Identification of Novel Independent Correlations between Cellular Components of the Immune System and Strain-Related Indices of Myocardial Dysfunction in CKD Patients and Kidney Transplant Recipients without Established Cardiovascular Disease.

The role of immune system components in the development of myocardial remodeling in chronic kidney disease (CKD) and kidney transplantation remains an open question. Our aim was to investigate the associations between immune cell subpopulations in the circulation of CKD patients and kidney transplant recipients (KTRs) with subclinical indices of myocardial performance. We enrolled 44 CKD patients and 38 KTRs without established cardiovascular disease. A selected panel of immune cells was measured by flow cytometry. Classical and novel strain-related indices of ventricular function were measured by speckle-tracking echocardiography at baseline and following dipyridamole infusion. In CKD patients, the left ventricular (LV) relative wall thickness correlated with the CD14++CD16- monocytes (ß = 0.447, p = 0.004), while the CD14++CD16+ monocytes were independent correlates of the global radial strain (ß = 0.351, p = 0.04). In KTRs, dipyridamole induced changes in global longitudinal strain correlated with CD14++CD16+ monocytes (ß = 0.423, p = 0.009) and CD4+ T-cells (ß = 0.403, p = 0.01). LV twist and untwist were independently correlated with the CD8+ T-cells (ß = 0.405, p = 0.02 and ß = -0.367, p = 0.03, respectively) in CKD patients, whereas the CD14++CD16+ monocytes were independent correlates of LV twist and untwist in KTRs (ß = 0.405, p = 0.02 and ß = -0.367, p = 0.03, respectively). Immune cell subsets independently correlate with left ventricular strain and torsion-related indices in CKD patients and KTRs without established CVD.

The Role of Prognostic Scores in Assessing the Prognosis of Patients Admitted in the Cardiac Intensive Care Unit: Emphasis on Heart Failure Patients.

Background/Objectives: Patient care in Cardiac Intensive Care Units (CICU) has evolved but data on patient characteristics and outcomes are sparse. This retrospective observational study aimed to define clinical characteristics and risk factors of CICU patients, their in-hospital and 30-day mortality, and compare it with established risk scores. Methods: Consecutive patients (n = 294, mean age 70 years, 74% males) hospitalized within 15 months were studied; APACHE II, EHMRG, GWTG-HF, and GRACE II were calculated on admission. Results: Most patients were admitted for ACS (48.3%) and acute decompensated heart failure (ADHF) (31.3%). Median duration of hospitalization was 2 days (IQR = 1, 4). In-hospital infection occurred in 20%, 18% needed mechanical ventilation, 10% renal replacement therapy and 4% percutaneous ventricular assist devices (33%, 29%, 20% and 4%, respectively, for ADHF). In-hospital and 30-day mortality was 18% and 11% for all patients (29% and 23%, respectively, for ADHF). Established scores (especially APACHE II) had a good diagnostic accuracy (area under the curve-AUC). In univariate and multivariate analyses in-hospital intubation and infection, history of coronary artery disease, hypotension, uremia and hypoxemia on admission were the most important risk factors. Based on these, a proposed new score showed a diagnostic accuracy of 0.954 (AUC) for in-hospital mortality, outperforming previous scores. Conclusions: Patients are admitted mainly with ACS or ADHF, the latter with worse prognosis. Several patients need advanced support; intubation and infections adversely affect prognosis. Established scores predict mortality satisfactorily, but larger studies are needed to develop CICU-directed scores to identify risk factors, improve prediction, guide treatment and staff training.

Myocardial Perfusion Imaging and C-Reactive Protein in Myocardial Ischemia: A Retrospective Single-Center Study.

BACKGROUND: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coronary heart disease. We investigated the relationship of CRP with findings from myocardial perfusion imaging (MPI). METHODS: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) who underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6 mg/L) within 1 month from MPI were included. The patients had no infection or recent acute coronary syndrome. RESULTS: The median CRP level was 4 mg/L (2, 10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (p = 0.006) and summed rest score (SRS) (p = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, p = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (p = 0.027 and p = 0.005, respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). CONCLUSION: a high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

The Potential Role of Salivary NT-proBNP in Heart Failure.

