Dobutamine stress echocardiography for detection and assessment of coronary artery disease.

Stress echocardiography with dobutamine infusion for detection of coronary artery disease is a potential alternative to exercise stress testing with some theoretic advantages. Fifty patients who were not receiving cardioactive medication were prospectively studied with two-dimensional echocardiography and 12-lead electrocardiography (ECG) during incremental dobutamine infusion (5, 10, 15 and 20 micrograms/kg body weight per min, each dose for 8 min). Images were analyzed by using an 11-segment left ventricular model. All patients underwent correlative exercise ECG and coronary angiography, which revealed normal coronary arteries in 14 and significant disease (greater than or equal to 70% diameter stenosis) in 36. Peak rate-pressure product during dobutamine infusion was 18,845 +/- 4,156 versus 23,740 +/- 6,158 mm Hg/min on exercise (p less than 0.01). Interobserver concordance for wall motion analysis was good (kappa coefficient = 0.77). The use of baseline (n = 14) or reversible (n = 24) regional asynergy to define an abnormal dobutamine echocardiogram resulted in a sensitivity for detecting coronary artery disease of 78% and a specificity of 93%. Corresponding data for the dobutamine ECG were 47% and 71% and for the exercise ECG were 72% and 71%, respectively. The development of new mitral regurgitation on Doppler color flow imaging (n = 4) improved sensitivity to 81% without loss of specificity. Inducible asynergy or new mitral regurgitation was observed in 6 (50%) of 12 patients with single-, 6 (60%) of 10 with double- and 12 (86%) of 14 with triple-vessel disease. The site of transient asynergy provided additional localizing information. Exercise duration and time to diagnostic ST segment shift were shorter in patients with coronary artery disease with versus those without echocardiographic evidence of ischemia (both p less than 0.05). Side effects during dobutamine infusion were mild and short-lived. Dobutamine stress echocardiography is well tolerated, is useful for detection and assessment of coronary artery disease and is applicable to patients unable to exercise.

Magnitude of myocardial dysfunction is greater in painful than in painless myocardial ischemia: an exercise echocardiographic study.

OBJECTIVES: This study sought to assess the presence and extent of inducible myocardial dysfunction during painful and painless (silent) myocardial ischemia in a homogeneous patient cohort with coronary artery disease and no previous myocardial infarction. BACKGROUND: The functional significance of painless versus painful demand-driven ischemia remains controversial, with conflicting results in published reports regarding the amount of myocardium in jeopardy. METHODS: Exercise echocardiography was performed in 89 patients (mean [+/- SD] age 59.3 +/- 8.2 years) with significant coronary artery disease and positive exercise stress test results. Patients were taking no antianginal medications and were classified into painless and painful cohorts after the outcome of a symptom-limited treadmill exercise test. No patients had previous coronary artery bypass surgery. Images were acquired in digital format before and immediately after treadmill exercise testing. RESULTS: Fifty-eight patients had painful and 31 painless myocardial ischemia. Clinical and demographic characteristics as well as coronary artery anatomy were similar in both groups. Patients with painless ischemia achieved better exercise performance with greater exercise duration (p < 0.001) and higher maximal rate-blood pressure product (p < 0.001) than those with painful ischemia. New wall motion abnormalities were seen in 54 patients (93%) with painful versus 17 (55%) with painless ischemia (p < 0.001). Total ischemic score was greater in patients with painful than in those with painless ischemia (15.9 +/- 3.7 vs. 12 +/- 1.4, p < 0.001, respectively), with a greater number of ischemic myocardial segments in painful than in painless ischemia (101 [16%] vs. 21 [6%], p < 0.001, respectively). CONCLUSIONS: Patients with painless ischemia frequently have regional myocardial dysfunction on exertion detected by echocardiography, but painful episodes are accompanied by a greater magnitude of myocardial dysfunction.

Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects of a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3,100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean +/- SD, -17 +/- 14%), increases in mean right atrial (31 +/- 21%), mean pulmonary artery (14 +/- 14%) and mean pulmonary capillary wedge (17 +/- 14%) pressures and an increase in cardiac index (18 +/- 10%) due to an increased heart rate without any significant change in stroke volume. During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease. It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients.

