Validation in the canine model of a new non-invasive method of measuring coronary blood flow reserve: split dose thallium-201 rest/stress imaging.

Diffusely impaired coronary blood flow reserve is difficult to measure non-invasively. We developed and tested a quantitative non-invasive method of measuring coronary blood flow reserve using thallium-201 perfusion imaging. Ten anesthetized dogs were injected simultaneously at rest with thallium-201 and either Ru-103 or Sn-113 microspheres. SPECT images were obtained followed by varying doses of intravenous adenosine, and a second thallium-201 dose was injected simultaneously with either Nb-95 or Sc-46 microspheres. SPECT images were then repeated. The heart was removed, sectioned and counted, along with arterial blood samples. Blood flow was calculated at rest and stress. Peak resting counts in four regions in each of three SPECT slices were subtracted from stress values and stress/rest thallium-201 count ratios (coronary flow reserve (CFR)) were calculated and correlated with the corresponding microsphere flow ratios. Overall correlation of the imaging and microsphere flow ratios was 0.77 (p = 0.0001). Regional correlation coefficients ranged from 0.65-0.86 (p = 0.0001). Coronary blood flow reserve ratios by the microsphere method ranged from 0.7 to 5.3, and by thallium-201 imaging from 0.33-2.45. The non-invasively measured coronary blood flow reserve with thallium-201 imaging and adenosine stress correlates well with microsphere-measured coronary blood flow reserve over a wide range of coronary flows, and should be useful in clinical studies of CFR impairment.

Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension.

Dihydropyridine and nondihydropyridine calcium channel blockers (CCB) differ in pharmacologic characteristics. Few clinical studies distinguish effects of CCB as monotherapy. We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension. Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were randomly assigned to either nifedipine-GITS or verapamil-SR. Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks. Clinic blood pressure (BP), 24-h ambulatory BP, exercise BP, left ventricular mass, systolic and diastolic function by echocardiography, and coronary flow reserve by split-dose thallium-201 imaging with adenosine were assessed at baseline, end of titration, 3 months and 6 months of treatment. Plasma renin activity, atrial natriuretic peptide, norepinephrine, and epinephrine were assayed. Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index. Compared to nifedipine-GITS, verapamil-SR produced a significantly lower resting and peak exercise heart rate. Nifedipine-GITS elicited a lower peak exercise systolic BP. At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels, no longer apparent by 6 months. Plasma norepinephrine was lower with verapamil-SR, also at end titration and at 3 months, but not at 6 months. Plasma epinephrine and plasma renin activity were unchanged by either drug. There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments. Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension. Differences in their hemodynamic profiles and neurohormonal responses are consistent with preclinical pharmacologic characteristics. The clinical implications of their similarities and differences remain to be fully evaluated in outcome studies.

Predictive value of left ventricular ejection fraction in stem cell transplantation.

We evaluated predictive value of left ventricular ejection fraction at rest (REF) and its increment with exercise (deltaEF) on autologous and allogeneic stem cell transplantation mortality. In a 7 year period, a total of 163 patients evaluated for stem cell transplantation were studied. All were followed for at least 3 months after the transplant. REF was discriminatory for peritransplant mortality only in younger (<43 years) patients (n = 66), particularly those who underwent autologous transplantation (n = 30). Resting ejection fraction was not a discriminator for early death in any other subgroup. Cardiac reserve (deltaEF) was significantly lower in patients (n = 35), who died early. The finding was most prominent in younger patients who underwent autologous transplantation (n = 26). Combination of decreased REF and low deltaEF (n = 18) was associated with high peritransplant mortality (56%), after both autologous and allogeneic transplantation. A low REF with an appropriate deltaEF (n = 43) was associated with a 19% peritransplant mortality and no deaths in the autologous group. These observations indicate that resting ejection fraction is of only limited value for pretransplant evaluation. However, measurement of cardiac reserve during exercise can provide important prognostic information before stem cell transplantation.

