Tumour necrosis factor-alpha serum level is an independent predictor of medium-term all-cause mortality after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a suitable treatment for patients with severe aortic stenosis and severely increased operative risk. There is need for a better preoperative risk assessment for TAVI candidates. AIM: To determine whether Tumour necrosis factor-alfa (TNFα) is an independent predictor of survival 500 days after TAVI. METHODS: Sixty patients undergoing TAVI were enrolled in the study. TNFα was determined. The CT measured low-density muscle fraction (LDM%) of the psoas muscle was determined. Operative risk assessment by Logistic EuroSCORE, EuroSCORE II, and STS score was performed. Frailty scores (FRAIL scale and Barthel index) were determined. RESULTS: Mean age was 81.01 ± 7.54 years. Twenty-six (43.3%) of the patients were males. In the univariable analyses, FRAIL scale and Barthel index were no predictors of survival after TAVI. In the multivariable analysis, including EuroSCORE II, LDM% and TNFα serum concentration, TNFα serum level was an independent predictor of survival 500 days after TAVI (HR: 3.167; 95%: 1.279-7.842; p = 0.013). The multivariable analysis, including TNFα as a categorical variable, showed that compared to patients in the conjugated first and second TNFα serum level tertile, patients in the third tertile had a hazard ratio (HR) of 10.606 (95%CI: 1.203 - 93.467) (p = 0.033). CONCLUSION: TNFα is an incremental independent predictor of long-term survival after TAVI.

Adiponectin serum level is an independent and incremental predictor of all-cause mortality after transcatheter aortic valve replacement.

BACKGROUND: Quantifiable biomarkers may be useful for a better risk and frailty assessment of patients referred for transcatheter aortic valve implantation (TAVI). HYPOTHESIS: To determine if adiponectin serum concentration predicts all-cause mortality in patients undergoing TAVI. METHODS: 77 consecutive patients, undergoing TAVI, were analyzed. The CT axial slices at the level of the fourth lumbar vertebra were used to measure the psoas muscle area, and its low-density muscle fraction (LDM (%)). To assess the operative risk, the STS (Society of Thoracic Surgeons Predicted Risk of Mortality) score, Log. Euroscore, and Euroscore II were determined. A clinical frailty assessment was performed. ELISA kits were used to measure adiponectin serum levels. We searched for a correlation between serum adiponectin concentration and all-cause mortality after TAVI. RESULTS: The mean age was 80.8 ± 7.4 years. All-cause mortality occurred in 22 patients. The mean follow-up was 1779 days (range: 1572-1825 days). Compared with patients with the lowest adiponectin level, patients in the third tertile had a hazards ratio of all-cause mortality after TAVI of 4.155 (95% CI: 1.364-12.655) (p = .004). In the multivariable model, including STS score, vascular access of TAVI procedure, LDM (%), and adiponectin serum concentration, serum adiponectin level, and LDM(%) were independent predictors of all-cause mortality after TAVI (p = .178, .303, .042, and .017, respectively). Adiponectin level was a predictor of all-cause mortality in females and males (p = .012 and 0.024, respectively). CONCLUSION: Adiponectin serum level is an independent and incremental predictor of all-cause mortality in patients undergoing TAVI.

Dual versus triple antithrombotic therapy after percutaneous coronary intervention: the prospective multicentre WOEST 2 Study.

BACKGROUND: For patients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI), European guidelines have recently changed their recommendations to dual antithrombotic therapy (DAT; P2Y12 inhibitor and OAC) without aspirin. AIMS: The prospective WOEST 2 registry was designed to obtain contemporary real-world data on antithrombotic regimens and related outcomes after PCI in patients with an indication for OAC. METHODS: In this analysis, we compare DAT (P2Y12 inhibitor and OAC) to triple antithrombotic therapy (TAT; aspirin, P2Y12 inhibitor, and OAC) on thrombotic and bleeding outcomes after one year. Clinically relevant bleeding was defined as Bleeding Academic Research Consortium classification (BARC) grade 2, 3, or 5; major bleeding as BARC grade 3 or 5. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, ischaemic stroke, and transient ischaemic attack. RESULTS: A total of 1,075 patients were included between 2014 and 2021. Patients used OAC for atrial fibrillation (93.6%) or mechanical heart valve prosthesis (4.7%). Non-vitamin K oral anticoagulants (NOAC) were prescribed in 53.1% and vitamin K antagonists in 46.9% of patients. At discharge, 60.9% received DAT, and 39.1% TAT. DAT was associated with less clinically relevant and similar major bleeding (16.8% vs 23.4%; p<0.01 and 7.6% vs 7.7%, not significant), compared to TAT. The difference in MACCE between the two groups was not statistically significant (12.4% vs 9.7%; p=0.17). Multivariable adjustment and propensity score matching confirmed these results. CONCLUSIONS: Dual antithrombotic therapy is associated with a substantially lower risk of clinically relevant bleeding without a statistically significant penalty in ischaemic events.

