Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis.

ABSTRACT: The aim of this study was to synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure. We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced heart failure treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving left ventricular ejection fraction. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved B-type brain natriuretic peptide and left ventricular ejection fraction. Regarding safety, hypotension events were observed more frequently in the levosimendan and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.

Clinical Interventions and Hemodynamic Monitoring in the Setting of Left Ventricular Systolic Heart Failure in Children: Insights From a Physiologic Simulator.

BACKGROUND: In pediatric critical care, vasoactive/inotropic support is widely used in patients with heart failure, but it remains controversial because the influence of multiple medications and the interplay between their inotropic and vasoactive effects on a given patient are hard to predict. Robust evidence supporting their use and quantifying their effects in this group of patients is scarce. STUDY QUESTION: The aim of this study was to characterize the effect of vasoactive medications on various cardiovascular parameters in pediatric patient with decreased ejection fraction. STUDY DESIGN: Clinical-data based physiologic simulator study. MEASURE AND OUTCOMES: We used a physics-based computer simulator for quantifying the response of cardiovascular parameters to the administration of various types of vasoactive/inotropic medications in pediatric patients with decreased ejection fraction. The simulator allowed us to study the impact of increasing medication dosage and the simultaneous administration of some vasoactive agents. Correlation and linear regression analyses yielded the quantified effects on the vasoactive/inotropic support. RESULTS: Cardiac output and systemic venous saturation significantly increased with the administration of dobutamine and milrinone in isolation, and combination of milrinone with dobutamine, dopamine, or epinephrine. Both parameters decreased with the administration of epinephrine and norepinephrine in isolation. No significant change in these hemodynamic parameters was observed with the administration of dopamine in isolation. CONCLUSIONS: Milrinone and dobutamine were the only vasoactive medications that, when used in isolation, improved systemic oxygen delivery. Milrinone in combination with dobutamine, dopamine, or epinephrine also increased systemic oxygen delivery. The induced increment on afterload can negatively affect systemic oxygen delivery.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

Which Inotropic Drug, Dobutamine or Milrinone, Is Clinically More Effective in the Treatment of Postligation Cardiac Syndrome in Preterm Infants?

OBJECTIVE: This study aimed to detect which of the two main medicines suggested in the treatment of postligation cardiac syndrome (PLCS)-dobutamine or mirinone-possesses a more therapeutic effect. While doing this, clinicians are provided with a broader perspective on the treatment and follow-up of cases. The desire was to increase the treatability and monitor ability of the cases in question and hence their survivability. STUDY DESIGN: A retrospective review of a cohort of infants with PLCS was conducted between March 2012 and December 2018. In the treatment of infants with PLCS, dobutamine (dobutamine study group-DSG) or milrinone (milrinone study group-MSG) was used. The respiration, cardiac, echocardiography, and perfusion parameters of the cases were assessed both before and after ligation. Based on the data obtained, both the effects of the medicines on PLCS and the difference between their therapeutic effects were studied. The accuracy of prognostication was assessed with receiver operating characteristic analyses. RESULTS: PLCS was detected in 29 (34.1%) of 85 patent ductus arteriosus ligation cases in total. Of all the PLCS cases, 13 (44.8%) were treated with dobutamine and 16 (55.2%) with milrinone. It was observed that the effects of the medicines on the respiratory system and cardiovascular system manifested in the third and 6th hour, respectively. It was detected that both medicines had more effect on the systolic blood pressure (SBP) (area under the curve [AUC]: 0.997/0.996, p = 0.001/0.002) than on the diastolic blood pressure (AUC: 0.911/0.843, p = 0.032/0.046). CONCLUSION: Dobutamine and milrinone, two primary medicines that can be used in the treatment of cases with PLCS, possess similar therapeutic effects on this pathology. In addition, their postoperative therapeutic effects on the SBP are more in the foreground.

Practical instructions for using drugs in CT and MR cardiac imaging.

