Manejo con control de temperatura en los cuidados posparada cardiaca: documento de expertos / Management of temperature control in post-cardiac arrest care: an expert report

Actualmente, el control estricto de temperatura mediante hipotermia inducida (entre 32 y 36 oC) se considera un tratamiento de primera línea en el manejo de pacientes con parada cardiaca recuperada que ingresan en Unidades de Cuidados Intensivos. Su objetivo es disminuir el daño neurológico secundario a anoxia cerebral. Aunque existen múltiples evidencias sobre sus beneficios, el empleo de esta técnica en nuestro país es pobre y todavía existen temas controvertidos como temperatura óptima, velocidad de instauración, duración y proceso de calentamiento. El objetivo de este trabajo es desarrollar la evidencia científica actual y las recomendaciones de las principales guías internacionales. El enfoque de este documento se centra también en aplicación práctica del control estricto de la temperatura en la parada cardiaca recuperada en nuestras Unidades de Cuidados Intensivos Generales o Cardiológicas, principalmente en los métodos de aplicación, protocolos, manejo de las complicaciones y elaboración del pronóstico neurológico. (AU)

Targeted temperature management (TTM) through induced hypothermia (between 32-36 oC) is currently regarded as a first-line treatment during the management of post-cardiac arrest patients admitted to the Intensive Care Unit (ICU). The aim of TTM is to afford neuroprotection and reduce secondary neurological damage caused by anoxia. Despite the large body of evidence on its benefits, the TTM is still little used in Spain. There are controversial issues referred to its implementation, such as the optimal target body temperature, timing, duration and the rewarming process. The present study reviews the best available scientific evidence and the current recommendations contained in the international guidelines. In addition, the study focuses on the practical implementation of TTM in post-cardiac arrest patients in general and cardiological ICUs, with a discussion of the implementation strategies, protocols, management of complications and assessment of the neurological prognosis. (AU)

Management of temperature control in post-cardiac arrest care: an expert report. / Manejo con control de temperatura en los cuidados posparada cardiaca: documento de expertos.

Targeted temperature management (TTM) through induced hypothermia (between 32-36 oC) is currently regarded as a first-line treatment during the management of post-cardiac arrest patients admitted to the Intensive Care Unit (ICU). The aim of TTM is to afford neuroprotection and reduce secondary neurological damage caused by anoxia. Despite the large body of evidence on its benefits, the TTM is still little used in Spain. There are controversial issues referred to its implementation, such as the optimal target body temperature, timing, duration and the rewarming process. The present study reviews the best available scientific evidence and the current recommendations contained in the international guidelines. In addition, the study focuses on the practical implementation of TTM in post-cardiac arrest patients in general and cardiological ICUs, with a discussion of the implementation strategies, protocols, management of complications and assessment of the neurological prognosis.

Role of coronary angiography in patients with a non-diagnostic electrocardiogram following out of hospital cardiac arrest: Rationale and design of the multicentre randomized controlled COUPE trial.

BACKGROUND: Coronary artery disease (CAD) is a major cause of out-of-hospital cardiac arrest (OHCA). The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following cardiac arrest in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. AIMS: We aim to assess whether emergency CAG and PCI, when indicated, will improve survival with good neurological outcome in post-OHCA patients without STEMI who remain comatose. METHODS: COUPE is a prospective, multicentre and randomized controlled clinical trial. A total of 166 survivors of OHCA without STEMI will be included. Potentially non-cardiac aetiology of the cardiac arrest will be ruled out prior to randomization. Randomization will be 1:1 for emergency (within 2 h) or deferred (performed before discharge) CAG. Both groups will receive routine care in the intensive cardiac care unit, including therapeutic hypothermia. The primary efficacy endpoint is a composite of in-hospital survival free of severe dependence, which will be evaluated using the Cerebral Performance Category Scale. The safety endpoint will be a composite of major adverse cardiac events including death, reinfarction, bleeding and ventricular arrhythmias. CONCLUSIONS: This study will assess the efficacy of an emergency CAG versus a deferred one in OHCA patients without STEMI in terms of survival and neurological impairment.

