Diagnostic value of left ventricular layer strain and specific regional strain patterns in cardiac amyloidosis and Fabry disease.

Aims: Layer-specific left ventricular (LV) strain alterations have been suggested as a specific finding in Fabry disease (FD). Our study aimed to assess the diagnostic value of layer-specific radial strain (RS) indices compared to the established LV regional strain pattern in cardiac amyloidosis (CA) and FD, i.e. apical sparing and posterolateral strain deficiency (PLSD). Methods and results: We retrospectively analysed the global, subendocardial, subepicardial LV radial strain, the corresponding strain gradient, as well as the regional and global longitudinal strain. The diagnostic accuracy of the diverse LV strain analyses was comparatively assessed using receiver operating characteristic curve and multivariable regression analyses. In 40 FD and 76 CA patients, CA featured more reduced layer strain values [global RS -12.3 (-15.6 to -9.6) in CA vs. -16.7 (-20.0 to -13.6) in FD; P < 0.001; subendocardial RS -22.3 (-27.4 to -15.9) vs. -28.3 (-31.8 to -23.6), P < 0.001; subepicardial RS -6.6 (-8.6 to -4.7) in CA vs. -8.9 (-11.7 to - 6.5) in FD; P < 0.001]. Global radial and longitudinal strain held an area under the curve (AUC) of 0.75 (0.66-0.84) and AUC 0.73 (0.63-0.83). While the apical sparing and PLSD strain pattern showed the highest accuracy as single parameters [AUC 0.87 (0.79-0.95) and 0.81 (0.72-0.89), P < 0.001], the combination of subendocardial RS and the apical sparing pattern featured the highest diagnostic accuracy [AUC 0.92 (0.87-0.97)]. Conclusion: Combining radial strain-derived parameters to the established strain pattern apical sparing and PLSD improve the diagnostic accuracy in the echocardiographic assessment in suspected storage disease.

Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis.

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.

Right heart and left atrial strain to differentiate cardiac amyloidosis and Fabry disease.

Echocardiographic differentiation of cardiac amyloidosis (CA) and Fabry disease (FD) is often challenging using standard echocardiographic parameters. We retrospectively analyzed the diagnostic accuracy of right heart and left atrial strain parameters to discriminate CA from FD using receiver operating characteristic curve analyses and logistic regression models. A total of 47 FD and 88 CA patients with left ventricular wall thickening were analyzed. The comparison of both cardiomyopathies revealed significantly reduced global and free wall longitudinal right ventricular strain (RVS; global RVS: CA - 13 ± 4%, n = 67, vs. FD - 18 ± 4%, n = 39, p < 0.001) as well as right atrial strain (RAS; reservoir RAS: CA 12 ± 8%, n = 70, vs. FD 26 ± 9%, n = 40, p < 0.001) and left atrial strain (LAS) in CA patients. Individually, global RVS as well as phasic LAS and RAS showed the highest diagnostic accuracy to distinguish CA and FD. The best diagnostic accuracy was achieved by combining the age, basal RV diameter, global RVS, and reservoir and conduit RAS (area under the curve 0.96 [95% CI 0.90-1.00]). Differential echocardiographic diagnostic work-up of patients with suspected CA or FD can be improved by integrating structural and functional parameters of the right heart and the left atrium.Trial registration: DRKS00027403.

Diagnostic value of papillary muscle hypertrophy and mitral valve thickness to discriminate cardiac amyloidosis and Fabry disease.

