Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study.

Although there have been anecdotal reports of cardiac toxicity associated with fluorouracil (5-FU) therapy, this phenomenon has not been studied in a systematic fashion. We prospectively performed continuous ambulatory ECG monitoring on 25 patients undergoing 5-FU infusion for treatment of solid tumors in order to assess the incidence of ischemic ST changes. Patients were monitored for 23 +/- 4 hours before 5-FU infusion, and 98 +/- 9 hours during 5-FU infusion. Anginal episodes were rare: only one patient had angina (during 5-FU infusion). However, asymptomatic ST changes (greater than or equal to 1 mm ST deviation) were common: six of 25 patients (24%) had ST changes before 5-FU infusion v 17 (68%) during 5-FU infusion (P less than .002). The incidence of ischemic episodes per patient per hour was 0.05 +/- 0.02 prior to 5-FU infusion v 0.13 +/- 0.03 during 5-FU infusion (P less than .001); the duration of ECG changes was 0.6 +/- 0.3 minutes per patient per hour before 5-FU v 1.9 +/- 0.5 minutes per patient per hour during 5-FU (P less than .01). ECG changes were more common among patients with known coronary artery disease. There were two cases of sudden death, both of which occurred at the end of the chemotherapy course. We conclude that 5-FU infusion is associated with a significant increase in silent ST segment deviation suggestive of ischemia, particularly among patients with coronary artery disease. The mechanism and clinical significance of these ECG changes remain to be determined.

The autoperfusion balloon angioplasty catheter limits myocardial ischemia and necrosis during prolonged balloon inflation.

A new balloon angioplasty catheter with multiple proximal and distal side holes has previously been shown to allow significant protection from ischemia during a 3 min balloon inflation in a coronary artery. Because of the potential benefits of very long periods of inflation, 21 anesthetized thoracotomized dogs were randomized to left circumflex coronary artery occlusion with either a standard or an autoperfusion balloon catheter for 90 min. Nine dogs sustained ventricular fibrillation before completing the study, eight after standard balloon inflation and one after autoperfusion balloon inflation (p = 0.04). ST segment elevation was 0.45 +/- 0.13 mV after 15 min of standard balloon inflation versus -0.03 +/- 0.03 mV after autoperfusion balloon inflation (p less than 0.001). Regional myocardial blood flow was 0.02 +/- 0.01 ml/min per g after 30 min of standard balloon inflation compared with 0.78 +/- 0.23 ml/min per g in the group subjected to autoperfusion balloon inflation (p = 0.01). The area of necrosis/area at risk in the standard catheter group was 40.4 +/- 19.3% versus 1.2 +/- 1.2% for the autoperfusion catheter group (p = 0.01). Thus, the autoperfusion catheter preserves blood flow and limits myocardial ischemia and necrosis despite 90 min of balloon inflation.

Prognostic significance of the treadmill exercise test performance 6 months after myocardial infarction.

A submaximal treadmill exercise test performed before hospital discharge after an uncomplicated myocardial infarction is often utilized to estimate prognosis and guide management, but there is little experience with a maximal exercise test performed 6 months after infarction to identify prognosis later in the convalescent period. The performance characteristics during an exercise test 6 months after myocardial infarction were related to the development of death, recurrent nonfatal myocardial infarction and coronary artery bypass surgery in the subsequent 12 months (that is, 6 to 18 months after infarction) in 473 patients. Mortality was significantly greater in patients who exhibited any of the following: inability to perform the exercise test because of cardiac limitations, the development of ST segment elevation of 1 mm or greater during the exercise test, an inadequate blood pressure response during exercise, the development of any ventricular premature depolarizations during exercise or the recovery period and inability to exercise beyond stage I of the modified Bruce protocol. By utilizing a combination of four high risk prognostic features from the exercise test, it was possible to stratify patients in terms of risk of mortality, from 1% if none of these features were present to 17% if three or four were present. Recurrent nonfatal myocardial infarction was predicted by an inability to perform the exercise test because of cardiac limitations, but not by any characteristics of exercise test performance. Coronary artery bypass surgery was associated with the development of ST segment depression of 1 mm or greater during the exercise test. Although clinical evidence of angina and heart failure 6 months after infarction was predictive of subsequent mortality among all survivors, among the low risk group without severely limiting cardiac disease, the exercise test provided unique prognostic information not available from clinical assessment alone. Therefore, a maximal exercise test performed 6 months after myocardial infarction is a valuable, noninvasive tool to evaluate prognosis. It provides information that is independent of and additive to clinical evaluation performed at the same time.

