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.).
Patients with preclinical left ventricular (LV) diastolic dysfunction (DD) are prone to develop heart failure with preserved ejection fraction. Although left atrial (LA) enlargement and deterioration ...of LA function in apparent DD and heart failure with preserved ejection fraction have been previously described, data regarding phasic LA strain (LAS) in preclinical DD are scarce.
In a cross-sectional trial, echocardiographic parameters of DD, LA volume index, and global LA reservoir, conduit, and pump function were prospectively analyzed in 473 women from the general population in Berlin, Germany (BErlin Female RIsk evaluation (BEFRI) study), using standard and two-dimensional speckle-tracking echocardiography.
One hundred thirty-one women (29.7%) showed early-stage DD (impaired relaxation DD1) and 22 (5.0%) showed an echocardiographically more advanced stage of DD (pseudonormal filling DD2). Compared with women with normal diastolic function (DD0), those with DD1 displayed lower LA reservoir and conduit function (DD0, 43.2 ± 8.5% and 27.2 ± 8.0%; DD1, 33.3 ± 8.0% and 16.1 ± 7.1%; P < .001) but significantly higher LA pump function (DD0, 17.6 ± 5.4%; DD1, 18.9 ± 5.5%; P < .05). In patients with DD2, all three phases of LAS were markedly impaired compared with those with DD0 (reservoir, conduit, and pump function, 29.0 ± 6.3%, 15.1 ± 5.4% P < .001, and 14.9 ± 4.1% P < .05, respectively). LA reservoir and conduit function was significantly associated with DD; in receiver operating characteristic curve analysis, these parameters showed higher diagnostic accuracy in detecting early DD compared with LA volume index. In multivariate analysis, LA reservoir strain remained significantly associated with DD.
All three components of LAS showed specific alterations in different stages of DD. LA reservoir and conduit function was markedly reduced before symptoms, LA enlargement, and elevations of noninvasively estimated LV filling pressures occurred. Analysis of LA function featured higher discriminative strength in diagnosing early-stage DD compared with the well-established parameter LA volume index. Assessment of LAS allows diagnosis of impaired LA function and DD in a subclinical stage and might enable timely preventive and therapeutic interventions.
Due to progressive abdominal-venous congestion severe tricuspid regurgitation (TR) is a common cause of cardiorenal and cardiohepatic syndrome. We initiated the TRICAVAL study to compare ...interventional valve implantation into the inferior vena cava (CAVI) versus optimal medical therapy (OMT) in severe TR. In the present subanalysis, we aimed to evaluate the effects of CAVI on clinical signs of congestion, renal and hepatic function. TRICAVAL was an investigator-initiated, randomized trial. Twenty-eight patients with severe TR were randomized to OMT or CAVI using an Edwards Sapien XT valve. Probands who completed the 3-month follow-up (CAVI n = 8, OMT n = 10) were evaluated by medical history, clinical examination, and laboratory testing at baseline, 3 and 12 months. After 3 months, the CAVI group exhibited a significant reduction of body weight (from 80.7 69.0-87.7 kg to 75.5 63.8-84.6 kg, p < 0.05) and abdominal circumference (from 101.5 ± 13.8 cm to 96.3 ± 15.4 cm, p ≤ 0.01) and a trend to lower doses of diuretics compared to OMT. Renal and hepatic function parameters did not change significantly. Within a short-term follow-up, CAVI led to an improvement of clinical signs of venous congestion and a non-significant reduction of diuretic doses compared to OMT.
The contradictory findings of recent prospective randomized controlled trials assessing the impact of percutaneous edge-to-edge repair in patients with functional or secondary mitral regurgitation ...have triggered a lively discussion about an “integrated” echocardiographic approach for grading severity of mitral regurgitation. In the MITRA-FR trial, the COAPT trial and the REDUCE-FMR trial echocardiographic assessment of the severity of mitral regurgitation was consistent with principles set forth by the current echocardiographic guidelines and analysed in its best settings by expert international leaders in the field of echocardiography. However, serious inconsistencies appeared in the presented echocardiographic assessments regarding cardiac output and regurgitant fraction. A new term “disproportionate functional mitral regurgitation” was introduced describing a situation where the increase of effective regurgitant orifice area exceeds the enlargement of the left ventricular end-diastolic volumes. Further discussion resulted in the idea of a “new conceptional framework” for distinguishing “proportionate” and “disproportionate” functional mitral regurgitation. The aim of this viewpoint is to dispute conclusions based on the term “disproportionate” mitral regurgitation. A “disproportionate” FMR is highly questionable because disproportionateness of flow in communication vessels cannot exist. In addition, a proposal of echocardiographic assessment based on a conventional comprehensive transthoracic echocardiography is given to avoid obvious hemodynamic contradictions.
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.
