Search

Aims: Advanced heart failure (AdvHF) poses significant treatment challenges, particularly when mechanical circulatory support or transplant options are unavailable, highlighting a gap in evidence-based medical management. The aim of this study was to evaluate the safety and effectiveness of sodium nitroprusside infusion (SNP) for enhancing systemic and renal perfusion in patients with AdvHF, with or without concomitant inotropic support., Methods and Results: We retrospectively analyzed the medical records of 406 patients with AdvHF admitted between October 2014 and September 2018 who received nocturnal SNP infusions for at least one week. In 55 patients with symptomatic hypotension or signs of peripheral hypoperfusion (differential systemic BP < 15 mmHg), continuous dobutamine infusion was added. In a subset of 155 patients who required multiple hospitalizations (median 3), data from the last hospitalization were used. No symptomatic hypotension leading to discontinuation of SNP (mean dose: 0.5 ± 0.1 μg/kg/min) was reported. Patients showed a significant increase in differential systemic blood pressure after infusion (29.2 ± 8.1 to 36.8 ± 11.6 mmHg, p < 0.001) independent of dobutamine use. Administration of SNP and dobutamine resulted in greater weight loss compared to SNP alone (-5.33 ± 7.02 vs -3.32 ± 4.0 kg, p < 0.003), but it was also associated with a significant increase in creatinine levels compared to SNP alone (+0.24 ± 0.87 vs +0.02 ± 0.43, p = 0.005)., Conclusions: The results show that SNP is a safe therapeutic choice in AdvHF patients with or without concomitant inotropic support and highlight the potential efficacy of nitroprusside in improving systemic and renal perfusion in these advanced patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Laparoscopic ovariectomy under general anesthesia was planned in a 10-year-old, 146 kg, apparently healthy female African lion (Panthera leo). The lion was immobilized via intramuscular darts containing midazolam (0.033 mg/kg), medetomidine (50 µg/kg) and ketamine (2.5 mg/kg), and intubated using an endotracheal tube (16 mm internal diameter). The anesthesia was maintained using sevoflurane (0.9-2.1% end-tidal concentration), in combination with remifentanil (0.1 µg/kg/min) and ketamine (11 µg/kg/min) at a constant rate infusion (CRI), with Hartmann's solution (5 mL/kg/hr). Surgery was conducted with stable vital signs, but hypotension (mean arterial blood pressure 55 mmHg) developed, requiring dobutamine treatment. The hypotension was effectively controlled by adjusting dobutamine from 5 µg/kg/min to 0.2 to 0.3 µg/kg/min. This case suggests possibilities that dosages in this range can be clinically useful for peri-anesthetic hypotension in lions.

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., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The relationship between VIS max and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VIS max and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VIS max was calculated (VIS max  = 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. VIS max was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VIS max (≤ 5), those with the high VIS max (> 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 VIS max 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 VIS max 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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 21 st 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., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: None declared., (Thieme. All rights reserved.)

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 VFT peak , compared with VFT rest . Mean VFT rest was 2.46 (0.73) and mean VFT peak 1.67 (0.57) with mean VFT i  - 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., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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., (Copyright © 2021. Published by Elsevier Inc.)

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.

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 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.

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 (V Max ), integral of kinetic energy (iK), and maximal power (P Max ) 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 V Max of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear P Max 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 P Max and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear V Max of BCG, rather than the V Max of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. P Max and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.

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.

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.

