Safety of dobutamine or adenosine stress cardiac magnetic resonance imaging in patients with left ventricular thrombus.

BACKGROUND: Left ventricular (LV) thrombus formation is a common but potentially serious complication, typically occurring after myocardial infarction. Due to perceived high thromboembolic risk and lack of safety data, stress cardiac magnetic resonance (CMR) imaging especially with dobutamine is usually avoided despite its high diagnostic yield. This study aimed to investigate the characteristics, safety and outcome of patients with LV thrombus undergoing dobutamine or vasodilator stress CMR. METHODS: Patients undergoing stress CMR with concomitant LV thrombus were retrospectively included. Risk factors, comorbidities, and previous embolic events were recorded. Periprocedural safety was assessed for up to 48 h following the examination. Major adverse cardiac events (MACE) 12 months before the diagnosis were compared to 12 months after the exam and between patients and a matched control group. Additionally, patients were followed up for all-cause mortality. RESULTS: 95 patients (78 male, 65 ± 10.7 years) were included. Among them, 43 patients underwent dobutamine (36 high-dose, 7 low-dose) and 52 vasodilator stress CMR. Periprocedural safety was excellent with no adverse events. During a period of 24 months, 27 MACE (14.7%) occurred in patients and controls with no statistical difference between groups. During a median follow-up of 33.7 months (IQR 37.6 months), 6 deaths (6.3%) occurred. Type of stress agent, thrombus mobility, or protrusion were not correlated to embolic events or death. CONCLUSION: The addition of a stress test to a CMR exam is safe and does increase the generally high cardioembolic event rate in LV thrombus patients. Therefore, it is useful to support reperfusion decision-making.

Dobutamine-induced Takotsubo syndrome in a paediatric heart transplant patient.

Takotsubo syndrome is a potentially reversible cause of acute systolic dysfunction. Takotsubo syndrome is rare in children, with no reported dobutamine-induced cases to date. We present a 14-year-old male with prior history of heart transplantation, who developed Takotsubo syndrome during dobutamine stress echocardiography. We highlight the importance of its early recognition to ensure supportive measures with avoidance of inotropic medications.

Incidence and Predictors of Eosinophilic Myocardial Hypersensitivity in Patients Receiving Home Dobutamine.

ABSTRACT: We sought to examine incidence and predictors of eosinophilic myocardial hypersensitivity (EMH) in a cohort of patients in the home inotrope program of a quaternary cardiac transplant center. Patients on home inotropes with progression to heart transplantation or ventricular assist device (VAD) between January 2000 and May 2020 were included. EMH was diagnosed by the presence of an interstitial predominate eosinophilic infiltrate within the myocardium by experienced cardiac pathologists. From a cohort of 74 patients, 58% (43) were on dobutamine and 42% (31) were on milrinone. Dobutamine was associated with EMH incidence of 14% (6/43), with zero cases in the milrinone cohort. Mean age was 52 ± 12 years, 22% were female. More than half (62%) were nonischemic dilated cardiomyopathies, the remainder were ischemic cardiomyopathy. Dobutamine dose [250 (200-282) vs. 225 (200-291) µg/min] and duration of therapy [41 (23-79) vs. 53 (24-91) days] was similar between those with and without EMH. Median change in eosinophil count was 0.31 × 10 9 /L in the EMH group compared with only 0.03 × 10 9 /L in the non-EMH cohort, P = 0.02. Increase in peripheral eosinophil count of >0.20 × 10 9 /L demonstrated good discrimination between those with and without EMH, c-statistic 0.83 (95% CI 0.66-1.0). Heart failure hospitalization occurred in 83% of the EMH group versus 59% in the non-EMH group, P = 0.26. Requirement for VAD was significantly higher in the EMH group (83% vs. 41%, P = 0.05). In conclusion, EMH occurred in 14% of patients receiving home dobutamine. Rising eosinophil count should prompt physicians to consider EMH and switch to milrinone to avoid possible escalation to VAD.

Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

BACKGROUND: Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice. METHODS: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome. RESULTS: A total of 192 participants (96 in each group) were enrolled. The treatment groups did not differ significantly with respect to the primary outcome; a primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group (relative risk, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P = 0.47). There were also no significant differences between the groups with respect to secondary outcomes, including in-hospital death (37% and 43% of the participants, respectively; relative risk, 0.85; 95% CI, 0.60 to 1.21), resuscitated cardiac arrest (7% and 9%; hazard ratio, 0.78; 95% CI, 0.29 to 2.07), receipt of mechanical circulatory support (12% and 15%; hazard ratio, 0.78; 95% CI, 0.36 to 1.71), or initiation of renal replacement therapy (22% and 17%; hazard ratio, 1.39; 95% CI, 0.73 to 2.67). CONCLUSIONS: In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite outcome or important secondary outcomes. (Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; ClinicalTrials.gov number, NCT03207165.).