Transarterial aortic valve implantation (TAVI) is a promising method for the treatment of high-risk patients with aortic stenosis. Because gender differences are known in aortic stenosis, the aim of ...this study was to compare procedural and short-term outcomes, left ventricular remodeling, and inflammatory status after TAVI in men and women. One hundred consecutive patients (42 men, 58 women) who underwent transfemoral TAVI (CoreValve in 83%, SAPIEN in 17%) were prospectively analyzed. Aortic stenosis severity was higher in women (mean valve area 0.7 ± 0.3 vs 0.8 ± 0.2 cm2 ). Women had better ejection fractions, smaller end-diastolic and end-systolic diameters, and more concentric hypertrophy at baseline. There were no differences in device success rate (99%), 30-day total mortality (2.4% in men, 3.4% in women), stroke (2.4% in men, 1.7% in women), or pacemaker rate (26.2% in men, 15.5% in women). Periprocedural complications and 3-month outcome were not different between the genders. After TAVI, regression of hypertrophy occurred in men and women, but improvement of the ejection fraction was significant only in women. N-terminal pro–B-type natriuretic peptide decreased to similar levels in the 2 genders. C-reactive protein and interleukin-6, elevated at baseline more in men than in women, decreased after TAVI and normalized at 3 months only in women. In conclusion, women clinically benefit from TAVI to a degree similar to that of men. However, there are gender differences involving the recovery response of the left ventricle after TAVI.
Objectives This study sought to determine whether adding myocardial computed tomography perfusion (CTP) to computed tomography angiography (CTA) improves diagnostic performance for coronary stents. ...Background CTA of coronary stents has been limited by nondiagnostic studies caused by metallic stent material and coronary motion. Methods CTA and CTP were performed in 91 consecutive patients with stents before quantitative coronary angiography, the reference standard for obstructive stenosis (≥50%). If a coronary stent or vessel was nondiagnostic on CTA, adenosine stress CTP in the corresponding myocardial territory was read for combined CTA/CTP. Results Patients had an average of 2.5 ± 1.8 coronary stents (1 to 10), with a diameter of 3.0 ± 0.5 mm. Significantly more patients were nondiagnostic for stent assessment by CTA (22%; mainly due to metal artifacts 75% or motion 25%) versus CTP (1%; p < 0.001; severe angina precluded CTP in 1 case). The per-patient diagnostic accuracy of CTA/CTP for stents (87%, 95% confidence interval CI: 78% to 93%) was significantly higher than that of CTA alone (71%, 95% CI: 61% to 80%; p < 0.001), mainly because nondiagnostic examinations were significantly reduced (p < 0.001). In the analysis of any coronary artery disease, diagnostic accuracy and nondiagnostic rate were also significantly improved by the addition of CTP (p < 0.001). CTA/CTP (7.9 ± 2.8 mSv) had a significantly lower effective radiation dose than angiography (9.5 ± 5.1 mSv; p = 0.005). The area under the receiver-operating characteristic curve for CTA/CTP (0.82, 95% CI: 0.69 to 0.95) was superior to that for CTA (0.69, 95% CI: 0.57 to 0.82; p < 0.001) in identifying patients requiring stent revascularization. Conclusions Combined coronary CTA and myocardial CTP improves diagnosis of CAD and in-stent restenosis in patients with stents compared with CTA alone. (Coronary Artery Stent Evaluation With 320-Slice Computed Tomography—The CArS 320 Study CARS-320; NCT00967876 )
According to recent recommendations on echocardiographic assessment of aortic valve stenosis direct measurement of transvalvular peak jet velocity, calculation of transvalvular mean gradient from the ...velocities using the Bernoulli equation and calculation of the effective aortic valve area by continuity equation are the appropriate primary key instruments for grading severity of aortic valve stenosis. It is obvious that no gold standard can be declared for grading the severity of aortic stenosis. Thus, conclusions of the exclusive evaluation of aortic stenosis by Doppler echocardiography seem to be questionable due to the susceptibility to errors caused by methodological limitations, mathematical simplifications and inappropriate documentation. The present paper will address practical issues of echocardiographic documentation to satisfy the needs to analyze different scenarios of aortic stenosis due to various flow conditions and pressure gradients. Transesophageal and multidimensional echocardiography should be implemented for reliable measurement of geometric aortic valve area and of cardiac dimensions at an early stage of the diagnostic procedure to avoid misinterpretation due to inconsistent results.
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.
Background
We aimed to evaluate the predictive value of left atrial (LA) reservoir, conduit, and contractile function parameters as assessed by speckle tracking echocardiography (STE) for invasively ...measured hemodynamic parameters in a patient cohort with myocardial and valvular diseases.
Methods
Sixty‐nine patients undergoing invasive hemodynamic assessment were enrolled into the study. Invasive hemodynamic parameters were obtained by left and right heart catheterization. Transthoracic echocardiography assessment of LA reservoir, conduit, and contractile function was performed by STE.
Results
Forty‐nine patients had sinus rhythm (SR) and 20 patients had permanent atrial fibrillation (AF). AF patients had significantly reduced LA reservoir function compared to SR patients. In patients with SR, LA reservoir, conduit, and contractile function inversely correlated with pulmonary capillary wedge pressure (PCWP), left ventricular end‐diastolic pressure, and mean pulmonary artery pressure (PAP), and showed a moderate association with cardiac index. In AF patients, there were no significant correlations between LA reservoir function and invasively obtained hemodynamic parameters. In SR patients, LA contractile function with a cutoff value of 16.0% had the highest diagnostic accuracy (area under the curve, AUC: 0.895) to predict PCWP ≥18 mm Hg compared to the weaker diagnostic accuracy of average E/Eʹ ratio with an AUC of 0.786 at a cutoff value of 14.3. In multivariate analysis, LA contractile function remained significantly associated with PCWP ≥18 mm Hg.
Conclusion
In a cohort of patients with a broad spectrum of cardiovascular diseases LA strain shows a valuable prediction of hemodynamic parameters, specifically LV filling pressures, in the presence of SR.
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