Comparison of Arctic Front Advance Pro and POLARx cryoballoons for ablation therapy of atrial fibrillation: an intraprocedural analysis.

INTRODUCTION: Cryoballoon (CB) ablation has become a popular method for pulmonary vein isolation (PVI) in atrial fibrillation (AF) treatment. This study aimed to compare the intraprocedural ablation characteristics of two cryoballoons, Arctic Front Advance Pro™ (AFA-Pro, Medtronic) and POLARx™ (Boston Scientific). METHODS AND RESULTS: In this retrospective single-center study, 230 symptomatic paroxysmal or persistent AF patients underwent CB ablation with either AFA-Pro or POLARx. Propensity-score matching resulted in two cohorts of 114 patients each. Baseline and procedural characteristics were comparable between both CBs. POLARx achieved lower minimal temperatures (e.g., left superior pulmonary vein, LSPV: AFA-Pro - 49.0 °C vs. POLARx - 59.5 °C) and lower temperatures at time-to-isolation (TTI). Additionally, POLARx reached lower temperatures faster, as evidenced by lower temperatures after 40 and 60 s, and a larger mean temperature change between 20 and 40 s. POLARx also had a greater area under the curve below 0 °C and a longer thawing phase. Both CBs achieved comparable high rates of final PV-isolation. TTI, minimal esophagus temperature, and first-pass isolation rates were similar between groups. Periprocedural complications, including phrenic nerve injuries, were comparable. Troponin levels in the left atrium were elevated with both systems. Values and change in troponin were numerically higher in the POLARx group (delta troponin: AFA-Pro 36.3 (26.4, 125.4) ng/L vs. POLARx 104.9 (49.5, 122.2) ng/L), p = 0.077). CONCLUSION: AFA-Pro and POLARx are both highly effective and safe CB systems for PVI. POLARx exhibited significant faster and lower freezing characteristics, and numerically higher troponin levels might indicate greater myocardial injury. However, these differences did not translate into improved performance, procedural efficiency, or safety.

Follow-Up and Outcome after Coronary Bypass Surgery Preceded by Coronary Stent Implantation.

BACKGROUND: Guidelines on myocardial revascularization define recommendations for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Only little information exists on long-term follow-up and quality of life (QoL) after CABG preceded by PCI. The aim of our study was to evaluate the impact of prior PCI on outcome and QoL in patients with stable coronary artery disease who underwent CABG. METHODS: In our retrospective study, CABG patients were divided in: CABG preceded by PCI: PCI-first (PCF), and CABG-only (CO) groups. The PCF group was further divided in guideline-conform (GCO) and guideline nonconform (GNC) subgroups, according to the SYNTAX score (2014 European Society of Cardiology [ESC]/European Association for Cardio-Thoracic Surgery [EACTS] guidelines). Thirty days mortality, major adverse cardiac events, and QoL using the European Quality-of-Life-5 Dimensions were evaluated. RESULTS: A total of 997 patients were analyzed, of which 784 underwent CABG without (CO), and 213 individuals with prior PCI (PCF). The latter group consisted of 67 patients being treated in accordance (GCO), and 24 in discordance (GNC) to the 2014 ESC/EACTS guidelines. Reinfarction (PCF: 3.8% vs. CO: 1.0%; p = 0.024), re-angiography (PCF: 17.6% vs. CO: 9.0%; p = 0.004), and re-PCI (PCF: 10.4% vs. CO: 3.0%; p < 0.001) were observed more frequently in PCF patients. Also, patients reported better health status in the CO compared to PCF group (CO: 72.48 ± 19.31 vs. PCF: 68.20 ± 17.86; p = 0.01). Patients from the guideline nonconform subgroup reported poorer health status compared to the guideline-conform group (GNC: 64.23 ± 14.56 vs. GCO: 73.42 ± 17.66; p = 0.041) and were more likely to require re-PCI (GNC: 18.8% vs. GCO: 2.4%; p = 0.03). Also, GNC patients were more likely to have left main stenosis (GCO: 19.7% vs. GNC: 37.5%; p < 0.001) and showed higher preinterventional SYNTAX score (GCO: 18.63 ± 9.81 vs. GNC: 26.67 ± 5.07; p < 0.001). CONCLUSION: PCI preceding CABG is associated with poorer outcomes such as reinfarction, re-angiography, and re-PCI, but also worse health status and higher rehospitalization. Nevertheless, results were better when PCI was guideline-conformant. This data should impact the Heart Team decision.

