Case Report: tacrolimus toxicity in the setting of concurrent Paxlovid use in a heart-transplant recipient.

Background: Tacrolimus toxicity in patient's status post-orthotropic heart transplantation is not commonly reported. Given its narrow therapeutic window and drug-drug interactions, it must be closely monitored by providers who are experienced in transplant management. There are no case series of patients with tacrolimus toxicity in the setting of treatment for Sars-2-CoV-19 (COVID 19) for heart-transplant recipients. We present a case of tacrolimus toxicity in the setting of concurrent ritonavir-nirmatrelvir (Paxlovid) use. Case summary: The patient was a 74-year-old male with a prior significant history of heart transplantation and on maintenance immunosuppression with tacrolimus. He contracted COVID-19 and was prescribed antiviral therapy with Paxlovid by an outside provider prior to admission. The patient complained of severe headaches, dehydration, and tremors. After eliminating acute intracranial processes with imaging, laboratory investigation revealed a severely elevated tacrolimus level with acute renal injury. The patient was taken off tacrolimus and treated conservatively with intravenous hydration. The symptoms improved, particularly the headaches. He was discharged with instructions to resume his home dosing of tacrolimus and return to clinic in 1 week with a repeat trough level. The subsequent trough level was no longer supra-therapeutic. Discussion: Tacrolimus has a potent drug-drug interaction with Paxlovid (ritonavir-nirmatrelvir) and can be supra-therapeutic. Toxicity is associated with multiple adverse effects, including but not limited to, acute renal injury, neurotoxicity, and infections due to over-immunosuppression. As Paxlovid is effective in treating Sars-2-CoV-19 in heart-transplant recipients, knowledge and understanding of drug-drug interactions is crucial in preventing and mitigating toxicity.

Trends and predictors of implantable cardioverter defibrillator implantation after sudden cardiac arrest: Insight from the national inpatient sample.

BACKGROUND: Implantable cardioverter defibrillator (ICD) has a class IA indication in survivors of sudden cardiac arrest (SCA) provided no reversible cause is identified. We sought to determine trends and predictors of ICD implant in SCA patients from a national sample of the United States population. METHODS AND RESULTS: Data were gathered from National Inpatient Sample (NIS) from January 2003 to December 2014. All patients ≥18 years of age with a primary discharge diagnosis of SCA, ventricular fibrillation (VF), ventricular flutter, and ventricular tachycardia (VT) were included. Patients died during hospitalization, had a previous ICD implant, and with a reversible cause of SCA were excluded. Primary outcome of interest was rate of new ICD implant at discharge. Logistic regression analysis was then performed to determine predictors for ICD implantation. A total of 176,876 patients were identified to have SCA, VF, ventricular flutter, and VT. After applying exclusion criteria, we were left with 22,054 patients. Out of this, 6,908 (31%) patients were implanted with an ICD prior to discharge. There was a linear trend toward reduced ICD utilization over our study period (40% in 2003 vs 25% in 2014, P trend = 0.0004). Advanced age, black race, and chronic renal disease are independently associated with low ICD utilization. CONCLUSION: We found low trend of ICD implant in survivors of SCA without any reversible cause. There is a need to identify etiologies behind low ICD utilization in this vulnerable group who are at most risk for a subsequent SCA.

Trends and Outcomes of Aortic Valve Replacement in Patients With End-Stage Renal Disease on Hemodialysis.

Hemodialysis (HD) patients with aortic stenosis are less likely to undergo aortic valve replacement (AVR) due to their excess perioperative mortality. We aimed to evaluate contemporary utilization and outcomes of combined and isolated AVR in HD patients. The Nationwide Inpatient Sample was used to identify 142,046 patients who underwent AVR in 2005 to 2014, of whom 2,264 (1.6%) were on HD. Crude and adjusted in-hospital outcomes and costs were assessed in unmatched and propensity-matched cohorts of HD and non-HD patients, respectively. The utilization of AVR in HD patients increased significantly (p = 0.047), with a significant decrease in mortality (p = 0.013). Compared with patients not on HD, crude in-hospital mortality in HD patients was twice higher (11.8% vs 6.2%, p <0.0001). HD patients had more blood transfusion and a trend toward more strokes. Lengths of stay and hospital charges, and rates of nonhome discharges were also higher in the HD group. In the propensity-matched cohorts of HD versus non-HD patients, in-hospital mortality rates after AVR remained twofold higher in the HD group (8.1% vs 3.9%, p <0.001). Rates of blood transfusion, cardiac tamponade, length of stay, hospital charges, and nonhome discharges were also higher in HD patients. In conclusion, AVR utilization in HD patients increased and its associated mortality decreased over the last decade. However, AVR mortality in HD patients remained twofold higher compared with non-HD patients. Also, AVR in HD patients was associated with higher cost, longer hospitalizations, and more frequent nonhome discharges.

Detecting initial orthostatic hypotension: a novel approach.

Our purpose, by modification of standard bedside tilt-testing, was to search for lesser known but important initial orthostatic hypotension (IOH), occurring transiently within the first 30 seconds of standing, heretofore only detectable with sophisticated continuous photoplethysmographic monitoring systems, not readily available in most medical facilities. In screened outpatients over 60 years of age, supine blood pressure (BP) parameters were recorded. To achieve readiness for immediate BP after standing, the cuff was re-inflated prior to standing, rather than after. Immediate, 1-, and 3-minute standing BPs were recorded. One hundred fifteen patients were studied (mean age, 71.1 years; 50.5% male). Eighteen (15.6%) had OH, of whom 14 (12.1%) had classical OH, and four (3.5%) had IOH. Early standing BP detection time was 20.1 ± 5.3 seconds. Immediate transient physiologic systolic BP decline was detected in non-OH (-8.8 ± 9.9 mm Hg; P < .0001). In contrast to classical OH (with lesser but persistent orthostatic BP decrements), IOH patients had immediate mean orthostatic systolic/diastolic BP change of -32.8 (±13.8) mm Hg/-14.0 (±8.5) mm Hg (P < .02), with recovery back to baseline by 1 minute. Two of the four IOH patients had pre-syncopal symptoms. For the first time, using standard inflation-deflation BP equipment, immediate transient standing physiologic BP decrement and IOH were demonstrated. This preliminary study confirms proof of principle that manual BP cuff inflation prior to standing may be useful and practical in diagnosing IOH, and may stimulate direct comparative studies with continuous monitoring systems.