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Background Inflammation is increasingly recognized as an important pathogenic feature in cardiovascular disease. In patients with STEMI, C-reactive protein (CRP), the prototype human acute phase protein, is a marker of poor prognosis and independently predicts 30-day mortality. In STEMI, CRP may indeed be intimately involved in myocardial damage by activating the complement system in the ischemic tissue. In animal experiments, CRP removal after STEMI reduces infarct size and results in a significantly better left ventricular ejection fraction (LVEF). Recently, in the multi-center matched-control pilot study on CRP apheresis in Acute Myocardial Infarction (CAMI1), a newly designed CRP adsorber has been demonstrated to efficiently and selectively lower CRP plasma levels in humans. Here, we present preliminary data of the ongoing trial. Methods Up to the present day, 67 STEMI patients were enrolled in the study following complete coronary revascularization. 32 patients received CRP apheresis, whereas 35 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (MRI) 5±3 days after STEMI. Results Apheresis sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 12 mg/l to 279 mg/l. The peak CRP level after AMI can be calculated precisely with at 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.95. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the apheresis patients no longer correlate with the control with regard to the endpoints infarct size, LVEF, longitudinal strain and circumferential strain. They perform significantly better at all endpoints. The CRP apheresis reduced the development of myocardial damage. Conclusions Here, an unequivocal association between infarct size and CRP is demonstrated for the first time. CRP apheresis following STEMI is feasible and safe. Our preliminary results in a small cohort show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis may emerge as a new therapeutic approach in the treatment of acute myocardial infarction.

The indication for cardiac resynchronization therapy (CRT) using biventricular pacing or ICD systems has to be highly differentiated to optimize the proportion of patients who derive significant symptomatic benefit from this therapy, on the one hand, and to avoid this invasive treatment in patients with a low probability of clinical success of CRT, on the other hand. As a consensus in 2005, it can be put forward that there is sufficient evidence for an indication for CRT from clinical studies for the following characteristics: 1) Heart failure in NYHA functional class III or IV (if cardiac recompensation to class III is at least temporarily successful), 2) left ventricular ejection fraction < or =35%, 3) QRS duration >130 ms, particularly if left bundle branch block is present, 4) sinus rhythm. In addition, available data also suggest an indication for CRT in patients with atrial fibrillation if the other criteria listed above are met. The indication for CRT is unclear in patients with other intraventricular conduction delay (particularly right bundle branch block) while patients with left bundle branch block and a QRS duration of 120-130 ms seem to benefit if echocardiographic criteria demonstrate ventricular dyssynchrony. Since a multiplicity of echocardiographic criteria of ventricular dyssynchrony exists which is neither standardized nor evaluated in large-scale randomized trials, ventricular dyssynchrony on echocardiography alone cannot be regarded as an established indication for CRT without a QRS complex > or =120 ms. Similarly, whether heart failure in functional state NYHA II should be regarded as a CRT indication is currently being investigated in the randomized RAFT and MADIT-CRT trials.

Background Risk of heart failure (HF) is increased in patients with rheumatoid arthritis (RA) and the predominantly prevalent type is diastolic HF with normal ejection fraction (HFNEF). Traditional cardiovascular risk factors are overrepresented in RA but chronic inflammation is an independent significant contributor to myocardial dysfunction. However, there is great variance in reported prevalence of HF in RA due to differing diagnostic standards and HFNEF is apparently underestimated. Objectives To determine prevalence of heart failure in a community-based RA-cohort compared to age- and gender-matched controls using the 2008 European Society of Cardiology (ESC) diagnostic guidelines. Methods A prospective cross-sectional study including 157 consecutively recruited RA-patients from our outpatient clinic during a 3 months period. Inclusion criteria were written consent and diagnosis of RA fulfilling ACR/EULAR-criteria. Blinded to any health information an age- and gender-matched control group (n=77) was recruited from a district office and veterans of our hospital staff. Demographic and clinical data were obtained using standardized questionnaire and evaluation of Framingham criteria. Lab tests included NT-proBNP (Roche). Echocardiography of all subjects contained tissue doppler and strain imaging. Results The cohorts were comparable in gender distribution (67% vs. 69% females) and age (mean (SD) 61 years (±13) vs. 59 (±12). RA median DAS28 was 2.8 (Interquartile range (IQR) 2.0-3.4), median HAQ 1.1 (IQR 0.8-2.0) with remission (DAS28<2.6) in 45%, mild disease activity (DAS28 2.6-3.2) in 25% and higher disease activity (DAS28>3.2) in 30%. Prevalence of HF was significantly higher in RA vs. controls (38 (24%) vs. 5 (6%), p<0.001). Of all diagnosed HF, only 2 RA patients showed reduced ejection fraction. Significantly more RA patients reported on dyspnea on exertion (DOE, 66 (44%) vs. 14 (19%), p<0.001). RA patients showed significantly higher mean BMI 29 (±5) vs. 27 (±4), p<0.001 and higher prevalence of hypertension (59% vs. 40%, p=0.019). No significant differences were found for diabetes type 2 (13% vs. 8%), chronic kidney disease (GFR<60ml/min; 15% vs. 6%) and coronary artery disease (8% vs. 3%). Analyzing age decades, HF was found 10 years earlier and always more often in RA patients. Subgroup analysis revealed highest prevalence of HF in higher disease activity (37%, RR 5.7, p<0.001 compared to controls), 30% during mild disease activity (RR 4.6, p=0.0015) and 13% during remission (RR 1.95, p=0.264). In multivariate analysis adjusted for age and gender, remaining risk factors for HF in RA were DAS28≥2.6 (OR 3.4, 95%CI 1.3-9.8), RA-duration>10years (OR 2.6, 95%CI 1.2-5.8), CRP median>10mg/l (OR 4.8, 95%CI 1.1-21), and ESR>16mm/h (OR 5.4, 95%CI 2.1-16). Conclusions According to ESC guidelines, HF was found elevated 4-6fold in active RA and 2fold increased still in states of controlled disease. Heart failure with normal ejection fraction i.e. of diastolic type is found in as many as a quarter of all RA...

