Theodore J. Kolias

Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

The Development of Aortic Insufficiency in Left Ventricular Assist Device-Supported PatientsClinical Perspective

Background—Aortic insufficiency (AI) following left ventricular assist device (LVAD) placement can affect device performance. The aim of this study was to examine AI development following LVAD implantation. Methods and Results—Echocardiograms (n=315) from 78 subjects undergoing HeartMate-XVE (n=25 [32%]) or HeartMate-II (n=53 [68%]) implantations from 2004 to 2008 were reviewed. Studies were obtained preoperatively and at 1, 3, 6, 12, 18, and 24 months after surgery. AI was graded on an interval scale (0=none, 0.5=trivial, 1=mild, 1.5=mild-moderate, 2=moderate, 2.5=moderate-severe, 3=severe), and the change in AI at follow-up was analyzed with significance tests. Kaplan–Meier estimates for freedom from moderate or worse AI at follow-up were generated. Mixed-model linear regression was used to identify correlates of AI progression during LVAD support. The median (25th, 75th percentile) duration of LVAD support was 239 (112, 455) days, and preoperative AI grade was 0.0 (0.0, 0.0). At 6 months, 89±4% of subjects (n=49 at risk) were free from moderate or worse AI, but this was reduced to 74±7% (n=29 at risk) and 49±13% (n=13 at risk) by 12 and 18 months, respectively. Correlates (slope±SE) of AI progression included female sex (0.002±0.001; P=0.01), smaller body surface area (−0.003±0.001 per m2; P=0.0017), and HeartMate-II model type (0.002±0.001; P=0.039). Correlates (&bgr;±SE) of progressive AI on postoperative echocardiogram included increasing aortic sinus diameter (0.04±0.01 per mm; P=0.001), an aortic valve that remained closed (0.42±0.06; P<0.001) or only intermittently opened (0.34±0.09; P<0.001), and lower left ventricular diastolic (−0.002±0.0004 per cm3; P<0.001) and systolic (−0.002±0.0004 per cm3; P<0.001) volumes. Conclusions—AI progresses over time in LVAD-supported patients. As we move toward an era of long-term cardiac support, more studies are needed to determine the clinical significance of these findings.

The Development of Aortic Insufficiency in Left Ventricular Assist Device-Supported Patients

Background—Aortic insufficiency (AI) following left ventricular assist device (LVAD) placement can affect device performance. The aim of this study was to examine AI development following LVAD implantation. Methods and Results—Echocardiograms (n=315) from 78 subjects undergoing HeartMate-XVE (n=25 [32%]) or HeartMate-II (n=53 [68%]) implantations from 2004 to 2008 were reviewed. Studies were obtained preoperatively and at 1, 3, 6, 12, 18, and 24 months after surgery. AI was graded on an interval scale (0=none, 0.5=trivial, 1=mild, 1.5=mild-moderate, 2=moderate, 2.5=moderate-severe, 3=severe), and the change in AI at follow-up was analyzed with significance tests. Kaplan–Meier estimates for freedom from moderate or worse AI at follow-up were generated. Mixed-model linear regression was used to identify correlates of AI progression during LVAD support. The median (25th, 75th percentile) duration of LVAD support was 239 (112, 455) days, and preoperative AI grade was 0.0 (0.0, 0.0). At 6 months, 89±4% of subjects (n=49 at risk) were free from moderate or worse AI, but this was reduced to 74±7% (n=29 at risk) and 49±13% (n=13 at risk) by 12 and 18 months, respectively. Correlates (slope±SE) of AI progression included female sex (0.002±0.001; P=0.01), smaller body surface area (−0.003±0.001 per m2; P=0.0017), and HeartMate-II model type (0.002±0.001; P=0.039). Correlates (&bgr;±SE) of progressive AI on postoperative echocardiogram included increasing aortic sinus diameter (0.04±0.01 per mm; P=0.001), an aortic valve that remained closed (0.42±0.06; P<0.001) or only intermittently opened (0.34±0.09; P<0.001), and lower left ventricular diastolic (−0.002±0.0004 per cm3; P<0.001) and systolic (−0.002±0.0004 per cm3; P<0.001) volumes. Conclusions—AI progresses over time in LVAD-supported patients. As we move toward an era of long-term cardiac support, more studies are needed to determine the clinical significance of these findings.

