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Background: Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking. Objectives: To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation. Methods: Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed. Results: Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase. Conclusions: In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: Event rates after percutaneous coronary interventions (PCI) are higher in small than large coronary vessels but may vary between different drug-eluting stent (DES) types. Aim: To assess the efficacy of two different DES in small vessel disease. Material and methods: Patients with small vessel PCI were randomised 1 : 1 to a first-generation paclitaxel- vs. a second-generation zotarolimus-eluting stent. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularisation after 2 years. Results: Overall, 191 patients were enrolled: 100 with a paclitaxel- and 91 with a zotarolimus-eluting stent. Baseline characteristics were similar in both groups. After 2 years, rates of the primary endpoint were numerically higher for zotarolimus- than paclitaxel- eluting stents (9.9% vs. 5.0%, hazard ratio 2.09, 95% confidence interval (CI) 0.7–6.2, p = 0.19), which was mainly driven by higher rates of target vessel revascularisation (6.6% vs. 2.0%, hazard ratio 3.39, 95% CI: 0.68–16.78, p = 0.14). Based on this, a total of 1,019 patients would be necessary to demonstrate at least non-inferiority between the DES used. Conclusions: In this pilot study, paclitaxel-eluting stents had a favourable efficacy profile in small vessel disease, although the numbers were too small to draw final conclusions. Based on the prohibitively high sample size for a randomized controlled trial between DES, other treatment options should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Chronic kidney disease (CKD) is associated with worse outcomes in patients with coronary artery disease (CAD). How CKD influences the benefit-risk balance of drug-eluting stents (DES) versus bare-metal stents (BMS) is less known. Methods and results: In the multicentre BASKET-PROVE trial, 2314 patients in need of large coronary stenting (≥3.0mm) were randomised 2:1 to DES or BMS. In an a priori planned secondary analysis, outcomes were evaluated according to renal function defined by estimated glomerular filtration rates (eGFR; normal: eGFR≥60ml/min/1.73m2; CKD: eGFR<60ml/min/1.73m2). The primary endpoint was the first major adverse cardiac event (MACE: cardiac death, myocardial infarction, target vessel revascularisation) up to 2years. A Cox proportional-hazard model was used to evaluate adjusted relative risks (hazard rates, HRs) for BMS versus DES. The interaction of stent type and renal function was tested. CKD patients (189 (11.2%)/1681 with such data) had a 2-year MACE rate of 8.5% versus 7.4% in those without CKD [HR 0.98 (0.56–1.72), p=0.95] with cardiac mortalities of 5.3% and 1.5%, respectively (p=0.002, non-significant after baseline adjustments). The MACE rate was lower in CKD patients with DES than with BMS [4.9% versus 15.2%, p=0.017, HR 0.29(0.10–0.80)] as was the MACE rate in patients without CKD [5.6% with DES versus 11.1% with BMS, p<0.0001, HR 0.51(0.35–0.75)]. No significant interaction between stent type and renal function was found. Conclusions: This analysis of patients needing large coronary artery stenting confirms the increased mortality of CKD patients and documents a long-term benefit of DES compared to BMS irrespective of kidney function. [Copyright &y& Elsevier]

Aims Specific causes and modes of death (COD and MOD) of patients with heart failure (HF) are not well described, particularly in those with preserved ejection fraction >45% (HFPEF) and at old age. Thus, using the database of the TIME-CHF study, patients with HFPEF were compared with those with reduced ejection fraction ≤45% (HFREF), and patients ≥75 with those 60–74 years of age to identify MOD and COD, predictors of death, and event rates before death as compared with survivors. Methods and results During the 18-month follow-up, 132/622 patients (21%) died, with similar rates in patients with HFPEF and HFREF and a trend to higher rates in patients aged ≥75 years (24% vs. 17%, P = 0.06). COD and MOD (ACME system) were not different in the age groups. COD was more often non-cardiovascular in HFPEF patients than in HFREF patients (33% vs. 16%, P < 0.05) and cardiac MOD were more frequent in HFREF patients (75% vs. 56%, P < 0.05), mainly due to more sudden deaths (25% vs. 7%, P < 0.05). Patients who died experienced a median of four adverse events (interquartile range 1–7) and one (0–1) hospitalization within 60 days prior to death compared with 0.7 (0.4–1.4) and 0.1 (0.0–0.2) during a randomly selected 60 days in survivors (all P < 0.0001). Conclusion Despite similar 18-month mortality in patients with HFREF and those with HFPEF, important differences in COD and MOD were found which were not observed between the two age groups. A high rate of adverse events and hospitalizations preceded death. These observations may be relevant for the management of HF patients. [ABSTRACT FROM AUTHOR]

