Hemodynamic Changes During Physiological and Pharmacological Stress Testing in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Although disease etiologies differ, heart failure patients with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) both present with clinical symptoms when under stress and impaired exercise capacity. The extent to which the adaptation of heart rate (HR), stroke volume (SV), and cardiac output (CO) under stress conditions is altered can be quantified by stress testing in conjunction with imaging methods and may help to detect the diminishment in a patient's condition early. The aim of this meta-analysis was to quantify hemodynamic changes during physiological and pharmacological stress testing in patients with HF. A systematic literature search (PROSPERO 2020:CRD42020161212) in MEDLINE was conducted to assess hemodynamic changes under dynamic and pharmacological stress testing at different stress intensities in HFpEF and HFrEF patients. Pooled mean changes were estimated using a random effects model. Altogether, 140 study arms with 7,248 exercise tests were analyzed. High-intensity dynamic stress testing represented 73% of these data (70 study arms with 5,318 exercise tests), where: HR increased by 45.69 bpm (95% CI 44.51-46.88; I 2 = 98.4%), SV by 13.49 ml (95% CI 6.87-20.10; I 2 = 68.5%), and CO by 3.41 L/min (95% CI 2.86-3.95; I 2 = 86.3%). No significant differences between HFrEF and HFpEF groups were found. Despite the limited availability of comparative studies, these reference values can help to estimate the expected hemodynamic responses in patients with HF. No differences in chronotropic reactions, changes in SV, or CO were found between HFrEF and HFpEF. When compared to healthy individuals, exercise tolerance, as well as associated HR and CO changes under moderate-high dynamic stress, was substantially impaired in both HF groups. This may contribute to a better disease understanding, future study planning, and patient-specific predictive models. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020161212].

Image-Based Computational Model Predicts Dobutamine-Induced Hemodynamic Changes in Patients With Aortic Coarctation.

BACKGROUND: Pharmacological stress testing can help to uncover pathological hemodynamic conditions and is, therefore, used in the clinical routine to assess patients with structural heart diseases such as aortic coarctation with borderline indication for treatment. The aim of this study was to develop and test a reduced-order model predicting dobutamine stress induced pressure gradients across the coarctation. METHODS: The reduced-order model was developed based on n=21 imaging data sets of patients with aortic coarctation and a meta-analysis of subjects undergoing dobutamine stress testing. Within an independent test cohort of n=21 patients with aortic coarctation, the results of the model were compared with dobutamine stress testing during catheterization. RESULTS: In n=19 patients responding to dobutamine stress testing, pressure gradients across the coarctation during dobutamine stress increased from 15.7±5.1 to 33.6±10.3 mm Hg (paired t test, P<0.001). The model-predicted pressure gradients agreed with catheter measurements with a mean difference of -2.2 mm Hg and a limit of agreement of ±11.16 mm Hg according to Bland-Altman analysis. Significant equivalence between catheter-measured and simulated pressure gradients during stress was found within the study cohort (two 1-sided tests of equivalence with a noninferiority margin of 5.0 mm Hg, 33.6±10.33 versus 31.5±11.15 mm Hg, P=0.021). CONCLUSIONS: The developed reduced-order model can instantly predict dobutamine-induced hemodynamic changes with accuracy equivalent to heart catheterization in patients with aortic coarctation. The method is easy to use, available as a web-based calculator, and provides a promising alternative to conventional stress testing in the clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02591940.

Wearable devices can predict the outcome of standardized 6-minute walk tests in heart disease.

Wrist-worn devices with heart rate monitoring have become increasingly popular. Although current guidelines advise to consider clinical symptoms and exercise tolerance during decision-making in heart disease, it remains unknown to which extent wearables can help to determine such functional capacity measures. In clinical settings, the 6-minute walk test has become a standardized diagnostic and prognostic marker. We aimed to explore, whether 6-minute walk distances can be predicted by wrist-worn devices in patients with different stages of mitral and aortic valve disease. A total of n = 107 sensor datasets with 1,019,748 min of recordings were analysed. Based on heart rate recordings and literature information, activity levels were determined and compared to results from a 6-minute walk test. The percentage of time spent in moderate activity was a predictor for the achievement of gender, age and body mass index-specific 6-minute walk distances (p < 0.001; R 2 = 0.48). The uncertainty of these predictions is demonstrated.

Variability of Myocardial Strain During Isometric Exercise in Subjects With and Without Heart Failure.

