Renato A. K. Kalil

Randomized study of surgical isolation of the pulmonary veins for correction of permanent atrial fibrillation associated with mitral valve disease

OBJECTIVE Chronic permanent atrial fibrillation is often due to mitral valve disease. The Cox maze procedure is the gold standard for treating this arrhythmia. Simpler techniques and ablation methods should have their efficacy tested in clinical practice. Our objective was to evaluate the effectiveness of surgical pulmonary vein isolation as compared with the Cox maze procedure. METHODS Sixty patients were randomly assigned to control group, modified maze group (Cox maze III), and surgical isolation of the pulmonary veins (SPVI) group from July 1999 to October 2004. All patients had mitral valve lesions treated concomitantly. Preoperative characteristics were similar between groups. RESULTS There were 4 deaths: 3 in the Cox maze group and 1 in the SPVI group (P = .31). The Cox maze group presented longer times of extracorporeal circulation and myocardial ischemia (P < .001). The relative risk of late postoperative development of atrial fibrillation was 0.07 in the SPVI group (P < .001; 95% confidence intervals: 0.02-0.27) and 0.195 in the Cox maze group (P = .002; 95% confidence intervals: 0.07-0.56) as compared with the control group. No difference was found between the SPVI and Cox maze groups concerning prevention of atrial fibrillation recurrence (relative risk: 0.358; P = .215; 95% confidence intervals: 0.08-1.67). CONCLUSIONS The modified Cox maze procedure and surgical pulmonary vein isolation were similarly effective in restoring sinus or regular rhythm in permanent atrial fibrillation associated with mitral valve disease. These results favor the adoption of surgical isolation as a preferable technique, simpler and equally effective in controlling atrial fibrillation. The results also can bring further information for understanding the mechanisms involved in origins and treatment of chronic permanent atrial fibrillation.

Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician

Patients with prosthetic heart valves require chronic oral anticoagulation. In this clinical scenario, physicians must be mindful of the thromboembolic and bleeding risks related to chronic anticoagulant therapy. Currently, only vitamin K antagonists are approved for this indication. This paper reviews the main heart valve guidelines focusing on the use of oral anticoagulation in these patients.

Myocardial viability and impact of surgical ventricular reconstruction on outcomes of patients with severe left ventricular dysfunction undergoing coronary artery bypass surgery: Results of the Surgical Treatment for Ischemic Heart Failure trial

OBJECTIVES In the Surgical Treatment for Ischemic Heart Failure trial, surgical ventricular reconstruction plus coronary artery bypass surgery was not associated with a reduction in the rate of death or cardiac hospitalization compared with bypass alone. We hypothesized that the absence of viable myocardium identifies patients with coronary artery disease and left ventricular dysfunction who have a greater benefit with coronary artery bypass graft surgery and surgical ventricular reconstruction compared with bypass alone. METHODS Myocardial viability was assessed by single photon computed tomography in 267 of the 1000 patients randomized to bypass or bypass plus surgical ventricular reconstruction in the Surgical Treatment for Ischemic Heart Failure. Myocardial viability was assessed on a per patient basis and regionally according to prespecified criteria. RESULTS At 3 years, there was no difference in mortality or the combined outcome of death or cardiac hospitalization between those with and without viability, and there was no significant interaction between the type of surgery and the global viability status with respect to mortality or death plus cardiac hospitalization. Furthermore, there was no difference in mortality or death plus cardiac hospitalization between those with and without anterior wall or apical scar, and no significant interaction between the presence of scar in these regions and the type of surgery with respect to mortality. CONCLUSIONS In patients with coronary artery disease and severe regional left ventricular dysfunction, assessment of myocardial viability does not identify patients who will derive a mortality benefit from adding surgical ventricular reconstruction to coronary artery bypass graft surgery.

Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action.

