Improvement of renal function after transcatheter aortic valve replacement in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease is commonly found in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and has marked impact in their prognosis. It has been shown however that TAVR may improve renal function by alleviating the hemodynamic barrier imposed by AS. Nevertheless, the predictors of and clinical consequences of renal function improvement are not well established. Our aim was to assess the predictors of improvement of renal function after TAVR. METHODS: The present work is an analysis of the Brazilian Registry of TAVR, a national non-randomized prospective study with 22 Brazilian centers. Patients with baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) were stratified according to renal function after TAVR: increase >10% in eGFR were classified as TAVR induced renal function improvement (TIRFI); decrease > 10% in eGFR were classified as acute kidney injury (AKI) and stable renal function (neither criteria). RESULTS: A total of 819 consecutive patients with symptomatic severe AS were included. Of these, baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) was present in 577 (70%) patients. Considering variance in renal function between baseline and at discharge after TAVR procedure, TIRFI was seen in 197 (34.1%) patients, AKI in 203 (35.2%), and stable renal function in 177 (30.7%). The independent predictors of TIRFI were: absence of coronary artery disease (OR: 0.69; 95% CI 0.48-0.98; P = 0.039) and lower baseline eGFR (OR: 0.98; 95% CI 0.97-1.00; P = 0.039). There was no significant difference in 30-day and 1-year all-cause mortality between patients with stable renal function or TIRFI. Nonetheless, individuals that had AKI after TAVR presented higher mortality compared with TIRFI and stable renal function groups (29.3% vs. 15.4% vs. 9.5%, respectively; p < 0.001). CONCLUSIONS: TIRFI was frequently found among baseline impaired renal function individuals but was not associated with improved 1-year outcomes.

Late clinical outcomes of myocardial hybrid revascularization versus coronary artery bypass grafting for complex triple-vessel disease: Long-term follow-up of the randomized MERGING clinical trial.

OBJECTIVES: This article aimed to compare the outcomes after hybrid revascularization with conventional coronary artery bypass grafting (CABG) surgery. BACKGROUND: The concept of hybrid coronary revascularization combines the advantages of CABG and percutaneous coronary intervention to improve the treatment of patients with complex multivessel disease. METHODS: The Myocardial hybrid revascularization versus coronary artERy bypass GraftING for complex triple-vessel disease-MERGING study is a pilot randomized trial that allocated 60 patients with complex triple-vessel disease to treatment with hybrid revascularization or conventional CABG (2:1 ratio). The primary outcome was the composite of all-cause death, myocardial infarction, stroke, or unplanned repeat revascularization at 2 years. RESULTS: Clinical and anatomical characteristics were similar between groups. After a mean follow-up of 802 ± 500 days, the primary endpoint rate was 19.3% in the hybrid arm and 5.9% in the CABG arm (p = NS). The incidence of unplanned revascularization increased over time in both groups, reaching 14.5 versus 5.9% in the hybrid and in the CABG groups, respectively (p = .4). Of note, in the hybrid group, there were no reinterventions driven by the occurrence of stent restenosis. CONCLUSIONS: Hybrid myocardial was feasible but associated with increasing rates of major adverse cardiovascular events during 2 years of clinical follow-up, while the control group treated with conventional surgery presented with low rates of complications during the same period. In conclusion, before more definitive data arise, hybrid revascularization should be applied with careful attention in practice, following a selective case-by-case indication.

Impacto del daño renal agudo en el seguimiento a corto y a largo plazo tras el implante percutáneo de válvula aórtica / Impact of acute kidney injury on short- and long-term outcomes after transcatheter aortic valve implantation