The progressive increase in numbers of noninvasive cardiac imaging examinations broadens the spectrum of knowledge radiologists are expected to acquire in the management of drugs during CT coronary angiography (CTCA) and cardiac MR (CMR) to improve image quality for optimal visualization and assessment of the coronary arteries and adequate MR functional analysis. Aim of this review is to provide an overview on different class of drugs (nitrate, beta-blockers, ivabradine, anxiolytic, adenosine, dobutamine, atropine, dipyridamole and regadenoson) that can be used in CTCA and CMR, illustrating their main indications, contraindications, efficacy, mechanism of action, metabolism, safety, side effects or complications, and providing advices in their use.

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Comparison of the dyssynchrony parameters recorded with gated SPECT in ischemic cardiomyopathy according to their repeatability at rest and to their ability to detect a synchrony reserve under dobutamine infusion.

BACKGROUND: This study aimed to determine whether the repeatability of dyssynchrony assessment using gated myocardial perfusion SPECT (GSPECT) allows the detection of synchrony reserve during low-dose dobutamine infusion. METHODS AND RESULTS: Sixty-one patients with ischemic cardiomyopathy and LV ejection fraction < 50% were prospectively included in 10 centers. Each patient underwent two consecutive rest GSPECT with 99mTc-labeled tracer (either tetrofosmin or sestamibi) to assess the repeatability of LV function and dyssynchrony parameters, followed by a GSECT acquisition during low-dose dobutamine infusion. LV dyssynchrony was assessed using QGS software through histogram bandwidth (BW), standard deviation of the phase (SD), and entropy. Repeatability was assessed with Lin's concordance correlation coefficient (CCC). Entropy showed a higher CCC (0.80) compared to BW (0.68) and SD (0.75). On average, dobutamine infusion yielded to improve both BW (P = .049) and entropy (P = .04) although significant improvements, setting outside the 95% confidence interval of the repeatability analysis, were documented in only 6 and 4 patients for BW and entropy, respectively. CONCLUSIONS: A synchrony reserve may be documented in patients with ischemic cardiomyopathy through the recording of BW and entropy with low-dose dobutamine GSPECT, with the additional advantage of a higher repeatability for entropy.

Hybrid Assessment of Myocardial Ischemia Using Stress-Only Nuclear Myocardial Perfusion Imaging and Rest Computed Tomography Perfusion Imaging.

BACKGROUND: Sequential assessment using CT coronary angiography (coronary CT) and nuclear myocardial perfusion imaging (MPI) is considered an anatomical and functional evaluation of coronary artery disease (CAD). However, there can be unexpected radiation exposure. Hybrid MPI with stress-only nuclear MPI and rest CT-MPI using coronary CT may contribute to reducing the radiation dose in sequential assessment with nuclear MPI after coronary CT. We analyzed the diagnostic performance and total radiation dose of hybrid MPI for detection of significant CAD compared with sequential assessment using nuclear MPI after coronary CT.Methods and Results:The results for 101 patients who underwent coronary CT, nuclear MPI and invasive coronary angiography within 3 months of all imaging were analyzed. We calculated the summed difference score (SDS) from standard nuclear MPI and hybrid SDS from hybrid MPI, which revealed myocardial ischemia. The diagnostic performance of SDS and hybrid SDS for detecting significant CAD was analyzed using receiver-operating characteristic (ROC) curve analysis. We also compared the total radiation dose of both methods. The area under the ROC curve was not different between SDS and hybrid SDS (0.901 and 0.815, P=0.079). Total radiation dose of hybrid MPI was significantly lower than standard nuclear MPI with CT angiography (4.62 mSv vs. 9.72 mSv, P<0.0001). CONCLUSIONS: Hybrid MPI showed a precise diagnostic accuracy for significant CAD detection.

The clinical significance of the incorporation of tissue Doppler imaging into low-dose Dobutamine stress echocardiography in patients with aortic stenosis prior to Transcatheter aortic valve implantation.