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. METHODS: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. RESULTS: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. CONCLUSIONS: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Pharmacokinetic study (phase I-II) of a new dobutamine formulation in preterm infants immediately after birth.

BACKGROUND: Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated. METHODS: Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection. RESULTS: Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP. CONCLUSIONS: The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose. IMPACT: Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth. Age-related differences in drug pharmacokinetics may result in suboptimal treatments. The lack of formal studies in preterms results in inadequate data on efficacy and safety. This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation. There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated. This information is crucial for planning future trials on cardiovascular support.

Application of dopamine combined with dobutamine in children with pneumonia and heart failure.

Pediatric pneumonia and heart failure is a common critical illness in pediatrics. This article observes the clinical effects of dopamine and dobutamine in the treatment of pneumonia and heart failure. As a key neurotransmitter in the hypothalamus and pituitary gland, dopamine plays a very important role in the central nervous excitement of the human body. Dopamine could also promote excitement in the respiratory center and reduces oxygen consumption in the breath, thereby improving the symptoms of respiratory failure in children. Observe and compare the clinical efficacy of the two groups of children, the disappearance of lung rales, the time to correct heart failure and the length of hospital stay. The total effective rate in the observation group was 91%; the total effective rate in the control group was 65.4%. There was a significant difference in the total effective rate between the two groups of children. The time of disappearance of lung rales, the time of correction of heart failure and the length of hospital stay in the observation group were significantly shorter than those in the control group (P <0.05). The clinical effects of dopamine and dobutamine on pneumonia and heart failure are significant.

High-Dose Dobutamine for Inducibility of Atrial Arrhythmias During Atrial Fibrillation Ablation.

OBJECTIVES: This study sought to compare the effect of high-dose dobutamine (DBT) with that of high-dose isoproterenol (IPN) in eliciting triggers during atrial fibrillation (AF) ablation. BACKGROUND: High-dose IPN is commonly used to elicit triggers during AF ablation. However, it is not available worldwide and, in the United States, its cost per dose has significantly increased. DBT is a similarly nonselective ß-agonist and, as such, is a potential alternative. METHODS: This was a prospective, randomized 2×2 crossover study of patients undergoing AF ablation. Patients were assigned to receive IPN (20 to 30 µg/min for 10 min) followed by DBT (40 to 50 µg/kg/min for 10 min) or vice versa in a 1:1 fashion. The type, number, and location of triggers as well as heart rate, blood pressure, and side effects were noted. RESULTS: Fifty patients were included in the study. Both drugs caused a significant increase in heart rate, with a consistently lower peak for DBT. Blood pressure significantly increased with DBT, while there was a significant reduction with IPN, despite phenylephrine support. Atrial arrhythmias induced during DBT were comparable to that induced during IPN. In patients with IPN-inducible outflow tract premature ventricular contractions, a similar effect was noted with DBT. No major complications occurred during either drug challenge. CONCLUSIONS: High-dose DBT is safe and comparable to high-dose IPN in respect of eliciting AF triggers, with the advantage to maintain systemic pressure without the need of additional vasopressor support. This study supports the use of high-dose DBT in electrophysiology laboratories in which IPN is not readily available and for those patients in whom hypotension is a concern.

Análise da Segurança e Exequibilidade do Ecocardiograma sob Estresse com Dobutamina em Dez Mil e Seis Exames de uma População Geral / Analysis of the Safety and Feasibility of Dobutamine Stress Echocardiography in Ten Thousand and Six Tests of a General Population

