Prognostic performance of soluble urokinase plasminogen activator receptor for heart failure or mortality in Western and Asian patients with acute breathlessness.

AIMS: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF. METHODS AND RESULTS: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.2 ng/mL vs 3.1 ng/mL, P < 0.0001). The discriminative power of suPAR for endpoint prediction was c-statistic of 0.77 in the combined population, but was superior in Singapore than NZ (c-statistic: 0.83 vs 0.71, P < 0.0001). Although the highest suPAR tertile (>4.37 ng/mL) was associated with risks of >4-fold in NZ, >20-fold in Singapore, and ≥3-fold in HF for incurring the outcome, there was no interaction between country and suPAR levels after adjustment. Multivariable analysis indicated suPAR to be robust in predicting HF/death at 1-year [hazard ratio: 1.9 (95% CI:1.7 to 2.0) per SD increase] and improved risk discrimination for outcome prediction in HF (∆0.06) and for those with NT-proBNP >1000 pg/mL (∆0.02). CONCLUSION: suPAR is a strong independent predictor of HF and/or death at 1 year in acutely breathless patients, in both Asian and Western cohorts, and in HF. suPAR may improve stratification of acutely breathless patients, and in acute HF, for risk of later onset of heart failure or mortality.

Convalescent Growth Differentiation Factor-15 and Long-Term Outcomes after an Acute Coronary Syndrome.

BACKGROUND: Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome. METHODS: GDF-15 concentrations were measured in 1945 patients who were recruited between 2002 and 2009 to the Coronary Disease Cohort Study. For this analysis, follow-up was curtailed at 10 years and association of GDF-15 with all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure hospitalizations were assessed with multivariate Cox proportional hazard regression analysis. RESULTS: After 10 years of follow-up, there were 648 deaths (348 from cardiovascular causes), 500 admissions for myocardial infarction, and 436 for heart failure. Four-month convalescent GDF-15 demonstrated a robust independent association with all endpoints, which remained after adjustment for Global Registry of Acute Coronary Events score and other convalescent biomarkers. When compared to the lowest quartile of GDF-15 concentrations, those in the highest quartile had a 3-fold increased risk of all-cause death. CONCLUSIONS: Convalescent plasma GDF-15 is a strong and independent predictor of 10-year all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure admission following an acute coronary syndrome. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY TRIAL ID: ACTRN12605000431628.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Implantable Hemodynamic Monitors Improve Survival in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Trials evaluating implantable hemodynamic monitors to manage patients with heart failure (HF) have shown reductions in HF hospitalizations but not mortality. Prior meta-analyses assessing mortality have been limited in construct because of an absence of patient-level data, short-term follow-up duration, and evaluation across the combined spectrum of ejection fractions. OBJECTIVES: The purpose of this meta-analysis was to determine whether management with implantable hemodynamic monitors reduces mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to confirm the effect of hemodynamic-monitoring guided management on HF hospitalization reduction reported in previous studies. METHODS: The patient-level pooled meta-analysis used 3 randomized studies (GUIDE-HF [Hemodynamic-Guided Management of Heart Failure], CHAMPION [CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients], and LAPTOP-HF [Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy]) of implantable hemodynamic monitors (2 measuring pulmonary artery pressures and 1 measuring left atrial pressure) to assess the effect on all-cause mortality and HF hospitalizations. RESULTS: A total of 1,350 patients with HFrEF were included. Hemodynamic-monitoring guided management significantly reduced overall mortality with an HR of 0.75 (95% CI: 0.57-0.99); P = 0.043. HF hospitalizations were significantly reduced with an HR of 0.64 (95% CI: 0.55-0.76); P < 0.0001. CONCLUSIONS: Management of patients with HFrEF using an implantable hemodynamic monitor significantly reduces both mortality and HF hospitalizations. The reduction in HF hospitalizations is seen early in the first year of monitoring and mortality benefits occur after the first year.

