Cognitive performance is lower among individuals with overlap syndrome than in individuals with COPD or obstructive sleep apnea alone: association with carotid artery stiffness.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack years, and postbronchodilator FEV1/FVC. We also examined the association between CCA stiffness and cognitive performance among each group separately. Individuals with overlap syndrome (n = 12) had greater CCA ß-stiffness index (P = 0.015) and lower executive function-processing speed (P = 0.019) than individuals with COPD alone (n = 47), OSA alone (n = 9), and former smoker controls (n = 21), differences that remained significant after adjusting for age, BMI, sex, pack years, and FEV1/FVC. Higher CCA ß-stiffness index was associated with lower executive function-processing speed in individuals with overlap syndrome (r = -0.58, P = 0.047). These data suggest that CCA stiffness is greater and cognitive performance is lower among individuals with overlap syndrome compared with individuals with COPD or OSA alone and that CCA stiffening may be an underlying mechanism contributing to the lower cognitive performance observed in patients with overlap syndrome.NEW & NOTEWORTHY Previous studies have demonstrated greater carotid artery stiffness and lower cognitive function among individuals with COPD alone and OSA alone. However, the present study is the first to demonstrate that individuals that have both COPD and OSA (i.e., overlap syndrome) have greater carotid artery stiffness and lower executive function-processing speed than individuals with either disorder alone. Furthermore, among individuals with overlap syndrome greater carotid artery stiffness is associated with lower executive function-processing speed.

Daily Activities: The Impact of COPD and Cognitive Dysfunction.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD. METHOD: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD. RESULTS: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression. CONCLUSION: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities.

Carotid Artery Stiffness is Associated With Cognitive Performance in Former Smokers With and Without Chronic Obstructive Pulmonary Disease.

Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery ß-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (ß=-0.49, SE=0.14; P=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. ß-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.

Reduced Attention in Former Smokers with and without COPD.

BACKGROUND: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention. METHODS: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable. RESULTS: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model. CONCLUSION: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.

Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function.

INTRODUCTION: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function. METHODS: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs. RESULTS: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy. CONCLUSIONS: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression.

Subjective cognitive complaints and neuropsychological performance in former smokers with and without chronic obstructive pulmonary disease.

OBJECTIVE: This study examined the association of perceived cognitive difficulties with objective cognitive performance in former smokers. We hypothesized that greater perceived cognitive difficulties would be associated with poorer performance on objective executive and memory tasks. METHOD: Participants were 95 former smokers recruited from the COPDGene study. They completed questionnaires (including the Cognitive Difficulties Scale [CDS] and the Hospital Anxiety and Depression Scale [HADS]), neuropsychological assessment, and pulmonary function testing. Pearson correlations and t-tests were conducted to examine the bivariate association of the CDS (total score and subscales for attention/concentration, praxis, delayed recall, orientation for persons, temporal orientation, and prospective memory) with each domain of objective cognitive functioning (memory recall, executive functioning/processing speed, visuospatial processing, and language). Simultaneous multiple linear regression was used to further examine all statistically significant bivariate associations. The following covariates were included in all regression models: age, sex, pack-years, premorbid functioning (WRAT-IV Reading), HADS total score, and chronic obstructive pulmonary disease (COPD) status (yes/no based on GOLD criteria). RESULTS: In regression models, greater perceived cognitive difficulties overall (using CDS total score) were associated with poorer performance on executive functioning/processing speed tasks (b = -0.07, SE = 0.03, p = .037). Greater perceived cognitive difficulties on the CDS praxis subscale were associated with poorer performance on executive functioning/processing speed tasks (b = -3.65, SE = 1.25, p = .005), memory recall tasks (b = -4.60, SE = 1.75, p = .010), and language tasks (b = -3.89, SE = 1.39, p = .006). CONCLUSIONS: Clinicians should be aware that cognitive complaints may be indicative of problems with the executive functioning/processing speed and memory of former smokers with and without COPD.

Right ventricular diastolic function and exercise capacity in COPD.

