Diastolic function assessment with four-dimensional flow cardiovascular magnetic resonance using automatic deep learning E/A ratio analysis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow-based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning-based and two semi-automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold-standard echo-based methods. METHODS: Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow-based E/A ratio values were computed using three different approaches; two semi-automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). RESULTS: MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R2 = 0.26, 0.57). CONCLUSION: Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the E/A ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ∼40 seconds. As both semi-automatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of E/A ratio.

Deployment of Point-of-Care Echocardiography to Improve Cardiac Diagnostic Access Among American Indians.

BACKGROUND: American Indians face significant barriers to diagnosis and management of cardiovascular disease. We sought to develop a real-world implementation model for improving access to echocardiography within the Indian Health Service, the American Indian Structural Heart Disease Partnership. METHODS AND RESULTS: The American Indian Structural Heart Disease Partnership was implemented and evaluated via a 4-step process of characterizing the system where it would be instituted, building point-of-care echocardiography capacity, deploying active case finding for structural heart disease, and evaluating the approach from the perspective of the clinician and patient. Data were collected and analyzed using a parallel convergent mixed methods approach. Twelve health care providers successfully completed training in point-of-care echocardiography. While there was perceived usefulness of echocardiography, providers found it difficult to integrate screening point-of-care echocardiography into their workday given competing demands. By the end of 12 months, 6 providers continued to actively utilize point-of-care echocardiography. Patients who participated in the study felt it was an acceptable and effective approach. They also identified access to transportation as a notable challenge to accessing echocardiograms. Over the 12-month period, a total of 639 patients were screened, of which 36 (5.6%) had a new clinically significant abnormal finding. CONCLUSIONS: The American Indian Structural Heart Disease Partnership model exhibited several promising strategies to improve access to screening echocardiography for American Indian populations. However, competing priorities for Indian Health Service providers' time limited the amount of integration of screening echocardiography into outpatient practice. Future endeavors should explore community-based solutions to develop a more sustainable model with greater impact on case detection, disease management, and improved outcomes.

Assessment of transmitral and left atrial appendage flow rate from cardiac 4D-CT.

BACKGROUND: Cardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however. METHODS: To measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients. RESULTS: For the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml). There are larger differences in the diastolic peak flow rates, with a larger bias for the early flow rate than the late flow rate. The peak LAA outflow rate measured with both modalities matches well (bias: -6 ml/s). CONCLUSIONS: Overall, the developed algorithm provides accurate tracking of dynamic cardiac geometries resulting in similar flow rates at the MV and LAA compared to 4D flow MRI.

Assessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart.

Out-of-pocket expenditure for administration of benzathine penicillin G injections for secondary prophylaxis in patients with rheumatic heart disease: A registry-based data from a tertiary care center in Northern India.

BACKGROUND: Costs can be a major barrier to medication adherence in low and middle-income countries and are an important target for policy-level interventions. The use of benzathine penicillin G (BPG) for secondary prevention of rheumatic heart disease (RHD) averts substantial morbidity and mortality, yet the total out-of-pocket costs for patients receiving this intervention are unknown. OBJECTIVE: To estimate the total out-of-pocket costs for obtaining BPG prophylaxis among RHD patients in India. METHODS: We prospectively collected self-reported drug-, transportation-, and provider-related costs for secondary prophylaxis among RHD patients presenting for follow-up to a tertiary care centre in New Delhi, India. Monthly costs were estimated by adjusting unit costs by frequency of drug administration. RESULTS: The cost data provided by 420 patients [mean age (±SD) 11.6 (±2.9) years] was analysed. Majority of the patients were male (65.2%), hailed from rural areas (87.1%), and belonged to lower socioeconomic strata (73.3%). The median monthly total out-of-pocket costs (IQR) for obtaining BPG injections was Indian rupee (INR) 62.5 (42.5-117.0). The median costs for procuring the drug (IQR) was INR 34.0(30.0-39.0). Whereas median costs (IQR) for health care provider and transportation was INR 16.0 [0-32.0]) and INR 11 [0-31.0] respectively. When expressed as mean (SD), the costs for transportation constituted 50% of the total costs, whereas the mean cost for drug procurement and drug administration constituted 30% and 22% of the total costs respectively. CONCLUSION: RHD patients receiving BPG prophylaxis incur substantial out-of-pocket costs, with transportation costs constituting nearly half of the total expenditures. National investments in RHD control must be strategically directed at improving health care access and drug supply in order to lower the total costs of secondary prophylaxis and improve adherence rates.

Extending Cardiac Functional Assessment with Respiratory-Resolved 3D Cine MRI.

This study aimed to develop a cardiorespiratory-resolved 3D magnetic resonance imaging (5D MRI: x-y-z-cardiac-respiratory) approach based on 3D motion tracking for investigating the influence of respiration on cardiac ventricular function. A highly-accelerated 2.5-minute sparse MR protocol was developed for a continuous acquisition of cardiac images through multiple cardiac and respiratory cycles. The heart displacement along respiration was extracted using a 3D image deformation algorithm, and this information was used to cluster the acquired data into multiple respiratory phases. The proposed approach was tested in 15 healthy volunteers (7 females). Cardiac function parameters, including the end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), were measured for the left and right ventricle in both end-expiration and end-inspiration. Although with the proposed 5D cardiac MRI, there were no significant differences (p > 0.05, t-test) between end-expiration and end-inspiration measurements of the cardiac function in volunteers, incremental respiratory motion parameters that were derived from 3D motion tracking, such as the depth, expiration and inspiration distribution, correlated (p < 0.05, correlation coefficient, Mann-Whitney) with those volume-based parameters of cardiac function and varied between genders. The obtained initial results suggested that this new approach allows evaluation of cardiac function during specific respiratory phases. Thus, it can enable investigation of effects related to respiratory variability and better assessment of cardiac function for studying respiratory and/or cardiac dysfunction.