BACKGROUND: Cardiac amyloidosis (CA) and Fabry disease (FD) cause myocardial damage but may also affect the valvular and subvalvular apparatus. We aimed to evaluate the diagnostic accuracy of new echocardiographic indices including mitral valve thickness and papillary muscle (PM) hypertrophy to differentiate CA and FD. METHODS: In patients with confirmed CA and FD, a detailed assessment of valvular function, mitral valve leaflet thickness and PM area as well as PM left ventricular area ratio (PM/LV-ratio) was performed in offline analyses. Receiver operating characteristic curve analyses were conducted to determine the diagnostic accuracy of mitral valve thickness, PM hypertrophy, and PM/LV-ratio to distinguish CA from FD. RESULTS: We retrospectively analyzed a cohort of 129 patients (FD n = 49, CA n = 80). CA patients showed significantly more thickened mitral valve leaflets (4.1 ± 1.3 mm vs. 2.9 ± 1.1 mm, p < 0.001) and a higher PM area [4.0 (3.1-4.6) mm2 vs. 2.8 (2.1-4.6) mm2, p = 0.009] with a comparable PM/LV-ratio in both groups. Mitral valve thickness showed the highest diagnostic accuracy to discriminate CA [AUC 0.77 (95% CI 0.67-0.87)]. The prevalence of aortic, tricuspid, and pulmonary valve regurgitation was significantly higher in CA (aortic regurgitation ≥ II° 13% vs. 4%, tricuspid regurgitation≥ II° 19% vs. 8%, p < 0.001). CONCLUSION: Our results suggest that the assessment of mitral valve thickness may be a new useful echocardiographic parameter to differentiate CA and FD, whereas papillary muscle hypertrophy and PM/LV-ratio showed a limited diagnostic performance to discriminate CA. German clinical trials registry: DRKS00027403.

Spotty calcium deposits within acute coronary syndrome (ACS)-causing culprit lesions impact inflammatory vessel-wall interactions and are associated with higher cardiovascular event rates at one year follow-up: Results from the prospective translational OPTICO-ACS study program.

BACKGROUND AND AIMS: Spotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients. METHODS: CL of the first 155 consecutive ACS-patients from the translational OPTICO-ACS-study program were investigated by OCT-characterization of the calcium phenotype at ACS-causing culprit lesions. Simultaneous immunophenotyping by flow-cytometric analysis and cytokine bead array technique across the CL gradient (ratio local/systemic levels) was performed and incidental major adverse cardiovascular events plus (MACE+) at 12 months after ACS were assessed. RESULTS: SCD were observed within 45.2% of all analyzed ACS-causing culprit lesions (CL). Culprits containing spotty calcium were characterized by an increased culprit ratio of innate effector cytokines interleukin (IL)-8 [2.04 (1.24) vs. 1.37 (1.10) p < 0.05], as well as TNF (tumor necrosis factor)-α [1.17 (0.93) vs. 1.06 (0.89); p < 0.05)] and an increased ratio of circulating neutrophils [0.96 (0.85) vs. 0.91 (0.77); p < 0.05] as compared to culprit plaques without SCD. Total monocyte levels did not differ between the two groups (p = n.s.). However, SCD-containing CLs were characterized by an increased culprit ratio of intermediate monocytes [(1.15 (0.81) vs. 0.96 (0.84); p < 0.05)] with an enhanced surface expression of the integrin receptor CD49d as compared to intermediate monocytes derived from SCD-free CLs [(1.06 (0.94) vs. 0.97 (0.91)] p < 0.05. Finally, 12 months rates of MACE+ were higher in patients with, as compared to patients without SCD at CL (16.4% vs. 5.3%; p < 0.05). CONCLUSIONS: This study for the first time identified a specific inflammatory profile of CL with SCD, with a predominance of neutrophils, intermediate monocytes and their corresponding effector molecules. Hence, this study advances our understanding of ACS-causing CL and provides the basis for future personalized anti-inflammatory, therapeutic approaches to ACS.

Consensus recommendations on holistic care in hereditary ATTR amyloidosis: an international Delphi survey of patient advocates and multidisciplinary healthcare professionals.

