Left Atrial Roof Enlargement Is a Distinct Feature of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: It remains unknown to what extent intrinsic atrial cardiomyopathy or left ventricular diastolic dysfunction drive atrial remodeling and functional failure in heart failure with preserved ejection fraction (HFpEF). Computational 3-dimensional (3D) models fitted to cardiovascular magnetic resonance allow state-of-the-art anatomic and functional assessment, and we hypothesized to identify a phenotype linked to HFpEF. METHODS: Patients with exertional dyspnea and diastolic dysfunction on echocardiography (E/e', >8) were prospectively recruited and classified as HFpEF or noncardiac dyspnea based on right heart catheterization. All patients underwent rest and exercise-stress right heart catheterization and cardiovascular magnetic resonance. Computational 3D anatomic left atrial (LA) models were generated based on short-axis cine sequences. A fully automated pipeline was developed to segment cardiovascular magnetic resonance images and build 3D statistical models of LA shape and find the 3D patterns discriminant between HFpEF and noncardiac dyspnea. In addition, atrial morphology and function were quantified by conventional volumetric analyses and deformation imaging. A clinical follow-up was conducted after 24 months for the evaluation of cardiovascular hospitalization. RESULTS: Beyond atrial size, the 3D LA models revealed roof dilation as the main feature found in masked HFpEF (diagnosed during exercise-stress only) preceding a pattern shift to overall atrial size in overt HFpEF (diagnosed at rest). Characteristics of the 3D model were integrated into the LA HFpEF shape score, a biomarker to characterize the gradual remodeling between noncardiac dyspnea and HFpEF. The LA HFpEF shape score was able to discriminate HFpEF (n=34) to noncardiac dyspnea (n=34; area under the curve, 0.81) and was associated with a risk for atrial fibrillation occurrence (hazard ratio, 1.02 [95% CI, 1.01-1.04]; P=0.003), as well as cardiovascular hospitalization (hazard ratio, 1.02 [95% CI, 1.00-1.04]; P=0.043). CONCLUSIONS: LA roof dilation is an early remodeling pattern in masked HFpEF advancing to overall LA enlargement in overt HFpEF. These distinct features predict the occurrence of atrial fibrillation and cardiovascular hospitalization. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621.

Reduced dynamic changes in pulmonary artery compliance during isometric handgrip exercise in patients with heart failure.

Exercise intolerance is a debilitating symptom in heart failure (HF), adversely affecting both quality of life and long-term prognosis. Emerging evidence suggests that pulmonary artery (PA) compliance may be a contributing factor. This study aims to non-invasively assess PA compliance and its dynamic properties during isometric handgrip (HG) exercise in HF patients and healthy controls, using cardiovascular magnetic resonance (CMR). We prospectively enrolled 36 subjects, comprising 17 HF patients (NYHA class II and III) and 19 healthy controls. Participants performed an HG test, and we assessed changes in PA compliance and hemodynamic flow parameters using advanced CMR techniques. We also explored the relationship between CMR-derived PA compliance metrics and established clinical indicators, ensuring the validity of our findings through intra- and interobserver agreements. HF patients had significantly lower resting PA compliance compared to controls (28.9% vs. 50.1%, p < 0.01). During HG exercise, HF patients exhibited a dampened adaptability in PA compliance. Hemodynamic responses, including heart rate and blood pressure, were not significantly different between the groups. Further analyses revealed a significant correlation between changes in PA compliance and functional capacity, and an inverse relationship with NYHA class. Our study demonstrates a marked difference in PA vascular responses during HG exercise between HF patients and healthy controls. The compromised adaptability in PA compliance in HF patients is correlated with diminished functional capacity. These findings have significant clinical implications and may guide future interventional strategies in HF management.

Cardiac fibrosis as a predictor for sudden cardiac death after transcatheter aortic valve implantation.

