Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study.

BACKGROUND: The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward. METHOD: We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses. RESULTS: Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4-12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1-5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49-4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04-0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02-0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20-0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08-7.67, p-value; 0.035) was associated with severe PPD only. CONCLUSION: The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.

Volatile anaesthesia and peri-operative outcomes related to cancer: a feasibility and pilot study for a large randomised control trial.

Published data suggest that the type of general anaesthesia used during surgical resection for cancer may impact on patient long-term outcome. However, robust prospective clinical evidence is essential to guide a change in clinical practice. We explored the feasibility of conducting a randomised controlled trial to investigate the impact of total intravenous anaesthesia with propofol vs. inhalational volatile anaesthesia on postoperative outcomes of patients undergoing major cancer surgery. We undertook a randomised, double-blind feasibility and pilot study of propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia during cancer resection surgery at three tertiary hospitals in Australia and the USA. Patients were randomly allocated to receive propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia. Primary outcomes for this study were successful recruitment to the study and successful delivery of the assigned anaesthetic treatment as per randomisation arm. Of the 217 eligible patients approached, 146 were recruited, a recruitment rate of 67.3% (95%CI 60.6-73.5%). One hundred and forty-five patients adhered to the randomised treatment arm, 99.3% (95%CI 96.2-100%). Intra-operative patient characteristics and postoperative complications were comparable between the two intervention groups. This feasibility and pilot study supports the viability of the protocol for a large, randomised controlled trial to investigate the effect of anaesthesia technique on postoperative cancer outcomes. The volatile anaesthesia and peri-operative outcomes related to cancer (VAPOR-C) study that is planned to follow this feasibility study is an international, multicentre trial with the aim of providing evidence-based guidelines for the anaesthetic management of patients undergoing major cancer surgery.

Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials.

OBJECTIVES: Two identical 12-week, randomized, double-blind, placebo-controlled, multi-arm, parallel-group Phase III studies (Study P012, NCT00560833; Study P013, NCT00535288) evaluated the efficacy and safety of esmirtazapine, an investigational medicine, for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women. METHODS: Participants were randomized to placebo or esmirtazapine (2.25, 4.5, 9.0, or 18.0 mg). Co-primary efficacy endpoints (daily frequency and severity of moderate to severe VMS, both at weeks 4 and 12) were based on participative LogPad daily diaries. Adverse events (AEs) were recorded. RESULTS: In Studies P012 and P013, 942 and 946 participants were randomized, respectively. Compared with placebo, esmirtazapine significantly reduced the mean daily frequency by 1.4-2.2 moderate to severe VMS at weeks 4 and 12 (both ≥4.5 mg) and mean daily severity by 0.06-0.08 symptoms at weeks 4 (≥4.5 mg) and 12 (9.0 mg P012; 18.0 mg P013 only). Esmirtazapine was generally well tolerated with a more favorable safety profile at lower doses. Somnolence and fatigue were the most frequently reported AEs. CONCLUSIONS: Esmirtazapine reduced the frequency and severity of moderate to severe VMS associated with menopause and was generally well tolerated in the study population.

Inhalational versus propofol-based total intravenous anaesthesia: practice patterns and perspectives among Australasian anaesthetists.

Increasing evidence suggests that total intravenous anaesthesia (TIVA) may be the preferred anaesthetic for cancer resection surgery. To assist the preparation of a randomised controlled trial (RCT) examining Volatile (versus TIVA) Anaesthesia and Perioperative Outcomes Related to Cancer (VAPOR-C) we developed an 18-question electronic survey to investigate practice patterns and perspectives (emphasising indications, barriers, and impact on cancer outcomes) of TIVA versus inhalational general anaesthesia in Australasia. The survey was emailed to 1,000 (of 5,300 active Fellows) randomly selected Australian and New Zealand College of Anaesthetists (ANZCA) Fellows. The response rate was 27.5% (n=275). Of the respondents, 18% use TIVA for the majority of cases. In contrast, 46% use TIVA 20% of the time or less. Respondents described indications for TIVA as high risk of nausea, neurosurgery, and susceptibility to malignant hyperthermia. Lack of equipment, lack of education and cost were not considered barriers to TIVA use, and a significant proportion (41%) of respondents would use TIVA more often if setup were easier. Of the respondents, 43% thought that TIVA was associated with less cancer recurrence than inhalational anaesthesia, while 46% thought that there was no difference. Yet, only 29% of respondents reported that they use TIVA often or very often for cancer surgery. In Australasia, there is generally a low frequency of TIVA use despite a perception of benefit when compared with inhalational anaesthesia. Anaesthetists are willing to use TIVA for indications where sufficient evidence supports a meaningful level of improvement in clinical outcome. The survey explores attitudes towards use of TIVA for cancer surgery and demonstrates equipoise in anaesthetists' opinions regarding this indication. The inconsistent use of TIVA in Australasia, minimal barriers to its use, and the equipoise in anaesthetists' opinions regarding the effect of TIVA versus inhalational anaesthesia on cancer outcomes support the need for a large prospective RCT.