Transverse aortic constriction-induced heart failure leads to increased levels of circulating microparticles.

BACKGROUND: Circulating microparticles represent one type of signal transmission between cells. Previous studies revealed increased levels of circulating microparticles in patients with heart failure, while composition, temporal occurrence and biological effects are largely unknown. METHODS: Circulating microparticles were quantified by flow cytometry in mice following TAC. Microparticles were characterized by NTA and immunoblotting for Flotillin-1. Microparticle content was investigated by microRNA analyses. RESULTS: After TAC induction of heart failure could be demonstrated. Simultaneously we observed increased numbers of circulating microparticles in the first week after TAC with a rapid decline thereafter. The most relevant fraction of circulating EVs after TAC derived from lymphocytes containing has-miR-26a-5p and / -146b-5p known to be involved in inflammatory processes. CONCLUSION: This work provides a previously unknown timely limited occurrence of circulating microparticles after new onset of heart failure which might have important influence on disease development and progression and thereby are of probable therapeutic relevance.

Extended neuromonitoring in aortic arch surgery : A case series.

BACKGROUND: Aortic arch repair for aortic dissection is still associated with a high mortality rate. Providing adequate means of neuromonitoring to guide cerebral hemodynamics is advantageous, especially during selective anterior cerebral perfusion (SACP). OBJECTIVE: We aimed to investigate an easy multimodal neuromonitoring set-up consisting of processed electroencephalography (EEG), near infrared spectroscopy (NIRS), and transcranial doppler sonography (TCD). MATERIAL AND METHODS: We collected intraoperative data from six patients undergoing surgery for aortic dissection. In addition to standard hemodynamic monitoring, patients underwent continuous bilateral NIRS, processed EEG with bispectral index (BIS), and intermittent transcranial doppler sonography of the medial cerebral artery (MCA) with a standard B­mode ultrasound device. Doppler measurements were taken bilaterally before cardiopulmonary bypass (CPB), during CPB, and during SACP at regular intervals. RESULTS: Of the patients four survived without neurological deficits while two suffered fatal outcomes. Of the survivors two suffered from transient postoperative delirium. Multimodal monitoring led to a change in CPB flow or cannula repositioning in three patients. Left-sided mean flow velocities of the MCA decreased during SACP, as did BIS values. CONCLUSION: Monitoring consisting of BIS, NIRS, and TCD may have an impact on hemodynamic management in aortic arch operations.

Single tests of implantable cardioverter defibrillators can be performed in selected patients at a low risk of neuronal damage.

BACKGROUND: Defibrillator testing (DFT) is still used in selected patients to ensure adequate therapy. To do so, ventricular fibrillation is induced and terminated by the implanted cardioverter defibrillator (ICD). Studies have shown increases in neuronal damage markers without a measurable clinical effect in patients after defibrillator threshold testing with multiple shocks. OBJECTIVE: The aim of this study was to measure clinical outcomes, neuronal damage parameters (NSE and S100), and intraoperative cerebral perfusion (Doppler, near infra-red spectroscopy [NIRS]) in patients undergoing single DFT after transvenous ICD implantation and comparing them to untested patients. METHOD: We included 23 patients. Nine underwent surgery with a single DFT, 14 were not tested. Cognitive impairment was tested using the Mini-Mental-Status Test (MMST) and the DEMTECt 24 h prior and postsurgery. We also measured S100 and Neuron-Specific Enolase (NSE) at these timepoints. During surgery we measured medial cerebral artery velocity and cerebral tissue oxygen saturation (rSO2 ). RESULTS: We found no significant differences between the patient groups except for a significant increase in mean arterial blood pressure and an increase in rSO2 after testing. One patient with cerebral vasculopathy had a significant increase in his NSE values without showing clinical symptoms. This patient also had low rSO2 measurements and a decrease in medial cerebral artery velocity after DFT, other than the other patients. CONCLUSION: Single DFT did not lead to signs of neuronal damage or cognitive impairment except in one case with pre-existing cerebral vasculopathy. Therefore, our results support the use of DFT in carefully selected patients.

Surgical Revascularization of Chronically Occluded Coronary Arteries-What You See Is What You Get?

