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Introduction: Elite breath-hold divers (BHD) possess several oxygen conserving adaptations to endure long dives similar to diving mammals. During dives, Bottlenose Dolphins may increase the alveolar ventilation (VA) to perfusion (Q) ratio to increase alveolar oxygen delivery. We hypothesized that BHD possess similar adaptive mechanisms during apnea. Methods and results: Pulmonary blood volume (PBV) was determined by echocardiography, 15O-H2O PET/CT, and cardiac MRi, (n = 6) during and after maximum apneas. Pulmonary function was determined by body box spirometry and compared to matched controls. After 2 min of apnea, the PBV determined by echocardiography and 15O-H2O-PET/CT decreased by 26% and 41%, respectively. After 4 min of apnea, the PBV assessed by echocardiography and cardiac MRi decreased by 48% and 67%, respectively (n = 6). Fractional saturation (F)O2Hb determined by arterial blood-gas-analyses collected after warm-up and a 5-minute pool-apnea (n = 9) decreased by 43%. Compared to matched controls (n = 8), spirometry revealed a higher total and alveolar-lung-capacity in BHD (n = 9), but a lower diffusion-constant. Conclusion: Our results contrast with previous studies, that demonstrated similar lung gas transfer in BHD and matched controls. We conclude that elite BHD 1) have a lower diffusion constant than matched controls, and 2) gradually decrease PBV during apnea and in turn increase VA/Q to increase alveolar oxygen delivery during maximum apnea. We suggest that BHD possess pulmonary adaptations similar to diving mammals to tolerate decreasing tissue oxygenation. New and noteworthy: This manuscript addresses novel knowledge on tolerance to hypoxia during diving, which is shared by elite breath-hold divers and adult diving mammals: Our study indicates that elite breath-hold divers gradually decrease pulmonary blood volume and in turn increase VA/Q, to increase alveolar oxygen delivery during maximum apnea to tolerate decreasing oxygen levels similar to the Bottlenose Dolphin.
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Introduction: Elite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD (n = 11) and matched controls (n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD. Methods and results: After 4 min of apnea, left ventricular myocardial mass (LVMM) determined by 15O-H2O-PET/CT (n = 6) and cardiac MRI (n = 6), was unaltered compared to rest. During maximum apnea (â¼6 min), lower extremity volume assessed by DXA-scan revealed a â¼268 mL decrease, and spleen volume, assessed by ultrasonography, decreased â¼102 mL. Compared to age, BMI and VO2max matched controls (n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations. Conclusion: Our results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans.
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BACKGROUND: Evaluation of sufficient adenosine response constitutes a significant challenge in myocardial perfusion imaging (MPI). Splenic switch-off in MPI studies denotes a visually (qualitatively) reduced splenic radiotracer signal during adenosine stress and is considered indicative of sufficient cardiac vasodilation. In this study, we examined semi-quantitative and quantitative approaches to splenic switch-off assessment using [15O]H2O-PET with either summed activity images or calculated parametric splenic blood flow images. METHODS: Cohort 1: 90 clinical patients undergoing [15O]H2O MPI in whom adenosine response was considered clinically adequate were identified to characterize the corresponding splenic switch-off. Spleen stress/rest-ratio (SSR-ratio) was calculated as spleen stress signal intensity/spleen rest signal intensity on both summed activity and parametric blood flow images. Cohort 2: Twenty-five patients with repeat MPI due to suspected insufficient adenosine response were identified to observe if splenic switch-off on the initial MPI could predict the outcome of the repeat MPI. Cohort 3: Fifty-four patients who were considered adenosine responders on MPI and who had a coronary angiogram (CAG) follow-up within 3 months after MPI served as a separate validation group. RESULTS: Splenic switch-off was present in most patients with a clinically sufficient adenosine response (Cohort 1), illustrated by both visual (74.4%-86.7%), semi-quantitative (summed activity images) (85.6%), and quantitative (parametric blood flow images) (92.2%) evaluation, which corresponds to the distribution in patients with sufficient adenosine response and follow-up CAG (Cohort 3). In patients suspected of insufficient adenosine response on the initial MPI (Cohort 2), the repeat MPI only yielded different myocardial blood flow (MBF) results if the initial SSR-ratio was >0.90 on splenic parametric blood flow images. CONCLUSION: quantitative splenic switch-off assessment on parametric blood flow images was superior to the semi-quantitative splenic switch-off approach. Patients with a suspected insufficient initial adenosine response and SSR-ratio >0.90 can benefit from a repeat MPI. Thus, the integration of quantitative splenic switch-off using parametric blood flow images in the evaluation of adenosine response may support future clinical decision-making.