Effect of long-term eprosartan versus enalapril antihypertensive therapy on left ventricular mass and coronary flow reserve in stage I-II hypertension. Eprosartan Study Group.

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Dobutamine thallium 201 perfusion imaging in candidates for lung transplantation.

BACKGROUND: Thallium-201 stress imaging is the most often used noninvasive test for detection of coronary artery disease. Its utility in patients with end-stage lung disease has not been defined. METHODS: Feasibility, safety, and reliability of thallium 201 perfusion imaging was evaluated in 23 consecutive candidates for lung transplantation. All underwent graded dobutamine thallium 201 single photon emission computed tomography imaging. The perfusion imaging results were correlated with results of coronary angiography, radionuclide angiography, and right heart catheterization. RESULTS: The testing was completed without complications in all patients. No perfusion abnormality was detected in five patients, and none had evidence of coronary artery disease on coronary angiography. In 18 patients with abnormal thallium 201 imaging, coronary artery disease was detected in four patients only, and no angiographic data was available in three patients. Thus, in at least 11 of 23 patients, thallium 201 imaging was falsely positive. There was a trend toward lower left ventricular ejection fraction in patients with abnormal thallium 201 imaging. No correlation was found between thallium 201 results, pulmonary artery and right atrial pressures at rest. Possible noncoronary origin of the perfusion defects include the following (1) presence of sarcoid in the myocardium, (2) left ventricular attenuation by hypertrophied right ventricle, and (3) altered left ventricular anatomy, function, and coronary perfusion as a result of right ventricular pressure overload. CONCLUSIONS: Dobutamine thallium 201 stress test can be safely performed in lung transplant candidates. However, its specificity for detection of coronary artery disease is low. Selective use of coronary angiography in patients with multiple risk factors is likely a more cost-effective approach.

Patient perception of a long-term clinical trial: experience using a close-out questionnaire in the Studies of Left Ventricular Dysfunction (SOLVD) Trial. SOLVD Close-out Working Group.

A close-out questionnaire was distributed to the participants in a long-term heart failure trial, Studies of Left Ventricular Dysfunction (SOLVD). The respondents' primary motivation for enrollment, positive and negative experiences, and reported changes in habitual behavior was analyzed. Seventy-four percent (N = 3522) of the eligible patients responded to the survey. The most commonly cited reason for enrollment was recommendation by the primary physician. A wish "to contribute to medical science" and "to help others" was also a frequent incentive. A majority of the respondents were satisfied with participation and would be willing to participate in a future clinical trial. Most negative experiences included transportation to and from the clinic and frequent staff changes. A significant number of the patients reported changes in their smoking habits, alcohol intake, and diet despite the absence of behavioral interventions in the study protocol. There were minor differences between attitudes and perceptions of the male and female participants. No differences were found between patients who had previously participated in a clinical trial and those who had not.

Clinical utility of technetium-99m-teboroxime myocardial washout imaging.

UNLABELLED: The purpose of this study was to evaluate the clinical utility of 99mTc-teboroxime myocardial washout imaging. The differential washout after a single tracer injection has been proposed as an alternative for characterization of the perfusion defects. METHODS: Fifty-six patients received 5-min adenosine infusion. The stress dose of 99mTc-teboroxime was injected at 4.5 min and stress imaging with a single-headed SPECT gamma camera was started at 6 min, washout imaging followed immediately. At 20 min, the rest tracer dose was injected at rest and imaging was started at 21.5 min. The reversibility of the perfusion defects on the washout and rest images was compared visually and quantitatively. RESULTS: There was no statistical difference in the number of stress defects that improved on the washout and rest images. The visual interpretation of the perfusion abnormalities was confirmed by quantitative analysis of relative segmental activity. CONCLUSION: Thus, 99mTc-teboroxime-adenosine washout myocardial perfusion imaging can be safely and quickly accomplished. Detected reversibility of the perfusion defects did not significantly differ from reversibility observed on the rest images.

