Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Predictors of Long-Term Outcomes in Symptomatic Hypertrophic Obstructive Cardiomyopathy Patients Undergoing Surgical Relief of Left Ventricular Outflow Tract Obstruction
- Combined Effects of Child and Adult Elevated Blood Pressure on Subclinical Atherosclerosis: The International Childhood Cardiovascular Cohort Consortium
- Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
- The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
- Anatomical and Procedural Features Associated With Aortic Root Rupture During Balloon-Expandable Transcatheter Aortic Valve Replacement
- Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System: Lessons From a Tick Salivary Protein
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Predictors of Long-Term Outcomes in Symptomatic Hypertrophic Obstructive Cardiomyopathy Patients Undergoing Surgical Relief of Left Ventricular Outflow Tract Obstruction
We report long-term outcomes in 699 symptomatic hypertrophic cardiomyopathy patients (47±11 years, 63% male) undergoing surgical relief of left ventricular outflow tract obstruction (myectomy±mitral valve surgery), along with their potential predictors. During a mean follow-up of 6.2±3 years, 86 patients (12%) met the composite end point (death, appropriate internal cardioverter defibrillator discharges, resuscitated sudden death, documented stroke, and admission for congestive heart failure) with 30-day, 1-year, and 2-year event rates of 0.7%, 2.8%, and 4.7%, respectively. There was 0% mortality at 30 days postoperatively. Residual postoperative atrial fibrillation or AF (hazard ratio 2.12 [1.37–3.34], P=0.001), and increasing age (hazard ratio 1.49 [1.22–1.82], P=0.001) as independent predictors of long-term composite outcomes. In a contemporary population of symptomatic adult hypertrophic cardiomyopathy patients undergoing surgery for relief of left ventricular outflow tract obstruction, there are excellent surgical results and a very low event rate during long-term follow-up. Worse outcomes were predicted by increasing age and presence of residual AF during follow up. See p 209.
Combined Effects of Child and Adult Elevated Blood Pressure on Subclinical Atherosclerosis: The International Childhood Cardiovascular Cohort Consortium
Hypertension is a major modifiable risk factor for atherosclerosis. The atherosclerotic process begins in early life, and blood pressure (BP) levels in childhood predict increased occurrence of subclinical atherosclerosis. However, it is not precisely known if the effects of elevated BP during childhood on atherosclerotic markers are permanent or reversible should the individual acquire normal BP levels by adulthood. Within an international consortium of cardiovascular risk factor studies initiated in childhood known as the International Childhood Cardiovascular Cohort (i3C) Consortium, we examined data for 4210 individuals from 4 cohorts to determine the combined effects of child and adult elevated BP on carotid intima-media thickness (a preclinical marker of atherosclerosis). The main aim was to examine whether a change from elevated BP status in childhood to normal BP in adulthood is associated with an attenuated risk of developing increased carotid intima-media thickness. In pooled analyses of the cohorts, among individuals with elevated BP in childhood and normal BP in adulthood the risk of increased carotid intima-media thickness in adulthood was not significantly increased (relative risk, 1.24; 95% confidence interval, 0.92–1.67) in comparison with those who had persistently normal BP. In contrast, adults with elevated BP, irrespective of their childhood BP status, had significantly increased risk of high carotid intima-media thickness with relative risks of 1.82 (95% confidence interval, 1.47–2.38) among those with persistently elevated BP and 1.57 (95% confidence interval, 1.22–2.02) among those with elevated BP only in adulthood. These results suggest that the effects of elevated BP in childhood on early atherosclerosis can be mostly reversed if normal BP levels are achieved by adulthood. See p 217.
Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
The ischemic myocardium releases macrophage migration inhibitory factor (MIF), which acts locally to increase the cardioprotective action of AMP-activated protein kinase (AMPK). AMPK is activated by hypoxia, and this response is impaired in aging. There are also common, functional polymorphisms in MIF that influence the strength of the cellular AMPK response to hypoxia. We identified pharmacological agonists of MIF that increase its binding to its cognate cell surface receptor CD74, and, in the present study, we show that a first-in-class MIF agonist, MIF20, augments the activation of the MIF receptor in cardiomyocytes and increases the downstream tissue-protective action of AMPK on glucose uptake and metabolism. In mouse hearts perfused with MIF20, postischemic left ventricular function improved commensurately with an increase in cardiac MIF-AMPK activation. Mice treated with MIF20 followed by left coronary artery occlusion and reperfusion also showed a reduction in infarcted myocardium. Augmentation of endogenous myocardial MIF signaling by small-molecular MIF agonists may offer a novel approach in selected clinical settings to compensate for intrinsic age or genetic deficiencies in protective AMPK responses. See p 225.