Computed tomography measured psoas muscle attenuation predicts mortality after transcatheter aortic valve implantation.

AIMS: The aim of this study was to determine if computed tomography (CT) psoas muscular attenuation measurements may predict all-cause mortality in patients undergoing TAVI. METHODS: Ninety-four consecutive patients undergoing TAVI were analysed. The CT axial slice at the level of the fourth lumbar vertebra was selected. The psoas muscle areas were manually contoured. The circumferential surface area (CSA) of both psoas muscles was determined by selecting the voxels with attenuation values, ranging from 0 to 100 Hounsfield Units (HU). The mean CT attenuation coefficient of the psoas muscle (Psoas mean HU) was measured. The muscle was subdivided into a low-density muscle (LDM) (0-29 HU) and high-density muscle (HDM) (30-100 HU) portion. The HDM/LDM ratio was calculated. We searched for a correlation between HDM/LDM, CSA LDM (%), Psoas mean HU and all-cause mortality. RESULTS: The mean age was 81.2 ±â€Š7.5 years. Thirty patients had adverse outcome (all-cause mortality). Compared with patients with the lowest CSA LDM (%), patients in the third and second tertiles had an increased hazard ratio for mortality (2.871; 95% confidence interval 0.880-9.371 and 5.044; 95% confidence interval 1.641-15.795, respectively) in a multivariable model with EuroSCORE II, Barthel frailty index and CSA LDM (%) (P = 0.231, 0.097 and 0.019, respectively). HDM/LDM and Psoas mean HU (as continuous variable) were also independent predictors of all-cause mortality (P = 0.019, P = 0.013, respectively). CONCLUSION: CSA LDM (%), Psoas mean HU and HDM/LDM are independent and incremental predictors of all-cause mortality in patients undergoing TAVI.

Comparison of radial access versus femoral access with the use of a vascular closure device for the prevention of vascular complications and mortality after percutaneous coronary intervention.

BACKGROUND: Radial access (RA) and vascular closure devices (VCD) have been shown to be superior to transfemoral access (TFA) with regard to the prevention of vascular complications after percutaneous coronary intervention (PCI). OBJECTIVE: The present study evaluates whether RA is associated with less vascular complications and a lower mortality than VCD. METHODS: A total of 6999 consecutive PCI patients were studied through a single-centre prospective registry from January 2011 to August 2015. RA was applied in 1385 patients (20%), VCDs with Angio-Seal were implanted in 2145 patients (30%) and manual compression of TFA was performed in 3468 patients (50%). RESULTS: RA and VCD patients had comparable baseline risk profiles. The overall vascular complication rate was 2.0% (n = 137) and was composed of false aneurysms (n = 85), clinically relevant haematomas (n = 27), arteriovenous fistulas (n = 12), arterial occlusions (n = 11) and local infections (n = 2). Vascular complications occurred in 0.6% of RA patients, 1.8% of VCD patients and 2.6% of TFA patients (p < .01). In-hospital mortality was 0.8% in RA patients, 0.8% in VCD patients and 3.8% in TFA patients (p < .01). In a multivariate logistic regression model, RA, compared to VCD, was found to be independently associated with a lower rate of vascular complications (OR: 0.34, 95% CI: 0.16-0.75), but not with lower mortality rates (OR: 1.20, 95% CI: 0.51-2.85). CONCLUSION: In this large all-comers PCI population, the radial approach, compared to the femoral approach with VCD use (Angio-Seal), was independently associated with a reduction of vascular complications, but not with lower mortality rates.