BACKGROUND: Revascularization strategy in coronary artery bypass grafting (CABG) surgery usually depends on coronary dimension and stenosis severity. Little is known about the relation of preoperative evaluation of scarcely or invisibly chronic occluded coronary arteries (chronic total occlusion [CTO]) and revascularization rate or anastomosis quality. We aimed to evaluate the success rates of CTO revascularization in CABG surgery and determine the influence of coronary lumen visibility and collateralization in preoperative angiograms on revascularization rates, bypass blood flow, and target vessel diameter. METHOD: Preoperative coronary angiograms were evaluated for 938 consecutive patients who underwent isolated CABG surgery between 2014 and 2016 and screened for occluded coronary arteries. The occluded vessels were scored for visibility using the Rentrop grading of collateral filling. Intraoperatively, dimensions of the occluded arteries were measured using conventional vessel probes, and anastomosis quality was assessed by transit time flow measurement. RESULTS: A total of 404 (43.1%) patients were identified with at least one CTO. Revascularization rates differed from 96.2% in the left anterior descending artery, to 85.0% in left circumflex artery-dependent vessels, and 78.8% in right coronary artery territory. Coronary visibility and grade of collateralization in the preoperative angiogram had no influence on intraoperatively measured coronary diameter. Bypass blood flow in grafts revascularizing CTOs lacking collateralization were not significantly lower than those grafts leading to CTOs with higher Rentrop scores. CONCLUSION: Preoperative coronary assessment often differs from intraoperative findings. Our study confirms that even patients with scarcely collateralized CTOs and impaired visibility in the coronary angiogram have a high chance of complete revascularization during CABG surgery.

Timely extracorporeal membrane oxygenation assist reduces mortality after bypass surgery in patients with acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk when undergoing emergency coronary artery bypass graft (CABG)-surgery. Their outcome remains poor despite increased use of extracorporeal membrane oxygenation (ECMO). We investigated the impact of timing for perioperative ECMO-support in these patients. METHODS: In this retrospective double-center study, we evaluated 201 patients with AMI undergoing CABG, dividing them into the following groups: No-ECMO (n = 101), preoperative ECMO (pre-ECMO, n = 6), intraoperative ECMO (ECC-ECMO, n = 67), and postoperative ECMO (post-ECMO, n = 27). We evaluated the impact of ECMO timing on postoperative mortality, organ function, and length of stay, comparing these to predicted outcome using different risk-scores. RESULTS: Post-ECMO patients showed lowest 30-day-survival (40.7%), while earlier ECMO-start was associated with better outcome (50.7% in extracorporeal circulation [ECC]-ECMO and 66.7% in pre-ECMO patients). On admission, only pre-ECMO and ECC-ECMO patients showed higher surgery- and intensive-care-unit (ICU)-related risk-scores. In pre- and ECC-ECMO patients, the first significant increase in lactate-levels (>4 mmol/L) was observed preoperatively, while this occurred 1 hour postoperatively in post-ECMO patients. Bilirubin was increased in all patients, decreasing after 3 and 12 days in pre- and ECC-ECMO patients, respectively, but only after 18 days in post-ECMO patients. Multiple ICU risk-scores did not discriminate survival-probability correctly. Only the ECMO-related survival after veno-arterial-ECMO-score correctly predicted the significantly lower survival in post-ECMO patients. CONCLUSION: Our study shows that timely ECMO-support is associated with earlier bilirubin-downtrend and higher survival in patients with AMI after CABG. Lactate-increase greater than 4 mmol/L seems to be a helpful threshold to trigger the timely onset of ECMO-therapy, providing better survival.

CB2-deficiency is associated with a stronger hypertrophy and remodeling of the right ventricle in a murine model of left pulmonary artery occlusion.

