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Abstract 540: Correlation of Improved Cholesterol Efflux Capacity of High Density Lipoprotein With Survival and Allograft Vasculopathy in Cardiac Transplant Recipients
- Ali Javaheri,
- Payman Zamani,
- Maria Molina,
- Amrith Rodrigues,
- Susan Chambers,
- Patricia Stutman,
- Wilhelmina Maslanek,
- Mary Williams,
- Daniya Lukmanova,
- Antonino Picataggi,
- Scott Lilly,
- Peter S Heeger,
- Mohamed H Sayegh,
- Anil K Chandraker,
- Randall C Sarling,
- David M Briscoe,
- Kevin P Daly,
- Joseph Stehlik,
- David Ikle,
- Jason Christie,
- Y. Joseph Woo,
- Lee R Goldberg,
- Jeffrey Billheimer and
- Daniel J Rader
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 35, Issue suppl_11 May 2015

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Background: Coronary allograft vasculopathy (CAV) is an important cause of mortality after cardiac transplantation. High density lipoprotein (HDL) cholesterol efflux capacity has been inversely associated with coronary artery disease and is impaired in cardiac transplant recipients. We performed a single center case-cohort study to test the hypothesis that reduced efflux capacity is a risk factor for mortality and a second, multi-center retrospective study to test if efflux capacity is associated with CAV progression.Methods: We designed a single center case-cohort study in which we identified cardiac transplant patients who died between 2009-2012 (cases, n=34) and controls as cardiac transplant patients who were alive as of the fourth quarter of 2013 (n=57). Efflux capacity was measured by incubating apolipoprotein B-depleted serum with macrophages in a validated ex vivo system. In a second study, we utilized pre-transplant samples from the Clinical Trials in Organ Transplantation 5 (CTOT5) study to determine the association between ATP-binding-cassette (ABC) A1-dependent cholesterol efflux and CAV progression at 1 year.Results: In our single center study, the average time from transplant to study entry was well-matched between cases and controls (7.6±1.0 vs 7.7±0.8 years, respectively, p=0.48). Multivariable Cox proportional hazard ratios demonstrated that higher levels of HDL cholesterol efflux capacity were associated with survival (HR 0.61, 95% CI 0.43-0.85), even after adjustment for HDL cholesterol mass. To determine whether excess mortality observed in subjects with reduced efflux could be attributable to CAV progression, we tested the relationship between intravascular ultrasound (IVUS) progression of CAV and cholesterol efflux capacity using linear regression. ABCA1-dependent efflux and IVUS progression were significantly associated (β = -0.90, 95% CI [-1.73 - -0.07], p = 0.037, R2 = 0.37).Conclusion: Reduced efflux capacity is an important mediator of CAV progression and mortality in cardiac transplant recipients. This finding suggests that interventions to increase HDL cholesterol efflux capacity may provide clinical benefit in cardiac transplant recipients.
Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery
- Eric M Teichner,
- Robert C Subtirelu,
- Arjun B Ashok,
- Yvonne Su,
- Victoria A Anderson,
- Milo Writer,
- Omar Al‐Daoud,
- Miraziz Ismoilov,
- Chitra Parikh,
- William Y Raynor,
- Sahithi Talasila,
- Poul F Høilund‐Carlsen,
- Abass Alavi and
- Mona‐Elisabeth Revheim
Stroke: Vascular and Interventional Neurology Volume 3, Issue S21 November 2023

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IntroductionCerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk.MethodsOur study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas.ResultsNaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1).ConclusionOur findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.
NEXN Gene in Cardiomyopathies and Sudden Cardiac Deaths: Prevalence, Phenotypic Expression, and Prognosis
- Alexis Hermida,
- Flavie Ader,
- Gilles Millat,
- Guillaume Jedraszak,
- Phillipe Maury,
- Romain Cador,
- Pierre-Antoine Catalan,
- Gaël Clerici,
- Nicolas Combes,
- Pascal De Groote,
- Delphine Dupin-Deguine,
- Romain Eschalier,
- Laurence Faivre,
- Patricia Garcia,
- Benoit Guillon,
- Alexandre Janin,
- Beatrice Kugener,
- Marylin Lackmy,
- Mikael Laredo,
- Xavier Le Guillou,
- François Lesaffre,
- Hugues Lucron,
- Antoine Milhem,
- Gwenaël Nadeau,
- Karine Nguyen,
- Aurélien Palmyre,
- Elodie Perdreau,
- François Picard,
- Nicolas Rebotier,
- Pascale Richard,
- Caroline Rooryck,
- Julien Seitz,
- Alain Verloes,
- Agathe Vernier,
- Pierre Winum,
- Grace-A-Dieu Yabeta,
- Océane Bouchot,
- Philippe Chevalier,
- Philippe Charron and
- Estelle Gandjbakhch
Circulation: Genomic and Precision Medicine Volume 17, Issue 11 February 2024