Pancreatitis inducida por drogas / DRUG-INDUCED ACUTE PANCREATITIS

Introducción. Las Reacciones Adversas Medicamentosas (RAM) son una de las principales causas de hospitalización y mortalidad en el sistema de salud (en países desarrollados y en vías de desarrollo), y la relevancia va creciendo año tras año. El objetivo de este estudio fue determinar la incidencia de pancreatitis aguda inducida por drogas y los grupos de drogas que más frecuentemente se ven involucrados. Material y Métodos: Se realizó un estudio retrospectivo tomando como fuente una base de datos de farmacovigilancia del Hospital General de Agudos ¨Dr. Cosme Argerich¨ con información de los últimos cinco años. Resultados: Se detectaron siete casos de pancreatitis inducida por drogas de los cuales fueron dos por quimioterápicos (lapatinib e imatinib), tres por antirretrovirales, uno por inmunosupresores y uno por antihipertensivos (enalapril). En cinco casos fue necesaria la hospitalización y un evento fue mortal. Conclusión: De acuerdo a la bibliografía internacional, a pesar de que los fármacos son solo responsables del 1-2% de casos de pancreatitis aguda inducida por drogas, es importante destacar que es difícil encontrar la causalidad entre el fármaco y el cuadro del paciente, lo que lleva muchas veces a un subdiagnóstico como una pancreatitis idiopática. En el presente estudio, estos casos deben considerarse por su impacto, no solo a nivel de la salud del paciente

Adverse Drug Reactions (ADR) are nowadays an increasing problem in health systems and represents between the 4th and the 6th cause of death in developing countries. Drug induced pancreatitis in a rare ADR but reports are increasing with antiretroviral drugs and new antiviral and anticancer drugs. The aim of this study was to determine the incidence of drug ­ induced pancreatitis in a tertiary care hospital. We used a pharmacovigilance database applying de Naranjo Score for drug causality in adverse medical events. From a total of 2990 ADR we detected 7 cases of pancreatitis. Antiretroviral and anticancer drugs were the drugs most frequently involved.

Mehran contrast nephropathy risk score: Is it still useful 10 years later?

BACKGROUND: Nowadays, contrast-induced nephropathy (CIN) is the third cause of acquired acute renal impairment in hospital. CIN is related to increased in-hospital morbidity, mortality, costs of medical care, and long admissions. Because of this, we hypothesized it would be useful to determine the risk of CIN with scores such as the Mehran score. The aim of this study was to validate the Mehran score in a contemporary cohort of Spanish patients with acute coronary syndrome (ACS). METHODS: We assessed the calibration and discriminatory capacity of Mehran score to predict CIN in a cohort of 1520 patients with a definitive diagnosis of ACS and who underwent coronary angiography between March 2008 and June 2012. We excluded patients on chronic dialysis and those without data of contrast volume. The calibration of the model was assessed with the Hosmer-Lemeshow goodness-of-fit test and discriminatory capacity was assessed by C-statistic, which is equivalent to the area under the receiver-operating characteristic curve. RESULTS: From the total group, 118 patients (7.8%) developed CIN. They were older, with higher rates of diabetes (DM) and hypertension and worse renal function and anemia (p<0.001). The odds ratios for different score components in Mehran's population versus our study were similar except for DM, hypotension, and intra-aortic balloon pump (1.6%, 2.68%, 2.55% vs 0.9%, 1.89%, and 2.86%, respectively). Calibration and discriminatory capacity of Mehran score were excellent with a Hosmer-Lemeshow p=0.7, C-statistic value >0.8. CONCLUSIONS: Mehran risk score has been validated in our study as a good score for predicting CIN in patients with ACS who underwent coronary angiography. According to this, we support its use in patients hospitalized for ACS in order to identify the ones at risk, and to optimize CIN prophylactic therapy prior to and after catheterization.

Evolution of hepatorenal syndrome after orthotopic liver transplantation: comparative analysis with patients who developed acute renal failure in the early postoperative period of liver transplantation.

OBJECTIVE: The purpose of this study was to ascertain the prognosis of patients with hepatorenal syndrome (HS) prior to orthotopic liver transplantation (OLT) by comparisons with a group of selected patients with normal renal function (NRF) pretransplantation who developed acute renal failure (ARF) in the early postoperative period. MATERIALS AND METHODS: Fifty-two OLT cases developed ARF in the early postoperative period between March 1999 and October 2004; 17 cases experienced HS prior to OLT. ARF was defined as serum creatinine level (Cr) >1.5 mg/dL or a creatinine clearance (CrCl) <50 mL/min. The immunosuppressive therapy was the same in both groups: low doses of tacrolimus were prescribed to reach trough levels of 5 ng/mL in the first week after OLT, where patients were administered monoclonal antibodies and corticosteroids. RESULTS: No differences were observed between the groups for gender, age or APACHE II Score in the first 24 hours after OLT. Patients with HS pretransplantation showed higher Cr and urea (U) levels than the other group (Cr: 2.1 +/- 0.8 HS vs 0.9 +/- 0.2, P = .000; U: 93.6 +/- 51.9 HS vs 42.1 +/- 19.3, P = .001). The ICU days of stay were similar (12.8 +/- 0.5 HS vs 19.7 +/- 15.2, P = .053). At the end of 1 year follow-up after OLT there were no differences in mortality (35% HS vs 26%), need for renal replacement therapy (23% HS vs 34%), infection (59% HS vs 51%), or rejection (6% HS vs 29%, P = .06). CONCLUSIONS: Patients with HS prior to OLT showed a similar prognosis to a group of selected patients with NRF pretransplantation, but developed ARF in the early postoperative period which was treated with monoclonal antibodies and low doses of tacrolimus.