Background: Dobutamine stress echocardiography (DSE) and coronary computed tomography angiography (CTA) can provide perioperative prognostic information in risk stratification of patients undergoing noncardiac surgery. This study directly compared the prognostic value of DSE and CTA in patients undergoing noncardiac surgery., Methods: Between 2014 and 2016, 215 patients with more than one clinical risk factor for perioperative cardiovascular (CV) events were enrolled prospectively. They received both DSE and CTA before noncardiac surgery. Perioperative clinical risk was classified according to the revised cardiac risk index (RCRI), DSE results were categorized as abnormal (inducible ischemia and/or nonviable infarction) or not. CTA results were assessed using the severity of stenosis, with significant stenosis being ≥50% of the luminal diameter). After the exclusion, a total of 206 patients remained. Perioperative CV events were defined as CV death, non-fatal myocardial infarction (MI), myocardial injury, pulmonary edema, non-fatal stroke, and systemic embolism within 30 days after surgery., Results: Twenty-four patients (12%) had perioperative cardiac events (1 cardiac death, 10 non-fatal MI, 8 myocardial injury, 11 pulmonary edema, 1 non-fatal stroke, and 1 pulmonary embolism). Following adjustment for baseline RCRI score, abnormal result on DSE (OR, 6.08, 95% CI, 2.41 to 15.31, P < 0.001), significant CAD on CTA (OR, 18.79; 95% CI, 5.24 to 67.42, P < 0.001), and high CACS (OR, 4.19; 95% CI, 1.39 to 12.60, P = 0.011) remained significant predictors of perioperative CV events., Conclusions: DSE and CTA are independent predictive factors of events in patients undergoing noncardiac surgery. Among them, assessment of significant CAD using CTA might show a higher prognostic value compared with DSE before noncardiac surgery., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02250963., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Negative stress echocardiography (NSE) is associated with low cardiovascular morbidity and overall mortality. We aimed to determine the clinical and echocardiographic predictors of overall and cardiovascular outcomes following NSE. Patients who underwent SE between 2013 and 2017 were reviewed. Patients with a history of solid organ transplant or being evaluated for transplant, history of end-stage renal or liver disease, and positive SE were excluded. NSE results were divided into negative diagnostic if patient reached target heart rate (THR) and had no wall motion abnormality (WMA) at rest or stress; negative non-diagnostic if patient had no WMA but did not reach THR or if image quality was non-diagnostic; and abnormal non-ischemic if patient had a resting WMA not worsened at stress along with a personal history of coronary artery disease (CAD). New CAD lesion at 1 year was defined as ≥ 50% stenosis on cardiac catheterization. Of 4119 patients with SE, 2575 were included. All-cause mortality rate was 1.1%/year and CAD rate was 3.1%/year. Predictors of all-cause mortality were age, male gender, history of smoking and being selected for dobutamine SE. Predictors of a new CAD lesion at 1 year were male gender, diabetes, personal history of CAD and abnormal non-ischemic SE. We identified clinical and echocardiographic characteristics in a subset of NSE patients who are at higher risk for subsequent adverse events. These characteristics should be accounted for during the clinical interpretation of SE, and patients found at increased risk for morbidity and mortality warrant continued follow-up.

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.

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.

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.

Objective: Due to the low prevalence of obstructive coronary artery disease (CAD) in women, stress testing has a relatively low predictive value for this. Additionally, conventional cardiovascular risk scores underestimate risk in women. This study sought to evaluate the role of atherosclerosis assessment using carotid ultrasound (CU) in women attending for stress echocardiography (SE)., Methods: This was a prospective study in which consecutive women with recent-onset suspected angina, who were referred for clinically indicated SE, underwent CU., Results: 415 women (mean age 61±10 years, 29% diabetes mellitus, mean body mass index 28) attending for SE underwent CU. 47 women (11%) had inducible wall motion abnormalities, and carotid disease (CD) was present in 46% (carotid plaque in 41%, carotid intima-media thickness >75th percentile in 15%). Women with CD were older (65 vs 58 years, p<0.001), and more likely to have diabetes (41% vs 21%, p=0.001), hypertension (67% vs 36%, p<0.01) and a higher pretest probability of CAD (59% vs 41%, p<0.001). 40% of women classified as low Framingham risk were found to have evidence of CD.The positive predictive value of SE for flow-limiting CAD was 51%, but with the presence of carotid plaque, this was 71% (p<0.01). Carotid plaque (p=0.004) and ischaemia (p=0.01) were the only independent predictors of >70% angiographic stenosis. In women with ischaemia on SE and no carotid plaque, the negative predictive value for flow-limiting disease was 88%.During a follow-up of 1058±234 days, there were 15 events (defined as all-cause mortality, non-fatal myocardial infarction, heart failure admissions and late coronary revascularisation). Age (HR 1.07 (1.00-1.15), p=0.04), carotid plaque burden (HR 1.65 (1.36-2.00), p<0.001) and ischaemic burden (HR 1.41 (1.18-1.68), p<0.001) were associated with outcome. There was a stepwise increase in events/year from 0.3% when there were no ischaemia and atherosclerosis, 1.1% when there was atherosclerosis and no ischaemia, 2.2% when there was ischaemia and no atherosclerosis and 10% when there were both ischaemia and atherosclerosis (p<0.001)., Conclusion: CU significantly improves the accuracy of SE alone for identifying flow-limiting disease on coronary angiography, and improves risk stratification in women attending for SE, as well identifying a subset of women who may benefit from primary preventative measures., Competing Interests: Competing interests: RS has received speaker fees from Bracco (Italy), Phillips (Netherlands) and Lantheus Medical Imaging., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In recent years, home medical care has been strongly promoted. As a consequence, the conditions managed in home medical care have become increasingly diverse. Heart failure is one of the most common disorders after malignant diseases. Patients with chronic heart failure (CHF) are often forced into hospitalization because of the inability to control symptoms with oral medications, even though they hope to stay at home. Recently, we have experienced a case where the patient required continuous administration of dobutamine at home. In order to carry out CHF care at home successfully, it is necessary to adjust the doses of catecholamine and furosemide swiftly in response to changes in patients' conditions. In this case, the patient was able to spend four months at home thanks to the cooperation of a team of a physician, nurses, and pharmacists. Catecholamine-dependent patients with terminal CHF require expensive medical infusion pumps for precise administration. However, the economic assistance to such patients remains insufficient. Furthermore, dobutamine and furosemide injections are not dispensed extramurally, and therefore might become an impediment to the cooperation of the team. In this symposium, I consider and discuss the role of pharmacists in a home medical care team for patients with terminal CHF.

