Athena Poppas

Serial Assessment of the Cardiovascular System in Normal Pregnancy Role of Arterial Compliance and Pulsatile Arterial Load

BACKGROUNDnTemporal changes in systemic arterial compliance and wave propagation properties (pulsatile arterial load) and their role in ventricular-systemic arterial coupling during gestation have not been explored. Noninvasive methods combined with recently developed mathematical modeling techniques were used to characterize vascular and left ventricular (LV) mechanical adaptations during normal gestation.nnnMETHODS AND RESULTSnFourteen healthy women were studied at each trimester of pregnancy and again postpartum. Experimental measurements included instantaneous aortic pressure (subclavian pulse tracings) and flow (aortic Doppler velocities) and echocardiographic imaging of the LV. A small increase in LV muscle mass and end-diastolic chamber dimension occurred by late gestation, with no significant alterations in myocardial contractility. Cardiac output increased and the steady component of arterial load (total vascular resistance) decreased during pregnancy. Several changes in pulsatile arterial load were noted: Global arterial compliance increased (approximately 30%) during the first trimester and remained elevated thereafter. The magnitude of peripheral wave reflections at the aorta was reduced. The mathematical model-based analysis revealed that peripheral wave reflections at the aorta were delayed and that both conduit and peripheral vessels contributed to the increased arterial compliance. Finally, coordinated changes in the pulsatile arterial load and LV properties were responsible for maintaining the efficiency of LV-to-arterial system energy transfer.nnnCONCLUSIONSnThe rapid time course of compliance changes and the involvement of both conduit and peripheral vessels are consistent with reduced vascular tone as being the main underlying mechanism. The pulsatile arterial load alterations during normal pregnancy are adaptive in that they help to accommodate the increased intravascular volume while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure.

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type alpha subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death.

Randomized, Controlled Evaluation of Short- and Long-Term Benefits of Heart Failure Disease Management Within a Diverse Provider Network The SPAN-CHF Trial

Background—Several trials support the usefulness of disease management (DM) for improving clinical outcomes in heart failure (HF). Most of these studies are limited by small sample size; absence of concurrent, randomized controls; limited follow-up; restriction to urban academic centers; and low baseline use of effective medications. Methods and Results—We performed a prospective, randomized assessment of the effectiveness of HF DM delivered for 90 days across a diverse provider network in a heterogeneous population of 200 patients with high baseline use of approved HF pharmacotherapy. During a 90-day follow-up, patients randomized to DM experienced fewer hospitalizations for HF [primary end point, 0.55±0.15 per patient-year alive versus 1.14±0.22 per patient-year alive in control subjects; relative risk (RR), 0.48, P=0.027]. Intervention patients experienced reductions in hospital days related to a primary diagnosis of HF (4.3±0.4 versus 7.8±0.6 days hospitalized per patient-year; RR, 0.54; P<0.001), cardiovascular hospitalizations (0.81±0.19 versus 1.43±0.24 per patient-year alive; RR, 0.57; P=0.043), and days in hospital per patient-year alive for cardiovascular cause (RR, 0.64; P<0.001). Intervention patients showed a trend toward reduced all-cause hospitalizations and total hospital days. On long-term (mean, 283 days) follow-up, there was substantial attrition of the 3-month gain in outcomes, with sustained significant reduction only in days in hospital for cardiac cause. Conclusions—In a population with high background use of standard HF therapy, a DM intervention, uniformly delivered across varied clinical sites, produced significant short-term improvement in HF-related clinical outcomes. Longer-term benefit likely requires more active chronic intervention, even among patients who appear clinically stable.

Systemic hypoperfusion is associated with executive dysfunction in geriatric cardiac patients

The present study examines the relationship between systemic hypoperfusion via cardiac output (CO) and neuropsychological performances emphasizing executive function in an aging cohort. Geriatric outpatients with treated, stable cardiovascular disease (CVD) and no history of neurological illness (n=72, ages 56-85) were administered cognitive measures with an emphasis on executive functioning. Echocardiogram findings were used to stratify participants into two groups: low CO (<4.0 L/min) and normal CO (> o r=4.0 L/min). Between-group comparisons were made using ANCOVAs adjusting for systolic blood pressure. The low CO group performed significantly worse than the normal CO group on DKEFS Tower Test and DKEFS Trail Making Test. No significant between-group differences were noted for any of the other cognitive indices. Findings suggest that reduced CO is associated with poorer executive functioning among geriatric outpatients with stable CVD, as the cognitive profile emphasizes a relationship between systemic hypoperfusion and problems with sequencing and planning. The executive dysfunction profile may be secondary to reduced blood flow to vulnerable subcortical structures implicated in frontal-subcortical circuitry.

