RESUMEN
New mechanistic insight into how the kidney responds to cardiac injury during acute myocardial infarction (AMI) is required. We hypothesized that AMI promotes inflammation and matrix metalloproteinase-9 (MMP9) activity in the kidney and studied the effect of initiating an Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO) before coronary reperfusion during AMI. Adult male swine were subjected to coronary occlusion and either reperfusion (ischemia-reperfusion; IR) or support with either Impella or VA-ECMO before reperfusion. IR and ECMO increased while Impella reduced levels of MMP-9 in the myocardial infarct zone, circulation, and renal cortex. Compared to IR, Impella reduced myocardial infarct size and urinary KIM-1 levels, but VA-ECMO did not. IR and VA-ECMO increased pro-fibrogenic signaling via transforming growth factor-beta and endoglin in the renal cortex, but Impella did not. These findings identify that AMI increases inflammatory activity in the kidney, which may be attenuated by Impella support.
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Oxigenación por Membrana Extracorpórea , Corazón Auxiliar , Infarto del Miocardio , Animales , Masculino , Metaloproteinasa 9 de la Matriz , Choque Cardiogénico , PorcinosRESUMEN
Background: We describe the association between longitudinal hemodynamic changes and clinical outcomes in patients with cardiogenic shock (CS) receiving acute mechanical circulatory support devices (AMCS) at a single center. We hypothesized that improved right atrial pressure is associated with better survival in CS. Methods: Retrospective analysis of patients from Tufts Medical Center that received AMCS for CS. Baseline characteristics and invasive hemodynamics were collected, analyzed, and correlated against outcomes. Hemodynamics were recorded at different time intervals during index admission [pre-AMCS, 24 h after AMCS (post AMCS), and last available set of hemodynamics (final-AMCS)]. Logistic regression was performed to determine variables associated with in-hospital mortality. Results: A total of 76 patients had longitudinal hemodynamics available. In hospital mortality occurred in 46% of the cohort. Mean baseline right atrial pressure (RAP) was significantly higher among non-survivors vs. survivors (19.5+6.6 vs. 16.4+5.3 mmHg). Change in right atrial pressure from baseline to before device removal (ΔRA:final AMCS-pre AMCS) was significantly different between survivors and non survivors (-6.5 ± 6.9 mmHg vs. -2.5 ± 6.2 mmHg p = 0.03). Unadjusted logistic regression revealed baseline RAP (OR: 1.1 95% CI: 1.0-1.2), 24 h post device implant RAP (OR: 1.3 95% CI: 1.1-1.4), and final RAP (OR: 1.3 95% CI: 1.1-1.5) to be significant predictors of in-hospital mortality. In a multivariate logistic regression baseline RAP was no longer significantly associated with mortality in the overall cohort, while 24 h (OR: 1.26 95% CI: 1.1-1.5) and final RAP (OR: 1.3 95% CI: 1.1-1.6) remained statistically significant. Conclusion: We report a novel retrospective analysis of hemodynamic changes in patients with CS receiving AMCS. Our findings identify the potential importance of venous congestion as a prognostic marker of mortality. Furthermore, early decongestion or reduced RA pressure is associated with better survival in these critically ill CS patients. These observations suggest the need for further study in larger retrospective and prospective cohorts of patients with varying degrees of CS severity.
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BACKGROUND: Risk stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) stages as an approach to identify patients at risk for in-hospital mortality remains under investigation. We studied the utility of the SCAI stages and further explored the impact of hemodynamic congestion on clinical outcomes. METHODS: The CS Working Group registry includes patients with CS from 8 medical centers enrolled between 2016 and 2019. Patients were classified by the maximum SCAI stage (B-E) reached during their hospital stay according to drug and device utilization. In-hospital mortality was evaluated for association with SCAI stages and hemodynamic congestion. RESULTS: Of the 1414 patients with CS, the majority were due to decompensated heart failure (50%) or myocardial infarction (MI; 35%). In-hospital mortality was 31% for the total cohort, but higher among patients with MI (41% versus 26%, MI versus heart failure, P<0.0001). Risk for in-hospital mortality was associated with increasing SCAI stage (odds ratio [95% CI], 3.25 [2.63-4.02]) in both MI and heart failure cohorts. Hemodynamic data was available in 1116 (79%) patients. Elevated biventricular filling pressures were common among patients with CS, and right atrial pressure was associated with increased mortality and higher SCAI Stage. CONCLUSIONS: Our findings support an association between the proposed SCAI staging system and in-hospital mortality among patient with heart failure and MI. We further identify that venous congestion is common and identifies patients with CS at high risk for in-hospital mortality. These findings provide may inform future management protocols and clinical studies.
