Phenotypes in Pulmonary Hypertension.

The clinical classification of pulmonary hypertension (PH) has guided diagnosis and treatment of patients with PH for several decades. Discoveries relating to underlying mechanisms, pathobiology, and responses to treatments for PH have informed the evolution in this clinical classification to describe the heterogeneity in PH phenotypes. In more recent years, advances in imaging, computational science, and multi-omic approaches have yielded new insights into potential phenotypes and sub-phenotypes within the existing clinical classification. Identification of novel phenotypes in pulmonary arterial hypertension (PAH) with unique molecular profiles, for example, could lead to new precision therapies. Recent phenotyping studies have also identified groups of patients with PAH that more closely resemble patients with left heart disease (group 2 PH) and lung disease (group 3 PH), which has important prognostic and therapeutic implications. Within group 2 and group 3 PH, novel phenotypes have emerged that reflect a persistent and severe pulmonary vasculopathy that is associated with worse prognosis but still distinct from PAH. In group 4 PH (chronic thromboembolic pulmonary disease) and sarcoidosis (group 5 PH) the current approach to patient phenotyping integrates clinical, hemodynamic and imaging characteristics to guide treatment but applications of multi-omic approaches to sub-phenotyping in these areas are sparse. The next iteration of the PH clinical classification is likely to reflect several emerging PH phenotypes and improve the next generation of prognostication tools, clinical trial design, and improve treatment selection in clinical practice.

Frailty and outcomes in heart failure patients from high-, middle-, and low-income countries.

BACKGROUND AND AIMS: There is little information on the incremental prognostic importance of frailty beyond conventional prognostic variables in heart failure (HF) populations from different country income levels. METHODS: A total of 3429 adults with HF (age 61 ± 14 years, 33% women) from 27 high-, middle- and low-income countries were prospectively studied. Baseline frailty was evaluated by the Fried index, incorporating handgrip strength, gait speed, physical activity, unintended weight loss, and self-reported exhaustion. Mean left ventricular ejection fraction was 39 ± 14% and 26% had New York Heart Association Class III/IV symptoms. Participants were followed for a median (25th to 75th percentile) of 3.1 (2.0-4.3) years. Cox proportional hazard models for death and HF hospitalization adjusted for country income level; age; sex; education; HF aetiology; left ventricular ejection fraction; diabetes; tobacco and alcohol use; New York Heart Association functional class; HF medication use; blood pressure; and haemoglobin, sodium, and creatinine concentrations were performed. The incremental discriminatory value of frailty over and above the MAGGIC risk score was evaluated by the area under the receiver-operating characteristic curve. RESULTS: At baseline, 18% of participants were robust, 61% pre-frail, and 21% frail. During follow-up, 565 (16%) participants died and 471 (14%) were hospitalized for HF. Respective adjusted hazard ratios (95% confidence interval) for death among the pre-frail and frail were 1.59 (1.12-2.26) and 2.92 (1.99-4.27). Respective adjusted hazard ratios (95% confidence interval) for HF hospitalization were 1.32 (0.93-1.87) and 1.97 (1.33-2.91). Findings were consistent among different country income levels and by most subgroups. Adding frailty to the MAGGIC risk score improved the discrimination of future death and HF hospitalization. CONCLUSIONS: Frailty confers substantial incremental prognostic information to prognostic variables for predicting death and HF hospitalization. The relationship between frailty and these outcomes is consistent across countries at all income levels.

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.

Medical Therapy for Heart Failure Associated With Pulmonary Hypertension.

The past 2 decades have witnessed a >40% improvement in mortality for patients with heart failure and left ventricular systolic dysfunction. 1 This success has coincided with the stepwise availability of drugs that target neurohormonal activation: ß-adrenergic receptor blockers (ß-blockers), ACE (angiotensin-converting enzyme) inhibitors and ANG (angiotensin) II blockers, neprilysin inhibitors, and aldosterone antagonists. Our understanding of right heart failure (RHF) has lagged behind and many proven targeted therapies for left heart failure do not appear to provide similar benefits for RHF. Until recently, the right ventricle (RV) has often been viewed as less important than the left ventricle and in contemporary literature received the moniker "The Forgotten Ventricle". Recent advances in echocardiography and magnetic resonance imaging have enabled detailed assessments of RV anatomy and physiology in both health and disease allowing us to more accurately describe the clinical sequelae and end-organ manifestations of RHF. RV function is now recognized as one of the most important predictors of prognosis in many cardiovascular disease states. 2 Despite the significance of RV function to survival, there are no clinically approved therapies that directly nor selectively improve RV function. As well, relative to our understanding of left heart failure, the basis for RHF remains poorly understood. This article aims to condense the current knowledge on RV adaptation and failure, review current management strategies for RHF, and explore evolving therapeutic approaches.

