Platelet to lymphocyte ratio in acute aortic dissection.

BACKGROUND: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet-lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD. METHODS: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched. RESULTS: PLR was significantly higher in group I vs both groups II and III (P < .001). There was an excellent correlation of PLR with neutrophil/lymphocyte ratio (NLR) in all three groups (P < .001 for all). After adjustment for hemoglobin, RDW did not differ but RPR remained significantly higher in group I compared to groups II and III (P < .001). The best cutoff value of PLR to predict dissection was 159 with 53% sensitivity and 86% specificity. No association between PLR, RDW, and RPR and mortality in group I was found. CONCLUSIONS: Indices derived from full cell blood count may provide diagnostic information in patients with AAD; whether these indices may contribute to prognosis assessment should be further investigated.

Transcatheter aortic valve implantation: restoring the qualities of life in old age.

Transcatheter aortic valve implantation (TAVI) is a tremendous therapeutic advance for patients with severe aortic stenosis and high-surgical risk. Since TAVI-treated patients are elderly with multiple co-existing conditions, limited life expectancy and disproportionate health-care expenditures, the aspect of the health-related quality of life (HRQoL) benefits becomes of fundamental importance. Based on recent evidence, TAVI appears to improve significantly HRQoL measures compared with optimal standard care, which are restored to age-adjusted population norms over time.

Caseous calcification of the mitral annulus presenting as recurrent strokes.

Although caseous calcification of the mitral annulus is usually diagnosed incidentally, it can cause embolic complications. The current report describes the case of caseous calcification revealed by recurrent episodes of stroke in a 64-year-old female patient. After her last ischemic episode, cerebral magnetic resonance imaging confirmed the presence of a thrombus in the right middle cerebral artery. Transthoracic echocardiogram revealed calcification of the mitral annulus and an echo-dense mass with mobile borders fixed posteriorly. Transesophageal echocardiogram allowed better evaluation of the lesion. A medical approach was preferred, with no recurrence thereafter. Learning objective: Caseous calcification of the mitral annulus is a rare form of mitral annular calcification which is associated with high risk of strokes.Medical management with optimal anticoagulation can be effective over long-term follow up.

Prospective Phenotyping of Right Ventricle Function Following Intra-Aortic Balloon Pump Counterpulsation in Left Ventricular Assist Device Candidates: Outcomes and Predictors of Response.

Intra-aortic balloon pump (IABP) may be applied to optimize advanced heart failure (AHF) patients and improve right ventricular (RV) function before left ventricular assist device (LVAD) implantation. We aimed to evaluate the outcome of this intervention and define RV response predictors. Decompensated AHF patients, not eligible for LVAD because of poor RV function, who required IABP for stabilization were enrolled. Echocardiography and invasive hemodynamics were serially applied to determine fulfillment of prespecified "LVAD eligibility RV function" criteria (right atrium pressure [RA] <12 mm Hg, pulmonary artery pulsatility index [PAPi] >2.00, RA/pulmonary capillary wedge pressure [PCWP] <0.67, RV strain <-14.0%). Right ventricular-free wall tissue was harvested to assess interstitial fibrosis. Eighteen patients (12 male), aged 38 ± 14 years were supported with IABP for 55 ± 51 (3-180) days. In 11 (61.1%), RV improved and fulfilled the prespecified criteria, while seven (38.9%) showed no substantial improvement. Histopathology revealed an inverse correlation between RV interstitial fibrosis and functional benefit following IABP: interstitial fibrosis correlated with post-IABP RA ( r = 0.63, p = 0.037), RA/PCWP ( r = 0.87, p = 0.001), PAPi ( r = -0.83, p = 0.003). Conclusively, IABP improves RV function in certain AHF patients facilitating successful LVAD implantation. Right ventricular interstitial fibrosis quantification may be applied to predict response and guide preoperative patient selection and optimization. http://links.lww.com/ASAIO/A995.

Skeletal muscle abnormalities in chronic heart failure.

Skeletal muscle abnormalities are well-established in patients with heart failure from an early stage in the progression of the disease and contribute to their symptoms and the limitation of physical activity. Heart failure-induced skeletal muscle pathology includes morphologic, histologic, and enzymatic changes along with derangements in skeletal muscle metabolism and autonomic function. These alterations influence both peripheral and ventilatory muscles, are present at rest, and deteriorate during exercise and their occurrence depends upon the severity and the duration of CHF syndrome. Future studies will be needed to elucidate the origin of skeletal "myopathy" and its reversibility, which is associated with improvement in exercise capacity, observed after physical training programs.