BACKGROUND: Serum natriuretic peptides (NPs) have an established role in heart failure (HF) diagnosis. Saliva NT-proBNP that may be easily acquired has been studied little. METHODS: Ninety-nine subjects were enrolled; thirty-six obese or hypertensive with dyspnoea but no echocardiographic HF findings or raised NPs served as controls, thirteen chronic HF (CHF) patients and fifty patients with acute decompensated HF (ADHF) requiring hospital admission. Electrocardiogram, echocardiogram, 6 min walking distance (6MWD), blood and saliva samples, were acquired in all participants. RESULTS: Serum NT-proBNP ranged from 60-9000 pg/mL and saliva NT-proBNP from 0.64-93.32 pg/mL. Serum NT-proBNP was significantly higher in ADHF compared to CHF (p = 0.007) and in CHF compared to controls (p < 0.05). There was no significant difference in saliva values between ADHF and CHF, or between CHF and controls. Saliva and serum levels were positively associated only in ADHF patients (R = 0.352, p = 0.012). Serum NT-proBNP was positively associated with NYHA class (R = 0.506, p < 0.001) and inversely with 6MWD (R = -0.401, p = 0.004) in ADHF. Saliva NT-proBNP only correlated with age in ADHF patients. CONCLUSIONS: In the current study, saliva NT-proBNP correlated with serum values in ADHF patients, but could not discriminate between HF and other causes of dyspnoea. Further research is needed to explore the value of saliva NT-proBNP.

The Role of Myocardial Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events at 1 Year Follow-Up: A Single Center's Experience.

BACKGROUND: Myocardial perfusion imaging via single-photon emission computed tomography (SPECT MPI) is a well-established method of diagnosing coronary artery disease (CAD). The purpose of this study was to assess the role of SPECT MPI in predicting major cardiovascular events. METHODS: The study population was composed of 614 consecutive patients (mean age: 67 years, 55% male) referred for SPECT MPI due to symptoms of stable CAD. The SPECT MPI was performed using a single-day protocol. We conducted a follow-up on all patients at 12 months via a telephone interview. RESULTS: The majority of our patients (78%) presented findings suggestive of reversible ischemia, fixed defects or both. Extensive perfusion defects were found in 18% of the population, while LV dilation was found in 7%. During the 12-month follow-up, 16 deaths, 8 non-fatal MIs and 20 non-fatal strokes were recorded. There was no significant association of SPECT findings with the combined endpoint of all-cause death, non-fatal MI and non-fatal stroke. The presence of extensive perfusion defects was an independent predictor of mortality at 12 months (HR: 2.90, 95% CI: 1.05, 8.06, p = 0.041). CONCLUSIONS: In a high-risk patient population with suspected stable CAD, only large reversible perfusion defects in SPECT MPI were independently associated with mortality at 1 year. Further trials are needed to validate our findings and refine the role of SPECT MPI findings in the diagnosis and prognosis of cardiovascular patients.

Coronary microcirculation and left ventricular diastolic function but not myocardial deformation indices are impaired early in patients with chronic kidney disease.

AIM: To investigate abnormalities in myocardial strain and classic echocardiographic indices and coronary flow reserve (CFR), in younger versus older CKD patients. METHODS: Sixty consecutive CKD patients (<60 years old n = 30, ≥60 years old n = 30) and 30 healthy controls (age- and gender-matched with younger CKD patients) were recruited. An echocardiographic assessment including myocardial strain indices (i.e. global longitudinal strain -GLS -, TWIST, UNTWIST rate) was performed at baseline and following dipyridamole administration in all participants. RESULTS: Younger CKD patients had higher E/e', left ventricular mass index and relative wall thickness and lower E' (p < .005 for all) compared to healthy controls. Older CKD patients had lower E/A and E' (p < .05 for both) compared to younger CKD patients; these differences did not remain significant after adjustment for age. CFR was higher in healthy controls compared to younger and older CKD patients (p < .05 for both) without a significant difference between CKD groups. There were no significant differences in GLS, TWIST or UNTWIST values among the three groups of patients. Dipyridamole-induced changes did not differ significantly among the three groups. CONCLUSIONS: Compared to healthy controls, impaired coronary microcirculation and left ventricular diastolic function, but not myocardial strain abnormalities, are found in young CKD patients and deteriorate with aging.

Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease.

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. METHOD: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. RESULTS: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50-0.87; p = 0.004). CONCLUSION: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events.

The effect of SGLT2 inhibitors, GLP1 agonists, and their sequential combination on cardiometabolic parameters: A randomized, prospective, intervention study.

BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We aim to compare the effect of empagliflozin, liraglutide and their sequential combination on arterial stiffness indices in patients with type 2 diabetes (T2D). METHODS: This was a randomized single blind study evaluating the effect of empagliflozin vs liraglutide in adult patients with T2D. Patients were randomized to liraglutide titrated gradually to 1.8 mg or empagliflozin 25 mg in 1:1 ratio. Three months later empagliflozin was added to the liraglutide group, and liraglutide was added to the empagliflozin group. Patients were assessed with non-invasive tests for arterial stiffness (i.e., carotid-femoral PWV and AIx of aortic pressure) at baseline, 3-month and 9-month visits (final visit was extended for 3 months from the initial design due to Covid 19 pandemic). The primary outcome was the between-group difference of PWV change (ΔPWV) and ΔAIx at 3 months. Secondary outcomes included the between-group difference of ΔPWV and ΔAIx at 9 months, as well as the ΔPWV and ΔAIx between baseline and 9-month visit when total study population was assessed. RESULTS: A total of 62 patients with T2D (30 started liraglutide; 32 empagliflozin, mean age 63 years, 25 % with established cardiovascular disease) participated in the study. We failed to show any significant between-group differences of ΔPWV and ΔΑΙx at 3 and 9 months, as well as between-group difference of ΔPWV and ΔAIx for the total study population between baseline and 9-month visit. In contrast, systemic vascular resistance and lipoprotein(a) levels improved, showing better results with liraglutide than empagliflozin. Favorable effects were also observed on body weight, body mass index, body and visceral fat, blood pressure, HbA1c, and uric acid levels. CONCLUSION: No evidence of a favorable change in arterial stiffness indices was seen with empagliflozin or liraglutide or their combination in this study. Well-designed powerful studies are needed to address any potential effects on arterial stiffness in selected populations.

Body Mass Index Is Independently Associated with the Presence of Ischemia in Myocardial Perfusion Imaging.

Background and Objectives: Obesity has been linked to various cardiovascular risk factors, increased incidence of coronary artery disease, and myocardial perfusion defects. The aim of this study was to investigate if body mass index (BMI) and waist circumference (WC) were associated with myocardial perfusion defects. Materials and Methods: A total of 308 consecutive patients who had myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) and a complete medical record on file were studied retrospectively. Results: The median age was 69 (61−76) years, the BMI was 27.6 (24.4−30.7) kg/m2, and the WC was 110 (102−118) cm. Of the 308 patients, 239 patients (77.6%) had myocardial ischemia. A positive test for ischemia was more frequent in men compared to women (72 vs. 28%, p < 0.001). Within the male group, BMI and WC were not significantly different between the ischemia and non-ischemia groups. In contrast, within the female group, both BMI (30.2 vs. 27.1 kg/m2, p = 0.002) and WC (112 vs. 105.5 cm, p = 0.020) were significantly higher in the ischemia group. Multivariable logistic regression showed that male sex and BMI were the only two independent predictors of ischemia in our patient population. Conclusions: This study showed that BMI was an independent predictor of ischemia in our patient population.

Myocardial Ischemia on MPI SPECT in a Patient with Acute Myeloid Leukemia Without Significant Coronary Artery Disease.

Herein, we report the case of a 56-year-old male patient with acute myeloid leukemia (AML) in remission who had asymptomatic myocardial ischemia on myocardial perfusion imaging and transthoracic echocardiography. Angiography did not reveal any significant coronary artery disease. Although the etiology is not entirely clear, this case suggested that myocardial perfusion imaging should be considered in patients with AML who received idarubicin to screen for possible myocardial dysfunction.

Venous Thromboembolism in Patients with Heart Failure.

Heart failure (HF) and venous thromboembolism (VTE) are common clinical entities, closely interrelated, sharing multiple pathophysiological mechanisms. Their co-incidence is associated with further worsening of the prognosis of one another. Despite their frequent co-existence, important clinical questions still remain unanswered. The risk of VTE especially in chronic HF patients appears to vary widely in clinical studies, while the VTE-associated risk in HF patients is still not well determined and cannot be accurately predicted. Although scientific guidelines recommend venous thromboprophylaxis in patients hospitalized with an acute HF syndrome, venous thromboprophylaxis has not been studied adequately in prospective trials in ambulatory HF patients. In the present review, we aimed to summarize the current knowledge on the epidemiology of VTE and HF, the risk prediction for VTE occurrence in HF patients, the impact on patient outcome, and the need for anticoagulation in certain HF subgroups to improve prognosis, while we sought to identify gaps in knowledge that need to be addressed in the future.

Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review.

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.

Heart Failure diagnosis based on deep learning techniques.