BACKGROUND: Hereditary transthyretin-mediated amyloidosis is a rare, progressive and potentially life-limiting multisystem disease, affecting every aspect of a patient's life. OBJECTIVES: This online international Delphi survey aimed to evolve clinical-patient-led practical guidance, to inspire and encourage a holistic approach to care that is managed in specialist settings by multidisciplinary teams and supported by allied healthcare professionals (HCPs) and patient advocacy groups (PAGs). DESIGN: A 14-member joint patient advocate-HCP primary panel was convened including representation from PAGs and key clinical specialties (neurology, cardiology, internal medicine, physiotherapy, clinical psychology, dietetics and specialist nursing). Guidance evolved on the care provision needed to support seven core goals: early diagnosis and treatment; disease monitoring and organisation of care; maintenance of physical and mental health; family-centred care and caregiver support; patient-doctor dialogue; access to social support and social networking. PARTICIPANTS: From June to October 2022, 252 HCPs and 51 PAG representatives from 27 countries were invited to participate in a Delphi survey. Of the 122 respondents who answered at least one survey question, most were HCPs (100, 82%) from specialist centres; the remainder were PAG representatives (22, 18%). MAIN OUTCOME MEASURE: Both level of agreement and feasibility in practice of each recommendation was tested by two anonymised online Delphi voting rounds. RESULTS: Based on an a priori threshold for consensus of ≥75% agreement, the clinical-patient community endorsed all but one recommendation. However, only 17/49 (35%) recommendations were identified by most HCPs as a core part of routine care; the remainder (32/49 (65%)) were identified as part of core care by <50% of HCPs respondents, or as largely achievable by 30%-45% of HCPs. By comparison, PAGs recorded lower implementation levels. CONCLUSIONS: Further consideration is needed on how to evolve multidisciplinary services (supported by allied HCPs and PAGs) to address the complex needs of those affected by this disease.

Prevalence, one-year-incidence and predictors of carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) caused by neuroendocrine tumours (NET) is associated with an increased morbidity and mortality due to valvular dysfunction and right sided heart failure. The present study aimed to assess the prevalence and one-year-incidence of CHD in NET patients. Tumour characteristics, laboratory measurements, and echocardiographic findings were evaluated to identify predictors of CHD manifestation. METHODS: The study was an investigator-initiated, monocentric, prospective trial. Patients with NET without previously diagnosed CHD were included and underwent comprehensive gastroenterological and oncological diagnostics. Echocardiographic examinations were performed at baseline and after one year. RESULTS: Forty-seven NET patients were enrolled into the study, 64% of them showed clinical features of a carcinoid syndrome (CS). Three patients presented with CHD at baseline and three patients developed cardiac involvement during the follow-up period corresponding to a prevalence of 6% at baseline and an incidence of 6.8% within one year. Hydroxyindoleacetic acid (5-HIAA) was identified to predict the occurrence of CHD (OR, 1.004; 95% CI, 1.001-1.006 for increase of 5-HIAA), while chromogranin A (CgA), and Kiel antigen 67 (Ki 67%) had no predictive value. Six patients with CHD at twelve-month follow-up revealed a tendency for larger right heart diameters and increased values of myocardial performance index (MPEI) at baseline compared to NET patients. CONCLUSION: The prevalence at baseline and one-year-incidence of CHD was 6-7%. 5-HIAA was identified as the only marker which predict the development of CHD.

Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome.

AIMS: Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. METHODS AND RESULTS: This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1ß. Circulating plasma levels of interleukin-1ß decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. CONCLUSION: This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.

Same same, but different? The neurological presentation of wildtype transthyretin (ATTRwt) amyloidosis.

