CardioHepatology: Exploring the Interplay Between Cirrhosis, Cirrhotic Cardiomyopathy, Coronary Artery Disease, and Liver Transplantation.

Morphological overview of cardiovascular comorbidities in chronic obstructive pulmonary disease: Frank's sign

Background: Some metastatic breast cancer (MBC) treatments are associated with cardiac toxicity. Real-world data regarding baseline cardiac comorbidities in patients with MBC prior to chemotherapy initiation are scarce. Such information would be useful in guiding treatment decisions. This study aims to describe the cardiac comorbidity profile of patients with MBC initiating doxorubicin-based (DOX) versus non-doxorubicin-based (Non-DOX) chemotherapy regimens from a managed-care perspective.Methods: Medical claims from the Ingenix Impact National Managed Care Database between 07/2002 and 06/2008 were analyzed. Patients included were aged ≥ 18 years, and had ≥ 2 diagnoses for breast cancer as well as ≥ 1 diagnosis for metastatic site within 12 months of chemotherapy initiation. Cardiac comorbidities [hypertension (HTN), cardiac arrhythmia (CAr), coronary artery disease (CAD), congestive heart failure (CHF), and myocardial infarction (MI)] were evaluated within 6 months prior to chemotherapy initiation. Patients were categorized based on receipt of DOX vs. Non-DOX-based chemotherapy.Results: A total of 12,345 patients (Non-DOX: 7,023, DOX: 5,322) formed the study population. Compared with the DOX group, the Non-DOX group was slightly older. Both groups reported a significant proportion of patients with cardiac comorbidities prior to chemotherapy, with significantly greater proportions reported in the Non-DOX group. Mean age (SD)HTNCArCADCHFMINon-DOX (n=7,023)56.9 (10.6)35.7%11.8%5.5%3.5%1.3%DOX (n=5,322)52.1 (9.1)30.8%8.1%3.3%2.0%0.5%P-value<.001<.001<.001<.001<.001<.001 Conclusions: Cardiac comorbidities were commonly reported in women with MBC prior to chemotherapy, with significantly greater proportions reported in the Non-DOX group. Such information is useful to healthcare professionals when considering potential interventions for patients with MBC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2078.

Invited Commentary

Introduction. Metabolic dysfunction-associated steatotic liver disease and coronary artery disease often exacerbate each other, leading to a more severe course of both conditions. The aim of this study is to evaluate the role of coronary artery disease in dislipidemia and liver fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Forty-six patients with metabolic dysfunction-associated steatotic liver disease were examined. Patients were divided into two groups based on the presence of concomitant coronary artery disease: group I (n=24) included patients with both metabolic dysfunction-associated steatotic liver disease and coronary artery disease, while group II (n=22) included patients with metabolic dysfunction-associated steatotic liver disease only. A third group (Group III) comprised healthy individuals. Specific lipid metabolism parameters, obesity stage, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) activity, and platelet count were examined. Fibrosis stage was evaluated using the FIB-4 score. The findings obtained were statistically processed. Results. Arterial hypertension was more prevalent in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease. In group I, arterial hypertension was observed in 95.8% of cases, whereas in group II, it was observed in 40.9% of cases (χ2=16.35, p=0.00005). Patients with metabolic dysfunction-associated steatotic liver disease exhibited elevated levels of total cholesterol, low-density lipoproteins, and triglycerides, leading to an increased atherogenic index. Conversely, high-density lipoprotein levels were decreased (p>0.05). The degree of fibrosis according to the FIB-4 score was 1.45 times higher in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease compared to those without coronary artery disease.

Background The optimal management of patients with concomitant coronary artery disease (CAD) and severe carotid artery stenosis remains a controversy. We performed a systematic review of studies comparing early outcomes of synchronous or staged carotid artery stenting (CAS) and coronary artery bypass grafting (CABG) in the treatment of patients with concomitant CAD and severe carotid artery stenosis. Methods Multiple databases were systematically searched to identify studies of synchronous or staged CAS and CABG in the treatment of concomitant severe carotid and coronary artery disease published from 2005 to 2015. The quality of studies was assessed using the MINORS scale. The demographic data, risk factors, 30-day outcomes, and antiplatelet strategy were extracted. Results 23 studies were identified with a total of 873 and 459 patients in the staged and synchronous group, respectively. The observed overall death/stroke/MI rate was 8.5% (95% CI: 7.6-9.4%) in staged group and 4.8% (95% CI: 3.8-5.8%) in synchronous group. It seems that the synchronous group has better 30-day outcomes, but these data could not be compared statistically. Conclusion Our systematic review suggests either synchronous or staged CAS and CABG can be chosen for the treatment of concomitant carotid and coronary artery disease. It seems that the synchronous approach is relatively convenient and the antiplatelet strategy is relatively definite. For these patients, hybrid revascularization by synchronous CAS and CABG might be a feasible and promising therapeutic strategy. Our conclusions and the quality of the existing data suggest that a randomized controlled trial is needed to define the best treatment for patients with concomitant carotid and coronary artery disease.