In chronic stable angina of mild or moderate severity, there is an ongoing debate as to which treatment strategy should be offered to patients: intense medical drug therapy combined with revascularization if medical therapy fails, or direct coronary angiography in view of immediate revascularization in all patients if feasible, both combined with strict risk factor control and secondary prevention. Findings of two large randomized controlled trials, COURAGE and BARI 2D showed that in selected patients with mild to moderate angina and documented coronary disease by coronary angiography suitable for revascularization, there was no difference in death or myocardial infarction between the two strategies. It remains unclear, however, how these findings can be generalized to the broader spectrum of patients with unknown coronary anatomy. This review describes both treatment strategies, their strengths and limitations, and stresses the importance of the documentation of the extent of myocardial ischemia in risk stratifying such patients. Based on the available trial evidence, an algorithm is proposed how to tailor the management strategy to each patient's individual situation. [ABSTRACT FROM AUTHOR]

The article presents a review of two randomised controlled trials for the management of mild-to-moderate chronic stable coronary artery disease. Results of the studies have triggered a debate about whether an initial strategy of revascularization or a conservative approach with drugs is most effective. Among the three main treatment goals in patients with chronic stable coronary artery disease is relief of symptoms and ischaemia. A summary of the major randomised controlled trials is also presented.

The aim of this study was to compare ST-segment depression (STD) during bicycle ergometry and extent of myocardial ischaemia assessed by myocardial perfusion SPECT (MPS) in a large patient cohort. Consecutive patients ( n = 955) referred for MPS with bicycle ergometry and interpretable stress ECG were evaluated with respect to ECG and MPS findings of ischaemia. The maximal STD was recorded and exercise ECG was considered ischaemic if STD was horizontal or downsloping (≥1 mm). MPS was interpreted using a 20-segment model with a scale of 0 to 4. A summed stress (SSS), summed rest (SRS) and summed difference score (SDS = SSS−SRS, e.g. extent of ischaemia) were derived. Ischaemia was defined as an SDS ≥ 2. An exercise-induced STD was present in 215 patients (22%) and myocardial ischaemia on MPS was present in 366 patients (38%). The extent of ST-segment depression and the number of ECG leads with significant STD were each strongly and significantly associated with increasing severity of ischaemia and the number of coronary territories involved ( p < 0.01 for all correlations). These data demonstrate a strong correlation between the extent of STD, number of ischaemic leads and severity of myocardial ischaemia as assessed by MPS during bicycle ergometry. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease" in the June 11, 2009 issue of the "New England Journal of Medicine."

The article presents a randomized controlled trial which compared brain natriuretic peptide (BNP) therapy versus symptom-guided therapy for treatment of elderly patients with congestive heart failure. 499 patients aged 60 years or older with systolic heart failure, New York Heart Association class II or greater, N-terminal BNP level of two or more times the upper limit of normal, and prior hospitalization for heart failure within one year were included in the study. 18 month survival with no hospitalizations and quality of life were primary outcomes. Researchers found that BNP therapy did not improve overall clinical outcomes or quality of life compared with symptom-guided therapy.

We evaluated the use and outcomes of drug-eluting stents (DESs) and bare metal stents (BMSs) in a large primary percutaneous coronary intervention (PCI) acute ST-elevation myocardial infarction (MI) trial. Recently concerns have been raised with “off-label” use of DESs for short- and long-term clinical outcomes. Limited randomized data exist evaluating DESs versus BMSs in ST-elevation MI. Patients (n = 5,745) in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial were categorized by stent type used. Baseline variables and clinical outcomes were collected at 90 days and 6 months. Outcomes by stent type were adjusted for using conventional multivariable predictors of 90-day mortality (age, anterior location, total ST-segment deviation, and Killip class), time to PCI, and Thrombolysis In Myocardial Infarction grade flow. Stents were deployed (at the investigator''s discretion) in 5,124 patients (89.2%) with acute MI, with DES use in 2,221 (43.3%) and BMS use in 2,903 (56.7%). Patients receiving DESs were younger (median 59 vs 63 years of age, p <0.001), had left anterior descending coronary artery PCI (57.9% vs 48.1%, p <0.001), and often were treated in the United States (58.2%). DES-treated patients had a lower adjusted mortality at 90 days (hazard ratio 0.73, 95% confidence interval [CI] 0.54 to 0.99, p = 0.046) and trended toward lower mortality (hazard ratio 0.77, 95% CI 0.58 to 1.03, p = 0.084) and recurrent MI (hazard ratio 0.81, 95% CI 0.59 to 1.11, p = 0.186) at 6 months compared with BMSs. In conclusion, in this observational analysis of stent use from a large primary percutaneous intervention for acute MI trial, DESs appear as safe as BMSs with similar 6-month clinical outcomes with regard to death and recurrent MI. [Copyright &y& Elsevier]