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AIMS: Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated (i) whether atrial fibrillation (AF) reduces global hyperaemic myocardial blood flow (MBF) and (ii) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. METHODS AND RESULTS: We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperaemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD, and AF-CAD. Hyperaemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way analysis of variance P < 0.0001]. In multiple linear regression, ongoing AF was independently associated with reduced hyperaemic MBF. Every 0.1â mL/min/g decrease in hyperaemic MBF was associated with a 23% increase in odds of early revascularization. Receiver operating characteristic (ROC) analysis of vessel-specific hyperaemic MBF to predict early revascularization yielded the following areas under the ROC curve: SR-noCAD: 0.95 (P < 0.0001); AF-noCAD: 0.79 (P < 0.0001); SR-CAD: 0.78 (P < 0.0001); and AF-CAD: 0.88 (P < 0.0001). CONCLUSION: Ongoing AF is associated with 19-25% reduced global hyperaemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel-specific hyperaemic MBF still predicts early revascularization in patients with AF.
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Fibrilación Atrial , Imagen de Perfusión Miocárdica , Revascularización Miocárdica , Radioisótopos de Oxígeno , Tomografía de Emisión de Positrones , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Femenino , Masculino , Imagen de Perfusión Miocárdica/métodos , Estudios Prospectivos , Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/complicaciones , Angina de Pecho/diagnóstico por imagen , Estudios de Cohortes , Angiografía Coronaria/métodos , Curva ROC , Índice de Severidad de la Enfermedad , Medición de RiesgoRESUMEN
BACKGROUND: [15O]H2O PET/CT allows noninvasive quantification of tissue perfusion and can potentially play a future role in the diagnosis and treatment of peripheral artery disease. We aimed to evaluate the reliability of dynamic [15O]H2O PET imaging for measuring lower extremity skeletal muscle perfusion. Ten healthy participants underwent same-day test-retest study with six dynamic [15O]H2O PET scans of lower legs and feet. Manual volume-of-interests were drawn in skeletal muscles, and PET time activity curves were extracted. K1 values (mL/min/100 mL) were estimated using a single-tissue compartment model (1TCM), autoradiography (ARG), and parametric imaging with blood input functions obtained from separate heart scans. RESULTS: Resting perfusion values in the muscle groups of the lower legs ranged from 1.18 to 5.38 mL/min/100 mL (ARG method). In the muscle groups of the feet, perfusion values ranged from 0.41 to 3.41 mL/min/100 mL (ARG method). Test-retest scans demonstrated a strong correlation and good repeatability for skeletal muscle perfusion with an intraclass correlation coefficient (ICC) of 0.88 and 0.87 and a repeatability coefficient of 34% and 53% for lower legs and feet, respectively. An excellent correlation was demonstrated when comparing volume-of-interest-based methods (1TCM and ARG) (lower legs: ICC = 0.96, feet: ICC = 0.99). Parametric images were in excellent agreement with the volume-of-interest-based ARG method (lower legs: ICC = 0.97, feet: ICC = 0.98). CONCLUSION: Parametric images and volume-of-interest-based methods demonstrated comparable resting perfusion values in the lower legs and feet of healthy individuals. The largest variation was seen between individuals, whereas a smaller variation was seen between muscle groups. Repeated measurements of resting blood flow yielded a strong overall correlation for all methods.
