New prognostic markers in pulmonary arterial hypertension: CRP to albumin ratio and uric acid.

INTRODUCTION: Idiopathic pulmonary hypertension(IPAH) is a rare disease that causes severe morbidity and mortality despite advances in treatment management. Evaluating the prognosis of the disease is critical in determining therapeutic approaches. We aimed to evaluate the prognostic significance of C-reactive protein/albumin ratio (CAR) and uric acid, which is an easily applicable and inexpensive parameter in patients with IPAH. METHODS: Seventy-two IPAH patients and 99 consecutive non-IPAH patients as a control group were enrolled in the study retrospectively. Right heart catheterization(RHC), echocardiography, and laboratory parameters of the two groups and those who died and survived among the IPAH patients were compared. RESULTS: IPAH and control group were compared at the first stage and CAR (1.98(0.28-10.74), 0.75(0.22-4.7),respectively;p < 0.01) and uric acid (0.33(0.19-0.87), 0.3(0.11-0.48) mmol/L, respectively; p = 0.03) values were significantly higher in the pulmonary hypertension group compared to the control group. Compared with the surviving IPAH patients, CAR (4.60(1.39-10.74),1.54(0.28-6.74),respectively;p < 0.001) and uric acid levels (0.458(0.26-0.87), 0.315(0.19-0.56) mmol/L, respectively; p < 0.001) were significantly higher in the group of patients who died. In the multivariate Cox regression models uric acid(p < 0.001) and CAR(p < 0.001) were found to be associated with survival time. Receiver operating characteristic curves (ROC) analyses showed that > 1.54 CAR value (AUC = 0.81,Sens:85.7%,Spec:56.9%,p < 0.001) and > 5.85 mg/dL (>0.348 mmol/L) uric acid value (AUC = 0.864, Sens:85.7%, Spec:78.4%, p < 0.001) are strong predictors for mortality. CONCLUSION: In this study, we showed that simple markers such as CAR, which augment the inflammation marker feature of CRP, and uric acid can give prognostic information in PAH patients.

Prediction of fractional flow reserve with angiographic DILEMMA score.

OBJECTIVE: Angiographic assessment of stenosis has limited predictive value for functionally significant lesions compared with fractional flow reserve (FFR). The recently developed angiographic DILEMMA score, which consists of minimal lumen diameter (MLD), lesion length (LL) and Bypass Angioplasty Revascularization Investigation (BARI) Myocardial Jeopardy Index (MJI) was found to have diagnostic value in predicting FFR ≤0.80. The present study was an investigation of prediction of FFR ≤0.80 using DILEMMA score and its relationship to resting distal coronary artery pressure/aortic pressure (Pd/Pa). METHODS: Records of consecutive patients who underwent coronary angiography and FFR were retrospectively analyzed. Assessment of MLD and LL was performed using quantitative coronary angiography. BARI MJI was calculated using angiographic calculation index. RESULTS: A total of 185 pressure wire analysis data sets from 150 patients were analyzed retrospectively. There were 82 lesions in FFR >0.80 group and 103 lesions in FFR ≤0.80 group. Negative correlation was found between FFR and DILEMMA score (r=-0.494; p<0.001), FFR and BARI-MJI (r=-0.378; p<0.001), and between FFR and LL (r=-0.314; p<0.001). Positive correlation was found between FFR and baseline Pd/Pa (r=0.713; p<0.001), and between FFR and MLD (r=0.415; p<0.001). DILEMMA score had negative correlation with resting Pd/Pa (r=-0.389; p<0.001). In receiver operating characteristic analysis for diagnosing FFR≤0.80, area under curve values of resting Pd/Pa, DILEMMA score, MLD, BARI-MJI, and LL were 0.862, 0.793, 0.780, 0.728, and 0.686, respectively. CONCLUSION: DILEMMA score had moderately strong correlation with FFR and good accuracy in diagnosing significant FFR, but it had weak correlation with resting Pd/Pa.

