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Cardiac Causes of Stroke.

At least 20% of all ischemic strokes are cardioembolic. Cardiac conditions that cause cerebral embolism are classified as major or minor depending on whether the causal link has or has not been fully established between the underlying cardiac condition and the stroke. Atrial fibrillation, acute myocardial infarction, valvular heart disease, infective endocarditis, nonbacterial thrombotic endocarditis, and atrial myxoma are the main cardiac causes of cerebral embolism. Patent foramen ovale, atrial septal aneurysm, mitral valve prolapse, mitral annular calcification, calcific aortic stenosis, and mitral valve strands are cardiac conditions with a potential causal link to cerebral embolism, but until now, either they have been found to be poor predictors of recurrent stroke or their risk of recurrent stroke is unknown. The management of patients with a stroke of cardiac source is twofold: 1) treatment of the acute phase of stroke and 2) prophylactic treatment of recurrent thromboembolism. When possible, primary prevention of cerebral embolism should be recommended, particularly in cardiac conditions with known high risk of stroke (eg, atrial fibrillation, mitral stenosis, or presence of mechanical prosthetic heart valves).

Journal Article↗

Cardiac loading conditions modify the ventricular repolarization in conscious dogs with heart failure.

Changes in myocardial loading conditions influence the ventricular action potential via mechanoelectric feedback, a mechanism impaired in pathology. In vivo the QT interval of the electrocardiogram which reflects the action potential duration allows appropriate determination of its modifications. The effects of changes in cardiac loading conditions (load reduction with trinitrin; volume loading with Plasmion) on regional function and ventricular local electrogram were investigated in conscious dogs before (control) and after 4 weeks of rapid pacing (dilated cardiomyopathy, DCM). In controls both interventions increased heart rate. Trinitrin increased end-diastolic wall thickness (EDWth, P<0.001) and reduced absolute QT interval duration (P<0.05). Plasmion decreased EDWth (P<0.001) and increased left ventricular end diastolic pressure (LVEDP, P<0.001) without QT interval alteration. However, the corrected QT interval was unchanged in both interventions. In DCM, trinitrin did not change the QT interval. Plasmion increased LVEDP (P<0.01) and prolonged QT and corrected QT intervals (P<0.01) despite the tachycardia. In controls the changes in cardiac loading conditions did not modify the QT interval, suggesting intact endogenous regulation of repolarization. The impaired adaptation observed in DCM contributed to an increase in QT interval following volume loading. In this model, a prolonged repolarization after abrupt volume loading may result from enhanced or disclosed mechanoelectric feedback.

Animals↗

Chronic adaptations to physical conditioning in cardiac patients. Implications regarding exercise trainability.

Physical conditioning in patients with coronary heart disease can result in increased functional capacity, symptomatic relief of angina pectoris, favorable reduction of risk factors, enhanced psychological status, and improved quality of life. The mechanisms underlying the adaptations to training are poorly understood, but it is clear that several factors affect exercise trainability. Guidelines are available that suggest the appropriate intensity, frequency, and duration of exercise needed to obtain beneficial physiologic adaptations.

Adaptation, Physiological↗

Causes of death for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team cohort study.