Congestive heart failure is a growing public health problem worldwide, particularly in the elderly population, in whom it has a substantial impact on quality of life and survival. Despite the fact that heart failure is the most common reason for hospitalisation over the age of 65 years, most clinical trials have excluded the elderly population. This is unfortunate because it may not be generally assumed that elderly patients are similar to younger ones. Nonspecific symptoms and co-morbidities in the elderly may make diagnosis of heart failure difficult. In addition, physiology changes with age, polypharmacy complicates therapy and the aim of therapy may change in the presence of co-morbidities such as cancer or dementia. Furthermore, drug interactions and adverse effects are frequent in heart failure in general, but increase significantly with age. Nevertheless, there is little evidence that treatment of heart failure should be fundamentally different in elderly patients compared with younger patients, although careful monitoring of medical therapy is of particular importance in elderly heart failure patients. Therefore, general guidelines on diagnosis and therapy of heart failure also apply to elderly patients, but therapy may need to be adjusted to cater for individual needs, potential interactions and altered elimination of drugs. This article summarises the evidence available for treatment in elderly patients with heart failure, discusses potential differences in elderly subjects compared with their younger counterparts and provides recommendations for clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. Background: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. Methods: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI. Results: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. Conclusions: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis. [Copyright &y& Elsevier]

Context: The risk-benefit ratio of invasive vs medical management of elderly patients with symptomatic chronic coronary artery disease (CAD) is unclear. The Trial of Invasive versus Medical therapy in Elderly patients (TIME) recently showed early benefits in quality of life from invasive therapy in patients aged 75 years or older, although with a certain excess in mortality. Objective: To assess the long-term value of invasive vs medical management of chronic CAD in elderly adults in terms of quality of life and prevention of major adverse cardiac events. Design: One-year follow-up analysis of TIME, a prospective randomized trial with enrollment between February 1996 and November 2000. Setting and Participants: A total of 282 patients with Canadian Cardiac Society class 2 or higher angina despite treatment with 2 or more anti-anginal drugs who survived for the first 6 months after enrollment in TIME (mean age, 80 years [range, 75-91 years]; 42% women), enrolled at 14 centers in Switzerland. Interventions: Participants were randomly assigned to undergo coronary angiography followed by revascularization (if feasible) (n = 140 surviving 6 months) or to receive optimized medical therapy (n = 142 surviving 6 months). Main Outcome Measures: Quality of life, assessed by standardized questionnaire; major adverse cardiac events (death, nonfatal myocardial infarction, or hospitalization for acute coronary syndrome) after 1 year. Results: After 1 year, improvements in angina and quality of life persisted for both therapies compared with baseline, but the early difference favoring invasive therapy disappeared. Among invasive therapy patients, later hospitalization with revascularization was much less likely (10% vs 46%; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.11-0.32; P<.001). However, 1-year mortality (11.1% for invasive; 8.1% for medical; HR, 1.51; 95% CI, 0.72-3.16; P = .28) and death or nonfatal myocardial infarction rates (17.0% for invasive; 19.6%... [ABSTRACT FROM AUTHOR]

The authors reflect on the possible benefit of dual antiplatet therapy (DAPT) with clopidogrel and aspirin in coronary heart disease (CAD) in high-risk patients with or without revascularization. They note the success of DAPT in preventing stent thrombosis (ST) after coronary stent implantation. They examine evidence on the therapeutic effects of clopidogrel. They also suggest that the risk-benefit balance of the therapy must be questioned due to increased rate of surgery-related bleedings.

A response by C. Kaiser and colleagues to a letter to the editor about their article "Drug-Eluting Versus Bare-Metal Stents in Large Coronary Arteries," in the December 9, 2010 issue is presented.

The article presents the author's perspectives on the new guidance by the Great Britain National Institute for Health and Clinical Excellence (NICE) regarding the use of drug-eluting stents (DES) in percutaneous coronary intervention for the treatment of coronary artery disease. He contends that the NICE instructions for DES use calls for comments regarding the importance of cost-effectiveness analyses in a changing field of technology and stenting practice and patient outcome.

Context Right ventricular involvement in acute myocardial infarction and cardiogenic shock has received little attention by clinicians and researchers, although its pathophysiology, clinical presentation, and natural history are distinctly different from those of left ventricular infarction and associated cardiogenic shock. Right ventricular shock has important therapeutic implications for the management of patients, which need to be recognised. Starting point Investigators at the SHOCK Registry Alice Jacobs and colleagues, J Am Coll Cardiol 2003; 341: 1273--79) evaluated 49 patients with cardiogenic shock predominantly due to right ventricular infarction and compared them with 884 patients with cardiogenic shock and predominantly left ventricular failure. Perhaps surprisingly, these investigators found that the in-hospital mortality of patients with right ventricular shock was not significantly lower than that of patients with left ventricular shock (53% vs 61%, p=0.296), despite the fact that patients with right ventricular shock were younger, with a lower prevalance of previous infarctions, fewer anterior infarct locations, and less multivessel disease. There was a shorter median time between index infarction and diagnosis of shock in patients with right ventricular shock. In multivariate analysis, right ventricular shock was not an independent predictor of lower in-hospital mortality. Where next? The unexpectedly high mortality of patients with cardiogenic shock due to predominantly right ventricular infarction challenges the general notion that right ventricular involvement in myocardial infarction has only little relevance for patient's outcome. Therefore, more attention should be given to the detection of right ventricular involvement in acute myocardial infarction and particularly in cardiogenic shock. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Prasugrel Plus Aspirin Beyond 12 Months Is Associated With Improved Outcomes After TAXUS Liberté Paclitaxel-Eluting Coronary Stent Placement" by Raban V. Jeger and Matthias E. Pfisterer in the previous issue.