BACKGROUND: Cardiac fibrosis plays a major pathophysiological role in any form of chronic heart disease, and high levels are associated with poor outcome. Diffuse and focal cardiac fibrosis are different subtypes, which have different pathomechanisms and prognostic implications. The total fibrosis burden in endomyocardial biopsy tissue was recently proved to play an independent prognostic role in aortic stenosis patients after transcatheter aortic valve implantation (TAVI). AIMS: Here, for the first time, we aim to assess the specific impact of different fibrosis subtypes on sudden cardiac death (SCD) as a primary reason for cardiovascular mortality after TAVI. METHODS: The fibrosis pattern was assessed histologically in the left ventricular biopsies obtained during TAVI interventions in 161 patients, who received a structured follow-up thereafter. RESULTS: Receiver operating characteristic analyses, performed 6, 12, 24 and 48 months after TAVI, showed diffuse, but not focal, fibrosis as a significant predictor for SCD at all timepoints, with the highest area under the curve at the first time point and a decrease in its SCD predictivity over time. In both multivariate Cox proportional hazards and Fine-Gray competing risk models, including both fibrosis subtypes, as well as age, sex and ejection fraction, high diffuse fibrosis remained statistically significant. Accordingly, it represents an independent SCD predictor, most importantly for the occurrence of early events. CONCLUSIONS: The burden of diffuse cardiac fibrosis plays an important and independent prognostic role regarding SCD early after TAVI. Therefore, the histological evaluation of fibrosis topography has value as a prognostic tool for TAVI patients and may help to tailor individualised approaches to optimise their postinterventional management.

CMR-based cardiac phenotyping in different forms of heart failure.

Heart failure (HF) is a heterogenous disease requiring precise diagnostics and knowledge of pathophysiological processes. Since structural and functional imaging data are scarce we hypothesized that cardiac magnetic resonance (CMR)-based analyses would provide accurate characterization and mechanistic insights into different HF groups comprising preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF). 22 HFpEF, 17 HFmrEF and 15 HFrEF patients as well as 19 healthy volunteers were included. CMR image assessment contained left atrial (LA) and left ventricular (LV) volumetric evaluation as well as left atrioventricular coupling index (LACI). Furthermore, CMR feature-tracking included LV and LA strain in terms of reservoir (Es), conduit (Ee) and active boosterpump (Ea) function. CMR-based tissue characterization comprised T1 mapping as well as late-gadolinium enhancement (LGE) analyses. HFpEF patients showed predominant atrial impairment (Es 20.8%vs.25.4%, p = 0.02 and Ee 8.3%vs.13.5%, p = 0.001) and increased LACI compared to healthy controls (14.5%vs.23.3%, p = 0.004). Patients with HFmrEF showed LV enlargement but mostly preserved LA function with a compensatory increase in LA boosterpump (LA Ea: 15.0%, p = 0.049). In HFrEF LA and LV functional impairment was documented (Es: 14.2%, Ee: 5.4% p < 0.001 respectively; Ea: 8.8%, p = 0.02). This was paralleled by non-invasively assessed progressive fibrosis (T1 mapping and LGE; HFrEF > HFmrEF > HFpEF). CMR-imaging reveals insights into HF phenotypes with mainly atrial affection in HFpEF, ventricular affection with atrial compensation in HFmrEF and global impairment in HFrEF paralleled by progressive LV fibrosis. These data suggest a necessity for a personalized HF management based on imaging findings for future optimized patient management.

Comprehensive characterization of cardiac contraction for improved post-infarction risk assessment.

This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P < 0.001). The combination of these 3 directions of enhancement towards a final CMR risk model improved MACE prediction by 13% compared to clinical baseline (0.774 (0.771-0.777) vs. 0.683 (0.681-0.685) cross-validated AUC, P < 0.001). The study evidences the contribution of the novel contraction characterization, enabled by a fully automated pipeline, to post-infarction assessment.

Rest and exercise-stress estimated pulmonary capillary wedge pressure using real-time free-breathing cardiovascular magnetic resonance imaging.