CS1, a controlled-release formulation of valproic acid, for the treatment of patients with pulmonary arterial hypertension: Rationale and design of a Phase 2 clinical trial.

Although rare, pulmonary arterial hypertension (PAH) is associated with substantial morbidity and a median survival of approximately 7 years, even with treatment. Current medical therapies have a primarily vasodilatory effect and do not modify the underlying pathology of the disease. CS1 is a novel oral, controlled-release formulation of valproic acid, which exhibits a multi-targeted mode of action (pulmonary pressure reduction, reversal of vascular remodeling, anti-inflammatory, anti-fibrotic, and anti-thrombotic) and therefore potential for disease modification and right ventricular modeling in patients with PAH. A Phase 1 study conducted in healthy volunteers indicated favorable safety and tolerability, with no increased risk of bleeding and significant reduction of plasminogen activator inhibitor 1. In an ongoing randomized Phase 2 clinical trial, three doses of open-label CS1 administered for 12 weeks is evaluating the use of multiple outcome measures. The primary endpoint is safety and tolerability, as measured by the occurrence of adverse events. Secondary outcome measures include the use of the CardioMEMS™ HF System, which provides a noninvasive method of monitoring pulmonary artery pressure, as well as cardiac magnetic resonance imaging and echocardiography. Other outcomes include changes in risk stratification (using the REVEAL 2.0 and REVEAL Lite 2 tools), patient reported outcomes, functional capacity, 6-min walk distance, actigraphy, and biomarkers. The pharmacokinetic profile of CS1 will also be evaluated. Overall, the novel design and unique, extensive clinical phenotyping of participants in this trial will provide ample evidence to inform the design of any future Phase 3 studies with CS1.

Deuterium metabolic imaging for 3D mapping of glucose metabolism in humans with central nervous system lesions at 3T.

PURPOSE: To explore the potential of 3T deuterium metabolic imaging (DMI) using a birdcage 2 H radiofrequency (RF) coil in both healthy volunteers and patients with central nervous system (CNS) lesions. METHODS: A modified gradient filter, home-built 2 H volume RF coil, and spherical k-space sampling were employed in a three-dimensional chemical shift imaging acquisition to obtain high-quality whole-brain metabolic images of 2 H-labeled water and glucose metabolic products. These images were acquired in a healthy volunteer and three subjects with CNS lesions of varying pathologies. Hardware and pulse sequence experiments were also conducted to improve the signal-to-noise ratio of DMI at 3T. RESULTS: The ability to quantify local glucose metabolism in correspondence to anatomical landmarks across patients with varying CNS lesions is demonstrated, and increased lactate is observed in one patient with the most active disease. CONCLUSION: DMI offers the potential to examine metabolic activity in human subjects with CNS lesions with DMI at 3T, promising for the potential of the future clinical translation of this metabolic imaging technique.

High-Sensitivity Cardiac Troponin for Risk Assessment in Patients With Chronic Coronary Artery Disease.

BACKGROUND: Cardiac troponin is used for risk stratification of patients with acute coronary syndromes; however, the role of testing in other settings remains unclear. OBJECTIVES: The aim of this study was to evaluate whether cardiac troponin testing could enhance risk stratification in patients with chronic coronary artery disease independent of disease severity and conventional risk measures. METHODS: In a prospective cohort of consecutive patients with symptoms suggestive of stable angina attending for outpatient coronary angiography, high-sensitivity cardiac troponin I was measured before angiography, and clinicians were blinded to the results. The primary outcome was myocardial infarction or cardiovascular death during follow-up. RESULTS: In 4,240 patients (age 66 years [IQR: 59-73 years], 33% female), coronary artery disease was identified in 3,888 (92%) who had 255 (6%) primary outcome events during a median follow-up of 2.4 years (IQR: 1.3-3.6 years). In patients with coronary artery disease, troponin concentrations were 2-fold higher in those with an event compared with those without (6.7 ng/L [IQR: 3.2-14.2 ng/L] vs 3.3 ng/L [IQR: 1.7-6.6 ng/L]; P < 0.001). Troponin concentrations were associated with the primary outcome after adjusting for cardiovascular risk factors and coronary artery disease severity (adjusted HR: 2.3; 95% CI: 1.7-3.0, log10 troponin; P < 0.001). A troponin concentration >10 ng/L identified patients with a 50% increase in the risk of myocardial infarction or cardiovascular death. CONCLUSIONS: In patients with chronic coronary artery disease, cardiac troponin predicts risk of myocardial infarction or cardiovascular death independent of cardiovascular risk factors and disease severity. Further studies are required to evaluate whether routine testing could inform the selection of high-risk patients for treatment intensification. (Myocardial Injury in Patients Referred for Coronary Angiography [MICA]; ISRCTN15620297).

