[Heart failure with preserved left ventricular ejection fraction (HFpEF)].

INTRODUCTION: Heart failure with preserved left ventricular ejection fraction (HFpEF) is a common and very important disease entity because of its association with frequent repeat hospitalization and high mortality. Hallmarks of the underlying pathophysiology include a small left ventricular cavity due to concentric remodeling, impaired left ventricular compliance and left atrial dysfunction. This leads to an increase in left atrial and pulmonary pressure on exertion and in advanced stages of the disease already at rest with consecutive exertional dyspnea and exercise intolerance. Additional cardiovascular mechanisms including atrial fibrillation, chronotropic incompetence and coronary artery disease as well as non-cardiac co-morbidities contribute to a variable extent to the clinical picture. The diagnostic work-up is demanding and complex but the concepts have significantly improved during the last years. The study results of the Sodium Glucose cotransporter-2 inhibitors (SGLT-2-inhibitors) have revolutionized the treatment of HFpEF. In the present article, we provide an overview about the current understanding of the pathophysiology of HFpEF, the principles of the diagnostic pathways and a summary of the intervention studies in the field, and we propose an approach for the treatment in clinical practice.

Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics. METHODS: We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland. FINDINGS: Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group. INTERPRETATION: The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation.

Estimated glomerular filtration rate, haemodynamics, and mortality in patients with aortic stenosis.

BACKGROUND: In aortic stenosis (AS), estimated glomerular filtration rate (eGFR) is an important prognostic marker but its haemodynamic determinants are unknown. We investigated the correlation between eGFR and invasive haemodynamics and long-term mortality in AS patients undergoing aortic valve replacement (AVR). METHODS: We studied 503 patients [median (interquartile range) age 76 (69-81) years] with AS [indexed aortic valve area .42 (.33-.49) cm2 /m2 ] undergoing cardiac catheterization prior to surgical (72%) or transcatheter (28%) AVR. Serum creatinine was measured on the day before cardiac catheterization for eGFR calculation (CKD-EPI formula). RESULTS: The median eGFR was 67 (53-82) mL/min/1.73 m2 . There were statistically significant correlations between eGFR and mean right atrial pressure (r = -.13; p = .004), mean pulmonary artery pressure (mPAP; r = -.25; p < .001), mean pulmonary artery wedge pressure (r = -.19; p < .001), pulmonary vascular resistance (r = -.21; p < .001), stroke volume index (r = .16; p < .001), extent of coronary artery disease, and mean transvalvular gradient but not indexed aortic valve area. In multivariate linear regression, higher age, lower haemoglobin, lower mean transvalvular gradient (i.e. lower flow), lower diastolic blood pressure, and higher mPAP were independent predictors of lower eGFR. After a median post-AVR follow-up of 1348 (948-1885) days mortality was more than two-fold higher in patients in the first eGFR quartile compared to those in the other three quartiles [hazard ratio 2.18 (95% confidence interval 1.21-3.94); p = .01]. CONCLUSION: In patients with AS, low eGFR is a marker of an unfavourable haemodynamic constellation as well as important co-morbidities. This may in part explain the association between low eGFR and increased post-AVR mortality.

Temporal trends in cardiovascular risk factors' prevalence in patients with myocardial infarction.

INTRODUCTION AND OBJECTIVES: Little is known about changes in cardiovascular risk factors (CVRF) profile over time in patients presenting with acute myocardial infarction (AMI). METHODS: We assessed changes in age and CVRF profile in consecutive AMI patients enrolled in the Swiss nationwide AMIS Plus registry between 1 January 1997 and 31 December 2018. RESULTS: A total of 57 995 AMI patients were included in the analysis. Mean age at presentation was 71.5 ± 11.3 years for women and 63.9 ± 12.8 years for men and did not change over time. Overall, the mean (standard deviation) number of CVRF increased from 1.76 (1.07) in 1997/98 to 2.26 (1.10) in 2017/18 in men (Ptrend  < .001), while the corresponding rates in females were 1.83 (1.11) and 2.24 (1.08) (Ptrend  < .001). In terms of active smoking, no significant trend was detected for males, while there was a significant increase in females (P < .001). As a result, the gap in smoking rates between men and women presenting with AMI decreased from 19.9% (45.3% vs 25.4%) in 1997/98 to 7.9% (41.2% vs 33.3%) in 2017/18. Reassuring was the stability in terms of diabetes prevalence for both genders. Obesity was more prevalent over time in men, while the prevalence of hypertension and dyslipidemia increased in both genders. CONCLUSION: Among patients with AMI in Switzerland over two decades, age at presentation remained stable, while the mean number of CVRF increased in both men and women. Striking was the increase in the prevalence of smoking in women, leading to a reduction of the gender gap over time.

