Frank Ruschitzka

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure : The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC

Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chairperson) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK), Volkmar Falk (Germany), José Ramón González-Juanatey (Spain), Veli-Pekka Harjola (Finland), Ewa A. Jankowska (Poland), Mariell Jessup (USA), Cecilia Linde (Sweden), Petros Nihoyannopoulos (UK), John T. Parissis (Greece), Burkert Pieske (Germany), Jillian P. Riley (UK), Giuseppe M. C. Rosano (UK/Italy), Luis M. Ruilope (Spain), Frank Ruschitzka (Switzerland), Frans H. Rutten (The Netherlands), Peter van der Meer (The Netherlands)

2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA).

2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy : The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA)

Acute heart transplant rejection due to Saint John's wort

We report here acute rejection in two transplant patients due to a metabolic interaction of St Johns wort and cyclosporin.

Anti–Tumor Necrosis Factor-α Treatment Improves Endothelial Function in Patients With Rheumatoid Arthritis

Background— Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-α in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-α antibody infliximab on disease activity and endothelial function in patients with active RA. Methods and Results— Eleven RA patients (mean age 46±5 years; disease duration 9±2 years) with high disease activity despite treatment with stable doses of methotrexate (≤25 mg/wk) and prednisone (≤10 mg/d) were investigated. Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasoun...

2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy

### Abbreviations 1st AV : First-degree atrioventricular block AF : atrial fibrillation AT : atrial tachyarrhythmia ATP : Anti-tachycardia pacing AV : atrioventricular BBB : bundle branch block CHF : congestive heart failure CI : confidence interval CPG : Committee for Practice Guidelines CRT : cardiac resynchronization therapy CRT-D : cardiac resynchronization therapy and defibrillator CRT-P : cardiac resynchronization therapy and pacemaker ECG : electrocardiogram EDMD : Emery-Dreifuss muscular dystrophy EF : ejection fraction EPS : electrophysiological study ESC : European Society of Cardiology HCM : hypertrophic cardiomyopathy HF : heart failure HR : hazard ratio HV : His-ventricular ICD : implantable cardioverter defibrillator ILR : implantable loop recorder IVCD : intraventricular conduction delay LBBB : left bundle branch block LQTS : long QT syndrome LV : left ventricular LVEF : left ventricular ejection fraction LVSD : left ventricular systolic dysfunction MR : mitral regurgitation MRI : magnetic resonance imaging NYHA : New York Heart Association PM : pacemaker OR : odds ratio QALY : quality-adjusted life year RBBB : right bundle branch block RCT : randomized controlled trial RV : right ventricular SB : sinus bradycardia SNRT : sinus node recovery time SR : sinus rhythm SSS : sick sinus syndrome TAVI : transcatheter aortic valve implantation VF : ventricular fibrillation VT : ventricular tachycardia VV : interventricular (delay) ### Acronyms of the trials referenced in the recommendations or reported in the tables ADEPT : ADvanced Elements of Pacing Randomized Controlled Trial ADOPT : Atrial Dynamic Overdrive Pacing Trial AOPS : Atrial Overdrive Pacing Study APAF : Ablate and Pace in Atrial Fibrillation ASSERT : ASymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial ATTEST : ATrial Therapy Efficacy and Safety Trial AVAIL CLS/CRT : AV Node Ablation with CLS and CRT Pacing Therapies for Treatment of AF trial B4 : Bradycardia detection in Bundle Branch Block BELIEVE : Bi vs. Left Ventricular Pacing: an International Pilot Evaluation on Heart Failure Patients with Ventricular Arrhythmias BIOPACE : Biventricular pacing for atrioventricular block to prevent cardiac desynchronization BLOCK-HF : Biventricular versus right ventricular pacing in patients with AV block B-LEFT : Biventricular versus LEFT Univentricular Pacing with ICD Back-up in Heart Failure Patients CARE-HF : CArdiac REsynchronization in Heart Failure CLEAR : CLinical Evaluation on Advanced Resynchronization COMBAT : COnventional vs. Biventricular Pacing in Heart Failure and Bradyarrhythmia COMPANION : COmparison of Medical Therapy, Pacing and Defibrillation in Heart Failure DANPACE : DANish Multicenter Randomized Trial on Single Lead Atrial PACing vs. Dual Chamber Pacing in Sick Sinus Syndrome DECREASE-HF : The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure FREEDOM : Optimization Study Using the QuickOpt Method GREATER-EARTH : Evaluation of Resynchronization Therapy for Heart Failure in Patients with a QRS Duration GREATER Than 120 ms LESSER-EARTH : Evaluation of Resynchronization Therapy for Heart Failure in Patients with a QRS Duration Lower Than 120 ms HOBIPACE : HOmburg BIventricular PACing Evaluation IN-CHF : Italian Network on Congestive Heart Failure ISSUE : International Study on Syncope of Unexplained Etiology MADIT : Multicenter Automatic Defibrillator Trial MIRACLE : Multicenter InSync RAndomized CLinical Evaluation MOST : MOde Selection Trial in Sinus-Node Dysfunction MUSTIC : MUltisite STimulation In Cardiomyopathies OPSITE : Optimal Pacing SITE PACE : Pacing to Avoid Cardiac Enlargement PAVE : Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation PATH-CHF : PAcing THerapies in Congestive Heart Failure II Study Group PIPAF : Pacing In Prevention of Atrial Fibrillation Study PIRAT : Prevention of Immediate Reinitiation of Atrial Tachyarrhythmias POT : Prevention Or Termination Study PREVENT-HF : PREventing VENTricular Dysfunction in Pacemaker Patients Without Advanced Heart Failure PROSPECT : PRedictors Of Response to Cardiac Resynchronization Therapy RAFT : Resynchronization–Defibrillation for Ambulatory Heart Failure Trial RethinQ : Cardiac REsynchronization THerapy IN Patients with Heart Failure and Narrow QRS REVERSE : REsynchronization reVErses Remodelling in Systolic left vEntricular dysfunction SAFARI : Study of Atrial Fibrillation Reduction SCD HeFT : Sudden Cardiac Death in Heart Failure Trial SMART-AV : The SMARTDelay Determined AV Optimization: a Comparison with Other AV Delay Methods Used in Cardiac Resynchronization Therapy SYDIT : The SYncope DIagnosis and Treatment SYNPACE : Vasovagal SYNcope and PACing TARGET : TARgeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy THEOPACE : Effects of Oral THEOphylline and of Permanent PACEmaker on the Symptoms and Complications of Sick Sinus Syndrome VASIS-PM : VAsovagal Syncope International Study on PaceMaker therapy V-HeFT : Vasodilator in HEart Failure Trial VPSII : Second Vasovagal Pacemaker Study (VPS II) Additional references are mentioned with ‘w’ in the main text and can be found on the online addenda along with 5 figures (1, 6, 7, 9, 11, 12) and 10 tables (3, 4, 5, 9, 11, 12, 19, 21, 22, 23). They are available on the ESC website only at http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/cardiac-pacing-and-cardiac-resynchronisation-therapy.aspx Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue, with the …