Non-invasive Assessment of Systolic and Diastolic Cardiac Function During Rest and Stress Conditions Using an Integrated Image-Modeling Approach.

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 ± 0.3 to 2 ± 0.5 (p = 0.038)] and relaxation constant [from 37.2 ± 6.9 to 46.1 ± 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 ± 0.04 s to 0.3 ± 0.03 s (p = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics of pathophysiology that are otherwise difficult to obtain non-invasively in clinical practice.

Assessment of left ventricular hemodynamic forces in healthy subjects and patients with dilated cardiomyopathy using 4D flow MRI.

We hypothesized that the direction of global left ventricular (LV) hemodynamic forces during diastolic filling are concordant with the main flow axes in normal LVs, but that this pattern would be altered in dilated and dysfunctional LVs. Therefore, we aimed to assess the LV hemodynamic filling forces in a group of healthy subjects and compare them to the results from a group of patients with dilated cardiomyopathy (DCM). Ten healthy subjects and 10 DCM patients were enrolled. Morphological short- (SAx) and long-axis (LAx) images and 4D flow MRI data were acquired at 1.5T. The LV pressure gradients were computed from the 4D flow data using the Navier-Stokes equations. By integrating the pressure gradients over the LV volume at each time frame, the magnitude and direction of the global hemodynamic force was calculated over the cardiac cycle. The hemodynamic forces acting in the SAx- and LAx-directions were used to calculate the "SAx-max/LAx-max"-ratio for the early (E-wave) and late (A-wave) diastolic filling. In the LAx-plane, the temporal progression of the hemodynamic force followed a consistent pattern in the healthy subjects. The "SAx-max/LAx-max"-ratio was significantly larger at both E-wave (0.53 ± 0.15 vs. 0.23 ± 0.12, P < 0.0001) and A-wave (0.44 ± 0.21 vs. 0.26 ± 0.09, P < 0.03) in the DCM patients compared to the healthy subjects. 4D flow MRI data allow quantification of LV hemodynamic forces acting on the LV myocardial wall. The LV hemodynamic filling forces showed a similar temporal progression among healthy subjects, whereas DCM patients had forces that were more heterogeneous in their direction and magnitude during diastole.

Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals.

BACKGROUND: HIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals. METHODS AND RESULTS: We studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all). CONCLUSION: In HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death.

Exhaustion of food budgets at month's end and hospital admissions for hypoglycemia.

One in seven US households cannot reliably afford food. Food budgets are more frequently exhausted at the end of a month than at other points in time. We postulated that this monthly pattern influenced health outcomes, such as risk for hypoglycemia among people with diabetes. Using administrative data on inpatient admissions in California for 2000-08, we found that admissions for hypoglycemia were more common in the low-income than the high-income population (270 versus 200 admissions per 100,000). Risk for hypoglycemia admission increased 27 percent in the last week of the month compared to the first week in the low-income population, but we observed no similar temporal variation in the high-income population. These findings suggest that exhaustion of food budgets might be an important driver of health inequities. Policy solutions to improve stable access to nutrition in low-income populations and raise awareness of the health risks of food insecurity might be warranted.

In vitro assessment of flow patterns and turbulence intensity in prosthetic heart valves using generalized phase-contrast MRI.

PURPOSE: To assess in vitro the three-dimensional mean velocity field and the extent and degree of turbulence intensity (TI) in different prosthetic heart valves using a generalization of phase-contrast MRI (PC-MRI). MATERIALS AND METHODS: Four 27-mm aortic valves (Björk-Shiley Monostrut tilting-disc, St. Jude Medical Standard bileaflet, Medtronic Mosaic stented and Freestyle stentless porcine valve) were tested under steady inflow conditions in a Plexiglas phantom. Three-dimensional PC-MRI data were acquired to measure the mean velocity field and the turbulent kinetic energy (TKE), a direction-independent measure of TI. RESULTS: Velocity and TI estimates could be obtained up- and downstream of the valves, except where metallic structure in the valves caused signal void. Distinct differences in the location, extent, and peak values of velocity and TI were observed between the valves tested. The maximum values of TKE varied between the different valves: tilting disc, 100 J/m(3); bileaflet, 115 J/m(3); stented, 200 J/m(3); stentless, 145 J/m(3). CONCLUSION: The TI downstream from a prosthetic heart valve is dependent on the specific valve design. Generalized PC-MRI can be used to quantify velocity and TI downstream from prosthetic heart valves, which may allow assessment of these aspects of prosthetic valvular function in postoperative patients.

Assessment of fluctuating velocities in disturbed cardiovascular blood flow: in vivo feasibility of generalized phase-contrast MRI.

PURPOSE: To evaluate the feasibility of generalized phase-contrast magnetic resonance imaging (PC-MRI) for the noninvasive assessment of fluctuating velocities in cardiovascular blood flow. MATERIALS AND METHODS: Multidimensional PC-MRI was used in a generalized manner to map mean flow velocities and intravoxel velocity standard deviation (IVSD) values in one healthy aorta and in three patients with different cardiovascular diseases. The acquired data were used to assess the kinetic energy of both the mean (MKE) and the fluctuating (TKE) velocity field. RESULTS: In all of the subjects, both mean and fluctuating flow data were successfully acquired. The highest TKE values in the patients were found at sites characterized by abnormal flow conditions. No regional increase in TKE was found in the normal aorta. CONCLUSION: PC-MRI IVSD mapping is able to detect flow abnormalities in a variety of human cardiovascular conditions and shows promise for the quantitative assessment of turbulence. This approach may assist in clarifying the role of disturbed hemodynamics in cardiovascular diseases.