BACKGROUND: Decreased exercise capacity in chronic obstructive pulmonary disease (COPD) is incompletely explained by pulmonary pathologic and physiologic abnormalities. We evaluated the extent to which right ventricular diastolic function (RVDF) is associated with exercise capacity in COPD. METHODS: Fifty-one patients with COPD were evaluated by echocardiography, spirometry, and the 6 min walk test (6MWT). RVDF was assessed using 4 echocardiographic parameters: 1) the ratio of tricuspid valve (TV) early (E) and late (A) inflow velocities (TV E/A) 2) TV early tissue Doppler velocity (TV e') 3) TV deceleration time (DT) and 4) the ratio of TV E and e' velocities (TV E/e'). Multiple linear regression was used to examine the extent to which these parameters were associated with 6MWT distance. All models adjusted for age, sex, post-bronchodilator FEV1/FVC, resting heart rate, and use of supplemental O2 during 6MWT. A regression model was calculated for each of the 4 markers of RVDF. RESULTS: Forty-seven percent of the sample had GOLD stage III or IV COPD. All 51 subjects had preserved left ventricular ejection fraction (LVEF, mean = 71.7%, SD = 7.8%). A higher TV E/A ratio was associated with increased 6MWT distance (p = 0.001). TV e', TV DT and TV E/e' did not have a statistically significant association with 6MWT distance in regression models. CONCLUSIONS: In a cohort with moderate to severe COPD and normal LVEF, TV E/A was associated with 6MWT distance after adjusting for relevant demographic and medical covariates. RV diastolic dysfunction may independently contribute to exercise intolerance in COPD.

Sex differences in the effects of type 2 diabetes on exercise performance.

PURPOSE: People with uncomplicated type 2 diabetes (T2D) have impaired peak exercise performance compared with that of their nondiabetic counterparts. This impairment may represent the earliest indication of cardiovascular (CV) abnormalities in T2D. Women with T2D are known to have worse CV outcomes than those in men with T2D. We hypothesized that women with diabetes have a greater exercise impairment than that in men with diabetes compared with that in their nondiabetic counterparts. METHODS: We studied 15 women (premenopausal) and 14 men with T2D as well as their nondiabetic counterparts (22 women and 13 men). Exercise testing was performed. Additional outcomes included measurements of insulin sensitivity, endothelial function, blood flow, and resting cardiac function. RESULTS: Men and women with T2D but not controls had impaired insulin sensitivity. Women with T2D had a lower peak oxygen consumption (V˙O2peak) compared with that of nondiabetic women (24%, P < 0.05) than men with diabetes compared with that in nondiabetic men (16%, P < 0.05) (P value between groups < 0.05). The time constants (phase 2) of the V˙O2 kinetic response tended to be slower in men and women with T2D than those in nondiabetic controls (P = 0.08). There were no differences in resting ventricular function by Doppler echocardiography techniques between groups. Women with T2D had significantly lower flow-mediated dilation and blood flow responses to hyperemia than those in nondiabetic women (both P < 0.05), whereas men with T2D had lower flow-mediated dilation but not lower blood flow than those in nondiabetic men. CONCLUSIONS: Although both men and women with uncomplicated T2D had a lower V˙O2peak, the abnormality in women with T2D compared with that in nondiabetic women was greater than that seen in men. Because V˙O2peak has a strong inverse correlation with mortality, sex disparities observed in exercise capacity among people with T2D suggest a possible rationale for the increased CV morbidity and mortality observed in women compared with those observed in men with uncomplicated T2D.

Saline contrast echocardiography for the detection of patent foramen ovale in hypoxia: a validation study using intracardiac echocardiography.

