Echocardiographic detection of early diabetic myocardial disease

OBJECTIVES: We sought to determine whether disturbances of myocardial contractility and reflectivity could be detected in diabetic patients without overt heart disease and whether these changes were independent and incremental to left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular (LV) dysfunction is associated with diabetes mellitus, but LVH is common in this population and the relationship between diabetic LV dysfunction and LVH is unclear. METHODS: We studied 186 patients with normal ejection fraction and no evidence of CAD: 48 with diabetes mellitus only (DM group), 45 with LVH only (LVH group), 45 with both diabetes and LVH (DH group), and 48 normal controls. Peak strain and strain rate of six walls in apical four-chamber, long-axis, and two-chamber views were evaluated and averaged for each patient. Calibrated integrated backscatter (IB) was assessed by comparison of the septal or posterior wall with pericardial IB intensity. RESULTS: All patient groups (DM, DH, LVH) showed reduced systolic function compared with controls, evidenced by lower peak strain (p < 0.001) and strain rate (p = 0.005). Calibrated IB, signifying myocardial reflectivity, was greater in each patient group than in controls (p < 0.05). Peak strain and strain rate were significantly lower in the DH group than in those in the DM alone (p < 0.03) or LVH alone (p = 0.01) groups. CONCLUSIONS: Diabetic patients without overt heart disease demonstrate evidence of systolic dysfunction and increased myocardial reflectivity. Although these changes are similar to those caused by LVH, they are independent and incremental to the effects of LVH.     

Assessment of myocardial viability by dobutamine stress echocardiography in patients with ischemic heart disease

Detection of viable (hibernating) myocardium is necessary for determination of prognosis and tactics of treatment of patients with ischemic heart disease. For detection of viable myocardium and investigation of possibilities of its restoration 60 patients with ischemic heart disease (54 men, mean age 52+/-8 years) were examined before coronary artery bypass grafting or coronary angioplasty. Presence of viable myocardium was characteristic for patients with multivessel coronary artery disease (83%) with stenoses >90%, with well developed collateral circulation (81%). Sustained restoration of contractility of hibernating segments for 1 year after revascularization was noted in 70% of cases. Dobutamine stress echocardiography was found to have high diagnostic potential for detection of viable myocardium.     

Acute myocardial infarction during a dobutamine stress echocardiography, in a patient with angiographically normal coronaries

We report a case of acute myocardial infarction during a dobutamine stress echo (DSE) study in a middle age man. Our patient experienced a severe crushing retrosternal pain at peak DSE study, at the time the ECG recorded an episode of non-sustained ventricular tachycardia followed by a persistent significant ST segment elevation in V2-V6 leads. Symptoms and ECG findings remained despite the use of intravenous (IV) nitrates and therefore thrombolysis was given. A subsequent coronary angiogram revealed only mild atheromatous changes but no stenosis.     

Effects of dobutamine on left ventricular performance and myocardial metabolic demands in patients with ischemic heart disease

Sixteen patients with coronary artery disease undergoing cardiac catheterization were studied. Eleven had previous infarcts and the patients were divided into two groups: In group I were 7 patients with no left ventricular dysfunction, no increase in ventricular size, or symptoms of congestive failure; group II included 9 patients with ventricular dysfunction, increased ventricular size, and 7 of the 9 had congestive failure. Each patient underwent a continuous infusion of dobutamine from 2.5 to 10 μUg/kg min^-1 with dosage increments of 2.5 μUg/kg at 15-minute intervals. Systemic and coronary hemodynamic measurements were obtained at the end of the 5 and 10 μUg/kg min^-1 infusion doses. Left ventricular performance improved (higher cardiac index, left ventricular stroke work index and mean systolic ejection rate, and lower left ventricular end-diastolic pressure), while heart rate, mean arterial pressure, and coronary sinus blood flow increased after dobutamine in the 16 patients. While patients in both groups had a rise in cardiac index, a reduction in left ventricular end-diastolic pressure, an unchanged mean arterial pressure and a rise in coronary blood flow, only patients in group I had a significant increase in heart rate, and only patients in group II had significant increases in left ventricular stroke work index and mean systolic ejection rate, and a significant reduction in systemic vascular resistance. Left ventricular oxygen consumption did not increase significantly in either group. However, 5 patients showed a decreased myocardial lactate extraction after 10 μUg/kg min^-1 of intravenous dobutamine, 3 from group I and 2 from group II. These 5 patients had less ventricular dysfunction than patients with a normal lactate response to intravenous dobutamine. We conclude that the improvement in left ventricular performance observed after dobutamine administration in patients with ischemic heart disease is not usually associated with a major increase in left ventricular oxygen consumption or with marked aggravation of myocardial ischemia. This appears to be particularly true in patients with relatively severe left ventricular dysfunction.     