The value of exercise SPET for the detection of coronary artery steal syndrome secondary to unligated major side branch of left internal mammary artery.

OBJECTIVE: The clinical significance of unligated major left internal mammary artery (LIMA)-side branches (SB) remains controversial in patients with previous coronary artery bypass graft (CABG) surgery. The aim of this study was to investigate the clinical significance of unligated major LIMA-SB by using exercise myocardial perfusion imaging (MPI) with single-photon emission tomography. SUBJECTS AND METHODS: We conducted a retrospective analysis of 2819 consecutive patients who underwent diagnostic angiography. There were 407 CABG patients with LIMA graft. The demographic, laboratory, pre-angiographic stress test and angiographic data of these patients were collected. A subgroup of patients with unligated major LIMA-SB who were referred to angiography with the diagnosis of stable angina pectoris and positive exercise MPI was identified and divided into two groups for comparison: anterior wall vs non-anterior wall ischemia groups. RESULTS: Among 407 patients with LIMA graft, 112 (27.5%) patients were found to have unligated major LIMA-SB. In a subgroup of patients (n=45) with positive exercise MPI and patent LAD-LIMA system with unligated major LIMA-SB, the median values of diameter and length of unligated major LIMA-SB were statistically higher in anterior wall ischemia group (n=24) compared to non-anterior wall ischemia group (1.8mm vs 0.6mm, P<0.001 and 17.0cm vs 8.0cm, P<0.001, respectively). The cut-off values of unligated major LIMA-SB length and diameter were 11cm and 1.3mm respectively. Unligated major LIMA-SB with a length of ≥11.0cm and a diameter of >1.3cm had 95.8% of sensitivity and 100% of specificity for predicting anterior wall ischemia on exercise MPI. In patients with anterior wall ischemia, summed stress score and summed difference score were improved after percutaneous coil embolization of large unligated major LIMA-SB with ≥11.0cm length and >1.3mm diameter. CONCLUSION: Large unligated major LIMA-SB with ≥11.0cm length and >1.3mm diameter seems to be a potential source of ischemia in CABG patients. We suggest that exercise MPI might be a first option noninvasive test in evaluating the clinical significance of unligated major LIMA-SB and the effectiveness of embolization therapy.

Bleeding complications during cardiac electronic device implantation in patients receiving antithrombotic therapy: is there any value of local tranexamic acid?

BACKGROUND: The perioperative use of antithrombotic therapy is associated with increased bleeding risk after cardiac implantable electronic device (CIED) implantation. Topical application of tranexamic acid (TXA) is effective in reducing bleeding complications after various surgical operations. However, there is no information regarding local TXA application during CIED procedures. The purpose of our study was to evaluate bleeding complications rates during CIED implantation with and without topical TXA use in patients receiving antithrombotic treatment. METHODS: We conducted a retrospective analysis of consecutive patients undergoing CIED implantation while receiving warfarin or dual antiplatelet (DAPT) or warfarin plus DAPT treatment. Study population was classified in two groups according to presence or absence of topical TXA use during CIED implantation. Pocket hematoma (PH), major bleeding complications (MBC) and thromboembolic events occuring within 90 days were compared. RESULTS: A total of 135 consecutive patients were identified and included in the analysis. The mean age was 60 ± 11 years old. Topical TXA application during implantation was reported in 52 patients (TXA group). The remaining 83 patients were assigned to the control group. PH occurred in 7.7 % patients in the TXA group and 26.5 % patients in the control group (P = 0.013). The MBC was reported in 5.8 % patients in the TXA and 20.5 % patients in control group (P = 0.024). Univariate logistic regression analysis identified age, history of recent stent implantation, periprocedural spironolactone use, periprocedural warfarin use, perioperative warfarin plus DAPT use, cardiac resynchronization therapy, and topical TXA application during CIED implantation as predicting factors of PH. Multivariate analysis showed that perioperative warfarin plus DAPT use (OR = 10.874, 95 % CI: 2.496-47.365, P = 0.001) and topical TXA application during CIED procedure (OR = 0.059, 95 % CI: 0.012-0.300, P = 0.001) were independent predictors of PH. Perioperative warfarin plus DAPT use and topical TXA application were also found to be independent predictors of MBC in multivariate analyses. No thromboembolic complications was recorded in the study group. CONCLUSION: The present study demonstrated that the topical TXA application during CIED implantation is associated with reduced PH and MBC in patients with high bleeding risk.

