Search

Background: Severe early graft dysfunction (EGD) is defined by mechanical circulatory support (MCS) <24 hours of heart transplantation (HT). We classified severe EGD based on timing of post-HT MCS: ''Immediate'' intra-operative vs ''Delayed'' post-operative MCS (after admission into intensive care unit (ICU) from operating theater). We hypothesized that (1) risk factors and clinical course differ between ''Immediate'' and ''Delayed'' MCS; and (2) diastolic perfusion pressure (DPP=diastolic blood pressure-central venous pressure) and Norepinephrine equivalents (NE=sum of vasopressor doses), as measures of vasoplegia are related to ''Delayed'' MCS., Methods: Two-center study of 216 consecutive patients who underwent HT. Recipient, donor, vasopressor doses and hemodynamic data at T0 and T6 (on admission and 6 hours after admission into ICU) were collected., Results: Of the 216 patients, 67 patients had severe EGD (''Immediate'' MCS: n = 43, ''Delayed'' MCS: n = 24). The likelihood of ''immediate'' MCS but not ''delayed'' MCS increased with increasing warm ischemic and cardiopulmonary bypass times on multinomial regression analysis with ''no MCS'' as the referent group. One-year mortality was highest in ''Immediate'' MCS vs ''no MCS'' and ''delayed'' MCS (34.9% vs 3.4% and 8% respectively, p < 0.001). Of the patients who had no immediate post-transplant MCS, DPP and NE at T6 were independently associated with subsequent ''delayed'' MCS. Sensitivity and specificity of NE≥ 0.2 mcg/kg/min for ''Delayed'' MCS were 71% and 81%. Sensitivity and specificity of DPP of ≥40 mmHg for No MCS were 83% and 74%. The discriminatory value of systemic vascular resistance for ''Delayed'' MCS was poor., Conclusion: Risk factors and 1-year survival differed significantly between ''Immediate'' and ''Delayed'' post-HT MCS. The latter is related to lower DPP and higher NE, which is consistent with vasoplegia as the dominant pathophysiology., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: Troponin elevation after noncardiac surgery is associated with an elevated risk of 30-day mortality. Little is known about relative merit of using a high-sensitivity Troponin T (hsTnT), the fifth-generation assay, vs the nonhigh sensitivity Troponin T (non-hsTnT), the fourth-generation assay, in the noncardiac surgery setting. We aimed to identify whether hsTnT can identify additional patients at risk that would have gone undetected with non-hsTnT measurement., Methods: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure)., Results: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001)., Conclusions: Within the first 3 postoperative days, fifth-generation hsTnT identified at least 1 in 3 patients with troponin elevation that would have gone undetected by fourth-generation non-hsTnT using published thresholds in this setting. Furthermore, fifth-generation hsTnT identified patients with an elevation earlier than fourth-generation non-hsTnT, indicating potential to improve postoperative risk stratification., Competing Interests: Disclosures FKB holds a Research Early Career Award from Hamilton Health Sciences, and has received grants from Roche Diagnostics and SIEMENS for investigator initiated research grants, and honorarium for lectures or participation in as advisory board from Roche Diagnostics and Novartis. ED reports research grants for investigator-initiated studies and honoraria for participation in advisory board from Roche Diagnostics and research grant for investigator-initiated study from Abbott Laboratories. PK has received grants/reagents/consultant/advisor/ honoraria from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Quidel, Randox Laboratories, Roche Diagnostics, Siemens Healthcare Diagnostics, and Thermo Fisher Scientific . McMaster University has filed patents with PK listed as an inventor in the acute cardiovascular biomarker field. OB Received research grants from AstraZeneca, Pfizer, Bayer, Amgen, Servier, Novartis, BMS and Boeheringer-Ingelheim unrelated to the submitted work PJD reports grants from Canadian Institutes of Health Research and from Ontario Strategy for Patient Oriented Research Support Unit/Ministry of Health and Long-Term Care during the conduct of the study; and grants from Abbott Diagnostics, Roche Diagnostics, and Siemens, CloudDX, Philips Healthcare, outside the submitted work. Declares to be consultant for Abbott Canada, Renibus, Roche Canada and Trimedic. Declares be a member of advisory board of Bayer, Quidel and speaker for Velocit. DIS, MT, AP, YL, DH, SS, WC, CC, SNO, SP, AK, AT and ACT declare no conflict of interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys. Exosome-associated miRNA exhibited distinctive trends when compared to miRNAs quantified in whole urine, which may reflect a different urinary excretion mechanism of miRNAs than those released passively into the urine. Although further research and mechanistic studies are required to elucidate how these miRNAs regulate signaling in disease pathways, we present, for the first time, data that several miRNAs displayed strong correlations with histopathology scores, thus indicating their potential use as biomarkers to predict the development of DIKI in preclinical studies and clinical trials. Also, these findings can potentially be translated into other non-clinical species or human for the detection of DIKI., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The following authors are employed in the pharmaceutical industries (at the time of article submission): P.K.M., B.B., A.E., E.V., T.S., D.D.W., A.S, T.R.V. The opinions presented here are those of the authors. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion., Methods and Results: We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B-lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub-acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients (n = 25), change in weight was correlated with both change in device TI (Spearman correlation [r sp ] = -0.64, p = 0.002) and change in device S3 (r sp  = -0.53, p = 0.014). In the haemodialysis cohort (n = 21), B-lines and TI were strongly correlated before (r sp  = -0.71, p < 0.001) and after (r sp  = -0.77, p < 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (r sp  = 0.49, p = 0.024). In the RHC cohort (n = 20), PCWP measured at one time point and device S3 were not significantly correlated (r sp  = 0.230, p = 0.204). There were no device-related adverse events., Conclusions: A non-invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs., (© 2024. The Author(s).)

Traditional approaches to preclinical drug safety assessment have generally protected human patients from unintended adverse effects. However, these assessments typically occur too late to make changes in the formulation or in phase 1 and beyond, are highly dependent on animal studies and have the potential to lead to the termination of useful drugs due to liabilities in animals that are not applicable in patients. Collectively, these elements come at great detriment to both patients and the drug development sector. This phenomenon is particularly problematic in the area of cardiovascular safety assessment where preclinical attrition is high. We believe that a more efficient and translational approach can be defined. A multi-tiered assessment that leverages our understanding of human cardiovascular biology, applies human cell-based in vitro characterizations of cardiovascular responses to insult, and incorporates computational models of pharmacokinetic relationships would enable earlier and more translational identification of human-relevant liabilities. While this will take time to develop, the ultimate goal would be to implement such assays both in the lead selection phase as well as through regulatory phases., Competing Interests: Author BB was employed by B2 Pathology Solutions, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berridge, Pierson, Pettit and Stockbridge.)