- Analysis of Ventricular Activation Using Surface Electrocardiography to Predict Left Ventricular Reverse Volumetric Remodeling During Cardiac Resynchronization Therapy
- Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome: Results From the FINGER Brugada Syndrome Registry
- Mortality in First 5 Years in Infants With Functional Single Ventricle Born in Texas, 1996 to 2003
- Association Between Kidney Function and Albuminuria With Cardiovascular Events in HIV-Infected Persons
- Burden of Cardiovascular Risk Factors, Subclinical Atherosclerosis, and Incident Cardiovascular Events Across Dimensions of Religiosity: The Multi-Ethnic Study of Atherosclerosis
- Longitudinal Tracking of Left Atrial Diameter Over the Adult Life Course: Clinical Correlates in the Community
- Juvenile Exposure to Anthracyclines Impairs Cardiac Progenitor Cell Function and Vascularization Resulting in Greater Susceptibility to Stress-Induced Myocardial Injury in Adult Mice
- Therapeutic Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-11 Ameliorates Cardiac Fibrosis After Myocardial Infarction
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Analysis of Ventricular Activation Using Surface Electrocardiography to Predict Left Ventricular Reverse Volumetric Remodeling During Cardiac Resynchronization Therapy
Ventricular conduction delay due to left bundle branch block alters the left ventricular (LV) electric activation sequence. The resulting electric asynchrony is manifest in prolonged QRS durations due to slow myocardial conduction. This causes regional heterogeneity in contraction and stretch (mechanical asynchrony) that reduces pump function and stimulates negative LV reverse remodeling, indicated by increased LV volumes. The conceptual basis of cardiac resynchronization therapy (CRT) for asynchronous heart failure is to minimize LV conduction delay, which reduces contractile asynchrony and instantaneously improves LV mechanics. Sustained resynchronization of electromechanical activation induces “reverse” remodeling (LV volume reductions) and improved pump function (increased LV ejection fraction). Reverse LV remodeling is associated with reduced heart failure morbidity and mortality. Up to one third of CRT patients do not improve. The reasons for this are complex and incompletely characterized but can be explained by interactions between substrate conditions and pacing-induced changes in ventricular activation derived from analysis of the standard 12-lead ECG before and after CRT. Longer LV activation time and smaller LV scar volume during left bundle branch block on the baseline ECG predict higher probability of reverse remodeling. Evidence for activation wavefront fusion on the CRT-paced ECG, indicating conduction defect reversal, also predicts reverse remodeling and provides the translational mechanism for volumetric reverse remodeling. Knowledgeable application of the standard 12-lead ECG can be used to accurately predict the probability of a reverse remodeling response to CRT. See p 626.
Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome: Results From the FINGER Brugada Syndrome Registry
Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death. Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of sudden cardiac death in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. The registry included 1029 consecutive individuals (72% men). In the registry, 36% of the patients were symptomatic, and 64% were asymptomatic. The cardiac event rate per year was 7.7% in patients with aborted sudden cardiac death, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of sudden cardiac death, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. In the FINGER registry, the rate of cardiac events in the asymptomatic Brugada syndrome patients was low, and the inducibility of ventricular tachyarrhythmias during electrophysiological study did not properly stratify the arrhythmic risk. See p 635.
Mortality in First 5 Years in Infants With Functional Single Ventricle Born in Texas, 1996 to 2003
Although several postoperative outcome studies have indicated improvement in survival of functional single ventricles, none have included deaths before referral or surgery or patients lost to follow-up. This population-based study of 782 Texas liveborn infants with functional single ventricle includes deaths occurring before referral or surgery during their first 5 years of life anywhere in the United States. The overall 5-year survival for hypoplastic left heart syndrome was 38%; for pulmonary atresia with intact ventricular septum, 56%; for single ventricle, 56%; and for tricuspid atresia, 75%. Five-year survival in patients with significant extracardiac defects was 21% for hypoplastic left heart syndrome, 28% for single ventricle, 50% for pulmonary atresia with intact ventricular septum, and 58% for tricuspid atresia. For infants weighing <1500 g, mortality was 6-fold greater than for those with birth weights of ≥2500 g. The adjusted 5-year mortality for those born in 2001 to 2003 was 47% lower than for those born in 1996 to 2000, indicating a significant improvement in outcome. This study provides important data on specific risk factors affecting mortality in the first 5 years of life. Such information should enable physicians to estimate more realistically the outlook for an infant with functional single ventricle during discussions with family. See p 644.