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 ( P interaction =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 ( P interaction =0.116), physical limitation ( P interaction =0.461), quality of life ( P interaction =0.689), EuroQOL 5 quality-of-life score ( P interaction =0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class ( P interaction =0.693), and treadmill exercise time ( P interaction =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.

Background: The regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of α- and β-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis., Methods: Murine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), β1 (dobutamine), or β2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (ia) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity., Results: Treatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia)., Conclusion: Whereas the β-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Background: A laboratory investigation was initiated after a renal failure patient had a 2.18 mg/dL decrease in serum creatinine, which was not explained through medical intervention. The investigation revealed specimens providing questionably low results had been collected from a peripherally inserted central catheter (PICC) line., Methods: Patient specimens and serum pools were analyzed by the Siemens Vista enzymatic creatinine measurement procedure. A simulation of the patient's infusion protocol examined potential PICC line carryover and specimen collection technique., Results: A simultaneously collected specimen set, arterial line and PICC line, yielded a difference of 1.86 mg/dL. Infusion and collection simulation studies suggested the most likely scenario was the infusion pump was not shut off while the specimen collection occurred and contaminated the specimen., Conclusion: Providers should be aware of erroneously low creatinine results when administering catecholamine drugs and collecting specimens through the same catheter. The mechanism of specimen contamination is consistent with a siphoning effect from one lumen to the other during collection with the infusion pumps still running., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: This study determined the test performance of dobutamine stress echocardiography (DSE) in end-stage liver disease (ESLD)., Background: The reported sensitivity of DSE in ESLD has been variable., Methods: Data from 633 ESLD patients who had coronary angiography within 6 months after DSE was analyzed., Results: The prevalence of coronary arterial disease (CAD) (≥70% stenosis by quantitative angiography) was 12% (74 of 633 patients). DSE sensitivity was 24% (17 of 72 patients), and specificity was 90% (503 of 559 patients). The positive and negative predictive values were 23% (17 of 73 patients) and 90% (503 of 558 patients), respectively. Stratifying the cohort into low-, intermediate-, and high-risk CAD groups yielded sensitivities of 0%, 21%, and 32%, respectively. Independent predictors of an accurate ischemic DSE result included left ventricular internal dimension at end-diastole (LVIDd) >4.8 cm and assigning ischemia based on tardokinesis or lack of low-to-peak dose hyperkinesis (p < 0.05 for all). DSE sensitivity was 38% in LVIDd >4.8 cm versus 13% with LVIDd ≤4.8 cm (p = 0.013). The sensitivity was 67% when tardokinesis or lack of hyperkinesis was considered abnormal versus 15% (p < 0.001) for readings that did not consider tardokinesis or lack of hyperkinesis abnormal. There was a higher frequency of cardiac events in patients with significant CAD who had abnormal (45%) versus normal (18%) DSE (p = 0.01)., Conclusions: The sensitivity of DSE in ESLD was low. DSE sensitivity was higher for those with larger cavity dimension and when tardokinesis or lack of hyperkinesis was considered abnormal. An abnormal DSE in those with significant CAD was associated with worse outcome., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The role of coronary microvascular disease and its impact on functional and energetic reserve in heart failure with preserved ejection fraction (HFpEF) remains unclear. We hypothesized that in response to submaximal pharmacologic stress (dobutamine), patients with HFpEF have impairment in left ventricular (LV) myocardial mechanical (external work [EW]), energetic (myocardial O 2 consumption [MVO 2 ]), and myocardial blood flow (MBF) reserve. We further assessed whether coupling of MBF to EW is impaired in HFpEF and associated with compensatory increases or pathological decreases in myocardial O 2 extraction. Lastly, we assessed whether coupling of MVO 2 to EW (mechanical efficiency) was impaired in HFpEF., Methods and Results: In prospectively enrolled patients with HFpEF (n=19) and age/sex-matched healthy controls (n=19), we performed 11 C-acetate positron emission tomography assessing MVO 2 and MBF at rest and during dobutamine infusion. EW was calculated as stroke volume (echo)×end-systolic pressure×heart rate. At rest, compared with controls, patients with HFpEF had higher LV EW, MVO 2 , and MBF. With dobutamine, LV EW, MVO 2 , and MBF increased in both HFpEF and controls; however, the magnitude of increases was significantly smaller in HFpEF. In both groups, MBF increased in relation to EW, but in HFpEF, the slope of the relationship was significantly smaller than in controls. Myocardial O 2 extraction was increased in HFpEF. Mechanical efficiency was similar in HFpEF and controls. In a post hoc analysis, HFpEF patients with LV hypertrophy (n=10) had significant reductions in LV mechanical efficiency relative to controls., Conclusions: In HFpEF during submaximal dobutamine stress, there is myocardial mechanical-, energetic- and flow-reserve dysfunction with impaired coupling of blood flow to demand and slight increases in myocardial O 2 extraction. These findings provide evidence that coronary microvascular dysfunction is present in HFpEF, limits O 2 supply relative to demand, and is associated with reserve dysfunction.

