Clinical Impact of Patient-Prosthesis Mismatch After Aortic Valve Replacement With a Mechanical or Biological Prosthesis.

BACKGROUND: Patient-prosthesis mismatch (PPM) may impair functional capacity and survival after aortic valve replacement. This study aimed to investigate the impact of PPM on long-term survival and quality of life after mechanical and biological aortic valve replacement. METHODS: This study included 595 consecutive patients who had undergone isolated aortic valve replacement. Patients were divided into 2 groups according to prosthesis type. The baseline and operative characteristics, survival rates, complications, and quality of life of the groups with and without PPM were compared for up to 6 years. The PPM calculation was performed using the effective orifice area value provided by the manufacturer divided by the patient's body surface area. RESULTS: The moderate to severe PPM rates were 69.8% and 3.7% after biological and mechanical prosthesis implantation, respectively. Mean survival for patients in the biological group who had PPM was statistically significantly shorter (50.2 months [95% CI, 45.2-55.3]) than for patients in the biological group without PPM (60.1 months [95% CI, 55.7-64.4]; P = .04). In the mechanical prosthesis group, there was no difference in mean survival between the subgroup with PPM (66.6 months [95% CI, 58.3-74.9]) and the subgroup without PPM (64.9 months [95% CI, 62.6-67.2]; P = .50). A quality-of-life questionnaire's scores did not differ between the groups. CONCLUSION: Mismatch is common after biological valve implantation and statistically significantly affects long-term survival and quality of life. If the risk of PPM after implantation of a biological prosthesis is suspected, adopting strategies to avoid PPM at the time of surgery is warranted.

The Clinical Impact of the Extension of Acute Type A Aortic Surgery on Long-Term Outcomes: Should We Tend to Be Conservative?

Background and Objectives: Despite advances in surgical techniques, industry adjuncts, and cerebral perfusion techniques, the in-hospital mortality rate of type A acute dissection (TAAD) remains at 15-30%. This study aimed to investigate the influence of different extents of aortic resection on survival and quality of life (QoL) after long-term follow-up. Materials and Methods: A retrospective observational trial was performed, including 165 patients operated upon for TAAD. Patients were divided into two groups according to the extent of their aortic repair: the first group comprised patients who had ascending aorta replacement and the second included patients who had hemiarch or total arch replacement. The groups were compared with regard to their baseline characteristics, operative characteristics, survival, complications, and QoL during nine years of follow-up. Results: The mean follow-up time was 75.6 months (1-108 months). The mean survival in the ascending aorta repair group was 89.651 (81.242-98.061) months and was 54.801 (40.053-69.548) months in the hemiarch and arch group; the difference between the groups was significant (log-rank p < 0.001). The rate of new postoperative neurological deficits was statistically higher in the hemiarch and arch group (17.5% vs. 8.4%, p = 0.045), the most common being stroke, and was also more frequent in the hemiarch and arch group than in the ascending aorta group (with statistical significance (15.7% vs. 6.5%)). The mean SF-12 physical score from the QoL questionnaire was higher in the ascending aorta replacement group than in the hemiarch and arch group (50.1 ± 7.3 vs. 44.0 ± 11.9, p = 0.017). Additionally, the mean SF-12 mental score was higher in the ascending aorta replacement group (52.3 ± 7.3 vs. 47.1 ± 12.8, p = 0.032). Conclusions: A more aggressive approach involving aortic arch repair means a lower survival rate and lesser quality of life after long-term follow-up in comparison with the replacement of the ascending aorta. If clinically applicable, a more defensive strategy may be considered.

Coronary revascularisation outcome questionnaire: validation study of the Serbian version.

