Eric Boersma

A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease

AIMS To identify the characteristics, treatment, and outcomes of contemporary patients with valvular heart disease (VHD) in Europe, and to examine adherence to guidelines. METHODS AND RESULTS The Euro Heart Survey on VHD was conducted from April to July 2001 in 92 centres from 25 countries; it included prospectively 5001 adults with moderate to severe native VHD, infective endocarditis, or previous valve intervention. VHD was native in 71.9% of patients and 28.1% had had a previous intervention. Mean age was 64+/-14 years. Degenerative aetiologies were the most frequent in aortic VHD and mitral regurgitation while most cases of mitral stenosis were of rheumatic origin. Coronary angiography was used in 85.2% of patients before intervention. Of the 1269 patients who underwent intervention, prosthetic replacement was performed in 99.0% of aortic VHD, percutaneous dilatation in 33.9% of mitral stenosis, and valve repair in 46.5% of mitral regurgitation; 31.7% of patients had > or =1 associated procedure. Of patients with severe, symptomatic, single VHD, 31.8% did not undergo intervention, most frequently because of comorbidities. In asymptomatic patients, accordance with guidelines ranged between 66.0 and 78.5%. Operative mortality was <5% for single VHD. CONCLUSIONS This survey provides unique contemporary data on characteristics and management of patients with VHD. Adherence to guidelines is globally satisfying as regards investigations and interventions.

Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study.

BACKGROUND Stent thrombosis is a safety concern associated with use of drug-eluting stents. Little is known about occurrence of stent thrombosis more than 1 year after implantation of such stents. METHODS Between April, 2002, and Dec, 2005, 8146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3823) or paclitaxel-eluting stents (PES; n=4323) at two academic hospitals. We assessed data from this group to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0-30 days) and late (>30 days) stent thrombosis and between SES and PES. FINDINGS Angiographically documented stent thrombosis occurred in 152 patients (incidence density 1.3 per 100 person-years; cumulative incidence at 3 years 2.9%). Early stent thrombosis was noted in 91 (60%) patients, and late stent thrombosis in 61 (40%) patients. Late stent thrombosis occurred steadily at a constant rate of 0.6% per year up to 3 years after stent implantation. Incidence of early stent thrombosis was similar for SES (1.1%) and PES (1.3%), but late stent thrombosis was more frequent with PES (1.8%) than with SES (1.4%; p=0.031). At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients (p<0.0001). Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2.28, 95% CI 1.29-4.03) and diabetes (2.03, 1.07-3.83). INTERPRETATION Late stent thrombosis was encountered steadily with no evidence of diminution up to 3 years of follow-up. Early and late stent thrombosis were observed with SES and with PES. Acute coronary syndrome at presentation and diabetes were independent predictors of stent thrombosis.

Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour.

BACKGROUND There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment. METHODS The relation between treatment delay and short-term mortality (up to 35 days) was evaluated using tabulated data from all randomised trials of at least 100 patients (n = 22; 50,246 patients) that compared fibrinolytic therapy with placebo or control, reported between 1983 and 1993. FINDINGS Benefit of fibrinolytic therapy was 65 (SD 14), 37 (9), 26 (6) and 29 (5) lives saved per 1000 treated patients in the 0-1, 1-2, 2-3, and 3-6 h intervals, respectively. Proportional mortality reduction was significantly higher in patients treated within 2 h compared to those treated later (44% [95% CI 32, 53] vs 20% [15, 25]; p = 0.001). The relation between treatment delay and mortality reduction per 1000 treated patients was expressed significantly better by a non-linear (19.4-0.6x(+)29.3x-1) than a linear (34.7 - 1.6x) regression equation (p = 0.03). INTERPRETATION The beneficial effect of fibrinolytic therapy is substantially higher in patients presenting within 2 h after symptom onset compared to those presenting later.

Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials.

