Initiation of noninvasive surveillance for allograft rejection in heart transplant patients > 1 year after transplant.

BACKGROUND: Gene expression profiling (GEP) and donor-derived, cell-free DNA (dd-cfDNA) measurement are alternative methods to endomyocardial biopsy (EMB) to monitor for rejection following heart transplantation. We aim to describe our use of GEP and dd-cfDNA in heart transplant recipients > 1-year post-transplantation. METHODS: This is a single-center, retrospective study in post-transplant recipients. For patients who were > 1-year post-transplantation and deemed to be at elevated clinical risk for rejection, we collected both GEP and dd-cfDNA every 3 months. Baseline characteristics including GEP, dd-cfDNA levels, rejection episodes, and number of biopsies were obtained. RESULTS: Since July 2019, there were 18 patients being followed with GEP and dd-cfDNA who were > 1-year post-transplantation. Nine EMBs had been performed in seven patients due to as follows; three due to elevated GEP ({greater than or equal to} 34), one due to elevated dd-cfDNA ({greater than or equal to} .20%), two due to elevations of both GEP and dd-cfDNA, two due to clinical rejection and one to follow up a post rejection episode. One of the two biopsies due to elevations of both GEP and dd-cfDNA showed acute cellular rejection grade 2R. None of the biopsies due to either an elevation in the GEP or dd-cfDNA revealed any significant rejection. CONCLUSION: In this study, the use of both GEP and dd-cfDNA led to an increased number of EMB in patients > 1-year post-transplantation. Further studies are needed to validate these findings and evaluate long-term consequences of these diagnostic tests in this population.

Elevated Lactate Secondary to Gastrointestinal Beriberi.

Thiamine deficiency usually occurs with prolonged nutritional deficiency and is almost universally identified with Wernicke's encephalopathy or beriberi. It is also, however, a rare cause of elevated lactate and gastroenterological symptoms. This case report describes a 30-year-old man with 2 weeks of gastroenterological symptoms and intermittent oral intake, who was found to have an elevated lactate level. Neurological exam was normal and an extensive workup was negative, but after being treated with thiamine, his lactate level improved overnight and all of his symptoms resolved. Thiamine levels returned low at 44 nmol/L (normal 78-185 nmol/L). Lack of recognition of this phenomenon, while rare, can lead to unnecessary tests and procedures and increased morbidity and mortality.

HIV and coronary artery calcium score: comparison of the Hawaii Aging with HIV Cardiovascular Study and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts.

OBJECTIVES: To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. METHODS: Cross-sectional study comparing baseline data of males from Hawaii Aging with HIV - Cardiovascular Study (HAHCS) with the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The cohorts were pooled to determine effects of HIV on CAC and explore immunologic and inflammatory factors that may explain development of CAC in HIV. Multivariable regression models compared CAC prevalence in HAHCS with MESA adjusting for coronary heart disease (CHD) risk profiles. RESULTS: We studied 100 men from HAHCS and 2733 men from MESA. Positive CAC was seen in 58% HAHCS participants and 57% MESA participants. Mean CAC was 260.8 in HAHCS and 306.5 in MESA. Using relative risk (RR) regression, HAHCS participants had a greater risk (RR = 1.20, P < 0.05) of having positive CAC than MESA when adjusting for age, smoking status, diabetes, antihypertensive therapy, BMI, systolic blood pressure, total cholesterol, and HDL cholesterol. Among participants with positive CAC, HIV infection was not associated with larger amounts of CAC. Among HAHCS participants, current HIV viral load, CD4, length of HIV, interleukin 6 (IL-6), fibrinogen, C-reactive protein (CRP), and D-dimer were not associated with the presence or amount of CAC. DISCUSSION: HIV was independently associated with a positive CAC in men with increased likelihood occurring between 45 and 50 years of age. Current HIV viral load, CD4 count, length of HIV, and inflammatory markers were unrelated to either presence or amount of CAC.

Wild-Type Transthyretin Cardiac Amyloidosis in a Transplanted Heart.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is more prevalent than appreciated in the elderly. We present the case of an 88-year-old woman who underwent heart transplantation for ischemic cardiomyopathy and then presented 21 years later with new onset atrial flutter, found on endomyocardial biopsy to have new ATTRwt-CM. (Level of Difficulty: Advanced.).

Uncommon obstacle: management of end-stage heart failure in thrombocytopenia with absent radii (TAR) syndrome.

Thrombocytopenia with absent radii (TAR) syndrome is a rare genetic condition causing absent radial bones and thrombocytopenia. Management is generally supportive although there may be a role for platelet-stimulating agents such as romiplostim. In this case, we highlight the obstacles in managing end-stage heart failure in a patient with TAR syndrome.

Fibroelastic Tissue Ring Causing ECMO Catheter Obstruction: An Unusual Complication of Avalon Elite Catheter Insertion.

The Avalon Elite catheter (Maquet Cardiopulmonary, Rastatt, Germany) is a bicaval catheter for single-site cannulation that can be used in the initiation of venovenous extracorporeal membrane oxygenation (ECMO) or as a transition from venoarterial ECMO. We report a unique complication of tissue obstructing the outflow aperture during insertion. (Level of Difficulty: Advanced.).

A Case Report of Congenitally Absent Pericardium Masquerading as Recurrent Pericarditis.

