Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Missense Mutations in Plakophilin-2 Cause Sodium Current Deficit and Associate With a Brugada Syndrome Phenotype
- Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) Study
- Application of the American Heart Association/American College of Sports Medicine Adult Preparticipation Screening Checklist to a Nationally Representative Sample of US Adults Aged ≥40 Years From the National Health and Nutrition Examination Survey 2001 to 2004
- Sodium Excretion and Risk of Developing Coronary Heart Disease
- Comparison of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease From the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) Trial
- Histone Deacetylase Inhibition Blunts Ischemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy
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Missense Mutations in Plakophilin-2 Cause Sodium Current Deficit and Associate With a Brugada Syndrome Phenotype
Brugada syndrome (BrS) is an inherited arrhythmogenic disease primarily associated with loss of sodium channel function. Arrhythmogenic cardiomyopathy (also called arrhythmogenic right ventricular cardiomyopathy) is mostly consequent to mutations in desmosomal proteins. Although early studies proposed that these 2 diseases shared common features, BrS and arrhythmogenic cardiomyopathy have been defined as 2 separate entities. Recent evidence, however, showed that reduced expression of plakophilin-2 (PKP2), a desmosomal protein, leads to sodium channel dysfunction. We thus proposed that some cases of BrS may associate with PKP2 mutations. Here, we report missense mutations in the gene coding for PKP2 in 5/200 patients with a diagnosis of BrS and no identified mutations in genes coding for sodium or calcium channels. Cellular and molecular analysis involving a cell expression system (HL-1 cells), and induced pluripotent stem cell cardiomyocytes from a patient with arrhythmogenic cardiomyopathy, as well, revealed decreased sodium current amplitude in cells expressing the mutations. Additional studies led us to propose that PKP2 is necessary for the delivery of sodium channels to the intercalated discs by the microtubule network. Overall, this is the first evidence that mutations in PKP2 can associate with 2 different phenotypes, BrS and arrhythmogenic cardiomyopathy, reconciling the hypothesis that they represent 2 poles of a common spectrum of manifestations. Data need confirmation in independent cohorts of patients before routine screening for PKP2 variants in BrS patients is recommended. Yet, in the presence of a negative genotype, it seems reasonable to consider the possibility that clinically affected patients may harbor PKP2 mutations. See p 1092.
Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) Study
Patients with chronic kidney disease requiring myocardial revascularization represent a challenging group often affected by multivessel disease and complex coronary lesions. Percutaneous coronary interventions in these patients have shown suboptimal results. Indeed, given the multiple concomitant individual variables present in such patients, the comparison of neointimal growth after percutaneous coronary interventions is complex and difficult to assess. The Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) study is the first prospective, randomized, multicenter study aimed to directly compare the efficacy in the prevention of clinical restenosis of a new-generation everolimus-eluting stent (Xience V) and bare-metal stent with identical design (Multi-Link Vision), both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease. The use of an intraindividual design allows obviation for the multiple and unpredictable potential baseline differences of this complex population. Our study shows that the incidence of ischemia-driven target vessel revascularization is significantly lower in drug-eluting stents in comparison with the bare-metal stent group at 1 year. Interestingly, the different ischemia-driven target vessel revascularization rate in favor of drug-eluting stents in comparison with bare-metal stent was consistent among different grades of renal dysfunction. See p 1104.
Application of the American Heart Association/American College of Sports Medicine Adult Preparticipation Screening Checklist to a Nationally Representative Sample of US Adults Aged ≥40 Years From the National Health and Nutrition Examination Survey 2001 to 2004
Among adults aged >40 years, coronary artery disease is the most common underlying pathology in cases of exercise-associated sudden cardiac death. Accordingly, preparticipation screening among this demographic usually centers on cardiovascular disease history, symptoms, and risk factors. The present results suggest that, among US adults aged ≥40 years, an endorsed self-screening tool would result in recommended preexercise physician consultations for 95.5% of women and 93.5% of men. The high referral proportions were likely attributed to a broad range of questions with high proportions of affirmative responses. The clinical ramifications of such a high referral proportion could include increased burden on the healthcare system and the erection of an additional barrier to exercise participation, despite a lack of evidence that preparticipation physician consultation improves exercise safety. The present results were used to support a revision focused on positive history and current symptoms of cardiovascular disease, as well as known but untreated high blood pressure. The revised tool resulted in referral proportions of 70.7% for women and 60.4% for men, which better matched those of the Physical Activity Readiness Questionnaire, a previously validated screening tool. See p 1113.
