Safety and Success Rates of Excimer Laser Sheath-Assisted Retrieval of Embedded Inferior Vena Cava Filters.

Importance: Despite historically high rates of use, most inferior vena cava (IVC) filters are not retrieved. The US Food and Drug Administration safety communications recommended retrieval when the IVC filter is no longer indicated out of concern for filter-related complications. However, failure rates are high when using standard techniques for retrieval of long-dwelling filters, and until recently, there have been no devices approved for retrieval of embedded IVC filters. Objective: To evaluate the safety and success of excimer laser sheath-assisted retrieval of embedded IVC filters. Design, Setting, and Participants: A retrospective, multicenter, clinical cohort study of excimer laser sheath-assisted IVC filter retrievals from 7 US sites was conducted between March 1, 2012, and February 28, 2021, among 265 patients who underwent IVC filter retrieval using the laser. Patients were substratified between a high-volume single center and a multicenter data set. A blinded physician committee adjudicated reported complications and their association with use of the laser. Exposures: Retrieval of IVC filters using excimer laser sheath. Main Outcomes and Measures: The primary safety end point was device-related major complication rate (Society of Interventional Radiology categories C to F, which included any adverse event associated with morbidity or disability that increases the level of care, results in hospital admission, or substantially lengthens the hospital stay). The primary success end point was technical success of IVC filter retrieval. The primary end points were compared with literature-derived, meta-analysis-suggested target performance goals. Results: The single-center experience included 139 participants (mean [SD] age, 52 [16] years; 78 female participants [56.1%]), and the multicenter experience included 126 participants (mean [SD] age, 52 [16] years; 75 female participants [59.5%]). The device-related major complication rate was 2.9% (4 of 139; 95% CI, 0.8%-7.2%; P = .001) for the single-center experience and 4.0% (5 of 126; 95% CI, 1.3%-9.0%; P = .01) for the multicenter experience, both of which were significantly lower than the primary safety performance goal (10%). No major complications were considered to be definitively associated with use of the laser. The technical success rate was 95.7% (133 of 139; 95% CI, 90.8%-98.4%; P = .007) for the single-center experience and 95.2% (120 of 126; 95% CI, 89.9%-98.2%; P = .02) for the multicenter experience, both of which were significantly higher than the primary performance goal (89.4%). Conclusions and Relevance: This cohort study demonstrated high technical success and low complication rates of excimer laser sheath-assisted retrieval of embedded IVC filters in centers with variable case volume and experience, which suggests a wide applicability of the technique with proper training. The excimer laser sheath offers physicians a valuable tool for retrieval of challenging embedded IVC filters.

Percutaneous occlusion balloon as a bridge to surgery in a swine model of superior vena cava perforation.

BACKGROUND: Superior vena cava (SVC) perforation is a rare but potentially fatal complication of transvenous lead removal. OBJECTIVE: The aim of this study was to evaluate the feasibility of hemodynamic stabilization using an occlusion balloon during SVC tear in a porcine model. METHODS: A surgically induced SVC perforation was created in Yorkshire cross swine (n = 7). Three animals were used to develop and test surgical repair methods. Four animals were used to evaluate hemodynamic, behavioral, and neurological effects up to 5 days after SVC tear and repair. An occlusion balloon (Bridge Occlusion Balloon, Spectranetics Corporation, Colorado Springs, CO) was percutaneously delivered through the femoral vein to the location of the injury and inflated. Once hemodynamic control was achieved, the perforation was surgically repaired. RESULTS: After SVC perforation and clamp release, the rate of blood loss was 7.0 ± 0.8 mL/s. Mean time from SVC tear to occlusion balloon deployment was 55 ± 12 seconds, during which mean arterial pressure decreased from 56 ± 2 to 25 ± 3 mm Hg and heart rate decreased from 76 ± 7 to 62 ± 7 beats/min. After the deployment of the occlusion balloon, the rate of blood loss decreased by 90%, to 0.7 ± 0.2 mL/s. The mean time of balloon occlusion of the SVC was 16 ± 4 minutes and hemodynamic measures returned to baseline levels during this time. Study animals experienced no major complications, demonstrated stable recovery, and exhibited normal neurological function at each postoperative assessment. CONCLUSION: Endovascular temporary balloon occlusion may be a feasible option to reduce blood loss, maintain hemodynamic control, and provide a bridge to surgery after SVC injury.

Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.

Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.

New approaches in small animal echocardiography: imaging the sounds of silence.

