Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans
- Impact of Partner Bereavement on Quality of Cardiovascular Disease Management
- Mortality Among High-Risk Patients With Acute Myocardial Infarction Admitted to US Teaching-Intensive Hospitals in July: A Retrospective Observational Study
- Validation of Contrast-Enhanced Magnetic Resonance Imaging to Monitor Regenerative Efficacy After Cell Therapy in a Porcine Model of Convalescent Myocardial Infarction
- Impact of Preoperative Moderate/Severe Mitral Regur gitation on 2-Year Outcome After Transcatheter and Surgical Aortic Valve Replacement: Insight From the Placement of Aortic Transcatheter Valve (PARTNER) Trial Cohort A
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Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans
Noninvasive atrial fibrillation (AF) therapies are based on 2 separate strategies: rate or rhythm control aiming to slow ventricular rate to normal or to restore sinus rhythm, respectively. Hence, in rate control, AF itself is not resolved, whereas the curtailment of ventricular frequency reduces exercise tolerance. Rhythm control, on the other hand, is hampered by adverse effects such as ventricular proarrhythmia. Therefore, better insight into the contribution of ion channels, present in the atria but not the ventricles, to AF and the concordant exploration of possible atrium-specific therapies are essential if we are to diminish the burden of adverse effects in AF treatment. Previous studies showed that the acetylcholine-dependent potassium current (IK,ACh), governed by the atrium-specific Kir3.x channels, can become constitutively active (IK,ACh-C) in patients with AF. In the present study, we demonstrate the contribution of IK,ACh-C and Kir3.x to the initiation, maintenance, and termination of AF. We show for the first time that IK,ACh-C increases the chance of AF initiation through its steepening effects on the action potential duration and conduction velocity restitution curves, causing action potential duration and amplitude alternans. In addition, IK,ACh-C is shown to facilitate AF maintenance by stabilizing rotor dynamics, whereas AF termination can be elicited by blockade of IK,ACh-C, causing alternans-mediated rotor destabilization. Our findings provide evidence for a causal relationship between IK,ACh-C, alternans, and the initiation, maintenance, and termination of AF. Thus, not only IK,ACh-C or Kir3.x but also its consequent alternans might be an interesting atrium-specific target for future AF rhythm control or pharmacological cardioversion. See p 2732.
Impact of Partner Bereavement on Quality of Cardiovascular Disease Management
The year after bereavement is a period of increased risk of cardiovascular death. In addition to physiological responses to grief and lifestyle changes, changes in the quality of cardiovascular care may increase risk after bereavement. Our study identifies poorer uptake of key measures of routine care, such as lipid or blood pressure monitoring, in the year before partner bereavement with recovery in the year after bereavement. In addition, we describe a reduction in cardiovascular medication prescribing, including lipid-lowering and antiplatelet therapy, starting shortly before bereavement and lasting up to 3 months. Both these changes will adversely influence cardiovascular risk and contribute to increased cardiovascular events after bereavement. Poorer care in the year before bereavement means that individuals enter the bereavement period with higher baseline cardiovascular risk. Cessation of some cardiovascular medication, such as antiplatelet therapy, is believed to be a trigger for myocardial infarction. Improving cardiovascular care before and after bereavement has the potential for reducing the adverse health effects of bereavement. Clinicians caring for individuals whose partner is suffering from a life-limiting condition need to facilitate maintenance of normal cardiovascular monitoring and care. Such care for the partner may be appropriately included in palliative care programs. After a recent bereavement, clinicians need to encourage medication adherence and monitor prescribing coverage as part of wider social and psychological support for bereaved individuals. See p 2745.