Diastolic function in hypertrophic cardiomyopathy: relation to exercise capacity.

Doppler echocardiography was used to assess diastolic function in 40 patients with hypertrophic cardiomyopathy and to relate it to the patients' symptoms, anaerobic threshold and maximal oxygen consumption during cardiopulmonary exercise testing. The patients had a smaller early (E wave) (p less than 0.01), higher late (A wave) (p less than 0.05) mitral diastolic flow velocity, larger A/E ratio (p less than 0.01), longer isovolumetric relaxation time and E wave duration (p less than 0.001) and slower deceleration rate of the E wave (p less than 0.001) than 40 age- and gender-matched normal subjects. In the patients with hypertrophic cardiomyopathy, maximal oxygen consumption and anaerobic threshold were, respectively, 26.3 +/- 9.2 and 21.1 +/- 6.1 ml/kg per min compared with 47 (range 39 to 68) (p less than 0.01) and 41 (range 27 to 58) ml/kg per min (p less than 0.01) in normal subjects. There was no relation between Doppler indexes and symptoms but symptomatic patients had lower maximal oxygen consumption and anaerobic threshold compared with asymptomatic patients (21.4 +/- 7 vs. 30.7 +/- 10, p less than 0.001 and 18.6 +/- 4.7 vs. 23.1 +/- 5.7, respectively, p less than 0.001). In conclusion, Doppler echocardiography can identify abnormalities of left ventricular filling in patients with hypertrophic cardiomyopathy. However, these indexes measured at rest do not correspond to the patient's professed symptomatic status or exercise capacity measured objectively. Conversely, cardiopulmonary exercise testing reveals a depressed maximal oxygen consumption and anaerobic threshold even in the least symptomatic patients.

Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension.

Endothelium-dependent vasodilation of the pulmonary vascular bed was investigated in five patients with primary pulmonary hypertension. Three endothelium-dependent vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in two patients]) were infused sequentially into the right atrium, followed by nicardipine given orally during full hemodynamic monitoring. Acetylcholine, calcitonin gene-related peptide and substance P had no effect on pulmonary artery pressure, total pulmonary vascular resistance or cardiac output, although calcitonin gene-related peptide significantly decreased systemic arterial systolic pressure from 132 +/- 34 to 113 +/- 33 mm Hg. In contrast, oral nicardipine decreased total pulmonary vascular resistance from 23 +/- 12 to 13 +/- 8 U, with a concomitant increase in cardiac output from 3.1 +/- 1 to 4.7 +/- 2 liters.min-1 and decrease in systemic vascular resistance from 30 +/- 9 to 13 +/- 4 U. Thus, despite the presence of a reversible component in these five patients with primary pulmonary hypertension, pulmonary vascular resistance did not decrease in response to the infused endothelium-dependent vasodilator agents, indicating that endothelium-dependent vasodilation is impaired in these patients.

A double-blind, placebo-controlled crossover trial of nadolol and verapamil in mild and moderately symptomatic hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to determine whether therapy with a beta-adrenergic or calcium channel blocking agent can improve the functional capacity and quality of life of patients with mild or moderately symptomatic hypertrophic cardiomyopathy. BACKGROUND: Both beta-blockers and calcium channel blockers may alleviate symptoms in hypertrophic cardiomyopathy, but previous studies have been performed in hospitalized patients or have been open studies without control subjects. METHODS: A randomized, double-blind crossover trial of nadolol, verapamil and placebo, administered for periods of 4 weeks each, was performed in 18 patients with mild or moderately symptomatic hypertrophic cardiomyopathy (10 men, 8 women; mean age +/- SD 39 +/- 17 years). A detailed symptom assessment, bicycle exercise testing, echocardiography and Holter monitoring were performed in each period. RESULTS: Two patients withdrew from the study owing to symptomatic sinus bradycardia during nadolol therapy. Neither drug improved maximal oxygen consumption (placebo 26 +/- 8, verapamil 23 +/- 6, nadolol 21 +/- 7 ml/kg per min; p = 0.1). Peak exercise work load was reduced by > or = 10 W in 13 patients (81%) during nadolol therapy and in 4 patients (25%) during verapamil therapy (p = 0.005, nadolol vs. verapamil). Despite the effects on exercise capacity, 13 patients (81%) preferred drug treatment (8 verapamil, 5 nadolol) over placebo (p = 0.001). Verapamil improved reported performance at work compared with nadolol (p = 0.01) and tended to improve other measures of health-related behavior and symptoms compared with nadolol and placebo. CONCLUSIONS: In patients with mild or moderately symptomatic hypertrophic cardiomyopathy, exercise capacity was not improved by nadolol or verapamil, and individuals were more often impaired by nadolol than with verapamil. Nevertheless, many patients derived symptomatic benefit from drug therapy, especially with verapamil.