PURPOSE: To translate, culturally adapt and validate the Coronary Revascularisation Outcome Questionnaire (CROQ), a disease-specific tool for measuring health-related quality of life (HRQoL) in patients with ischaemic heart disease (IHD), into Serbian language (CROQ-S). METHODS: Validation study was performed at the Clinic for Cardiac Surgery and Clinic for Cardiology, University Clinical Centre of Serbia. We included a convenience sample of 600 patients with IHD divided into four groups. Acceptability, reliability and validity of the CROQ-S were assessed. RESULTS: CROQ-S was acceptable to patients as demonstrated by less than 1% of missing data for each single item. Cronbach's Alpha was higher than the criterion of 0.70 for all scales in each version except the Cognitive Functioning scale which only met this criterion in the CABG pre-revascularisation version. Mean values of item-total correlations were greater than 0.30 for all scales except the Cognitive Functioning scale in both the pre-revascularisation groups. Compared to the original version, exploratory factor analysis in our study showed more factors; however, the majority of items had a factor loading greater than 0.3 on the right scale. Correlations of CROQ-S scales with the 36-Item Short Form Health Survey and Seattle Angina Questionnaire showed the expected pattern whereby scales measuring similar constructs were most highly correlated. CONCLUSION: CROQ-S is an acceptable, reliable and valid disease-specific instrument for measuring HRQoL in this sample of Serbian speaking patients with IHD both before and after coronary revascularisation. However, the Cognitive Functioning scale did not meet all the psychometric criteria and further validation of its responsiveness is required.

Oxidative Stress in Patients before and after On-Pump and Off-Pump Coronary Artery Bypass Grafting: Relationship with Syntax Score.

OBJECTIVE: Coronary artery bypass grafting (CABG) represents the significant source of increased oxidative stress (OS). We aimed to follow the OS status parameters (i.e., ischemia-modified albumin (IMA), malondialdehyde (MDA), superoxide anion, prooxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), and superoxide-dismutase (SOD)) change through the predefined study times in two different surgical procedures, i.e., cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting (OPCAB). Additionally, we aimed to investigate those OS status parameters in specific study times according to SYNTAX score (SS), an established angiographic score for evaluating the extensity and severity of coronary artery disease. Patients and Methods. A total of 107 patients that were planned to undergo CABG were included (i.e., 47 patients in OPCAB and 60 patients in CPB group). Blood samples were taken at 6 time intervals: before surgery (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after termination of the operation (t6). RESULTS: IMA levels were higher in CPB than that in OPCAB baseline and rose in CPB group in t2 point. TOS decreased in both study groups, compared to baseline values, but without statistical significance. Superoxide anion and PAB significantly increased in t3-t6 study times, in both groups. MDA significantly increased only in CPB group in t5 and t6 interval. MDA was significantly higher in CPB group compared to OPCAB in t6 study point. CPB patients had significantly lower TAS compared to OPCAB patients at the beginning and in t2 and t3 study points. They also had significantly lower SOD activities compared to OPCAB, baseline, and in several study points. Moreover, TAS, SOD, and TAS/TOS ratio were significantly lower, whereas PAB and TOS/TAS were significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of high SS. CONCLUSION: CPB patients were in more severe ischemia baseline than OPCAB group and IMA rose in CPB patients immediately after the surgery end, but not later. Also, the antioxidant status was significantly lower, whereas the prooxidant status was significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of CAD (as determined with SS), showing that SOD and IMA had very good discriminatory capability towards higher SS status.

New Markers of Platelet Activation and Reactivity and Oxidative Stress Parameters in Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVE: Recent studies have shown that the red cell distribution width- (RDW-) to-platelet (PLT) count ratio (i.e., RPR) and the mean platelet volume (MPV)/PLT ratio (i.e. MPR) are more sensitive markers of atherosclerosis-connected risk than RDW and PLT alone. The present study is aimed at investigating the oxidative stress status and these two new markers of platelet activation in two different heart surgery modalities: cardiopulmonary bypass (CPB) and off-pump coronary artery bypass (OPCAB). We also aimed to test the possible relationship between RPR and MPR, respectively, and the severity and complexity of atherosclerotic plaque, measured as Syntax Score. Patients and Methods. A total of 107 patients encompassed this prospective study (i.e., 60 patients in CPB group and 47 patients in OPCAB). Blood samples were drawn at several time intervals: before skin incision (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after cessation of the operation (t6). RESULTS: The values of RPR and MPR were similar in CPB and OPCAB before surgery and started to rise in t2 (i.e., immediately after the intervention). This increase lasted to t5 (i.e., 48 hours after the intervention), when it became the highest. After that, both markers started to regress about the 96th hour after the beginning of surgery. Nominal values of both indices were higher in CPB than in OPCAB in all study points after the surgery. Furthermore, a significantly higher level of antioxidative parameters (i.e., total sulfhydryl groups and paraoxonase 1) in the OPCAB group compared to the CPB group was noted at t5 study point (i.e., 48 hours after the surgery), whereas no significant difference was noted in prooxidant levels (i.e., lipid hydroperoxides and advanced oxidation protein products) between these groups at this study point. MPR and RPR correlated positively with Syntax Score at several study points after the surgery completion. Syntax Score, MPR, and RPR showed good clinical accuracy in surgery-related complication prediction ((AUC = 0.736), 95th CI (0.616-0.856), P = 0.003)). CONCLUSION: When combined, MPV, RDW, and platelet count, such as MPR and RPR, could be good predictors of coronary artery disease status, regarding the aspect of joint inflammation, oxidative stress, and thrombosis.

