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ESC Heart Failure Oct 2023The use of tolvaptan is increasing in clinical practice in Japan. However, the characteristics of patients who used tolvaptan and the timing of its use in patients with...
AIMS
The use of tolvaptan is increasing in clinical practice in Japan. However, the characteristics of patients who used tolvaptan and the timing of its use in patients with acute heart failure (AHF) are not fully elucidated.
METHODS AND RESULTS
Among consecutive 4056 patients in the Kyoto Congestive Heart Failure registry, we analysed 3802 patients after excluding patients on dialysis, prior or unknown tolvaptan use at admission, and unknown timing of tolvaptan use, and we divided them into two groups: tolvaptan use (N = 773) and no tolvaptan use (N = 3029). The prevalence of tolvaptan use varied widely from 48.7% to 0% across the participating centres. Factors independently associated with tolvaptan use were diabetes, poor medical adherence, oedema, pleural effusion, hyponatraemia, estimated glomerular filtration rate < 30 mL/min/1.73 m , moderate/severe tricuspid regurgitation, dobutamine infusion within 24 h, and additional inotropes infusion beyond 24 h after admission. The mortality rate at 90 days after admission was significantly higher in the tolvaptan use group than in the no tolvaptan use group (14.3% vs. 8.6%, P = 0.049). However, after adjustment, the excess mortality risk of tolvaptan use relative to no tolvaptan use was no longer significant (hazard ratio = 1.53, 95% confidence interval = 0.77-3.02, P = 0.22). Patients with tolvaptan use had a longer hospital stay [median (interquartile range): 22 (15-34) days vs. 15 (11-21) days, P < 0.0001] and a higher prevalence of worsening renal failure (47.0% vs. 31.8%, P < 0.0001) and worsening heart failure (24.8% vs. 14.4%, P < 0.0001) than those without.
CONCLUSIONS
AHF patients with tolvaptan use had more congestive status with poorer in-hospital outcomes and higher short-term mortality than those without tolvaptan use.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) and https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).
PubMed: 37644779
DOI: 10.1002/ehf2.14494 -
American Journal of Physiology. Heart... Jul 2024Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory... (Observational Study)
Observational Study
Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m ( < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m, < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg ( = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index. This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.
Topics: Humans; Isoproterenol; Heart Transplantation; Middle Aged; Male; Pulmonary Artery; Female; Ventricular Function, Right; Retrospective Studies; Adult; Hemodynamics; Aged; Ventricular Dysfunction, Right; Heart Failure; Dobutamine; Treatment Outcome; Heart Rate; Recovery of Function; Cardiotonic Agents
PubMed: 38700470
DOI: 10.1152/ajpheart.00200.2024 -
Journal of Interventional Cardiac... Jan 2024Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol...
BACKGROUND
Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature.
OBJECTIVE
To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS.
METHODS
From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing.
RESULTS
For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted.
CONCLUSION
In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.
Topics: Humans; Dobutamine; Isoproterenol; Heart Conduction System; Atrioventricular Node; Arrhythmias, Cardiac; Atrioventricular Block
PubMed: 37227538
DOI: 10.1007/s10840-023-01573-1 -
BMC Pediatrics Oct 2023Cardiovascular dysfunction is common in hypoxic-ischemic encephalopathy (HIE), which is one of the leading causes of multi-organ failure in neonates. We aimed to assess...
PURPOSE
Cardiovascular dysfunction is common in hypoxic-ischemic encephalopathy (HIE), which is one of the leading causes of multi-organ failure in neonates. We aimed to assess troponin I and creatine kinase myocardial band (CK-MB) levels, inotropic score (IS) in HIE patients, and their associations with HIE staging and mortality.
METHOD
The medical records of all HIE infants admitted to our unit between 2016 and 2018 were retrospectively analyzed. Demographic characteristics of the infants, seizures, anticonvulsive therapies, maximum inotrope doses, and the derived IS (dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min]) and CK-MB and troponin-I levels obtained in the first six hours of life were compared according to HIE staging. Comparisons between survivors and non-survivors were made.
