Reproducibility of peripheral arterial tonometry measurements in male cardiovascular patients

BACKGROUND Assessment of endothelial function of the microvasculature by peripheral arterial tonometry (EndoPAT(®)) has gained increasing popularity in patients with cardiovascular risk factors. Only limited knowledge about its reproducibility in patients with coronary artery disease (CAD) is available. We therefore aimed to quantify reproducibility of EndoPAT(®) parameters in patients with stable CAD. DESIGN EndoPAT(®) measurements were performed repeatedly in 78 male patients (age 66 ± 8 years) with CAD on stable medication. We calculated overall mean, standard deviation (SD), coefficient of variation (CV) and intraclass correlation coefficient (ICC) of the following parameters: reactive hyperemic index (RHI), PAT ratio of the postocclusion period 90-150 s as used for calculation of the RHI (PAT ratio90-150 s) and 90-120 s (PAT ratio90-120 s) as used for the often employed Framingham RHI (F-RHI), as well as PAT ratio of the peak hyperemic response (PAT ratiopeak response). Additionally, least significant changes (LSC) for individual subjects and minimum sample sizes for parallel and cross-over design studies were calculated. RESULTS Mean RHI was 1·84 (SD 0·36). For RHI, PAT ratio90-150 s , PAT ratio90-120 s , and PAT ratiopeak response the CVs were 17·0%, 25·4%, 26·1%, and 25·0%, respectively. The ICCs were 0·45, 0·49, 0·48 and 0·51, respectively, and LSC for RHI was 47·2%. CONCLUSIONS CV of RHI in our population was moderate; however, we consider this precision insufficient to monitor changes in individual patients, as they would need to exceed 47% to show a significant change. Further, the poor ICCs reflect the difficulty of detecting treatment effects in homogenous populations, such as patients with stable CAD.

Effect of a Tibetan herbal mixture on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation

In this 6-week prospective, randomized, placebo-controlled and double-blind study, we investigated the effects of a natural herbal remedy based on a recipe from Tibet (Padma® 28), on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation in 80 coronary artery disease (CAD) patients (age 66 ± 8 years) on guideline-based medication for secondary prevention. We found no significant effects of Padma 28 and conclude that the addition of Padma 28 to guideline-based secondary prevention treatment of CAD did not lead to significant effects on important surrogate markers in elderly male CAD patients.

Open issues in transcatheter aortic valve implantation. Part 1: patient selection and treatment strategy for transcatheter aortic valve implantation.

An exponential increase in the use of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis has been witnessed over the recent years. The current article reviews different areas of uncertainty related to patient selection. The use and limitations of risk scores are addressed, followed by an extensive discussion on the value of three-dimensional imaging for prosthesis sizing and the assessment of complex valve anatomy such as degenerated bicuspid valves. The uncertainty about valvular stenosis severity in patients with a mismatch between the transvalvular gradient and the aortic valve area, and how integrated use of echocardiography and computed tomographic imaging may help, is also addressed. Finally, patients referred for TAVI may have concomitant mitral regurgitation and/or coronary artery disease and the management of these patients is discussed.

Performance of the resolute zotarolimus-eluting stent in small vessels.

BACKGROUND Drug eluting stents for the treatment of small vessel coronary artery disease have traditionally yielded inferior clinical outcomes compared to the use of DES in large vessels. The benefit of the second-generation Resolute zotarolimus-eluting stent (R-ZES) in small vessels was examined. METHODS Two-year clinical outcomes from five combined R-ZES studies were compared between patients with small (reference vessel diameter [RVD] ≤2.5 mm; n = 1,956) and large (RVD >2.5 mm; n = 3174) vessels. RESULTS Despite a higher incidence of comorbidities in the small vessel group, there was no significant difference in target lesion failure (TLF) (10.1% vs. 8.7%; P = 0.54) at 2 years. When the subgroup of patients with diabetes was examined (n = 1,553) there was no significant difference in 2-year TLF in small compared to large vessels (11.2% vs. 11.1%; P = 0.17). Similarly, within the small vessel cohort, no significant difference was seen regarding TLF at 2 years between people with and without diabetes (11.2% vs 9.6%; P = 0.28). CONCLUSION When used for the treatment of small vessels, the R-ZES appears to provide acceptable clinical results at 2 years when compared to its performance in large vessels.