Machine learning analyses of antibody somatic mutations predict immunoglobulin light chain toxicity.

In systemic light chain amyloidosis (AL), pathogenic monoclonal immunoglobulin light chains (LC) form toxic aggregates and amyloid fibrils in target organs. Prompt diagnosis is crucial to avoid permanent organ damage, but delayed diagnosis is common because symptoms usually appear only after strong organ involvement. Here we present LICTOR, a machine learning approach predicting LC toxicity in AL, based on the distribution of somatic mutations acquired during clonal selection. LICTOR achieves a specificity and a sensitivity of 0.82 and 0.76, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.87. Tested on an independent set of 12 LCs sequences with known clinical phenotypes, LICTOR achieves a prediction accuracy of 83%. Furthermore, we are able to abolish the toxic phenotype of an LC by in silico reverting two germline-specific somatic mutations identified by LICTOR, and by experimentally assessing the loss of in vivo toxicity in a Caenorhabditis elegans model. Therefore, LICTOR represents a promising strategy for AL diagnosis and reducing high mortality rates in AL.

Pulmonary Artery Hypertension as A Risk Factor for Long-Term Survival after Heart Transplantation.

BACKGROUND: Heart failure is the most frequent cause of pulmonary artery hypertension (PAH) and its severity may predict the development of heart failure (HF) and is known to be a prognostic factor of poor outcome after heart transplant (HTx). The aim of this study was to investigate the impact of preoperative PAH related to left-sided HF on long-term survival after HTx and to identify the hemodynamic parameters of PAH that predict survival after HTx. METHODS: A prospective observational trial was performed, and it included 44 patients subjected to heart transplantation. Patients were divided into two groups: The first one with the preoperative diagnosis of PAH and the second one without the PAH diagnosed prior to the HTx. The two groups were compared for baseline characteristics, operative characteristics, survival, and hemodynamic parameters obtained by right heart catheterization. Survival was analyzed using Kaplan Meyer analysis, and Cox regression analysis was performed to determine independent predictors of survival. RESULTS: The median follow-up time was 637.4 days (1-2028 days). The median survival within the group of patients with preoperative PAH was 1144 days (95% CI 662.884-1625.116) and 1918.920 days (95% CI 1594.577-2243.263) within the group of patients without PAH (P = .023), HR 0.279 (95% [CI]: 0.086-0.910; P = .034. The 30-day mortality in patients within PAH group was significantly higher, six versus two patients in the non PAH group (χ2 = 5.103, P < .05), while the long-term outcome after this period did not differ between the groups. Patients with preoperative PAH had significantly higher values of MPAP, PCWP, TPG and PVRI, while CO and CI did not differ between the two groups. Mean PVRI was 359.1 ± 97.3 dyn·s·cm-5 in the group with preoperative PAH and 232.2 ± 22.75 dyn·s·cm-5 in the group without PAH, P < .001. TPG values were 11.95 ± 5.08 mmHg in the PAH group while patients without PAH had mean values of 5.16 ± 1.97 mmHg, P < .001. Cox regression analysis was done for the aforementioned parameters. Hazard ratio for worse survival after HTx for elevated values of PVRI was 1.006 (95% [CI]: 1.001-1.012; P = .018) TPG had a hazard ratio of 1.172 (95% [CI]: 1.032-1.233; P = .015). CONCLUSION: Pulmonary artery hypertension is an independent risk factor for higher 30-day mortality after HTx, while it does not affect the long-term outcome. Hemodynamic parameters obtained by right heart catheterization in heart transplant candidates could predict postoperative outcome. PVRI and TPG have been identified as independent predictors of higher 30-day postoperative mortality.

The routine use of platelet function tests in elective coronary artery bypass grafting: A prospective observational trial.