Fundamento: Durante o ecocardiograma sob estresse com dobutamina, podem ocorrer efeitos adversos e exames inconclusivos. Objetivo: Avaliar em uma grande população geral a segurança e a exequibilidade do ecocardiograma sob estresse com dobutamina. Métodos: Estudo de 10.006 ecocardiogramas sob estresse com dobutamina realizados no período de julho de 1996 a setembro de 2007. A dobutamina foi administrada em quatro estágios (10, 20, 30 e 40 µcg.kg-1.min-1) para pesquisa de isquemia miocárdica e iniciada com 5 µcg.kg- ¹.min-1 apenas na análise de viabilidade miocárdica. A atropina foi iniciada conforme os protocolos vigentes. Foram verificados dados clínicos, hemodinâmicos e efeitos adversos associados ao ecocardiograma sob estresse com dobutamina. Resultados: Durante os ecocardiogramas sob estresse com dobutamina, ocorreu angina típica (8,9%), pico hipertensivo (1,7%), ectopias ventriculares isoladas (31%), taquiarritmia supraventricular (1,89%), fibrilação atrial (0,76%) e taquicardia ventricular não sustentada (0,6%). Os efeitos adversos citados foram mais frequentes nos pacientes com ecocardiogramas sob estresse com dobutamina positivos para isquemia. A desaceleração sinusal paradoxal (0,16%) não ocorreu em ecocardiogramas sob estresse com dobutamina positivo. As três complicações graves ocorreram em ecocardiogramas sob estresse com dobutamina positivos para isquemia. Foram dois casos (0,02%) com fibrilação ventricular e um caso de síndrome coronariana aguda (0,01%). Não houve caso de taquicardia ventricular sustentada, ruptura cardíaca, assistolia ou óbito. Comparados aos exames concluídos, nos inconclusivos, os pacientes usaram menos atropina (81,5% versus 49,9%; p< 0,001) e mais betabloqueador (4,7% versus 19%; p< 0,001), apresentando mais pico hipertensivo (1,1% versus 14,2%; p = 0,0001) e taquicardia ventricular não sustentada (0,5% versus 2,2%; p< 0,001). Conclusão: O ecocardiograma sob estresse com dobutamina realizado de forma apropriada é seguro e apresenta elevada exequibilidade.

Background: Adverse effects and inconclusive results may occur on dobutamine stress echocardiography. Objective: To assess the safety and feasibility of dobutamine stress echocardiography in a large general population. Methods: A total of 10,006 dobutamine stress echocardiographies were performed between July 1996 and September 2007. Dobutamine was administered in four stages (10, 20, 30, and 40 µcg·kg-1·min-1) to research myocardial ischemia starting with 5 µcg·kg- ¹·min-1 to analyze myocardial viability. Atropine administration was initiated according to current protocols. Clinical, hemodynamic, and adverse effect data associated with dobutamine stress echocardiography findings were verified. Results: Typical angina (8.9%), hypertensive peak (1.7%), isolated ventricular ectopias (31%), supraventricular tachyarrhythmia (1.89%), atrial

Coronary artery spasm following dobutamine stress echocardiogram.

A 53-year-old woman with atypical chest pain underwent a dobutamine stress echocardiogram (DSE) and developed a coronary spasm (CS) with severe pain and dramatic ST-segment elevation 9 min after dobutamine infusion was discontinued. The spasm resolved after sublingual nitroglycerin administration. The same-day coronary angiogram showed non-significant stenosis in the three coronary territories. Retrospectively, we found that the patient had vasospastic angina (VSA), a condition that has been strongly associated with the development of dobutamine-induced CS. Mechanisms of dobutamine-induced CS are not fully understood and include endothelial dysfunction leading to deficient nitric oxide-mediated coronary vasodilation in response to increased myocardial oxygen demand as well as imbalance between ß1 and ß2 adrenergic effects of dobutamine. Dobutamine-induced CS has also been much more frequently reported in patients from Asian descent with VSA. VSA should be systemically recognised in patients considered for DSE and, if present, other modalities of stress imaging should be discussed.

Comparison of Positive Inotropic Agents in the Management of Acute Decompensated Heart Failure.

Current guidelines recommend the consideration of positive inotropes in patients with acute decompensated heart failure (ADHF) who have low cardiac index and evidence of systemic hypoperfusion or congestion. However, there is no evidence detailing the first line agent for the management of ADHF. The purpose of this study was to compare the safety and efficacy of dobutamine to milrinone for the treatment of ADHF. This was a single-center, retrospective study at a tertiary academic medical center, approved by Partner's Health Care Institutional Review Board. Patients included in this study were those admitted with ADHF who received dobutamine or milrinone from June 2015 to July 2017. A total of 95 dobutamine and 40 milrinone patients were included in the analysis. Median hospital length of stay was 12 days in the dobutamine group versus 10 days in the milrinone group (P = 0.34). Rehospitalization within 30 days occurred in 29.5% of patients in the dobutamine group versus 17.5% of patients in the milrinone group (P = 0.15). Median intensive care unit length of stay was 4.5 days in the dobutamine group versus 10 days in the milrinone group (P < 0.01). All other minor end points including all-cause mortality, progression to renal failure within 72 hours, rehospitalization in 90 days, and urine output within 72 hours of therapy were not found to be statistically significant. In addition, a post hoc analysis compared major and minor outcomes between milrinone and dobutamine using linear and logistic regression with adjustment for baseline characteristics. There were not any statistically significant findings in the post hoc analysis. Overall, there were no statistically significant differences in outcomes between the 2 groups other than longer intensive care unit length of stay in the milrinone group.

Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants.

Introduction: Extremely premature infants are susceptible to fluctuations in cerebral blood flow due to immaturity of cerebral autoregulation. Inotropes may cause rapid changes to systemic blood pressure and consequently cerebral blood flow, especially within the first 72 hours of life. This period is recognized to carry the greatest risk for cerebral hemorrhage. This study evaluates the incidence of death and/or severe brain injury in extremely preterm infants treated with inotropes in the first 72 hours of life.Methods: Prospective cohort study of infants born ≤29+0 weeks gestational age (GA) between January 2013 and December 2016. Severe brain injury was defined based on head ultrasound as presence of: grade III or IV intraventricular hemorrhage (IVH), moderate to severe post-hemorrhagic ventricular dilatation (PHVD), or cystic periventricular leukomalacia (cPVL). The association between inotrope use and death and/or brain injury was explored via logistic regression controlling for predefined confounding risk factors.Results: Of 497 eligible infants, 97 (19.5%) received inotropes during the first 72 hours. GA at birth, birth weight (BW), and 5-minute Apgar scores were lower among infants who received early inotropes compared to those not treated with inotropes. A stepwise logistic regression of the predefined confounding factors showed GA, exposure for antenatal steroids, and admission hypothermia to be significant confounding factors. Adjusting for those factors, early use of inotropes was associated with increased risk of death and/or severe brain injury (AOR 4.5; 95%CI: 2.4-8.5), severe brain injury (AOR 4.2; 95% CI: 1.9-8.9), and IVH of any grade (AOR 2.9; 95%CI: 1.7-4.9).Conclusion: Early inotropes use was associated with higher risk of death and/or severe brain injury. Strict indications and strategies for minimizing inotrope use while preventing hypotension should be implemented in the early postnatal care of infants at risk for severe brain injury.

Effective dose of dobutamine in augmenting free flap blood flow during reconstructive surgery of the lower extremity.

Success of surgical free flap transfer depends on achieving and maintaining adequate perfusion across the microvascular anastomosis. The purpose of this prospective study was to determine the optimal infusion rate of dobutamine to augment duplex ultrasound measured blood flow to the tissue flap during surgery.Twenty-one patients undergoing general anesthesia for lower limb reconstructive surgery were recruited. The optimal dobutamine dose was evaluated using the modified Dixon's up-and-down method, starting at 6 µg·kg·min, and then titrated in increments of 1 µg·kg·min.The optimal dose of dobutamine for improving blood flow to the tissue flap was 3.50 ±â€Š0.57 µg·kg·min in 50% of patients. The 95% effective dose of dobutamine calculated by probit analysis was 4.46 µg·kg·min (95% confidence interval: 3.99-7.00 µg·kg·min).The results of our study suggest that a dobutamine infusion rate less than 5 µg·kg·minprovides significant improvement of blood flow to the tissue flap, while minimizing cardiovascular side effects.

Occurrence of Atrial Fibrillation During Dobutamine Stress Echocardiography.

Dobutamine stress echocardiography (DSE) is a widely used examination for assessment of coronary ischemia, but several complications have been reported. The aim of this study was to assess the incidence of atrial fibrillation (AF) during DSE, and a systematic review and meta-analysis were also performed to determine an accurate estimate of the AF incidence. Over a 16-year period, we reviewed all patients referred for DSE. We systematically analyzed all ECG performed during DSE to detect AF during the examination. DSE was completely performed in 4,818 patients (mean age: 62.1 ± 11.7 years). AF was observed in 40 patients (31 men, mean age: 79.7 ± 8.9 years). Incidence of AF during DSE was 0.83%. Regarding the meta-analysis, the combined AF incidence was 0.86%. In our study, patients with AF occurrence had more frequent previous history of paroxysmal AF (p = 0.02) were also older (p < 0.0001) and incidence of AF during DSE increased with age: 0% below 60 years, 0.45% in patients 60 to 69 years, 1.3% in patients 70 to 79 years, and 4% in patients >80 years (p < 0.0001). In multivariate analysis, the factors significantly associated with an increased risk of AF were age (adjusted odds ratio (aOR) = 2.4, 95% confidence interval: 1.5 to 3.3, p = 0.003) and previous history of paroxysmal AF (aOR = 1.5, 95% confidence interval: 1.1 to 1.9; p = 0.04). In conclusion, AF is uncommon during DSE, and elderly patients and patients with previous history of paroxysmal AF are at risk of AF during DSE.

Treatments targeting inotropy.

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.

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.