Structural and functional cardiac changes in endomyocardial fibrosis treated with endomyocardial resection: Disease progression captured by multimodality imaging.

Eosinophilic myocarditis, a rare and under-recognized disease process, occurs due to cytotoxic inflammation of the endomyocardium that over time may lead to a restrictive cardiomyopathy. We report clinical, multimodality imaging, and pathologic findings in a 45-year-old woman over a 17-month period as she progressed from suspected acute eosinophilic myocarditis to phenotypic endomyocardial fibrosis resulting in recurrent ascites. Interval echocardiograms demonstrate definitive pathologic structural changes that reflect the hemodynamic consequences of the underlying cardiomyopathy. Despite a negative myocardial biopsy, characteristic findings on cardiovascular magnetic resonance imaging clarified the diagnosis which led to successful treatment with endomyocardial resection and valve replacements.

Lipoprotein-associated phospholipase A2, a novel cardiovascular inflammatory marker, in HIV-infected patients.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging biomarker of cardiovascular disease. This study was conducted to describe the distribution of Lp-PLA2 in a cohort of human immunodeficiency virus (HIV)-infected adults and to determine associations between Lp-PLA2, cardiometabolic risk factors, and subclinical atherosclerosis in this population. METHODS: Lp-PLA2 was assessed in 341 (25% women, 52% white, 74% on highly active antiretroviral therapy [HAART]) participants of a cohort with detailed characterization of atherogenic risk factors, including surrogate markers of carotid and coronary atherosclerosis. RESULTS: Mean Lp-PLA2 mass was 313 ± 105 ng/mL and activity 173 ± 49 nmol/minute/mL. Seventy-five percent of participants had abnormal Lp-PLA2. Those in the highest Framingham Risk Score tertile had significantly higher Lp-PLA2 activity. Participants with abnormal carotid intima-media thickness (cIMT) had higher Lp-PLA2 mass and activity. Those with coronary artery calcium (CAC) scores >100 had significantly higher Lp-PLA2 mass than those with lower or nondetectable calcium. Those on HAART and protease inhibitor (PI)-based treatment had significantly higher Lp-PLA2 mass and activity than those who were treatment-naive or not on PIs. In multivariate regression, HAART and PI use were positively associated with Lp-PLA2 activity and mass after adjusting for age, race, sex, low-density and high-density lipoprotein cholesterol levels, triglyceride level, and smoking. Adding Lp-PLA2 activity tertiles to the model improved the predictive value for abnormal common cIMT, but not internal cIMT or CAC score. CONCLUSIONS: Lp-PLA2 is highly abnormal in HIV-infected patients and is associated with several cardiovascular and HIV treatment-specific risk factors. Lp-PLA2 may be used as an additional and more vascular specific biomarker for cardiovascular risk stratification in HIV-positive patients.

The syndrome of degenerative calcific aortic stenosis: prevalence of multiple pathophysiologic disorders in association with valvular stenosis and their implications.

BACKGROUND: We hypothesized that degenerative calcific aortic stenosis (DCAS) is a syndrome influenced by factors beyond aortic valve stenosis (AS). The aim of this study was to assess how frequently DCAS is complicated by increased vascular load, systolic and/or diastolic left ventricular (LV) dysfunction, and comorbid disorders. METHODS: In 215 consecutive patients > 60 years of age with severe and moderate AS, we analyzed systemic arterial compliance, global hemodynamic load, LV ejection fraction (EF), the presence of diastolic dysfunction, and other valvular or systemic disorders. RESULTS: A total of 164 patients had severe AS and 51 had moderate AS. In patients with severe AS, the prevalence of increased vascular load was 42%; LV systolic and diastolic dysfunction was present in 27% and 42%; other valve diseases in 23%; and comorbid disorders in 82%. In the moderate AS group, abnormal vascular load was found in 52%; LV systolic and diastolic dysfunction was prevalent in 26% and 31%; other valve diseases in 17%; and comorbid disorders in 78% patients. More than half the patients in both groups had symptoms. In both severe and moderate AS groups, the prevalence of increased vascular load and systolic dysfunction was higher in the symptomatic group. CONCLUSION: Considerable number of patients with DCAS have abnormal vascular load, abnormal LV function, and significant coexisting disorders. These could influence the total pathophysiologic burden on the heart and symptom expression. Thus, DCAS should not be considered just as valvular stenosis, but a syndrome of DCAS because of the diagnostic, prognostic, and therapeutic implications of various factors associated with it.

