Role of Nuclear Imaging in Cardiac Stereotactic Body Radiotherapy for Ablation of Ventricular Tachycardia.

Ventricular tachycardia (VT) is a life-threatening arrhythmia common in patients with structural heart disease or nonischemic cardiomyopathy. Many VTs originate from regions of fibrotic scar tissue, where delayed electrical signals exit scar and re-enter viable myocardium. Cardiac stereotactic body radiotherapy (SBRT) has emerged as a completely noninvasive alternative to catheter ablation for the treatment of recurrent or refractory ventricular tachycardia. While there is no common consensus on the ideal imaging workflow, therapy planning for cardiac SBRT often combines information from a plurality of imaging modalities including MRI, CT, electroanatomic mapping and nuclear imaging. MRI and CT provide detailed anatomic information, and late enhancement contrast imaging can indicate regions of fibrosis. Electroanatomic maps indicate regions of heterogenous conduction voltage or early activation which are indicative of arrhythmogenic tissue. Some early clinical adopters performing cardiac SBRT report the use of myocardial perfusion and viability nuclear imaging to identify regions of scar. Nuclear imaging of hibernating myocardium, inflammation and sympathetic innervation have been studied for ventricular arrhythmia prognosis and in research relating to catheter ablation of VT but have yet to be studied in their potential applications for cardiac SBRT. The integration of information from these many imaging modalities to identify a target for ablation can be challenging. Multimodality image registration and dedicated therapy planning tools may enable higher target accuracy, accelerate therapy planning workflows and improve patient outcomes. Understanding the pathophysiology of ventricular arrhythmias, and localizing the arrhythmogenic tissues, is vital for successful ablation with cardiac SBRT. Nuclear imaging provides an arsenal of imaging strategies to identify regional scar, hibernation, inflammation, and sympathetic denervation with some advantages over alternative imaging strategies.

Real-world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real-world Evidence Working Group.

This manuscript on real-world evidence (RWE) in pulmonary hypertension (PH) incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative Real-World Evidence Working Group. We aim to strengthen the research community's understanding of RWE in PH to facilitate clinical research advances and ultimately improve patient care. Herein, we review real-world data (RWD) sources, discuss challenges and opportunities when using RWD sources to study PH populations, and identify resources needed to support the generation of meaningful RWE for the global PH community.

Pharmacological and metabolic parameters of [18F]flubrobenguane in clinical imaging populations.

BACKGROUND: Cardiac sympathetic nervous system molecular imaging has demonstrated prognostic value. Compared with meta-[11C]hydroxyephedrine, [18F]flubrobenguane (FBBG) facilitates reliable estimation of SNS innervation using similar analytical methods and possesses a more convenient physical half-life. The aim of this study was to evaluate pharmacokinetic and metabolic properties of FBBG in target clinical cohorts. METHODS: Blood sampling was performed on 20 participants concurrent to FBBG PET imaging (healthy = NORM, non-ischemic cardiomyopathy = NICM, ischemic cardiomyopathy = ICM, post-traumatic stress disorder = PTSD). Image-derived blood time-activity curves were transformed to plasma input functions using cohort-specific corrections for plasma protein binding, plasma-to-whole blood distribution, and metabolism. RESULTS: The plasma-to-whole blood ratio was 0.78 ± 0.06 for NORM, 0.64 ± 0.06 for PTSD and 0.60 ± 0.14 for (N)ICM after 20 minutes. 22 ± 4% of FBBG was bound to plasma proteins. Metabolism of FBBG in (N)ICM was delayed, with a parent fraction of 0.71 ± 0.05 at 10 minutes post-injection compared to 0.53 ± 0.03 for PTSD/NORM. While there were variations in metabolic rate, metabolite-corrected plasma input functions were similar across all cohorts. CONCLUSIONS: Rapid plasma clearance of FBBG limits the impact of disease-specific corrections of the blood input function for tracer kinetic modeling.

Vascular calcification maladaptively participates in acute phosphate homeostasis.