Anaemia is associated with higher mortality among patients with heart failure with preserved systolic function.

OBJECTIVE: To investigate the prevalence of anaemia and its influence on mortality among hospitalised patients with congestive heart failure (CHF) with preserved left ventricular systolic function (LVSF). METHOD AND RESULTS: 210 patients with preserved LVSF admitted to the cardiology department of a tertiary hospital for CHF between 1 January 2000 and 31 December 2002 were analysed. Anaemic patients, who constituted 46% of the whole group, were older (75 v 72 years, p = 0.036); were in hospital longer (mean (SD) 13 v 11 days, p = 0.007); had a higher prevalence of ischaemic heart disease (54% v 35%, p = 0.009), left bundle branch block (12% v 4%, p = 0.018), and kidney failure (56% v 34%, p = 0.003); and had faster erythrocyte sedimentation rates (mean (SD) 50 v 26 mm in the first hour, p < 0.001), a tendency to lower serum cholesterol concentration (mean (SD) 4.65 v 5.22 mmol/l, p = 0.073), and smaller body mass index (mean (SD) 27 v 29 kg/m2, p = 0.126) than their non-anaemic counterparts. Kaplan-Meier analysis showed the anaemic group to have significantly poorer survival (p = 0.0001), with a one year survival rate of 72.2% versus 90.5% in the non-anaemic group. Multivariate analysis showed anaemia to be the most powerful independent predictor of mortality, increasing the risk of death by a factor of 2.7 (p = 0.007). CONCLUSION: Anaemia is a very prevalent condition in hospitalised patients with CHF with preserved LVSF and is independently associated with higher mortality. Appropriately designed randomised studies are needed to determine whether the prevention or treatment of anaemia can improve survival of these patients.

Características clínicas y pronóstico de la insuficiencia cardíaca de origen isquémico e hipertensivo / Clinical characteristics and prognoses of ischemic and hypertensive heart failure

Objetivos. Nos propusimos evaluar las características clínicas y la supervivencia de pacientes con insuficiencia cardíaca de origen isquémico o hipertensivo que requirieron ingreso hospitalario. Métodos. Analizamos las características clínicas de 229 pacientes con insuficiencia cardíaca en clase III-IV debida a cardiopatía isquémica o hipertensión arterial (en este grupo se excluyeron los hipertensos con lesiones coronarias o manifestaciones clínicas de cardiopatía isquémica, así como los casos debidos a otras cardiopatías) que requirieron ingreso hospitalario entre el 1 de enero de 1991 y el 31 de diciembre de 1994. Su situación vital se evaluó mediante consulta o contacto telefónico en los meses de abril y mayo de 1998, con un período medio de seguimiento de 4 años. Se obtuvieron datos de 144 pacientes con insuficiencia cardíaca de origen isquémico y 69 pacientes de etiología hipertensiva. La edad media del grupo total era de 70 ñ 11 años, 70 ñ 9 de los 69 pacientes incluidos en el grupo hipertenso y 69 ñ 11 años en el isquémico. Resultados. El 49 por ciento de los isquémicos era también hipertenso. El 72 por ciento de los hipertensos y el 73 por ciento de los isquémicos se encontraban en clase IV en el ingreso hospitalario. La presencia de edema (periférico y pulmonar) era significativamente más frecuente en los pacientes con insuficiencia cardíaca hipertensiva, 49 por ciento frente al 20 por ciento; p = 0,0001, así como la existencia de cardiomegalia en radiografía de tórax: 97 por ciento frente al 84 por ciento, p = 0,01. También la hipertrofia ventricular izquierda en ECG (58 por ciento frente al 31 por ciento; p = 0,0001) y la fibrilación auricular (47 por ciento frente al 19 por ciento; p = 0,0001) eran significativamente más frecuentes en el grupo hipertenso. La disfunción sistólica de ventrículo izquierdo (FE < 50 por ciento) fue más frecuente, aunque no de forma significativa, en los pacientes que tenían cardiopatía isquémica (82 por ciento frente al 68 por ciento; p = 0,057). No se observaron diferencias en la supervivencia de ambos grupos con una supervivencia a 3 años del 58,5 por ciento y 58,6 por ciento de los pacientes incluidos en el grupo hipertenso e isquémico y a los 5 años del 47,7 por ciento y 45,9 por ciento, respectivamente. Conclusiones. El grupo de pacientes con insuficiencia cardíaca de etiología isquémica ingresados en nuestro hospital presenta, a largo plazo una elevada mortalidad similar a la del grupo hipertensivo, siendo la supervivencia a cinco años menor del 50 por ciento en ambos grupos (AU)

