J. Kern Buckner

Saline contrast echocardiography for the detection of patent foramen ovale in hypoxia: a validation study using intracardiac echocardiography.

Although the “3 beat rule” is widely utiized to discriminate patent foramen ovale (PFO)‐mediated right‐to‐left shunt (RTLS) from intrapulmonary RTLS using saline contrast transthoracic echocardiography (SCE), SCE diagnostic performance has yet to be validated using an invasive intracardiac standard. Percutaneous PFO occluder placement was recently shown to ameliorate hypoxia in patients with suspected PFO‐mediated RTLS. We evaluated the ability of SCE to predict PFO presence and size using intracardiac echocardiography (ICE) as a gold standard in a hypoxic cohort. Sixty‐three hypoxic patients with suspected PFO‐mediated RTLS who underwent SCE at rest, with Valsalva maneuver, and with cough prior to ICE were evaluated retrospectively. PFO RTLS was defined by ICE findings including PFO anatomy, RTLS by saline contrast and color Doppler, and probe patency. SCE shunt severity and timing of left heart saline target appearance were compared to the presence of ICE‐defined PFO RTLS. Forty‐seven patients (75%) met criteria for PFO‐mediated RTLS. A 4 beat cutoff for resting SCE provided optimal diagnostic performance for detection of PFO‐mediated RTLS with a 71% sensitivity, 94% specificity, and 97% positive predictive value (PPV). Valsalva and cough maneuvers improved sensitivity compared to rest SCE (89% and 80%, respectively). Valsalva SCE shunt severity more accurately predicted PFO size than resting SCE. In contrast to the widely accepted “3 beat rule,” resting SCE for the detection of PFO RTLS in a hypoxic population performs optimally using a 4‐cycle cutoff with both excellent specificity and PPV.

Cystatin C: A potential biomarker for pulmonary arterial hypertension

Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested.

Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension

Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = –0.74, P < 0.001), mean pulmonary pressure (ρ = –0.64, P = 0.006), and elastance (ρ = –0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = –0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR-based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH.

4D magnetic resonance flow imaging for estimating pulmonary vascular resistance in pulmonary hypertension

To develop an estimate of pulmonary vascular resistance (PVR) using blood flow measurements from 3D velocity‐encoded phase contract magnetic resonance imaging (here termed 4D MRI).

Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension.

Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e′). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = −0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e′ (Rho = 0.63, P = 0.001), and lateral e′ (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e′ (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency.

4D-flow cardiac magnetic resonance-derived vorticity is sensitive marker of left ventricular diastolic dysfunction in patients with mild-to-moderate chronic obstructive pulmonary disease

Aims To investigate the possibility that vorticity assessed by four-dimensional flow cardiac magnetic resonance (4D-Flow CMR) in the left ventricle of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is a potential marker of early LV diastolic dysfunction (LVDD) and more sensitive than standard echocardiography, and whether changes in vorticity are associated with quantitative computed tomography (CT) and clinical markers of COPD, and right ventricular (RV) echocardiographic markers indicative of ventricular interdependency. Methods and results Sixteen COPD patients with presumptive LVDD and 10 controls underwent same-day 4D-Flow CMR and Doppler echocardiography to quantify early and late diastolic vorticity as well as standard evaluation for LVDD. Furthermore, all patients underwent detailed CT analysis for COPD markers including percent emphysema and air trapping. The 4D-Flow CMR derived diastolic vorticity measures were correlated with CT measures, standard clinical and CMR markers, and echocardiographic diastolic RV metrics. Early diastolic vorticity was significantly reduced in COPD patients (P < 0.0001) with normal left ventricular (LV) mass, geometry, systolic function, and no or mild signs of Doppler LVDD when compared with controls. Vorticity significantly differentiated COPD patients without echocardiographic signs of LVDD (n = 11) from controls (P < 0.0001), and from COPD patients with stage I LVDD (n = 5) (P < 0.0180). Vorticity markers significantly correlated with CT computed measures, CMR-derived RV ejection fraction, echocardiographic RV diastolic metrics, and 6-minute walk test. Conclusion 4D-Flow CMR derived diastolic vorticity is reduced in patients with mild-to-moderate COPD and no or mild signs of LVDD, implying early perturbations in the LV flow domain preceding more obvious mechanical changes (i.e. stiffening and dilation). Furthermore, reduced LV vorticity appears to be driven by COPD induced changes in lung tissue and parallel RV dysfunction.