Human immunodeficiency virus type 1 impairs sumoylation.

During infection, the human immunodeficiency virus type 1 (HIV-1) manipulates host cell mechanisms to its advantage, thereby controlling its replication or latency, and evading immune responses. Sumoylation is an essential post-translational modification that controls vital cellular activities including proliferation, stemness, or anti-viral immunity. SUMO peptides oppose pathogen replication and mediate interferon-dependent anti-viral activities. In turn, several viruses and bacteria attack sumoylation to disarm host immune responses. Here, we show that HIV-1 impairs cellular sumoylation and targets the host SUMO E1-activating enzyme. HIV-1 expression in cultured HEK293 cells or in CD4+ Jurkat T lymphocytes diminishes sumoylation by both SUMO paralogs, SUMO1 and SUMO2/3. HIV-1 causes a sharp and specific decline in UBA2 protein levels, a subunit of the heterodimeric SUMO E1 enzyme, which likely serves to reduce the efficiency of global protein sumoylation. Furthermore, HIV-1-infected individuals display a significant reduction in total leukocyte sumoylation that is uncoupled from HIV-induced cytopenia. Because sumoylation is vital for immune function, T-cell expansion and activity, loss of sumoylation during HIV disease may contribute to immune system deterioration in patients.

Sumoylation of Cas9 at lysine 848 regulates protein stability and DNA binding.

CRISPR/Cas9 is a popular genome editing technology. Although widely used, little is known about how this prokaryotic system behaves in humans. An unwanted consequence of eukaryotic Cas9 expression is off-target DNA binding leading to mutagenesis. Safer clinical implementation of CRISPR/Cas9 necessitates a finer understanding of the regulatory mechanisms governing Cas9 behavior in humans. Here, we report our discovery of Cas9 sumoylation and ubiquitylation, the first post-translational modifications to be described on this enzyme. We found that the major SUMO2/3 conjugation site on Cas9 is K848, a key positively charged residue in the HNH nuclease domain that is known to interact with target DNA and contribute to off-target DNA binding. Our results suggest that Cas9 ubiquitylation leads to decreased stability via proteasomal degradation. Preventing Cas9 sumoylation through conversion of K848 into arginine or pharmacologic inhibition of cellular sumoylation enhances the enzyme's turnover and diminishes guide RNA-directed DNA binding efficacy, suggesting that sumoylation at this site regulates Cas9 stability and DNA binding. More research is needed to fully understand the implications of these modifications for Cas9 specificity.

Long-term quality of life improvement after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a novel therapeutic option for severe aortic stenosis in old patients with high surgical risk. The aim of this study was to assess changes in quality of life (QoL) along with functional status and late survival after this procedure. METHODS: Thirty-six consecutive patients (80.5 ± 5.9 years, 21 men and 15 women) with a logistic Euroscore of 29.7 ± 13.7 underwent TAVI using the 18-Fr CoreValve prosthesis. Aortic valve prosthesis was inserted retrograde using a femoral or a subclavian arterial approach. QoL was evaluated by administering the Short Form 36 (SF-36) tool and the shorter SF-12 version 2 (SF-12v2) questionnaires before and 1-year after TAVI. RESULTS: TAVI was successfully performed in all patients. The estimated 1-year overall survival rate using Kaplan-Meier method was 68%. One-year follow-up also showed a marked improvement in echocardiographic parameters (peak gradient 76.2 ± 26.1 vs 15.4 ± 7.8 mm Hg, P < .001; aortic valve area 0.7 ± 0.1 vs 2.6 ± 2.7 cm(2), P < .001) with a significant change in New York Heart Association class (3 ± 0.7 vs 1.2 ± 0.4, P < .001). Both preprocedural summary SF-36 and SF-12v12 physical and mental scores showed a significant improvement 1 year after TAVI (21.6 vs 46.7, P < .001; 42.9 vs 55.2, P < .001; 22 vs 48.9, P < .001; 43.3 vs 52.2, P < .001, respectively). CONCLUSIONS: Our results show a marked 1-year clinical benefit in functional status and physical and mental health in patients who underwent TAVI.

Cytokine gene polymorphisms are associated with markers of disease severity and prognosis in patients with idiopathic dilated cardiomyopathy.