Objective — to investigate the influence of the combination of L‑arginine and L‑carnitine on prooxidant‑antioxidant status and arginine‑citrulline cycle in patients with multiple myeloma (MM) and concomitant coronary artery disease (CAD) during the chemotherapy. Materials and methods. 59 patients with multiple myeloma progression and concomitant coronary artery disease were examined. According to the presence of concomitant coronary artery disease and prescribed treatment, all patients were divided into groups: I (n=20) — patients with multiple myeloma and no concomitant diseases of the cardiovascular system, who received the standard chemotherapy, II (n=22) — patients with multiple myeloma and concomitant coronary artery disease, who received standard chemotherapy and basic treatment of coronary artery disease, III (n=17) — patients with multiple myeloma and concomitant coronary artery disease who received standard chemotherapy, basic treatment of coronary artery disease in combination with L‑arginine and L‑carnitine. All patients obtained bortezomib‑containing schemes of chemotherapy. Patients were examined twice: before the initiation of chemotherapy and before the fifth course of chemotherapy. The concentration of L‑arginine, citrulline, thiobarbituric acid reactants (TBAR), and the activity of arginase and catalase in blood serum were measured. Results. During the multiple myeloma progression in patients of groups II and III, the concentration of TBAR‑substances was increased by 1.3 times (р <0.0001) compared with patients of group I. Simultaneously, in patients of groups II and III, the catalase activity decreased by 1.3 times (р <0.0001), and the concentration of serum citrulline was 1.7 times (р <0.0001) and 1.9 times (р <0.0001) higher than in patients of group I. Before the fifth course of chemotherapy in patients of group III, the concentration of serum L‑arginine was 1.1 times ((71.11 (68.74; 77.79) vs. 64.25 (59.41; 69.47)) µmol/l, р=0.0001) higher than in patients of group II. Simultaneously, the concentration of serum citrulline was increased by 1.3 times ((250.5 (205.4; 285.3) vs. 197.0 (175.0; 243.5)) µmol/l. р=0.007) compared with group II. In patients of groups I and III the activity of catalase in blood serum was increased by 1.1 times ((13.77 (12.50; 14.86) vs. 15.37 (14.24; 16.01)) µkat/l. р <0.05) and by 1.4 times ((10.43 (9.55; 10.75) vs. 14.26 (12.45; 15.81)) µkat/l, р <0.001), respectively, compared with the initial examination. However, in patients of group II, it was decreased by 1.3 times ((10.07 (9.40; 10.25) vs. 8.00 (7.74; 8.23)) µkat/l. р <0.001) compared to the initial examination. Multiple myeloma progression was accompanied by prooxidant‑antioxidant status disorders, which were represented by increasing concentrations of TBAR‑substances independent from the presence of concomitant coronary artery disease. However, in patients with multiple myeloma and concomitant coronary artery disease, serum concentration of TBAR‑substances was significantly higher compared with patients with multiple myeloma without concomitant diseases of the cardiovascular system. According to our study, the administration of L‑arginine and L‑carnitine significantly increases the concentration of L‑arginine in the blood serum, which decreases the level of endothelial dysfunction by the augmentation of nitric oxide production in the background of reduced oxidative stress and arginase activity. Conclusions. Addition of L‑arginine and L‑carnitine to the supportive therapy of patients with multiple myeloma with concomitant coronary artery disease leads to a significant decrease of TBAR‑substances concentration in the blood serum with simultaneous augmentation of catalase activity in the blood serum (р <0.05) during the chemotherapy, which makes these indicators equivalent to those of patients with multiple myeloma without concomitant disease of the cardiovascular system (р >0.05). L‑arginine and L‑carnitine significantly increase the concentration of L‑arginine in the blood serum of patients with multiple myeloma and concomitant coronary artery disease during the chemotherapy (р >0.05), which contributes to the decreasing of oxidative stress severity and improvement of endothelial function by efficient NOS‑dependent L‑arginine unitization with NO formation.