Renal response to candoxatrilat in patients with heart failure.

OBJECTIVES: Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied. BACKGROUND: Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study. METHODS: In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing. RESULTS: All doses of candoxatrilat increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h). CONCLUSIONS: Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.

Relation of left ventricular function and prognosis in hypertrophic cardiomyopathy: an angiographic study.

Left ventricular cineangiograms performed at the time of diagnosis in 88 patients with hypertrophic cardiomyopathy were digitized to evaluate the relation of left ventricular function and prognosis in hypertrophic cardiomyopathy. Eleven patients died suddenly after a mean follow-up period of 7.5 +/- 7 years, 10 patients died of congestive heart failure or after cardiac surgery and 67 were alive after a mean follow-up period of 8.6 +/- 4 years. Measurements of left ventricular volume, ejection fraction, peak rate of ejection and filling and time to peak rate of ejection and filling were derived from curves of ventricular volume and its rate of change during the cardiac cycle. Patients who died suddenly had a lower peak rate of ventricular ejection (stroke volume-normalized peak ejection rate 5.41 +/- 0.69 versus 6.24 +/- 1.33 s-1; p = 0.006) and lower peak rate of ventricular filling (end-diastolic volume-normalized peak filling rate 4.02 +/- 0.94 versus 4.88 +/- 1.53 s-1; p = 0.02) and stroke volume-normalized peak filling rate (4.75 +/- 1.08 versus 5.82 +/- 1.70 s-1; p = 0.01) compared with survivors. Stepwise regression analysis revealed that sudden death was best predicted by the combination of increased end-diastolic volume, small end-systolic volume and low peak filling rate (predictive accuracy 32%, false negative 18% and false positive 28%). The addition of clinical features and hemodynamic measurements to the analysis improved predictive accuracy to 43% (false negative 18% and false positive 18%). Ambulatory electrocardiographic monitoring performed in 57 of the 88 patients 1 month to 17 years (median 8 years) after diagnosis revealed ventricular tachycardia in 14 (25%). Of these, 10 who survived had hyperkinetic systolic function at diagnosis, whereas the 4 who died suddenly had impaired systolic function (end-diastolic volume-normalized peak ejection rate 5.93 +/- 1.2 versus 4.01 +/- 1.2 s-1, respectively; p = 0.04). In hypertrophic cardiomyopathy, ventricular tachycardia is a sensitive but nonspecific marker of adults who are at risk of sudden death. Impaired systolic function may be an important determinant of which patients with ventricular tachycardia die suddenly. This study shows that indexes of ventricular function contribute to the identification of patients at particular risk of sudden death. However, the predictive power of the clinical features and hemodynamic and angiographic measurements that could be assessed was poor.(ABSTRACT TRUNCATED AT 400 WORDS)

Significance of abnormal electrocardiograms in highly trained athletes.

Electrocardiographic and other abnormalities of highly trained athletes are well recorded but not well enough known, and the more extreme changes still cause diagnostic confusion. This problem was exemplified by 10 athletes, all referred to us by cardiologists because of a diagnosis of organic heart disease. After thorough investigation, including catheter studies, all but 1 of these patients was regarded as normal and all returned to competitive sports. The criteria for diagnosing heart disease in athletes are discussed in light of the findings in 10 patients. Exercise electrocardiography and echocardiography help to exclude organic disease, but left heart catheterization is justified when doubt still exists.

