Effect of Three-Day Atorvastatin Administration on Coagulation Factors in Patients With Prior Venous Thromboembolism and Healthy Subjects: A Preliminary Study.

ABSTRACT: Statins exert antithrombotic effects, which might contribute to reduced risk of venous thromboembolism (VTE). Rosuvastatin 20 mg/d administered for 4 weeks has been reported to decrease coagulation factors (F) VII, FVIII, and FXI in VTE patients. Moreover, in accordance with recent registry data in non-VTE subjects, statins usage was associated with lower FXI. We investigated whether 3 doses of a statin decrease coagulation factors activity and if such changes can alter fibrin clot properties in VTE patients and healthy subjects. We enrolled 28 consecutive first-ever prior VTE patients after 6 months of anticoagulation and 25 healthy controls well-matched for demographics and lipid profiles (aged 44 [interquartile range 34-51] years) in an interventional nonrandomized study. Before and after 3 doses of atorvastatin 40 mg/d, activity of FVII, FVIII, FIX, and FXI was measured, along with fibrin clot properties, including permeability (Ks) and clot lysis using 3 various assays. After a 3-day statin administration, we observed the decrease of FVII (by 6.2%, P = 0.046) and FXI (by 8.6%, P = 0.044), irrespective of low-density lipoprotein cholesterol reduction (by 24%, P < 0.001), whereas other coagulation factors remained unaltered. Reduction of FVII and FXI activity was inversely correlated with Ks alterations (R = -0.292, P = 0.034 and R = -0.335, P = 0.014, respectively). After adjustment for age, studied group, and fibrinogen level, the reduction of FXI was independently associated with an increase of fibrin clot permeability (B = -0.084, P = 0.027). In conclusion, a 3-day 40 mg atorvastatin administration is sufficient to reduce FVII and FXI activity in our pilot study, which is associated with favorable fibrin clot properties modification.

Reduced fibrin clot permeability on admission and elevated E-selectin at 3 months as novel risk factors of residual pulmonary vascular obstruction in patients with acute pulmonary embolism.

BACKGROUND: Residual pulmonary vascular obstruction (RPVO) is common following pulmonary embolism (PE) but its association with fibrin clot properties is poorly understood. We investigated whether prothrombotic state and hypofibrinolysis markers can identify patients with RPVO. METHODS: In 79 normotensive noncancer patients (aged 56 ± 13.3 years) with acute PE, we determined fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), fibrinolysis proteins, oxidative stress markers, and E-selectin on admission before initiation of anticoagulant therapy, after 5-7 days, and 3 months of anticoagulation. RPVO was diagnosed using computed tomography angiography 3-6 months since PE. RESULTS: Patients with RPVO (n = 23, 29.1%) had at baseline higher simplified Pulmonary Embolism Severity Index (sPESI) (P = 0.004), higher N-terminal brain natriuretic propeptide (P = 0.006) and higher D-dimer (P = 0.044). Patients with versus without RPVO had lower Ks (P < 0.001) and longer CLT (P < 0.05), both at baseline and 5-7 days since admission, but not at 3 months. Patients with RPVO showed 40.6% higher E-selectin (P < 0.001) solely at 3 months. By multivariable logistic regression, baseline Ks (odds ratio [OR] 0.010, 95% confidence interval [CI] 0.001-0.837, P = 0.042, per 10- 9 cm2), baseline D-dimer (OR 1.105, 95% CI 1.000-1.221, P = 0.049, per 100 ng/ml), and E-selectin levels after 3 months (OR 3.874, 95% CI 1.239-12.116, P = 0.020, per 1 ng/ml) were associated with RPVO. CONCLUSIONS: RPVO patients despite anticoagulation characterize with the formation of denser fibrin clots on admission and higher E-selectin at 3 months. Those parameters could be the potential novel RPVO risk factors that warrant further evaluation in an independent cohort.

Endothelial Cell Apoptosis but Not Necrosis Is Inhibited by Ischemic Preconditioning.