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OBJECTIVE: A ketogenic diet (KD) characterized by very low carbohydrate intake and high fat consumption may simultaneously induce weight loss and be cardioprotective. The "thrifty substrate hypothesis" posits that ketone bodies are more energy efficient compared with other cardiac oxidative substrates such as fatty acids. This work aimed to study whether a KD with presumed increased myocardial ketone body utilization reduces cardiac fatty acid uptake and oxidation, resulting in decreased myocardial oxygen consumption (MVO2 ). METHODS: This randomized controlled crossover trial examined 11 individuals with overweight or obesity on two occasions: (1) after a KD and (2) after a standard diet. Myocardial free fatty acid (FFA) oxidation, uptake, and esterification rate were measured using dynamic [11 C]palmitate positron emission tomography (PET)/computed tomography, whereas MVO2 and myocardial external efficiency (MEE) were measured using dynamic [11 C]acetate PET. RESULTS: The KD increased plasma ß-hydroxybutyrate, reduced myocardial FFA oxidation (p < 0.01) and uptake (p = 0.03), and increased FFA esterification (p = 0.03). No changes were observed in MVO2 (p = 0.2) or MEE (p = 0.87). CONCLUSIONS: A KD significantly reduced myocardial FFA uptake and oxidation, presumably by increasing ketone body oxidation. However, this change in cardiac substrate utilization did not improve MVO2 , speaking against the thrifty substrate hypothesis.
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Dieta Cetogénica , Humanos , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Cuerpos Cetónicos/metabolismo , Miocardio/metabolismo , Sobrepeso/metabolismo , Consumo de Oxígeno , Estudios CruzadosRESUMEN
BACKGROUND: Ketones are increasingly recognized as an important and possibly oxygen sparing source of energy in vital organs such as the heart, the brain and the kidneys. Drug treatments, dietary regimens and oral ketone drinks designed to deliver ketones for organ and tissue energy production have therefore gained popularity. However, whether ingested ketones are taken up by various extra-cerebral tissues and to what extent is still largely unexplored. It was therefore the aim of this study to use positron emission tomography (PET) to explore the whole body dosimetry, biodistribution and kinetics of the ketone tracer (R)-[1-11C]ß-hydroxybutyrate ([11C]OHB). Six healthy subjects (3 women and 3 men) underwent dynamic PET studies after both intravenous (90 min) and oral (120 min) administration of [11C]OHB. Dosimetry estimates of [11C]OHB was calculated using OLINDA/EXM software, biodistribution was assessed visually and [11C]OHB tissue kinetics were obtained using an arterial input function and tissue time-activity curves. RESULTS: Radiation dosimetry yielded effective doses of 3.28 [Formula: see text]Sv/MBq (intravenous administration) and 12.51 [Formula: see text]Sv/MBq (oral administration). Intravenous administration of [11C]OHB resulted in avid radiotracer uptake in the heart, liver, and kidneys, whereas lesser uptake was observed in the salivary glands, pancreas, skeletal muscle and red marrow. Only minimal uptake was noted in the brain. Oral ingestion of the tracer resulted in rapid radiotracer appearance in the blood and radiotracer uptake in the heart, liver and kidneys. In general, [11C]OHB tissue kinetics after intravenous administration were best described by a reversible 2-tissue compartmental model. CONCLUSION: The PET radiotracer [11C]OHB shows promising potential in providing imaging data on ketone uptake in various physiologically relevant tissues. As a result, it may serve as a safe and non-invasive imaging tool for exploring ketone metabolism in organs and tissues of both patients and healthy individuals. Trial registration Clinical trials, NCT0523812, Registered February 10th 2022, https://clinicaltrials.gov/ct2/show/NCT05232812?cond=NCT05232812&draw=2&rank=1 .
