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Background: Pulmonary hypertension associated with left heart disease (PH-LHD) prevalence ranges significantly across studies with limited real-world evidence., Objectives: To investigate the prevalence and prognostic influence of PH-LHD in a nationwide sample., Methods: Using the 2018 US Nationwide Inpatient Sample we calculated the prevalence of PH across heart failure (HF), cardiomyopathies, aortic, and mitral valve disease. We used logistic regression to assess the impact of PH on LHD and to find significant contributors to in-hospital mortality in the PH-LHD population., Results: Among 6,270,625 hospitalizations with LHD, 801,535 (12.8 %) had a secondary PH diagnosis. PH-LHD prevalence was 17.2 % in HF with preserved ejection fraction (HFpEF), 11.8 % in HF with reduced ejection fraction (HFrEF), 16.8 % in dilated cardiomyopathy, 12.6 % in hypertrophic cardiomyopathy, 18.7 % in mitral regurgitation, 28.5 % in mitral stenosis, 13.5 % in aortic stenosis, and 13.9 % in aortic regurgitation. PH was associated with increased in-hospital mortality in HFpEF (OR 1.23; 95%CI 1.17-1.28), hypertrophic cardiomyopathy (1.42; 1.06-1.89), mitral regurgitation (1.17; 1.07-1.28), and aortic stenosis (1.14; 1.04-1.26), but not in HFrEF (1.04; 0.99-1.10), or dilated cardiomyopathy (1.13; 0.99-1.29). Among PH-LHD, in-hospital mortality was associated with age, atrial fibrillation/flutter, cancer, and acute cardiac (acute right HF, myocardial infarction, ventricular arrhythmia), or extra-cardiac (stroke, sepsis, pneumonia, acute renal failure, venous thromboembolism) diagnoses., Conclusion: In a nationwide inpatient analysis the prevalence of PH-LHD was lower than previously reported indicating reduced recognition of this disease in real world clinical practice. The diagnosis of PH-LHD was associated with worse fatality rates across all forms of LHD, except for HFrEF., Competing Interests: Declaration of competing interest LH received lecture/consultant fees from MSD and Actelion, outside the submitted work. SVB has served in unpaid trial activities for Abbott, Edwards Lifesciences, and University of Göttingen (IIT); and has served on an advisory or Speakers Bureau for Abbott Cardiovascular, Bioventrix, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, and Neochord. PL has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, and ReCor, honoraria from Edwards Lifesciences, Abbott Medical, Innoventric, ReCor, Boehringer Ingelheim, Daiichi Sankyo and has stock options with Innoventric. SR reports grants or contracts from Actelion, AstraZeneca, Bayer, Janssen, and Novartis; consulting fees from Abbott, Acceleron, Actelion, Bayer, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor; payment or honoraria from Actelion, Bayer, BMS, Ferrer, GSK, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor. SVK reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol Myers Squibb/Pfizer. GG has received speaker or consulting fees from ELPEN Pharmaceuticals, Galenica, GlaxoSmithKline, and Janssen Pharmaceutical Companies of Johnson & Johnson and MSD, outside the submitted work. The rest of the authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension., Methods: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline., Results: Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P =0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P =0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group., Conclusions: The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points., Registration: URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595., Competing Interests: Dr Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, AOP Health, Bayer, Ferrer, GossamerBio, Janssen, Keros, and MSD. Max Wissmüller has received lecture fees from Janssen. Hanno Leuchte has received fees for consultations and/or lectures from Acceleron, Jansse-Cilag, Bayer, Boehringer-Ingelheim, Ferrer, MSD, and Pfizer. Michael Halank has received fees for lectures and/or consultations from AstraZeneca, Janssen-Cilag, and MSD. In addition, he has received support for attending meetings and/or travel from AOP Health and Janssen-Cilag. Hans-Jürgen Seyfarth has received fees for lectures and/or consultations from Janssen-Cilag and MSD. Stephan Baldus has received fees for lectures and/or consultations from Abbott, Edwards, Jenavalve, AstraZeneca, Bayer, Daiicho Sankyo, and Amgen, as well as research grants from Abbott, AstraZeneca, and Daiichi Sankyo. Johann Bauersachs has received fees for lectures and/or consultations from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardior, Corvia, CVRx, Edwards, Norgine, Novartis, Pfizer, Roche and Vifor. In addition, institutional grants have been provided by Abiomed, CVRx, Norgine, Roche, and Zoll. He holds patents for microRNA and downstream targets for diagnostics and therapeutic purposes (PCT/EP2007/008772 and PCT/EP2009/051986). Michael Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project No. 