This study aimed to assess the influence of ischemic preconditioning (IP) on hypoxia/reoxygenation (HR)-induced endothelial cell (EC) death. Human umbilical vein endothelial cells (HUVECs) were subjected to 2 or 6 h hypoxia with subsequent reoxygenation. IP was induced by 20 min of hypoxia followed by 20 min of reoxygenation. Necrosis was assessed by the release of lactate dehydrogenase (LDH) and apoptosis by double staining with propidium iodide/annexin V (PI/AV), using TUNEL test, and Bcl-2 and Bax gene expression measured using RT-PCR. In PI/AV staining, after 24 h of reoxygenation, 30-33% of EC were necrotic and 16-21% were apoptotic. In comparison to HR cells, IP reduced membrane apoptosis after 24 h of reoxygenation by 50% but did not influence EC necrosis. Nuclear EC apoptosis affected about 15-17% of EC after 24 h of reoxygenation and was reduced with IP by 55-60%. IP was associated with a significantly higher Bcl-2/Bax ratio, at 8 h 2-4 times and at 24 h 2-3 times as compared to HR. Longer hypoxia was associated with lower values of Bcl-2/Bax ratio in EC subjected to HR or IP. IP delays, without reducing, the extent of HR-induced EC necrosis but significantly inhibits their multi-level evaluated apoptosis.

Coronary Slow-Flow Phenomenon in Takotsubo Syndrome: The Prevalence, Clinical Determinants, and Long-Term Prognostic Impact.

Patients with takotsubo syndrome (TTS) may present coronary slow flow (CSF) in angiography performed in the acute myocardial infarction (MI). However, the detailed clinical relevance and its long-term impact remain poorly understood. Among 7771 MI patients hospitalized between 2012 and 2019, TTS was identified in 82 (1.1%) subjects. The epicardial blood flow was assessed with thrombolysis in myocardial infarction (TIMI) scale and corrected TIMI frame count (TFC), whereas myocardial perfusion with TIMI myocardial perfusion grade (TMPG). CSF was defined as TIMI-2 or corrected TFC > 27 frames in at least one epicardial vessel. CSF was identified in 33 (40.2%) TTS patients. In the CSF-TTS versus normal-flow-TTS group, lower values of left ventricular ejection fraction on admission (33.5 (25-40) vs. 40 (35-45)%, p = 0.019), more frequent midventricular TTS (27.3 vs. 8.2%, p = 0.020) and the coexistence of both physical and emotional triggers (9.1 vs. 0%, p = 0.032) were noted. Within a median observation of 55 months, higher all-cause mortality was found in CSF-TTS compared with normal-flow TTS (30.3 vs. 10.2%, p = 0.024). CSF was identified as an independent predictor of long-term mortality (hazard ratio 10.09, 95% confidence interval 2.12-48.00, p = 0.004). CSF identified in two-fifths of TTS patients was associated with unfavorable long-term outcomes.

Screening diagnosis of dementia in patients following heart failure decompensation is associated with a higher relative wall thickness.

BACKGROUND: The usefulness of echocardiographic characteristics for dementia prediction in patients with heart failure decompensation (HFD) is not determined. Therefore, we sought to investigate the echocardiographic features of patients with HFD and screening diagnosis of dementia (SDD). METHODS: 139 patients aged over 65 years were hospitalized with the diagnosis of HFD. Clinical characteristics and echocardiographic characteristics were recorded during hospitalization. SDD was defined based on the result of ALFI- MMSE of <17 points. RESULTS: Patients with SDD were older (p=0.013), had thicker IVSd (p=0.021), thicker PWd (p=0.005) and had a higher RWT (0.40 vs 0.35, p=0.004) than patients without SDD, without differences in LVMI (p=0.13). There was no correlation between RWT and LVMI (r=-0.01, p=0.88). In the multivariate analysis, an older age (ß=-0.116, 95% CI -0.224 - -0.008, p=0.035, per year) and a higher RWT (ß=-0.069, 95% CI -0.137 - -0.002, p=0.045, per 0.01) influenced a lower ALFI-MMSE. For a prediction of SDD, the RWT reached the area under a ROC curve of 0.67 (95% CI 0.56-0.77, p=0.004 with sensitivity of 60% and specificity of 70% for RWT of ≥0.375). CONCLUSIONS: Apart from age, RWT reflecting left ventricular geometry changes but not hypertrophy was independently but moderately associated with SDD in patients following HFD (Tab. 4, Fig. 1, Ref. 35).

Clinical utility of complex assessment with evoked potentials in acute lymphoblastic leukemia survivors: comparison of various treatment protocols.