AIMS: Non-renal extravasation of phosphate from the circulation and transient accumulation into tissues and extracellular fluid is a regulated process of acute phosphate homeostasis that is not well understood. This process is especially relevant in the setting of chronic kidney disease (CKD), where exposure to increased phosphate is prolonged due to inefficient kidney excretion. Furthermore, CKD-associated mineral dysregulation induces pathological accumulation of phosphate causing vascular calcification (VC). Our objective was to determine whether the systemic response to acute phosphate challenges is altered by VC. METHODS AND RESULTS: After bolus phosphate administration, circulating and tissue deposition of this challenge was assessed in two rat models of VC using a radiolabelled phosphate tracer. In an adenine-induced model of CKD (N = 70), animals with VC had a blunted elevation of circulating 33PO4 following oral phosphate administration (P < 0.01), and the discordant deposition could be traced to the calcified arteries (11.4 [7.5-13.1] vs.43.0 [35.5-53.7] pmol/ng tissue, P < 0.001). In a non-CKD model of VC, calcification was induced with 0.5 ug/kg calcitriol and then withdrawn (N = 24). New phosphate uptake by the calcified vasculature correlated to the pre-existing burden of calcification (r = 38, P < 0.001) and was substantially attenuated in the absence of calcification stimulus (P < 0.01). Phosphate accrual was stimulated by the phosphate challenge and not present to the same degree during passive disposition of circulating phosphate. Further, the form of phosphate that deposited to the vasculature was predominately amorphous inorganic phosphate and not that which was bound in matured calciprotein particles. CONCLUSIONS: In the process of calcification, arteries acutely deposit substantial amorphous phosphate while blunting the elevation in the circulation, thereby altering the systemic disposition of phosphate and identifying VC as a participatory mineral homeostatic organ. This study demonstrates the negative vascular consequence of acute fluctuations in circulating phosphate, and supports the importance of phosphate bioavailability and diet management in CKD patients as a mediator of cardiovascular risk.

Right Ventricular Maladaptation to Pressure Overload in Fischer Rats Is Associated With Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics.

BACKGROUND: We explored the mechanism of maladaptive right ventricular (RV) remodeling in Fischer compared with Sprague-Dawley (SD) rats exposed to pressure overload. METHODS: Pulmonary hypertension was induced by injection of the VEGFR antagonist, SU5416, followed by a 3-week exposure to hypoxia (Sugen chronic hypoxia). In vivo oxidative metabolism was assessed by RV/left ventricle ratio of [11C]acetate positron emission tomography clearance (kmono). Unbiased, global transcriptional and proteomic profiling was performed in Fischer and SD rats at baseline and after Sugen chronic hypoxia. RESULTS: All Fischer rats succumbed to RV failure by 5 weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (P<0.0001). Fischer rats exhibited increased oxidative metabolism at 4 weeks (P<0.05) and impaired RV efficiency compared with SD (work metabolic index: 52±10 versus 91±27 mmHg·mL/cm2, respectively; P<0.05), but no differences in mitochondrial complex activity. AK1 (adenylate kinase 1) was among the top 10 differentially expressed genes between Fischer and SD rats, with markedly lower RV expression in Fischer rats (FC: 3.36, P<0.05), confirmed by proteomic analysis and validated by Western blotting (>10-fold reduction, P<0.001). While whole-genome sequencing failed to reveal any coding region mutations in Fischer rats, there was a unique variant in a highly conserved upstream flanking region likely involved in the regulation of AK1 expression. CONCLUSIONS: Therefore, Fischer rats exhibit profound AK1 deficiency and inefficient cardiac energetics likely related to reduced adenosine triphosphate shuttling from the mitochondria to the contractile fibers. This represents a novel mechanism for RV failure in response to chronic increases in afterload.

Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Does quantification of [11C]meta-hydroxyephedrine and [13N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.

BACKGROUND: In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [11C]meta-hydroxyephedrine (HED) vs [13N]ammonia (NH3), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination. METHODS: This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NH3 positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH3 uptake, as well as HED distribution volume and NH3 myocardial blood flow by kinetic modeling. RESULTS: During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH3, especially in the lowest tertile of perfusion abnormality (P < .001). Parametric defects were larger than their respective tracer uptake defects (P < .001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC = 0.73 or 0.70) compared to HED uptake defect scores (AUC = 0.67). CONCLUSION: Quantification of HED distribution volume and NH3 myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs HED uptake alone.

Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Current risk assessment approaches fail to identify the majority of patients at risk of sudden cardiac arrest (SCA). Noninvasive imaging of the cardiac sympathetic nervous system using single-photon emission computed tomography and positron emission tomography offers the potential for refining SCA risk assessment. While various [11C]meta-hydroxyephedrine quantification parameters have been proposed, it is currently unknown whether regional denervation or global innervation yields greater SCA risk discrimination. The aim of the study was to determine whether the global innervation parameters yield any independent and additive prognostic value over the regional denervation alone. METHODS: In a post hoc competing-risks analysis of the PAREPET trial (Prediction of Arrhythmic Events With Positron Emission Tomography), we compared global innervation and regional denervation parameters using the norepinephrine analog [11C]meta-hydroxyephedrine for SCA risk discrimination. Patients with ischemic cardiomyopathy (n=174) eligible for an implantable cardioverter-defibrillator for the primary prevention of SCA were recruited into the trial. [11C]meta-hydroxyephedrine uptake and clearance rates were measured to assess global (left ventricle mean) retention index and volume of distribution. Regional defects were quantified as the percentage of the left ventricle having values <75% of the maximum. RESULTS: During a median follow-up of 4.2 years, there were 56 cardiac-related deaths, of which 26 were SCAs. For any given regional denervation volume, there was substantial heterogeneity in global innervation scores. Global retention index and distribution volume did not decrease until regional defects exceeded 40% left ventricle. Global scale parameters, retention index, and distribution volume (area under the curve=0.61, P=0.034, P=0.046, respectively), yielded inferior SCA risk discrimination compared to regional heterogeneity (area under the curve=0.74). CONCLUSIONS: Regional denervation volume has superior cause-specific mortality prediction for SCA versus global parameters of sympathetic innervation. These results have widespread implications for future cardiac sympathetic imaging, which will greatly simplify innervation analysis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01400334.

[11C]meta-hydroxyephedrine PET evaluation in experimental pulmonary arterial hypertension: Effects of carvedilol of right ventricular sympathetic function.

BACKGROUND: Little is known about the sequelae of chronic sympathetic nervous system (SNS) activation in patients with pulmonary arterial hypertension (PAH) and right heart failure (RHF). We aimed to, (1) validate the use of [11C]-meta-hydroxyephedrine (HED) for assessing right ventricular (RV) SNS integrity, and (2) determine the effects of ß-receptor blockade on ventricular function and myocardial SNS activity in a PAH rat model. METHODS: PAH was induced in male Sprague-Dawley rats (N = 36) using the Sugen+chronic hypoxia model. At week 5 post-injection, PAH rats were randomized to carvedilol (15 mg·kg-1·day-1 oral; N = 16) or vehicle (N = 16) for 4 weeks. Myocardial SNS function was assessed with HED positron emission tomography(PET). RESULTS: With increasing PAH disease severity, immunohistochemistry confirmed selective sympathetic denervation within the RV and sparing of parasympathetic nerves. These findings were confirmed on PET with a significant negative relationship between HED volume of distribution(DV) and right ventricular systolic pressure (RVSP) in the RV (r = -0.90, p = 0.0003). Carvedilol did not reduce hemodynamic severity compared to vehicle. RV ejection fraction (EF) was lower in both PAH groups compared to control (p < 0.05), and was not further reduced by carvedilol. Carvedilol improved SNS function in the LV with significant increases in the HED DV, and decreased tracer washout in the LV (p < 0.05) but not RV. CONCLUSIONS: PAH disease severity correlated with a reduction in HED DV in the RV. This was associated with selective sympathetic denervation. Late carvedilol treatment did not lead to recovery of RV function. These results support the role of HED imaging in assessing SNS innervation in a failing right ventricle.

Reproducible Quantification of Regional Sympathetic Denervation with [11C]meta-Hydroxyephedrine PET Imaging.