Heavy Drinking Habits Are Associated with Worse In-Hospital Outcomes in Patients with Acute Coronary Syndrome: An Insight from the AMIS Plus Registry.

BACKGROUND: The association between alcohol consumption and the occurrence of coronary heart disease is well described in the literature, while data regarding the impact of regular alcohol consumption on in-hospital outcomes in the setting of acute coronary syndrome (ACS) are lacking. We aimed to evaluate the impact of self-reported alcohol consumption on in-hospital outcomes in patients with ACS. METHODS: Data derived from patients enrolled between 2007 and 2019 in the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry were retrospectively analyzed. Patients were stratified based on alcohol drinking pattern. Primary outcome was all-cause in-hospital mortality, while secondary outcomes were set as incidence of major adverse cardiac and cerebrovascular events (MACCEs). Outcome comparisons according to quantity of daily alcohol intake were also performed. RESULTS: Records concerning alcohol consumption were available in 25,707 patients; 5,298 of them (21%) fulfilled the criteria of regular alcohol consumption. Regular drinkers were predominantly male, younger, smokers, more comorbid and with a worse clinical presentation as compared with abstainers/occasional drinkers. Daily alcohol intake was reported in 4,059 (77%) of these patients (regular drinkers). Among them, 2,640 were light drinkers (≤2 drinks/day) and 1,419 heavy drinkers (>2 drinks/day). In-hospital mortality and MACCEs of heavy drinkers were significantly higher compared with those of light drinkers (5.4 vs. 3.3% and 7.0 vs. 4.4%, both p = 0.001). When tested together with Global Registry of Acute Coronary Events risk score parameters, heavy alcohol consumption was independently associated with in-hospital mortality (p = 0.004). CONCLUSIONS: Our results support that heavy alcohol consumption is an independent predictor of in-hospital mortality in patients presenting with ACS.

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Importance: Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective: To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants: Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions: Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results: Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance: Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration: ClinicalTrials.gov Identifier: NCT00512759.

Clinical Outcomes in Patients with Severe Aortic Valve Stenosis Treated with a Portico Transcatheter Aortic Valve System.

The Portico™ transcatheter aortic valve implantation (TAVI) system (Abbott Vascular, Santa Clara, CA, USA) was specifically designed to reduce some of the limitations associated with first-generation TAVI devices. Most of the currently available clinical evidence was obtained from randomized studies that compared TAVI to aortic valve replacement using first-generation transcatheter heart valve devices. The aim of this review is to describe the characteristics of the repositionable and retrievable Portico™ system and the technique of implantation, as well as to provide an overview of the most recent outcomes in the literature, along with our institutional experience.

Impact of total ischemic time on manual thrombus aspiration benefit during primary percutaneous coronary intervention.

