Trends in diagnosis, referral, red flag onset, patient profiles and natural outcome of de novo cardiac amyloidosis and their multidisciplinary implications.

BACKGROUND: Cardiac amyloidosis (CA) is often overlooked or misdiagnosed. Effects of growing disease awareness, diagnostic ameliorations and novel treatment options on CA diagnosis and management are scarcely reported. OBJECTIVE: To report trends in diagnosis, referral routes, clinical presentation, early onset diagnostic red flags and outcome in de novo CA subjects. METHODS: An unselected cohort of 139 de novo CA patients over an 8-year period in a tertiary referral hospital was recruited. RESULTS: Transthyretin (ATTR, 82%, n = 114) was the most common CA form; Light-chain (AL, 15%, n = 21) and secondary (AA, 3%, n = 4) are less prevalent. Increased awareness over time led to a marked ATTR diagnostic surge, steep non-invasive diagnostic approach increment and increased nuclear medicine and external cardiologist referrals (all p < 0.001). A total of 41% (n = 57/139) of patients were referred by non-cardiology specialist disciplines. Specific referral to rule out CA (24-36%) and diagnostic time lag from symptom onset (9 ± 12 to 8 ± 14 months), however, did not improve (all p > 0.050). Multiple early red flag events preceded CA diagnose several years in ATTR: Left ventricular hypertrophy (LVH, 60%, 4.9 ± 4.3 y), heart failure (54%, 2.5 ± 3.5 y), atrial fibrillation (47%, 5.9 ± 6.7 y), bilateral carpal tunnel syndrome (43%, 9.5 ± 5.7 y) and spinal stenosis (40%, 7.4 ± 6.5 y). LVH ≥ 12 mm was absent in 11% ATTR (n = 13/114) and 5% AL (n = 1/21) patients. Hypertension was common in both ATTR (n = 70/114, 62%) and AL (n = 10/21, 48%). 56% (n = 78/139) of CA presented with heart failure. Cumulative 1 and 5-year mortality of 10%/66%, 40%/52% and 75%/75% for ATTR, AL, and AA, respectively, remains high. CONCLUSIONS: Although CA diagnostic uptake and referral improve, specialist-specific disease and diagnostic red flag ignorance result in non-timely diagnosis and unfavourable outcome.

Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study.

BACKGROUND: Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation. METHODS: Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µg thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression. RESULTS: Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm. CONCLUSIONS: Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.

"White Thyroid" on Unenhanced Computed Tomography in Amiodarone-Induced Thyrotoxicosis Type 2.

Amiodarone-induced thyrotoxicosis is a common complication of long-term amiodarone treatment. In a patient with amiodarone-induced lung toxicity and amiodarone-induced thyrotoxicosis type 2 (AIT2), a "white thyroid" was incidentally observed on an unenhanced chest computed tomography (CT) scan. This "white thyroid" resembled a thyroid image on a contrast-enhanced CT scan. Therefore, the thyroid density was prospectively evaluated on unenhanced CT scans in cases of AIT2, in euthyroid patients on amiodarone (AEuth), and in unexposed controls. The aim was to test the hypothesis of a higher thyroid density in AIT2 compared to AEuth. The thyroid density, as measured in Hounsfield Units on unenhanced CT scans, is higher in AIT2 compared to AEuth and much higher than in controls. The causality of this association and its potential diagnostic use require further study.

Coronary artery ectasia due to microfistulae.

The pathogenesis of coronary artery ectasia (CAE) is not fully understood and associated with a vast group of disorders. We present a rare case of CAE of the left coronary artery associated with microfistulae. Microfistulae bypass myocardial capillaries and decrease the distal blood flow. The coronary artery responds to this coronary steal phenomenon with a compensatory dilatation, causing diffuse ectasia to catch up for the considerable decrease in coronary diastolic perfusion pressure. Although segmental dilatation is frequently seen in association with hypertension, one should think of microfistulae as an underlying cause of diffuse coronary ectasia.

Evaluation of true diffusion, perfusion factor, and apparent diffusion coefficient in non-necrotic liver metastases and uncomplicated liver hemangiomas using black-blood echo planar imaging.