Bone marrow mononuclear cells (BMMC) effects have been investigated in small series of nonischemic dilated cardiomyopathy (NIDC). Left ventricular myocardial contractility improvements occur, but doubt remains about their mechanism of action. We compared contractility changes in areas treated (free wall) and nontreated (septal wall) with BMMC, in selected patients who have showed significant ventricular improvement after free wall-only intramyocardial stem cells injection. From 15 patients with functional class III/IV (NYHA) and LVEF inferior to 35%, who received 9.6 ± 2.6 × 107 BMMC divided into 10 points over the left ventricular free wall, 7 (46.7%) showed LVEF relative improvement greater than 15%. Those patients were selected for further contractility study. BMMC were collected from iliac bone and isolated with Ficoll-Hypaque. Magnetic resonance imaging was used to measure the systolic thickening of the septal (nontreated) and free wall (treated) before injection and 3 months postoperatively. Mean systolic septal wall thickening increased from 0.46 to 1.23 mm (an absolute 0.77 ± 1.3 mm and relative 167.4% increase) and in the free wall from 1.13 to 1.87 mm (an absolute 0.74 ± 1.5 mm and relative increase of 65.5%). There was no difference in the rate of absolute or relative systolic thickening between the two walls (p = 0.866 and 1.0, respectively), when cells were injected only in the left ventricular free wall. BMMC transplantation in nonischemic dilated cardiomyopathy can improve ventricular function by an overall effect, even in areas that are not directly injected. This finding favors the existence of a diffuse mechanism of action, rather than a local effect, and should be reminded when the pathophysiology of stem cells is considered.

Comparison of Surgical Cut and Sew versus Radiofrequency Pulmonary Veins Isolation for Chronic Permanent Atrial Fibrillation: A Randomized Study

Background: Surgical pulmonary veins isolation (PVI) is done to restore sinus rhythm (SR) in patients with chronic permanent atrial fibrillation (CPAF) and mitral valve disease. Here we compare the efficacy of electrical block lines performed with radiofrequency (RF) compared with conventional surgery.

Incidência de complicações pulmonares na cirurgia de revascularização do miocárdio

BACKGROUND despite the increasingly careful attempts to reduce perioperative risks, pulmonary complications following surgery are still very common, leading to longer length of hospital stays or death. OBJECTIVE to describe the incidence of pulmonary complications and identify their association with duration of extracorporeal circulation (ECC), surgery and ischemia, number of bypass grafts performed, location of drains and length of drainage following myocardial revascularization (MRV). METHODS this contemporaneous cohort consisted of 202 patients undergoing elective myocardial revascularization (MRV) with saphenous vein graft and internal mammary artery graft and ECC, at a referral university cardiology hospital in Southern Brazil, from April 2006 to November 2007. The following outcomes were analyzed: duration of mechanical ventilation; pneumonia onset; atelectasis; pleural effusion; location of drains and time of removal; and length of hospital stay. RESULTS of the 202 patients, 90 developed some sort of pulmonary complication. The incidence of pleural effusion was 84%, whereas atelectasis was 65%. The following variables were associated with pulmonary complications: duration of ECC (p = 0.003), surgery (p = 0.040) and ischemia (p = 0.001); length of drainage (p = 0.050) and location of pleural drains (p = 0.033); age (p = 0.001); ejection fraction (p = 0.010); diagnosis of asthma (p = 0.047) and preoperative abnormal chest X-ray findings (p = 0.029). CONCLUSION variables related to the complexity of the surgery and preexisting comorbidities are associated with a high incidence of postoperative pulmonary complications. These data reinforce the importance of having patients undergo perioperative clinical assessment to detect early respiratory complications after MRV.FUNDAMENTO: No periodo do peri-operatorio, os cuidados tem sido cada vez mais criteriosos, entretanto, as complicacoes pulmonares apos a abordagem cirurgica ainda sao frequentes, predispondo o paciente a um maior tempo de internacao ou ao obito. OBJETIVO: Descrever a incidencia de complicacoes pulmonares e identificar a sua associacao com tempos de circulacao extracorporea (CEC); cirurgia e isquemia; numero de enxertos; localizacao e tempo de drenos apos cirurgia de revascularizacao do miocardio (CRM). METODOS: Nesta coorte contemporânea, foram estudados 202 pacientes em hospital universitario de referencia para cardiologia no sul do Brasil, submetidos a CRM eletiva com ponte safena e arteria mamaria interna com CEC, no periodo de abril/2006 a novembro/2007. Os desfechos considerados foram: tempo de ventilacao mecânica; surgimento de pneumonia; atelectasia; derrame pleural; hora da retirada e localizacao dos drenos; e tempo de internacao. RESULTADOS: Observou-se algum tipo de complicacao pulmonar em 90 dos 202 pacientes. A frequencia de derrame pleural foi de 84% e a de atelectasia foi de 65%. Apresentaram associacao com complicacoes pulmonares os tempos de CEC (p = 0,003), cirurgico (p = 0,040) e isquemia (p = 0,001); o tempo de permanencia de drenos (p = 0,050) e a localizacao pleural dos drenos (p = 0,033), alem de idade (p = 0,001), fracao de ejecao (p = 0,010), diagnostico de asma (p = 0,047) e exame radiologico de torax pre-operatorio anormal (p = 0,029). CONCLUSAO: Variaveis relacionadas a complexidade do ato cirurgico e comorbidades pre-existentes estao associadas a uma alta incidencia de complicacoes pulmonares no pos-operatorio. Esses dados reforcam a importância da avaliacao clinica peri-operatoria para deteccao precoce de complicacao respiratoria apos CRM.

VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells

Background Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. Objective We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. Methods The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. Results A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9th and 27th was comparable to that at baseline. Conclusion We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on 9th and 27thdays.

Use of intra-aortic balloon pump in cardiac surgery: analysis of 80 consecutive cases

BACKGROUND About 10% to 15% of patients undergoing cardiac surgery may develop low cardiac output syndrome in the perioperative period; of this total, 2% require mechanical support for adequate hemodynamic control. OBJECTIVE To describe the mortality rates of patients who required the use of IABP in the perioperative or postoperative period of cardiac surgery, identifying preoperative variables associated with a worse outcome, as well as to describe the postoperative complications and medium-term survival. METHODS Retrospective cohort study including 80 consecutive cases between January/2009 and September/ 2011. The patients had on average 62.9 ± 11.3 years and 58.8% were male; 81.3% were hypertensive, 50.0% had prior myocardial infarction and 38.8% has NYHA III/IV heart failure. The mainsurgery performed was isolated coronary artery bypass grafting (37.5%). RESULTS Hospital mortality was 53.8% (IC 95%: 42.7-64.9), and cross-clamp time > 90 minutes was an independent predictor of mortality in multivariate analysis (OR 1.52 CI 95%: 1.04-2.22). 71.3% of patients (CI 95%: 61.2-81.4) had at least one additional complication in the perioperative period, with lower limb ischemia observed in 5.0% patients. One-year survival was 43.6%, with a plateau in survival rates after a sharp initial drop, related to hospital mortality. CONCLUSION Patients who require IABP comprise a group of very high risk for morbidity and mortality. IABP use, however, enables the recovery of many patients from an evolution that would invariably be fatal, and patients discharged from hospital have a good medium-term survival.

Insuficiência renal oculta acarreta risco elevado de mortalidade após cirurgia de revascularização miocárdica

