Fabian Knebel

Potential Role of Autoantibodies Belonging to the Immunoglobulin G-3 Subclass in Cardiac Dysfunction Among Patients With Dilated Cardiomyopathy

Background—Immunoadsorption capable of removing circulating autoantibodies represents an additional therapeutic approach in dilated cardiomyopathy (DCM). The role played by autoantibodies belonging to the immunoglobulin (Ig) subclass G-3 in cardiac dysfunction remains to be elucidated. Methods and Results—Patients with DCM (left ventricular ejection fraction <30%) participated in this case-control study. Nine patients underwent immunoadsorption with protein A (low affinity to IgG-3), and 9 patients were treated with anti-IgG, which removes all IgG subclasses. Immunoadsorption was performed in 4 courses at 1-month intervals until month 3. In the 2 groups, immunoadsorption induced comparable reduction of total IgG (>80%). IgG-3 was effectively eliminated only by anti-IgG adsorption (eg, during the first immunoadsorption course; protein A, −37±4%; anti-IgG, −89±3%;P <0.001 versus protein A). The &bgr;1-receptor autoantibody was effectively reduced only by anti-IgG (P <0.01 versus protein A). Hemodynamics did not change in the protein A group. In the anti-IgG group during the first immunoadsorption course, cardiac index increased from 2.3±0.1 to 3.0±0.1 L · min−1 · m−2 (P <0.01 versus protein A). After 3 months, before the last immunoadsorption course, cardiac index was 2.2±0.1 L · min−1 · m−2 in the protein A group and 3.0±0.2 L · min−1 · m−2 in the anti-IgG group (P <0.01 versus protein A). Left ventricular ejection fraction increased only in the anti-IgG group (P <0.05 versus protein A). Conclusions—Autoantibodies belonging to IgG-3 may play an important role in cardiac dysfunction of DCM. The removal of antibodies of the IgG-3 subclass may represent an essential mechanism of immunoadsorption in DCM.

Computed Tomography Angiography and Myocardial Computed Tomography Perfusion in Patients With Coronary Stents: Prospective Intraindividual Comparison With Conventional Coronary Angiography

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).

Early right ventricular systolic dysfunction in patients with systemic sclerosis without pulmonary hypertension: a Doppler Tissue and Speckle Tracking echocardiography study

BackgroundIsovolumetric acceleration (IVA) is a novel tissue Doppler parameter for the assessment of systolic function. The aim of this study was to evaluate IVA as an early parameter for the detection of right ventricular (RV) systolic dysfunction in patients with systemic sclerosis (SSc) without pulmonary hypertension.Methods22 patients and 22 gender- and age-matched healthy subjects underwent standard echocardiography with tissue Doppler imaging (TDI) and speckle tracking strain to assess RV function.ResultsTricuspid annular plane systolic excursion (TAPSE) (23.2 ± 4.1 mm vs. 26.5 ± 2.9 mm, p < 0.006), peak myocardial systolic velocity (Sm) (11.6 ± 2.3 cm/s vs. 13.9 ± 2.7 cm/s, p = 0.005), isovolumetric contraction velocity (IVV) (10.3 ± 3 cm/s vs. 14.8 ± 3 cm/s, p < 0.001) and IVA (2.3 ± 0.4 m/s2 vs. 4.1 ± 0.8 m/s2, p < 0.001) were significant lower in the patient group. IVA was the best parameter to predict early systolic dysfunction with an area under the curve of 0.988.ConclusionIVA is a useful tool with high-predictive power to detect early right ventricular systolic impairment in patients with SSc and without pulmonary hypertension.

Impact of gender on three-month outcome and left ventricular remodeling after transfemoral transcatheter aortic valve implantation.

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 cm(2)). 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.

Long-term Follow-up of a Fenestrated Amplatzer Atrial Septal Occluder in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease, with right-heart failure being the main cause of death. In patients refractory to conventional drug therapy, atrial septostomy can serve as palliative treatment or as a bridge to transplantation. A 41-year-old woman with a 15-year history of PAH associated with a corrected atrial septal defect presented with severe deterioration of symptoms. Echocardiography confirmed reocclusion of an atrial septal stoma that had been created several months before. After performing a repeat atrial septostomy, we implanted a custom-made atrial septostomy device, an Amplatzer septal occluder that had been fenestrated to serve as a custom-made atrial septostomy device. This resulted in an improvement in cardiac output and a marked symptomatic relief. During the 6-year follow-up, the patient was clinically stable with limited but constant exercise tolerance, under specific medical therapy. Repeated echocardiography confirmed long-term patency of the device.