AIMS: Pulmonary hypertension (PH) leads to right ventricular (RV) adaptation and remodeling and has deleterious long-term effects on RV function. The endocannabinoid receptor CB2 has been associated with protective effects in adaptation and remodeling of the left ventricle after ischemia. Therefore, we investigated the role of CB2 receptor in RV adaptation after occlusion of the left pulmonary artery (LPA) in a murine model. MAIN METHODS: C57/Bl6 (WT)- and CB2 receptor-deficient (Cnr2-/-)-mice underwent paramedian sternotomy and LPA was occluded using a metal clip. Right heart hemodynamic study (Millar®) preceded organ harvesting for immunohistochemistry and mRNA analysis 7 and 21 days (d) post-occlusion. KEY FINDINGS: LPA occlusion led to higher RV systolic pressure in Cnr2-/--hearts, while hemodynamics were comparable with WT-hearts after 21d. Cnr2-/--hearts showed higher macrophage infiltration and lower interleukin-10 expression after 7 d, but otherwise a comparable inflammatory mediator expression profile. Cardiomyocyte-hypertrophy was stronger in Cnr2-/--mice, presenting with higher tenascin-C expression than WT-hearts. Planimetry revealed higher collagen area in Cnr2-/--hearts and small areas of cardiomyocyte-loss. Surrounding cardiomyocytes were cleaved caspase-3- and TUNEL positive in Cnr2-/--hearts. This was associated by maladaptation of myosin heavy-chain isoforms and lower reactive oxygen scavenger enzymes induction in Cnr2-/--hearts. We found comparable morphological changes in both lungs between the two genotypes. SIGNIFICANCE: LPA occlusion led to increased systolic pressure and adaptation of RV in CB2-deficient mice. CB2 receptor seems to modulate RV adaptation through expression of contractile elements, reactive oxygen scavenger enzymes, and inflammatory response in order to prevent cardiomyocyte apoptosis.

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice.

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to perform a partial thoracotomy to visualize the transverse aortic arch. However, the surgical trauma caused by the thoracotomy in open-chest models changes the respiratory physiology as the ribs are dissected and left unattached after chest closure. To prevent this, we established a minimally invasive, closed chest approach via lateral thoracotomy. Herein we approach the aortic arch via the 2nd intercostal space without entering the chest cavities, leaving the mouse with a less traumatic injury to recover from. We perform this operation using standard laboratory settings for open chest TAC procedures with equal survival rates. Apart from maintaining physiological breathing patterns due to the closed chest approach, the mice seem to benefit by showing rapid recovery, as the less invasive technique appears to facilitate a fast healing process and to reduce immune response after trauma.

Long-Term Outcome and Quality of Life in Aortic Type A Dissection Survivors.

BACKGROUND: Aortic dissection is a severe and sophisticated disease that is often linked with a number of possible complications. Our study concerns with long-term outcome and quality of life (QoL) in acute aortic dissection type A (AADA) survivors. METHODS: From January 1999 until December 2006, 120 consecutive patients with AADA received an emergency operation. Of the total number of patients, 84 were males (70.0%) and 36 females (30.0%), mean aged 59.8 ± 12 years with a mean follow-up (FU) of 99.2 ± 6 months. RESULTS: Overall mortality was 39.1% during the observational period with a maximum of 156 months. SF-36 observation showed a significant decay in both Physical Component Summary (PCS) and Mental Component Summary (MCS) in FUII (PCS = 38.4) versus FUI (PCS = 43.4, p = 0.013). CONCLUSION: With ongoing postoperative time, patients did not recover but instead have got worse in terms of QoL. The decrease in MCP and linked subscores is an underestimated factor in QoL and long-term outcome after AADA. This is especially true in younger patients, which are judged to compensate better than older patients.

Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm.

Human aortic aneurysms have been associated with inflammation and vascular remodeling. Since the endocannabinoid system modulates inflammation and tissue remodeling, we investigated its components in human aortic aneurysms. We obtained anterior aortic wall samples from patients undergoing elective surgery for aortic aneurysm or coronary artery disease as controls. Histological and molecular analysis (RT-qPCR) was performed, and endocannabinoid concentration was determined using LC-MRM. Patient characteristics were comparable between the groups except for a higher incidence of arterial hypertension and diabetes in the control group. mRNA level of cannabinoid receptors was significantly higher in aneurysms than in controls. Concentration of the endocannabinoid 2-arachidonoylglycerol was significantly higher, while the second endocannabinoid anandamide and its metabolite arachidonic acid and palmitoylethanolamide were significantly lower in aneurysms. Histology revealed persistent infiltration of newly recruited leukocytes and significantly higher mononuclear cell density in adventitia of the aneurysms. Proinflammatory environment in aneurysms was shown by significant upregulation of M-CSF and PPARγ but associated with downregulation of chemokines. We found comparable collagen-stained area between the groups, significantly decreased mRNA level of CTGF, osteopontin-1, and MMP-2, and increased TIMP-4 expression in aneurysms. Our data provides evidence for endocannabinoid system activation in human aortic aneurysms, associated with persistent low-level inflammation and vascular remodeling.