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Aims: We wanted to assess if 15O-H2O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization [coronary angiography (CAG)], execution of percutaneous coronary intervention (PCI), and post-PCI angina relief for patients with angina and previous coronary artery bypass graft (CABG). Methods and results: We analysed 172 symptomatic CABG patients referred for 15O-H2O positron emission tomography (PET) MPI at Aarhus University Hospital Department of Nuclear Medicine & PET Centre, of which five did not complete the scan. In total, 145 (87%) enrolled patients had an abnormal MPI. Of these, 86/145 (59%) underwent CAG within 3 months; however, no PET parameters predicted referral to CAG. During the CAG, 25/86 (29%) patients were revascularized by PCI. Relative flow reserve (RFR) (0.49 vs. 0.54 P = 0.03), vessel-specific myocardial blood flow (MBF) (1.53 vs. 1.88â mL/g/min, P < 0.01), and vessel-specific myocardial flow reserve (MFR) (1.73 vs. 2.13, P < 0.01) were significantly lower in patients revascularized by PCI. Receiver operating characteristic analysis of the vessel-specific parameters yielded optimal cutoffs of 1.36â mL/g/min (MBF) and 1.28 (MFR) to predict PCI. Angina relief was experienced by 18/24 (75%) of the patients who underwent PCI. Myocardial blood flow was an excellent predictor of angina relief on both a global [area under the curve (AUC) = 0.85, P < 0.01] and vessel-specific (AUC = 0.90, P < 0.01) level with optimal cutoff levels of 1.99â mL/g/min and 1.85â mL/g/min, respectively. Conclusion: For CABG patients, RFR, vessel-specific MBF, and vessel-specific MFR measured by 15O-H2O PET MPI predict whether subsequent CAG will result in PCI. Additionally, global and vessel-specific MBF values predict post-PCI angina relief.
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BACKGROUND: Coincidental extracardiac findings with increased perfusion were reported during myocardial perfusion imaging (MPI) with various retention radiotracers. Clinical parametric O-15-H2O PET MPI yielding quantitative measures of myocardial blood flow (MBF) was recently implemented at our facility. We aim to explore whether similar extracardiac findings are observed using O-15-H2O. METHODS AND RESULTS: All patients (2963) were scanned with O-15-H2O PET MPI according to international guidelines and extracardiac findings were collected. In contrast to parametric O-15-H2O MBF images, extracardiac perfusion was assessed using summed images. Biopsy histopathology and other imaging modalities served as reference standards. Various malignant lesions with increased perfusion were detected, including lymphomas, large-celled neuroendocrine tumour, breast, and lung cancer plus metastases from colonic and renal cell carcinomas. Furthermore, inflammatory and hyperplastic benign conditions with increased perfusion were observed: rib fractures, gynecomastia, atelectasis, sarcoidosis, pneumonia, chronic lung inflammation and fibrosis, benign lung nodule, chronic diffuse lung infiltrates, pleural plaques and COVID-19 infiltrates. CONCLUSIONS: Malignant and benign extracardiac coincidental findings with increased perfusion are readily visible and frequently seen on O-15-H2O PET MPI. We recommend evaluating the summed O-15-H2O PET images in addition to the low-dose CT attenuation images.
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COVID-19 , Imagen de Perfusión Miocárdica , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Imagen de Perfusión Miocárdica/métodos , Perfusión , Tomografía de Emisión de Positrones/métodosRESUMEN
ABSTRACT: A persistent left-sided superior vena cava (PLSVC) is an uncommon finding with a prevalence of up to 0.5% in the general population. The PLSVC appears when the left anterior cardinal vein fails to regress as the ligament of Marshall during embryologic development. It is usually asymptomatic and discovered incidentally; however, its recognition is important because it might complicate invasive cardiovascular procedures. In this case, we report an incidental finding of a PLSVC detected on the O-15-H 2 O PET/CT of a patient who was referred for myocardial perfusion imaging.