A higher volume of fibrotic tissue on virtual histology prior to coronary stent implantation predisposes to more pronounced neointima proliferation.

BACKGROUND: Since neointima smooth muscle cells (SMC) mainly originate from the vessel wall, we investigated whether atherosclerotic plaque composition influences subsequent in-stent neointima proliferation and restenosis. METHODS: We performed intravascular ultrasound (IVUS) with virtual histology in 98 patients prior to elective bare-metal stent (BMS) implantation in de novo coronary artery lesions. Virtual histology variables pre-percutaneous coronary intervention (PCI) were related to in-stent neointima proliferation six months after implantation assessed as late luminal loss of 0.88 mm (interquartile range (IQR) 0.37-1.23 mm) on angiography and as maximal percentage area stenosis of 42% (IQR 33-59%) and percentage volume intima hyperplasia of 27% (IQR 20-36%) on IVUS. A ridge-trace based multiple linear regression model was constructed to account for multicollinearity of the virtual histology variables and was corrected for implanted stent length (18 mm, IQR 15-23 mm), stent diameter (3.0 mm, IQR 2.75-3.5 mm) and lesion volume (146 mm³, IQR 80-201 mm³) prior to PCI. RESULTS: Fibrous tissue volume prior to PCI (49 mm³, IQR 30-77 mm³) was significantly and independently related to late luminal loss (p = .038), maximal percentage area stenosis (p = .041) and percentage volume intima hyperplasia (p = .004). Neither absolute nor relative amounts of fibrofatty, calcified or necrotic core tissue appeared related to any of the restenosis parameters. Subgroup analysis after exclusion of acute coronary syndrome (ACS) patients yielded similar results. CONCLUSION: Lesions with more voluminous fibrotic tissue pre-PCI show more pronounced in-stent neointima proliferation, even after correction for lesion plaque volume.

Assessing the landscape of percutaneous coronary chronic total occlusion treatment in Belgium and Luxembourg: the Belgian Working Group on Chronic Total Occlusions (BWGCTO) registry.

Background: Important developments in materials, devices, and techniques have improved outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI), and resulted in a growing interest in CTO-PCI. The Belgian Working Group on Chronic Total Occlusions (BWGCTO) working group aims to assess the evolution within the CTO-PCI landscape over the next years. Methods: From May 2016 onwards, patients undergoing CTO-PCI were included in the BWGCTO registry by 15 centres in Belgium and Luxemburg. Baseline, angiographic, and procedural data were collected. Here, we report on the one-year in-hospital outcomes. Results: Over the course of one year, 411 procedures in 388 patients were included with a mean age of 64 ± 11 years. The majority were male (81%). Relatively complex CTOs were treated (Japanese CTO score =2.2 ± 1.2) with a high procedure success rate (82%). Patient- and lesion-wise success rates were 83 and 85%, respectively. Major adverse in-hospital events were acceptably low (3.4%). Antegrade wire escalation technique was applied most frequently (82%). On the other hand, antegrade dissection and re-entry and retrograde strategies were more frequently applied in higher volume centres and successful for lesions with higher complexity. Conclusion: Satisfactory procedural outcomes and a low rate of adverse events were obtained in a complex CTO population, treated by operators with variable experience levels. Antegrade wire escalation was the preferred strategy, regardless of operator volume.

Failed Downregulation of Circulating MicroRNA-155 in the Early Phase after ST Elevation Myocardial Infarction Is Associated with Adverse Left Ventricular Remodeling.

