Menco G. Niemeyer

Dipyridamole thallium testing: noncardiac side effects, cardiac effects, electrocardiographic changes and hemodynamic changes after dipyridamole infusion with and without exercise

Thallium-201 scintigraphy in combination with intravenous dipyridamole has been reported to be useful in patients who are unable to perform maximal exercise stress testing. Few reports have dealt with side effects in large numbers of patients. For that reason noncardiac side effects, cardiac effects, electrocardiographic changes, as well as hemodynamic changes were studied in 301 consecutive patients, examined by dipyridamole thallium-201 imaging because of suspected coronary artery disease. The patients were divided into two groups (A and B). Patients in group A (101 patients) received an infusion of 0.14 mg/kg per minute dipyridamole for four minutes. Patients in group B (200 patients) received the same dose of dipyridamole followed by low level exercise (60 rpm/30 Watts) for three minutes to achieve maximal coronary blood flow and to diminish thallium-201 uptake in the gastrointestinal organs. The likelihood of having hemodynamically significant coronary artery disease was the same in both groups. Patients in group B experienced significantly less side effects than patients in group A (11% vs 43%, P less than 0.05). In group B changes in systolic blood pressure (P less than 0.05), heart rate (P less than 0.05), and rate pressure product (P less than 0.05) were more distinct. The occurrence of angina was the same in both groups (47% vs 44%, NS), but ischemic ST segment changes were significantly more frequent in group B than in group A (25% vs 12%, P less than 0.05). Thus, exercise added to dipyridamole infusion compared to dipyridamole infusion alone results in fewer noncardiac side effects, the same prevalence of angina pectoris, and a higher incidence of ST segment changes.

Normal values and reproducibility of left ventricular filling parameters by radionuclide angiography

Background. In physiologic situations age, heart rate (HR) and left ventricular ejection fraction (EF) may influence left ventricular filling rate. In this study, we determined normal values for radionuclide angiography (RNA) derived diastolic filling parameters, the correlations with age, HR and EF and their reproducibility. Methods. The study was performed in 20 patients, 40–76 years old (mean 57), with normal findings at coronary angiography and left ventriculography. The first RNA was performed at rest (RNA1). Then, five minutes bicycle ergometry was performed and the patients were allowed five minutes rest before RNA was repeated (RNA2). From the left ventricular time activity curve we determined peak filling rate (PFR), time to peak filling rate (TPFR) and atrial contribution (AC) to ventricular filling. Results. Values for PFR1 were 2.2 ± 0.6 EDV/sec (PFR2 2.4 ± 0.7 EDV/sec, r = 0.82), for TPFR1 198 ± 22 msec (TPFR2 203 ± 24 msec, r = 0.45) and for AC1 31 ± 11% (AC2 31 ± 10%, r = 0.72). The correlations of PFR and TPFR with age were statistically significant (respectively r = - 0.68 and r = 0.48, P < 0.05). PFR was also influenced by HR and EF (resp. r = 0.51 and r = 0.50, P < 0.05). TPFR however was not influenced by HR and EF, whereas AC was positively correlated with HR (r = 0.79, P < 0.01). Conclusions. Radionuclide angiography is a reliable and reproducible method to assess parameters of diastolic left ventricular filling in individual patients. It may therefore be used to serially follow diastolic function. When used for interindividual comparison the dependency of RNA derived left ventricular filling parameters on age, HR and EF should however be considered.

Comparison of Multiple-Dose and Once-Daily Nitrate Therapy in 1212 Patients with Stable Angina Pectoris: Effects on Quality of Life Indices

Background: Nitrates, although important for the management of anginal symptoms, produce significant side effects. Little is known about their net effects on health-related, quality-of-life indices. Methods: In a self-controlled, 6-month study, the effects on symptoms and quality of life of multiple-dose and once-daily nitrate therapy were evaluated in 1212 patients with stable angina pectoris. Quality of life was assessed by a test battery based on the exercise- tolerance index of Wiklund, the psychological well-being index of Dupuy, and the Short Form 36 questionnaire of Stewart. The internal consistency and reliability of the multi- item scales were estimated by Cronbachs alpha coefficients. Results: The effects of the two treatment regimens on pain index and number of addi tional sublingual nitrate tablets required were not different. However, based on the New York Heart Association (NYHA) angina classification, patients improved better on the once-daily than on the multiple-dose regimen: by > 1 category in 281 vs 62 of the patients (P<0.0001) ; mobility and psychological distress indices also improved (P = 0.006, and P=0.007). Conclusions: Once-daily nitrate therapy not only provides a better NYHA angina classifi cation than multiple-dose therapy does, but also provides a better quality of life as estimated by improvement of mobility and distress indices, the most important indicators of quality of life in this category of patients.