BACKGROUND: Identification of increased pulmonary capillary wedge pressure (PCWP) by right heart catheterization (RHC) is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF). Recently, cardiovascular magnetic resonance (CMR) imaging estimation of PCWP at rest was introduced as a non-invasive alternative. Since many patients are only identified during physiological exercise-stress, we hypothesized that novel exercise-stress CMR-derived PCWP emerges superior compared to its assessment at rest. METHODS: The HFpEF-Stress Trial prospectively recruited 75 patients with exertional dyspnea and diastolic dysfunction who then underwent rest and exercise-stress RHC and CMR. HFpEF was defined according to PCWP (overt HFpEF ≥15 mmHg at rest, masked HFpEF ≥25 mmHg during exercise-stress). CMR-derived PCWP was calculated based on previously published formula using left ventricular mass and either biplane left atrial volume (LAV) or monoplane left atrial area (LAA). RESULTS: LAV (rest/stress: r = 0.50/r = 0.55, p < 0.001) and LAA PCWP (rest/stress: r = 0.50/r = 0.48, p < 0.001) correlated significantly with RHC-derived PCWP while numerically overestimating PCWP at rest and underestimating PCWP during exercise-stress. LAV and LAA PCWP showed good diagnostic accuracy to detect HFpEF (area under the receiver operating characteristic curve (AUC) LAV rest 0.73, stress 0.81; LAA rest 0.72, stress 0.77) with incremental diagnostic value for the detection of masked HFpEF using exercise-stress (AUC LAV rest 0.54 vs stress 0.67, p = 0.019, LAA rest 0.52 vs stress 0.66, p = 0.012). LAV but not LAA PCWP during exercise-stress was a predictor for 24 months hospitalization independent of a medical history for atrial fibrillation (hazard ratio (HR) 1.26, 95% confidence interval 1.02-1.55, p = 0.032). CONCLUSION: Non-invasive PCWP correlates well with the invasive reference at rest and during exercise stress. There is overall good diagnostic accuracy for HFpEF assessment using CMR-derived estimated PCWP despite deviations in absolute agreement. Non-invasive exercise derived PCWP may particularly facilitate detection of masked HFpEF in the future.

Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF stress trial.

BACKGROUND: With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests. METHODS: The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e' > 8) who underwent simultaneous rest and exercise-stress echocardiography and right heart catheterisation (RHC). HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15 mmHg stress: ≥25 mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e'). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH). RESULTS: The final study population included 68 patients (HFpEF n = 34 and NCD n = 34) of which 23 reached the clinical endpoint, 1 patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p < 0.001) compared to patients with a score ≤ 4. LA compliance at rest outperformed E/e' (AUC 0.78 vs 0.87, p = 0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p = 0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p < 0.001) irrespective of concomitant atrial fibrillation. CONCLUSIONS: LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.

Impact of epicardial adipose tissue on cardiac function and morphology in patients with diastolic dysfunction.

AIMS: This study aimed to identify the impact of increased epicardial adipose tissue (EAT) and its regional distribution on cardiac function in patients with diastolic dysfunction. METHODS AND RESULTS: Sixty-eight patients with exertional dyspnoea (New York Heart Association ≥II), preserved ejection fraction (≥50%), and diastolic dysfunction (E/e' ≥ 8) underwent rest and stress right heart catheterization, transthoracic echocardiography, and cardiovascular magnetic resonance (CMR). EAT volumes were depicted from CMR short-axis stacks. First, the impact of increased EAT above the median was investigated. Second, the association of ventricular and atrial EAT with myocardial deformation at rest and during exercise stress was analysed in a multivariable regression analysis. Patients with high EAT had higher HFA-PEFF and H2FPEFF scores as well as N-terminal prohormone of brain natriuretic peptide levels (all P < 0.048). They were diagnosed with manifest heart failure with preserved ejection fraction (HFpEF) more frequently (low EAT: 37% vs. high EAT: 64%; P = 0.029) and had signs of adverse remodelling indicated by higher T1 times (P < 0.001). No differences in biventricular volumetry and left ventricular mass (all P > 0.074) were observed. Patients with high EAT had impaired atrial strain at rest and during exercise stress, and impaired ventricular strain during exercise stress. Regionally increased EAT was independently associated with functional impairment of the adjacent chambers. CONCLUSIONS: Patients with diastolic dysfunction and increased EAT show more pronounced signs of diastolic functional failure and adverse structural remodelling. Despite similar morphological characteristics, patients with high EAT show significant cardiac functional impairment, in particular in the atria. Our results indicate that regionally increased EAT directly induces atrial functional failure, which represents a distinct pathophysiological feature in HFpEF.

Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

BACKGROUND: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. METHODS AND RESULTS: Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse-wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. CONCLUSIONS: This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.

Epicardial adipose tissue as an independent predictor of long-term outcome in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Accurate risk stratification is important to improve patient selection and outcome of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). As epicardial adipose tissue (EAT) is discussed to be involved in cardiovascular disease, it could be useful as a marker of poor prognosis in patients with severe AS undergoing TAVR. METHODS: A total of 416 patients diagnosed with severe AS by transthoracic echocardiography were assigned for TAVR and enrolled for systematic assessment. Patients underwent clinical surveys and 5-year long-term follow-up, with all-cause mortality as the primary endpoint. EAT volume was quantified on pre-TAVR planning CTs. Patients were retrospectively dichotomized at the median of 74 cm3 of EAT into groups with low EAT and high EAT volumes. Mortality rates were compared using Kaplan-Meyer plots and uni- and multivariable cox regression analyses. RESULTS: A total number of 341 of 416 patients (median age 80.9 years, 45% female) were included in the final analysis. Patients with high EAT volumes had similar short-term outcome (p = 0.794) but significantly worse long-term prognosis (p = 0.023) compared to patients with low EAT volumes. Increased EAT volumes were associated with worse long-term outcome (HR1.59; p = 0.031) independently from concomitant cardiovascular risk factors, general type of AS, and functional echocardiography parameters of AS severity (HR1.69; p = 0.013). CONCLUSION: Increased EAT volume is an independent predictor of all-cause mortality in patients with severe AS undergoing TAVR. It can be easily obtained from pre-TAVR planning CTs and may thus qualify as a novel marker to improve prognostication and management of patient with severe AS. TRIAL REGISTRATION: DRKS, DRKS00024479.

Assessment of the cardiac output at rest and during exercise stress using real-time cardiovascular magnetic resonance imaging in HFpEF-patients.

This methodological study aimed to validate the cardiac output (CO) measured by exercise-stress real-time phase-contrast cardiovascular magnetic resonance imaging (CMR) in patients with heart failure and preserved ejection fraction (HFpEF). 68 patients with dyspnea on exertion (NYHA ≥ II) and echocardiographic signs of diastolic dysfunction underwent rest and exercise stress right heart catheterization (RHC) and CMR within 24 h. Patients were diagnosed as overt HFpEF (pulmonary capillary wedge pressure (PCWP) ≥ 15mmHg at rest), masked HFpEF (PCWP ≥ 25mmHg during exercise stress but < 15mmHg at rest) and non-cardiac dyspnea. CO was calculated using RHC as the reference standard, and in CMR by the volumetric stroke volume, conventional phase-contrast and rest and stress real-time phase-contrast imaging. At rest, the CMR based CO showed good agreement with RHC with an ICC of 0.772 for conventional phase-contrast, and 0.872 for real-time phase-contrast measurements. During exercise stress, the agreement of real-time CMR and RHC was good with an ICC of 0.805. Real-time measurements underestimated the CO at rest (Bias:0.71 L/min) and during exercise stress (Bias:1.4 L/min). Patients with overt HFpEF had a significantly lower cardiac index compared to patients with masked HFpEF and with non-cardiac dyspnea during exercise stress, but not at rest. Real-time phase-contrast CO can be assessed with good agreement with the invasive reference standard at rest and during exercise stress. While moderate underestimation of the CO needs to be considered with non-invasive testing, the CO using real-time CMR provides useful clinical information and could help to avoid unnecessary invasive procedures in HFpEF patients.

