Marko Boban

Obesity dilemma in the global burden of cardiovascular diseases

Obesity is a well‐known risk factor in the cardiovascular disease continuum. However, its clinical effects are multimodal, perplexed and non‐unanimously understood. Our aim was to assess the prevalence and effects of obesity on the cardiometabolic risk factors and systolic function of left ventricle ejection fraction (LVEF) in patients scheduled for cardiovascular rehabilitation.

The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: a systematic review.

Excessive bleeding after cardiopulmonary bypass (CPB) operations remains to be a persistent problem and weak platelet function certainly contributes to bleeding diathesis. Antiplatelet therapy (APT) is an integral component of perioperative management in patients undergoing cardiac surgery procedures, both with and without use of CPB. In addition to individual variability in platelet function, different preoperative APT administration/discontinuation management further affects platelet function, which in turn may reflect bleeding tendency. However, the impact of drug-induced platelet inhibition on early postoperative bleeding extent remains difficult to predict. Herein, we reviewed the available evidence on the association between platelet function testing values and the extent of bleeding and transfusion requirements in early perioperative period. Currently, the association between platelet function measured by ex vivo assay and the occurrence of bleeding events remains uncertain. The intent of this review is to provide comprehensive literature insight into published evidence, investigating the possibility of platelet function tests to predict bleeding extent as well as transfusion requirements in cardiac surgery patients.

Platelet function testing and prediction of bleeding in patients exposed to clopidogrel undergoing coronary artery surgery

We read with great interest the recently published study by Reed et al.1 The authors conducted a proof-of-principle, prospective, observational pilot study of 39 clopidogreltreated patients scheduled for on-pump coronary artery surgery (CAS).1 Briefly, the authors found that the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) can predict bleeding within the first 24 hours after CAS.1 This pilot study certainly adds to the current knowledge; however, some methodological considerations should be addressed. It is important to note that 37 (95%) patients were exposed to aspirin doses of 81 to 325 mg for ≥7 days prior to enrollement.1 Of those, 31 (80%) patients were exposed to aspirin doses ≥324 mg in close proximity (within 24 hours) to surgery.1 Considering preoperative antiplatelet therapy management, in particular aspirin dosage and discontinuation management, we may assume that the lack of aspirin-specific platelet function testing was a major drawback of the study.1 The VerifyNow system provides 2 different assays, (1) VerifyNow P2Y12 and (2) VerifyNow aspirin. VerifyNow aspirin incorporates the agonist arachidonic acid to activate platelets and has been shown to reliably detect aspirin effect.2 Recently, we have conducted a prospective observational study with the aim to assess bleeding risk using a pointof-care impedance aggregometer in patients undergoing CAS.3 Patients transfused with packed red blood cells had significantly lower aspirin-sensitive platelet function test values,3 and those values significantly correlated to the amount of 24-hour chest tube output.3 In our study, patients were preoperatively exposed to a daily aspirin dose of 100 mg.3 Thus, we assume that prediction of bleeding using aspirin-sensitive platelet function testing could be even more accurate in a group of patients exposed to more aggressive preoperative aspirin dosage regimens. This assumption may be further corroborated by the fact that, when coadministered, aspirin and clopidogrel achieve greater inhibitory effects on platelet aggregation than either agent alone.4 The role of aspirin should not be underestimated. By disregarding the variability in the individual responsiveness to aspirin, as well as the possibility that some patients can actually have a profound platelet inhibitory effect on higher aspirin doses, the authors have negated the possible independent contribution of aspirin response as a confounding variable in their pilot study.1 To the best of our knowledge, 2 other studies previously addressed the prediction of bleeding complications using the same VerifyNow device in CAS patients.5,6 Of those studies, one was retrospective analysis,5 whereas another study was conducted in a prospective observational fashion.6 Still, small cohorts in studies may not be overcome with pooling of the evidence due to heterogeneity in both study designs and definitions of excessive bleeding. Findings are further elusive due to the separate prediction of bleeding amount and transfusion requirements, which is reasonably expected to be inversely related. Apparently, we need the composite outcome consisting of both bleeding amount and transfusion requirements.5 Standardization of outcomes is very important for further pooling of the evidence, and to date, Dyke et al7 provide the most comprehensive and reliable grading of bleeding outcomes that should be consistently used and validated through further research. Finally, our working group would underline some important considerations for studies evaluating the role of point-of-care platelet function test devices in CAS patients. First, preoperative platelet function testing may be useful in terms of preoperative bleeding risk stratification that would direct preoperative antiplatelet drug management as well as timing of surgery. Drug-specific platelet function tests should inextricably evaluate platelet inhibitory response to both aspirin and clopidogrel. Furthermore, point-of-care assessment of platelet function should be continued to time points during and after cardiopulmonary bypass, as measurements at these time points may more accurately detect hemostatic alterations, and thus more reliably predict bleeding complications by accounting for accumulative effects of both preoperative antiplatelet therapy and cardiopulmonary bypass on platelet function. Second, emerging evidence on early postoperative platelet hyperactivity suggests the need for postoperative platelet function assessment aiming to detect patients with high residual on-treatment platelet reactivity. The comprehensive approach to patients based on point-of-care platelet function tests should finally yield a comprehensive algorithm for personalized management of perioperative antiplatelet therapy. In such an approach, the risk of excessive bleeding associated with antiplatelet therapy must always be weighed against the risk for adverse ischemic events. The definition of a perioperative ‘‘therapeutic window’’ for the most commonly administered antiplatelet drugs, as well as the development of a personalized algorithm based on point-of-care platelet function assessment, warrants further investigations that would test the hypotheses about reduction of both bleeding and adverse ischemic events in the preand postoperative phase associated with implementation of point-of-care–guided antiplatelet therapy management.