Renal, hemodynamic, and electrocardiographic effects of low versus high osmolality contrast agents on the transplanted heart.

The effects of low and high osmolality ionic contrast agents on the transplanted heart were studied in 75 consecutive patients. Renal function remained unchanged 24 hours after coronary angiography in both groups. Hemodynamic changes were transient and more pronounced after administration of the high osmolality agent; ECG changes and cineangiography quality were similar after both agents. The manyfold increase in cost of the low osmolality contrast agents may not be justified for use in stable patients after heart transplantation.

Long-term effect of thrombolytic therapy on left ventricular ejection fraction after acute myocardial infarction.

To assess the long-term effect of thrombolytic therapy on left ventricular (LV) systolic function, 222 patients with acute myocardial infarction treated with intravenous tissue plasminogen activator within 4 hours of symptom onset underwent assessment of LV ejection fraction (EF) by radionuclide equilibrium angiography at hospital discharge and 1 year later. Mean EF at hospital discharge (46 +/- 12) was similar to that at 1 year (45 +/- 13). Stepwise multivariate linear regression analysis identified EF at discharge and patency of the infarct-related artery before discharge as independent predictors of EF change at 1 year (p = 0.0002 and 0.003, respectively). Random assignments to invasive versus conservative treatment strategies or to early versus delayed beta-blocker therapy did not affect EF change during follow-up. No significant deterioration of EF was observed in patients with larger infarcts. However, EF decreased from 45 +/- 10 at hospital discharge to 39 +/- 12 (p = 0.005) at 1-year follow-up in a subgroup of patients with history of prior infarction. Thus, patients with acute myocardial infarction, treated with intravenous tissue plasminogen activator early after onset of symptoms, appear to have stable LV function between hospital discharge and 1 year follow-up. The change in EF between hospital discharge and 1 year can be predicted from the EF value at discharge, patency of the infarct-related artery before discharge and history of previous myocardial infarction.

Coronary artery to right ventricle fistula in heart transplant recipients: a complication of endomyocardial biopsy.

In a series of 74 heart transplant recipients undergoing annual coronary angiography, a coronary artery to right ventricle fistula was observed in 4 patients, an incidence rate of 5.4%, which is much higher than the expected incidence of congenital coronary artery fistula (0.1% to 0.2%). A traumatic origin of the fistulas is unlikely because none of the heart donors had evidence of chest trauma. An endomyocardial biopsy-related etiology of the fistulas is postulated. All fistulas were located in the biopsy sampling area. Patients with a fistula underwent more biopsies before the diagnosis compared with patients without a fistula (20 +/- 11 versus 14 +/- 6, p = 0.05). At least one large arteriole (diameter greater than 0.16 mm) was found on pathologic examination of the biopsy specimens from each of the patients with a fistula (100%) but in only 2 (16.7%) (p less than 0.01) of 12 randomly selected patients without a fistula. The size of the fistula appears to be hemodynamically insignificant in all four patients, judging from angiographic size, normal intracardiac pressures and normal cardiac output values at rest. The diagnosis of a coronary artery to right ventricle fistula is possible and should be entertained at the time of coronary angiography of heart transplant recipients. The clinical significance of the finding is unclear. As long as endomyocardial biopsy remains the diagnostic method of identifying tissue rejection, prevention of the described complication is unlikely.

Cortical blindness after left internal mammary artery to left anterior descending coronary artery graft angiography.

We describe a case of transient cortical blindness following internal mammary artery to left anterior descending coronary artery graft angiography. This dramatic, infrequent, and self-limiting complication so far has not been described in the cardiovascular literature. In the present era of internal mammary artery use for the left coronary artery grafting, the angiographer should be familiar with the diagnosis, prevention, and management of complications previously seen mostly during the posterior cerebral circulation angiography.