Bojan Biočina

Cardiac myxoma the great imitators: Comprehensive histopathological and molecular approach

Cardiac myxomas are rare benign and slowly proliferating neoplasms of uncertain histogenesis with heterogeneous histomorphology and variable and sometimes clinically quite malignant pathological manifestations. Majority of cardiac myxoma occur sporadically while a relatively small proportion of diagnosed cases develop as a part of Carney complex syndrome with established familial pattern of inheritance. Although histologically indistinguishable these two forms of cardiac myxoma exhibit distinct cytogenetic make-up and apparent pathological differences important for their clinical presentation and prognosis. Additional problem is presented with secondary lesions with more aggressive histology and significantly faster cell proliferation suggesting their successive malignant alteration. Surgical resection of cardiac myxoma is currently the only treatment of choice. However, to avoid potentially hazardous operating procedures and possible postoperative complications and to prevent recurrence of the neoplastic lesions it is necessary to develop alternative approaches and identify a possible drug targets for their successful pharmacological treatment. Due to the rarity of the disease, a small number of cases in one institution and lack of comprehensive experimental data particularly concerning the cases of metastatic dissemination and secondary lesions with malignant nature, a comprehensive multi-institutional approach is required for better understanding of their molecular pathology and illumination of key molecular, genetic as well as epigenetic markers and regulatory pathways responsible for their development. In this article we provide comprehensive pathohistological, molecular and cytogenetic overview of sporadic cardiac myxoma cases restating the major hypothesis concerning their histogenesis and emphasizing potential approaches for their further reexamination.

Meta-analysis of concomitant mitral valve repair and coronary artery bypass surgery versus isolated coronary artery bypass surgery in patients with moderate ischaemic mitral regurgitation.

Ischaemic mitral regurgitation (IMR) is a complication of coronary artery disease with normal chordal and leaflet morphology. Controversy surrounds the issue of appropriate surgical management of moderate IMR. With the present meta-analysis, we aimed to determine whether the addition of mitral valve (MV) repair to coronary artery bypass grafting (CABG) improved clinical outcome over CABG alone in patients with moderate IMR. Databases were searched for studies reporting on clinical outcomes after CABG and MV repair or CABG alone for moderate IMR. Clinical end-points were operative mortality, survival, New York Heart Association (NYHA) class ≥2 and MR grade ≥2 at last follow-up. A total of five observational and four randomized controlled trials (RCTs) were identified. The mean follow-up was 2.7 years. An analysis of all studies revealed increased operative risk in the concomitant CABG and MV repair group {risk ratio [RR] 2.02 [95% confidence interval (CI) 1.15, 3.56], P = 0.01, I(2) = 0%}. However, an analysis of RCTs only showed that the operative risk was equivalent [RR 1.05 (95% CI 0.34, 3.30), P = 0.93, I(2) = 0%]. Pooled hazard ratio (HR) on survival did not favour either procedure [all studies: HR 1.08 (95% CI 0.77, 1.50), P = 0.66, I(2) = 0%; RCTs only: HR 0.89 (95% CI 0.47, 1.70), P = 0.73, I(2) = 0%]. The incidence of exercise intolerance quantified as NYHA class ≥2 was similar between groups (all studies: RR 0.72 (95% CI 0.42, 1.24), P = 0.24, I(2) = 77%; RCTs only: RR 0.61 (95% CI 0.24, 1.55), P = 0.30, I(2) = 83%]. Risk of residual MR grade ≥2 was higher in the CABG only group [all studies: RR 0.30 (95% CI 0.16, 0.60), P < 0.001, I(2) = 83%; RCTs only: RR 0.20 (95% CI 0.04, 0.90), P = 0.04, I(2) = 72%]. There is neither increased operative mortality nor survival benefit associated with concomitant CABG and MV repair for IMR of moderate degree over CABG alone. Further studies with long-term follow-up data and sub-group analyses of current data are needed to define a subset of patients whose survival and functional status may improve with the concomitant MV repair.