Editorial. Offers a look at raised cardiac troponins as biomarkers for the diagnosis of diseases. Decision of the European Society of Cardiology, the American College of Cardiology and the American Heart Association that raised cardiac troponins are a standard biomarker for the diagnosis of acute myocardial infarction and for diagnosis and management of acute coronary syndromes; Report that cardiac troponins are raised in many patients with conditions other than acute coronary syndromes; Importance of electrocardiograms and clinical investigations in diagnosis; Immunological tests offered by various manufacturers for the detection of troponins; Mechanisms leading to raised troponins.

A letter to the editor is presented in response to the Dual Antiplatelet Therapy study discussed in a previous issue of the "New England Journal of Medicine," particularly, about an observation of an increase in the risk of myocardial infarction after discontinuation of dual antiplatelet therapy.

Replies to reader comment on research by the author about the outcome of medical and invasive therapy for aged patients with angina. Idea that the issue was quality of life and not mortality in the TIME study.

Background: The Basel Asymptomatic High-Risk Diabetics' Outcome Trial (BARDOT) demonstrated that asymptomatic diabetic patients with an abnormal myocardial perfusion scintigraphy (MPS) were at increased risk of major adverse cardiovascular events (MACEs) at 2-year follow-up. It remains unclear whether this finding holds true even for a longer follow-up. Methods: Four hundred patients with type 2 diabetes, neither history nor symptoms of coronary artery disease (CAD), were evaluated clinically and with MPS. Patients were followed up for 5 years. Major adverse cardiovascular events (MACEs) were defined as all-cause death, myocardial infarction, or late coronary revascularization. Results: At baseline, an abnormal MPS (SSS ≥ 4 or SDS ≥ 2) was found in 87 of 400 patients (22%). MACE within 5 years occurred in 14 patients with abnormal MPS (16.1%) and in 22 with normal scan (1.7%), p = 0.009; 15 deaths were recorded. Patients with completely normal MPS (SSS and SDS = 0) had lower rates of MACEs than patients with abnormal scans (2.5% vs. 7.0%, p = 0.032). Patients with abnormal MPS who had undergone revascularization had a lower mortality rate and a better event-free survival from MI and revascularization than patients with abnormal MPS who had either undergone medical therapy only or could not be revascularized (p = 0.002). Conclusions: MPS may have prognostic value in asymptomatic diabetic patients at high cardiovascular risk over a follow-up period of 5 years. Patients with completely normal MPS have a low event rate and may not need retesting within 5 years. Patients with an abnormal MPS have higher event rates and may benefit from a combined medical and revascularization approach. [ABSTRACT FROM AUTHOR]

Abstract: In contrast to their established role in the evaluation of acute dyspnea in emergency department (ED) patients, applications of B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) in patients outside of the ED are less well defined. A PubMed-based electronic and hand search for articles dealing with BNP and NT-proBNP in settings other than the ED was performed. We found that currently available evidence is sufficient to support the use of BNP and NT-proBNP in four cardiovascular settings outside of the ED: i) evaluation of patients with suspected heart failure (HF) referred from primary care, ii) risk stratification in patients with HF, iii) risk stratification in stable coronary artery disease, and iv) risk stratification in pulmonary artery hypertension. Recent studies indicate that BNP and NT-proBNP might also be helpful in guiding therapy in patients with chronic HF. Despite active research in many additional fields, the use of BNP/NT-proBNP in other settings is not yet based on solid evidence and, therefore, seems not to be useful. [Copyright &y& Elsevier]

The article presents a study which compares the incidence of late clinical events after withdrawal of clopidogrel, an oral antiplatelet agent, between patients treated with drug-eluting stents (DES) and those with bare-metal stents (BMS). The study utilizes 826 consecutive subjects who were randomly assigned to treatment with DES or BMS. Results of the study revealed that the incidence of cardiac death or myocardial infarction after discontinuance of clopidogrel was higher with DES subjects.

The diagnosis of left ventricular (LV) hypertrophy, an independent predictor of death and cardiovascular events, is difficult without using echocardiography. This study tested the hypothesis whether C-reactive protein (CRP) and B-type natriuretic peptide (BNP) would be useful to exclude echocardiographic LV hypertrophy. Consecutive hypertensive outpatients were asked to participate. Exclusion criteria were overt heart failure, severe renal insufficiency or any other severe concomitant illness. A venous blood sample was taken to measure plasma CRP and BNP concentrations. Echocardiographic LV hypertrophy was defined as LV mass ≥125 g/m2 for men and ≥110 g/m2 for women. In total, 320 patients were studied, and 37 patients (12%) had echocardiographic LV hypertrophy. Patients with LV hypertrophy were significantly older and had higher CRP and BNP concentrations and higher systolic blood pressure than those without LV hypertrophy. The optimal cut-off points for the diagnosis of LV hypertrophy were 35 pg/ml for BNP (sensitivity 73%, specificity 72%) and 2.5 mg/L for CRP (sensitivity 68%, specificity 59%). Only 1 of 123 patients with values of BNP and CRP less than the optimal cut-off point had echocardiographic LV hypertrophy, resulting in a high negative predictive value of 99% for the 2 blood tests combined to exclude LV hypertrophy. In conclusion, in hypertensive patients, echocardiographic LV hypertrophy can be excluded on the basis of a single blood sample for the determination of BNP and CRP. [Copyright &y& Elsevier]

Presents a case of an 85-year-old man with a lung mass. Case history; Chest radiographic finding; Medical history; Vital signs; Laboratory tests; Medications; Pulmonary tissue reaction to lipid material; Common cause of exogenous lipoid pneumonia.