Background: Fast strain-encoded cardiac magnetic resonance imaging (cMRI, fast-SENC) is a novel technology potentially improving characterization of heart failure (HF) patients by quantifying cardiac strain. We sought to describe the impact of isometric handgrip exercise (HG) on cardiac strain assessed by fast-SENC in HF patients and controls. Methods: Patients with stable HF and controls were examined using cMRI at rest and during HG. Left ventricular (LV) global longitudinal strain (GLS) and global circumferential (GCS) were derived from image analysis software using fast-SENC. Strain change < -0.5 and > +0.5 was classified as increase and decrease, respectively. Results: The study population comprised 72 subjects, including HF with reduced, mid-range and preserved ejection fraction and controls (HFrEF n = 18 HFmrEF n = 18, HFpEF n = 17, controls: n = 19). In controls, LV GLS remained stable in 36.8%, increased in 36.8% and decreased in 26.3% of subjects during HG. In HF subgroups, similar patterns of LV GLS response were observed (HFpEF: stable 41.2%, increase 35.3%, decrease: 23.5%; HFmrEF: stable 50.0%, increase 16.7%, decrease: 33.3%; HFrEF: stable 33.3%, increase 22.2%, decrease: 44.4%, p = 0.668). Mean change between LV GLS at rest and during HG ranged close to zero with broad standard deviation in all subgroups and was not significantly different between subgroups (+1.2 ± 5.4%, -0.6 ± 8.3%, -1.7 ± 10.7%, and -3.1 ± 19.4%, p = 0.746 in controls, HFpEF, HFmrEF and HFrEF, respectively). However, the absolute value of LV GLS change-irrespective of increase or decrease-was significantly different between subgroups with 4.4 ± 3.2% in controls, 5.9 ± 5.7% in HFpEF, 6.8 ± 8.3% in HFmrEF and 14.1 ± 13.3% in HFrEF (p = 0.005). The absolute value of LV GLS change significantly correlated with resting LVEF, NTproBNP and Minnesota Living with Heart Failure questionnaire scores. Conclusion: The response to isometric exercise in LV GLS is heterogeneous in all HF subgroups and in controls. The absolute value of LV GLS change during HG exercise is elevated in HF patients and associated with measures of HF severity. The diagnostic utility of fast-SENC strain assessment in conjunction with HG appears to be limited. Trial Registration: URL: https://www.drks.de; Unique Identifier: DRKS00015615.

Impact of valve morphology, hypertension and age on aortic wall properties in patients with coarctation: a two-centre cross-sectional study.

OBJECTIVE: We aimed to investigate the combined effects of arterial hypertension, bicuspid aortic valve disease (BAVD) and age on the distensibility of the ascending and descending aortas in patients with aortic coarctation. DESIGN: Cross-sectional study. SETTING: The study was conducted at two university medical centres, located in Berlin and London. PARTICIPANTS: A total of 121 patients with aortic coarctation (ages 1-71 years) underwent cardiac MRI, echocardiography and blood pressure measurements. OUTCOME MEASURES: Cross-sectional diameters of the ascending and descending aortas were assessed to compute aortic area distensibility. Findings were compared with age-specific reference values. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology statement and reporting guidelines. RESULTS: Impaired distensibility (below fifth percentile) was seen in 37% of all patients with coarctation in the ascending aorta and in 43% in the descending aorta. BAVD (43%) and arterial hypertension (72%) were present across all ages. In patients >10 years distensibility impairment of the ascending aorta was predominantly associated with BAVD (OR 3.1, 95% CI 1.33 to 7.22, p=0.009). Distensibility impairment of the descending aorta was predominantly associated with arterial hypertension (OR 2.8, 95% CI 1.08 to 7.2, p=0.033) and was most pronounced in patients with uncontrolled hypertension despite antihypertensive treatment. CONCLUSION: From early adolescence on, both arterial hypertension and BAVD have a major impact on aortic distensibility. Their specific effects differ in strength and localisation (descending vs ascending aorta). Moreover, adequate blood pressure control is associated with improved distensibility. These findings could contribute to the understanding of cardiovascular complications and the management of patients with aortic coarctation.

Hemodynamic Changes During Physiological and Pharmacological Stress Testing in Healthy Subjects, Aortic Stenosis and Aortic Coarctation Patients-A Systematic Review and Meta-Analysis.

