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Cardiovascular disease (CVD) and particularly heart failure (HF) have been associated with cognitive impairment in cross-sectional studies, but it is unclear how cognitive impairment progresses over time in older adults with these conditions.The aim of this study was to prospectively examine cognitive function in patients with HF versus other forms of CVD.Seventy-five older adults (aged 53-84 years) with CVD underwent Doppler echocardiogram to evaluate cardiac status and 2 administrations of the Dementia Rating Scale (DRS), a test of global cognitive functioning, 12 months apart.Although DRS performance did not statistically differ between groups at either administration, a significant between-group difference in the rate of cognitive change emerged (lambda = 0.87; F = 10.50; P = .002; omega 2 = 0.11). Follow-up analyses revealed that patients with HF improved significantly on global DRS performance, whereas patients with other forms of CVD remained stable. More specifically, patients with HF showed improvement on subscales of attention, initiation/perseveration, and conceptualization. Exploratory analyses indicated that higher diastolic blood pressure at baseline was associated with improved DRS performance in patients with HF (r = 0.38; P = .02).Patients with HF exhibited modest cognitive improvements during 12 months, particularly in attention and executive functioning. Higher diastolic blood pressure at baseline was associated with improvement. These results suggest that cognitive impairment in patients with HF may be modifiable and that improved blood pressure control may be an important contributor to improved function. Further prospective studies are needed to replicate results and determine underlying mechanisms.

Poor cardiac pumping efficiency has shown to lead to cognitive impairments in patients with cardiovascular disease (CVD). The current study examined the relationship between left ventricular ejection fraction and sustained attention and inhibitory processes measured by the Adaptive Rate Continuous Performance Task and the Go/No-go test. Participants were 67 older outpatients (age 68.5 ± 7.4) with a range of CVD. Associations between cognition and ejection fraction were examinedvialinear regression analysis. Results were consistent with the hypothesis that lower ejection fraction is significantly associated with decrements in sustained attention and vigilance. Overall, the results provide support for the hypothesis that a change in cardiac pumping leads to decrements in some aspects of attention; however, inhibitory processes are relatively spared. (JINS, 2009,15, 137–141.)

To prospectively relate C-reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1-year follow-up period.Prospective 1-year follow-up.Outpatient university medical setting.Seventy-eight adults (aged 56-84; 39% female) with cardiovascular disease.CRP levels were measured using a high-sensitivity assay, and participants completed a neuropsychological battery at study entry. Neuropsychological assessment was repeated 1 year later.The association between CRP and change in cognition over the 1-year follow-up was examined using hierarchical linear regression modeling for five cognitive domains (global cognition, language, memory, visuospatial abilities, and attention-executive-psychomotor). High CRP levels were associated with subtle declines in attention-executive-psychomotor performance (CRP beta=-0.22, P=.04) after adjusting for the effects of age and cognitive performance at study entry. CRP was not significantly associated with change in language, memory, or visuospatial performance.These data provide preliminary evidence that inflammation, potentially contributing to atherosclerotic processes, may underlie the association between high CRP and changes in attention-executive-psychomotor performance.

To 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.Decreased systemic perfusion has been implicated as an etiologic factor in the development of cognitive deficits in cardiovascular disease.Thirty-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.Patients 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.Findings 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.

Cardiac resynchronization therapy (CRT) improves heart failure (HF) symptoms in patients (pts) with EF 120ms, and NYHA class 3 and 4 HF. The aim of this study was to compare the effects of CRT in pts with EF 130, and class 2 vs 3/4 HF. We enrolled 25 patients. All received ECGs, transthoracic echocardiograms, 6 minute walk tests, and Minnesota quality of life questionnaires pre-op and three months post-op. Fourteen pts were class 2, 10 patients were class 3, and 1 class 4. Ischemic cardiomyopathy accounted for 7 out of the 14 class 2 pts and 5 out of the 11 class 3/4 pts. As a group, all patients had a significant increase in 6 minute walk (1150 vs 1249, p=0.02), increase in EF (30% vs 39%, p ). Nonischemic pts had greater response than ischemic pts. Class 2 HF pts reported greater improvement in mental health than class 3 and 4. Younger patients reported greater functional improvement, while pts with higher BMI reported less physical benefit. Summary: Pts with NYHA class 2 symptoms derive similar hemodynamic benefit from CRT as pts with class 3/4 symptoms and may derive greater mental health benefits than class 3/4 pts. Comparison of Pre and Post-Implant Parameters Between Class 2 and 3/4 Patients

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.