BACKGROUND: Low-dose dobutamine stress echocardiography (DSE) is indicated in patients with low flow (stroke volume index [SVi] < 35 ml/m2) low gradient (mean pressure gradient < 40 mmHg) and left ventricular ejection fraction (LVEF) < 50% aortic stenosis (AS) to assess LV contractile reserve (> 20% increase in SVi) and severity grade of AS. Severe AS is defined by a mean pressure gradient of 40 mmHg occurring at any time during the test when aortic valve area remains < 1.0 cm2. CASE PRESENTATION: This case report highlights the utility of mitral annular systolic velocity (S') by tissue Doppler imaging and peak LV outflow tract (LVOT) velocity as markers of LV intrinsic contractile function during DSE in a patient with low flow low gradient AS and reduced EF prior to transcatheter aortic valve implantation (TAVI). CONCLUSIONS: Mitral annular S' and peak LVOT velocities are reliable markers of LV intrinsic contractile function and should be incorporated into routine low-dose DSE.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease.

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( Pinteraction=0.318) or iFR ( Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( Pinteraction<0.00001) and decreasing iFR ( Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( Pinteraction=0.849) or iFR ( Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( Pinteraction=0.693) nor iFR ( Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Anatomical location, sex, and age influence murine arterial circumferential cyclic strain before and during dobutamine infusion.

BACKGROUND: One of the primary biomechanical factors influencing arterial health is their deformation across the cardiac cycle, or cyclic strain, which is often associated with arterial stiffness. Deleterious changes in the cardiovascular system, e.g., increased arterial stiffness, can remain undetected until the system is challenged, such as under a cardiac stressor like dobutamine. PURPOSE: To quantify cyclic strain in mice at different locations along the arterial tree prior to and during dobutamine infusion, while evaluating the effects of sex and age. STUDY TYPE: Control/cohort study. ANIMAL MODEL: Twenty C57BL/6 mice; male, female; ∼12 and 24 weeks of age; n = 5 per group. FIELD STRENGTH/SEQUENCE: 7T; CINE MRI with 12 frames, velocity compensation, and prospective cardiac gating. ASSESSMENT: Prior to and during the infusion of dobutamine, Green-Lagrange circumferential cyclic strain was calculated from perimeter measurements derived from CINE data acquired at the carotid artery, suprarenal and infrarenal abdominal aorta, and iliac artery. STATISTICAL TESTS: Analysis of variance (ANOVA) followed by post-hoc tests was used to evaluate the influence of dobutamine, anatomical location, sex, and age. RESULTS: Heart rates did not differ between groups prior to or during dobutamine infusion (P = 0.87 and P = 0.08, respectively). Dobutamine increased cyclic strain in each group. Within a group, increases in strain were similar across arteries. At the suprarenal aorta, strain was reduced in older mice at baseline (young 27.6 > mature 19.3%, P = 0.01) and during dobutamine infusion (young 53.0 > mature 36.2%, P = 0.005). In the infrarenal aorta, the response (dobutamine - baseline) was reduced in older mice (young 21.9 > mature 13.5%, P = 0.04). DATA CONCLUSION: Dobutamine infusion increases circumferential cyclic strain throughout the arterial tree of mice. This effect is quantifiable using CINE MRI. The results demonstrate that strain prior to and during dobutamine is influenced by anatomical location, sex, and age. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:69-80.

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VO2max in Fontan patients.

BACKGROUND: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity. METHODS: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 µg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_volavg cycle, KEavg cycle, ELavg cycle). The relation to maximum oxygen uptake (VO2 max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data. RESULTS: Dobutamine stress caused a significant 88 ± 52% increase in KE (KEavg cycle: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (ELavg cycle: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_volavg cycle: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO2 max (KEavg cycle: r = - 0.83, P = 0.003; ELavg cycle: r = - 0.80, P = 0.006; vorticity_volavg cycle: r = - 0.64, P = 0.047). CONCLUSIONS: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO2 max.

Echocardiographic assessment at rest and during stress in patients with intermittent claudication.

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n = 111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.