Prognostic value of dobutamine echocardiography in patients with high pretest likelihood of coronary artery disease.

To examine the value of transient regional asynergy on dobutamine stress echocardiography as a noninvasive predictor of future cardiac events, 51 symptomatic patients (aged 54 +/- 9 years) with suspected coronary artery disease (CAD) were studied using an incremental regimen of 5, 10, 15 and 20 micrograms/kg/min. Pretest likelihood of CAD was (mean +/- standard error of the percentage) 79.7 +/- 5.6% before and 83.4 +/- 5.2% after exercise electrocardiography using probability analysis based on age, sex and symptoms. Two-dimensional images were analyzed with reference to an 11-segment model and gave good interrater agreement. During 24 +/- 4 months (range 19 to 32) of follow-up, 23 patients had events (1 myocardial infarction, 9 unstable angina, 10 coronary bypass surgery, 3 coronary angioplasty) and 28 were event free. Age, proportion with baseline asynergy and both pretest echocardiographic ejection fraction and its response to dobutamine were similar in these 2 groups (all p = not significant). Transient asynergy was seen in 17 of 23 patients (74%) with and 8 of 28 patients (29%) without events (p < 0.01); 5 of 6 patients (83%) with involvement of 3 segments had events. Myocardial infarction or unstable angina occurred in 8 of 25 (32%) with a positive and 2 of 26 (8%) with a negative stress echocardiogram (p < 0.05). Both exercise duration (389 +/- 195 vs 517 +/- 237 seconds, p < 0.05) and time to diagnostic ST-segment shift (291 +/- 192 vs 447 +/- 212 seconds, p = 0.05) were shorter in those with inducible asynergy.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of dipyridamole-Doppler echocardiography for detection of myocardial ischemia and coronary artery disease.

Doppler assessment of left ventricular filling and ejection during dipyridamole stress may supplement wall motion analysis for detection of myocardial ischemia and coronary artery disease (CAD). Thirty-four patients taking no cardioactive therapy were studied using intravenous dipyridamole (0.6 mg/kg) during 2-dimensional and pulsed Doppler echocardiography. Twelve patients had normal coronary arteries (group 1) and the remainder, who had significant CAD, were divided into groups 2 (n = 11) and 3 (n = 11). Only subjects in group 2 developed myocardial ischemia manifest as reversible regional asynergy and ST-segment depression. Heart rate increased (16 +/- 9 beats/min, p less than 0.01) and mean blood pressure decreased (-5 +/- 8 mm Hg, p = not significant) uniformly across groups. Exaggerated hyperkinesia of normally contracting wall segments was the common response to dipyridamole infusion in patients with CAD. The respective mean percent changes in peak early diastolic velocity, peak atrial velocity, their ratio and ejection peak velocity, and mean acceleration for groups 1 (20, 42, -13, 20 and 23%), 2 (22, 32, -2, 10 and 14%) and 3 (23, 33, -6, 16 and 18%) were similar. Comparisons between normal patients and those with CAD and between groups 2 and 3 revealed no significant differences in the effect of dipyridamole on any variable. However, a decrease in both peak velocity and mean acceleration of left ventricular ejection was seen in 3 of 4 group 2 patients who developed severe ischemia. Dipyridamole-Doppler echocardiography is insensitive for detection of CAD and appears unable to identify myocardial ischemia unless this is severe. Hemodynamic changes and compensatory wall motion induced by dipyridamole may explain these findings.

Adrenergic hypersensitivity after beta-blocker withdrawal in hypertrophic cardiomyopathy.