BACKGROUND: One of the greatest success of pediatric hematology is a prominent improvement of survival in acute lymphoblastic leukemia (ALL). Therefore, special attention needs to be paid to long-term side effects of the treatment such as neurotoxicity. One of the few diagnostic methods that allow an objective assessment of sensory systems are evoked potentials (EP). METHODS: The analyzed group consisted of 167 ALL long-term survivors, aged 4.9-28.4 years, without auditory, visual and sensory deviations. Patients were treated with New York (NY, n = 35), previous modified Berlin-Frankfurt-Münster (pBFM, n = 47) and BFM95 (n = 85) protocols. In order to assess the impact of radiotherapy on recorded EP, a joint analysis of NY and pBFM groups was performed. The control group consisted of 35 patients, aged 6-17 years. The analyzed patients underwent a complex assessment with visual EP (VEP), somatosensory EP (SEP) and brainstem auditory EP (BAEP) in accordance with current standards. RESULTS: ALL treatment contributed to the shortening of wave I latency (1.59 vs 1.90, P = 0.003) and prolongation of I-III (2.23 vs 2.04, P = 0.004) and I-V (4.57 vs 4.24, P = 0.002) interwave latencies of BAEP. A significant effect was also noticed in P100 (106.32 vs 101.57, P < 0.001) and N135 (151.42 vs 138.22, P < 0.001) latencies of VEP and N18 amplitude (3.24 vs 4.70, P = 0.007) and P25 latency (21.32 vs 23.39, P < 0.001) of SEP. The distribution of abnormalities between protocols was similar in BAEP (NY - 68.6%, pBFM - 61.7%, BFM95-69.4%, P = 0.650), VEP (NY - 68.6%, pBFM - 42.5%, BFM95-58.3%, P = 0.053) and significantly different for SEP (NY - 62.9%, pBFM - 36.2%, BFM95-53.0%, P = 0.045). The harmful effect of radiotherapy was most clearly marked in numerous disturbances of SEP parameters. CONCLUSIONS: The presented analysis indicates a high frequency of subclinical abnormalities in EP regardless of the analyzed protocol. To our knowledge current study is the largest and one of the most complex research examining the role of EP in ALL patients. The obtained results indicate the possibility of using a single, objective and non-invasive measurement of EP in ALL survivors in order to stratify the risk of developing sensory abnormalities in adulthood.

Typical variant of takotsubo cardiomyopathy in oncological patients. Two case reports and review of the literature.

Takotsubo cardiomyopathy (TCM) represents an acute systolic left ventricular dysfunction typically triggered by severe psychological or physical stress. Oncological patients due to emotional distress of the diagnosis, proinflammatory and prothrombotic nature of cancer and also physical stress often following complex anticancer therapies are at high-risk of TCM. Moreover, there are also few reports of TCM associated with oncological treatment, mostly chemotherapy. Recent data from large registries indicate a surprisingly high incidence of malignancy in TCM, significant differences in clinical characteristics and unfavorable short- and long-term clinical outcomes in this specific group of patients. Therefore, we present two case reports of TCM that occurred during active anticancer therapy. Both women were admitted with suspicion of acute coronary syndrome. The first patient underwent mastectomy two years before due to hormone receptor-positive breast cancer and on admission she was during adjuvant hormonotherapy with tamoxifen. The admission of the second patient was preceded by fifteen fractions of adjuvant external beam radiotherapy due to intermediate-risk endometrial cancer after radical hysterectomy. Based on coronary angiography type I of acute coronary syndrome was excluded. Both patients negated stressful situations in the period immediately before the symptoms onset. Within hospital course baseline apical ballooning observed in both cases fully recovered and enabled subsequent completion of oncological treatment in accordance with adopted treatment protocols without recurrence of TCM. To our knowledge, presented cases are the first reports showing direct relationship between TCM and adjuvant hormonotherapy with tamoxifen or pelvic radiotherapy.

The awareness and knowledge about heart failure in Poland - lessons from the Heart Failure Awareness Day and internet surveys.

BACKGROUND: Heart failure (HF) is a life-threatening condition which affects up to 2% of contemporary populations. Generally, it is a chronic and progressive disease, however in many cases it can be prevented or treated. Nevertheless, effective control of this disease requires awareness of symptoms in the society. AIMS: The aim of the study was to assess the level of HF knowledge in the Polish population. METHODS: The questionnaire concerning knowledge about HF prepared by the Competence Network HF under the patronage of the European Heart Failure Association of the ESC, was used. The survey included 534 contributors who formed three groups: medical students - in vast majority at first half of the study course (MS) - 198 (37.1%), HF Awareness Day participants (HFDP) - 134 (25.1%) and other (OP) - 202 (37.8%). RESULTS: Study groups differed in terms of gender, age and level of education. As predicted, MS achieved the highest score (22.5 [20.0-24.0]), compared to HFDP (20.0 [17.0-22.0], P <0.001) and OP (19.0[16.0-21.0], P <0.001). Knowledge on typical HF symptoms was alarmingly low in the analyzed groups - dyspnea (MS - 96.0%, HFDP - 78.4%, OP - 74.6%), ankle edema (MS - 79.8%, HFDP - 50.6%, OP - 32.2%), body weight gain (MS - 14.1%, HFDP - 17.2%, OP - 4.5%). By multivariate model medical education (ß 3.372, 95% CI 2.738-4.005) and own illness or having relatives or friends with HF (ß 0.654, 95% CI 0.066-1.242) independently affected the score of awareness questionnaire. CONCLUSIONS: The basic knowledge on HF in Poland is not sufficient. It is moderately better among MS. Further campaigns improving HF awareness are necessary.

