A new complication of chemotherapy administered via permanent indwelling central venous catheter

BACKGROUND: The use of permanent intravenous access devices for chemotherapy administration has become a common practice in clinical oncology. Therefore, awareness of potential complications is important. The authors previously reported the use of high dose 5-fluorouracil (5-FU) (2600 mg/m2) and leucovorin (500 mg/m2) as a weekly 24-hour infusion for patients with colorectal carcinoma. In this report, a new complication of permanent indwelling catheters with high dose 5-fluorouracil (2600 mg/m2) and leucovorin (500 mg/m2) as a weekly 24-hour infusion for colorectal carcinoma is described. METHODS: Twenty-two patients in the previous Phase II trial on weekly high dose 5-FU and leucovorin were included in this study. All patients had either a single-lumen Port-o-cath (Pharmacia Deltec, St. Paul, MN) or Hickman catheter (Travenol Laboratories, Deerfield, IL). Occluded catheters were explanted, and the material found in their lumen was analyzed using infrared spectroscopy. RESULTS: Eleven of 22 patients had catheter blockage, and calcium carbonate formation (Calcite 100%) was identified within these catheters. CONCLUSION: Calcite formation causing catheter occlusion is a new and important complication resulting from using intravenous access devices for chemotherapy administration. Oncologists should be alerted to this phenomenon when high dose 5-FU and leucovorin are administered for 24 hours by continuous infusion using a single-port port-o-cath.     

The role of lipogenesis in the development of obesity and diabetes in Israeli sand rats (Psammomys obesus)

In order to optimize the therapeutic index of combining etoposide, epirubicin, cisplatin, 5-fluorouracil (5-FU), leucovorin (EEPFL) chemotherapy in the treatment of advanced gastric cancer, a trial of a novel schedule of weekly administration was conducted. Weekly EEPFL treatment consisted of a concomitant boost of etoposide 40 mg m(-2) i.v. over 30 min, epirubicin 10 mg m(-2) i.v. over 5 min to a backbone regimen, weekly PFL chemotherapy with cisplatin 25 mg m(-2), 5-FU 2200 mg m(-2), leucovorin 120 mg m(-2) given simultaneously by 24-h i.v. infusion. Response, survival and toxicity were evaluated. Forty-two patients were studied. Median age was 69 (range 31-84) years. Twenty-six per cent of patients showed complete response and 45% partial response. The overall response rate was 71% (95% confidence interval 58-84%). For a total of 507 weekly EEPFL cycles delivered, the incidence of grade 4 leucopenia was 1% of cycles. One patient died of neutropenia septicaemia. There was no other grade 4 toxicity. Grade 3 and 2 leucopenia occurred in 7% and 14% of cycles. The incidence of grade 3 and 2 mucositis was 1% and 3% of cycles. Grade 3 and 2 diarrhoea occurred in 0.4% and 1.6% of cycles. Overall median survival was 10 months (range 3-41+ months). Weekly EEPFL chemotherapy is an effective regimen with tolerable toxicities in the treatment of advanced gastric cancer. A randomized controlled clinical trial to formally assess the efficacy and benefit of EEPFL chemotherapy is under way.     

Cervical meningoceles and myelocystoceles: a unifying hypothesis

We initiated a pilot study of adjuvant hepatic arterial infusion chemotherapy (AHAIC) using 5-fluorouracil (5-FU) and leucovorin. Hepatic arterial infusion ports were placed in 15 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen consisted of a weekly infusion of 5-FU (12 mg m 2 per day) and leucovorin (200 mg m 2 per day) for 12 months. The mean follow-up was 22 months (range 3-62 months, SD 21-37 months). There were no clinical or biological complications related to chemotherapy, except for sharp epigastric burns in four patients immediately after 5-FU infusions. Catheter irreversible occlusions led to early cessation of the treatment in three patients. Four of the 15 evaluable patients developed recurrent disease. The site of relapse was the liver in two patients and extra-hepatic sites in the two remaining patients. Three of these four patients died of their recurrent disease. These results suggest that 5-FU and leucovorin can be combined for AHAIC in a long duration regimen with a very low rate of side-effects. This protocol could be safely employed in a prospective randomized study in combination with 5-FU systemic infusions.     

