Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p>The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM.</p> <p>Methods</p> <p>cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk).</p> <p>Results</p> <p>One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058).</p> <p>Conclusions</p> <p>Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.</p

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis

Aims The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials. Methods and results We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (−3.17 mL/m², 95% CI: −4.86 to −1.47, P < 0.001; −2.60 mL/m², 95% CI −3.84 to −1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes. Conclusion Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therap

Regional myocardial function after intracoronary bone marrow cell injection in reperfused anterior wall infarction - a cardiovascular magnetic resonance tagging study

<p>Abstract</p> <p>Background</p> <p>Trials have brought diverse results of bone marrow stem cell treatment in necrotic myocardium. This substudy from the Autologous Stem Cell Transplantation in Acute Myocardial Infarction trial (ASTAMI) explored global and regional myocardial function after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) in acute anterior wall myocardial infarction treated with percutaneous coronary intervention.</p> <p>Methods</p> <p>Cardiovascular magnetic resonance (CMR) tagging was performed 2-3 weeks and 6 months after revascularization in 15 patients treated with intracoronary stem cell injection (mBMC group) and in 13 controls without sham injection. Global and regional left ventricular (LV) strain and LV twist were correlated to cine CMR and late gadolinium enhancement (LGE).</p> <p>Results</p> <p>In the control group myocardial function as measured by strain improved for the global LV (6 months: -13.1 ± 2.4 versus 2-3 weeks: -11.9 ± 3.4%, p = 0.014) and for the infarct zone (-11.8 ± 3.0 versus -9.3 ± 4.1%, p = 0.001), and significantly more than in the mBMC group (inter-group p = 0.027 for global strain, respectively p = 0.009 for infarct zone strain). LV infarct mass decreased (35.7 ± 20.4 versus 45.7 ± 29.5 g, p = 0.024), also significantly more pronounced than the mBMC group (inter-group p = 0.034). LV twist was initially low and remained unchanged irrespective of therapy.</p> <p>Conclusions</p> <p>LGE and strain findings quite similarly demonstrate subtle differences between the mBMC and control groups. Intracoronary injection of autologous mBMC did not strengthen regional or global myocardial function in this substudy.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00199823">NCT00199823</a></p

Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

<p>Abstract</p> <p>Background</p> <p>Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease.</p> <p>Methods</p> <p>Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation.</p> <p>Results</p> <p>Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3). Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR). Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3). There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function had higher plasma CCN2 levels than those with normal or mildly reduced RV function (p < 0.001). Plasma CCN2 ≥ 77 μg/L was an independent predictor of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88% sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was elevated in patients with mild or greater TR/PR compared to those with no or minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe TR/PR (p = 0.03).</p> <p>Conclusions</p> <p>Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.</p

Sex differences in circulating proteins in heart failure with preserved ejection fraction

Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83–2.63), p = 0.18. Conclusion In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF

Accuracy and cost of advanced cardiological diagnostic techniques in evaluation of coronary artery disease in heart transplant patients.

Medical imaging has rapidly increased in numbers and cost. Evaluation of diagnostic methods has much focused on accuracy, but less on cost and hazard. Advanced tests for coronary artery disease are expensive and carry a risk. In heart transplant (HTx) patients, coronary vasculopathy is prevalent, and annual follow-up comprises a coronary angiography. Less costly and low-risk techniques with adequate accuracy are desired. In this study we tested the diagnostic accuracy and cost of three available medical techniques to detect coronary artery stenosis (CAD) in HTx patients. Methods: Fifty stable HTx patients aged (mean&amp;plusmn;SD) 57&amp;plusmn;8 years were studied during annual routine control with dobutamine stress echocardiography (dobECHO), dobutamine 99mTc-tetrofosmin emission tomography (dobSPET) and exercise ECG (exECG), and compared with coronary angiography. Cost of methods were derived from hospital accountancy data. Results: Significant coronary artery stenosis in &amp;ge;1 major epicardial vessel was present in 14 patients (28.0%), but only 16 (32.0%) had complete normal angiograms. Sensitivity, specificity, and accuracy for CAD as compared to angiograms, was for dobECHO: 67%, 91%, and 82%; for dobSPET: 71%, 74%, and 73%; and for exECG: 20%, 91%, and 70%, respectively. By combining dobECHO with echocardiographic wall motion analysis, the rate of false negatives was reduced to 4%. Cost of dobECHO, dobSPET and exECG was estimated to 0.58, 1.45, and 0.25 times cost of angiography. DobSPET gives similar radiation exposure (7 mSv) as angiography. Conclusion: DobECHO and dobSPET are feasible tests in HTx patients. DobECHO or dobSPET alone or combined with echocardiographic resting wall motion analysis, can be used with acceptable accuracy for identifying HTx patients in whom routine coronary angiography intermittently can be deferred. Of these, dobECHO is the least expensive, and carries the least risk to the patient. ExECG has low accuracy and cannot be recommended in HTx in spite of low cost

Automatic measurement of aortic annulus diameter in 3-dimensional transoesophageal echocardiography

Background Transcatheter aortic valve implantation involves percutaneously implanting a biomechanical aortic valve to treat severe aortic stenosis. In order to select a proper device, precise sizing of the aortic valve annulus must be completed. Methods In this paper, we describe a fully automatic segmentation method to measure the aortic annulus diameter in patients with aortic calcification, operating on 3-dimensional transesophageal echocardiographic images. The method is based on state estimation of a subdivision surface representation of the left ventricular outflow tract and aortic root. The state estimation is solved by an extended Kalman filter driven by edge detections normal to the subdivision surface. Results The method was validated on echocardiographic recordings of 16 patients. Comparison against two manual measurements showed agreements (mean ±SD) of -0.3±1.6 and -0.2±2.3 mm for perimeter-derived diameters, compared to an interobserver agreement of -0.1±2.1 mm. Conclusions With this study, we demonstrated the feasibility of an efficient and fully automatic measurement of the aortic annulus in patients with aortic disease. The algorithm robustly measured the aortic annulus diameter, providing measurements indistinguishable from those done by cardiologists

Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy

Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines

Eliciting Patient Risk Willingness in Clinical Consultations as a Means of Improving Decision-Making of Aortic Valve Replacement

Background: Treatment decisions for aortic valve replacement (AVR) should be sensitive to patient preferences. However, we lack knowledge of patient preferences and how to obtain them. Methods and Results: We assessed the mortality risk patients were willing to accept when undergoing AVR by using the Standard Gamble method and aimed to show how this risk willingness was affected by level of disease burden. We report findings from 439 patients, aged >18 years with severe aortic stenosis who were referred for evaluation of AVR to our institution. The vast majority of patients accepted a mortality risk regarded as high or prohibitive according to current guidelines. Of the 439 patients, 51% patients were willing to forego surgery with high mortality risk (8–50%) and 19% were willing accept a prohibitive mortality risk (>50%) as defined in current guidelines. However, the risk willingness varied considerably. Acceptance of prohibitive risk willingness (>50%) was associated with reporting of 3 to 5 different restricting symptoms, with an odds ratio of 4.07 (95% CI 1.56–10.59) opposed by increasing score on EuroQol–Visual Analog Scale, with an odds ratio of 0.99 (95% CI 0.97–1.00). The poor ability to predict risk willingness based on available clinical variables and health status suggests that other factors may be important advocating the need for tools for soliciting patient's preferences individually. Conclusion: When undergoing AVR, patients were willing to accept considerably higher perioperative risk than what is considered acceptable in current guidelines and practice. Patient preferences varied considerably, and they should be directly assessed and taken into account in decision‐making and guidelines