Disección coronaria espontánea: aspectos diagnósticos y terapéuticos / Spontaneous coronary dissection: diagnostic and therapeutic approach

Presentamos dos casos de disección espontánea coronaria, que corresponden a dos mujeres sin factores de riesgo que presentaron un síndrome coronario agudo que cursó con importantes cambios electrocardiográficos. Se realizó en ambos casos una coronariografía urgente, que demostró una disección del tronco de la coronaria izquierda en el primer caso y una disección del segmento proximal de la arteria descendente anterior en el segundo. Ambos casos fueron revascularizados quirúrgicamente. (AU)

FMR1 and the fragile X syndrome: human genome epidemiology review.

The fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is one of the most common forms of inherited mental retardation. The cognitive, behavioral, and physical phenotype varies by sex, with males being more severely affected because of the X-linked inheritance of the mutation. The disorder-causing mutation is the amplification of a CGG repeat in the 5' untranslated region of FMR1 located at Xq27.3. The fragile X CGG repeat has four forms: common (6-40 repeats), intermediate (41-60 repeats), premutation (61-200 repeats), and full mutation (>200-230 repeats). Population-based studies suggest that the prevalence of the full mutation, the disorder-causing form of the repeat, ranges from 1/3,717 to 1/8,918 Caucasian males in the general population. The full mutation is also found in other racial/ethnic populations; however, few population-based studies exist for these populations. No population-based studies exist for the full mutation in a general female population. In contrast, several large, population-based studies exist for the premutation or carrier form of the disorder, with prevalence estimates ranging from 1/246 to 1/468 Caucasian females in the general population. For Caucasian males, the prevalence of the premutation is approximately 1/1,000. Like the full mutation, little information exists for the premutation in other populations. Although no effective cure or treatment exists for the fragile X syndrome, all persons affected with the syndrome are eligible for early intervention services. The relatively high prevalence of the premutation and full mutation genotypes coupled with technological advances in genetic testing make the fragile X syndrome amenable to screening. The timing as well as benefits and harms associated with the different screening strategies are the subject of current research and discussion.

[Coronary ischemia caused by pseudoxanthoma elasticum and myocardial revascularization with double arterial graft]. / Isquemia coronaria producida por seudoxantoma elástico y revascularización miocárdica con doble injerto arterial.

We present a case of an 18 year-old woman with pseudoxanthoma elasticum, who had a biopsy taken from a lesion. Although she was asymptomatic, we tried to rule out myocardial ischemia with a treadmill and cardiac gammagraphy with Talio. The isotopic studies and the ergometry were positive and the patient underwent coronariography. This study showed a severe triple-vessel disease. We did an angiography of the supraaortic arteries, mamarian artery, and mesenteric artery. These studies showed no obstructive lesions. The treatment of patient was a double by-pass with internal mammary artery and one by-pass with safena vein grafts with satisfactory results.

Infarto agudo de miocardio y trombosis coronaria inducidos por cocaína / Acute myocardial infarction and coronary thrombosis induced by cocaine

Un joven de 28 años con antecedentes de ulcus gástrico sufre un infarto agudo de miocardio anterolateral después de haber consumido en los días previos gran cantidad de cocaína. La coronariografía evidenció la presencia de un trombo oclusivo en el segmento proximal de la arteria descendente anterior, que se extendía hacia la porción distal del tronco de la coronaria izquierda. Se decidió realizar trombolisis intracoronaria con urocinasa. El trombo fue parcialmente lisado y la evolución posterior fue satisfactoria. En el control angiográfico se observaron unas arterias coronarias epicárdicas sin lesiones obstructivas (AU)

Step-down of enalapril treatment for arterial hypertension.

