A machine learning-derived risk score to predict left ventricular diastolic dysfunction from clinical cardiovascular magnetic resonance imaging.

Introduction: The evaluation of left ventricular diastolic dysfunction (LVDD) by clinical cardiac magnetic resonance (CMR) remains a challenge. We aimed to train and evaluate a machine-learning (ML) algorithm for the assessment of LVDD by clinical CMR variables and to investigate its prognostic value for predicting hospitalized heart failure and all-cause mortality. Methods: LVDD was characterized by echocardiography following the ASE guidelines. Eight demographic and nineteen common clinical CMR variables including delayed enhancement were used to train Random Forest models with a Bayesian optimizer. The model was evaluated using bootstrap and five-fold cross-validation. Area under the ROC curve (AUC) was utilized to evaluate the model performance. An ML risk score was used to stratify the risk of heart failure hospitalization and all-cause mortality. Results: A total of 606 consecutive patients underwent CMR and echocardiography within 7 days for cardiovascular disease evaluation. LVDD was present in 303 subjects by echocardiography. The performance of the ML algorithm was good using the CMR variables alone with an AUC of 0.868 (95% CI: 0.811-0.917), which was improved by combining with demographic data yielding an AUC 0.895 (95% CI: 0.845-0.939). The algorithm performed well in an independent validation cohort with AUC 0.810 (0.731-0.874). Subjects with higher ML scores (>0.4121) were associated with increased adjusted hazard ratio for a composite outcome than subjects with lower ML scores (1.72, 95% confidence interval 1.09-2.71). Discussion: An ML algorithm using variables derived from clinical CMR is effective in identifying patients with LVDD and providing prognostication for adverse clinical outcomes.

Association of pulmonary transit time by cardiac magnetic resonance with heart failure hospitalization in a large prospective cohort with diverse cardiac conditions.

BACKGROUND: Longer pulmonary transit time (PTT) is closely associated with hemodynamic abnormalities. However, the implications on heart failure (HF) risk have not been investigated broadly in patients with diverse cardiac conditions. In this study we examined the long-term risk of HF hospitalization associated with longer PTT in a large prospective cohort with a broad spectrum of cardiac conditions. METHODS: All subjects were prospectively recruited to undergo cardiac magnetic resonance (CMR). The dynamic images of first-pass perfusion were acquired to assess peak-to-peak pulmonary transit time (PTT) which was subsequently normalized to RR interval duration. The risk of HF was examined using Cox proportional hazards models adjusted for baseline confounding risk factors. RESULTS: Among 506 consecutively consented patients undergoing clinical cardiac MR with diverse cardiac conditions, the mean age was 63 ± 14 years and 373 (73%) were male. After a mean follow up duration of 4.5 ± 3.0 years, 70 (14%) patients developed hospitalized HF and of these 6 died. A normalized PTT ≥ 8.2 was associated with a significantly increased adjusted HF hazard ratio of 3.69 (95% CI 2.02, 6.73). The HF hazard ratio was 1.26 (95% CI 1.18, 1.33) for each 1 unit increase in PTT which was higher among those preserved (1.70, 95% CI 1.20, 2.41) compared to those with reduced left ventricular ejection fraction (< 50%) (1.18, 95% CI 1.09, 1.27). PTT remained a significant risk factor of hospitalized HF after additional adjustment for N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) or left ventricular global longitudinal strain with additionally demonstrated incremental model improvement through likelihood ratio testing. CONCLUSIONS: Our findings support the role of PTT in assessing HF risk among patients with broad spectrum of cardiac conditions with reduced as well as preserved ejection fraction. Longer PTT duration is an incremental risk factor for HF when baseline global longitudinal strain and NT-proBNP are taken into consideration.

Left Ventricular Mass, Myocardial Structure, and Function in Severe Aortic Stenosis: an Echocardiographic and Cardiac Magnetic Resonance Imaging Study.