Objective: The present study examined the relationship between multiple indices of blood pressure (BP) and cognitive function (as measured by the Dementia Rating Scale). Background: Cardiovascular disease (CVD) is associated with cognitive dysfunction and cerebrovascular pathology in the elderly and is a known risk factor for stroke and Alzheimer disease. Yet, the mechanisms for the effects of CVD on cognitive function are not well understood. Methods: Participants were 97 nondemented older adults with CVD who underwent neuropsychologic assessment, and a 2-hour cardiovascular laboratory protocol. Results: After controlling for age and years of education, results of hierarchical linear regression analyses indicate a significant positive relationship between a function of BP variability (SD of systolic BP divided by the average diastolic BP) and cognitive function (R 2 change = 0.042, F (1, 85) = 5.434, P < 0.05). No relationship emerged between any other BP index and cognitive function. Conclusions: Contrary to expectations, greater BP variability was associated with better, not poorer, cognitive test performance. These findings suggest that the relationship between BP and cognitive function is more complicated than originally conceptualized and requires further investigation.

Cardiovascular disease (CVD) is associated with cognitive deficits long before the onset of stroke or dementia. Recent work has extended these findings and shown that patients with congestive heart failure also exhibit reduced cognitive performance. Brain natriuretic peptide (BNP) is used to help diagnose heart failure, but no study has examined whether BNP predicts cognitive dysfunction in older patients with CVD. BNP values and performance on the Dementia Rating Scale were assessed in 56 older adults with documented CVD. Forty-eight percent of the participants were women, and their average age was 70 +/- 8 years. All participants had Mini-Mental State Examination scores greater than the cutoff for dementia and no histories of neurologic or severe psychiatric disorders. The average BNP level was 122 +/- 202 pg/ml. Hierarchical regression analyses showed that log-transformed BNP levels predicted Dementia Rating Scale total score after adjusting for possible demographic and medical confounders (DeltaR2 = 0.09, F[1, 44] = 6.14, p = 0.017). Partial correlation analysis adjusting for these possible confounders showed a particularly strong relation to the conceptualization subtest (r = -0.44, p = 0.002), a measure of verbal and nonverbal abstraction abilities. In conclusion, the results of the present study provide the first evidence for an independent relation between BNP and cognitive dysfunction in older adults with CVD.

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 (

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 P =0.043), and days in hospital per patient-year alive for cardiovascular cause (RR, 0.64; P 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.

This study was designed to test the hypothesis that raising myocardial O2 via diffusion of a hyperbaric oxygen solution (AO) administered through the anterior interventricular vein (AIV) will reduce infarct size by reducing reperfusion injury associated with reduced neutrophil activation. In three pilot open-chest swine experiments, myocardial tissue Po2 was monitored using an oxygen probe during coronary occlusion (Occl) and reperfusion (Rep). One control experiment had no AIV infusion; a second control received arterial blood drawn from the femoral artery infused into the AIV during Rep. In a third open-chest experiment, AO mixed with arterial blood was infused through the AIV at Rep. In controls, tissue Po2 in the risk region (RR) rose early in Rep and then fell to Occl levels, whereas in AO-treated animals, myocardial Po2 remained above baseline. The following three groups of five swine then underwent 60 min of left anterior descending coronary artery Occl and Rep: 1) arterial blood infused at Rep as controls (Con), 2) AO infused beginning 30 min after Rep (AO 30 min), and 3) AO infused immediately at Rep (AO 0 min). There were no differences among the three groups in hemodynamics or myocardial blood flow during baseline (BL) or Occl or in RR size. However, endocardial blood flow was significantly higher in RR during Rep in AO 0 min vs. control and AO 30 min ( P = 0.01). Both infarct size (IS) as %heart and IS as %RR were lower in AO 0 min compared with Con and AO 30 min ( P < 0.01 for both), and myeloperoxidase values were lower for epicardial ( P < 0.001), midmyocardial ( P = 0.03), and endocardial ( P < 0.001) layers in AO 0 min. AO infused into the AIV immediately at Rep diffuses into the RR and reduces IS by reducing Rep injury associated with neutrophil activation.

Region-by-region comparison of data concerning left ventricular (LV) status is difficult to perform quantitatively if the data was acquired from disparate imaging modalities. We validated a method for comparing measurements obtained by electromechanical mapping (EMM) catheter with dobutamine stress echocardiography (DSE) via biplane contrast ventriculography, with the assistance of three-dimensional (3-D) echocardiographic data. The ventriculograms were traced and the borders were used to reconstruct the LV in 3-D with the aid of a database of 3-D echocardiographic studies. The 3-D LV was oriented to the EMM data based on the body coordinates and then manually scaled and translated to fit. The EMM data were mapped to the 3-D surface. The 3-D surface was divided into the 16 regions defined for echocardiographic assessment. The mean EMM value for local linear shortening, a parameter of function, was computed in each segment. The EMM and semiquantitative echocardiographic assessments of regional myocardial function were compared by segment, and the volume of the 3-D LV was compared with the volume computed from the ventriculogram. The volume of the 3-D surface correlated closely with that of the ventriculogram (r = 0.97, SEE = 27.4 ml) but with a significant overestimation of 63 /spl plusmn/ 35 ml. There was a highly significant (p < 0.0001) agreement in regional function between EMM and echo. Local linear shortening correlated significantly (p < 0.0001) with echocardiographic severity of wall motion, averaging 9.5/spl plusmn/6.5, 8.1/spl plusmn/5.4, 5.9/spl plusmn/4.8, and 6.2/spl plusmn/3.3 in segments read as normal, hypokinetic, akinetic, and dyskinetic, respectively. The method presented is valid for comparing cardiac parameters derived from disparate image data on a region-by-region basis by employing anatomic landmarks on 3-D reconstructions of the LV endocardial surface.

