVOTGs) were similar across the age groups at baseline (62, 66, and 68 mm Hg, respectively; P = NS for all comparisons). LVOTGs and dyspnea were significantly and similarly improved in all age groups immediately after ASA and through 12 months of follow-up (P < 0.001 for before and after comparisons; P = NS for intergroup comparisons). Complication rates were similar for young and middle-aged patients but higher for elderly patients (9.1 and 6.3% vs. 20.8%, respectively; P ≤ 0.016 for elderly vs. others). Mortality rates for young and middle-aged patients were lower than for elderly patients, but the differences were not statistically significant., Conclusions: Patients undergoing ASA had significant and similar improvements in LVOTGs and symptoms regardless of age. Procedural complications were increased in elderly patients, who had numerically but not statistically significantly higher mortality rates., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction., Methods and Results: Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity., Conclusions: We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR.

Objectives: To demonstrate that fractional flow reserve (FFR) of vessels in patients with high left ventricular mass index (LVMI) should be similar to that of matched vessels in patients with normal LVMI., Background: FFR is a physiologic index of coronary lesion severity. It is not known whether FFR remains useful in the setting of increased LVMI, when microvascular abnormalities may be present., Methods: LVMI was calculated in 84 patients using contrast left ventriculography after validation with cardiac magnetic resonance imaging. Cardiac risk factors, LV ejection fraction (LVEF), minimal lumen diameter (MLD), percent diameter stenosis (%DS), lesion length and FFR were compared in 22 patients with high LVMI to 62 patients with normal LVMI and angiographically-matched vessels., Results: LVMI was 126 +/- 21 g/m2 in the high LVMI group and 84 +/- 21 g/m2 in the normal LVMI group. There were no differences in age, LVEF, diabetes, hypertension or dyslipidemia between groups. Angiographic lesion characteristics were well matched in patients with high versus normal LVMI (MLD 1.3 +/- 0.6 mm vs. 1.3 +/- 0.6 mm, %DS 61 +/- 13% vs. 62 +/- 13%, and lesion length 14.2 +/- 7.0 mm vs. 14.3 +/- 7.0 mm; p = NS for all). Importantly, no difference in FFR was observed (0.79 +/- 0.12 vs. 0.78 +/- 0.16; p = NS) between the groups, and LVMI did not correlate with FFR in a multivariate analysis., Conclusions: FFR of coronary lesions in patients with high LVMI is no different than FFR of angiographically-matched lesions in patients with normal LVMI, suggesting that high LV mass should not limit the utility of FFR as an index of coronary lesion severity.

Objectives: To determine the outcome of consecutive patients with and without acute coronary syndromes (ACS) in whom revascularization was deferred on the basis of fractional flow reserve (FFR)., Background: FFR < 0.75 correlates with ischemia on noninvasive tests and deferral of treatment on the basis of FFR is associated with low event rates in selected populations. Whether these low event rates apply to patients undergoing assessment of moderate stenoses in association with an ACS is not known and is an important clinical question., Methods: Retrospective analysis and 12 month follow-up of consecutive, moderate (50-70%) de novo coronary lesions assessed with FFR., Results: Revascularization was deferred in 120 lesions (111 patients) with FFR > or = 0.75. ACS was present in 35 patients (40 lesions). The clinical, angiographic and coronary hemodynamic characteristics of patients with and without ACS were similar. Among the 35 patients with ACS, there were 3 deaths, 1 MI, and 6 target vessel revascularizations (TVRs) (15% of lesions). Among the 76 patients without ACS, there were 5 deaths, 1 MI, and 7 TVR's (9% of lesions)., Conclusions: Deferral of revascularization based on FFR in patients with ACS and moderate coronary stenoses is associated with acceptable and low event rates at 1 year.

Objectives: The goal of this study was to determine the proportion of patients with left main coronary disease (LMCD) with unfavorable characteristics for percutaneous coronary intervention (PCI)., Background: Published series suggest that LMCD can be treated percutaneously, however, the proportion of patients in whom PCI is an option based on angiographic criteria is unknown., Methods: In 13,228 consecutive coronary angiograms, 476 (3.6%) patients had < or =60% stenosis of the left main. In 232 patients with unprotected LMCD, the clinical characteristics and angiograms were reviewed with six features chosen as "unfavorable" for PCI: (1) Bifurcation LMCD, (2) occlusion of a major coronary, (3) ejection fraction <30%, (4) occlusion of a dominant RCA, (5) left dominant circulation, and (6) coexisting three-vessel disease. Treatment modality and 1 year mortality were determined., Results: The mean age was 69 years and 68% were male. Unfavorable characteristics were common with at least one unfavorable characteristic seen in 80%. Bifurcation disease was the most common unfavorable characteristic observed (53%) and coexisting three-vessel disease was seen in 38%. Treatment consisted of CABG in 205 (88%), medical therapy in 24 (10%) and PCI in 3 (1%). Among patients referred for CABG, 1 year survival was 88% with similar rates of survival for those with favorable characteristics (86%) compared to those with at least one unfavorable characteristic (88%)., Conclusions: Most patients with LMCD have at least one unfavorable characteristic for PCI suggesting that PCI may be a technically difficult option for most patients with LMCD.

Background: Diabetic nephropathy is associated with increased cardiovascular events. Coronary atherosclerosis is responsible for many of these events, but other mechanisms such as impaired flow reserve may be involved. The purpose of this study was to define the prevalence and mechanism of abnormal coronary velocity reserve (CVR) in patients with diabetes mellitus who have nephropathy and a normal coronary artery., Methods: Patients undergoing catheterization for clinical purposes were enrolled. CVR was measured with a Doppler ultrasound scanning wire in a normal coronary in 32 patients without diabetes mellitus, 11 patients with diabetes mellitus who did not have renal failure, and 21 patients with diabetes mellitus who had nephropathy. A CVR <2.0 was considered to be abnormal., Results: Patients with diabetes mellitus who had renal failure had a higher incidence of hypertension and left ventricular hypertrophy. The average peak velocity (APV) at baseline was higher in patients with diabetes mellitus who had renal failure. At peak hyperemia, APV increased in all 3 groups, with no difference between groups. The mean CVR for patients without diabetes was 2.8 +/- 0.8 and was not different from that in patients with diabetes mellitus who did not have renal failure (2.7 +/- 0.7), but was lower than that in patients with diabetes mellitus who had renal failure (1.6 +/- 0.5; P < 0.001). Abnormal CVR was observed in 9% of patients without diabetes mellitus, 18% of patients with diabetes mellitus who did not have renal failure, and 57% of patients with diabetes mellitus who had renal failure, and abnormal CVR was caused by an elevation of baseline APV in 66% of these cases. The baseline heart rate and the presence of diabetes mellitus with renal failure were independent predictors of abnormal CVR by multivariable analysis., Conclusions: Patients with diabetic nephropathy have abnormalities in CVR in the absence of angiographically evident coronary disease.