New methods and techniques in interventional cardiology. Evaluation the knowledge of medical students of Jagiellonian University Medical College.

INTRODUCTION: Interventional cardiology (IC) is a rapidly expanding field of medicine. Medical studies should provide students the necessary level of knowledge about new techniques in IC. The aim of the study was to assess the medical students' knowledge about various new areas of IC. MATERIAL AND METHODS: Self-designed questionnaire was used to assess student's knowledge. It contained 31 questions. The initial 3 questions concerned general information, the remaining ones were related to different IC techniques: Transcatheter Aortic Valve Implantation (TAVI), Bioresorbable Vascular Scaffold (BVS), percutaneous mitral regurgitation repair methods, Left Atrial Appendage Occlusion (LAAO), Renal DeNervation (RDN), Balloon Aortic Valvuloplasty (BAV) and Atrial Septal Defect/Persistent Foramen Ovale (ASD/PFO). One point for each correct answer was awarded. RESULTS: In our study participated 104 students. Mean score was 15.9 ± 5.8 points. 24% of participants were 3rd year students, 38% - 4th, 20% - 5th and 18% - 6th. There was no differences in level of knowledge between students of different years of studies (p = 0.2). Students from Students Research Groups (SRG) achieved higher score in comparison with students no attending SRG (19.3 ± 6.3 vs 13.3 ± 3.7; p <0.001) as well as students interested in cardiology comparison with other (19.6 ± 5.9 vs 13.0 ± 3.8; p <0.001). Students from SRG and interested in cardiology reached also higher results in practically every area of IC in comparison with other. CONCLUSIONS: Participants have insufficient, outdated and incomplete knowledge of new methods in IC. There was no significant difference in students of different years of studies. Students belonging to cardiological SRG and interested in cardiology have greater knowledge in IC.

Elevated plasma factor XI is associated with postthrombotic syndrome.

INTRODUCTION: Postthrombotic syndrome (PTS), a common complication of deep vein thrombosis (DVT), is largely inflammatory by nature with contribution of prothrombotic mechanisms. The role of factor (F)XI in PTS has not been explored yet. We investigated whether elevated FXI is associated with PTS occurrence. MATERIALS AND METHODS: We enrolled 180 consecutive patients (aged 43 ± 13 years) with first-ever DVT. After 3 months FXI levels were measured, along with inflammatory markers, thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. We assessed PTS using the Villalta score and recorded symptomatic venous thromboembolism (VTE) at a 1-year and venous ulcers at a median 53 months follow-up. RESULTS: Baseline median FXI was 102 % [IQR 92-113 %] and showed positive association with Villalta score (R = 0.474, P < 0.001). Patients with PTS (n = 48, 26.7 %) had 16.1 % higher FXI (P < 0.001) and FXI ≥120 % occurred more often in PTS patients (odds ratio [OR] 5.55, 95 % confidence interval [CI] 2.28-13.47). There were associations of baseline FXI with Ks and CLT along with thrombin activatable fibrinolysis inhibitor (TAFI) activity, C-reactive protein, and interleukin-6, but not with fibrinogen, or thrombin generation. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1 % 1.06, 95 % CI 1.02-1.09) and VTE recurrence (OR 1.03, 95 % CI 1.01-1.06). At long-term follow-up, patients with venous ulcers had 13.6 % higher baseline FXI (P = 0.002). CONCLUSIONS: Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT.

Clinical characteristics and long-term outcomes of patients with heart failure with improved ejection fraction. First Polish experience from LECRA-HF registry.