Novel Approaches to Myocardial Perfusion: 3D First-Pass CMR Perfusion Imaging and Oxygenation-Sensitive

This article reviews technical aspects and the current status of novel cardiovascular magnetic resonance (CMR) approaches to assessing myocardial perfusion, specifically oxygenation-sensitive magnetic resonance imaging, comparing their diagnostic targets and clinical role with those of other imaging approaches. The paper includes discussions of relevant pathophysiological aspects of myocardial ischemia and the clinical context of revascularization in patients with suspected or known coronary artery disease. Research using oxygenation-sensitive CMR may play an important role for a better understanding of the interplay of coronary artery stenosis, blood flow reduction, and their impact on actual myocardial ischemia.

Should we perform a screening ECG among asymptomatic adults?

The resting ECG is a safe, low cost and widely available in the clinical investigation of several cardiac symptoms. However, there is controversy regarding the use as a screening tool or routine cardiovascular (CV) risk assessment test among healthy asymptomatic adults. Two recent studies reported that ECG adds supplemental information in the estimation of coronary artery disease (CAD) risk in asymptomatic patients, especially in those with intermediate risk. However, we currently need more data on the impact of ECG on the prevention of clinical CV outcomes, especially in a randomized clinical trial, and on additional costs of testing and treatment. For the time being, routine ECG testing is not recommended for the prevention of CV events among healthy asymptomatic adults.

Clinical outcomes and revascularization strategies in patients with low-flow, low-gradient severe aortic valve stenosis according to the assigned treatment modality

OBJECTIVES This study compared clinical outcomes and revascularization strategies among patients presenting with low ejection fraction, low-gradient (LEF-LG) severe aortic stenosis (AS) according to the assigned treatment modality. BACKGROUND The optimal treatment modality for patients with LEF-LG severe AS and concomitant coronary artery disease (CAD) requiring revascularization is unknown. METHODS Of 1,551 patients, 204 with LEF-LG severe AS (aortic valve area <1.0 cm(2), ejection fraction <50%, and mean gradient <40 mm Hg) were allocated to medical therapy (MT) (n = 44), surgical aortic valve replacement (SAVR) (n = 52), or transcatheter aortic valve replacement (TAVR) (n = 108). CAD complexity was assessed using the SYNTAX score (SS) in 187 of 204 patients (92%). The primary endpoint was mortality at 1 year. RESULTS LEF-LG severe AS patients undergoing SAVR were more likely to undergo complete revascularization (17 of 52, 35%) compared with TAVR (8 of 108, 8%) and MT (0 of 44, 0%) patients (p < 0.001). Compared with MT, both SAVR (adjusted hazard ratio [adj HR]: 0.16; 95% confidence interval [CI]: 0.07 to 0.38; p < 0.001) and TAVR (adj HR: 0.30; 95% CI: 0.18 to 0.52; p < 0.001) improved survival at 1 year. In TAVR and SAVR patients, CAD severity was associated with higher rates of cardiovascular death (no CAD: 12.2% vs. low SS [0 to 22], 15.3% vs. high SS [>22], 31.5%; p = 0.037) at 1 year. Compared with no CAD/complete revascularization, TAVR and SAVR patients undergoing incomplete revascularization had significantly higher 1-year cardiovascular death rates (adj HR: 2.80; 95% CI: 1.07 to 7.36; p = 0.037). CONCLUSIONS Among LEF-LG severe AS patients, SAVR and TAVR improved survival compared with MT. CAD severity was associated with worse outcomes and incomplete revascularization predicted 1-year cardiovascular mortality among TAVR and SAVR patients.

Sudden cardiac death among general population and sport related population in forensic experience

PURPOSE: The goal of the study was to assess the causes and analyze the cases of sudden cardiac death (SCD) victims referred to the department of forensic medicine in Lausanne, with a particular focus on sports-related fatalities including also leisure sporting activities. To date, no such published assessment has been done nor for Switzerland nor for the central Europe. METHODS: This is a retrospective study based on autopsy records of SCD victims, from 10 to 50 years of age, performed at the University Centre of Legal Medicine in Lausanne from 1995 to 2010. The study population was divided into two groups: sport-related (SR) and not sport-related (NSR) SCDs. RESULTS: During the study period, 188 cases of SCD were recorded: 166 (88%) were NSR and 22 (12%) SR. The mean age of the 188 victims was 37.3 +/- 10.1 years, with the majority of the cases being male (79%). A cause of death was established in 84%, and the pathology responsible for death varied according to the age of the victims. In the NSR group, the mean age was 38.2 +/- 9.2 years and there was 82% of male. Coronary artery disease (CAD) was the main diagnosis in the victims aged 30-50 years. The majority of morphologically normal hearts were observed in the 15-29 year age range. There was no case in the 10-14 year age range. In the SR group, 91% of victims died during leisure sporting activities. In this group the mean age was 30.5 +/- 13.5 years, with the majority being male (82%). The main cause of death was CAD, with 6 cases (27%) and a mean age of 40.8 +/- 5.5 years. The youngest victim with CAD was 33 years old. A morphologically normal heart was observed in 5 cases (23%), with a mean age of 24.4 +/- 14.9 years. The most frequently implicated sporting activities were hiking (26%) and swimming (17%). CONCLUSION: In this study, CAD was the most common cause of death in both groups. Although this pathology most often affects adults over 35 years of age, there were also some victims under 35 years of age in both groups. SCDs during sport are mostly related to leisure sporting activities, for which preventive measures are not yet usually established. This study highlights also the need to inform both athletes and non athletes of the cardiovascular risks during sport activities and the role of a forensic autopsy and registries involving forensic pathologists for SR SCD.

Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. METHODS AND RESULTS Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Arterial healing following primary PCI using the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) versus the durable polymer everolimus-eluting metallic stent (XIENCE) in patients with acute ST-elevation myocardial infarction: rationale and design of the randomised TROFI II study

AIMS The Absorb bioresorbable vascular scaffold (Absorb BVS) provides similar clinical outcomes compared with a durable polymer-based everolimus-eluting metallic stent (EES) in stable coronary artery disease patients. ST-elevation myocardial infarction (STEMI) lesions have been associated with delayed arterial healing and impaired stent-related outcomes. The purpose of the present study is to compare directly the arterial healing response, angiographic efficacy and clinical outcomes between the Absorb BVS and metallic EES. METHODS AND RESULTS A total of 191 patients with acute STEMI were randomly allocated to treatment with the Absorb BVS or a metallic EES 1:1. The primary endpoint is the neointimal healing (NIH) score, which is calculated based on a score taking into consideration the presence of uncovered and malapposed stent struts, intraluminal filling defects and excessive neointimal proliferation, as detected by optical frequency domain imaging (OFDI) six months after the index procedure. The study will provide 90% power to show non-inferiority of the Absorb BVS compared with the EES. CONCLUSIONS This will be the first randomised study investigating the arterial healing response following implantation of the Absorb BVS compared with the EES. The healing response assessed by a novel NIH score in conjunction with results on angiographic efficacy parameters and device-oriented events will elucidate disease-specific applications of bioresorbable scaffolds.

Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization: Fifty Years of Revascularization: Where Are We and Where Are We Heading?

The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, urgent, and emergency settings. The 2014 document updates and extends the effort started in 2010, year of the first edition of these guidelines. Importantly, this latest edition provides a systematic review of all randomized clinical trials performed since 1980, comparing different strategies of myocardial revascularization, including coronary artery bypass graft (CABG), balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first- and second-generation drug-eluting stents (DES). This review aims to highlight the most relevant novelties introduced by the 2014 edition of the ESC/EACTS myocardial revascularization guidelines as compared with the previous edition and to describe similarities and differences with the American societies' guidelines.

Post-Procedural Troponin Elevation and Clinical Outcomes Following Transcatheter Aortic Valve Implantation.

BACKGROUND Biomarkers of myocardial injury increase frequently during transcatheter aortic valve implantation (TAVI). The impact of postprocedural cardiac troponin (cTn) elevation on short-term outcomes remains controversial, and the association with long-term prognosis is unknown. METHODS AND RESULTS We evaluated 577 consecutive patients with severe aortic stenosis treated with TAVI between 2007 and 2012. Myocardial injury, defined according to the Valve Academic Research Consortium (VARC)-2 as post-TAVI cardiac troponin T (cTnT) >15× the upper limit of normal, occurred in 338 patients (58.1%). In multivariate analyses, myocardial injury was associated with higher risk of all-cause mortality at 30 days (adjusted hazard ratio [HR], 8.77; 95% CI, 2.07-37.12; P=0.003) and remained a significant predictor at 2 years (adjusted HR, 1.98; 95% CI, 1.36-2.88; P<0.001). Higher cTnT cutoffs did not add incremental predictive value compared with the VARC-2-defined cutoff. Whereas myocardial injury occurred more frequently in patients with versus without coronary artery disease (CAD), the relative impact of cTnT elevation on 2-year mortality did not differ between patients without CAD (adjusted HR, 2.59; 95% CI, 1.27-5.26; P=0.009) and those with CAD (adjusted HR, 1.71; 95% CI, 1.10-2.65; P=0.018; P for interaction=0.24). Mortality rates at 2 years were lowest in patients without CAD and no myocardial injury (11.6%) and highest in patients with complex CAD (SYNTAX score >22) and myocardial injury (41.1%). CONCLUSIONS VARC-2-defined cTnT elevation emerged as a strong, independent predictor of 30-day mortality and remained a modest, but significant, predictor throughout 2 years post-TAVI. The prognostic value of cTnT elevation was modified by the presence and complexity of underlying CAD with highest mortality risk observed in patients combining SYNTAX score >22 and evidence of myocardial injury.