Introduction: Exercise testing has become a diagnostic standard in the evaluation and management of heart disease. While different methods of exercise and pharmacological stress testing exist, only little is known about their comparability. We aimed to assess hemodynamic changes during dynamic exercise, isometric exercise, and dobutamine stress testing at different stress intensities in healthy subjects and patients with aortic stenosis (AS) and aortic coarctation (CoA). Methods: A systematic literature search (PROSPERO 2017:CRD42017078608) in MEDLINE of interventional trials was conducted to identify eligible studies providing evidence of changes in hemodynamic parameters under different stress conditions acquired by MRI or echocardiography. A random effects model was used to estimate pooled mean changes in hemodynamics. Results: One hundred and twenty-eight study arms with a total of 3,139 stress-examinations were included. In healthy subjects/(where available) in AS, pooled mean changes (95% CIs) during light dynamic stress were 31.78 (27.82-35.74) bpm in heart rate (HR) and 6.59 (2.58-10.61) ml in stroke volume (SV). Changes during light pharmacological stress were 13.71 (7.87-19.56)/14.0 (9.82-18.18) bpm in HR, and 5.47 (0.3-10.63)/8.0 (3.82-12.18) ml in SV. Changes during light isometric stress were 18.44 (10.74-26.14)/5.0 (-1.17-11.17) bpm in HR and -4.17 (-14.37-6.03)/-4.0 (-16.43-8.43) ml in SV. Changes during moderate dynamic stress were 49.57 (40.03-59.1)/46.45 (42.63-50.27) bpm in HR and 11.64 (5.87-17.42) ml in SV. During moderate pharmacological stress, changes in HR were 42.83 (36.94-48.72)/18.66 (2.38-34.93) bpm and in SV 6.29 (-2.0-14.58)/13.11 (7.99-18.23) ml. During high intensity dynamic stress changes in HR were 89.31 (81.46-97.17)/55.32 (47.31-63.33) bpm and in SV 21.31 (13.42-29.21)/-0.96 (-5.27-3.35) ml. During high pharmacological stress, changes in HR were 53.58 (36.53-70.64)/42.52 (32.77-52.28) bpm, and in SV 0.98 (-9.32-11.27)/14.06 (-1.62-29.74) ml. HR increase and age were inversely correlated at high stress intensities. In CoA, evidence was limited to single studies. Conclusion: This systematic review and meta-analysis presents pooled hemodynamic changes under light, moderate and high intensity exercise and pharmacological stress, while considering the potential influence of age. Despite limited availability of comparative studies, the reference values presented in this review allow estimation of the expected individual range of a circulatory response in healthy individuals and patients with AS and may contribute to future study planning and patient-specific models even when stress testing is contraindicated.

Patient-specific requirements and clinical validation of MRI-based pressure mapping: A two-center study in patients with aortic coarctation.

BACKGROUND: Invasive peak-to-peak pressure gradients are the current clinical reference standard for assessing aortic coarctation. To obtain them, patients need to undergo arterial heart catheterization. Unless an intervention is performed, the procedure remains purely diagnostic, while the concomitant risks remain. PURPOSE: To validate MRI-based pressure mapping against pressure drop derived from heart catheterization and to define minimal clinical requirements. STUDY TYPE: Prospective clinical validation study. POPULATION: Twenty-seven coarctation patients with an indicated heart catheterization were enrolled at two clinical centers. MRI SEQUENCES: 1.5T including 4D velocity-encoded MRI and 3D anatomical imaging of the aorta. ASSESSMENT: Pressure drop across the stenosis was calculated by pressure mapping based on the pressure Poisson equation. Calculated pressure drops were compared with catheter measured data. Spatial and temporal resolution were analyzed using in silico phantom-based data as well as in vivo measurements. STATISTICS: Pressure drop was compared to peak-to-peak measurements. A two-sample paired mean equivalence test was used. RESULTS: In patients without imaging artifacts and a required spatial resolution ≥5 voxel/diameter, significant equivalence of pressure mapping compared to heart catheterization was found (17.5 ± 6.49 vs. 16.6 ± 6.53 mmHg, P < 0.001). DATA CONCLUSION: Pressure mapping provides equivalent accuracy to pressure drop obtained from heart catheterization in patients 1) without previous stenting and 2) with sufficient spatial image resolution (at least 5 voxels/diameter). In these patients the method can reliably be performed prior to the actual procedure, and thus allows safe noninvasive treatment planning based on MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:81-89.