BACKGROUND:In the PROACTIVE-HF trial, remote heart failure (HF) management using comprehensive vital signs and seated mean pulmonary artery pressure (mPAP) was safe and resulted in a low reported rate of HF hospitalization (HFH) and all-cause mortality (HFH/D) through 12 months. In this report, we extend the results from the PROACTIVE-HF study through 2 years, stratified by ejection fraction (EF). METHODS AND RESULTS:PROACTIVE-HF was a prospective, multicenter, open-label, single-arm trial evaluating the safety and efficacy of patient management using the Cordella PA pressure sensor system in patients with New York Heart Association class III symptoms, regardless of EF. In the first 24 months, the incidence of HF events (HFE)/D was 0.89 (95% CI 0.81-0.99) events per patient, driven by HFH. Patients with HF with reduced EF had greater HFE/D rates than those with HF with preserved EF (1.0 vs 0.8 events per patient, P = .048). CONCLUSIONS:For patients with HF experiencing moderate-to-severe symptoms, management using the Cordella PA sensor system was associated with low event rates and improved health status at 2 years, regardless of EF. Comprehensive remote monitoring of vital signs, seated PAP, and patient-reported symptoms via a digital platform supports sustained benefit for high-risk patients with HF.

BACKGROUND:In the PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients) trial, remote heart failure (HF) management using seated mean pulmonary artery pressure (mPAP) and vital signs was safe and resulted in a low rate of HF hospitalizations and mortality through 6 months. OBJECTIVES:The authors evaluated the effect of managing seated mPAP with the Cordella system on outcomes in patients with HF through 12 months. METHODS:In a single-arm, open-label trial, conducted in 75 European and U.S. centers, the authors enrolled HF patients with NYHA functional class III symptoms, irrespective of ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The prespecified, powered, secondary effectiveness endpoint at 12 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.70 events/patient/12 months, established from previous hemodynamic monitoring trials. Device/system-related complications, pressure sensor failure, and serious adverse events were examined. RESULTS:Between February 7, 2020, and March 31, 2023, 456 patients were implanted in a modified intent-to-treat cohort. The 12-month event rate was 0.36 (95% CI: 0.31-0.42), which was significantly lower than the performance goal (0.36 vs 0.70; P < 0.0001). There were no device/system-related complications or pressure sensor failures beyond the 6-month primary results (0.8% and 0.2%, respectively). CONCLUSIONS:Remote HF management using seated mPAP and vital signs in NYHA functional class III patients is safe and results in a low rate of HF hospitalizations and mortality over 12 months. These results support the use of seated mPAP monitoring and extend the evidence that pulmonary artery pressure-guided management improves HF outcomes. (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients [PROACTIVE-HF Trial]; NCT04089059).

Introduction An implantable pulmonary artery pressure (PAP) sensor is approved to reduce heart failure hospitalizations (HFH) in symptomatic patients. Key trials have excluded those with advanced chronic kidney disease (CKD), or eGFR <25 mL/min per 1.73 m². Real-world use of ambulatory hemodynamic monitoring in advanced CKD has not been well-described. Methods Hemodynamic Frontiers in Heart Failure (HF2) is an academic consortium of 14 US centers that developed a registry to collect data on patients following implantation with a PAP sensor, including demographics, hemodynamics, and clinical events (ED visits, HFH, or death). We analyzed patients with at least 12 months of hemodynamic monitoring data, comparing events in patients with normal kidney function (eGFR ≥60), mild to moderate CKD (eGFR 30-59), and advanced CKD (eGFR <30). Baseline demographic and implant hemodynamic data were compared using One-Way ANOVA test (IBS SPSS Statistics Version 29.0). In time-to-event analysis, patients who had no events were censored at their 12 month follow up as their last seen date. Those with an event > 12 months from the implant date were censored. The Registry has IRB approval from individual sites and is supported by CTSA Award UL1TR002366. Results Of 236 total patients, 70 (29.7%) had advanced and 112 (47.5%) had mild to moderate CKD (Table 1A). Those with CKD were more likely to be older, diabetic, and with higher baseline right atrial and pulmonary artery mean pressures. Patients with CKD had more frequent hospitalizations and those with advanced CKD had more frequent death and progression to LVAD/transplant or ESRD/dialysis (Table 1B). Of those with advanced CKD, only 2 (1.5%) progressed to ESRD. Conclusion Longitudinal real-world data from the HF2 Registry demonstrates use of PAP sensors in patients with a broad range of kidney function. Although ambulatory hemodynamic monitoring has been shown to reduce HFH, the same may not be true for those with advanced CKD. More research is needed in this high-risk population.