Although the "3 beat rule" is widely utiized to discriminate patent foramen ovale (PFO)-mediated right-to-left shunt (RTLS) from intrapulmonary RTLS using saline contrast transthoracic echocardiography (SCE), SCE diagnostic performance has yet to be validated using an invasive intracardiac standard. Percutaneous PFO occluder placement was recently shown to ameliorate hypoxia in patients with suspected PFO-mediated RTLS. We evaluated the ability of SCE to predict PFO presence and size using intracardiac echocardiography (ICE) as a gold standard in a hypoxic cohort. Sixty-three hypoxic patients with suspected PFO-mediated RTLS who underwent SCE at rest, with Valsalva maneuver, and with cough prior to ICE were evaluated retrospectively. PFO RTLS was defined by ICE findings including PFO anatomy, RTLS by saline contrast and color Doppler, and probe patency. SCE shunt severity and timing of left heart saline target appearance were compared to the presence of ICE-defined PFO RTLS. Forty-seven patients (75%) met criteria for PFO-mediated RTLS. A 4 beat cutoff for resting SCE provided optimal diagnostic performance for detection of PFO-mediated RTLS with a 71% sensitivity, 94% specificity, and 97% positive predictive value (PPV). Valsalva and cough maneuvers improved sensitivity compared to rest SCE (89% and 80%, respectively). Valsalva SCE shunt severity more accurately predicted PFO size than resting SCE. In contrast to the widely accepted "3 beat rule," resting SCE for the detection of PFO RTLS in a hypoxic population performs optimally using a 4-cycle cutoff with both excellent specificity and PPV.

Predictors of cardiac sarcoidosis using commonly available cardiac studies.

Cardiac involvement affects ≤40% of patients with sarcoidosis and accounts for ≤25% of deaths. The diagnosis of cardiac sarcoidosis is challenging using the existing screening tests and often relies on expensive cardiac magnetic resonance imaging (cMRI) and cardiac 18-fluorodeoxuyglucose positron emission tomography (FDG-cPET). We developed a scoring system using common clinical tests to predict positive imaging findings using cMRI or FDG-cPET. A retrospective chart review of subjects undergoing cMRI or FDG-cPET was performed. The data were extracted and scored using a predetermined system. Our cohort was predominantly white, with a mean age of 55 years, and 60% were women. The scoring system was compared with the findings from cMRI and FDG-cPET to determine the ability to predict the imaging results that define cardiac sarcoidosis. The scoring system for the patients who had undergone both FDG-cPET and cMRI suggested predictability, but the differences were not statistically significant. However, the positive results from just 1 study were as predictive as having positive findings from both studies. A 1-point increase in the total score increased the probability of positive findings from cMRI or FDG-cPET by 14% (95% confidence interval 3% to 25% increase; p = 0.01). The scoring system seemed to be driven more by the findings from cMRI than by those from FDG-cPET. In patients who had undergone cMRI alone, for each 1-point increase in the total score, the probability of positive cMRI findings increased 11% (95% confidence interval 1% decrease to 25% increase, p = 0.08). All screening modalities were analyzed. No modality was sensitive or specific, although major findings (defined in our scoring system) were most predictive of positive imaging findings. In conclusion, commonly available cardiac screening tools used together in a composite score provide reasonable results to predict positive cardiac sarcoidosis findings on imaging, but the system needs refinement. Our data suggest that major findings from screening studies are more likely to correlate with cMRI findings than with findings from FDG-cPET.

Hypoxia caused by persistent left superior vena cava connecting to the left atrium a rare clinical entity.

We relate the case of a 40-year-old man with a history of premature birth and dextroposition of the heart who presented for an evaluation of persistent hypoxia. An unrevealing pulmonary evaluation and agitated-saline echocardiogram led to cardiac magnetic resonance imaging. This revealed a very unusual finding: a persistent left superior vena cava with insertion into the left atrium and a small connecting vein between the right and left superior venae cavae. The implications, embryology, and pathogenesis of this rare condition are discussed.

Implantable cardioverter defibrillator therapy in patients with cardiac sarcoidosis.