The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The MILIS Study Group.

Patients with diabetes mellitus experience a more adverse outcome after acute myocardial infarction compared with nondiabetic patients, although the mechanisms responsible for these findings are not clear. From the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study, the course of acute infarction in 85 diabetic patients was compared with that in 415 nondiabetic patients, all of whom had serial assessments of left ventricular function. The diabetic patients experienced a more complicated in-hospital and postdischarge course than did the nondiabetic patients, including a higher incidence of postinfarction angina, infarct extension, heart failure and death, despite the development of a smaller infarct size and similar levels of left ventricular ejection fraction. Although diabetic patients had a worse profile of cardiovascular risk factors at the time of the index infarction, the increased incidence of adverse outcomes among them persisted despite adjustment for these baseline imbalances. Diabetic women had a poor baseline risk profile compared with the other groups categorized by gender and diabetic status, and experienced an almost twofold increase in cardiac mortality despite development of the smallest infarct size during the index event. The duration of diabetes and the use of insulin at the time of the index infarction were associated with a better in-hospital mortality rate, but the duration of diabetes did not exert a major influence on the outcome of the diabetic patients. The factors responsible for the increased incidence of adverse outcomes among diabetic patients may be related to an acceleration of the atherosclerotic process, diastolic left ventricular dysfunction associated with diabetic cardiomyopathy or other unidentified unfavorable processes.

Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location.

To determine the relative prognostic significance of location (anterior or inferior) and type (Q wave or non-Q wave) of infarction, the hospital course and follow-up outcome (mean duration 30.8 months) of 471 patients with a first infarction were analyzed. Analyses were performed grouping the patients according to infarct location (anterior, n = 253; inferior, n = 218), infarct type (Q wave, n = 323; non-Q wave, n = 148), and both location and type (inferior non-Q wave, n = 85; inferior Q wave, n = 133; anterior non-Q wave, n = 63; and anterior Q wave, n = 190). Patients with anterior infarction had a substantially worse in-hospital and follow-up clinical course compared with those with inferior infarction, evidenced by a larger infarct size (21.2 versus 14.9 g Eq/m2 creatine kinase, MB fraction [MB CK], p less than 0.001), lower admission left ventricular ejection fraction (38.1 versus 55.3%, p less than 0.001) and higher incidence of heart failure (40.7 versus 14.7%, p less than 0.001), serious ventricular ectopic activity (70.2 versus 58.9%, p less than 0.05), in-hospital death (11.9 versus 2.8%, p less than 0.001) and total cumulative cardiac mortality (27 versus 11%, p less than 0.001). Patients with Q wave infarction similarly experienced a worse in-hospital course compared with patients with non-Q wave infarction, evidenced by a larger infarct size (20.7 versus 12.7 MB CK g Eq/m2, p less than 0.001), lower admission left ventricular ejection fraction (43.7 versus 50.6%, p less than 0.001), and a higher incidence of heart failure (31.9 versus 21.6%, p less than 0.05) and in-hospital death (9.3 versus 4.1% p less than 0.05). However, there was no increased rate of reinfarction or mortality in hospital survivors with non-Q wave infarction compared with those with Q wave infarction, and total cardiac mortality was similar (16 versus 21%, p = NS). To evaluate the role of infarct location and type independent of infarct size, patients were grouped according to quartile of infarct size, and outcome was reanalyzed within each group. Patients with anterior infarction demonstrated a lower left ventricular ejection fraction on admission and after 10 days than did patients with inferior infarction, even after adjustment for infarct size, as well as a higher incidence of congestive heart failure and cumulative cardiac mortality.(ABSTRACT TRUNCATED AT 400 WORDS)

Deleterious cardiac effects of captopril during acute myocardial ischaemia in the dog.

OBJECTIVE: The aim was to evaluate the effects of the angiotensin converting enzyme inhibitor captopril on acute myocardial ischaemia. METHODS: Seventeen anaesthetised open chest dogs were randomised to 3 minute angioplasty balloon occlusions of the left circumflex coronary artery before and after intravenous infusion of captopril (n = 8) or placebo (n = 9). RESULTS: There was apparent worsening of ischaemia during balloon inflation after captopril infusion, when compared with control inflation, as suggested by further ST segment elevation of 1.8 (SD 1.8) mm, p less than 0.03, and by further lowering of regional myocardial pH [-0.05(0.05), p = 0.06], and peak positive and peak negative dP/dt [-439(337)mm Hg.s-1, p less than 0.008; -470(316) mm Hg.s-1, p less than 0.004, respectively]. The increase in ischaemia occurred despite reduced double product after captopril administration. Regional myocardial blood flow in the ischaemic artery distribution was lower during post captopril balloon occlusion [-0.1(0.06) ml.min-1.g-1, p less than 0.005] than during control balloon inflation, while coronary vascular resistance increased by 161(172)% (range 45 to 497%, p less than 0.04). There were no significant differences in ST segments, pH, haemodynamic variables, or blood flow during balloon inflations before and after saline infusion. CONCLUSIONS: Despite lower myocardial metabolic demands, acute intravenous administration of captopril was associated with increased ischaemia during transient coronary artery occlusion.