A 24-year-old female with a history of Swyer-James-MacLeod syndrome presented with acute onset of pleuritic chest pain and was initially diagnosed with acute pericarditis. The 12-lead electrocardiogram demonstrated typical diffuse ST-segment elevation and PR-segment depression. Symptoms resolved rapidly with anti-inflammatory therapy consisting of ibuprofen and colchicine. After completing a 3-month course of the latter, her symptoms rapidly recurred. Workup, including labs and cardiac imaging consisting of a transthoracic echocardiogram and cardiac magnetic resonance imaging, was initially interpreted as normal. Re-review of her cardiac imaging revealed the patient had signs of a congenitally absent pericardium, including a "Snoopy Sign" on her posterior-anterior chest X-ray, which is characterized by levoposition of the cardiac silhouette, a lucent area between the pulmonary artery and aorta because of the presence of lung tissue, a lucent area between the base of the heart and the left hemidiaphragm, loss of the right heart border, a prominent pulmonary artery, and a flattened and elongated left ventricular contour. The patient had a cardiac computed tomography scan, which confirmed the diagnosis. In conclusion, a congenitally absent pericardium is a rare disorder, often undetected or misdiagnosed. There are characteristic findings on imaging such as a "Snoopy Sign" on a posterior-anterior chest X-ray, which can be easily missed because of its rarity. Our goal of this report is to educate health care providers about this rare disorder.

A Case Report of a Left Atrial Mass: The Importance of a Detailed Physical Exam.

Cardiac myxomas are rare clinical findings. They are frequently found in the left atrium and more commonly affect women. Clinical presentation can vary widely and symptoms can be vague and non-specific. We present a case of a 67-year-old woman presenting with 3 weeks of progressive heart failure symptoms that failed to respond to oral diuretic therapy. On physical exam, she was found to have a diastolic murmur, rumble and an early diastolic plop. Transthoracic echocardiogram revealed a 5.6 cm × 2.5 cm × 4.3 cm left atrial mass attached to the mitral valve causing left atrial outflow obstruction. The patient subsequently underwent surgical resection of the mass with resolution of symptoms immediately thereafter. Lack of recognition of this pathologic process as a cause of heart failure symptoms and lack of a quality physical exam can lead to a delay in diagnosis and treatment.

Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV- individuals.

OBJECTIVE: Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. METHOD: Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. RESULTS: HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. CONCLUSIONS: This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. SIGNIFICANCE: A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

The Cost-Benefit Balance of Statins in Hawai'i: A Moving Target.

Statins are lipid-lowering medications used for primary and secondary prevention of atherosclerotic disease and represent a substantial portion of drug costs in the United States. A better understanding of prescribing patterns and drug costs should lead to more rational utilization and help constrain health care expenditures in the United States. The 2013 Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File for the State of Hawai'i was analyzed. The number of prescriptions for statins, total annual cost, and daily cost were calculated by prescriber specialty and drug. Potential savings from substituting the highest-cost statin with lower-cost statins were calculated. Over 421,000 prescriptions for statins were provided to Medicare Part D beneficiaries in Hawai'i in 2013, which cost $17.6M. The three most commonly prescribed statins were simvastatin (33.4%), atorvastatin (33.4%), and lovastatin (13.9%). Although rosuvastatin comprised 5.4% of the total statin prescriptions, it represented 30.1% of the total cost of statins due to a higher daily cost ($5.53/day) compared to simvastatin ($0.25/day) and atorvastatin ($1.10/day). Cardiologists and general practitioners prescribed the highest percentage of rosuvastatin (8% each). Hypothetical substitution of rosuvastatin would have resulted in substantial annual cost savings (Simvastatin would have saved $1.3M for 25% substitution and $5.1M for 100% substitution, while atorvastatin would have saved $1.1M for 25% substitution and $4.3M for 100% substitution). Among Medicare Part D beneficiaries in Hawai'i, prescribing variation for statins between specialties were observed. Substitution of higher-cost with lower-cost statins may lead to substantial cost savings.

A comparison of methods for estimating glomerular filtration rate for a population in Hawai'i with non-valvular atrial fibrillation.

Warfarin is the primary treatment for those with atrial fibrillation at increased risk for stroke. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RELY) trial demonstrated that dabigatran, a direct thrombin inhibitor, was associated with lower rates of systemic embolism compared to warfarin.1 Although individuals with a creatinine clearance of less than 30 mL/min were excluded from the trial, the FDA approved the use of dabigatran for those with creatinine clearances as low as 15 mL/min, with a lower dose of dabigatran recommended for individuals with creatinine clearances below 30 mL/min. This study calculated Glomerular Filtration Rates (GFR) via three existing formulas with varying levels of accuracy (ie, the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) to evaluate how patient eligibility for the RELY trial may have varied depending upon the formula used. A retrospective study was performed based on a chart review conducted at a private cardiologist's office in Honolulu, Hawai'i using patients with non-valvular atrial fibrillation. Patients included were those with a BUN/Creatinine assessment within 12 months of the chart review and a CHADS2 (Congestive Heart Disease, hypertension, age greater than 75, diabetes mellitus, and stroke or transient ischemic attack) score of 1 or greater. Of 376 subjects assessed, 64 subjects who failed to meet criteria for the RELY trial when using the Cockcroft-Gault formula (ie, GFR estimates were lower than 30 mL/min) met eligibility criteria when the MDRD formula was used (ie, GFR estimates exceeded 30 mL/min). Subgroup analysis of the 64 subjects revealed that subjects were 89-years-old on average, predominantly female (76.5%), and mostly Japanese (62.5%). Nearly one in five individuals (17%) in the studied population would have received a lower dose of dabigatran if the Cockcroft-Gaunt formula was used for estimating GFRs. The authors recommend caution while dosing dabigatran in the Asian population, as the estimates of kidney functioning vary substantially depending on the formula used to estimate GFR, which may in turn lead in some cases of inadequate dosing of dabigatran.