Postoperative outcomes following cardiac surgery in non-anaemic iron-replete and iron-deficient patients - an exploratory study.

Iron deficiency anaemia is strongly associated with poor outcomes after cardiac surgery. However, pre-operative non-anaemic iron deficiency (a probable anaemia precursor) has not been comprehensively examined in patients undergoing cardiac surgery, despite biological plausibility and evidence from other patient populations of negative effect on outcome. This exploratory retrospective cohort study aimed to compare an iron-deficient group of patients undergoing cardiac surgery with an iron-replete group. Consecutive non-anaemic patients undergoing elective coronary artery bypass grafting or single valve replacement in our institution between January 2013 and December 2015 were considered for inclusion. Data from a total of 277 patients were analysed, and were categorised by iron status and blood haemoglobin concentration into iron-deficient (n = 109) and iron-replete (n = 168) groups. Compared with the iron-replete group, patients in the iron-deficient group were more likely to be female (43% vs. 12%, iron-replete, respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have a higher pre-operative EuroSCORE (median IQR [range]) 3 (2-5 [0-10]) vs. 3 (2-4 [0-9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7) g.l-1 . Univariate analysis suggested that iron-deficient patients had a longer hospital length of stay (7 (6-9 [2-40]) vs. 7 (5-8 [4-23]) days; p = 0.013) and fewer days alive and out of hospital at postoperative day 90 (83 (80-84 [0-87]) vs. 83 (81-85 [34-86]), p = 0.009). There was no evidence of an association between iron deficiency and either lower nadir haemoglobin or higher requirement for blood products during inpatient stay. After adjusting the model for pre-operative age, sex, renal function, EuroSCORE and haemoglobin, the mean increase in hospital length of stay in the iron-deficient group relative to the iron-replete group was 0.86 days (bootstrapped 95%CI -0.37 to 2.22, p = 0.098). This exploratory study suggests there is weak evidence of an association between non-anaemic iron deficiency and outcome after cardiac surgery after controlling for potentially confounding variables.

Leukocyte counts, myeloperoxidase, and pregnancy-associated plasma protein a as biomarkers for cardiovascular disease: towards a multi-biomarker approach.

We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk.

Joint one-sided and two-sided simultaneous confidence intervals.

For the analysis of multiarmed clinical trials often a set consisting of a mixture of one- and two-sided tests can be preferred over a set of common two-sided hypotheses settings. Here we show the straightforward application of existing multiple comparison procedures for the difference and ratio of normally distributed means to complex trial designs, involving one and two test directions. The proposed contrast tests provide a more flexible framework than the existing methods at nearly similar power. An application is illustrated for an example with multiple treatment doses and two active controls; statistical software codes are included for R and SAS System.

[Panic disorder in patients with chest pain and palpitations: an often unrecognized relationship]. / Paniekstoornis bij patiënten met pijn op de borst en palpitaties: een onvoldoende onderkend verband.

The prevalence of panic disorder in patients who present with chest pain or palpitations to a First Heart Aid setting varies in the literature between 0%-59%. In a high percentage of cases, panic disorder is not recognized by the cardiologist in patients who present initially with chest pain or palpitations. Patients with panic disorder have a large and ongoing medical consumption. A selective serotonin reuptake inhibitor and/or cognitive therapy appear to be good treatment of panic disorder in patients who present initially with chest pain or palpitations. A CO2 challenge test elicits the symptoms in patients with panic disorder with high sensitivity and specificity but this test has not been validated in patients who present initially with chest pain or palpitations and in whom the diagnosis 'panic disorder' is not yet established.

[Panic disorder, chest pain and palpitations: a pilot study of a Dutch First Heart Aid]. / Paniekstoornissen, pijn op de borst en palpitaties: een pilotonderzoek op een Nederlandse Eerste Harthulp.

