Natrecor (nesiritide) / J&J - LARVOL DELTA

Limb-girdle muscular dystrophy type 2Y with cardiac involvement in a 23-year-old woman: a case report. (PubMed, Eur Heart J Case Rep) - "During hospitalisation for acute HF, she was treated with intravenous diuretic, nesiritide, levosimendan and guideline-directed medical therapy (GDMT). Early diagnosis and tailored management, including GDMT for HF, are critical for improving patient outcomes. Additionally, this case highlights the importance of close cardiac monitoring in LGMD subtypes prone to cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Muscular Dystrophy • Myositis

Pathophysiology and clinical use of agents with vasodilator properties in acute heart failure. A scientific statement of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). (PubMed, Eur J Heart Fail) - "Other vasodilators, such as nesiritide, lead to balanced vasodilatation in the arteries and veins, decreasing left ventricular afterload and preload...In parallel with the development of novel vasodilators, changing the design of clinical trials for AHF to consider phenotype diversity of AHF patients remains an unmet need. New randomized clinical trials should particularly focus on subgroups that may mechanistically derive benefit from vasodilators, which may entail moving enrolment of patients to clinical settings close to moment of decompensation, such as the emergency department."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Respiratory Diseases

Mechanism(s) Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 1 (clinicaltrials.gov) - P4 | N=4 | Terminated | Sponsor: Vanderbilt University Medical Center | N=32 ➔ 4 | Trial completion date: Dec 2025 ➔ Dec 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Dec 2024; An alternative study was developed to replace this study.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Hypertension

Comparative efficacy of different drugs in acute heart failure with renal dysfunction: a systematic review and network meta-analysis. (PubMed, Front Cardiovasc Med) - "After screening 30,697 citations, 13 studies (21,745 patients) were included, and drugs including nesiritide, dopamine, tolvaptan, levosimendan, dobutamine, furosemide, and spirolactone, and high dose of diuretics (HDD, furosemide, and spirolactone) were estimated. Hence, HDD and levosimendan may be optimal agents in the treatment of AHF with renal dysfunction. PROSPERO, identifier (CRD42023454616)."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction. (PubMed, Circ Heart Fail) - "Compared with a reference model, which included sex, ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) score, history of HF and NT-proBNP (N-terminal pro-B-type natriuretic peptide), the 5-mRNA signature had a better discrimination capability, with an increased area under the curve from 0.696 to 0.813 in the test set and from 0.712 to 0.848 in the validation set...The net reclassification improvement and integrated discrimination improvement indicated that the composite model significantly improved patient classification compared with the reference model in both sets (P<0.001). The 5-mRNA signature is a promising predictive tool for 1-year all-cause death and shows improved prognostic power over the established risk scores and NT-proBNP in patients with heart failure with preserved ejection fraction."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Mechanism(s) Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 1 (clinicaltrials.gov) - P4 | N=32 | Active, not recruiting | Sponsor: Vanderbilt University Medical Center | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

Metabolic Effects of Natriuretic Peptide Hormones (clinicaltrials.gov) - P4 | N=5 | Terminated | Sponsor: VA Office of Research and Development | N=14 ➔ 5 | Active, not recruiting ➔ Terminated; Study drug no longer available

Enrollment change • Trial termination • Cardiovascular • Genetic Disorders • Obesity

Prognostic Significance of Blood Pressure at Rest and after Performing the Six-Minute Walk Test in Patients with Acute Heart Failure. (PubMed, Am J Hypertens) - "Higher BP levels and BP ratios immediately after 6MWT conferred lower risk of adverse health outcomes. Our observations highlight that 6MWT-related BP level and response may refine risk estimates in patients hospitalized AHF and may help further investigation for the development of HF preventive strategies."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Common Variants on FGD5 Increase Hazard of Mortality or Rehospitalization in Patients With Heart Failure From the ASCEND-HF Trial. (PubMed, Circ Heart Fail) - P3 | "In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in FGD5 were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether FGD5 could be a therapeutic target."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure

Investigator-Reported versus Adjudicated Clinical Events for Worsening Heart Failure (AHA 2022) - " The ASCEND-HF trial compared nesiritide vs. placebo among patients hospitalized for HF, regardless of ejection fraction, and adjudicated endpoints through 30-day follow-up... CEC and trial investigators had modest rates of agreement for characterizing WHF death and high rates of agreement for WHF rehospitalization. Multiple patient factors were associated with CEC-investigator discordance and levels of agreement for WHF endpoints varied across geographic regions."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Metabolic Effects of Natriuretic Peptide Hormones (clinicaltrials.gov) - P4 | N=14 | Active, not recruiting | Sponsor: VA Office of Research and Development | Trial completion date: Jun 2023 ➔ Feb 2024 | Trial primary completion date: Jan 2023 ➔ Jul 2023

Trial completion date • Trial primary completion date • Cardiovascular • Genetic Disorders • Obesity

The First Dedicated Comprehensive Heart Failure Program in the US: the Division of Circulatory Physiology at Columbia Presbyterian (1992-2004). (PubMed, J Card Fail) - "The major research achievements of the Division included: (1) the development of beta-blockers for heart failure, from initial hemodynamic assessments to proof-of-concept studies to large-scale international trials; (2) the development and definitive assessment of flosequinan, amlodipine and endothelin antagonists; (3) initial clinical trials and concerns with nesiritide; (4) large-scale trials evaluating dosing of angiotensin converting-enzyme inhibitors and the efficacy and safety of neprilysin inhibition; (5) identification of key mechanisms in heart failure, including neurohormonal activation, microcirculatory endothelial dysfunction, deficiencies in peripheral vasodilator pathways, noncardiac factors in driving dyspnea, and the first identification of subphenotypes of heart failure and a preserved ejection fraction; (6) the development of a volumetric approach to the assessment of myocardial shortening; (7) conceptualization and early studies of cardiac..."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Disease • Transplant Rejection • Transplantation

Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. (PubMed, J Card Fail) - "The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. (PubMed, Eur J Heart Fail) - "The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Prognostic value of Growth differentiation factors 15 in Acute heart failure patients with preserved ejection fraction. (PubMed, ESC Heart Fail) - "In hospitalized patients with HFpEF, GDF-15 measured within 48 h of admission is a strong independent biomarker for 1 year HF readmission and even better than NT-proBNP. GDF-15 combined with the traditional indicators provided incremental prognostic value in this population."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • GDF15 • NPPB

Comparing Patient Reported Outcomes and New York Heart Association Class Among Patients Hospitalized for Heart Failure (AHA 2022) - "How this clinician-reported classification compares with patient-reported outcomes among patients hospitalized for HF is unclear. ASCEND-HF was a global randomized trial comparing nesiritide versus placebo among patients hospitalized for HF, irrespective of EF... In patients hospitalized for HF, the majority exhibited discordance between the clinician-reported NYHA class and patient-reported health status. Discordance was more often due to worse NYHA class. Multiple patient factors were independently associated with higher likelihood of moderate-severe discordance."

Clinical • Patient reported outcomes • Cardiovascular • Congestive Heart Failure • Heart Failure

Performance of the heart failure risk scores in predicting 1 year mortality and short-term readmission of patients. (PubMed, ESC Heart Fail) - "Currently assessed risk scores have limited clinical utility, with fair accuracy and calibration in assessing patients' 1 year risk of death and poor accuracy in assessing patients' risk of readmission. There is a need to incorporate more patient-level information, use more advanced technologies, and develop models for different subgroups of patients to achieve more practical, innovative, and accurate risk assessment tools."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Comparing New York Heart Association Class and Patient-Reported Outcomes Among Patients Hospitalized for Heart Failure. (PubMed, Circ Heart Fail) - P3 | " ASCEND-HF was a global randomized trial comparing nesiritide versus placebo among patients hospitalized for HF, irrespective of ejection fraction (EF)...Multiple patient factors were independently associated with moderate-severe discordance, and patients who perceived their health status as worse than the clinician's perception had higher mortality. Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique Identifier: NCT00475852."

Journal • Patient reported outcomes • Cardiovascular • Congestive Heart Failure • Heart Failure

Efficacy of pharmacologic therapies in patients with acute heart failure: A network meta-analysis. (PubMed, Front Pharmacol) - " After screening 14,888 citations, 23 RCTs (17,097 patients) were included, focusing on nesiritide, placebo, serelaxin, rhANP, omecamtiv mecarbil, tezosentan, KW-3902, conivaptan, tolvaptan, TRV027, chlorothiazide, metolazone, ularitide, relaxin, and rolofylline. No drug was superior to the other drugs for the secondary outcomes and safety outcomes. Current drugs for AHF show similar efficacy and safety."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

"Xigris/activated protein C in sepsis and Natrecor come to mind 🙈🙉🙊" (@doublenaught00)

Infectious Disease • Septic Shock

"J&J's Scios to plead guilty, pay $85M in Natrecor case | ⁦@FiercePharma⁩ https://t.co/1b22ink988" (@FuerstIttleman)

Metabolic Effects of Natriuretic Peptide Hormones (clinicaltrials.gov) - P4 | N=14 | Active, not recruiting | Sponsor: VA Office of Research and Development | N=50 ➔ 14

Enrollment change • Cardiovascular • Genetic Disorders • Obesity

Role of Vasodilator Therapy in Acute Heart Failure. (PubMed, Cureus) - "These four trials have evaluated the efficacy of different types of vasodilators such as nesiritide, ulatritide, and serelaxin in the setting of AHF. Also, we compared comprehensive vasodilator therapy versus standard therapy to see if there is any effect on mortality and re-hospitalization."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Evidence based review of management of cardiorenal syndrome type 1. (PubMed, World J Methodol) - "Six clinical studies have been included in this review that include different treatment strategies such as nesiritide, dopamine, levosimendan, tolvaptan, dobutamine, and ultrafiltration. Treatment strategies for CRS type 1 are derived based on the current literature. Early recognition and treatment of CRS can improve the outcomes of the patients significantly."

Journal • Review • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Infectious Disease • Inflammation • Nephrology • Renal Disease

[VIRTUAL] Incremental efficacy of medical therapy for chronic heart failure with a reduced ejection fraction: a systematic review and network meta-analysis (HEART FAILURE 2021) - "Background Over the last three decades, the step-wise addition of new drugs, including beta-blockers (BB), angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), ivabradine (IVA), and angiotensin receptor neprilysin inhibitor (ARNI), has improved the outcomes of heart failure with reduced ejection fraction (HFrEF)...The risk of the adverse outcomes was also lower with IVA or vericiguat (VERI) on top of BB+ACEi+MRA than with triple neurohormonal inhibition alone, while it was comparable with nesiritide or omecamtiv mecarbil (OM) in addition to BB+ACEi+MRA vs. BB+ACEi+MRA (Figure 2). Conclusions The reduction in mortality and hospitalization in HFrEF attained by medical therapy is incremental and further enhance by at least some of the most recent drugs. According to RCTs, state-of-the-art pharmacotherapy diminishes by about 65% the risk of death and by about 75% the one of HHF in HFrEF patients."

Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure