Implementation of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary 'GDMT Team' on medical therapy prescription for HFrEF.
Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage continues to be associated with high levels of morbidity and mortality. This complication had long been thought to occur secondary to severe cerebral vasospasm, but expert opinion now favors a multifactorial etiology, opening the possibility of new therapies. To date, no definitive treatment option for DCI has been recommended as standard of care, highlighting a need for further research into potential therapies. Milrinone has been identified as a promising therapeutic agent for DCI, possessing a mechanism of action for the reversal of cerebral vasospasm as well as potentially anti-inflammatory effects to treat the underlying etiology of DCI. Intra-arterial and intravenous administration of milrinone has been evaluated for the treatment of DCI in single-center case series and cohorts and appears safe and associated with improved clinical outcomes. Recent results have also brought attention to the potential outcome benefits of early, more aggressive dosing and titration of milrinone. Limitations exist within the available data, however, and questions remain about the generalizability of results across a broader spectrum of patients suffering from DCI. The development of a standardized protocol for milrinone use in DCI, specifically addressing areas requiring further clarification, is needed. Data generated from a standardized protocol may provide the impetus for a multicenter, randomized control trial. We review the current literature on milrinone for the treatment of DCI and propose a preliminary standardized protocol for further evaluation of both safety and efficacy of milrinone.
Left ventricular systolic dysfunction is the hallmark pathology in heart failure with reduced ejection fraction. Increasing left ventricular contractility with beta-adrenergic receptor agonists, phosphodiesterase-3 inhibitors, or levosimendan has failed to improve clinical outcomes and, in some situations, increased the risk of sudden cardiac death. Beta-adrenergic receptor agonists and phosphodiesterase-3 inhibitors retain an important role in advanced heart failure. Thus, there remains an unmet need for safe and effective therapies to improve left ventricular systolic function. Two novel cardiac myotropes, omecamtiv mecarbil and danicamtiv, target cardiac myosin to increase left ventricular systolic performance. Neither omecamtiv mecarbil nor danicamtiv affects cardiomyocyte calcium handling, the proposed mechanism underlying the life-threatening arrhythmias associated with cardiac calcitropes and calcium sensitizers. Phase 2 clinical trials have demonstrated that these cardiac myosin activators prolong left ventricular systolic ejection time and promote left ventricular and atrial reverse remodeling. At higher plasma concentrations, these agents may be associated with myocardial ischemia and impaired diastolic function. An ongoing phase 3 clinical trial will estimate the clinical efficacy and safety of omecamtiv mecarbil. An additional study of these agents, which have minimal hemodynamic and renal effects, is warranted in patients with advanced heart failure refractory to guideline-directed neurohormonal blockers.
Background Diagnosing heparin‐induced thrombocytopenia (HIT) in patients with end‐stage renal disease (ESRD) can be difficult, as they are frequently exposed to heparin and have multiple etiologies for thrombocytopenia. Objective To correlate 4T scores, IgG heparin–platelet factor 4 (PF4‐heparin) ELISA results, and serotonin release assay (SRA) results in patients with ESRD. Methods We performed a retrospective review of patients with ESRD (creatinine clearance < 15 mL/min or on renal replacement therapy [RRT]) who underwent PF4‐heparin ELISA testing from October 2015 to September 2019. True‐positive PF4s required an intermediate to high 4T score (≥4), a positive SRA, and receipt of treatment for a HIT diagnosis. False‐positive PF4s were defined as a positive PF4 with a negative SRA, low 4T score (<4), or lack of treatment for HIT. Indeterminant cases were classified on the basis of clinical assessment by the treating team (eg, hematology or vascular medicine). Results Of 254 patients with ESRD (92% on RRT), 29 patients (11.4%) had a positive PF4. Eleven (37.9%) had a confirmed diagnosis of HIT: 10 patients who met all of the above criteria, and one who met the 4T criteria and was treated for HIT but did not have SRA testing due to high clinical suspicion and a positive PF4 test. False‐positive PF4 values occurred in 8 patients (27.5%). Of 10 (34.5%) indeterminant cases of patients with a negative SRA but intermediate to high 4T and positive PF4, only 3 patients were treated for HIT, whereas the other 7 were judged not to have HIT as assessed by the treating clinician. In patients with an intermediate to high 4T score and PF4 optical density > 0.4 but negative SRA, who were not treated for HIT, there were no adverse outcomes documented such as new or progressive thrombosis. Conclusion In our ESRD population, 4T scores and PF4 testing were not predictive of a clinical diagnosis of HIT.
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