Impact of reduced creatinine clearance on early heart transplantation outcomes: A propensity score adjusted analysis

We aimed to determine the independent effect of preoperative creatinine clearance (CrCl) on HTx outcomes. Patients and Methods: 220 patients underwent HTx in Croatia from 2008 to 2014. Four patients were excluded due to missing data. Patients were dichotomized according to a CrCl cut-off value of 50 ml/ min (Group A: CrCl≤50 ml/min; Group B: CrCl>50 ml/min). Sixty-three patients (29%) had a CrCl≤50 ml/ min. Propensity score (PS) adjustment was performed by accounting for recipient age and gender, AF, smoking, ischemic time, CPB time, BMI, mechanical circulatory assistance (MCS) and reoperation. Results: Patients in Group A were older (56±11 vs. 49±12 years, P<0.001) and had longer donor ischemic times (197±65 vs. 162±62 min, P<0.001). No significant differences were noted in recipient gender (48/63 (76%) vs. 125/153 (82%) male, P=0.355), donor age (39±13 vs. 39±12 years, P=0.875), donor gender (46/63 (73%) vs. 100/153 (65%) male, P=0.338), PVR (213±107 vs. 188±96 dyn*s*cm −5 , P=0.145), diabetes (18/63 (29%) vs. 34/153 (22%), P=0.382), reoperation (18/63 (29%) vs. 34/153 (22%), P=0.382), CPB duration (175±62 vs. 158±56 min, P=0.06) or preoperative MCS (6/63 (10%) vs. 17/153 (11%), P=0.813). Six-month mortality was higher in patients with a CrCl≤50 ml/min (18/63 (29%) vs. 19/153 (12%); unadjusted OR 2.82 [95% CI 1.36-5.84]; P=0.009). Similarly, group A patients were more likely to require renal replacement therapy (RRT) (16/63 (25%) vs. 17/153 (11%); OR 2.72 (1.28-5.82); P=0.012). After PS adjustment these differences remained significant for both 6-month mortality and RRT (OR 2.44 [95% CI 1.09-5.49]; P=0.030 and OR 3.36 [95% CI 1.43-7.92]; P=0.005, respectively). Con Clusions: Patients with a CrCl≤50 ml/min undergoing isolated HTx had inferior 6-month survival and required RRT more commonly. The impact of CrCl remained significant after adjustment for multiple perioperative covariates. Hrvoje Gasparovic 1

Connections between nutritional status and proton pump inhibitor therapy in patients scheduled for cardiovascular rehabilitation after treatment for ischaemic and valvular heart disease

BACKGROUND Multiple and yet uncertain connections exist between cardiovascular diseases and the nutritional status of patients, particularly in relation to cardiovascular treatments. Proton pump inhibitors (PPI) are among the most commonly used group of drugs. AIM To analyse utilisation of PPI in association with nutritional risk of patients scheduled for rehabilitation after treatment for ischaemic and valvular heart disease. METHODS Retrospective analyses on a consecutive sample of patients, which included drug utilisation of PPI and nutritional risk screening, using a standardised NRS-2002 tool. The patients (n = 536) were divided into groups based on previous cardiovascular treatments and use of PPI. RESULTS Nearly half of the patients (244, 46.1%) had PPI in their chronic therapy despite the clinically negligible prevalence of conditions that are their fundamental indications. The odds for using PPI in patients with increased nutritional risk, estimated by logistic regression, were 3.34 (95% confidence intervals [CI] 2.26-4.94), p < 0.001. Receiver operating curve analyses also revealed significant differences of PPI utilisation in connection with NRS-2002 > 3: positive likelihood-ratio (LR) 2.35 (95% CI 2.10-2.60); negative LR 0.46 (95% CI 0.4-0.6); area under the curve (AUC) 0.720; p < 0.001; as well as the percentage weigh loss history > 6.36% (positive LR 2.22 [95% CI 2.00-2.50]; negative LR 0.41 [95% CI 0.30-0.50]; AUC 0.707; p < 0.001). CONCLUSIONS Utilisation of PPI was found to be of relatively high prevalence and significantly associated with parameters of nutritional risk screening. Furthermore, it was in correlation with the age of patients and the existence of chronic kidney disease, which are well-established predispositions for poor nutritional status. Nutritional risk seems to be additionally negatively challenged by utilisation of PPI due to gastric malabsorption and anaemia.

No difference in 1-year wound morbidity following no-touch versus conventional vein harvesting for coronary artery bypass surgery: a new beginning