We investigated the influence of the extent of viability using low dose dobutamine wall motion score index (WMS) on the survival benefit of surgical revascularization (CABG) versus medical therapy. In the STICH trial, viability assessment was not helpful in determining the benefit of CABG. However, the extent of viable myocardium with contractile function was not assessed in the trial. Dobutamine echocardiography was performed in 250 patients with ischemic left ventricular dysfunction (125-medically treated, 125-CABG). The mean ejection fraction (EF) was 32% in both groups. WMS during low dose dobutamine infusion was used to classify patients into groups with extensive (WMS < 2.00), intermediate (WMS 2.00-2.49), and limited (WMS ≥ 2.50) viability. Survival free of cardiac death was assessed at 2 years and for the complete duration of follow-up. There were 44 (35.2%) and 67 (53.6%) cardiac deaths in the revascularized and medically treated patients respectively (follow-up of 5.7 ± 5.8 years). Revascularized and medically treated patients with extensive viability had similar 2-year survival (p = 0.567) but revascularized patients had improved long-term survival (p = 0.0001). In those with intermediate viability, revascularization improved both 2 year (p = 0.014) and long-term survival (p = 0.0001). In patients with limited viability, 2-year survival was worse in revascularized patients (p = 0.04) and long-term survival was similar (p = 0 .25) in revascularized and medically treated groups. Patients with extensive and intermediate amounts of viability have improved survival with CABG but those with limited viability have poorer short-term outcome and no long-term benefit.

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&#95;vol avg cycle , KE avg cycle, EL avg cycle ). The relation to maximum oxygen uptake (VO 2 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 (KE avg cycle : 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (EL avg cycle : 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity&#95;vol avg cycle : 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO 2 max (KE avg cycle : r = - 0.83, P = 0.003; EL avg cycle : r = - 0.80, P = 0.006; vorticity&#95;vol avg 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 VO 2 max.

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis., Competing Interests: The authors have declared that no competing interests exist.

Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.

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.