Two-dimensional speckle tracking of the left ventricle in patients with systemic sclerosis for an early detection of myocardial involvement

AIMS Myocardial involvement is associated with poor prognosis in patients with systemic sclerosis (SSc). Two-dimensional speckle-tracking echocardiography (STE) is a powerful novel modality for the assessment of subclinical cardiac left ventricular (LV) dysfunction that, so far, has not been investigated in SSc patients. The aim of this study was to evaluate deformation analyses derived from STE for early detection of LV systolic dysfunction in patients with SSc having preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS Twenty-two patients with SSc (57.1 ± 13.3 years, LVEF 64 ± 3.1%, mean time of 5.4 ± 4.6 years from diagnosis) and 22 gender- and age-matched healthy subjects (57.4 ± 14.0 years, LVEF 65 ± 2.7%) underwent echocardiography with STE to assess global and regional LV function. The global longitudinal 2D peak systolic strain (PSS) of the left ventricle was significantly lower in the SSc group compared with controls: -19.0 ± 2.4 vs. -21.1 ± 2.5% (P = 0.008). This was mainly driven by a reduced strain in the basal segments. Strain in the medial segments and in the apex did not differ significantly. In addition, there was a significant difference between both groups regarding the global longitudinal PSS rate of the left ventricle (-1.19 ± 0.18 vs. -1.43 ± 0.26 s(-1), P = 0.001). CONCLUSION LV deformation analysis by STE is a sensitive method to detect early LV systolic impairment primarily in the basal segments in patients with SSc having preserved LVEF.

Effects of immunoadsorption and subsequent immunoglobulin G substitution on cardiopulmonary exercise capacity in patients with dilated cardiomyopathy

BACKGROUND Recent data indicate that cardiac antibodies play an active role in the pathogenesis of dilated cardiomyopathy (DCM) and may contribute to cardiac dysfunction in patients with DCM. The present study investigated the influence of immunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) on cardiopulmonary exercise capacity in patients with DCM. METHODS Sixty patients with DCM (New York Heart Association II-IV, left ventricular ejection fraction < or =45%) were included in this single-center university hospital-based case-control study. Patients either were treated with IA/IgG (n = 30) or were followed without IA/IgG (n = 30). At baseline and after 3 months, we compared echocardiographic assessment of left ventricular function and spiroergometric exercise parameters. RESULTS In contrast to controls, left ventricular ejection fraction improved significantly in the IA/IgG group from 33.0% +/- 1.2% to 40.1% +/- 1.5% (P < .001). In the control group, spiroergometric exercise parameters did not change during follow-up. After 3 months, maximum achieved power increased in the treatment group from 114.2 +/- 7.4 to 141.9 +/- 7.9 W (P = .02). Total exercise time increased in the treatment group from 812 +/- 29 to 919 +/- 30 seconds (P < .05). Peak oxygen uptake (Vo(2)) increased from 17.3 +/- 0.9 to 21.8 +/- 1.0 mL min(-1) kg(-1) after IA/IgG (P < .01). Oxygen pulse (peak Vo(2)/maximum heart rate) increased in the treatment group (10.7 +/- 0.7 vs 13.6 +/- 0.7 mL beat(-1) min(-1), P < .01). The Vo(2) at the gas exchange anaerobic threshold increased after 3 months in the treatment group from 10.3 +/- 0.5 to 13.2 +/- 0.5 mL min(-1) kg(-1) (P < .001). The ventilatory response to exercise (V(E)/Vco(2) slope) decreased after IA/IgG therapy from 32.3 +/- 1.5 to 28.7 +/- 0.9 (P = .02). CONCLUSIONS In patients with DCM, IA/IgG therapy may induce improvement in echocardiographic and cardiopulmonary exercise parameters.

Transesophageal echocardiography in patients with cryptogenic cerebral ischemia

BackgroundIn about one third of all patients with cerebral ischemia, no definite cause can be identified (cryptogenic stroke). In many patients with initially suspected cryptogenic stroke, however, a cardiogenic etiology can eventually be determined. Hence, the aim of this study was to describe the prevalence of abnormal echocardiographic findings in a large number of these patients.MethodPatients with cryptogenic cerebral ischemia (ischemic stroke, IS, and transient ischemic attack, TIA) were included. The initial work-up included a neurological examination, EEG, cCT, cMRT, 12-lead ECG, Holter-ECG, Doppler ultrasound of the extracranial arteries, and transthoracic echocardiography. A multiplane transeophageal echocardiography (TEE, including i.v. contrast medium application [Echovist], Valsalva maneuver) was performed in all patientsResults702 consecutive patients (380 male, 383 IS, 319 TIA, age 18–90 years) were included. In 52.6% of all patients, TEE examination revealed relevant findings. Overall, the most common findings in all patients were: patent foramen ovale (21.7%), previously undiagnosed valvular disease (15.8%), aortic plaques, aortic valve sclerosis, atrial septal aneurysms, regional myocardial dyskinesia, dilated left atrium and atrial septal defects. Older patients (> 55 years, n = 291) and patients with IS had more relevant echocardiographic findings than younger patients or patients with TIA, respectively (p = 0.002, p = 0.003). The prevalence rates of PFO or ASD were higher in younger patients (PFO: 26.8% vs. 18.0%, p = 0.005, ASD: 9.6% vs. 4.9%, p = 0.014).ConclusionA TEE examination in cryptogenic stroke reveals contributing cardiogenic factors in about half of all patients. Younger patients had a higher prevalence of PFO, whereas older patients had more frequently atherosclerotic findings. Therefore, TEE examinations seem indicated in all patients with cryptogenic stroke – irrespective of age – because of specific therapeutic consequences.