Inotropic and lusitropic effects of incremental doses of dobutamine in dogs with right ventricular apical pacing-induced cardiac dysfunction.

This study aimed to assess the effects of incremental doses of dobutamine on diastolic function in healthy and rapid ventricular apical pacing (RVAP)-induced cardiac dysfunction anesthetized dogs. Inotropic and lusitropic effects of dobutamine (2, 4, 8, and 12 µg kg-1  min-1 ) were assessed through left ventricle (LV) pressure-volume relation and Doppler echocardiography in six female dogs before and after 8 weeks of RVAP. Peak rate of LV pressure fall (-dP/dtmin ) improved with doses >4 µg kg-1  min-1 in healthy (4,490 ± 970 vs. 3,265 ± 471 mmHg/s, p < 0.05) and >8 µg kg-1  min-1 in RVAP dogs (3,385 ± 1,122 vs. 1,864 ± 849 mmHg/s, p < 0.05) while the time constant of relaxation (tau) reduced with doses >4 µg kg-1  min-1 in both groups (healthy: 24.0 ± 3.7 vs. 28.2 ± 4.9 ms; RVAP: 32.6 ± 8.5 vs. 37.5 ± 11.4 ms, p < 0.05) comparing with baseline. Indices of relaxation (-dP/dtmin and tau) suggested preserved lusitropic response in contrast with markedly reduced indices of contractility in the RVAP group compared with healthy group at same infusion rates. Doppler echocardiography showed significant reduction of elastic recoil in failing hearts. The results of this study demonstrated maximal positive lusitropic effects of dobutamine at a dose of 8 µg kg-1  min-1 in ventricular pacing-induced cardiac dysfunction without further impairment of ventricular filling.

The hemodynamic response to constant dobutamine infusion: the effect of ADRB1 389 polymorphism and sex.

OBJECTIVES: Prolonged activation of the ß-1 adrenergic receptor (ADRB1) is associated with receptor desensitization. This process has been suggested to have important pathophysiological and clinical implications in conditions such as congestive heart failure. The contribution of genetic factors to this process is a subject of ongoing research. We have previously shown that the ADRB1 389 polymorphism affects the response to incremental dose infusion of the ADRB agonist dobutamine. The aim of the current study was to determine whether the ADRB1 389 polymorphism affects the hemodynamic response to constant dose infusion of dobutamine in healthy patients. PATIENTS AND METHODS: Healthy patients were recruited according to their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly patients (all Ser49Ser), 21 men and 14 women]. Following a standardized protocol of dose increase, 6 mcg/kg/min dobutamine was infused over 2 h. Heart rate (HR), blood pressure (BP), and active plasma renin (PR) were measured. Standardized exercise (1 min) was performed at three time points during infusion. RESULTS: In all patients, resting systolic BP was significantly decreased during infusion [144.4±11.5 vs. 140.3±12.2 mmHg (mean±SD), P=0.007]. There was no change in HR, and PR following 120 min of dobutamine infusion. ADRB1 389 genotypes were not associated with HR, systolic BP, and PR changes during dobutamine infusion (all P>0.05, repeated measures analysis of variance). Sex was associated with response to dobutamine. Among women, but not in men, resting HR significantly increased, and diastolic blood pressure (DBP) significantly decreased during dobutamine infusion [HR: 76.0±7.3 to 86.3±17.5 beats per minute (P=0.023), and DBP 78.5±8.49 mmHg to 72.36±6.16 (P=0.041) (repeated measures analysis of variance)]. CONCLUSION: In healthy patients, the ADRB1 389 genotype was not associated with hemodynamic changes during constant dobutamine infusion. In women, but not in men, HR significantly increased and DBP decreased during 2 h of infusion.

Asymptomatic myocardial ischemia forecasts adverse events in cardiovascular magnetic resonance dobutamine stress testing of high-risk middle-aged and elderly individuals.