OBJECTIVE: To determine how many patients, presenting to a First Heart Aid (FHA) with chest pain or palpitations without a cardiac origin for their complaints, have a panic disorder and/or depression. DESIGN: Prospective and questionnaire investigation. METHOD: In 3 months (November 1st 1998-January 31st 1999) all patients presenting to the FHA of the University Hospital Maastricht, the Netherlands, and who were not admitted, were screened for the presence of psychopathology by means of a questionnaire, the 'Hospital anxiety and depression scale' (HADS). Patients scoring above 8 on the HADS with no cardiac cause for their initial complaint were interviewed using the 'Mini international neuropsychiatric interview' (MINI) to determine whether there was a panic disorder and/or a depressive episode. RESULTS: Of a total of 621 patients 251 met the inclusion criteria; 134 (53%) gave informed consent (72 (54%) men and 62 (46%) women, with a mean age of 55.9 (SD: 13.2; range: 23-84)). Of the 134, 77 had a HADS score > or = 8; in 59 (30 men; 29 women) the MINI was carried out; in 49 (83%) panic disorder (n = 45) or depression (n = 4) was diagnosed. In 7/45 the cardiologist had diagnosed a psychiatric disorder ('Hyperventilation'). CONCLUSION: In 83% of the patients who visited the Maastricht FHA with cardiac complaints but without a cardiac origin and who had a HADS score > or = 8, panic disorder and/or depression was diagnosed.

Treatment of recent onset atrial fibrillation with intravenous sotalol and/or flecainide.

AIM: The purpose of our study (conducted between August 1995 and September 1996) was to evaluate prospectively the efficacy of intravenous administration (in 10 min) of sotalol, flecainide or the combination of these drugs to restore sinus rhythm in patients (without cardiac/pulmonary failure) who came to the First Heart Aid of our hospital with atrial fibrillation lasting less than 24 h. METHODS AND RESULTS: Patients in whom the rhythm was not converted to sinus rhythm by intravenous sotalol within 60 min, we started to give flecainide intravenously (2 mg/kg). In patients on oral beta blockade we started flecainide intravenously (2 mg/kg) over 10 min. Of the 92 patients who fulfilled the entry criteria 51 were on oral beta blocking agents for angina, hypertension or to prevent atrial fibrillation. Of these patients, 43 (84%) converted to sinus rhythm with intravenous flecainide. The 41 patients not on a beta blocking agents were treated with 40 mg sotalol intravenously which led to sinus rhythm in 22 patients (54%). Sixteen of the 19 remaining patients (84%) converted to sinus rhythm after subsequent administration of flecainide. Therefore of the whole group of 70 patients treated with flecainide, 59 (84%) were successfully converted. Out of the 92 patients, 11 patients were not converted to sinus rhythm. Six were treated successfully by electrical cardioversion. The others were treated with oral flecainide/sotalol or digoxine with persistence of atrial fibrillation. CONCLUSION: The findings of this study suggest that intravenous sotalol is a good choice for termination of recent onset atrial fibrillation in a patient with a good left ventricular function. If not successful then flecainide had to be added.

Efficacy of mibefradil compared with amlodipine in suppressing exercise-induced and daily silent ischemia: results of a multicenter, placebo-controlled trial.

BACKGROUND: Mibefradil is a new benzimidazolyl-substituted tetraline-derivative calcium antagonist. Its vasodilatory activity combined with an ability to lower heart rate without negative inotropic effects as well as its long duration of action make it a promising anti-ischemic agent. METHODS AND RESULTS: Three hundred nine patients with coronary artery disease, stable angina pectoris, and positive exercise tests were randomized to receive mibefradil (50, 100, or 150 mg), amlodipine (10 mg), or placebo. The anti-ischemic effects of mibefradil on exercise test and silent ischemia parameters were assessed. At doses of 100 and 150 mg, mibefradil increased exercise duration (by 55.5 and 51.0 seconds, respectively; P<.001 for both), increased time to onset of angina (by 98.3 and 82.7 seconds, respectively; P<.001), and increased time to 1-mm ST depression (by 81.7 and 94.3 seconds, respectively; P<.001). By comparison, a 10 mg/d dose of amlodipine significantly improved only time to onset of angina (treatment effect: 38.5 seconds, P=.036). Mibefradil 100 mg and 150 mg decreased the number of episodes of silent ischemia (treatment effects: -3.1 and -3.6, respectively; P<.001) and the duration of silent ischemia (treatment effects: -9.2 minutes, P=.048, and -14.6 minutes, P=.002, respectively). The decrease in the number of episodes of silent ischemia was also statistically significant in the group receiving 10 mg of amlodipine (-1.5; P=.036). CONCLUSIONS: Once-daily doses of 100 and 150 mg mibefradil were effective in improving exercise tolerance and reducing ischemic episodes during ambulatory monitoring in patients with coronary artery disease.