BACKGROUND: Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to (1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant® and Corridor4DM®; (2) evaluate test-retest repeatability of regional denervation scores. METHODS: N = 190 dynamic [11C]meta-hydroxyephedrine (HED) PET scans were reviewed from the PAREPET trial in ischemic cardiomyopathy patients with reduced left ventricular ejection fraction(LVEF ≤ 35%). N = 12 scans were excluded due to non-diagnostic quality. N = 178 scans were analyzed using FlowQuant and Corridor4DM software, each by two observers. Test-retest scans from N = 20 patients with stable heart failure were utilized for test-retest analysis. Denervation scores were defined as extent × severity of relative uptake defects in LV regions with < 75% of maximal uptake. Results were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman coefficient of repeatability (RPC). RESULTS: Inter-observer, inter-software, and test-retest ICC values were excellent (ICC = 94% to 99%) and measurement variability was small (RPC < 11%). Mean differences between observers ranged .2% to 1.1% for Corridor4DM (P = .28), FlowQuant (P < .001), and between software programs (P < .001). Kaplan-Meier analysis demonstrated HED scores from both programs were predictive of SCA. CONCLUSION: Inter-rater reliability for both analysis programs was excellent and test-retest repeatability was consistent. The minimal difference in scores between FlowQuant and Corridor4DM supports their use in future trials.

Increased myocardial oxygen consumption rates are associated with maladaptive right ventricular remodeling and decreased event-free survival in heart failure patients.

BACKGROUND: Reduced left ventricular (LV) function is associated with increased myocardial oxygen consumption rate (MVO2) and altered sympathetic activity, the role of which is not well described in right ventricular (RV) dysfunction. METHODS AND RESULTS: 33 patients with left heart failure were assessed for RV function/size using echocardiography. Positron emission tomography (PET) was used to measure 11C-acetate clearance rate (kmono), 11C-hydroxyephedrine (11C-HED) standardized uptake value (SUV), and retention rate. RV MVO2 was estimated from kmono. 11C-HED SUV and retention indicated sympathetic neuronal function. A composite clinical endpoint was defined as unplanned cardiac hospitalization within 5 years. Patients with (n = 10) or without (n = 23) RV dysfunction were comparable in terms of sex (male: 70.0 vs 69.5%), LV ejection fraction (39.6 ± 9.0 vs 38.6 ± 9.4%), and systemic hypertension (70.0 vs 78.3%). RV dysfunction patients were older (70.9 ± 13.5 vs 59.4 ± 11.5 years; P = .03) and had a higher prevalence of pulmonary hypertension (60.0% vs 13.0%; P = .01). RV dysfunction was associated with increased RV MVO2 (.106 ± .042 vs .068 ± .031 mL/min/g; P = .02) and decreased 11C-HED SUV and retention (6.05 ± .53 vs 7.40 ± 1.39 g/mL (P < .001) and .08 ± .02 vs .11 ± .03 mL/min/g (P < .001), respectively). Patients with an RV MVO2 above the median had a shorter event-free survival (hazard ratio = 5.47; P = .01). Patients who died within the 5-year follow-up period showed a trend (not statistically significant) for higher RV MVO2 (.120 ± .026 vs .074 ± .038 mL/min/g; P = .05). CONCLUSIONS: RV dysfunction is associated with increased oxygen consumption (also characterized by a higher risk for cardiac events) and impaired RV sympathetic function.

Regional Distribution of Fluorine-18-Flubrobenguane and Carbon-11-Hydroxyephedrine for Cardiac PET Imaging of Sympathetic Innervation.