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor, Servier and Vifor. Hossein-Ardeschir Ghofrani has received honoraria for consultations and/or speaking at conferences from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis. He is member of the Advisory Board for Acceleron, Bayer HealthCare AG, Pfizer, GSK, Actelion, Lilly, Merck, Encysive, and Ergonex. He has also received governmental grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, State Government of Hessen, and the German Ministry for Education and Research. Stavros Konstantinides reports personal lecture/advisory fees and research grants to his institution from Bayer AG, Boston Scientific, Daiichi-Sankyo, LumiraDx, and Penumbra, as well as personal lecture/advisory fees from MSD and Pfizer–Bristol-Myers Squibb. Karen M. Olsson has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Ferrer, GSK, Janssen, MSD, Pfizer, and United Therapeutics. Rolf Wachter has received fees for lectures and/or consultation from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, Novartis, Pfizer, Pharmacosmo, Sciarc, Servier, and Vifor. His institution has received research grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Union, and Medtronic. Carolyn S.P. Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from NovoNordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corp, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and non–executive director of Us2.ai. Stephan Rosenkranz has received fees for lectures and/or consultations from Abbott, Acceleron, Actelion, Aerovate, AOP, AstraZeneca, Bayer, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, and United Therapeutics. His institution has received research grants from Actelion, AstraZeneca, Bayer, Janssen, and Lempo. The other authors report no conflicts.

Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF., (© 2024 European Society of Cardiology.)

Aims: In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months., Methods and Results: SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%., Conclusions: Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality., Aims: The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD)., Methods: This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation., Design: The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies., Processes: Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs., Assessments: Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status., Discussion of the Design: The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts., Conclusion: The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain., (© 2024. The Author(s).)

Patients with left heart disease (LHD) often display pulmonary hypertension (PH), which impacts morbidity and mortality. The pathophysiology of PH is complex and entails pulmonary congestion due to elevated left-sided filling pressures, pulmonary vasoconstriction as well as vascular remodeling. The recent ESC/ERS Guidelines on pulmonary hypertension updated the hemodynamic definitions of pulmonary hypertension in general, and the subclassification of post-capillary PH. This review summarizes recent advances in the diagnostic work-up and management strategies of PH associated with LHD. Specifically, we summarize revisited hemodynamic definitions and the characteristics of isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). Furthermore, we review the current knowledge on the pathogenesis of PH-LHD, the prognostic relevance of hemodynamic parameters, and the management strategies, differentiating between treatment of the underlying left heart disease and therapies targeting the pulmonary circulation. The article emphasises the need for precise diagnostic work-up and individualized treatment strategies in patients with PH-LHD., Competing Interests: MW: Vortragshonorare von Janssen; JA: Vortragshonorare von Janssen und MSD; CH: Honorare für Vorträge und/oder Beratertätigkeiten: Actelion, Bayer, MSD, Pfizer; SR: Honorare für Vorträge und/oder Beratertätigkeiten: Abbott, Acceleron, Actelion, Aerovate, Altavant, AOP Orphan, AstraZeneca, Bayer, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, United Therapeutics, Vifor; Forschungsunterstützung an Institution: Actelion, AstraZeneca, Bayer, Janssen; JD, LO, TT und SB: keine Interessenkonflikte im Zusammenhang mit diesem Artikel., (Thieme. All rights reserved.)