Aim: Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF).Methods and Results: In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF.Conclusions: Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation. [ABSTRACT FROM AUTHOR]

Background: The relationship between longitudinal clinical congestion pattern and heart failure outcome is uncertain. This study was designed to assess the prevalence of congestion over time and to investigate its impact on outcome in chronic heart failure.Methods: A total of 588 patients with chronic heart failure older than 60 years of age with New York Heart Association (NYHA) functional class ≥II from the TIME-CHF study were included. The endpoints for this study were survival and hospitalization-free heart failure survival. Orthopnea, NYHA ≥III, paroxysmal nocturnal dyspnea, hepatomegaly, peripheral pitting edema, jugular venous distension, and rales were repeatedly investigated and related to outcomes. These congestion-related signs and symptoms were used to design a 7-item Clinical Congestion Index.Results: Sixty-one percent of patients had a Clinical Congestion Index ≥3 at baseline, which decreased to 18% at month 18. During the median [interquartile range] follow-up of 27.2 [14.3-39.8] months, 17%, 27%, and 47% of patients with baseline Clinical Congestion Index of 0, 1-2, and ≥3 at inclusion, respectively, died (P <.001). Clinical Congestion Index was identified as an independent predictor of mortality at all visits (P <.05) except month 6 and reduced hospitalization-free heart failure survival (P <.05). Successful decongestion was related to better outcome as compared to persistent congestion or partial decongestion (log-rank P <0.001).Conclusions: The extent of congestion as assessed by means of clinical signs and symptoms decreased over time with intensified treatment, but it remained present or relapsed in a substantial number of patients with heart failure and was associated with poor outcome. This highlights the importance of appropriate decongestion in chronic heart failure. [ABSTRACT FROM AUTHOR]

Abstract Background Whether the clinical presentation and in particular prevalence of symptoms and signs of heart failure (HF) is different in elderly versus younger patients and in those with reduced (HFrEF) versus preserved (HFpEF) left ventricular ejection fraction (LVEF) is a matter of ongoing debate. Aims To compare detailed clinical characteristics of these important subgroups and to develop a prediction rule for the differentiation of HFpEF and HFrEF based on clinical parameters. Methods The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising 622 patients ≥60 years with HF including the whole LVEF spectrum. Results In the groups ≥75 years and with HFpEF typical symptoms and clinical signs of HF were more prevalent as compared to those <75 years or with HFrEF, respectively. The burden of comorbidities was higher in the older age group. HFrEF could not be differentiated from HFpEF by symptom history and clinical examination alone. However, a combination of age, presence of pulmonary rales, systolic blood pressure, cause of heart failure, osteoporosis, current smoking, NT-proBNP, haemoglobin, QRS width and heart rhythm allowed to identify HFrEF versus HFpEF with a sensitivity of 81% and specificity of 90% (c-statistics 0.91). Conclusions More symptoms and signs of HF were present both in the older age group and in patients with HFpEF. HFpEF versus HFrEF could be differentiated by a set of simple clinical, laboratory and ECG parameters but not by symptom history and physical examination alone. Highlights • Clinical presentation of heart failure was different in patients 60–74 vs ≥75 years. • Clinical presentation of heart failure was different in HFrEF vs HFpEF. • Symptoms and signs of HF were more prevalent in particular in the older age group. • HFrEF vs HFpEF could not be identified by symptom history and physical examination. • HFrEF vs HFrEF might be differentiated by clinical, laboratory and ECG parameters. [ABSTRACT FROM AUTHOR]

Aims: While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown whether patients with HF and mid-range LVEF (HFmrEF, LVEF 40-49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy.Methods and Results: The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising a population with established HF including the whole spectrum of LVEF. Of the 622 patients, 108 (17%) were classified as having HFmrEF. This group was in general found to be 'intermediate' regarding clinical characteristics with a comparable and high burden of comorbidities and equally impaired quality of life but was more likely to have coronary artery disease as compared with the HFpEF group. During a median follow-up of 794 days, mortality was 39.7% without significant differences between groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided as compared with standard therapy resulted in improved survival free of HF hospitalizations in HFrEF and HFmrEF, but not in HFpEF.Conclusion: Although the 'intermediate' clinical profile of HFmrEF between HFrEF and HFpEF would support the conclusion that HFmrEF is a distinct clinical entity, we hypothesize that HFmrEF has to be categorized as HFrEF because of the high prevalence of coronary artery disease and the similar benefit of NT-proBNP-guided therapy in HFrEF and HFmrEF, in contrast to HFpEF. [ABSTRACT FROM AUTHOR]

