Historic characteristics and mortality of patients in the Swiss Amyloidosis Registry.

AIMS OF THE STUDY: Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005-2014 and prospectively from 2015 onwards. METHODS: Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually. RESULTS: Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33-4.87); it was 4.87 years (95% CI 3.14-7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48-3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4-95.3%), 68.5% (95% CI 57.4-81.7%) and 66.0% (95% CI 54.6-79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2-99.8%), 77.0% (95% CI 63.4-93.7%) and 50.6% (95% CI 31.8-80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81). CONCLUSION: During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented. Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia.

Importance: Heparin-induced thrombocytopenia (HIT) is a life-threatening condition that requires urgent diagnostic clarification. However, knowledge of the diagnostic utility of the recommended diagnostic tests is limited in clinical practice. Objective: To evaluate the current diagnostic practice for managing the suspicion of HIT. Design, Setting, and Participants: This prospective diagnostic study was conducted from January 2018 to May 2021 among consecutive patients with suspected HIT from 11 study centers in Switzerland, Germany, and the United States. Detailed clinical data and laboratory information were recorded. Platelet factor 4/heparin antibodies were quantified using an automated chemiluminescent immunoassay (CLIA). A washed-platelet heparin-induced platelet activation (HIPA) test was used as a reference standard to define HIT. Exposures: Suspicion of HIT. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests. Results: Of 1448 patients included between 2018 and 2021, 1318 were available for the current analysis (median [IQR] age, 67 [57-75] years; 849 [64.6%] male). HIPA was positive in 111 patients (prevalence, 8.4%). The most frequent setting was intensive care unit (487 [37.0%]) or cardiovascular surgery (434 [33.0%]). The 4Ts score was low risk in 625 patients (46.8%). By 2 × 2 table, the numbers of patients with false-negative results were 10 (9.0%; 4Ts score), 5 (4.5%; CLIA), and 15 (13.5%; recommended diagnostic algorithm). The numbers of patients with false-positive results were 592 (49.0%; 4Ts score), 73 (6.0%; CLIA), and 50 (4.1%; recommended diagnostic algorithm), respectively. Conclusions and Relevance: In this diagnostic study of patients suspected of having HIT, when the recommended diagnostic algorithm was used in clinical practice, antibody testing was required in half the patients. A substantial number of patients were, however, still misclassified, which could lead to delayed diagnosis or overtreatment. Development of improved diagnostic algorithms for HIT diagnosis should be pursued.

Evaluation and management of patients with coronary chronic total occlusions considered for revascularisation. A clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the European Association of Cardiovascular Imaging (EACVI) of the ESC, and the ESC Working Group on Cardiovascular Surgery.

Chronic total occlusions (CTOs) of coronary arteries can be found in the context of chronic or acute coronary syndromes; sometimes they are an incidental finding in those apparently healthy individuals undergoing imaging for preoperative risk assessment. Recently, the invasive management of CTOs has made impressive progress due to sophisticated preinterventional assessment, including advanced non-invasive imaging, the availability of novel and dedicated tools for CTO percutaneous coronary intervention (PCI), and experienced interventionalists working in specialised centres. Thus, it is crucial that referring physicians who see patients with CTO be aware of recent developments and of the initial evaluation requirements for such patients. Besides a careful history and clinical examination, electrocardiograms, exercise tests, and non-invasive imaging modalities are important for selecting the patients most suitable for CTO PCI, while others may be referred to coronary artery bypass graft or optimal medical therapy only. While CTO PCI improves angina and reduces the use of antianginal drugs in patients with symptoms and proven ischaemia, hibernation and/or wall motion abnormalities at baseline or during stress, the effect of CTO PCI on major cardiovascular events is still controversial. This clinical consensus statement specifically focuses on referring physicians, providing a comprehensive algorithm for the preinterventional evaluation of patients with CTO and the current evidence for the clinical effectiveness of the procedure. The proposed care track has been developed by members and with the support of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI), and the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery.

Cardiac structure, function, and coronary anatomy 10 years after isolated contemporary adjuvant radiotherapy in breast cancer patients with low cardiovascular baseline risk.