Endothelial function and soluble endoglin in smokers with heart failure.

BACKGROUND: Although cigarette smoking is a risk factor for heart failure (HF), smokers with HF have lower mortality rates during/following hospitalization compared to nonsmokers. We examined vascular endothelial function in chronic smokers and nonsmokers with HF as it relates to this smoker's paradox. HYPOTHESIS: Smokers with HF will have attenuated endothelial dysfunction compared to non-smokers with HF. METHODS: Brachial artery flow-mediated dilation (FMD), a measure of conduit vessel endothelial function, was measured in 33 smoking and nonsmoking patients with HF vs controls. In addition, soluble endoglin (sEng), a circulating mediator of endothelial function, was measured in a separate group of 36 smoking and nonsmoking patients with HF vs controls. RESULTS: FMD was significantly lower in smokers without HF compared to the nonsmokers without HF (P < 0.05). FMD was significantly higher in smokers with HF vs nonsmokers with HF (P < 0.05) and did not differ from values seen in nonsmokers without HF (P > 0.05). There were no differences in sEng between smokers and nonsmokers without HF (P > 0.05). sEng was lower in smokers with HF vs nonsmokers with HF (P < 0.05) and did not differ from values seen in nonsmokers without HF (P > 0.05). CONCLUSIONS: Smokers with HF had higher brachial FMD and lower sEng than nonsmokers with HF, and values were comparable to nonsmokers without HF. These findings offer novel insight into the smoker's paradox and suggest that improved short-term outcome in patients hospitalized with HF may in part be mediated by preservation of vascular endothelial function in this setting.

Assessor-blinded study of the metabolic syndrome and surrogate markers of increased cardiovascular risk in children with moderate-to-severe psoriasis compared with age-matched population of children with warts.

Adult patients with psoriasis have an increased prevalence of the metabolic syndrome (MetS) and cardiovascular disease (CVD) risk factors due to elevations of Tumor Necrosis Factor and other inflammatory cytokines.1,2 Recently, higher rates of hyperlipidemia, obesity, hypertension, and diabetes mellitus were seen in patients with juvenile psoriasis.3 Here, we report the interim results of an ongoing study of MetS and CVD risk factors in pediatric psoriasis patients.

Pre-operative left atrial mechanical function predicts risk of atrial fibrillation following cardiac surgery.

OBJECTIVES: The purpose of this study was to examine whether left atrial (LA) mechanical function, as measured by LA total emptying fraction (TEF), is a predictor for the development of post-operative atrial fibrillation (POAF) following cardiac surgery. BACKGROUND: POAF is an important and frequent complication of cardiac surgery. LA enlargement has been reported to be a risk factor for POAF, but the relationship between LA mechanical function and POAF is not well understood. We examined the relationship between pre-operative LA function and POAF in patients without a history of atrial fibrillation. METHODS: A total of 101 subjects (mean age 64 ± 13 years) underwent pre-operative transthoracic echocardiograms and were followed for occurrence of POAF during the hospitalization for cardiac surgery. The left atrial maximum volume (LAVmax) and left atrial minimum volume (LAVmin) were measured and indexed to body surface area (LAVmaxI and LAVminI, respectively). LA TEF was calculated as: {[(LAVmax - LAVmin)/LAVmax] × 100%}. Univariate and multivariate analyses examined clinical and echocardiographic predictors of POAF. RESULTS: POAF occurred in 41% of subjects. Mean LA TEF was 49 ± 15%, mean LAVmaxI was 38 ± 15 ml/m(2), and mean LAVminI was 20 ± 13 ml/m(2). Age, LA TEF, and LAVminI were independent predictors of POAF. LA TEF was lower in patients with POAF compared with those without POAF (43 ± 15% vs. 55 ± 13%, p < 0.001), and patients with a LA TEF <50% had a high risk of POAF (odds ratio: 7.94, 95% confidence interval: 3.23 to 19.54, p < 0.001). Compared with LAVmaxI >32 ml/m(2), LA TEF <50% had higher discriminatory power for POAF, which remained significantly higher when adjusted for age (p = 0.04). CONCLUSIONS: LA TEF is an independent predictor of POAF and is a stronger predictor of POAF than LAVmaxI is. Impaired LA mechanical function may help to identify patients who are most likely to benefit from prophylaxis for POAF.

