A retrospective observational study evaluating the association between vasoactive-inotropic score and mortality after major abdominal surgery.

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16-12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09-6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64-0.75) and 0.67 (95% CI 0.62-0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.

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.

Pulmonary 4D-flow MRI imaging in landrace pigs under rest and stress.

4D-flow MRI is a promising technique for assessing vessel hemodynamics. However, its utilization is currently limited by the lack of reference values, particularly for pulmonary vessels. In this work, we have analysed flow and velocity in the pulmonary trunk (PT), left and right pulmonary arteries (LPA and RPA, respectively) in Landrace pigs at both rest and stress through the software MEVISFlow. Nine healthy Landrace pigs were acutely instrumented closed-chest and transported to the CMR facility for evaluation. After rest measurements, dobutamine was administered to achieve a 25% increase in heart rate compared to rest. 4D-flow MRI images have been analysed through MEVISFlow by two independent observers. Inter- and intra-observer reproducibility was quantified using intraclass correlation coefficient. A significant difference between rest and stress regarding flow and velocity in all the pulmonary vessels was observed. Mean flow increased 55% in PT, 75% in LPA and 40% in RPA. Mean peak velocity increased 55% in PT, 75% in LPA and 66% in RPA. A good-to-excellent reproducibility was observed in rest and stress for flow measurements in all three arteries. An excellent reproducibility for velocity was found in PT at rest and stress, a good one for LPA and RPA at rest, while poor reproducibility was found at stress. The current study showed that pulmonary flow and velocity assessed through 4D-flow MRI follow the physiological alterations during cardiac cycle and after stress induced by dobutamine. A clinical translation to assess pulmonary diseases with 4D-flow MRI under stress conditions needs investigation.

Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

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.

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.

Viabilidade miocárdica na prática clínica / Assessing myocardial viability in clinical practice

Embora a avaliação da viabilidade miocárdica seja comum na prática do cardiologista, muitos médicos têm dúvidas a respeito dos resultados dos métodos diagnósticos. A medicina nuclear tem papel importante nos estudos de viabilidade, mas os laudos precisam ser interpretados num contexto clínico e fisiopatológico. Este artigo teve o objetivo de revisar a origem e a evolução do conceito da viabilidade miocárdica. São expostos os métodos diagnósticos com ênfase na medicina nuclear com uma explicação funcional sobre cada tipo de exame. A partir disso, são mostradas imagens como exemplos e é proposta uma maneira de atuar nesses casos baseada na clínica, na porcentagem de miocárdio acometido e na topografia das lesões coronarianas (proximais ou distais). (AU)

Although assessing myocardial viability is a common cardiology practice, many physicians question the results of diagnostic methods. Nuclear medicine plays an important role in viability studies, but the reports require interpretation in a clinical and pathophysiological context. this article was aimed at reviewing the origin and evolution of myocardial viability. Here we present diagnostic methods by emphasizing nuclear medicine and provide a functional explanation of each test type using example images. We also propose how to act in these cases based on clinic examination findings, the percentage of affected myocardium, and coronary lesion topography (proximal or distal).(AU)

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced with dopamine or dobutamine infusion.

BACKGROUND: In the adult brain, increases in neural activity lead to increases in local blood flow. However, in the preterm neonate, studies of cerebral functional haemodynamics have yielded inconsistent results, including negative responses suggesting decreased perfusion and localised tissue hypoxia, probably due to immature neurovascular coupling. Furthermore, the impact of vasoactive medications, such as dopamine and dobutamine used as inotropic therapies in preterm neonates, on cerebrovascular responses to somatosensory input is unknown. We aimed to characterise the cerebral haemodynamic functional response after somatosensory stimulation in the preterm newborn brain, with and without dopamine or dobutamine treatment. METHODS: We studied the cerebral haemodynamic functional response in 13 anaesthetised preterm lambs, using near infrared spectroscopy to measure changes in cerebral oxy- and deoxyhaemoglobin (ΔoxyHb, ΔdeoxyHb) following left median nerve stimulation using stimulus trains of 1.8, 4.8 and 7.8 s. The 4.8 and 7.8 s stimulations were repeated during dopamine or dobutamine infusion. RESULTS: Stimulation always produced a somatosensory evoked response. Majority of preterm lambs demonstrated positive functional responses (i.e. increased ΔoxyHb) in the contralateral cortex following stimulus trains of all durations. Dopamine increased baseline oxyHb and total Hb, whereas dobutamine increased baseline deoxyHb. Both dopamine and dobutamine reduced the evoked ΔoxyHb responses to 4.8 and 7.8 s stimulations. CONCLUSIONS: Somatosensory stimulation increases cerebral oxygenation in the preterm brain, consistent with increased cerebral blood flow due to neurovascular coupling. Notably, our results show that dopamine/dobutamine reduces oxygen delivery relative to consumption in the preterm brain during somatosensory stimulations, suggesting there may be a risk of intermittent localised tissue hypoxia which has clear implications for clinical practice and warrants further investigation.