BACKGROUND: The benefits of manual thrombus aspiration (TA) during primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) remain uncertain. We assessed the influence of total ischemic time (TIT) on clinical outcomes among STEMI patients undergoing manual TA during pPCI. METHODS AND RESULTS: We conducted a retrospective study of patients enrolled in the Acute Myocardial Infarction in Switzerland Plus registry. STEMI patients undergoing pPCI with (TA group) or without (PCI-alone group) manual TA were stratified based on short (<3 hours), intermediate (3-6 hours), and long (>6 hours) TIT. The primary endpoint was in-hospital all-cause mortality. The secondary endpoint was in-hospital major adverse cardiac events (MACE), a composite of all-cause death, myocardial reinfarction and stroke. Between 2008 and 2014, 4'154 patients (TA 48%) were included. Risk-adjusted in-hospital all-cause mortality was not different between TA and PCI-alone groups (OR 1.29; 95%CI 0.83-1.98; p=0.26), whereas there was significantly increased risk of MACE (OR 1.52; 95%CI 1.05-2.19; p=0.03) in patients treated with manual TA compared with PCI-alone. There was no significant difference between manual TA and PCI-alone with respect to risk-adjusted all-cause mortality according to TIT groups, but risk-adjusted MACE rates were significantly higher in the group of patients with long TIT treated with manual TA compared with PCI-alone (OR 2.42; 95%CI 1.16-5.04; p=0.02). CONCLUSION: In a large registry of STEMI patients, manual TA was not associated with lower risk-adjusted in-hospital all-cause mortality compared with PCI-alone regardless of TIT but was associated with significantly greater risk of MACE. In patients with prolonged TIT, manual TA was associated with higher risk-adjusted MACE rates compared with PCI-alone.

Coronary angiography with or without percutaneous coronary intervention in patients with hemophilia-Systematic review.

OBJECTIVES: We aimed to summarize the evidence for periprocedural and long-term strategies to both minimize the bleeding risk and ensure sufficient anticoagulation and antiaggregation in hemophilia patients undergoing coronary angiography with or without percutaneous coronary interventions (PCI). BACKGROUND: Hemophilia patients undergoing coronary angiography and PCI are at risk of bleeding due to deficiency of the essential clotting factors VIII or IX combined with the need of peri-interventional anticoagulation and antiaggregation and dual antiplatelet therapy (DAPT) after PCI. METHODS: We report on a patient with moderate hemophilia B undergoing single-vessel PCI with administration of factor IX concentrate during the procedure and during the 1-month DAPT period. In addition, a systematic review of patients (n = 54, mean age 58 ± 10 years) with hemophilia A (n = 45, 83%) or B (n = 9, 17%) undergoing coronary angiography with or without PCI is presented. RESULTS: Peri-interventional factor substitution was performed in the majority (42 of 54, 78%) but not all patients. In 38 of 54 (70%) patients undergoing coronary angiography, PCI with balloon dilation (n = 5), bare metal (n = 31), or drug-eluting stents (n = 2) was performed. For PCI unfractioned heparin (n = 24), low molecular weight heparin (n = 2), bivalirudin (n = 4), or no periprocedural anticoagulation at all (n = 8) were used. PCI was successful in all cases. After stenting, the majority (28 of 33; 85%) was treated with DAPT (median duration 1 month). Major periprocedural bleeding episodes occurred in 3 of 54 (6%) patients. Bleeding during follow-up occurred in 11 of 54 (20%) patients. CONCLUSIONS: Coronary angiography and PCI in patients with hemophilia are effective and safe when applying individualized measures to prevent bleeding.

Feasibility and safety of transfemoral sheathless portico aortic valve implantation: Preliminary results in a single center experience.

BACKGROUND: Feasibility of transfemoral (TF) transcathteter aortic valve replacement (TAVR) is limited by the smallest diameter, the calcification and tortuosity of the iliofemoral access vessels. The use of the Portico system without delivery sheath results in significantly lower profile delivery system compared to standard technique. We herein report our single center experience, feasibility and safety of such an approach. METHODS: The Portico valve was implanted sheathless in 81 high-risk patients with severe aortic stenosis utilizing percutaneous femoral access. Mean minimal diameter of the ileo-femoral arterial access was 7.06 ± 1.89 mm. In most cases a multidetector computed tomography was performed before the intervention to assess the feasibility of vascular access and for aortic annulus measurements. The vascular access site was preclosed using two ProGlide suture systems. RESULTS: Device implantation was successful 98.7% of patients. Valve recapturing and repositioning as well as valve-in-valve deployment was performed in only one case (1.2%). There were no infarctions, 2 strokes (2.4%) and 2 acute kidney failure (2.4%), 1 major vascular complication1 (1.2%) 4 major bleedings (4.9%), 11 conductions disturbances and relative pace-maker implantations (14.2%). The mean gradient decreased from 42.3 ± 17 to 6.3 ± 2.78 mm Hg. Paravalvular regurgitation as assessed by TTE at discharge was absent or trivial in 19 patients, mild in 60 and moderate 1. Thirty-day mortality was 2.4%. CONCLUSIONS: Sheathless use of the Portico valve is feasible and appears to be safe, with excellent rates of complications and mortality in the short-term. Such an approach has the potential to further expand feasibility of TF TAVR to patients with severe peripheral arterial disease. Feasibility in patients with smaller femoral access and more challenging anatomy has to be proven in further studies. © 2017 Wiley Periodicals, Inc.

[Heart failure with preserved ejection fraction (HFpEF)]. / Herzinsuffizienz mit erhaltener linksventrikulärer Auswurffraktion (HFpEF).

Heart failure with preserved ejection fraction (HFpEF) Abstract. Heart failure with preserved left ventricular ejection fraction (HFpEF) is a very common form of heart failure typically seen in older patients and associated with poor prognosis. Patients with HFpEF are characterized by a s small left ventricle with concentric remodeling and abnormal compliance, which under the impact of additional cardiovascular mechanisms and non-cardiac comorbidities, leads to the cardinal symptoms of dyspnea and exercise intolerance. The diagnosis of HFpEF is still under debate, and the therapeutic options are limited despite intensive research efforts. In the present review article, we provide an overview of the current understanding of the pathiohysiology of HFpEF, the current diagnostic approach, and a summary of the available evidence on treatment.

Left bundle-branch block in patients with acute myocardial infarction: Presentation, treatment, and trends in outcome from 1997 to 2016 in routine clinical practice.

BACKGROUND: Whether patients with acute myocardial infarction presenting with new or presumed new left bundle-branch block (LBBB) should be treated in the same way as those presenting with ST-elevation (STE) is still a matter of debate. METHODS: Data from 28,358 patients enrolled in AMIS Plus from 1997 to 2016 were analyzed to evaluate differences in treatment and outcome of patients presenting with LBBB (n=2295) or STE (n=26,090) on their initial electrocardiogram using descriptive statistics and multivariate logistic regression. RESULTS: LBBB patients were older (75.0 vs 64.3 years, P<.001) with a greater burden of risk factors and comorbidities. They were admitted 80 minutes later and more frequently in Killip III/IV (20% vs 7%, P<.001). Even after adjustment for age and gender, LBBB patients were less likely to receive aspirin (odds ratio [OR] 0.40, 95% CI 0.34-0.47), P2Y12 inhibitors (OR 0.50, 95% CI 0.45-0.54), ß-blockers (OR 0.81, 95% CI 0.76-0.89), and statins (OR 0.70, 95% CI 0.63-0.76) or undergo percutaneous coronary interventions (OR 0.38, 95% CI 0.35-0.42). Crude in-hospital mortality of patients with LBBB was 16.2% versus 6.5% for patients with STE, but adjusted OR was 1.07 (95% CI 0.93-1.24). Mortality of LBBB patients decreased from 22.6% in 1997-2001 to 11.9% in 2012-2016. CONCLUSIONS: Acute myocardial infarction patients with new or presumed new LBBB presence are at high risk of morbidity and mortality. They were treated less aggressively, and although mortality has halved during the last 20 years, there may be room for further improvement. Additional studies are needed to better identify those patients with LBBB who may maximally benefit from an early invasive treatment strategy.

Spontaneous Coronary Artery Dissection: Angiographic Follow-Up and Long-Term Clinical Outcome in a Predominantly Medically Treated Population.