RESULTS
The study included data from 195 patients. Twenty-five patients were classified as stage 3, 116 as stage 2, and 54 as stage 1 HIE. Median Troponin-I, CK-MB level, and IS significantly differed by HIE staging (p < 0.01). The deceased infants had significantly higher median troponin I level [0.36 (0.02-3) vs. 0.16 (0.01-1.1) ng/ml; p = 0.006], median IS [20 (5-120) vs. 5 (5-10); p < 0.001], however, CK-MB values were comparable with survivors [129 (51-300) vs. 60.7 (31-300) ng/ml; p = 0.57]. The area under the curve was 0.93 for IS and 0.81 for Troponin I to predict mortality.
CONCLUSION
Troponin I, CK-MB, and IS could be successfully used as disease severity markers in HIE furthermore, troponin I and IS, are good predictors of mortality. These results need to be confirmed with larger prospective multi-center studies.
Topics: Infant; Infant, Newborn; Humans; Troponin I; Creatine Kinase; Retrospective Studies; Creatine Kinase, MB Form; Hypoxia-Ischemia, Brain; Prospective Studies; Infant Mortality; Biomarkers
PubMed: 37845609
DOI: 10.1186/s12887-023-04311-8 -
JACC. Cardiovascular Imaging Jun 2024
PubMed: 38934977
DOI: 10.1016/j.jcmg.2024.04.018 -
Frontiers in Cardiovascular Medicine 2023The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close...
INTRODUCTION
The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.
METHODS
The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.
RESULTS
No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, < 0.01). After adjusting for age, ECV ( = 0.01) and MPR ( = 0.048) still showed significant differences among the three groups.
CONCLUSION
Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.
PubMed: 37663419
DOI: 10.3389/fcvm.2023.1214249 -
Anesthesiology Aug 2023Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains... (Observational Study)
Observational Study
BACKGROUND
Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains understudied. Therefore, the authors sought to quantify patient-, anesthesiologist-, and hospital-related contributions to variation in inotrope use.
METHODS
In this observational study, nonemergent adult cardiac surgeries using cardiopulmonary bypass were reviewed across a multicenter cohort of academic and community hospitals from 2014 to 2019. Patients who were moribund, receiving mechanical circulatory support, or receiving preoperative or home inotropes were excluded. The primary outcome was an inotrope infusion (epinephrine, dobutamine, milrinone, dopamine) administered for greater than 60 consecutive min intraoperatively or ongoing upon transport from the operating room. Institution-, clinician-, and patient-level variance components were studied.
RESULTS
Among 51,085 cases across 611 attending anesthesiologists and 29 hospitals, 27,033 (52.9%) cases received at least one intraoperative inotrope, including 21,796 (42.7%) epinephrine, 6,360 (12.4%) milrinone, 2,000 (3.9%) dobutamine, and 602 (1.2%) dopamine (non-mutually exclusive). Variation in inotrope use was 22.6% attributable to the institution, 6.8% attributable to the primary attending anesthesiologist, and 70.6% attributable to the patient. The adjusted median odds ratio for the same patient receiving inotropes was 1.73 between 2 randomly selected clinicians and 3.55 between 2 randomly selected institutions. Factors most strongly associated with increased likelihood of inotrope use were institutional medical school affiliation (adjusted odds ratio, 6.2; 95% CI, 1.39 to 27.8), heart failure (adjusted odds ratio, 2.60; 95% CI, 2.46 to 2.76), pulmonary circulation disorder (adjusted odds ratio, 1.72; 95% CI, 1.58 to 1.87), loop diuretic home medication (adjusted odds ratio, 1.55; 95% CI, 1.42 to 1.69), Black race (adjusted odds ratio, 1.49; 95% CI, 1.32 to 1.68), and digoxin home medication (adjusted odds ratio, 1.48; 95% CI, 1.18 to 1.86).
CONCLUSIONS
Variation in inotrope use during cardiac surgery is attributable to the institution and to the clinician, in addition to the patient. Variation across institutions and clinicians suggests a need for future quantitative and qualitative research to understand variation in inotrope use affecting outcomes and develop evidence-based, patient-centered inotrope therapies.
