Rejection! Or is it? Correlation among molecular microscope diagnostic system, histopathology and clinical judgement following heart transplantation.

PURPOSE: Little is known about clinical decision making among discordant findings concerning for rejection with endomyocardial biopsy (EMBx) and Molecular Microscope Diagnostic System (MMDx) in patients following heart transplantation. METHODS: Two hundred and twenty-eight corresponding EMBx and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed. Rejection was classified as t-cell mediated rejection ≥2R and/or antibody mediated rejection ≥1. Clinical decision making among concordant and discordant cases of EMBx and MMDx results were reviewed. RESULTS: Patient characteristics were comparable between concordant and discordant patient groups (median age 60 yrs., 76% male, and 71% White). A total of 167/228 specimens (73%) were concordant for no rejection with 98% agreement in clinical decision making and 25/228 (11%) concordant for rejection with 64% agreement in clinical decision making. Among the 36/228 (16%) discordant samples, clinical decision-making agreed on treatment for rejection in five of the MMDx samples and three of the EMBx samples. CONCLUSIONS: MMDx can be an additional tool to diagnose rejection not detected by the traditional EMBx and influence clinical decision making in guiding appropriate treatment. Ongoing investigation into the clinical utility of MMDx is warranted to determine the significance of discordant findings among diagnostic modalities when assessing for rejection.

Effectiveness and Safety Profile of Remote Pulmonary Artery Hemodynamic Monitoring in a "Real-World" Veterans Affairs Healthcare System.

Ambulatory hemodynamic monitoring has demonstrated the ability to reduce heart failure-related hospitalization, regardless of left ventricular ejection fraction; however, real-world data in a Veterans Affairs patient population are limited. The present study retrospectively reviewed 53 patients with New York Heart Association class III heart failure, regardless of left ventricular ejection fraction, implanted with a pulmonary artery pressure sensor (CardioMEMS) at our single Veterans Affairs institution. Heart failure-related hospitalizations were assessed in patients for 6 and 12 months after the implantation of the device and compared with the 6- and 12- month periods before implantation in the same patient cohort. Pulmonary arterial pressures and medication doses were also recorded at baseline, 6- months, and 12- months and procedural safety data were also assessed. Implantation of a remote pulmonary artery pressure sensor was associated with a 52% (95% confidence interval 30% to 68%, p <0.001) and a 44% (95% confidence interval 24% to 59%, p <0.001) reduction in heart failure-related hospitalization at 6 and 12 months after implant, respectively, compared with the 6- and 12-month preimplant periods. Mean pulmonary arterial pressures also demonstrated significant reductions from baseline to 6 and 12 months after implant. A total of 3 procedure-related adverse events were noted. In conclusion, pulmonary artery pressure sensor implantation is relatively safe and associated with significant reductions in heart failure-related hospitalization and decreased mean pulmonary artery pressures in patients within the Veterans Affairs system with New York Heart Association class III symptoms, regardless of ejection fraction.

Evolving the surveillance and workup of heart transplant rejection: A real-world analysis of the Molecular Microscope Diagnostic System.

The Molecular Microscope Diagnostic System (MMDx) analyzes RNA transcripts of transplanted heart tissue to differentiate among T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), injury, and healthy tissue. However, little is known about its performance in relation to other modalities in a real-world heart transplant population. We evaluated whether MMDx performs in agreement with other validated modalities. Two hundred and twenty-eight corresponding endomyocardial biopsies (EMBx) and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed with correlating donor-derived cell-free DNA (dd-cfDNA). Rejection was classified on EMBx in 29 specimens (TCMR ≥ 2R and/or AMR ≥ 1), on MMDx in 56 specimens, and in 74 values with dd-cfDNA ≥0.20%. Despite moderate agreement between EMBx and MMDx (84% agreement, Cohen's kappa, 0.48, p < .001), systematic differences were observed (McNemar's test, p < .001) where MMDx classified 32 of 37 discordant cases as rejection. MMDx and dd-cfDNA demonstrated slight agreement (72% agreement, Cohen's kappa, 0.39, p < .001); however, systematic differences were also apparent where MMDx classified 12 of 50 discordant specimens as rejection when dd-cfDNA was <0.20% (McNemar's test, p < .001). Our findings provide insight on the performance of MMDx relative to other modalities in a heart transplant cohort and have implications on the surveillance and workup of allograft rejection in heart transplantation.