An update on levosimendan in acute cardiac care: applications and recommendations for optimal efficacy and safety.

Introduction: In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption.Areas covered: Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors.Expert opinion:Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.

Assessment of left ventricular twist by 3D ballistocardiography and seismocardiography compared with 2D STI echocardiography in a context of enhanced inotropism in healthy subjects.

Ballistocardiography (BCG) and Seismocardiography (SCG) assess the vibrations produced by cardiac contraction and blood flow, respectively, by means of micro-accelerometers and micro-gyroscopes. From the BCG and SCG signals, maximal velocities (VMax), integral of kinetic energy (iK), and maximal power (PMax) can be computed as scalar parameters, both in linear and rotational dimensions. Standard echocardiography and 2-dimensional speckle tracking imaging echocardiography were performed on 34 healthy volunteers who were infused with increasing doses of dobutamine (5-10-20 µg/kg/min). Linear VMax of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear PMax of both SCG and BCG and the linear iK of BCG are the best predictors of the LV ejection fraction (LVEF) (p < 0.0001). This result is further confirmed by mathematical models combining the metrics from SCG and BCG signals with heart rate, in which both linear PMax and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear VMax of BCG, rather than the VMax of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. PMax and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.

Accuracy of global and regional longitudinal strain at peak of dobutamine stress echocardiography to detect significant coronary artery disease.

Dobutamine stress echocardiography (DSE) is sensitive but subjective diagnostic tool to detect inducible ischemia. Nowadays, speckle tracking allows an objective quantification of regional wall function. We aimed to investigate the feasibility and accuracy of global (GLS) and regional longitudinal strain (RLS) during DSE to detect significant coronary stenosis (SCS). We conducted a prospective observational multicenter study including patients undergoing DSE for suspected SCS. 50 patients with positive DSE underwent coronary angiography. Besides visual regional wall motion score index (WMSI), GLS and RLS were determined at rest and at peak stress by Automated Function Imaging. DSE GLS feasibility was 96%. Among 35 patients with SCS, 12 patients were affected by multivessel disease, 18 had stenosis of left anterior descending artery (LAD), 18 of left circumflex (LCX) and 15 of right coronary artery (RCA). At peak stress, both GLS reduction (p = 0.037) and WMSI worsening (p = 0.04) showed significant agreement with coronary angiography for detecting SCS. When single lesion was considered, peak stress GLS and LAD RLS were lower in the obstructed LAD regions than in normo-perfused territories (17.4 ± 5.5 vs. 20.5 ± 4.4%, p = 0.03; 17.1 ± 7.6 vs. 21.6 ± 5.5%, p < 0.02, respectively). Furthermore, the addition of RLS to regional WMSI was able to improve accuracy in LAD SCS prediction (AUC 0.68, p = 0.037). Conversely, in presence of LCX or RCA SCS, LS was less accurate than WMSI at peak stress. In conclusion, DSE strain analysis is feasible and may improve prediction of LAD SCS, whereas regional WMSI assessment performs better in presence of SCS of LCX and RCA.

The Effect of Dobutamine Stress Testing on Vortex Formation Time in Patients Evaluated for Ischemia.