AIMS: The effects of isolated contemporary low-dose breast cancer (BC) radiotherapy (RT) on the heart remain poorly understood. This study aims to assess the long-term impacts of BC-RT on cardiac structure and function. METHODS AND RESULTS: Seventy-six women (62 ± 7 years) without history of prior heart disease, who had undergone RT for either first left (n = 36) or right (n = 40) BC, without additional medical oncology therapy apart from hormonal treatment 11 ± 1 years earlier, underwent transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), computed tomography coronary angiography (CTCA), NT-proBNP, and a 6-min walk test (6MWT). They were compared with 54 age-matched healthy female controls. By CTCA, 68% of BC patients exhibited no or very mild coronary disease, while only 11% had moderate stenosis (50-69%) and 3% had significant stenosis (>70%). Despite slightly reduced regional echocardiographic midventricular strains, BC patients exhibited similar global left and right ventricular volumes, ejection fractions, and global strains by echocardiography and CMR as controls. Mitral E/e' ratios were slightly higher, and mitral deceleration times were slightly lower, but NT-proBNP was similar to controls. Also, 6MWT was normal. None had late gadolinium enhancement, and extracellular volume fraction was similar in BC (28 ± 3 vs. 29 ± 3, P = 0.15) and controls. No differences were observed relative to dose or side of RT. CONCLUSION: Aside from minor alterations of regional strains and diastolic parameters, women who received isolated RT for BC had low prevalence of coronary disease, normal global systolic function, NT-proBNP, and exercise capacity and showed no structural changes by CMR, refuting significant long-term cardiotoxicity in such low-risk patients.

Amyloid detection and typing yield of skin biopsy in systemic amyloidosis and polyneuropathy.

OBJECTIVE: Disease-modifying therapies are available for amyloidosis but are ineffective if end-organ damage is severe. As small fiber neuropathy is an early and common feature of amyloidosis, we assessed detection and typing yield of skin biopsy for amyloid in patients with confirmed systemic amyloidosis and neuropathic symptoms. METHODS: In this case-control study, patients with transthyretin and light chain amyloidosis (ATTRv, ATTRwt, and AL) were consecutively recruited. They were sex and age-matched to three control groups (1) non-neuropathic controls (NNC), (2) monoclonal gammopathy of undetermined significance (MGUS), and (3) other neuropathic disease controls (ONC). Patients underwent a double 3 mm skin biopsy in proximal and distal leg. Amyloid index and burden, protein typing by immuno-electron microscopy, intraepidermal nerve fiber density, electroneuromyography, and clinical characteristics were analyzed. RESULTS: We studied 15 subjects with confirmed systemic amyloidosis, 20 NNC, 18 MGUS, and 20 ONC. Amyloid was detected in 100% of patients with amyloidosis (87% in ankle and 73% in thigh). It was not detected in any of the control groups. A small fiber neuropathy was encountered in 100% of amyloidosis patients, in 80% of MGUS, and in 78% of ONC. Amyloid burden was higher in ATTRv, followed by AL and ATTRwt. The ultrastructural examination allowed the identification of the precursor protein by immunotyping in most of the cases. INTERPRETATION: Skin biopsy is a minimally invasive test with optimal sensitivity for amyloid. It allows amyloid typing by electron microscope to identify the precursor protein. The diagnostic work up of systemic amyloidosis should include a skin biopsy.

Tricuspid annular dynamics, not diameter, predicts tricuspid regurgitation after mitral valve surgery: Results from a prospective randomized trial.

Objective: Current guidelines advise using prophylactic tricuspid valve annuloplasty during mitral valve surgery, especially in the presence of annular diameter enlargement. However, several retrospective studies and a prospective randomized study from our department could not confirm that diameter enlargement is predictive of late regurgitation. We examined whether 2- and 3-dimensional echocardiographic and clinical characteristics could identify patients who will develop moderate or severe recurrent tricuspid regurgitation. Methods: Patients with less than severe functional tricuspid regurgitation (FTR) were randomized not to receive tricuspid annuloplasty, and 11 of 53 of them were excluded from the study because 3-dimensional echocardiographic analysis was not possible. Cox regression was used to estimate the model-based probability of moderate or severe FTR (vena contracta ≥3 mm) or progression of TR and FTR regression using valve dimensions (annulus area, diameter perimeter, nonplanar angle, and sphericity index), dynamics (annulus contraction, annulus displacement, and displacement velocity), and clinical parameters as possible predictors. Results: At a median follow-up of 3.8 years (range, 3-5.6 years), 17 patients had moderate or severe FTR or progression, and 13 had FTR regression. Our models identified annular displacement velocity as a significant predictor for FTR recurrence and nonplanar angle as a significant predictor for FTR regression. Conclusions: Annular dynamics, not the dimension, predict recurrence and regression of FTR. Annular contraction should be systematically investigated as a possible surrogate of right ventricle function to prophylactically treat the tricuspid valve.

Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis.

BACKGROUND: Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS. METHODS: Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC). RESULTS: Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (p < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, p = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed. CONCLUSIONS: Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.

Impact of early versus class I-triggered surgery on postoperative survival in severe aortic regurgitation: An observational study from the Aortic Valve Insufficiency and Ascending Aorta Aneurysm International Registry.

OBJECTIVES: Class I triggers for severe and chronic aortic regurgitation surgery mainly rely on symptoms or systolic dysfunction, resulting in a negative outcome despite surgical correction. Therefore, US and European guidelines now advocate for earlier surgery. We sought to determine whether earlier surgery leads to improved postoperative survival. METHODS: We evaluated the postoperative survival of patients who underwent surgery for severe aortic regurgitation in the international multicenter registry for aortic valve surgery, Aortic Valve Insufficiency and Ascending Aorta Aneurysm International Registry, over a median follow-up of 37 months. RESULTS: Among 1899 patients (aged 49 ± 15 years, 85% were male), 83% and 84% had class I indication according to the American Heart Association and European Society of Cardiology, respectively, and most were offered repair surgery (92%). Twelve patients (0.6%) died after surgery, and 68 patients died within 10 years after the procedure. Heart failure symptoms (hazard ratio, 2.60 [1.20-5.66], P = .016) and either left ventricular end-systolic diameter greater than 50 mm or left ventricular end-systolic diameter index greater than 25 mm/m2 (hazard ratio, 1.64 [1.05-2.55], P = .030) predicted survival independently over and above age, gender, and bicuspid phenotype. Therefore, patients who underwent surgery based on any class I trigger had worse adjusted survival. However, patients who underwent surgery while meeting early imaging triggers (left ventricular end-systolic diameter index 20-25 mm/m2 or left ventricular ejection fraction 50% to 55%) had no significant outcome penalty. CONCLUSIONS: In this international registry of severe aortic regurgitation, surgery when meeting class I triggers led to postoperative outcome penalty compared with earlier triggers (left ventricular end-systolic diameter index 20-25 mm/m2 or ventricular ejection fraction 50%-55%). This observation, which applies to expert centers where aortic valve repair is feasible, should encourage the global use of repair techniques and the conduction of randomized trials.

Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study.

BACKGROUND: Anecdotal reports suggest that the correlation between heparin/platelet factor 4 (PF4) antibody assays for the diagnosis of heparin-induced thrombocytopenia (HIT) is limited. OBJECTIVES: To investigate the correlation between widely used assays and examine possible factors contributing to variability. METHODS: This is a large, prospective cohort study with 10 participating tertiary care hospitals including 1393 patients with suspected HIT in clinical practice. HIT was defined by a positive heparin-induced platelet activation (HIPA) assay (washed platelet reference standard test). Three different immunoassays were used to measure heparin/PF4 antibodies: chemiluminescent immunoassay, enzyme-linked immunosorbent assay, and particle gel immunoassay. Various factors that could influence the assays were examined: sex (male or female), age (<65 years or ≥65 years), unfractionated heparin exposure, presence of thrombosis, cardiovascular surgery, and intensive care unit. Spearman's correlation coefficients were calculated. Z-scores and diagnostic odds ratios were determined in the aforementioned subgroups of patients. RESULTS: Among 1393 patients, 119 were classified as HIT-positive (prevalence, 8.5%). The median 4Ts score was 5 (IQR, 4-6) in patients with HIT compared with 3 (IQR, 2-4) in patients without HIT. Correlations (rs) between immunoassays were weak (0.53-0.65). Inconsistencies between immunoassays could not be explained by further analyses of z-scored test results and diagnostic odds ratios in subgroups of patients. CONCLUSION: The correlation between widely used heparin/PF4 antibody assays was weak, and key factors could not explain this variability. Standardization of immunoassays is requested to improve comparability.

Acquired haemophilia A in southern Switzerland from 2013 to 2019: a case series.

