Residual cardiovascular risk reduction guided by lifetime benefit estimation in patients with symptomatic atherosclerotic disease: effectiveness and cost-effectiveness.

AIMS: To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. METHODS AND RESULTS: For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained. CONCLUSION: Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.

Randomised comparison of a balloon-expandable and self-expandable valve with quantitative assessment of aortic regurgitation using magnetic resonance imaging.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for inoperable, intermediate- or high-risk patients with severe symptomatic aortic stenosis and has been associated with excellent clinical outcomes. A clinically relevant remaining problem is aortic regurgitation (AR) post-TAVI, which is associated with increased mortality. Therefore, we conducted a prospective randomised trial to assess the safety and efficacy of a first-generation self-expandable valve (SEV; CoreValve) and a third-generation balloon-expandable valve (BEV; Sapien 3) with respect to clinical outcomes and AR as determined quantitatively by magnetic resonance imaging (MRI). METHODS: The ELECT study was an investigator-initiated, single-centre trial involving patients with severe symptomatic aortic stenosis and with a clinical indication for transfemoral TAVI. Fifty-six patients were randomly assigned to the BEV or SEV group. RESULTS: AR determined quantitatively by MRI was lower in the BEV than in the SEV group [regurgitant fraction: 1.1% (0-8.0) vs 8.7% (3.0-14.8) for SEV; p = 0.01]. Secondary endpoints according to the criteria of the Second Valve Academic Research Consortium (VARC-2) showed BEV to have better early safety [0 (0%) vs 8 (30%); p = 0.002] at 30 days and a lower risk of stroke [0 (0%) vs 5 (21%); p = 0.01], major adverse cardiac and cerebrovascular events [0 (0%) vs 10 (38%); p < 0.001] or death [0 (0%) vs 5 (19%); p = 0.02] in the 1st year compared with SEV. CONCLUSIONS: The use of the latest generation of BEV was associated with less AR as quantitatively assessed by MRI. Although the use of MRI to quantify AR is not feasible in daily clinical practice, it should be considered as a surrogate endpoint for clinical outcomes in comparative studies of valves for TAVI. ClinicalTrials.gov number NCT01982032.

Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus.

AIM: To evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies. METHODS: We included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model. RESULTS: In patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95-1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99-1.14)]. CONCLUSION: There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.

Relation between adiposity and vascular events, malignancy and mortality in patients with stable cerebrovascular disease.

BACKGROUND: Abdominal adiposity is associated with various risk factors including hypertension, and is therefore particularly relevant in patients with stable cerebrovascular disease (CeVD). A U-shaped relation between body mass index (BMI, kg m-2) and cardiovascular events is often described. Whether this U-shape persists for abdominal adiposity, and consequently which reference values should guide clinical practice, is unclear. We described the relation between multiple adiposity measurements and risk of vascular events, vascular mortality, malignancy and all-cause mortality in patients with clinically stable CeVD. METHODS: During a median follow-up time of 6.8 years, 1767 patients were prospectively followed. Relations were assessed using multivariable adjusted Cox proportional hazards models. Adiposity was assessed with BMI, waist circumference (stratified by gender) and the contribution of visceral fat to total abdominal fat (VAT%) measured using ultrasound. Relations were nonlinear if the χ2-statistic of the nonlinear term was significant (P-value<0.05). Nadirs were reported for nonlinear and hazard ratios (HRs) for linear relations. RESULTS: The relations between BMI and outcomes were nonlinear with nadirs ranging between 27.1 (95% confidence interval (CI) 21.9-29.3) kg m2 for vascular mortality and 28.1 (95% CI, 19.0-38.2)) kg m-2 for malignancy. The relation between waist circumference and all-cause mortality was nonlinear with a nadir of 84.0 (95% CI, 18.7-134.8) cm for females and 94.8 (95% CI, 80.3-100.1) cm for males. No nonlinearity was detected for VAT%. A 1-s.d. (9.8%) increase in VAT% was related to both vascular (HR, 1.23, 95% CI 1.00-1.51) and all-cause mortality (HR, 1.22, 95% CI 1.05-1.42). CONCLUSIONS: In patients with CeVD, a BMI around 27-28 kg m-2 relates to the lowest risk of vascular events, vascular mortality, malignancy and all-cause mortality. However, increasing abdominal adiposity confers a higher risk of all-cause mortality. Thus, whereas traditional BMI cutoffs may be re-evaluated in this population, striving for low abdominal obesity should remain a goal.