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Hemodinámica , Mortalidad Hospitalaria , Choque Cardiogénico/clasificación , Choque Cardiogénico/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Choque Cardiogénico/fisiopatología , Estados UnidosRESUMEN
Congestion is a major determinant of clinical outcomes in heart failure (HF). We compared the acute hemodynamic effects of occlusion of the superior (SVC) versus the inferior vena cava (IVC) and tested a novel SVC occlusion system in swine models of HF. IVC occlusion acutely reduced left ventricular (LV) systolic and diastolic pressures, LV volumes, cardiac output (CO), and mean arterial pressure (MAP). SVC occlusion reduced LV diastolic pressure and volumes without affecting CO or MAP. The preCARDIA system is a balloon occlusion catheter and pump console which enables controlled delivery and removal of fluid into the occlusion balloon. At 6, 12, and 18 h, SVC therapy with the system provided a sustained reduction in cardiac filling pressures with stable CO and MAP. Intermittent SVC occlusion is a novel approach to reduce biventricular filling pressures in HF. The VENUS-HF trial will test the safety and feasibility of SVC therapy in HF.
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Oclusión con Balón , Insuficiencia Cardíaca/terapia , Vena Cava Superior/fisiopatología , Función Ventricular Izquierda , Presión Ventricular , Animales , Presión Arterial , Gasto Cardíaco , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Prueba de Estudio Conceptual , Sus scrofa , Factores de Tiempo , Presión VenosaRESUMEN
Background Unloading the left ventricle and delaying reperfusion reduces infarct size in preclinical models of acute myocardial infarction. We hypothesized that a potential explanation for this effect is that left ventricular (LV) unloading before reperfusion increases collateral blood flow to ischemic myocardium. Methods and Results Acute myocardial infarction was induced by balloon occlusion of the left anterior descending artery for 120 minutes in adult swine, followed by reperfusion for 180 minutes. After 90 minutes of occlusion, animals were assigned to 30 minutes of continued occlusion (n=6) or to 30 minutes of support with either an Impella CP (n=4) or venoarterial extracorporeal membrane oxygenation (n=5) with persistent occlusion. The primary end point was measures of microcirculatory blood flow including the collateral flow index (CFI) during left anterior descending artery occlusion as (Pw-RA)/(Pa-RA), where Pa, Pw, and RA are aortic, coronary wedge, and right atrial pressure, respectively. Infarct size was quantified using triphenyltetrazolium chloride. Compared with continued occlusion, Impella, not venoarterial extracorporeal membrane oxygenation, reduced infarct size relative to the area at risk. Before reperfusion, Impella reduced LV stroke work by 25% and increased the CFI by 75%, but venoarterial extracorporeal membrane oxygenation did not. Among all groups, the change in CFI between 90 and 120 minutes correlated inversely with the change in LV stroke work (r2=0.44, P=0.01) and infarct size (r2=0.41, P=0.02). Conclusions We report for the first time that 30 minutes of LV unloading during coronary occlusion increases the CFI, which correlates inversely with LV stroke work and infarct size. Venoarterial extracorporeal membrane oxygenation failed to increase the CFI and did not reduce infarct size.
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Circulación Asistida/métodos , Circulación Colateral , Circulación Coronaria , Oxigenación por Membrana Extracorpórea/métodos , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Reperfusión Miocárdica , Miocardio/patología , Animales , Cateterismo Cardíaco , Cateterismo de Swan-Ganz , Vasos Coronarios , Corazón Auxiliar , Masculino , Microcirculación , Daño por Reperfusión Miocárdica/terapia , Presión , Índice de Severidad de la Enfermedad , Sus scrofa , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Acutely decompensated heart failure remains a major clinical problem. Volume overload promotes cardiac and renal dysfunction and is associated with increased morbidity and mortality in heart failure. We hypothesized that transient occlusion of the superior vena cava (SVC) will reduce cardiac filling pressures without reducing cardiac output or systemic blood pressure. The objective of this proof of concept study was to provide initial evidence of safety and feasibility of transient SVC occlusion in patients with acutely decompensated heart failure and reduced ejection fraction. METHODS AND RESULTS: In eight patients with systolic heart failure, SVC occlusion was performed using a commercially available occlusion balloon. Five minutes of SVC occlusion reduced biventricular filling pressures without decreasing systemic blood pressure or total cardiac output. In three of the eight patients, a second 10-minutes occlusion had similar hemodynamic effects. SVC occlusion was well-tolerated without development of new symptoms, new neurologic deficits, or any adverse events including stroke, heart attack, or reported SVC injury or thrombosis at 7 days of follow up. CONCLUSION: We report the first clinical experience with transient SVC occlusion as a potentially new therapeutic approach to rapidly reduce cardiac filling pressures in heart failure. No prohibitive safety signal was identified and further testing to establish the clinical utility of transient SVC occlusion for acute decompensated heart failure is justified.