Association Between Kidney Function and Albuminuria With Cardiovascular Events in HIV-Infected Persons
Cardiovascular disease is now a leading cause of death in HIV-infected persons. In recognition of the need to improve the quality of cardiovascular disease care in HIV infection, the American Heart Association recently convened a panel of experts to identify urgent clinical issues and research challenges facing this population. During this conference, the need to identify characteristics that will aid in cardiovascular disease risk stratification was designated as a research priority. We conducted this study to describe the association between markers of kidney disease—estimated glomerular filtration rate and albuminuria—and cardiovascular events in HIV-infected persons. To address this question, we used a national registry of HIV-infected persons receiving care in the Veterans Health Administration, which is the largest provider of HIV care in the United States. Both estimated glomerular filtration rate and albuminuria were strongly associated with the risk of incident cardiovascular disease (defined as coronary, cerebrovascular, and peripheral arterial disease) and heart failure in a graded, independent manner. In addition, both markers provided complementary prognostic information. In contrast to many novel risk factors, estimated glomerular filtration rate and albuminuria are already recommended for chronic kidney disease screening in all patients at diagnosis of HIV and annually in high-risk groups. Therefore, our findings may have immediate clinical application in aiding clinicians to risk stratify HIV-infected persons for future cardiovascular events and provide rationale for interventional studies aimed at treatment of kidney disease or reduction of albuminuria. See p 651.
Burden of Cardiovascular Risk Factors, Subclinical Atherosclerosis, and Incident Cardiovascular Events Across Dimensions of Religiosity: The Multi-Ethnic Study of Atherosclerosis
A variety of behaviors can benefit or harm one’s cardiovascular health, and it has been observed that religious beliefs and practices may influence one’s health behaviors significantly. We sought to determine whether and to what extent different aspects of religiosity may be associated with cardiovascular health. Using a large, ethnically diverse, community-based sample of men and women ages 45 to 84 years who were asymptomatic at baseline, we compared the prevalence of cardiovascular risk factors, the presence and burden of subclinical cardiovascular disease, and the incidence of cardiovascular events across different levels of religiosity. We adjusted for sociodemographic factors to ensure that these potential confounders were not responsible for associations found between religion and cardiovascular health. We observed that those who attended services frequently and those who prayed frequently were significantly less likely to smoke than those who never attended services or prayed. Perhaps more surprisingly, we found that frequent service attendees and those who prayed often were significantly more likely to be obese. We did not observe any significant associations between religiosity and presence/extent of subclinical disease or incident cardiovascular events. The consistent and significant association found between religiosity and obesity in this cross-sectional study raises some interesting questions. What is the temporal nature of the association? If being more religious makes one more likely to be obese, then why does this occur? Ultimately, this observation should encourage interaction between healthcare providers, public health officials, and the religious community in an effort to improve obesity education and prevention. See p 659.
