Cardiology Research and Practice

Objectives. The upper limit of recipient age for combined heart-kidney transplantation (HKT) remains controversial. This study evaluated the outcomes of HKT in patients aged ≥65 years. Methods. The United Network of Organ Sharing (UNOS) was used to identify patients undergoing HKT from 2005 to 2021. Patients were stratified by age at transplantation: <65 and ≥ 65 years. The primary outcome was one-year mortality. Secondary outcomes included 90-day and 5-year mortality, postoperative new-onset dialysis, postoperative stroke, acute rejection prior to discharge, and rejection within one-year of HKT. Survival was compared using Kaplan–Meier analysis, and risk adjustment for mortality was performed using Cox proportional hazards modeling. Results. HKT in recipients aged ≥65 significantly increased from 5.6% of all recipients in 2005 to 23.7% in 2021 (). Of 2,022 HKT patients in the study period, 372 (18.40%) were aged ≥65. Older recipients were more likely to be male and white, and fewer required dialysis prior to HKT. There were no differences between cohorts in unadjusted 90-day, 1-year, or 5-year survival in Kaplan–Meier analysis. These findings persisted after risk-adjustment, with an adjusted hazard for one-year mortality for age ≥65 of 0.91 (95% CI (0.63–1.29), ). As a continuous variable, increasing age was not associated with one-year mortality (HR 1.01 (95% CI (1.00–1.02), ) per year). Patients aged ≥65 more frequently required new-onset dialysis prior to discharge (11.56% vs. 7.82%, ). Stroke and rejection rates were comparable. Conclusion. Combined HKT is increasing in older recipients, and advanced age ≥65 should not preclude HKT.

Background. Reversible P2Y12 inhibition can be obtained with cangrelor administered intravenously. More experience with cangrelor use in acute PCI with unknown bleeding risk is needed. Objectives. To describe real-world use of cangrelor including patient and procedure characteristics and patient outcomes. Methods. We performed a single-centre, retrospective, and observational study including all patients treated with cangrelor in relation to percutaneous coronary intervention at Aarhus University Hospital during the years 2016, 2017, and 2018. We recorded procedure indication and priority, the indications for cangrelor use, and patient outcomes within the first 48 hours after initiation of cangrelor treatment. Results. We treated 991 patients with cangrelor in the study period. Of these, 869 (87.7%) had an acute procedure priority. Among acute procedures, patients were mainly treated for STEMI (n = 723) and the remaining were treated for cardiac arrest and acute heart failure. Use of oral P2Y12 inhibitors prior to percutaneous coronary intervention was rare. Fatal bleeding events (n = 6) were only observed among patients undergoing acute procedures. Stent thrombosis was observed in two patients receiving acute treatment for STEMI. Thus, cangrelor can be used in relation to PCI under acute circumstances with advantages in terms of clinical management. The benefits and risks, in terms of patient outcomes, should ideally be assessed in randomized trials.

Definitive diagnosis of familial hypercholesterolemia (FH) is paramount for the risk management of patients and their relatives. The present study aimed to investigate the frequency of gene variants contributing to low-density lipoprotein cholesterol (LDL-C) metabolism and their clinical relevance in patients with early-onset coronary artery disease (EOCAD). Among 63 consecutive patients with EOCAD (men <55 years or women <65 years) who underwent percutaneous coronary intervention (PCI) from 2013 to 2019 at Keio University Hospital, 52 consented to participate in this retrospective study. Targeted sequencing of LDLR, PCSK9, APOB, and LDLRAP1 was performed. Of the 52 patients enrolled (42 men; mean age: 50 ± 6 years), one (LDLR, c.1221_1222delCGinsT) harbored a pathogenic mutation, and one (APOB, c.10591A>G) harbored variants of uncertain significance. Both the patients harboring the variants were male, showing no history of diabetes mellitus or chronic kidney disease, no family history of EOCAD, and no physical findings of FH (i.e., tendon xanthomas or Achilles tendon thickening). Patients harboring the LDLR variant had three-vessel disease, were on a statin prescription at baseline, and had stable LDL-C levels; however, the case showed a poor response to the intensification of medication after PCI. Approximately 3.8% of patients with EOCAD harbored variants of gene related to LDL-C metabolism; there were no notable indicators in the patients’ background or clinical course to diagnose FH. Given the difficulty in diagnosing FH based on clinical manifestations and family history, genetic testing could enable the identification of hidden risk factors and provide early warnings to their relatives.

Secreted frizzled related protein 4 (SFRP4), a member of the SFRPs family, contributes to a significant function in metabolic and cardiovascular diseases. However, there is not enough evidence to prove the antiatherosclerosis effect of SFRP4 in ApoE knock-out (KO) mice. ApoE KO mice were fed a western diet and injected adenovirus (Ad)-SFRP4 through the tail vein for 12 weeks. Contrasted with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing SFRP4 was reduced significantly. Plasma high-density lipoprotein cholesterol was elevated in the Ad-SFRP4 group. RNA sequence analysis indicated that there were 96 differentially expressed genes enriched in 10 signaling pathways in the mRNA profile of aortic atherosclerosis lesions. The analysis data also revealed the expression of a number of genes linked to metabolism, organism system, and human disease. In summary, our data demonstrates that SFRP4 could play an important role in improving atherosclerotic plaque formation in the aorta.

Background. Percutaneous coronary intervention using a drug-eluting stent (DES) is a common therapeutic option for acute coronary syndrome (ACS). However, stent-associated complications, such as bleeding associated with dual antiplatelet therapy, in-stent restenosis, stent thrombosis, and neoatherosclerosis, remain. Drug-coated balloons (DCBs) are expected to reduce stent-associated complications. This study aimed to assess the efficacy of DCB therapy and compare it with that of DES therapy in patients with ACS. Materials and Methods. In this single-center, retrospective, observational study, we examined all patients with ACS treated with DCB or DES between July 2014 and November 2020. Patients with left main trunk lesions were excluded. The primary outcome was a composite of major adverse cardiovascular events (MACE: cardiac death, myocardial infarction, and target lesion revascularization) at one year. Results. Three hundred and seventy-two patients were treated with DES, and 83 patients were treated with DCB. MACE occurred in 10 (12.0%) patients in the DCB group and in 50 (13.4%) patients in the DES group (). Conclusions. DCB is a valuable and effective therapy for patients with ACS. Moreover, DCB may become an alternative therapy for DES in patients with ACS.

Background. Chronic Chagas heart disease (CCHD) and systemic arterial hypertension (SAH) frequently coexists in areas where Chagas disease is endemic. The effects of the association of both conditions (CCHD-SAH) on the extracellular matrix (ECM) remodeling are unknown. Matrix metalloproteinases (MMP) 2 and 9 are involved in ECM remodeling. The aim of this study was to evaluate MMP 2 and MMP9 in CCHD-SAH patients and to correlate their levels with those of the profibrogenic cytokine TGF-beta. Methods. We included 19 patients with CCHD-SAH, 14 patients with CCHD alone, and 19 controls matched by sex and age. MMP-2 and MMP-9 plasma levels were studied by gel zymography and showed as optical densities (OD). TGF-beta plasma levels were measured by double-ligand ELISA and expressed as pg/mL. Results. Median (5^th, 95^th) MMP-2 plasma levels were 1224.7 OD (1160, 1433.5) in patients with CCHD alone, 1424.1 OD (1267.5, 1561) in patients with CCHD-SAH, and 940 OD (898.1, 1000.8) in controls (). MMP-9 plasma levels were 1870 OD (1740, 1904.1) in patients with CCHD alone, 1754.6 OD (1650, 2049) in those with CCHD-SAH and 89.7 OD (80, 96) in controls (). MMP-9 plasma levels were higher than those of MMP 2 in patients with CCHD-SAH (). No correlation was found between TGF-beta plasma levels with MMP-2 serum levels (r = 0.12; ), but a moderate negative correlation (r = −0.46; ) was observed between TGF-beta and MMP-9 plasma levels. Conclusions. MMP-2 and especially MMP-9 may play a role in the ECM remodeling process in patients with CCHD-SAH. TGF-Beta may counteract the MMP effect on the ECM remodeling process in patients with CCHD-SAH.