Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report.

BACKGROUND: Tenofovir disoproxil fumarate is widely used in Botswana as part of the first-line antiretroviral regimen in the 'Treat All' strategy implemented in 2016 by the Ministry of Health. Its use has been associated with several uncommon adverse renal effects, though rarely all in conjunction or without the combined use of protease inhibitors. CASE PRESENTATION: A 49-year-old woman living with HIV whose viral load is suppressed on tenofovir disoproxil fumarate, lamivudine, and dolutegravir presented with 1 day of generalized weakness and myalgia causing an inability to ambulate. This was associated with nausea and vomiting and profound fatigue. She was found to have an acute kidney injury, non-anion-gap metabolic acidosis, hypernatremia, hypokalemia, and hypophosphatemia. Urinalysis revealed pyuria with white blood cell casts, glucosuria, and proteinuria. The diagnosis was made of tenofovir-induced nephrotoxicity. The tenofovir was discontinued, and the patient was initiated on intravenous fluids and electrolyte and bicarbonate supplementation with improvement in her symptoms and laboratory values. CONCLUSIONS: This report suggests the possibility of severe tenofovir-induced nephrotoxicity with combined acute kidney injury, Fanconi syndrome, and nephrogenic diabetes insipidus in the absence of other provoking factors such as use with protease inhibitors or advanced HIV disease, chronic kidney disease, and age. With its wide use in Botswana and other countries, health-care providers should have a high index of suspicion for tenofovir-induced nephrotoxicity for HIV patients on tenofovir with deranged renal function tests and electrolytes.

Clinical Clues and Diagnostic Workup of Cardiac Amyloidosis.

Cardiac amyloidosis is increasingly recognized as an underlying cause of left ventricular wall thickening, heart failure, and arrhythmia with variable clinical presentation. Due to the subtle cardiac findings in early transthyretin cardiac amyloidosis and the availability of therapies that can modify but not reverse the disease progression, early recognition is vital. In light chain amyloidosis, timely diagnosis and treatment can significantly improve survival. In this manuscript, we review the clinical, imaging, and electrocardiographic clues that should raise suspicion for cardiac amyloidosis and provide a simplified diagnostic workup algorithm that ensures an accurate diagnosis. The evolution of the noninvasive diagnosis of cardiac amyloidosis has significantly influenced our understanding of disease prevalence, presentations, and outcomes. However, clinical recognition of clues and red flags remains the most important factor in advancing the care of patients with cardiac amyloidosis.

Routine ambulatory heart rhythm monitoring for detection of atrial arrhythmias in transthyretin cardiac amyloidosis.

BACKGROUND: Atrial fibrillation and flutter (AF/AFL) are common in transthyretin cardiac amyloidosis (ATTR-CM) which in turn is associated with higher risk of thromboembolism. Detecting AF/AFL may be especially important, but the role of routine ambulatory monitoring in ATTR-CM patients is unclear. OBJECTIVE: The objective is therefore to determine prevalence and outcomes of subclinical AF/AFL on routine ambulatory rhythm monitoring. METHODS: We report outcomes of an observational study of patients at our Amyloidosis Center with wild-type or variant ATTR-CM diagnosed between 2005 and 2019. Patients without known AF/AFL at baseline had ambulatory ECG monitoring (duration 2-30 days) every 6 months while those with cardiovascular implantable electronic devices (CIEDs) had device interrogations instead. RESULTS: Eighty-four patients with ATTR-CM (mean age 73.5 ± 9.7 years, 94% male) had mean follow-up 2.3 ± 1.9 years. Forty patients (48%) had AF/AFL before ATTR-CM diagnosis. In the remainder, 21 (48%) were subsequently diagnosed with AF/AFL: 10 (48%) based on symptoms, and 11 (52%) by monitoring. Anticoagulation (AC) was started in 9/11 (82%) patients with incidental AF/AFL. Among the entire cohort, stroke occurred in 9 patients (11%): 1 hemorrhagic and 8 ischemic (7 in patients with AF/AFL). No strokes occurred in patients on AC. CONCLUSION: Almost half of patients in our cohort had AF/AFL diagnosed prior to their ATTR-CM diagnosis. In the remainder, approximately half of AF/AFL diagnoses were established incidentally by routine monitoring, most of whom were promptly anticoagulated. Incidence of stroke was high overall, but no strokes occurred in anticoagulated patients. Optimal frequency and duration of monitoring needs further investigation.

Pregnancy Management in a Patient With Congenital Heart Disease and Severe Right Ventricle to Pulmonary Artery Conduit Stenosis.

Background: Pregnancy causes multiple hemodynamic changes that place significant stress on the cardiovascular system. With advancements in medical care, individuals with complex congenital heart disease are living into their childbearing years. Much remains to be understood about the effects and management of pregnancy in individuals with complex congenital heart disease. Case Report: We describe the management and delivery of a 29-year-old pregnant female with repaired tetralogy of Fallot or ventricular septal defect with pulmonary atresia. The patient presented at 21 weeks' gestation with New York Heart Association class II symptoms and pulmonary conduit stenosis, with a mean gradient of 52 mmHg. At 36.5 weeks' gestation, she developed severe pulmonary conduit stenosis with a mean gradient of >75 mmHg. The patient was admitted at 37 weeks' gestation for planned delivery. After a successful cesarean section and bilateral tubal ligation, the patient had an uncomplicated postoperative course. She was scheduled for follow-up for severe conduit stenosis at 6 weeks postpartum to discuss management options. Conclusion: Management of a pregnant patient with adult congenital heart disease should involve risk stratification for complications (commonly congestive heart failure exacerbation and arrhythmias) using tools such as the modified World Health Organization pregnancy risk classification. Based on the risk category, decisions must be made about frequency of follow-up, anesthesia, and mode of delivery. Patients in moderate to high-risk stratification should be managed by a multidisciplinary team at a specialty center, and all patients should undergo an anesthesia consultation prior to delivery. The decision for vaginal or cesarean delivery should be made on a case-by-case basis with consideration given to patient preference. Patients with asymptomatic moderate to severe pulmonic stenosis can be managed conservatively with appropriate follow-up and cardiac imaging, allowing intervention to be completed after delivery.