HomeCirculationVol. 129, No. 1Circulation: Clinical Summaries Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation: Clinical SummariesOriginal Research Put Into Perspective for the Practicing Clinician Originally published7 Jan 2014https://doi.org/10.1161/01.cir.0000441950.26700.5dCirculation. 2014;129:2–4Effect of Remote Ischemic Preconditioning on Platelet Activation and Reactivity Induced by Ablation for Atrial FibrillationRadiofrequency ablation is an established therapy for atrial fibrillation. Radiofrequency ablation, however, has been associated with some risk of thromboembolic events, which have been reported to occur in up to 7% of patients despite the use of appropriate antithrombotic therapy. Platelet activation occurs during the procedure and likely contributes to this increased risk. In this randomized, controlled study, we show that remote ischemic preconditioning, achieved before radiofrequency catheter ablation of paroxysmal atrial fibrillation by the application of 3 short episodes (5 minutes) of forearm ischemia by cuff sphygmomanometer inflation separated by 5 minutes of reperfusion, reduced platelet activation induced by the procedure compared with a sham control group. The most relevant potential clinical implication of our findings is that remote ischemic preconditioning might be applied to reduce platelet activation and reactivity during radiofrequency ablation, with possible favorable effects on the occurrence of thromboembolic events. This potential clinical effect, however, needs to be assessed in appropriately designed large clinical trials. See p 11.Clinical Outcomes of Surgical Pulmonary Valve Replacement After Repair of Tetralogy of Fallot and Potential Prognostic Value of Preoperative Cardiopulmonary Exercise TestingPulmonary regurgitation is common in adult patients with tetralogy of Fallot predisposing to right ventricular dilatation, ventricular dysfunction, exercise intolerance, and eventually life-threatening arrhythmia and sudden cardiac death. Implantation of a competent pulmonary valve is increasingly undertaken to mitigate such adverse clinical outcomes. In this single-center surgical series of 221 consecutive pulmonary valve replacement operations in adults spanning a 17-year period (1993–2010), we report low and improving early and late mortality rates. Cardiopulmonary exercise testing is increasingly used as part of routine medical surveillance in these patients. More recently, impaired or deteriorating peak oxygen consumption during exercise (peak o2) has been used as an indication to expedite pulmonary valve replacement, before the onset of symptoms that are volunteered late. Our data suggest that impaired peak o2 preceding pulmonary valve replacement was predictive of early perioperative mortality (5.7% when peak o2 was <20 mL·kg−1·min−1 versus 0% when peak o2 was ≥20 mL·kg−1·min−1). This cutoff value of 20 mL·kg−1·min−1 (100% sensitivity, 56% specificity) may therefore be used as a risk stratifier for perioperative issues. These preoperative peak o2 data may assist clinical decision making on the optimal timing of pulmonary valve replacement and support the notion for early pulmonary valve replacement. Operating earlier while preoperative peak o2 remains relatively preserved enables patients to undergo surgery with lower perioperative surgical risk, an advantage to be balanced with the finite longevity of currently available interventions. See p 18.Cardiovascular Events Associated With Smoking Cessation Pharmacotherapies: A Network Meta-AnalysisPatients often use pharmacotherapies to aid in smoking cessation. Current licensed pharmacotherapies include nicotine replacement therapies, bupropion, and varenicline. Recently, there has been widespread public concern that varenicline may be associated with an increase in cardiovascular disease (CVD) events. Clinicians and the public are unsure about which smoking cessation therapies will offer the greatest likelihood of quitting with the safest adverse event profile. Using a statistical approach that permits the synthesis of direct and indirect randomized, clinical trial evidence, we compared the cardiovascular safety of nicotine replacement therapies, bupropion, and varenicline. We examined 2 categories of events: a composite of all CVD events that included both minor and major events and only major adverse CVD events. We included 63 randomized, clinical trials that reported CVD events. We found no increase in the risk of all CVD events with bupropion or varenicline. Nicotine replacement therapies had a statistically elevated risk that was driven predominantly by less serious events such as tachycardia. When the analysis was restricted to only major CVD events, we found a protective effect with bupropion and no clear evidence of harm with varenicline or nicotine replacement therapies. Our findings indicate that there is no clear evidence of major CVD events associated with smoking cessation. The