AIMS: To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-ß1)+869 T/C (codon10 Leu→Pro), TGF-ß1 +915 G/C (codon25 Arg→Pro), interleukin (IL)-6 -174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 -1082A/G, IL-10 -819T/C and IL-10 -592A/C gene polymorphisms. In homozygous TT patients for TGF-ß1 +869 T/C polymorphism mean VO(2) max was significantly higher than in CC homozygous patients (25.67±6.73ml/kg/min vs. 20.29±6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex (p = 0.009). C carriers of TGF-ß1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III-IV) than non C carriers [OR: 4.25, 95% CI (1.53-11.80), p = 0.006]. Patients GG homozygous for IL-6 -174G/C polymorphism presented greater left ventricle end-systolic (p = 0.018) and end-diastolic (p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism (p = 0.02) and the combination of the TGF-ß1 +869 T/C and TGF-ß1 +915 G/C genotypes were associated with adverse outcome (p = 0.014). CONCLUSION: Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

Gender-specific differences in biomarkers responses to acute coronary syndromes and revascularization procedures.

A growing body of gender-related research in coronary artery disease is beginning to gradually elucidate differences between women and men. In patients presenting with acute coronary syndromes (ACS), these sex differences include varying risk factor profiles, accuracy of diagnostic testing, clinical presentations, treatment practices and outcomes. There is also a differential expression of cardiac biomarkers by sex, which remains unexplained. This paper reviews all the available information on the effect of gender on cardiac biomarkers by search of MEDLINE using the terms gender differences, biomarkers, ACS and revascularization procedures. A better understanding of the sex disparities in biomarkers along with all other clinical information is essential to optimal management and patient care in the future.

Ischemia modified albumin changes - review and clinical implications.

Ischemia modified albumin (IMA), as measured using the albumin cobalt binding test, is currently the most promising biomarker for early detection of ischemia before the onset of irreversible cardiac injury. This paper reviews the information available on IMA, including its pathophysiology, analysis, clinical applications and future perspectives. The data provided was identified by a search of MEDLINE using the terms IMA, biomarkers and ischemia. IMA may be useful to cover the complete diagnostic window of patients presenting with acute coronary syndromes (ACS) in the Emergency Department, along with the electrocardiogram and cardiac troponins. Preliminary data regarding the significance of IMA in the prognosis of either ACS or following revascularization need further study.

Heart type fatty acid binding protein in relation to pharmacologic scintigraphy in coronary artery disease.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a marker of myocardial necrosis, but whether it increases during myocardial ischemia is not known. This study investigated whether serum levels of H-FABP change during adenosine stress testing and nuclear imaging in patients with stable coronary artery disease. METHODS: Thirty stable patients with established coronary artery disease on their medications were studied. Sampling was performed before the stress test, at the end of adenosine infusion, as well as 1, 2 and 3 h after the completion of the infusion. RESULTS: No difference in H-FABP serum levels were found at the five pre-specified time points in the overall group (p=0.99); furthermore, there was no significant difference regardless of the test result--positive (p=1) or negative (p=0.98). CONCLUSIONS: It is concluded that H-FABP does not change significantly during pharmacologic stress testing in patients with known coronary artery disease and there is no difference whether there is inducible ischemia or not.

Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3-year follow-up study.

OBJECTIVES: Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD). METHODS: In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 2.25, maximum 3.9 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons. RESULTS: Baseline lnOPN levels were directly related to age (r = 0.27, P < 0.001) and inversely to left ventricular ejection fraction (r = -0.32, P < 0.01). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (beta = -0.013, P = 0.02). Median OPN value was 55 ng mL(-1). In the univariate Cox-regression analysis, OPN levels > 55 ng mL(-1) (n = 50) were significantly related to adverse cardiac outcome (HR = 2.40, 95% CI: 1.11-5.23, P = 0.027). In multivariate model, OPN levels > 55 ng mL(-1) remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 2.88, 95% CI: 1.09-7.58, P = 0.032). CONCLUSION: OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD.

Ischaemia-modified albumin in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) may be associated with subendocardial ischaemia. We investigated whether ischaemia-modified albumin (IMA), an established marker of ischaemia, is elevated in stable patients with PH. METHODS: We studied 32 patients with PH and an equal number of age-matched normal volunteers. We assessed serum IMA levels with the albumin cobalt-binding test. RESULTS: Patients' mean +/- SD (range) pulmonary arterial pressure was 56 +/- 12 (33-73) mmHg and their exercise capacity was 394 +/- 145 (121-688) m in the 6-min walk test. IMA was 92 +/- 14 (69-115) U ml(-1) in the patient group and 93 +/- 9.4 (76-122) U ml(-1) in the control group with no significant difference between the two (p = 0.85), although almost one-third of the patients had detectable troponin-I. CONCLUSIONS: We conclude that IMA, a marker of ischaemia, does not differ in patients with advanced clinically stable PH compared with normal subjects.

