Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management: Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial
- Function of Natural Internal Mammary–to–Coronary Artery Bypasses and Its Effect on Myocardial Ischemia
- Transfer of Patients With ST-Elevation Myocardial Infarction for Primary Percutaneous Coronary Intervention: A Province-Wide Evaluation of “Door-in to Door-Out” Delays at the First Hospital
- Endothelial Cell–Specific Reactive Oxygen Species Production Increases Susceptibility to Aortic Dissection
- Single Delivery of an Adeno-Associated Viral Construct to Transfer the CASQ2 Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age
- Predictors of Poor Outcomes After Transcatheter Aortic Valve Replacement: Results From the PARTNER (Placement of Aortic Transcatheter Valve) Trial
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Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management: Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial
Periprocedural thromboembolic and hemorrhagic events represent serious complications of radiofrequency catheter ablation of atrial fibrillation (AF). Indeed, the incidence of thromboembolic events varies from 0.9% to 5%, depending on the anticoagulation strategy used in the periprocedural period. Although discontinuation of warfarin 3 to 5 days before ablation with and without bridging with low-weight-molecular heparin has shown a higher thromboembolic risk than radiofrequency catheter ablation without warfarin discontinuation under therapeutic international normalized ratio, no randomized, controlled trial on this topic existed. The Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) trial is the first randomized, multicenter study comparing AF ablation performed with and without warfarin discontinuation. Notably, the majority of enrolled patients had a high risk for stroke (nonparoxysmal AF and CHADS2 score >2) in ≈70% of the cases. The incidence of thromboembolic events (primary end point) was 4.9% in group 1 (off warfarin) and 0.25% in group 2 (on warfarin; P<0.001). The majority of events occurred in patients with nonparoxysmal AF. No significant difference in major bleeding and pericardial effusion was seen, whereas a significantly higher number of patients had minor bleeding (especially groin hematomas) in group 1 (22%) compared with group 2 (4.1%; P<0.001). Preprocedural transesophageal echocardiography was not performed in the on-warfarin group with therapeutic international normalized ratio. AF ablation on therapeutic international normalized ratio appears safer than the off-warfarin strategy. Randomized studies assessing the protective value of newer oral anticoagulants during radiofrequency catheter ablation should be performed only in comparison with on-warfarin treatment and possibly in nonparoxysmal AF patients. See p 2638.
Function of Natural Internal Mammary–to–Coronary Artery Bypasses and Its Effect on Myocardial Ischemia
Until now, the prevalence, functional relevance, and effect on myocardial ischemia of extracardiac coronary collateral supply via natural internal mammary artery (IMA) bypasses have been unknown. The present study in patients without and with coronary artery disease tested the hypotheses that coronary collateral function increases in the presence versus the absence of distal IMA balloon occlusion and that the former is reflected by reduced myocardial ischemia. The study among 120 patients with chronic stable coronary artery disease undergoing coronary angiography found that there is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral (ie, during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion) but not via contralateral natural IMA bypasses. On the basis of the findings presented here, an anti-ischemic therapeutic approach alternative to IMA bypass grafting, that is, distal IMA occlusion by invasive techniques, can be considered. In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory. See p 2645.
Transfer of Patients With ST-Elevation Myocardial Infarction for Primary Percutaneous Coronary Intervention: A Province-Wide Evaluation of “Door-in to Door-Out” Delays at the First Hospital
In many regions, such as the province of Quebec, Canada, transfer for primary percutaneous coronary intervention is the predominant reperfusion treatment strategy for ST-elevation myocardial infarction. Transfer for primary percutaneous coronary intervention is associated with longer delays to reperfusion, and the guideline-recommended benchmark of a “first hospital door-in to first hospital door-out” (DIDO) time within 30 minutes is rarely achieved. The present systematic field evaluation examined DIDO times for 988 patients with ST-elevation myocardial infarction transferred during a 6-month period in a populous and extensive geographic region. For a large majority of the present study patients, we were able to link hospital chart and ambulance time data to further examine processes at the first emergency department. Timely DIDO was rarely achieved (for 14.1%). The major contributors to the time spent at the first hospital were the delays (1) from the initial in-hospital ECG acquisition to transfer activation by the emergency physician and (2) from arrival of the transfer ambulance at the first hospital to departure of the ambulance for the primary percutaneous coronary intervention center. When DIDO was timely, treatment was far more frequently within guideline-recommended delays. The present findings suggest that facilitation of the transfer decision, particularly when emergency physicians are faced with difficult-to-interpret ECGs (ie, not a clear-cut ST-elevation myocardial infarction on the ECG), is likely to have the most favorable impact on reducing DIDO time, followed by keeping the door-in ambulance on standby for transfer. The present results point to the importance of increasing support for emergency physicians for the interpretation of difficult ECGs, especially in settings with lower volumes of ST-elevation myocardial infarction settings. See p 2653.