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Oclusión con Balón , Insuficiencia Cardíaca/terapia , Vena Cava Superior/fisiopatología , Función Ventricular Izquierda , Función Ventricular Derecha , Presión Ventricular , Anciano , Oclusión con Balón/efectos adversos , Oclusión con Balón/instrumentación , Estudios de Factibilidad , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Recuperación de la Función , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Dispositivos de Acceso Vascular , Vena Cava Superior/diagnóstico por imagenRESUMEN
BACKGROUND: Acute heart failure refractory to medical therapy is a major cause of morbidity and mortality. The Aortix device (Procyrion Inc) is a percutaneously delivered entrainment pump positioned in the descending aorta. METHODS AND RESULTS: Using the newest generation Aortix device in 8 adult male Yorkshire swine, we tested the hypothesis that positioning in the abdominal aorta may provide superior hemodynamic effects than thoracic positioning in a swine model of postinfarct left ventricular injury.Abdominal activation generated significantly larger transaortic gradients (proximal minus distal mean aortic pressures) than thoracic positioning at all pump speeds. Compared with baseline values, activation in the abdominal, not thoracic, position significantly increased cardiac output, reduced arterial elastance, and systemic vascular resistance at low speeds. Compared with baseline values, abdominal activation also increased transpulmonary pressure gradients at medium and high speed, which was driven by trends toward higher mean pulmonary artery pressure and lower pulmonary capillary wedge pressure. CONCLUSIONS: This is the first report to determine that in contrast to thoracic positioning, abdominal positioning of the newest generation Aortix device reduces left ventricular afterload and increases cardiac output at low speeds. These findings have potentially important implications for the design of early clinical studies by suggesting that device position and speed are major determinants of improved hemodynamic efficacy.
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Aorta Abdominal/fisiopatología , Gasto Cardíaco , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Implantación de Prótesis/métodos , Función Ventricular Izquierda , Animales , Aorta Torácica/fisiopatología , Presión Arterial , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Masculino , Diseño de Prótesis , Recuperación de la Función , Sus scrofa , Factores de TiempoRESUMEN
BACKGROUND: Myocarditis complicated by cardiogenic shock remains a complex problem. The use of acute mechanical circulatory support devices for cardiogenic shock is growing. We explored the utility of Impella transvalvular microaxial flow catheters in the setting of myocarditis with cardiogenic shock. METHODS AND RESULTS: We retrospectively analyzed data from 21 sites within the cVAD registry, an ongoing multicenter voluntary registry at sites in North America and Europe that have used Impella in patients with myocarditis. Myocarditis was defined by endomyocardial biopsy (nâ¯=â¯11) or by clinical history without angiographic evidence of coronary disease (nâ¯=â¯23). A total of 34 patients received an Impella 2.5, CP, 5.0, or RP device for cardiogenic shock complicating myocarditis. Baseline characteristics included age 42 ± 17 years, left ventricular ejection fraction (LVEF) 18% ± 10%, cardiac index 1.82 ± 0.46 L·min-1·m-2, pulmonary capillary wedge pressure 25 ± 7 mm Hg, and lactate 27 ± 31 mg/dL. Before Impella placement, 32% (nâ¯=â¯11) of patients required intra-aortic balloon pump. Mean duration of Impella support was 91 ± 74 hours; 21 of 34 patients (62%) survived the index hospitalization and were discharged with an improved mean LVEF of 37.32% ± 20.31% (Pâ¯=â¯.001); 15 patients recovered with successful support, 5 patients were transferred to another hospital on initial Impella support, 1 patient underwent orthotopic heart transplantation. Ten patients required transition to another mechanical circulatory support device. CONCLUSIONS: This is the largest analysis of Impella-supported myocarditis cases to date. The use of Impella appears to be safe and effective in the settings of myocarditis complicated by cardiogenic shock.