Modification of left ventricular response to pacing tachycardia in nifedipine in patients with coronary artery disease.

The calcium blocking agent nifedipine was shown to protect the isolated left ventricle against the development of altered diastolic compliance during severe global ischemia. To assess the influence of nifedipine during myocardial ischemia in human subjects, we studied the effect of nifedipine (20 mg sublingually) on the hemodynamic response to pacing tachycardia (heart rate 66 +/- 4 to 143 +/- 4 beats per minute) in 17 patients with multivessel coronary artery disease. Typical anginal pain occurred in all patients during pacing tachycardia before nifedipine, but in only 3 of 17 patients during pacing after nifedipine. In 11 patients a significant (greater than or equal to 5 mm Hg) increase in postpacing left ventricular end-diastolic pressure (LVEDP, 15 +/- 2 mm Hg to 28 +/- 2 mm Hg, p less than 0.01) developed, and was associated with an upward shift of the left ventricular diastolic pressure-volume curve. In these patients, pretreatment with nifedipine did not alter resting LVEDP or aortic pressure, but did attenuate or abolish the increase n LVEDP and the shift in left ventricular diastolic pressure-volume curves after pacing tachycardia to the same rate and for the same duration. The antianginal effect of nifedipine was not associated with a reduction in contractility, because there was no change in LV + dp/dt after nifedipine. However, the increase in left ventricular systolic pressure achieved in response to pacing tachycardia was less after nifedipine. We conclude that nifedipine favorably modifies the symptomatic and hemodynamic response to pacing tachycardia in patients with coronary artery disease. The mechanism is uncertain and could involve a direct myocardial effect, peripheral vasodilation, coronary vasodilation or a combination of these effects.

Amelioration of ischemia during angioplasty of the left anterior descending coronary artery with an autoperfusion catheter.

A new autoperfusion balloon angioplasty catheter with sideholes proximal and distal to the balloon--facilitating distal blood flow during inflation--was compared with standard angioplasty catheters in a prospective, randomized study with blinded data analysis. Hemodynamic and electrocardiographic markers of ischemia after 1 minute of standard or autoperfusion catheter inflations were compared with ischemia after control inflation with standard balloons. In the patient group randomized to standard balloon inflation only, ST-segment elevation after control inflation with a standard balloon catheter was 0.37 +/- 0.04 mV; ST-segment elevation after final balloon inflation with a standard catheter was unchanged at 0.35 +/- 0.04 mV (difference not significant). In the group randomized to the autoperfusion catheter, control inflation with a standard catheter resulted in 0.48 +/- 0.1 mV ST elevation; final inflation with the autoperfusion catheter demonstrated 0.16 +/- 0.09 mV ST elevation (p less than 0.005). Autoperfusion catheter inflation was continued for 2 minutes without change in electrocardiographic findings: ST segments remained at 0.08 +/- 0.03 mV, unchanged from 0.07 +/- 0.03 mV before angioplasty (difference not significant). Thus, while coronary angioplasty performed with standard catheters resulted in marked ST-segment elevation, in patients undergoing angioplasty with the autoperfusion catheter, ischemia was generally not seen, despite sustained balloon inflation for 2 minutes.

Dose-related efficacy and bleeding complications of double-chain tissue plasminogen activator in acute myocardial infarction. The Wellcome Tissue Plasminogen Activator Study Group.

Although the efficacy of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double-chain rt-PA subsequently used in the Third International Study of Infarct Survival, in a multicenter trial of 267 patients with evolving acute myocardial infarction assigned to receive 1 of 6 weight-adjusted doses. The primary end point was infarct vessel patency after 90 minutes of drug infusion. Patency was defined as Thrombolysis in Myocardial Infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatment assignment. Patency was present in 48% of patients receiving the lowest dose range and 78% of those receiving the highest, with an association between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt-PA infused (p = 0.003). Bleeding complications were primarily related to instrumentation; blood loss requiring transfusion or otherwise deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt-PA are associated both with increased efficacy and increased risk of serious bleeding complications. Weight-adjusted dosing may provide an optimal risk-benefit ratio for thrombolysis during acute myocardial infarction.

Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients.

Over a 34.5-month period, all admissions to 5 university hospital coronary care units were screened for eligibility for the Multicenter Investigation of the Limitation of Infarct Size (MILIS), an ongoing study of the effects of hyaluronidase, propranolol and placebo on myocardial infarct (MI) size. Of 3,697 patients with greater than or equal to 30 minutes of discomfort that was thought to reflect myocardial ischemia who were assessed for the presence or absence of certain electrocardiographic abnormalities at the time of hospital admission, the electrocardiogram was considered predictive of acute MI if greater than or equal to 1 of the following abnormalities was present: new or presumably new Q waves (greater than or equal to 30 ms wide and 0.20 mV deep) in at least 2 of the 3 diaphragmatic leads (II, III, aVF), or in at least 2 of the 6 precordial leads (V1 to V6), or in I and aVL; new or presumably new ST-segment elevation or depression of greater than or equal to 0.10 mV in 1 of the same lead combinations; or complete left bundle branch block. In the screened population, the diagnostic sensitivity of the electrocardiographic criteria was 81%, whereas the overall infarct rate in the total population screened was 49%. The diagnostic specificity of these entry criteria was 69% and the predictive value 72%.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (A MILIS Study).

Methods for detecting acute myocardial infarction (AMI) were compared in a prospective study of 726 patients with pain presumed to be caused by ischemia that lasted 30 minutes or longer and was associated with electrocardiographic changes (ST-segment deviation greater than or equal to 0.1 mV and/or new Q waves or left bundle branch block). Using MB-CK values of more than 12 IU/liter as the standard criterion for detection of AMI, 639 patients (88%) were judged to have AMI. Total plasma CK values, technetium-99m stannous pyrophosphate images 48 to 72 hours after admission, and serial 12-lead electrocardiograms over 10 days were analyzed by investigators blinded to other clinical and laboratory data. For detection of AMI, total CK, electrocardiograms (ECGs) and pyrophosphate imaging were all highly accurate and sensitive (total CK accuracy 97%, ECG 92%, pyrophosphate 88%; total CK sensitivity 98%, ECG 96% and pyrophosphate 91%). However, both pyrophosphate and ECG were less specific than total CK (p less than 0.01) (total CK specificity 89%, pyrophosphate 64% and ECG 59%). The sensitivity (p less than 0.05) and accuracy (p less than 0.01) of total CK and pyrophosphate for those patients with Q-wave development were slightly greater than for those in whom Q waves did not evolve. The ECG was less accurate (p less than 0.02) and pyrophosphate was less specific (p less than 0.04) in patients with prior MI compared with those with initial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Implications for acute intervention related to time of hospital arrival in acute myocardial infarction.

The time from onset of symptoms to arrival in the hospital emergency room (ER) was studied in 778 patients randomized into a study of acute myocardial infarction (AMI) size limitation. Patients at relatively high risk of death after AMI (including those with preexisting diabetes mellitus, systemic hypertension or congestive heart failure), women and older patients arrived significantly later in the ER than did patients without these characteristics. A significantly higher mortality rate was observed in patients who arrived late, i.e., those who arrived more than 2 hours after the onset of chest pain, even though patients with hemodynamic compromise (bradycardia, hypotension) tended to arrive earlier. The difference in long-term mortality between those who arrived early (within 2 hours of onset of chest pain) and those who arrived late was accounted for by the baseline differences between these 2 groups. These baseline differences may influence the effects of early interventions in AMI. In addition, these findings have implications for education of high-risk patients who could benefit the most from aggressive early intervention.

A simplified method to predict occurrence of complete heart block during acute myocardial infarction.

Data were analyzed from 698 patients with proved acute myocardial infarction (AMI) to develop a method to predict the occurrence of complete heart block (CHB). The presence of electrocardiographic abnormalities of atrioventricular or intraventricular conduction during hospitalization was determined for each patient. The electrocardiographic risk factors considered were: first-degree atrioventricular block, Mobitz type I atrioventricular block, Mobitz type II atrioventricular block, left anterior hemiblock, left posterior hemiblock, right bundle branch block and left bundle branch block. A CHB risk score was developed that consisted of the sum of each patient's individual risk factors. CHB risk scores of 0, 1, 2 or 3 or more were associated with incidences of CHB of 1.2, 7.8, 25.0 and 36.4%, respectively. When applied to an independent AMI data base, as well as to the summed results of 6 previously reported series that identified predictors of CHB during AMI, a similar incremental risk of CHB as predicted by the risk score method was demonstrated.