Metoprolol Reverses Left Ventricular Remodeling in Patients With Asymptomatic Systolic Dysfunction The REversal of VEntricular Remodeling with Toprol-XL (REVERT) Trial

Background— There are no randomized, controlled trial data to support the benefit of &bgr;-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether &bgr;-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction. Method and Results— Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m2), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14±3 mL/m2 decrease (least square mean±SE) in end-systolic volume index and a 6±1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14±3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4±1% (P<0.05 versus baseline and placebo). Conclusion— &bgr;-Blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Doppler-derived dP/dt and -dP/dt predict survival in congestive heart failure

OBJECTIVES The purpose of this study was to evaluate the ability of novel Doppler indices of left ventricular (LV) systolic and diastolic function to predict survival in patients with congestive heart failure (CHF). BACKGROUND Congestive heart failure is associated with an increased risk of death or cardiac transplantation, yet techniques to predict survival are limited. METHODS Doppler-derived dP/dt and - dP/dt were determined prospectively from the continuous-wave Doppler spectrum of the mitral regurgitation jet (dP/dt = 32/time between 1 and 3 m/s; -dP/dt = 32/time between 3 and 1 m/s) in 56 patients with chronic CHF (age, 60 +/- 15 years; LV ejection fraction, 23 +/- 9%). Baseline clinical and echocardiographic variables were also obtained, and clinical follow-up was performed in all patients. RESULTS Twenty-four patients experienced a primary event of cardiac death (n = 15), United Network for Organ Sharing status I (inotrope-dependent) heart transplant (n = 3) or urgent implantation of a LV assist device (n = 6). Doppler-derived dP/dt (dichotomized to > or = or <600 mm Hg/s; p = 0.0002) and -dP/dt (trichotomized to <450, 450 to 550 and >550 mm Hg/s; p = 0.0001) predicted event-free survival, as did Doppler-derived risk groups determined by the combination of the two (low risk, dP/dt > or = 600; intermediate risk, dP/dt < 600 and -dP/dt > or = 450; high risk, dP/dt < 600 and -dP/dt < 450; p = 0.0001). Multivariable analysis revealed Doppler-derived risk groups, intravenous inotrope requirement and blood urea nitrogen as significant independent predictors of outcome. CONCLUSION New Doppler indices of dP/dt, - dP/dt and risk groups defined by the combination of dP/dt and -dP/dt predict event-free survival in patients with CHF.

Low-Sodium Dietary Approaches to Stop Hypertension Diet Reduces Blood Pressure, Arterial Stiffness, and Oxidative Stress in Hypertensive Heart Failure With Preserved Ejection Fraction

Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In ‘salt-sensitive’ HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155 to 138 mmHg, p=.02) and diastolic BP (79 to 72 mmHg, p=.04), 24-hour ambulatory systolic (130 to 123 mmHg, p=.02) and diastolic BP (67 to 62 mmHg, p=.02), and carotid-femoral pulse wave velocity (12.4 to 11.0 m/s, p=.03). Urinary F2-isoprostanes decreased by 31% (209 to 144 pmol/mmol Cr, p=.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of ‘salt-sensitive’ hypertension, a phenotype present in many HFPEF animal models, and suggest shared pathophysiological mechanisms linking these two conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In salt-sensitive HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155–138 mm Hg; P=0.02) and diastolic blood pressure (79–72 mm Hg; P=0.04), 24-hour ambulatory systolic (130–123 mm Hg; P=0.02) and diastolic blood pressure (67–62 mm Hg; P=0.02), and carotid-femoral pulse wave velocity (12.4–11.0 m/s; P=0.03). Urinary F2-isoprostanes decreased by 31% (209–144 pmol/mmol Cr; P=0.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of salt-sensitive hypertension, a phenotype present in many HFPEF animal models and suggest shared pathophysiological mechanisms linking these 2 conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

Low-Sodium DASH Diet Improves Diastolic Function and Ventricular–Arterial Coupling in Hypertensive Heart Failure With Preserved Ejection Fraction