Schedule-selective biochemical modulation of 5-fluorouracil: a phase II study in advanced colorectal cancer

Based on experimental findings suggesting that 5-fluorouracil (FUra) may have different mechanisms of action depending on the schedule of administration, we generated the hypothesis that biochemical modulation of this fluoropyrimidine should be schedule specific. We thus tested the activity of a hybrid regimen consisting of two biweekly cycles of FUra bolus (600 mg/m2) modulated by pretreatment (24-h interval) with methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). Thirty-three consecutive patients with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study from February 1992 to August 1993. They were treated with two biweekly cycles of FUra bolus (600 mg/m2) preceded by (24-h interval) methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). The median Eastern Cooperative Oncology Group performance status was 1; the liver was the only metastatic site in 17 patients. Treatment outcome was evaluated by computed tomographic scan in all patients, except for two. Three complete and 13 partial responses were obtained among these 33 patients (response rate, 48%; 95% confidence limits, 31-66%). Performance status (Eastern Cooperative Oncology Group) influenced clinical response. The combined complete response and partial response rate was 69%, 33%, and 25% in patients with an Eastern Cooperative Oncology Group performance status of 0, 1, and 2, respectively (chi2, 4.6, P = 0.032, two-tailed Mantel test for trend). After a median follow-up time of 26 months, 10 patients are still alive. The median progression-free survival and overall survival were 9.5 and 20.2 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3%, and vomiting 3% for the bolus part and 21%, 3%, and 6%, respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.     

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

Adjuvant chemotherapy in colorectal cancer with high-dose leucovorin and fluorouracil: impact on disease-free survival and overall survival

PURPOSE: The rationale for using adjuvant chemotherapy in colorectal cancer is to achieve better disease control and thus reduce the high rates of tumor recurrence and mortality in patients who undergo curative surgery. The current literature, including relevant abstracts, on clinical trials of fluorouracil (5-FU) in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer is reviewed. The intent is not to present new data, but to present the reader with a broad perspective and larger patient experience on which to base well-reasoned treatment decisions. DESIGN: Published clinical trials and abstracts presented at the 1996 American Society of Clinical Oncology (ASCO) meeting that assessed 5-FU in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer were surveyed. End points of interest were disease-free survival (DFS), overall survival, and toxicity. RESULTS: In randomized trials that used high-dose leucovorin at doses that ranged from daily-times-five 200 mg/m2 to weekly 500 mg/m2 in combination with 5-FU, significant improvements in both DFS and overall survival were observed over surgery alone (control). In patients treated with high-dose leucovorin/5-FU, DFS rates ranged from 71% to 77% compared with control (58% to 64%). A similar trend was seen in overall survival, with a range of 75% to 84% compared with control (63% to 77%). Toxicities observed for high-dose leucovorin administered on a weekly or daily-times-five schedule were diarrhea, stomatitis, myelosuppression, and nausea. CONCLUSION: Overall, the results of these randomized trials support the use of high-dose leucovorin/5-FU as adjuvant therapy for colorectal cancer. Longer follow-up studies are needed to compare the benefits of these different regimens in terms of survival and to characterize adverse effects, especially those that may not be immediately evident. Adjuvant therapy with high-dose leucovorin/5-FU is an effective regimen that is well tolerated by many patients with colorectal cancer.     

In-hospital outcome of elderly patients with acute inferior myocardial infarction and right ventricular involvement

BACKGROUND: There are some specific high-risk subgroups of patients with acute inferior myocardial infarction, such as older patients and those with right ventricular involvement. However, the clinical implications of right ventricular infarction in elderly subjects have not been studied previously. METHODS AND RESULTS: To determine the clinical impact of right ventricular involvement in elderly patients with inferior myocardial infarction, we studied the in-hospital outcome of 198 consecutive patients > or = 75 years of age with a first acute inferior myocardial infarction according to the presence of ECG or echocardiographic criteria of right ventricular infarction. In patients with right ventricular involvement (41%), in-hospital case fatality rate was 47% (mainly because of nonreversible low cardiac output cardiogenic shock) compared with 10% in patients without right ventricular involvement (P<.001). Patients with right ventricular involvement also had a significantly higher incidence of cardiogenic shock (32% versus 5%), which was independent of left ventricular ejection fraction, complete AV block (33% versus 9%), and interventricular septal rupture (9% versus 0%). After adjustment for age, sex, diabetes, shock on admission, left ventricular systolic dysfunction, and complete AV block, right ventricular infarction remained a powerful independent predictor of in-hospital death (adjusted odds ratio, 4.0; 95% confidence interval, 1.3 to 14.2). CONCLUSIONS: Elderly patients with acute inferior myocardial infarction have a substantially increased risk of death during hospitalization when right ventricular involvement is present. The poorer outcome is due mainly to the high incidence of cardiogenic shock and its infrequent reversibility.     