PURPOSE: Heart failure (HF) with improved ejection fraction (HFimpEF) is a new category of HF introduced in the newest European Society of Cardiology guidelines. However, clinical characteristics and long-term outcomes of HFimpEF patients remain insufficiently elucidated. We sought to characterize Polish HFimpEF patients and determine their long-term mortality. MATERIAL AND METHODS: Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) registry between 2009 and 2019 and hospitalized due to HF decompensation, 340 (28.7%) were those with HF with reduced ejection fraction (HFrEF). Based on follow-up echocardiography, 61 (17.9%) of them were classified as HFimpEF and the remaining as HFnon-impEF. RESULTS: HFimpEF patients were more frequently females (P â€‹< â€‹0.001), had higher baseline left ventricular ejection fraction (LVEF, P â€‹< â€‹0.001), had less often a history of diabetes (P â€‹= â€‹0.024), severe chronic kidney disease (P â€‹= â€‹0.026) or prior myocardial infarction (P â€‹= â€‹0.008) than HFnon-impEF patients. By multivariable analysis the HFimpEF diagnosis was independently predicted by baseline NYHA I/II (odds ratio [OR] 2.347, 95% confidence interval [95%CI] 1.020-5.405), non-ischemic etiology (OR 3.096, 95%CI 1.587-6.024), lack of diabetes mellitus (OR 2.016, 95%CI 1.059-3.846) and higher baseline LVEF (OR 1.084, 95%CI 1.042-1.126, per 1%). Within the median 49 (25-77) months all-cause mortality was lower in HFimpEF than in HFnon-impEF (10.8 vs 16.4%/year, P â€‹= â€‹0.004). CONCLUSIONS: Our findings indicate that every sixth Polish patient with HFrEF has a chance to improve LVEF during follow-up and to become a HFimpEF patient. Baseline characteristics of HFimpEF patients are different from HFnon-impEF. Simultaneously, the HFimpEF diagnosis is associated with higher long-term survival.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: Mitral Fibrin Study.

INTRODUCTION: Intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is further complicated by an elevated risk of thromboembolic events. Studies published so far offer inconclusive insight into the interplay between mitral regurgitation (MR) and the coagulation system. OBJECTIVES: This study aimed to investigate the impact of transcatheter edge­to­edge repair (TEER) on specific coagulation parameters in HF patients. PATIENTS AND METHODS: A cohort of 31 HF patients with severe MR treated with TEER underwent a systematic evaluation at 3 visits (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability, and clot lysis time (CLT) were assessed (n = 27 at V2; n = 25 at V3). RESULTS: TEER induced changes in fibrinogen levels (P = 0.01; V3 vs V2) and improved fibrin clot properties over 50­day follow­up (P = 0.01; V3 vs V2). No significant differences were observed between time points in the analyzed blood clot parameters. Correlation analysis showed that baseline CLT was associated with ΔN­terminal pro-B­type natriuretic peptide (NT­proBNP) level (P = 0.049; r = 0.4). Multivariable analysis identified baseline CLT as an independent predictor of early post­TEER NT­proBNP change (R2 = 0.55; P = 0.02). CONCLUSIONS: We found decreased level of fibrinogen and increased permeation coefficient over a median 50 (interquartile range, 32.5-75.5)-day post­TEER follow­up, as compared with early postprocedural assessments. Other blood coagulation parameters remained unchanged from baseline at both follow­up time points after TEER. Finally, CLT was an independent predictor of early NT­proBNP increase, emphasizing its role as an indicator of hemodynamic response to TEER.

Effect of high-dose statin therapy on coagulation factors: Lowering of factor XI as a modifier of fibrin clot properties in coronary artery disease.

BACKGROUND: Multiple pleiotropic effects of statins include antithrombotic properties with formation of looser fibrin networks more susceptible to lysis. Recently, rosuvastatin 20 mg/d has been reported to decrease coagulation factors (F) VII, FVIII and FXI in venous thrombosis patients. OBJECTIVES: We investigated how high-dose statin therapy recommended in coronary artery disease (CAD) alters plasma levels of coagulation factors and if such changes might affect fibrin clot properties. METHODS: We studied 130 advanced CAD patients, who initially did not achieve the target low-density lipoprotein cholesterol (LDL-C). Before high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) and 6-12 months after its initiation, FII, FV, FVII, FVIII, FIX, FX, FXI and fibrinogen were assessed. We evaluated the impact of statin-induced alterations to the factors on plasma fibrin clot permeability (Ks) reflecting a fibrin pore size, and clot lysis time (CLT) reflecting fibrinolytic potential. RESULTS: At baseline LDL-C (median 3.2, interquartile range 2.7-3.7 mmol/L) was independently associated solely with FXI (ß = 0.58, P < 0.001). Median LDL-C reduction by 25% (P < 0.001) on high-dose statin treatment was accompanied by lowering of FVII, FVIII, and FXI (for all P < 0.001). On high-dose statin treatment, Ks (R = 0.65, P < 0.001) inversely associated with CRP (ß = -0.41, P < 0.001), LDL-C (ß = -0.26, P = 0.001), and FXI (ß = -0.18, P = 0.016). In turn, CLT (R = 0.45, P < 0.001) was positively associated with LDL-C (ß = 0.19, P = 0.043) and FXI (ß = 0.17, P = 0.049). CONCLUSIONS: High-dose statin therapy in CAD patients decreases FVII, FVIII, and FXI. The statin-induced reduction in FXI may contribute to less prothrombotic fibrin clot phenotype, indicating additional antithrombotic effect of high-dose statins.