Background Women have been underrepresented in heart failure (HF) trials, including key trials for implantable pulmonary artery pressure (PAP) sensors. Sex-specific analysis of the use of ambulatory hemodynamic monitoring devices are lacking. Methods Hemodynamic Frontiers in Heart Failure (HF2) is an academic consortium of 14 US centers that has developed a registry to collect data on patients following PAP sensor implantation. We analyzed patients with at least 12 months of hemodynamic monitoring data and compared patients based on reported sex. Clinical events including ED visits, HF hospitalizations, and death have been captured. Baseline demographic and implant hemodynamic data were compared using independent samples t-test (IBM SPSS Statistics Version 29.0). The registry has IRB approval from individual sites and is supported by CTSA Award UL1TR002366. Results Of 238 patients, 100 (42%) were female. Women were more likely to have lower creatinine, higher BMI and ejection fraction (Table 1). They were less likely to have ischemic etiology or baseline SGLT2 inhibitor use. There were no significant differences in baseline hemodynamics. Female patients had fewer total events than their male counterparts (1.49 vs 1.91 events/person-year) and fewer HF hospitalizations (Figure 1). The majority of ED visits were non-cardiac and the majority of hospitalizations were not HF-related. There were 5 deaths total: 3 HF-related in males, 1 HF-related in a female and 1 non-cardiac in a female. Four patients progressed to LVAD, 3 of which were males. Three patients progressed to ESRD, all males. Conclusion The HF2 Registry is a real-world, multi-center registry of an approved PAP sensor. As compared to key trials leading to initial and expanded indications for the devices, this registry houses a higher proportion of female patients. Although there were no differences in baseline hemodynamics, there were substantial sex-based variations in other demographics and in outcomes. More research is needed to understand potential sex-specific effects and to encourage higher female representation in HF device trials and utilization.

Background: Pulmonary capillary wedge pressure (PCWP) provides an objective assessment of congestion status in heart failure (HF) patients, but its use is limited by the need for an invasive procedure, trained personnel, and specialized equipment to obtain a measurement. Cardiosense (Chicago, IL) has developed a machine learning (ML) algorithm that detects elevated PCWP non-invasively from data acquired by a chest-worn wearable device (CardioTag). We present data for a potential in-clinic point-of-care tool that improves the identification of hemodynamic congestion, with a focus on outpatient and low-acuity settings. Methods: The ePCWP System is a ML model developed to identify elevated PCWP (>18 mmHg) using non-invasive physiological biosignals from the CardioTag device, which simultaneously collects electrocardiogram, seismocardiogram, and photoplethysmogram data. Concurrent CardioTag and right-heart catheterization (RHC) data were collected prospectively in an observational study across 15 US sites from 1,116 patients undergoing standard-of-care RHC. Patients were either diagnosed with HFrEF, HFpEF, HFmrEF, or were suspected of HF before the RHC procedure. Standard of care physical examination, used to evaluate congestion status, was captured and used for comparative analysis. The training dataset contained 726 subjects and the validation dataset contained 153 subjects. Results: Five-fold cross-validation of the training dataset showed an overall accuracy of 0.79, sensitivity of 0.75 (CI: [0.69, 0.80]), and a specificity of 0.81 (CI: [0.77, 0.78]). The validation dataset showed an overall accuracy of 0.81, sensitivity of 0.76 (CI: [0.63, 0.86]), and a specificity of 0.82 (CI: [0.66, 0.89]). Figure 1 shows the overall classification performance of the ePCWP System (left) and a comparison to standard-of-care physical exam (right). Conclusion: We developed a non-invasive point-of-care tool that is capable of providing rapid, accurate assessments of congestion for patients with HF. This tool might be used to support convenient, frequent inpatient monitoring to augment discharge decisions and guide post-discharge follow-up care towards timely interventions and improvements in patient outcomes.