increase in nicotine replacement therapy–associated CVD events was driven by well-known and largely benign events such as tachycardia and palpitations. See p 28.Association of Low-Grade Albuminuria With Adverse Cardiac Mechanics: Findings From the Hypertension Genetic Epidemiology Network (HyperGEN) StudyAlbuminuria, as measured by the urine albumin to creatinine ratio (UACR), predicts cardiovascular events in hypertension, diabetes mellitus, and heart failure. The reasons underlying the association between elevated UACR and worse cardiovascular outcomes are unclear but may be attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. We therefore sought to study the relationship between UACR and cardiac mechanics (measured by speckle-tracking echocardiography) in the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertensive and normotensive individuals. In a sample of 1894 HyperGEN participants, all of whom had ejection fraction >50% and normal wall motion, we demonstrated a continuous, linear relationship between UACR and cardiac mechanics, especially global longitudinal strain. The relationship between increased UACR and worse longitudinal strain persisted after adjustment for multiple confounders and in subgroup analyses. These associations were even present in individuals with UACR levels in the normal range (< 30 mg/g). Observing this relationship in the diverse, ambulatory HyperGEN cohort after controlling for comorbidities—especially diabetes mellitus and hypertension—suggests that UACR, as a marker for endothelial dysfunction, may share a pathophysiologic link with intrinsic myocardial dysfunction even in very early, asymptomatic stages. These findings highlight the possibility that early treatment of endothelial dysfunction may be a way to prevent the onset of myocardial dysfunction in at-risk patients. See p 42.Sex Difference in Risk of Second but Not of First Venous Thrombosis: Paradox ExplainedIn this study, we showed that the risk of a first venous thrombosis is twice as high in men as in women who are not exposed to the reproductive risk factors of oral contraception use, pregnancy/puerperium, and postmenopausal hormone therapy (odds ratio, 1.9; 95% confidence interval, 1.7–2.2). This finding, which is in line with findings from previous studies that showed that venous thrombosis recurs twice as often in men as in women, suggests that the intrinsic risk of venous thrombosis is higher in men than in women. Prediction models for recurrent venous thrombosis already advocate differential treatment strategies for men and women after a first venous thrombosis. From our results, it seems that a differential approach to the prevention of first venous thrombosis in men and in women without reproductive risk factors may also be indicated. For instance, men may benefit from a lower threshold for prophylactic treatment than women without reproductive risk factors when encountering high-risk situations for venous thrombosis. Male sex could be included in a prediction model in the same way as, for example, oral contraceptive use in women is sometimes included now. Alternatively, men may require a higher dose of prophylactic anticoagulation therapy than women without reproductive risk factors to reduce their venous thrombosis risk to the same extent. Further studies on the sex-specific risk and treatment of venous thrombosis are warranted to optimize the prevention of venous thrombosis in men and women. See p 51.Anticoagulation and Survival in Pulmonary Arterial Hypertension: Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)The use of anticoagulants in patients with pulmonary arterial hypertension (PAH) has been a controversial subject for decades. Several clinical studies have suggested beneficial effects of anticoagulation in patients with idiopathic PAH (IPAH; formerly called primary pulmonary hypertension), but most of these studies were retrospective and small. There are even less data on the use of anticoagulants in patients with other forms of PAH. Acknowledging the lack of compelling evidence, current guidelines recommend the use of anticoagulation in patients with IPAH but do provide a more ambiguous recommendation for other forms of PAH. Against this background, we analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European-based registry that prospectively enrolls patients with pulmonary hypertension. The sample consisted of 1283 consecutive patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation. Multivariable regression analysis confirmed the beneficial effect of anticoagulation on survival of IPAH patients (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH; in fact, there was a trend (P=0.08) towards a worse outcome associated with anticoagulation in patients with scleroderma-associated PAH. These data support the use of anticoagulation in patients with IPAH, but not in other forms of PAH. See p 57.Endothelial Junctional Adhesion Molecule-A