Anders Nelsson

Background: Pulmonary congestion in heart failure (HF) is challenging to quantify. Recent advances in cardiovascular magnetic resonance (CMR) using routine clinical perfusion scans make it possible to calculate the pulmonary blood volume indexed to body surface area (PBVi) as a prognostic marker of congestion. The aims were to assess if PBVi normalizes after onset of treatment and if PBVi differs in different HF subtypes compared to healthy controls. Methods: In this prospective cohort study, a total of 115 subjects (22 healthy controls, 93 HF patients of which 19 newly diagnosed) underwent CMR at 1.5T. PBVi was calculated as the transit time for a contrast bolus from the right to the left side of the heart during a perfusion scan, multiplied by the cardiac output from 2D aortic flow. Results: Patients with newly diagnosed HF showed signs of pulmonary congestion in terms of an increased PBVi compared to controls (394 vs 302 ml/m2 p = 0·004). After treatment, PBVi normalized to similar levels as controls (296 ml/m2, p > 0·99). There were no differences in PBVi between controls and chronic out-patients with preserved (HFpEF, n = 19, p > 0·999), mildly reduced (HFmrEF, n = 24, p > 0·999) or reduced ejection fraction (HFrEF, n = 31, p = 0·146). Conclusion: This proof-of-concept study demonstrates for the first time that non-invasive PBVi normalizes following initiation of guideline-directed medical therapy, while PBVi remained within normal range in treated patients with HFpEF or HFmrEF. Assessment by CMR may provide incremental clinical value as a marker of pulmonary congestion in suspected HF and for evaluating response to decongestive treatment.

Aims: Peak oxygen uptake (VO2peak) is closely related to total heart volume (THV) in healthy individuals. This study aimed to investigate (i) the association between VO2peak and THV in subjects with sub-clinical diastolic dysfunction, athletes, healthy controls, and patients with established heart failure with and without preserved ejection fraction (HFpEF and HFrEF), and (ii) whether VO2peak/THV-index can distinguish between subjects with sub-clinical diastolic dysfunction, HFpEF, HFrEF, and healthy controls. Methods and results: Seventy participants were included: 15 with sub-clinical diastolic dysfunction (defined as showing only 1–2 echocardiographic signs of diastolic dysfunction, not meeting clinical diagnostic criteria), 10 athletes, 15 healthy controls, and 30 heart failure patients (15 HFpEF and 15 HFrEF). VO2peak was assessed by cardiopulmonary exercise testing and THV by cardiovascular magnetic resonance imaging. In sub-clinical diastolic dysfunction, THV was a weak determinant of VO2peak (R2 = 0.41, P = 0.01), and even weaker in heart failure (R2 = 0.16, P = 0.03). However, THV strongly predicted VO2peak in athletes and controls combined (R2 = 0.87, P < 0.0001). VO2peak/THV did not distinguish healthy controls from sub-clinical diastolic dysfunction but could reliably discriminate between healthy controls and patients with heart failure. Conclusion: Subjects with sub-clinical diastolic dysfunction may have an altered relationship between VO2peak and THV, approaching that of patients with established heart failure. Thus, this proof-of-concept study indicates that sub-clinical diastolic dysfunction constitutes a group of patients that may be of interest to follow over time to prevent continued deterioration of cardiac function. Furthermore, the VO2peak/THV ratio can be used to distinguish between healthy controls and overt heart failure.

