Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Clinical presentation of cardiac symptoms following treatment with tumor-infiltrating lymphocytes: diagnostic challenges and lessons learned.

BACKGROUND: Treatment with tumor-infiltrating lymphocytes (TILs) is rapidly evolving for patients with solid tumors. Following metastasectomy, TILs (autologous, intratumoral CD4+ and CD8+ T cells with the potential to recognize tumor-associated antigens) are isolated and non-specifically expanded ex vivo in the presence of interleukin-2 (IL-2). Subsequently, the TILs are adoptively transferred to the patients after a preconditioning non-myeloablative, lymphodepleting chemotherapy regimen, followed by administration of high-dose (HD) IL-2. Here, we provide an overview of known cardiac risks associated with TIL treatment and report on seven patients presenting with cardiac symptoms, all with different clinical course and diagnostic findings during treatment with lymphodepleting chemotherapy, TIL, and HD IL-2, and propose a set of clinical recommendations for diagnosis and management of these symptoms. PATIENTS AND METHODS: This single-center, retrospective study included selected patients who experienced TIL treatment-related cardiac symptoms at the Netherlands Cancer Institute. In addition, 12 patients were included who received TIL in the clinical trial setting without experiencing cardiac symptoms, from whom complete cardiac biomarker follow-up during treatment was available [creatine kinase (CK), CK-myocardial band, troponin T and N-terminal pro-B-type natriuretic peptide]. RESULTS: Within our TIL patient population, seven illustrative cases were chosen from the patients who developed symptoms suspected of severe cardiotoxicity: myocarditis, myocardial infarction, peri-myocarditis, atrial fibrillation, acute dyspnea, and two cases of heart failure. An overview of their clinical course, diagnostics carried out, and management of the symptoms is provided. CONCLUSIONS: In the absence of evidence-based guidelines for the treatment of TIL therapy-associated cardiotoxicity, we provided an overview of literature, case descriptions, and recommendations for diagnosis and management to help physicians in daily practice, as the number of patients qualifying for TIL treatment is rapidly increasing.

A randomised comparison of the effect of haemodynamic monitoring with CardioMEMS in addition to standard care on quality of life and hospitalisations in patients with chronic heart failure : Design and rationale of the MONITOR HF multicentre randomised clinical trial.

BACKGROUND: Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. AIMS: To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. METHODS: The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including health care utilisation and formal cost-effectiveness analysis. CONCLUSION: The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672.

Understanding heart failure with preserved ejection fraction: where are we today?

Heart failure with preserved ejection fraction (HFpEF) represents a complex and heterogeneous clinical syndrome, which is increasingly prevalent and associated with poor outcome. In contrast to heart failure with reduced ejection fraction (HFrEF), modern heart failure pharmacotherapy did not improve outcome in HFpEF, which was attributed to incomplete understanding of HFpEF pathophysiology, patient heterogeneity and lack of insight into primary pathophysiological processes. HFpEF patients are frequently elderly females and patients demonstrate a high prevalence of non-cardiac comorbidities, which independently adversely affect myocardial structural and functional remodelling. Furthermore, although diastolic left ventricular dysfunction represents the dominant abnormality in HFpEF, numerous ancillary mechanisms are frequently present, which also negatively impact on cardiovascular reserve. Over the past decade, clinical and translational research has improved insight into HFpEF pathophysiology and the importance of comorbidities and patient heterogeneity. Recently, a new paradigm for HFpEF was proposed, which states that comorbidities drive myocardial dysfunction and remodelling in HFpEF through coronary microvascular inflammation. Regarding the conceptual framework of HFpEF treatment, emphasis may need to shift from a 'one fits all' strategy to an individualised approach based on phenotypic patient characterisation and diagnostic and pathophysiological stratification of myocardial disease processes. This review will describe these novel insights from a pathophysiological standpoint.

NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system?

Reactive oxygen species play an important role in a variety of (patho)physiological vascular processes. Recent publications have produced evidence of a role for putative non-phagocyte NADP oxidase(s) in the vascular production of reactive oxygen species. In the present review, we discuss the detection of the different components of NADP oxidase(s) in the vascular system, together with the putative role of reactive oxygen species produced by vascular NADPH oxidase(s), in both in vitro and in vivo studies.