Impaired border zone formation and adverse remodeling after reperfused myocardial infarction in cannabinoid CB2 receptor deficient mice.

AIMS: Reperfusion ofmyocardial infarction is associated with inflammatory reaction and subsequentmyocardial remodeling with a rapid scar formation in mice. The cannabinoid receptor CB2 has been associated with cardioprotection and regulation ofmacrophage function.Weinvestigated its role in remodeling of reperfused infarction. MAIN METHODS: One hour LAD-occlusion was followed by reperfusion over 6 h and 1, 3 and 7 days in wild-type C57/BL6J (WT) and CB2 receptor-deficient (Cnr2−/−)mice (n=8/group). Hearts were processed for functional, morphological and mRNA/protein analysis, and tissue concentration of endocannabinoidswas determined using liquid chromatography-multiple reaction monitoring. KEY FINDINGS: In contrast to a rapid formation of granulation tissue and a compacted non-transmural scar inWT mice after 7 days of reperfusion, Cnr2−/− mice showed a non-compacted transmural scar. Millar® left ventricular catheter measurements revealed a significantly worse function in Cnr2−/− mice.We found no compensatory elevation of endocannabinoid concentration in Cnr2−/− hearts. Macrophage infiltration was significantly stronger in Cnr2−/− hearts and affected also the remote septum, when compared to WT hearts.We found a cytokine-driven inflammatory response in Cnr2−/− hearts with no significant induction of chemokines. Immunohistochemistry for thrombospondin-1 revealed a dysfunctional infarction border zone formation in Cnr2−/− hearts. Cnr2−/−hearts showed no significant induction of tenascin C, collagen-Iα or lysil oxidase, thereby indicating adversemyocardial remodeling. SIGNIFICANCE: Endocannabinoids act via CB2 receptor in the modulation of inflammatory response and myocardial remodeling after infarction. CB2 receptor plays an important role in the formation of infarction border zone, collagen deposition and organization of stable scar during remodeling.

A migrated aortic stent graft causing erosive spondylopathy.

We report about a patient presenting with back pain 4 months after an uneventful endovascular implantation of an aortic stent graft. Computed tomography scan revealed a migration of the stent with consecutive endoleakage, kink formation, and movement of the stent toward the spine, which caused destruction of the aortic wall as well as vertebral necrosis. Explantation of the stent and replacement of the native aorta relieved the patient of his symptoms.

WRN protects against topo I but not topo II inhibitors by preventing DNA break formation.

The Werner syndrome helicase/3'-exonuclease (WRN) is a major component of the DNA repair and replication machinery. To analyze whether WRN is involved in the repair of topoisomerase-induced DNA damage we utilized U2-OS cells, in which WRN is stably down-regulated (wrn-kd), and the corresponding wild-type cells (wrn-wt). We show that cells not expressing WRN are hypersensitive to the toxic effect of the topoisomerase I inhibitor topotecan, but not to the topoisomerase II inhibitor etoposide. This was shown by mass survival assays, colony formation and induction of apoptosis. Upon topotecan treatment WRN deficient cells showed enhanced DNA replication inhibition and S-phase arrest, whereas after treatment with etoposide they showed the same cell cycle response as the wild-type. A considerable difference between WRN and wild-type cells was observed for DNA single- and double-strand break formation in response to topotecan. Topotecan induced DNA single-strand breaks 6h after treatment. In both wrn-wt and wrn-kd cells these breaks were repaired at similar kinetics. However, in wrn-kd but not wrn-wt cells they were converted into DNA double-strand breaks (DSBs) at high frequency, as shown by neutral comet assay and phosphorylation of H2AX. Our data provide evidence that WRN is involved in the repair of topoisomerase I, but not topoisomerase II-induced DNA damage, most likely via preventing the conversion of DNA single-strand breaks into DSBs during the resolution of stalled replication forks at topo I-DNA complexes. We suggest that the WRN status of tumor cells impacts anticancer therapy with topoisomerase I, but not topoisomerase II inhibitors.