No psychological distress in sportsmen aged 45 years and older after cardiovascular screening, including cardiac CT: The Measuring Athlete's Risk of Cardiovascular events (MARC) study.

BACKGROUND: Psychological distress caused by cardiovascular pre-participation screening (PPS) may be a reason not to implement a PPS program. We assessed the psychological impact of PPS, including cardiac computed tomography (CT), in 318 asymptomatic sportsmen aged ≥45 years. METHODS: Coronary artery disease (CAD) was defined as a coronary artery calcium score ≥100 Agatson units and/or ≥50% luminal stenosis on contrast-enhanced cardiac CT. Psychological impact was measured with the Impact of Event Scale (IES) (seven items) on a six-point scale (grade 0-5). A sum score ≥19 indicates clinically relevant psychological distress. A Likert scale was used to assess overall experiences and impact on sports and lifestyle. RESULTS: A total of 275 participants (86.5% response rate, 95% CI 83-90%) with a mean age of 54.5 ± 6.4 years completed the questionnaires, 48 (17.5%, 95% CI 13-22%) of whom had CAD. The median IES score was 1 (IQR 0-2, [0-23]). IES was slightly higher in those with CAD (mean rank 175 vs. 130, p < 0.001). One participant (with CAD) experienced clinically relevant psychological distress (IES = 23). Participants reported numerous benefits, including feeling safer exercising (58.6%, 95% CI 53-65%) and positive lifestyle changes, especially in those with CAD (17.2 vs. 52.1%, p < 0.001). The majority were satisfied with their participation (93.8%, 95% CI 91-97%). CONCLUSION: Cardiovascular PPS, including cardiac CT, causes no relevant psychological distress in older sportsmen. Psychological distress should not be a reason to forego screening in sportsmen.

Rationale and design of the Edwards SAPIEN-3 periprosthetic leakage evaluation versus Medtronic CoreValve in transfemoral aortic valve implantation (ELECT) trial : A randomised comparison of balloon-expandable versus self-expanding transcatheter aortic valve prostheses.

BACKGROUND AND OBJECTIVES: Periprosthetic aortic regurgitation (PPR) after transcatheter aortic valve implantation (TAVI) remains an important issue associated with impaired long-term outcomes. The current randomised study aims to evaluate potential differences between the balloon-expandable Edwards SAPIEN-3 and the self-expanding Medtronic CoreValve system with the main focus on post-TAVI PPR by means of novel imaging endpoints, and an additional focus on other clinical endpoints. ENDPOINTS: The primary endpoint of this study is quantitative assessment of the severity of post-procedural PPR using cardiac magnetic resonance imaging. Several other novel imaging modalities (X-ray contrast angiography, echocardiography) are used as secondary imaging modalities for the assessment of PPR following TAVI. Secondary objectives of the study include clinical outcomes such as cerebral and kidney injury related to TAVI, and quality of life. METHODS AND DESIGN: The ELECT study is a single-centre, prospective, two-armed randomised controlled trial. For the purpose of this study, 108 consecutive adult patients suitable for transfemoral TAVI will be randomly allocated to receive the SAPIEN-3 (n = 54) or the CoreValve system (n = 54). DISCUSSION: The ELECT trial is the first randomised controlled trial to quantitatively compare the extent of post-TAVI PPR between the SAPIEN-3 and CoreValve. Furthermore, it will evaluate potential differences between the two prostheses with regard to mid-term clinical outcome and quality of life.

Clinical Relevance of Cardiac Troponin Assessment in Patients Undergoing Carotid Endarterectomy.