BACKGROUND: To our knowledge, no previous study has systematically examined pneumonia-related and pneumonia-unrelated mortality. This study was performed to identify the cause(s) of death and to compare the timing and risk factors associated with pneumonia-related and pneumonia-unrelated mortality. METHODS: For all deaths within 90 days of presentation, a synopsis of all events preceding death was independently reviewed by 2 members of a 5-member review panel (C.M.C., D.E.S., T.J.M., W.N.K., and M.J.F.). The underlying and immediate causes of death and whether pneumonia had a major, a minor, or no apparent role in the death were determined using consensus. Death was defined as pneumonia related if pneumonia was the underlying or immediate cause of death or played a major role in the cause of death. Competing-risk Cox proportional hazards regression models were used to identify baseline characteristics associated with mortality. RESULTS: Patients (944 outpatients and 1343 inpatients) with clinical and radiographic evidence of pneumonia were enrolled, and 208 (9%) died by 90 days. The most frequent immediate causes of death were respiratory failure (38%), cardiac conditions (13%), and infectious conditions (11%); the most frequent underlying causes of death were neurological conditions (29%), malignancies (24%), and cardiac conditions (14%). Mortality was pneumonia related in 110 (53%) of the 208 deaths. Pneumonia-related deaths were 7.7 times more likely to occur within 30 days of presentation compared with pneumonia-unrelated deaths. Factors independently associated with pneumonia-related mortality were hypothermia, altered mental status, elevated serum urea nitrogen level, chronic liver disease, leukopenia, and hypoxemia. Factors independently associated with pneumonia-unrelated mortality were dementia, immunosuppression, active cancer, systolic hypotension, male sex, and multilobar pulmonary infiltrates. Increasing age and evidence of aspiration were independent predictors of both types of mortality. CONCLUSIONS: For patients with community-acquired pneumonia, only half of all deaths are attributable to their acute illness. Differences in the timing of death and risk factors for mortality suggest that future studies of community-acquired pneumonia should differentiate all-cause and pneumonia-related mortality.

Cause of Death↗

Mice lacking connexin45 conditionally in cardiac myocytes display embryonic lethality similar to that of germline knockout mice without endocardial cushion defect.

The gap junction protein connexin45-deficient (Cx45-KO) mice die shortly after the hearts begin to beat. In addition to the heart defect, they also show defective vascular development which may be closely related with the cardiac phenotype. Therefore, we created mice whose floxed-Cx45 locus could be removed conditionally. We utilized cardiac alpha-actin-Cre transgenic mice to investigate the specific cardiac muscular function of Cx45 in vivo. The resultant conditional mutants were lethal, showing conduction block similar to that of the Cx45-KO mice. Unlike Cx45-KO, development of the endocardial cushion was not disrupted in the conditional mutants. X-gal staining was detected in the embryonic cardiac myocytes as a hallmark of Cre-loxP mediated floxed-Cx45 deletion. These results reconfirm the requirement of Cx45 for developing cardiac myocytes. These also indicate that establishing the first contractions is a crucial task for the early hearts.

Animals↗

Biological adaptation of the myocardium to a permanent change in loading conditions.

Cardiac hypertrophy due to permanent mechanical overloading is only one example among thousands of the general process of biological adaptation. The process is randomly governed and results in at least one thermodynamical benefit: to be adaptational and to induce several changes in gene expression. Some of these changes are detrimental, some can even be useless. The cascade of events which finally leads to a permanent modification of the genetic expression involves an initial signal, likely to be the stretch, a pathway which transducts the signal, and a transient change in genetic expression which transmits competence to the cell to be transformed. The permanent modifications occur at all cellular levels including the sarcomere, sarcolemma, energy metabolism, and extra-cellular matrix, but they are species-specific and differ in the ventricles and the atria.

Adaptation, Physiological↗

Transmural inhomogeneity of energy metabolism during acute global ischemia in the isolated rat heart: dependence on environmental conditions.

Cardiac energy metabolism is one of the earliest metabolic activities affected when either anoxia or ischemia are induced, as evidenced by the rapid decline of the tissue high-energy phosphate content of creatinephosphate (CrP) and ATP. Several reports deal with the spatial inhomogeneity of these changes and it is generally found, that the subendocardium is more sensitive to ischemia than the subepicardium. The metabolic transmural gradients observed during in vivo ischemia were attributed to both variations in wall tension and collateral flow. Lowe et al. recently presented evidence that in addition to these variations the higher vulnerability of the subendocardium to ischemia could be secondary to an increased metabolic rate.

Adenosine Triphosphate↗

Isoproterenol infusion promotes nitrogen washout in rats under normobaric conditions.

