Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Rhythm Versus Rate Control Therapy and Subsequent Stroke or Transient Ischemic Attack in Patients With Atrial Fibrillation
- Fetal Heart Rate Predictors of Long QT Syndrome
- Randomized Comparison of Sevoflurane Versus Propofol to Reduce Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery
- Relationship Between Healthy Diet and Risk of Cardiovascular Disease Among Patients on Drug Therapies for Secondary Prevention: A Prospective Cohort Study of 31 546 High-Risk Individuals From 40 Countries
- Prognosis of Individuals With Asymptomatic Left Ventricular Systolic Dysfunction in the Multi-Ethnic Study of Atherosclerosis (MESA)
- Comprehensive Annular and Subvalvular Repair of Chronic Ischemic Mitral Regurgitation Improves Long-Term Results With the Least Ventricular Remodeling
- Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib
- Effects of Interleukin-1β Inhibition With Canakinumab on Hemoglobin A1c, Lipids, C-Reactive Protein, Interleukin-6, and Fibrinogen: A Phase IIb Randomized, Placebo-Controlled Trial
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Rhythm Versus Rate Control Therapy and Subsequent Stroke or Transient Ischemic Attack in Patients With Atrial Fibrillation
Despite anticoagulation, stroke remains a complication of atrial fibrillation. Several randomized controlled trials have compared rate and rhythm control approaches in patients with atrial fibrillation and demonstrated a similar impact on mortality, but most trials had inadequate sample size to assess their relative effect on stroke outcome. In the current observational study, we compared the rates of stroke/transient ischemic attack in patients treated with rhythm (n=16 325) or rate (n=41 193) control strategies in a large population-based cohort of patients with recently diagnosed atrial fibrillation. Crude stroke/ transient ischemic attack incidence in the rhythm control group was 1.74 per 100 person-years in comparison with 2.49 in the rate control group (P<0.001). Although at baseline, patients receiving rhythm control therapy had fewer risk factors for stroke in comparison with patients receiving rate control therapy, the association between rhythm control treatment and lower stroke rates remained after multivariate analysis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87) and propensity score analysis (adjusted hazard ratio, 0.77; 95% confidence interval, 0.68, 0.87), which balanced patients' characteristics between groups. Once stratified by CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or transient ischemic attack) score, the rhythm control group had a lower stroke risk than the rate control group only for patients with high- and moderate-risk CHADS2 scores. The results of this study provide additional information to guide clinicians' choice of treatment strategy by considering the outcome of stroke. This study may stimulate future large randomized trials comparing the effectiveness of rhythm versus rate control strategies on the risk of stroke and emphasizes the need for the development of new therapies for atrial fibrillation. See p 2680.
Fetal Heart Rate Predictors of Long QT Syndrome
Long QT syndrome (LQTS) may be as common as 1/2500 individuals, yet fewer than 100 cases have been recognized during fetal life. Fetal torsades de pointes and 2° AV block are easily attributed to LQTS. However, these complex arrhythmias are present in only 25% of fetal LQTS; the majority of LQTS fetuses have asymptomatic bradycardia that may not be recognized as an LQTS marker due to its subtle features. The standard obstetrical definition of bradycardia is fetal heart rate (FHR) ≤ 110 bpm. To improve recognition of perinatal LQTS we evaluated the FHR/gestational age (GA) relationship of fetal LQTS mutations versus a normal control group. We found GA dependent FHR predictors of LQTS; for example, when compared to a FHR of 110 bpm at any GA, a FHR ≤3rd percentile for GA improves ascertainment of LQTS subjects from 15 to 85%. Fetuses with the lowest FHR tended to have de novo and genetically elusive LQTS mutations, and in addition to bradycardia, also manifested complex LQTS rhythms. Identification of LQTS in the fetus with a heart rate of <3rd also led to diagnosis of LQTS in unsuspecting family members. Thus, postnatal evaluation of individuals with a FHR ≤3rd percentile for GA improves ascertainment of LQTS both before and after birth. See p. 2688.
