BACKGROUND Several clinical studies have evaluated the association between ST2 and outcome in patients with heart failure (HF). However, little is known about the predictive value of frequently measured ST2 levels in patients with acute HF. OBJECTIVES This study sought to describe the prognostic value of baseline and repeated ST2 measurements in patients with acute HF. METHODS In the TRIUMPH (Translational Initiative on Unique and novel strategies for Management of Patients with Heart failure) clinical cohort study, 496 patients with acute HF were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured in a central laboratory. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. Associations between repeated biomarker measurements and the primary endpoint were assessed using a joint model. RESULTS Median age was 74 years, and 37% of patients were women. The primary endpoint was reached in 188 patients (40%) during a median follow-up of 325 days (interquartile range: 85 to 401). The median baseline ST2 level was 71 ng/ml (interquartile range: 46 to 102). After adjustment for clinical factors and NT-proBNP, baseline ST2 was associated with an increased risk of the primary endpoint, and the hazard ratio per 1 SD increase of the baseline ST2 level (on the log(2) scale) was 1.30 (95% confidence interval: 1.08 to 1.56; p = 0.005). When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the ST2 level (on the log(2) scale) during follow-up increased to 1.85 (95% confidence interval: 1.02 to 3.33; p = 0.044), adjusted for clinical factors and repeated measurements of NT-proBNP. Furthermore, ST2 levels appeared to elevate several weeks before the time of the primary endpoint. CONCLUSIONS Repeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF, independent of repeatedly measured NT-proBNP. Hence ST2 may be helpful in clinical practice for prognostication and treatment monitoring. (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure [TRIUMPH]; NTR1893) (C) 2017 by the American College of Cardiology Foundation.

Background Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. The aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of Sirolimus-Eluting Stent (SES) as compared to BMS in patients undergoing primary angioplasty for STEMI. Methods The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following keywords were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. Results A total of 9 trials were included in the meta-analysis, involving 2,769 patients (1389 or 50.2% randomized to DES and 1,380 or 49.8% randomized to BMS). At 12 months follow-up, SES was associated with a significant reduction in TVR (4.9% vs. 13.6%, p < 0.0001), with a trend in benefits in mortality (2.9% vs. 4.2%, p = 0.08) and reinfarction (3.0% vs. 4.3%, p = 0.06), without any significant difference in stent thrombosis (1.9% vs. 2.5%, p = 0.36). Safety and efficacy of DES were confirmed at 2-3 years follow-up (data available from 4 trials including 569 patients). Conclusions This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES as compared to BMS is safe and associated with a significant reduction in TVR at 1 and 2-3 years follow-up.

AIMS To assess the long-term benefit-risk ratio of drug-eluting (DES) vs. bare-metal stents (BMS) relative to stent size. METHODS AND RESULTS All 826 consecutive BASKET (BAsel Stent Kosten-Effektivitäts Trial) patients randomized 2:1 to DES vs. BMS were followed after 3 years. Data were analysed separately for patients with small stents (<3.0 mm vessel/<4.0 mm bypass grafts, n = 268) vs. only large stents (> or =3.0 mm native vessels, n = 558). Clinical events were related to stent thrombosis. Three-year clinical target-vessel revascularization rates remained borderline reduced after DES [9.9 vs. 13.9% (BMS), P = 0.07], particularly in patients with small stents (10.7 vs. 19.8%, P = 0.03; large stents: 9.5 vs. 11.5%, P = 0.44). Cardiac death/myocardial infarction (MI) rates (12.7 vs. 10.0%, P = 0.30) were similar, however, death/MI beyond 6 months was higher after DES [9.1 vs. 3.8% (BMS), P = 0.009], mainly due to increased late death/MI in patients with large stents (9.7 vs. 3.1%, P = 0.006). The results paralleled findings for stent thrombosis. CONCLUSION The clinical benefit of DES was maintained at no overall increased risk of death or death/MI up to 3 years. However, death/MI rates were increased in DES vs. BMS patients beyond 6 months, particularly in patients with large stents, paralleling findings for stent thrombosis. Thus, stent size seems to influence the 3-year benefit-risk ratio after DES implantation.

Drug-eluting stents reduce clinical events related to restenosis but may be complicated by late stent-thrombosis. Whereas assessment of target-vessel ischemia by myocardial perfusion scintigraphy identifies relevant restenosis noninvasively, it is unknown whether this technique may also predict late clinical events related to late stent-thrombosis and to restenosis after drug-eluting stent implantation. Methods: All 826 patients treated with stenting between May 2003 and May 2004 were included in the Basel Stent Cost Effectiveness Trial (Basel Stent Kosten-Effektivitats, Trial, or BASKET) and randomized (2:1) to drug-eluting stents or bare metal stents. Myocardial scintigraphy was performed on 476 (64%) of 747 patients without major events after 6 mo. Patients were followed for 1 y for cardiac death, nonfatal myocardial infarction, and target-vessel revascularization due to restenosis or late stent-thrombosis. Results: The rate of target-vessel ischemia in these patients was lower with drug-eluting stents than with bare metal stents (5.4% vs. 10.4%, P = 0.045), similar to the rates of symptom-driven target-vessel revascularization up to 6 mo (4.6% vs. 7.8%, P 0.08). Ischemia was silent in 68%. During follow-up, patients with target-vessel ischemia had higher event rates than did patients without ischemia (32.4% vs. 6.1 %, P < 0.001); however, ischemia did not predict late stent-thrombosis (0/11 cases). Conclusion: The rate of clinical restenosis assessed scintigraphically was lower with drug-eluting stents than with bare metal stents and paralleled that of symptom-driven target-vessel revascularization. Target-vessel ischemia independently predicted late clinical events related to restenosis but not to late stent-thrombosis.