In severe aortic stenosis (AS), there are conflicting data on the prognostic implications of left ventricular (LV) hypertrophy (LVH). We aimed to characterize the LV geometry, myocardial matrix structural changes, and prognostic stratification using cardiac magnetic resonance imaging (CMR) and echocardiography in subjects with severe AS with and without LVH. Consecutive patients who had severe isolated AS and sufficient quality echocardiography and CMR within 6 months of each other were evaluated for LVH, cardiac structure, morphology, and late gadolinium-enhancement imaging. Kaplan-Meier curves, linear models, and proportional hazards models were used for prognostic stratification. There were 93 patients enrolled (mean age 74 ± 11 years, 48% female), of whom 38 (41%) had a normal LV mass index (LVMI), 41 (44%) had LVH defined at CMR by LVMI >2 SD higher than normal, and 14 (15% of the total) with >4 SD higher than the reference LVMI (severely elevated). The Society of Thoracic Surgeons scores were similar among the LVMI groups. Compared with those with normal LVMI, patients with LVH had higher LV end-diastolic and end-systolic volumes, increased late gadolinium-enhancement burden, and lower LV ejection fraction. Most notably, CMR feature-tracking global radial strain, 2-dimensional speckle-tracking echocardiography global longitudinal strain, and left atrial reservoir function were significantly worse. On the survival analyses, LVMI was not associated with a composite of all-cause mortality and/or heart failure hospitalization. In conclusion, compared with normal LVMI, elevated LVMI was not associated with a higher risk of adverse outcomes.

The Prognostic Value of Left Atrial Global Longitudinal Strain and Left Atrial Phasic Volumes in Patients Undergoing Transcatheter Valve Implantation for Severe Aortic Stenosis.

INTRODUCTION: The changes and the prognostic implications of left atrial (LA) volumes (LAV), LA function, and vascular load in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) are less known. METHODS: We enrolled 150 symptomatic patients (mean age 82 ± 8 years, 58% female, and pre-TAVI aortic valve area 0.40 ± 0.19 cm/m2) with severe AS who underwent 2D transthoracic echocardiography and 2D speckle tracking echocardiography at average 21 ± 35 days before and 171 ± 217 days after TAVI. The end point was a composite of new onset of atrial fibrillation, hospitalization for heart failure and all-cause death (major adverse cardiac events [MACE]). RESULTS: After TAVI, indexed maximal LA volume and minimum volume of the LA decreased by 2.1 ± 10 mL/m2 and 1.6 ± 7 mL/m2 (p = 0.032 and p = 0.011, respectively), LA function index increased by 6.8 ± 11 units (p < 0.001), and LA stiffness decreased by 0.38 ± 2.0 (p = 0.05). No other changes in the LA phasic volumes, emptying fractions, and vascular load were noted. Post-TAVI, both left atrial and ventricular global peak longitudinal strain improved by about 6% (p = 0.01 and 0.02, respectively). MACE was reached by 37 (25%) patients after a median follow-up period of 172 days (interquartile range, 20-727). In multivariable models, MACE was associated with both pre- and post-TAVI LA global peak longitudinal strain (hazard ratio [HR] 0.75, CI 0.59-0.97; and HR 0.77, CI 0.60-1.00, per 5 percentage point units, respectively), pre-TAVI LV global endocardial longitudinal strain (HR 1.37, CI 1.02-1.83 per 5 percentage point units), and with most of the LA phasic volumes. CONCLUSION: Within 6 months after TAVI, there is reverse LA remodeling and an improvement in LA reservoir function. Pre- and post-TAVI indices of LA function and volume remain independently associated with MACE. Larger studies enrolling a greater diversity of patients may provide sufficient evidence for the utilization of these imaging biomarkers in clinical practice.

Prolonged central circulation transit time in patients with HFpEF and HFrEF by magnetic resonance imaging.