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy

BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

High-Density Lipoprotein Restores Endothelial Function in Hypercholesterolemic Men

Background—Hypercholesterolemia is a risk factor for atherosclerosis-causing endothelial dysfunction, an early event in the disease process. In contrast, high-density lipoprotein (HDL) cholesterol inversely correlates with morbidity and mortality representing a protective effect. Therefore, we investigated the effects of reconstituted HDL on endothelial function in hypercholesterolemic men. Methods and Results—Endothelium-dependent and -independent vasodilation to intraarterial acetylcholine and sodium nitroprusside (SNP), respectively, was measured by forearm venous occlusion plethysmography in healthy normo- and hypercholesterolemic men. In hypercholesterolemics, the effects of reconstituted HDL (rHDL; 80 mg/kg IV over 4 hours) on acetylcholine- and SNP-induced changes in forearm blood flow were assessed in the presence or absence of the nitric oxide (NO) synthase inhibitor L-NMMA. Hypercholesterolemics showed reduced vasodilation to acetylcholine but not to SNP compared with normocholesterolemics (P <0.0001). rHDL infusion increased plasma HDL cholesterol from 1.3±0.1 to 2.2±0.1 mmol/L (P <0.0001, n=18) and significantly enhanced the acetylcholine-induced increase in forearm blood flow without affecting that induced by SNP. rHDL infusion also improved flow-mediated dilation of the brachial artery (to 4.5±0.9% from 2.7±0.6%, P =0.02). NO synthase inhibition prevented the improvement in acetylcholine-induced vasodilation while leaving the response to SNP unchanged. Albumin infusion in an equivalent protein dose had no effect on vasomotion or lipid levels. Conclusions—In hypercholesterolemic patients, intravenous rHDL infusion rapidly normalizes endothelium-dependent vasodilation by increasing NO bioavailability. This may in part explain the protective effect of HDL from coronary heart disease and illustrates the potential therapeutic benefit of increasing HDL in patients at risk from atherosclerosis.

Cardiac-Resynchronization Therapy in Heart Failure with a Narrow QRS Complex

BACKGROUND Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. METHODS We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. RESULTS On March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). CONCLUSIONS In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease

Background—There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined. Methods and Results—Fourteen male patients (mean age, 66±3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis >75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3±0.4% versus 2.0±0.5%, P =0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0±1.6% versus 9.5±1.3%, P =0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3±0.4 mg/L) than after placebo (1.8±0.5 mg/L, P =0.019), as was oxidized LDL (43.6±2.4 versus 47.6±2.6 U/L, P =0.028), whereas prostaglandins did not change. Conclusions—This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease.

Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial

BACKGROUND Endothelin-receptor blockade provides haemodynamic benefit in experimental and clinical heart failure. We aimed to measure the effects of long-term endothelin-blockade on left-ventricular (LV) remodelling and clinical outcomes in patients with chronic heart failure. METHODS 642 patients with chronic heart failure were assigned the oral endothelin(A)-antagonist darusentan at 10, 25, 50, 100, or 300 mg daily or placebo for 24 weeks in addition to standard therapy in a randomised, double-blind, placebo-controlled trial. In the 50-300 mg groups, darusentan was uptitrated over 6 weeks. Primary endpoint was change in LV end-systolic volume (LVESV) at 24 weeks from baseline, measured by MRI. All patients for whom assessable MRI scans were available at baseline and follow-up were included in the analysis. FINDINGS Darusentan was well tolerated. LVESV could be assessed in 485 (76%) patients with paired MRI data at baseline and 6 months. The change in LVESV was not significantly different from that with placebo at any dose (mean difference from placebo 1.27 mL [95% CI -9.9 to 12.4] with 10 mg dose, -1.84 mL [-13.0 to 9.3] with 25 mg, -5.68 mL [-16.9 to 5.6] with 50 mg, -4.05 mL [-15.5 to 7.4] with 100 mg, and -4.34 mL [-15.7 to 7.0] with 300 mg). Heart failure worsened in 71 (11.1%) patients, and 30 (4.7%) died during the study with no difference between groups. INTERPRETATION Endothelin(A) blockade with darusentan did not improve cardiac remodelling or clinical symptoms or outcomes in patients with chronic heart failure receiving an angiotensin-converting-enzyme inhibitor, beta blocker, or aldosterone antagonist. Thus, endothelin(A) blockade is unlikely to be useful as an add-on treatment in such patients.