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.

Adapted from: Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association.

BACKGROUND: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. METHODS AND RESULTS: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. CONCLUSIONS: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

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.

Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association.

BACKGROUND: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. METHODS AND RESULTS: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. CONCLUSIONS: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Improved Efficiency of Intraventricular Blood Flow Transit Under Cardiac Stress: A 4D Flow Dobutamine CMR Study.

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion. Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate ~60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated. Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase. Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusitropy, elicited by dobutamine infusion, the efficiency of intraventricular blood flow transit improves, as quantified by an increased relative volume and pre-systolic KE of the most efficient DF component of the LV volume. The change in these markers may allow a novel assessment of LV function and LV dysfunction over a range of stress.

Publisher Correction: Bridging the gap between measurements and modelling: a cardiovascular functional avatar.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association.

Myocardial infarction in the absence of obstructive coronary artery disease is found in ≈5% to 6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition. As such, it is important that patients are appropriately diagnosed and an evaluation to uncover the correct cause is performed so that, when possible, specific therapies to treat the underlying cause can be prescribed. This statement provides a formal and updated definition for the broadly labelled term MINOCA (incorporating the definition of acute myocardial infarction from the newly released "Fourth Universal Definition of Myocardial Infarction") and provides a clinically useful framework and algorithms for the diagnostic evaluation and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

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.

Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association.

BACKGROUND: Chagas disease, resulting from the protozoan Trypanosoma cruzi, is an important cause of heart failure, stroke, arrhythmia, and sudden death. Traditionally regarded as a tropical disease found only in Central America and South America, Chagas disease now affects at least 300 000 residents of the United States and is growing in prevalence in other traditionally nonendemic areas. Healthcare providers and health systems outside of Latin America need to be equipped to recognize, diagnose, and treat Chagas disease and to prevent further disease transmission. METHODS AND RESULTS: The American Heart Association and the Inter-American Society of Cardiology commissioned this statement to increase global awareness among providers who may encounter patients with Chagas disease outside of traditionally endemic environments. In this document, we summarize the most updated information on diagnosis, screening, and treatment of T cruzi infection, focusing primarily on its cardiovascular aspects. This document also provides quick reference tables, highlighting salient considerations for a patient with suspected or confirmed Chagas disease. CONCLUSIONS: This statement provides a broad summary of current knowledge and practice in the diagnosis and management of Chagas cardiomyopathy. It is our intent that this document will serve to increase the recognition of Chagas cardiomyopathy in low-prevalence areas and to improve care for patients with Chagas heart disease around the world.

Fixed volume particle trace emission for the analysis of left atrial blood flow using 4D Flow MRI.

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow=particle traces that enter and leave the atrium in one heartbeat, Retained flow=particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed-volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

Mechanical dyssynchrony alters left ventricular flow energetics in failing hearts with LBBB: a 4D flow CMR pilot study.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy.

Bridging the gap between measurements and modelling: a cardiovascular functional avatar.

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.

Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block.

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r2 = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

Altered Diastolic Flow Patterns and Kinetic Energy in Subtle Left Ventricular Remodeling and Dysfunction Detected by 4D Flow MRI.

AIMS: 4D flow magnetic resonance imaging (MRI) allows quantitative assessment of left ventricular (LV) function according to characteristics of the dynamic flow in the chamber. Marked abnormalities in flow components' volume and kinetic energy (KE) have previously been demonstrated in moderately dilated and depressed LV's compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling. METHODS AND RESULTS: We acquired 4D flow and morphological MRI data from 26 patients with chronic ischemic heart disease with New York Heart Association (NYHA) class I and II and with no to mild LV systolic dysfunction and remodeling, and from 10 healthy controls. A previously validated method was used to separate the LV end-diastolic volume (LVEDV) into functional components: direct flow, which passes directly to ejection, and non-ejecting flow, which remains in the LV for at least 1 cycle. The direct flow and non-ejecting flow proportions of end-diastolic volume and KE were assessed. The proportions of direct flow volume and KE fell with increasing LVEDV-index (LVEDVI) and LVESV-index (LVESVI) (direct flow volume r = -0.64 and r = -0.74, both P<0.001; direct flow KE r = -0.48, P = 0.013, and r = -0.56, P = 0.003). The proportions of non-ejecting flow volume and KE rose with increasing LVEDVI and LVESVI (non-ejecting flow volume: r = 0.67 and r = 0.76, both P<0.001; non-ejecting flow KE: r = 0.53, P = 0.005 and r = 0.52, P = 0.006). The proportion of direct flow volume correlated moderately to LVEF (r = 0.68, P < 0.001) and was higher in a sub-group of patients with LVEDVI >74 ml/m2 compared to patients with LVEDVI <74 ml/m2 and controls (both P<0.05). CONCLUSION: Direct flow volume and KE proportions diminish with increased LV volumes, while non-ejecting flow proportions increase. A decrease in direct flow volume and KE at end-diastole proposes that alterations in these novel 4D flow-specific markers may detect LV dysfunction even in subtle or subclinical LV remodeling.

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.

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.

BACKGROUND: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. METHODS AND RESULTS: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. CONCLUSIONS: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.