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

Background: Diastolic dysfunction is a common finding in heart failure with preserved ejection fraction (HFpEF) and is considered a key mechanism for limiting exercise performance. Meanwhile, subclinical diastolic dysfunction (SDD) without heart failure is a growing concern and may be common in the general population [1,5[. The kinetic energy (KE) of intracardiac blood flow reflects the work spent on accelerating blood [3] and may provide a novel window into diastolic filling dynamics [2,4]. Our aim was therefore to quantify left ventricular KE in HFpEF patients and compare with healthy controls, subjects with SDD, and heart failure patients with moderately reduced (HFmrEF) or reduced ejection fraction (HFrEF). Methods: We studied 12 healthy controls, 22 healthy subjects with 1–2 echocardiographic criteria of diastolic dysfunction (SDD), 16 HFpEF, 9 HFmrEF, and 16 HFrEF patients. All subjects underwent CMR imaging at 1.5T with acquisition of anatomical cines and 4D flow from a box covering the heart. The LV was delineated over the cardiac cycle and KE inside the segmentation calculated as 0.5 × m × v2, where v is the instantaneous velocity vector magnitude and m is blood mass. Group comparisons of peak and average values were performed using Kruskal-Wallis test with Dunn's uncorrected post hoc test. Significance was assigned at p<0.05. Median values are given. Results: Groups were similar with regard to sex, blood pressure, and body surface area. HFpEF (median 72 years) and HFrEF patients (67 years) were significantly older than subjects with SDD (62 years, p=0.001). Examples of KE are shown in Fig. 1. Systolic peak and average KE did not differ between groups (p=0.81 and p=0.54 respectively, Fig. 2). Diastolic peak KE was higher in all groups of heart failure compared to controls (p<0.03 for all) and diastolic average KE was higher in HFmrEF and HFrEF compared to controls (p<0.02). The standard deviation for SDD was wider than in controls (1.6 mJ vs 0.8 mJ for systolic peaks, 2.7 mJ vs 1.1 mJ for diastolic peaks) and more closely resembled the HFpEF group (2.1 mJ in systole, 2.3 mJ in diastole). Conclusions: Systolic kinetic energy expenditures are on average similar between controls, subjects with subclinical diastolic dysfunction, and heart failure patients, indicating that cardiac pumping involves approximately the same amount of systolic acceleration for a given afterload. Conversely, diastolic KE was found more dispersed both in heart failure and in asymptomatic individuals with subclinical diastolic dysfunction. Higher peak values of KE were seen in diastole for all types of heart failure including HFpEF, indicating more work is spent filling the ventricle. Measurements of KE in diastole could potentially be a new tool for assessment of heart failure, including early stages of disease development in some individuals with subclinical diastolic dysfunction. Funding Acknowledgement: Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung FoundationRegion of Scania, Sweden

Background. Kinetic energy (KE) of intracardiac blood flow reflects myocardial work spent on accelerating blood and provides a mechanistic window into diastolic filling dynamics. Diastolic dysfunction may represent an early stage in the development of heart failure (HF). Here we evaluated the hemodynamic effects of impaired diastolic function in subjects with and without HF, testing the hypothesis that left ventricular KE differs between controls, subjects with subclinical diastolic dysfunction (SDD), and HF patients. Methods. We studied 77 subjects (16 controls, 20 subjects with SDD, 16 HFpEF, 9 HFmrEF, and 16 HFrEF patients, age- and sex-matched at the group level). Cardiac magnetic resonance at 1.5T included intracardiac 4D flow and cine imaging. Left ventricular KE was calculated as 0.5*m*v². Results. Systolic KE was similar between groups (p>0.4), also after indexing to stroke volume (p=0.25), and was primarily driven by ventricular emptying rate (p2=0.52). Diastolic KE was higher in heart failure patients than controls (p0.18), correlating with inflow conditions (E-wave velocity, p2=0.24) and end-diastolic volume (p=0.0003, R²=0.17) but not with average e' (p=0.07). Conclusions. Diastolic KE differs between controls and heart failure, suggesting more work is spent filling the failing ventricle, while systolic KE does not differentiate between well-matched groups with normal ejection fraction even in the presence of relaxation abnormalities and heart failure. Mechanistically, KE reflects the acceleration imparted on the blood and is driven by variations in ventricular emptying and filling rates, volumes, and heart rate, regardless of underlying pathology.