OBJECTIVE: Myocardial infarction (MI) is a frequent complication of carotid endarterectomy (CEA), yet most events are silent. Routine post-operative monitoring of cardiac troponin was implemented to facilitate timely recognition of MI and stratify high risk patients. The aim was to evaluate the incidence of troponin elevation after CEA and its association with adverse cardiovascular events. METHODS: This analysis included patients ≥60 years old who underwent CEA, whose troponin-I levels were routinely monitored post-operatively and were included in a cohort study that assessed clinical outcomes. A clinical troponin cutoff of 60 ng/L was used. The primary endpoint was the composite of MI, stroke, and cardiovascular death. Secondary endpoints were MI, stroke, coronary intervention, cardiovascular death, and all cause death. RESULTS: 225 consecutive patients were included in the analysis. Troponin elevation occurred in 34 patients (15%) and a post-operative MI was diagnosed in eight patients. After a median follow up of 1.8 years (IQR 1.0-2.6), the primary endpoint occurred in 29% of patients with troponin elevation versus 6.3% without (HR 5.6, 95% CI 2.4-13), MI in 24% versus 1.6% (HR 18.0, 95% CI 4.7-68), stroke in 5.9% versus 4.2% (HR 1.4, 95% CI 0.3-6.7), coronary intervention in 5.9% versus 2.6% (HR 2.7, 95% CI 0.5-14), cardiovascular death in 5.9% versus 0.5% (HR 11.8, 95% CI 1.1-131), and all cause death in 15% versus 5.8% (HR 3.0, 95% CI 1.0-8.7), respectively. Incidences of the primary endpoint and all cause mortality in patients with a post-operative MI versus "troponin only" were 25% versus 7.7% and 25% versus 12%, respectively. CONCLUSION: Troponin elevation after CEA occurred in 15% of patients. The incidence of adverse cardiovascular events was significantly higher in patients with troponin elevation, which was mainly attributable to silent non-ST segment elevation MIs that occurred in the early post-operative phase.

Rationale and design of the Measuring Athlete's Risk of Cardiovascular events (MARC) study : The role of coronary CT in the cardiovascular evaluation of middle-aged sportsmen.

BACKGROUND: More than 90 % of exercise-related cardiac arrests occur in men, predominantly those aged 45 years and older with coronary artery disease (CAD) as the main cause. The current sports medical evaluation (SME) of middle-aged recreational athletes consists of a medical history, physical examination, and resting and exercise electrocardiography. Coronary CT (CCT) provides a minimally invasive low radiation dose opportunity to image the coronary arteries. We present the study protocol of the Measuring Athlete's Risk of Cardiovascular events (MARC) study. MARC aims to assess the additional value of CCT to a routine SME in asymptomatic sportsmen ≥45 years without known CAD. DESIGN: MARC is a prospective study of 300 asymptomatic sportsmen ≥45 years who will undergo CCT if the SME does not reveal any cardiac abnormalities. The prevalence and determinants of CAD (coronary artery calcium score ≥100 Agatston Units (AU) or ≥50 % luminal stenosis) will be reported. The number needed to screen to prevent the occurrence of one cardiovascular event in the next 5 years, conditional to adequate treatment, will be estimated. DISCUSSION: We aim to determine the prevalence and severity of CAD and the additional value of CCT in asymptomatic middle-aged (≥45 years) sportsmen whose routine SME revealed no cardiac abnormalities.

The effects of intraoperative dexamethasone on left atrial function and postoperative atrial fibrillation in cardiac surgical patients.

Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and postoperative inflammation may contribute to PNAF by inducing atrial dysfunction. Corticosteroids reduce inflammation and may thus reduce atrial dysfunction and PNAF development. This study aimed to determine whether dexamethasone protects against left atrial dysfunction and PNAF in cardiac surgical patients. Cardiac surgical patients were randomised to a single dose of dexamethasone (1 mg.kg(-1)) or placebo after inducing anaesthesia. Transoesophageal echocardiography was performed in patients before and after surgery. Primary outcome was left atrial total ejection fraction (LA-TEF) after sternal closure; secondary outcomes included left atrial diameter and PNAF. 62 patients were included. Baseline characteristics were well balanced. Postoperative LA-TEF was 36.4 % in the dexamethasone group and 40.2 % in the placebo group (difference -3.8 %; 95 % confidence interval (CI) -9.0 to 1.4 %; P = 0.15). Postoperative left atrial diameter was 4.6 and 4.3 cm, respectively (difference 0.3; 95 % CI -0.2 to 0.7; P = 0.19). The incidence of PNAF was 30 % in the dexamethasone group and 39 % in the placebo group (P = 0.47). Intraoperative high-dose dexamethasone did not protect against postoperative left atrial dysfunction and did not reduce the risk of PNAF in cardiac surgical patients.

The separate and combined effects of adiposity and cardiometabolic dysfunction on the risk of recurrent cardiovascular events and mortality in patients with manifest vascular disease.