Pulmonary hypertension (PH) is a common condition in patients with left heart disease (LHD) that is highly relevant for morbidity and mortality. While post-capillary in nature, the pathophysiology of PH in patients with LHD (heart failure/cardiomyopathy, valvular heart disease; other: congenital/acquired) is complex, and decisions about management strategies are challenging. Recently, the updated European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of PH revisited hemodynamic definitions and the sub-classification of post-capillary PH, and provided numerous new recommendations on the diagnosis and management of PH associated with various types of LHD. Here, we review several novel aspects that focus on: (a) updated hemodynamic definitions, including the distinction between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH); (b) the pathogenesis of PH-LHD, considering various components contributing to PH, such as pulmonary congestion, vasoconstriction, and vascular remodeling; (c) the prognostic relevance of PH and hemodynamic markers; (d) the diagnostic approach to PH-LHD; (e) management strategies in PH-LHD, distinguishing between targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function. In conclusion, precise clinical and hemodynamic characterization and detailed phenotyping are essential for prognostication and the management of patients with PH-LHD., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aims: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults with pulmonary arterial hypertension (PAH)., Methods and Results: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. This included (i) the identification of key domains of care for the management of PAH, (ii) the proposal of candidate QIs following systematic review of the literature, and (iii) the selection of a set of QIs using a modified Delphi method. The process was undertaken in parallel with the writing of the 2022 ESC/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension and involved the Task Force chairs, experts in PAH, Heart Failure Association (HFA) members and patient representatives. We identified five domains of care for patients with PAH: structural framework, diagnosis and risk stratification, initial treatment, follow-up, and outcomes. In total, 23 main and one secondary QIs for PAH were selected., Conclusion: This document presents the ESC QIs for PAH, describes their development process and offers scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and improve patient outcomes., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose of Review: Since CRS is critically dependent on right heart function and involved in interorgan crosstalk, assessment and monitoring of both right heart and kidney function are of utmost importance for clinical outcomes. This systematic review aims to comprehensively report on novel diagnostic and therapeutic paradigms that are gaining importance for the clinical management of the growing heart failure population suffering from CRS., Recent Findings: Cardiorenal syndrome (CRS) in patients with heart failure is associated with poor outcome. Although systemic venous congestion and elevated central venous pressure have been recognized as main contributors to CRS, they are often neglected in clinical practice. The delicate hemodynamic balance in CRS is particularly determined by the respective status of the right heart. The consideration of hemodynamic and CRS profiles is advantageous in tailoring treatment for better preservation of renal function. Assessment and monitoring of right heart and renal function by known and emerging tools like renal Doppler ultrasonography or new biomarkers may have direct clinical implications., (© 2022. The Author(s).)

Aim: The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) investigated safety and efficacy of pulmonary artery pressure (PAP)-guided remote patient management (RPM) in New York Heart Association (NYHA) class III outpatients with at least one heart failure hospitalization (HFH) during the previous 12 months. This pre-specified subgroup analysis investigated whether RPM effects depended on presence and subtype of pulmonary hypertension (PH)., Methods and Results: In 106/234 MEMS-HF participants, Swan-Ganz catheter tracings obtained during sensor implant were available for off-line manual analysis jointly performed by two experts. Patients were classified into subgroups according to current PH definitions. Isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH) were present in 38 and 36 patients, respectively, whereas 31 patients had no PH. Clinical characteristics were comparable between subgroups, but among patients with PH pulmonary vascular resistance was higher (p = 0.029) and pulmonary artery compliance lower (p = 0.003) in patients with CpcPH. During 12 months of PAP-guided RPM, all PAPs declined in IpcPH and CpcPH subgroups (all p < 0.05), whereas only mean and diastolic PAP decreased in patients without PH (both p < 0.05). Improvements in post- versus pre-implant HFH rates were similar in CpcPH (0.639 events/patient-year; hazard ratio [HR] 0.37) and IpcPH (0.72 events/patient-year; HR 0.45) patients. Participants without PH benefited most (0.26 events/patient-year; HR 0.17, p = 0.04 vs. IpcPH/CpcPH patients). Quality of life and NYHA class improved significantly in all subgroups., Conclusions: Outpatients with NYHA class III symptoms with at least one HFH during 1 year pre-implant benefitted significantly from PAP-guided RPM during post-implant follow-up irrespective of presence or subtype of PH at baseline., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Remote monitoring of patients with New York Heart Association (NYHA) functional class III heart failure (HF) using daily transmission of pulmonary artery (PA) pressure values has shown a reduction in HF-related hospitalizations and improved quality of life in patients., Objectives: PASSPORT-HF is a prospective, randomized, open, multicenter trial evaluating the effects of a hemodynamic-guided, HF nurse-led care approach using the CardioMEMS™ HF-System on clinical end points., Methods and Results: The PASSPORT-HF trial has been commissioned by the German Federal Joint Committee (G-BA) to ascertain the efficacy of PA pressure-guided remote care in the German health-care system. PASSPORT-HF includes adult HF patients in NYHA functional class III, who experienced an HF-related hospitalization within the last 12 months. Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy. Patients will be randomized centrally 1:1 to implantation of a CardioMEMS™ sensor or control. All patients will receive post-discharge support facilitated by trained HF nurses providing structured telephone-based care. The trial will enroll 554 patients at about 50 study sites. The primary end point is a composite of the number of unplanned HF-related rehospitalizations or all-cause death after 12 months of follow-up, and all events will be adjudicated centrally. Secondary end points include device/system-related complications, components of the primary end point, days alive and out of hospital, disease-specific and generic health-related quality of life including their sub-scales, and laboratory parameters of organ damage and disease progression., Conclusions: PASSPORT-HF will define the efficacy of implementing hemodynamic monitoring as a novel disease management tool in routine outpatient care., Trial Registration: ClinicalTrials.gov; NCT04398654, 13-MAY-2020., (© 2022. The Author(s).)

