BACKGROUND:

Recent data suggest that aspirin may be effective for reducing cancer mortality.

OBJECTIVE:

To examine whether including a cancer mortality-reducing effect influences which men would benefit from aspirin for primary prevention.

DESIGN:

We modified our existing Markov model that examines the effects of aspirin among middle-aged men with no previous history of cardiovascular disease or diabetes. For our base case scenario of 45-year-old men, we examined costs and life-years for men taking aspirin for 10 years compared with men who were not taking aspirin over those 10 years; after 10 years, we equalized treatment and followed the cohort until death. We compared our results depending on whether or not we included a 22 % relative reduction in cancer mortality, based on a recent meta-analysis. We discounted costs and benefits at 3 % and employed a third party payer perspective. MAIN MEASURE: Cost per quality-adjusted life year (QALY) gained. KEY

RESULTS:

When no effect on cancer mortality was included, aspirin had a cost per QALY gained of $22,492 at 5 % 10-year coronary heart disease (CHD) risk; at 2.5 % risk or below, no treatment was favored. When we included a reduction in cancer mortality, aspirin became cost-effective for men at 2.5 % risk as well (cost per QALY, $43,342). Results were somewhat sensitive to utility of taking aspirin daily; risk of death after myocardial infarction; and effects of aspirin on stroke, myocardial infarction, and sudden death. However, aspirin remained cost-saving or cost-effective (< $50,000 per QALY) in probabilistic analyses (59 % with no cancer effect included; 96 % with cancer effect) for men at 5 % risk.

CONCLUSIONS:

Including an effect of aspirin on cancer mortality influences the threshold for prescribing aspirin for primary prevention in men. If such an effect is real, many middle-aged men at low cardiovascular risk would become candidates for regular aspirin use.

The authors hypothesized that prospective, systematic Internet searches could identify occurrences of sudden cardiac death (SCD) in athletes and would be useful for establishing a system of active surveillance. Weekly advanced Google searches of the Internet were conducted for cases of SCD in young athletes during a 12-month period (2007-2008). Athletes ages 11-30 years who collapsed during a game, practice, or within an hour of exercise were included in the study. Individuals with known histories of cardiac issues and events occurring outside the United States were excluded. Verification of SCD was by autopsy reports and death certificates from county coroner offices and vital record agencies. Initially, 71 events were identified. Verification for the cause of death by coroner reports was possible in 45 cases, 43 (96 %) of which were confirmed to be SCDs. A total of 69 individuals 11-30 years of age (mean 17 ± 5 years) died suddenly of cardiovascular causes while participating in 15 different organized sports and a variety of nonorganized physical activities. The most common cause of death was hypertrophic cardiomyopathy (30 %), followed by coronary artery anomalies (9 %), and myocarditis (9 %). The incidence of athlete SCD, the types of sports involved, and the cardiac causes of death in our study were comparable with those of previous reports. Readily available Internet searches have the potential to be a powerful tool for identifying occurrences of athlete SCD. An active surveillance system using Google searches followed by coroner report verification can provide important epidemiologic and clinical information.

BACKGROUND:

The aim of the present paper is to review the evolution of concepts regarding the use of Class I and III antiarrhythmic drugs (AADs) in myocardial infarction over the past four decades.

METHODS:

Results of animal experiments carried out by the authors and papers published between 1970 and 2012 in journals and the PubMed search system were used.

RESULTS:

Animal experiments carried out as early as the 1970s showed that Class IB and IC AADs lose their antiarrhythmic effect and electrically destabilize ventricles in the very early phase of myocardial ischemic focus formation. The cause of this is interaction between Class IB and IC AADs as well as Class III AADs with sympathetic neural activation (SNA) of the heart in the early phase of myocardial ischemia. Given the extremely high and uneven distribution of noradrenaline in tissue, SNA results in dispersion of the depolarization and repolarization processes in the ventricles. The clinical sequels of the interaction between the effects of AADs and SNA are as follows: the antiarrhythmic effect of AADs is restored in AMI once SNA has resolved; membrane-destabilization of the ventricles can be restored any time in the presence of randomly occurring SNA not only due to increasing myocardial ischemia but, also, as a result of psychological stress (emotions), and any pre-existing structural heart disease will enhance the pro-fibrillatory effect of a randomly occurring SNA.

CONCLUSIONS:

Despite the above risks, AADs continue to play an irreplaceable role in suppressing post-myocardial arrhythmias and in preventing sudden cardiac death following ICD placement. The risk of AADs' proarrhythmic effect in SNA can be reduced by combining them with beta-blockers. The last recourse when attempting to suppress malignant ventricular tachyarrhythmias is left sympathetic denervation of the heart.

ABSTRACT

BACKGROUND:

Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure. The efficacy of implantable cardioverter-defibrillator (ICD) therapy has not been determined in heart failure patients with COPD.

