Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Type A Aortic Dissection After Nonaortic Cardiac Surgery
- β1-Adrenergic Receptor and Sphingosine-1-Phosphate Receptor 1 (S1PR1) Reciprocal Downregulation Influences Cardiac Hypertrophic Response and Progression to Heart Failure: Protective Role of S1PR1 Cardiac Gene Therapy
- The Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Nonischemic Dilated Cardiomyopathy
- Impact of Appropriate Use on the Prognostic Value of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging
- Function and Distribution of Apolipoprotein A1 in the Artery Wall Are Markedly Distinct From Those in Plasma
- Early Dual Versus Mono Antiplatelet Therapy for Acute Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack: An Updated Systematic Review and Meta-Analysis
- Relationship Between the Magnitude of Reduction in Mitral Regurgitation Severity and Left Ventricular and Left Atrial Reverse Remodeling After MitraClip Therapy
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Type A Aortic Dissection After Nonaortic Cardiac Surgery
Nonaortic cardiac surgery is associated with a low but significant incidence of type A aortic dissection (AAD). Because there are important differences in clinical presentation, surgical management, and prognosis between spontaneous and late AAD following cardiac surgery, this large multicenter study sought to determine the conditions associated with the high surgical mortality of AAD repair as a complication of nonaortic cardiac surgery and to identify management pathways to improve outcome. We found that operative mortality depends on the type of initial surgery, time to AAD, and, importantly, influenceable management factors. AAD occurred mainly in patients with preexisting aortic wall pathology, identifiable with a slightly enlarged aorta, and hypertension at sites of iatrogenic mechanical trauma. This finding emphasizes most careful surgical handling and potentially a low threshold for prophylactic replacement of the ascending aorta that is without additional operative risk in experienced centers. Diagnosis of AAD warrants a mandatory high index of suspicion and depends primarily on imaging. The majority of patients with previous cardiac surgery had no or nonspecific symptoms when AAD was detected. The single most important factor that was associated with a lower operative mortality was implementation of preoperative coronary angiography and appropriate operative management of CAD and graft disease in patients with previous CABG. Because cardiac tamponade and hemodynamic instability are rare (1%), patients with previous cardiac surgery in stable condition should undergo preoperative native coronary and graft status assessment and appropriate operative planning, including aggressive revascularization and the use of deep hypothermic cardiac arrest. See p 1602.
β1-Adrenergic Receptor and Sphingosine-1-Phosphate Receptor 1 (S1PR1) Reciprocal Downregulation Influences Cardiac Hypertrophic Response and Progression to Heart Failure: Protective Role of S1PR1 Cardiac Gene Therapy
In chronic heart failure (HF), sympathetic nervous system overdrive induces the upregulation of G-protein–coupled receptor kinase 2 (GRK2) with a consequent β-adrenergic receptor downregulation/desensitization. Importantly, in failing myocardium, β-adrenergic receptor dysregulation is clinically seen by loss of inotropic reserve. Currently, β-blockers represent a solid “pillar” of HF therapy that at the molecular level efficiently counteracts both β-adrenergic receptor downregulation and GRK2 upregulation. GRK2 inhibition represents a promising new strategy to rescue the failing heart, and we have recently demonstrated that in some animal models, it could be used as a substitute for or in conjunction with β-blockers. GRK2 inhibition may be effective by interfering with other intracellular processes. The present study provides the first evidence of a direct and GRK2-dependent interaction between the β1-adrenergic receptor and the sphingosine-1-phosphate receptor 1 (S1PR1). We show that the reciprocal downregulation between these 2 predominant G-protein–coupled receptors in the heart appears to have significant physiological effects on cardiac hypertrophy, apoptosis, and remodeling. Clinically, HF-related S1PR1 downregulation worsens left ventricular dysfunction in a setting of established myocardial damage. We show that the increase of S1PR1 density, through gene therapy, in failing cardiomyocytes may represent a novel therapeutic strategy for HF. This study clearly opens a new chapter in the understanding of the molecular mechanisms involved in HF, demonstrating that besides the well-documented therapeutic effects of β-adrenergic receptor signaling “resensitization” in HF via GRK2 inhibition or β-blockade, a new field of research could be the reconstitution of S1PR1 cardioprotective signaling as a new therapeutic target along with other unexplored signaling pathways. See p 1612.
The Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Nonischemic Dilated Cardiomyopathy
Risk stratification in dilated cardiomyopathy focuses primarily on the assessment of left ventricular ejection fraction, with the result that the role of right ventricular systolic dysfunction (RVSD) in prognostication has been relatively neglected. Cardiovascular magnetic resonance (CMR) is the gold-standard imaging modality for the assessment for right ventricular ejection fraction. However, to date, there has been no dedicated CMR study of the prognostic value of RVSD in either general or specific heart failure populations. In the present study, we evaluate the prevalence and prognostic significance of RVSD in a contemporary cohort of 250 patients with dilated cardiomyopathy, who were accurately characterized by late gadolinium enhancement CMR and exhibited a broad spectrum of phenotypic severity. CMR provided high inter- and intraobserver reproducibility for right ventricular ejection fraction measurement. RVSD, defined by right ventricular ejection fraction ≤45%, was present in approximately one-third of the patients. Over a median follow-up of 6.8 years, RVSD was an independent predictor of transplant-free overall survival, transplant-free cardiovascular survival, and major heart failure events. The prognostic value of RVSD was incremental to other significant risk predictors that included left ventricular parameters and midwall fibrosis. The assessment of right ventricular ejection fraction therefore offers additive prognostic information beyond other CMR measures, further enriching the prognostic armory of CMR in dilated cardiomyopathy. These findings add to the growing body of evidence that supports the routine application of CMR for the detailed phenotypic characterization and prognostic assessment of patients with dilated cardiomyopathy. See p 1623.
