A Rare Case of Cyclophosphamide-Induced Posterior Reversible Encephalopathy Syndrome in a Patient With Acute Lupus Nephritis Flare.

Posterior reversible encephalopathy syndrome (PRES) is a syndrome encompassing both clinical and radiological manifestations with white matter vasogenic edema predominantly of the posterior and parietal lobes of the brain. It may accompany several medical conditions including immunosuppressive/cytotoxic drugs. We present a case of cyclophosphamide-induced PRES in a patient treated for acute lupus flare with biopsy-proven lupus nephritis. A 23-year-old African American female presented with non-specific symptoms over a six-month period on a medical background of systemic lupus erythematosus and biopsy-proven focal lupus nephritis class III on hydroxychloroquine, prednisone, and mycophenolate mofetil for which she was non-compliant. She was borderline hypertensive, tachycardic, saturating well on ambient air, and alert and oriented. Laboratory workup revealed electrolyte imbalance, elevated serum urea, creatinine, and B-type natriuretic peptide, low serum complements, and elevated double-stranded DNA (dsDNA) with negative lupus anticoagulant, anti-cardiolipin, and B2 glycoprotein antibody. Chest imaging revealed cardiomegaly with small pericardial effusion, left pleural effusion, and trace atelectasis, with no deep vein thrombosis on Doppler ultrasound. She was admitted to the intensive care unit for lupus flare with severe hyponatremia and was continued on mycophenolate mofetil, hydroxychloroquine, and prednisone 60 mg for induction therapy as well as intravenous fluids. Hyponatremia resolved, and blood pressure was controlled. She became fluid overloaded and anuric, with pulmonary edema and worsening hypoxic respiratory failure not responding to diuretic challenges. Daily hemodialysis was started, and she was intubated. Prednisone was tapered down, mycophenolate was switched to cyclophosphamide/mesna. She became agitated, restless, and confused, with waxing and waning consciousness and hallucinations. She was continued on bi-weekly cyclophosphamide for induction therapy. After the second dose of cyclophosphamide, her mentation worsened. Non-contrast MRI showed extensive bilateral cerebral and cerebella deep white matter high-intensity signals suggestive of PRES, which was new compared to one year prior. Cyclophosphamide was held and her mentation improved. She was successfully extubated and discharged to a rehabilitation center. The exact pathophysiological mechanism of PRES is not known. Endothelial damage and vasogenic edema have been hypothesized as possible mechanisms. Severe anemia, fluid overload, and renal failure are some of the causes of endothelial dysfunction and vasogenic edema with disruption of the blood-brain barrier, which were found in our patient, but repeated dosing of cyclophosphamide worsened her condition. Discontinuation of cyclophosphamide led to a significant improvement and complete reversal of her neurologic symptoms, implying that prompt recognition and management of PRES is vital to prevent permanent damage and even death in these patients.

Comparative Analysis of Established Risk Scores and Novel Hemodynamic Metrics in Predicting Right Ventricular Failure in Left Ventricular Assist Device Patients.

BACKGROUND: Right ventricular failure (RVF) portends poor outcomes after left ventricular assist device (LVAD) implantation. Although numerous RVF predictive models have been developed, there are few independent comparative analyses of these risk models. METHODS AND RESULTS: RVF was defined as use of inotropes for >14 days, inhaled pulmonary vasodilators for >48 hours or unplanned right ventricular mechanical support postoperatively during the index hospitalization. Risk models were evaluated for the primary outcome of RVF by means of logistic regression and receiver operating characteristic curves. Among 93 LVAD patients with complete data from 2011 to 2016, the Michigan RVF score (C = 0.74 [95% CI 0.61-0.87]; P = .0004) was the only risk model to demonstrate significant discrimination for RVF, compared with newer risk scores (Utah, Pitt, EuroMACS). Among individual hemodynamic/echocardiographic metrics, preoperative right ventricular dysfunction (C = 0.72 [95% CI 0.58-0.85]; P = .0022) also demonstrated significant discrimination of RVF. The Michigan RVF score was also the best predictor of in-hospital mortality (C = 0.67 [95% CI 0.52-0.83]; P = .0319) and 3-year survival (Kaplan-Meier log-rank 0.0135). CONCLUSIONS: In external validation analysis, the more established Michigan RVF score-which emphasizes preoperative hemodynamic instability and target end-organ dysfunction-performed best, albeit modestly, in predicting RVF and demonstrated association with in-hospital and long-term mortality.

Right atrial to left atrial volume index ratio is associated with increased mortality in patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. METHODS: We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH. LA and RA volume indices were measured in the four-and two-chamber views by two independent researchers. Multivariable logistic regression was used to model the independent association of RAVI/LAVI with survival. RESULTS: Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.91, 95% CI: 1.20-3.04). In a multivariable logistic regression, each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.73, 95% CI: 1.003-2.998). Furthermore, RAVI/LAVI in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary artery wedge pressure ratio (RAP/PAWP) (0.76 ± 0.41, P = 0.02) compared with the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes, and mortality in PH. CONCLUSIONS: Increased RAVI/LAVI in PH is associated with decreased survival and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index in predicting outcomes in PH.