OBJECTIVES: The aim of this study was to investigate the regional distribution of novel 18F-labeled positron emission tomographic (PET) tracer flubrobenguane (FBBG) (whose longer half-life could enable more widespread use) to assess myocardial presynaptic sympathetic nerve function in humans in comparison to [11C]meta-hydroxyephedrine (HED). BACKGROUND: The sympathetic nervous system (SNS) is vitally linked to cardiovascular regulation and disease. SNS imaging has shown prognostic value. HED is the most commonly used PET tracer for evaluation of sympathetic function in humans, but widespread clinical use is limited because of the short half-life of 11C. METHODS: A total of 25 participants (n = 6 healthy; n = 14 ischemic cardiomyopathy, left ventricular [LV] ejection fraction [EF] = 34 ± 5%; and n = 5 nonischemic cardiomyopathy, EF = 33 ± 3%) underwent 2 separate PET imaging visits 8.7 ± 7.6 days apart. On 1 visit, participants underwent dynamic HED PET imaging. On a different visit, participants underwent dynamic FBBG PET imaging. The order of testing was random. HED and FBBG global innervation (retention index [RI] and distribution volume [DV]) and regional denervation (% nonuniformity) were quantified to assess regional presynaptic sympathetic innervations. RESULTS: FBBG RI (r2 = 0.72; ICC = 0.79; p < 0.0001), DV (r2 = 0.62; ICC = 0.78; p < 0.0001), and regional denervation (r2 = 0.97; ICC = 0.98; p < 0.0001) correlated highly with HED. Average LV RI values were highly similar between HED (7.3 ± 2.4%/min) and FBBG (7.0 ± 1.7%/min; p = 0.33). Post-hoc analysis did not reveal any between-tracer differences on a regional level (17-segment), suggesting equivalent regional distributions in both patients with and without ischemic cardiomyopathy. CONCLUSIONS: FBBG and HED yield equivalent global and regional distributions in both patients with and without ischemic cardiomyopathy. 18F-labeled PET tracers, such as FBBG, are critical for widespread distribution necessary for multicenter clinical trials and to maximize patient impact.

Emerging therapies for right ventricular dysfunction and failure.

Therapeutic options for right ventricular (RV) dysfunction and failure are strongly limited. Right heart failure (RHF) has been mostly addressed in the context of pulmonary arterial hypertension (PAH), where it is not possible to discern pulmonary vascular- and RV-directed effects of therapeutic approaches. In part, opposing pathomechanisms in RV and pulmonary vasculature, i.e., regarding apoptosis, angiogenesis and proliferation, complicate addressing RHF in PAH. Therapy effective for left heart failure is not applicable to RHF, e.g., inhibition of adrenoceptor signaling and of the renin-angiotensin system had no or only limited success. A number of experimental studies employing animal models for PAH or RV dysfunction or failure have identified beneficial effects of novel pharmacological agents, with most promising results obtained with modulators of metabolism and reactive oxygen species or inflammation, respectively. In addition, established PAH agents, in particular phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulators, may directly address RV integrity. Promising results are furthermore derived with microRNA (miRNA) and long non-coding RNA (lncRNA) blocking or mimetic strategies, which can target microvascular rarefaction, inflammation, metabolism or fibrotic and hypertrophic remodeling in the dysfunctional RV. Likewise, pre-clinical data demonstrate that cell-based therapies using stem or progenitor cells have beneficial effects on the RV, mainly by improving the microvascular system, however clinical success will largely depend on delivery routes. A particular option for PAH is targeted denervation of the pulmonary vasculature, given the sympathetic overdrive in PAH patients. Finally, acute and durable mechanical circulatory support are available for the right heart, which however has been tested mostly in RHF with concomitant left heart disease. Here, we aim to review current pharmacological, RNA- and cell-based therapeutic options and their potential to directly target the RV and to review available data for pulmonary artery denervation and mechanical circulatory support.

PTH suppression by calcitriol does not predict off-target actions in experimental CKD.