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Vena Cava Superior Izquierda Persistente , Humanos , Vena Cava Superior/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , CorazónRESUMEN
The coupling between coronary artery disease and the development of ischemic heart failure is well-established. For these patients, assessment of potentially viable but dysfunctional myocardial tissue (hibernation) is considered critical to guide optimal surgical treatment. Assessment with positron emission tomography (PET) theoretically provides measurements of hibernating tissue and maximal myocardial glucose uptake (MGU) in all cardiac territories. However, the clinical benefits of these measures are not thoroughly studied. We therefore aimed to investigate whether cardiac viability testing with combined Rubidium-82 (82Rb) and 18F-fluorodeoxyglucose (18F-FDG) predicts post-intervention improvement in left ventricle ejection fraction (LVEF) and survival. This retrospective study consisted of 131 patients with ischemic heart failure referred for dynamic 82Rb/18F-FDG PET viability testing prior to revascularization. The FDG viability scan was done during a hyperinsulinemic-euglycemic clamp and included PET measures static FDG hibernation and absolute MGU as well as myocardial blood flow and coronary flow reserve. In total, 44/131 patients undergoing viability testing were subsequently revascularized. Following revascularization, 26 patients had LVEF improvement of at least 5% while 18 patients had no improvement. A poor correlation between areas of intervention and areas of hibernation was observed. Receiver operating characteristics for all PET metrics did not predict improvement in LVEF. Furthermore, hibernation failed to predict survival regardless of whether patients underwent subsequent revascularization. Dynamic viability PET metrics (hibernation and MGU) do not predict post-intervention improvement in LVEF or overall survival in ischemic heart failure patients undergoing revascularization. In a clinical setting, the value of these measurements may therefore be limited. Kindly check and confirm the Given names and Family names for all the authors.All names are correct!
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Fluorodesoxiglucosa F18 , Insuficiencia Cardíaca , Humanos , Estudios Retrospectivos , Radiofármacos , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Tomografía de Emisión de Positrones/métodos , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapiaRESUMEN
AIMS: Myocardial external efficiency (MEE) is the ratio of cardiac work in relation with energy expenditure. We studied MEE in patients with different aetiologies and stages of heart failure (HF) to discover the role and causes of deranged MEE. In addition, we explored the impact of patient characteristics such as sex, body mass index (BMI), and age on myocardial energetics. METHODS AND RESULTS: Cardiac energetic profiles were assessed with 11C-acetate positron emission tomography (PET) and left ventricular ejection fraction (LVEF) was acquired with echocardiography. MEE was studied in 121 participants: healthy controls (n = 20); HF patients with reduced (HFrEF; n = 25) and mildly reduced (HFmrEF; n = 23) LVEF; and patients with asymptomatic (AS-asymp; n = 38) and symptomatic (AS-symp; n = 15) aortic stenosis (AS). Reduced MEE coincided with symptoms of HF irrespective of aetiology and declined in tandem with deteriorating LVEF. Patients with AS-symp and HFmrEF had reduced MEE as compared with controls (22.2 ± 4.9%, P = 0.041 and 20.0 ± 4.2%, P < 0.001 vs. 26.1 ± 5.8% in controls) and a further decline was observed in patients with HFrEF (14.7 ± 6.3%, P < 0.001). Disproportionate left ventricular hypertrophy was a major cause of reduced MEE. Female sex (P < 0.001), a lower BMI (P = 0.001), and advanced age (P = 0.03) were associated with a lower MEE. CONCLUSION: MEE was reduced in patients with HFrEF, HFmrEF, and HF due to pressure overload and MEE may therefore constitute a treatment target in HF. Patients with LVH, advanced age, female sex, and low BMI had more pronounced reduction in MEE and personalized treatment within these patient subgroups could be relevant.