Withdrawal of beta-blocker therapy has been associated with the development of adrenergic hypersensitivity and adverse clinical effects in patients with coronary artery disease and hypertension. The aim of this study was to establish the occurrence and clinical significance of adrenergic hypersensitivity after abrupt withdrawal of long-term beta blockade in hypertrophic cardiomyopathy. Beta-adrenergic sensitivity was measured using the isoprenaline chronotropic dose25. Symptom assessment chronotropic dose25 calculation, bicycle exercise, echocardiography and Holter monitoring were performed while the patient received beta-blocker therapy and repeated on days 2, 4, 6, 8 (acute withdrawal period) and on day 21 after abrupt withdrawal. The study was terminated after 7 patients had been studied because all patients experienced a marked deterioration in symptoms and several clinical events had occurred. The chronotropic dose25 (mean +/- standard deviation) demonstrated beta 1-adrenergic hypersensitivity with a minimal value of 1.6 +/- 0.8 micrograms during the acute withdrawal period compared with 3.8 +/- 1.7 micrograms on day 21 (p = 0.003). Heart rates during rest and exercise showed an overshoot increase during the acute withdrawal period. The maximal 24-hour ventricular ectopic count was higher during the acute withdrawal period than during day 21 (p = 0.04). Of 3 patients with inducible outflow tract gradients, 2 developed resting gradients greater than 30 mm Hg during the acute withdrawal period. There was an increase in peak late filling velocity of mitral inflow after beta-blocker withdrawal. In conclusion, transient beta-adrenergic hypersensitivity occurs after beta-blocker withdrawal in hypertrophic cardiomyopathy and is associated with significant physiologic changes and adverse clinical consequences.

Influence of left ventricular hypertrophy and function on the occurrence of ventricular tachycardia in hypertrophic cardiomyopathy.

Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2-dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine the relation between the degree of left ventricular (LV) hypertrophy and dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT. Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses, was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p = not significant). Furthermore, no significant differences were found between the 2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11 mm). An LV outflow tract gradient was detected in 25% of patients with and 35% without VT (p = not significant). One or more Doppler indexes of diastolic function were abnormal in 70% of patients, but no difference in any of these indexes was found between those with and without VT. In summary, the occurrence of VT in hypertrophic cardiomyopathy is not related to the degree of LV hypertrophy, outflow tract gradient or dysfunction. This finding suggests a dissociation between the arrhythmogenic substrate and echocardiographic features of the disease.

Detection of atherosclerotic lesions in the aorta by transesophageal echocardiography.

Transesophageal echocardiographic studies were prospectively performed in 152 consecutive patients older than age 40 years referred to the echocardiography laboratory to assess the prevalence of atherosclerosis in the thoracic aorta and relate this to a history of systemic embolization. Forty-four patients (29%) had at least 1 atherosclerotic lesion in the thoracic aorta. This was associated with a higher prevalence of coronary artery disease (78% of all patients with coronary artery disease), carotid artery disease (88% of all patients with carotid artery disease) and peripheral vascular disease (all symptomatic patients). Forty-two of all patients (28%) had systemic emboli, 20 (48%) of whom had at least 1 atheromatous lesion in the thoracic aorta. Conversely, only 24 of 110 patients (22%) without previous systemic emboli had atheromatous lesions (p < 0.001). It is concluded that atherosclerotic lesions in the thoracic aorta can readily be identified with transesophageal echocardiography. The detection of atherosclerotic plaques of the aorta represents a marker of diffuse atherosclerotic disease, often associated with carotid, coronary and peripheral vascular disease and with the occurrence of systemic emboli. Transesophageal echocardiography may be used serially to investigate whether dietary or pharmacologic maneuvers, or both, can shrink established atherosclerotic plaques in the thoracic aorta.

Arrhythmia in hypertrophic cardiomyopathy: exercise and 48 hour ambulatory electrocardiographic assessment with and without beta adrenergic blocking therapy.