Vortex formation time (VFT) is a dimensionless index used to quantify duration of vortex ring formation during diastole. We sought to investigate the effect of pharmaceutical stress on VFT in patients evaluated for ischemia. For this purpose, a standard dobutamine stress echo (DSE) protocol was performed in 50 consecutive patients, and VFT was calculated at rest and at peak. VFT was calculated from echocardiography measurements using a previously developed mathematical equation. VFTi was calculated as the percentage of change of VFTpeak, compared with VFTrest. Mean VFTrest was 2.46 (0.73) and mean VFTpeak 1.67 (0.57) with mean VFTi - 30.0% (19.8). In 14 (28%) patients, an ischemic response (DSE+) was documented. VFTi was significantly lower in DSE+ patients a finding which remained significant in the multivariate analysis after adjusting for age, sex, hypertension, diabetes, history of coronary artery disease, and relative increase of heart rate during stress. Graphical Abstract.

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.

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

Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults.

BACKGROUND: To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry. METHODS: We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 µg/kg/min landiolol. RESULTS: Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started. The dobutamine effects were rapidly antagonized by landiolol within 16 min. A further slight decrease in heart rate during 20-60 min of the landiolol infusion occurred as well. Upon termination of landiolol infusion, heart rate and blood pressure recovered rapidly in response to the persisting dobutamine infusion but did not return to the maximum values before landiolol infusion. The pharmacokinetic parameters of landiolol in presence of dobutamine showed a short half-life (3.5 min) and a low distribution volume (0.3 l/kg). No serious adverse events were observed. CONCLUSION: Landiolol can antagonize the dobutamine-induced increases in heart rate and blood pressure in a fast way. A rapid bradycardic effect until steady-state plasma levels is followed by a slow heart rate reduction. The latter can be attributed to an early desensitization to dobutamine. Consequently, after termination of landiolol, the heart rate did not achieve maximum pre-landiolol values. The pharmacokinetics of landiolol during dobutamine infusion are similar when compared to short- and long-term data in Caucasian subjects. Landiolol in the given dose can thus serve as an antagonist of dobutamine-induced cardiac effects. TRIAL REGISTRATION: Registration number 2010-023311-34 at the EU Clinical Trials Register, registration date 2010-12-21.

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.

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.

Does myocardial viability detection improve using a novel combined 99mTc sestamibi infusion and low dose dobutamine infusion in high risk ischemic cardiomyopathy patients?

OBJECTIVE: Early identification of viable myocardium in ischemic cardiomyopathy (ICM) patients is essential for early intervention and better clinical outcome. 99mTechnetium (99mTc) sestamibi gated myocardial perfusion imaging (gMPI) is a well-established technique for myocardial viability evaluation. Detection of potentially viable segments is a predictor of hibernating myocardium. ICM patients with hibernation have a better prognosis after revascularization. We used a novel infusion technique to determine better viability detection preoperatively in challenging situations. Like thallium, does prolonged availability of sestamibi in circulation with additional low dose dobutamine steady infusion (DS Inf) facilitate improved myocardial viability? METHODS: A total of 58 ICM patients with infarct and left ventricular ejection fraction (LVEF) <45% underwent 99mTc sestamibi bolus injection followed by slow intravenous infusion single-photon emission computed tomography (SPECT) using a 2 day protocol. After acquiring the second set of 99mTc sestamibi infusion images, a third SPECT gMPI was performed during DS Inf. RESULTS: A 17-segment myocardial model was used; 52 of 58 patients (548/986 segments) demonstrated perfusion defects (nonviable myocardium) on bolus study. Only 24 patients demonstrated viable segments by standard bolus imaging protocol. The slow MIBI infusion study demonstrated 158 viable segments (12 ICM patients), while combined infusion (99mTc sestamibi+DS Inf) exhibited an additional 6 patients with improved myocardial viability. Thus, 18 high risk patients benefited by this novel infusion technique to demonstrate viable myocardium on SPECT. There was a significantly higher sensitivity (p=0.05) and positive predictive value (p=0.01) in viability identification with the combined DS Inf technique. In dysfunctional segments, the rate of concordance for detecting viability between infusion and bolus techniques was 65%. Paired t test showed statistically significant improvement in viability detection with combined infusion compared to the bolus study (p=0.001). CONCLUSION: This novel infusion technique was shown to be feasible and incremental in viability detection in ICM patients with severe left ventricular dysfunction. It is a robust tool to guide revascularization, in high risk ICM patients. This study also showed that patients with large transmural MI demonstrated no significant improvement in myocardial perfusion status using either protocol.