Randomized Comparison of Sevoflurane Versus Propofol to Reduce Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery
On the basis of promising evidence in patients undergoing on-pump coronary artery bypass graft surgery, the American College of Cardiology/American Heart Association guidelines recommend the use of volatile anesthetics as beneficial in hemodynamically stable patients at cardiovascular risk undergoing noncardiac surgery (class IIa recommendation). In the present randomized, controlled trial, anesthesia maintenance with sevoflurane compared with propofol did not reduce the incidence of perioperative myocardial ischemia in patients with coronary artery disease or at risk for it undergoing major noncardiac surgery. In addition, the data did not suggest any effect of sevoflurane on postoperative N-terminal prohormone of brain natriuretic peptide release or on major adverse cardiac events at 12 months. These results are in agreement with observational data and data generated in a small randomized trial. This growing evidence questions the recommendation to preferentially use volatile anesthetics in noncardiac surgical patients at cardiac risk. See p 2696.
Relationship Between Healthy Diet and Risk of Cardiovascular Disease Among Patients on Drug Therapies for Secondary Prevention: A Prospective Cohort Study of 31 546 High-Risk Individuals From 40 Countries
Although healthy diets have been shown to be associated with a lower risk of cardiovascular disease (CVD) in populations without prior CVD, much less is known about those with established CVD. We studied the association between overall diet quality and the recurrence of CVD among 31 546 individuals (age, 66.5± 6.2 years) with a history of CVD enrolled in 2 randomized trials, the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects With Cardiovascular Disease (TRANSCEND), from 40 middle- and high-income countries. A healthy diet consisted of high intake of fruits, vegetables, whole grains, nuts, and fish relative to meat and eggs. A graded association between diet quality and recurrence of CVD events across all regions and various income levels and across different categories of risk factors and comorbidities was observed. These associations were observed in people receiving proven drug therapies for secondary prevention, suggesting that the benefits of dietary modifications were in addition to those from the medications. These data suggest that at least 20% recurrence of CVD could be avoided by adhering to a healthy diet. Highlighting the importance of healthy eating by health professionals and advising high-risk individuals to improve their diet quality would substantially reduce CVD recurrence beyond drug therapy alone and save lives globally. See p 2705.
Prognosis of Individuals With Asymptomatic Left Ventricular Systolic Dysfunction in the Multi-Ethnic Study of Atherosclerosis (MESA)
Individuals with congestive heart failure still endure high morbidity and mortality despite recent advances in management. Studies have shown that early identification and treatment of individuals with the asymptomatic phase of heart failure could slow the progression to the symptomatic phase and reduce subsequent morbidity and mortality. However, data on the prevalence and prognosis of individuals with asymptomatic left ventricular systolic dysfunction (ALVSD) are limited. The few available data included ALVSD individuals with known myocardial infarction, a subgroup who most likely have had contact with healthcare professionals and have been prescribed the needed therapy. The public health impact of screening for this subgroup of ALVSD is likely to be of limited value. The present study used a large multiethnic cohort, free of clinical cardiovascular disease including myocardial infarction to show that ALVSD is uncommon (prevalence of 1.7%). This low prevalence, however, translates into several hundred thousand, if not millions of community-dwelling Americans. The highest prevalence was in blacks (2.6%) and the least in Chinese Americans (0.15%). Black men with hypertension had the highest prevalence of ALVSD. The risk of developing congestive heart failure was ≈9 times higher in individuals with ALVSD in comparison with those without ALVSD after 9 years of follow-up. Individuals with ALVSD were about twice as likely to die or develop a cardiovascular event as those without ALVSD during the follow-up period. Current debate and more research should focus on how best to screen for ALVSD in individuals without clinical cardiovascular disease, because our data suggest that these individuals are at higher risk for congestive heart failure, cardiovascular disease events, and all-cause mortality. See p 2713.