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BACKGROUND:Few clinical data are available on NEXN mutation carriers, and the gene’s involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants.METHODS:DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected.RESULTS:Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0–49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25–50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events.CONCLUSIONS:Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed—especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established.
Constrasts and similarities of acute hemodynamic responses to specific antagonism of angiotensin II ([Sar1, Thr8] A II) and to inhibition of converting enzyme (captopril).
- F M Fouad,
- J M Ceimo,
- R C Tarazi and
- E L Bravo
Circulation Volume 61, Issue 11 January 1980

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The early blood pressure and hemodynamic effects of the converting enzyme inhibitor (CEI), captopril, were compared in 23 hypertensive patients with those of a specific angiotensin II antagonist (AA), [Sar1, Thr8] A II. AA reduced mean arterial pressure (MAP) greater than 10 mm Hg only in seven of 23 patients vs 15 of 23 who responded to CEI (p less than 0.02). With both drugs, changes in MAP were not associated with significant changes in cardiac output (p greater than 0.10 for both drugs), but correlated with changes in systemic resistance (TPR); r = 0.84, p less than 0.001 for AA and r = 0.71, p less than 0.001 for CEI. Changes in TPR and MAP correlated significantly and inversely with log plasma renin activity in both instances; for AA, r = 0.829 and for CEI, r = -0.737; p less than 0.001 for both. The slopes of the two regression lines were not significantly different but the intercepts were +8.47 mm Hg for AA vs -10.17 mm Hg for CEI (p less than 0.001). This quantitative difference in response could be attributed either to an agonistic effect of [Sar1, Thr8] A II or to an additional vasodilator effect of captopril.
Role of intrarenal angiotensin II and alpha-adrenoceptors in renal vasoconstriction with acute hypoxemia and hypercapnic acidosis in conscious dogs.
- C E Rose,
- J E Vance,
- W S Dacus,
- V L Brashers,
- M J Peach and
- R M Carey
Circulation Research Volume 69, Issue 11 July 1991

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To evaluate our previous observation of renal vasoconstriction during combined acute hypoxemia and hypercapnic acidosis preceded by acute hypoxemia, we studied 13 conscious mongrel uninephrectomized dogs with chronic renal catheters and controlled sodium intake (80 meq/day for 4 days). Five dogs were studied during combined acute hypoxemia (PaO2, 37 +/- 1 mm Hg) and hypercapnic acidosis (PaCO2, 59 +/- 1 mm Hg; pH 7.20 +/- 0.01). Each dog was studied during infusion of 1) the intrarenal vehicle (n = 5), 2) the intrarenal alpha 1-antagonist prazosin (0.2 micrograms.kg-1.min-1, n = 5), 3) intrarenal [Sar1,Ala8]angiotensin II (70 ng.kg-1.min-1, n = 5), and 4) intrarenal prazosin and [Sar1,Ala8]angiotensin II (n = 4). Immediate induction of combined hypoxemia and hypercapnic acidosis after control measurements during intrarenal vehicle infusion resulted in a decrease in effective renal plasma flow and glomerular filtration rate, increase in renal vascular resistance, and decrease in filtered sodium load in the first 20 minutes of the blood gas derangement. Intrarenal administration of [Sar1,Ala8]angiotensin II failed to reverse the effects of the combined blood gas derangement on renal function. In contrast, intrarenal prazosin administration either alone or in combination with [Sar1,Ala8]angiotensin II abrogated the increase in renal vascular resistance, decrease in glomerular filtration rate, and fall in filtered sodium load. These studies identify a major role for alpha 1-adrenoceptors in the renal vasoconstriction during combined hypoxemia and hypercapnic acidosis.
Hemodynamics of a new angiotensin antagonist, [Sar1, Thr8]A II, in hypertensive man.
- R J Cody,
- R C Tarazi,
- F M Fouad and
- E L Bravo
Circulation Volume 61, Issue 21 February 1980

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Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy
- Friederike Austein,
- Christian Riedel,
- Tina Kerby,
- Johannes Meyne,
- Andreas Binder,
- Thomas Lindner,
- Monika Huhndorf,
- Fritz Wodarg and
- Olav Jansen
Stroke Volume 47, Issue 91 September 2016

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Background and Purpose—Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy.Methods—Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke.Results—In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland–Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients.Conclusions—Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software.
Evidence for the existence of a family of biologically active angiotensin I-like peptides in the dog central nervous system.
- A Husain,
- F M Bumpus,
- R R Smeby,
- K B Brosnihan,
- M C Khosla,
- R C Speth and
- C M Ferrario
Circulation Research Volume 52, Issue 41 April 1983

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A family of angiotensin I-like peptides has been derived from endogenous precursors present in dog cerebrospinal fluid after incubation with species homologous renin. These peptides are immunologically and pharmacologically similar to [Ile5]angiotensin I, and have molecular weights ranging between 1300 and 2200 daltons. The presence of precursors in the cerebrospinal fluid able to generate various biologically active angiotensin I-like peptides dissimilar to plasma angiotensin I supports the concept of a local angiotensin I-forming system in the brain.
Efficacy of dopamine, dobutamine, and epinephrine during emergence from cardiopulmonary bypass in man.
- P A Steen,
- J H Tinker,
- J R Pluth,
- D A Barnh;rst and
- S Tarhan
Circulation Volume 57, Issue 21 February 1978