Aims: Implantable pulmonary artery pressure (PAP) sensors have been shown to reduce heart failure hospitalizations (HFH) in selected patients. The goal of this study was to evaluate the safety and efficacy of a novel wireless PAP monitoring system in patients with heart failure (HF)., Methods and Results: This is a prospective, multi-centre, open-label, single-arm trial evaluating the safety and efficacy of the Cordella™ PA Sensor System including the comprehensive Cordella™ Heart Failure System (CHFS) in patients with New York Heart Association (NYHA) Class III heart failure with a heart failure hospitalization and/or increase of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) within 12 months of enrolment. The primary efficacy endpoint was the accuracy of PA sensor mean PAP measurements, compared with fluid-filled catheter mean PAP measurements obtained by standard right heart catheterization (RHC) at 90 days post-implant, assessed in all patients with a successful implant. The primary safety endpoint was freedom from adverse events associated with use of the Cordella PA Sensor System through 30 days post-implant, assessed in all patients who entered the cath lab for PA sensor implant. The PA sensor was successfully implanted in 70 patients. Equivalence between the PA sensor and RHC for mean pulmonary artery pressures was excellent with measurements confined within the equivalence bounds of -4.0 to 4.0 mmHg (mean PAP: 0.0 to 2.9 mmHg, P = 0.003). The device safety profile was excellent with 98.6% freedom from Device System Related Complications, defined as invasive treatment, device explant or death. There were no pressure sensor failures. Patients' adherence to daily measurement transmissions of PAP and vital signs was 94%., Conclusions: This trial supports the safety and efficacy of the Cordella PA Sensor System and in conjunction with the CHFS enables comprehensive HF management in NYHA class III heart failure patients., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing and there are limited data on response to PAH-targeted therapies in this population. These post hoc analyses explored the effect of selexipag in PAH patients with cardiovascular comorbidities in the GRIPHON study., Methods and Results: Randomized patients (n = 1156) were classified using three methods: (i) by subgroups defined according to previously published comorbidity count and restrictive haemodynamic criteria: Subgroup A (<3 comorbidities and haemodynamic criteria met; n = 962) and Subgroup B (≥3 comorbidities and/or haemodynamic criteria not met; n = 144); comorbidities included body mass index ≥30 kg/m 2 , essential hypertension, diabetes, history of coronary artery disease; (ii) by number of comorbidities, with addition of atrial fibrillation (0, 1, 2, 3, 4, or 5); (iii) by presence of individual comorbidities. Selexipag to placebo hazard ratios (HR) and 95% confidence intervals (CI) for morbidity/mortality (primary composite endpoint) were estimated using Cox regression adjusting selexipag effect for baseline covariates. Approximately half of the patients in GRIPHON (n = 584; 50.5%) had comorbidities. Selexipag reduced the risk of a morbidity/mortality event compared with placebo in both Subgroup A (HR 0.66, 95% CI 0.53, 0.82) and Subgroup B (HR 0.50, 95% CI 0.26, 0.96), with no evidence of an inconsistent treatment effect between subgroups (interaction p = 0.432). Consistent results were observed in analyses by number and by specific type of comorbidity., Conclusion: Selexipag reduces the risk of a morbidity/mortality event vs. placebo irrespective of patient comorbidity status, suggesting that comorbidity status does not influence the treatment effect of selexipag., (© 2021 Actelion Pharmaceuticals Ltd and Janssen Pharmaceuticals Company of Johnson & Johnson. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose of Review: Pulmonary hypertension is a common phenomenon in heart failure patients that is highly relevant for morbidity and outcome. Although postcapillary in nature, the pathophysiology of pulmonary hypertension in patients with heart failure with reduced or preserved ejection fraction is complex, and decisions about management strategies remain challenging., Recent Findings: Recently, the hemodynamic definitions and subclassification of postcapillary pulmonary hypertension have been revisited. The distinction between isolated postcapillary pulmonary hypertension (IpcPH) and combined post and precapillary pulmonary hypertension (CpcPH) and their definition are essential. Novel data on the prognostic impact of hemodynamic variables and right ventricular function highlight the importance of cardiopulmonary interaction in patients with left-sided heart failure (LHF). Furthermore, the impact of management strategies including medical therapy, remote hemodynamic monitoring, and interventional approaches on hemodynamics and outcome has recently been investigated. Here, we critically review recent developments and future considerations in this field, and highlight distinct treatment strategies targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function., Summary: Detailed hemodynamic characterization and proper phenotyping are essential for prognostication and the management of patients with pulmonary hypertension associated with LHF, both in clinical practice and when addressing research questions.