Real-time pulmonary artery pressure monitoring in heart failure patients: an updated cost-effectiveness analysis.

AIMS: Previous cost-effectiveness analysis suggests that CardioMEMS is cost-effective compared with usual care for patients with persistent New York Heart Association class III symptoms and at least one heart failure (HF) hospitalization within 12 months. The aim of the paper is to perform an update of the cost-effectiveness analysis of CardioMEMS using the most recent data from the published literature. METHODS AND RESULTS: A Microsoft Excel Markov model from a previous UK cost-effectiveness study of CardioMEMS was updated using the clinical effectiveness of pulmonary artery pressure (PAP)-guided treatment derived from the pivotal trials. The model included the device costs (and the implantation procedure and related complications), costs of remote monitoring, costs of HF-related hospitalizations, and costs of usual care. Quality-adjusted life years (QALYs) were estimated based on utilities from pivotal trials and published literature. Cost-effectiveness results were estimated as incremental cost per QALY gained of CardioMEMS compared with usual care. Scenario analyses were also performed using data from real-world studies that showed a significant decrease in HF-related hospitalizations. In the base case analysis over a time horizon of 10 years, PAP-guided HF therapy increased cost compared with usual care by £6337 (i.e. from £22 770 in usual care to £29 107 in PAP-guided HF therapy) and the QALYs per patient for usual care and PAP-guided patients were 2.62 and 2.94, respectively, reflecting an increase of 0.32 QALYs with PAP-guided treatment. The resultant incremental cost-effectiveness ratio (ICER), the ratio between incremental costs and the QALYs, is estimated at £19 761/QALY. Scenario analyses suggest that the ICER for CardioMEMS can range from being dominant to £27 910/QALY. Probabilistic sensitivity analyses suggested that PAP-guided HF therapy has 81.9% probability of being cost-effective at a threshold of £30 000/QALY. CONCLUSIONS: Our model suggests that CardioMEMS is likely to be cost-effective in the United Kingdom, at the currently considered thresholds of £20 000-30 000/QALY.

Temporal Changes in Coronary 18F-Fluoride Plaque Uptake in Patients with Coronary Atherosclerosis.

Coronary 18F-sodium fluoride (18F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary 18F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary 18F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary 18F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary 18F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary 18F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary 18F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary 18F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary 18F-fluoride uptake is a temporally stable marker of established and progressive disease.

Paired risk scores to predict ischaemic and bleeding risk twenty-eight days to one year after an acute coronary syndrome.