PURPOSE: To assess the added value of true diffusion (D), perfusion factor (f) and apparent diffusion coefficient at low b-values (ADC(low)) for differentiation between liver metastases and hemangiomas based on respiratory-triggered high-resolution Black-Blood Single-Shot SpinEcho Echo Planar Imaging (BB SS SE-EPI). MATERIALS AND METHODS: Twenty-five patients suspected for malignant colorectal liver lesions were included in this study. A total of 106 lesions were examined. Different b-value images were compared for lesion conspicuity, image quality and artifacts using rank order statistic (RIDIT) and Student's t-test. D, f, and ADC(low) values were calculated. Pearson correlation coefficient is used for comparison of interobserver variability. RESULTS: Best lesion conspicuity (p<0.05) was achieved with BB SS SE-EPI (b=0 and 10s/mm(2)); best image quality (p<0.05) with b=10s/mm(2). Image artifacts were lowest (p<0.05) with b=0s/mm(2). Over the whole sample, D in metastases (D(met)) was significantly (p<0.05) lower than D in hemangiomas (D(hem)); f and ADC(low) of metastases (f(met), respectively, ADC(lowmet)) were significantly (p<0.05) higher than f and ADC(low) of hemangiomas (f(hem), respectively, ADC(lowhem)). All Pearson correlations were statistically significant at a 0.01 level. CONCLUSIONS: This preliminary study shows the potential of BB SS SE-EPI as a useful technique to aid in differentiating between liver metastasis and hemangioma. The calculation of D, f and ADC(low) provides useful additional information for differentiating metastases from hemangiomas.

MRI of the cranial nerves--more than meets the eye: technical considerations and advanced anatomy.

Magnetic resonance (MR) imaging is the method of choice to evaluate the cranial nerves. Although the skull base foramina can be seen on CT, the nerves themselves can only be visualized in detail on MR. To see the different segments of nerves I to XII, the right sequences must be used. Detailed clinical information is needed by the radiologist so that a tailored MR study can be performed. In this article, MR principles for imaging of the cranial nerves are discussed. The basic anatomy of the cranial nerves and the cranial nerve nuclei as well as their central connections are discussed and illustrated briefly. The emphasis is on less known or more advanced extra-axial anatomy, illustrated with high-resolution MR images.

Symptomatic arrhythmogenic right ventricular dysplasia/cardiomyopathy. A two-centre retrospective study of 15 symptomatic ARVD/C cases and focus on the diagnostic value of MRI in symptomatic ARVD/C patients.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with sudden death in the young and heart failure in the elderly. The purpose is to review 15 symptomatic ARVD/C cases and also to describe the use of MRI as a diagnostic tool. METHODS AND RESULTS: This retrospective analysis includes 15 patients who presented with symptomatic ARVD/C. Diagnosis was made upon the criteria proposed by the European Society of Cardiology. In all patients there was at least 1 or more abnormal MRI sign. The most frequent abnormalities were focal right ventricular dyskinesia (64%), MRI fatty infiltration (57%) and right ventricular aneurysm or right ventricular outflow tract microaneurysms (57%). Presenting symptoms were palpitations (60%), atypical chest pain (46%), syncope (40%), and aborted sudden death (26%). T-inversion in V2-V3 was seen in 60% of the patients. Thirteen patients (86%) received an ICD implantation. The mean follow-up per patient was 89 months, which resulted in a total follow-up of 111 patient years. Forty-six percent of the patients with an ICD had one or more appropriate shocks during follow-up. To this date no mortality was reported. CONCLUSION: This retrospective study demonstrates that symptomatic ARVD/C patients typically present with symptoms of syncope, palpitations in association with ventricular tachycardia and in a quarter of the cases with aborted sudden cardiac death. The electrocardiogram mostly shows T inversion in the anterior leads. All patients were treated with medication and ICD-implantation or VT-ablation. The malignant nature of the disease in symptomatic ARVD/C patients is stressed by the fact that the presenting symptom is aborted sudden death in a quarter of the cases and the fact that nearly half of the patients with an ICD had at least one appropriate shock during follow-up. There was an abnormal MRI in 100% of the investigated patients. In 20% (3 patients), the MRI criterion (right ventricular dilatation/bulging/aneurysm) was necessary to meet the ESC criteria. Therefore it has become an important tool in our diagnostic work-up when ARVD/C is suspected. We also suggest a change in the diagnostic criteria of ARVD/C. Whereas fatty infiltration seen on RV biopsy is a major criterion, MRI fatty infiltration is not regarded as a diagnostic criterion by the task force to this day.

An acute posterior myocardial infarction complicated with late pseudoaneurysm of the posterior wall.

Diagnostic image: An 80-year-old man is referred because of an acute posterior infarction. Because of persisting pain and apparition of a new murmur, an echocardiography is performed showing inferoposterolateral akinesis complicated by ventricular wall pseudoaneurysm. After discussing with patient and family, conservative therapy was continued. A clue for diagnosis of pseudoaneurysm is the presence of a systolic murmur.