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Background/Objectives: Previous trials reported comparable results with PASCAL and earlier MitraClip generations. Limited comparative data exist for more contemporary MitraClip generations, particularly the large MitraClip XT(R/W). We aimed to evaluate acute and 30-day outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) with one of the large devices, either PASCAL P10 or MitraClip XT(R/W) (3rd/4th generation). Methods: A total of 309 PASCAL-treated patients were matched by propensity score to 253 MitraClip-treated patients, resulting in 200 adequately balanced pairs. Procedural, clinical, and echocardiographic outcomes were collected for up to 30 days, including subgroup analysis for mitral regurgitation (MR) etiologies. Results: PASCAL and MitraClip patients were comparable regarding age (80 vs. 79 years), sex (female: 45.5% vs. 50.5%), and MR etiology (degenerative MR: n = 94, functional MR [FMR]: n = 96, mixed MR: n = 10 in each group). Technical success rates were comparable (96.5% vs. 96.0%; p > 0.999). At discharge, the mean gradient was higher (3.3 mmHg vs. 3.0 mmHg; p = 0.038), and the residual mitral valve orifice area was smaller in MitraClip patients (3.0 cm2 vs. 2.3 cm2; p < 0.001). At discharge, the reduction to MR ≤ 2+ was comparable (92.4% vs. 87.8%; p = 0.132). However, reduction to MR ≤ 1+ was more frequently observed in PASCAL patients (67.7% vs. 56.6%; p = 0.029), driven by the FMR subgroup (74.0% vs. 60.0%; p = 0.046). No difference was observed in 30-day mortality (p = 0.204) or reduction in NYHA-FC to ≤II (p > 0.999). Conclusions: Both M-TEER devices exhibited high and comparable rates of technical success and MR reduction to ≤2+. PASCAL may be advantageous in achieving MR reduction to ≤1+ in patients with FMR.
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Introduction: Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO's role in monocyte function. Methods and results: Here, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms. Conclusion: Taken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury.
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Monocitos , Infarto del Miocardio , Peroxidasa , Animales , Infarto del Miocardio/inmunología , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Peroxidasa/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Humanos , Ratones , Masculino , Movimiento Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Femenino , Neutrófilos/inmunología , Neutrófilos/metabolismo , Ratones Noqueados , Receptores CCR2/metabolismo , Persona de Mediana EdadRESUMEN
The aim of this case study was to investigate the effects of an 8-wk combined exercise intervention, consisting of visual-coordinative and high-intensity interval training (HIIT), on the physical and visuomotor-functional capacity, performance, and physiological profile of a moderately active 29-yr-old man diagnosed with choroidal melanoma of the left eye. Data were collected on three occasions: at the initial diagnosis (T0), after hospitalization and radiotherapy treatment (T1), and following the recovery through the exercise intervention (T2), spanning a total of 17 wk. The primary outcome variables consisted of visuomotor and functional tests (VFTs), cardiorespiratory fitness (CRF), and microvascular circulation measured via flicker light-induced dilation (FiD). For visuomotor tests in general, a significant decline was observed between baseline T0 and T1 (by 6%-22%), followed by significant improvements at T2 (by 11%-36%), surpassing the initially observed T0 values. The cardiopulmonary exercise testing (CPET)-derived parameters exhibited a similar pattern, declining from T0 to T1 [by 8%-12% for peak VÌo2, peak power output (PO), and CPET duration, respectively], with a subsequent recovery observed in response to 8 wk of exercise training (T2), resulting in increases of 11%-25% for VÌo2, peak PO, and CPET duration. Interestingly, the dilation of both arteries and veins in response to the FiD stimulus exhibited a twofold increase compared with baseline levels. Our results suggest that the 8-wk exercise intervention improved patients' VFT and CRF profiles and exceeded baseline values. Additional investigation, particularly through randomized controlled trials, is needed to comprehensively explain changes in FiD.NEW & NOTEWORTHY Results presented here suggest that combined visual-coordinative and HIIT training improves the visual-functional capacity, performance, and physiological profile of choroidal melanoma patients during treatment recovery. This case study lays the groundwork for further research concerning exercise therapy in this unique patient population. In addition, further investigation is required to fully comprehend the combined effects of exercise and radiation therapy on vasculature and oxygenation in patients with choroidal melanoma.