Ischemia-modified albumin in acute aortic dissection.

BACKGROUND: Acute aortic dissection (AOD) is associated with high mortality and early diagnosis and treatment are essential. Ischemia-modified albumin (IMA) is a marker of myocardial ischemia whereas cardiac enzymes are released when myocardial necrosis occurs. We investigated, for the first time, whether IMA increases in AOD either at presentation or after surgery. METHODS: We studied 46 consecutive patients with documented AOD; we also evaluated 13 consecutive patients with dilated ascending aortas scheduled for elective surgery and admitted for preoperative coronary angiography; 46 age-matched normal subjects served as controls. Only patients with acute onset of symptoms were included. We evaluated IMA, cardiac enzymes, N-terminal pro-B-type natriuretic peptide, albumin, C-reactive protein (CRP), and D-dimers on admission, 24 hr post-operatively and 4 days post-operatively. Duration from symptom onset to the first sample was 23±17 hr. RESULTS: IMA did not differ between patients with AOD at presentation (93±19 U/ml), patients with chronic aneurysms (90±14 U/ml) and normal controls (91±9 U/ml). In addition, IMA did not change significantly after surgical repair. IMA, at baseline, however, correlated positively with time from symptom onset as well as CRP levels (P=0.05 and P=0.007, respectively). CONCLUSION: IMA is not elevated in AOD when blood sampling is performed within 23±17 hr after symptom onset nor increases after surgery.

Increased ischaemia modified albumin following coronary artery bypass grafting.

BACKGROUND: Any increase of cardiac biomarkers after coronary artery bypass grafting (CABG) indicates myocyte necrosis and is likely to be related to an impaired outcome. We investigated whether ischaemia-modified albumin (IMA), a biomarker of ischaemia, is also raised following CABG. METHODS: We studied 50 stable consecutive patients undergoing elective isolated CABG on cardiopulmonary bypass, of whom 46 were men and four women, aged 64 +/- 9 years. Blood samples were obtained the day before the operation (pre-op) as well as immediately after the operation, 24 h postoperatively (post-op) and the fourth day post-op and assayed for creatine kinase, the MB isoenzyme of creatine kinase, cardiac troponin-I, albumin and IMA. RESULTS: The typical rising and falling pattern of myocardial necrosis of all three cardiac enzymes was observed post-op (p <0.0001). IMA increased significantly following CABG at all three time points (113 +/- 43, 106.7 +/- 22.6 and 110.2 +/- 12.5 U ml(-1), respectively) compared with pre-op values (91.7 +/- 10.5 U ml(-1)), (p <0.0001); the sample immediately post-op was significantly higher compared with the following samples (immediately post-op vs 24 h, p = 0.008 and immediately post-op vs 4 days, p = 0.03, with no significant difference between the last two). IMA level changes during the study course were independent of the albumin changes. Haemoglobin decreased significantly post-op (p <0.0001 vs baseline) whereas serum creatinine did not differ during the study period. CONCLUSIONS: IMA increases significantly following CABG but whether or not this carries a prognostic significance remains to be elucidated.

Increases in serum concentration of human heart-type fatty acid-binding protein following elective coronary intervention.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is considered a marker of myocardial necrosis but whether or not it is modified by myocardial ischemia is not clear. We sought to investigate if H-FABP serum levels increase following non-urgent coronary angioplasty. METHODS: We studied 31 patients undergoing coronary angioplasty. Peripheral venous samples were drawn immediately before angioplasty, 1 h after the first balloon inflation and 24 h after the procedure and assayed for H-FABP. RESULTS: Serum levels of H-FABP increased significantly at 1 h vs baseline from 2554 +/- 1268 to 3322 +/- 245 pg ml(-1) (p = 0.024). However, no differences were observed between 1 h and 24 h after angioplasty (3268 +/- 1861 vs 3322 +/- 2459 pg ml(-1), p = 0.87). Moreover, no significant difference was observed when we compared 24 h after angioplasty with the baseline (3268 +/- 1861 vs 2554 +/- 1268 pg ml(-1), p = 0.112). CONCLUSIONS: We conclude that H-FABP significantly increases after elective coronary angioplasty at 1 h compared with baseline values; whether or not this has any prognostic significance for future events, as it occurs with troponins, needs to be studied further.