Aims While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown whether patients with HF and mid-range LVEF (HFmrEF, LVEF 40–49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy. Methods and results The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising a population with established HF including the whole spectrum of LVEF. Of the 622 patients, 108 (17%) were classified as having HFmrEF. This group was in general found to be ‘intermediate’ regarding clinical characteristics with a comparable and high burden of comorbidities and equally impaired quality of life but was more likely to have coronary artery disease as compared with the HFpEF group. During a median follow-up of 794 days, mortality was 39.7% without significant differences between groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided as compared with standard therapy resulted in improved survival free of HF hospitalizations in HFrEF and HFmrEF, but not in HFpEF. Conclusion Although the ‘intermediate’ clinical profile of HFmrEF between HFrEF and HFpEF would support the conclusion that HFmrEF is a distinct clinical entity, we hypothesize that HFmrEF has to be categorized as HFrEF because of the high prevalence of coronary artery disease and the similar benefit of NT-proBNP-guided therapy in HFrEF and HFmrEF, in contrast to HFpEF. [ABSTRACT FROM AUTHOR]

Background Clinical and cost-effectiveness of prasugrel vs. clopidogrel in acute coronary syndrome (ACS) was only evaluated using TRITON-TIMI 38 event rates. A comparative analysis of both drugs in contemporary European ACS patients is lacking. Methods To address this issue, cardiac and bleeding events of 2 “sister” multicenter stent trials, BASKET-PROVE (BP) I with clopidogrel and BPII with prasugrel (for 12 months each) were used in a hybrid analysis. Medication costs were 2015 sales prices, event costs modelled for Denmark (DNK), Germany (GER) and Switzerland (SUI) and quality adjusted life years (QALY) by EQ-5D-3L questionnaire. Results In BPI and II, 1012 and 985 ACS-patients received drug eluting stents, respectively, followed-up for 2 years. Compared to clopidogrel, prasugrel-treated patients had no more major cardiac events (5.2% vs. 6.4%, p = 0.422) nor cardiac deaths (1.6% vs. 1.0%, p = 0.255), but more major bleedings (4.0% vs. 1.7%, p < 0.001) and altogether no difference in QALYs (− 0.027 (95%CI: − 0.064/0.011)). Prasugrel caused higher total expenditures per patient: 1116.3 (DNK), 1063.5 (GER) and 880.8 (SUI) EURO, respectively. Accordingly, incremental cost-effectiveness was negative for prasugrel vs. clopidogrel with ratios of − 45,907 (DNK), − 39,909 (GER) and − 33,435 (SUI) EURO/QALY gained, making clopidogrel an economically dominant strategy, even after accounting for the non-randomized comparison. Conclusion Findings of this contemporary European ACS-cohort showed markedly lower cardiac event rates than TRITON-TIMI 38 and no significant difference in 2-year QALYs between prasugrel and clopidogrel-treated patients. At current drug prices, clopidogrel use resulted in an economically dominant treatment strategy in Western European patients. [ABSTRACT FROM AUTHOR]

Aims Evaluation of predictors of silent coronary artery disease (SCAD) in high-risk asymptomatic diabetic patients and to evaluate their two-year outcome. Methods and results Four hundred diabetic patients without prior CAD but at high CAD risk underwent myocardial perfusion scintigraphy (MPS) in this prospective multicentre outcome trial. MPS were abnormal in 22% of patients. Male sex (OR 2.223, 1.152–4.290; p = 0.017), diabetes duration (OR 1.049,1.015–1.085; p = 0·005), peripheral artery disease (OR 2.134, 1·150–3.961; p = 0.016), smoking (OR 2.064, 1.109–3.839; p = 0·022), systolic blood pressure (OR 1.014, 1.00–1.03, p = 0·056), brain natriuretic peptide (OR 1.002, 1.001–1.004, p = 0·005) independently predicted an abnormal MPS: if < 2 and > 3 predictors were present, 3.2% and 47% patients had an abnormal MPS, respectively (p < 0·001). Two-year major adverse cardiac event rates increased from 2·9% to 14·6%, cardiac death rates from 0·6% to 4·1% in patients with summed stress scores ≤ 10 and > 10%, respectively (each p < 0.045). Conclusions Male sex, diabetes duration, peripheral artery disease, smoking, elevated systolic blood pressure and increased brain-natriuretic peptides independently predicted SCAD. In presence of > 3 predictors, almost 50% of patients had an abnormal MPS. They may benefit from screening by MPS since the extent of the MPS abnormality discriminated clearly between a favourable compared to a bad 2-year outcome. However, even highest risk patients without objective evidence of CAD had a benign prognosis without need for specific evaluation or therapy. Trial Registration Number: ISRCTN87953632. [ABSTRACT FROM AUTHOR]