Endothelial function and white matter hyperintensities in older adults with cardiovascular disease.

Background and Purpose— The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume. Methods— Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined. Results— Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume. Conclusions— These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.

Lower Cardiac Output Is Associated with Greater White Matter Hyperintensities in Older Adults with Cardiovascular Disease

OBJECTIVES: To preliminarily examine the association between cardiac output, a measure of systemic blood flow, and structural brain magnetic resonance imaging indices of white matter hyperintensities (WMHs).

Vascular and cognitive functions associated with cardiovascular disease in the elderly.

This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56–85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease.

Cardiac dysfunction and cognition in older adults with heart failure.

ObjectivesTo characterize cognition in patients with moderate to severe heart failure and examine the association between 2 measures of systemic perfusion (ie, ejection fraction and cardiac index) and cognition. BackgroundDecreased systemic perfusion has been implicated as an etiologic factor in the development of cognitive deficits in cardiovascular disease. MethodThirty-one patients with moderate to severe heart failure and 31 patients with cardiovascular disease and no heart failure completed a medical history interview and neuropsychologic assessment. Participants with heart failure additionally underwent an echocardiogram to assess cardiac function. ResultsPatients with heart failure performed significantly worse than the cardiovascular disease-no heart failure group on several measures of executive functioning and psychomotor speed. Among the heart failure group, lower ejection fraction was associated with weaker global cognition, performance on several, but not all, measures of executive functioning, and was marginally associated with delayed memory. Decreased cardiac index was associated with poorer immediate memory and weakly associated with global cognition. ConclusionsFindings suggest that depressed systemic perfusion is associated with cognitive deficits among patients with heart failure. Research including measures of cardiac function, cerebral perfusion, and cognition will be necessary to clarify the causal nature of the suggested mechanism.

C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease

Cardiovascular disease (CVD) is a risk factor for cognitive impairment and dementia. Recent studies implicate homocysteine (HCY) and C-reactive protein (CRP) in this increased risk, as both are associated with cognitive dysfunction in demented and non-demented patients. However, it remains unclear whether they confer added risk in older adults with CVD. A total of 126 older CVD patients underwent blood and neuropsychological evaluation as part of a prospective examination of the neurocognitive consequences of CVD. A subset of these participants (n=37) also underwent neuroimaging to quantify the degree of white matter disease. After adjusting for demographic and medical factors, no significant relationship emerged between HCY and cognitive performance. In contrast, CRP showed significant independent relationships to test performance, including global cognitive performance, attention/psychomotor function, executive function, memory, and visuospatial abilities. Neither HCY nor CRP was related to extent of white matter disease or whole brain volume on magnetic resonance imaging. Further study is needed to identify mechanisms by which inflammatory processes impact on cognitive function and to determine whether reducing circulating levels of inflammatory markers results in improved cognition.

Longitudinal Trajectories of Cognitive Decline among Older Adults with Cardiovascular Disease

Background: The long-term course of cognitive impairments secondary to cardiovascular disease (CVD) is unclear. In this study, we prospectively investigated the temporal pattern, rate and hierarchy of cognitive decline attributable to CVD – a risk factor for the development of vascular cognitive impairment (VCI) – and examined the influence of cardiac surgery and heart failure on cognitive decline. Methods: A total of 172 older adults with CVD were administered a comprehensive battery of neuropsychological tests at study entry, and at 12 and 36 months thereafter. Random coefficient regressions were used to investigate the temporal course, rate and hierarchy of cognitive decline, as well as to examine the effect of heart failure (reported by 21% of the sample) and cardiac surgery (reported by 44% of the sample) on trajectories of cognitive change. Results: The course of decline in cognition was linear for language and attention-executive function-psychomotor speed, and curvilinear for visuospatial abilities, memory and overall cognition. The decline in attention-executive function-psychomotor speed was smaller than the decline in other domains. The greatest decline occurred in visuospatial abilities. The rate of decline in cognition was not altered by a history of heart failure. Patients who had undergone cardiac surgery exhibited slower deceleration in their rates of decline in overall cognition. At baseline, patients with a history of heart failure had comparatively poorer attention-executive function-psychomotor speed, overall cognition and, to a lesser extent, visuospatial scores. Conclusion: There is measurable decline in neurocognitive function among patients with CVD. This decline is linear in some cognitive domains and curvilinear in others and is not attributable to the normal aging process. Cardiac surgery, but not heart failure, significantly affects the trajectory of cognitive decline. Because most vascular risk factors are modifiable, preventive measures such as lifestyle changes may be useful in retarding cognitive decline among patients with CVD, thus preventing the onset of VCI.