Elevated mean pulmonary artery pressure in patients with mild-to-moderate mitral stenosis: a useful predictor of worsening renal functions?

OBJECTIVE: Renal dysfunction commonly accompanies the course of cardiac disorders and strongly associates with increased morbidity and mortality. Elevated central venous pressure is related to worsening renal function in patients with heart failure. However, predictors of worsening renal function in mitral stenosis-whose pathophysiologic process is similar to heart failure with regard to right heart dysfunction-are unknown. This study aimed to evaluate whether clinical and echocardiographic parameters might predict worsening renal function in patients with mild-to-moderate mitral stenosis. METHODS: The current study has a prospective cohort design. Sixty consecutive patients (9 male, 51 female, mean age 50±13 years) with mild-to-moderate mitral stenosis were followed up for 34±13 months (range 1-60) and their renal functions were monitored. Worsening renal function was defined as a decline in glomerular filtration rate of ≥ 20% on follow-up. In order to presence or absence of worsening renal functions, study patients divided into two groups. Statistical analysis was performed using the Chi-square, Independent samples t / Mann-Whitney U tests, univariate and multivariate Cox proportional hazards analyses, receiver operating characteristic (ROC) and Kaplan-Meier curve analyses. RESULTS: Worsening renal function was observed in 14 patients (23%). In univariate analysis, male gender, mean pulmonary artery pressure (mPAP), peak tricuspid regurgitation velocity, systolic pulmonary artery pressure, digitalis and antiplatelet usage, right atrial size, and TEI index were determined to be predictors of worsening renal function. In a multivariate Cox proportional hazards model, mPAP (HR=1.136, 95% CI: 1.058-1.220, p<0.001) and male gender (HR=4.110, 95% CI: 1.812-9.322, p=0.001) were associated with increased risk of worsening renal function during the follow-up period. In ROC curve analysis, the optimal cut-off value of mPAP to predict worsening renal function was measured as more than 21 mmHg, with 78.6% sensitivity and 58.7% specificity (AUC 0.725, 95% CI 0.595-0.838). According to the Kaplan-Meier curve, a significant difference was found between those who had mPAP of >21 mmHg, and those who did not have, in terms of worsening renal function (p=0.006), and the difference between the groups increased after 30 months of follow-up. CONCLUSION: Elevated mean pulmonary artery pressure at the time of initial evaluation, in patients with mild-to-moderate mitral stenosis, might help to predict worsening renal function.

Atrial fibrillation is associated with increased mean platelet volume in patients with type 2 diabetes mellitus.

Platelet abnormalities in diabetes mellitus (DM) and atrial fibrillation (AF) may underline the etiology of a prothrombotic state in these conditions. Increased mean platelet volume (MPV) is a marker of abnormal platelet function and activation. We aimed to investigate the possible association of chronic AF with MPV in patients who have type 2 DM. Patients who had type 2 DM with either chronic (≥6 months) AF or normal sinus rhythm (NSR) were included in the study. A total of 162 patients (aged 38-89 years) were divided into 2 groups according to the presence of either AF or NSR. Group 1 consisted of 81 diabetic patients with AF, and group 2 consisted of 81 diabetic patients with NSR. The two groups were not significantly different in terms of age, and gender, as well as in hypertension, smoking, history of coronary artery disease, previous cerebrovascular accidents, microalbuminuria, retinopathy, duration of DM, body mass index, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride (p > 0.05 for all variables). Although no significant difference was present between groups concerning platelet count; for patients with AF, MPV was higher compared with patients with NSR (9.0 ± 0.2 fl vs. 8.4 ± 0.2 fl; p = 0.001). Furthermore, no significant difference was noted between groups regarding routine medications received by patients. In multivariate logistic regression analysis, MPV was the only variable independently related to AF (OR = 2.659; 95% CI, 1.286-5.498; p = 0.008). Consequently, it is concluded that AF is associated with increased MPV in patients with type 2 DM, suggesting the presence of tentatively related processes leading to reciprocal interaction.