Controversy surrounding the issue of greater wound morbidity when using the ‘no-touch’ (NT) saphenous vein graft (SVG) when compared with the conventional (CON) harvesting technique has been addressed for the first time by the recent study of Verma et al .[ 1], who showed no significant difference in wound complications and functional recovery after 1 year of follow-up. Due to the relatively low use of the NT technique, introduced in 1996, data are limited to a single randomized study showing that NT harvesting of the SVG results in a superior patency over CON [2]. Various vasculoprotective mechanisms in NT SVGs have been demonstrated. Although the primary outcome measure of the paper by Verma et al. shows a decreased vascular injury in NT SVGs, we find the results of the secondary study, regarding leg wound healing and functional outcome, to be crucial for the NT technique to attain warranted popularity. We congratulate the authors on conducting this study and point out a few additional factors that we believe should be considered when interpreting the results. It is difficult to understand why no differences in intima, media and adventitial thicknesses were seen between the two groups particularly as CON veins were stripped of its adventitial layer. Also, an earlier study on NT versus CON vessel morphology has shown differences in media thickness [3]. Although there appears no clear evidence of a difference in the risk of infection when staples rather than sutures are used to close leg wounds after SVG harvesting during coronary artery bypass grafting (CABG) [4], information regarding the proportion of wounds closed using staples is missing. To maintain as high homogeneity of the sample as possible all patients should either have staples or absorbable cuticular sutures, particularly in the larger, ongoing, SUPERIOR-SVG trial (clinicaltrials.gov identifier: NCT01047449). In the light of recent data indicating that antibacterial sutures reduce the incidence of infections after CON harvesting in CABG patients by 35% [5], we consider that the data regarding the suture material used are both relevant and necessary for adequate interpretation of the results. SVG harvest-site complications are often managed in legs with arterial insufficiency. Did the patient with peripheral vascular disease have an equal severity of the disease in both legs and was he/she included in the leg assessment analysis? The importance of accounting for arterial insufficiency in the donor site is crucial when comparing postoperative leg wound morbidity rates between groups. The vast majority of patients included in the study by Verma et al .[ 1] were men (94%). Whether these results will remain similar in a mixed sex population remains to be seen. The Materials and Methods section points to Supplementary data on leg wound healing and functional outcomes, although no such data can be found. Finally, there was a single crossover; a CON SVG was harvested from the leg assigned to NT. This patient developed a leg wound infection of the leg assigned to NT and analysed according to intention to treat. What impact would per treatment analysis have on the 3-month follow-up results of leg assessment? When considering that reduced leg wound morbidity has resulted in the recent adoption of endoscopic vein harvesting as a standard of care in spite of dubious graft patency [6], resolving the issue of NT wound morbidity is more important for greater uptake of the technique. We congratulate the authors once again on conducting this study and hope they find our comments useful for the SUPERIOR-SVG ‘NT versus CON’ trial that is underway.

Definition of aspirin resistance using whole blood impedance aggregometry in patients undergoing coronary artery surgery: methodological challenges and outcome improvement opportunities

Methods Prospective observational trial at University Hospital Center Zagreb enrolled 131 patients scheduled for CABG, and divided them into 4 groups with respect to preoperative antiplatelet therapy (APT). Group 1 received 100 mg ASA per day, Group 2 100 mg ASA + 75 mg clopidogrel per day, Group 3 75 mg clopidogrel per day, and Group 4 did not receive any APT. MEA with ASPI test (sensitive to ASA) and ADP test (sensitive to clopidogrel) was performed prior to surgery. In Group 1, patients were characterized as ASA resistant if their ASPI test value exceeded the 75th percentile distribution. Results Study enrolled 131 patients. Significant differences both in the ASPI (p<0.001) and the ADP test (p=0.038) were observed between patients in different APT groups. In Group (1) ASPI test value of 30 AUC presented 75th percentile of distribution, thus indicating ASA resistance. Group 2 patients had slightly lower ADP test values, but no significant difference occurred (mean 60.05 vs. 63.32 AUC, p=0.469). In Group 1 and 2, significant correlations between the ADP test and both, platelet count (r=0.347, p<0.001) and fibrinogen level (r=0.364, p<0.001) were observed.

Blunt chest trauma caused rupture of the left main coronary artery in a 15 year old motocross rider

Case report A 15 year old man suffered chest trauma as a participant of the international motocross race. After falling of the motorcycle, he was run over his chest by another diver. He was unconscious, Glasgow Coma Score was 5 and eye pupils did not react. Resuscitation with sedation, relaxation, analgesia and endotracheal intubation with mechanical ventilation were performed in the emergency vehicle. Mild hypotension and microhemathuria was present. Blood coming from the airways was aspirated periodically. Physical examination revealed excoriations and haemathomas of the face, lower left hemithorax and extremities were noticed. CT scan of the head, thorax and abdomen was performedbilateral contusion of the lung was revealed. On the ECG ST-segment denivelation is noticed. Troponin, lactate dehydrogenasis (LDH) and creatin phosphate kinaze (CPK) levels were elevated. Transthoracic echocardiogram (TTE) revealed 10 mm thick pericardial effusion. There are no pathologic findings on ECG. That was indication for emergent cardiac surgery operation. After conventional median sternotomy and pericardiotomy was performed, 150 ml of blood was evacuated from pericardial space. Patient was placed on cardiopulmonary bypass (CPB) with bicaval venous and aortic cannulation. After crossclamping aorta MPA was transected to approach LMCA. Damage of intimal layer of the MPA was found, originating just above the pulmonary valve and ending at bifurcation of pulmonary artery. After aortotomy the probe was inserted in the lumen of the LMCA. Subepicardial haemathoma of the left ventricle was found just next to LMCA. Defect of the LMCA wall was not suitable for reconstruction because its size was too big. So ligation of the left anterior descending artery (LAD) and circumflex artery (Cx) and coronary artery bypass (CABG) was performed. LAD was bypassed with left internal thoracic artery (LITA) and Cx with saphenous conduit. After aortotomy was sutured and clamp removed, MPA was closed. On transesophageal echosonography, ishemia of the anterior wall of the LV was noticed. We tried to wean the patient from CPB but it was unsuccessful. Patient died because of the left heart failure following irreversible myocardial damage following ischemia.

The change in pulmonary vascular resistance after left ventricular assist device implantation - the predictive role of platelets revisited

E-mail: marijan.pasalic@yahoo.com Purpose: While analyzing the group of patients implanted with a left ventricular assist device (LVAD) at our institution to verify which of the preand postoperative factors constitute the optimal survival outcome predictors, we determined a significant increase in postoperative pulmonary vascular resistance (PVR) values in the expired patients1. The aim of this study was to further analyze the data in order to determine which of the preoperative factors were related to the aforementioned increase in postoperative PVR values. Methods: For the 20 patients (18 M, 2 F; mean age 58.7±8.3 years) that have been implanted with an LVAD in our institution during the past 2 years, preimplantation echocardiography, right heart catheterization (RHC) and laboratory data were collected and compared according to the values of the postimplantation PVR. The groups were compared by using the adequate statistical test (t-test, Mann Whitney U test, statistical significance set at 0.05). Correlation analysis and linear regression were performed. Results: Among the 20 patients, 14 had postoperative RHC data and 4 of them were proven to have elevated PVR values (>2.4 WU). When comparing the pts. with elevated to those with normal PVR values, no significant difference was found neither in the RV function (FAC 33±7% vs 22±12%, TAPSE 1,0±0,7 cm vs 1.6±0.5 cm, NS), nor in the RV and LV dimensions (RVIDd 34±9 mm vs 35±12 mm, LVIDd 65±10 mm vs 73±9 mm). The borderline significance was found in the left ventricular EF (28±3% vs 19±8%, p=0.06) and the degree of the MR (median values 1 vs 2, p=0.05). The preoperative RHC parameters were not found to be predictive of changes in postoperative PVR (preoperative PVR 4,2±3,4 vs 3,4±1,5 WU, C.I. 1,8±0,7 vs 1,9±0,4 L/min/m, TPG 14±11 vs 13±4 mmHg and RVSWI 11,4±2,2 vs 8,9±2,1, NS). As for the laboratory values, only the platelet count significantly differed between the groups (128 ±73 vs 246±65 E3/mm, p<0.05). The correlation analysis showed a strong negative correlation between the platelet count and postoperative PVR values (r=-0,761, p<0.01). The linear regression verified the following relationship between the variables PVR=6,247-0,017xPLT, p<0.01). Conclusion: These preliminary data show that the platelet count is a significant predictor of the postoperative PVR values in patients with an LVAD (a previously shown survival predictor1). Further investigation will be conducted to explain the role of platelets in the etiology of PVR in our group of pts.

The relationship between superior vena caval and mixed venous saturations after cardiac surgery

Results The difference between the MvO2 and SSVCO2 widened over the monitored period (0.08±8.66 at T0, -1.17 ± 7.62 at T1 and -3.12 ± 5.88 at T2). Patients with a larger postoperative negative MvO2-SSVCO2 gradient had longer CPB and cross-clamp times (122 ± 74 vs. 97 ± 40, P = 0.08; 87 ± 48 vs. 68 ± 26, P = 0.04). This did not correlate with inferior clinical outcomes or laboratory markers of hypoperfusion.

Influence of atrial ultrastructural remodeling on its early mechanical transport following surgery for atrial fibrillation and mitral insufficiency

Methods We enrolled 32 patients operated for severe mitral regurgitation. Half of the patients had no history of AF constituting the SR group. The remaining half had concomitant RFA for longstanding persistent AF, the RFA group. Intraoperative transesophageal echocardiography was used for tissue Doppler indices (TDI) data acquisition at the left atrial (LA) lateral wall. During post-procedural data acquisition all patients were in SR. LA biopsies were obtained during surgery and quantified for fibrosis after Mallory’s trichrome staining.