Multimodality Evaluation of Aortic Insufficiency and Aortitis in Rheumatologic Diseases.

Aortic insufficiency is commonly observed in rheumatologic diseases such as ankylosing spondylitis, systemic lupus erythematosus, antiphospholipid syndrome, Behçet's disease, granulomatosis with polyangiitis, and Takayasu arteritis. Aortic insufficiency with an underlying rheumatologic disease may be caused by a primary valve pathology (leaflet destruction, prolapse or restriction), annular dilatation due to associated aortitis or a combination of both. Early recognition of characteristic valve and aorta morphology on cardiac imaging has both diagnostic and prognostic importance. Currently, echocardiography remains the primary diagnostic tool for aortic insufficiency. Complementary use of computed tomography, cardiac magnetic resonance imaging and positron emission tomography in these systemic conditions may augment the assessment of underlying mechanism, disease severity and identification of relevant non-valvular/extracardiac pathology. We aim to review common rheumatologic diseases associated with aortic insufficiency and describe their imaging findings that have been reported in the literature.

Imaging Assessment of Endothelial Function: An Index of Cardiovascular Health.

Endothelial dysfunction is a key early mechanism in a variety of cardiovascular diseases and can be observed in larger conduit arteries as well as smaller resistance vessels (microvascular dysfunction). The presence of endothelial dysfunction is a strong prognosticator for cardiovascular events and mortality, and assessment of endothelial function can aid in selecting therapies and testing their response. While the gold standard method of measuring coronary endothelial function remains invasive angiography, several non-invasive imaging techniques have emerged for investigating both coronary and peripheral endothelial function. In this review, we will explore and summarize the current invasive and non-invasive modalities available for endothelial function assessment for clinical and research use, and discuss the strengths, limitations and future applications of each technique.

Cardiovascular Imaging in Stress Cardiomyopathy (Takotsubo Syndrome).

Stress cardiomyopathy (Takotsubo syndrome) is a reversible syndrome stemming from myocardial injury leading to systolic dysfunction and is usually noted in the setting of a stressful event, be it an emotional or physical trigger. While the exact pathophysiology behind stress cardiomyopathy is yet unknown, there is ample evidence suggesting that neurocardiogenic mechanisms may play an important role. Although historically stress cardiomyopathy was generally thought to be a relatively benign condition, there is growing recognition of the cardiovascular complications associated with it despite its reversibility. Our review aims to shed light onto key cardiovascular imaging modalities used to diagnose stress cardiomyopathy while highlighting the role that imaging plays in assessing disease severity, identifying complications, dictating treatment approaches, and in short-term and long-term prognosis.

Defining the Role of Point-of-Care Ultrasound in Cardiovascular Disease.

Echocardiography is the foundation for diagnostic cardiac testing, allowing for direct identification and management of various conditions. Point-of-care ultrasound (POCUS) has emerged as an invaluable tool for bedside diagnosis and management. The objective of this review is to address the current use and clinical applicability of POCUS to identify, triage, and manage a wide spectrum of cardiac conditions. POCUS can change diagnosis and management decisions of various cardiovascular conditions in a range of settings. In the outpatient setting, it is used to risk stratify and diagnose a variety of medical conditions. In the emergency department (ED) and critical care settings, it is used to guide triage and critical care interventions. Furthermore, the skills needed to perform POCUS can be taught to noncardiologists in a way that is retained and allows identification of normal and grossly abnormal cardiac findings. Various curricula have been developed that teach residents and advanced learners how to appropriately employ point-of-care ultrasound. In conclusion, POCUS can be a useful adjunct to the physical exam, particularly in critical care applications.

A novel bedside cardiopulmonary physical diagnosis curriculum for internal medicine postgraduate training.

