Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer.

Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case-control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.

Auxiliary diagnostic potential of ventricle geometry and late gadolinium enhancement in left ventricular non-compaction; non-randomized case control study.

BACKGROUND: There are still ambiguities existing in regard to left ventricular non-compaction (LVNC) diagnostic imaging. The aim of our study was to analyze diagnostic potential of late gadolinium enhancement (LGE) and ventricle geometry in patients with LVNC and controls. METHODS: Data on cardiac magnetic resonance imaging (CMR) studies for LVNC were reassessed from the hospital's database (3.75 years; n=1975 exams). Matching sample of controls included cases with no structural heart disease, hypertrophic or dilative cardiomyopathy, arrhythmogenic right ventricular dysplasia or subacute myocarditis. Eccentricity of the left ventricle was measured at end diastole in the region with pronounced NC and maximal to minimal ratio (MaxMinEDDR) was calculated. RESULTS: Study included 255 patients referred for CMR, 100 (39.2%) with LVNC (prevalence in the studied period 5.01%) and 155 (60.8%) controls. Existing LGE had sensitivity of 52.5% (95%-CI:42.3-62.5), specificity of 80.4% (95%-CI:73.2-86.5) for LVNC, area under curve (AUC) 0.664 (95%-CI:0.603-0.722);p<0.001. MaxMinEDDR>1.10 had sensitivity of 95.0% (95%-CI:88.7-98.4), specificity of 82.6% (95%-CI: 75.7-88.2) for LVNC, AUC 0.917 (95%-CI:0.876-0.948); p<0.001. LGE correlated with Max-Min-EDD-R (Rho=0.130; p=0.038) and there was significant difference in ROC analysis ΔAUC0.244 (95%-CI:0.175-0.314); p<0.001. LGE also correlated negatively with stroke volume and systolic function (both p<0.05, respectively). CONCLUSIONS: LGE was found to be frequently expressed in patients with LVNC, but without sufficient power to be used as a discriminative diagnostic parameter. Both LGE and eccentricity of the left ventricle were found to be relatively solid diagnostic landmarks of complex infrastructural and functional changes within the failing heart.

The association of ventricular tachycardia and endothelial dysfunction in the setting of acute myocardial infarction with ST elevation.

BACKGROUND: Ventricular tachycardia (VT) is frequently seen in ischemic settings like acute myocardial infarction with ST segment elevation (STEMI). Endothelial dysfunction (ED) represents inflammation and the loss of all protective features of the endothelium. We aimed to examine the association between VT and ED in patients with STEMI. MATERIAL/METHODS: The study included 90 subjects (30 with VT and acute STEMI, 30 with STEMI without VT, and 30 controls). Sera of all subjects were tested on ED markers by enzyme immunoassay: sICAM-1 (intracellular adhesive molecule-1), sVCAM-1 (vascular adhesive molecule-1), P- and E-selectins, and VEGF (vascular endothelial growth factor). In addition, CRP (C-reactive protein) was detected. RESULTS: Significantly increased values of low-density lipoprotein, triglycerides, leukocytes, creatinine, and the number of cigarettes smoked were observed among patients with VT+STEMI in comparison to controls. The levels of E-selectin were significantly lower in the VT+STEMI group than in the other groups, while the levels of VCAM-1 were significantly higher in the groups with STEMI and VT+STEMI compared to the controls. Lower levels of VEGF were recorded in STEMI and VT+STEMI groups compared to the control group. A significant correlation between CRP and VCAM-1 in patients with VT +STEMI was demonstrated. CONCLUSIONS: We showed that ED may have a role in the immunopathogenesis of VT in patients with STEMI. The role of sE- selectin and correlation of sVCAM-1 with CRP as possible ED predictive markers in patients with VT+STEMI should be further investigated in a large cohort of patients.

Successful primary percutaneous coronary intervention in the first trimester of pregnancy.

A 28-year-old patient, medical nurse, in 10th week of her second pregnancy suffered ventricular fibrillation just after entering the waiting room of the emergency department. After she was successfully defibrillated, electrocardiography revealed a large acute anteroseptolateral ST elevation myocardial infarction. Urgent coronarography was done (premedication with 300 mg of aspirin and 600 mg of clopidogrel) with 90 min door-to-balloon time. Proximal left anterior descending occlusion was found, primary percutaneous coronary intervention was done using Amazonia CroCo 3.0/12 bare-metal stent, and Thrombolysis in Myocardial Infarction III flow was achieved. During the procedure, the patient was wrapped in lead apron. Because of postresuscitational agitation, procedure was done in intravenous anesthesia. The revealed risk factors were smoking and hypercholesterolemia. PAI-1 gene 4G/4G genotype and Apo E gene E2/E4 genotype were also found. Estimated X-ray dosage that fetus received during the procedure was 0.45 mSv, which is less than the upper safe limit in pregnancy. All drugs given to our patient (clopidogrel, aspirin, ivabradine, bisoprolol, anesthetics, low-molecular-weight heparin, and unfractionated heparin) have B or C Food and Drug Administration Pregnancy Category. Fetal ultrasonography showed normal fetal growth, and, after consultation with our team, the patient decided to maintain the pregnancy. Before discharge echocardiography showed left ventricle of normal size with anteroseptolateral hypokinesia, small apical aneurysm, left ventricular ejection fraction of 40-45%, and diastolic dysfunction grade II, without pulmonary hypertension. At the 36th week of pregnancy, the patient was hospitalized and closely monitored; clopidogrel and aspirin were discontinued, and low-molecular-weight heparin was administered. She gave birth to a normal boy by vaginal delivery with epidural anesthesia and without any complication.