Fabian Kerwagen

BACKGROUND: Previous randomized trials of different remote patient management (RPM) strategies have yielded heterogeneous results in heart failure (HF) populations. It remains unclear whether the effects of RPM are modulated by patient sex and marital status. METHODS: We conducted a secondary analysis of the multicenter, randomized E-INH study (Extended Interdisciplinary Network Heart Failure), which enrolled patients hospitalized with acute systolic HF and a left ventricular ejection fraction ≤40% between 2004 and 2007. Participants were assigned in a 1:1 ratio to receive a telephone-based, nurse-coordinated multidisciplinary RPM strategy (HeartNetCare-HF) plus usual care or usual care alone for 18 months, followed by 42 months of intervention-free follow-up. Patients with available marital status information were included in the present analysis. Flexible parametric Royston-Parmar survival models were used to assess interactions between RPM, sex, and marital status for all-cause death, HF hospitalization, and the composite end point at 18 and 60 months. RESULTS: Of the 1022 randomized participants, 1008 provided information on marital status (mean age, 68±13 years; 28% were women, and 63% were married). Sex and marital status modified the effect of RPM on all-cause death, with a significant 3-way interaction at 18 ( P =0.015) and 60 ( P =0.004) months. At 60 months, all-cause mortality ranged from 28% among married women receiving RPM to almost 60% among unmarried men receiving usual care. The greatest impact of RPM versus usual care on all-cause death was observed among married women: adjusted hazard ratios were 0.32 (95% CI, 0.10–0.98) and 0.44 (0.22–0.88) at 18 and 60 months, respectively. CONCLUSIONS: These findings indicate that the benefits from the RPM strategy HeartNetCare-HF in patients discharged after hospitalization for acute systolic HF were modulated by sex and marital status, both individually and in combination. Future studies are needed to evaluate whether tailoring RPM interventions according to patient sex and marital status optimizes outcomes in patients with HF.

Graphical Abstract For image description, please refer to the figure legend and surrounding text.

Background: Cardiac papillary fibroelastoma are rare benign tumours of the endocardium, often arising from heart valves. Despite their benign histology, papillary fibroelastoma carry high embolic potential and can lead to ischaemic events. In contrast to stroke, ocular embolization including central retinal artery occlusion is a rather rare first manifestation. Case summary: We report a 61-year-old female with sudden painless monocular vision loss due to central retinal artery occlusion. Initial stroke and cardiovascular work-up revealed a very small floating mass (0.6 × 0.4 × 0.2 cm) on the aortic valve by transesophageal echocardiography. The patient underwent successful surgical excision, with histopathology confirming papillary fibroelastoma. Discussion: Central retinal artery occlusion as a primary manifestation of papillary fibroelastoma highlights the embolic potential of these tumours. Multimodality imaging, especially transesophageal echocardiography, is crucial in diagnosis. Even very small papillary fibroelastoma may cause devastating embolic events such as irreversible monocular blindness. Surgical excision is the treatment of choice to prevent recurrence.

Aims: Myocardial response to exercise and its differences between heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) remain incompletely understood. Myocardial work (MyW) enables a non-invasive assessment of left ventricular performance under physiological stress. We investigated exercise-induced MyW responses in patients with chronic heart failure and healthy controls. Methods and results: MyStress Pilot study enrolled 24 individuals (12 chronic heart failure patients (6 HFrEF, 6 HFpEF) and 12 healthy controls), aged 40–80 years, who underwent semi-supine exercise stress echocardiography (ESE) using a standardized protocol up to 75 Watt. MyW indices (global work index [GWI], global constructive work [GCW], global wasted work [GWW], global work efficiency [GWE]) were derived using pressure-strain analysis. Linear mixed-effects models assessed workload-dependent changes. Patients with HFrEF and HFpEF were older and achieved lower peak workloads than controls. At rest, GCW was reduced in HFrEF, while GWW was elevated in both heart failure groups. During exercise, controls demonstrated substantial increases in GCW and GWI. In contrast, HFrEF patients exhibited little or no augmentation of GCW and GWI, indicating absent contractile reserve, whereas HFpEF patients showed a blunted increase in GCW accompanied by an abnormal increase in GWW. These differences persisted despite similar systolic blood pressure trajectories across groups, indicating that altered MyW responses were not simply due to afterload. Diastolic parameters increased steeply in HFpEF, unmasking impaired diastolic reserve. Conclusion: MyW analysis during ESE revealed distinct systolic and diastolic response patterns in heart failure phenotypes and controls. These findings illustrate how pressure-strain analysis can enrich ESE beyond conventional metrics.

