Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume.

BACKGROUND: Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. METHODS: Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). RESULTS: Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to - 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (- 2 ± 7%). CONCLUSIONS: CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV.

Diastolic Filling in Patients After Heart Transplantation Is Impaired Due to an Altered Geometrical Relationship Between the Left Atrium and Ventricle.

BACKGROUND: The geometrical relationship between atrial and ventricular short-axis cross-sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle. METHODS AND RESULTS: This retrospective, cross-sectional study included 25 HTx patients (median age, 52 [range, 25-70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52-75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56-82] years), and 15 healthy controls (median age, 64 [range, 58-67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short-axis area minus the largest atrial short-axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07-0.19]) compared with controls (median, 0.05 [range, 0.03-0.08], P <0.001), whereas left ventricular volume normalized for THV (left ventricular end-diastolic volume/THV) was similar between HTx and controls (median, 0.19 [range, 0.12-0.24] and median, 0.22 [range, 0.20-0.25], respectively). At end diastole, when atrioventricular area difference reached its largest positive value in controls, 11 HTx patients (44%) had a negative atrioventricular area difference, indicating impaired diastolic filling. CONCLUSIONS: Diastolic filling is impaired in HTx patients due to an altered geometrical relationship between the left atrium and ventricle. When performing cardiac transplantation, a surgical technique that creates a smaller left atrium may improve diastolic filling by aiding hydraulic forces.

Left ventricular dysfunction in pulmonary arterial hypertension is attributed to underfilling rather than intrinsic myocardial disease: a CMR 2D phase contrast study.

The pathophysiology underlying impaired LV function in PAH remains unclear, with some studies implicating intrinsic myocardial dysfunction and others pointing to LV underfilling. Evaluation of pulmonary vein area (PVA) and flow may offer novel, mechanistic insight by distinguishing elevated LV filling pressure common in myocardial dysfunction from LV underfilling. This study aimed to elucidate LV filling physiology in PAH by assessing PVA and flow using cardiac magnetic resonance (CMR) and compare pulmonary vein flow in PAH with HFrEF as a model representing elevated filling pressures, in addition to healthy controls. Patients with PAH or heart failure with reduced ejection fraction (HFrEF) referred for CMR were retrospectively reviewed, and healthy controls were included as reference. Pulmonary vein S, D and A-wave were compared between groups. Associations between pulmonary vein area (PVA) by CMR and echocardiographic indices of LV filling pressure were evaluated. Nineteen patients with PAH, 25 with HFrEF and 24 controls were included. Both PAH and HFrEF had lower ejection fraction and S-wave velocity than controls. PAH displayed smaller LV end-diastolic volumes than controls, while HFrEF demonstrated larger PVA and higher A-wave reversal. PVA was associated with mitral E/e' ratio (r2 = 0.10; p = 0.03), e' velocity (r2 = 0.23; p = 0.001) and left atrial volume (r2 = 0.07; p = 0.005). Among PAH, PVA was not associated with LV-GLS. A PVA cut-off of 2.3cm2 displayed 87% sensitivity and 72% specificity to differentiate HFrEF and PAH (AUC = 0.82). PAH displayed lower pulmonary vein S-wave velocity, smaller LV volume and reduced function compared with controls. Reduced LV function in PAH may be owing to underfilling rather than intrinsic myocardial disease. PVA demonstrates promise as a novel, non-invasive imaging marker to assess LV filling status.

Hemodynamic force analysis is not ready for clinical trials on HFpEF.

Hemodynamic force analysis has been proposed as a novel tool for early detection of subclinical systolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Here we investigated the ability of hemodynamic forces to discriminate between healthy subjects and heart failure patients with varying degrees of systolic dysfunction. We studied 34 controls, 16 HFpEF patients, and 25 heart failure patients with mid-range (HFmrEF) or reduced ejection fraction (HFrEF) using cardiac magnetic resonance with acquisition of cine images and 4D flow at 1.5 T. The Navier-Stokes equation was used to compute global left ventricular hemodynamic forces over the entire cardiac cycle. Forces were analyzed for systole, diastole, and the entire heartbeat, with and without normalization to left ventricular volume. Volume-normalized hemodynamic forces demonstrated significant positive correlation with EF (r2 = 0.47, p < 0.0001) and were found significantly lower in heart failure with reduced ejection fraction compared to controls (p < 0.0001 for systole and diastole). No difference was seen between controls and HFpEF (p > 0.34). Non-normalized forces displayed no differences between controls and HFpEF (p > 0.24 for all analyses) and did not correlate with EF (p = 0.36). Left ventricular hemodynamic force analysis, whether indexed to LV volumes or not, is not ready for clinical trials on HFpEF assessment.

Kinetic energy of left ventricular blood flow across heart failure phenotypes and in subclinical diastolic dysfunction.