BACKGROUND: MicroRNA are noncoding RNA that have a significant role in both inflammatory and cardiovascular diseases. AIMS: We aimed to assess whether the inflammation-related microRNA-155 is associated with the development of adverse left ventricular (LV) remodeling following ST elevation myocardial infarction (STEMI). METHODS: Peripheral blood samples were collected in the inflammatory (day 2), proliferative (day 5), and maturation phases (6 months) after STEMI (n = 20). Granulocytes, monocytes, and lymphocytes were enumerated with flow cytometry. The changes in LV volumes were assessed with 3-D echocardiography on day 1 and after 6 months. Adverse remodeling was defined as a >20% increase in end-diastolic volume. Healthy subjects were recruited as controls. RESULTS: MicroRNA-155 measured on day 5 correlated positively with the relative change in end-diastolic volume (ρ = 0.490, p = 0.028). MicroRNA-155 (day 5) was significantly higher in patients with compared to patients without adverse LV remodeling. The expression level was similar in healthy subjects (n = 8) and in patients with LV remodeling. There was a positive correlation between microRNA-155 and the amount of monocytes (day 5, ρ = 0.463, p = 0.046). CONCLUSION: Impaired downregulation of microRNA-155 during the second phase of the post- STEMI inflammatory response is a determinant of the development of adverse LV remodeling.

Adiponectin and ischemia-reperfusion injury in ST segment elevation myocardial infarction.

BACKGROUND: Models of experimental ischemia-reperfusion (IR) in adiponectin knockout animals have shown that adiponectin mediates protection against the development of IR injury. However, the role of adiponectin in IR injury in humans is largely unknown. METHODS: In a total of 234 ST segment elevation myocardial infarction (STEMI) patients, baseline circulating total adiponectin concentration was correlated with IR injury after primary percutaneous coronary intervention (pPCI) and with major adverse cardiac events (MACE, death and cardiac hospitalization) during one year of follow up. IR injury was defined by serial electrocardiography (ECG) as >30% persistent ST segment elevation despite successful restoration of vessel patency and by angiography as thrombolysis in myocardial infarction (TIMI) blush grade<2. RESULTS: IR injury was present in 31% of patients according to ECG criteria and in 28% of patients according to angiographic criteria. The median adiponectin level was 6.8 µg/ml in patients with ECG signs of IR injury and 6.5 µg/ml in patients without ECG signs of IR (p=0.26). When the angiographic criteria of IR were used, the median adiponectin level was 6.9 µg/ml for patients with IR versus 6.3 µg/ml for patients without IR (p=0.06). MACE occurred in 27% of the patients. Median adiponectin levels were similar in patients with MACE and in those without MACE: 6.3 vs. 6.4 µg/ml (p=0.24). In a multivariate model, no significant relation between circulating adiponectin levels and IR injury or MACE was evident. CONCLUSION: In the current era of pPCI, IR injury still occurs in almost one third of STEMI patients. Our findings do not support a major protective role of adiponectin in the prevention or attenuation of IR injury in these patients.

Usefulness of early rule-in and rule-out biomarker protocols to estimate ischemia-induced myocardial injury in early chest pain presenters.

Protocols to minimize the time between 2 measurements of troponin or a combination with copeptin have been developed to rapidly rule-in or rule-out myocardial injury (MI) in patients with chest pain. These fast track protocols to rule-in and rule-out MI are not sufficiently validated for early chest pain presenters. The "early presenter" model was tested in 107 stable patients after a short period of myocardial ischemia, induced by stenting of a significant coronary artery stenosis. High-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI), and copeptin were measured at the start and 90, 180, and 360 minutes after stent implantation. MI was defined as a troponin level more than the upper limit of normal (ULN) and an absolute increase of >50% ULN on the 360-minute sample. A single combined measurement of troponin and copeptin 90 minutes after the onset of ischemia has a low diagnostic value. This increases when serial measurements with 90-minute intervals are included. For ruling in MI, the highest positive predictive value (with a 95% confidence interval [CI]) can be obtained when focusing only on the increase in troponin level, with a positive predictive value of 86% (70, 93) and 80% (67, 90) for hsTnT and hsTnI, respectively. For ruling out MI, a combined absence of any troponin more than the ULN and any significant increase in troponin level perform best with a negative predictive value of 75% (55, 89) and 75% (55, 89) for hsTnT and hsTnI, respectively. In conclusion, in early presenters, rapid biomarker protocols underestimate MI. A standard biomarker assessment after 3 hours is required to adequately rule-in or rule-out myonecrosis.

Percutaneous mitral valve repair in high-risk patients: initial experience with the Mitraclip system in Belgium.