Submaximal treadmill exercise electrocardiography and 48 hour ambulatory electrocardiographic monitoring were performed in 30 patients with hypertrophic cardiomyopathy both with and without beta adrenergic blocking therapy. During ambulatory electrocardiographic monitoring 1 patient (3 percent) had no arrhythmia, 14 patients (46 percent) had supraventricular tachycardia or paroxysmal atrial fibrillation, 13 (43 percent) had multiform or paired ventricular extrasystoles and 8 (26 percent) had ventricular tachycardia. The frequency of these ventricular arrhythmias was almost identical with and without beta adrenergic blocking drugs (mean dose in "propranolol equivalents" 280 mg daily). With beta blocking therapy fewer patients had supraventricular tachycardia; however, the difference was not significant. During exercise testing 18 patients (60 percent) had ventricular extrasystoles and 3 patients (10 percent) had paired ventricular extrasystoles and the frequency was almost identical with and without beta adrenergic blocking therapy. No routine echocardiographic or hemodynamic measurement predicted the serious ventricular arrhythmias. It is concluded that asymptomatic ventricular arrhythmia is a common occurrence in patients with hypertrophic cardiomyopathy and its frequency is not reduced with beta adrenergic blocking therapy. Because occult arrhythmia may be the cause of sudden death it is important to detect it in these patients so that an effort can be made to improve prognosis with specific antiarrhythmic treatment.

The functional defect in amyloid heart disease. The "stiff heart" syndrome.

Left ventricular performance was studied in three patients with heart failure due to amyloid deposits. The diagnosis of amyloidosis was proved by cardiac biopsy in two patients and by rectal biopsy in the third. One patient had myelomatosis, but the other two had no other identifiable disease. The investigative technique allowed simultaneous measurements of pressure and volume in the left ventricle. The functional defect with slow cardiac filling at high pressure and greatly reduced left ventricular contraction differed from that of constrictive pericarditis and other heart muscle disease. These features of a "stiff heart" are probably unique to amyloidosis and should make possible positive recognition of the condition on the basis of echocardiographic, angiographic and hemodynamic findings.

Comparison of usefulness between exercise capacity and echocardiographic indexes of left ventricular function in cardiac amyloidosis.

In patients with primary systemic amyloidosis (AL), the echocardiographic assessment of ventricular function alone does not always correspond to patients' symptoms and functional status. Peak oxygen uptake and anaerobic threshold (AT), in contrast, constitute 2 objective, reliable and reproducible indicators of functional status in patients with circulatory failure. Thirty-two consecutive patients (mean age 50 +/- 13 years) with histologic evidence of systemic primary AL were studied (29 AL, 3 hereditary). There were 16 with echocardiographic features of cardiac infiltration (group I) and 16 without (group II). Twenty age- and gender-matched healthy subjects were also studied for comparison. Of the 32 patients, 12 were in New York Heart Association functional class I, 9 were in class II, and 11 were in class III. Each subject underwent 2-dimensional and Doppler echocardiography and cardiopulmonary exercise testing using a modified Bruce protocol. Left atrial (LA), left ventricular (LV) dimensions, wall thickness, and LV fractional shortening, as well as transmitral flow velocities and their E/A ratio were measured. Peak oxygen consumption (VO2max [ml/kg/min]), AT (ml/kg/min), and exercise duration (seconds) were also measured. VO2max and AT were lower in patients with AL than in controls (20.8 +/- 7.0 vs 35.0 +/- 8.5, p <0.001 and 13.1 +/- 3.7 vs 27.0 +/- 4.2, p <0.001, respectively). As a group, symptomatic patients had lower VO2max, AT, and exercise duration than those without symptoms (17.1 +/- 3.6 vs 27.0 +/- 6.9, p = 0.0001, 11.1 +/- 2.1 vs 16.2 +/- 3.6, p = 0.0001, and 489 +/- 235 vs 843 +/- 197, p = 0.0001, respectively), whereas LV dimensions only showed a small difference (p = 0.03). VO2max, AT, and exercise duration of patients in functional class I were higher than those in functional classes II and III (p = 0.01, p <0.05, and p = 0.007, respectively). Asymptomatic patients had lower VO2max, AT, and exercise duration than controls (p <0.0001). VO2max, AT, and exercise duration were poorly related to LA diameter, LV dimensions, fractional shortening, wall thickness, peak velocities of E and A waveforms, and E/A ratio. Patients with VO2max > 15 ml/kg/min had a better survival than patients with VO2max < 15 ml/kg/min. Thus, in patients with primary systemic AL, cardiorespiratory exercise testing is the preferred way of assessing functional capacity. Echocardiographic Doppler indexes at rest are not predictive of a patient's symptoms and exercise capacity. Furthermore, VO2max is a strong independent predictor of survival in these patients.