Combined assessment of technetium-99m SESTAMIBI planar myocardial perfusion images at rest and during exercise with rest/exercise left ventricular wall motion studies evaluated from gated myocardial perfusion studies

The favorable physical characteristics of technetium-99m-labeled 2-methoxy-2-methylisopropyl-1-isonitril (Tc-SESTAMIBI) enable the combined evaluation of both myocardial perfusion and left ventricular wall motion. To assess the potential of rest and exercise regional myocardial function as an adjunct to planar myocardial perfusion imaging, 60 patients with coronary artery disease and documented arteriographic findings were studied with both protocols during a single study. Exact segmental concordance between myocardial perfusion and wall motion studies was 77% (701/900 segments). Overall sensitivity and specificity to detect hemodynamically significant coronary artery disease with Tc-SESTAMIBI myocardial perfusion imaging were 89% and 79%, respectively, with resting wall motion studies 83% and 71%, respectively, and with rest/exercise wall motion studies, 85% and 71%, respectively. If the results of both perfusion and rest/exercise studies were combined, sensitivity increased to 96% and specificity decreased to 64%. The differences with perfusion studies alone were not statistically significant. Thus despite a good correlation between regional left ventricular function and perfusion, no statistically significant incremental diagnostic value was found when the results of both perfusion and wall motion studies were combined.

Raynaud's syndrome, an enigma after 130 years.

The recent literature concerning Raynauds syndrome is reviewed. Ray nauds syndrome is as common as hypertension and diabetes. In spite of its generally benign character, it causes a lot of discomfort to individuals and sick ness absenteeism to society, especially in the colder regions of the world. The etiology remains an enigma 130 years after its first description, perhaps even more so than ever before, the many new theories proposed in the litera ture. Clearly, in a condition where seventy different etiologic theories are advo cated, the culprit lesion is obviously missing, or there is not a culprit lesion but an accumulation of conditions having nothing in common but a few symptoms. Moreover a Raynaud attack may result, not from a single event, but from a cascade of events, just as, for example, hemostasis does. Controversy about diagnosis exists all over. For example, how does one make a diagnosis? Patient history has been considered unreliable. A standardized cold test, though highly reproducible in the authors hands, is far from common property. Raynauds syndrome is a condition for which thirty-eight therapies have been advocated in the last three years, but the curative answer is still to come.

NUCLEAR CARDIOLOGY, CURRENT APPLICATIONS IN CLINICAL-PRACTICE

The clinical applications of nuclear cardiology have rapidly expanded since the introduc tion of suitable imaging cameras and readily applicable isotopes. The currently available methods can provide useful data on estimates of ventricular function and detection of myocardial ischemia for adequate patient management. Two standard procedures are routinely used: (1) myocardial perfusion scintigraphy, eg, with thallium 201; and (2) radionuclide angiocardiography by using technetium 99m-labeled red blood cells. Myocardial perfusion scintigraphy provides information on regional viability and estimates regional myocardial perfusion by measuring regional tracer activity. Thallium 201 is the agent used for noninvasive assessment of myocardial perfusion and for improving the results of exercise electrocardiography. Alternative tests, such as pharmacologic stress testing with dipyridamole, have been proposed as a reliable substitute for exercise testing. Additional quantitative analysis and computed tomography have increased the sensi tivity and specificity of thallium scintigraphy. Radionuclide angiography techniques are used for the noninvasive evaluation of cardiac function, right and left ventricular function, and wall motion abnormalities. As in perfusion scintigraphy, radionuclide angiography has proven its value for the detection of coronary artery disease (CAD). Abnormal regional wall motion abnormalities are specific for CAD.

Patients with a normal exercise thallium-201 myocardial scintigram : always a good prognosis?

The prognostic value of a normal exercise thallium-201 scintigram was determined in 211 patients with a normal exercise and resting scintigram. Endpoints were sudden cardiac death, non-fatal acute myocardial infarction and coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Forty patients (19%) had a history of a previous myocardial infarction and 40 (19%) were known to have had a previous percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. Sixty-four patients (31%) were on treatment with β-blocking agents. After a mean follow-up period of 23.5 months, 22 patients had had a cardiac event (1 cardiac death, 6 myocardial infarction, 15 revascularization). For the total group, the 1-year event rate for cardiac death, myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting was 7.0%. For cardiac death or myocardial infarction alone the event rate was 2.8%. The only parameter independently predictive for cardiac events was the regular use of β-blocking agents. The high event rate in patients on β-blocking treatment is partly due to the fact that these patients were more symptomatic for coronary artery disease. The sustained β-adrenergic blockade in this patient group, even in patients advised to stop medication, was suspected to interfere with the results of 201Tl scintigraphy. Therefore, more attention should be paid to patient instruction regarding the discontinuation of medication before the test.