Aims: Right heart failure due to pulmonary hypertension is a major cause for morbidity and mortality in cardiac surgical patients especially after heart transplantation (HTx) and mitral valve surgery. We present our experience with the use of oral Sildenafil in the pre- and postoperative treatment of elevated pulmonary resistance (PVR) in 10 patients.

Objectives: In patients with heart failure (HF), peak oxygen consumption (peak VO2), the relationship between minute ventilation and carbon dioxide production (VE/VCO2 slope) and heart rate recovery (HRR) are established prognostic predictors. However, treadmill exercise has been shown to elicit higher peak VO2 values than bicycle exercise. We sought to assess whether the VE/VCO2 slope and HRR in HF also depend on the exercise mode. Methods: Twenty-one patients with mild HF on chronic β-blocker therapy underwent treadmill and bicycle cardiopulmonary exercise testing for measurement of peak VO2 and the VE/VCO2 slope. In patients with sinus rhythm (n = 16), HRR at 1 (HRR-1) and 2 min (HRR-2) after exercise termination was assessed. Results: Peak VO2 was higher during treadmill as compared with bicycle testing (21.7 ± 4.6 vs. 19.6 ± 3.4 ml/kg/min; p = 0.006). HRR-1 tended to be slower (15 bpm, interquartile range 8–19, vs. 18 bpm, interquartile range 11–22; p = 0.16), and HRR-2 was significantly slower after treadmill exercise (26 bpm, interquartile range 20–39, vs. 31 bpm, interquartile range 22–41; p = 0.04). In contrast, VE/VCO2 slope values did not differ between the test modes (32.9 ± 5.5 vs. 32.3 ± 5.0; p = 0.56). Conclusions: In contrast to peak VO2 and HRR, the VE/VCO2 slope is not affected by the exercise mode in patients with mild HF.

Congestive heart failure (CHF) has kept its progressive nature despite significant advances in therapy. With more advanced disease, medical therapy is broadened. Even so, some patients remain severely symptomatic. However, before additional action is taken, it should be regarded if therapy really fails. Often, therapy is not increased sufficiently because of assumed rather than actual intolerability. Thus, increase in serum creatinine up to 30-50%, hyperkaliemia up to 5.5 mmol/l, and asymptomatic hypotension and bradycardia are usually acceptable. Cautious and slow start and uptitration are the more important the more severe heart failure is, but these patients also profit most from this therapy. If patients remain severely symptomatic despite adequate medical therapy, cardiac resynchronisation therapy (CRT) should be considered. It significantly improves both symptoms and prognosis. Although implantable defibrillators (ICD) are less effective in end-stage CHF, CRT and ICD may be combined as CRT may improve function status, making patients eligible also for ICD therapy. In selected patients, heart transplantation is still an option if no other therapeutic options are effective and there are no contraindications. In these patients, prognostic assessment of CHF is particularly important. Assist devices are used as bridge to transplant or more seldom to recovery only in many countries, but destination therapy may become more important in future therapy with improved devices. Many other therapies are under investigation at present. Thus, therapeutic options for end-stage CHF may further broaden in the near future.

Background: Altitude-induced pulmonary hypertension has been suggested to cause left ventricular (LV) diastolic dysfunction due to ventricular interaction. In this study, we evaluate the effects of exercise- and altitude-induced increase in pulmonary artery pressures on LV diastolic function in an interventional setting investigating high-altitude pulmonary edema (HAPE) prophylaxis.Methods: Among 39 subjects, 29 were HAPE susceptible (HAPE-S) and 10 served as control subjects. RAPE-S subjects were randomly assigned to prophylactic tadalafil (10 mg), dexamethasone (S mg), or placebo bid, starting I day before ascent. Doppler echocardiography at rest and during submaximal exercise was performed at low altitude (490 m) and high altitude (4,559 m). The ratio of early transmitral inflow peak velocity (E) to atrial transmitral inflow peak velocity (A), pulmonary venous flow parameters, and tissue velocity within the septal mitral annulus during early diastole W) were used to assess LV diastolic properties. LV filling pressures were estimated by E/E'. Systolic right ventricular to atrial pressure gradients (RVPGs) were measured in order to estimate pulmonary artery pressures.Results: At 490 m, E/A decreased similarly with exercise in HAPE-S and control subjects (HAPE-S, 1.5 +/- 0.3 to 1.3 +/- 0.3; control, 1. 7 +/- 0.4 to 1.3 +/- 0.3; p = 0. 12 between groups) [mean +/- SD], whereas RVPG increased significantly more in HAPE-S subjects (20 +/- 5 to 43 +/- 9 mm Hg vs 18 +/- 3 to 28 3 nun Hg, p < 0.001). Changes in RVPG levels during exercise did not correlate with changes in E/A (p > 0.1). From 490 to 4,559 m, no correlations between changes in RVPG and changes in E/A or atrial reversal (both p > 0. 1) were observed. Neither of the groups showed an increase in E/E' frorn 490 to 4,559 m.Conclusion: Increased pulmonary artery pressure associated with exercise and acute exposure to 4,559 m appears not to cause LV diastolic dysfunction in healthy subjects. Therefore, ventricular interaction seems not to be of hemodynamic relevance in this setting.