BACKGROUND: Current guidelines for assessing the risk of experiencing a hospitalized cardiovascular (CV) event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged < 60 years, and do not address the possibility of unrecognized "silent myocardial ischemia" in middle aged and older adults. METHODS: We performed dobutamine cardiovascular magnetic resonance (CMR) stress testing in 327 consecutively recruited participants aged > 55 years without CV-related symptoms nor known coronary artery disease, but otherwise at increased risk for a future CV event due to pre-existing hypertension or diabetes mellitus for at least 5 years. After adjusting for the demographics and CV risk factors, log-rank test and Cox proportional hazards models determined the additional predictive value of the stress test results for forecasting hospitalized CV events/survival. Either stress-induced LV wall motion abnormalities or perfusion defects were used to indicate myocardial ischemia. RESULTS: Participants averaged 68 ± 8 years in age; 39% men, 75% Caucasian. There were 38 hospitalized CV events or deaths which occurred during a mean follow-up of 58 months. Using Kaplan-Meier analyses, myocardial ischemia identified future CV events/survival (p <  0.001), but this finding was more evident in men (p <  0.001) versus women (p = 0.27). The crude hazard ratio (HR) of myocardial ischemia for CV events/survival was 3.13 (95% CI: 1.64-5.93; p < 0.001). After accounting for baseline demographics, CV risk factors, and left ventricular ejection fraction/mass, myocardial ischemia continued to be associated with CV events/survival [HR: 4.07 (95% CI: 1.95-8.73) p < 0.001]. CONCLUSIONS: Among asymptomatic middle-aged individuals with risk factors for a sentinel CV event, the presence of myocardial ischemia during dobutamine CMR testing forecasted a future hospitalized CV event or death. Further studies are needed in middle aged and older individuals to more accurately characterize the prevalence, significance, and management of asymptomatic myocardial ischemia. TRIAL REGISTRATION: ( ClinicalTrials.gov identifier): NCT00542503 and was retrospectively registered on October 11th, 2007.

Prevention of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery: A Double-Blind Randomized Clinical Pilot Study Comparing Dobutamine and Milrinone.

OBJECTIVES: Dobutamine and milrinone are commonly used after open-heart surgery to prevent or treat low cardiac output syndrome. We sought to compare efficacy and safety of these drugs in pediatric patients. DESIGN: Prospective, single-center, double-blinded, randomized clinical pilot study. SETTING: Tertiary-care university children's hospital postoperative pediatric cardiac ICU. PATIENTS: After written consent, 50 consecutive patients (age, 0.2-14.2 yr; median, 1.2 yr) undergoing open-heart surgery for congenital malformations were included. INTERVENTIONS: After cardiopulmonary bypass, a continuous infusion of either dobutamine or milrinone was administered for the first 36 postoperative hours. Maximum dose: dobutamine 6 µg/kg/min, milrinone 0.75 µg/kg/min. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in demographic data, complexity of surgery, and intraoperative characteristics between the two study groups (dobutamine vs milrinone). Efficacy was defined as need for additional vasoactive support, which did not differ between groups (dobutamine 61% vs milrinone 67%; p = 0.71). Sodium nitroprusside was used more often in the dobutamine group (42% vs 13%; p = 0.019). Systolic blood pressure showed a trend toward higher values in the dobutamine group, whereas both drugs increased heart rate early postoperatively. Echocardiography demonstrated a consistently good cardiac function in both groups. Central venous oxygen saturation, serum lactate levels, urine output, time to chest tube removal, length of mechanical ventilation, ICU, and hospital stay were similar in both groups. Both drugs were well tolerated, no serious adverse events occurred. CONCLUSIONS: Dobutamine and milrinone are safe, well tolerated, and equally effective in prevention of low cardiac output syndrome after pediatric cardiac surgery. The hemodynamic response of the two drugs is comparable. In uncomplicated cases, a trend toward the more cost-saving dobutamine might be anticipated; however, milrinone demonstrated a trend toward higher efficacy in afterload reduction.