Chemotherapy of colorectal cancers with metastases

The chemotherapy of metastatic colorectal cancer has demonstrated a symptomatic benefit and a prolongation in survival. The modulation of 5-fluorouracil (5-FU) by leucovorin is the current standard treatment. The best protocols include 5-FU 24 or 48 hour continuous infusion on a weekly or bimonthly schedule. The response rate is about 30%, the median progression-free survival is 6 to 8 months and the median survival 10 to 15 months. The toxicity is moderate. New drugs are available or under evaluation: 5-FU prodrugs, raltitrexed, CPT11, oxaliplatin, trimetrexate. Synergisms with 5-FU allow to consider more effective polychemotherapies.     

High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy

BACKGROUND: In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS: To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS: Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P < 0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P < 0.01, log rank test). CONCLUSIONS: The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.     

Phase II clinical and pharmacological study of pirarubicin in combination with 5-fluorouracil and cyclophosphamide in metastatic breast cancer

Doxorubicin containing combination chemotherapy regimens are widely used for treatment of breast and other cancers. However, these regimens are associated with significant toxicities including myocardial dysfunction and alopecia. Analogues of doxorubicin are being developed to reduce these side effects. We conducted a Phase II trial of an anthracycline analogue, pirarubicin, administered in combination with 5-fluorouracil and cyclophosphamide every 3 weeks, as front-line chemotherapy in women with metastatic breast cancer. Patients who had received prior anthracycline therapy were excluded. The chemotherapy doses were as follows: 5-fluorouracil (500 mg/m2 on days 1 and 8), pirarubicin (50 mg/m2 on day 1), and cyclophosphamide (500 mg/m2 on day 1). Among 40 evaluable patients treated on this protocol, a major response (partial or complete remission) was observed in 26 patients (response rate, 62%; 95% confidence interval, 46-77). The median response duration was 8 months, and median survival was 16 months. Grade III/IV myelosuppression occurred in 81% of the courses. The median cumulative pirarubicin dose was 410 (range, 90-870) mg/m2. A significant decrease in left ventricular ejection fraction occurred in 12 patients (at a median cumulative pirarubicin dose of 460 mg/m2) and led to congestive heart failure in 4 of these patients (cumulative pirarubicin doses of 500, 520, 590, and 730 mg/m2, respectively). Eleven patients underwent endomyocardial biopsy, either because they experienced a drop in left ventricular ejection fraction or because they had received a cumulative pirarubicin dose of 600 mg/m2 and were still responding to the treatment. Of these, only one biopsy was found to be more than grade 1.0 (in an individual who had received a cumulative dose of 705 mg/m2). Severe alopecia occurred in two-thirds of the patients. Pharmacokinetic studies revealed a triphasic elimination of pirarubicin with alpha, beta and gamma half-lives of 0.12, 1.44, and 33.9 h, respectively. Total clearance of drug was 4.2 liters.1 h/kg while the cumulative 24-h urinary excretion was less than 10% of the administered dose. The activity of the combination appears to be similar to doxorubicin-containing regimens, while the incidence of alopecia appears to be lower than the historical experience with doxorubicin. However, cardiotoxicity remains a significant problem.     

Clinical tolerance of oral loading with elevated doses of amiodarone in a group of patients with heart failure

Amiodarone is a choice drug for the treatment of patients suffering from life-threatening hyperkinetic ventricular arrhythmias and depressed ventricular function. The drug is characterized by a remarkably long halflife and a delayed initial activity after oral administration of the usual loading levels. The aim of this study was to establish: -the clinical tolerance to elevated doses in patients with heart failure presenting complex, hyperkinetic ventricular arrhythmias; -the possibility to shorten hospitalization as a result of the oral loading; -whether this administration route would take less time to be efficacious. For this purpose, 30 patients with heart failure and complex, hyperkinetic ventricular arrhythmias were treated with 0.50 mg/kg body weight of amiodarone for three days and with 0.30 mg/kg on the 4th and 5th days, followed by a maintenance period of treatment with 200-400 mg daily. All patients underwent a 24-h Holter test before and after administration and an echocardiographic examination showing an average ejection fraction of approximately 30%. Amiodarone was clinically well tolerated; only 2 patients required discontinuation of therapy whereas, among the the remaining 28 patients, 2 cases of transient hypotension and 3 cases of gastroenteric disorders were observed. It was concluded that elevated doses of amiodarone were well tolerated, which allowed to reduce the loading period and, therefore, hospitalization.     