OBJECTIVE: We sought to assess the angiographic and long-term clinical outcomes in a predominantly medically treated population with spontaneous coronary artery dissection (SCAD). BACKGROUND: There are little data on the angiographic and long-term outcome in patients with SCAD. METHODS: We studied 64 patients with SCAD (mean age 53 years, 94% females, three peripartum) with acute coronary syndrome who were treated using coronary bypass grafting (n = 1), percutaneous coronary intervention (n = 7), or medical therapy (n = 56). A repeat angiogram was performed in 40/64 (63%) patients. The median clinical follow-up was 4.5 years. RESULTS: Five (8%) patients had a major cardiac event. One patient with peripartum left main SCAD and cardiogenic shock died during PCI. One patient with conservatively treated SCAD of the posterior descending artery suffered out-of-hospital cardiac arrest 16 days after the initial angiogram but survived. Three patients experienced a second SCAD in another vessel 3.7, 4.7, and 7.9 years after the index event while the initial dissection had healed. Thirty medically treated patients underwent a scheduled repeat angiogram showing healing of the dissection in all but one patient. After a median follow-up of 4.5 (1.8-8.4) years, all 63 patients surviving the index event were alive and free of symptoms suggestive of myocardial ischemia. CONCLUSIONS: In general, the long-term outcome of patients with SCAD is excellent, and medical therapy can be safely applied in the majority of patients. However, SCAD can be a life-threatening and sometimes catastrophic event, and some patients experience early or late complications including SCAD of another vessel. © 2015 Wiley Periodicals, Inc.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

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, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

Can the optimal type of stent be predicted based on clinical risk factors? A subgroup analysis of the randomized BASKET-PROVE trial.

BACKGROUND: The randomized BASKET-PROVE study showed no significant differences between sirolimus-eluting stents (SES), everolimus-eluting stents (EES), and bare-metal stents (BMS) with respect to the primary end point, rates of death from cardiac causes, or myocardial infarction (MI) at 2 years of follow-up, in patients requiring stenting of a large coronary artery. Clinical risk factors may affect clinical outcomes after percutaneous coronary interventions. We present a retrospective analysis of the BASKET-PROVE data addressing the question as to whether the optimal type of stent can be predicted based on a cumulative clinical risk score. METHODS: A total of 2,314 patients (mean age 66 years) who underwent coronary angioplasty and implantation of ≥1 stents that were ≥3.0 mm in diameter were randomly assigned to receive SES, EES, or BMS. A cumulative clinical risk score was derived using a Cox model that included age, gender, cardiovascular risk factors (hypercholesterolemia, hypertension, family history of cardiovascular disease, diabetes, smoking), presence of ≥2 comorbidities (stroke, peripheral artery disease, chronic kidney disease, chronic rheumatic disease), a history of MI or coronary revascularization, and clinical presentation (stable angina, unstable angina, ST-segment elevation MI). RESULTS: An aggregate drug-eluting stent (DES) group (n = 1,549) comprising 775 patients receiving SES and 774 patients receiving EES was compared to 765 patients receiving BMS. Rates of death from cardiac causes or nonfatal MI at 2 years of follow-up were significantly increased in patients who were in the high tertile of risk stratification for the clinical risk score compared to those who were in the aggregate low-mid tertiles. In patients with a high clinical risk score, rates of death from cardiac causes or nonfatal MI were lower in patients receiving DES (2.4 per 100 person-years, 95% CI 1.6-3.6) compared with BMS (5.5 per 100 person-years, 95% CI 3.7-8.2, hazard ratio 0.45, 95% CI 0.26-0.80, P = .007). However, they were not significantly different between receivers of DES and BMS in patients in the low-mid risk tertiles. CONCLUSIONS: This exploratory analysis suggests that, in patients who require stenting of a large coronary artery, use of a clinical risk score may identify those patients for whom DES use may confer a clinical advantage over BMS, beyond lower restenosis rates.

Interaction of Galectin-3 Concentrations with the Treatment Effects of ß-Blockers and RAS Blockade in Patients with Systolic Heart Failure: A Derivation-Validation Study from TIME-CHF and GISSI-HF.