Vitamin D receptor agonist (VDRA) therapy for PTH suppression is a mainstay for patients with severe CKD. Calcitriol (1,25-(OH)2 D3 ) is a former first-line VDRA in CKD treatment. However, a consequence of its use in CKD is accelerated vascular calcification (VC). An experimental CKD model was used to determine whether altering the calcitriol delivery profile to obtain different PTH suppression levels could improve vascular health outcomes. High adenine diet (0.25%) was used to generate experimental CKD in rats. CKD rats were treated using different calcitriol dosing strategies: (a) 20 ng/kg SD (n = 8), (b) 80 ng/kg SD (n = 8), (c) 5 ng/kg QID (n = 9), or (d) 20 ng/kg QID (n = 9). Multiple targets of calcitriol were assessed which include arterial calcium and phosphate as well as circulating calcium, phosphate, PTH, FGF-23, VWF, and vitamin D metabolome. PTH suppression occurred dose-dependently after 1-week calcitriol treatment (P < .01), but the suppressive effect was lost over time. Both VC and circulating FGF-23 increased > 10× in all calcitriol-treated rats (P < .05 and P < .001, respectively); similarly, circulating VWF increased at all time points (P < .05). Ad-hoc analysis of CKD morbidities in treated rats indicated no differences in negative outcomes based on PTH suppression level (minimal-, target-, and over-). Comparing different calcitriol dosing strategies revealed the following: (a) despite initial calcitriol-influenced PTH suppression across all treatments, the ability to continually suppress PTH was markedly reduced by study conclusion and (b) PTH suppression level is not an adequate proxy for improvements in overall CKD morbidity. These findings show (a) a more holistic approach to evaluate CKD treatment efficacy aside from PTH suppression is needed and (b) that other VDRA therapies should be examined in CKD treatment.

The Future of Cardiac Molecular Imaging.

Molecular imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) serves numerous applications in clinical cardiology and research. Similar to other medical imaging technologies, this area has undergone and continues to experience rapid changes resulting from technological and medical advances. These have immediate impacts on diagnosis, treatment planning, and patient care, as well as supplying innovative tools for fundamental and translational research. A broad shift toward hybrid PET systems and incorporation of advanced computational tools has been accompanied by mechanism-specific, targeted radiopharmaceuticals that seek to address long-standing limitations in cardiac imaging. While this review addresses some of the still-emerging clinical uses of established radiopharmaceuticals, it too highlights newer imaging probes, applications, and imaging techniques and instrumentation on the horizon. We highlight molecular imaging advances in inflammatory and infiltrative myocardial conditions, heart metabolism, vascular and valvular diseases, neurohormonal dysregulation, and transformational technical advances such as the rise of artificial intelligence and theranostic approaches to cardiovascular disease.

Incorporation of renal function in mortality risk assessment for pulmonary arterial hypertension.

BACKGROUND: Risk assessment is important for prognostication and individualized treatment decisions for patients with pulmonary arterial hypertension (PAH). The purpose was (1) to compare contemporary risk assessment tools and (2) to determine the prognostic significance of risk parameters of kidney function and whether they can further improve risk prediction for patients with PAH. METHODS: We identified a cohort of treatment-naive patients (n = 211) who received an incident diagnosis of PAH at the University of Ottawa Heart Institute. Using demographics, disease characteristics, and hemodynamic data at diagnosis, we categorized patients as low, intermediate, or high risk according to current European guidelines (European Society of Cardiology [ESC]) and registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL) risk scores. The primary end-point was transplant-free survival (TFS). RESULTS: Patients were predominantly women (64.6%) with World Health Organization function Class III symptoms (66.5%). The median TFS was 7.09 years. There was little agreement between ESC- and REVEAL-based risk estimates (weighted kappa = 0.21-0.34). Although both the ESC (log-rank, p = 0.0002) and REVEAL algorithms stratified TFS risk (p < 0.0001), the REVEAL score provided superior discrimination (C-statistic = 0.70 vs 0.59, p = 0.004). Renal function at diagnosis (p < 0.0001) and Δ renal function at 6 months (p < 0.0001) were identified as novel risk parameters and served to reclassify some patients in the intermediate-risk category to a lower or higher risk stratum (p < 0.0001). CONCLUSION: REVEAL-based strategies provide superior TFS risk discrimination to ESC/European Respiratory Society-based approaches. However, the classification of intermediate-risk patients varied significantly across tools. We demonstrate the importance of renal function, which further improved the stratification of risk in patients with PAH, particularly in patients who are considered intermediate risk.

Correction to: PET imaging of sympathetic innervation with [18F]Flubrobenguane vs [11C]mHED in a patient with ischemic cardiomyopathy.

At time of initial publication, the USAN Council had assigned the generic name for LMI1195 as Flurobenguan. However, the Council has since changed and finalized this compound name as Flubrobenguane which is recommended as the generic name to be used in the future.