BACKGROUND Platelet glycoprotein IIb/IIIa inhibitors have been shown to reduce cardiac complications in patients undergoing percutaneous coronary intervention. The clinical efficacy of these drugs in acute coronary syndromes, however, is still unclear. We did a meta-analysis of all large randomised trials designed to study the clinical efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. METHODS Inclusion criteria were: randomisation of patients with acute coronary syndromes but without persistent ST elevation; comparison of a glycoprotein IIb/IIIa inhibitor with placebo or control therapy; non-recommendation of early coronary revascularisation during study-drug infusion; and enrollment of at least 1000 patients. Data on individual patients were obtained from all participants in these trials. FINDINGS Six trials, enrolling 31402 patients, fulfilled the inclusion criteria. 30 days after randomisation, 3530 (11.2%) patients died or developed a myocardial infarction. At 30 days, a 9% reduction in the odds of death or myocardial infarction was seen with glycoprotein IIb/IIIa inhibitors compared with placebo or control (10.8% [1980/18297] vs 11.8% [1550/13105] events; odds ratio 0.91 [95% CI 0.84-0.98]; p=0.015). The relative treatment benefit was similar in subgroups of patients according to important clinical baseline characteristics; hence, the absolute treatment benefit was largest in high-risk patients. An unexpected and significant interaction was seen between sex and allocated treatment, with a treatment benefit in men (0.81 [0.75-0.89] but not in women (1.15 [1.01-1.30]). However, once patients were stratified according to troponin concentration, there was no evidence of a sex difference in treatment response, and a risk reduction was seen in men and women with raised troponin concentrations. Major bleeding complications were increased by glycoprotein IIb/IIIa inhibitors (2.4% [445/18297] vs 1.4% [180/13105]; p<0.0001), but intracranial bleeding was not (16 [0.09%] vs 8 [0.06%]; p=0.40). INTERPRETATION Glycoprotein IIb/IIIa inhibitors reduce the occurrence of death or myocardial infarction in patients with acute coronary syndromes not routinely scheduled for early revascularisation. The event reduction is greatest in patients at high risk of thrombotic complications. Treatment with a glycoprotein IIb/IIIa inhibitor might therefore be considered especially in such patients early after admission, and continued until a decision about early coronary revascularisation has been made.

Predictors of Outcome in Patients With Acute Coronary Syndromes Without Persistent ST-Segment Elevation Results From an International Trial of 9461 Patients

BACKGROUND Appropriate treatment policies should include an accurate estimate of a patients baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.

Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After Cardiac Resynchronization Therapy

Background— Currently, one third of patients treated with cardiac resynchronization therapy (CRT) do not respond. Nonresponse to CRT may be explained by the presence of scar tissue in the posterolateral left ventricular (LV) segments, which may result in ineffective LV pacing and inadequate LV resynchronization. In the present study, the relationship between transmural posterolateral scar tissue and response to CRT was evaluated. Methods and Results— Forty consecutive patients with end-stage heart failure (NYHA class III/IV), LV ejection fraction ≤35%, QRS duration >120 ms, left bundle-branch block, and chronic coronary artery disease were included. The localization and transmurality of scar tissue were evaluated with contrast-enhanced MRI. Next, LV dyssynchrony was assessed at baseline and immediately after implantation with tissue Doppler imaging. Clinical parameters, LV volumes, and LV ejection fraction were assessed at baseline and at a 6-month follow-up. Fourteen patients (35%) had a transmural (>50% of LV wall thickness) posterolateral scar. In contrast to patients without posterolateral scar tissue, these patients showed a low response rate (14% versus 81%; P<0.05) and did not show improvement in clinical or echocardiographic parameters. In addition, LV dyssynchrony remained unchanged after CRT implantation (84±46 versus 78±41 ms; P=NS). Patients without posterolateral scar tissue and severe baseline dyssynchrony (≥65 ms) showed an excellent response rate of 95% compared with patients with a posterolateral scar and/or absent LV dyssynchrony (11%). Conclusions— CRT does not reduce LV dyssynchrony in patients with transmural scar tissue in the posterolateral LV segments, resulting in clinical and echocardiographic nonresponse to CRT.