Aortic valve stenosis (AVS) share pathobiology and risk factors with atherosclerosis. However, medical treatment effective against atherosclerosis lack ability to halt the progression of AVS. The aims of this study were to (i) determine the prevalence of coronary artery disease (CAD) in surgical AVS patients and (ii) to establish predictors of CAD in AVS patients and (iii) to identify differential aortic valve transcriptomic profiles depending on concomitant CAD. The study cohort consisted of 256 consecutive AVS patients with surgically verified tricuspid aortic valves, of which 74 aortic valves were collected. CAD defined as coronary artery stenosis requiring concomitant bypass surgery or previous acute coronary syndrome or percutaneous coronary intervention Transcriptomic data were obtained from microarray analysis of tissues from three different stages of AVS process (healthy, intermediate, and calcified tissue). All comparisons were sex and tissue adjusted. Non-coding probes were removed and a variance filter was applied prior to analysis which yielded 5121 genes. The prevalence of CAD in AVS was 49%. A logistic regression model revealed male sex, claudication, diabetes and current smoking as significant predictors of CAD when age, sex, peak transaortic velocity, hsCRP, eGFR and BMI were held constant. 28 genes were significantly (q<0.05) differentially expressed when aortic valves from patients with (n=43) and without (n=31) CAD were compared. A comparison of patients with concomitant multi vessel disease (2–3 affected vessel territories, n=20) and patients without CAD or single vessel disease (n=54) revealed 189 significantly expressed genes and an optimal visual separation on heatmap (Figure 2). Active-subnetwork-oriented-enrichment analysis identified upregulated aortic valve atherosclerosis associated pathways in multi vessel disease patients related to reactive oxygen species and cytokine signaling. This study provides a novel observation of differential aortic valve gene expression profile depending on concomitant severe CAD. The results revealed that patients with concomitant severe CAD exhibited underlying atherosclerosis-related mechanisms to their aortic valve disease. Therefore, future precision medicine against AVS may be facilitated by assessing concomitant CAD. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Karolinska Institute - Clinical Science Training ProgrammeSwedish Heart Lung Foundation Predictors of concomitant CADDEGs in AVs stratified on severe CAD

Chronic obstructive pulmonary disease (COPD) is a global health issue with high social and economic costs. Concomitant chronic cardiac disorders are frequent in patients with COPD, likely owing to shared risk factors (e.g., aging, cigarette smoke, inactivity, persistent low-grade pulmonary and systemic inflammation) and add to the overall morbidity and mortality of patients with COPD. The prevalence and incidence of cardiac comorbidities are higher in patients with COPD than in matched control subjects, although estimates of prevalence vary widely. Furthermore, cardiac diseases contribute to disease severity in patients with COPD, being a common cause of hospitalization and a frequent cause of death. The differential diagnosis may be challenging, especially in older and smoking subjects complaining of unspecific symptoms, such as dyspnea and fatigue. The therapeutic management of patients with cardiac and pulmonary comorbidities may be similarly challenging: bronchodilators may have cardiac side effects, and, vice versa, some cardiac medications should be used with caution in patients with lung disease. The aim of this review is to summarize the evidence of the relationship between COPD and the three most frequent and important cardiac comorbidities in patients with COPD: ischemic heart disease, heart failure, and atrial fibrillation. We have chosen a practical approach, first summarizing relevant epidemiological and clinical data, then discussing the diagnostic and screening procedures, and finally evaluating the impact of lung-heart comorbidities on the therapeutic management of patients with COPD and heart diseases.