Aims: Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)-guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland., Methods and Results: A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP-guided HF management. One-year rates of freedom from device- or system-related complications and from sensor failure (co-primary outcomes) were 98.3% [95% confidence interval (CI) 95.8-100.0] and 99.6% (95% CI 97.6-100.0), respectively. Survival rate was 86.2%. For the 12 months post- vs. pre-implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient-year; hazard ratio 0.38, 95% CI 0.31-0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9-item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001)., Conclusion: Haemodynamic-guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician-directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to harbor high morbidity and mortality. The main consequence of PH is right-sided heart failure which causes a complex clinical syndrome affecting multiple organ systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal muscle, as well as the endocrine, immune, and autonomic systems. Interorgan crosstalk and interdependent mechanisms include hemodynamic consequences such as reduced organ perfusion and congestion as well as maladaptive neurohormonal activation, oxidative stress, hormonal imbalance, and abnormal immune cell signaling. These mechanisms, which may occur in acute, chronic, or acute-on-chronic settings, are common and precipitate adverse functional and structural changes in multiple organs which contribute to increased morbidity and mortality. While the systemic character of PH and right-sided heart failure is often neglected or underestimated, such consequences place additional burden on patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the current state-of-the-art understanding of the systemic consequences of PH and right-sided heart failure on multiple organ systems, focusing on self-perpetuating pathophysiological mechanisms, aspects of increased susceptibility of organ damage, and their reciprocal impact on the course of the disease.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coincide in a significant number of patients. Recent population-based registries suggest that spirometry is largely underused in patients with HF to diagnose comorbid COPD and that patients with COPD frequently do not receive the recommended beta-blocker (BB) treatment. This state-of-the-art review summarizes: 1) current challenges in the implementation of recommended spirometry for COPD diagnosis in patients with HF; and 2) current underuse and underdosing of BBs in patients with HF and COPD despite guideline recommendations. Open issues in the therapeutic management of patients with HF and COPD are discussed in the third section, including the use of the nonselective BB carvedilol, target BB doses in patients with HF and COPD, BB and bronchodilator management during HF hospitalization with and without COPD exacerbation, and the use of BBs in patients with COPD with right HF or free from cardiovascular disease. The whole scenario described herein advocates for a bipartisan initiative to drive immediate attention to the translation of guideline recommendations into clinical practice for patients with HF with co-occurring COPD., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Pulmonary hypertension (PH) is a frequent hemodynamic condition that is highly prevalent in patients with heart failure and reduced (HFrEF) or preserved ejection fraction (HFpEF). Irrespective of left ventricular EF, the presence of PH and right ventricular (RV) dysfunction are highly relevant for morbidity and mortality in patients with heart failure. While elevated left-sided filling pressures and functional mitral regurgitation primarily lead to post-capillary PH, current guidelines and recommendations distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH), the latter being defined by a pulmonary vascular resistance (PVR) of ≥3 Wood units. Here, we describe the pathophysiology and clinical relevance of these distinct entities, and report on the diagnostic work-up including remote pulmonary artery pressure (PAP) monitoring. Furthermore, we highlight strategies to manage PH and improve RV function in heart failure, which may include optimized management of HFrEF and HFpEF (medical and interventional), sufficient volume control, catheter-based mitral valve repair, and-in selected cases-targeted PH therapy. In this context, we also highlight gaps in evidence and the need for further research.