Cardiac output and the rate of N2 elimination were measured simultaneously in unanesthetized rats during isobaric desaturation with 100% O2. Whole-body N2-washout curves for the rat are characterized by three compartment half times derived by exponential stripping, representing the slow, intermediate, and fast components of the system. During saline infusion (control) the respective half times for these compartments were 120, 15, and 2 min. Isoproterenol infusion increased cardiac output by 40% and the volume of N2 eliminated by 10% over a 2-h washout. More importantly, the half time of the slowest compartment decreased from 120 to 70 min. The intermediate compartment half time shortened from 15 to 13 min, while the fast compartment was unaffected. The decrease in slow compartment half time will contribute significantly to the shortening of the duration of stay during decompression. A plot of slow compartment rate constants vs. measured cardiac output (range 280-690 ml X min-1 X kg-1) demonstrated a linear relationship between perfusion and the tissue-blood gas exchange rate. The results indicate that enhanced cardiac output and generalized vasodilation shorten the time required to desaturate the slower body tissues. Various maneuvers or drugs that demonstrate similar cardiovascular responses should be beneficial during prolonged decompression procedures involved in saturation diving.

Animals↗

[The effectiveness of trapidil and some derivatives on heart function under in vitro and in vivo conditions].

Cardiac and coronary effects of trapidil (Rocornal) and some derivatives were investigated in isolated heart preparations and rabbit hearts in vivo. All substances showed a comparable increase of the coronary flow. Contrary to the cardiotonic influence of trapidil the trapidil derivates induced a negative inotropic effect, possibly due to a weak calcium antagonism. Heart rate was slightly diminished, but in some cases higher doses caused an acute tachycardia. I.v. application of the substances to rabbits in doses of 10 mg/kg and 30 mg/kg induced an initial depression of blood pressure normalizing within 3-5 min. An increase of the myocardial prostacyclin biosynthesis is only demonstrable under trapidil. The results indicate that the cardiac effects of trapidil derivatives are possibly caused by a direct influence on the contractile system and the membrane potential of the cardiac muscle cell.

Anesthesia↗

Predictors of depression three months after cardiac hospitalization.

OBJECTIVE: Depression occurs comorbidly in patients hospitalized for a range of cardiac conditions and procedures. This study examines the fluctuations in depressive symptomatology from index hospitalization to 3 months after hospitalization and determines predictors of depression 3 months after hospital admission for a cardiac condition or procedure. METHODS: Baseline clinical and demographic variables collected from a prospective study of the natural history of depression in 833 hospitalized cardiac patients were entered into a multinomial regression analysis. RESULTS: Similar proportions of participants were found to have no, mild, or moderate to severe depression at baseline and at 3 months, although 35.8% of participants had moved from one depression level to another during that period. Baseline characteristics predicting depression at 3 months after hospitalization were: a mild or moderate to severe level of depressive symptoms at hospitalization; younger age; smoking; self-reported previous diagnosis of a cardiac condition; and self-reported history of depression, anxiety, or stress. CONCLUSIONS: The five clinically accessible variables identified as predictors in this study may assist physicians in identification of cardiac patients who are at risk of persistent depression and who may require active intervention. Given that depression in cardiac patients is related to increased mortality and morbidity and that it is currently poorly diagnosed, these findings may have implications for preventing adverse outcomes.

Adolescent↗

[Cardiopathy and acute cerebrovascular insufficiency. Prospective study with two-dimensional echocardiography].

Many cardiac disorders can cause acute cerebrovascular insufficiency. The spectrum of potentially embolic cardiac conditions is wide; early recognition may determine a definite change in the management and prognosis of patients. In recent years the relevance of echocardiography in the screening of patients with cerebral ischemia has been emphasized. In order to identify potentially embolic cardiac conditions, 180 consecutive non selected patients with cerebrovascular insufficiency, underwent a clinical cardiological evaluation and an echocardiogram. The study population included 132 men and 48 women; the mean age was 51.7 years (range 19 to 72 years). A technically adequate echocardiogram was obtained in 153 patients. In 131 patients echocardiography was negative; cardiac lesions were detected in 22 patients (14.4%): mitral stenosis in 2, calcified aortic stenosis in 1, valvular endocarditis vegetations in 3, dilatative cardiomyopathy in 2, hypertrophic cardiomyopathy in 4, mitral valve prolapse in 4, regional left ventricular diskynesia in 5, mitral anulus calcification in 1. Patients were divided into 3 groups according to the results of cerebral angiography: 68 patients with normal angiography (Group I), 54 patients with atheromasic lesions on cerebral angiography (Group II), 31 patients in whom cerebral angiography was not performed (Group III). A higher incidence of cardiac diseases was found in the patients of Group I. The lack of lesions on cerebral angiography and the presence of embolic high-risk cardiac conditions strengthened a causal relationship of the cardiac disorder with cerebrovascular insufficiency in 10 of the 23 patients. In the mean follow-up period of 18 months of these 10 patients who underwent cardiac surgery or anticoagulation, no further attacks of cerebrovascular insufficiency were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