UNLABELLED: ICD Shocks in Cardiac Sarcoidosis. BACKGROUND: An implantable cardioverter defibrillator (ICD) is indicated for some patients with cardiac sarcoidosis (CS) for prevention of sudden death. However, there are little data regarding the event rates of ICD therapies in these patients. We sought to identify the incidence and characteristics of ICD therapies in this patient population. METHODS: We performed a cohort study of patients with ICDs at 3 institutions. Cases were those patients with CS and an ICD implanted for primary or secondary prevention of sudden death. Additionally, we included a comparison with historical controls of ICD therapy rates reported in clinical trials evaluating the ICD for primary and secondary prevention of sudden death. RESULTS: Of the 112 CS subjects identified, 36 (32.1%) received appropriate therapies for ventricular tachyarrhythmias (VT) over a mean follow-up period of 29.2 months. VT storm (>3 episodes in 24 hours) occurred in 16 (14.2%) CS subjects. Inappropriate therapies occurred in 13 CS subjects (11.6%). Covariates associated with appropriate ICD therapies included left ventricular ejection fraction (LVEF) <55% (OR 6.52 [95% CI 2.43-17.5]), right ventricular dysfunction (OR 6.73 [95% CI 2.69-16.8]), and symptomatic heart failure (OR 4.33 [95% CI 1.86-10.1]). CONCLUSIONS: In our cohort of patients with CS and ICDs, almost one-third receive appropriate therapies. This may be due to a myocardial inflammatory process leading to increased triggered activity and subsequent scarring leading to reentrant tachyarrhythmias. Adjusted predictors of ICD therapies in this population include left or right ventricular dysfunction. (J Cardiovasc Electrophysiol, Vol. 23, pp. 925-929, September 2012).

Management of cardiac sarcoidosis in the United States: a Delphi study.

BACKGROUND: No formal guidelines exist to guide physicians caring for patients with sarcoidosis in their screening for management of patients with cardiac sarcoidosis. We conducted a modified Delphi study to investigate if a consensus could be reached on the best approaches for screening for and management of cardiac sarcoidosis. METHODS: A modified Delphi study design with two rounds of questionnaires was used to investigate if a consensus existed among sarcoid experts in the United States on the best management approaches for cardiac sarcoidosis. Experts were identified based on their national reputation as sarcoid experts and by being actively involved in sarcoidosis clinics at their institutions. RESULTS: Overall agreement was low to moderate. Agreement was reached on the role of history, physical examination, and 12-lead ECG in screening, echocardiogram, Holter monitor, myocardial fluorodeoxyglucose PET scan, and cardiac MRI in workup, and steroids in treatment. Agreement was not reached on the role of signal-averaged ECG in screening, optimum dose of prednisone, use of steroid-sparing agents, and duration of treatment. Several comments underscore the diverse approaches and uncertainty that exist in managing cardiac sarcoidosis. CONCLUSIONS: Our study highlights the dilemma that sarcoid experts face in their approach to cardiac sarcoidosis. It also highlights the lack of agreement among sarcoid experts on key aspects of diagnosis and management and stresses the importance of collaborative efforts to investigate the best strategies for screening for and management of cardiac sarcoidosis.

Diagnostic utility of signal-averaged electrocardiography for detection of cardiac sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) occurs in up to 25% of patients with pulmonary involvement. Early diagnosis is critical because sudden death from ventricular arrhythmias can be the initial presentation. We sought to evaluate the diagnostic utility of signal-averaged ECG (SAECG) for detection of cardiac involvement of sarcoidosis. METHODS: Subjects with biopsy proven sarcoidosis and symptoms suggestive of possible cardiac involvement were included in the cohort. Standard criteria for SAECG were used. Subjects were considered to have CS if they met criteria established by the Japanese Ministry of Health and Welfare modified to include cardiac MRI. RESULTS: Of the 88 patients in the cohort 27 had evidence of CS independent of the SAECG results. The SAECG was abnormal in 14 of these 27 patients and 11 of the 61 of the subjects without cardiac involvement (P < 0.01). The sensitivity of SAECG detection of CS was 52% with a specificity of 82%. For the entire cohort, SAECG had a positive predictive value (PPV) of 0.56 and a negative predictive value (NPV) of 0.79. Within a subgroup of 67 patients with an unfiltered QRS duration of <100 ms, the specificity for diagnosing cardiac sarcoidosis improves to 100% with a reduced sensitivity of 36.8. Of the SAECG parameters, LAS40 was significantly associated with the diagnosis of cardiac sarcoidosis for the entire cohort (P < 0.01) and among the subgroup of patients with an unfiltered QRS duration of <100 ms (P < 0.01). CONCLUSIONS: SAECG is a useful screening tool in the evaluation of sarcoidosis for detection of cardiac involvement.