The aim of the study is to address the heart failure (HF) diagnosis with the application of deep learning approaches. Seven deep learning architectures are implemented, where stacked Restricted Boltzman Machines (RBMs) and stacked Autoencoders (AEs) are used to pre-train Deep Belief Networks (DBN) and Deep Neural Networks (DNN). The data is provided by the University College Dublin and the 2nd Department of Cardiology from the University Hospital of Ioannina. The features recorded are grouped into: general demographic information, physical examination, classical cardiovascular risk factors, personal history of cardiovascular disease, symptoms, medications, echocardiographic features, laboratory findings, lifestyle/habits and other diseases. The total number of subjects utilized is 422. The deep learning methods provide quite high results with the Autoencoder plus DNN approach to demonstrate accuracy 91.71%, sensitivity 90.74%, specificity 92.31% and f-score 89.36%.

Relationship between Indices of Vascular Function and Presence of Overt Cardiovascular Disease among Persons with Poorly Controlled Type 2 Diabetes.

The aim of this study was to assess the factors associated with impaired vascular function in patients with poorly controlled type 2 diabetes (DM2) with and without overt cardiovascular disease (CVD). Ninety-five patients with DM2 and poor glycemic control were recruited and divided into two groups: Group 1, with known CVD (n = 38), and Group 2, without CVD (n = 57). Patients in Group 2 were further subdivided into those with short (<5 years, group 2b) and long (>5 years, group 2a) diabetes duration. Subclinical markers of atherosclerosis were assessed. Glycemic control was similar in the two groups (HbA1c: 9.2% (1.5) vs. 9.4% (1.8), p = 0.44). In Group 1, lower FMD (3.13 (2.16)% vs. 4.7 (3.4)%, p < 0.05) and higher cIMT (1.09 (0.3) mm vs. 0.96 (0.2) mm, p < 0.05) was seen compared with Group 2, whereas PWV was similar (12.1 (3.4) vs. 11.3 (3.0) m/s, p = 0.10). Patients in Group 2b had significantly lower PWV and cIMT and higher FMD compared to Group 1 (p < 0.05). Among patients with poorly controlled T2D, more pronounced vascular dysfunction was present in those with overt macrovascular disease. In patients with T2D without known CVD, vascular dysfunction was associated with disease duration. The use of vascular indices for cardiovascular risk stratification in patients with T2D requires further study.

A Machine Learning Approach for Chronic Heart Failure Diagnosis.

The aim of this study was to address chronic heart failure (HF) diagnosis with the application of machine learning (ML) approaches. In the present study, we simulated the procedure that is followed in clinical practice, as the models we built are based on various combinations of feature categories, e.g., clinical features, echocardiogram, and laboratory findings. We also investigated the incremental value of each feature type. The total number of subjects utilized was 422. An ML approach is proposed, comprising of feature selection, handling class imbalance, and classification steps. The results for HF diagnosis were quite satisfactory with a high accuracy (91.23%), sensitivity (93.83%), and specificity (89.62%) when features from all categories were utilized. The results remained quite high, even in cases where single feature types were employed.

Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01-2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24-4.29], P < 0.001). CONCLUSIONS: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality.

Vascular effects following intensification of glycemic control in poorly controlled patients with long-standing type 2 diabetes mellitus.

PURPOSE: The aim of the present study was to investigate the effect of intensive antidiabetic therapy on vascular indices in type 2 diabetes mellitus (T2DM) patients. METHODS: Poorly controlled T2DM patients (n = 62, mean age 64 years, T2DM duration 14 years, HbA1c ≥ 7.5%) were studied at baseline and following intensive treatment to achieve optimal glycemic control. Brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, central augmentation index, large and small (C2) artery compliance, carotid intima-media thickness (cIMT), and ankle-brachial index were assessed at baseline and follow-up. RESULTS: HbA1c decreased from 8.8% (8.1, 10.1) (median, interquartile range-IQ) to 7.4% (6.9, 7.8), p < 0.001. Triglycerides and high-sensitivity C-reactive protein levels were decreased by ~ 10% and 50%, respectively (p < 0.05). Maximum cIMT and C2 increased at follow-up (0.97 ± 0.25 to 1.03 ± 0.27 mm and 3.3 (2.7, 4.2) to 4.2 (3.2, 5.4) ml/mmHg × 10, respectively, p < 0.05). In subgroup analysis, the observed changes in vascular indices were not affected by diabetes duration, presence of cardiovascular disease, or insulin treatment. CONCLUSION: In patients with long-standing T2DM, short-term aggressive glycemic control was associated with an improvement of microvascular function (C2) and deterioration of carotid atherosclerosis (IMT) without any effect on the elastic properties of large arteries.