Topics: Humans; Male; Female; Adolescent; Adult; Middle Aged; Aged; Aged, 80 and over; Myocardial Contraction; Cardiotonic Agents; Cardiac Surgical Procedures; Epinephrine; Dopamine; Dobutamine; Milrinone; Intraoperative Care
PubMed: 37094103
DOI: 10.1097/ALN.0000000000004593 -
European Heart Journal. Acute... Oct 2023Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue...
AIMS
Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies.
METHODS AND RESULTS
FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015].
CONCLUSION
Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer.
Topics: Humans; Male; Middle Aged; Aged; Aged, 80 and over; Female; Shock, Cardiogenic; Prospective Studies; Dobutamine; Norepinephrine; Neoplasms
PubMed: 37410588
DOI: 10.1093/ehjacc/zuad072 -
Animals : An Open Access Journal From... Sep 2023This retrospective study investigated the effect of a xylazine infusion on heart rate; mean arterial pressure; blood gases; anesthetic and dobutamine requirements;...
This retrospective study investigated the effect of a xylazine infusion on heart rate; mean arterial pressure; blood gases; anesthetic and dobutamine requirements; recovery quality and duration; percentage of death/survival; and days to die/discharge in horses after colic surgery under partial intravenous anesthesia with isoflurane and lidocaine infusion. Anesthetic records of equine colic surgery were reviewed from similar periods in 2020-2021 and 2021-2022. In both groups, after sedation with xylazine 0.7 mg/kg intravenously (IV) and induction with ketamine 2.2 mg/kg and midazolam 0.06 mg/kg IV, anesthesia was maintained with isoflurane and lidocaine (bolus 1.5 mg/kg IV, infusion 2 mg/kg/h). Group L (2020-2021, = 45) received xylazine 0.2 mg/kg IV before recovery, group XL (2021-2022, = 44) received xylazine 0.5 mg/kg/h IV intraoperatively. In group XL, minimal ( = 0.04) and average ( = 0.04) heart rate, intraoperative hematocrit ( = 0.001), minimal ( = 0.002) and maximal ( = 0.04) dobutamine administration rate, animals requiring ketamine top-ups ( = 0.04), and the number of days to discharge ( = 0.02), were significantly lower compared to group L. During recovery in group XL, the time to sternal recumbency ( = 0.03) and time to first attempt ( = 0.04) were significantly longer. This retrospective study suggests that a xylazine infusion may have beneficial effects on horses undergoing colic surgery. Further prospective studies are necessary.
PubMed: 37760302
DOI: 10.3390/ani13182902 -
Cardiovascular Research Jul 2023Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the...
AIMS
Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges.
METHODS AND RESULTS
Male rats overexpressing the cardiac-specific VEGF-B transgene (VEGF-B TG) were treated for 3 or 6 weeks with deoxycorticosterone-acetate combined with a high-salt (HS) diet (DOCA + HS) to induce hypertension and cardiac damage. Extensive longitudinal echocardiographic studies of HF progression were conducted, starting at baseline. Sham-treated rats served as controls. To evaluate the metabolic alterations associated with HF, cardiac proteomics by mass spectrometry was performed. Hypertrophic non-treated VEGF-B TG hearts demonstrated high oxygen and adenosine triphosphate (ATP) demand with early onset of diastolic dysfunction. Administration of DOCA + HS to VEGF-B TG rats for 6 weeks amplified the progression from cardiac hypertrophy to HF, with a drastic drop in heart ATP concentration. Dobutamine stress echocardiographic analyses uncovered a significantly impaired systolic reserve. Mechanistically, the hallmark of the failing TG heart was an abnormal energy metabolism with decreased mitochondrial ATP, preceding the attenuated cardiac performance and leading to systolic HF.
CONCLUSIONS
This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF.
Topics: Rats; Male; Animals; Vascular Endothelial Growth Factor B; Desoxycorticosterone Acetate; Heart Failure, Systolic; Proteomics; Hypertension; Myocardium; Heart Failure; Cardiomegaly
PubMed: 36951047
DOI: 10.1093/cvr/cvad040