Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial.

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).

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Sacubitril/valsartan versus angiotensin inhibitors and arrhythmia endpoints in heart failure with reduced ejection fraction.

BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF). OBJECTIVES: We performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit. METHODS: We searched PubMed, Embase, and ClinicalTrials.gov. Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate. RESULTS: We included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63-0.96; P = .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25-0.79; P = .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21-0.74; P = .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58-3.68; P < .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen. CONCLUSION: ARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

Bicaval vs biatrial anastomosis techniques in orthotopic heart transplantation: An updated analysis of the UNOS database.

BACKGROUND: Despite the significant increase in the number of orthotopic heart transplants (OHT) performed yearly using the bicaval anastomosis technique, the impact on long-term outcomes remains a topic of debate. We analyzed the United Network for Organ Sharing (UNOS) database in search of the latest insight. METHODS: We performed a retrospective analysis of the UNOS database from 2006 to 2016 to identify first-time OHT recipients. Patients were primarily stratified according to anastomosis technique: bicaval vs biatrial. Baseline characteristics and clinical status were recorded. The primary endpoint was all-cause mortality. Secondary outcomes included need for permanent pacemaker (PPM), and length of hospital stay (LOS). The Kaplan-Meier method was used to compare survival between the two groups. The Cox proportional hazards regression model was used to conduct multivariable analysis. Statistical significance established at P < .0001. RESULTS: A total of 26 990 patients were identified. Of those who met the inclusion criteria (21 597), 16 573 (77%) underwent bicaval anastomosis. There were no major differences in baseline characteristics between the two groups. The bicaval anastomosis technique was not associated with increased survival during the study period (hazard ratio: 0.97; P = .3557), but the bicaval group required postoperative PPM less often (2.51% vs 5.79%, P < .0001) and was associated with shorter LOS on multivariable analysis. CONCLUSIONS: The use of either bicaval or biatrial anastomosis during OHT offers comparable survival advantage. Nonetheless, bicaval anastomosis is associated with less need for postoperative PPM and slightly shorter LOS.

A 10-Year Trend Analysis of Heart Failure in the Less Developed Brazil.

BACKGROUND: Data on heart failure (HF) epidemiology in less developed areas of Brazil are scarce. OBJECTIVE: Our aim was to determine the HF morbidity and mortality in Paraiba and Brazil and its 10-year trends. METHODS: A retrospective search was conducted from 2008 to 2017 using the DATASUS database and included patients ≥ 15 years old with a primary diagnosis of HF. Data on in-hospital and population morbidity and mortality were collected and stratified by year, gender and age. Pearson correlation and linear-by-linear association test for trends were calculated, with a level of significance of 5%. RESULTS: From 2008 to 2017, HF admissions decreased 62% (p = 0.004) in Paraiba and 34% (p = 0.004) in Brazil. The in-hospital mortality rate increased in Paraiba and Brazil [65.1% (p = 0.006) and 30.1% (p = 0.003), respectively], but the absolute in-hospital mortality had a significant decrease only in Paraiba [37.5% (p = 0.013)], which was maintained after age stratification, except for groups 15-19, 60-69 and > 80 years. It was observed an increase in the hospital stay [44% (p = 0.004) in Paraiba and 12.3% (p = 0.004) in Brazil]. From 2008 to 2015, mortality rate for HF in the population decreased 10.7% (p = 0.047) in Paraiba and 7.7% (p = 0.017) in Brazil. CONCLUSIONS: Although HF mortality rate has been decreasing in Paraiba and Brazil, an increase in the in-hospital mortality rate and length of stay for HF has been observed. Hospital-based clinical studies should be performed to identify the causes for these trends of increase.