Systolic functional response of normal older and younger adult left ventricles to dobutamine

To determine the systolic functional response of the aged left ventricle to catecholamines, 16 healthy, physically active subjects aged 62 to 72 years (group A) and 19 healthy adults aged 18 to 28 years (group B) were evaluated before and during infusion of 8 micrograms/kg/min of dobutamine. Phonocardiograms, electrocardiograms and M-mode echocardiograms were recorded simultaneously with a carotid pulse tracing. End-diastolic dimension and end-systolic pressure remained unchanged in the 2 groups. End-systolic dimension decreased 0.3 cm (p less than 0.001) in group A and 0.5 cm (p less than 0.001) in group B. Fractional shortening increased (p less than 0.001) from 34 +/- 4% to 38 +/- 5% in group A and from 34 +/- 4% to 43 +/- 4% in group B. Mean velocity of circumferential fiber shortening (Vcf) increased 0.6 circ/s (p less than 0.001) in group A and 1 circ/s (p less than 0.001) in group B. End-systolic pressure/dimension ratio increased 3 mm Hg/cm (p less than 0.001) in group A and 8 mm Hg/cm (p less than 0.001) in group B. The changes in end-systolic dimension, fractional shortening, Vcf and end-systolic pressure/dimension ratio were more significant in group B (p less than 0.001). Thus, the left ventricular systolic functional response to dobutamine is diminished in healthy older persons.     

A sodium channel enhancer, LY341311, increases myocardial contractile performance without increasing heart rate in conscious normal dogs: a comparison with dobutamine

BACKGROUND: Catecholamines and many inotropic agents increase cardiac contractility but also cause excessive myocardial O2 consumption (MVO2). We determined if the novel Na+ channel enhancer LY341311, which increases myocardial contractility independent of beta receptors, can produce significant cardiac inotropic effects compared with dobutamine but at lower oxygen cost in conscious dogs. METHODS AND RESULTS: Mongrel dogs were chronically instrumented for measurement of arterial pressure, left ventricular (LV) pressure and internal diameter, coronary blood flow, and arterial and coronary sinus O2 content. Both LY341311 and dobutamine produced dose-dependent increases in LV dP/dt, dP/dt/40, fractional shortening, and cardiac stroke work and minute work estimated from the LV pressure-diameter loop. The major difference between LY341311 and dobutamine was an opposing effect on heart rate with LY341311 slightly reducing it but dobutamine markedly increasing it. LY341311 caused a significantly smaller increase in MVO2 than dobutamine (P <.05) and produced similar cardiac inotropic effects, yielding a higher cardiac mechanical efficiency than dobutamine. However, after pacing to match heart rate with dobutamine LY341311 increased MVO2 markedly, approaching the same level as with dobutamine. CONCLUSIONS: The novel Na+ channel enhancer LY341311 caused significant increases in myocardial contractility and contractile performance without increasing heart rate. It had a beneficial energetic effect on the heart with significantly less O2 cost and improved cardiac mechanical efficiency.     

Radionuclide assessment of a normal left ventricular response to exercise in patients without evidence of heart disease

The aim of this study was to define normal left ventricularperformance at rest and during supine bicycle exercise withequilibrium radionuclide ventriculography in a normal populationother than young healthy volunteers. Thirty-one patients (meanage 45 years ± 9 SD) with chest pain of varying originandno evidence of heart disease proven by means of noninvasiveand invasive techniques were studied. Left ventricular ejectionfraction (LVEF) at rest averaged 0.64 ± 007 SD and increasedwith peak exercise to 0.73 ± 008 SD (P<0.005). Changein LVEF from rest to maximum exercise ranged within 0–0.19.Six patients (19%) failed to augment LVEF with exercise to morethan 0.05; none of the patients dropped LVEF during exercise.Multivariate analysis revealed no significant predictors ofLVEF response to exercise. However, there was a tendency thatresting LVEF and enddiastolic volume index with exercise mightinfluence LVEF response to exercise. Peak left ventricular ejectionrate (LVER) at rest averaged 3.3s^–1 ± 0.6 SD andincreased to 51 s^–1 ± 11 SD (P<0.005) with exercise.Peak left ventricular early filling rate (LVFR) was 2.8s^–1± 0.6 SD at rest and was measured 5.5 s^–1 ±l.3 SD at maximum exercise (P<0.005). Left ventricular enddiastolicvolume (EDV) did not change significantly from rest to maximumexercise, whereas left ventricular endsystolic volume (ESV)decreased to 79% ± 19 SD (P<0.01) of the value atrest. In conclusion, in a normal population other than healthy youngvolunteers LVEF does not necessarily have to increase with exercise.Moreover, besides an augmentation of heart rate a normal leftventricular response to supine exercise is associated with anincrease of LVER and LVFR, a decrease in ESV and no significantchange in EDV, suggesting augmented contractility and a virtuallynegligible role of the Frank-Starling mechanism during exercise.     