1052 Background: Observational data are sparse regarding cardiac comorbidities in patients with metastatic breast cancer (MBC) newly initiated on chemotherapy. As some MBC treatments are associated with cardiac toxicity, such information would be useful in guiding treatment decisions. The objective of this analysis was to understand the frequency of cardiac comorbidities in MBC patients prior to chemotherapy initiation based on the Medicare 5% standard analytical file (SAF). Methods: The Medicare 5% SAF was used to investigate claims for women with breast neoplasm and > 1 distant metastatic site (based on ICD-9 diagnosis codes) that subsequently received chemotherapy (based on claims with a chemotherapy J code). Cardiac comorbidities [hypertension (HTN), coronary artery disease (CAD), myocardial function (MI), and congestive heart failure (CHF)] prior to initial chemotherapy were reported as non-mutually exclusive categories. The index quarter was based on chemotherapy initiation that occurred between 7/2001 and 12/2006. Patients were categorized based on receipt of non doxorubicin-based chemotherapy (non-DOX) vs DOX-based chemotherapy. Results: The study included 2,587 women with MBC that received cytotoxic chemotherapy subsequent to the diagnosis of MBC. The mean age was higher in the non-DOX group. Both groups reported a significant proportion of patients with cardiac comorbidities prior to chemotherapy, with greater proportions reported in the non-DOX group (table). Conclusions: Cardiac comorbidities were commonly reported in women with MBC prior to chemotherapy. Such information is useful to health care professionals when considering potential interventions for patients with MBC. [Table: see text] [Table: see text]

Multidetector computed tomography assessment of cardiac comorbidity in patients with chronic obstructive pulmonary disease

BackgroundEvidence guiding optimal transfusion practice for patients with myelodysplastic syndromes (MDS) is lacking. Many patients have concurrent cardiac disease. Data on practice are sparse. We aimed to describe the use of red blood cell (RBC) transfusion and the prevalence of cardiac comorbidities in patients with MDS within Australia's largest public hospital network to better understand real‐world practices and outcomes.MethodsWe conducted a retrospective cohort study of patients aged ≥18 years with MDS, MDS/myeloproliferative overlap neoplasm or chronic myelomonocytic leukemia admitted from 2016 to 2018 to determine RBC transfusion‐related endpoints.ResultsOne hundred and seventy‐nine patients (median age 78 years, 61.5% male) were included, with a median follow‐up of 46 weeks. Of these, 102 (57.0%) received RBC transfusion. Transfused patients had lower presenting Hb (87 vs. 105 g/L, p < 0.0001), higher rates of cardiac disease (29.4% vs. 12.9%, p = 0.009) and 5‐azacytidine use (31.4% vs. 13.0%, p = 0.004). Sixty‐five patients (36.3%) received outpatient RBC transfusions, with a median of 2 units RBC per transfusion and 14 days between transfusions. The median pre‐transfusion Hb was 80 g/L (IQR 74–86 g/L). Forty patients (22.4%) had evidence of cardiac disease, with similar pre‐transfusion Hb for patients with and without cardiac disease (median Hb 79 g/L vs. 81 g/L, p = 0.1).DiscussionPatients with MDS frequently require RBC transfusion, and restrictive transfusion strategies predominate despite many patients having cardiac comorbidities. Further research is needed to address optimal transfusion strategies in such patients and associated cardiac outcomes.

(cellular and humoral immunity, mucosal immunity, the complement system, and so on). With features of immune system in the elderly people related some of clinical problems: hypersensitivity to non- and intra-hospital infections, subacute infection that increases concomitant diseases, especially cardiovascular. Aim of this work was determination of the characteristics of immunological changes in patients with community-acquired pneumonia and concomitant coronary heart disease and their dynamics during treatment with Simvastatin. Material and methods. 50 patients with community acquired pneumonia the third group and 30 healthy individuals were included in an open prospective study. Immunogram definition was made by lymphocytes phenotyping tests rosette of particles coated with monoclonal antibodies. Immunoglobulin G, A, M were determined by radial immunodiffusion Agar gel by Mancini using monospecific sera. Also absorption capacity of the neutrophil count phagocytic index, phagocytic index, neutrophil bacterial activity by a test restore them of nitroblue tetrazolium were defined. Results. Subanalysis in patients with pneumonia with concomitant coronary artery disease, who were randomly assigned to receiving simvastatin, after treatment showed a statistically significant increase of IgG to 18.6% (p=0.02) of 9.57±4.64 to 11.36±3.7. The rest of the performance was not likely changed. After treatment of pneumonia with concomitant coronary artery disease treated and not treated with Simvastatin group the following immunogram indicators significantly differed: the relative number of lymphocytes, the number of CD8 relative and absolute number of CD22 cells, complement activity, completion of the index of phagocytosis. Thus in patients receiving Simvastatin after treatment were lower rates relative number of CD8 cells by 38% (p=0.037) – 18.2±7.38 vs 25.1±8.0; complement activity by 33% (p=0.03) – 66.9±14.8 vs 89.0±17.8; the absolute number of CD22 cells by 26.7% (p=0.005) – 17.68±7.03 vs 24.11±5.87; completion phagocytosis index by 6.3% (p=0.01) – 0.89±0.10 vs 0.95±0.11; and was higher by 36% (p=0.02), relative number of lymphocytes (27.07±5.94 vs 17.32±7.26), than patients who did not receive simvastatin. Conclusions. The Simvastatin use in the treatment of patients with community acquired pneumonia with concomitant coronary artery disease is accompanied by the following positive changes in the immunogram: reducing the number of stick-nuclear leukocytes by 52% and 36% of ESR, increasing content of IgG 18.6%. However, patients with coronary artery disease who did not use Simvastatin in the treatment of pneumonia, had further growth in immuno-reactivity index by 4% and reduction of IgG 12.6%. Immunogram in patients with coronary artery disease who received Simvastatin After a course of treatment was characterized by significantly lower performance of the relative number of CD8 cells by 38% (p=0.037); complement activity by 33% (p=0.03); the absolute number of CD22 cells by 26.7% (p=0.005); completion phagocytosis index by 6.3% (p=0.01); and higher by 36% (p=0.02) relative quantity of the number of lymphocytes than in patients who did not receive Simvastatin. The article presents data of changes in immune status in patients with community acquired pneumonia. There are positive changes in the cellular link of immunity in these patients. In pneumonia patients with concomitant coronary artery disease indicators of immuno- cellular reactivity after Simvastatin treatment were not changed significantly, but humoral immunity has been changed towards in growing of Ig G and M content.