BACKGROUND: Physicians spend less time at the bedside in the modern hospital setting which has contributed to a decline in physical diagnosis, and in particular, cardiopulmonary examination skills. This trend may be a source of diagnostic error and threatens to erode the patient-physician relationship. We created a new bedside cardiopulmonary physical diagnosis curriculum and assessed its effects on post-graduate year-1 (PGY-1; interns) attitudes, confidence and skill. METHODS: One hundred five internal medicine interns in a large U.S. internal medicine residency program participated in the Advancing Bedside Cardiopulmonary Examination Skills (ACE) curriculum while rotating on a general medicine inpatient service between 2015 and 2017. Teaching sessions included exam demonstrations using healthy volunteers and real patients, imaging didactics, computer learning/high-fidelity simulation, and bedside teaching with experienced clinicians. Primary outcomes were attitudes, confidence and skill in the cardiopulmonary physical exam as determined by a self-assessment survey, and a validated online cardiovascular examination (CE). RESULTS: Interns who participated in ACE (ACE interns) by mid-year more strongly agreed they had received adequate training in the cardiopulmonary exam compared with non-ACE interns. ACE interns were more confident than non-ACE interns in performing a cardiac exam, assessing the jugular venous pressure, distinguishing 'a' from 'v' waves, and classifying systolic murmurs as crescendo-decrescendo or holosystolic. Only ACE interns had a significant improvement in score on the mid-year CE. CONCLUSIONS: A comprehensive bedside cardiopulmonary physical diagnosis curriculum improved trainee attitudes, confidence and skill in the cardiopulmonary examination. These results provide an opportunity to re-examine the way physical examination is taught and assessed in residency training programs.

Tetralogy of Fallot and aortic root dilation: a long-term outlook.

Dilation of the sinus of Valsalva (SoV) has been increasingly observed after repaired tetralogy of Fallot (TOF). We estimate the prevalence of SoV dilation in adults with repaired TOF and analyze possible factors related to aortic disease. Adults with TOF [n = 109, median age 33.2 years (range 18.1 to 69.5)] evaluated at Johns Hopkins Hospital from 2001 to 2009 were reviewed in an observational retrospective cohort study. Median follow-up was 27.3 (range 0.1-48.8) years. SoV dilation was defined as >95 % confidence interval adjusted for age and body surface area (z-score > 2). The prevalence of SoV dilation was 51 % compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥ 4 cm in 39 % (42 of 109), ≥ 4.5 cm in 21 % (23 of 109), ≥ 5 cm in 8 % (9 of 109), and ≥ 5.5 cm in 2 % (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8 % and aortic root or ascending aorta (AA) replacement surgery in 2.8 % of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR) = 3.09, p = 0.005], residual ventricular septal defect (VSD) (OR = 4.14, p < 0.02), and TOF with pulmonary atresia (TOF/PA) (OR = 6.75, p = 0.03) were associated with increased odds of dilated aortic root. SoV dilation after TOF repair is common and persists with aging. AR, residual VSD, and TOF/PA are associated with increased odds of dilation. AA evaluation beyond the SoV is important. Indexed values are imperative to avoid bias on the basis of age and body surface area.

Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.

A three-stage approach was undertaken using genome-wide, case-control, and case-only association studies to identify genetic variants associated with heart failure mortality. In an Amish founder population (n = 851), cardiac hypertrophy, a trait integral to the adaptive response to failure, was found to be heritable (h² = 0.28, p = 0.0002) and GWAS revealed 21 candidate hypertrophy SNPs. In a case (n = 1,610)-control (n = 463) study in unrelated Caucasians, one of the SNPs associated with hypertrophy (rs2207418, p = 8 × 10⁻6), was associated with heart failure, RR = 1.85(1.25-2.73, p = 0.0019). In heart failure cases rs2207418 was associated with increased mortality, HR = 1.51(1.20-1.97, p = 0.0004). There was consistency between studies, with the GG allele being associated with increased ventricular mass (~13 g/m²) in the Amish, heart failure risk, and heart failure mortality. This SNP is in a gene desert of chromosome 20p12. Five genes are within 2.0 mbp of rs2207418 but with low LD between their SNPs and rs2207418. A region near this SNP is highly conserved in multiple vertebrates (lod score = 1,208). This conservation and the internal consistency across studies suggests that this region has biologic importance in heart failure, potentially acting as an enhancer or repressor element. rs2207418 may be useful for predicting a more progressive form of heart failure that may require aggressive therapy.

Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension.