Introduction HFrEF remains associated with high morbidity and mortality despite advancements in its management. Great strides have been taken to understand the autonomic imbalances which play a key role in symptom generation and disease progression in HFrEF. The Barostim device is a breakthrough technology designed to address these imbalances via inhibition of the sympathetic outflow and activation of the parasympathetic nervous system. It is the first neuromodulator technology approved by the FDA for HFrEF. Baroreflex Activation therapy (BAT) has been shown to improve exercise capacity, 6MHW distance, NYHA class, NT-proBNP and quality of life when implanted in patients receiving GDMT. Hypothesis The effects of BAT on diuretic utilization in patients with HFrEF have not been studied. The objective of our study is to find whether BAT is beneficial in reducing diuretic utilization in patients with HFrEF. Methods A single-center, retrospective cohort study was done performed at Prisma Health Richland Hospital in Columbia, South Carolina. Data was collected by reviewing electronic medical records. A total of 25 patients underwent Barostim implantation (background table included). The primary outcome measure is percent change from baseline in weekly furosemide equivalent dose(mg) at 3-and-6-month intervals after Barostim implantation. A Wilcoxon single rank test was used because of the small sample size and p value <0.05 was considered significant. Results We found a trend in reduced percentage change from baseline in weekly furosemide equivalent dose at 3 months after Barostim implantation. However, this was not clinically significant with p-value from Wilcoxon signed rank test: 0.22. Moreover, we found a clinically significant reduction in percentage change from baseline in weekly furosemide equivalent dose at 6 months after Barostim implantation, p-value from Wilcoxon signed rank test: 0.01 (Figure1). Conclusion BAT in patients with HFrEF reduced diuretic utilization at 6 months. Despite the limited sample size, the evidence supports BAT with GDMT could improve patients' quality of life via dependence on diuretics for symptom management and potentially, help avoid adverse outcomes associated with excessive diuretic use. Multi-center randomized trials are needed to gather further evidence on BAT and diuretic utilization in patients with HFrEF.

The use of guideline-directed medical therapy (GDMT) has substantially prolonged and improved the lives of patients with heart failure (HF). Nevertheless, adherence rates remain suboptimal. Even when successfully maximized and adhered to, there is a substantial residual risk of recurrent HF hospitalization and death. In light of this, there is a strong need for effective interventions that can decrease the high residual risk seen in patients with HF. Several device options exist that are approved by the US Food and Drug Administration and that have been shown to decrease morbidity and/or mortality in patients among whom GDMT is maximized. These strategies include valvular interventions (aortic valve replacement, mitral valve repair, and tricuspid valve repair or replacement), cardiac resynchronization, cardiac contractility modulation, remote hemodynamic monitoring, and baroreceptor activation therapy. The pivotal trials for each of these interventions, and the patient populations for which they have been approved, are discussed. Current rates of device use in clinical practice remain very low. For many device classes, the vast majority of eligible patients are not offered or prescribed the device. Several reasons may explain this mismatch, foremost of which is a lack of clinical awareness about when to escalate therapy, how to identify patients requiring more than GDMT, and access to centers with sufficient experience. To aid the appropriate uptake of device therapy in clinical practice, we propose a simple mnemonic for use by clinicians that can prompt the early identification and prompt referral of patients with HF who likely merit consideration of additional device-based therapy in addition to GDMT.