Tomographic myocardial imaging with technetium-99m tetrofosmin. Comparison with tetrofosmin and thallium planar imaging and with angiography.

Technetium-99m tetrofosmin is a new myocardial imaging agent with improved handling and kinetic characteristics. The purpose of this study was to compare the ability of planar and SPECT Tc-99m tetrofosmin imaging with Thallium-201 planar data to detect coronary artery disease and individual vessel lesions ( > 50% diameter stenosis). Seventy-two patients with definite or suspected coronary artery disease were included. Sixty-three had angiographic evidence of coronary artery disease, among whom 42 had had a previous myocardial infarction, while 21 had not. The total number of diseased arteries was 111. Patients underwent symptom-limited treadmill or bicycle exercise to similar endpoints. Thallium and tetrofosmin images were analysed separately by consensus reading. Interpretation was made for five standard anatomical regions (anterior, septal, inferior, lateral and apex), classified into four categories (normal, reversible, fixed and mixed defects). Sensitivity and specificity to detect coronary artery disease were 71% and 78% for Thallium-201 vs 68% and 78% for tetrofosmin by planar imaging, and 87% and 89% for tetrofosmin by SPECT. The improved sensitivity of SPECT was confirmed both in patients with and without previous myocardial infarction. The sensitivity to detect individual vessel lesions was improved by SPECT (59% tetrofosmin SPECT vs 50% thallium planar and 51% tetrofosmin planar). Individual vessel lesion detection by SPECT was 50% for the left anterior descending coronary artery, 42% for the left circumflex and 86% for the right coronary artery. This study confirms the value of technetium-99m tetrofosmin as a myocardial imaging agent. Improvements in diagnosis and in evaluating extent of disease can be expected from using SPECT.

Myocardial perfusion imaging with 99mTc tetrofosmin. Comparison to 201Tl imaging and coronary angiography in a phase III multicenter trial. Tetrofosmin International Trial Study Group.

BACKGROUND: Our objective was to compare the sensitivity and specificity of tetrofosmin, a new 99mTc-labeled myocardial perfusion imaging agent for the detection of myocardial perfusion abnormalities, with those of 201Tl and coronary angiography. Our hypothesis was that same-day stress/rest tetrofosmin imaging could provide data comparable to those of 201Tl imaging. Myocardial perfusion imaging plays an important role for the evaluation of coronary artery disease. Newer 99mTc-labeled agents offer several advantages over 201Tl, the conventional myocardial perfusion imaging agent. Tetrofosmin is a new 99mTc-labeled agent with promising results in preliminary studies. METHODS AND RESULTS: Two hundred fifty-two patients with suspected coronary artery disease were enrolled in 10 centers in the United States and Europe. All patients underwent exercise and rest myocardial perfusion imaging with 99mTc-tetrofosmin using two separate injections of the radiotracer 4 hours apart on the same day. Planar images were obtained in three standard views 15 to 60 minutes after radiotracer injection. Patients also underwent standard exercise and redistribution planar 201Tl imaging within 2 weeks of tetrofosmin imaging. In addition, 58 healthy subjects with low likelihood of coronary artery disease underwent exercise and rest tetrofosmin imaging. Coronary angiograms were available in 181 patients with suspected coronary artery disease. All radionuclide images were processed in the central core laboratory and interpreted blindly by a panel of four experienced readers. 201Tl images and tetrofosmin images were read separately. Discrepancies were resolved by consensus. The workload, peak heart rate, and double products were comparable during exercise for both imaging agents. Technically acceptable paired 201Tl and tetrofosmin images were available in 224 of 252 patients. Tetrofosmin images were generally of good quality, with low extracardiac activity, and easy to interpret. Patients were categorized as showing normal, ischemia, infarction, or mixture with each imaging modality. Precise concordance for each of these categories was 59.4% (kappa = 0.44; 95% CI, 0.35 to 0.53). When patients were categorized as normal or abnormal, the concordance was 80.4% (kappa = 0.55; 95% CI, 0.43 to 0.67). When each of five anatomic territories (septal, anterior, inferior, lateral, and apical) was categorized as normal versus abnormal, the concordance varied from 81% to 90%. When similar comparison was made for the specific category of abnormality, the concordance was 64% to 84%. When coronary angiography was used as the criterion, the sensitivity and positive and negative predictive accuracy of tetrofosmin and 201Tl were comparable. The normalcy rate of tetrofosmin images in the healthy subjects with low likelihood of coronary artery disease was 97%. CONCLUSIONS: 99mTc tetrofosmin is a new myocardial imaging agent with favorable imaging characteristics with results comparable to those of 201Tl.