Cardiac Event Rates in Patients with Newly Diagnosed and Relapsed Multiple Myeloma in US Clinical Practice.

Objectives The aim of this study is to assess long-term-outcomes of patients with concomitant CAD and COD treated with different revascularization strategies. Background Multisite artery disease is common and patients with combined disease have poor prognosis. The best therapeutic strategy for patients with concomitant carotid obstructive disease (COD) and coronary artery disease (CAD) remains controversial. Methods This observational registry enrolled, between January 2006 and December 2012, 1022 consecutive patients from high volume institutions with concomitant CAD and COD suitable for endovascular, surgical, or hybrid revascularization in both territories selected by consensus of a multidisciplinary team. Results The cumulative incidence of 5-year major cardiovascular events (MACCE) including cardiovascular death, myocardial infarction (MI), or stroke in the overall population was 12%. The incidence of 5-year MACCE was not statistically different in the surgical, endovascular, or hybrid patients group (10.1% vs. 13.0% vs. 13.2%, P = .257, respectively). However, the hybrid group exhibited rates of myocardial infarction, chronic kidney disease, and cumulative incidence of all clinical events higher than the surgical group. After propensity score matching, the incidence of 5-year MACCE was similar in the three groups (13.0% vs. 15.0% vs. 16.0%, p = .947, respectively). Conclusions An individualized revascularization approach of patients with combined CAD and COD yields very good results at long-term follow-up, despite the high risk of this multilevel population even when the baseline clinical features are equalized.

It is often stated that heart disease is underdiagnosed in COPD. Evidence for this statement comes from primary studies, but these have not been synthesised to provide a robust estimate of the burden of undiagnosed heart disease. A systematic review of studies using active diagnostic techniques to establish the prevalence of undiagnosed major cardiac comorbidities in patients with COPD was carried out. MEDLINE, Embase, Scopus and Web of Science were searched for terms relating to heart failure (specifically, left ventricular systolic dysfunction (LVSD), coronary artery disease (CAD) and atrial fibrillation), relevant diagnostic techniques and COPD. Studies published since 1980, reporting diagnosis rates using recognised diagnostic criteria in representative COPD populations not known to have heart disease were included. Studies were classified by condition diagnosed, diagnostic threshold used and whether participants had stable or exacerbated COPD. Random-effects meta-analysis of prevalence was conducted where appropriate. In general, prevalence estimates for undiagnosed cardiac comorbidities in COPD had broad confidence intervals, with significant study heterogeneity. Most notably, a prevalence of undiagnosed LVSD of 15.8% (11.1-21.1%) was obtained when defined as left ventricular ejection fraction <50%. Undiagnosed CAD was found in 2.3-18.0% of COPD patients and atrial fibrillation in 1.4% (0.3-3.5%). Further studies using recent diagnostic advances, and investigating therapeutic interventions for patients with COPD and heart disease are needed.