Ischaemia-modified albumin in dilated cardiomyopathy.

BACKGROUND: Biomarkers of myocardial necrosis may be increased in patients with chronic heart failure. We investigated whether ischaemia-modified albumin (IMA), a marker of ischaemia, is also elevated in patients with compensated heart failure, due to dilated cardiomyopathy (DCM). METHODS: We studied 42 patients with DCM and an equal number of age-matched normal volunteers. We assessed IMA serum levels with the albumin cobalt binding test. RESULTS: IMA was 89.9 +/- 13.1 (71-117) KU/L in the patient group and 93.9 +/- 9.9 (76-122) KU/L in the control group, with no significant difference between the two (P = 0.11). However, IMA differed significantly according to the New York Heart Association classification (P = 0.003) and was negatively correlated with the left ventricular ejection fraction (r = -0.40, P = 0.014). CONCLUSIONS: We conclude that IMA, a marker of ischaemia, does not differ in patients with clinically stable DCM compared with normal subjects, but varies significantly in relation to the severity of the disease.

Missed Heparin-Induced Thrombocytopenia (HIT) Diagnosis in a Patient with Acute Stent Thrombosis.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, characterized by thrombocytopenia and high risk for venous and arterial thrombosis. CASE REPORT We report an unusual case of acute stent thrombosis secondary to delayed HIT. A 74-year-old man with non-ST-segment elevation myocardial infarction had a coronary angiography which revealed 2-vessel disease. A bolus of unfractionated heparin (UFH) was administered at admission and he received fondaparinux during his hospitalization. We performed elective percutaneous coronary intervention (PCI) with stents to LAD and LCx. Two hours after PCI, the patient developed acute pulmonary edema, and repeat angiography revealed an occlusive thrombus in the ostial LAD and the LCx. A turbidimetric assay for the rapid detection of plasma anti-PF4/heparin antibodies was negative. After repeated unsuccessful attempts of balloon angioplasty and continuous thrombosis, the patient was transferred for emergency surgical revascularisation and was treated with additional UFH followed by enoxaparin. Platelets decreased gradually to 38 k/µl 7 days after surgery, at which time enoxaparin was replaced with fondaparinux. The subsequent HIT test results were positive. CONCLUSIONS HIT should be considered in patients with multiple recent exposures to anticoagulants, independent of the platelet count, if there are signs and symptoms of thrombosis.

Ischemia modified albumin in relation to pharmacologic stress testing in coronary artery disease.

BACKGROUND: Ischemia modified albumin (IMA) is considered a biomarker of myocardial ischemia. We sought to investigate whether IMA plasma levels change during pharmacological stress test, in patients with stable coronary artery disease. METHODS: We studied 37 patients undergoing non-invasive evaluation with a pharmacological stress test, either with radionuclide myocardial perfusion imaging with adenosine or stress echocardiography with dobutamine. Peripheral venous samples were collected before the stress test (baseline), at the end of adenosine infusion or at the peak dose of dobutamine and 60 min after the completion of the stress test for IMA measurement. RESULTS: IMA plasma levels significantly increased at peak vs. baseline (91.28+/-9.59 U/ml vs. 97.97+/-9.69 U/ml, p<0.0001) and subsequently, decreased significantly at 60 min compared to peak (97.97+/-9.69 U/ml vs. 94+/-15.22 U/ml, p=0.016), returning to values similar to those at baseline (p=0.134). Similarly, in patients with a negative stress test, IMA significantly increased at peak compared to baseline (91.08+/-10.03 U/ml vs. 99.58+/-8.43 U/ml, p=0.006) and returned to baseline at 60 min (99.58+/-8.43 U/ml vs. 91.83+/-7.93 U/ml, p=0.019), the 60 minute levels being similar to baseline values (p=0.212). Conversely, in patients with a positive stress test, IMA significantly increased at peak compared to baseline (91.38+/-10.13 U/ml vs. 97.17+/-10.34 U/ml, p=0.006) and although decreased at 1 h, this did not reach statistical significance compared either to the baseline or to the peak values (95.04+/-17.76 U/ml vs. 91.38+/-10.13 U/ml, p=0.315 and 95.04+/-17.76 U/ml vs. 97.17+/-10.34 U/ml, p=0.235, respectively). CONCLUSION: IMA plasma levels change significantly during pharmacologic stress testing, in patients with coronary artery disease, but with no difference between the positive and the negative tests.