Karima Addetia

Hemodynamic Ramp Tests in Patients With Left Ventricular Assist Devices

OBJECTIVES This study tested whether combined invasive hemodynamic and echocardiographic ramp tests can help optimize patient management. BACKGROUND Guidelines for optimizing speed and medications in continuous flow ventricular assist device (cfLVAD) patients are mainly based on expert opinion. METHODS Thirty-five cfLVAD patients (21 HeartMate II [Thoratec, Pleasanton, California] and 14 HVAD [HeartWare International, Framingham, Massachusetts]) underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography. Data were recorded at up to 9 speed settings. Speed changes were in steps of 400 revolutions per minute (RPM) for HeartMate II (8,000 to 12,000 RPM) and 100 RPM for HVAD (2,300 to 3,200 RPM) patients. RESULTS Only 42.9% of patients had normal CVPs and PCWPs at their original RPM settings. Going from lowest to highest speeds, cardiac output improved by 0.16 ± 0.19 l/min/step (total change 1.28 ± 1.41 l/min) and PCWP decreased by 1.23 ± 0.85 mm Hg/step (total change 9.9 ± 6.5 mm Hg). CVP and systolic blood pressure did not change significantly with RPM. RPM were adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in 56% of patients. For the remainder, results indicated which type of medical management should be pursued. CONCLUSIONS Use of combined hemodynamic and echocardiographic ramp tests in patients provides objective means of optimizing RPM, and has the potential to guide medical management. It remains to be tested whether this strategy has a beneficial impact on quality of life or clinical outcomes.

Prognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection Fraction: Risk Stratification Using Cardiovascular Magnetic Resonance.

Background—Cardiac sarcoidosis is associated with an increased risk of heart failure and sudden death, but its risk in patients with preserved left ventricular ejection fraction is unknown. Using cardiovascular magnetic resonance in patients with extracardiac sarcoidosis and preserved left ventricular ejection fraction, we sought to (1) determine the prevalence of cardiac sarcoidosis or associated myocardial damage, defined by the presence of late gadolinium enhancement (LGE), (2) quantify their risk of death/ventricular tachycardia (VT), and (3) identify imaging-based covariates that predict who is at greatest risk of death/VT. Methods and Results—Parameters of left and right ventricular function and LGE burden were measured in 205 patients with left ventricular ejection fraction >50% and extracardiac sarcoidosis who underwent cardiovascular magnetic resonance for LGE evaluation. The association between covariates and death/VT in the entire group and within the LGE+ group was determined using Cox proportional hazard models and time-dependent receiver–operator curves analysis. Forty-one of 205 patients (20%) had LGE; 12 of 205 (6%) died or had VT during follow-up; of these, 10 (83%) were in the LGE+ group. In the LGE+ group (1) the rate of death/VT per year was >20× higher than LGE− (4.9 versus 0.2%, P<0.01); (2) death/VT were associated with a greater burden of LGE (14±11 versus 5±5%, P<0.01) and right ventricular dysfunction (right ventricular EF 45±12 versus 53±28%, P=0.04). LGE burden was the best predictor of death/VT (area under the receiver-operating characteristics curve, 0.80); for every 1% increase of LGE burden, the hazard of death/VT increased by 8%. Conclusions—Sarcoidosis patients with LGE are at significant risk for death/VT, even with preserved left ventricular ejection fraction. Increased LGE burden and right ventricular dysfunction can identify LGE+ patients at highest risk of death/VT.

3D Echocardiographic Location of Implantable Device Leads and Mechanism of Associated Tricuspid Regurgitation