INTRODUCTION AND OBJECTIVES Preoperative chronic renal dysfunction is an independent predictor of mortality in cardiac surgery. As normal range serum creatinine is not representative of normal renal function, we compared mortality rates, total hospital stay and post-surgical hospital stay for patients who underwent isolated coronary artery bypass surgery with serum creatinine < 1.5mg/dL as to their estimated creatinine clearance, normal or impaired. METHODS In 4,765 patients submitted to coronary artery bypass surgery between January/1996 and June/2004, the creatinine clearance was estimated by the Cockroft-Gault equation. Impaired renal function was considered as a creatinine clearance <60 mL/min/1.73 m² (chronic renal disease stage 3 - National Kidney Foundation-USA). In hospital mortality, total hospital stay, and post-surgical hospital stay were compared. RESULTS 4,688 patients had the required data, and 4,403 presented serum creatinine < 1.5 mg/dL - 3,177 with creatinine clearance > 60 mL/min (Group A), and 1,226 with <60 mL/min (Group B). Group B patients had significantly higher total hospital stay and post-surgical hospital stay than those in Group A (respectively 2.85 and 1.79 more days--P < 0.0001). Relative risk of in-hospital death was 2.09 to Group B (95%CI:1.54-2.84) when compared to Group A. CONCLUSIONS More than one quarter of the patients with serum creatinine <1.5 mg/dL had creatinine clearance <60 mL/min. This expressive number of patients, that would not have their renal dysfunction detected by the serum creatinine parameter alone, had double the risk of death, longer total hospital stay and post-surgical hospital stay than the other patients with serum creatinine < 1.5mg/dL.

Coronary angiogenesis as an endogenous response to myocardial ischemia in adults

El proceso de angiogenesis involucra una serie compleja de estimulos y de respuestas integradas, como la estimulacion de las celulas endoteliales (CE), para su proliferacion y migracion, estimulacion de la matriz extracelular, para la atraccion de pericitos y macrofagos, estimulacion de las celulas musculares lisas, para su proliferacion y migracion, y formacion de nuevas estructuras vasculares. La angiogenesis es principalmente una respuesta adaptativa a la hipoxia tisular y depende de la acumulacion del factor de crecimiento inducido por la hipoxia (FIH-1 α) en la zona del miocardio isquemico, que sirve para aumentar la transcripcion del factor de crecimiento endotelial vascular (con sus siglas en ingles: VEGF vascular endotelial growth factor), y sus receptores VEGF-R, por las CE en el sufrimiento isquemico. Esos pasos aglutinan mecanismos enzimaticos y proteasas activadoras del plasminogeno, metaloproteinasas (MMP) de la matriz extracelular (MEC), y cinasas que provocan la degradacion molecular proteolitica de la MEC, como tambien la activacion y la liberacion de factores de crecimiento, tales como: factor basico de crecimiento de los fibroblastos (FCFb), VEGF y factor de crecimiento insulinico-1 (FCI-1). Posteriormente, viene la fase intermedia de estabilizacion del nuevo brote neovascular inmaduro y la fase final de maduracion vascular de la angiogenesis fisiologica. Como conclusiones generales, podemos afirmar que la angiogenesis coronaria en adultos es fundamentalmente, una respuesta paracrina de la red capilar preexistente en condiciones fisiopatologicas de isquemia e inflamacion.The process of angiogenesis involves a complex sequence of stimuli and integrated responses, such as stimulation of endothelial cells (ECs) for their proliferation and migration, stimulation of the extracellular matrix (ECM) for the attraction of pericytes and macrophages, stimulation of smooth muscle cells for their proliferation and migration, and formation of new vascular structures. Angiogenesis is mainly an adaptive response to tissue hypoxia and depends on the accumulation of the hypoxia-inducible factor (HIF-1α) in the ischemic myocardial area, which increases the transcription of the vascular endothelial growth factor (VEGF) and its receptors VEGF-R by the ECs undergoing ischemia. Those steps involve enzymatic mechanisms and plasminogen activator proteases, metalloproteinases (MMP) of the ECM, and kinases that cause proteolytic molecular degradation of the ECM and activation and release of growth factors, such as: basic fibroblast growth factor (bFGF), VEGF, and insulin growth factor-1 (IGF-1). In the intermediate phase, stabilization of the immature neovascular sprout occurs. The final phase is characterized by vascular maturation of the physiological angiogenesis. In conclusion, coronary angiogenesis in adults is fundamentally a paracrine response of the preexisting capillary network under pathophysiological condition of ischemia and inflammation.