The dominant left ventricular assist device: lessons from an era.

The production and distribution of the HeartWare ventricular assist device has come to an abrupt end, but with this end comes the opportunity to reflect upon lessons learned from its lifespan. Running counter to the standard of evidence-based practice, the era of the HeartWare ventricular assist device was marred with fragmented data in relation to its primary counterpart, the HeartMate III. This created an incomplete understanding of devices, limited individualized patient care, and effectively positioned providers to make inferences regarding device superiority. We briefly review pertinent literature on this topic among the most commonly implanted durable devices from the era, detail the inherent limitations of this data, and argue the necessity of randomized clinical trials among novel devices towards the optimization of patient care.

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection.

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.

Mitral stenosis produced by infective endocarditis involving a previously anatomically normal valve.

Described herein is a 63-year-old man who developed methicillin-sensitive Staphylococcus aureus endocarditis on a previously anatomically normal mitral valve. The resulting vegetations were so large that severe mitral stenosis resulted. The development of valve stenosis due exclusively to infective endocarditis is extremely rare.

Effect of sleeve gastrectomy on hypertension.

The objective of this study was to determine the effect of laparoscopic sleeve gastrectomy (LSG) on blood pressure in private practice settings. This study involved a retrospective review of 870 consecutive adult patients >18 y of age who underwent LSG over a period of 12 mo in a private bariatric surgery center. Data were collected from the preoperative and postoperative follow-up visits at 1, 3, 6, and 12 mo. The study population consists of 694 hypertensive and 176 normotensive patients. From the baseline to 12 mo after LSG, (1) mean body weight/body mass index decreased from 123 kg/44 kg/m2 to 94 kg/34 kg/m2 (P < .001); (2) mean systolic/diastolic blood pressure in hypertensive patients decreased from 131.9/79.9 to 127.6/77.1 mm Hg (P < .001); 3) only mean systolic blood pressure decreased in normotensive patients from 117.5 to 114.0 mm Hg (P < .001). One month after LSG, mean systolic blood pressure had decreased from 131.9 to 126.2 mm Hg (P < 0. 001) and the average number of antihypertensive medications per patient declined from 1.5 at the baseline to 0.6 (P < .001). Over the following 11 mo, blood pressure remained stable despite reduced antihypertensive therapy. Patients requiring more than two antihypertensive agents fell from 49% at the baseline to 22% at 12 mo. Hypertension resolved in 34% of patients. Linear regression analysis showed no association between change in body weight and change in systolic blood pressure. Within 1 mo of LSG, hypertensive patients experienced a significant decline in systolic blood pressure and antihypertensive therapy that remains unchanged at 12 mo in the face of major reductions in antihypertensive medications. Weight loss and blood pressure reduction may not be directly related.

Physiologic assessment of moderate coronary lesions: a step towards complete revascularization in coronary artery bypass grafting.