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p < 0.05 vs. T and AL). ESV absolute values were moderately correlated: T versus S (r rest = 0.746, p < 0.01, n = 100; r stress = 0.794, p < 0.01, n = 100); T vs. AL (r = 0.603 p < 0.01, n = 100, at rest and r = 0.820 p < 0.01 n = 100 at peak stress). LVCR values were tightly correlated independently of the method employed: T versus S (r = 0.899, p < 0.01, n = 100), and T versus AL (r = 0.845, p < 0.01, n = 100). LVCR can be accurately determined with all three methods used to extract the raw values of ESV necessary to generate the calculation of Force. Although S is known to be more precise in determining absolute ESV values, the relative (rest-stress) changes can be assessed, with comparable accuracy, with simpler and more feasible T and AL methods, characterized by higher success rate, shorter imaging and analysis time.

Objectives: To evaluate the advantages and disadvantages of using different standard concentration infusions for high-alert inotropic and vasoactive drugs in paediatric intensive care units (ICUs)., Methods: Retrospective data analysis was performed on drug prescriptions for patients in paediatric ICUs. A matrix was developed based on optimal concentration recommendations for each drug, taking into consideration solution stability and patient safety. Hypothetical volumes were calculated for three standard solutions (high concentration - HC, low concentration - LC and fluid restriction - FR) and compared to the actual administered volumes to evaluate the impact of the volumes of each standard solution for varying weight ranges in paediatric care. Finally, a risk assessment of the standard infusions was conducted using the NPSA 20 tool along with an assessment of the pharmacoeconomic impact., Key Findings: The results suggest the need for at least two standard concentrations for each of the studied drugs in order to attend to the different weight ranges and clinical conditions of paediatric patients in intensive care., Conclusions: High concentration is ideal for patients up to 20 kg. For patients over 20 kg, FR is recommended, while LC should only be used in specific situations. Modifying the hospital pharmacotherapy system to include standard solutions is safer and reduces the risks of adverse effects. The pharmacoeconomic analysis did not show any impact on costs, although a reduction in adverse effects should be considered., (© 2019 Royal Pharmaceutical Society.)

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 ± 0.57 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.

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/dt min ) 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/dt min 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., (© 2019 John Wiley & Sons Ltd.)

Previous studies have suggested a decline in positivity of stress cardiac imaging based on regional wall motion abnormalities (RWMA). To assess the rate of RWMA positivity of stress echocardiography (SE) over 3 decades in the same primary care SE lab. We retrospectively assessed the rate of SE positivity in 7626 SE tests (dipyridamole in 5053, dobutamine in 2496, exercise in 77) in consecutive patients with known or suspected coronary artery disease and /or heart failure who performed SE in a primary care referral center from April 1991 to May 2018. Starting April 2005, SE based on RWMA was complemented by assessment of coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery. Starting October 2016, we added left ventricular contractile reserve (LVCR). Starting October 2016, we also added B-lines by lung ultrasound. There was a progressive decline over time in the rate of SE positivity based on RWMA from 24% (1991-1999) to 10% (2000-2009) down to 4% (2010-2018) (p < 0.0001). Positivity rate was 29% with CFVR, 16% with LVCR, and 12% with B-lines. Over three decades, we observed a dramatic decline in SE positivity rate based on classical RWMA. In the last decade, the positivity rate rose sharply thanks to the stepwise introduction of CFVR, LVCR and B-lines as additional positivity criteria in integrated quadruple SE.

The aim of the current study was to investigate whether stress echocardiography improves selection of patients who might have clinical benefit from percutaneous mitral valve repair with the MitraClip. In total, 39 patients selected for MitraClip implantation underwent preprocedural low-dose stress (dobutamine or handgrip) echocardiography from which stroke volume, ejection fraction and MR grade were measured. Outcome after MitraClip implantation was determined by New York Heart Association classification and Quality of Life questionnaires. Clinical benefit from MitraClip treatment was defined as survival and NYHA class I-II at 6 months follow-up. In total, 36 patients with a technically successful procedure were included in the analysis (mean age 79 ± 8 years, 47% male, 50% functional MR). Clinical benefit was achieved in 18 patients. All seven patients with MR decreasing during stress remained in NYHA III-IV or died within 6 months, while 62% (18 out of 29) of the patients with stable or increased MR during stress had clinical benefit (p = 0.008). Significant increase in Quality of Life on 4/8 subscales of the RAND Short Form-36 questionnaire was observed: Physical Functioning (p < 0.001), Social Functioning (p < 0.001), Mental Health (p = 0.022) and Vitality (p = 0.026) was seen in patients with an increase in stroke volume during stress echocardiography. Patients with a decreased MR during preprocedural stress echocardiography remained more symptomatic than patients with a stable or increased MR during stress. Stress echocardiography may support patient selection for percutaneous mitral valve repair.