Objective: Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and CpcPH., Methods: In 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH who were treated with a PDE5i for at least 12 months, the therapeutic effect on 6-minute walk distance (6MWD), WHO functional class (FC), NTproBNP levels, right ventricular function, and hospitalization rates was evaluated., Results: Patients' mean age was 73 ± 9 years, and comorbidities were frequent (78% hypertension, 58% atrial fibrillation, 35% diabetes). Initially, 38 patients (95%) were in WHO-FC III and 2 patients (5%) in WHO-FC II. Prior to PDE5i initiation, mean PAPm was 46.2 ± 10.3 mmHg, PAWP 21.2 ± 4.7 mmHg, DPG 5.5 ± 7.2 mmHg, and PVR 6.2 ± 3.0 WU. After 12 months of PDE5i therapy, the 6MWD increased from initially 277 ± 17 to 340 ± 18 m (p < 0.001), and the proportion of patients in WHO-FC I/II increased from 5% to 37.5%. NTproBNP levels decreased by 33% (p = 0.004), and TAPSE improved from 16.8 ± 0.7 mm at baseline to 18.2 ± 0.6 mm (p = 0.01). The rate of HF-associated hospitalizations was substantially lower in the 12 months post PDE5i initiation compared to the prior 12 months. The DPG had no impact on the response to therapy. No deaths occurred, and typical side effects of PDE5i were observed., Conclusion: These data indicate that at least a subset of precisely characterized patients with HFpEF and CpcPH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub-population is warranted., (Copyright © 2018. Published by Elsevier B.V.)

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH associated with left heart disease. In this context, the European Guidelines point out that the drugs currently approved to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, sGC stimulators) have not sufficiently been investigated in other forms of PH. However, despite the lack of respective efficacy data, an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. In that sense, the distinction between isolated post-capillary pulmonary hypertension (IpcPH) and combined post- and pre-capillary pulmonary hypertension (CpcPH) and their proper definition may be of particular relevance. The detailed results and recommendations of the working group on PH associated with left heart disease, which were last updated in the spring of 2018, are summarized in this article., (Copyright © 2018. Published by Elsevier B.V.)

Background: Wireless monitoring of pulmonary artery (PA) pressures with the CardioMEMS HF™ system is indicated in patients with New York Heart Association (NYHA) class III heart failure (HF). Randomized and observational trials have shown a reduction in HF-related hospitalizations and improved quality of life in patients using this device in the United States., Objective: MEMS-HF is a prospective, non-randomized, open-label, multicenter study to characterize safety and feasibility of using remote PA pressure monitoring in a real-world setting in Germany, The Netherlands and Ireland., Methods and Results: After informed consent, adult patients with NYHA class III HF and a recent HF-related hospitalization are evaluated for suitability for permanent implantation of a CardioMEMS™ sensor. Participation in MEMS-HF is open to qualifying subjects regardless of left ventricular ejection fraction (LVEF). Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy as tolerated. The study will enroll 230 patients in approximately 35 centers. Expected duration is 36 months (24-month enrolment plus ≥ 12-month follow-up). Primary endpoints are freedom from device/system-related complications and freedom from pressure sensor failure at 12-month post-implant. Secondary endpoints include the annualized rate of HF-related hospitalization at 12 months versus the rate over the 12 months preceding implant, and health-related quality of life. Endpoints will be evaluated using data obtained after each subject's 12-month visit., Conclusions: The MEMS-HF study will provide robust evidence on the clinical safety and feasibility of implementing haemodynamic monitoring as a novel disease management tool in routine out-patient care in selected European healthcare systems., Trial Registration: ClinicalTrials.gov; NCT02693691.