BACKGROUND: An accurate diagnostic assessment of coronary artery disease is crucial for patients undergoing coronary artery bypass grafting (CABG). Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) to guide complete revascularization have not been adequately studied in patients prior to CABG. We compared an anatomic to a physiologic assessment of moderate coronary lesions (40-70% stenosis) in patients referred for CABG. METHODS: We retrospectively reviewed 109 medical records of patients who underwent CABG at Tulane Medical Center from 2014 to 2016. Patients were divided into an FFR/iFR-guided and an angiography-guided group. Clinical characteristics, procedural outcomes, and clinical outcomes for the two groups were compared over an 18-month follow-up period. RESULTS: There were significantly higher rates of three-vessel anastomoses (85.7% vs. 74.7%, P<0.05) and venous grafting (85.7% vs. 76.8%, P<0.05) in the FFR/iFR group. The FFR/iFR group had a lower rate of grafts placed to the left anterior descending artery (LAD) distribution than the angiography group (7.1% vs. 29.5%, P<0.05). The FFR/iFR group had a higher rate of grafts placed to the left circumflex (LCx) artery distribution than the angiography group (28.6% vs. 9.5%, P<0.05). We observed a trend toward reduction in major adverse cardiac events (MACEs) (7.1% vs. 11.6%, P=0.369) and angina (0.0% vs. 6.3%, P=0.429) in the FFR/iFR group compared to the angiography group over 18 months. CONCLUSIONS: Physiologic assessment of coronary lesions can effectively guide complete revascularization in patients undergoing CABG. Moreover, FFR/iFR-guided CABG was associated with significantly higher rates of three-vessel anastomoses, venous grafting, and graft distribution to the circumflex system.

Visceral Adipose Tissue Accumulation and Residual Cardiovascular Risk.

PURPOSE OF THE REVIEW: Low-grade systemic inflammation increases residual cardiovascular risk. The pathogenesis of low-grade systemic inflammation is not well understood. RECENT FINDINGS: Visceral adipose tissue accumulates when the subcutaneous adipose tissue can no longer store excess nutrients. Visceral adipose tissue inflammation initially facilitates storage of nutrients but with time become maladaptive and responsible for low-grade systemic inflammation. Control of low-grade systemic inflammation requires reversal of visceral adipose tissue accumulation with intense and sustained aerobic exercise or bariatric surgery. Alternatively, pharmacologic inhibition of the inflammatory signaling pathway may be considered. Reversal visceral adipose tissue accumulation lowers residual cardiovascular risk.

Coronary sinus thrombosis: Echocardiographic visualization in a patient with known risk factors.

Coronary sinus thrombosis is a rare and often overlooked diagnosis that can have fatal consequences. We report a case of acute coronary sinus thrombosis in a patient with systolic heart failure who had undergone recent right-heart catheterization. The patient presented with recurrent presyncope, syncope, and shortness of breath. An echogenic focus consistent with a coronary sinus thrombus was visualized on transthoracic echocardiography that had not been seen previously on recent imaging. The patient was managed on oral anticoagulation. Awareness of patients at risk for coronary sinus thrombosis can lead to early detection via bedside echocardiography and early management.

Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization.

Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species.

Quantitative 1H-NMR spectrometry method for quality control of Aloe vera products.

An 1H-NMR spectrometry method was developed and validated to quantify acetylated polysaccharides, glucose, malic acid, lactic acid, and acetic acid in Aloe vera products. Nicotinamide was selected as an internal standard (IS) in this quantification method. The quantity of marker compounds was calculated by the relative ratio of the integrals of each compound to the IS. The method validation included specificity, linearity, accuracy, robustness, reproducibility, LOD, and LOQ on two samples--A. vera inner leaf standard and decolorized aloe whole leaf Standard from the International Aloe Science Council. Eighteen A. vera commercial products were analyzed with this NMR spectrometry method.

Nucleophilic addition to iminium ethers in the preparation of functionalized N-alkyl heterocycles.

Bicyclic iminium ethers can be synthesized by the reactions of ketones with hydroxyalkyl azides. These cationic species react with a variety of nucleophiles via two possible pathways. The initially formed, kinetic product arises from direct addition to the iminium carbon in the substrate. In some cases, the initial adduct reverts to the starting iminium ether and the ultimate product arises from nucleophilic displacement at the O-alkyl group to afford the terminally functionalized N-substituted amide. The behavior of a range of nucleophiles was studied by using several iminium ethers. In general, the relevant pathway could be identified by characterization of the product formed. For hydroxide addition, which can afford only one product regardless of mechanism, the reaction was shown to arise by the kinetic pathway, using (18)O-labeled hydroxide. A one-pot synthesis of functionalized lactams entailing treatment of ketones first with hydroxyalkyl azides followed by nucleophilic addition was also developed.