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von Willebrand Factor (VWF) destruction is common with current heart pumps. This study evaluates VWF activity with ModulHeart, a novel device using 3 micropumps in parallel. In model 1, ModulHeart was compared with Impella devices in vitro. In model 2, 3 healthy swine received ModulHeart. Model 3 includes VWF data from patients who underwent protected percutaneous coronary intervention with ModulHeart. In models 1, 2, and 3, ModulHeart resulted in preservation of VWF, whereas there was a 27% and 19% reduction in VWF activity with the Impella CP and 5.0, respectively. ModulHeart features a unique design and demonstrated preservation of VWF activity.
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BACKGROUND: ModulHeart (Puzzle Medical Devices Inc) is a novel percutaneous flow entrainment pump anchored in the descending aorta. The current study evaluates the hemodynamic effect of ModulHeart support and its impact on cerebral, myocardial, and renal blood flow. METHODS: ModulHeart was implanted in the descending aorta of four healthy calves. A ramp protocol (2000 RPM increments) was performed with the pump operating at five different speeds from 14 000 to 22 000 RPM. For each speed, pressures proximal and distal to the pump, and right heart catheterization measurements were recorded. Stable-isotope labeled microspheres were injected in the left ventricle to evaluate organ perfusion. RESULTS: Thermodilution cardiac output increased by 23% at 22 000 RPM. Greater pump speeds resulted in greater pump gradients, up to 10 mm Hg in mean arterial pressure at 22 000 RPM, without significant reduction of proximal perfusion pressures. Arterial pulse pressure remained stable at all speeds. ModulHeart was not associated with a reduction in cerebral or myocardial blood flow at any speed. Renal cortical and medullary blood flow increased by up to 50% and 40%, respectively. CONCLUSION: The ModulHeart device implanted in the descending aorta of healthy calves resulted in significant arterial pressure gradients and preserved pulse pressure. Greater pump speeds translated into greater increases in renal blood flow, with no decrease in cerebral or myocardial perfusion.
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Insuficiência Cardíaca , Coração Auxiliar , Animais , Bovinos , Humanos , Insuficiência Cardíaca/terapia , Hemodinâmica/fisiologia , Pressão Sanguínea , Miocárdio , Ventrículos do CoraçãoRESUMO
OBJECTIVES: The INSPIRIS aortic valve combines the RESILIA proprietary tissue preservation process and an expandable stent frame to benefit future transcatheter valve-in-valve procedures. As the INSPIRIS valve became commercially available in 2017, mid-term outcome reports are scarce. We aimed to evaluate mid-term safety and echocardiographic performance of the INSPIRIS valve in comparison to its predecessor, the Carpentier Edwards Perimount Magna Ease (ME). METHODS: This study was a retrospective single-centre study. Clinical results included early postoperative outcomes, mid-term mortality and readmission for cardiovascular cause or stroke. Echocardiographic follow-up (FU) was performed at discharge and 1-3, 6, 12 and 24 months. Clinical end point analyses were accomplished with a propensity score matching analysis and FU echocardiographic data comparisons using pairwise analyses and linear mixed-effect models. RESULTS: We included 953 patients who received an INSPIRIS (n = 488) or ME (n = 463) bioprosthesis between January 2018 and July 2021. In the matched population (n = 217 per group), no significant difference in short-term outcomes was observed, survival was similar at 30 months (INSPIRIS: 94% vs ME: 91%, P = 0.89), but freedom from readmission was higher in the INSPIRIS group (94% vs 86%, P = 0.014). INSPIRIS valves had a lower gradient at discharge (â¼10 vs 14 mmHg, P < 0.001), 1-3 months (â¼10 vs 12 mmHg, P < 0.001) and 24 months (â¼11 vs 17 mmHg, P < 0.001) in paired analyses and significantly lower evolution of mean transvalvular gradients compared to ME. CONCLUSIONS: This study represents the largest comparative evaluation of the INSPIRIS to the ME valves, which demonstrated safe clinical outcomes and favourable haemodynamic performance at 2 years. Long-term FU is underway.