Aims The British National Institute of Clinical Excellence ( NICE) guidelines recommend to use drug-eluting stents ( DES) instead of bare-metal stents ( BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis ( ISR) in the BASKET- PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. Methods/Results The BASKET- PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios ( ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years ( QALYs) gained and target lesion revascularizations ( TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. Conclusion In the BASKET- PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length. [ABSTRACT FROM AUTHOR]

Background Prediction of events in chronic heart failure (CHF) patients is still difficult and available scores are often complex to calculate. Therefore, we developed and validated a simple-to-use, multidimensional prognostic index for such patients. Methods A theoretical model was developed based on known prognostic factors of CHF that are easily obtainable: Body mass index (B), Age (A), Resting systolic blood pressure (R), Dyspnea (D), N-termInal pro brain natriuretic peptide (NT-proBNP) (I), Cockroft-Gault equation to estimate glomerular filtration rate (C), resting Heart rate (H), and Exercise performance using the 6-min walk test (E) (the BARDICHE-index). Scores were given for all components and added, the sum ranging from 1 (lowest value) to 25 points (maximal value), with estimated risk being highest in patients with highest scores. Scores were categorized into three groups: a low (≤ 8 points); medium (9–16 points), or high (> 16 points) BARDICHE-score. The model was validated in a data set of 1811 patients from two prospective CHF-cohorts (median follow-up 887 days). The primary outcome was 5-year all-cause survival. Secondary outcomes were 5-year survival without all-cause hospitalization and 5-year survival without CHF-related hospitalization. Results There were significant differences between BARDICHE-risk groups for mortality (hazard ratio = 3.63 per BARDICHE-group, 95%-CI 3.10–4.25), mortality or all-cause hospitalization (HR = 2.00 per BARDICHE-group, 95%-CI 1.83–2.19), and mortality or CHF-related hospitalization (HR = 3.43 per BARDICHE-group, 95%-CI 3.01–3.92; all P < 10–50). Outcome was predicted independently of left ventricular ejection fraction (LVEF) and gender. Conclusions The BARDICHE-index is a simple multidimensional prognostic tool for patients with CHF, independently of LVEF. [ABSTRACT FROM AUTHOR]

The article presents a response from Hans-Peter Brunner La Rocca, Peter Buser, and Matthias Pfisterer to a letter to the editor discussing their article "BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial," published in a previous issue.

A response by Dr. Paul Erne and colleagues to a letter to the editor concerning their article "Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISS II randomized controlled trial" in a previous issue is presented.

Background Cardiac remodeling and its reversibility are key in HF outcomes. The ST2-R2 score was recently developed to predict relevant left ventricular (LV) reverse remodeling (R2) in patients with heart failure (HF). In the present study we sought to validate the ST2-R2 score for grading improvement in LV ejection fraction (EF) and LV size at one year, and to evaluate its prognostic implication up to 4 years. Methods A total of 569 patients with baseline LVEF < 40% from three international cohorts (Barcelona, TIME-CHF, and PROTECT) were included in the study. Patients were classified into four strata based on their ST2-R2 score, which took into account concentrations of the biomarker ST2, non-ischemic etiology, absence of left bundle branch block, HF duration, baseline LVEF, and β-blocker treatment. Results A significant relationship was observed between ST2-R2 scores and changes in LVEF and indexed LV sizes. LVEF recovery (from + 5.6% to + 17.3%; p < 0.001), percentage reduction in LV end-systolic volume index (from − 6.1% to − 32.1%; p < 0.001) and in LV end-systolic diameter index (from − 1.1% to − 18.6%; p < 0.001) increased over the ST2-R2 strata. A similar trend was observed with diastolic parameters. Improvement in LV function and size was inversely predictive of mortality. Hazard ratios for risk of death, using the lower ST2-R2 score strata (< 9) as a reference, were 0.49 (p < 0.001; score 9–11), 0.27 (p < 0.001; score 12–14), and 0.17 (p < 0.001; score 15–17). Conclusions The ST2-R2 score predicts reverse LV remodeling in HF patients and is useful for predicting mortality up to 4 years. [ABSTRACT FROM AUTHOR]

Aims: Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.Methods and Results: To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).Conclusion: The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. [ABSTRACT FROM AUTHOR]

Aims Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear. Methods and results To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62 - 0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67 - 0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76 - 1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67 - 1.53, P = 0.97; interactions P < 0.02). Age (74 ' 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02). Conclusion The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. [ABSTRACT FROM AUTHOR]

Background In chronic heart failure, left ventricular ejection fraction (LVEF) is considered to be stable. Intensified therapy may improve survival, but little is known whether this is associated with reverse remodeling and dependent on age and NT-proBNP guidance. We aimed to define the evolution of LVEF under intensified therapy in relation to age and NT-proBNP guidance. Methods and results Echocardiography was performed at baseline, 12 and 18 months in TIME-CHF, a trial comparing NT-proBNP versus symptom-guided therapy in patients aged 60 to 74 and ≥ 75 years. LVEF, LV end diastolic volume index (LVEDVI) and end systolic volume index (LVESVI) were assessed. LVEF increased from 31.3 ± 10.7% to 39.1 ± 11.8% at 18 months (p < 0.001) in symptom-guided, and from 30.3 ± 11.7% to 44.0 ± 13.2% (p < 0.001) in NT-proBNP-guided patients. The increase in LVEF was significantly larger in the NT-proBNP-guided treatment group (p for interaction = 0.006), which was true for both age groups (p for interaction in both = 0.091). LVEDVI and LVESVI decreased without influence by study group allocation. Conclusions In elderly heart failure patients, intensified medical therapy leads to an improvement in LVEF and to reverse remodeling. NT-proBNP guided therapy was associated with a larger improvement in LVEF than symptom guided therapy both in patients aged 60 to 74 and ≥ 75 years. [ABSTRACT FROM AUTHOR]