Effect of benazepril on complex ventricular arrhythmias in older patients with congestive heart failure, prior myocardial infarction, and normal left ventricular ejection fraction

Sixty patients, mean age 82 +/- 8 years, with congestive heart failure, prior myocardial infarction, normal left ventricular ejection fraction, and > or = 30 ventricular premature complexes per hour detected by 24-hour ambulatory electrocardiograms, and who were treated with diuretics, were randomized to treatment with benazepril 20 to 40 mg/day (30 patients) or to no benazepril (30 patients). At a median of 6 months after treatment, follow-up 24-hour ambulatory electrocardiograms showed that compared with no benazepril, benazepril caused no significant reduction in the number of ventricular premature complexes per hour or in the number of runs of ventricular tachycardia per 24 hours.     

Outpatient echocardiography as a predictor of perioperative cardiac morbidity after peripheral vascular surgical procedures

PURPOSE: A variety of preoperative provocative tests have been used to define the risk of cardiac morbidity and mortality after peripheral vascular procedures, including dipyridamole myocardial scintigraphy and dobutamine stress echocardiography. Although highly sensitive, these tests are time-consuming and associated with significant expense. We investigated outpatient echocardiography as a less resource-intensive means of assessing cardiac risk with operation. METHODS: Over a 2-year period 250 consecutive patients underwent outpatient transthoracic echocardiography before elective peripheral vascular operation was performed. The accuracy of the Goldman, Detsky, and the American Society of Anesthesiologists' Physical Status Classification clinical indexes of cardiac risk were assessed with regard to the development of cardiac complications such as unstable angina, myocardial infarction, life-threatening ventricular arrhythmias, severe congestive heart failure, and cardiogenic shock. The accuracy of echocardiographically determined left ventricular ejection fraction was determined at threshold values between 20% and 60%. RESULTS: Perioperative cardiac events developed in 23 (9.2%) of the patients, and nine (3.6%) of the patients died as a result of these complications. Clinical indexes lacked sensitivity in the preoperative prediction of cardiac complications. Receiver operating curve analysis defined a left ventricular ejection fraction of less than 50% as an appropriate threshold for defining patients at high risk, with a sensitivity of 78% and a specificity of 81% in the identification of patients who had cardiac morbidity. The positive predictive value was 27%, and the negative predictive value was 97%. The economic impact of outpatient echocardiography was well below that of dipyridamole myocardial scintigraphy or dobutamine stress echocardiography. CONCLUSIONS: Outpatient echocardiography appears to offer a cost-efficient compromise between clinical criteria alone and provocative cardiac testing such as dipyridamole myocardial scintigraphy and dobutamine stress echocardiography in the preoperative screening of patients undergoing peripheral vascular surgical procedures.     

Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent

BACKGROUND:Cardiopulmonary bypass can be associated with vasodilatory hypotension requiring pressor support. We have previously found arginine vasopressin to be a remarkably effective pressor in a variety of vasodilatory shock states. We investigated the incidence and clinical predictors of vasodilatory shock in a general population of cardiac surgical patients and the effects of low-dose arginine vasopressin as treatment of this syndrome in patients with heart failure. METHODS: Patients undergoing cardiopulmonary bypass (n = 145) were studied prospectively. Preoperative ejection fraction, medications, and perioperative hemodynamics were recorded, and postbypass serum arginine vasopressin levels were measured. Vasodilatory shock was defined as a mean arterial pressure lower than 70 mm Hg, a cardiac index greater than 2.5 L/min/m2, and norepinephrine dependence. Predictors of vasodilatory shock were investigated by logistic regression analysis. The hemodynamic responses of patients who received arginine vasopressin infusions for vasodilatory shock after cardiopulmonary bypass for left ventricular assist device placement or heart transplantation were analyzed retrospectively. RESULTS: Eleven of 145 general cardiac surgery patients (8%) met criteria for postbypass vasodilatory shock. By multivariate analysis, an ejection fraction lower than 0.35 and angiotensin-converting enzyme inhibitor use were independent predictors of postbypass vasodilatory shock (relative risks of 9.1 and 11.9, respectively). Vasodilatory shock was associated with inappropriately low serum arginine vasopressin concentrations (12.0 +/- 6.6 pg/mL). Retrospective analysis found 40 patients with postbypass vasodilatory shock who received low-dose arginine vasopressin infusions, resulting in increased mean arterial pressure and decreased norepinephrine requirements. CONCLUSIONS: Low ejection fraction and angiotensin-converting enzyme inhibitor use are risk factors for postbypass vasodilatory shock, and this syndrome is associated with vasopressin deficiency. In patients exhibiting this syndrome after high-risk cardiac operations, replacement of arginine vasopressin increases blood pressure and reduces catecholamine pressor requirements.     