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Insuficiencia Cardíaca , Ecocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/etiología , Humanos , Miocardio , Pronóstico , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND & AIMS: The connection between peripheral insulin resistance (IR) and coronary artery disease is well-established. Both are major risk factors for the development of ischemic cardiomyopathy potentially leading to heart failure (HF). Whether cardiac IR also impacts overall survival and morbidity is still debated. We therefore aimed to test if cardiac IR predicts mortality and major cardiovascular events (MACE) in patients with HF scheduled for cardiac viability testing before revascularization. METHODS: This retrospective study included 131 patients with a clinical diagnosis of ischemic HF (114 (87%) male, 33 (25%) with diabetes) referred to a viability Rubidium-82 (perfusion) and dynamic 18F-Fluorodeoxyglucose (metabolism) positron emission tomography combined with computed tomography prior to a potential revascularization procedure. Cardiac IR was assessed by myocardial glucose uptake (MGU) in a remote (non-scarred) area of the left ventricle during a hyperinsulinemic-euglycemic clamp (1mIE/kg/min). RESULTS: MGU correlated with skeletal muscle glucose uptake (p < 0.001) and whole-body glucose uptake (M-value) (p < 0.001), whereas no association was observed for individuals with diabetes. MGU did not predict the risk of death or MACE. However, both overt diabetes and reduced coronary flow reserve predicted overall survival. CONCLUSION: Even though diabetes and related small-vessel disease is associated with increased mortality, cardiac IR per se does not predict cardiovascular morbidity and mortality.
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Circulación Coronaria , Diabetes Mellitus Tipo 2/fisiopatología , Fluorodesoxiglucosa F18/administración & dosificación , Resistencia a la Insulina , Isquemia Miocárdica/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Femenino , Humanos , Masculino , Isquemia Miocárdica/mortalidad , Estudios RetrospectivosRESUMEN
AIMS: We aim to evaluate changes in invasive haemodynamics, right ventricular (RV) function, and perfusion during the first year after heart transplantation (HTx) and to determine the relation between RV function and myocardial perfusion. METHODS AND RESULTS: Thirty patients were prospectively enrolled at the time of HTx. Right heart catheterization (RHC), comprehensive 2D and 3D echocardiography and cardiac biomarkers were performed at baseline (≤2 weeks after HTx) and at follow-up 1, 3, 6, and 12 months after HTx. At 12 months, HTx patients were subjected to an exercise stress test with assessment of maximal oxygen consumption (VO2 max). RV myocardial perfusion reserve was evaluated by 15 O-H2 O positron emission tomography at baseline and at 3 and 12 months after HTx. A group of 43 healthy subjects served as echocardiographic controls and a subgroup comprising 16 healthy controls underwent exercise stress test with simultaneous RHC. At baseline, HTx patients had higher pulmonary artery wedge pressure (PAWP) and right atrial pressure (RAP) and pulmonary vascular resistance (PVR) than healthy controls whereas cardiac index (CI) was reduced (PAWP; 14 mmHg [8;17] vs. 8 mmHg [7;10]; RAP: 7 mmHg [4;11] vs. 5 mmHg [4;6]; PVR: 1.9 wood units [1.3;2.6] vs. 1.1 wood units [1.0;1.4]; CI 2.4 L/min/m2 [2.2;2.8] vs. 3.3 L/min/m2 [2.8;.3.6], all P < 0.05). Normalization of filling pressures and CI was seen 3-6 months after HTx. During follow-up, RV function in terms of 3D ejection fraction (EF) and longitudinal strain (LS) improved in HTx patients but remained reduced compared with healthy controls at 12 months follow-up (3D RV EF: 52 ± 7% vs. 60 ± 8%; RV LS: 22 ± 4% vs. 28 ± 5%, both P < 0.001). During follow-up, RV perfusion reserve improved (baseline 2.1 ± 0.9; 3 months follow-up 3.2 ± 0.8; 12 months follow-up 3.7 ± 1.1, P < 0.0001). RV perfusion reserve significantly correlated to cardiac markers in terms of troponin T (r = -0.62, P < 0.0001), NT-proBNP (r = -0.65, P < 0.0001), RAP (r = -0.43, P < 0.01) and CI (r = 0.37, P < 0.01) and with VO2 max 12 months after HTx (r = 0.75, P < 0.01). CONCLUSIONS: Normalization of left and right atrial filling pressures is demonstrated within the first 3 to 6 months after HTx. RV function and RV perfusion reserve correlated and gradually improved during the first year after HTx but RV function remained reduced in HTx patients compared with healthy controls.