Longitudinal Tracking of Left Atrial Diameter Over the Adult Life Course: Clinical Correlates in the Community
Preventing atrial fibrillation (AF) is a public health priority in light of the high lifetime risk for this condition, the projected increase in population burden, and the substantial morbidity and mortality associated with the disease. Increased left atrial diameter (LAD), a marker of left atrial remodeling, is associated with elevated risk of AF (new onset and recurrent). This association has led to the hypothesis that increased LAD may represent an intermediate phenotype in the progression from risk factors to AF, especially in older individuals. Information is limited, however, on short- and long-term clinical correlates of LAD across the adult life course. In this investigation of a large, community-based sample, we used multilevel modeling to evaluate correlates of LAD during a 16-year period and also related these risk factors to short-term change in LAD (during a 4-year period). We identified higher blood pressure and greater body mass index as key correlates of both short-term LAD change and long-term tracking of LAD. Using sex-specific growth curves for LAD, we also observed that LAD at baseline and over time was positively associated with greater risk factor burden. The results of our study suggest that maintenance of optimal levels of blood pressure and body mass during adulthood may be critical for preventing atrial remodeling and AF. See p 667.
Juvenile Exposure to Anthracyclines Impairs Cardiac Progenitor Cell Function and Vascularization Resulting in Greater Susceptibility to Stress-Induced Myocardial Injury in Adult Mice
Anthracyclines such as doxorubicin are effective chemotherapeutic agents used for treatment of many cancers. Unfortunately, their clinical use is limited by the risk of severe cardiotoxicity and heart failure that may not manifest until years later. Anthracyclines are of special concern in pediatric oncology because the youngest children are at the greatest risk of developing late-onset cardiotoxicity. In this study, we present the first evidence that anthracycline exposure in juvenile mice reduces the size of the cardiac progenitor pool, impairs their ability to differentiate into cells of cardiac and vascular lineages, and adversely affects vascular development in the heart. Despite normal development and hemodynamic function as adults, these mice develop rapid heart failure in response to physiological or pathological stress. This animal model recapitulates many of the features of late-onset anthracycline toxicity in humans and explains why younger children, who have more dividing progenitor cells, are more vulnerable. Our findings suggest that anthracycline-mediated effects on the progenitor cells might underlie the reduced ability to accomplish physiological hypertrophy as well as cardiac repair and neovascularization. Injection of stem cell mobilizing factors has been shown to enhance migration of bone marrow cells to the heart and to attenuate acute doxorubicin cardiotoxicity. The therapeutic potential of progenitor cells has been demonstrated in animal models in which successful engraftment of progenitor cells improved left ventricular function after myocardial infarction. If progenitor cells are required for neovascularization accompanying physiological hypertrophy or repair, then stem cell mobilization or replacement may ameliorate late-onset heart failure due to anthracyclines. See p 675.
Therapeutic Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-11 Ameliorates Cardiac Fibrosis After Myocardial Infarction
In ischemic heart diseases, myocardial damage is initially induced by reduction of blood supply and is subsequently expanded by cardiac remodeling, leading to heart failure. A therapeutic strategy to limit myocardial remodeling, such as angiotensin-converting enzyme inhibitors and β-blockers, improves the survival rate; however, the prognosis of heart failure is still not satisfactory. Cardiac remodeling is positively or negatively regulated by a number of neurohumoral factors and cytokines. Here, we examined whether interleukin (IL)-11, a member of the IL-6 family of cytokines, ameliorates postinfarct remodeling, using a model of myocardial infarction by coronary ligation. Treatment with IL-11 reduced fibrosis after myocardial infarction, with attenuation of myocardial dysfunction. IL-11 decreased the frequency of cardiomyocyte death and increased capillary density. IL-11 treatment resulted in STAT3 activation in cardiomyocytes in vivo. Using conditional knockout mice and cardiac-specific transgenic mice, we demonstrated that activation of STAT3 in cardiomyocytes was necessary and sufficient for IL-11–mediated prevention of cardiac adverse remodeling. These findings suggest that IL-11 treatment may be useful as a therapeutic strategy against the onset of heart failure after myocardial infarction. Because human recombinant IL-11, oprelvekin, is clinically used for thrombocytopenia, with a tolerable level of adverse drug effects providing some proof of its safety, our results suggest that IL-11 treatment is a promising novel cytokine therapy for prevention against heart failure. See p 684.
- Mortality in First 5 Years in Infants With Functional Single Ventricle Born in Texas, 1996 to 2003
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