Aims: Prolonged central circulation transit time (TT) has long been associated with heart failure (HF) and left ventricular (LV) dysfunction. In this study, we assessed the central circulation TT using cardiovascular magnetic resonance imaging (CMR) in patients with HF of preserved ejection fraction (HFpEF) and of reduced EF (HFrEF) and investigated its relation to haemodynamics. Methods and results: Fifty eight prospectively recruited volunteers underwent CMR. TT was taken as the time between the peaks of time-intensity curves from first pass perfusion images and normalized to cardiac cycle length intervals. Left ventricular ejection fraction was 55 ± 3%, 57 ± 7%, and 28 ± 10% in control (N = 10), HFpEF (N = 20), and HFrEF (N = 28), respectively (P < 0.001). Global central TT from right atrium to ascending aorta was significantly prolonged in patients with HFrEF [17 ± 5 cardiac cycles (cc)] and HFpEF (12 ± 3 cc) when compared to the normal controls (8 ± 1 cc) (P < 0.001). Regional TT was also prolonged in HF patients between right atrium and pulmonary artery (PA), PA and left atrium (LA), and LA and ascending aorta (all P-value < 0.001) with the longest delay seen between PA and LA. Among 48 HF patients, 28 underwent same day cardiac catheterization. Multivariate regression analysis suggested while reduced left and right ventricular EF were the strongest correlates for HFrEF increased pulmonary capillary wedge (PCWP) and reduced PA oxygen saturation were the strongest correlates for HFpEF. Conclusions: Global and regional central TT can be assessed in the first pass perfusion imaging. Prolonged normalized global TT correlates with reduced EF in HFrEF and increased PCWP in HFpEF.

Effects of hemodynamics on global and regional lung perfusion: a quantitative lung perfusion study by magnetic resonance imaging.

BACKGROUND: Cardiac hemodynamics affect pulmonary vascular pressure and flow, but little is known of the effects of hemodynamics on lung perfusion at the tissue level. We sought to investigate the relationship between hemodynamic abnormalities in patients with left heart failure and global and regional lung perfusion using lung perfusion quantification by magnetic resonance imaging. METHODS AND RESULTS: Lung perfusion was quantified in 10 normal subjects and 28 patients undergoing clinically indicated left and right heart catheterization and same day research cardiac magnetic resonance imaging. A total of 228 lung slices were evaluated. Global lung perfusion, determined as the average of 6 coronal lung slices through the anterior, mid, and posterior left and right lungs, was significantly lower in patients with reduced cardiac index (<2.5 L/min per m(2)): 94±30 mL/100 mL per minute versus 132±40 mL/100 mL per minute in those with preserved cardiac index (≥2.5 L/min per m(2); P=0.003). The gravitational anterior to posterior perfusion gradient was inversely associated with left ventricular end-diastolic pressure (r=-0.728; P<0.001), resulting in a blunted perfusion gradient in patients with elevated left ventricular end-diastolic pressure, a finding largely attributed to the perfusion reduction in posterior lung regions. In a multivariate regression analysis adjusting for all hemodynamic variables, altered lung perfusion gradient was most closely associated with increased mean pulmonary arterial pressure (P=0.016). CONCLUSIONS: Increased left ventricular filling pressure and the resultant increase in pulmonary arterial pressure are associated with disruption of the normal gravitational lung perfusion gradient. Our findings underscore the complexity of heart-lung interaction in determining pulmonary hemodynamics in left heart failure.

Effects of respiratory cycle and body position on quantitative pulmonary perfusion by MRI.

PURPOSE: To evaluate the performance of lung perfusion imaging using two-dimensional (2D) first pass perfusion MRI and a quantitation program based on model-independent deconvolution algorithm. MATERIALS AND METHODS: In eight healthy volunteers 2D first pass lung perfusion was imaged in coronal planes using a partial Fourier saturation recovery stead state free precession (SSFP) technique with a temporal resolution of 160 ms per slice acquisition. The dynamic signal in the lung was measured over time and absolute perfusion calculated based on a model-independent deconvolution program. RESULTS: In the supine position mean pulmonary perfusion was 287 ± 106 mL/min/100 mL during held expiration. It was significantly reduced to 129 ± 68 mL/min/100 mL during held inspiration. Similar differences due to respiration were observed in prone position with lung perfusion much greater during expiration than during inspiration (271 ± 101 versus 99 ± 38 mL/min/100 mL (P < 0.01)). There was a linear increase in pulmonary perfusion from anterior to posterior lung fields in supine position. The perfusion gradient reversed in the prone position with the highest perfusion in anterior lung and the lowest in posterior lung fields. CONCLUSION: Lung perfusion imaging using a 2D saturation recovery SSFP perfusion MRI coupled with a model-independent deconvolution algorithm demonstrated physiologically consistent dynamic heterogeneity of lung perfusion distribution.