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Animal studies are often required to evaluate new cardiovascular medical devices before they reach the market. Moreover, first-generation novel devices including aortic endovascular prostheses and circulatory support devices are often larger than later iterations or tested in a limited range of sizes. One of the challenges in evaluating these devices is finding a model that is both accessible and anatomically similar to humans, as there is a paucity of data on vascular dimensions in large animals. We set out to complete a comprehensive review of available reports on vascular dimensions in swine, ovine, and bovine models, with a particular focus on the descending aorta and ilio-femoral arteries. We searched Embase and MEDLINE databases for reports of descending aorta and peripheral vascular dimension in large animal models. Data from swine, ovine, and bovine models were separated by weight into 3 categories: 40 to 60 kg, 61 to 80 kg, and >80 kg. We also incorporate our computed tomography angiography data from 4 large sheep and 9 calves into this review. Swine, sheep, and calf >80 kg may serve as the best models to maximize aortic diameter resemblance to humans. If device implantation can be achieved in aortas of smaller dimensions, care should be taken to ensure access site suitability such as the common femoral artery in these smaller animals.
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Angiografia , Aorta , Humanos , Animais , Bovinos , Ovinos , Suínos , Angiografia por Tomografia Computadorizada , Modelos AnimaisRESUMO
BACKGROUND: P-glycoprotein (P-gp), a member of the ATP Binding Cassette B1 subfamily (ABCB1), confers resistance to clinically relevant anticancer drugs and targeted chemotherapeutics. However, paradoxically P-glycoprotein overexpressing drug resistant cells are "collaterally sensitive" to non-toxic drugs that stimulate its ATPase activity. METHODS: Cell viability assays were used to determine the effect of low concentrations of tamoxifen on the proliferation of multidrug resistant cells (CHORC5 and MDA-Doxo400), expressing P-gp, their parental cell lines (AuxB1 and MDA-MB-231) or P-gp-CRISPR knockout clones of AuxB1 and CHORC5 cells. Western blot analysis was used to estimate P-gp expression in different cell lines. Apoptosis of tamoxifen-induced cell death was estimated by flow cytometry using Annexin-V-FITC stained cells. Oxidative stress of tamoxifen treated cells was determined by measuring levels of reactive oxygen species and reduced thiols using cell-permeant 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and 5,5-dithio-bis-(2-nitrobenzoic acid) DTNB, respectively. RESULTS: In this report, we show that P-gp-expressing drug resistant cells (CHORC5 and MDA-Doxo400) are collaterally sensitive to the anti-estrogen tamoxifen or its metabolite (4-hydroxy-tamoxifen). Moreover, P-gp-knockout clones of CHORC5 cells display complete reversal of collateral sensitivity to tamoxifen. Drug resistant cells exposed to low concentrations of tamoxifen show significant rise in reactive oxygen species, drop of reduced cellular thiols and increased apoptosis. Consistent with the latter, CHORC5 cells expressing high levels of human Bcl-2 (CHORC5-Bcl-2) show significant resistance to tamoxifen. In addition, the presence of the antioxidant N-acetylcysteine or P-gp ATPase inhibitor, PSC-833, reverse the collateral sensitivity of resistant cells to tamoxifen. By contrast, the presence of rotenone (specific inhibitor of mitochondria complex I) synergizes with tamoxifen. CONCLUSION: This study demonstrates the use of tamoxifen as collateral sensitivity drug that can preferentially target multidrug resistant cells expressing P-gp at clinically achievable concentrations. Given the widespread use of tamoxifen in the treatment of estrogen receptor-positive breast cancers, this property of tamoxifen may have clinical applications in treatment of P-gp-positive drug resistant breast tumors.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Resistência a Múltiplos Medicamentos , Humanos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Tamoxifeno/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adenosina Trifosfatases/metabolismo , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular TumoralRESUMO
Congestion is the most common manifestation of acute decompensated heart failure (ADHF). Residual congestion despite initial medical therapy is common and is recognized to be associated with worse outcomes; however, there are currently no standardized definition regarding decongestion end point. In the second part of this 2-part review, we provide a critical appraisal of decongestion definitions previously used in ADHF studies, review alternative metrics to define severity of volume overload, and propose a more granular 4-class congestion grading scheme and decongestion end point definitions that could potentially be included in future ADHF trials and consensus definitions.
