Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-Term Progression of Atrial Fibrillation in Sick Sinus Syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study
- Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial
- Mitochondrial DNA Damage Can Promote Atherosclerosis Independently of Reactive Oxygen Species Through Effects on Smooth Muscle Cells and Monocytes and Correlates With Higher-Risk Plaques in Humans
- Right Ventricular Systolic Dysfunction in Young Adults Born Preterm
- Use and Associated Risks of Concomitant Aspirin Therapy With Oral Anticoagulation in Patients With Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry
- Magnetic Resonance T1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis
- Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography
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Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-Term Progression of Atrial Fibrillation in Sick Sinus Syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study
In patients with sick sinus syndrome, the occurrence of atrial fibrillation (AF) after pacemaker implantation is associated with an increased risk of stroke, systemic embolism, heart failure, and mortality. The present study, a single-blinded, 2×2 factorial randomized, multicenter trial in 385 patients with sick sinus syndrome and paroxysmal AF and a 3.1-year follow-up, investigated whether long-term atrial pacing at the right atrial appendage versus the low right atrial septum with or without a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. Our results showed that neither low right atrial septal pacing to reduce P-wave duration nor the use of continuous atrial overdrive pacing to increase atrial pacing significantly affect the long-term development of persistent AF. No clinical variables could predict any potential benefit of either alternative site pacing or rate on progression to persistent AF. Other secondary end points, including AF burden, atrial high-rate episode >6 minutes, quality of life, and adverse events, were unaffected by the atrial pacing site and rate. In conclusions, among patients with sick sinus syndrome and paroxysmal AF who required pacemaker implantation, the use of an alternative atrial pacing site at the lower right atrial septum or continuous atrial overdrive pacing provided no incremental benefit to atrial-based pacing with minimized ventricular pacing in preventing the development of persistent AF. See p 687.
Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial
Diabetes mellitus is frequently associated with ischemic heart disease and may alter the disease process. Data gathered on patients with heart failure and diabetes mellitus are highly relevant to improve our current knowledge in the field. We aimed to investigate the influence of innovative implantable cardioverter-defibrillator programming in patients with diabetes mellitus and to determine whether these patients derive benefit similar to that in patients without diabetes mellitus. It is of great importance to evaluate the differences in the risk of inappropriate therapy and appropriate therapy and subsequent outcome in patients with diabetes mellitus to provide tailored treatment strategies. Our novel finding is that both patients with and without diabetes mellitus gain a reduction of inappropriate therapy using innovative implantable cardioverter-defibrillator programming with high-rate cutoff or delayed therapy. However, diabetes mellitus was associated with a significantly lower risk of inappropriate therapy caused by supraventricular tachycardia and sinus tachycardia, whereas the risk of atrial fibrillation was similar in patients with and without diabetes mellitus. These findings suggest that different mechanisms are responsible for inappropriate therapy and that diabetics may have higher thresholds for implantable cardioverter-defibrillator firing as a result of reduced autonomic cardiovascular reflexes. The risk of appropriate therapy was higher in diabetic patients and was associated with increased mortality, suggesting that patients with diabetes mellitus may be more prone to develop ventricular tachyarrhythmias and may be more vulnerable to appropriate ICD shock therapy than nondiabetics. Our findings may help improve ICD programming in patients with diabetes mellitus and may raise awareness about the importance of optimized treatment strategy after an appropriate shock to improve clinical outcome. See p 694.
Mitochondrial DNA Damage Can Promote Atherosclerosis Independently of Reactive Oxygen Species Through Effects on Smooth Muscle Cells and Monocytes and Correlates With Higher-Risk Plaques in Humans
Damage to mitochondria, the powerhouse of the cell, has been found in human atherosclerosis and is associated with increased levels of free radicals and oxidative stress. Indeed, to date, it has been thought that free radicals mediate almost all of the effect of mitochondrial DNA (mtDNA) damage in atherosclerosis. We show that mtDNA damage occurs early in atherosclerosis in both the vessel wall and circulating cells and is sufficient to cause mitochondrial dysfunction. Using mice, we show that mtDNA damage directly promotes atherosclerosis and features of unstable plaques independently of oxidative stress. mtDNA damage inhibits cell proliferation, promotes cell death, and increases the proinflammatory activity of monocytes. Using virtual histology intravascular ultrasound, we show that mtDNA damage is associated with higher-risk plaques in patients, is independent of other risk factors, and decreases after treatment in patients with acute coronary syndrome. Thus, mtDNA damage in the vessel wall and circulating cells is widespread and causative, indicates higher risk in atherosclerosis, and can promote disease independently of oxidative stress. mtDNA damage may be useful as a biomarker for high-risk atherosclerosis, and protection against mtDNA damage and improvement in mitochondrial function are potential areas for new therapeutics. See p 702
Right Ventricular Systolic Dysfunction in Young Adults Born Preterm
Advances in perinatal care mean that infants born preterm now routinely survive into adult life. As a result, up to 1 in 10 young adults will now have been born preterm. Using cardiovascular magnetic resonance in a large prospective study, we have found that these young adults have a unique cardiovascular structure and function. Their right ventricles are significantly smaller and thickened, and they have significant reductions in right ventricular systolic function. Of those studied, 6% had ejection fractions below the clinically accepted lower limit of normal for the right ventricle, and 21% fell below the lower limit of normality defined by our young adult control group. These changes in the right ventricle are proportionally greater than the differences we have previously reported in the left ventricle for adults born preterm. Future work will determine the impact of this reduced function on cardiovascular health during later adult life. Understanding how these changes occur will allow the design of targeted approaches to optimize function. See p 713.