Endothelium-dependent vasodilation is associated with exercise capacity in smokers and non-smokers.

Smoking is an established cardiovascular risk factor that impairs endothelial function and reduces exercise capacity. Peripheral vascular endothelial function correlates with exercise capacity, but whether this association prevails in smokers is unknown. The purpose of this investigation was to examine the association between endothelial function and exercise capacity in chronic smokers and non-smoking controls. Brachial artery flow-mediated dilation (FMD, endothelium-dependent) following 5 minutes of upper arm occlusion was compared in 26 smokers (age 58 +/- 2 years; 15 female; BMI (body mass index) = 28 +/- 1) and 39 non-smokers (age 58 +/- 2 years; 24 female; BMI = 28 +/- 1) using ultrasound. Exercise treadmill time (ETT) was recorded from a standard Bruce protocol during symptom limited stress testing. There was found to be a significant positive association between FMD and ETT in smokers (r = 0.60, p < 0.05) and non-smokers (r = 0.28, p < 0.05). FMD was significantly lower in smokers versus non-smokers (8.9 +/- 0.9 vs 12.6 +/- 0.7%, p < 0.05). ETT was significantly lower in smokers (425 +/- 35 seconds) versus non-smokers (522 +/- 25 seconds, p < 0.05). After adjusting for FMD, there were no longer group differences in ETT. When patients were matched according to FMD, there were no differences in ETT between smokers and non-smokers. In conclusion, peripheral endothelial dysfunction is a correlate of low exercise capacity in smokers and non-smokers alike. Future research is needed to examine if improving endothelial function will lead to concomitant increases in exercise capacity in chronic smokers.

Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events.

AIMS: There is growing need for the identification of novel non-invasive methodologies for the identification of individuals at risk for adverse cardiovascular (CV) events. We examined whether endothelial dysfunction, as detected by non-invasive peripheral arterial tonometry (EndoPAT), can predict late CV events. METHODS AND RESULTS: Reactive hyperaemia (RH) was induced following upper arm occlusion of systolic blood pressure in 270 outpatients (54 +/- 12 years, 48% female). The natural logarithmic scaled RH index (L_RHI) was calculated from the ratio between the digital pulse volume during RH and at baseline. The patients were followed for CV adverse events (AE: cardiac death, myocardial infarction, revascularization or cardiac hospitalization) during a 7-year follow-up (inter-quartile range = 4.4-8). Cox models were used to estimate the association of EndoPAT results with AE adjusted for age. During the follow-up, AE occurred in 86 patients (31%). Seven-year AE rate was 48% in patients with L_RHI < 0.4 vs. 28% in those with L_RHI >or= 0.4 (P = 0.03). Additional univariate predictors of AE were advancing age (P = 0.02) and prior coronary bypass surgery (P = 0.01). The traditional Framingham risk score was not higher in patients with AE. Multivariate analysis identified L_RHI < 0.4 as an independent predictor of AE (P = 0.03). CONCLUSION: A low RH signal detected by EndoPAT, consistent with endothelial dysfunction, was associated with higher AE rate during follow-up. L_RHI was an independent predictor of AE. Non-invasive assessment of peripheral vascular function may be useful for the identification of patients at risk for cardiac AEs.

Modestly overweight women have vascular endothelial dysfunction.