Background—Heart failure with preserved ejection fraction (HFPEF) involves failure of cardiovascular reserve in multiple domains. In HFPEF animal models, dietary sodium restriction improves ventricular and vascular stiffness and function. We hypothesized that the sodium-restricted dietary approaches to stop hypertension diet (DASH/SRD) would improve left ventricular diastolic function, arterial elastance, and ventricular–arterial coupling in hypertensive HFPEF. Methods and Results—Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD (target sodium, 50 mmol/2100 kcal) for 21 days. We measured baseline and post-DASH/SRD brachial and central blood pressure (via radial arterial tonometry) and cardiovascular function with echocardiographic measures (all previously invasively validated). Diastolic function was quantified via the parametrized diastolic filling formalism that yields relaxation/viscoelastic (c) and passive/stiffness (k) constants through the analysis of Doppler mitral inflow velocity (E-wave) contours. Effective arterial elastance (Ea) end-systolic elastance (Ees) and ventricular–arterial coupling (defined as the ratio Ees:Ea) were determined using previously published techniques. Wilcoxon matched-pairs signed-rank tests were used for pre–post comparisons. The DASH/SRD reduced clinic and 24-hour brachial systolic pressure (155±35 to 138±30 and 130±16 to 123±18 mm Hg; both P=0.02), and central end-systolic pressure trended lower (116±18 to 111±16 mm Hg; P=0.12). In conjunction, diastolic function improved (c=24.3±5.3 to 22.7±8.1 g/s; P=0.03; k=252±115 to 170±37 g/s2; P=0.03), Ea decreased (2.0±0.4 to 1.7±0.4 mm Hg/mL; P=0.007), and ventricular–arterial coupling improved (Ees:Ea=1.5±0.3 to 1.7±0.4; P=0.04). Conclusions—In patients with hypertensive HFPEF, the sodium-restricted DASH diet was associated with favorable changes in ventricular diastolic function, arterial elastance, and ventricular–arterial coupling. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00939640.

Two-dimensional strain imaging of controlled rabbit hearts.

Ultrasound strain imaging using 2-D speckle tracking has been proposed to quantitatively assess changes in myocardial contractility caused by ischemia. Its performance must be demonstrated in a controlled model system as a step toward routine clinical application. In this study, a well-controlled 2-D cardiac elasticity imaging technique was developed using two coplanar and orthogonal linear probes simultaneously imaging an isolated retroperfused rabbit heart. Acute ischemia was generated by left anterior descending (LAD) artery ligation. An excitation-contraction decoupler, 2,3-butanedione monoxime, was applied at a 4-mM concentration to reversibly reduce myocardial contractility. Results using a single probe demonstrate that directional changes in the in-plane principal deformation axes can help locate the bulging area as a result of LAD ligation, which matched well with corresponding Evans Blue staining, and strains or strain magnitude, based on principal stretches, can characterize heart muscle contractility. These two findings using asymmetric displacement accuracy (i.e., normal single-probe measurements with good axial but poor lateral estimates) were further validated using symmetric displacement accuracy (i.e., dual-probe measurements using only accurate axial tracking estimates from each). However, the accuracy of 2-D cardiac strain imaging using a single probe depends on the probes orientation because of the large variance in lateral displacement estimates.

The Development of Aortic Insufficiency in LVAD Supported Patients

Background—Aortic insufficiency (AI) following left ventricular assist device (LVAD) placement can affect device performance. The aim of this study was to examine AI development following LVAD implantation. Methods and Results—Echocardiograms (n=315) from 78 subjects undergoing HeartMate-XVE (n=25 [32%]) or HeartMate-II (n=53 [68%]) implantations from 2004 to 2008 were reviewed. Studies were obtained preoperatively and at 1, 3, 6, 12, 18, and 24 months after surgery. AI was graded on an interval scale (0=none, 0.5=trivial, 1=mild, 1.5=mild-moderate, 2=moderate, 2.5=moderate-severe, 3=severe), and the change in AI at follow-up was analyzed with significance tests. Kaplan–Meier estimates for freedom from moderate or worse AI at follow-up were generated. Mixed-model linear regression was used to identify correlates of AI progression during LVAD support. The median (25th, 75th percentile) duration of LVAD support was 239 (112, 455) days, and preoperative AI grade was 0.0 (0.0, 0.0). At 6 months, 89±4% of subjects (n=49 at risk) were free from moderate or worse AI, but this was reduced to 74±7% (n=29 at risk) and 49±13% (n=13 at risk) by 12 and 18 months, respectively. Correlates (slope±SE) of AI progression included female sex (0.002±0.001; P=0.01), smaller body surface area (−0.003±0.001 per m2; P=0.0017), and HeartMate-II model type (0.002±0.001; P=0.039). Correlates (&bgr;±SE) of progressive AI on postoperative echocardiogram included increasing aortic sinus diameter (0.04±0.01 per mm; P=0.001), an aortic valve that remained closed (0.42±0.06; P<0.001) or only intermittently opened (0.34±0.09; P<0.001), and lower left ventricular diastolic (−0.002±0.0004 per cm3; P<0.001) and systolic (−0.002±0.0004 per cm3; P<0.001) volumes. Conclusions—AI progresses over time in LVAD-supported patients. As we move toward an era of long-term cardiac support, more studies are needed to determine the clinical significance of these findings.