Food and Drug Administration Malfunction Recalls of Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) are being increasingly implanted given the increasing prevalence of patients with advanced heart failure stages. However, they are not exempt from device malfunctions. A PubMed search for the key words (left ventricular assist device malfunction) (ventricular assist system malfunction) was performed. We identified 28 publications in the US Food and Drug Administration (FDA) website database that addressed LVAD malfunction. Twenty-nine FDA recalls were identified regarding LVAD malfunctions: 17 regarding HeartWare ventricular assist device, six for HeartMate II, three for HeartMate 3, and three for total artificial heart. Mechanisms involved in LVAD malfunction include battery malfunction, loose driveline connector, malfunction of the system controller, loose power supply connector ports, malfunction of the driveline splice kit, problems with the percutaneous lead connection, disconnection of the bend relief and outflow graft and outflow graft occlusion among others. Multiple mechanisms could be linked to LVAD malfunction. However, multiple device modifications have been developed over the past decade to avoid recurrent malfunctions. Constant improvements and research in biotechnology are needed to prevent these complications. It remains to be seen if newer generation devices will lead to improved patient outcomes over the long term.

A 10-Year Trend Analysis of Heart Failure in the Less Developed Brazil / Insuficiência Cardíaca no Brasil Subdesenvolvido: Análise de Tendência de Dez Anos

Abstract Background: Data on heart failure (HF) epidemiology in less developed areas of Brazil are scarce. Objective: Our aim was to determine the HF morbidity and mortality in Paraiba and Brazil and its 10-year trends. Methods: A retrospective search was conducted from 2008 to 2017 using the DATASUS database and included patients ≥ 15 years old with a primary diagnosis of HF. Data on in-hospital and population morbidity and mortality were collected and stratified by year, gender and age. Pearson correlation and linear-by-linear association test for trends were calculated, with a level of significance of 5%. Results: From 2008 to 2017, HF admissions decreased 62% (p = 0.004) in Paraiba and 34% (p = 0.004) in Brazil. The in-hospital mortality rate increased in Paraiba and Brazil [65.1% (p = 0.006) and 30.1% (p = 0.003), respectively], but the absolute in-hospital mortality had a significant decrease only in Paraiba [37.5% (p = 0.013)], which was maintained after age stratification, except for groups 15-19, 60-69 and > 80 years. It was observed an increase in the hospital stay [44% (p = 0.004) in Paraiba and 12.3% (p = 0.004) in Brazil]. From 2008 to 2015, mortality rate for HF in the population decreased 10.7% (p = 0.047) in Paraiba and 7.7% (p = 0.017) in Brazil. Conclusions: Although HF mortality rate has been decreasing in Paraiba and Brazil, an increase in the in-hospital mortality rate and length of stay for HF has been observed. Hospital-based clinical studies should be performed to identify the causes for these trends of increase.

Resumo Fundamento: Dados sobre a epidemiologia da insuficiência cardíaca (IC) em áreas pouco desenvolvidas são escassos. Objetivos: Nosso objetivo foi determinar a morbidade e a mortalidade por IC na Paraíba e no Brasil, e sua tendência em dez anos. Métodos: Realizou-se uma busca retrospectiva de 2008 a 2017 utilizando-se o banco de dados do DATASUS incluindo pacientes com idade ≥ 15 anos, com diagnóstico primário de IC. Os dados da morbimortalidade por IC foram coletados e estratificados por ano, sexo e idade. Foram realizados correlação de Pearson e teste para tendências de Mantel-Haenzsel. Um nível de 5% foi definido como estatisticamente significativo. Resultados: De 2008 a 2017, as internações por IC diminuíram 62% (p = 0,004) na Paraíba, e 34% (p = 0,004) no Brasil. A taxa de mortalidade hospitalar aumentou na Paraíba e no Brasil [65,1% (p = 0,006) e 30,1% (p = 0,003), respectivamente], mas a mortalidade hospitalar em números absolutos apresentou uma diminuição significativa somente na Paraíba [37,5% (p = 0,013)], o que foi mantido após a estratificação por idade, exceto para os grupos 15-19, 60-69 e > 80 anos. Observou-se um aumento no período de internação [44% (p = 0,004) na Paraíba e 12,3% (p = 0,004) no Brasil]. De 2008 a 2015, a taxa de mortalidade por IC na população diminuiu 10,7% na Paraíba (p = 0,047) e 7,7% (p = 0,017) no Brasil. Conclusões: Apesar de a taxa de mortalidade por IC estar diminuindo na Paraíba e no Brasil, observou-se um aumento na taxa de mortalidade hospitalar e na duração da internação por IC. Devem ser realizados estudos clínicos em hospitais para serem identificadas as causas dessa tendência de aumento.