OBJECTIVES: A remarkable variation exists in the cardiometabolic consequences of obesity. We evaluated the separate and combined effects of adiposity and cardiometabolic dysfunction on the occurrence of cardiovascular events and mortality in patients with vascular disease. METHODS: We prospectively followed 5231 patients with a history of clinical cardiovascular disease without diabetes from the Second Manifestations of ARTerial disease (SMART) study. Patients were classified according to body mass index and cardiometabolic function. The presence of cardiometabolic dysfunction was defined as ≥3 of the modified National Cholesterol Education Program (NCEP) metabolic syndrome criteria (waist circumference replaced by elevated C-reactive protein). Cox proportional-hazards analysis was used to estimate HRs for cardiovascular events and mortality. RESULTS: The prevalence of cardiometabolic dysfunction was 40% in normal weight, 58% in overweight and 75% in obese patients. During a median follow-up of 6.1 years, 769 patients died and 705 patients experienced a major cardiovascular event. In the absence of cardiometabolic dysfunction, overweight (HR 1.18, 95% CI 0.90 to 1.55) and obese patients (HR 0.93, 95% CI 0.53 to 1.64) were not at increased risk of recurrent major cardiovascular events compared with normal weight patients without cardiometabolic dysfunction. An increased cardiovascular risk was observed in patients with cardiometabolic dysfunction and normal weight (HR 1.58, 95% CI 1.23 to 2.04), overweight (HR 1.35, 95% CI 1.07 to 1.70) and obesity (HR 1.50, 95% CI 1.12 to 2.00) compared with normal weight patients without cardiometabolic dysfunction. A similar pattern was observed for vascular and all-cause mortality. CONCLUSIONS: In patients with vascular disease, the cardiometabolic consequences of adiposity rather than adiposity per se increase the risk of recurrent cardiovascular events and mortality.

The aetiology of myocardial injury after non-cardiac surgery.

Recognition of myocardial injury after non-cardiac surgery is difficult, since strong analgesics (e.g. opioids) can mask anginal symptoms, and ECG abnormalities are subtle or transient. Thorough knowledge of the pathophysiological mechanisms is therefore essential. These mechanisms can be subdivided into four groups: type I myocardial infraction (MI), type II MI, non-ischaemic cardiac pathology, and non-cardiac pathology. The incidence of type I MI in patients with a clinical suspicion of perioperative acute coronary syndrome (ACS) is 45-57 %. This percentage is higher in patients with a high likelihood of MI such as patients with ST-elevation ACS. Of note, the generalisability of this statement is limited due to significant study limitations. Non-ischaemic cardiac pathology and non-cardiac pathology should not be overlooked as a cause of perioperative myocardial injury (PMI). Especially pulmonary embolism and dysrhythmias are a common phenomenon, and may convey important prognostic value. Implementation of routine postoperative troponin assessment and accessible use of minimally invasive imaging should be considered to provide adequate individualised therapy. Also, addition of preoperative imaging may improve the stratification of high-risk patients who may benefit from preoperative or perioperative interventions.

Beta-blocker therapy in unstable severe heart failure, evidence or experience?

Currently, no evidence exists on the effects of beta-receptor blocker (BRB) treatment in patients with unstable severe heart failure. When confronted with this specific patient category, clinical experience in our centre has consistently guided us to lower the dose or stop BRB therapy. To share this experience, we present three clinical case scenarios and discuss background literature motivating our approach in these patients.

Continuous-flow left ventricular assist device support in patients with advanced heart failure: points of interest for the daily management.

Today, continuous-flow left ventricular assist devices (cf-LVADs) are implanted more often in patients with end-stage heart failure. Because of greater durability they can be implanted for an extended period of time. As a result of increased numbers of patients on cf-LVAD support, healthcare professionals should be aware of the potential complications inherent to this therapy. Both bleeding and thrombosis may occur, and also complications related either to the device itself or to the ensuing altered haemodynamics, valvular pathology, and rhythm disturbances such as ventricular tachycardias and fibrillation. Accurate clinical evaluation, together with an electrocardiogram and, if necessary, combined with an echocardiogram, is obligatory in these situations. This review summarizes common complications complemented by a few clinical cases.

One-year clinical follow-up of a registry evaluating a percutaneous revascularisation strategy combining a pre-specified simple selection process with the use of a new thin-strut bare cobalt-chromium stent.