AIMS OF THE STUDY: Acquired haemophilia A is a rare disease with an annual incidence of 1.48 per million. Based on clinical observations, we suspect a higher incidence in southern Switzerland, and aimed at providing local epidemiological data, and clinical information regarding diagnosis, treatment and outcome in our region. METHODS: All adult patients with acquired haemophilia A treated between 2013 and 2019 in our facility were included in the present retrospective analysis. RESULTS: We treated 11 patients with acquired haemophilia A between 2013 and 2019, resulting in an annual incidence of 4.5 per million (95% confidence interval [CI] 0-9.0). Median delay from first symptoms to diagnosis was 4.5 days, and the median age at diagnosis was 79 years (range 23-87). Possible causative conditions were: pregnancy (n = 1), polyarteritis nodosa (n = 1), myelodysplastic syndrome (n = 1), chronic human immunodeficiency virus (HIV) (n = 1), and HIV postexposure prophylaxis (n = 1). In five patients no underlying or associated condition was identified. Median activated partial thromboplastin time (aPTT)) at baseline was 79 seconds (65-117; ref. value <38 sec), and FVIII:C 2.15% (<1-3.75%). A FVIII:C <1% was present in 4/10 patients. Median FVIII-inhibitor titre was 10.3 BU/ml (2.4-75.0 BU/ml). All patients had bleeding symptoms, 5/10 patients had major bleedings, and 7/10 patients were treated with bypassing agents. All patients received corticosteroids; 7/10 patients received immunosuppressive combination therapy. FVIII levels of ≥50% were achieved after a median of 40 days (8-62). One patient had a severe immunosuppressive therapy-related infection. An 87-years-old woman died for reasons not related to acquired haemophilia A or immunosuppressive therapy. CONCLUSIONS: Acquired haemophilia A is a rare disease, but manageable despite the advanced patient age and comorbidities. Its incidence in Southern Switzerland is higher than previously suspected.

Quantification of primary mitral regurgitation by echocardiography: A practical appraisal.

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed "moderate" MR.

Role of Cardiovascular Magnetic Resonance in Native Valvular Regurgitation: A Comprehensive Review of Protocols, Grading of Severity, and Prediction of Valve Surgery.

Valvular regurgitation is common in developed countries with an increasing prevalence due to the aging of the population and more accurate diagnostic imaging methods. Echocardiography is the gold standard method for the assessment of the severity of valvular heart regurgitation. Nonetheless, cardiovascular magnetic resonance (CMR) has emerged as an additional tool for assessing mainly the severity of aortic and mitral valve regurgitation in the setting of indeterminate findings by echocardiography. Moreover, CMR is a valuable imaging modality to assess ventricular volume and flow, which are useful in the calculation of regurgitant volume and regurgitant fraction of mitral valve regurgitation, aortic valve regurgitation, tricuspid valve regurgitation, and pulmonary valve regurgitation. Notwithstanding this, reference values and optimal thresholds to determine the severity and prognosis of valvular heart regurgitation have been studied lesser by CMR than by echocardiography. Hence, further larger studies are warranted to validate the potential prognostic relevance of the severity of valvular heart regurgitation determined by CMR. The present review describes, analyzes, and discusses the use of CMR to determine the severity of valvular heart regurgitation in clinical practice.

Dissemination of patient blood management practices in Swiss intensive care units: a cross-sectional survey.