[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.

Validation of multiparametric rubidium-82 PET myocardial blood flow quantification for cardiac allograft vasculopathy surveillance.

BACKGROUND: We previously demonstrated high diagnostic accuracy of Rubidium-82 positron emission tomography (PET) myocardial blood flow (MBF) quantification for CAV. The purpose of this study was to validate multiparametric PET detection of CAV by combined rate-pressure-product-corrected myocardial flow reserve (cMFR), stress MBF, and coronary vascular resistance (CVR) assessment. METHODS AND RESULTS: Diagnostic CAV cut-offs of cMFR < 2.9, stress MBF < 2.3, CVR > 55 determined in a previous study (derivation) were assessed in heart transplant recipients referred for coronary angiography and intravascular ultrasound (IVUS) (validation). CAV was defined as International Society of Heart and Lung Transplantation CAV1-3 on angiography; and maximal intimal thickness ≥ 0.5 mm on IVUS. Eighty patients (derivation n = 40, validation n = 40) were included: 80% male, mean age 54±14 years, 4.5±5.6 years post transplant. The prevalence of CAV was 44% on angiography and 78% on IVUS. Combined PET cMFR < 2.9, stress MBF < 2.3, CVR > 55 CAV assessment yielded high 88% (specificity 75%) and 83% (specificity 40%) sensitivity for ≥ 1 abnormal parameter and high 88% (sensitivity 59%) and 90% (sensitivity 43%) specificity for 3 abnormal parameters, in the derivation and validation cohorts, respectively. CONCLUSION: We validate the diagnostic accuracy of multiparametric PET flow quantification by cMFR, stress MBF, and CVR for CAV.

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.

Reliable quantification of myocardial sympathetic innervation and regional denervation using [11C]meta-hydroxyephedrine PET.

PURPOSE: Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [11C]meta-hydroxyephedrine (HED) positron emission tomography (PET) quantification of cardiac SNS innervation, regional denervation, and myocardial blood flow (MBF). METHODS: Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (VT), and MBF. Values were also compared with and without regional partial-volume correction. Regional denervation was quantified as %LV defect size of values < 75% of the LV-maximum. Test-retest repeatability and observer reproducibility were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient of repeatability (NPC). RESULTS: Intra- and inter-observer correlations of both VT and RI were excellent (ICC = 0.93-0.99). Observer reproducibility (NPC = 3-13%) was lower than test-retest repeatability (NPC = 12-61%). Both regional (%LV defect size) and global (LV-mean) measures of sympathetic innervation were more repeatable using the simple RI model compared to VT (NPC = 12% vs. 19% and 30% vs. 54%). Using either model, quantification of regional denervation (defect size) was consistently more reliable than the global LV-mean values of RI or VT. Regional partial-volume correction degraded repeatability of both the global and regional VT measures by 2-12%. Test-retest repeatability of MBF estimation was relatively poor (NPC = 30-61%) compared with the RI. CONCLUSIONS: Quantitative measures of global and regional SNS innervation were most repeatable using the simple RI method of analysis compared with the more complex VT. Observer variability was significantly lower than the test-retest repeatability using a highly automated analysis program. These results support the use of the simple RI method for reliable analysis of HED PET images in clinical research studies for future evaluation of new therapies and for risk stratification in patients with heart failure.

Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics.

Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV1-2 (mild-moderate CAV), CAV3 (severe CAV), and CAV0 (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies.

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.

Sex-Specific Trends in Incidence and Mortality for Urban and Rural Ambulatory Patients with Heart Failure in Eastern Ontario from 1994 to 2013.

BACKGROUND: Differences in outcomes have previously been reported between urban and rural settings across a multitude of chronic diseases. Whether these discrepancies have changed over time, and how sex may influence these findings is unknown for patients with ambulatory heart failure (HF). We examined the temporal incidence and mortality trends by geography in these patients. METHODS AND RESULTS: We conducted a retrospective cohort study of 36,175 eastern Ontario residents who were diagnosed with HF in an outpatient setting from 1994 to 2013. The primary outcome was 1-year mortality. We examined temporal changes in mortality risk factors with the use of multivariable Cox proportional hazard models. The incidence of HF decreased in women and men across both rural and urban settings. Age-standardized mortality rates also decreased over time in both sexes but remained greater in rural men compared with rural women. CONCLUSIONS: The incidence of HF in the ambulatory setting was greater for men than women and greater in rural than urban areas, but mortality rates remained higher in rural men compared with rural women. Further research should focus on ways to reduce this gap in the outcomes of men and women with HF.