We describe a patient with a prosthetic aortic valve who developed fatal valve thrombosis due to an interaction between phenprocoumon and cholestyramine. The general practitioner who had prescribed cholestyramine was aware of a potential interaction between these two drugs and the patient ingested cholestyramine exactly according to the rules of the manufacturer (>1 h before phenprocoumon). However, due to enterohepatic cycling and the long half-life of phenprocoumon, an interaction between these two drugs could not be avoided. We therefore recommend that cholestyramine not be administered to patients treated with drugs undergoing enterohepatic cycling, such as oral anticoagulants. [Copyright &y& Elsevier]

Background: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, late stent thrombosis attributed to the durable polymer should no longer appear. A comprehensive evaluation of these aspects of BP-DES within one long-term trial is lacking, however. Methods: Between April 2010 and May 2014,2291 patients presenting with acute or stable coronary disease needing stents >3.0mm in diameter were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES or thin-strut silicon-carbide-coated BMS in eight European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary endpoint was combined cardiac death, myocardial infarction and clinically indicated target-vessel revascularization within two years. The combined secondary safety endpoint was stent thrombosis with related myocardial infarction or death.Findings: The cumulative incidence of the primary endpoint was 7.6% with BP-DES, 6.8% with DP-DES and 12.7% with BMS. By intention-to-treat BP-DES were non-inferior compared to DP-DES (absolute risk difference 0.78%, [-1,93%,3.50%], p for non-inferiority 0.042) and superior to BMS (absolute risk difference -5.16,1-8.32,-2.01], p=0.0011)).The three stent groups did not differ in the combined safety endpoint, with no decrease in these events, particularly stent thrombosis, >1 year with BP-DES.Interpretation: BP-DES proofed non-inferior to DP-DES and more effective than thin-strut BMS, but there was no evidence for a reduced rate of late stent thrombosis and related clinical events with BP-DES. Findings challenge the concept that durable polymers are key in late stent thrombosis formation. [ABSTRACT FROM AUTHOR]

Aims Renal failure is a major challenge in treating heart failure ( HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function ( WRF) and the relationship to outcome. Methods and results This post-hoc analysis of TIME-CHF ( NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit ( n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/ dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system ( RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses ( P = 0.0002) and more spironolactone ( P = 0.02), whereas beta-blockers ( P = 0.69) did not differ and lower doses of RAS-blockers were given ( P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given ( P = 0.001), but not with low doses ( P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients ( P <0.001), but most in those with WRF III ( P <0.05 for interaction). RAS-blockade was associated with improved outcome ( P = 0.006), irrespective of WRF III. Conclusion Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. [ABSTRACT FROM AUTHOR]

Abstract: Background: Elevated heart rate (HR) is associated with mortality in a number of heart diseases. We examined the long-term prognostic significance of HR at discharge in a contemporary population of patients with stable angina (SAP), non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI) revascularized with percutaneous coronary intervention (PCI). Methods: Patients from the BASKET-PROVE trial, an 11-center randomized all-comers trial comparing bare-metal and drug-eluting stenting in large coronary vessels, were included. Discharge HR was determined from a resting ECG. Long-term outcomes (7days to 2years) were evaluated for all-cause mortality and cardiovascular death and non-fatal myocardial infarction. Results: A total of 2029 patients with sinus rhythm were included, 722 (35.6%) SAP, 647 (31.9%) NSTE-ACS, and 660 (32.5%) STEMI. Elevated discharge HR was associated significantly with all-cause mortality: when compared to a reference of <60beats per minute (bpm), the adjusted hazard ratios were (95% CI) 4.5 (1.5–13.5, p=0.006) for 60–69bpm, 3.8 (1.2–11.9, p=0.022) for 70–79bpm, 4.3 (1.2–15.6, p=0.025) for 80–89bpm, and 16.9 (5.2–55.0, p<0.001) for >90bpm. For cardiovascular death/myocardial infarction, a discharge HR >90bpm was associated with a hazard ratio of 6.2 (2.5–15.5, p<0.001) compared to a HR <60bpm. No interaction was found for disease presentation, diabetes or betablocker use. Conclusion: In patients revascularized with PCI for stable angina or acute coronary syndromes an elevated discharge HR was independently associated with poor prognosis. Conversely, a HR <60bpm at discharge was associated with a good long-term prognosis irrespective of indication for PCI. [Copyright &y& Elsevier]