Real-time cardiovascular magnetic resonance imaging for non-invasive characterisation of heart failure with preserved ejection fraction: final outcomes of the HFpEF stress trial.

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. CLINICALTRIALS: gov: NCT03260621.

Low-flow in aortic valve stenosis patients with reduced ejection fraction does not depend on left ventricular function.

BACKGROUND: Patients with severe aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF) can be distinguished into high- (HG) and low-gradient (LG) subgroups. However, less is known about their characteristics and underlying (pathophysiological) hemodynamic mechanisms. METHODS: 98 AS patients with reduced LVEF were included. Subgroup characteristics were analyzed by a multimodal approach using clinical and histological data, next-generation sequencing (NGS) and applying echocardiography as well as cardiovascular magnetic resonance (CMR) imaging. Biopsy samples were analyzed with respect to fibrosis and mRNA expression profiles. RESULTS: 40 patients were classified as HG-AS and 58 patients as LG-AS. Severity of AS was comparable between the subgroups. Comparison of both subgroups revealed no differences in LVEF (p = 0.1), LV mass (p = 0.6) or end-diastolic LV diameter (p = 0.12). Neither histological (HG: 23.2% vs. LG: 25.6%, p = 0.73) and circulating biomarker-based assessment (HG: 2.6 ± 2.2% vs. LG: 3.2 ± 3.1%; p = 0.46) of myocardial fibrosis nor global gene expression patterns differed between subgroups. Mitral regurgitation (MR), atrial fibrillation (AF) and impaired right ventricular function (MR: HG: 8% vs. LG: 24%; p < 0.001; AF: HG: 30% vs. LG: 51.7%; p = 0.03; RVSVi: HG 36.7 vs. LG 31.1 ml/m2, p = 0.045; TAPSE: HG 20.2 vs. LG 17.3 mm, p = 0.002) were more frequent in LG-AS patients compared to HG-AS. These pathologies could explain the higher mortality of LG vs. HG-AS patients. CONCLUSION: In patients with low-flow severe aortic stenosis, low transaortic gradient and cardiac output are not primarily due to LV dysfunction or global changes in gene expression, but may be attributed to other additional cardiac pathologies like mitral regurgitation, atrial fibrillation or right ventricular dysfunction. These factors should also be considered during planning of aortic valve replacement.

Inter-study reproducibility of cardiovascular magnetic resonance-derived hemodynamic force assessments.

Cardiovascular magnetic resonance (CMR)-derived hemodynamic force (HDF) analyses have been introduced recently enabling more in-depth cardiac function evaluation. Inter-study reproducibility is important for a widespread clinical use but has not been quantified for this novel CMR post-processing tool yet. Serial CMR imaging was performed in 11 healthy participants in a median interval of 63 days (range 49-87). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, diastolic deceleration as well as atrial thrust acceleration forces. Inter-study reproducibility and study sample sizes required to demonstrate 10%, 15% or 20% relative changes of HDF measurements were calculated. In addition, intra- and inter-observer analyses were performed. Intra- and inter-observer reproducibility was excellent for all HDF parameters according to intraclass correlation coefficient (ICC) values (> 0.80 for all). Inter-study reproducibility of all HDF parameters was excellent (ICC ≥ 0.80 for all) with systolic parameters showing lower coeffients of variation (CoV) than diastolic measurements (CoV 15.2% for systolic impulse vs. CoV 30.9% for atrial thrust). Calculated sample sizes to detect relative changes ranged from n = 12 for the detection of a 20% relative change in systolic impulse to n = 200 for the detection of 10% relative change in atrial thrust. Overall inter-study reproducibility of CMR-derived HDF assessments was sufficient with systolic HDF measurements showing lower inter-study variation than diastolic HDF analyses.