RATIONALE: Transthoracic Doppler echocardiography is recommended for screening for the presence of pulmonary hypertension (PH). However, some recent studies have suggested that Doppler echocardiographic pulmonary artery pressure estimates may frequently be inaccurate. OBJECTIVES: Evaluate the accuracy of Doppler echocardiography for estimating pulmonary artery pressure and cardiac output. METHODS: We conducted a prospective study on patients with various forms of PH who underwent comprehensive Doppler echocardiography within 1 hour of a clinically indicated right-heart catheterization to compare noninvasive hemodynamic estimates with invasively measured values. MEASUREMENTS AND MAIN RESULTS: A total of 65 patients completed the study protocol. Using Bland-Altman analytic methods, the bias for the echocardiographic estimates of the pulmonary artery systolic pressure was -0.6 mm Hg with 95% limits of agreement ranging from +38.8 to -40.0 mm Hg. Doppler echocardiography was inaccurate (defined as being greater than +/-10 mm Hg of the invasive measurement) in 48% of cases. Overestimation and underestimation of pulmonary artery systolic pressure by Doppler echocardiography occurred with a similar frequency (16 vs. 15 instances, respectively). The magnitude of pressure underestimation was greater than overestimation (-30 +/- 16 vs. +19 +/- 11 mm Hg; P = 0.03); underestimates by Doppler also led more often to misclassification of the severity of the PH. For cardiac output measurement, the bias was -0.1 L/min with 95% limits of agreement ranging from +2.2 to -2.4 L/min. CONCLUSIONS: Doppler echocardiography may frequently be inaccurate in estimating pulmonary artery pressure and cardiac output in patients being evaluated for PH.

Diagnostic accuracy of arterial phase 64-slice multidetector CT angiography for left atrial appendage thrombus in patients undergoing atrial fibrillation ablation.

INTRODUCTION: Multidetector CT (MDCT) is used prior to atrial fibrillation ablation (AFA) to anatomically guide ablation procedures. Whether 64-slice MDCT also can be used to diagnose left atrial thrombus is not known. METHODS: We sought to determine the accuracy and interobserver variability of MDCT in the evaluation of left atrial thrombus prior to AFA. We enrolled 50 patients scheduled for AFA who underwent 64-slice MDCT scan and transesophageal echocardiography prior to the procedure. Three experienced observers reviewed all the MDCT images for the presence of a left atrial thrombus, and two different readers interpreted the transesophageal echocardiograms (TEE), which were used as the gold standard. All observers were blinded to clinical data and each other. RESULTS: Interobserver variability between the three MDCT readers was poor (highest kappa statistic 0.43, P = 0.001). Diagnostic accuracy was highly variable, with sensitivities ranging from 100% to 50% and specificities ranging from 85% to 44%. TEE reader agreement was 98%. CONCLUSION: MDCT demonstrates high interobserver variability and has only modest diagnostic accuracy for the detection of left atrial thrombus in patients undergoing AFA procedure. Potential factors affecting the accuracy of MDCT include image quality and the difficulty of distinguishing clot from pectinate muscle. MDCT likely is not the optimal method to detect left atrial thrombus using current techniques and standards of interpretation.

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension.

OBJECTIVES: Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow-mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. METHODS: Thirteen adults (nine men, aged 65 +/- 2 years) with isolated systolic hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure < 90 mmHg or pulse pressure > 60 mmHg) on stable antihypertensive therapy were studied. Subjects received placebo (2 weeks) then oral alagebrium (ALT-711; 210 mg twice a day for 8 weeks). Subjects and data analyses were blinded to treatment. Arterial stiffness was assessed by carotid augmentation index (AI) and brachial artery distensibility (ArtD) using applanation tonometry and Doppler echo, and endothelial function by brachial FMD. Serum markers of collagen metabolism and vascular inflammation were assessed. RESULTS: Alagebrium reduced carotid AI by 37% (P = 0.007) and augmented pressure (16.4 +/- 10 to 9.6 +/- 9 mmHg; P < 0.001). Heart rate, arterial pressures, and ArtD, were unchanged. FMD increased from 4.6 +/- 1.1 to 7.1 +/- 1.1% with alagebrium (P < 0.05), and was unrelated to altered shear stress or regional arterial distensibility. However, FMD change was inversely related to markers of collagen synthesis, p-selectin and intracellular cell adhesion molecule (all P < 0.05). Alagebrium-associated changes in plasma nitrite plus nitrate was inversely correlated with plasma matrix metalloproteinase 9 and type I collagen (P = 0.007). CONCLUSIONS: Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE-crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling.

Exercise-induced hypertension, endothelial dysfunction, and coronary artery disease in a marathon runner.