Effects of intravenous milrinone followed by titration of high-dose oral vasodilator therapy on clinical outcome and rehospitalization rates in patients with severe heart failure

This study evaluated the efficacy of intravenous milrinone in improving hemodynamics and facilitating the titration of high-dose oral vasodilator therapy to improve clinical status. Fourteen patients (mean age 52 +/- 12 years) with severe heart failure and a left ventricular ejection fraction of 18 +/- 6% underwent right-side heart catheterization and an intravenous milrinone infusion followed by titration of oral vasodilator and diuretic therapy. Milrinone significantly (p <0.05) improved right atrial pressure (12 +/- 5 to 8 +/- 5 mm Hg), pulmonary capillary wedge pressure (23 +/- 7 to 15 +/- 7 mm Hg), cardiac index (1.9 +/- 0.4 to 3.4 +/- 0.5 L/min/m2), systemic vascular resistance (1,809 +/- 526 to 891 +/- 144 dynes/s/cm(-5)), and pulmonary vascular resistance (285 +/- 151 to 163 +/- 68 dynes/s/cm(-5)), which was maintained in 10 patients with titration of high-dose oral vasodilator therapy. Oral angiotensin-converting enzyme inhibitor and diuretic doses were increased 318% and 89%, respectively. Four patients also received hydralazine to optimize hemodynamics. New York Heart Association functional class improved from 3.8 +/- 0.4 to 2.6 +/- 0.6 following therapy. Ten patients who responded to therapy had fewer hospitalized days during the subsequent year compared with the year before treatment (4 +/- 17 vs 17 +/- 15), and no patient died. In contrast, the 3 patients who responded poorly to therapy tended to have more hospitalized days at 12 months compared with pretreatment (31 +/- 11 vs 20 +/- 18; NS); 1 patient died. We conclude that intravenous milrinone followed by optimization of oral medical therapy may be used as a therapeutic trial to identify patients in need of cardiac transplantation.     

Distinction between arrhythmic and nonarrhythmic death after acute myocardial infarction based on heart rate variability, signal-averaged electrocardiogram, ventricular arrhythmias and left ventricular ejection fraction

OBJECTIVES: We investigated whether heart rate variability, the signal-averaged electrocardiogram (ECG), ventricular arrhythmias and left ventricular ejection fraction predict the mechanism of cardiac death after myocardial infarction. BACKGROUND: Postinfarction risk stratification studies have almost exclusively focused on predicting the risk of arrhythmic death. The factors that identify and distinguish persons at risk for arrhythmic and nonarrhythmic death are poorly known. METHODS: Heart rate variability, the signal-averaged ECG, ventricular arrhythmias and left ventricular ejection fraction were assessed in 575 survivors of acute myocardial infarction. The patients were followed up for 2 years; arrhythmic and nonarrhythmic cardiac deaths were used as clinical end points. During the follow-up period, 47 cardiac deaths occurred, 29 (62%) arrhythmic and 18 (38%) nonarrhythmic. RESULTS: All risk factors were associated with cardiac mortality in univariate analysis. With the exception of left ventricular ejection fraction, they were also predictors of arrhythmic death. Depressed heart rate variability (p < 0.001), ventricular ectopic beats (p < 0.001) and low ejection fraction (p < 0.001) were related to nonarrhythmic death. In multivariate analysis, depressed heart rate variability (p < 0.001) and runs of ventricular tachycardia (p < 0.05) predicted arrhythmic death. Nonarrhythmic death was associated with depressed heart rate variability (p < 0.001), ventricular ectopic beats (p < 0.001) and low ejection fraction (p < 0.01). By selecting patients with depressed heart rate variability, long filtered QRS duration or ventricular arrhythmias and excluding patients with the lowest ejection fraction, we identified a group in which 75% of deaths were arrhythmic. Similarly, by selecting patients with a low ejection fraction and excluding patients with the lowest heart rate variability, we identified a group in which 75% of deaths were nonarrhythmic. CONCLUSIONS: Arrhythmic death was associated predominantly with depressed heart rate variability and ventricular tachycardia runs, and nonarrhythmic death with low ejection fraction, ventricular ectopic beats and depressed heart rate variability. A combination of risk factors identified patient groups in which a majority of deaths were either arrhythmic or nonarrhythmic.     