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Despite recent advances in the treatment of patients with chronic heart failure, acute decompensated heart failure remains associated with significant mortality and morbidity because many novel therapies have failed to demonstrate meaningful benefit. Persistent congestion in the setting of escalating diuretic therapy has been repeatedly shown to be a marker of poor prognosis and is currently being targeted by various emerging device-based therapies. Because these therapies inherently carry procedural risk, patient selection is key in the future trial design. However, it remains unclear which patients are at a higher risk of residual congestion or adverse outcomes despite maximally tolerated decongestive therapy. In the first part of this 2-part review, we aimed to outline patient risk factors and summarize current evidence for early recognition of high-risk profile for residual congestion and adverse outcomes. These factors are classified as relating to the following: (1) previous clinical course, (2) severity of congestion, (3) diuretic response, and (4) degree of renal impairment. We also aimed to provide an overview of key inclusion criteria in recent acute decompensated heart failure trials and investigational device studies and propose potential criteria for selection of high-risk patients in future trials.
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Venous anomalies are typically asymptomatic and may be discovered unexpectedly at the time of implantation of a cardiac implantable electronic device. We report a case of leadless pacemaker implantation in a patient with hypoplasia of the left brachiocephalic vein who had previously undergone multiple interventions for relapsing right-sided breast cancer. The prevalence and etiology of this anatomic variant remain unknown. However, awareness of its existence may prevent complications during left-sided interventions. such as placement of a central venous line or a cardiac implantable electronic device. Alternative diagnostics and implantation strategies are discussed.
Les anomalies veineuses sont généralement asymptomatiques et peuvent être découvertes de façon inattendue au moment de l'implantation d'un dispositif cardiaque électronique. Nous présentons un cas d'implantation d'un stimulateur cardiaque sans sonde chez une patiente atteinte d'hypoplasie de la veine brachiocéphalique gauche qui avait déjà subi de nombreuses interventions en raison de la rechute d'un cancer du sein du côté droit. On ignore la prévalence et l'étiologie de cette variante anatomique. Toutefois, la sensibilisation à son existence peut permettre de prévenir les complications durant les interventions du côté gauche telles que la pose d'un cathéter veineux central ou l'implantation d'un dispositif cardiaque électronique. Les autres diagnostics et stratégies d'implantation font l'objet de discussions.
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Oxigenação por Membrana Extracorpórea , Embolia Pulmonar , Oxigenação por Membrana Extracorpórea/efeitos adversos , Fibrinólise , Humanos , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Terapia Trombolítica/efeitos adversos , Resultado do TratamentoRESUMO
Background: ModulHeart (Puzzle Medical Devices Inc) is a modular device providing hemodynamic support through 3 endovascular pumps inserted in series and assembled in parallel into a self-expandable anchor implanted in the descending aorta. The current study evaluates the feasibility and safety of cardiorenal support with ModulHeart among patients undergoing high-risk percutaneous coronary intervention (PCI). Methods: This study was a prospective, single-center, first-in-human study. The primary end point was procedural success, defined as successful delivery, function, and removal of the ModulHeart device. Secondary end points included pump hemodynamics, cardiac hemodynamics, and urine output. Results: On June 28 and 29, 2022, 4 patients were enrolled and underwent high-risk PCI with ModulHeart implanted via transfemoral approach. All 4 patients achieved procedural success. The mean delivery time was 8 minutes, the mean support time was 49 minutes, and the mean pump removal time was 7 minutes. The mean pressure gradient across the pump was 5 ± 2 mm Hg. Under ModulHeart support, cardiac index increased by 25%, central venous pressure decreased by 37%, and left ventricular end-diastolic pressure decreased by 78%. Urine output increased by â¼9-fold after 15 minutes of support. No device malfunction or procedural or device-related adverse events occurred. There was no evidence of pump thrombosis. All 4 patients were alive at 30 days. Conclusions: This first-in-human study demonstrated the feasibility and safety of cardiorenal support with ModulHeart among patients undergoing high-risk PCI. ModulHeart demonstrated significant improvement in cardiac output, left ventricular end-diastolic pressure, and urine output. Future studies are planned to assess outcomes associated with ModulHeart support in patients with heart failure.