METHODS:

We examined the incidence of ICD shocks and mortality in 628 consecutive patients who underwent defibrillator implantation at the Minneapolis Veterans Affairs Medical Center from 2006 to 2010.

RESULTS:

Mean age of the patients was 67±10 years and 99% were male. Patients with COPD (n=246, 39%) were functionally more limited (p&lt;0.0001) and more likely to have ICD for primary prevention of sudden death (p=0.04) than those without COPD. Over a median 4.1 years [IQR25,75 2.2, 5.7] of follow-up, COPD patients had a higher incidence of appropriate shocks (29% vs.17%; p&lt;0.0001) compared to those without COPD, whereas the incidence of inappropriate shocks was similar (9% vs. 10%, respectively; p=0.61). In multivariable analysis, COPD was associated with a 2-fold increase in the odds of appropriate ICD shock (95% confidence interval 1.3-2.9; p=0.001). Incidence of ICD shocks did not vary with severity of COPD. Although all-cause mortality was higher in COPD patients than those without COPD (29% vs. 21% respectively; p=0.029), one-year mortality (5.3% vs. 2.6%, respectively; p=0.08) and the average time from first appropriate ICD shock to death was comparable (median 2.3 years [IQR25,75 1.2, 4.4] vs. 2.8 years [IQR25,75 1.4, 5.3], respectively, p=0.29).

CONCLUSIONS:

Patients with COPD have a higher incidence of ICD shocks than those without COPD and appear to benefit from ICD therapy.

BACKGROUND:

Higher levels of resting heart rate (HR) have been associated with sudden cardiac death (SCD) but mechanisms are poorly understood. We hypothesized that severe left ventricular systolic dysfunction (LVSD) and rate-modulating drugs explain the HR-SCD relationship.

OBJECTIVE:

We evaluated the relationship between HR, severe LVSD, rate-affecting medications and SCD in the community, using a case-control approach.

METHODS:

From the ongoing Oregon Sudden Unexpected Death Study, SCD cases (n=378) aged ≥35 years and with EKG-documented resting HR, were compared to 378 age- and gender-matched control subjects with coronary artery disease (68±13 years, 69% male). Associations with SCD were assessed using multivariable logistic regression.

RESULTS:

Mean resting HR was significantly higher among SCD cases compared to controls (7.5bpm difference, p<0.0001). Heart rate was a significant determinant of SCD after adjustment for significant co-morbidities and medications [OR for 10 bpm increase = 1.26; 95% CI (1.14 - 1.38); p<0.0001]. After considering LVSD, resting HR was slightly attenuated but remained significantly associated with SCD (p=0.005). In addition to diabetes, and digoxin as well as pulmonary and renal disease, LVSD was also independently associated with SCD (OR 1.79, 95% CI 1.11-2.87, p=0.02).

CONCLUSION:

Contrary to expectations, the significant relationship between increased resting HR and SCD persisted even after adjustment for LVSD and rate-modulating drugs. These findings suggest a potential role for additional, novel interventions/therapies that modulate autonomic tone.

The last decade has witnessed major advances in our understanding of the epidemiology and pathophysiology of HIV-related cardiovascular disease in sub-Saharan Africa. In this review, we summarise these and discuss clinically relevant advances in diagnosis and treatment. In the Heart of Soweto Study, 10% of patients with newly diagnosed cardiovascular disease were HIV positive, and the most common HIV-related presentations were cardiomyopathy (38%), pericardial disease (13%) and pulmonary arterial hypertension (8%). HIV-related cardiomyopathy is more common with increased immunosuppression and HIV viraemia. With adequate antiretroviral therapy, the prevalence is low. Contributing factors such as malnutrition and genetic predisposition are under investigation. In other settings, pericardial disease is the most common presentation of HIV-related cardiovascular disease (over 40%), and over 90% of pericardial effusions are due to Mycobacterium tuberculosis (TB) pericarditis. HIV-associated TB pericarditis is associated with a greater prevalence of myopericarditis, a lower rate of progression to constriction, and markedly increased mortality. The role of steroids is currently under investigation in the form of a randomised controlled trial. HIV-associated pulmonary hypertension is significantly more common in sub-Saharan Africa than in developed countries, possibly as a result of interactions between HIV and other infectious agents, with very limited treatment options. It has recently been recognised that patients with HIV are at increased risk of sudden death. Infection with HIV is independently associated with QT prolongation, which is more marked with hepatitis C co-infection and associated with a 4.5-fold higher than expected rate of sudden death. The contribution of coronary disease to the overall burden of HIV-associated cardiovascular disease is still low in sub-Saharan Africa.