Guideline-directed medical therapy is the backbone of heart failure treatment. However, patients continue to experience heart failure symptoms, impaired quality of life, and reduced functional status despite guideline-directed medical and device treatment. There is a void in treatment alternatives between guideline-directed therapy and the advanced heart failure surgical options of heart transplant (HT) and left ventricular assist device (LVAD). Cardiac contractility modulation and baroreceptor activation therapies are shown to improve heart failure symptoms, quality of life, and exertional capacity in select patients and complement our current treatment paradigm. The purpose of this paper is to review these novel Food and Drug Administration (FDA)-approved heart failure therapies and facilitate the identification of appropriate candidates.

BACKGROUND:Remote hemodynamics-guided management of heart failure (HF) with implantable pulmonary artery pressure sensors has been shown to reduce HF hospitalizations. The widespread clinical adoption of this procedure is constrained by its invasive nature and high cost. We present a noninvasive technology based on a wearable sensor (CardioTag; Cardiosense) and machine learning (ML) for estimating pulmonary capillary wedge pressure (PCWP) in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES:The authors developed and evaluated (against right heart catheterization [RHC]) an ML model to estimate PCWP with the use of electrocardiography, seismocardiography, and photoplethysmography signals from CardioTag. METHODS:A multicenter prospective study was performed, and 310 patients with HFrEF (EF ≤40%) were recruited in both inpatient and outpatient settings. A blinded core laboratory adjudicated the RHC PCWP tracings to yield criterion-standard PCWP labels against which the model was trained and tested. The data were separated into 2 sets: a training set for model training and fine-tuning, and a held-out testing set unseen until final evaluation. RESULTS:The patients were 61± 13 years of age, 38% female, 44% White, and 39% African American, and had a PCWP of 18.1 ± 9.45 mm Hg. The model estimated PCWP values in the held-out test set with error of 1.04 ± 5.57 mm Hg (limits of agreement of -9.9 to 11.9 mm Hg), with consistent performance across sex, race, ethnicity, and body mass index. CONCLUSIONS:The CardioTag and its ML algorithm estimate PCWP with accuracy approaching implantable hemodynamic sensors, potentially offering a more accessible and cost-effective option for hemodynamics-guided management in HFrEF patients.

The baroreflex system is involved in modulating several physiological functions of the cardiovascular system and can modulate cardiac output, blood pressure, and cardiac electrophysiology directly and indirectly. In addition, it is involved in regulating neurohormonal pathways involved in the cardiovascular function, such as the renin-angiotensin-aldosterone system and vasopressin release. Baroreflex dysfunction is characterized by sympathetic overactivation and parasympathetic withdrawal and is associated with several cardiovascular diseases, such as hypertension, heart failure, and coronary artery disease. Targeting the baroreflex system via invasive (eg, baroreflex activation therapy and endovascular baroreceptor amplification) and noninvasive approaches (eg, slow breathing exercises and exercise training) has emerged as a novel pathway to manage cardiovascular diseases. Studies examining the long-term safety and efficacy of such interventions in various cardiovascular diseases are needed.

BACKGROUND:Monitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. OBJECTIVES:The purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. METHODS:Following GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. RESULTS:Between February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. CONCLUSIONS:Remote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure-guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059).