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BACKGROUND: In Canada, tissue distribution is managed by provincial entities. In 2014, Hema-Quebec established a cryopreserved vascular tissue bank accessible to all Canadian hospitals. The objectives of this report were to review the first 5 years of activity of Hema-Quebec's vascular bank and to briefly assess the competitiveness of its products. METHODS: Deceased donors, ages 15 to 60, were screened for common blood-borne diseases. Grafts were treated in a triple-antibiotic solution at 35°C before preservation at -100°C. Hema-Quebec's vascular graft records were analyzed from 2014 to 2019 inclusively. RESULTS: The average donor age was 35 years old and 78% of donors were men. Overall, 63% of harvested grafts cleared the quality management system. Positive microbial cultures and morphologic defects were the major reasons for graft discard. As such, a total of 60 grafts were delivered between 2016 and 2019 to 8 hospital centers. Moreover, the bank achieved a mean activity increase of 55% per year and Hema-Quebec's homografts were 48% less costly compared with similar homographs from for-profit organizations. CONCLUSIONS: Our findings demonstrate that Hema-Quebec has established a viable cryopreserved vascular tissue bank with steady increase in activity and an acceptable graft discard rates and pricing. Based on our findings, we recommend that efforts should be directed to expand the tissue bank graft distribution outside the province of Quebec.
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Antibacterianos/uso terapêutico , Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Vasos Sanguíneos/transplante , Criopreservação , Soluções para Preservação de Órgãos/uso terapêutico , Bancos de Tecidos , Coleta de Tecidos e Órgãos , Adolescente , Adulto , Antibacterianos/efeitos adversos , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/microbiologia , Seleção do Doador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos/efeitos adversos , Avaliação de Programas e Projetos de Saúde , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is one of the most common genetic cardiac diseases and encompasses an array of clinical presentations. Little is known about the impact of genetic background on outcomes after septal myectomy (SM). The aim of this study was to evaluate the effect of specific genetic mutations on midterm outcomes in adults undergoing SM for HOCM. METHODS: From 2003 to 2020, a total of 59 patients (male = 66%, mean age = 52 ± 13) underwent SM after a preoperative genetic test. Patients were divided into two groups according to their test result (positive or negative). Preoperative echocardiograms were examined to identify phenotypical characteristics of each mutation. RESULTS: A total of thirty-one patients (53%) had a positive genetic test. MYBPC3 was the most common mutation (15/31 patients). Four different phenotypes were identified on preoperative echocardiograms. Overall, Type 1 phenotype was the most common (37% of the cohort). Type 3 was found exclusively in patients with a positive genetic test. Following SM, none of the patients required a redo myectomy or septal ablation. At 10 years, the survival was 97 ± 3% and 100% in patients with a positive and negative genetic test (p = .33), respectively. CONCLUSION: Although our results suggest that the multiple gene mutations present with different characteristics and phenotypes, midterm results of SM appear to be good regardless of genetic mutation presence.