In a retrospective pilot study, we showed that the induction of heart-reactive autoantibodies (HRA) in the wake of acutely decompensated heart failure predicts worse outcomes. To gain deeper insights into the immunological mechanisms causing induction of HRA after heart failure decompensation we initiated the prospective ‘Acute Heart Failure-Immunomonitoring Cohort Study’ (AHF-ImmunoCS). For this study, 380 patients were enrolled and will be followed up, including serial collection of biomaterials, for a period of 18 months after the index hospitalisation for AHF. Analysis of AHF-ImmunoCS samples obtained at baseline and at 6-month follow-up from 110 patients showed de novo induction of HRA - as detected by indirect immunofluorescence (IFT) - in 21% of patients (previously published percentage: 32%). The IFT results did not reflect induction of broad anti-heart autoimmunity as autoantibodies against other cardiac antigens like Troponin I3 or Myosin Light Chain 7 were not induced in parallel. To understand what drives HRA induction in these patients we longitudinally immunophenotyped peripheral blood leukocytes at baseline, 6-week and 6-month follow-up by high-resolution spectral flow cytometry. Among lymphocytes, induction of HRA in the wake of acute decompensation of heart failure was associated with a higher proportion of CD4 ⁺ T cells among lymphocytes, more CD45RA ⁺ CCR7 ⁺ naive conventional, i.e. non-regulatory, and more CXCR3 ⁺ CCR4 ^- Th1 cells among CD4 ⁺ T cells at baseline. Among myeloid cells, there were no differences at baseline between patients going on to develop HRA and those that did not. However, patients developing HRA had higher proportions of eosinophils (six-month follow-up) and lower proportions of Arginase ⁺ HLA-DR ^- polymorphnuclear myeloid-derived suppressor cells among myeloid cells (six-week and six-month follow-up). Our data, thus, implicate that alterations in the composition of both the lymphoid and the myeloid compartments might drive HRA induction which impacts disease progression and prognosis in AHF.

Despite major advances in recent years, the timely detection and prevention of incipient congestion in patients with chronic heart failure remains challenging. Most approaches are either invasive or require the acquisition of additional hardware. Leveraging voice analysis for the purposes of diagnosing, predicting risks, and telemonitoring clinical outcomes of patients with heart failure represents a promising, cost-effective, and convenient alternative compared with hitherto deployed methods. To expand this field, close collaboration of several disciplines of medicine and computer science is an obligatory requirement. The current review aims to lay out the state-of-the-art in this quickly advancing area of research. It elucidates the foundation for voice feature extraction, describes the prospective capabilities of this evolving technology, and outlines the challenges involved in identifying vocal biomarkers both in general and in the context of heart failure.

Acute heart failure (AHF) is a life-threatening condition and a common cause of hospitalization. The defining clinical feature of AHF is volume overload, leading to pulmonary and peripheral edema and consequently to weight gain. Vocal biomarkers have the potential to facilitate the early detection of worsening HF and the prevention of AHF episodes by offering a non-invasive, low-barrier monitoring tool. The AHF-Voice study is a prospective monocentric cohort study designed to investigate the trajectories of voice alterations during and after episodes of AHF, identify potential vocal biomarkers, and enhance the understanding of the pathophysiological mechanisms underlying these voice changes. It will examine the characteristics and determinants of vocal biomarkers, analyzing their correlations with patients' clinical status and comparing them to alternative clinical parameters in HF. Further, it aims to determine whether specific vocal biomarkers can accurately map different HF phenotypes and assess their association with patient trajectories. The study phenotypes patients hospitalized for AHF at admission and discharge, and follows them for a period of 6 months. During hospitalization, daily voice recordings are collected using a specially-designed smartphone app. Following discharge, patients are requested to continue daily voice recordings with their own smartphone for the subsequent six months the 6-month follow-up. Patient-reported outcome measures and body composition are assessed in the hospital and at follow-up visits. Sub-studies explore vocal fold oscillation through video-laryngostroboscopy and assess the feasibility of combining voice analysis with in-ear sensor technology for comprehensive digital phenotyping. A total of 131 patients were enrolled between April 2023 and November 2024: their mean age was 75 years (SD 10), 31% were women, 86% were in NYHA functional class III or IV, and 38% presented with de novo heart failure. Additionally, 59% of participants owned smartphones. The AHF-Voice study will provide insights into the potential of vocal biomarkers as reliable indicators of congestion, paving the way for innovative and accessible tools to support heart failure management.