A 19-year-old male patient with a history of asthma was in good health until he developed a sudden-onset, right side pleuritic chest discomfort and shortness of breath. At that time, he was on a cruise to Puerto Rico. He returned home 1 week later and was evaluated in the emergency room at that time. On further history, he denied cough, fever, chills, night sweats, weight loss, sputum production, haemoptysis or other symptoms. He did not recall recent sick contacts or exposure to tuberculosis. He was born in the USA and this cruise was his only recent travel. He worked in a law firm and denied significant occupational exposures, any tobacco or drug use, allergies or significant family history of lung or cardiovascular disease. Tachycardia was the only abnormality on his physical examination, and initial laboratory testing were completely normal. His pulse oximetry measurement was 97% O2 saturation on room air at rest. His ECG was consistent with sinus tachycardia, with a rate of 108/min and no ST–T wave changes. He was admitted to the hospital for further investigation of his chest pain. His chest radiograph (figure 1A) and chest CT scan (angiogram protocol) (figure 1B) were abnormal but showed no evidence of pneumothorax or pulmonary embolism. A small unilateral pleural effusion was present but was too small to sample using bedside ultrasonography. All subsequent blood tests in the hospital including cardiac enzymes, immunoglobulins levels and vasculitis screen were all unremarkable. The chest …

Background Temporal 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. Methods and Results Fourteen 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 (≈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. Conclusions The 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.

We report a case of a 53 year-old man with a history of hypertension presenting with acute left lower extremity parasthesias and pulselessness initially presumed to be secondary to arterial thrombosis or embolism. Work-up included a transthoracic echocardiogram which revealed an aortic dissection at the level of the aortic root extending to the visualized portions of the descending aorta. Type A aortic dissections are relatively rare, with the vast majority of patients presenting with chest pain. Timely diagnosis of Type A aortic dissections are critical as to facilitate rapid surgical repair. To our knowledge, this is the first report of a painless Type A aortic dissection presenting with isolated lower extremity vascular insufficiency and demonstrates the potential role of transthoracic echocardiography as a rapid, non-invasive bedside modality in visualizing Type A aortic dissections.

Background: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated with the vascular responses. Methods: Eighty-eight independent, community-dwelling older adults (70.02 ± 7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-D ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. Results: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. Conclusions: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

Lactoferrin has been reported to inhibit the production of colony-stimulating factor (CSF); thus we sought to study its possible effects on myelopoiesis in vivo. The characteristics of rebound myelopoiesis in C57BL mice injected with a sublethal dose of cyclophosphamide (CY) were used to test lactoferrin for any granulopoietic activity. An experimental group received daily injections of 50 micrograms of human lactoferrin beginning 24 hr after CY injections. By measuring the total nucleated cellularity of the femoral marrow, the peripheral blood count, and the incorporation of tritiated thymidine by the marrow in six replicate experiments, no statistically significant difference was noted between the lactoferrin injected groups and the control groups. Neither the route of lactoferrin administration (i.v. or i.p.) nor the sex of the animal altered the myelopoietic recovery. Lactoferrin had no stimulatory or inhibitory effect on murine rebound myelopoiesis in vivo contrary to the reported in vitro results.

Transesophageal echocardiography has been used as a diagnostic tool in the critical care unit. However, long-term serial evaluation of ventricular function with transesophageal echocardiography is difficult because of the current probe sizes and intolerance to prolonged oral intubation. We performed 139 intubations (64 oral and 75 transnasal) with a new prototype probe in 128 patients referred for transesophageal echocardiography. Transnasal intubation with the prototype probe was possible in 63/75 attempts. Oral intubation was successful in all 64 attempts. Patients tolerated transnasal intubation well when mildly sedated or awake. Two-dimensional echocardiographic views obtained with the nasal probe were similar to those obtained with a standard monoplane probe. Image quality was rated as good or acceptable in nearly all cases. Transgastric short-axis imaging of the left ventricle combined with acoustic quantification provided stable left ventricular area waveforms. Using custom developed software we showed the feasibility of monitoring left ventricular performance with minimal probe adjustment while graphically displaying and updating left ventricular area and fractional area change. Thus, transesophageal echocardiography with a prototype miniaturized monoplane probe passed transnasally is feasible, safe, and well tolerated by patients. This probe provides excellent two-dimensional echocardiographic images and may allow long-term echocardiographic monitoring of ventricular performance.