Clonal haematopoiesis of indeterminate potential-related mutations and outcome in dilated and ischaemic cardiomyopathy.

AIMS: Clonal haematopoiesis of indeterminate potential (CHIP)-associated mutation is a risk factor for the development of ischaemic cardiomyopathy (ICM), but its association with non-ischaemic dilated cardiomyopathy (DCM) remains unclear. We aimed to determine the prevalence of CHIP in patients with DCM and define its risk for disease progression. METHODS AND RESULTS: Next-generation sequencing targeting 54 common CHIP-associated genes was performed in 48 ICM and 52 DCM patients. The patients were monitored for a median of 3.1 years, and a COX proportional hazards model was used to examine the association between CHIP and adverse clinical outcome with regard to all-cause death or all-cause hospitalization. Overall, the prevalence of CHIP mutations was 19% and 13% in DCM and ICM, respectively. Seventeen per cent of ICM patients over 75 years were CHIP carriers. In DCM cohort, mutation event had already been observed in the patients who were under the age of 45 (13%). Among 54 genes analysed, DNMT3A had the highest mutation frequency, followed by TET2 and CUX1. Kaplan-Meier curve over a median of 3.1 year tracking period showed a trend towards poor clinical outcome in the DCM patients who carried DNMT3A or TET2 mutation; however, such association was not statistically significant. CONCLUSIONS: The prevalence of CHIP is detected at a young age in DCM, and accumulation of mutational frequency in DCM patients is independent of age. However, a larger patient cohort is required to validate the association between CHIP and clinical progression in the DCM patients.

A case report of a 37-year-old woman with pulmonary arterial hypertension first presented during her 3rd pregnancy and favourable long-term vasoreactive response.

BACKGROUND: Pulmonary arterial hypertension is a rare disease associated with high rates of mortality and can significantly complicate pregnancy posing health risks for the mother and child alike. CASE SUMMARY: We present the case of a 37-year-old female patient with World Health Organisation functional Class IV symptoms during the 34th week of her 3rd pregnancy. Initial echocardiography showed a significantly elevated estimated systolic pulmonary artery pressure of 86 mmHg + central vein pressure as well as signs of chronic pulmonary hypertension. After a successful emergent caesarean section, pulmonary hypertension was confirmed via right heart catheterization. After exclusion of secondary aetiologies of pulmonary hypertension, the diagnosis of Class 1 pulmonary artery hypertension was made. We initially treated the patient with the phosphodiesterase-5 inhibitor sildenafil (20 mg oral bid trice daily) and later extended the medication with the dual endothelin receptor antagonist Macicentan (10 mg daily). Since the patient remained symptomatic vasodilator testing was performed and showed a significant response to intravenous Epoprostenol. We initiated a high-dose calcium channel blocker (CCB) therapy with amlodipine (20 mg daily) which led to symptomatic relief, increased exercise capacity as well as reduction in mean pulmonary artery pressure and pulmonary vascular resistance as confirmed by another right heart catheterization after therapy initiation. DISCUSSION: Since the presentation is usually non-specific, the diagnosis of pulmonary artery hypertension can be challenging and cause a delay in treatment initiation. Even though rare vasodilator testing and invasive haemodynamic measurements should be performed to identify patients with favourable long-term response to high-dose CCB.

Acute myocarditis after COVID-19 vaccination with mRNA-1273 in a patient with former SARS-CoV-2 infection.

We describe a case of a 20-year-old healthy man developing chest pain and classical symptoms of vaccine reactogenicity 12 h after receiving the first dose of mRNA-1273 (Moderna). Cardiac troponin T was increased, and subepicardial inflammation and focal contractile dysfunction were detected by cardiac magnetic resonance imaging and echocardiography. We confirmed the diagnosis of acute myocarditis by endomyocardial biopsy demonstrating significant infiltration of monocytes and T lymphocytes. Although we detected IgG against nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicating prior infection, the patient repeatedly tested negative for SARS-CoV-2 and had been asymptomatic for several months. Furthermore, viral genome analysis of endomyocardial biopsy samples was negative for SARS-CoV-2 and other potential cardiotropic viruses. These findings and the strong temporal relation between the vaccination and the symptom onset imply a potential side effect of mRNA-1273.

Therapy limitation in octogenarians in German intensive care units is associated with a longer length of stay and increased 30 days mortality: A prospective multicenter study.

PURPOSE: The approach to limit therapy in very old intensive care unit patients (VIPs) significantly differs between regions. The focus of this multicenter analysis is to illuminate, whether the Clinical Frailty Scale (CFS) is a suitable tool for risk stratification in VIPs admitted to intensive care units (ICUs) in Germany. Furthermore, this investigation elucidates the impact of therapeutic limitation on the length of stay and mortality in this setting. METHODS: German cohorts' data from two multinational studies (VIP-1, VIP-2) were combined. Univariate and multivariate logistic regression were used to evaluate associations with mortality. RESULTS: 415 acute VIPs were included. Frail VIPs (CFS > 4) were older (85 [IQR 82-88] vs. 83 [IQR 81-86] years p < .001) and suffered from an increased 30-day-mortality (43.4% versus 23.9%, p < .0001). CFS was an independent predictor of 30-day-mortality in a multivariate logistic regression model (aOR 1.23 95%CI 1.04-1.46 p = .02). Patients with any limitation of life-sustaining therapy had a significantly increased 30-day mortality (86% versus 16%, p < .001) and length of stay (144 [IQR 72-293] versus 96 [IQR 47.25-231.5] hours, p = .026). CONCLUSION: In German ICUs, any limitation of life-sustaining therapy in VIPs is associated with a significantly increased ICU length of stay and mortality. CFS reliably predicts the outcome.