Introducción y objetivos: El daño renal agudo (DRA) ocurre con frecuencia tras el implante percutáneo de válvula aórtica (TAVI) y se asocia con una mayor mortalidad. Sin embargo, el impacto del DRA en la evolución a largo plazo continúa siendo controvertida. Por dicho motivo se evalúa el impacto del DRA el resultado a corto y largo plazo tras el TAVI usando los criterios Valve Academic Research Consortium 2. Métodos: Se incluyeron 794 pacientes consecutivos con estenosis aórtica grave en un registro multicéntrico brasileño. Para la identificación de los predictores de DRA se utilizó el análisis de regresión logística. La supervivencia a 4 años se determinó mediante las curvas de Kaplan-Meier y para determinar el impacto del DRA en la mortalidad entre los supervivientes a 12 meses se usó un análisis de punto de referencia ajustado. Resultados: La incidencia de DRA tras el TAVI fue del 18%. Los predictores independientes de DRA fueron: edad, diabetes mellitus, hemorragia mayor o amenazante para la vida y la malaposición valvular. El DRA se asoció independientemente con un riesgo mayor de muerte total (HR ajustada = 2,8; IC95%, 2,0-3,9; p < 0,001) y cardiovascular (HR ajustada = 2,9; IC95%, 1,9-4,4; p < 0,001) durante el periodo de seguimiento completo. Sin embargo, cuando se consideró solo los supervivientes a 12 meses, no hubo diferencias en ambos objetivos clínicos (HR ajustada = 1,2; IC95%, 0,5-2,4; p = 0,71, y HR = 0,7; IC95%, 0,2-2,1; p = 0,57, respectivamente). Conclusiones: El DRA es una complicación frecuente tras el TAVI. La edad avanzada, la diabetes, la hemorragia mayor o amenazante para la vida y la malaposición valvular eran factores predictivos de DRA. El DRA se asoció con el pronóstico a corto y largo plazo, sin embargo, el impacto del DRA sobre la mortalidad se limitó al primer año tras el TAVI

Introduction and objectives: Acute kidney injury (AKI) is frequently observed after transcatheter aortic valve implantation (TAVI) and is associated with higher mortality. However, the impact of AKI on long-term outcomes remains controversial. Therefore, we sought to evaluate the impact of AKI on short- and long-term outcomes following TAVI using the Valve Academic Research Consortium 2 criteria. Methods: Consecutive patients (n = 794) with severe aortic stenosis who underwent TAVI were included in a multicenter Brazilian registry. Logistic regression analysis was used to identify predictors of AKI. Four-year outcomes were determined as Kaplan-Meier survival curves, and an adjusted landmark analysis was used to test the impact of AKI on mortality among survivors at 12 months. Results: The incidence of AKI after TAVI was 18%. Independent predictors of AKI were age, diabetes mellitus, major or life-threatening bleeding and valve malpositioning. Acute kidney injury was independently associated with higher risk of all-cause death (adjusted HR, 2.8; 95%CI, 2.0-3.9; P < .001) and cardiovascular mortality (adjusted HR, 2.9; 95%CI, 1.9-4.4; P < .001) over the entire follow-up period. However, when considering only survivors at 12 months, there was no difference in both clinical endpoints (adjusted HR, 1.2; 95%CI, 0.5-2.4; P = .71, and HR, 0.7; 95%CI, 0.2-2.1; P = .57, respectively). Conclusions: Acute kidney injury is a frequent complication after TAVI. Older age, diabetes, major or life-threatening bleeding, and valve malpositioning were independent predictors of AKI. Acute kidney injury is associated with worse short- and long-term outcomes. However, the major impact of AKI on mortality is limited to the first year after TAVI

Impact of Acute Kidney Injury on Short- and Long-term Outcomes After Transcatheter Aortic Valve Implantation.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is frequently observed after transcatheter aortic valve implantation (TAVI) and is associated with higher mortality. However, the impact of AKI on long-term outcomes remains controversial. Therefore, we sought to evaluate the impact of AKI on short- and long-term outcomes following TAVI using the Valve Academic Research Consortium 2 criteria. METHODS: Consecutive patients (n = 794) with severe aortic stenosis who underwent TAVI were included in a multicenter Brazilian registry. Logistic regression analysis was used to identify predictors of AKI. Four-year outcomes were determined as Kaplan-Meier survival curves, and an adjusted landmark analysis was used to test the impact of AKI on mortality among survivors at 12 months. RESULTS: The incidence of AKI after TAVI was 18%. Independent predictors of AKI were age, diabetes mellitus, major or life-threatening bleeding and valve malpositioning. Acute kidney injury was independently associated with higher risk of all-cause death (adjusted HR, 2.8; 95%CI, 2.0-3.9; P < .001) and cardiovascular mortality (adjusted HR, 2.9; 95%CI, 1.9-4.4; P < .001) over the entire follow-up period. However, when considering only survivors at 12 months, there was no difference in both clinical endpoints (adjusted HR, 1.2; 95%CI, 0.5-2.4; P = .71, and HR, 0.7; 95%CI, 0.2-2.1; P = .57, respectively). CONCLUSIONS: Acute kidney injury is a frequent complication after TAVI. Older age, diabetes, major or life-threatening bleeding, and valve malpositioning were independent predictors of AKI. Acute kidney injury is associated with worse short- and long-term outcomes. However, the major impact of AKI on mortality is limited to the first year after TAVI.

Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction.

Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.

Ultrassom e microbolhas na recanalização de artérias coronarianasno infarto agudo do miocárdio / Ultrasound and microbubbles for coronary artery recanalization in acute myocardial infarction

Fundamento: Microbolhas intravenosas (MB) e ultrassom (US) têm sido utilizados para recanalizar vasos epicárdicos em modelos animais de infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-SST). Nenhum estudo prévio demonstrando o valor dessa técnica foi realizado em humanos. Objetivo: Estudo piloto realizado com o objetivo de avaliar a eficácia da utilização de MB e US (sonotrombólise) sobre as taxas iniciais de recanalização de artérias coronarianas em pacientes com IAM-SST. Método: Estudamos 24 pacientes (18 homens, média etária de 58 ± 9 anos) que deram entrada no serviço de emergência com IAM-SST. Pacientes foram randomizados em um dos três grupos: MB + US especificamente desenvolvido para este protocolo, com duração de pulso 4-20 useg e índice mecânico (IM) >1.0 (n = 7), MB + US com impulsos repetitivos de alto IM (1.0), com duração de pulso < 2 useg (n = 8), ou grupo controle (n = 9) que recebeu MB + US apenas paraanalisar a perfusão dentro da área de risco. As MB utilizadas no estudo consistiam em solução de Definity 3%. Todos os pacientes foram submetidos a intervenção coronariana percutânea (ICP). Resultados: As médias dos tempos porta-balão foram 76 ± 35 minutos no grupo MB + US 4-20 useg, 70 ± 20 minutos no grupo MB + US impulsos repetitivos e 81 ± 13 minutos no grupo controle (p = NS). Recanalização angiográfica antes da angioplastia foi observada em 75% dos pacientes tratados com MB + US impulsos repetitivos, em 43% nogrupo tratado com MB + US 4-20 useg e em 11% do grupo controle (p = < 0,05). Conclusão: Utilização de MB e US com impulsos repetitivos pode ser um método para recanalização precoce de artérias epicárdicas em pacientes com IAM-SST.

Background: Intravenous microbubbles (MB) and transthoracic ultrasound (US) have been utilized to recanalize epicardial vessels in animalmodels of ST segment elevation myocardial infarction (STEMI). The feasibility of such an ultrasound-guided approach in humans with STEMIhave not been studied. Objective: Pilot study with the aim to evaluate the efficacy of MB plus US on coronary artery recanalization rate in patients with STEMI. Methods: Twenty-four patients (18 men, mean age 58 ± 9 years) admitted to the emergency room with STEMI were randomized into 3 groups. Patients either received MB plus custom designed high mechanical index (MI) impulses at 4-20 usec pulse duration (n = 7), MB plus diagnostichigh MI (MI = 1.0) with multiple impulses < 2 usec pulse duration (n = 8) or MB plus limited diagnostic high MI impulses (< 5) just to analyzemyocardial perfusion, control group (n = 9). MB utilized in the study consisted of a solution of Definity 3%. All randomized groups underwent emergent PCI.Results: The mean door-to-balloon time were 76 ± 35 minutes in group US 4-20 usec, 70 ± 20 minutes in group US multiple impulses and 81 ± 13 minutes in control group (p = NS). Angiographic recanalization before PCI was observed in 75% of patients treated with US multiple impulses, in 43% for US 4-20 usec and 11% in control (p = <0.05).Conclusion: Utilization of MB and diagnostic US with multiple impulses may be a method of achieving early recanalization in acute STEMI.