BACKGROUND: Both hereditary transthyretin (ATTRv) amyloidosis and wildtype transthyretin (ATTRwt) amyloidosis can be associated with neurological diseases such as carpal tunnel syndrome and polyneuropathy. While ATTRv amyloidosis has been extensively studied, to date little is known about neurological complications of ATTRwt amyloidosis. In particular, the prevalence, pattern and extent of polyneuropathy and autonomic dysfunction has not been adequately investigated in the context of ATTRwt amyloidosis. To tackle this issue, we aimed to characterise the neurological presentation of ATTRwt amyloidosis and to compare between the presentations of ATTRv and ATTRwt amyloidoses. PATIENTS AND METHODS: Between November 2019 and September 2020, we included 50 patients with ATTRwt amyloidosis in this cohort study. All patients presented to the amyloidosis centre in Berlin, Germany and underwent neurological, cardiological and radiological work-up including neurological examination, laboratory testing, nerve conduction studies (NCS), echocardiography and scintigraphy. Patients were screened for symptoms of autonomic dysregulation and a subgroup of patients underwent tilt-table testing for orthostatic dysregulation. RESULTS: The cohort included 46 men and 4 women; the mean age of the study participants was 80.6 (standard deviation [SD] ± 5.0) years. All patients showed signs of cardiomyopathy on echocardiography. Neurological examination revealed peripheral, symmetric and length-depended predominately sensory polyneuropathy in 74% (n = 37) of patients. Neuropathy impairment scores (NIS) ranged from 0 to 50 with an average score of 8.4 (SD ± 10.1) indicating mild to moderate impairment. 90% and 92% of patients were classified as FAP stage I and PND stage I, respectively. Unilateral or bilateral carpal tunnel syndrome (CTS) was present in 70% (n = 35) and spinal stenosis was seen in 11% (n = 5) of patients. We detected a low rate of autonomic symptoms with a median COMPASS-31 total score of 18.4 points (IQR 32.4 points). Additional tilt-table testing of a subgroup of 8 patients yielded negative results for orthostatic intolerance. CONCLUSION: Distal-symmetric, predominantly sensory polyneuropathy is a common neurological complication in ATTRwt amyloidosis besides carpal tunnel syndrome and spinal stenosis, further substantiating the systemic character of the disease. Compared to ATTRv amyloidosis, the severity of polyneuropathy in ATTRwt amyloidosis is milder and without relevant motor involvement. Symptoms of autonomic dysfunction were not common in this cohort. Nevertheless, ATTRwt amyloidosis is a treatable disease and should be included in the differential diagnosis of sensory polyneuropathy in the elderly.

Comparative analysis of phasic left atrial strain and left ventricular posterolateral strain pattern to discriminate Fabry cardiomyopathy from other forms of left ventricular hypertrophy.

BACKGROUND: "Classical" echocardiographic signs of Fabry cardiomyopathy (FC), such as left ventricular hypertrophy (LVH), posterolateral strain impairment (PLSI), and papillary muscle hypertrophy may be of limited diagnostic accuracy in clinical practice. Our aim was to evaluate the diagnostic value of left atrial (LA) strain impairment compared to "classical" echocardiographic findings to discriminate FC. METHODS: In standard echocardiographic assessments, we retrospectively analyzed the diagnostic value of the "classical" red flags of FC as well as LA strain in 20 FC patients and in 20 subjects with other causes of LVH. Receiver operating characteristic (ROC) curve analysis was performed to assess the respective diagnostic accuracy. RESULTS: FC was confirmed in 20 patients by genetic testing. In the LVH group, 12 patients were classified by biopsy to have hypertrophic cardiomyopathy, two had hypertensive heart disease, and six LVH combined with borderline myocarditis. Global and regional left ventricular (LV) strain was not significantly different between groups while LA strain was significantly impaired in FC (Left atrial reservoir strain (LASr) 19.1%±8.4 in FC and 25.6%±8.9 in LVH, p = 0.009; left atrial conduction strain (LAScd) -8.4%±4.9 in FC and -15.9%±8.4 in LVH, p < 0.01). LAScd, with an area under the curve (AUC) of .81 (95% confidence interval [CI] .66-.96) showed the highest diagnostic accuracy to discriminate FC. The PLSI pattern showed an AUC of .49, quantification of papillary muscle hypertrophy an AUC of .47. CONCLUSION: Adding LA strain analysis to a comprehensive echocardiographic work-up of unclear LVH may be helpful to identify FC as a possible cause.

Hereditary transthyretin-related amyloidosis is frequent in polyneuropathy and cardiomyopathy of no obvious aetiology.