Mortality Among High-Risk Patients With Acute Myocardial Infarction Admitted to US Teaching-Intensive Hospitals in July: A Retrospective Observational Study
Each summer US teaching hospitals experience a turnover of resident physicians, raising the possibility that patient outcomes suffer as a result of operational disruption and relative inexperience of new physicians (July effect). Although most studies of the July effect find small if any mortality increases in July, these studies generally do not distinguish between patients of varying predicted inpatient mortality risk. Mortality outcomes of patients at low risk of inpatient mortality may be unaffected by resident inexperience in July, whereas mortality among higher risk patients may be more affected by errors or relative inexperience at the start of the residency year. We studied inpatient mortality among a national sample of patients admitted with acute myocardial infarction to US hospitals during May and July 2002 to 2008. We stratified patients into low- and high-predicted risk of inpatient mortality and studied whether the July effect—defined as the difference in mortality in teaching-intensive hospitals in July relative to May, compared with the difference in mortality in non–teaching-intensive hospitals during these months (control group)—varied according to predicted mortality risk. We found that high-risk acute myocardial infarction patients admitted to teaching-intensive hospitals in July experienced substantial increases in mortality compared to May, whereas low-risk patients did not. Differences in rates of percutaneous coronary intervention or bleeding complications could not explain our findings. Recognition of the unique impact of resident turnover on the outcomes of high-risk patients in teaching-intensive hospitals may shape policies to improve outcomes in this vulnerable population. See p 2754.
Validation of Contrast-Enhanced Magnetic Resonance Imaging to Monitor Regenerative Efficacy After Cell Therapy in a Porcine Model of Convalescent Myocardial Infarction
Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that autologous cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium post-myocardial infarction (MI). However, the validity of contrast-enhanced MRI in characterizing tissue viability after cell therapy has been called into question. Administered cells may promote changes in vessel density or architecture that could affect gadolinium-contrast myocardial kinetics, therefore compromising the ability of MRI to distinguish scar from viable myocardium in cell-treated hearts. We tested the validity of contrast-enhanced MRI to characterize myocardial tissue viability after intracoronary infusion of allogeneic CDCs in a porcine model of convalescent MI. We find that cell therapy with CDCs neither alters gadolinium contrast myocardial kinetics, nor induces changes in vascular density or architecture in viable and scarred myocardium. Using postmortem histology as the gold standard, we demonstrate that contrast-enhanced MRI readily distinguishes viable myocardium and scar and provides accurate measurements of scar size, scar mass, and viable myocardial mass in cell-treated hearts. Microscopic analysis ruled out myocyte hypertrophy as a contributor to the increase in viable myocardium observed after CDC therapy, and revealed that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis). The present works validates MRI as a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy of cell therapy. See p 2764.
Impact of Preoperative Moderate/Severe Mitral Regur gitation on 2-Year Outcome After Transcatheter and Surgical Aortic Valve Replacement: Insight From the Placement of Aortic Transcatheter Valve (PARTNER) Trial Cohort A
Mitral regurgitation (MR) is a common finding in patients with aortic stenosis. At the time of aortic valve replacement (AVR), up to two thirds of patients with aortic stenosis have varying degrees of MR. The type of concomitant MR can be considered degenerative or functional. There is a general consensus that severe MR associated with aortic stenosis should be corrected at the time of AVR, particularly if the type is degenerative. However, the surgical management of mild to moderate MR in the setting of severe aortic stenosis remains controversial. Few studies, and with discordant results, have examined the clinical impact of preoperative MR on outcome after transcatheter aortic valve replacement (TAVR), and there are no direct comparisons between the impact of AVR and TAVR. In this study, we examined the impact of moderate and severe MR on outcomes after TAVR and AVR in cohort A of the randomized, multicenter Placement of Aortic Transcatheter Valve (PARTNER) trial. We found that improvements in symptoms and functional class, similar changes in left ventricular remodeling, and improvement in LV function were found with both TAVR and AVR, regardless of the severity of MR. However, the importance of significant MR appears to differ in patients undergoing TAVR or AVR. We reported that preoperative moderate or severe MR (mostly moderate) was associated with increased 2-year mortality after surgical AVR but not after TAVR, suggesting that TAVR may be a reasonable option in selected high-risk patients with combined aortic and mitral valve disease. See p 2776.
- © 2013 American Heart Association, Inc.
- Impact of Partner Bereavement on Quality of Cardiovascular Disease Management
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