Kinetic energy (KE) of intracardiac blood flow reflects myocardial work spent on accelerating blood and provides a mechanistic window into diastolic filling dynamics. Diastolic dysfunction may represent an early stage in the development of heart failure (HF). Here we evaluated the hemodynamic effects of impaired diastolic function in subjects with and without HF, testing the hypothesis that left ventricular KE differs between controls, subjects with subclinical diastolic dysfunction (SDD), and patients with HF. We studied 77 subjects [16 controls, 20 subjects with SDD, 16 heart failure with preserved ejection fraction (HFpEF), 9 heart failure with mildly reduced ejection fraction (HFmrEF), and 16 heart failure with reduced ejection fraction (HFrEF) patients, age- and sex-matched at the group level]. Cardiac magnetic resonance at 1.5 T included intracardiac four-dimensional (4-D) flow and cine imaging. Left ventricular KE was calculated as 0.5 × m × v2. Systolic KE was similar between groups (P > 0.4), also after indexing to stroke volume (P = 0.25), and was primarily driven by ventricular emptying rate (P < 0.0001, R2 = 0.52). Diastolic KE was higher in patients with heart failure than in controls (P < 0.05) but similar between SDD and HFpEF (P > 0.18), correlating with inflow conditions (E-wave velocity, P < 0.0001, R2 = 0.24) and end-diastolic volume (P = 0.0003, R2 = 0.17) but not with average e' (P = 0.07). Diastolic KE differs between controls and heart failure, suggesting more work is spent filling the failing ventricle, whereas systolic KE does not differentiate between well-matched groups with normal ejection fractions even in the presence of relaxation abnormalities and heart failure. Mechanistically, KE reflects the acceleration imparted on the blood and is driven by variations in ventricular emptying and filling rates, volumes, and heart rate, regardless of underlying pathology.NEW & NOTEWORTHY Here we present the first study of left ventricular kinetic energy in individuals with subclinical diastolic dysfunction and in heart failure patients with preserved or impaired systolic function. Kinetic energy differs between groups in diastole, and reflects altered filling and emptying processes. Kinetic energy analysis should be considered in studies seeking to characterize myocardial energetics comprehensively.

Noninvasive Assessment of Left Ventricular Pressure-Volume Relations: Inter- and Intraobserver Variability and Assessment Across Heart Failure Subtypes.

A novel method to derive pressure-volume (PV) loops noninvasively from cardiac magnetic resonance images has recently been developed. The aim of this study was to evaluate inter- and intraobserver variability of hemodynamic parameters obtained from noninvasive PV loops in healthy controls, subclinical diastolic dysfunction (SDD), and patients with heart failure with preserved ejection fraction, mildly reduced ejection fraction, and reduced ejection fraction. We included 75 subjects, of whom 15 were healthy controls, 15 subjects with SDD (defined as fulfilling 1 to 2 echocardiographic criteria for diastolic dysfunction), and 15 patients with preserved ejection fraction, 15 with mildly reduced ejection fraction, and 15 with reduced ejection fraction. PV loops were computed using time-resolved left ventricular volumes from cardiac magnetic resonance images and a brachial blood pressure. Inter- and intraobserver variability and intergroup differences of PV loop-derived hemodynamic parameters were assessed. Bias was low and limits of agreement were narrow for all hemodynamic parameters in the inter- and intraobserver comparisons. Interobserver difference for stroke work was 2 ± 9%, potential energy was 4 ± 11%, and maximal ventricular elastance was -4 ± 7%. Intraobserver for stroke work was -1 ± 7%, potential energy was 3 ± 4%, and maximal ventricular elastance was 1 ± 5%. In conclusion, this study presents a fully noninvasive left ventricular PV loop analysis across healthy controls, subjects with SDD, and patients with heart failure with preserved or impaired systolic function. In conclusion, the method for PV loop computation from clinical-standard manual left ventricular segmentation was rapid and robust, bridging the gap between clinical and research settings.

Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome.

BACKGROUND: Aggregates formed between leukocytes and platelets in the circulation lead to release of tissue factor (TF)-bearing microparticles contributing to a prothrombotic state. As enterohemorrhagic Escherichia coli (EHEC) may cause hemolytic uremic syndrome (HUS), in which microthrombi cause tissue damage, this study investigated whether the interaction between blood cells and EHEC virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS) led to release of TF. METHODOLOGY/PRINCIPAL FINDINGS: The interaction between Stx or LPS and blood cells induced platelet-leukocyte aggregate formation and tissue factor (TF) release, as detected by flow cytometry in whole blood. O157LPS was more potent than other LPS serotypes. Aggregates formed mainly between monocytes and platelets and less so between neutrophils and platelets. Stimulated blood cells in complex expressed activation markers, and microparticles were released. Microparticles originated mainly from platelets and monocytes and expressed TF. TF-expressing microparticles, and functional TF in plasma, increased when blood cells were simultaneously exposed to the EHEC virulence factors and high shear stress. Stx and LPS in combination had a more pronounced effect on platelet-monocyte aggregate formation, and TF expression on these aggregates, than each virulence factor alone. Whole blood and plasma from HUS patients (n = 4) were analyzed. All patients had an increase in leukocyte-platelet aggregates, mainly between monocytes and platelets, on which TF was expressed during the acute phase of disease. Patients also exhibited an increase in microparticles, mainly originating from platelets and monocytes, bearing surface-bound TF, and functional TF was detected in their plasma. Blood cell aggregates, microparticles, and TF decreased upon recovery. CONCLUSIONS/SIGNIFICANCE: By triggering TF release in the circulation, Stx and LPS can induce a prothrombotic state contributing to the pathogenesis of HUS.