OBJECTIVE: The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. We designed paired ischaemic and major bleeding risk scores to inform this decision. METHODS: New Zealand (NZ) patients with ACS investigated with coronary angiography are recorded in the All NZ ACS Quality Improvement registry and linked to national health datasets. Patients were aged 18-84 years (2012-2020), event free at 28 days postdischarge and without atrial fibrillation. Two 28-day to 1-year postdischarge multivariable risk prediction scores were developed: (1) cardiovascular mortality/rehospitalisation with myocardial infarction or ischaemic stroke (ischaemic score) and (2) bleeding mortality/rehospitalisation with bleeding (bleeding score). FINDINGS: In 27 755 patients, there were 1200 (4.3%) ischaemic and 548 (2.0%) major bleeding events. Both scores were well calibrated with moderate discrimination performance (Harrell's c-statistic 0.75 (95% CI, 0.74 to 0.77) and 0.69 (95% CI, 0.67 to 0 .71), respectively). Applying these scores to the 2020 European Society of Cardiology ACS antithrombotic treatment algorithm, the 31% of the cohort at elevated (>2%) bleeding and ischaemic risk would be considered for an abbreviated DAPT duration. For those at low bleeding risk, but elevated ischaemic risk (37% of the cohort), prolonged DAPT may be appropriate, and for those with low bleeding and ischaemic risk (29% of the cohort) short duration DAPT may be justified. CONCLUSION: We present a pair of ischaemic and bleeding risk scores specifically to assist clinicians and their patients in deciding on DAPT duration beyond the first month post-ACS.

Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides.

BACKGROUND: In patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). OBJECTIVES: This study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. METHODS: In the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. RESULTS: Of 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre-COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre-COVID-19 analysis (interaction P = 0.58). CONCLUSIONS: Consistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813).

Coronary Atherosclerotic Plaque Activity and Future Coronary Events.

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Latent Coronary Plaque Morphology From Computed Tomography Angiography, Molecular Disease Activity on Positron Emission Tomography, and Clinical Outcomes.

BACKGROUND: Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction. METHODS: Patients with known coronary artery disease underwent coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction. RESULTS: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P=0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P=0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P=0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P=0.02). CONCLUSIONS: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.

Pulmonary Artery Pressure-Guided Heart Failure Management Reduces Hospitalizations in Patients With Chronic Kidney Disease.

BACKGROUND: Hemodynamic-guided heart failure management is a superior strategy to prevent decompensation leading to hospitalization compared with traditional clinical methods. It remains unstudied if hemodynamic-guided care is effective across severities of comorbid renal insufficiency or if this strategy impacts renal function over time. METHODS: In the CardioMEMS US PAS (Post-Approval Study), heart failure hospitalizations were compared from 1 year before and after pulmonary artery sensor implantation in 1200 patients with New York Heart Association class III symptoms and a previous hospitalization. Hospitalization rates were evaluated in all patients grouped into baseline estimated glomerular filtration rate (eGFR) quartiles. Chronic kidney disease progression was evaluated in patients with renal function follow-up data (n=911). RESULTS: Patients with stage 2 or greater chronic kidney disease at baseline exceeded 80%. Heart failure hospitalization risk was lower in all eGFR quartiles ranging from a hazard ratio of 0.35 (0.27-0.46; P<0.0001) in patients with eGFR >65 mL/min per 1.73 m2 to 0.53 (0.45-0.62; P<0.0001) in patients with eGFR ≤37 mL/min per 1.73 m2. Renal function was preserved or improved in most patients. Survival was different between quartiles and lower in quartiles with more advanced chronic kidney disease. CONCLUSIONS: Hemodynamic-guided heart failure management using remotely obtained pulmonary artery pressures is associated with lower hospitalization rates and general preservation of renal function in all eGFR quartiles or chronic kidney disease stages.

Role of computed tomography cardiac angiography in acute chest pain syndromes.

Use of CT coronary angiography (CTCA) to evaluate chest pain has rapidly increased over the recent years. While its utility in the diagnosis of coronary artery disease in stable chest pain syndromes is clear and is strongly endorsed by international guidelines, the role of CTCA in the acute setting is less certain. In the low-risk setting, CTCA has been shown to be accurate, safe and efficient but inherent low rates of adverse events in this population and the advent of high-sensitivity troponin testing have left little room for CTCA to show any short-term clinical benefit.In higher-risk populations, CTCA has potential to fulfil a gatekeeper role to invasive angiography. The high negative predictive value of CTCA is maintained while also identifying non-obstructive coronary disease and alternative diagnoses in the substantial group of patients presenting with chest pain who do not have type 1 myocardial infarction. For those with obstructive coronary disease, CTCA provides accurate assessment of stenosis severity, characterisation of high-risk plaque and findings associated with perivascular inflammation. This may allow more appropriate selection of patients to proceed to invasive management with no disadvantage in outcomes and can provide a more comprehensive risk stratification to guide both acute and long-term management than routine invasive angiography.