Impact of temporal and spatial resolution on atrial feature tracking cardiovascular magnetic resonance imaging.

BACKGROUND: Myocardial deformation assessment by cardiovascular magnetic resonance-feature tracking (CMR-FT) has incremental prognostic value over volumetric analyses. Recently, atrial functional analyses have come to the fore. However, to date recommendations for optimal resolution parameters for accurate atrial functional analyses are still lacking. METHODS: CMR-FT was performed in 12 healthy volunteers and 9 ischemic heart failure (HF) patients. Cine sequences were acquired using different temporal (20, 30, 40 and 50 frames/cardiac cycle) and spatial resolution parameters (high 1.5 × 1.5 mm in plane and 5 mm slice thickness, standard 1.8 × 1.8 × 8 mm and low 3.0 × 3.0 × 10 mm). Inter- and intra-observer reproducibility were calculated. RESULTS: Increasing temporal resolution is associated with higher absolute strain and strain rate (SR) values. Significant changes in strain assessment for left atrial (LA) total strain occurred between 20 and 30 frames/cycle amounting to 2,5-4,4% in absolute changes depending on spatial resolution settings. From 30 frames/cycle onward, absolute strain values remained unchanged. Significant changes of LA strain rate assessment were observed up to the highest temporal resolution of 50 frames/cycle. Effects of spatial resolution on strain assessment were smaller. For LA total strain a general trend emerged for a mild decrease in strain values obtained comparing the lowest to the highest spatial resolution at temporal resolutions of 20, 40 and 50 frames/cycle (p = 0.006-0.046) but not at 30 frames/cycle (p = 0.140). CONCLUSION: Temporal and to a smaller extent spatial resolution affect atrial functional assessment. Consistent strain assessment requires a standard spatial resolution and a temporal resolution of 30 frames/cycle, whilst SR assessment requires even higher settings of at least 50 frames/cycle.

Noninvasive evaluation of pulmonary artery stiffness in heart failure patients via cardiovascular magnetic resonance.

Heart failure (HF) presents manifestations in both cardiac and vascular abnormalities. Pulmonary hypertension (PH) is prevalent in up 50% of HF patients. While pulmonary arterial hypertension (PAH) is closely associated with pulmonary artery (PA) stiffness, the association of HF caused, post-capillary PH and PA stiffness is unknown. We aimed to assess and compare PA stiffness and blood flow hemodynamics noninvasively across HF entities and control subjects without HF using CMR. We analyzed data of a prospectively conducted study with 74 adults, including 55 patients with HF across the spectrum (20 HF with preserved ejection fraction [HFpEF], 18 HF with mildly-reduced ejection fraction [HFmrEF] and 17 HF with reduced ejection fraction [HFrEF]) as well as 19 control subjects without HF. PA stiffness was defined as reduced vascular compliance, indicated primarily by the relative area change (RAC), altered flow hemodynamics were detected by increased flow velocities, mainly by pulse wave velocity (PWV). Correlations between the variables were explored using correlation and linear regression analysis. PA stiffness was significantly increased in HF patients compared to controls (RAC 30.92 ± 8.47 vs. 50.08 ± 9.08%, p < 0.001). PA blood flow parameters were significantly altered in HF patients (PWV 3.03 ± 0.53 vs. 2.11 ± 0.48, p < 0.001). These results were consistent in all three HF groups (HFrEF, HFmrEF and HFpEF) compared to the control group. Furthermore, PA stiffness was associated with higher NT-proBNP levels and a reduced functional status. PA stiffness can be assessed non-invasively by CMR. PA stiffness is increased in HFrEF, HFmrEF and HFpEF patients when compared to control subjects.Trial registration The study was registered at the German Clinical Trials Register (DRKS, registration number: DRKS00015615).