Use and Associated Risks of Concomitant Aspirin Therapy With Oral Anticoagulation in Patients With Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry
The risks and benefits of concomitant aspirin (ASA) therapy in patients with atrial fibrillation receiving oral anticoagulation (OAC) are unclear. We assessed concomitant ASA use and its association with clinical outcomes among atrial fibrillation patients treated with OAC in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Of 10 126 patients from 176 US practices, 7347 were on OAC. Overall, 35% (n=2543) also received ASA (OAC+ASA) without any other antiplatelet therapy. Patients receiving OAC+ASA were more likely to be male (66% versus 53%; P<0.0001) and had more comorbid illness than those on OAC alone, including risk factors for cardiovascular disease. However, more than one third of patients (39%) on OAC+ASA did not have a history of atherosclerotic disease, yet 17% had elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding risk scores (>5). Major bleeding (adjusted hazard ratio, 1.67; 95% confidence interval, 1.18–2.37) and bleeding hospitalizations (adjusted hazard ratio, 1.53; 95% confidence interval, 1.02–2.3) were significantly higher in those on OAC+ASA compared with those on OAC alone. Rates of ischemic events were low across groups. Patients with atrial fibrillation receiving OAC are often treated with concomitant ASA, even when they do not have cardiovascular disease. Use of OAC+ASA was associated with significantly increased risk for bleeding, and clinicians need to carefully determine if and when the benefits of concomitant ASA outweigh the risks in atrial fibrillation patients already on OAC. See p 721.
Magnetic Resonance T1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis
The paradigm of deep venous thrombosis management is changing with a greater focus on restoring vein patency by the use of catheter-directed thrombolysis and pharmacomechanical adjuncts with the aim of reducing the incidence of the postthrombotic syndrome. Selection criteria used to identify thrombi that are most susceptible to lysis remain controversial. Thrombus age is currently the main determinant for thrombolysis, but clinical history and signs at presentation are subjective and unreliable. Not all young thrombi can be successfully lysed, whereas some old thrombi may be amenable to lysis. In this study, we show that fast T1 mapping can be used as a surrogate measure of the organization of experimental venous thrombi and that this technique identifies those thrombi most suitable for lysis. Experiments in this study were performed with the use of a clinical 3-T field strength MRI scanner without contrast agent, which facilitates the immediate translation of T1 mapping of thrombosis to the clinic. See p 729.
Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography
Peripheral artery disease of the lower extremities is a common disease and present in 15% to 20% of persons older than 65 years. Endovascular or surgical therapy fails or is not applicable in approximately one fourth of patients who would need revascularization therapies, which makes alternative approaches such as arteriogenesis (the positive remodeling of preformed collateral arterioles) necessary. Despite the fact that numerous studies have pursued the important therapeutic strategy of improving collateral function, there is no method available to quantify collateral arterial function of the lower limb and thus to determine therapeutic effects. The present study demonstrates for the first time a quantitatively assessed functional and clinically relevant collateral circulation in the lower limb. Using direct invasive pressure measurements in humans, we show that collateral flow index of the superficial femoral artery in the absence of any significant stenosis amounts to more than half the normal antegrade flow at rest (45±17% after 1 minute, 55±17% after 3 minutes). The amount of collateral flow observed in the present study is remarkably high, especially compared with what has been described previously for normal (18±8%) and stenotic (22±15%) coronary arteries. Importantly, this preexistent collateral blood supply in the absence of significant stenoses is sufficient to completely prevent symptoms during 5 minutes of acute ischemia at rest. Because only indirect and weak end points have been used in past studies to evaluate collateral growth, we propose that the method described in the present study may possibly be used as a gold standard in future clinical studies. See p 737.
- © 2013 American Heart Association, Inc.
- Right Ventricular Systolic Dysfunction in Young Adults Born Preterm
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