Current guidelines for the treatment of patients with rheumatic fever.

Rheumatic fever is a multisystem inflammatory disease that occurs as a delayed sequelae to group A streptococcal pharyngitis. The important clinical manifestations are migratory polyarthritis, carditis, chorea, subcutaneous nodules and erythema marginatum occurring in varying combinations. The pathogenesis of this disorder remains elusive: an antigenic mimicry hypothesis best explains the affliction of various organ systems after a lag period following pharyngeal infection. In its classic milder form, the disorder is largely self-limited and resolves without sequelae, but carditis may be fatal in severe forms of the disease. Chronic and progressive damage to the heart valves leads to the most important public health manifestations of the disease. Anti-inflammatory agents provide dramatic clinical improvement, but do not prevent the subsequent development of rheumatic heart disease. The role of corticosteroids in treatment of carditis is uncertain and controlled studies have failed to demonstrate improved long term prognosis. Chorea, once considered a benign self-limited disease, is now felt to require more aggressive treatment, in particular with sedatives. Prevention of first and subsequent attacks of rheumatic fever is the mainstay in the limited arsenal available to alter the natural history of this disease.

Balloon coarctation angioplasty: follow-up of 103 patients.

OBJECTIVE: To evaluate the role of balloon coarctation angioplasty (BCA) in the management of patients with native coarctation of the aorta. BACKGROUND: BCA has emerged as an alternative to surgery for patients with native coarctation of the aorta. However, its role remains controversial. METHODS: Over a 7-year period, 103 patients undergoing BCA were enrolled in the study. Hemodynamic evaluation was obtained at baseline and immediately following BCA; 75% of patients returned for follow-up evaluation at 26 +/- 20 months. RESULTS: The systolic gradient across the coarcted segment decreased from 59 +/- 18 mmHg to 10 +/- 11 mmHg following BCA (p < 0.001). The procedure was successful in 82% of patients, and partial improvement was obtained in 17%. Repeat intervention was performed in 13% of the follow-up group. Surgical intervention was needed in 8 patients. CONCLUSION: Balloon angioplasty is an effective first-line intervention in patients with native coarctation of the aorta.

Ten years' clinical experience with telemedicine in prenatal care in Hungary.

A multicentre randomized clinical trial of prenatal home care of pregnant women was carried out in Hungary. Pregnant women registered contraction activity of the uterus daily using a portable contraction monitor. The data were transmitted directly to the physician's PC for analysis. Of 748 women who entered the study, only 263 fulfilled all the requirements of randomization, monitoring and treatment. The preterm birth rate in the study group was half that of the control group. Telemedical prenatal monitoring improves perinatal results by providing more intensive and better observation of pregnant women.

High-throughput screening of saliva for early detection of oral cancer: a pilot study.

The success of tumour therapy depends considerably on early diagnosis. Therefore, we aimed to develop a widely available, cheap, non-invasive, high-throughput method suitable for screening high-risk populations, at least, for early signs of malignant transformation in the oral cavity. First, in order to identify suitable tumour marker candidates, we compared the protein patterns of five selected saliva samples obtained from healthy controls and tumour patients after electrophoretic separation, excised the bands that were consistently up-regulated in the tumour patients only, and performed matrix-assisted laser-desorption ionisation (MALDI)-time of flight (TOF) tandem mass spectrometry (MS/MS) analysis of the proteins in these bands after in-gel tryptic digestion. From the panel of proteins identified, we chose annexin 1 and peroxiredoxin 2 for further studies based on their presence in the saliva of all five oral cancer patients only. Then, we performed a homology search of protein databases using the primary sequence of each in silico tryptic fragment peptide of these two proteins as bait, and selected a unique peptide for each. Finally, we performed targeted MALDI-TOF MS peptide analysis in a blinded fashion on all samples obtained from 20 healthy controls and 22 tumour patients for the presence of these peptides. We found both peptides present in the saliva samples of all cancer patients only. Even though these tumour markers should be validated in a wider population, our results indicate that targeted MALDI-TOF MS analysis of unique peptides of putative saliva protein tumour biomarkers could be the method of choice for cost-efficient, high-throughput screening for the early detection of oral cancer.