Left ventricular assist device recovery: does duration of mechanical support matter?

Heart failure is a widespread condition in the United States that is predicted to significantly increase in prevalence in the next decade. Many heart failure patients are given a left ventricular assist device (LVAD) while they wait for a heart transplant, while those that are not able to undergo a heart transplant may be given an LVAD permanently. However, past studies have observed a small subset of heart failure patients that recovered cardiac function of their native heart after being placed on an LVAD. As a result, some patients have been able to have their LVAD explanted and no longer needed a heart transplant. In this review, we analyzed the data of 15 studies that observed recovery of cardiac function in LVAD patients in order to investigate the effects that duration of LVAD support has on patient outcomes. From our review, we identified that there may be negative consequences of prolonged duration of mechanical support such as myocardial atrophy and abnormal calcium cycling as well as circumstances that may allow for a longer duration of LVAD support such as in patients using a continuous-flow LVAD, non-ischemic cardiomyopathy patients, and the specific pharmacological therapy.

Sex-Specific Outcome Disparities in Patients Receiving Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-analysis.

Continuous-flow left ventricular assist devices (CF-LVADs) decrease mortality and improve quality of life in patients with advanced heart failure (HF). Their widespread utilization has led to concerns regarding increased adverse effects, especially in women. Nevertheless, sex-specific data remain limited. We searched Medline, Embase, Scopus, and the Cochrane Library for publications reporting sex-specific outcomes after CF-LVADs from January 2008 through January 2017. Outcomes were compared under the random-effects model and heterogeneity examined via χ test and I statistics. A total of 10 studies including 4,493 CF-LVAD recipients were included in the analysis (23.5% women). The overall rate of stroke was significantly higher in women (odds ratio [OR] 1.94; 95% confidence interval [CI] 1.32-2.84; p = 0.0007). This was true for ischemic strokes (OR 2.03; 95% CI 1.21-3.42; p = 0.008) and hemorrhagic strokes (OR 2.03; 95% CI 1.21-3.42; p = 0.008). Women were also more likely to develop right HF necessitating right ventricular assist device (RVAD) implantation (OR 2.12; 95% CI 1.08-4.15; p = 0.03). Other adverse events including renal failure, bleeding, and device-related infection were comparable for both genders. The overall mortality while on CF-LVAD was similar in both groups (OR 1.05; 95% CI 0.81-1.36; p = 0.71). Our analysis suggests that women are at greater risk of significant complications such as cerebrovascular events and right HF necessitating RVAD after CF-LVAD implantation. Further research is needed to better understand the mechanisms underlying these sex-specific outcome disparities.

Driveline Infection in Ventricular Assist Devices and Its Implication in the Present Era of Destination Therapy.

Advances in mechanical circulatory support devices provided the technology to develop long-term, implantable left ventricular assist devices as bridge to transplant, destination therapy, and in a lesser group of patients, as bridge to recovery. Despite the benefits from this innovative therapy, with their increased use, many complications have been encountered, one of the most common being infections. With the driveline acting as a portal to the exterior environment, an infection involving this structure is the most frequent one. Because patients with destination therapy are expected to receive circulatory support for a longer period of time, we will focus this review on the risk factors, prevention, and treatment options for driveline infections.

Incidence of Hemolysis in Patients with Cardiogenic Shock Treated with Impella Percutaneous Left Ventricular Assist Device.