Shear-wave Amplitudes Measured with Cardiac MR Elastography for Diagnosis of Diastolic Dysfunction

PURPOSE To test whether shear-wave amplitudes (SWAs) in the myocardium measured with cardiac magnetic resonance (MR) elastography enable diagnosis of myocardial relaxation abnormalities in patients with diastolic dysfunction. MATERIALS AND METHODS Each subject gave written informed consent to participate in this institutional review board-approved prospective study. Electrocardiographically triggered SWA-based cardiac MR elastography with 24.13-Hz external vibration frequency was performed in 50 subjects grouped into asymptomatic young (n = 10, 18-39 years) and asymptomatic old (n = 10, 40-68 years) subjects and patients with echocardiographically proved mild, moderate, or severe diastolic dysfunction (n = 30, 44-73 years). SWA images were analyzed in the left ventricular (LV) region and were normalized against reference SWA of the thoracic wall. Analysis of variance with Bonferroni-corrected pairwise comparison and Pearson correlation were used for statistical evaluation. RESULTS Young and old control subjects had normalized mean LV SWA of 0.67 ± 0.04 (standard error of the mean) and 0.56 ± 0.04 (P = .18, F test), respectively. Compared with the control groups, patients with mild, moderate, and severe diastolic dysfunction displayed significantly reduced normalized mean LV SWA of 0.37 ± 0.04, 0.34 ± 0.04, and 0.29 ± 0.04 (P < .001, F test), respectively, which was inversely correlated to the severity of diastolic dysfunction (R = -0.61, P < .001). The best cutoff value to differentiate between asymptomatic volunteers and patients was 0.43, yielding an area under the receiver operating characteristic curve of 0.92, with 90% sensitivity and 89.7% specificity. CONCLUSION LV SWA measured with cardiac MR elastography provides image contrast sensitive to myocardial relaxation abnormalities and shows significantly lower values in patients with diastolic dysfunction.

Acute regional improvement of myocardial function after interventional transfemoral aortic valve replacement in aortic stenosis: A speckle tracking echocardiography study

BackgroundTranscatheter aortic valve implantation (TAVI) is a promising therapy for patients with severe aortic stenosis (AS) and high perioperative risk. New echocardiographic methods, including 2D Strain analysis, allow the more accurate measurement of left ventricular (LV) systolic function. The goal of this study was to describe the course of LV reverse remodelling immediately after TAVI in a broad spectrum of patients with symptomatic severe aortic valve stenosis.MethodsThirty consecutive patients with symptomatic aortic valve stenosis and preserved LVEF underwent transfemoral aortic valve implantation. We performed echocardiography at baseline and one week after TAVI. Echocardiography included standard 2D and Doppler analysis of global systolic and diastolic function as well as 2D Strain measurements of longitudinal, radial and circumferential LV motion and Tissue Doppler echocardiography.ResultsThe baseline biplane LVEF was 57 ± 8.2%, the mean pressure gradient was 46.8 ± 17.2 mmHg and the mean valve area was 0.73 ± 0.27 cm2. The average global longitudinal 2D strain of the left ventricle improved significantly from -15.1 (± 3.0) to -17.5 (± 2.4) % (p < .001). This was reflected mainly in improvement in the basal and medial segments while strain in the apex did not change significantly [-11.6 (± 5.2) % to -15.1 (± 5.5) % (p < .001), -13.9 (± 5.1) % to -16.8 (± 5.6) % (p < .001) and -19.2 (± 7.0) % to -20.0 (± 7.2) % (p = .481) respectively]. While circumferential strain [-18.1 (± 5.1) % vs. -18.9 (± 4.2) %, p = .607], radial strain [36.5 (± 13.7) % vs. 39.7 (± 17.2) %, p = .458] and the LVEF remained unchanged after one week [57.0 (± 8.2) % vs. 59.1 (± 8.1) %, p = .116].ConclusionThere is an acute improvement of myocardial longitudinal systolic function of the basal and medial segments measured by 2D Strain analysis immediately after TAVI. The radial, circumferential strain and LVEF does not change significantly in all patients acutely after TAVI. These data suggest that sensitive new echo methods can reliably detect early regional changes of myocardial function after TAVI before benefits in LVEF are detectable.