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Trasplante de Corazón , Ecocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Hemodinámica , Humanos , PerfusiónRESUMEN
BACKGROUND: Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings. METHODS: From previous studies of [82Rb]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [68Ga]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [68Ga]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions. RESULTS: [68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [82Rb]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [68Ga]Ga-PSMA-11 and [82Rb]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1-2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p ≤ 0.025). CONCLUSION: PSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa.
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PURPOSE: Tumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na+/K+-ATPase density, which is relevant as 82Rb is transported intracellularly via the Na+/K+-ATPase. METHODS: One hundred and two patients were included for pelvic 82Rb PET scan prior to magnetic resonance imaging (MRI)-guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82Rb PET for TBF measurement. Immunohistochemical Na+/K+-ATPase staining was subsequently performed on biopsies. RESULTS: TBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = -0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na+/K+-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na+/K+-ATPase density determined tumour 82Rb uptake. CONCLUSION: TBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.
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Adenosina Trifosfatasas , Neoplasias de la Próstata , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Radioisótopos de Rubidio , Tomografía Computarizada por Rayos XRESUMEN
The positron emission tomography (PET) flow tracer 82Rubidium is a known potassium analogue. During our studies of tumor blood flow in prostate cancer, we found that approximately 10% of the patients had high urinary 82Rubidium activity. In roughly half of these patients, the increased renal rubidium/potassium excretion was either causing hypokalemia or explained by Thiazide treatment. In the other half, there was no obvious explanation or clinical consequence of the renal rubidium/potassium excretion. This is the first time enhanced renal potassium excretion is visualized on 82Rubidium PET/CT.
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Ischemic heart disease ranges in severity from slightly reduced myocardial perfusion with preserved contractile function to chronic occlusion of coronary arteries with myocardial cells replaced by acontractile scar tissue-ischemic heart failure (iHF). Progression towards scar tissue is thought to involve a period in which the myocardial cells are acontractile but still viable despite severely reduced perfusion. This state of reduced myocardial function that can be reversed by revascularization is termed "hibernation." The concept of hibernating myocardium in iHF has prompted an increasing amount of requests for preoperative patient workup, but while the concept of viability is widely agreed upon, no consensus on clinical testing of hibernation has been established. Therefore, a variety of imaging methods have been used to assess hibernation including morphology based (MRI and ultrasound), perfusion based (MRI, SPECT, or PET) and/or methods to assess myocardial metabolism (PET). Regrettably, the heterogeneous body of literature on the subject has resulted in few robust prospective clinical trials designed to assess the impact of preoperative viability testing prior to revascularization. However, the PARR-2 trial and sub-studies has indicated that >5% hibernating myocardium favors revascularization over optimized medical therapy. In this paper, we review the basic concepts and current evidence for using PET to assess myocardial hibernation and discuss the various methodologies used to process the perfusion/metabolism PET images. Finally, we present our experience in conducting PET viability testing in a tertiary referral center.
Asunto(s)
Miocardio/patología , Tomografía de Emisión de Positrones , Centros de Atención Terciaria , Supervivencia Tisular , Circulación Coronaria , Humanos , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/patología , Isquemia Miocárdica/fisiopatologíaRESUMEN
AIMS: The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes. METHODS AND RESULTS: Thirty-six HFrEF patients (ejection fraction 37 ± 8%; median age 66 years) were randomised to metformin (n = 19) or placebo (n = 17) for 3 months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by 11 C-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 ± 550 mg/day) increased WMI [absolute mean difference, 1.0 mmHg·mL·m-2 ·106 ; 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6 mL O2 ·100 g-1 ·min-1 ; P = 0.014). Cardiac stroke work was preserved (-2 J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2 kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups. CONCLUSION: Metformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.