Phenomapping in patients experiencing worsening renal function during hospitalization for acute heart failure.

AIMS: The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis. METHODS AND RESULTS: Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all-cause death and re-hospitalization due to heart failure, with those of a propensity score-matched, non-WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m2 ), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m2 ), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3. CONCLUSIONS: Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function.

Acute Myocardial Infarction in an Adolescent Receiving Anagrelide for Essential Thrombocythemia with Underlying Persistent Coronary Endothelial Dysfunction.

Essential thrombocythemia (ET) is a Philadelphia chromosome-negative myeloproliferative disorder that is characterized by the overproduction of platelets and a marked increase in the numbers of mature megakaryocytes present in the bone marrow. Thrombohemorrhagic disorders are major morbidities of ET, especially those with mutations in the gene encoding Janus kinase 2 (JAK2). In this study, we report the case of an 18-year-old patient with ET carrying JAK2 mutation who developed acute ST-elevation myocardial infarction (STEMI) 5 months after a commencement of anagrelide. Coronary endothelial dysfunction confirmed by positive acetylcholine provocation test lasted a year after the occurrence of STEMI. Furthermore, intracoronary imaging using optical coherence tomography demonstrated non-atheromatous intimal fibrosis possibly due to chronic endothelial damage. The coronary pathologies reflected chronic change potentially associated with properties of ET and JAK2 mutation in addition to hyperviscosity. These observations suggest that the side effect of anagrelide in our patient was considered causative, while underlying chronic endothelial dysfunction and adverse endothelial remodeling may be predisposing factors to his fatal cardiovascular events.