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Biotronik SE & Co. KG Woermannkehre 1 12359 Berlin Background The prevalence of chronotropic incompetence (CI) in heart failure (HF) population is high and negatively impacts prognosis. Rate-adaptive pacing (RAP) is an important treatment option for CI. However, only a proportion of HF patients treated with cardiac resynchronisation therapy (CRT) devices benefit from accelerometer-based RAP in terms of exercise tolerance, functional capacity, and quality of life (QoL). Further research is needed to identify patient characteristics predicting positive response to RAP, and to evaluate performance of alternative sensors such as closed loop stimulation (CLS) driven by cardiac impedance measurements. An optimal outcome measure is represented by ventilatory efficiency (VE) slope during cardio-pulmonary exercise test (CPX) because of superior prognostic value. Purpose The purpose of the BIO|Create pilot study was to assess the benefit of CLS in CRT patients with CI. In this predefined subanalysis, we identify predictors of positive response to CLS (reduction of VE slope by ≥5%) and compare study outcomes in responders vs non-responders. Methods The study enrolled CRT patients with NYHA class II or III and severe CI (&lt;75% of age-predicted maximum heart rate [HR] or &lt;50% of HR reserve utilised at end-exercise). Patients were randomised to DDD-CLS mode or to DDD pacing at 40 beats/min for 1 month, followed by crossover for another month. At 1- and 2-month follow-ups, exercise tolerance was assessed by treadmill CPX, functional capacity by 6-min walk test, and QoL by the EQ-5D-5L and Minnesota Living with HF (MLHFQ) questionnaires. Results Among 17 patients with full follow-up datasets, 8 (47%) were responders to CLS. Compared to non-responders, responders had larger left ventricular (LV) ejection fraction at baseline (46 ± 3 vs 36 ± 9 %; p = 0.0070), smaller end-diastolic (121 ± 34 vs 181 ± 41 ml; p = 0.0085) and end-systolic (65 ± 23 vs 114 ± 39 ml; p = 0.0076) LV volumes, and were predominantly in NYHA class II (p = 0.0498). For study outcomes, the mean difference between DDD-CLS and DDD-40 modes in responders vs non-responders was - 6.1 (-16.4%) vs +2.7 (+6.8%) for VE slope (both p &lt; 0.05), +0.5 vs -0.2 ml/min (O2 uptake efficiency slope), +1.3 vs -0.3 ml/kg/min (peak O2 uptake), +1.4 vs -0.75 mmHg (end-exercise end-tidal CO2), 16 vs 7 m (6-min walk distance), 0.08 vs 0.06 (EQ-5D-5L index), 1.9 vs 0 (EQ-5D-5L scale), and -2.5 vs +1.75 (MLHFQ). Conclusions For the first time, predictors for positive outcome of RAP in CRT patients have been identified. Patients with less advanced HF were responders to RAP driven by CLS principle. In addition, a consistent increase in exercise and functional capacity and QoL in these patients could be achieved. In contrast, patients with advanced HF experienced worse exercise capacity and QoL during RAP, suggesting caution if RAP is desirable due to CI. Further clinical research is needed to evaluate if positive response to RAP can improve hard clinical outcomes.