BACKGROUND: Patient blood management (PBM) promotes the routine detection and treatment of anaemia before surgery, optimising the management of bleeding disorders, thus minimising iatrogenic blood loss and pre-empting allogeneic blood utilisation. PBM programmes have expanded from the elective surgical setting to nonsurgical patients, including those in intensive care units (ICUs), but their dissemination in a whole country is unknown. METHODS: We performed a cross-sectional, anonymous survey (10 October 2018 to 13 March 2019) of all ordinary medical members of the Swiss Society of Intensive Care Medicine and the registered ICU nurses from the 77 certified adult Swiss ICUs. We analysed PBM-related interventions adopted in Swiss ICUs and related them to the spread of PBM in Swiss hospitals. We explored blood test ordering policies, blood-sparing strategies and red blood cell-related transfusion practices in ICUs. RESULTS: A total of 115 medical doctors and 624 nurses (response rates 27% and 30%, respectively) completed the surveys. Hospitals had implemented a PBM programme according to 42% of physicians, more commonly in Switzerland's German-speaking regions (Odds Ratio [OR] 3.39, 95% confidence interval [CI] 1.23-9.35; p = 0.018) and in hospitals with more than 500 beds (OR 3.91, 95% CI 1.48-10.4; p = 0.006). The PBM programmes targeted the detection and correction of anaemia before surgery (79%), minimising perioperative blood loss (94%) and optimising anaemia tolerance (98%). Laboratory tests were ordered in 70.4% by the intensivist during morning rounds; the nurses performed arterial blood gas analyses autonomously in 48.4%. Blood-sparing techniques were used by only 42.1% of nurses (263 of 624, missing: 6) and 47.0% of physicians (54 of 115). Approximately 60% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin threshold for the nonbleeding ICU population was 70 g/l and, therefore, was at the lower limit of current guidelines. CONCLUSIONS: Based on this survey, the estimated proportion of the intensivists working in hospitals with a PBM initiative is 42%, with significant variability between regions and hospitals of various sizes. The risk of iatrogenic anaemia is relevant due to liberal blood sample collection practices and the underuse of blood-sparing techniques. The reported transfusion threshold suggests excellent adherence to current international ICU-specific transfusion guidelines.

Anti-PD-L1 monoclonal antibody for the management of chronic disseminated intravascular coagulation secondary to a urothelial carcinoma: a case report.

BACKGROUND: Thrombocytopenia is often considered a risk factor for bleeding, but conversely may be associated with an increased thrombotic risk in several clinical situations. Here we present a patient with arterial thrombosis and chronic disseminated intravascular coagulation caused by metastatic urothelial carcinoma. As the treatment for a disseminated intravascular coagulation caused by a neoplasia is the treatment of the underlying disease itself, our case highlights a new therapeutic approach-immunotherapy-in a patient prone to hematological complications due to conventional chemotherapy. CLINICAL CASE: A 74-year-old Caucasian male patient with a history of urothelial carcinoma of the bladder and moderate thrombocytopenia had multiple arterial thrombotic events despite antiplatelet therapy and anticoagulation. A diagnosis of chronic disseminated intravascular coagulation in the setting of a metastatic bladder urothelial carcinoma was made. The patient was treated with an anti-PD-L1 monoclonal antibody, and achieved a rapid response with subsequent reversal of the disseminated intravascular coagulation. CONCLUSION: Unexplained arterial or venous thrombosis despite adequate thromboprophylaxis should be investigated, especially in the setting of thrombocytopenia. Chronic disseminated intravascular coagulation is a possible, life-threatening reason for this clinical picture, and should prompt rapid identification of the underlying disease. To the best of our knowledge, this is the second case of chronic disseminated intravascular coagulation due to neoplastic disease treated with immunotherapy.

Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis.

AIMS: Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro-)vascular dysfunction in CA pathophysiology remains still elusive. Because vascular function is associated with cardiovascular risk and severity of heart failure and represents a potential therapeutic target in CA, the present study investigated retinal vascular function, flow-mediated dilatation (FMD), and pulse-wave analysis and velocity (PWA/PWV) in patients with CA. METHODS AND RESULTS: Flicker-induced arterial dilatation (FIDa) was measured using dynamic retinal vessel analysis additionally to FMD and PWA/PWV. Thirty-three patients with CA [age 67 years [interquartile range, IQR, 62, 74], 14 with amyloid light-chain (AL) and 19 with transthyretin (ATTR) amyloidosis] were prospectively included in this cross-sectional, observational study and 70 healthy individuals (age 53 years [IQR 39, 67]) served as control. Potential confounders were balanced using entropy balancing propensity score analysis [inverse probability weighting (IPW)]. FIDa was reduced in CA patients (1.52 ± 1.73% vs. 3.09 ± 1.96%, P < 0.001, after IPW). While PWV was increased (8.74 ± 2.34 m/s vs. 7.49 ± 1.65 m/s, P = 0.018, after IPW), no difference in FMD was observed. FIDa was significantly associated with prognostic biomarkers of CA [estimated glomerular filtration rate (r = 0.33; P < 0.001), log-scaled troponin T (r = -0.49; P < 0.001), and N-terminal pro-B-type natriuretic peptide (r = -0.51; P < 0.001)]. CONCLUSIONS: Retinal vascular function is impaired, associated with cardiac and renal biomarkers of CA severity, and may represent a potential therapeutic target in patients with amyloidosis.