Sustained Reduction in Pulmonary Artery Pressures and Hospitalizations During 2 Years of Ambulatory Monitoring.

BACKGROUND: Therapy guided by pulmonary artery (PA) pressure monitoring reduces PA pressures and heart failure hospitalizations (HFH) during the first year, but the durability of efficacy and safety through 2 years is not known. METHODS AND RESULTS: The CardioMEMS Post-Approval Study investigated whether benefit and safety were generalized and sustained. Enrollment at 104 centers in the United States included 1200 patients with NYHA Class III symptoms on recommended HF therapies with prior HFH. Therapy was adjusted toward PA diastolic pressure 8-20 mmHg. Intervention frequency and PA pressure reduction were most intense during first 90 days, with sustained reduction of PA diastolic pressure from baseline 24.7 mmHg to 21.0 at 1 year and 20.8 at 2 years for all patients. Patients completing two year follow-up (n = 710) showed similar 2-year reduction (23.9 to 20.8 mmHg), with reduction in PA mean pressure (33.7 to 29.4 mmHg) in patients with reduced left ventricular ejection. The HFH rate was 1.25 events/patient/year prior to sensor implant, 0.54 at 1 year, and 0.37 at 2 years, with 59% of patients free of HFH during follow-up. CONCLUSIONS: Reduction in PA pressures and hospitalizations were early and sustained during 2 years of PA pressure-guided management, with no signal of safety concerns regarding the implanted sensor.

Hemodynamically-Guided Management of Heart Failure Across the Ejection Fraction Spectrum: The GUIDE-HF Trial.

BACKGROUND: Hemodynamically-guided management using an implanted pulmonary artery pressure sensor is indicated to reduce heart failure (HF) hospitalizations in patients with New York Heart Association (NYHA) functional class II-III with a prior HF hospitalization or those with elevated natriuretic peptides. OBJECTIVES: The authors sought to evaluate the effect of left ventricular ejection fraction (EF) on treatment outcomes in the GUIDE-HF (Hemodynamic-GUIDEd management of Heart Failure) randomized trial. METHODS: The GUIDE-HF randomized arm included 1,000 NYHA functional class II-IV patients (with HF hospitalization within the prior 12 months or elevated natriuretic peptides adjusted for EF and body mass index) implanted with a pulmonary artery pressure sensor, randomized 1:1 to a hemodynamically-guided management group (treatment) or a control group (control). The primary endpoint was the composite of HF hospitalizations, urgent HF visits, and all-cause mortality at 12 months. The authors assessed outcomes by EF in guideline-defined subgroups ≤40%, 41%-49%, and ≥50%, within the trial specified pre-COVID-19 period cohort. RESULTS: There were 177 primary events (0.553/patient-year) in the treatment group and 224 events (0.682/patient-year) in the control group (HR: 0.81 [95% CI: 0.66-1.00]; P = 0.049); HF hospitalization was lower in the treatment vs control group (HR: 0.72 [95% CI: 0.57-0.92]; P = 0.0072). Within each EF subgroup, primary endpoint and HF hospitalization rates were lower in the treatment group (HR <1.0 across the EF spectrum). Event rate reduction by EF in the treatment groups was correlated with reduction in pulmonary artery pressures and medication changes. CONCLUSIONS: Hemodynamically-guided HF management decreases HF-related endpoints across the EF spectrum in an expanded patient population of patients with HF. (Hemodynamic-GUIDEd Management of Heart Failure [GUIDE-HF]; NCT03387813).

Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development.

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.