Can pain intensity in osteoarthritis joint be indicator of the impairment of endothelial function

We propose that pathological remodeling in joint tissues of osteoarthritis (OA) patients persistently stimulates local secretion of pro-inflammatory mediators, which overflow into the blood, activating leukocytes that impair endothelial function and accelerate the atherosclerotic process. During periods of pain, endothelial dysfunction progresses more aggressively due to elevated secretion of these pro-inflammatory mediators, which are involved in both atherosclerosis and the sensation of pain. Concentrations of pro-inflammatory cytokines and their antagonists, activating and decoy receptors of the broad interleukin (IL)-1 and IL-17 families, IL-15, and monocyte chemotactic protein-1 should be measured in peripheral blood samples of OA patients and compared with (I) OA clinical severity; (II) subclinical parameters of atherosclerosis; (III) ischemic heart disease risk factors; (IV) soluble factors indicating endothelial dysfunction; (V) degree of bone destruction; and (VI) results of a six-minute walk test. Arthroscopy and joint replacement surgery provide an opportunity to estimate mRNA and protein expression of inflammatory mediators in specimens of synovial fluid, synovial membrane, cartilage, and/or subarticular bone. A range of methods, including questionnaires, X-ray, computed tomography, ultrasound, enzyme-linked immunosorbent assay, immunohistology, immunofluorescence, and reverse transcription and in situ polymerase chain reaction are available. Understanding the inflammatory and immune mechanisms underlying OA may allow the early identification of patients at high risk of cardiovascular disease, independently of classical coronary risk factors. Pain may constitute an extrinsic indicator of currently worsening endothelial function.

Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia

BACKGROUND Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. METHODS The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. RESULTS Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; p<0.001) and PCI 0.15 (CI: 0.10-0.22; p<0.001). The odds for having proton pump inhibitor in their chronic therapy were increased for atrial fibrillation 1.87 (CI: 1.08-3.23; p=0.025) and decreased for obesity 0.65 (CI: 0.45-0.96; p=0.035); surviving myocardial infarction 0.49 (CI: 0.29-0.83; p=0.035). Multinomial logistic regression controlled for existence of chronic renal disease found no significant association of renal dysfunction and PPI therapy. The existence of anemia was significantly increased in patients taking PPIs than controls; 6.00 (CI: 3.85-9.33; p<0.001). The use of PPI was also associated with worsening of metabolic profile, in part due to decreased utilization of ACE-inhibitors and statins. PPI consumption correlated with age of patients (Rho=0.216; p<0.001). CONCLUSIONS High proportion of cardiovascular, particularly surgical patients with ischemic and valvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs.

Supplementary Diagnostic Landmarks of Left Ventricular Non-Compaction on Magnetic Resonance Imaging