The costs of cardiorespiratory disease episodes in a study of emergency department use.

OBJECTIVE: The average per person direct cost of illness of cardiorespiratory disease episodes was estimated based on a prospective study of emergency department visits. METHODS: Economic modelling of health care costs using prospectively collected resource utilization data (9/1/94 to 8/31/95) from hospital emergency department visitors assigned a diagnosis of asthma, chronic obstructive pulmonary disease (COPD), respiratory infections or cardiac conditions. RESULTS: The total direct costs (1997 CDN$) [95% C.I.] per patient were $1,043.55 [$922.65, $1,164.47] for asthma, $1,690.11 [$1,276.92, $2,103.30] for COPD, $676.50 [$574.46, $778.54] for respiratory infections, and $3,318.74 [$2,937.72, $3,699.76] for cardiac conditions. CONCLUSIONS: This study showed that on average, patients diagnosed with a cardiac condition had the highest total direct cost. Hospitalization cost was the largest component of costs for all diagnoses except asthma, for which medications were the single largest component of direct costs.

Adult↗

Use of explanted human hearts as a model for the study of cardiac pathophysiologic conditions.

The purpose of this paper is to describe an isolated heart model that uses human hearts to study cardiomyopathy. Techniques of organ preparation and perfusion are described that result in successful restoration of explanted human hearts to a beating condition. Native hearts of transplant recipients were placed on an isolated perfusion circuit immediately after explant. After appropriate organ and circuit preparation these hearts were restored to a functional state. Studies were done to assess the stability over time and response to inotropic stimulation. Six of seven hearts were returned to a functional condition. Left ventricular pressure generation ranged from 56 to 118 mm Hg (mean 84.8 +/- 34.11) at physiologic loading conditions. Hearts remained functional from 67 to 271 minutes (mean 152 +/- 71.7) and retained up to 70% of functional capacity after 120 minutes. Hearts performed in isovolumic and ejecting modes. Hearts had a marked response to inotrope administration not previously described. We conclude that human hearts can be reproducibly restored to a functional condition after explant from transplant recipients and can be maintained in a beating state with reasonably stable pressure generation for an extended period of time, which makes this a useful model with which to study cardiac pathophysiologic conditions. These hearts demonstrate an appropriate response to inotropes not previously observed, most likely because of improved myocardial preservation and stringent control of perfusate chemical make-up.

Adult↗

Control strategy for maintaining physiological perfusion with rotary blood pumps.

We present arguments and simulation results in favor of a novel strategy for control of rotary blood pumps. We suggest that physiological perfusion is achieved when the blood pump is controlled to maintain an average reference differential pressure. In the case of rotary left ventricular assist devices, our simulations show that maintaining a constant average pressure difference between the left ventricle and aorta results in physiological perfusion over a wide range of physical activities and clinical cardiac conditions. We simulated rest, light, and strenuous exercise conditions, corresponding to cardiac demands of 4.92, 7.98, and 14.62 L/min, respectively. For different exercise levels, the clinical conditions ranged from normal to failing to asystolic heart. By maintaining a constant pressure difference of 75 mm Hg between the left ventricle and aorta, with either an axial or a centrifugal blood pump, a total cardiac output close to the physiological cardiac demand was achieved, irrespective of the heart condition. The simulations of the transitions between different levels of exercise indicate that with the same reference differential pressure, the proposed approach leads to rapid adaptation of the total cardiac output to physiological levels, while avoiding suction. Comparison with the traditional control strategy of maintaining a reference rotational speed (rpm) of the pump indicates that though the traditional approach has some degree of adaptability, it is only adequate over a narrow range of cardiac demand and clinical conditions of the patient. Our results indicate that the proposed approach is superior to the alternatives in providing an adequate and autonomous adaptation of the total cardiac output over a broad range of exercise conditions (expected when an assist device is used as a destination therapy) and clinical statuses of the native heart (such as further deterioration or recovery of cardiac function), while having the potential to improve the quality of life of patients by reducing the need for monitoring and frequent human intervention. The proposed approach can be clinically implemented using simple controllers, and requires the implantation of two pressure sensors, or estimation of the pressure difference based on other available measurements.