Heart failure (HF) is an emerging epidemic associated with significant morbidity and mortality, impaired quality of life and high healthcare costs. Despite major advances in pharmacological and device-based therapies, mortality and morbidity have remained high after an index hospitalization for acute cardiac decompensation (ACD). Randomized trials evaluating various forms of noninvasive telemonitoring failed to improve rehospitalization rates in such patients, possibly due to lack of sensitivity of clinical signs and symptoms as early indicators of HF. Among different implantable monitoring devices, wireless remote monitoring of the pulmonary artery pressure (PAP) with the CardioMEMS™ sensor (Abbott, Sylmar, CA, USA) has been shown to be safe and clinically effective in the USA. The patients showed substantial reductions in hospital admissions for ACD, irrespective of left ventricular pump function, because PAP-guided HF management facilitates timely recognition of incipient ACD and appropriate modification of medical treatment before hospitalization becomes unavoidable. These encouraging results have also stimulated evaluation of this novel technology outside the USA. Studies are also underway in Europe and European HF guidelines recommend considering implantation of a CardioMEMS™ sensor in high-risk patients (class IIb-B). More technologically refined implantable hemodynamic monitoring systems allowing, for example, left atrial pressure measurements, are under development. Promising novel approaches to using information from such devices include continuous hemodynamic monitoring and patient self-management based on the pressure information. Thus, pressure-guided HF management is likely to further expand in the future and may help improve clinical outcomes also in high-risk HF populations.

Aims: Although echocardiography is generally used for the diagnosis of heart failure with preserved ejection fraction (HFpEF), invasive measurements of filling pressures are the gold standard. Studies simultaneously performing echocardiography and invasive measurements in HFpEF are sparse., Methods and Results: Invasive haemodynamic and echocardiographic measurements were simultaneously performed in 98 patients with heart failure New York Heart Association class ≥II, left ventricular ejection fraction (LVEF) ≥45%, and suspected pulmonary hypertension on a previous echocardiogram. Multivariable linear regression analyses were used to establish echocardiographic predictors of pulmonary artery wedge pressure (PAWP), left ventricular end-diastolic pressure (LVEDP), and mean pulmonary arterial pressure (mPAP). Mean age of the study patients was 74 ± 9 years, 68% were female, mean LVEF was 57 ± 5%, and 30% had atrial fibrillation at the time of measurement. Mean PAWP, LVEDP and mPAP were 17.2 ± 6.2, 16.7 ± 5.8 and 30.9 ± 10.2 mmHg, respectively. Isovolumetric relaxation time (IVRT) and left atrial reservoir strain could moderately estimate PAWP (r = 0.656; P < 0.001). LVEDP was only modestly predicted by IVRT and right ventricular wall thickness (r = 0.548; P < 0.001). Surprisingly, a low correlation was found between E/e' mean and PAWP (r = 0.240; P = 0.019), E/e' mean and LVEDP (r = 0.081; P = 0.453). Correlation coefficients were similar in patients with and without atrial fibrillation., Conclusion: In patients with HFpEF, echocardiographic measurements, including the E/e' ratio, have a poor to moderate predictive value for the estimation of invasively acquired LVEDP and PAWP. This limitation should be taken into account for the diagnosis and evaluation of patients with HFpEF., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Pulmonary diseases frequently coexist in heart failure (HF), thus posing diagnostic and therapeutic challenges to cardiologists evaluating patients with overlapping symptoms and implementing recommended HF treatments. There is a growing body of evidence suggesting that pulmonary function testing might provide useful information for the best management of these patients. The availability of portable devices, allowing the measurement of spirometry and lung diffusion capacity for carbon monoxide outside of hospital-based pulmonary lung function laboratories, provides an opportunity for a more widespread use of these measures in the cardiology community, but their interpretation can be challenging. In this work, after a brief review of the methodologies, we discuss the interpretation of pulmonary function testing in patients with HF alone or associated with pulmonary diseases, and its contribution in differentiating cardiac and pulmonary symptoms and