Enalapril treatment (20 mg every 12 hours) of 24 patients with essential hypertension and left ventricular (LV) hypertrophy established normal blood pressures after 8 weeks, and after 5 years, it had reduced LV mass index by 39% (from 148+/-34 to 90+/-16 g/m(2)) and had normalized LV structure and function and QT dispersion. Stepwise reduction of the enalapril dosage from 40 to 30, 20, 10, and 5 mg/d during the eighth year caused no significant change in blood pressure, LV structure, LV systolic function, or QT dispersion, which all likewise remained unaltered during an additional 2-year period of the 5-mg/d regimen. We conclude that for hypertensive patients in whom prolonged treatment with high doses of enalapril has normalized blood pressure, LV structure, LV function, and QT dispersion, the dose may be reduced as much as 8-fold without detriment to cardiovascular control. The use of smaller doses is evidently advantageous from the point of view of health costs.

Haemodynamic performance of aortic pericardial bioprostheses and bileaflet prostheses at rest and during exercise: implications for the surgical management of patients with small aortic roots.

OBJECTIVE: To determine the haemodynamic behaviour, at rest and during exercise, of aortic valve pericardial bioprostheses and different sizes of bileaflet prosthesis. DESIGN: Observational study. SETTING: Tertiary medical centre. PATIENTS AND INTERVENTIONS: 74 patients (33 women, 41 men; mean age 64 years) in whom 40 pericardial bioprostheses and 34 bileaflet prostheses sized 19, 21, or 23 mm had been implanted to replace aortic valves. MAIN OUTCOME MEASURES: Doppler echocardiography at rest and at peak exercise, between 12 and 47 months after surgery. RESULTS: All patients achieved a significant increase in heart rate, systolic blood pressure, and cardiac output with exercise. Transvalvar pressure fall, valve area, and left ventricular systolic and diastolic function indices also underwent significant changes with exercise. Reductions in peak and mean transvalvar pressure, at rest and at peak exercise, were greater in patients with small valves (p < 0.05). Valve areas and effective area index were greater in the patients with larger valves (p < 0.001). There were no significant differences between patients with mechanical and biological prostheses with regard to transvalvar pressure fall and valve areas at rest and at peak exercise. CONCLUSIONS: 19 mm and 21 mm aortic prostheses and bioprostheses continue to create significant obstruction, particularly with exercise.

Maintenance of blood pressure control and left ventricular performance with small doses of enalapril.

Enalopril treatment (20 mg every 12 hours) of 24 patients with essential hypertension and left ventricular (LV) hypertrophy established normal blood pressure (BP) after 8 weeks, and after 7 years had reduced LV mass index by 39% from 148 +/- 34 to 90 +/- 16 g/m2, and had normalized LV structure and function and QT dispersion. Stepwise reduction of the enalapril dosage from 40 to 30, 20, 10, and 5 mg/day during the eighth year caused no significant changes in BP, LV structure, LV systolic function, or QT dispersion, which all likewise remained unaltered during a further year of the 5-mg/day regimen. We conclude that for hypertensive patients in whom prolonged treatment with standard doses of enalapril has normalized BP, LV structure and function, and QT dispersion, significantly smaller doses are sufficient to maintain these cardiovascular achievements.

Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.

A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.

Reduction of QT and QTc dispersion during long-term treatment of systemic hypertension with enalapril.

We report, in conjunction with other findings, the evolution of the dispersion of QT and QTc in patients who for the last 7 years have been treated with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. Twenty-four essential hypertensive patients who had received no previous treatment took enalapril (20 mg twice daily) for 7 years. In a pretreatment placebo phase and 8 weeks and 1, 3, 5, 6, and 7 years after the start of therapy, cardiovascular parameters were determined by two-dimensional guided M-mode echocardiography, and the QT interval and corrected QT interval (QTc) and their dispersions were obtained from amplified standard 12-lead electrocardiograms. Therapy rapidly reduced blood pressure (BP) from 156/105 mm Hg to normal values; at 7-year follow-up, BP was 130/84 mm Hg (p <0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5-year follow-up the reduction had reached 39% (p <0.001), after which neither LV mass index nor any structural parameter underwent any further significant change. LV pump function was also significantly better after 7 years of treatment. During this time, QT and QTc decreased significantly, as did the dispersion of both QT (from 61+/-21 to 37+/-14 ms) and QTc (from 67+/-27 to 41+/-16 ms). We conclude that long-term enalapril treatment of hypertensive patients with LV hypertrophy not only induces marked regression of LV mass and improved LV systolic function, but also reduces the dispersions of QT and QTc, which probably reduces the likelihood of ventricular arrhythmias and improves prognosis.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PURPOSE: The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. PATIENTS AND METHODS: Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. RESULTS: Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. CONCLUSION: After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.