Background: Hemodynamic Frontiers in Heart Failure (HF 2 ) is a multicenter research consortium of institutions with active remote pulmonary artery pressure monitoring programs that aims to promote research in this field. The consortium recently created a registry of patients with pulmonary artery hemodynamic (HD) monitors (HDM) to facilitate the research mission. Goals/Aims: HF 2 registry aims to collect demographic, clinical, laboratory, echocardiographic and HD data from HDM patients to create a test bed to advance scientific knowledge about ambulatory HD monitoring and quickly evaluate new therapies. Methods: HF 2 includes patients aged >18 who would have been implanted with a HDM as per FDA indications of NYHA Class III HF diagnosis with a prior hospitalization or patients with NYHA Class II or BNP elevation without hospitalization. HF 2 registry data warehouse rests through University of Kansas Medical Center (KUMC) and was approved by their institutional review board (IRB) board followed by local IRBs at participating institutions with required Data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC. Results: This initial data set includes 254 patients implanted from 2019 until May 2023. See Table 1 for initial demographic, comorbidity, laboratory, echocardiographic, and medication data. See Table 2 for HD measurements at time of implant. Conclusion: A real-world registry/test bed of patients with HDM can evaluate long-term outcomes in such patients, provide data in unique patient groups, and provide an opportunity to evaluate HD effects of new HF therapies in rapid turnaround cross over trials.

BackgroundIn this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor (CardioMEMS, Abbott).MethodsBetween 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise.ResultsIn our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) < 50% in 53%, mean 6MWT distance was 277 ± 95 meters. Resting seated PAPs were 31 ± 15 mmHg (systolic), 13 ± 8 mmHg (diastolic), and 20 ± 11 mmHg (mean). The pressures were lower in the seated rather than the supine position. After 6MWT, the pressures increased to PAP systolic 37 ± 19 mmHg (p < 0.0001), diastolic 15 ± 10 mmHg (p = 0.006), and mean 24 ± 13 mmHg (p < 0.0001). Patients with elevated PAP diastolic at rest (>15 mmHg) demonstrated a greater increase in post-exercise PAP.ConclusionThe measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures.

BackgroundHemodynamic Frontiers in Heart Failure (HF2) is a multicenter academic research consortium comprised of 14 US institutions with mature remote monitoring programs for ambulatory patients with heart failure (HF). The consortium developed a retrospective and prospective registry of patients implanted with a wireless pulmonary artery pressure (PAP) sensor.Goals/aimsHF2 registry collects demographic, clinical, laboratory, echocardiographic (ECHO), and hemodynamic data from patients with PAP sensors. The aims of HF2 are to advance understanding of HF and to accelerate development of novel diagnostic and therapeutic innovations.MethodsHF2 includes adult patients implanted with a PAP sensor as per FDA indications (New York Heart Association (NYHA) Class III HF functional class with a prior hospitalization, or patients with NYHA Class II or brain natriuretic peptide (BNP) elevation without hospitalization) at a HF2 member site between 1/1/19 to present. HF2 registry is maintained at University of Kansas Medical Center (KUMC). The registry was approved by the institutional review board (IRB) at all participating institutions with required data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC.ResultsThis initial data set includes 254 patients implanted from the start of 2019 until May 2023. At time of device implant, the cohort average age is 73 years old, 59.8% are male, 72% have NYHA Class III HF, 40% have left ventricular ejection fraction (LVEF) < 40%, 35% have LVEF > 50%, mean BNP is 560 pg/ml, mean N-Terminal pro-BNP (NTproBNP) is 5,490 pg/ml, mean creatinine is 1.65 mg/dl. Average baseline hemodynamics at device implant are right atrial pressure (RAP) of 11 mmHg, pulmonary artery systolic pressure (PASP) of 47 mmHg, pulmonary artery diastolic pressure (PADP) 21 mmHg, mean pulmonary artery pressure (mPAP) of 20 mmHg, pulmonary capillary wedge pressure (PCWP) of 19 mmHg, cardiac output (CO) of 5.3 L/min, and cardiac index (CI) of 2.5 L/min/m2.ConclusionA real-world registry of patients implanted with a PAP sensor enables long-term evaluation of hemodynamic and clinic outcomes in highly-phenotyped ambulatory HF patients, and creates a unique opportunity to validate and test novel diagnostic and therapeutic approaches to HF.