preventing acute cardiac decompensation. In addition, we examined recent evidence suggesting how the use of pulmonary function testing may provide independent prognostic information in HF patients with and without pulmonary disorders, and help therapeutic decisions to fill the treatment gap that still exists in HF patients with concomitant pulmonary diseases., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: Pulmonary hypertension (PH) is hemodynamically classified as pre-capillary (as seen in idiopathic pulmonary arterial hypertension [IPAH]) or post-capillary (as seen in heart failure with preserved ejection fraction [HFpEF]). Overlaps between these conditions exist. Some patients present with risk factors for left heart disease but pre-capillary PH, whereas patients with HFpEF may have combined pre- and post-capillary PH., Objectives: This study sought to further characterize similarities and differences among patient populations with either PH-HFpEF or IPAH., Methods: We used registry data to analyze clinical characteristics, hemodynamics, and treatment responses in patients with typical IPAH (<3 risk factors for left heart disease; n = 421), atypical IPAH (≥3 risk factors for left heart disease; n = 139), and PH-HFpEF (n = 226) receiving PH-targeted therapy., Results: Compared with typical IPAH, patients with atypical IPAH and PH-HFpEF were older, had a higher body mass index, had more comorbidities, and had a lower 6-min walking distance, whereas mean pulmonary artery pressure (46.9 ± 13.3 mm Hg vs. 43.9 ± 10.7 mm Hg vs. 45.7 ± 9.4 mm Hg, respectively) and cardiac index (2.3 ± 0.8 l/min/m(2) vs. 2.2 ± 0.8 l/min/m(2) vs. 2.2 ± 0.7 l/min/m(2), respectively) were comparable among groups. After initiation of targeted PH therapies, all groups showed improvement in exercise capacity, functional class, and natriuretic peptides from baseline to 12 months, but treatment effects were less pronounced in patients with PH-HFpEF than typical IPAH; with atypical IPAH in between. Survival rates at 1, 3, and 5 years were almost identical for the 3 groups., Conclusions: Patients with atypical IPAH share features of both typical IPAH and PH-HFpEF, suggesting that there may be a continuum between these conditions., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH including PH owing to left heart disease. The guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) have not been sufficiently investigated in other forms of PH. However, despite the lack of respective efficacy data an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary describes in detail the results and recommendations of the working group which were last updated in October 2011., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Multi-marker risk scores accurately predict prognosis in heart failure patients but calculation is complex., Aims: To compare the prognostic accuracy of the Seattle Heart Failure Survival Score (SHFS) and a model derived from the CHARM programme, with laboratory parameters NT-proBNP and glomerular filtration rate (GFR)., Methods and Results: In a sample of 290 heart failure patients, 39 patients died, 22 were hospitalised with acute heart failure and 4 underwent urgent cardiac transplantation during a median follow-up of 498 days. NT-proBNP, GFR, CHARM and SHFS showed an AUC for an endpoint during 1-year of 0.80, 0.72, 0.79 and 0.69, respectively. The hazard ratio for an endpoint during follow-up was 2.1, 2.6, 1.9 and 2.1 per 1 SD increase of log NT-proBNP and CHARM and per 1 SD decrease of GFR and SHFS, respectively. In multivariate analysis, log NT-proBNP and GFR added independent prognostic information to CHARM and SHFS, respectively., Conclusion: NT-proBNP and GFR independently predicted endpoint-free survival in systolic heart failure patients, with NT-proBNP being superior and equally predictive to the SHFS and CHARM score, respectively. Assessment of both laboratory markers can simplify prognostic stratification, addition to multi-marker scores should be evaluated.

The effect of the antiarrhythmic drug amiodarone on the human myocardial beta-adrenoceptor-G protein-adenylyl cyclase signalling cascade was investigated. Amiodarone had no effect on myocardial G proteins and maximal adenylyl cyclase activity, but acted as a beta-adrenoceptor antagonist. This mechanism might be at least partially responsible for the beneficial effects of the drug in patients with arrhythmia and heart failure.

An abstract of the study "Safe and Reliable Monitoring of Pulmonary Artery Pressure in Heart Failure Patients by the RemonCHF Device," by U. C. Hoppe and colleagues, is presented.