Left ventricular filling pressure assessment using left atrial transit time by cardiac magnetic resonance imaging.

BACKGROUND: Left atrial (LA) size and function reflect left ventricular (LV) hemodynamics. In the present study, we developed a novel method to determine LA circulation transit time (LATT) by MRI and demonstrated its close association with LV filling pressure. METHODS AND RESULTS: All subjects were prospectively recruited and underwent contrast-enhanced MR dynamic imaging. Mean LATT was determined as the time for contrast to transit through the LA during the first pass. In an invasive study group undergoing clinically indicated cardiac catheterization (n=25), LATT normalized by R-R interval (nLATT) was closely associated with LV early diastolic pressure (r=0.850, P=0.001), LV end-diastolic pressure (r=0.910, P<0.001), and mean diastolic pressure (r=0.912, P<0.001). In a larger noninvasive group (n=56), nLATT was prolonged in patients with LV systolic dysfunction (n=47) (10.1±3.0 versus 6.6±0.7 cardiac cycles in normal control subjects, n=9; P<0.001). Using a linear regression equation derived from the invasive group, noninvasive subjects were divided into 3 subgroups by estimated LV end-diastolic pressure: ≤10 mm Hg, 11 to 14 mm Hg, and ≥15 mm Hg. There were graded increases from low to high LV end-diastolic pressure subgroups in echocardiographic mitral medial E/e' ratio: 9±5, 11±4, and 13±3 (P=0.023); in B-type natriuretic peptide (interquartile range): 44 (60) pg/mL, 87 (359) pg/mL, and 371 (926) pg/mL (P=0.002); and in N-terminal pro-B-type natriuretic peptide: 57 (163) pg/mL, 208 (990) pg/mL, and 931 (1726) pg/mL (P=0.002), demonstrating the ability of nLATT to assess hemodynamic status. CONCLUSIONS: nLATT by cardiac MR is a promising new parameter of LV filling pressure that may provide graded noninvasive hemodynamic assessment.

Severe isolated aortic stenosis with normal left ventricular systolic function and low transvalvular gradients: pathophysiologic and prognostic insights.

BACKGROUND AND AIM OF THE STUDY: A significant proportion of patients with severe valvular aortic stenosis (AS) and preserved left ventricular (LV) systolic function have low transvalvular gradients. The study aim was to determine the mechanisms and outcome of patients with this hemodynamic profile of AS. METHODS: Among 1,679 patients who underwent transthoracic echocardiography for the evaluation of AS at the authors' institution, 215 (105 females, 110 males; mean age: 77 +/- 10 years) had isolated AS (mean aortic valve area index 0.39 +/- 0.1 cm2/m2), normal sinus rhythm and normal LV ejection fraction. The mean follow up was 23 +/- 12 months, and the end-points were mortality, aortic valve replacement (AVR), or mortality or AVR. RESULTS: Forty-seven patients had a transvalvular mean gradient (MG) <30 mmHg (MG(low)) and 168 had MG > or = 30 mmHg (MG(high)). Compared to MG(high), the MG(low) group had a higher prevalence of hypertension, lower LV end-diastolic volume index (47 +/- 9 versus 56 +/- 12 ml/m2, p <0.0001), lower LV stroke vol-ume index (37 +/- 12 versus 41 +/- 11 ml/beat, p <0.0002), a lesser severity of stenosis (aortic valve area index 0.37 +/- 0.09 versus 0.46 +/- 0.09 cm2/m2, p <0.0001) and a higher systemic vascular resistance (2163 +/- 754 versus 1879 +/- 528 dyne cm s(-5). The LV end-diastolic volume index, systemic vascular resistance and energy loss index were predictors of MG <30 mmHg (OR = 0.30, 95% CI, 0.12, 0.62; OR = 3.05, 95% CI, 1.71, 6.26; and OR = 6.76, 95% CI, 3.44,15.38, respectively). MG <30 mmHg (MGhigh) was associated with almost 50% lower referral to surgery and a two-fold increase in preoperative mortality. CONCLUSION: In severe AS with a normal LV ejection fraction, MG <30 mmHg is related to a lesser severity of stenosis, a smaller LV volume, a lower flow rate and a higher systemic vascular resistance. Compared to the MG(high) group, these patients were less frequently referred to surgery and had a higher mortality.

Mitral annular remodeling with varying degrees and mechanisms of chronic mitral regurgitation.

HYPOTHESES: Degree of mitral annular remodeling is directly associated with severity of chronic mitral regurgitation (MR). Mitral annular remodeling occurs in a symmetric fashion, regardless of MR severity. In addition to MR severity, MR mechanism plays a significant role in mitral annular remodeling. BACKGROUND: Limited data exists on mitral annular remodeling in patients with MR. Identification of annular changes may be important in aiding surgical repair. METHODS: Mitral annular dimensions (anteroposterior, intercommissural, surface area, and circumference) were measured in end systole and diastole using 3-dimensional reconstructive software in 83 patients: trace to no MR (23), mild MR (15), moderate MR (26), and severe MR (19). Annular sphericity indices were determined by dividing intercommissural by anteroposterior dimensions. Patients were further subgrouped by mechanism of MR. RESULTS: With increasing MR severity, there was a corresponding increase in all annular measurements, most pronounced in the anteroposterior dimension, circumference, and area. Larger increases were seen in patients with prolapse/flail and dilated mechanisms. Furthermore, the mitral annulus became more circular (sphericity index approached 1.0) with increasing MR severity. Patients with prolapse/flail mechanisms exhibited normal left ventricular volumes despite significant annular enlargement. CONCLUSIONS: Mitral annular remodeling is directly associated with MR severity and occurs in an asymmetric fashion, yet is not limited to one region of the annulus. Mechanism of MR plays a significant role in annular remodeling. Annular remodeling can occur independently of left ventricular remodeling.

Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the cause of the midsystolic drop (MSD) in left ventricular (LV) ejection velocities that are observed with hypertrophic cardiomyopathy (HCM) and severe obstruction. BACKGROUND: Dynamic obstruction is an important determinant of symptoms and adverse outcome. The MSD in velocity and flow occurs in patients with gradients >60 mm Hg. The nadir velocity in the LV occurs simultaneously with peak gradient. METHODS: We studied 36 patients with obstructive HCM and an MSD and compared them with 15 patients with HCM and no obstruction and with 25 age-matched normal control subjects. We measured LV ejection velocity proximal and distal to LV obstruction as well as tissue Doppler velocities and time intervals. RESULTS: The duration of contraction of both the septum and lateral wall is shorter in obstructed patients with the MSD than in nonobstructed HCM patients: septal contraction 203 +/- 68 ms vs. 271 +/- 41 ms (p < 0.001). Parallel reduction in the length of shortening was noted: 1.2 +/- 0.6 cm vs. 1.9 +/- 0.4 cm (p < 0.001). The ejection velocity nadir follows the septal and lateral peak velocities by 100 ms and 60 ms, respectively. The velocity nadir occurs as both walls rapidly decelerate to their premature termination: septal deceleration 79 +/- 35 cm/s2 vs. 48 +/- 21 cm/s2 (p < 0.001). With medical abolition of obstruction the MSD disappears and the duration and length of contraction normalizes. CONCLUSIONS: These data indicate that the MSD is caused by premature termination of LV segmental shortening and is a manifestation of systolic dysfunction.