Helicity and vorticity of pulmonary arterial flow in patients with pulmonary hypertension: Quantitative analysis of flow formations

Background Qualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular (RV) afterload and function in pulmonary hypertension (PH). We aimed to quantify flow hemodynamic formations in pulmonary arteries using 4‐dimensional flow cardiac magnetic resonance imaging and the spatial velocity derivatives helicity and vorticity in a heterogeneous PH population. Methods and Results Patients with PH (n=35) and controls (n=10) underwent 4‐dimensional flow magnetic resonance imaging study for computation of helicity and vorticity in the main pulmonary artery (MPA), the right pulmonary artery, and the RV outflow tract. Helicity and vorticity were correlated with standard RV volumetric and functional indexes along with MPA stiffness assessed by measuring relative area change. Patients with PH had a significantly decreased helicity in the MPA (8 versus 32 m/s2; P<0.001), the right pulmonary artery (24 versus 50 m/s2; P<0.001), and the RV outflow tract–MPA unit (15 versus 42 m/s2; P<0.001). Vorticity was significantly decreased in patients with PH only in the right pulmonary artery (26 versus 45 1/s; P<0.001). Total helicity computed correlated with the cardiac magnetic resonance imaging–derived ventricular‐vascular coupling (−0.927; P<0.000), the RV ejection fraction (0.865; P<0.0001), cardiac output (0.581; P<0.0001), mean pulmonary arterial pressure (−0.581; P=0.0008), and relative area change measured at the MPA (0.789; P<0.0001). Conclusions The flow hemodynamic character in patients with PH assessed via quantitative analysis is considerably different when compared with healthy and normotensive controls. A strong association between helicity in pulmonary arteries and ventricular‐vascular coupling suggests a relationship between the mechanical and flow hemodynamic domains.

GALECTIN 3: A POTENTIAL BIOMARKER FOR PULMONARY ARTERIAL HYPERTENSION

Galectin-3 (Gal 3) is a novel marker of left heart failure and cardiovascular mortality. We tested the hypothesis that Gal-3 predicts pulmonary artery pressure and right ventricular (RV) function in pulmonary arterial hypertension (PAH). Using a prospective study, 15 subjects with right heart

Reduced shear stress and associated aortic deformation in the thoracic aorta of patients with chronic obstructive pulmonary disease

Objective: Central aortic stiffness and chronic obstructive pulmonary disease (COPD) are associated with increased incidence of devastating aortopathies. However, the exact mechanism leading to elevated aortic stiffness in patients with COPD is unknown. The purpose of this study was to quantify flow and shear hemodynamic indices, known markers of vascular remodeling, in the thoracic aorta of patients with mild to moderate COPD (n = 16) and to compare these results with an age‐matched control group (n = 10). Methods: Four‐dimensional flow magnetic resonance imaging has been applied to measure hemodynamic wall shear stress (WSS) at four specific planes along the ascending aorta, aortic arch, and proximal descending aorta for all subjects. Peak systolic WSS and time‐averaged WSS, which respectively reflect magnitude and temporal shear variability, were calculated at standardized planes. Aortic deformation was measured by means of relative area change (RAC) at the midlevel of the ascending and descending aorta. Results: Compared with controls, patients with COPD had significantly reduced RAC in the mid ascending aorta (9% vs 18%; P < .0001) and descending aorta (15% vs 19%; P = .0206). Peak systolic WSS in COPD patients was significantly reduced in all considered planes, with the most dramatic difference occurring in the descending aorta (0.46 vs 0.86 N/m2; P < .0001). Peak systolic WSS and time‐averaged WSS were both significantly correlated with aortic RAC at each evaluated plane. Conclusions: Reduced flow shear metrics assessed at specific aortic regions correlated with RAC, a marker of aortic stiffness. Reduced hemodynamic WSS may then contribute to central aortic stiffening and perpetuate the risk for development of severe aortopathy. Clinical Relevance: Central aortic stiffness and chronic obstructive pulmonary disease are associated with increased incidence of devastating aortopathies including aneurysmal degeneration, aortic dissections, development of atherosclerosis, and overall increased cardiovascular morbidity and mortality. The exact mechanism leading to elevated aortic stiffness in patients with chronic obstructive pulmonary disease is yet to be determined. Hemodynamic forces can actively modulate endothelial cell alignment, extracellular matrix composition, vascular tone, and inflammation present in the wall of the aorta. In this study, we observed reduced flow shear assessed at specific aortic regions correlated with relative area strain, a marker of aortic stiffness.

Vorticity for the assessment of pulmonary vascular hemodynamics in pulmonary arterial hypertension

Background 4D flow CMR analysis of main pulmonary artery (MPA) flow in pulmonary arterial hypertension (PAH) has demonstrated vortical formations whose existence time correlates with mean pulmonary arterial pressure (MPAP). Vorticity can quantitate the rotation of these vortices and may represent a novel way to assess pulmonary arterial hemodynamics. We aimed to determine if MPA vorticity correlates with pulmonary vascular hemodynamics in PAH subjects when compared to controls using 4D flow CMR. Methods