Angiotensin-converting enzyme inhibitors, left ventricular dysfunction, and early heart failure.

A study was undertaken to examine the effects of the angiotensin-converting enzyme inhibitor lisinopril on exercise performance in 18 patients with major impairment of left ventricular systolic function. The study was a randomized, double-blind, crossover design, and patients received treatment with either once-daily lisinopril (2.5-10 mg) or placebo for a period of 6 weeks. A total of 15 patients completed the study. Compared with placebo, lisinopril had no significant effect on supine or standing blood pressure or heart rate. Although lisinopril had no effect on exercise duration during a low-intensity exercise protocol, in patients undergoing a high-intensity exercise protocol, there was a trend toward improved exercise time and peak oxygen consumption improved significantly. In addition, treatment with lisinopril resulted in an increase in renal blood flow and a reduction in glomerular filtration rate. Moreover, administration of once-daily lisinopril 10 mg resulted in a decrease in plasma concentrations of angiotensin II, aldosterone, and atrial natriuretic peptide, and an increase in plasma concentrations of active renin.

Effects of aging on neuroendocrine activation in subjects and patients in the presence and absence of heart failure with left ventricular systolic dysfunction.

The neuroendocrine profile and echocardiographic features of 40 patients (81 +/- 1 years, means +/- standard error) with heart failure and impaired left ventricular systolic function were compared with those of an age-matched group of healthy subjects, 20 younger patients with heart failure (aged 58 +/- 1 years) and 15 younger healthy subjects. Normal elderly subjects had a neuroendocrine profile similar to that of healthy younger subjects apart from elevated plasma norepinephrine (958 +/- 84 vs 302 +/- 118 pg/ml; p< 0.001) and atrial natriuretic peptide ( 40 +/- 6 vs 28 +/- 5 pg/ml; p<0.05). Despite a similar severity of heart failure, elderly patients had smaller ventricular dimensions (left ventricular internal dimension in diastole 51 +/- 2 vs 69 +/- 3 mm;p<0.0001 and greater impairment of ventricular compliance using Doppler indexes. Plasma norepinephrine was higher (1,191 +/- 80 vs 620 +/- 67 ppg/ml; p<0.01), and plasma atrial natriuretic peptide, plasma active renin, and angiotensin II were lower in elderly patients than in the younger patients with heart failure. As functional capacity declines with age, elderly patients may have less severe cardiac dysfunction for any given level of functional impairment, and this may account for most of the differences in neuroendocrine activity with age. Age appears to be an important determinant of plasma norepinephrine and may be a confounding factor in interpreting the prognostic significance of this hormone.

Effect of preload change on resting and exercise cardiac performance in hypertrophic cardiomyopathy.

The purpose of this study was to investigate the hemodynamic responses, at rest and on exercise, of patients with hypertrophic cardiomyopathy to changes in circulating volume. After Swan-Ganz and radial arterial cannulation, 13 patients with hypertrophic cardiomyopathy performed maximal exercise tests after diuretic (frusemide 20 mg intravenously) and after fluid loading (0.9% saline at 10 ml/kg body weight intravenously) on different days. At rest, right atrial and pulmonary capillary wedge pressures increased with volume loading and decreased with a diuretic. There were no significant changes in the resting, supine cardiac or stroke indexes but in the upright position, the cardiac index and stroke index were higher after volume loading (2.5 +/- 0.7 vs 2.2 +/- 0.5 liters/min/m2, p less than 0.05; 33 +/- 11 vs 27 +/- 9 ml/m2, p less than 0.005, respectively). Although the right atrial, pulmonary arterial and pulmonary capillary wedge pressures were higher during exercise after volume loading, there were no significant differences in exercise heart rate, systemic blood pressure, cardiac index, stroke index, systemic vascular resistance index or overall exercise capacity compared to exercise after diuresis. The data show that the cardiac index and stroke index, at supine rest and during upright exercise, were not influenced by the preload changes induced in these patients with hypertrophic cardiomyopathy. The results suggest that these patients are operating on the plateau of left ventricular Frank-Starling function (filling pressure/output) curve.