Disease management with home telemonitoring aimed at substitution of usual care in the Netherlands: Post-hoc analyses of the e-Vita HF study

BACKGROUND: Home telemonitoring in heart failure (HF) patients may reduce workload of HF nurses by reducing face-to-face contacts. The aim of this study is to assess whether telemonitoring as a substitution could have negative effects as expressed by less reduction in circulating natriuretic peptide levels between baseline and one-year of follow up compared to usual care. METHODS: A post-hoc analysis of the e-Vita HF trial, a three-arm parallel randomized trial conducted in stable HF patients. Patients were randomized into three arms: (i) usual HF outpatient care, (ii) usual care combined with the use of the website heartfailurematters.org, and (iii) telemonitoring (e-Vita HF platform) instead of face-to-face consultations. Mixed linear model analyses were applied to assess differences in the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels between the three arms over a year. RESULTS: A total of 223 participants could be included (mean age 67.1 ± 10.1 years, 27% women, New York Heart Association class I–IV; 39%, 38%, 14%, and 9%). The mean left ventricular ejection fraction was 35 ± 10%. The median of routine face-to-face contacts over a year was 1.0 lower (2.0 vs. 3.0) in the third arm compared with usual care. Median NT-proBNP levels did not significantly differ between the three arms. CONCLUSION: In stable and optimally treated HF patients, telemonitoring causing a reduction of routine face-to-face contacts seems not to negatively affect hemodynamic status as measured by NT-proBNP levels over time

Cardiac amyloidosis: the need for early diagnosis

Amyloidosis is a collection of systemic diseases characterised by misfolding of previously soluble precursor proteins that become infiltrative depositions, thereby disrupting normal organ structure and function. In the heart, accumulating amyloid fibrils lead to progressive ventricular wall thickening and stiffness, resulting in diastolic dysfunction gradually progressing to a restrictive cardiomyopathy. The main types of cardiac amyloidosis are amyloid light chain (AL) amyloidosis caused by an underlying plasma cell dyscrasia, amyloid transthyretin (TTR) amyloidosis of wild-type (normal) TTR at older age (ATTRwt) and hereditary or mutant amyloid TTR (ATTRm) in which a genetic mutation leads to an unstable TTR protein. Overall survival is poor once heart failure develops, underlining the need for early referral and diagnosis. Treatment for AL amyloidosis has improved markedly over the last decades, and TTR amyloidosis gene silencers and orally available transthyretin stabilisers are ready to enter the clinical arena after recent positive outcome trials. Novel therapies aiming at fibril degradation with monoclonal antibodies are under investigation. In this review, we focus on ‘red flag’ signs and symptoms, diagnosis and management of cardiac amyloidosis which differs considerably from the general management of heart failure. Only by increasing awareness, prognosis for patients with this devastating disease can be improved

Evaluation of the cardiac amyloidosis clinical pathway implementation: A real-world experience

AIMS: The aim of this study is to evaluate the implementation of the cardiac amyloidosis (CA) clinical pathway on awareness among referring cardiologists, diagnostic delay, and severity of CA at diagnosis. METHODS AND RESULTS: Patients with CA were retrospectively included in this study and divided into two periods: pre-implementation of the CA clinical pathway (2007–18; T1) and post-implementation (2019–20; T2). Patients’ and disease characteristics were extracted from electronic health records and compared. In total, 113 patients (mean age 67.8 ± 8.5 years, 26% female) were diagnosed with CA [T1 (2007–18): 56; T2 (2019–20): 57]. The number of CA diagnoses per year has increased over time. Reasons for referral changed over time, with increased awareness of right ventricular hypertrophy (9% in T1 vs. 36% in T2) and unexplained heart failure with preserved ejection fraction (22% in T1 vs. 38% in T2). Comparing T1 with T2, the diagnostic delay also improved (14 vs. 8 months, P < 0.01), New York Heart Association Class III (45% vs. 23%, P = 0.03), and advanced CA stage (MAYO/Gillmore Stage III/IV; 61% vs. 33%, P ≤ 0.01) at time of diagnosis decreased. CONCLUSION: After implementation of the CA clinical pathway, the awareness among referring cardiologists improved, diagnostic delay was decreased, and patients had less severe CA at diagnosis. Further studies are warranted to assess the prognostic impact of CA clinical pathway implementation

Inhibition of miR-223 reduces inflammation but not adverse cardiac remodelling after myocardial ischemia-reperfusion in vivo

Background: Coronary artery occlusion results in ischemic heart tissue and subsequent death of cardiomyocytes, followed by an inflammatory response to clear the infarcted area from dead cells. Invading inflammatory cells are suggested to contribute to myocardial ischemia-reperfusion (I/R) injury and adverse remodelling. Given the importance of the inflammatory phase during cardiac wound healing, better understanding is needed to develop novel interventions. In the present study, we investigated the role of the inflammatory-related miR-223 in the ischemic heart. Furthermore, we determined the effect of miR-223 modulation on inflammation and cardiac remodelling in a mouse model of myocardial I/R. Methods: Mice underwent 30 minutes of ischemia and received, 5 minutes before reperfusion, 8 mg/kg antagomiR-223 or mismatch-miR treatment, and consecutive injections at day 1 and 2 post-I/R. MiR-223 expression was quantified by in situ hybridization and PCR. Inflammatory cell influx was quantified by immunohistochemistry. By using magnetic resonance imaging (MRI), cardiac dimensions and function were assessed before and 28 days after surgery. Results: MiR-223 expression significantly increased 1 and 3 days after I/R, corresponding with the inflammatory phase upon cardiac injury. MiR-223 expression mainly increased in myocytes. Inhibition of miR-223 by antagomir treatment significantly reduced total leukocyte (CD45+ cells) and macrophages (Mac-3+ cells) influx at 3 days of reperfusion. End-diastolic volume (EDV) and end-systolic volume (ESV) showed a similar increase in both treatment groups, as well as a comparable decline in ejection fraction (EF) post-I/R. Conclusions: Although inhibition of miR-223 resulted in less inflammatory influx after reperfusion, this did not lead to less adverse cardiac remodelling. More research on the complex temporal and spatial role of miR-223 during the process of myocardial wound healing is necessary in order to understand the role of miR-223 upon I/R injury and whether it can be used as a novel therapeutic strategy

Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy

BACKGROUND: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care. OBJECTIVES: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives. METHODS: A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with “possible ARVC” (only genetic or familial predisposition) and “borderline ARVC” (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]). RESULTS: At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P 0.05). CONCLUSIONS: Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often