Thin-cap fibroatheroma and increased coronary intima-media thickness are associated with an altered balance of arginine metabolites.

INTRODUCTION: Arginase inhibition increases plasma citrulline and citrulline / ornithine (C/O) ratio, and reduces plasma ornithine and ornithine / arginine (O/A) ratio in an animal model of myocardial infarction (MI). OBJECTIVES: We hypothesized that the presence of thin­cap fibroatheroma (TCFA) in the culprit lesion and increased non­culprit intima­media thickness of an infarct­related artery (IRA) are associated with an altered balance of arginine metabolites. PATIENTS AND METHODS: Arginine and its metabolites were measured using liquid chromatography and tandem mass spectrometry in 100 consecutive MI patients upon admission and at 6­month follow­up. TCFA and adjacent to culprit lesion proximal and distal 10­mm segments were assessed with optical coherence tomography in the acute phase. Twenty five patients without coronary lesions on angiography served as controls. RESULTS: The C/O ratio increased 5.33 times (P <0.001), while the O/A ratio decreased 2.53 times (P <0.001) at the 6­month follow­up, as compared with the acute phase of MI. The patients with (n = 75) vs without (n = 25) TCFA had lower C/O ratio by 29% (P = 0.003), while the mean intima­media diameter of adjacent non­culprit region correlated with the follow­up O/A ratio (R = 0.337; P = 0.003). In a multivariable analysis, a higher acute phase C/O ratio was associated with a lower risk of TCFA presence (odds ratio, 0.978; 95% CI, 0.962-0.994; P = 0.006), whereas a higher follow­up O/A ratio correlated with larger intima­media diameter of the adjacent segments (ß coefficient, 0.227; 95% CI for ß coefficient, 0.045-0.409; P = 0.018). CONCLUSIONS: Enhanced arginase activity over nitric oxide synthase following ischemia was associated with the presence of TCFA in the culprit lesion, while a similar metabolic shift in the chronic phase correlated with a greater thickness of the intima­media in the adjacent non­culprit IRA segments.

Clinical Characteristics and Long-Term Outcomes of MINOCA Accompanied by Active Cancer: A Retrospective Insight Into a Cardio-Oncology Center Registry.

Background: Clinical characteristics and long-term outcomes of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and cancer are insufficiently elucidated. Objectives: We sought to characterize these patients hospitalized in a tertiary cardio-oncology center and to find the potential determinants affecting their long-term mortality. Methods: MINOCA was diagnosed in 72 of the 1,011 patients with consecutive myocardial infarction who underwent coronary angiography. Mortality rates and their determinants were analyzed within a median follow-up of 69.2 (37.8-79.9) months. Results: Active cancer was identified in 21 (29.2%) of patients with MINOCA and in 113 (12.0%) patients with myocardial infarction and obstructive coronary artery disease (MI-CAD) (p < 0.001). MINOCA patients with cancer were characterized by a higher incidence of anemia (47.6 vs. 21.6%, p = 0.03) and more frequently Takotsubo syndrome (19.1 vs. 2.0%, p = 0.01) than in non-cancer MINOCA. The troponin T/hemoglobin ratio was higher in both cancer MINOCA and MI-CAD groups when compared with their respective non-cancer patients (both p < 0.05). The age and sex-standardized mortality rates were significantly higher in cancer MINOCA (26.7%/year) when compared with non-cancer MINOCA (2.3%/year, p = 0.002) and in cancer MI-CAD (25.0%/year) vs. non-cancer MI-CAD (3.7%/year, p < 0.001). Active cancer (HR 3.12, 95% CI 2.41-4.04) was independently associated with higher long-term mortality, while higher hemoglobin levels (HR 0.93, 95% CI 0.88-0.99, per g/dl) and a MINOCA diagnosis (HR 0.69, 95% CI 0.47-0.97) improved long-term survival. Conclusion: Patients with MINOCA were comorbid with cancer more frequently than MI-CAD. In turn, an active malignancy was associated with an unfavorable long-term survival both in MI-CAD population and in patients with MINOCA.