BACKGROUND: Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4-5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology. METHOD: A multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"-TRAM study was performed in Germany, Austria, and Switzerland. RESULTS: A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various TTR variants (TTR-positive) were identified. Body Mass Index was lower in the TTR-positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in TTR-positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in TTR-positive patients. CONCLUSIONS: Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis" TRAM study and screened for pathogenic TTR variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.

An optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis.

BACKGROUND: In [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°). METHODS: In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i. RESULTS: In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence. CONCLUSIONS: Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

Atypical presentation of a locally advanced hepatocellular carcinoma: Extensive workup of an incidental finding on computed tomography performed for planning of transcatheter aortic valve implantation.

This case report presents the diagnostic workup of liver malignancy incidentally detected in a 72-year-old male patient on routine body computed tomography angiography (CTA) performed for planning transcatheter aortic valve implantation (TAVI). The patient initially presented to an outside hospital with chest discomfort, where routine diagnostic procedures in the emergency room revealed grade III aortic valve stenosis. Routine CTA for TAVI planning in our department then revealed tumor thrombosis of the portal vein suspicious for hepatic malignancy. In contrast-enhanced ultrasound (CEUS) only the left hepatic lobe was inhomogeneously transformed with early arterial contrast enhancement. Magnetic resonance imaging (MRI) confirmed a primary hepatic malignancy involving the left liver. Transcutaneous biopsy with ultrasound guidance established the diagnosis of hepatocellular carcinoma (HCC). Incidental findings may be of prognostic relevance for the patient and in a number of cases, TAVI can be a prerequisite for the appropriate therapy.

Serum creatinine and cystatin C-based estimates of glomerular filtration rate are misleading in acute heart failure.

AIMS: We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation-based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. METHODS: In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty-eight patients had two sequential GFR measurements 48 h apart. The co-primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. RESULTS: VFI-based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker-based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80-0.88, depending on equation used), precision (r2 , range 0.65-0.78) and accuracy (56%-74% of estimates scored within 30% of mGFR). Correlations of 48-h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35-0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%-46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR. CONCLUSIONS: In patients hospitalized for acute heart failure, serum creatinine- and cystatin C-based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.

Phasic left atrial strain analysis to discriminate cardiac amyloidosis in patients with unclear thick heart pathology.

AIMS: Traditional echocardiographic parameters for the assessment of suspected cardiac amyloidosis (CA) are of limited diagnostic accuracy. We sought to explore differences and the discriminative value of phasic left atrial strain (LAS) reductions and of regional longitudinal left ventricular (LV) strain alterations (relative apical sparing; RELAPS) in CA and other causes of LV wall thickening (LVH). METHODS AND RESULTS: We included 54 patients with unclear LVH (mean septal diastolic wall thickness 17.8 ± 3.5 mm); CA was bioptically confirmed in 35 patients (8 mATTR, 6 wtATTR, 20 AL, and 1 AA amyloidosis) and LVH in 19 subjects. We analysed RELAPS as well as LA reservoir (LASr), conduit (LAScd), and contraction strain (LASct) using 2D speckle tracking echocardiography (EchoPAC software, GE). RELAPS was higher (1.37 ± 0.94 vs. 0.86 ± 0.29, P < 0.007), whereas atrial mechanics were significantly reduced in CA (LASr, LAScd, and LASct: 9.7 ± 5.2%, -6.5 ± 3.5%, and -5.0 ± 4.1% in CA; and 22.7 ± 7.8%, -13.9 ± 5.2%, and -13.0 ± 5.5% in LVH, respectively; P < 0.001 each). With an area under the curve (AUC) of 0.91 [95% confidence interval (CI) 0.82-0.99], LASr showed a higher diagnostic accuracy in discriminating CA than RELAPS (AUC 0.74, 95% CI 0.59-0.88). LASr and LAScd remained significantly associated with CA in a multivariate regression model. CONCLUSION: Phasic LAS was significantly reduced in patients with CA and showed a higher diagnostic accuracy in discriminating CA than RELAPS. The additional assessment of phasic LAS may be useful to rule in the possible diagnosis of CA in patients with unclear LVH.