The human choroid plexuses in the ventricular system represent the main source of cerebrospinal fluid secretion and constitute a major barrier interface that controls the brain's environment. The present study focused on the choroid plexus of the fourth ventricle, the main cavity of the brainstem containing important nuclei and/or structures mediating autonomic vital functions. In serial sections of 84 brainstems of subjects aged from 17 gestational weeks to 8 postnatal months of life, the deaths due to both known and unknown causes, we examined the cytoarchitecture and the developmental steps of the fourth ventricle choroid plexus to determine whether this structure shows morphological and/or functional alterations in unexplained perinatal deaths (Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death Syndrome). High incidence of histological and immunohistochemical alterations (prevalence of epithelial dark cells, the presence of cystic cells in the stroma, decreased number of blood capillaries, hyperexpression of substance P and apoptosis) were prevalently observed in unexplained death victims (p<0.05 vs. controls). A significant correlation was found between maternal smoking in pregnancy and choroidal neuropathological parameters (p<0.01). This work underscores the negative effects of prenatal exposure to nicotine on the development of the autonomic nervous system, and in particular of the fourth ventricle choroid plexus that is a very vulnerable structure in the developing CSF-brain system.

Background and

Purpose:

Cardiac myxoma is a major primary heart tumor which often causes unexpected symptoms or sudden death. This present study was designed to investigate its clinical pathological features and biological behavior.

Methods:

A retrospective analysis of the clinical pathologic and immunohistochemical features of 66 cases with cardiac myxoma was conducted.

Results:

In 66 patients with cardiac myxoma, 61 cases had involvement of the left atrium, one case in both the right ventricular and left atria. The female: male ratio was 2.7:1. Patients had symptoms of blood flow obstruction and systemic alterations with performance of arterial embolization. Tumors were spherical, lobulated or irregular in shape, and soft and brittle. Immunohistochemical markers of vimentin and CD34 in tumor cells were positive.

Conclusion:

Cardiac myxoma always exists in the left atrium and is more common in women, with diverse clinical manifestations and pathomorphism. Although proliferative activity and the recurrence rate are low, in addition to thorough surgical resection, strengthened review is important for young patients.

Sudden cardiac death in athletes is a recurrent phenomenon at sporting events and during training. Recent studies have associated sudden cardiac death with such cardiovascular conditions as coronary artery anomalies, cardiomyopathies, and electrocardiographic abnormalities, most of which are screenable with modern imaging techniques. We recently inaugurated the Center for Coronary Artery Anomalies at the Texas Heart Institute, which is dedicated to preventing sudden cardiac death in the young and investigating coronary artery anomalies. There, we are conducting 2 cross-sectional studies intended to firmly establish and quantify, in a large group of individuals from a general population, risk factors for sudden cardiac death that arise from specific cardiovascular conditions. In a pilot screening study, we are using a brief, focused clinical questionnaire, electrocardiography, and a simplified novel cardiovascular magnetic resonance screening protocol in approximately 10,000 unselected 11- to 15-year-old children. Concurrently, we are prospectively studying the prevalence of these same conditions, their severity, and their relation to exercise and mode of death in approximately 6,500 consecutive necropsy cases referred to a large forensic center. Eventually, we hope to use our findings to develop a more efficient method of preventing sudden cardiac death in athletes. We believe that these studies will help quantify sudden cardiac death risk factors and the relevance of associated physical activities-crucial information in evaluating the feasibility and affordability of cardiovascular magnetic resonance-based screening. We discuss the rationale for and methods of this long-term endeavor, in advance of reporting the results.

AIMS:

Prolonged PR interval, or first degree AV block, has been traditionally regarded as a benign electrocardiographic finding in healthy individuals, until recent studies have suggested that it may be associated with increased mortality and morbidity. The aim of this study was to further elucidate clinical and prognostic importance of prolonged PR interval in a large middle-aged population with a long follow-up.

METHODS AND RESULTS:

We evaluated 12-lead electrocardiograms of 10 785 individuals aged 30-59 years (mean age 44 years, 52% males) recorded between 1966 and 1972, and followed the subjects for 30 ± 11 years. Prolonged PR interval was defined as PR >200 ms, with further analysis performed using PR ≥220 ms. Main endpoints were all-cause mortality, cardiovascular mortality, and sudden cardiac death, and other endpoints included hospitalizations due to cardiovascular causes. During the baseline examination, prolonged PR interval >200 ms was present in 2.1% of the subjects, but PR interval normalized to ≤200 ms in 30% of these individuals during the follow-up. No increase in mortality or in hospitalizations due to coronary artery disease, heart failure, atrial fibrillation, or stroke was associated with prolonged PR interval (P = non-significant for all endpoints). These results were not changed after multivariate adjustment or in several subanalyses.

CONCLUSION:

In the middle-aged general population, prolonged PR interval normalizes in a substantial proportion of subjects during the time course, and it is not associated with an increased risk of all-cause or cardiovascular mortality.