BACKGROUND The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.)

/pdf/empagliflozin-cardiovascular-outcomes-and-mortality-in-type-48se5zm30q.pdf

Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Mark A. Creager, MD, FACC, FAHA[#][1]

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[#][1]

Robert A

/pdf/2014-aha-acc-hrs-guideline-for-the-management-of-patients-1v8ficsqox.pdf

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

While immunomodulation plays an important role in the therapy of diseases of the rheumatic field, their application is continuously extended to other inflammation-related diseases. The evaluation of cardiac side effects of the numerous immune-modulating substances on the market is complex, since most studies include patients suffering from rheumatic diseases that are known to have an influence on cardiovascular risk factors and tend to be linked with an increased cardiovascular mortality rate. The IgE-neutralizing antibody omalizumab and the pyrimidine synthesis inhibitor leflunomide are potentially associated with increased cardiovascular risk. At the same time healthcare professionals are asked to use special precaution when treating heart failure patients with certain types of anti-TNF-α antibodies and CD20 antibodies, which were reported to be associated with the development of arrhythmias. Other substances are thought to be beneficial to the treatment of cardiovascular diseases. Thus IL-1β blockers were found to be of potential use in the treatment of heart failure. The IL-6 receptor blocker tocilizumab and the anti-p40 antibody ustekinumab have shown partly contradictory results and are still under current investigation regarding their potential beneficial effects on cardiovascular diseases. Intravenous gammaglobulin products and the cytokine profile-modulating therapy celacade have a more comprehensive influence on inflammation and have significant potential in the cardiovascular field. Finally, substances that are naturally produced in the body, such as vitamin D, alpha-1 antitrypsin, estrogen, or progesterone are currently gaining more attention regarding their potential use in the prevention of cardiovascular diseases.

Chapter 28 – Cardiac Immunomodulation

https://journals.sagepub.com/doi/pdf/10.1177/2047487320940103

Sodium glucose cotransporter 2 inhibitors for all HFrEF patients: can we afford it? A cost-effectiveness analysis of dapagliflozin

Ziel: Uber die Teilnehmergewinnung fur Praventionsmasnahmen in Bevolkerungen mit niedrigerem Sozialstatus ist wenig bekannt. Ergebnisse proaktiver Kontaktierung fur ein 2-stufiges kardiopraventives Untersuchungsprogramm (KUP) in 2 Jobcentern einer norddeutschen Region werden dargestellt. Methode: Uber jeweils 10 Wochen erhielten Jobcenter-Klienten im Alter zwischen 40 und 65 Jahren das Angebot, am KUP teilzunehmen. Dieses umfasste einen ersten Abschnitt im Jobcenter und einen zweiten in einem kardiovaskularen Untersuchungszentrum. Abschnitt 1 beinhaltete eine EDV-gestutzte Befragung, und bei Anwesenheit einer medizinischen Fachkraft, eine Blutdruckmessung und/oder Blutentnahme. Teilnehmer ohne kardiovaskulare Vorerkrankungen, interventionelle/operative Gefaseingriffe, Diabetes mellitus und einem Body-Mas Index≤35 kg/m2 erhielten das Angebot der Teilnahme an Abschnitt 2. Mittels logistischer Regressionsanalysen wurden fur beide Abschnitte Pradiktoren der Teilnahme analysiert. Dazu zahlten Lebensalter und Geschlecht, fur die Teilnahme an Abschnitt 2 die Entfernung zwischen Wohnadresse und Untersuchungszentrum, kardiovaskulare Risikofaktoren, subjektive Gesundheit und weitere soziodemografische Merkmale. Ergebnisse: In Abschnitt 1 nahmen 344 der 1 046 eingeladenen Personen an der Befragung teil. Dabei handelte es sich um uberzufallig mehr Frauen als Manner. Von diesen erhielten 253 das Angebot der Blutdruckmessung, der Blutentnahme sowie der postalischen Zusendung der Laborergebnisse. Die Teilnahme von 209 Personen war positiv mit dem Lebensalter assoziiert. An Abschnitt 2 nahmen 138 Personen teil. Je weiter vom Untersuchungszentrum entfernt die Personen wohnten, desto weniger nahmen sie dieses Angebot wahr. Von Tabakrauchern, Personen mit Hauptschulbildung bzw. solche mit nicht erhohten Blutfetten nahmen ebenfalls weniger teil. Schlussfolgerungen: Blutdruckmessung und Blutentnahme im Jobcenter treffen auf hohe Akzeptanz. Anforderungen zusatzlicher Wege fur praventive kardiovaskulare Untersuchungsangebote sind gering zu halten.

Soliciting Job Centre Clients for a Cardiopreventive Health Examination Programme

Self-reported physical activity differs from activity levels measured by device. We tested the effect of a video that visualizes the intensity levels of physical activity to increase the agreement between self-reported and accelerometer-based moderate-to-vigorous physical activity (MVPA) within a single-blinded, randomized study. Participants (N = 378, 40-75 years) wore an accelerometer for seven days. Prior to the collection of self-reported data by the IPAQ-SF, participants were randomly assigned (1:1) to a control group (CG) or a video group (VG). The outcome was the absolute difference between self-reported and accelerometer-based time spent in MVPA (Δ MVPAIPAQ-Accelerometry ). To examine the agreement, we used Spearman correlation coefficients and Bland-Altman analysis. To test the video effect, we used Wilcoxon signed-rank test, Bayes factor, and simultaneous-quantile regression. In total, 302 participants fulfilled the accelerometer wear time criteria (≥10 hours/day; ≥6 days) and completed self-reports within three days after the wearing period. The median of Δ MVPAIPAQ-Accelerometry was -9.0 min/day (IQR: -32.0 to 66.6) for CG and -11.5 min/day (IQR: -29.9 to 14.3) for VG. Wilcoxon signed-rank test revealed no differences in Δ MVPAIPAQ-Accelerometry between study groups whereas Bayes factor indicated insensitivity of the data. Simultaneous-quantile regression revealed no relationship between video presentation and Δ MVPAIPAQ-Accelerometry in the 25th percentile. In the 50th (b = -12.4 [95% CI = -23.2 to -1.5] and 75th percentile (b = -45.7 [95% CI = -70.5 to -20.9]), Δ MVPAIPAQ-Accelerometry was negatively associated with video presentation. To conclude, video-supported assessment may increase the accuracy of self-reported MVPA among individuals who slightly underestimated and those who overestimated their MVPA.

The effect of a video-supported assessment to increase the accuracy of self-reported physical activity.

Myocardial inflammation is one of the leading causes of dilated cardiomyopathy. Thereby abnormalities of the cellular and humoral immune system play a crucial role in the development and disease progression leading to heart failure. Many experimental and clinical studies suggest that disturbances of the humoral immune system involving the production of circulating cardiac antibodies are a key factor for the deterioration of cardiac function. Elimination of such pathogenic antibodies by immunoadsorption results not only in an improvement of cardiac function but also decreases myocardial inflammation. Current data suggest that this experimental treatment option may be a promising novel approach for patients suffering from dilated cardiomyopathy with serum cardiac antibodies, but evidence from a placebo-controlled multicentre study is still needed.

Marcus Dörr

Papers

Chapter 28 – Cardiac Immunomodulation

Sodium glucose cotransporter 2 inhibitors for all HFrEF patients: can we afford it? A cost-effectiveness analysis of dapagliflozin

Soliciting Job Centre Clients for a Cardiopreventive Health Examination Programme

The effect of a video-supported assessment to increase the accuracy of self-reported physical activity.

Immunomodulation and Immunoadsorption in Inflammatory Dilated Cardiomyopathy