Mary Corretti

Accuracy of Doppler Echocardiography in the Hemodynamic Assessment of Pulmonary Hypertension

RATIONALEnTransthoracic 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.nnnOBJECTIVESnEvaluate the accuracy of Doppler echocardiography for estimating pulmonary artery pressure and cardiac output.nnnMETHODSnWe 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.nnnMEASUREMENTS AND MAIN RESULTSnA 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.nnnCONCLUSIONSnDoppler echocardiography may frequently be inaccurate in estimating pulmonary artery pressure and cardiac output in patients being evaluated for PH.

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.

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 (nu2003= 851), cardiac hypertrophy, a trait integral to the adaptive response to failure, was found to be heritable (h2= 0.28, pu2003= 0.0002) and GWAS revealed 21 candidate hypertrophy SNPs. In a case (nu2003= 1,610)‐control (nu2003= 463) study in unrelated Caucasians, one of the SNPs associated with hypertrophy (rs2207418, pu2003= 8 × 10−6), was associated with heart failure, RR = 1.85(1.25–2.73, pu2003= 0.0019). In heart failure cases rs2207418 was associated with increased mortality, HR = 1.51(1.20–1.97, pu2003= 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. Clin Trans Sci 2011; Volume 4: 17–23

Omega-3 in SLE: a double-blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus

Accelerated atherosclerosis remains a major cause of death in late systemic lupus erythematosus (SLE). Omega-3 has been reported to have benefit for endothelial dysfunction, one of the earliest stages of atherosclerosis, and to reduce disease activity in SLE. We performed a randomized, double-blind placebo-controlled trial to examine the effect of Omega-3 on endothelial function, disease activity, inflammatory markers and lipids in SLE. SLE patients (nxa0=xa085, mean age 47, 55xa0% Caucasian, 38xa0% African-American, 94xa0% female) were randomly assigned to 3xa0g of Omega-3 (Lovaza, GSK) versus placebo for 12xa0weeks. Endothelial function was measured at baseline and at 12xa0weeks using flow-mediated dilation, calculated using high-resolution B-mode ultrasound of the brachial artery diameter in response to vasoactive stimuli (hyperemia). Disease activity was measured using the physician global assessment and SELENA-SLEDAI score. Inflammatory markers (sICAM-1, sVCAM-1, IL-6) and fasting lipid profile were done at baseline and 12-week follow-up. There was no difference between the treatment groups with respect to changes in flow-mediated dilation parameters or disease activity. An average increase in LDL cholesterol of 3.11xa0mg/dL (±21.99) was found with Omega-3 versus a decrease of 1.87xa0mg/dL (±18.29) with placebo (pxa0=xa00.0266). In this trial, Omega-3 did not improve endothelial function, disease activity, nor reduce inflammatory markers in SLE. Longer trials might be required if there are delayed clinical effects. There was evidence that Omega-3 may increase LDL cholesterol, but not the LDL/HDL ratio.

Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study

Transforming growth factor-beta (TGF-β) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-β signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-β inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (nxa0=xa053) or in combination with lomustine (nxa0=xa026). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2xa0months, monthly electrocardiograms, thorax computer tomography scans every 6xa0months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ≥6xa0months (nxa0=xa013). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-β inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials.

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 [nxa0=xa0109, median age 33.2xa0years (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 >95xa0% confidence interval adjusted for age and body surface area (z-scorexa0>xa02). The prevalence of SoV dilation was 51xa0% compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥4xa0cm in 39xa0% (42 of 109), ≥4.5xa0cm in 21xa0% (23 of 109), ≥5xa0cm in 8xa0% (9 of 109), and ≥5.5xa0cm in 2xa0% (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8xa0% and aortic root or ascending aorta (AA) replacement surgery in 2.8xa0% of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR)xa0=xa03.09, pxa0=xa00.005], residual ventricular septal defect (VSD) (ORxa0=xa04.14, pxa0<xa00.02), and TOF with pulmonary atresia (TOF/PA) (ORxa0=xa06.75, pxa0=xa00.03) 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.

Influence of Atrial Function and Mechanical Synchrony on LV Hemodynamic Status in Heart Failure Patients on Resynchronization Therapy

OBJECTIVESnThe aim of this study was to evaluate atrial and ventricular function in patients undergoing cardiac resynchronization therapy (CRT).nnnBACKGROUNDnRight atrial pacing (AP) in CRT induces delays in electrical and mechanical activation of the left atrium. The influence of atrial sensing (AS) versus AP on ventricular performance in CRT and the mechanisms underlying the differences between AS and AP in CRT have not been fully elucidated.nnnMETHODSnFifty-five patients with heart failure undergoing CRT for 9 ± 12.5 months and 22 control subjects without heart failure were enrolled. Conventional and tissue Doppler echocardiography was performed to examine atrial and ventricular mechanics and hemodynamic status.nnnRESULTSnThe optimal atrioventricular interval was shorter in AS compared with AP mode (126 ± 19 ms vs. 155 ± 20 ms, p < 0.0001). Left ventricular (LV) outflow tract time-velocity integral (22 ± 7 cm vs. 20 ± 7 cm, p < 0.001), diastolic filling period (468 ± 124 ms vs. 380 ± 93 ms, p < 0.001), and global strain (-32 ± 24% vs. -27 ± 22%, p = 0.001) were greater in AS compared with AP mode. Atrial strain was higher in AS compared with AP mode in the right atrium (-28.2 ± 8.6% vs. -22.6 ± 7.6%, p = 0.0007), interatrial septum (-17.1 ± 6.5% vs. -13.2 ± 5.4%, p = 0.002), and left atrium (-16.4 ± 11.0% vs. -13.6 ± 8.5%, p = 0.02). There was no difference in intraventricular dyssynchrony but significantly lower atrial dyssynchrony in AS compared with AP mode (31 ± 19 ms vs. 42 ± 24 ms, p = 0.0002).nnnCONCLUSIONSnAS is associated with preserved atrial contractility and atrial synchrony, resulting in optimal LV diastolic filling, stroke volume, and LV systolic mechanics. This pacing mode maximizes LV performance and the hemodynamic benefit of CRT in patients with heart failure.

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

BackgroundPhysicians 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.MethodsOne 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).ResultsInterns 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.ConclusionsA 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.

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.