Predictors of lower exercise capacity in patients with cancer.

Maintaining cancer patients' exercise capacity and therefore patients' ability to live a self-determined life is of huge importance, but little is known about major determinants. We sought to identify determinants of exercise capacity in patients with a broad spectrum of cancer types, who were already receiving cancer treatment or about to commence such therapy. Exercise capacity was assessed in 253 consecutive patients mostly suffering from advanced cancer using the 6-min walk test (6-MWT). All patients underwent echocardiography, physical examination, resting electrocardiogram, hand grip strength (HGS) measurement, and laboratory assessments. Patients were divided into two groups according to the median distance in the 6-MWT (459 m). Patients with lower exercise capacity were older, had significantly lower HGS and haemoglobin and higher values of high sensitive (hs) Troponin T and NT-proBNP (all p < 0.05). Whilst the co-morbidity burden was significantly higher in this group, no differences were detected for sex, body mass index, tumor type, or cachexia (all p > 0.2). Using multivariable logistic regression, we found that the presence of anaemia (odds ratio (OR) 6.172, 95% confidence interval (CI) 1.401-27.201, p = 0.016) as well as an increase in hs Troponin T (OR 3.077, 95% CI 1.202-5.301, p = 0.019) remained independent predictors of impaired exercise capacity. Increasing HGS was associated with a reduced risk of a lower exercise capacity (OR 0.896, 95% CI 0.813-0.987, p = 0.026). Screening patients for elevated hs troponin levels as well as reduced HGS may help to identify patients at risk of lower exercise capacity during cancer treatment.

Impact of myocardial deformation on risk prediction in patients following acute myocardial infarction.

Background: Strain analyses derived from cardiovascular magnetic resonance-feature tracking (CMR-FT) provide incremental prognostic benefit in patients sufferring from acute myocardial infarction (AMI). This study aims to evaluate and revalidate previously reported prognostic implications of comprehensive strain analyses in a large independent cohort of patients with ST-elevation myocardial infarction (STEMI). Methods: Overall, 566 STEMI patients enrolled in the CONDITIONING-LIPSIA trial including pre- and/or postconditioning treatment in addition to conventional percutaneous coronary intervention underwent CMR imaging in median 3 days after primary percutaneous coronary intervention. CMR-based left atrial (LA) reservoir (Es), conduit (Ee), and boosterpump (Ea) strain analyses, as well as left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) analyses were carried out. Previously identified cutoff values were revalidated for risk stratification. Major adverse cardiac events (MACE) comprising death, reinfarction, and new congestive heart failure were assessed within 12 months after the occurrence of the index event. Results: Both atrial and ventricular strain values were significantly reduced in patients with MACE (p < 0.01 for all). Predetermined LA and LV strain cutoffs enabled accurate risk assessment. All LA and LV strain values were associated with MACE on univariable regression modeling (p < 0.001 for all), with LA Es emerging as an independent predictor of MACE on multivariable regression modeling (HR 0.92, p = 0.033). Furthermore, LA Es provided an incremental prognostic value above LVEF (a c-index increase from 0.7 to 0.74, p = 0.03). Conclusion: External validation of CMR-FT-derived LA and LV strain evaluations confirmed the prognostic value of cardiac deformation assessment in STEMI patients. In the present study, LA strain parameters especially enabled further risk stratification and prognostic assessment over and above clinically established risk parameters. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02158468.

Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.

BACKGROUND: Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock despite a lack of evidence regarding its effect on mortality. METHODS: In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. RESULTS: A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P = 0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). CONCLUSIONS: In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov number, NCT03637205.).

Imaging Predictors of Left Ventricular Functional Recovery after Reperfusion Therapy of ST-Elevation Myocardial Infarction Assessed by Cardiac Magnetic Resonance.

BACKGROUND: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. RESULTS: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = -0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = -0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = -0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. CONCLUSION: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI.