BACKGROUND: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Recently, the HFpEF Stress Trial demonstrated feasibility and accuracy of non-invasive cardiovascular magnetic resonance (CMR) real-time (RT) exercise-stress atrial function imaging for early identification of HFpEF. However, no outcome data have yet been presented.
METHODS: The HFpEF Stress Trial (DZHK-17) prospectively recruited 75 patients with dyspnea on exertion and echocardiographic preserved EF and signs of diastolic dysfunction (E/e\' > 8). 68 patients entered the final study cohort and were characterized as HFpEF (n = 34) or non-cardiac dyspnea (n = 34) according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥ 15 mmHg stress: ≥ 25 mmHg). These patients were contacted by telephone and hospital charts were reviewed. The clinical endpoint was cardiovascular events (CVE).
RESULTS: Follow-up was performed after 48 months; 1 patient was lost to follow-up. HFpEF patients were more frequently compared to non-cardiac dyspnea (15 vs. 8, p = 0.059). Hospitalised patients during follow-up had higher H2FPEF scores (5 vs. 3, p < 0.001), and impaired left atrial (LA) function at rest (p ≤ 0.002) and stress (p ≤ 0.006). Impairment of CMR-derived atrial function parameters at rest and during exercise-stress (p ≤ 0.003) was associated with increased likelihood for CVE. CMR-Feature Tracking LA Es/Ee (p = 0.016/0.017) and RT-CMR derived LA long axis strain (p = 0.003) were predictors of CVE independent of the presence of atrial fibrillation.
CONCLUSIONS: Left atrial function emerged as the strongest predictor for 4-year outcome in the HFpEF Stress Trial. A combination of rest and exercise-stress LA function quantification allows accurate diagnostic and prognostic stratification in HFpEF.
RESULTS: gov: NCT03260621.

Background and Objectives: It would be important to know what happens to the volume and volume-based functional properties of one atrium if the size of the other atrium is larger or smaller than the average. Therefore, the present study aimed to perform three-dimensional speckle-tracking echocardiography (3DSTE)-derived quantification of left atrial (LA) and right atrial (RA) volumes and volume-based functional properties to examine these associations in healthy adults with mean and lower or higher than mean atrial volumes. Materials and Methods: The present study consisted of 179 healthy volunteers with a mean age of 32.3 ± 12.3 years (92 males). Three-dimensional speckle-tracking echocardiography-derived LA and RA volumes and volume-based functional properties were determined in all cases. Results: When different LA or RA volume groups were evaluated, both LA and RA showed the same pattern of volume changes in all phases of atrial function with higher LA or RA volumes. In case of low and mean LA volumes, RA volumes were higher compared to their LA counterpart. In case of mean and high RA volumes, RA volumes proved to be higher as well. In case of mean LA or RA volumes, differences between LA and RA stroke volumes (SVs) could not be detected, but all atrial emptying fractions (EFs) were lower for RA than for LA. Some differences were detected in counterpart LA/RA total, passive, and active atrial SVs and EFs values in the presence of lower/higher than mean LA/RA volume. Conclusions: In case of mean LA or RA volumes, RA volumes are higher compared to their LA counterpart, LA-SVs and RA-SVs are similar, but atrial EFs are lower for RA than for LA. If lower/higher than mean LA or RA volumes are present, some differences in patterns of changes in counterpart atrial volumes-SVs and EFs-could be detected.

In this study, we aimed to assess acute changes occurring on atrial function following single bouts of eccentric resistance exercise (ECC-RE) performed at two different loads. Twenty-five patients with chronic heart failure with middle range ejection fraction (HFmrEF) participated in three experimental sessions in a randomized order and on separate days: two sessions of ECC RE at 20% (ECC-20) of one-repetition maximum (1-RM) and 50% (ECC-50) 1-RM, and one session of control, without exercise. Each session lasted three minutes. Before and immediately after the sessions, patients underwent echocardiography and blood pressure and heart rate measurement. Peak atrial longitudinal strain (PALS) and peak atrial contractile strain (PACS) significantly increased after both ECC-20 (+16.3%) and ECC-50 (+18.1%) compared to control (between sessions p = 0.022). Peak atrial contractile strain (PACS) significantly increased after ECC-50 (+28.4%) compared to ECC-20 (+17.0%) and control (between sessions p = 0.034). The ratio of transmitral and annular velocities (E/E\') increased significantly after ECC-20 (+10.4%) and ECC-50 (+19.0%) compared to control (between groups p = 0.003). EF, left ventricular longitudinal strain, and stroke volume did not change after ECC-RE sessions compared to control. Cardiac output increased significantly after ECC-20 and ECC-50 compared to control, (between groups p = 0.025). In conclusion, both ECC-RE sessions were well tolerated, and LA functional reserve was properly mobilized in response to ECC-RE in patients with HFmrEF. Cardiac output increased at the cost of an increased LV filling pressure, but no detrimental changes of LV function occurred.

Left atrial (LA) size is often used as a surrogate marker of LA function in clinical practice, with larger atrial thought to represent a \"dysfunctioning\" atrium, since there is no accepted \'gold\' standard to evaluate LA function. The exact relationship between LA size and phasic function, and whether LA dysfunction occur before LA enlargement (LAE) may be of clinical interest while have not been fully studied. Two-dimensional speckle-tracking echocardiography (2D STE) was showed a promising method in measuring LA physical deformation.
A community cohort of 715 subjects at cardiovascular disease high risk accepted comprehensive echocardiography. LA longitudinal phasic strain Sa (absolute peak strain during atrial contraction), Se (peak strain at early diastole) and Stot (total atrial strain = Sa + Se), representing contractile, conduit, and reservoir function respectively, were measured using off-line 2D STE software in apical 4 chamber view, and data were compared among groups at different LA size and between subgroups in normal LA size with and without hypertension (HT).
With LAE (from normal size, mild, moderate to severe LAE), the Stot (21.74 ± 5.97, 20.75 ± 4.99, 20.49 ± 5.27, 17.75 ± 4.71, respectively, ANOVA P = 0.003) and Sa (11.84 ± 3.92, 11.00 ± 3.29, 10.11 ± 2.57, 8.55 ± 2.88, respectively, ANOVA P < 0.001) reduced while Se had no change. Stot of Severe LAE group was significantly lower than that of Normal LA size group (P = 0.002). Sa of the three LAE groups were all significantly lower than that of Normal LA size group (P = 0.024, P = 0.002, P < 0.001, respectively). In normal sized LA subgroups, Stot (21.35 ± 5.91 vs. 23.01 ± 6.02, P = 0.008) and Se (9.51 ± 4.41 vs. 11.17 ± 4.89, P < 0.001) reduced in subjects with HT comparing with those without.
LA phasic function remodeling occurs before LAE and continues with LAE, with reservoir, conduit and contractile function being affected unparalleled.

The role of the dysfunction of left atrium in the occurrence and development of cardiovascular disease has been gradually recognized. We aim to compare the impact on left atrial (LA) function between patients with hypertrophic cardiomyopathy (HCM) and hypertension (HTN) without LA enlargement using cardiovascular magnetic resonance feature tracking (CMR-FT), and if possible, explore the capability of LA function for providing clinical implication and predicting clinical adverse events in the early stage of cardiovascular disease.
Consecutive 60 HCM patients and 60 HTN patients with normal LA size among 1413 patients who underwent CMR were retrospectively analyzed as well as 60 controls. Left atrial and ventricular functions were quantified by volumetric and CMR-FT derived strain analysis from long and short left ventricular view cines. The primary endpoint was a composite of all-cause death, stroke, new-onset or worsening heart failure to hospitalization, and paroxysmal or persistent atrial fibrillation.
Compared to the controls, both HTN and HCM participants had impaired LA reservoir function (εs) and conduit function (εe) with the different stage of LA booster pump dysfunction (εa). LA strain was more sensitive than LV longitudinal strain (GLS) for evaluate primary endpoint (εs: 33.9% ± 7.5 vs. 41.2% ± 14.3, p = 0.02; εe: 13.6% ± 6.2 vs. 17.4% ± 10.4, p = 0.03; εa: 20.2% ± 6.0 vs. 23.7% ± 8.8, p = 0.07; GLS: -19.4% ± 6.4 vs. -20.0% ± 6.8, p = 0.70, respectively). After a mean follow-up of 6.8 years, 23 patients reached primary endpoint. Cox regression analyses indicated impaired LA reservoir and booster pump strain were associated with clinical outcomes in patients at the early stage of HTN and HCM (p < 0.05).
CMR-FT-derived strain is a potential and robust tool in demonstrating impaired LA mechanics, quantifying LA dynamics and underlining the impacts on LA-LV coupling in patients with HTN and HCM without LA enlargement. The corresponding LA dysfunction is a promising metric to assess clinical implication and predict prognosis at the early stage, superior to GLS.

Standard apical four-chamber and two-chamber views often maximize the long-axis of the left ventricle, resulting in artifactitious foreshortening of the left atrium (LA), which may overestimate LA longitudinal reservoir strain (LALS). We compared LALS values between 2D echocardiography (2DE) and 3D echocardiography (3DE) in healthy subjects to determine whether 2DE speckle tracking analysis overestimates the reference value of LALS.
In this study, 4 types of cohorts were included: 1. 105 normal subjects (retrospectively), 2. 53 patients with cardiovascular diseases (retrospectively), 3. 15 patients who received cardiac magnetic resonance (prospectively), and 4. 20 normal subjects (prospectively). LALS and LA length were measured using both 2DE and 3DE in 105 healthy subjects (median age: 42 years). Biplane LALS was measured in apical four- and two-chamber views using 2DE speckle tracking software, and 3DE LALS was measured using new 3DE LA strain software. To determine sensitivity, we also performed the same analysis in 53 patients with cardiovascular disease. The mean value of biplane LALS was 39.6%. LA length at both end-diastole (r = -0.43) and end-systole (r = -0.54) was negatively correlated with biplane LALS. Multivariate regression analysis revealed that both end-diastolic and end-systolic LA length had significant negative relationships with biplane LALS after adjusting for anthropometric and echocardiographic image quality parameters. 3DE LALS (23.7±7.6%) gave significantly lower values than 2DE LALS (39.5±12.0%, p<0.001) with a weak correlation (r = 0.33). LA length measured by 2DE was significantly shorter than that measured by 3DE. The same trend was observed in diseased patients.
Our results revealed that in 2DE, the LA cavity consistently appears longitudinally foreshortened in apical views, potentially overestimating LALS. 3DE may overcome this limitation.

BACKGROUND: Right heart catheterization using exercise stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiac magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary noninvasive alternative for diagnosing HFpEF.
METHODS: The HFpEF-Stress trial (CMR Exercise Stress Testing in HFpEF; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621. URL: https://dzhk.de/; Unique identifier: DZHK-17) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e\'>8, New York Heart Association class ≥II) to undergo echocardiography, right heart catheterization, and RT-CMR at rest and during exercise stress. HFpEF was defined according to pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during exercise stress). RT-CMR functional assessments included time-volume curves for total and early (1/3) diastolic left ventricular filling, left atrial (LA) emptying, and left ventricular/LA long axis strain.
RESULTS: Patients with HFpEF (n=34; median pulmonary capillary wedge pressure at rest, 13 mm Hg; at stress, 27 mm Hg) had higher E/e\' (12.5 versus 9.15), NT-proBNP (N-terminal pro-B-type natriuretic peptide; 255 versus 75 ng/L), and LA volume index (43.8 versus 36.2 mL/m2) compared with patients with noncardiac dyspnea (n=34; rest, 8 mm Hg; stress, 18 mm Hg; P≤0.001 for all). Seven patients were excluded because of the presence of non-HFpEF cardiac disease causing dyspnea on imaging. There were no differences in RT-CMR left ventricular total and early diastolic filling at rest and during exercise stress (P≥0.164) between patients with HFpEF and noncardiac dyspnea. RT-CMR revealed significantly impaired LA total and early (P<0.001) diastolic emptying in patients with HFpEF during exercise stress. RT-CMR exercise stress LA long axis strain was independently associated with HFpEF (adjusted odds ratio, 0.657 [95% CI, 0.516-0.838]; P=0.001) after adjustment for clinical and imaging measures and emerged as the best predictor for HFpEF (area under the curve at rest 0.82 versus exercise stress 0.93; P=0.029).
CONCLUSIONS: RT-CMR allows highly accurate identification of HFpEF during physiologic exercise and qualifies as a suitable noninvasive diagnostic alternative. These results will need to be confirmed in multicenter prospective research studies to establish widespread routine clinical use. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621. URL: https://dzhk.de/; Unique identifier: DZHK-17.