Impella assist devices have been increasingly used in cardiogenic shock (CS). This study aims to assess the incidence of hemolysis when Impella support is used longer than 6 hours in CS. We retrospectively studied all patients who required Impella between April 2009 and September 2013. Demographic data and hemolysis indicators were sampled and analyzed using paired t-test. A total of 118 devices were placed and 40 used longer than 6 hours. The average time of support was 86.63 hours, and the 30 and 90 days of survival were 65% and 60%, respectively. After 24 hours of support, the hemoglobin (Hb) decreased significantly despite 17% of patients receiving blood transfusion (p = 0.0001). By the time of removal, 65% of patients were transfused to maintain a Hb of 10 mg/dl (p = 0.0014). The lactate dehydrogenase (LDH) increased to 5,201 U/L (n = 22; p = 0.0096), the bilirubin to 5.6 mg/dl (p = 0.008), and the haptoglobin level was 15.4 mg/dl (n = 25). The cumulative incidence of hemolysis was 62.5%. Hemolysis is a common occurrence in patients with long-term Impella support for CS, evaluated by the persistent decline in Hb and haptoglobin as well as increase in LDH and bilirubin. Strict monitoring of hemolysis parameters at baseline and at frequent intervals is crucial.

Severe bioprosthetic mitral valve stenosis in pregnancy.

A 21-year-old woman in the 16th week of pregnancy was admitted due to acute presentation of severe exertional dyspnea. She had undergone mitral valve replacement (MVR) with bioprosthetic valve for infective endocarditis 2 years ago. She developed congestive heart failure from mitral bioprosthetic valve stenosis due to early structural valve deterioration. She also had severe pulmonary hypertension and underwent a redo MVR using a mechanical valve prosthesis with good maternal outcome but fetal demise. This report brings up the debate about what type of valve should be used in women in reproductive age, and discusses the management of severe mitral stenosis and stenosis of a bioprosthetic valve during pregnancy. Surgical options can almost always be delayed until fetal maturity is achieved and a simultaneous cesarean section can be performed. However, under certain circumstances when the maternal welfare is in jeopardy the surgical intervention is mandatory even before the fetus reaches viability.

Hepatocellular carcinoma to the right ventricle.

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer in the world, but metastatic disease to the heart is rare. We present a case of a 63-year-old man with history of hepatitis C and cirrhosis, which had progressed to HCC. The patient had undergone two prior liver transplantations. He presented to the hospital complaining of worsening lower extremity edema. His exam was also pertinent for jugular venous distension, a 3/6 crescendo-decrescendo murmur, and hepatosplenomegaly. A transthoracic echocardiogram showed a large irregular lobulated mass in the apex of the right ventricle with a mobile pedunculated component. An MRI of the heart revealed a 4.4 × 3.4 × 4.0 cm mass within the right ventricular apex, which was subsequently biopsied and found to be moderately differentiated HCC with myocardial fragments. The patient opted out of any further therapy, or intervention, and was enrolled in hospice care.

An unexpected cause of massive hemolysis in percutaneous left ventricular assist device.

We present the case of a 24 year-old patient that developed massive hemolysis shortly after percutaneous left ventricular assist device, Impella 2.5, was placed. The hemolysis occurred without device alarm while the device was in the correct position. Further investigation of the device revealed fiber wrapped around the tip of the device, as a culprit. This case emphasizes on the special caution applied during device preparation to minimize the possible adverse events.

Combined use of Impella left ventricular assist device and extracorporeal membrane oxygenation as a bridge to recovery in fulminant myocarditis.

Myocarditis may result in cardiogenic shock, and when medical therapy is unable to maintain adequate cardiac output, mechanical circulatory support is indicated. This is the first reported case of a percutaneous left ventricular assist device being used in combination with extracorporeal membrane oxygenation in a patient with biventricular and respiratory failure, as a bridge to recovery.