AIMS: Treatment with percutaneous edge-to-edge mitral valve repair (Mitraclip) has recently been recommended as an alternative to conventional mitral valve repair for high surgical risk patients with symptomatic severe mitral regurgitation (MR). In this study, we report the first use of Mitraclip therapy in Belgium. METHODS AND RESULTS: This prospective registry includes 41 consecutive patients treated with the Mitraclip in two Belgian centres from October 2010 to June 2013. Acute procedural success, in-hospital safety end points and clinical status were analysed on an intention-to-treat basis up to one year after the procedure. In addition, determinants of major adverse cardiac events (MACE, death, surgical mitral valve intervention, and rehospitalization for heart failure) were analysed. Acute procedural success (successful clip placement and reduction of colour Doppler flow MR to < or = 2) was obtained in 32 patients (78%) and 18 of these patients received two clips. The primary safety end point was reached in 36 pts (88%): one patient died due to intracranial bleeding, there were three urgent surgical interventions and one severe access site bleeding. The MACE rate after one year was 41% (17 patients). There were 11 deaths (27%), six surgical interventions (15%) and 10 rehospitalizations for heart failure (24%). Additional subgroup analysis revealed that the one-year MACE rate was particularly high in patients with left ventricular ejection fraction (LVEF) < 25%: 62% vs. 36% in patients with LVEF > or = 5% (P = 0.05). At one year, MR < or = 2+ and NYHA class < or = 2 was present in 83% of the surviving patients CONCLUSION: In high-risk patients with functional MR, treatment with the Mitraclip-device is a feasible and safe option resulting in improvement of MR severity and clinical symptoms. However, as MACE is high in some subgroups (e.g. LVEF < 25%), careful patient selection is crucial to ensure the maximum benefit from this new technique.

Cost-effectiveness of contemporary vascular closure devices for the prevention of vascular complications after percutaneous coronary interventions in an all-comers PCI population.

AIMS: The present observational case-control study assessed the cost-effectiveness of contemporary vascular closure devices (VCDs) for the prevention of vascular complications in an all-comers transfemoral percutaneous coronary intervention (PCI) population. METHODS AND RESULTS: A total of 8,292 consecutive PCI patients were enrolled from a single-centre prospective registry from January 2005 to December 2010. VCDs were available from July 2007 and, from that time point, VCDs were implanted in 1,780 of the 5,394 patients (33%). Vascular complications occurred in 221 (2.7%) patients. The use of VCDs was independently associated with a 53% risk reduction (OR 0.47, 95% CI: 0.3-0.7) in vascular complications (3.0% vs. 1.5%) and with a 65% risk reduction (IRR 0.37, 95% CI: 0.32-0.43) in the post-PCI length of hospital stay (LOS) (mean 2.8 vs. 1.5 days). Mainly due to the reduced LOS, the patients with VCDs accrued vascular direct medical costs (VCD, diagnosis and treatment of vascular complications, post-PCI LOS) that were on average 498€ less than those accrued by the non-VCD patients. The cost-effectiveness was present across all vascular risk profiles. CONCLUSIONS: In this large, all-comers transfemoral PCI population, the use of VCDs was independently associated with a reduction in the rate of vascular complications and the post-PCI length of hospital stay and proved to be cost-saving across all vascular risk profiles.

Levels of circulating CD34+/KDR+ cells do not predict coronary in-stent restenosis.

BACKGROUND: Angiographic and clinical parameters are poor predictors of in-stent restenosis. Bone marrow-derived CD34(+) cells that coexpress a receptor for vascular endothelial growth factor (kinase insert domain receptor [KDR]) are committed to endothelial lineage. Mobilization and infusion of CD34(+)/KDR(+) cells accelerates re-endothelialization and reduces neointimal thickness in vascular injury models. Bioengineered stents capturing CD34(+) cells also show expedited re-endothelialization. We examined whether circulating CD34(+)/KDR(+) cell counts can be used to predict restenosis in a bare-metal stent (BMS). METHODS: CD34(+)/KDR(+) cells were counted by flow cytometry in 124 nondiabetic patients before BMS implantation and the relation to in-stent late luminal loss (LLL) was examined by angiography at 6 months (primary end point). Neointima was also quantified as the maximum percentage area stenosis (M%AS) and percentage volume intima hyperplasia (%VIH) on intravascular ultrasonography (secondary end points). RESULTS: Multiple linear regression analysis, taking into account implanted stent length and diameter, revealed no relation between CD34(+)/KDR(+) cell counts and LLL (partial regression coefficient b = 0.11; 95% confidence interval [CI], -0.19-0.42; P = 0.46). Similarly, no relation between CD34(+)/KDR(+) cell counts and M%AS or %VIH could be demonstrated. Moreover, the increase in CD34(+)/KDR(+) cell counts over 6 months was unrelated to LLL (b = -0.15; 95% CI, -0.42-0.12; P = 0.28), M%AS, and %VIH. CONCLUSIONS: Although our study does not exclude a pathophysiologic role for CD34(+)/KDR(+) cells in the formation of neointima, cell counts before percutaneous coronary intervention proved to be unrelated to LLL or intravascular ultrasonographically derived restenosis parameters in coronary BMSs at 6 months.