Cardiometabolic predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots in patients at high cardiovascular risk: an 8-year prospective cohort study.

INTRODUCTION: Adiposity has a few phenotypes associated with various levels of risk for diabetes mellitus (DM), but their exact predictive value is not well understood. OBJECTIVES: We aimed to assess the predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots for long­term cardiometabolic risk. PATIENTS AND METHODS: A total of 150 patients with chronic coronary syndrome (CCS) scheduled for elective coronary angiography were enrolled and a comprehensive clinical and ultrasound assessment of adiposity was performed (2012-2013). Of them, 143 individuals were followed for 8 years for insulin resistance (IR) and / or DM development. RESULTS: At baseline, DM and prediabetes were found in 22% and 8% of the patients, respectively. It was established that 11.7% of the participants died during the follow­up. The rate of DM increased to 46% with a decrease in the prediabetes rate (3.5%). Significant correlations with the Homeostatic Model Assessment of Insulin Resistance and glycated hemoglobin were observed for major anthropometric and ultrasound variables. In the multivariable analysis, independent predictors of IR were preperitoneal fat thickness (PreFT) (per 10mm increase: odds ratio [OR], 1.63; 95% CI, 1.22-2.33; P = 0.003) and body surface area (per 0.1m2 increase: OR, 1.59; 95% CI, 1.11-2.39; P = 0.02). DM was independently predicted by the high­density lipoprotein cholesterol concentration (OR, 0.93; 95% CI, 0.87-0.97; P = 0.005) and body fat mass (OR, 1.09; 95% CI, 1.03-1.17; P = 0.003). CONCLUSIONS: A complex assessment of the adipose tissue in patients with CCS is a valuable method for improving metabolic risk stratification. Some anthropometric and ultrasound parameters, such as PreFT or body surface area, were associated with IR and DM development.

Various clinical scenarios of primary melanoma of the esophagus: A retrospective 20-year analysis from two university thoracic surgery centers.

BACKGROUND: Primary melanoma of the esophagus (PME) represents a rare type of gastrointestinal malignancy with an exceptionally poor diagnosis. So far, only few descriptions of PME which satisfactorily summarize their clinical characteristics and prognosis have been published. OBJECTIVES: The aim of our study was to summarize our experience with PME patients. MATERIAL AND METHODS: In a group of 1387 patients who underwent esophagectomy due to neoplastic process in the years 2000-2020 in 2 high-volume university thoracic surgery centers, we identified those with confirmed PME diagnosis. Subsequently, their clinical characteristics, imaging and histopathological results were compared. The data regarding the long-term survival were obtained from the Polish National Death Registry. RESULTS: The PME was identified in 4 (0.29%) patients. Three of them (75%) were males. The mean age on admission was 64.3 ±17.5 years. The main symptom in all patients was dysphagia. In 1 patient with the most advanced PME, the clinically relevant weight loss was noted. In 3 patients, Ivor Lewis esophagectomy was performed, and 1 patient underwent McKeown resection. Histopathologic examination revealed a metastasis of lymph nodes only in 1 patient. The average maximum size of tumor was 6.9 ±4.7 cm and all tumors were located in distal part of the esophagus. Two out of those 4 patients are still alive and the longest survival time is 17 years. One patient died due to postoperative massive gastrointestinal bleeding complicated with cardiac arrest and the other one due to progression of PME systemic dissemination 6 months after surgical treatment. CONCLUSION: The PME is an extremely rare diagnosis. A long-term survival can be achieved with the complete resection. Clinical scenarios of surgically treated PME patients may significantly differ.

Statin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality.