Prognostic significance of chronotropic response to dobutamine stress echocardiography in patients with peripheral arterial disease

Chronotropic response is important during exercise stress testing. Less is known about its role after dobutamine stress echocardiography. In addition, limited information exists regarding the long-term prognostic value of dobutamine stress echocardiography in patients who have peripheral arterial disease. We studied 2,138 patients who had peripheral arterial disease (1,317 men, 70 +/- 10 years old) and who underwent dobutamine stress echocardiography. Follow-up was completed for all-cause mortality and cardiovascular morbidity (nonfatal myocardial infarction and coronary revascularization). Death and cardiovascular morbidity occurred in 961 patients (45%) and 348 patients (16%), respectively, during a follow-up of 6.1 +/- 2.7 years. Failure to achieve 85% of age-predicted maximal heart rate (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.16 to 1.54, p = 0.0001) and percent of abnormal segments at peak stress (HR/10% increment 1.04, 95% CI 1.01 to 1.07, p = 0.02) were independent predictors of mortality and morbidity (HR 1.35, 95% CI 1.06 to 1.71, p = 0.01 and HR 1.14, 95% CI 1.08 to 1.20, p <0.0001, respectively). The effect of not achieving the target heart rate during normal dobutamine stress echocardiography on 1-, 3-, 5-, and 10-year survival probabilities was comparable to that of ischemia (86% vs 88%, 75% vs 71%, 62% vs 59%, and 33% vs 32%, respectively; p = 0.8). In a stepwise multivariate model, dobutamine stress echocardiography had incremental value over clinical data and echocardiographic data at rest for predicting rates of mortality (model chi-square increase from 301 to 322, p <0.0001) and morbidity (model chi-square increase from 37 to 118, p <0.0001). In conclusion, chronotropic response and extent of abnormal segments at peak dobutamine stress provide incremental prognostic information in patients who have peripheral arterial disease.     

Neuroadrenergic activation and response to dobutamine in congestive heart failure secondary to idiopathic dilated cardiomyopathy

Detection of contractile reserve is important in heart failure patients. To determine if detection of contractile reserve is influenced by neuroadrenergic activation, we examined the relation between dobutamine stress echocardiography (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with nonischemic left ventricular (LV) dysfunction (New York Heart Association class >III in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion score (WMS), and separately in WMS of hypokinetic segments and akinetic segments, were analyzed. A patient was considered to be responsive to dobutamine if the change in global WMS was >/=4. Twenty-three patients were responsive and 12 were not responsive to dobutamine. Plasma NE and baseline heart rate were significantly higher in nonresponsive patients (p <0.001). Changes in global WMS and in hypokinetic segment WMS were inversely related to either plasma NE (r -0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66, respectively). The change in akinetic segment WMS was related to plasma NE only (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV volume, baseline global WMS, or number of akinetic segments at baseline. Plasma NE >602 pg/ml predicted a blunted or absent contractile reserve at DSE (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence contractile reserve found at DSE in patients with heart failure due to nonischemic LV dysfunction.     

Depressed in vivo myocardial reactivity to dobutamine in streptozotocin diabetic rats: influence of exercise training

To assess the effects of chronic diabetes on in vivo myocardial reactivity to beta 1 adrenergic receptor stimulation and to evaluate the therapeutic effect of exercise training in preventing the cardiac abnormalities induced by diabetes four groups of rats were studied: sedentary control, trained control, sedentary diabetic, and trained diabetic. Trained rats were adapted to treadmill running before the induction of diabetes with streptozotocin 55 mg.kg-1 iv. The duration, speed, and grade of exercise were then progressively increased during eight weeks of training until the rats could run for 90 min at 18 m/min, 5% grade. A training effect was confirmed by an increase in plantaris muscle cytochrome oxidase activity. In vivo cardiac contractile performance was assessed by intracardiac catheterisation. Heart rate, left intraventricular peak systolic pressure, and positive and negative dP/dt were measured under basal conditions and after the intravenous administration of dobutamine 10(-10) to 5 x 10(-7) mol.kg-1 body weight. Under basal conditions, there were no differences among the four groups in left intraventricular peak systolic pressure, positive dP/dt, and heart rate, but negative dP/dt was lower in both diabetic groups. The response to dobutamine of the sedentary diabetic group, as reflected in the measured cardiodynamic variables, was significantly attenuated compared with that of the sedentary control group. Exercise training tended to improve cardiac function towards the level detected in the sedentary controls; however, the differences between sedentary and trained diabetic groups were not statistically significant. Exercise training also did not significantly alter the response of the control group to dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of levosimendan added to dobutamine in patients with decompensated advanced heart failure refractory to dobutamine alone

A 24-hour infusion of levosimendan was added to dobutamine in 18 patients (aged 63 +/- 9 years) hospitalized for management of decompensated New York Heart Association functional class IV heart failure refractory to a continuous 24-hour infusion of dobutamine (10 microg/kg/min) and furosemide (10 mg/hour); the primary study end point was a >or=40% increase in cardiac index and a >or=25% decrease in pulmonary capillary wedge pressure compared with pretreatment measurements.The primary end point was reached in one of the patients treated with dobutamine alone versus 7 patients (39%) treated with levosimendan and dobutamine combined (p = 0.008), whereas at 24 hours, the combined treatment was associated with a 0.76 +/- 0.78 L/min/m(2) (p = 0.001) mean increase in cardiac index and a 6.4 +/- 7.3 mm Hg (p = 0.002) mean decrease in pulmonary capillary wedge pressure compared with measurements obtained after 24 hours of dobutamine infusion alone. Symptoms were alleviated in all patients, and all but 3 were discharged from the hospital.