Comprehensive Annular and Subvalvular Repair of Chronic Ischemic Mitral Regurgitation Improves Long-Term Results With the Least Ventricular Remodeling
Chronic ischemic mitral regurgitation (MR) remains one of the most complex and unresolved aspects in the management of ischemic heart disease. Restrictive annuloplasty, combined with coronary revascularization, is currently the most commonly performed surgical procedure to treat chronic ischemic MR. However, the variable results, the potentially induced mitral stenosis, and the high rate of MR recurrence after this strategy create the need for a new approach that involves the subvalvular mitral valve apparatus. We previously demonstrated the efficacy of mitral valve leaflet chordal cutting in reducing chronic ischemic MR and left ventricular remodeling in an experimental model along with clinical applications. Chordal cutting, by decreasing the apical leaflet tenting, improves coaptation and decreases MR. Because the leaflet tethering is applied at both annular and papillary muscle levels, we conducted an experimental ovine study using our model of chronic ischemic MR to evaluate the potential benefit of associating undersized ring annuloplasty with chordal cutting versus each technique alone. Our results seem to demonstrate that cutting the secondary chordae associated with undersized annuloplasty in the chronic post–myocardial infarction setting improves the long-term results, with almost a disappearance of ischemic MR along with a regression of chronic left ventricular remodeling. We believe that this physiological therapeutic approach will have the potential to improve mitral valve repair results in the chronic ischemic MR setting and will provide an opportunity in the near future for a more tailored personal approach of mitral valve repair in the case of ischemic MR. See p 2720.
Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib
Endothelial barrier dysfunction is a major contributor to morbidity and mortality in the critically ill. Loss of the endothelial barrier follows exposure of the endothelium to inflammatory mediators and drives vascular leakage and edema formation. To date endothelial barrier function and vascular leakage still lack appropriate therapy. This study shows that imatinib—an US Food and Drug Administration–approved tyrosine kinase inhibitor—directly protects the endothelial barrier under inflammatory conditions. With the use of endothelial cells isolated from various vascular beds, it was shown that imatinib attenuates the loss of endothelial barrier on stimulation with inflammatory mediators. Imatinib protects against endothelial barrier dysfunction predominantly by inhibition of the tyrosine kinase Abl-related gene (Arg), a novel mediator of endothelial barrier disruption. The effect of imatinib on endothelial barrier was established in various mouse models of vascular leakage. Notably, imatinib attenuated vascular leakage in a murine model of sepsis, even when imatinib treatment was initiated considerable time after induction of sepsis. This study carries important clinical implications. First, imatinib may form a suitable therapy for treatment of diseases characterized by vascular leakage. The longstanding experience with imatinib, together with the fact that imatinib concentrations used in this study parallel plasma values in cancer patients, are apparent advantages in this case. Logical first steps in further development of imatinib involve Phase I and II trials to evaluate safety and efficacy of imatinib in patients with profound vascular leakage. Second, the identification of Arg as a novel and drugable target opens perspectives for more specific pharmaceutical interventions. See p 2728.
Effects of Interleukin-1β Inhibition With Canakinumab on Hemoglobin A1c, Lipids, C-Reactive Protein, Interleukin-6, and Fibrinogen: A Phase IIb Randomized, Placebo-Controlled Trial
Atherosclerosis in an inflammatory condition, and biomarkers of inflammation including CRP, IL-6, and fibrinogen associate with increased vascular risk. However, whether inhibiting inflammation will reduce vascular events is uncertain. One promising anti-inflammatory approach with potential relevance for cardiovascular disease is inhibition of the proinflammatory cytokine IL-1, particularly the IL-1β isoform that is secreted and acts locally but that also induces systemic effects. In a phase IIb randomized trial conducted among high-risk diabetic patients comparing placebo with canakinumab, a monoclonal antibody targeting IL-1β, we observed statistically significant dose-dependent reductions in all 3 of these inflammatory biomarkers without major effect on LDL-C or HDL-C. There were no differences in clinical adverse events between active and placebo patients, although a small increase in triglycerides was observed at higher canakinumab doses. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis. Indeed, in part on the basis of these data, a large-scale multinational hard outcomes trial, CANTOS, is being conducted that will address directly whether inhibition of IL-1β with canakinumab can reduce recurrent vascular event rates in a high-risk secondary prevention population. See p 2739.
- © 2012 American Heart Association, Inc.
- Fetal Heart Rate Predictors of Long QT Syndrome
- Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib
- Info & Metrics