BACKGROUND: Vascular endothelial dysfunction occurs early in the atherosclerotic process and is predictive of cardiovascular prognosis. However, the association between specific cardiovascular risk factors and endothelial dysfunction in women has not been well characterized. This study examined the relationship between endothelial dysfunction and cardiovascular risk factors (body mass index [BMI] >or= 25 kg/m(2), current smoking, age, diabetes, hypertension, hypercholesterolemia, and family history of early coronary heart disease) in a population of women that included those already being treated for risk factors. METHODS: Endothelial function was assessed by brachial artery ultrasound flow-mediated vasodilation (FMD) in 185 consecutive women without a history of coronary heart disease. Women with hypertension, diabetes, or hyperlipidemia were allowed to continue on their usual therapy. RESULTS: There was an inverse linear association between age and FMD. Subjects who were active smokers had lower FMD compared with nonsmokers, and subjects with BMI >or= 25 kg/m(2) had lower FMD than subjects with BMI < 25 kg/m(2). FMD in overweight women (BMI >or= 25 and < 30 kg/m(2)) was similar to that of obese women (BMI >or= 30 kg/m(2)). Multivariate analysis demonstrated that body mass index, current smoking, and age were independent predictors of endothelial dysfunction in this population. CONCLUSION: Modestly elevated BMI, smoking, and age predict endothelial dysfunction in women, even in the presence of treatment for other atherosclerotic risk factors. These findings demonstrate the importance of modest elevation in BMI as a risk factor for impaired vascular health in women, and underscore the need for focusing further attention on lifestyle modification as a component of cardiovascular disease prevention.

Has the clinical presentation and clinician's index of suspicion of cardiac tamponade changed over the past decade?

It remains unclear whether advances in the understanding of the pathophysiology and improvements in cardiovascular imaging over the years have impacted the clinician's recognition of cardiac tamponade (CT). We sought to evaluate signs and symptoms of CT in a present-day population and compare it to a similar group from a decade prior. We performed a retrospective analysis of two cohorts of patients presenting to a tertiary hospital with CT, all of whom underwent pericardial drainage (PD). Group 1 (Gp1) included subjects presenting from 1988 to 1991 and Group 2 (Gp2) included subjects from 2002 to 2005. Fifty-five patients comprised each group, with an average age of 55 years. Seventy-one percent of patients in Gp1 had identifiable cardiovascular symptoms 1 week prior to presentation, compared to 33% in Gp2. Dyspnea was the most common symptom in both groups, and was less frequent in Gp2. Compared with Gp1, chest pain, cough, and lethargy were also less frequent in Gp2. One day prior to PD, tachypnea and pulsus paradoxus were detected more frequently in Gp1 compared to Gp2. Large, circumferential pericardial effusions were the most frequent echocardiographic findings in both groups and the most common etiology of CT was malignancy in Gp1and postoperative bleeding in Gp2. Thus, the recognition of symptoms and physical signs in patients presenting with CT has changed over the past decade, as has etiology of pericardial effusions. However, the diagnosis of CT still remains delayed, and the present data emphasize the need for a heightened index of suspicion for recognizing this hemodynamically-important process.

Association of estrogen receptor beta gene polymorphisms with left ventricular mass and wall thickness in women.

BACKGROUND: Left ventricular (LV) hypertrophy is a significant risk factor for cardiovascular disease. Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure. METHODS: We studied 1249 unrelated individuals, 547 men and 702 women (mean age 59 years) from the Framingham Heart Study. Eight single nucleotide polymorphisms in the genes for estrogen receptor alpha and estrogen receptor beta (ESR2) were tested for association with 5 LV measures: LV mass (LVM), LV wall thickness (LVWT), LV internal diameter at end-diastole and end-systole, and fractional shortening. Sex-specific multiple regression analyses were performed adjusting for age, weight, height, systolic and diastolic blood pressure, hypertension treatment, diabetes, and in women, menopausal status. RESULTS: In men, there was no evidence of association between the estrogen pathway polymorphisms tested and LV structure or function. In women, however, two polymorphisms, ESR2 rs1256031 and ESR2 rs1256059, in linkage disequilibrium with one another, were associated with LVM and LVWT (P = .0007 to .03); the association was most pronounced in those women with hypertension (P = .0006 to .01). The association did not appear to be explained by variation in blood pressure, plasma lipoprotein levels, or hyperglycemia. CONCLUSIONS: The ESR2 polymorphisms are associated with LV structural differences in women with hypertension in a community-based population. These data are consistent with the hypothesis that genetic factors may mediate part of the observed sex-based differences in LV structure and remodeling.