C-type natriuretic peptide is associated with the severity of Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is characterized by vascular dysfunction, indicating the involvement of endothelial cells. C-type natriuretic peptide (CNP) plays a critical role in the coordination of vascular tone and is associated with the prognosis in critically ill patients such as those with sepsis and septic shock. We investigated whether CNP is related to the severity of CCHF. METHODS: Forty-eight consecutive patients with a laboratory confirmed diagnosis of CCHF and 40 age-sex-matched healthy volunteers as the control group were prospectively enrolled into the study. CCHF patients were classified according to the disease severity into a non-severe group (n=28) and a severe group (n=20). RESULTS: The CNP levels were detected to be 0.43 (0.4-0.7) ng/ml in the control group, 0.87 (0.7-1.0) ng/ml in the non-severe CCFH group, and 1.27 (0.8-1.7) ng/ml in the severe CCHF group. According to the receiver operating characteristics curve analysis, the optimal cut-off value of CNP to predict disease severity was >1.22 ng/ml, with 89.3% specificity and 55% sensitivity. CNP >1.22 ng/ml, lactate dehydrogenase >480 IU/l, and aspartate aminotransferase >202 IU/l were found to have prognostic significance in the univariate analysis. In the multivariate logistic regression analysis by forward stepwise method, CNP >1.22 ng/ml (odds ratio 8.336, p = 0.016) and lactate dehydrogenase >480 IU/l (odds ratio 16.206, p = 0.002) remained associated with disease severity after adjustment for confounding variables. CONCLUSIONS: CNP measurement could help in the risk stratification of patients with CCHF.

Gamma-glutamyltransferase to determine cardiovascular risk: shifting the paradigm forward.

Gamma-glutamyltransferase (GGT), regarded as a marker of excessive alcohol consumption or liver disturbances, is an enzyme catalyzing the first step in the extracellular degradation of the antioxidant glutathione (GSH) and may take part in atherogenesis. The marked relationship between GGT and the atherosclerotic process has shifted attention to the issue of whether its serum levels can aid in the detection of individuals at high risk for incident cardiovascular events. It is likely that the process entails the oxidation of low-density lipoprotein through GSH/GGT-dependent iron reduction within the plaque. In this context, oxidative stress is a probable mediator. Recent insights into the pathophysiological background of GGT in the precipitation and progression of atherosclerosis appear to be supported by relevant epidemiological observations as a cardiovascular risk predictor. Further understanding is, nevertheless, warranted to ameliorate the prognostic stratification of patients through GGT.

Cytokines: potential contributors to arrhythmogenesis in demyelinating syndromes?

Neurological disorders including chronic demyelinating syndromes (CDSs) have been known to elicit propensity to cardiac arrhythmias possibly due to autonomic imbalance, myocardial myocytolysis and some psychological conditions (major depression etc.) associated with these syndromes. CDSs are generally characterized by variable degrees of inflammatory response that may corrrelate with clinical disease activity (relapse, progression etc.). In the clinical setting, enhanced inflammatory response as measured with increased levels of inflammatory markers may predispose to cardiac arrhythmias via direct or indirect mechanisms. Therefore, substantial levels of inflammatory markers including pro-inflammatory cytokines associated with CDSs may serve as potential contributors to arrhythmogenesis indicating the possible link between disease activity and arrhythmia risk in patients with CDSs.