The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
Patients receiving dabigatran during the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial were eligible to continue their double-blind dose of dabigatran during an additional 2.3 years of follow-up as part of the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. The purpose of RELY-ABLE was to examine the long-term safety and efficacy of dabigatran. Not all countries or sites participated in RELY-ABLE and ≈25% of eligible patients declined to enroll in RELY-ABLE; thus, just under half of the 12 091 patients receiving dabigatran in RE-LY were entered into the RELY-ABLE long-term extension study. No patients on warfarin were enrolled in RELY-ABLE. RELY-ABLE was an observational study rather than a definitive clinical trial. Patients entering RELY-ABLE were somewhat different from patients enrolled in RE-LY but who did not enter RELY-ABLE. During RELY-ABLE, rates of stroke and systemic embolism on dabigatran were similar to rates observed during RE-LY. This is also true for rates of other important ischemic and thrombotic outcomes and for the safety outcome of major bleeding. Rates of hemorrhagic stroke during RELY-ABLE remained very low as seen during RE-LY. During RELY-ABLE, there was a trend for a lower rate of stroke or systemic embolism on the higher dose of dabigatran and a higher rate of major bleeding on the higher dose of dabigatran. Total mortality on the 2 dabigatran groups was similar. Thus, RELY-ABLE provides some reassurance that the rates of stroke, major bleeding, and death seen during RE-LY on dabigatran are likely to continue during an additional 2-year period of follow-up. See p 237.
Anatomical and Procedural Features Associated With Aortic Root Rupture During Balloon-Expandable Transcatheter Aortic Valve Replacement
Aortic root rupture, albeit infrequently observed, remains a significant concern with balloon-expandable transcatheter valve prostheses, owing to its extremely poor prognosis. To date, owing to its relative rareness (≈1%), we have lacked the ability to confidently identify predictors of these significant complications. Recently, 3-dimensional computed tomography has been shown to provide excellent anatomic detail and accurate assessment of the complex anatomic shape of the aortic root, allowing for the prediction of paravalvular regurgitation and other transcatheter aortic valve replacement–-related complications. In this multicenter study, 31 consecutive patients who experienced left ventricular outflow tract/annular/aortic contained/noncontained rupture during balloon-expandable transcatheter aortic valve replacement were compared with a propensity-matched control group of 31 consecutive patients without annular rupture who underwent pre-transcatheter aortic valve replacement computed tomography. In addition to confirming the extremely poor prognosis of annular rupture (48% in-hospital mortality rates), we identified 2 important features associated with this complication: (1) moderate or severe left ventricular outflow tract/ subannular calcification, and (2) significantly oversized prostheses (≥20% area oversizing). Clinical implications of these findings are important, because they support a more patient-specific approach to transcatheter heart valve sizing with the integration of both 3-dimensional annular dimensions and also information regarding potential root modifiers such as left ventricular outflow tract calcification of multidetector computed tomography. See p 244.
Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System: Lessons From a Tick Salivary Protein
It is of crucial importance that enzymes of the coagulation system and their cofactors circulate in an inactive form under physiological conditions and are activated promptly but only when necessary. In this study, we demonstrate, using a novel tick-derived coagulation inhibitor, that the activation of factor V by factor Xa is a crucial event in the initiation of thrombin generation. Efforts to introduce novel anticoagulants based on direct factor Xa or thrombin inhibition have provoked discussion about the implications these new strategies may have. In light of our findings, it can be hypothesized that this new class of direct inhibitors have a differential influence on the initial factor V activation. In other words, part of the anticoagulant mechanism of direct factor Xa inhibitors is potentially explained by inhibiting the generation of the first factor Va molecules. In addition, our findings may prompt to a new class of coagulation inhibitors that target this aspect of the initiation phase of coagulation. See p 254.
- © 2013 American Heart Association, Inc.
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