OBJECTIVES This study sought to: 1) determine the feasibility of using 3-dimensional transthoracic echocardiography (3D TTE) in patients with implantable cardiac resynchronization devices, pacemakers, and defibrillators to visualize the device leads in the right heart and their position relative to the tricuspid valve leaflets; 2) determine the prevalence of different lead positions; and 3) study the relationship between lead location and tricuspid regurgitation (TR) severity. BACKGROUND Pacemaker, defibrillator, and cardiac resynchronization device implantation is currently guided by fluoroscopy, not allowing targeted lead positioning relative to the tricuspid valve leaflets. These leads have been reported to cause TR of variable degrees, but echocardiography is not routinely used to elucidate the mechanisms of lead interference with tricuspid valve leaflets in individual patients. METHODS 3D TTE full-volume images of the right ventricle and/or zoomed images of the tricuspid valve were obtained in 121 patients with implanted devices. Images were viewed offline to determine the position of the device-lead relative to the tricuspid valve leaflets. Severity of TR was estimated on the basis of vena contracta measurements. RESULTS 3D TTE clearly depicted lead position in 90% of patients. The right ventricular lead was impinging on either the posterior (20%) or septal (23%) leaflet or was not interfering with leaflet motion (53%) when positioned near the posteroseptal commissure or in the central portion of the tricuspid valve orifice. In the remaining patients, leads were impinging on the anterior leaflet (4%) or positioned in either the anteroposterior or anteroseptal commissure (3%). Leads interfering with normal leaflet mobility were associated with more TR than nonimpinging leads (vena contracta: median 0.62 cm [1st and 3rd quartiles: 0.51, 0.84 cm] vs. 0.27 cm [1st and 3rd quartiles: 0.00, 0.48 cm]; p < 0.001). CONCLUSIONS 3D TTE showed a clear association between device lead position and TR. To minimize TR induced by device-leads, 3D TTE guidance should be considered for placement in a commissural position.

Sample Size and Cost Analysis for Pulmonary Arterial Hypertension Drug Trials Using Various Imaging Modalities to Assess Right Ventricular Size and Function End Points

Background—Placebo-controlled trials for pulmonary arterial hypertension are no longer acceptable because new therapies must show clinically significant effects on top of standard treatment. The purpose of this study was to estimate sample sizes and imaging costs for the planning of a hypothetical pulmonary arterial hypertension drug trial using imaging to detect changes in right ventricular size and function in response to combined therapy. Methods and Results—Same-day cardiovascular MR (CMR) and 2-dimensional (2D) and 3D transthoracic echocardiography (2DTTE and 3DTTE) were performed in 22 patients with pulmonary arterial hypertension (54±13 years of age) twice, 6 months apart. Short-axis CMR cines and full-volume 3DTTE data sets of the right ventricle were used to measure end-diastolic volume and ejection fraction. Fractional area change was obtained from 2DTTE. Sample size calculations used a 2-sample t test model incorporating differences between baseline and 6-month measurements. Cost estimates were made using the Medicare fee schedule. No significant differences were noted between baseline and follow-up measurements. Large SDs reflected variable progression of disease in individual patients on standard therapy and measurement variability. These sources of variability resulted in intertechnique differences in sample sizes: to detect a change of 5% to 15% in 3DTTE-derived right ventricular ejection fraction and fractional area change or change of 15 to 30 mL in 3DTTE right ventricular end-diastolic volume; sample sizes were 2× to 2.5× those required by CMR. As a result, the total cost of a trial using complete TTE was greater than CMR, which was greater than limited TTE. Conclusions—Because of lower measurement variability, CMR is more cost saving in pulmonary arterial hypertension drug trials than echocardiography, unless limited TTE is used.

Novel Approach to Three-Dimensional Echocardiographic Quantification of Right Ventricular Volumes and Function from Focused Views

BACKGROUND Echocardiographic assessment of the right ventricle is difficult because of its complex shape. Three-dimensional echocardiographic (3DE) imaging allows more accurate and reproducible analysis of the right ventricle than two-dimensional methodology. However, three-dimensional volumetric analysis has been hampered by difficulties obtaining consistently high-quality coronal views, required by the existing software packages. The aim of this study was to test a new approach for volumetric analysis without coronal views by using instead right ventricle-focused three-dimensional acquisition with multiple short-axis views extracted from the same data set. METHODS Transthoracic 3DE and cardiovascular magnetic resonance (CMR) images were prospectively obtained on the same day in 147 patients with wide ranges of right ventricular (RV) size and function. RV volumes and ejection fraction were measured from 3DE images using the new software and compared with CMR reference values. Comparisons included linear regression and Bland-Altman analyses. Repeated measurements were performed to assess measurement variability. RESULTS Sixteen patients were excluded because of suboptimal image quality (89% feasibility). RV volumes and ejection fraction obtained with the new 3DE technique were in good agreement with CMR (end-diastolic volume, r = 0.95; end-systolic volume, r = 0.96; ejection fraction, r = 0.83). Biases were, respectively, -6 ± 11%, 0 ± 15%, and -7 ± 17% of the mean measured values. In a subset of patients with suboptimal 3DE images, the new analysis resulted in significantly improved accuracy against CMR and reproducibility, compared with previously used coronal view-based techniques. The time required for the 3DE analysis was approximately 4 min. CONCLUSIONS The new software is fast, reproducible, and accurate compared with CMR over a wide range of RV size and function. Because right ventricle-focused 3DE acquisition is feasible in most patients, this approach may be applicable to a broader population of patients who can benefit from RV volumetric assessment.

Cardiac Sarcoidosis Detected by Late Gadolinium Enhancement and Prevalence of Atrial Arrhythmias

Cardiovascular magnetic resonance (CMR) imaging is being increasingly used to help identify patients with cardiac sarcoidosis (CS). Whereas ventricular arrhythmias have been well studied in this population, atrial arrhythmias have not been thoroughly investigated. We sought to better characterize the arrhythmia burden of a cohort of patients diagnosed with CS by CMR imaging. Patients with biopsy-proven extracardiac sarcoidosis were referred to the University of Chicago for evaluation of the presence of CS. CMR imaging was used to categorize the patients into 2 groups; those with and those without late gadolinium enhancement (LGE) for comparison of arrhythmic events. Arrhythmic evaluation included Holter monitor, event recorder, electrophysiology testing, or implantable cardioverter-defibrillator (ICD) interrogation; 192 consecutive patients were evaluated with CMR imaging, 57 of whom did not have ambulatory monitoring results and thus were excluded. LGE was present in 44 patients. Atrial arrhythmias were documented in 16 patients (36%) with myocardial LGE and in 11 patients (12%) without myocardial LGE (p = 0.002). Ventricular arrhythmias were documented in 27% of patients with myocardial LGE and 2.2% of LGE-negative patients (p = 0.00076). Of 26 LGE-positive patients with ICDs, 8 (30.8%) received therapies, 3 (11.5%) of which were inappropriate for atrial arrhythmias. In conclusion, atrial arrhythmias were documented more frequently than ventricular arrhythmias in patients with sarcoidosis with cardiac involvement and were 3 times more prevalent than in patients with sarcoidosis without cardiac involvement. Risk-benefit assessment of anticoagulation for primary prevention of stroke should be performed for patients with CS. In patients receiving implantable defibrillators, programming to minimize inappropriate ICD shocks for atrial arrhythmias must be considered.

Two-dimensional transthoracic echocardiographic normal reference ranges for proximal aorta dimensions: results from the EACVI NORRE study

Aims To report normal reference ranges for echocardiographic dimensions of the proximal aorta obtained in a large group of healthy volunteers recruited using state-of-the-art cardiac ultrasound equipment, considering different measurement conventions, and taking into account gender, age, and body size of individuals. Methods and Results A total of 704 (mean age: 46.0 ± 13.5 years) healthy volunteers (310 men and 394 women) were prospectively recruited from the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained in all subjects following pre-defined protocols. Aortic dimensions were obtained in systole and diastole, following both the leading-edge to leading-edge and the inner-edge to inner-edge conventions. Diameters were measured at four levels: ventricular-arterial junction, sinuses of Valsalva, sino-tubular junction, and proximal tubular ascending aorta. Measures of aortic root in the short-axis view following the orientation of each of the three sinuses were also performed. Men had significantly larger body sizes when compared with women, and showed larger aortic dimensions independently of the measurement method used. Dimensions indexed by height and body surface area are provided, and stratification by age ranges is also displayed. In multivariable analysis, the independent predictors of aortic dimensions were age, gender, and height or body surface area. Conclusion The NORRE study provides normal values of proximal aorta dimensions as assessed by echocardiography. Reference ranges for different anatomical levels using different (i) measurement conventions and (ii) at different times of the cardiac cycle (i.e. mid-systole and end-diastole) are provided. Age, gender, and body size were significant determinants of aortic dimensions.

Visualization and measurement of mitral valve chordae tendineae using three-dimensional transesophageal echocardiography from the transgastric approach.

BACKGROUND The evaluation of the submitral apparatus is challenging from the conventional transesophageal approach. The aim of this study was to test the feasibility of using three-dimensional (3D) transesophageal echocardiographic (TEE) imaging from the transgastric approach to visualize the submitral apparatus and quantify the lengths of the chordae tendineae by using multiplanar reconstruction analysis. METHODS Twenty-two patients who had transgastric full-volume 3D TEE data sets before mitral valve surgery underwent surgical measurement of chordal length. A short-axis plane at the chordal level was extracted from the 3D data set to identify leaflet segments and the corresponding primary chords. Then, for each chord, the optimal plane was selected to visualize and measure the entire chordal length from its origin at the leaflet margin to the papillary muscle tips. Measurements were performed at the phase of the cardiac cycle when chordal length reached its maximum. Measured values were compared with surgical measurements using linear regression and Bland-Altman analyses. RESULT One hundred forty-six primary chords were measured intraoperatively. Three-dimensional TEE imaging was able to measure the lengths of all these chords. The surgical and 3D TEE measurements (mean, 1.96 ± 0.56 vs 1.93 ± 0.50 cm, respectively) correlated highly (r = 0.93, P < .0001), with a minimal bias of 0.03 cm and narrow limits of agreement from -0.39 to 0.45 cm. CONCLUSION Transgastric 3D TEE imaging of the submitral apparatus allows visualization and accurate measurement of chordae tendineae lengths, which may be useful for planning mitral valve repair, including percutaneous transcatheter procedures.

Impact of Implantable Transvenous Device Lead Location on Severity of Tricuspid Regurgitation

BACKGROUND Implantable device leads can cause tricuspid regurgitation (TR) when they interfere with leaflet motion. The aim of this study was to determine whether lead-leaflet interference is associated with TR severity, independent of other causative factors of functional TR. METHODS A total of 100 patients who underwent transthoracic two-dimensional and three-dimensional (3D) echocardiography of the tricuspid valve before and after lead placement were studied. Lead position was classified on 3D echocardiography as leaflet-interfering or noninterfering. TR severity was estimated by vena contracta (VC) width. Logistic regression analysis was used to identify factors associated with postdevice TR, including predevice VC width, right ventricular end-diastolic and end-systolic areas, fractional area change, right atrial size, tricuspid annular diameter, TR gradient, device lead age, and presence or absence of lead interference. Odds ratios were used to describe the association with moderate (VC width ≥ 0.5 cm) or severe (VC width ≥ 0.7 cm) TR, separately, using bivariate and stepwise multivariate logistic regression analysis. RESULTS Forty-five of 100 patients showed device lead tricuspid valve leaflet interference. The septal leaflet was the most commonly affected (23 patients). On bivariate analysis, preimplantation VC width, right atrial size, tricuspid annular diameter, and lead-leaflet interference were significantly associated with postdevice TR. On multivariate analysis, preimplantation VC width and the presence of an interfering lead were independently associated with postdevice TR. Furthermore, the presence of an interfering lead was the only factor associated with TR worsening, increasing the likelihood of developing moderate or severe TR by 15- and 11-fold, respectively. CONCLUSION Lead-leaflet interference as seen on 3D echocardiography is associated with TR after device lead placement, suggesting that 3D echocardiography should be used to assess for lead interference in patients with significant TR.

Normal Values of Left Ventricular Mass Index Assessed by Transthoracic Three-Dimensional Echocardiography

BACKGROUND Pathologic left ventricular (LV) hypertrophy is closely coupled with adverse cardiovascular events. However, normal values of LV mass determined by three-dimensional echocardiography (3DE) have not been established in a large number of healthy subjects over a wide age range. The aims of this study were to (1) validate the accuracy of 3DE for LV mass measurements against cardiac magnetic resonance (CMR), (2) establish the normal range of LV mass index in healthy subjects, and (3) investigate the effects of age, gender, and ethnic diversity on LV mass index. METHODS In protocol 1, both transthoracic 3DE and CMR were performed on the same day in 57 patients who underwent clinically indicated CMR examinations. In protocol 2, full-volume data sets were acquired with 3DE in 390 healthy subjects. The LV endocardial and epicardial borders were semiautomatically determined at end-diastole using three-dimensional echocardiographic software. LV mass was calculated as (LV epicardial volume--LV endocardial volume) × 1.05. RESULTS Excellent correlation was observed between three-dimensional echocardiographic and CMR measurements of LV mass (r = 0.96). Bland-Altman analysis revealed bias of -4.8 g (-3.9% of the mean), with 95% limits of agreement of ± 27.7 g. Normal values of LV mass indexed to body surface area were found to be 70 ± 9 g/m(2) in men and 61 ± 8 g/m(2) in women. Significant age and gender dependence, but no racial dependence, was observed for LV mass index. CONCLUSIONS Three-dimensional echocardiography is an accurate method for measuring LV mass. Age and gender dependence, but no ethnic dependence, of LV mass index was observed in Japanese and American populations. The reported normal reference values of 3DE-determined LV mass index according to age and gender could potentially be useful for diagnosing LV hypertrophy with excellent accuracy.