Sodium Excretion and Risk of Developing Coronary Heart Disease
The health effects of dietary sodium have generated considerable interest and debate in the public and healthcare community. Despite compelling evidence for sodium’s adverse effects on blood pressure and risk of stroke, it remains uncertain whether excess sodium intake is a risk factor for coronary heart disease (CHD). In a prospective cohort study of nearly 8000 Dutch men and women, sodium excretion was measured in two 24-hour urine collections (considered the gold standard to assess sodium intake). The median 24-hour sodium excretion was 137 mmol, approximately equivalent to an intake of 8.4 g/d of sodium chloride or 3.3 g/d of sodium after accounting for nonurinary loss (for comparison, the American Heart Association recommends a sodium intake of <1.5 g/d). During a median follow-up of 10.5 years, 452 CHD events occurred. In the entire cohort, sodium excretion was not associated with risk of CHD. However, the association between sodium excretion and CHD risk was modified by plasma N-terminal pro-B-type natriuretic peptide, a marker of myocardial stretch and volume overload, and tended to be modified by blood pressure. In subjects with high N-terminal pro-B-type natriuretic peptide or with hypertension, each 1-g/d increment in sodium excretion was associated with a 16% and 14% increased CHD risk, respectively. These results are in line with the notion that excess sodium intake is associated with an increased risk of CHD, particularly among vulnerable groups who constitute a large portion of the population. See p 1121.
Comparison of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease From the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) Trial
The primary outcome analysis of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) trial has been described as a landmark study and thus may change the way coronary artery disease is investigated and may be incorporated into future clinical guidelines. These findings are relevant and of interest to all cardiologists and general physicians who are involved in the management of patients with coronary artery disease. However, it is well recognized that there are important sex-specific issues related to the diagnosis and management of coronary artery disease and that women are underrepresented in clinical trials. Despite the widespread use of single-photon emission computed tomography in women with suspected coronary artery disease, there is increasing concern about its diagnostic accuracy, perceived wisdom being that this relates in part to breast attenuation artifacts. This sex-specific analysis of the CE-MARC trial represents the largest prospective series of women evaluated by cardiovascular magnetic resonance compared with single-photon emission computed tomography, all with invasive coronary angiography. In addition to demonstrating superior diagnostic accuracy of cardiovascular magnetic resonance over single-photon emission computed tomography in women, we have provided insight into the reasons. It appears that the diagnostic limitation for single-photon emission computed tomography relates more to its inherent lower spatial resolution than to breast attenuation, as is the current belief. See p 1129.
Histone Deacetylase Inhibition Blunts Ischemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy
Coronary artery disease is the leading cause of heart failure that stems from reduced contractile performance of the heart. In this setting, reduced blood flow to the heart (ischemia) is typically followed by reperfusion, when the infarct-related artery recannulates, either spontaneously or in response to therapeutic intervention. This event, which restores oxygen and nutrients to the injured tissue, triggers a complex cascade of events and a second wave of injury. Indeed, cell death occurring during reperfusion is a major contributor to infarct size, approaching 50% of total injury burden. Yet, no standard therapies are available targeting reperfusion injury. We report that suberoylanilide hydroxamic acid, a histone deacetylase inhibitor approved by the US Food and Drug Administration for cancer treatment, reduces myocardial infarct size in a large-animal model, specifically by blunting reperfusion injury. Reactivation of ischemia/reperfusion–triggered downregulation of the intracellular protein recycling pathway, autophagy, is a major underlying mechanism. We submit that this therapeutic strategy holds promise in addressing the global scourge of ischemic cardiovascular disease. See p 1139.
- © 2014 American Heart Association, Inc.
- Sodium Excretion and Risk of Developing Coronary Heart Disease
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