The effects of atrial fibrillation (AF) catheter ablation on the left atrium (LA) are poorly understood.
To examine short- and long-term associations of AF catheter ablation with LA function using cardiac magnetic resonance (CMR).
Fifty-one AF patients (mean age 56 ± 8 years) underwent CMR at baseline, 1 day (n = 17) and 11 ± 2 months after ablation (n = 38). LA phasic volumes, emptying fractions (LAEF), and longitudinal strain were measured using feature-tracking CMR. LA fibrosis was quantified using late gadolinium enhancement (LGE).
There were no acute changes in volume; however, active, total LAEF, and peak LA strain decreased significantly compared to the baseline. During long-term follow-up, there was a decrease in maximum but not minimum LA volume (from 99 ± 5.2 ml to 89 ± 4.7 ml; p = .009) and a decrease in total LAEF (from 43 ± 1.8% to 39 ± 2.0%; p = .001). In patients with AF recurrence, LA volumes were unchanged. However, total LAEF decreased from 38 ± 3% to 33 ± 3%; p = .015. Patients without AF recurrence had no changes in LA functional parameters during follow-up. The amount of LA LGE at long-term follow-up was higher compared to the baseline, however, was significantly less compared to immediately post-procedure (37 ± 1.9% vs. 47 ± 2.8%; p = .015). A higher increase in LA LGE extent compared to the baseline was associated with a greater decrease in total LAEF (r = -.59; p < .001).
LA function is impaired acutely following AF catheter ablation. However, long-term changes of LA function are associated positively with the successful restoration of sinus rhythm and inversely with increased LA LGE.

OBJECTIVE: Smoking is a well-known risk factor for coronary artery diseases. It is also associated with nicotine-induced myocardial dysfunction. The aim of this study was to evaluate the right and left atrial and ventricular functions in apparently healthy smokers.
METHODS: We included consecutively 80 healthy smokers (56 males, mean age:35.5 ± 8.4 years) and 70 healthy nonsmokers (44 males, mean age:33.9 ± 9.5 years). None of the subjects had any additional cardiovascular risk factor other than smoking. The right and left atrial and ventricular functions were assessed by both conventional and speckle tracking echocardiography.
RESULTS: Although there was no significant difference in left ventricular ejection fraction, the smokers had significantly lower ventricular global longitudinal strain than controls (-19.9 ± 2.0% vs -21.2 ± 1.9%, P < .001 and -18.4 ± 2.1% vs -21.8 ± 2.2%, P < .001, respectively, for the left and right ventricle). Smokers had also lower atrial reservoir and conduit strains: 35.9 ± 11.1% vs 40.2 ± 11.2%, P = .022 and 16.7 ± 6.8% vs 19.4 ± 6.8%, P = .016, respectively, for the left atrium, and 33.0 ± 10.6% vs 37.6 ± 11.2%, P = .011 and 15.2 ± 5.6% vs 18.0 ± 6.3%, P = .004, respectively, for the right atrium).
CONCLUSIONS: Even in apparently healthy people with no other cardiovascular risk factors, smoking is associated with impaired atrial and ventricular functions.

In healthy adults, the right atrium (RA) serves as a reservoir for the systemic flow return from the superior vena cava (SVC) and inferior vena cava (IVC), preparing the two flows to be transferred to the right ventricle (RV) and pulmonary circulation. This study aims to quantify the haemodynamics of the RA and the associated SVC and IVC inflows, which have not been fully understood to date.
Eighteen adults with structurally normal hearts underwent 4D flow magnetic resonance imaging. The cardiac cycle was resolved to 20 temporal phases with a spatial resolution of 3 × 3 × 3 mm3. Analysis included objective visualisation of the flow structures in the RA identified by three different vortex identification criteria, kinetic energy (KE), enstrophy and dissipation. KE and helicity flux were also assessed in both caval veins.
Vortex identification methods confirmed that in the majority of participants the blood flow from the caval veins filling the RA during ventricular systole is not chaotic, but rather forms an organised pattern of a single coherent forward turning vortex structure. Thirteen participants displayed a single vortex flow structure, four showed multiple vortices and one had a helical flow pattern without a clear vortex structure. A strong positive correlation exists between the flow KE and enstrophy density.
This suggests that flow energy in the RA is mainly rotational, part of which is convected by the highly helical SVC and IVC inflows. Multiple vortices tend to be associated with higher dissipation rates in the central RA region due to turbulence. The rotational nature of the flow in the RA maintains KE better than non-rotational flow. RA flow characteristics are highly related to the helicity content in the caval veins, as well as the KE flux intensity. Lower caval helicity or IVC KE flux dominance tends to favour single vortex formation while the opposite tends to lead to multiple vortices or the rare helical flow patterns. Atria lacking single vortex flow are inclined to have a larger energy input from atrial contraction.