Peroneal osteocutaneous flap raised on reconstructed popliteal artery for delayed union following open tibial fractures

Cardiac function was assessed in long-term survivors of malignant bone tumors who were treated according to Rosen's T5 or T10 protocol, both including doxorubicin. Thirty-one patients, age 10-45 years (median age 17.8 years) were evaluated 2.3-14.1 years (median 8.9 years) following completion of treatment. Cumulative doses of doxorubicin were 225-550 mg/m2 (median dose 360). The evaluation consisted of a history, physical examination, electrocardiogram (ECG), signal averaged ECG, 24-hour ambulatory ECG, echocardiography and radionuclide angiography. Eighteen of 31 (58%) patients showed cardiac toxicity, defined as having one or more of the following abnormalities: late potentials, complex ventricular arrhythmias, left ventricular dilation, decreased shortening fraction, or decreased ejection fraction. The incidence of cardiac abnormalities increased with length of follow-up (P< or = .05). No correlation could be demonstrated between cumulative dose of doxorubicin and cardiac status, except for heart rate variability. When adjusted to body surface area, the left ventricular posterior wall thickness (LVPW index) was decreased in all patients. The incidence of doxorubicin-induced cardiotoxicity is high and increases with follow-up, irrespective of cumulative dose. Life-long cardiac follow-up in these patients is warranted. The results of our study suggest that heart rate variability and LVPW index could be sensitive indicators for cardiotoxicity.     

Heart rate changes during the Valsalva maneuver in patients with isolated aortic insufficiency

To determine the possible relationship between left ventricular dilatation and heart rate changes provoked by the Valsalva maneuver (Valsalva ratio), we studied 9 patients with isolated chronic aortic insufficiency. Left ventricular systolic function was assessed by two-dimensional echocardiography and cardiac catheterization. All patients were asymptomatic (functional class I of the New York Heart Association). The left ventricular internal diameters and volumes were significantly increased in all patients. The asymptomatic patients had either normal or slightly depressed ejection fraction (EF > 0.40). The Valsalva ratio of these asymptomatic patients showed no significant correlation with the left ventricular volumes or with the left ventricular ejection fraction. In other words, parasympathetic heart rate control, as expressed by the Valsalva ratio, was normal in the asymptomatic patients with left ventricular dilatation and preserved left ventricular ejection fraction. Therefore, left ventricular dilatation may not be the major mechanism responsible for the abnormal parasympathetic heart rate control of patients with acquired heart disease.     

Left ventricular hypercontractility and ST segment depression in patients with syndrome X

OBJECTIVES: This study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X. BACKGROUND: Clinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise. METHODS: The pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise. RESULTS: Left ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients. CONCLUSIONS: These findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.     

Perindopril in monotherapy of primary hypertension--6 month observation

We evaluated effects of perindopril (Prestarium-SERVIER) in the treatment of the primary hypertension in 41 patients (mean age 41.6) in the I or II degrees WHO using 24 ambulatory blood pressure measurement and echocardiography. Investigation were performed before and after 3 and 6 months of the treatment. Initially 4 mg of perindopril was given and individually was increased after 3 months to 8 mg according to 24 ambulatory blood pressure measurement results. We obtained significant decrease of blood pressure in 3 (134.6/86.6 mm Hg) and in 6 (135/88, 9 mm Hg) months of treatment in comparison to baseline values (141.8/91.1 mm Hg), decrease of left ventricular mass to 244.4 g in 3 and 248.8 g after 6 months (baseline 258.5 g), as well as index of left ventricular mass, wall thickness and left ventricular end diastolic volume. There was no significant differences in: ejection, heart rate, left ventricular inflow on the successive investigations. Good effect of perindopril we observed in 31 patients (75.6%) after 6 months of treatment. We did not observe any serious side effects of perindopril. CONCLUSION: Perindopril in treatment hypertension effectively reduces the level of blood pressure (systolic, diastolic and mean) without any effect on heart rate. Prestarium reduces left ventricular mass, intraseptal wall thickness and left ventricular end diastolic volume. There is no influence on inflow to the left ventricle as well as on ejection fraction.