Impact of Appropriate Use on the Prognostic Value of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging
Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a mainstay of risk assessment for ischemic heart disease. The expansion of MPI use prompted the development of appropriate use criteria to guide physicians on optimal implementation of SPECT-MPI in patient care. The impact of appropriateness of use on the prognostic value of stress MPI has never been evaluated. In this prospective, community-based, cohort study, we followed up for >2 years 1511 patients who were classified according to the 2009 appropriate use criteria. Among subjects with MPI classified as appropriate or uncertain, abnormal scans predicted a multifold increase in the rates of death, death or myocardial infarction, cardiac death or myocardial infarction, and revascularization procedures. However, among subjects with MPI classified as inappropriate, abnormal MPI failed to predict major adverse cardiac events, although it was associated with a high revascularization rate. Appropriate MPI use provided an incremental prognostic value beyond myocardial perfusion and ejection fraction. We concluded that the inappropriate use of SPECT-MPI severely impairs its value for risk assessment and negatively impacts cost-effectiveness. However, when performed for appropriate indications, SPECT-MPI maintains its robust prognostic value. This report describes the first prognostic validation of the appropriate use criteria for SPECT-MPI, thus solidifying their role in clinical practice, policy making, and reimbursement decisions. See p 1634.
Function and Distribution of Apolipoprotein A1 in the Artery Wall Are Markedly Distinct From Those in Plasma
Much of what is known about apolipoprotein A1 (apoA1) and high-density lipoprotein (HDL) comes from investigations using isolated HDL particles from the circulation with the use of buoyant density ultracentrifugation and not from HDL or apoA1 directly recovered from the human artery wall. A longstanding assumption is that measurement of circulating HDL cholesterol, apoA1, or even cholesterol efflux activity provides insights into biological processes relevant within the artery wall. ApoA1 recovered from human atherosclerotic lesions, however, is known to be highly oxidized, and ex vivo oxidation of apoA1 or HDL to an extent comparable to that observed in vivo both cross-links apoA1 and inhibits cholesterol efflux and lecithin-cholesterol acyltransferase activities of the lipoprotein. Herein we directly examined the function and distribution of apoA1 recovered from normal and atherosclerotic plaque-laden human aorta. Remarkably, the distribution and function of apoA1 in the artery wall were markedly distinct from those observed within the circulation. First, apoA1 was 100-fold enriched within atherosclerotic plaque compared with normal arterial tissue. Furthermore, arterial wall apoA1 was predominantly lipid-poor, not associated with HDL, extensively oxidatively cross-linked, and functionally impaired with respect to both cholesterol efflux and lecithin-cholesterol acyltransferase activities. Collectively, these findings argue that circulating levels of HDL cholesterol, HDL particles, or apoA1 inadequately reflect apoA1 biology within the artery wall. Instead, our findings suggest that examination of circulating lipid-poor apoA1 forms or detection of structurally specific oxidatively modified forms of apoA1 may better reflect processes important within the vessel wall and for rendering HDL dysfunctional. See p 1644.
Early Dual Versus Mono Antiplatelet Therapy for Acute Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack: An Updated Systematic Review and Meta-Analysis
Ischemic stroke and transient ischemic attack are common problems in clinical practice and, typically, treated with aspirin. However, the results of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) study (5170 patients, comparison of aspirin/clopidogrel versus aspirin alone) showed that the combination of antiplatelet therapies is superior for stroke prevention without a significant increase in bleeding. Building on these single-country findings, this updated systematic review and meta-analysis suggests that the results of the CHANCE study are consistent with previous studies done in other parts of the world. These findings, although suggestive of dual antiplatelet treatment for ischemic stroke and transient ischemic attack, need to be repeated in prospective/randomized trials to confirm their utility in a broader population. See p 1656.
Relationship Between the Magnitude of Reduction in Mitral Regurgitation Severity and Left Ventricular and Left Atrial Reverse Remodeling After MitraClip Therapy
Few data exist on the magnitude of mitral regurgitation (MR) reduction necessary to reverse left ventricular (LV) and left atrial (LA) dilation in patients with severe MR. MitraClip offers a unique ability to analyze such data because, unlike mitral valve surgery, it often leaves residual MR of varying degrees. This analysis was performed to evaluate the relationship between MR reduction and LV and LA volumes after MitraClip therapy. A total of 801 patients treated with MitraClip in the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) II randomized trial, a high-risk registry of poor operative candidates, and a continued access registry were evaluated. In addition, 80 patients treated surgically in EVEREST II were included as a comparator. MR severity, LV volumes at end-diastole and end-systole and LA volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an independent echochardiographic core laboratory. A linear repeated measures model was developed to determine the relationship between MR severity and time of measurement postindex procedure on longitudinal LV and LA volumes. Separate models were fit for functional and degenerative MR. In both degenerative and functional MR, reduction in LV volume at end-diastole was associated with degree of residual MR at 12 months (P<0.0001). LV volume at end-systole was significantly reduced in functional MR but not degenerative MR. LA volumes were significantly related to MR reduction in both groups. These findings demonstrate that reverse LV and LA remodeling occur whether MR is reduced to 1+ or 2+ by MitraClip therapy. See p 1667.
- © 2013 American Heart Association, Inc.
- Type A Aortic Dissection After Nonaortic Cardiac Surgery
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