Fluctuation in ventricular sensing leading to underdetection of ventricular fibrillation in a patient with cardiac sarcoidosis.

In this case report, we describe markedly fluctuating ventricular sensing through an implantable cardioverter defibrillator (ICD) over a period of 29 months in a patient with cardiac sarcoidosis. We conclude that the fluctuations in the measured R wave are the result of waxing and waning inflammation associated with sarcoid activity. The patient had a stable medical course throughout the time period studied, including stable immunosuppression and stable electrolytes. We believe this is an example of an important complication of ICD implants in patients with cardiac sarcoidosis and that frequent sensing evaluations are prudent in these patients.

Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron.

Chronic iron-overload is damaging to the heart, liver, and other organs. Better iron chelators are needed to treat this serious medical condition. The uptake and distribution of the lipid-soluble, hexadentate iron chelator desferri-Exochelin 772SM (D-Exo) is studied and its efficacy in removing iron from tissue in rodent models is evaluated. After an intravenous bolus of tritiated D-Exo to rats, counts rapidly disappeared from the blood and rapidly appeared in 15 organs studied, usually peaking within 15 min. There was considerable uptake in the heart and liver, 2 organs especially susceptible to damage from clinical iron overload. To assess actual decreases in cardiac and hepatic iron in response to D-Exo, mice loaded with 42 mg of iron dextran (2100 mg/kg) were studied. Untreated, iron-loaded mice sacrificed 9 weeks later had a 4-fold increase in cardiac iron and a 20-fold increase in hepatic iron compared with controls that were not iron-loaded. In iron-loaded mice treated with 7 mg of D-Exo intraperitoneally (i.p.) 4 days/week for 8 weeks (total 224 mg), tissue iron, measured by atomic absorption, was reduced by 20% in the liver and 25% in the heart (P < 0.01 for each organ). During the first 8 h after a D-Exo dose, iron was excreted in the urine. Mice treated with D-Exo gained weight normally and showed no evidence of toxicity. In conclusion, in this iron-overload mouse model, D-Exo administered intravenously or i.p. rapidly diffuses into multiple organs, including the heart and liver, and effectively removes iron without apparent toxicity.

Effects of angiotensin receptor blockade on haemodynamics and gene expression after myocardial infarction.

INTRODUCTION: Despite the fact that congestive heart failure (CHF) remains the most common disease in the developed world and has been extensively studied, there is little known about the molecular and cellular mechanisms of cardiac dysfunction. Angiotensin has been implicated as a mediator of cardiac injury; however, the mechanisms of its action have not been delineated. The objective of this study was to examine the relationship between the haemodynamic and molecular events during cardiac dysfunction and the role of the angiotensin system. STUDY DESIGN: We examined the effects of the angiotensin receptor blocker, valsartan, on changes in the haemodynamic and gene expression patterns in a postmyocardial infarction model in the rat. METHODS: Myocardial infarction (MI) was induced in rats by coronary artery ligation. Cardiac haemodynamics were monitored using echocardiography. Gene expression profiles after myocardial infarction were identified using Affymetrix Genechip oligonucleotide arrays. RESULTS: Myocardial contractility, as assessed by cardiac output and left ventricle (LV) fraction of shortening, was reduced in untreated animals by week 3 after MI (p < 0.05 versus baseline), and preserved with valsartan treatment as observed by the nonsignificant changes versus baseline. LV dilatation, as demonstrated by increases in LV systolic and diastolic diameters, developed by week 3 in untreated animals (p < 0.05 versus baseline) while valsartan-treated animals were protected and showed no significant increases in diameter size compared with baseline. LV hypertrophy, as shown by LV posterior wall thickness, was more profound in untreated animals (p < 0.05 versus baseline) than in those treated with valsartan at weeks 3 and 4. Changes in gene expression at 4 weeks after MI included those encoding muscle-specific genes, fibrous tissue proliferation, immune response and various others. Treatment with valsartan reversed these changes in 67% of overexpressed genes and 83% of underexpressed genes. CONCLUSION: Angiotensin receptor blockade with valsartan was found to protect cardiac function, and this beneficial effect was accompanied by a reversal of changes in gene expression induced by MI.