Guides Monocytes Into Flow-Dependent Predilection Sites of AtherosclerosisAtherosclerotic lesions develop in the larger arteries at sites of disturbed flow, but the mechanisms behind this observation still remain poorly defined. In this study, Schmitt and colleagues investigated the cell-specific roles of junctional adhesion molecule A (JAM-A) in a mouse model of atherosclerosis. Through the use of 2-photon laser scanning microscopy on intact mouse arteries, the authors discovered that under aberrant flow conditions and hyperlipidemia, the cellular localization of endothelial JAM-A changes from a defined junctional to a focal apical pattern, thereby facilitating the recruitment of monocytes to the developing plaque. In vitro studies revealed that the expression of JAM-A was decreased by micro RNA 145, a micro RNA that is preferentially expressed under laminar flow conditions. These results highlight endothelial JAM-A as a proinflammatory factor that links aberrant flow conditions to inflammatory cell recruitment. These findings might be used to design novel and specific molecular imaging probes for the noninvasive detection of early endothelial dysfunction and for the therapeutic targeting of JAM-A in vascular inflammatory disease. See p 66.Dyslipidemia, Coronary Artery Calcium, and Incident Atherosclerotic Cardiovascular Disease: Implications for Statin Therapy From the Multi-Ethnic Study of AtherosclerosisThis study examines individuals from the community who were free of clinically evident atherosclerotic cardiovascular disease and not taking statin therapy at baseline. The cohort was followed for a median of 7.6 years for myocardial infarction, angina resulting in revascularization, resuscitated cardiac arrest, stroke, and cardiovascular death. Examining risk for these cardiovascular events, we considered the relative value of coronary artery calcium versus lipid abnormalities. Practicing clinicians commonly use the latter approach, in conjunction with traditional risk factor assessment, to select patients for statin therapy. This study shows that many individuals with dyslipidemia have no coronary artery calcium, while many individuals without dyslipidemia have coronary artery calcium; in other words, there is considerable discordance between the 2 paradigms of risk assessment. We found that coronary artery calcium provided greater relative value compared with lipid abnormalities in the assessment of cardiovascular risk. Whether lipid abnormalities were categorized with the use of guideline cut points or data set quartiles of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, non–high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration, coronary artery calcium stratified cardiovascular risk across lipid categories. Individuals with 0 lipid abnormalities and coronary artery calcium ≥100 had a higher event rate compared with individuals with 3 lipid abnormalities but coronary artery calcium of 0 (22.7 versus 5.9 per 1000 person-years). Cardiovascular event rates similar to prior studies of secondary prevention populations were estimated for patients with coronary artery calcium ≥100 across the spectrum of dyslipidemia. This information has the potential to change the perspectives of practicing clinicians and guide discussions with patients regarding absolute risk and statin therapy. See p 77.Prognostic Value of Preoperative Right Ventricular Geometry and Tricuspid Valve Tethering Area in Patients Undergoing Tricuspid AnnuloplastyPatients who undergo tricuspid annuloplasty during left-side heart valve surgery have a poor postoperative clinical outcome, and 10-year survival is limited to 50% to 66%. However, preoperative right ventricular echocardiography parameters that predict adverse events in these patients are poorly understood. The present study evaluated 74 patients with significant tricuspid regurgitation who underwent tricuspid annuloplasty during left-side heart surgery. A total of 26 adverse events occurred during a mean follow-up of 26 months. Preoperative right ventricular midcavity diameter, right ventricular longitudinal dimension, and TV tethering area measured by right ventricular echocardiography were independently associated with adverse outcome after adjustment for age and New York Heart Association class. Furthermore, the presence of either >3.2-cm right ventricular midcavity diameter or >0.85-cm2 tricuspid valve tethering area was associated with adverse events at 1 year after tricuspid annuloplasty. Addressing these parameters by preoperative echocardiography may thus be important for risk stratification in patients undergoing tricuspid annuloplasty independently of the status of left-side heart valve disease. See p 87. Previous Back to top Next FiguresReferencesRelatedDetails January 7, 2014Vol 129, Issue 1 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/01.cir.0000441950.26700.5d Originally publishedJanuary 7, 2014 PDF download Advertisement