OBJECTIVE To determine the impact of mechanical ventilation (MV) and perfusion conditions on the efficacy of pulse-delivered inhaled nitric oxide (PiNO) in anesthetized horses. ANIMALS 27 healthy adult horses. PROCEDURES Anesthetized horses were allocated into 4 groups: spontaneous breathing (SB) with low (< 70 mm Hg) mean arterial blood pressure (MAP; group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Dobutamine was used to maintain MAP > 70 mm Hg. Data were collected after a 60-minute equilibration period and at 15 and 30 minutes during PiNO administration. Variables included Pao 2 , arterial oxygen saturation and content, oxygen delivery, and physiologic dead space-to-tidal volume ratio. Data were analyzed with Shapiro-Wilk, Mann-Whitney U, and Friedman ANOVA tests. RESULTS Pao 2 , arterial oxygen saturation, arterial oxygen content, and oxygen delivery increased significantly with PiNO in the SB-L, SB-N, and MV-N groups; were significantly lower in group MV-L than in group MV-N; and were lower in MV-N than in both SB groups during PiNO. Physiologic dead space-to-tidal volume ratio was highest in the MV-L group. CONCLUSIONS AND CLINICAL RELEVANCE Pulmonary perfusion impacted PiNO efficacy during MV but not during SB. Use of PiNO failed to increase oxygenation in the MV-L group, likely because of profound ventilation-perfusion mismatching. During SB, PiNO improved oxygenation irrespective of the magnitude of blood flow, but hypoventilation and hypercarbia persisted. Use of PiNO was most effective in horses with adequate perfusion.

Severe aortic stenosis (AS) is typically identified by a low valve area (≤1.0 cm 2 ) and high mean gradient (≥40 mm Hg). A subset of patients are found to have a less than severe mean gradient (<40 mm Hg) despite a low valve area. These latter types can present as either low ejection fraction with low-gradient AS (stage D2) or normal ejection fraction with low-gradient AS (stage D3). Determining the true severity of disease within these categories has proved difficult. In this review we illustrate both traditional and novel techniques that can be used for further valvular assessment. We also propose a simple algorithm that can be used to evaluate low-gradient AS., (Published by Elsevier Inc.)

Non-response cardiac resynchronization therapy (CRT) remains an issue, despite the refinement of selection criteria. The purpose of this study was to investigate the role of stress echocardiography along with dyssynchrony parameters for identification of CRT responders or late responders. 106 symptomatic heart failure patients were examined before, 6 months and 2-4 years after CRT implementation. Inotropic contractile reserve (ICR) and inferolateral (IL) wall viability were studied by stress echocardiography. Dyssynchrony was assessed by: (1) Septal to posterior wall motion delay (SPWMD) by m-mode. (2) Septal to lateral wall delay (SLD) by TDI. (3) Interventricular mechanical delay (IVMD) by pulsed wave Doppler for (4) difference in time to peak circumferential strain (TmaxCS) by speckle tracking. (5) Apical rocking (ApR) and septal flash (SF) by visual assessment. At 6 months there were 54 responders, with 12 additional late responders. TmaxCS had the greatest predictive value with an area under curve (AUC) of 0.835, followed by the presence of both ICR and viability of IL wall (AUC 0.799), m-mode (AUC = 0.775) and presence of either ApR or SF (AUC = 0.772). Predictive ability of ApR and of ICR is augmented if late responders are also included. Performance of dyssynchrony parameters is enhanced, in patients with both ICR and IL wall viability. Stress echocardiography and dyssynchrony parameters are simple and reliable predictors of 6-month and late CRT response. A stepwise approach with an initial assessment of ICR and viability and, if positive, further dyssynchrony analysis, could assist decision making.

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., (© 2018 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)