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Capacidad Cardiovascular , Melanoma , Neoplasias de la Úvea , Humanos , Masculino , Terapia por Ejercicio/métodos , Melanoma/terapia , Consumo de Oxígeno/fisiología , AdultoRESUMEN
BACKGROUND: We previously reported procedural and 30-day outcomes of a German early multicenter experience with the PASCAL system for severe mitral regurgitation (MR). This study reports 1-year outcomes of mitral valve transcatheter edge-to-edge repair with the PASCAL system according to MR etiology in a large all-comer cohort. METHODS AND RESULTS: Clinical and echocardiographic outcomes up to 1-year were investigated according to MR etiology (degenerative [DMR], functional [FMR], or mixed [MMR]) in the first 282 patients with symptomatic MR 3+/4+ treated with the PASCAL implant at 9 centers in 2019. A total of 282 patients were included (33% DMR, 50% FMR, 17% MMR). At discharge, MR reduction to ≤1+/2+ was achieved in 58%/87% of DMR, in 75%/97% of FMR, and in 78%/98% of patients with MMR (P=0.004). MR reduction to ≤1+/2+ was sustained at 30 days (50%/83% DMR, 67%/97% FMR, 74%/100% MMR) and at 1 year (53%/78% DMR, 75%/97% FMR, 67%/91% MMR) with significant differences between etiologies. DMR patients with residual MR 3+/4+ at 1-year had at least complex valve morphology in 91.7%. Valve-related reintervention was performed in 7.4% DMR, 0.7% FMR, and 0.0% MMR (P=0.010). At 1-year, New York Heart Association Functional Class was significantly improved irrespective of MR etiology (P<0.001). CONCLUSIONS: In this large all-comer cohort, mitral valve transcatheter edge-to-edge repair with the PASCAL system was associated with an acute and sustained MR reduction at 1-year in all causes. However, in patients with DMR, MR reduction was less pronounced, reflecting the high incidence of complex or very complex anatomies being referred for mitral valve transcatheter edge-to-edge repair.
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Procedimientos Quirúrgicos Cardíacos , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/epidemiología , Insuficiencia de la Válvula Mitral/etiología , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Resultado del Tratamiento , Sistema de Registros , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Cateterismo Cardíaco/efectos adversosRESUMEN
Vascular diseases like atherosclerosis and abdominal aortic aneurysm (AAA) are common pathologies in the western world, promoting various potentially fatal conditions. Here, we evaluate high-resolution (HR) ultrasound in mouse models of atherosclerosis and AAA as a useful tool for noninvasive monitoring of early vascular changes in vivo. We used Apolipoprotein E-deficient (ApoE-/-) mice as an atherosclerosis model and induced AAA development by the implementation of Angiotensin II-releasing osmotic minipumps. HR ultrasound of the carotid artery or the abdominal aorta was performed to monitor vascular remodeling in vivo. Images were analyzed by speckle tracking algorithms and correlated to histological analyses and subsequent automated collagen quantification. Consistent changes were observed via ultrasound in both models: Global radial strain (GRS) was notably reduced in the AAA model (23.8 ± 2.8% vs. 12.5 ± 2.5%, p = 0.01) and in the atherosclerotic mice (20.6 ± 1.3% vs. 15.8 ± 0.9%, p = 0.02). In mice with AAA, vessel distensibility was significantly reduced, whereas intima-media thickness was increased in atherosclerotic mice. The area and collagen content of the tunica media were increased in diseased arteries of both models as measured by automated image analysis of Picrosirius Red-stained aortic sections. Correlation analysis revealed a strong correlation of multiple parameters, predicting early vascular damage in HR ultrasound and histological examinations. In conclusion, our findings underscore the potential of HR ultrasound in effectively tracing early alterations in arterial wall properties in murine models of atherosclerosis and AAA.
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Aneurisma de la Aorta Abdominal , Aterosclerosis , Ratones , Animales , Modelos Animales de Enfermedad , Grosor Intima-Media Carotídeo , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/patología , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/patología , Aorta Abdominal/diagnóstico por imagen , Angiotensina II , Colágeno , Ratones Endogámicos C57BLRESUMEN
Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells exhibited increased MPO release upon exposition to DOX. DOX induced extensive nitrosative stress in cardiac tissue alongside with increased carbonylation of sarcomeric proteins in wildtype but not in Mpo-/- mice. Accordingly, co-treatment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with DOX and MPO aggravated loss of hiPSC-CM-contractility compared to DOX treatment alone. DOX-treated animals exhibited pronounced cardiac apoptosis and inflammation, which was attenuated in MPO-deficient animals. Finally, genetic MPO deficiency and pharmacological MPO inhibition protected mice from the development of AICM. The anticancer efficacy of DOX was unaffected by MPO deficiency. Herein we identify MPO as a critical mediator of AICM. We demonstrate that DOX induces cardiac neutrophil infiltration and release of MPO, which directly impairs cardiac contractility through promoting oxidation of sarcomeric proteins, cardiac inflammation and cardiomyocyte apoptosis. MPO thus emerges as a promising pharmacological target for prevention of AICM.