BACKGROUND: Preoperative use of platelet function tests contributes to the decrease of re-intervention rate due to bleeding and the necessity of transfusion in coronary artery bypass grafting (CABG) patients. The aim was to investigate the predictive value and to justify routine preoperative use of multiple electrode aggregometry in these patients. METHODS: A prospective observational trial which included 416 consecutive patients subjected to elective isolated CABG was conducted. The Multiplate® test was used to assess platelet function. Platelet function test results, postoperative blood loss, and transfusion requirements were compared between high and low bleeding risk patients. Receiver operating characteristic analysis was performed to assess the sensitivity and specificity of the arachidonic acid (ASPI) and adenosine di-phosphate high sensitive (ADPHS) tests. RESULTS: ADPHS and ASPI test results significantly predicted total bleeding > 1000 ml (AUC, 0.685, p < .001; 0.695, p = .039). Sensitivity and specificity were 62.9% and 40.0%, for ADPHS ≤602, and 70.8% and 41.8%, for ASPI ≤ 453. The sensitivity and specificity of cut-off values recommended by the manufacturer were 84.2% and 40.0% for ADPHS ≤ 500, while for ASPI < 600 the values were 54.7% and 62.2%. More platelets and cryoprecipitate were transfused in patients with ADPHS ≤ 602.5 (p < .001; p = .035). Patients with ADPHS ≤ 500 had a higher rate of red blood count, platelet and cryoprecipitate transfusion (p<.001p<.001; p = .013). The manufacturer's ASPI test cut-off values showed no statistically significant prediction for a higher transfusion rate. CONCLUSION: Preoperative platelet function tests should be conducted systematically for all elective CABG patients who were on dual antiplatelet therapy after adjusting test cut-off values for each population.

The Prospects of Secondary Moderate Mitral Regurgitation after Aortic Valve Replacement -Meta-Analysis.

Aortic valve replacement for aortic stenosis represents one of the most frequent surgical procedures on heart valves. These patients often have concomitant mitral regurgitation. To reveal whether the moderate mitral regurgitation will improve after aortic valve replacement alone, we performed a systematic review and meta-analysis. We identified 27 studies with 4452 patients that underwent aortic valve replacement for aortic stenosis and had co-existent mitral regurgitation. Primary end point was the impact of aortic valve replacement on the concomitant mitral regurgitation. Secondary end points were the analysis of the left ventricle reverse remodeling and long-term survival. Our results showed that there was significant improvement in mitral regurgitation postoperatively (RR, 1.65; 95% CI 1.36-2.00; p < 0.00001) with the average decrease of 0.46 (WMD; 95% CI 0.35-0.57; p < 0.00001). The effect is more pronounced in the elderly population. Perioperative mortality was higher (p < 0.0001) and long-term survival significantly worse (p < 0.00001) in patients that had moderate/severe mitral regurgitation preoperatively. We conclude that after aortic valve replacement alone there are fair chances but for only slight improvement in concomitant mitral regurgitation. The secondary moderate mitral regurgitation should be addressed at the time of aortic valve replacement. A more conservative approach should be followed for elderly and high-risk patients.

Successfully Resected Cardiac Metastatic Melanoma in a Lifesaving Cardiac Surgery: A Case Report.

INTRODUCTION: Metastatic tumors are the most frequent tumors of the heart with the melanoma metastasis being the most frequent. In cases of a cardiac tamponade or a low cardiac output syndrome due to the position of the tumor it could lead to an acute life-threatening condition for the patient. CASE REPORT: We present a case of a successfully treated metastatic cardiac melanoma in a lifesaving cardiac surgery. A 42-year-old woman was admitted to the emergency department of the Clinical Center of Serbia in a critical state with signs of tricuspid orifice obstruction with a tumor mass. Her previous medical history showed that she had an adequate surgical excision of the melanoma in the right lumbar region at the age of 39. An emergency cardiac surgery was performed with the resection of the tumor and the atrial wall. The postoperative course was uneventful and a HP exam once again confirmed the same type of melanoma as previously diagnosed. The patient was alive and well on follow-up exams for 4 months when she was diagnosed with metastatic tumor masses in the pelvis with ascites and melanosis of the entire skin followed by lethal outcome 5 months after the cardiac surgery. CONCLUSION: Surgical resection of metastatic cardiac melanoma can be safe and effective in an emergency scenario, especially in the case of solitary metastasis. It can be performed with excellent results and very few postoperative complications. However, due to the nature of the principal disease, the long-term survival rate remains low, giving the surgery a place in palliative treatment.