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Hemodynamic effects of dobutamine and dopamine (both 5, 10, 15 microgram/kg/min) and epinephrine (0.04 microgram/kg/min) were studied immediately following cessation of cardiopulmonary bypass in 34 patients with preoperative evidence of left ventricular dysfunction. Significant increases in mean cardiac index were seen with dobutamine (15, 25, and 26% respectively), and epinephrine (30%). The largest increases occurred with dopamine (44, 53, and 64 percent respectively). Responses varied from patient to patient, however. Seven patients developed marked output increases without concomitant increases in arterial pressure, whereas seven others showed "satisfying" increases in arterial pressure without appreciable output increases. Heart rate increases were small and few arrhythmias were noted. We conclude that dopamine, epinephrine, and dobutamine all are effective inotropic agents during the immediate post-bypass period, with variations discussed in detail. None possess the disturbing chronotropic and arrhythmogenic effects of isoproterenol (previously studied). Efficacy of administration of inotropic drugs seems best assessed by serial output measurements during this period.
The Total Right/Left-Volume Index: A New and Simplified Cardiac Magnetic Resonance Measure to Evaluate the Severity of Ebstein Anomaly of the Tricuspid Valve: A Comparison With Heart Failure Markers From Various Modalities
- Olga Hösch,
- Jan Martin Sohns,
- Thuy-Trang Nguyen,
- Peter Lauerer,
- Christina Rosenberg,
- Johannes Tammo Kowallick,
- Shelby Kutty,
- Christina Unterberg,
- Andreas Schuster,
- Martin Faßhauer,
- Wieland Staab,
- Thomas Paul,
- Joachim Lotz and
- Michael Steinmetz
Circulation: Cardiovascular Imaging Volume 7, Issue 41 July 2014

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Background—The classification of clinical severity of Ebstein anomaly still remains a challenge. The aim of this study was to focus on the interaction of the pathologically altered right heart with the anatomically—supposedly—normal left heart and to derive from cardiac magnetic resonance (CMR) a simple imaging measure for the clinical severity of Ebstein anomaly.Methods and Results—Twenty-five patients at a mean age of 26±14 years with unrepaired Ebstein anomaly were examined in a prospective study. Disease severity was classified using CMR volumes and functional measurements in comparison with heart failure markers from clinical data, ECG, laboratory and cardiopulmonary exercise testing, and echocardiography. All examinations were completed within 24 hours. A total right/left-volume index was defined from end-diastolic volume measurements in CMR: total right/left-volume index=(RA+aRV+fRV)/(LA+LV). Mean total right/left-volume index was 2.6±1.7 (normal values: 1.1±0.1). This new total right/left-volume index correlated with almost all clinically used biomarkers of heart failure: brain natriuretic peptide (r=0.691; P=0.0003), QRS (r=0.432; P=0.039), peak oxygen consumption/kg (r=−0.479; P=0.024), ventilatory response to carbon dioxide production at anaerobic threshold (r=0.426; P=0.048), the severity of tricuspid regurgitation (r=0.692; P=0.009), tricuspid valve offset (r=0.583; P=0.004), and tricuspid annular plane systolic excursion (r=0.554; P=0.006). Previously described severity indices ([RA+aRV]/[fRV+LA+LV]) and fRV/LV end-diastolic volume corresponded only to some parameters.Conclusions—In patients with Ebstein anomaly, the easily acquired index of right-sided to left-sided heart volumes from CMR correlated well with established heart failure markers. Our data suggest that the total right/left-volume index should be used as a new and simplified CMR measure, allowing more accurate assessment of disease severity than previously described scoring systems.

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Abstract 540: Correlation of Improved Cholesterol Efflux Capacity of High Density Lipoprotein With Survival and Allograft Vasculopathy in Cardiac Transplant Recipients

Abstract

Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery

Abstract

NEXN Gene in Cardiomyopathies and Sudden Cardiac Deaths: Prevalence, Phenotypic Expression, and Prognosis

Abstract

Constrasts and similarities of acute hemodynamic responses to specific antagonism of angiotensin II ([Sar1, Thr8] A II) and to inhibition of converting enzyme (captopril).

Abstract

Role of intrarenal angiotensin II and alpha-adrenoceptors in renal vasoconstriction with acute hypoxemia and hypercapnic acidosis in conscious dogs.

Abstract

Hemodynamics of a new angiotensin antagonist, [Sar1, Thr8]A II, in hypertensive man.

Abstract

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy

Abstract

Evidence for the existence of a family of biologically active angiotensin I-like peptides in the dog central nervous system.

Abstract

Efficacy of dopamine, dobutamine, and epinephrine during emergence from cardiopulmonary bypass in man.

Abstract

The Total Right/Left-Volume Index: A New and Simplified Cardiac Magnetic Resonance Measure to Evaluate the Severity of Ebstein Anomaly of the Tricuspid Valve: A Comparison With Heart Failure Markers From Various Modalities

Abstract