BACKGROUND: Galectin-3 predicts prognosis in heart failure (HF) and may help to select HF patients in need of intensified therapy. METHODS: This retrospective post hoc analysis included 219 patients from the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-HF) and 631 patients from Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) with HF who had reduced ejection fraction and available galectin-3 plasma concentrations. The interaction between galectin-3, ß-blockers, renin-angiotensin system (RAS) blockade, and spironolactone on outcome was evaluated in TIME-CHF and validated in GISSI-HF. End points were all-cause mortality and the composite of mortality with HF hospitalization or any hospitalization. RESULTS: High galectin-3 concentrations were associated with adverse outcome in both cohorts and remained significantly associated with death after multivariate adjustment [hazard ratio 2.42 (95% CI 1.17-5.01), P = 0.02, in TIME-CHF; 1.47 (1.02-2.10), P = 0.04, in GISSI-HF). In TIME-CHF, patients with low galectin-3 plasma concentrations had a better prognosis when ß-blockers were up-titrated, whereas patients with high galectin-3 plasma concentrations did not (interaction P < 0.05 for mortality and death with or without hospitalization). Opposite trends were seen for RAS blockade but were not statistically significant. Patients with high galectin-3 plasma concentrations had neutral prognosis when receiving spironolactone, whereas patients with low galectin-3 plasma concentrations had worse prognosis when receiving spironolactone (interaction P < 0.10 for death with or without hospitalization). In the GISSI-HF validation cohort, these interactions were confirmed for ß-blockers (P < 0.05 for all end points) and consistent for RAS blockade (P < 0.10 for death with or without hospitalization), but inconsistent for spironolactone. CONCLUSIONS: Galectin-3 is a mediocre prognostic marker, and galectin-3 concentrations interact with the treatment effect of ß-blockers and possibly RAS blockade in patients with systolic HF.

Comparison of preoperative continuation and discontinuation of aspirin in patients undergoing total hip or knee arthroplasty.

INTRODUCTION: Preoperative discontinuation of aspirin (acetylsalicylic acid) can reduce bleeding risk but may increase the risk of perioperative cardiovascular events. MATERIALS AND METHODS: We retrospectively assessed the impact of preoperative continuation versus discontinuation of aspirin compared with a control group in a cohort of 739 consecutive patients undergoing total hip (THA) (n = 396) or knee arthroplasty (TKA) (n = 343) at a tertiary hospital. Bleeding risk, local complications, orthopaedic outcome, and cardiac and cerebral complications were assessed. RESULTS: Four hundred and sixty-five patients did not receive antithrombotic or full-dose anticoagulant medication, 175 patients were taking low-dose aspirin, 99 vitamin K antagonists, clopidogrel, or a combination of these drugs. Of the patients taking aspirin, 139 discontinued and 36 continued aspirin. Blood loss and local bleeding complications were comparable in these two groups. TKA patients who continued aspirin more frequently showed marked knee swelling after 1 week than those discontinuing aspirin (35.1 vs. 81.3 %; p = 0.001). However, orthopaedic outcome did not differ significantly between the two groups. There was a trend towards an increased risk of cardiac complications in patients who discontinued aspirin (6.5 vs. 0.0 %; p = 0.107). CONCLUSIONS: Continuation or discontinuation of aspirin did not show a statistically significant difference in the risk of relevant perioperative bleeding complications in our study. Continuation of aspirin was associated with a transitory increase in knee swelling, but had no effect on orthopaedic outcome. Continuation of aspirin may be associated with a favourable perioperative cardiac outcome. Our data support perioperative continuation of aspirin intake in patients undergoing THA or TKA.

Differential prognostic impact of resting heart rate in older compared with younger patients with chronic heart failure--insights from TIME-CHF.

BACKGROUND: There is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF). METHODS AND RESULTS: In patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (≥70 vs <70 beats/min [bpm]) on 18-month outcomes were compared between older (≥75 years; n = 186) and younger (<75 years; n = 141) patients. Older patients with lower (61 ± 6 bpm) and higher (83 ± 9 bpm) HR had similar left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and survival and HF hospitalization-free survival. In contrast, younger patients with higher HR (81 ± 7 bpm) had higher NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death (hazard ratio 4.01 [95% confidence interval (CI) 1.17 -13.69]; P = .02) and death or HF hospitalization (hazard ratio 2.35 [95% CI 1.01-5.50]; P = .04) than those with lower HR (62 ± 5 bpm), with the association between higher HR and survival remaining significant after adjustment for NYHA functional class, LVEF, and NT-proBNP. CONCLUSIONS: In contrast to HF patients aged <75 years, we found no association between HR and worse outcomes in HF patients aged ≥75 years.

Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.

BACKGROUND: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined. METHODS: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models. RESULTS: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT. CONCLUSION: Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.