Coronary spasm after the topical use of cocaine in nasal surgery.

BACKGROUND: Cocaine is a frequently used recreational drug which imposes important health problems with even life-threatening cardiotoxicity. The therapeutic use of cocaine is nowadays restricted to topical anesthesia in ophthalmological and nasal surgery but the possible hazards of this local anesthesia are not always fully appreciated. CASE REPORT: A 51-year old male patient with moderate cardiovascular risk profile underwent elective nasal surgery and cocaine was used as a local anesthetic. During surgery, ventricular arrhythmias and cardiogenic shock occurred, mimicking an ST-segment elevation myocardial infarction (STEMI) in sinus rhythm. Coronary angiography showed diffuse spasm of the right coronary artery (RCA) which disappeared with intracoronary nitrates. Urine analysis was positive for cocaine. The patient recovered completely with a normal echocardiography and ECG at discharge. CONCLUSIONS: Cocaine cardiotoxicity is not uncommon in the community but a particular situation arises when used in medicine as a topical anesthetic. This is the first case report, to our knowledge, of a cardiogenic shock mimicking a STEMI with documentation of diffuse coronary spasm after cocaine use in nasal surgery. One must be aware of the potential life-threatening complications in this low-risk surgery, moreover when safer alternatives are available.

Difference in clinical target lesion revascularization between a silicon carbide-coated and an uncoated thin strut bare-metal stent: the PRO-Vision study.

BACKGROUND: Bare-metal stents trigger a foreign body reaction, resulting in neointima formation and restenosis. Silicon carbide (SiC) coating shields the metal from circulating blood and vessel wall, both potential sources of neointima smooth muscle cells. METHODS: We investigated whether SiC-coated stents (PRO-Kinetic) have lower clinical target lesion revascularization (TLR) rates than do uncoated bare-metal stents (Vision). Stents were implanted in 2731 patients during 2 consecutive 18-month periods. Clinical TLR was evaluated at 1 year. RESULTS: In the PRO-Kinetic group, TLR was significantly higher (9.0% vs 5.6%; unadjusted odds ratio, 1.61; 95% confidence interval [CI], 1.24-2.08; P < 0.001) compared with the Vision group. After adjustment for postintervention minimal luminal diameter (adjusted odds ratio [AOR], 0.56; 95% CI, 0.42-0.73), total implanted stent length (AOR, 1.01; 95% CI, 1.00-1.02), non-ST-segment elevation myocardial infarction or unstable angina at initial presentation (AOR, 1.89; 95% CI, 1.41-2.54), and triple vessel stenting (AOR, 2.68; 95% CI, 1.02-7.05), the use of PRO-Kinetic stents remained an independent predictor for revascularization (AOR, 1.57; 95% CI, 1.18-2.10; P = 0.002). Because strut thickness is lower in 2.0- to 3.0-mm PRO-Kinetic stents, a subgroup analysis (n = 2382 lesions) was performed. Even in this subgroup, PRO-Kinetic implantation proved an independent predictor of TLR (AOR, 1.62; 95% CI, 1.17-2.23; P = 0.003). CONCLUSION: In contrast to theoretical expectations, the SiC-coated PRO-Kinetic stent was associated with greater target lesion revascularization rates at 1 year compared with the uncoated Vision stent.