Myocardial imaging with technetium-99m-tetrofosmin: comparison of one-day and two-day protocols.

UNLABELLED: There is no evidence of myocardial redistribution after tetrofosmin injection, therefore, two separate injections are needed to differentiate scar from ischemia with this tracer. The injections can be given on the same day (one-day protocol) or on separate days (two-day protocol). As part of a Phase II clinical study, a one-day protocol was compared with a two-day protocol. METHODS: Fifty-five patients with suspected coronary artery disease were studied according to the following protocol: on the first day at rest, anterior, left lateral, left anterior oblique 40 degrees and 70 degrees images were acquired 30 min after injection of 8 mCi of tetrofosmin for 5 min each. Two days later, exercise and rest images were acquired on the same day. At peak exercise, 8 mCi of tetrofosmin were injected and 30 min later the same four standard planar images were recorded as on Day one. Four hours after the exercise injection, 24 mCi of tetrofosmin were injected at rest and imaging was repeated 30 min later. Qualitative comparisons between the one- and two-day protocols were performed in 50 patients in whom all data were available following blinded evaluation of images by three readers. RESULTS: All three readers reported identical results for the 26 patients. A difference in extent or location between the observers was found in seven patients, differences between normal and abnormal in eight patients, while discrepancies between ischemia and necrosis were noted in four patients. In five patients, an ischemic area was found according to the one-day protocol, but according to the data of the two-day protocol, this area was judged to be necrotic. One observer reported the opposite in one patient. These discrepancies between the reversibility of defects were restricted to the inferior wall. Comparison with 201Tl data showed no systematic pattern of variation. CONCLUSION: Tetrofosmin can be used in a one-day protocol. However, in planar imaging, the inferior wall should be reported with caution.

Technetium-99m-tetrofosmin myocardial imaging: a comparison with thallium-201 and angiography.

UNLABELLED: Images recorded after intravenous administration of 99mTc-tetrofosmin were compared to those obtained with 201Tl in a series of 40 patients with angiographically documented coronary artery disease. These patients were part of a Phase II tetrofosmin study and presented anamnestic or laboratory evidence suggestive of ischemic heart disease. METHODS: Thirty-seven patients had one or more coronary obstructions greater or equal to 70% of luminal diameter. Three patients studied after bypass surgery or angioplasty had patent grafts, absence of disease progression or no significant restenosis. Twenty-six patients had evidence of previous myocardial infarction. All images were processed into a common display format by a core laboratory. They were identified by code and read by concensus of four investigators. Each segment was classified as normal or abnormal and these readings were combined and categorized into normal, reversible, fixed or mixed regional defects. RESULTS: There was good segmental correspondence between thallium and tetrofosmin (kappa values ranged from 0.43 to 1.00). The ability of thallium and tetrofosmin to recognize and localize myocardial infarction was excellent, since corresponding abnormalities were present in respectively 24 and 25 of the 26 patients with previous myocardial infarction. Abnormalities in noninfarcted territories were recognized with both tracers in 16 of 28 patients presenting with coronary lesions involving vessels unrelated to the infarct. CONCLUSION: In comparison to rest tetrofosmin, thallium redistribution shows more reversibility in areas with myocardial infarction but less reversibility in areas of myocardial ischemia. Current Phase II results suggest that tetrofosmin is a sensitive and reliable tracer for detecting myocardial infarction and ischemia. Results should be confirmed in a larger group of patients.

Myocardial single-photon emission computed tomographic imaging with technetium 99m tetrofosmin: stress-rest imaging with same-day and separate-day rest imaging.