Purpose Diagnostic criteria for left ventricular non-compaction (LVNC) are still a matter of dispute. The aim of our present study was to test the diagnostic value of two novel diagnostic cardiac magnetic resonance (CMR) parameters: proof of non-compact (NC) myocardium blood flow using T2 sequences and changes in geometry of the left ventricle. Materials and Methods The study included cases with LVNC and controls, from a data base formed in a period of 3.5 years (n=1890 exams), in which CMR protocol included T2 sequences. Measurement of perpendicular maximal and minimal end diastolic dimensions in the region with NC myocardium from short axis plane was recorded, and calculated as a ratio (MaxMinEDDR), while flow through trabecula was proven by intracavital T2-weighted hyperintensity (ICT2HI). LVNC diagnosis met the following three criteria: thickening of compact (C) layer, NC:C>2.3:1 and NC>20%LV. Results The study included 200 patients; 71 with LVNC (35.5%; i.e., 3.76% of CMRs) and 129 (64.5%) controls. MaxMinEDDR in patients with LVNC was significantly different from that in controls (1.17±0.08 vs. 1.06±0.04, respectively; p<0.001). MaxMinEDDR >1.10 had sensitivity of 91.6% [95% confidence intervals (CI) 82.5–96.8], specificity of 85.3% (95% CI 78.0–90.0), and area under curve (AUC) 0.919 (95% CI 0.872–0.953; p<0.001) for LVNC. Existence of ICT2HI had sensitivity of 100.0% (95% CI 94.9–100.0), specificity of 91.5% (95% CI 85.3–95.7), and AUC 0.957 (95% CI 0.919–0.981; p<0.001) for LVNC. Conclusion Two additional diagnostic parameters for LVNC were identified in this study. ICT2HI and geometric eccentricity of the ventricle both had relatively high sensitivity and specificity for diagnosing LVNC.

Changes in pulmonary artery systolic pressure correlate with radiographic severity and peripheral oxygenation in adults with community‐acquired pneumonia

The aim of this prospective observational study was to evaluate the relationship between changes in pulmonary artery systolic pressure (ΔPASP) and both severity of community‐acquired pneumonia (CAP) and changes in peripheral blood oxygen partial pressure (PaO2).

Low productivity of stress cardiac magnetic resonance imaging for screening of coronary artery disease.

Coronary artery disease (CAD) is one of the most important chronic comorbidities in the general population, resulting in tremendous societal cost.1 It is responsible for an annual death toll of 4 000 000 throughout 28 European Union (EU) member states, of which 700 000 occur at an age younger than 65 years.2 Despite significant efforts to identify novel biomarkers, genome-wide-associated studies and conventional imaging modalities, the challenge of developing effective screening tools has still to be tackled in a sufficiently resourceful manner.1 Wider availability of diagnostic machinery, as well as their partial support by guidelines, has made some procedures such as adenosine stress cardiac magnetic resonance (CMR) very popular.3 ,4 With thoughtful application, adenosine stress CMR can offer clinically relevant prognostic information and affect subsequent therapeutic decisions. However, when used to screen for CAD, stress CMR is a questionable practice. If you consider that the effects of negative stress CMR perfusion on rates of long-term major adverse cardiovascular events are very similar to those accomplished by treadmill testing, the cost-efficiency of the former is debateable.3 If we were to try to screen the EU population for high-risk cases—theoretically and effectively covering 1.6 million people expected to have acute coronary syndrome (ACS) during the next year—and if this were to be undertaken by five CMR centres per 28 EU member states, each performing 10 …

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

BackgroundThere 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.MethodsData 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.ResultsStudy 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).ConclusionsLGE 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.

Muscle strength differ between patients with diabetes and controls following heart surgery

BACKGROUND The aim of our study was to analyze muscle strength in patients with recent surgical treatment for ischemic and combined ischemic-valvular heart disease, based on existence of diabetes mellitus. Connections existing between muscle strength and patient characteristics or conventional diagnostic tests were analyzed as well. METHODS Study prospectively included consecutive patients scheduled for cardiovascular rehabilitation 0-3months after heart surgery. Diagnostics covered drug utilization, anthropometrics, demographics, echocardiography, conventional laboratory, echocardiography, bioelectrical impedance analysis (BIA), and hand grip test (HGT). HGT was analyzed for dominant hand. RESULTS Patients with diabetes had significantly weaker muscle strength on HGT than controls; 29.4±12.2kg vs. 38.2±14.7kg (p=0.029), respectively. ROC analysis for HGT and existence of diabetes mellitus were significant; ≤40kg had sensitivity of 89.7% (95%CI: 72.6-97.8), specificity 43.7% (31.9-56.0); AUC 0.669 (0.568-0.760); p=0.002. HGT significantly correlated with hematocrit (Rho CC=0.247; p=0.013), whilst other laboratory or echocardiographic parameters were insignificant (all p>0.05). HGT also correlated with body weight (Rho CC=0.510; p<0.001); height (Rho CC=0.632; p<0.001); waist circumference (Rho CC=0.388; p<0.001); waist-to-hip ratio (Rho CC=0.274; p=0.006) and BIA (Rho CC=-0.412; p<0.001). CONCLUSIONS In postoperative recovery of patients with diabetes, muscle strength assessed by HGT is decreased and in relation with nutritional status. Clinically resourceful connections of HGT were also found to hematocrit and utilization of loop diuretics.