Sex differences in outcomes of heart failure in an ambulatory, population-based cohort from 2009 to 2013.

BACKGROUND: Heart failure remains a substantial cause of morbidity and mortality in women. We examined the sex differences in heart failure incidence, mortality and hospital admission in a population-based cohort. METHODS: All Ontario residents who were diagnosed with heart failure in an ambulatory setting between Apr. 1, 2009, and Mar. 31, 2014, were included in this study. Incident cases of heart failure were captured through physician billing using a validated algorithm. Outcomes were mortality and hospital admission for heart failure within 1 year of the diagnosis. Probability of death and hospital admission were calculated using the Kaplan-Meier method. The hazard of death was assessed using a multivariable Cox proportional hazard model. RESULTS: A total of 90 707 diagnoses of heart failure were made in an ambulatory setting during the study period (47% women). Women were more likely to be older and more frail, and had different comorbidities than men. The incidence of heart failure decreased during the study period in both sexes. The mortality rate decreased in both sexes, but remained higher in women than men. The female age-standardized mortality rate was 89 (95% confidence interval [CI] 80-100) per 1000 in 2009 and 85 (95% CI 75-95) in 2013, versus male age-standardized mortality rates of 88 (95% CI 80-97) in 2009 and 83 (95% CI 75-91) in 2013. Conversely, the rates of incident heart failure hospital admissions after heart failure diagnosis decreased in men and increased in women. INTERPRETATION: Despite decreases in overall heart failure incidence and mortality in ambulatory patients, mortality rates remain higher in women than in men, and rates of hospital admission for heart failure increased in women and declined in men. Further studies should focus on sex differences in health-seeking behaviour, medical therapy and response to therapy to provide guidance for personalized care.

Repeatable and reproducible measurements of myocardial oxidative metabolism, blood flow and external efficiency using 11C-acetate PET.

BACKGROUND: Non-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of 11C-acetate positron emission tomography (PET) imaging of oxidative metabolism. METHODS AND RESULTS: Dynamic 11C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients' clinical data used FlowQuant® to evaluate test-retest repeatability, as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO2), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient-of-repeatability (CR). Test-retest correlations and repeatability were better for MEE and WMI compared to MVO2. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test-retest repeatability values (22%-54%, P < 0.001). Repeatability was improved for all parameters using a newer PET-computed tomography (CT) scanner compared to older PET-only instrumentation. CONCLUSION: 11C-acetate PET measurements of WMI and MEE exhibited excellent test-retest repeatability and operator reproducibility. Newer PET-CT scanners may be preferred for longitudinal tracking of cardiac efficiency.

Effects of an endothelin receptor antagonist, Macitentan, on right ventricular substrate utilization and function in a Sugen 5416/hypoxia rat model of severe pulmonary arterial hypertension.

BACKGROUND: Altered myocardial energy metabolism has been linked to worsening of RV function in pulmonary arterial hypertension (PAH). The aim of this study was to evaluate RV glucose and fatty acid metabolism in vivo in a rat model of PAH using positron emission tomography (PET) and investigate the effects of Macitentan on RV substrate utilization. METHODS: PAH was induced in male Sprague-Dawley rats by a single subcutaneous injection of Sugen 5416 (20 mg/kg) followed by 3 weeks of hypoxia (10% oxygen). At week 5 post-injection, the PAH rats were randomized to Macitentan (30 mg/kg daily) treatment or no treatment. Substrate utilization was serially assessed 5 and 8 weeks post-injection with 2-[18F]fluoro-2-deoxyglucose (FDG) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) PET for glucose and fatty acid metabolism respectively and correlated with in vivo functional measurements. RESULTS: PAH induction resulted in a 2.5-fold increase in RV FDG uptake (standardized uptake value (SUV) of normal control: 1.6 ± 0.4, week 5: 4.1 ± 1.9, week 8: 4.0 ± 1.6, P < 0.05 for all groups vs. control). RV FTHA showed twofold increased uptake at week 5 (SUV control: 1.50 ± 0.39, week 5: 3.06 ± 1.10, P = 0.03). Macitentan significantly decreased RV FDG uptake at 8 weeks (SUV: 2.5 ± 0.9, P = 0.04), associated with improved RV ejection fraction and reduced RV systolic pressure, while FTHA uptake was maintained. CONCLUSION: PAH is associated with metabolic changes in the RV, characterized by a marked increase in FDG and FTHA uptake. Macitentan treatment reduced PAH severity and was associated with a decrease in RV FDG uptake and improved RV function.

Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

BACKGROUND: Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. METHODS AND RESULTS: Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). CONCLUSIONS: In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.

FDG PET imaging for identifying pulmonary hypertension and right heart failure.

Pulmonary arterial hypertension (PAH) is a syndrome characterized by lung vascular intimal lesions, smooth muscle layer hypertrophy, perivascular inflammation, and concomitant right ventricular (RV) remodeling which can ultimately lead to the RV function decline known as RV failure (RVF). A key determining factor for RVF development is the RV metabolic state defined by the level of ischemia and glycolysis which constitute a vicious cycle of hypoxia, metabolic shift from glucose oxidation (GO) to glycolysis, increased RV systolic pressure (RVSP), decreased RV output, and further myocardial ischemia. In this context, 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) has been used for the measurement of glucose uptake (GU) as an indicator of glucose metabolism in the right heart and pulmonary vasculature. The focus of this review is the application of FDG PET modality for assessing PAH severity and clinical outcome.

Prescription patterns of SGLT2 inhibitors in patients with type 2 diabetes and heart failure with reduced ejection fracture admitted to a tertiary care centre in Ontario, Canada.

OBJECTIVE: To assess early adoption patterns of SGLT2 inhibitors (SGLT2i) in eligible patients with type 2 diabetes (T2DM) and heart failure with reduced ejection fracture (HFrEF) and identify gaps in practice. METHODS: A retrospective chart review of patients with T2DM and HFrEF admitted with decompensated heart failure to The Ottawa Hospital under Cardiology or GIM from June 2019-May 2021 was conducted. Patterns were assessed at 8-months intervals (1 period before the release of Diabetes Canada 2020 guidelines and 2 periods afterwards). Baseline patient characteristics, co-morbidities and prescriber information was collected. RESULTS: Of the 98 patients that met the inclusion criteria, 36.7% had a prescription for an SGLT2i either on admission, discharge or follow-up. Trends showed a gradual increase over time. On admission, 9.8% of patients were on an SGLT2i in period 1, 19.2% in period 2 and 23.3% in period 3. Patients receiving a prescription for SGLT2i on discharge were 0.0% in period 1, 10.0% in period 2 and 9.5% in period 3, all which were admitted under Cardiology. On follow-up, 13.9% of eligible patients were started on an SGLT2i in period 1, 21.1% in period 2 and 35.0% in period 3. Endocrinology was the main prescriber of SGLT2i in the outpatient setting, followed by Cardiology. CONCLUSIONS: Overall, trends show a slow but steady increase in early prescriptions of SGLT2i. However, most eligible patients were not started on therapy during our study period with variability in practice between specialties, highlighting opportunities to boost uptake in the future.

Quality and Patient Safety Metrics: Developing a Structured Program for Improving Patient Care in the Department of Medicine at The Ottawa Hospital.

PROBLEM: Despite increasing recognition of the importance of quality and patient safety in academic medicine, challenges remain with ensuring physician participation in quality assurance and quality improvement efforts, such as lack of compensation and enabling resources. An organizational culture that includes physician leadership and a supportive infrastructure is needed to encourage physician backing of quality and patient safety initiatives. APPROACH: The authors describe the development of a robust quality and patient safety program in the Department of Medicine at The Ottawa Hospital over the past 7 years and highlight how the department changed its organizational culture by prioritizing quality and patient safety and establishing the necessary infrastructure to support this program. Program development was characterized by 4 overarching themes: incentives, administrative structure and physician leadership, training and support, and system enhancements. OUTCOMES: As a result of the program, the department broadly implemented a standardized framework for conducting quality committee meetings and morbidity and mortality rounds and reviewing patient safety incidents and patient experience across its 16 divisions. This has led to 100% departmental compliance on corporate quality assurance metrics each year (e.g., regular multidisciplinary divisional quality committee meetings), along with physician participation in formal quality improvement initiatives that align with larger corporate goals. NEXT STEPS: The authors reflect on lessons learned during the implementation of the program and the essential elements that contributed to its success. Next steps for the program include using a centralized repository of quality and patient safety data, including patient safety incident dashboards, to encourage greater divisional collaboration on quality improvement initiatives and continuous institutional learning over time. Another important avenue will be to create an academic hub for excellence in quality and a formal approach to reward and promote physicians for their quality work.