Dobutamine and Nitroglycerin Versus Milrinone for Perioperative Management of Pulmonary Hypertension in Mitral Valve Surgery. A Randomized Controlled Study.

OBJECTIVE: To compare the effects of dobutamine and nitroglycerin to milrinone in young patients with severe pulmonary hypertension undergoing mitral valve replacement. DESIGN: A prospective randomized, double-blinded, controlled study. SETTING: Single university hospital. PARTICIPANTS: Forty patients had systolic pulmonary arterial pressure ≥60 mmHg and were scheduled for elective mitral valve replacement. The patients were divided randomly into 2 equal groups according to the drugs given during the study. INTERVENTIONS: The patients in group I received 5 to 20 µg/kg/min of dobutamine and 0.5 to 3 µg/kg/min of nitroglycerin, and patients in group II received a loading dose of milrinone, 50 µg/kg over 10 minutes, followed by a maintenance dose of 0.25 to 0.75 µg/kg/min. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the effects of interventional drugs on mean pulmonary artery pressure. The secondary outcomes were the effects of interventional drugs on systemic and pulmonary hemodynamic parameters measured from induction of anesthesia until the first 12 hours in the intensive care unit stay. There was a more significant decrease in mean pulmonary artery pressure, pulmonary capillary wedge pressure, and central venous pressure in group II than group I at all time points after cardiopulmonary bypass. There were more significant increases in heart rate, mean arterial pressure, cardiac output, and mixed venous oxygen tension in group I than group II, which became more obvious in time. In both groups, there was a significant decrease in systemic vascular resistance and pulmonary vascular resistance at all times. CONCLUSION: Milrinone provides adequate cardiac performance, causing a greater reduction in pulmonary artery pressure and pulmonary capillary wedge pressure.

Stability of dobutamine in continuous ambulatory delivery devices.

WHAT IS KNOWN AND OBJECTIVE: Continuous infusion of dobutamine plays an important role in the management of patients with end-stage heart failure. Home infusion of dobutamine using a continuous ambulatory delivery device (CADD) facilitates the management of patients in their home, avoiding complications associated with long-term hospitalization. However, the stability of dobutamine in CADD is currently unknown. Therefore, this study investigated the physicochemical stability of dobutamine in CADDs at three different temperatures over various time points. METHODS: Six CADDs (three containing dobutamine 10 mg/mL in 0.9% sodium chloride and three containing dobutamine 10 mg/mL in 5% glucose) were prepared and stored at 4°C for 7 days, followed by 12 hours at 35°C and then for another 12 hours at 25°C. An aliquot (n = 3) was withdrawn aseptically at 0, 24, 48, 72, 96, 120, 144 and 168 hours when stored at 4°C, and at 0, 6 and 12 hours when stored at the other two temperatures. Each sample was analysed for dobutamine concentration using a stability-indicating high-performance liquid chromatography. All the samples were also evaluated for change in pH, colour and for particle content. RESULTS AND DISCUSSION: No evidence of particle formation, colour or pH change was observed throughout the study period. Dobutamine, when admixed with 0.9% sodium chloride or 5% glucose, was found to be chemically stable for at least 168 hours at 4°C and for another 12 hours at 35°C and for another 12 hours at 25°C. WHAT IS NEW AND CONCLUSIONS: Our findings will allow health professionals to provide a weekly supply of dobutamine-containing CADDs to patients for home infusions. Continuous infusion over a 24-hour period using one CADD per day will also decrease the number of exchanges required and thus reduce the risk of catheter-related bloodstream infections.

Persistent but reversible advanced atrio-ventricular block in a heart transplant man induced by dobutamine stress echocardiography.

Dobutamine when used for stress echocardiography (DSE), it rarely causes transient atrio-ventricular (AV) block. We report a heart transplant patient with high cardiovascular risk who developed symptomatic advanced AV block during DSE which persisted after termination of dobutamine administration, necessitating pacemaker implantation. To our knowledge, this is the first published case of persistent high grade AV block in a heart transplant patient induced by DSE.