Systolic and diastolic dysfunction of the left ventricle (LV) is a hallmark of most cardiac diseases. In vivo assessment of heart function in animal models, particularly mice, is essential to refining our understanding of cardiovascular disease processes. Ultrasound echocardiography has emerged as a powerful, noninvasive tool to serially monitor cardiac performance and map the progression of heart dysfunction in murine injury models. This review covers current applications of small animal echocardiography, as well as emerging technologies that improve evaluation of LV function. In particular, we describe speckle-tracking imaging-based regional LV analysis, a recent advancement in murine echocardiography with proven clinical utility. This sensitive measure enables an early detection of subtle myocardial defects before global dysfunction in genetically engineered and rodent surgical injury models. Novel visualization technologies that allow in-depth phenotypic assessment of small animal models, including perfusion imaging and fetal echocardiography, are also discussed. As imaging capabilities continue to improve, murine echocardiography will remain a critical component of the investigator's armamentarium in translating animal data to enhanced clinical treatment of cardiovascular diseases.

Mammalian enabled (Mena) is a critical regulator of cardiac function.

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

Dietary ω3 fatty acids modulate the substrate for post-operative atrial fibrillation in a canine cardiac surgery model.

AIMS: Pre-treatment with dietary ω3 polyunsaturated fatty acids (ω3-PUFA) has been reported to reduce the incidence of new-onset atrial fibrillation (AF) following cardiac surgery. In a canine cardiac surgery model, we evaluated the impact of dietary ω3-PUFA on atrial electrophysiological properties, inflammatory markers, the atrial endothelin-1 (ET-1) system, and the expression and distribution of connexin 43. METHODS AND RESULTS: Adult mongrel dogs received either normal chow (NC, n = 11) or chow supplemented with fish oil (FO, 0.6 g ω3-PUFA/kg/day, n = 9) for 3 weeks before surgery. A left thoracotomy was performed, and the left atrial appendage (LAA) was excised. Atrial pacing/recording wires were placed, and the pericardium/chest was closed. The atrial ratio of ω6/ω3 lipids decreased from 15-20 in NC to 2-3 in FO. FO treatment lowered pre-surgical and stabilized post-surgical arachidonate levels. Peak neutrophil to lymphocyte ratio was lower and decayed faster in FO-treated animals. Extensive inflammatory cell infiltration was present in NC atria, but was reduced in FO-treated dogs. FO-treated animals had lower post-surgical atrial expression of inducible nitric oxide synthase (iNOS) and reduced plasma ET-1. Expression of ET-1 and inositol trisphosphate receptor type-2 proteins in the LAA was also reduced. FO treatment prolonged post-operative atrial effective refractory period, slowed heart rate, and enhanced heart rate variability. Importantly, AF (>30 s) was inducible in four of six NC dogs, but no FO dogs. CONCLUSION: Dietary FO attenuated AF inducibility following cardiac surgery by modulating autonomic tone and heart rate. FO also reduced atrial inflammation, iNOS, and ET-1 expression.

Blockade of atrial-specific K+-currents increases atrial but not ventricular contractility by enhancing reverse mode Na+/Ca2+-exchange.

BACKGROUND: AVE0118 (2'-{[2-(4-Methoxy-phenyl)-acetylamino]-methyl}-biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide) blocks atrial ultrarapid delayed rectifier currents (I(Kur)) and prolongs the atrial action potential (AP) plateau without affecting ventricular repolarisation. In patients with atrial contractile dysfunction due to atrial tachyarrhythmias, this response might increase atrial contractility without risk of ventricular proarrhythmia. This study was designed to evaluate the inotropic mechanisms of AVE0118. METHODS AND RESULTS: In isometrically contracting atrial trabeculae, AVE0118 increased contractile force by 55.4% in sinus rhythm patients (n = 9) and by 107.4% in patients with atrial fibrillation (n = 8). In freshly isolated canine atrial myocytes studied under perforated patch current clamp (37 degrees C), AVE0118 increased myocyte fractional shortening from 3.8+/-0.6 to 9.6+/-0.8% and prolonged action potential duration at 30% repolarisation from 9+/-2 to 102+/-11 ms. Clamping cells to an AP waveform recorded during exposure to AVE0118 produced the same inotropic response as the drug itself. In action potential clamp, peak Ca2+ inward current (I(CaL)) current declined from 5.5+/-1.3 pA/pF during control to 4.1+/-0.7 pA/pF when an AP recorded in the presence of AVE0118 was used as command waveform. However, I(CaL) was more sustained with AVE0118 and the time integral did not change (135+/-37 vs. 173+/-30 pA/pFms, p = ns). Importantly, blockade of reverse mode Na+/Ca2+-exchanger activity with 5 microM KBR7943 or using a Na+-free pipette solution abolished the positive inotropic effect of the AP recorded in the presence of AVE0118. In ventricular myocytes AVE0118 did not elicit a positive inotropic response. CONCLUSIONS: Block of I(Kur) by AVE0118 enhances atrial contractility both in patients with sinus rhythm and atrial fibrillation. The positive inotropic effect is atrial-specific and due to the changes of the action potential configuration which enhances Ca2+ entry via reverse mode Na+/Ca2+ exchange.