BACKGROUND: Technetium 99m tetrofosmin is a new ethylene diphosphine ligand for myocardial perfusion imaging and has unique properties. We have compared stress-rest single-photon emission computed tomographic (SPECT) imaging with 99mTc tetrofosmin with same-day and separate-day rest imaging to detect myocardial perfusion defects. METHODS AND RESULTS: Myocardial SPECT imaging was performed in 22 patients with coronary artery disease who had undergone planar thallium 201 imaging and coronary angiography. Single-day (stress-rest) and separate-day rest 99mTc tetrofosmin SPECT protocols were compared in the same patient. Images were assessed by a blinded panel to identify myocardial infarction, ischemia, or normal scans. Overall sensitivity for identification of patients with coronary artery disease was 86% (19/22) by both same-day stress-rest and separate-day rest protocols with 99mTc tetrofosmin (p = NS). Of a total of 396 segments studied, 107 abnormal segments were identified at exercise and 76 and 81 at the same-day and separate-day rest tests, respectively (p = NS). Same-day stress-rest and separate-day rest 99mTc tetrofosmin SPECT protocols were also useful for detecting individual coronary stenosis with a greater than 50% lesion: 80% of the left anterior descending, 93% of the right coronary, and 75% of the left circumflex coronary arteries were detected. CONCLUSION: Excellent images were obtained with 99mTc tetrofosmin during both stress and rest. 99mTc tetrofosmin imaging with the same-day stress-rest and separate-day rest imaging protocols have similar diagnostic sensitivities for detection of coronary heart disease.

Comparison of myocardial perfusion imaging with technetium-99m tetrofosmin versus thallium-201 in coronary artery disease.

Technetium-99m (Tc-99m) tetrofosmin, a new myocardial perfusion imaging agent, was evaluated at exercise and rest in 50 patients with documented coronary artery disease to determine myocardial kinetics, redistribution and ideal imaging time. Planar imaging was performed at 5, 30, 60, 90, 120 and 240 minutes after an injection of Tc-99m tetrofosmin (8 to 10 mCi) at peak graded ergometric exercise. Reinjection (24 to 30 mCi) was performed at rest, 4 hours after the stress injection and also on a separate day, and imaging was repeated. All patients underwent thallium-201 (Tl-201) exercise and redistribution (4-hour) imaging. Perfusion defect to normal, and heart to lung ratios were calculated for exercise Tc-99m tetrofosmin images at each time point. The mean +/- SD defect to normal ratios were 0.75 +/- 0.10, 0.75 +/- 0.10, 0.74 +/- 0.09, 0.73 +/- 0.10, 0.73 +/- 0.10 and 0.72 +/- 0.10 at 5, 30, 60, 90, 120 and 240 minutes, respectively (p = NS), suggesting absence of redistribution. There was a significant increase in lung uptake of Tl-201 during exercise (p < 0.05), but not with Tc-99m tetrofosmin (p = NS). Washout of Tc-99m tetrofosmin was calculated in a subset of patients (n = 23). Rapid background clearance enabled postexercise diagnostic imaging as early as 5 minutes after injection. Myocardial retention curves after rest injection suggested that the optimal time for imaging was approximately 30 minutes later. Slow myocardial washout (4%/hour after exercise and 0.6%/hour after rest injection) enabled diagnostic images to be obtained up to 4 hours after each study.(ABSTRACT TRUNCATED AT 250 WORDS)

99mTc myocardial perfusion imaging.

For more than 15 years, 201Tl has been used for measuring myocardial perfusion and viability although its physical characteristics, which include a photon energy of 68 to 80 keV and a physical half-life of 73 hours, are far from ideal. In early 1991, 99mTc tracers from the group of compounds known as isonitriles and boronic acid adducts of technetium dioximes (BATO) compounds were made available for general use in the United States, with approval by the Food and Drug Administration in late 1990. The uptake of these agents in the myocardium is proportional to regional blood flow. Because these tracers have 99mTc as the radiolabel, they have better physical characteristics--a gamma photon energy of 140 keV and a half-life of 6 hours--than 201Tl. The isonitrile with the best properties for myocardial imaging is 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) (Cardiolite, DuPont, Wilmington, DE). It has transient hepatic uptake and little or no myocardial redistribution, making it an ideal single-photon emission CT tracer. The commercially developed agent of the BATO group is 99mTc-teboroxime (Cardiotec, Squibb, Princeton, NJ). Its extraction fraction by the myocardium is higher than that of 201Tl and 99mTc-MIBI but its washout is very rapid and flow related. Because of the lack of redistribution with 99mTc-MIBI and the rapid washout with 99mTc-teboroxime, two separate injections are necessary for these new tracers to enable them to distinguish ischemia from scar tissue. It is recommended to perform the rest study first, and then to do the exercise study if a 1-day protocol is being used.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris.

We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to recieve a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has antiischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.