Nitrate-Induced Headache in Patients with Stable Angina Pectoris: Beneficial Effect of Starting on a Low Dosage

Background: Nitrates, although important for the management of angina pectoris, cause significant headache in many patients. Methods: In a randomized, double-blind, crossover study, 89 patients with stable angina pectoris were studied to compare two different dosage strategies of isosorbide-5-monon itrate (5-ISMN). Patients were randomized to either 60 mg 5-ISMN once daily (od) for two weeks or to 30 mg 5-ISMN od for one week followed by 60 mg 5-ISMN od for one week. Then, there was a two-week placebo washout, after which the alternative treatment was given. The authors assessed the occurrence of angina pectoris and headache by diary cards while taking into account the numbers of isosorbide dinitrate sublingual puffs and paracetamole tablets required. Data were assessed for carryover and time effects. Results: The two dosage regimens were equally efficient for the relief of angina pectoris without development of tolerance. Thirty percent of the patients never experienced headache from the given dosages. In the remainder of them there was a highly significant time effect: the overall numbers of headache attacks in the first period of active treatment versus the second were 2,380 vs 1,400 (P < 0.003). Yet significantly fewer patients had headache on low dosage than on high dosage (45 vs 57, P < 0.02). Conclusions: (1) Starting on a low dosage was associated with a reduced frequency and severity of headache and did not notably influence the beneficial effect on angina pectoris. (2) One in 3 patients never experienced headache from the given dosages. (3) The overall number of headache attacks in the first period of active treatment was signif icantly higher than in the second period irrespective of the dosages given.

Changes in life-style in men under sixty years of age before and after acute myocardial infarction: a case-control study.

A case-control study was conducted to examine the presence of psychosocial factors before, during, and after acute myocardial infarction (AMI) in Dutch men under sixty years of age. The study included 42 AMI patients and 48 individuals in an age-adjusted sampled control group. The psychological factors included high level of psychological stress, of social isolation, type A1 and A2 behavior, and mental depression. They were assessed by means of the Health Insurance Questionnaire of Greater New York. Univariate analysis indicated that the presence of psychological factors was common at the onset of the myocardial infarction (MI). It clearly diminished, however, after the MI had taken place. In a stepwise logistic regression analysis after adjustment for the independent variables hypertension, cholesterol, and smoking, the following three characteristics were independently related to the risk of MI: no talking (item of social isolation, P = 0.008), need to excel (item of type A1 behavior, P = 0.04), and blue feeling (item of mental depression, P= 0.09). The authors conclude that in men under 60 with AMI, the presence of psychosocial characteristics is common and that this gruop is going to change its

A Randomized, Placebo-Controlled Study of Loop Diuretics in Patients with Essential Hypertension: The Bumetanide and Furosemide on Lipid Profile (BUFUL) Clinical Study Report

This study was conducted to determine whether loop diuretics are more effective than placebo in reducing blood pressure without raising serum lipid levels, and whether bumetanide is more effective than furosemide in this respect. In a double‐blind, 24‐week placebo‐controlled crossover study, 27 patients with essential hypertension were treated in four periods of 6 weeks each, including placebo twice, furosemide 40 mg daily, and bumetanide 1 mg daily. Several metabolic parameters, including serum lipid levels, and blood pressure were assessed. Overall levels of total cholesterol, triglycerides, and low‐density lipoprotein (LDL) cholesterol were 5%, 12.4%, and 4.8% higher, respectively, during loop diuretic therapy than during placebo treatment. Overall systolic and diastolic blood pressure measurements were 12 mmHg and 4 mmHg lower, respectively, during loop diuretic therapy than during placebo treatment. Any added effect of bumetanide on serum lipid levels and blood pressure compared with furosemide, however, could not be confirmed. Our results indicate that the loop diuretics bumetanide and furosemide are effective in reducing blood pressure, and influence serum lipid levels markedly less than do thiazide diuretics or chlorthalidone. In addition, these results indicate that differences in blood pressure reduction and serum lipid levels between the two compounds were small and nonsignificant.