Blood cyst of the mitral valve apparatus in a woman with a history of orthotopic liver transplantation.

Blood cysts within the heart are rare findings in adults. We describe a case of a woman with a history of orthotopic liver transplantation who presented for an echocardiogram to evaluate a potential source of cerebrovascular embolism. A cystic mass attached to the submitral valve apparatus was identified by transthoracic and confirmed by transesophageal echocardiography. Surgical exploration and pathologic examination confirmed the mass to be a blood cyst attached to the chordal apparatus of the posterior papillary muscle. This case report highlights the use of echocardiography in diagnosing intracardiac blood cysts.

Postoperative cardiac tamponade in the modern surgical era.

BACKGROUND: Pericardial effusions resulting in cardiac tamponade (CT) are uncommon after open heart surgery (OHS) and are associated with significant morbidity and mortality. Characteristics and outcomes of patients who develop postoperative CT are poorly defined. Our objective was to further analyze the population at risk for developing postoperative CT, identify potential perioperative and surgical risk factors, and evaluate the impact of CT on patient outcomes. METHODS: A retrospective analysis of 4,561 consecutive patients undergoing OHS at our institution was performed. Patients with clinical suspicion of pericardial effusion following surgery were evaluated by transthoracic or transesophageal echocardiography, and clinical parameters were analyzed. RESULTS: Forty-eight (1%) of the 4,561 patients were found to have echocardiographic evidence of a moderate or large pericardial effusion, of whom 36 (74%) had evidence of CT. The mean age of the patients with CT was 61 years. Coronary artery bypass grafting (CABG) had been performed in 24% of these patients, valve +/- CABG in 73%, and other OHS procedures in 3%. The incidence of CT following CABG alone was 0.2%, whereas it was 0.6% after valve +/- CABG. Females had a higher risk for developing CT, and this occurred earlier in the postoperative period when compared with men. Aspirin, heparin, or warfarin were given to 84% of patients within 3 days of surgery. Mean time to diagnosis of CT was 10 +/- 1 days after OHS. Prior to diagnosis of CT, the maximum international normalized ratio (INR) and partial thromboplastin time (PTT) were 2.7 +/- 0.3 and 68 +/- 5 seconds, respectively. Forty-nine percent of pericardial effusions were posterior and 46% were circumferential; one-third of the effusions were considered large by echocardiography. There was one in-hospital cardiovascular death. CONCLUSIONS: CT after OHS is more common following valve surgery than CABG alone and may be related to the preoperative use of anticoagulants. Females appear to be at higher risk for developing early postoperative CT. When diagnosed and treated promptly, postoperative CT should not significantly increase mortality.

Recent role of imaging in the diagnosis of pericardial disease.

Noninvasive cardiac imaging techniques have made a striking impact on the evaluation and management of pericardial disorders. Two-dimensional and Doppler echocardiography are the methods of choice in the evaluation of pericardial effusion and cardiac tamponade. Magnetic resonance imaging, computed tomography, and transesophageal echocardiography are valuable in the assessment of pericardial thickness in suspected cases of constrictive pericarditis. Filling dysfunction associated with constrictive pericarditis is well demonstrated by Doppler flow velocity recordings of intracardiac flow jets, and pulmonary and hepatic venous flow streams. Tissue Doppler echocardiography, by which tissue velocity of myocardial regions and mitral annulus are analyzed, offers additional information in the differentiation of constrictive pericarditis and restrictive cardiomyopathy. Magnetic resonance imaging and computed tomography are the techniques of choice in the recognition of unusual disorders such as pericardial cysts, tumors invading the pericardium, and congenital absence of pericardium. Noninvasive imaging aids not only in the diagnosis of pericardial diseases, but also in the guidance of optimal therapy.