Biomechanical Phenomena↗

Depression after myocardial infarction is a risk factor for declining health related quality of life and increased disability and cardiac complaints at 12 months.

OBJECTIVE: To study the prospective effects of post-myocardial infarction (MI) depressive disorder on health status, including self reported cardiac symptoms, disability, and health related quality of life, at 12 months after MI while controlling for cardiac condition and health status at three months after MI. METHODS: Longitudinal study of a cohort of 468 adults with MI recruited from four hospitals in the north of The Netherlands between September 1997 and September 2000. Assessment of depressive disorder in the year after MI according to International classification of disease, 10th revision criteria. Assessment of health status at three and 12 months by the RAND 36 item health survey, the health complaints scale, self rated cardiac complaints, and disability. RESULTS: Patients with post-MI depressive disorder were more likely than those without to have poor quality of life, more health complaints, more cardiac complaints, and more disability at 12 months' follow up. In multivariate analyses adjusted for cardiac condition, health status at three months, age, sex, and pre-MI depression, the prospective association of post-MI depression with poor health status remained for most of the indicators. Severity of the post-MI depression further contributed to aspects of poor health status. CONCLUSIONS: In a prospective study design, post-MI depression had strong effects on poor health status exceeding the effects of cardiac condition and its short term consequences. Efforts to improve health status after MI should therefore include standard assessment and guideline based treatment of post-MI depressive disorder.

Depressive Disorder↗

Regional variation in self-reported heart disease prevalence in Canada.

BACKGROUND: Cardiovascular disease is the leading cause of death in Canada. OBJECTIVE: To provide an analysis of the self-reported prevalence of heart disease and three specific cardiac conditions--myocardial infarction (MI), angina and congestive heart failure (CHF)--in subgroups of the Canadian population. METHODS: Data from the Public Use Microdata File from Statistics Canada's 2000/2001 Canadian Community Health Survey (CCHS) were used to estimate the crude self-reported prevalence of heart disease, MI, angina and CHF in Canada. The data are reported by age and sex groups, as well as by province or territory and health region. RESULTS: Based on the 2000/2001 CCHS data, it was estimated that among Canadians 12 years of age and older, 5.0% (n=1,286,000) have heart disease, 2.1% (n=537,000) have had a heart attack, 1.9% (n=483,000) have angina and 1.0% (n=264,000) have CHF. Marked variation in the prevalence of heart disease and the other specific cardiac conditions exists across age and sex groups, and across geographical regions. The prevalence of heart disease is low among those younger than 50 years; thereafter, the prevalence of heart disease increases and is more common among men than among women. By 70 years of age, at least one in four men and one in five women report having heart disease. Large differences in the burden of heart disease were observed across provinces, territories and health regions. Comparison of the highest and lowest prevalence rates among provinces and territories revealed a 1.9-fold difference for heart disease, a 2.8-fold difference for MI, a 2.3-fold difference for angina and a 3.3-fold difference for CHF. CONCLUSIONS: Large regional differences in the prevalence of heart disease and other specific cardiac conditions were observed across Canada. These data may assist health system planners to identify those regions and population subgroups most affected by heart disease, and to support the development of heart disease prevention and treatment programs.

Adolescent↗