Validity of visual assessment of aortic valve morphology in patients with aortic stenosis using two-dimensional echocardiography.

The diagnostic value of a visual assessment of aortic valve (AV) morphology for grading aortic stenosis (AS) remains unclear. A visual score (VS) for assessing the AV was developed and its reliability with respect to Doppler measurements and the calcium score (ctCS) derived by multislice computed tomography was evaluated. 99 Patients with AS of various severity and 38 patients without AS were included in the analysis. Echocardiographic studies were evaluated using the new VS which includes echogenicity, thickening, localization of lesions and leaflet mobility, with a total score ranging from 0 to 11. The association of VS with ctCS and the severity of AS was analyzed. There was a significant correlation of VS with AV hemodynamic parameters and with ctCS. The cut-off value for the detection of AS of any grade was a VS of 6 (sensitivity 95%, specificity 85% for women; sensitivity 85%, specificity 88% for men). A VS of 9 for women and of 10 for men was able to predict severe AS with a high specificity (96% in women and 94% in men, AUC 0.8 and 0.86, respectively). The same cut-off values were identified for the detection of ctCS of ≥ 1600 AU and ≥ 3000 AU with a specificity of 77% and 82% (AUC 0.69 and 0.81, respectively). Assessment of aortic valve morphology can serve as an additional diagnostic tool for the detection of AS and an estimation of its severity.

Isolated atrial amyloidosis suspected by electrophysiological voltage mapping and diagnosed by 99m Tc-DPD scintigraphy.

We present not-yet-seen multimodal images of a 55-year-old female patient with isolated atrial amyloidosis (IAA) who clinically suffered from multiple atrial arrhythmias and heart failure symptoms with preserved left ventricular ejection fraction. We aim to show structural and functional abnormalities detected by electrophysiological voltage mapping, cardiac magnetic resonance imaging (MRI) [cMRI; atrial strain measurements, late gadolinium enhancement (LGE) visualization], and 99m Tc-DPD scintigraphy. Bipolar voltage mapping performed during two electrophysiological procedures showed diffuse left atrial low-voltage areas (bipolar < 0.5 mV) and also a moderately diseased right atrium suspected of infiltrative cardiomyopathy. Catheter ablation did successfully treat a left atrial and two right atrial focal tachycardias. For further diagnostics, a 3T cMRI was performed, revealing a subendocardial circumferential left atrial LGE and pathological atrial strain measurements, especially during conduit and reservoir phase. Afterwards, nuclear imaging with 559 MBq of 99m Tc-DPD was performed. The scan revealed amyloid infiltration of the left atrium. Neither an uptake in the ventricular myocardium nor an extra-cardiac uptake of DPD was seen. Genetic testing for transthyretin amyloidosis mutations in this patient was negative, and peripheral neuropathy was ruled out by electromyogram analysis. The synopsis of these findings reveals IAA as the most possible diagnosis and showed isolated atrial nuclear tracer uptake with 99m Tc-DPD scintigraphy for the first time. Non-invasive imaging techniques might help in suggesting IAA but need further investigation.

Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus.

Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.).

Familial Oculo-Leptomeningeal Transthyretin Amyloidosis Caused by Leu55Arg Mutation.

Hereditary transthyretin amyloidosis (hATTR amyloidosis) is a multisystemic disease usually presenting in a mixed neurological and cardiological phenotype. We present a case of hATTR amyloidosis associated with Leu55Arg mutation causing a form of familial oculo-leptomeningeal amyloidosis. Two brothers and their mother presented with severe autonomic neuropathy, loss of visual acuity and lepto-meningeal involvement. One patient suffered subarachnoid hemorrhage as a possible complication of cerebral involvement. The patients suffered from treatment-refractory weight loss and recurring vitreous opacities. RNA interference-based treatment has led to stabilization of autonomic and peripheral neuropathy but has had no effect on ocular symptoms.