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery

The American College of Cardiology, American Heart Association, and the European Society of Cardiology are all in the process of completing updated versions of our Guidelines for Perioperative Care. Our respective writing committees are undertaking a careful analysis of all relevant validated studies and always incorporate appropriate new trials and meta-analyses into our evidence review. In the interim, our current joint position is that the initiation of beta blockers in patients who will undergo non-cardiac surgery should not be considered routine, but should be considered carefully by each patients treating physician on a case-by-case basis. Please see the expression of concern which is free to view in Eur Heart J (2013) 34 (44): 3460; doi: 10.1093/eurheartj/eht431. AAA : abdominal aortic aneurysm ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AHA : American Heart Association AR : aortic regurgitation ARB : angiotensin receptor blocker AS : aortic stenosis AF : atrial fibrillation BBSA : β-blocker in spinal anaesthesia BNP : brain natriuretic peptide CABG : coronary artery bypass grafting CARP : coronary artery revascularization prophylaxis CASS : coronary artery surgery study CI : confidence interval COX-2 : cyclooxygenase-2 COPD : chronic obstructive pulmonary disease CPET : cardiopulmonary exercise testing CPG : Committee for Practice Guidelines CRP : C-reactive protein CT : computed tomography cTnI : cardiac troponin I cTnT : cardiac troponin T CVD : cardiovascular disease DECREASE : Dutch Echocardiographic Cardiac Risk Evaluating Applying Stress Echo DES : drug-eluting stent DIPOM : Diabetes Postoperative Mortality and Morbidity DSE : dobutamine stress echocardiography ECG : electrocardiography ESC : European Society of Cardiology FEV1 : forced expiratory volume in 1 s FRISC : fast revascularization in instability in coronary disease HR : hazard ratio ICU : intensive care unit IHD : ischaemic heart disease INR : international normalized ratio LMWH : low molecular weight heparin LQTS : long QT syndrome LR : likelihood ratio LV : left ventricular MaVS : metoprolol after surgery MET : metabolic equivalent MI : myocardial infarction MR : mitral regurgitation MRI : magnetic resonance imaging MS : mitral stenosis NICE-SUGAR : normoglycaemia in intensive care evaluation and survival using glucose algorithm regulation NSTEMI : non-ST-segment elevation myocardial infarction NT-proBNP : N-terminal pro-brain natriuretic peptide NYHA : New York Heart Association OPUS : orbofiban in patients with unstable coronary syndromes OR : odds ratio PaCO2 : mixed expired volume of alveolar and dead space gas PAH : pulmonary arterial hypertension PETCO2 : end-tidal expiratory CO2 pressure PCI : percutaneous coronary intervention PDA : personal digital assistant POISE : PeriOperative ISchaemic Evaluation trial QUO-VADIS : QUinapril On Vascular ACE and Determinants of ISchemia ROC : receiver operating characteristic SD : standard deviation SMVT : sustained monomorphic ventricular tachycardia SPECT : single photon emission computed tomography SPVT : sustained polymorphic ventricular tachycardia STEMI : ST-segment elevation myocardial infarction SVT : supraventricular tachycardia SYNTAX : synergy between percutaneous coronary intervention with taxus and cardiac surgery TACTICS : treat angina with aggrastat and determine cost of therapy with an invasive or conservative strategy TIA : transient ischaemic attack TIMI : thrombolysis in myocardial infarction TOE : transoesophageal echocardiography UFH : unfractionated heparin VCO2 : carbon dioxide production VE : minute ventilation VHD : valvular heart disease VKA : vitamin K antagonist VO2 : oxygen consumption VPB : ventricular premature beat VT : ventricular tachycardia Guidelines and Expert Consensus Documents aim to present management and recommendations based on the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient suffering from a specific condition, taking into account not only the impact on outcome, but also the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.1 A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC guidelines and Expert Consensus Documents can be found on the ESC website in the guidelines section (www.escardio.org). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. …

Accuracy of currently available techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data.

OBJECTIVES This study evaluated the relative merits of the most frequently used techniques for predicting improvement in regional contractile function after coronary revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease. BACKGROUND Several techniques have been proposed for predicting improvement in regional contractile function after revascularization, including thallium-201 (Tl-201) stress-redistribution-reinjection, Tl-201 rest-redistribution, fluorine-18 fluorodeoxyglucose with positron emission tomography, technetium-99m sestamibi imaging and low dose dobutamine echocardiography (LDDE). METHODS A systematic review of all reports on prediction of functional recovery after revascularization in patients with chronic coronary artery disease (published between 1980 and March 1997) revealed 37 with sufficient details for calculating the sensitivity and specificity of each imaging modality. From the pooled data, 95% and 99% confidence intervals were also calculated. RESULTS Sensitivity for predicting regional functional recovery after revascularization was high for all techniques. The specificity of both Tl-201 protocols was significantly lower (p < 0.05) and LDDE significantly higher (p < 0.01) than that of the other techniques. CONCLUSIONS Pooled analysis of 37 studies showed that although all techniques accurately identify segments with improved contractile function after revascularization, the Tl-201 protocols may overestimate functional recovery. The evidence available thus far indicates that LDDE appears to have the highest predictive accuracy.

Statins Are Associated With a Reduced Incidence of Perioperative Mortality in Patients Undergoing Major Noncardiac Vascular Surgery

Background—Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. Methods and Results—To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%;P <0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. Conclusion—This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.

Incidence and correlates of drug-eluting stent thrombosis in routine clinical practice. 4-year results from a large 2-institutional cohort study.

OBJECTIVES We sought to determine the risk of late stent thrombosis (ST) during long-term follow-up beyond 3 years, searched for predictors, and assessed the impact of ST on overall mortality. BACKGROUND Late ST was reported to occur at an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation. METHODS A total of 8,146 patients underwent percutaneous coronary intervention with a sirolimus-eluting stent (SES) (n=3,823) or paclitaxel-eluting stent (PES) (n=4,323) and were followed up to 4 years after stent implantation. Dual antiplatelet treatment was prescribed for 6 to 12 months. RESULTS Definite ST occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient-years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30 days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI: 1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR: 1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively. CONCLUSIONS Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to 4 years. Diabetes is an independent predictor of early ST, whereas acute coronary syndrome, younger age, and PES implantation are associated with late ST.