Acute effects of passive smoking on endothelial function.

Impairment of endothelial functions has been shown to occur after acute and chronic exposure to passive smoking (PS), as assessed by flow-mediated dilatation (FMD) of the brachial artery. A total of 61 participants, 30 male and 31 female, mean ages 26 (18-36) were enrolled in the study. All were clinically well and nonsmokers. All participants stayed for 30 minutes in the smoking room. Carbon monoxide (CO) level was 7.42 ± 0.98 ppm (4.71-10.50). Mean carboxyhemoglobin (COHb) levels of participants were significantly elevated after PS. Mean FMD was 18.6% ± 9% and decreased to 12.4% ± 7% after PS (P < .001). In the current study, with more number of participants at lower CO concentrations (7.42 ppm) and with smaller increase in COHb (51%) significant reduction (33%, P < .001) in FMD was observed.

Natriuretic peptides: useful biomarkers in predicting the possibility of restoration and maintenance of sinus rhythm in patients with atrial fibrillation undergoing cardioversion?

Natriuretic peptides (NPs) have been regarded as of diagnostic and prognostic importance in a variety of clinical conditions including congestive heart failure (CHF). Paroxysmal and persistent atrial fibrillations (AFs) have been reported to be associated with high plasma levels of NPs that decline after restoration of sinus rhythm. Rhythm control of AF largely depends on the duration of the arrhythmia and the presence of underlying structural heart disease that may exert negative effects on the restoration and maintenance of sinus rhythm. AFs associated with structural heart disease or AFs of long duration may also be associated with disproportionately high plasma NP levels probably due to the outstanding increases in myocardial wall stretch, volume and pressure overload leading to significant NP release. Therefore, very high levels of baseline NP levels may be associated with lower rates of successful cardioversion and higher rates of AF recurrence on follow-up. It may be suggested that baseline NP levels may predict the possibility of successful rhythm control, and hence may help determine the appropriate therapeutic strategy (rhythm or rate control) in patients with AF.

CA125 levels among patients with advanced heart failure: an emerging independent predictor for survival.

Serum CA125, a high-molecular weight glycoprotein, is a tumor marker widely used for the diagnosis and follow-up of patients with ovarian cancer in clinical practice. Recently, increased serum CA125 values, in parallel with catecholamines and natriuretic peptides, have also been documented in patients with heart failure. As far as the relationship between CA125 and cardiac dysfunction is concerned; interleukin-6, interleukin-10, and tumor necrosis factor-α, which are all elevated in heart failure, might play a pivotal role, since there are data suggesting that the proliferation of CA125-producing cells is induced by proinflammatory cytokine network. However, little is known about the biologic role of this substance: whether it simply reflects the increased activation of the cytokine pathway (or other pathophysiologic pathways), or whether CA125 is an active substance truly responsible for myocardial and/or peripheral dysfunction. Further insight to the precise determinants for increased CA125 levels in this population would help establish the clinical usefulness of this emerging marker in predicting survival.

Geodesic pattern of coronary arteries as a predictor for cardiovascular risk: clinical perspectives.

Coronary angiography, despite current shortcomings, has been regarded as golden standard for the assessment of coronary arteries. Geodesic pattern of coronary arteries characterized by curvature, torsion and tortuosity parameters can also be determined through angiography. Apart from atherosclerosis; age, hypertension, left ventricular hypertrophy and coronary flow are some of the determinants for the geodesic pattern of coronary arteries. Besides, a unique feature of coronary vasculature that differs from all other arterial sites is the repetitive flexion during each cardiac contraction. Thus, the geodesic pattern of coronary arteries may conceivably possess an adjunctive merit in estimating cardiovascular risk and have promising implications for discerning those who require meticulous follow-up. A more thorough understanding of the precise determinants for the coronary geodesic pattern would help establish its potential causal interaction with cardiovascular risk.