Objectives. To evaluate clinical events in a specifically selected cohort of patients with obstructive coronary artery disease (CAD), using a new generation thin-strut bare cobalt-chromium coronary stent.Methods. Patients with single- or multi-vessel, stable or unstable CAD eligible for percutaneous implantation of at least one bare cobalt-chromium stent were evaluated in a single-centre registry. Prospective pre-specified criteria for bare cobalt-chromium stent implantation in our centre were: any acute ST-elevation myocardial infarction (MI), otherwise 1) de novo coronary lesion, and 2) lesion length <20 mm, and 3) reference vessel diameter >2.6 mm, and 4) no diabetes, unless reference vessel diameter >3.5 mm. Endpoints, retrospectively collected, were death, MI and clinically driven target-lesion revascularisation (TLR) and target-vessel revascularisation (TVR) after 12 months.Results. Between September 2005 and June 2007, 712 patients (48.7% one-vessel, 29.9% two-vessel, 20% three-vessel and 1.4% left main disease; 7.9% diabetics) were treated with 800 bare cobalt-chromium stents, for stable angina (40.9%), unstable angina (20.9%) or acute ST-elevation MI (38.2%). The procedural success rate was 99.3%. Peri-procedural MI rate was 2.2% in the semi-elective group. At 12 months there were 17 deaths (2.4%), of which nine non-cardiac, 20 (2.8%) MI, 19 (2.7%) TLR and 29 (4.1%) TVR. Early and late definite stent thrombosis occurred in four (0.6%) and three (0.4%) patients, respectively.Conclusion. A strategy aimed at minimising drug-eluting stent use and combining a pre-specified simple selection process with the use of a new thin-strut bare cobalt-chromium stent is safe and effective at one-year clinical follow-up. (Neth Heart J 2010;18:486-92.).

Coronary collaterals--insights in molecular determinants and prognostic relevance.

In the field of molecular cardiology, recently several determinants of coronary collateral circulation have been identified. Knowing these factors may aid risk-stratification and put forward targets for intervention by stimulating development of collateral blood vessels (arteriogenesis). However, prognostic importance of coronary collaterals is not yet beyond debate, and seems to be modified by the extent of atherosclerotic burden. Combining these insights is essential to increase our understanding of these mechanisms and to proceed with developing strategies for risk-stratification and therapeutic stimulation of arteriogenesis.

Stent thrombosis in real-world patients: a comparison of drug-eluting with bare metal stents.

BACKGROUND: Although the introduction of drugeluting stents (DES) has been associated with an impressive reduction in target vessel revascularisation, there has been concern about the safety profile. The aim of this study was to determine the incidence of stent thrombosis in real-world patients and evaluate the contribution of drug-eluting stents. METHODS: A prospective observational cohort study was conducted at a high-volume centre in Utrecht, the Netherlands. All patients who underwent a percutaneous coronary intervention (PCI) between 1 January and 31 December 2005 were evaluated. The patients were pretreated with aspirin and clopidogrel, which was continued for six months in bare metal stents (BMS) and 12 months in DES. RESULTS: In 2005, 1309 patients underwent a percutaneous coronary intervention procedure with stent implantation. After a median follow-up of nine months, 1.8% (n=23) of the patients had suffered from stent thrombosis. Two cases could be attributed to incorrect use of antiplatelet agents. In 8/23 cases, a technical reason was found such as an unrecognised dissection or stent underexpansion. The timing of stent thrombosis was acute in 1/23 patients, subacute in 20/23 patients and late in 2/23 patients. In both cases of late stent thrombosis, a BMS had been used. There were no differences in stent thrombosis rates between DES and BMS (1.4 vs. 1.9%, ns.). This is remarkable since DES were used in more complex and longer lesions. CONCLUSION: The use of DES in routine daily practice does not appear to be associated with a higher rate of stent thrombosis than BMS. (Neth Heart J 2007;15:382-6.Neth Heart J 2007;15:382-6).

[The polypill: optimal strategy for reduction of cardiovascular disease]. / De 'polypil': de beste strategie tegen hart- en vaatziekten.

Treating all persons above 55 years of age with a polypill for primary and secondary cardiovascular-disease prevention may reduce cardiovascular events by more than 80%. This strategy is expected to be cost-effective and the associated risk of side effects is estimated to be low.