Statin use and its impact on long-term clinical outcomes in active cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Of the 1011 consecutive acute MI patients treated invasively between 2012 and 2017, cancer was identified in 134 (13.3%) subjects. All patients were observed within a median follow-up of 69.2 (37.8−79.9) months. On discharge, statins were prescribed less frequently in MI patients with cancer as compared to the non-cancer MI population (79.9% vs. 91.4%, p < 0.001). The most common statin in both groups was atorvastatin. The long-term mortality was higher in MI patients not treated vs. those treated with statins, both in non-cancer (29.5%/year vs. 6.7%/year, p < 0.001) and cancer groups (53.9%/year vs. 24.9%/year, p < 0.05), respectively. Patient's age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.03−1.05, p < 0.001, per year), an active cancer (HR 2.42, 95% CI 1.89−3.11, p < 0.001), hemoglobin level (HR 1.14, 95% CI 1.09−1.20, p < 0.001, per 1 g/dL decrease), and no statin on discharge (HR 2.13, 95% CI 1.61−2.78, p < 0.001) independently increased long-term mortality. In MI patients, simultaneous diagnosis of an active cancer was associated with less frequently prescribed statins on discharge. Irrespective of cancer diagnosis, no statin use was found as an independent predictor of increased long-term mortality.

Dementia screening in elderly high-risk patients following heart failure decompensation may predict unfavorable long-term clinical outcomes.

BACKGROUND: Recently heart failure (HF) has been found to be a new dementia risk factor; nevertheless, their relations in patients following HF decompensation remain unknown. We sought to investigate whether a screening diagnosis for dementia (SDD) in this high-risk population may predict unfavorable long-term clinical outcomes. METHODS: One hundred forty-two patients following HF decompensation requiring hospitalization were enrolled. Within a median time of 55 months all patients were screened for dementia with ALFI-MMSE scale whereas their compliance was assessed with the Morisky Medication Adherence Scale. Any incidents of myocardial infarction, coronary revascularization, stroke or transient ischemic attack (TIA), revascularization, HF hospitalization and bleedings during follow-up were collected. RESULTS: SDD was established in 37 patients (26%) based on the result of an ALFI-MMSE score of <17 points. By multivariate analysis the lower results of the ALFI-MMSE score were associated with a history of stroke/TIA (ß=-0.29, P<0.001), peripheral arterial disease (PAD) (ß=-0.20, P=0.011) and lower glomerular filtration rate (ß=0.24, P=0.009). During the follow-up, patients with SDD were more often rehospitalized following HF decompensation (48.7% vs. 28.6%, P=0.042) than patients without SDD, despite a similar level of compliance (P=0.25). Irrespective of stroke/TIA history, SDD independently increased the risk of rehospitalization due to HF decompensation (HR 2.22, 95% CI: 1.23-4.01, P=0.007). CONCLUSIONS: In patients following decompensated HF, a history of stroke/TIA, PAD and impaired renal function independently influenced SDD. In this high-risk population, SDD was not related with patients' compliance but irrespective of the stroke/TIA history it was associated with the increased risk of HF rehospitalization.

Worse long-term prognosis in myocardial infarction occurring at weekends or public holidays with insight into myocardial infarction with nonobstructive coronary arteries.

INTRODUCTION: The weekend effect in Polish patients with myocardial infarction (MI) treated in the current network of catheterization laboratories is poorly understood. OBJECTIVES: We sought to investigate long­term prognosis of patients with MI admitted at weekends or public holidays (NWDs) and on working days (WDs). PATIENTS AND METHODS: We enrolled 865 patients with MI hospitalized between 2012 and 2017. The long­term mortality within the median (IQR) time of 68.5 (36.7-78.4) months was determined in 223 patients (25.8%) admitted on NWDs and in 642 (74.2%) on WDs. RESULTS: Patients admitted on NWDs more often had ST­segment elevation MI (41.3% vs 30.8%; P = 0.005), left anterior descending artery as an infarct­related artery (38.1% vs 30.2%; P = 0.031) and incomplete reperfusion expressed as Thrombolysis in Myocardial Infarction flow grade 0/1 following primary angioplasty (6.8% vs 1.6%; P <0.001) as compared with those hospitalized on WDs. Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurred less often on NWDs (4% vs 9%, P = 0.019). The all­cause long­term mortality was higher in NWD patients as compared with those admitted on WDs (36.3% vs 28.4%; P = 0.037). By the Cox proportional hazards model with time­dependent covariates, MI on NWDs (hazard ratio, 1.027; 95% CI, 1.022-1.032; P <0.001) but not MINOCA (hazard ratio, 0.971; 95% CI, 0.595-1.583; P = 0.91) was independently associated with long­term mortality. CONCLUSIONS: Patients hospitalized on NWDs as compared with those admitted on WDs had a larger ischemic territory and more often had transmural MI with incomplete epicardial reperfusion, which resulted in a higher long­term mortality. The latter outcome was not influenced by MINOCA.