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Cardiomiopatías , Células Madre Pluripotentes Inducidas , Peroxidasa , Animales , Humanos , Ratones , Antraciclinas/toxicidad , Cardiomiopatías/inducido químicamente , Cardiomiopatías/prevención & control , Doxorrubicina/toxicidad , Inflamación , Peroxidasa/genéticaRESUMEN
OBJECTIVE: To compare the measurement of aortic diameters using a novel flow-independent MR-Angiography (3D modified Relaxation-Enhanced Angiography without Contrast and Triggering (modified REACT)) and transthoracic echocardiography (TTE) in Marfan syndrome (MFS) patients. MATERIAL AND METHODS: This retrospective, single-center analysis included 46 examinations of 32 MFS patients (mean age 37.5 ± 11.3 years, 17 women, no prior aortic surgery) who received TTE and 3D modified REACT (ECG- and respiratory-triggering, Compressed SENSE factor 9 for acceleration of image acquisition) of the thoracic aorta. Aortic diameters (sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AoA)) were independently measured by two cardiologists in TTE (leading-edge) and two radiologists in modified REACT (inner-edge, using multiplanar reconstruction). Intraclass correlation coefficient, Bland-Altman analyses, and Pearson's correlation (r) were used to assess agreement between observers and methods. RESULTS: Interobserver correlation at the SV, STJ, and AoA were excellent for both, TTE (ICC = 0.95-0.98) and modified REACT (ICC = 0.99-1.00). There was no significant difference between TTE and modified REACT for diameters measured at the SV (39.24 ± 3.24 mm vs. 39.63 ± 3.76 mm; p = 0.26; r = 0.78) and the STJ (35.16 ± 4.47 mm vs. 35.37 ± 4.74 mm; p = 0.552; r = 0.87). AoA diameters determined by TTE were larger than in modified REACT (34.29 ± 5.31 mm vs. 30.65 ± 5.64 mm; p < 0.01; r = 0.74). The mean scan time of modified REACT was 05:06 min ± 02:47 min, depending on the patient's breathing frequency and heart rate. CONCLUSIONS: Both TTE and modified REACT showed a strong correlation for all aortic levels; however, at the AoA, diameters were larger using TTE, mostly due to the limited field of view of the latter with measurements being closer to the aortic valve. Given the excellent interobserver correlation and the strong agreement with TTE, modified REACT represents an attractive method to depict the thoracic aorta in MFS patients.
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Aorta Torácica , Síndrome de Marfan , Humanos , Femenino , Adulto , Persona de Mediana Edad , Aorta Torácica/diagnóstico por imagen , Síndrome de Marfan/diagnóstico por imagen , Estudios Retrospectivos , Ecocardiografía/métodos , Angiografía por Resonancia Magnética/métodos , Reproducibilidad de los ResultadosRESUMEN
Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence of ischemic cardiomyopathy, making it a major reason for hospitalization in the western world. The inflammatory response in the ischemic myocardium determines the extent of structural remodeling and functional deterioration, with neutrophils (PMN) being a key modulator of the propagation and resolution of inflammation. The heme enzyme myeloperoxidase (MPO) is abundantly expressed in PMN and is an important mediator of their inflammatory capacities. Here, we examine the effects of PMN reduction, MPO deficiency and MPO inhibition in two murine models of MI. Reduction in PMN count resulted in less scar formation and improved cardiac function. Similar results were obtained in genetically MPO deficient mice, suggesting that MPO is a critical factor in PMN-mediated cardiac remodeling. To test our findings in a therapeutic approach, we orally administered the MPO inhibitor AZM198 in the context of MI and could demonstrate improved cardiac function and reduced structural remodeling. Therefore, MPO appears to be a favorable pharmacological target for the prevention of long-term morbidity after MI.