Endothelial Cell–Specific Reactive Oxygen Species Production Increases Susceptibility to Aortic Dissection
Increased vascular reactive oxygen species (ROS) production is implicated in endothelial dysfunction and the development of cardiovascular diseases. However, it is unclear whether an increase in endothelial cell ROS production alone is sufficient to promote susceptibility to vascular disease. In this study, we generated an endothelial cell–targeted transgenic mouse to model the increase in endothelial Nox2 expression observed in vascular diseases. We found that increased endothelial cell ROS production is sufficient to promote susceptibility to aortic dissection in response to angiotensin II through increased endothelial vascular cell adhesion molecule-1 expression, CD45+ inflammatory cell recruitment, and matrix metalloproteinase activity. Crucially, the increase in ROS production in Nox2 transgenic endothelial cells increased the secretion of cyclophilin A, a novel cytokine that primes vascular smooth muscle cells and augments vascular smooth muscle cell ROS production, in response to angiotensin II stimulation. Our findings provide evidence for a specific and pivotal role for endothelial cells in promoting susceptibility to aortic dissection in response to angiotensin II. These data extend our understanding of the pathways leading to aortic dissection, identifying endothelial cell ROS and cyclophilin A secretion as potential therapeutic targets in the prevention of aortic dissection. See p 2661.
Single Delivery of an Adeno-Associated Viral Construct to Transfer the CASQ2 Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age
Homozygous mutations in the CASQ2 gene encoding for human calsequestrin-2, a protein that regulates calcium homeostasis, cause the recessive variant of catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT predisposes the hearts of patients to cardiac arrest elicited by stress and emotion. CPVT patients receive lifelong therapy with β-blockers to prevent cardiac arrest. Development of “curative” strategies to restore normal gene function is an attractive goal for the treatment of CPVT: a highly penetrant, life-threatening disease. In 2008, we developed and characterized a knock-in mouse model that recapitulates the human phenotype of recessive CPVT and harbors the R33Q mutation in the CASQ2 gene. Here, we explore the therapeutic potential of viral gene transfer of wild-type CASQ2 in R33Q mice using an adeno-associated virus serotype 9 (AAV9). In vivo delivery of the AAV9-CASQ2 to R33Q mice prevents the development of the CPVT phenotype when therapy is administered to newborn R33Q mice and reverts the manifestations of the disease when administered to adult R33Q mice with full-blown signs of the disease. In the R33Q CPVT mice model, our gene therapy strategy shows long-term efficacy and selective expression of the transgene in the heart. The present data provide the first demonstration that delivery of the wild-type CASQ2 gene is able not only to prevent the onset of disease but also to revert its multifaceted manifestations, including abnormal protein expression, altered architecture of junctional sarcoplasmic reticulum, and cardiac arrhythmias. These preclinical data provide the rational for envisioning viral gene transfer as a novel therapeutic approach in CPVT patients. See p 2673.
Predictors of Poor Outcomes After Transcatheter Aortic Valve Replacement: Results From the PARTNER (Placement of Aortic Transcatheter Valve) Trial
In patients with severe aortic stenosis at high surgical risk, transcatheter aortic valve replacement (TAVR) offers substantial reductions in mortality and improvement in quality of life compared with medical therapy and similar long-term outcomes to surgical valve replacement; however, a substantial proportion of patients do not improve functionally or live longer after TAVR. Using data from 2137 TAVR patients from the PARTNER (Placement of Aortic Transcatheter Valve) study, we sought to identify patients at high risk for poor outcome after TAVR using a novel approach that integrates both quality of life and mortality outcomes. We used these data to develop and validate a multivariable model to identify patients at high risk for poor outcome. Although model discrimination was moderate, we were able to identify a group of patients with a nearly 70% risk of poor outcome at 1 year. Although one cannot predict with certainty whether a particular patient will or will not have that poor outcome, this assessment of risk could be quite valuable to patients to improve decisional quality, reduce anxiety associated with the TAVR treatment decision, and provide patients and their families with realistic expectations of recovery. These models can also serve as the basis by which to test the incremental value of novel predictive markers of poor outcomes after TAVR, such as markers of frailty, thereby leading to further refinement of the models over time. See p 2682.
- © 2014 American Heart Association, Inc.
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