Uric Acid and Cardiovascular Events: A Mendelian Randomization Study

Obesity and diets rich in uric acid-raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid-regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.

Identification of genetic variation influencing apolipoprotein E levels: Follow-up of genome-wide linkage scans in the GENOA study

Apolipoprotein E (ApoE) plays a major role in the metabolism of high density and low density lipoproteins (HDL and LDL). Its common protein isoforms (E2, E3, E4) are risk factors for coronary artery disease (CAD) and explain between 16 to 23% of the inter-individual variation in plasma apoE levels. Linkage analysis has been completed for plasma apoE levels in the GENOA study (Genetic Epidemiology Network of Atherosclerosis). After stratification of the population by lipoprotein levels and body mass index (BMI) to create more homogeneity with regard to biological context for apoE levels, Hispanic families showed significant linkage on chromosome 17q for two strata (LOD=2.93 at 104 cM for a low cholesterol group, LOD=3.04 at 111 cM for a low cholesterol, high HDLC group). Replication of 17q linkage was observed for apoB and apoE levels in the unstratified Hispanic and African-American populations, and for apoE levels in African-American families. Replication of this 17q linkage in different populations and strata provides strong support for the presence of gene(s) in this region with significant roles in the determination of inter-individual variation in plasma apoE levels. Through a positional and functional candidate gene approach, ten genes were identified in the 17q linked region, and 62 polymorphisms in these genes were genotyped in the GENOA families. Association analysis was performed with FBAT, GEE, and variance-component based tests followed by conditional linkage analysis. Association studies with partial coverage of TagSNPs in the gene coding for apolipoprotein H (APOH) were performed, and significant results were found for 2 SNPs (APOH_20951 and APOH_05407) in the Hispanic low cholesterol strata accounting for 3.49% of the inter-individual variation in plasma apoE levels. Among the other candidate genes, we identified a haplotype block in the ACE1 gene that contains two major haplotypes associated with apoE levels as well as total cholesterol, apoB and LDLC levels in the unstratified Hispanic population. Identifying genes responsible for the remaining 60% of inter-individual variation in plasma apoE level, will yield new insights into the understanding of genetic interactions involved in the lipid metabolism, and a more precise understanding of the risk factors leading to CAD. ^

Roadmap for implementing the Chronic Care Model for weight management: Healthcare Institution's Response to Obesity (HIRO)

Background. Excess weight and obesity are at epidemic proportions in the United States and place individuals at increased risk for a variety of chronic conditions. Rates of diabetes, high blood pressure, coronary artery disease, stroke, cancer, and arthritis are all influenced by the presence of obesity. Small reductions in excess weight can produce significant positive clinical outcomes. Healthcare organizations have a vital role to play in the identification and management of obesity. Currently, healthcare providers do not adequately diagnose and manage excess weight in patients. Lack of skill, time, and knowledge are commonly cited as reasons for non-adherence to recommended standards of care. The Chronic Care Model offers an approach to healthcare organizations for chronic disease management. The model consists of six elements that work together to empower both providers and patients to have more productive interactions: the community, the health system itself, self-management support, delivery system design, decision support, and clinical information systems. The model and its elements may offer a framework through which healthcare organizations can adapt to support, educate, and empower providers and patients in the management of excess weight and obesity. Successful management of excess weight will reduce morbidity and mortality of many chronic conditions. Purpose. The purpose of this review is to synthesize existing research on the effectiveness of the Chronic Care Model and its elements as they relate to weight management and behaviors associated with maintaining a healthy weight. Methods: A narrative review of the literature between November 1998 and November 2008 was conducted. The review focused on clinical trials, systematic reviews, and reports related to the chronic care model or its elements and weight management, physical activity, nutrition, or diabetes. Fifty-nine articles are included in the review. Results. This review highlights the use of the Chronic Care Model and its elements that can result in improved quality of care and clinical outcomes related to weight management, physical activity, nutrition, and diabetes. Conclusions. Healthcare organizations can use the Chronic Care Model framework to implement changes within their systems to successfully address overweight and obesity in their patient populations. Specific recommendations for operationalizing the Chronic Care Model elements for weight management are presented.^