Aerobic activity performed on a regular basis is 1 of several lifestyle recommendations endorsed to reduce risk of coronary disease. However, 1 potential concern of arduous aerobic activity is exercise-induced hypertension. This is the first case to our knowledge, of accelerated coronary calcification in an otherwise asymptomatic middle-aged male marathon runner devoid of traditional cardiovascular risk factors. As a consequence of exercise-induced hypertension and associated oxidative stress, improvement of endothelial dysfunction occurred after antioxidant supplementation. In conclusion, vigorous aerobic activity in susceptible individuals may promote oxidative stress and coronary atherosclerosis.

Tricuspid annular displacement predicts survival in pulmonary hypertension.

RATIONALE: Right ventricular (RV) function is an important determinant of prognosis in pulmonary hypertension. However, noninvasive assessment of the RV function is often limited by complex geometry and poor endocardial definition. OBJECTIVES: To test whether the degree of tricuspid annular displacement (tricuspid annular plane systolic excursion [TAPSE]) is a useful echo-derived measure of RV function with prognostic significance in pulmonary hypertension. METHODS: We prospectively studied 63 consecutive patients with pulmonary hypertension who were referred for a clinically indicated right heart catheterization. Patients underwent right heart catheterization immediately followed by transthoracic echocardiogram and TAPSE measurement. RESULTS: In the overall cohort, a TAPSE of less than 1.8 cm was associated with greater RV systolic dysfunction (cardiac index, 1.9 vs. 2.7 L/min/m2; RV % area change, 24 vs. 33%), right heart remodeling (right atrial area index, 17.0 vs. 12.1 cm(2)/m), and RV-left ventricular (LV) disproportion (RV/LV diastolic area, 1.7 vs. 1.2; all p < 0.001), versus a TAPSE of 1.8 cm or greater. In patients with pulmonary arterial hypertension (PAH; n = 47), survival estimates at 1 and 2 yr were 94 and 88%, respectively, in those with a TAPSE of 1.8 cm or greater versus 60 and 50%, respectively, in subjects with a TAPSE less than 1.8 cm. The unadjusted risk of death (hazard ratio) in patients with a TAPSE less than 1.8 versus 1.8 cm or greater was 5.7 (95% confidence interval, 1.3-24.9; p = 0.02) for the PAH cohort. For every 1-mm decrease in TAPSE, the unadjusted risk of death increased by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.30; p = 0.006), which persisted after adjusting for other echocardiographic and hemodynamic variables and baseline treatment status. CONCLUSIONS: TAPSE powerfully reflects RV function and prognosis in PAH.

Oral contraceptives and polyp regression in familial adenomatous polyposis.

Epidemiologic and experimental reports suggest that female hormones protect against the development of colorectal cancer, but studies are limited. We describe a patient in the placebo arm of a 4-year primary chemoprevention trial who developed adenomatous polyps and then had eradication of polyps after the administration of oral contraceptives. No change in the prostaglandin levels in the colonic mucosa was noted after polyp elimination, making nonsteroidal anti-inflammatory drug ingestion unlikely as a cause. This report represents the regression of colorectal adenomas with the use of estrogen/progesterone compounds.

Effect of supplemental phytonutrients on impairment of the flow-mediated brachial artery vasoactivity after a single high-fat meal.

OBJECTIVES: Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide. BACKGROUND: Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h; however, co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect. METHODS: Flow-mediated brachial artery reactivity test (BART) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers (age 36.4 +/- 10.1 years). Subjects were randomized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate (Juice Plus [JP]) along with a complex supplement providing nutritional antioxidants and various herbal extracts (Vineyard [V]), JP alone, or a matching placebo. At three and four weeks, BART was repeated both before and after the high-fat meal. Serum nitrate/nitrite concentrations were measured at baseline and at four weeks. RESULTS: Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal (-47.5 +/- 23.4% at baseline vs. -1.7 +/- 9.7% at four weeks [p < 0.05]). Four weeks of JP alone had a similar beneficial effect (-45.1 +/- 19.7% at baseline vs. -16.6 +/- 10.3% at four weeks [p < 0.05]), whereas there was no substantial effect of the placebo. In the subjects treated with supplements, concentrations of serum nitrate/nitrite increased from 78 +/- 39 to 114 +/- 62 microm/l (p < 0.02). CONCLUSIONS: Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration.

Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.

Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology.