Joseph Sivak

Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension

Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects.

Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography Laboratory: Improving Care for Patients With Aortic Stenosis.

Background—The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. Methods and Results—The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography–catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). Conclusions—A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.

Use of outcome measures in pulmonary hypertension clinical trials.

OBJECTIVES To evaluate the use of surrogate measures in pulmonary hypertension (PH) clinical trials and how it relates to clinical practice. BACKGROUND Studies of pulmonary arterial hypertension (PAH) employ a variety of surrogate measures in addition to clinical events because of a small patient population, participant burden, and costs. The use of these measures in PH drug trials is poorly defined. METHODS We searched PubMed/MEDLINE/Embase for randomized or prospective cohort PAH clinical treatment trials from 1985 to 2013. Extracted data included intervention, trial duration, study design, patient characteristics, and primary and secondary outcome measures. To compare with clinical practice, we assessed the use of surrogate measures in a clinical sample of patients on PH medications at Duke University Medical Center between 2003 and 2014. RESULTS Between 1985 and 2013, 126 PAH trials were identified and analyzed. Surrogate measures served as primary endpoints in 119 trials (94.0%). Inclusion of invasive hemodynamics decreased over time (78.6%, 75.0%, 52.2%; P for trend = .02), while functional testing (7.1%, 60.0%, 81.5%; P for trend < .0001) and functional status or quality of life (0%, 47.6%, 62.8%; P for trend < .0001) increased in PAH trials over the same time periods. Echocardiography data were reported as a primary or secondary outcome in 32 trials (25.4%) with increased use from 1985-1994 to 1995-2004 (7.1% vs 35.0%, P = .04), but the trend did not continue to 2005-2013 (25.0%). In comparison, among 450 patients on PAH therapies at our institution between 2003 and 2013, clinical assessments regularly incorporated serial echocardiography and 6-minute walk distance tests (92% and 95% of patients, respectively) and repeat measurement of invasive hemodynamics (46% of patients). CONCLUSIONS The majority of PAH trials have utilized surrogate measures as primary endpoints. The use of these surrogate endpoints has evolved significantly over time with increasing use of patient-centered endpoints and decreasing or stable use of imaging and invasive measures. In contrast, imaging and invasive measures are commonly used in contemporary clinical practice. Further research is needed to validate and standardize currently used measures.

Grading Aortic Stenosis With Mean Gradient and Aortic Valve Area: A Comparison Between Preoperative Transthoracic and Precardiopulmonary Bypass Transesophageal Echocardiography

OBJECTIVE The authors hypothesized that average precardiopulmonary bypass (pre-CPB) transesophageal echocardiographic (TEE) mean gradient (PGm) and aortic valve area (AVA) values would be significantly different from preoperative transthoracic (TTE) values in the same patients and that these changes would affect pre-CPB TEE grading of aortic stenosis (AS). DESIGN Retrospective, observational design. SETTING Single university hospital. PARTICIPANTS The study comprised 92 patients who underwent aortic valve replacement with or without coronary artery bypass grafting between 2000 and 2012 at Duke University Hospital and who had PGm and AVA values recorded in both pre-CPB TEE and preoperative TTE reporting databases. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS PGm with pre-CPB TEE was lower by 6.6 mmHg (95% confidence interval, -4.0 to -9.3 mmHg; p<0.001), whereas AVA was higher by 0.10 cm(2) (95% confidence interval, 0.04 to 0.15 cm(2); p<0.001), compared with preoperative TTE values. When using PGm, pre-CPB TEE generated an AS severity 1 grade lower 39.1% of the time and revealed no difference 55.4% of the time compared to preoperative TTE. When using AVA by continuity, pre-CPB TEE generated an AS severity 1 grade lower 14.1% of the time and revealed no difference 81.5% of the time compared to preoperative TTE. When using either PGm or AVA, preoperative TTE exhibited moderate or severe AS for all study patients, whereas, pre-CPB TEE demonstrated mild AS in 5.4% (n = 92) of patients. CONCLUSIONS The authors confirmed their hypothesis that pre-CPB TEE generates different PGm and AVA values compared with preoperative TTE. These differences often underestimate AS severity. Hemodynamic standardizations or adjustments of pre-CPB TEE PGm and AVA values may be necessary in anesthetized patients before assigning an AS grade using these parameters.

Prevalence and Outcomes of Left‐Sided Valvular Heart Disease Associated With Chronic Kidney Disease

Background Chronic kidney disease (CKD) is an adverse prognostic marker for valve intervention patients; however, the prevalence and related outcomes of valvular heart disease in CKD patients is unknown. Methods and Results Included patients underwent echocardiography (1999–2013), had serum creatinine values within 6 months before index echocardiogram, and had no history of valve surgery. CKD was defined as diagnosis based on the International Classification of Diseases, Ninth Revision or an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Qualitative assessment determined left heart stenotic and regurgitant valve lesions. Cox models assessed CKD and aortic stenosis (AS) interaction for subsequent mortality; analyses were repeated for mitral regurgitation (MR). Among 78 059 patients, 23 727 (30%) had CKD; of these, 1326 were on hemodialysis. CKD patients were older; female; had a higher prevalence of hypertension, hyperlipidemia, diabetes, history of coronary artery bypass grafting/percutaneous coronary intervention, atrial fibrillation, and heart failure ≥mild AS; and ≥mild MR (all P<0.001). Five‐year survival estimates of mild, moderate, and severe AS for CKD patients were 40%, 34%, and 42%, respectively, and 69%, 54%, and 67% for non‐CKD patients. Five‐year survival estimates of mild, moderate, and severe MR for CKD patients were 51%, 38%, and 37%, respectively, and 75%, 66%, and 65% for non‐CKD patients. Significant interaction occurred among CKD, AS/MR severity, and mortality in adjusted analyses; the CKD hazard ratio increased from 1.8 (non‐AS patients) to 2.0 (severe AS) and from 1.7 (non‐MR patients) to 2.6 (severe MR). Conclusions Prevalence of at least mild AS and MR is substantially higher and is associated with significantly lower survival among patients with versus without CKD. There is significant interaction among CKD, AS/MR severity, and mortality, with increasingly worse outcomes for CKD patients with increasing AS/MR severity.

A Company of Equals: Success Through Friendship in Fellowship.

For the 2015 American College of Cardiology Scientific Sessions in San Diego, California, several Duke Cardiology fellows decided to try something different. Instead of staying in private hotel rooms, we rented a house in Old Town San Diego where we stayed together in a family-style atmosphere. We

Mitral Regurgitation After Orthotopic Lung Transplantation: Natural History and Impact on Outcomes

OBJECTIVE Progression of mitral regurgitation (MR) after orthotopic lung transplantation (OLT) may be an underrecognized phenomenon due to the overlapping symptomatology of pulmonary and valvular disease. Literature evaluating the progression of MR after OLT currently is limited to case reports. Therefore, the hypothesis that MR progresses after OLT was tested and the association of preprocedure MR with postoperative mortality was assessed. DESIGN A retrospective cohort. SETTING A tertiary-care hospital. PARTICIPANTS Patients who underwent OLT between January 1, 2003 and February 4, 2012. INTERVENTIONS After receiving institutional review board approval, a preprocedure transesophageal echocardiogram was compared with a postoperative transthoracic echocardiogram (TTE) to determine the progression of MR. Univariate and multivariate association between preprocedure MR grade and 1- and 5-year mortality was assessed. A p value of<0.05 was considered statistically significant. MEASUREMENTS AND MAIN RESULTS From 715 patients who underwent OLT, 352 had a postoperative TTE and were included in the evaluation of progression of MR. Five patients had progression of MR postoperatively, and the mean change in MR score of -0.04 was found to be nonsignificant (p = 0.25). Mortality data were available for 634 of the 715 patients. After covariate adjustment, there was no significant association between MR grade and 1-year mortality (p = 0.20) or 5-year mortality (p = 0.46). CONCLUSIONS This study rejected the hypothesis that primary and secondary MR progresses after OLT and found that preprocedure MR was not associated with increased postoperative mortality. Despite the findings that MR does not progress in all patients, there is a subset of patients for whom MR progression is clinically significant.

Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography LaboratoryCLINICAL PERSPECTIVE

Background—The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. Methods and Results—The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography–catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). Conclusions—A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.

Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography LaboratoryCLINICAL PERSPECTIVE: Improving Care for Patients With Aortic Stenosis

Background—The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. Methods and Results—The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography–catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). Conclusions—A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.

In vivo transthoracic measurements of acoustic radiation force induced displacements in the heart over the cardiac cycle

Myocardial elasticity is an important indicator of cardiac function and is affected in many disorders associated with heart failure. Ultrasound based interrogation of cardiac stiffness has been extensively studied in ex-vivo, open chest and intracardiac imaging environments. The ability to make these measurements robustly through non-invasive means such as transthoracic imaging would make them more clinically viable and widely applicable. However, transthoracic imaging is a challenging environment for displacement estimation due to poor SNR, acoustic clutter and complex cardiac motion. This work aims to address some of those challenges on a clinical ultrasound system. Sequences to make M-mode measurements of acoustic radiation force induced displacements in the heart over the entire cardiac cycle were implemented on the Siemens SC2000 and a cardiac phased array probe. Pulse inversion harmonic tracking was employed on the tracking beams to suppress the effect of stationary clutter on displacement estimation. Two families of motion filters, high pass filters and polynomial fit filters were analyzed for their performance in being able to remove the background cardiac motion and isolate the radiation force induced tissue response. Clinical data was acquired on 4 subjects and analyzed for repeatability of diastolic vs. systolic displacements. A high pass filter with a cutoff of 100 Hz and a 2nd order polynomial fit filter were found to be equally effective in suppressing intrinsic motion. Diastolic-to-systolic displacement ratios measured in the interventricular septum ranged from 1.3 to 2.2 across subjects but were found to be fairly consistent between the parasternal long axis and the parasternal short axis views for each subject.