Long Term Outcomes of The Off-Pump and On-Pump Coronary Artery Bypass Grafting In A High-Volume Center.

Coronary artery bypass grafting (CABG) remains the most frequent surgery in the practice of an adult cardiac surgeon and the most frequently performed cardiac surgical procedure worldwide. Despite the ongoing debates regarding the superiority or inferiority of off-pump coronary artery bypass grafting, it still comprises 15-30% of all CABG cases varying in different national registries. We performed a propensity matched study of 302 consecutive CABG patients,143 off -pump cases performed by the four experienced off-pump surgeons and the on-pump CABG cases performed by those surgeons and four other experienced coronary surgeons. The five year follow up was performed and data collected comprised of mortality, rehospitalization due to cardiac origin, repeated revascularization, myocardial infarction and cerebrovascular accident. Overall, the off-pump group of patients had a higher risk profile than the patients in the on-pump group. After matching, fewer differences were found between the groups. Propensity score matching analysis showed no difference in long-term survival as well as MACCE and repeated revascularization. The higher risk profile of the patients subjected to OPCAB and the comparable survival to lower risk CPB patients in this series indicate that in experienced hands, OPCAB is a valuable option in this important subgroup of patients.

Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development.

Transcription factors are proteins able to bind DNA and induce the transcription of specific genes. Consequently, they play a pivotal role in multiple cellular pathways and are frequently over-expressed or dysregulated in cancer. Here, we will focus on a specific "signal transducer and activator of transcription" (STAT3) factor that is involved in several pathologies, including cancer. For long time, the mechanism by which STAT3 exerts its cellular functions has been summarized by a three steps process: (1) Protein phosphorylation by specific kinases, (2) dimerization promoted by phosphorylation, (3) activation of gene expression by the phosphorylated dimer. Consequently, most of the inhibitors reported in literature aimed at blocking phosphorylation and dimerization. However, recent observations reopened the debate and the entire functional mechanism has been revisited stimulating the scientific community to pursue new inhibition strategies. In particular, the dimerization of the unphosphorylated species has been experimentally demonstrated and specific roles proposed also for these dimers. Despite difficulties in the expression and purification of the full length STAT3, structural biology investigations allowed the determination of atomistic structures of STAT3 dimers and several protein domains. Starting from this information, computational methods have been used both to improve the understanding of the STAT3 functional mechanism and to design new inhibitors to be used as anticancer drugs. In this review, we will focus on the contribution of structural biology to understand the roles of STAT3, to design new inhibitors and to suggest new strategies of pharmacological intervention.

Percutaneous implantation of self-expandable aortic valve in high risk patients with severe aortic stenosis: The first experiences in Serbia.

BACKGROUND/AIM: Aortic stenosis (AS) is the most common valvular heart disease in elderly people, with rather poor prognosis in symptomatic patients. Surgical valve replacement is the therapy of choice, but a significant number of patients cannot undergo surgical procedure. We presented initial experience of transcatheter aortic valve implantation (TAVI) performed in Catheterization Laboratory of the Clinic for Cardiology, Clinical Center of Serbia. METHODS: The procedures were performed in 5 patients (mean age 76 ± 6 years, 2 males, 3 female) with severe and symptomatic AS with contraindication to surgery or high surgical risk. The decision to perform TAVI was made by the heart team. Pre-procedure screening included detailed clinical and echocardiographic evaluation, coronary angiography and computed tomography scan. In all the patients we implanted a self-expandable aortic valve (Core Valve, Medtronic, USA). Six months follow-up was available for all the patients. RESULTS: All interventions were successfully performed without significant periprocedural complications. Immediate hemodynamic improvement was obtained in all the patients (peak gradient 94.2 ± 27.6 to 17.6 ± 5.2 mmHg, p < 0.001, mean pressure gradient 52.8 ± 14.5 to 8.0 ± 2.1 mmHg, p < 0.001). None of the patients developed heart block, stroke, vascular complication or significant aortic regurgitation. After 6 months, the survival was 100% with New York Heart Association (NYHA) functional improvement in all the patients. CONCLUSION: This successful initial experience provides a solid basis to treat larger number of patients with symptomatic AS and high surgical risk who are left untreated.