Epicardial adipose tissue and pericardial constraint in heart failure with preserved ejection fraction.

AIMS: Obesity and epicardial adiposity play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), and both are associated with increased filling pressures and reduced exercise capacity. The haemodynamic basis for these observations remains inaccurately defined. We hypothesize that an abundance of epicardial adipose tissue (EAT) within the pericardial sac is associated with haemodynamic signs of pericardial constraint. METHODS AND RESULTS: HFpEF patients who underwent invasive heart catheterization with simultaneous echocardiography were included. Right atrial pressure (RAP), right ventricular end-diastolic pressure, and pulmonary capillary wedge pressure (PCWP) were invasively measured. The presence of a square root sign on the right ventricular pressure waveform and the RAP/PCWP ratio (surrogate parameters for pericardial constraint) were investigated. EAT thickness alongside the right ventricle was measured on echocardiography. Sixty-four patients were studied, with a mean age of 73 ± 10 years, 64% women, and a mean body mass index (BMI) of 28.6 ± 5.4 kg/m2. In total, 47 patients (73%) had a square root sign. The presence of a square root sign was associated with higher BMI (29.3 vs. 26.7 kg/m2, P = 0.02), higher EAT (4.0 vs. 3.4 mm, P = 0.03), and higher RAP (9 vs. 6 mmHg, P = 0.04). Women had more EAT than men (4.1 vs. 3.5 mm, P = 0.04), despite a comparable BMI. Women with a square root sign had significantly higher EAT (4.3 vs. 3.3 mm, P = 0.02), a higher mean RAP (9 vs. 5 mmHg, P = 0.02), and a higher RAP/PCWP ratio (0.52 vs. 0.26, P = 0.002). In men, such associations were not seen, although there was no significant interaction between men and women (P > 0.05 for all analyses). CONCLUSIONS: Obesity and epicardial adiposity are associated with haemodynamic signs of pericardial constraint in patients with HFpEF. The pathophysiological and therapeutic implications of this finding need further study.

Prevalence and Incidence of Atrial Fibrillation in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: (Additive) Value of Implantable Loop Recorders.

BACKGROUND: Atrial fibrillation (AF) is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and has a negative impact on outcome. Reliable data on prevalence, incidence, and detection of AF from contemporary, prospective HFmrEF/HFpEF studies are scarce. METHODS: This was a prespecified sub-analysis from a prospective, multicenter study. Patients with HFmrEF/HFpEF underwent 12-lead electrocardiography (ECG), 24 h Holter monitoring, and received an implantable loop recorder (ILR) at the study start. During the 2 year follow-up, rhythm monitoring was performed via ILR, yearly ECG, and two yearly 24 h Holter monitors. RESULTS: A total of 113 patients were included (mean age 73 ± 8 years, 75% HFpEF). At baseline, 70 patients (62%) had a diagnosis of AF: 21 paroxysmal, 18 persistent, and 31 permanent AF. At study start, 45 patients were in AF. Of the 43 patients without a history of AF, 19 developed incident AF during a median follow-up of 23 [15-25] months (44%; incidence rate 27.1 (95% confidence interval 16.3-42.4) per 100 person-years). Thus, after the 2-year follow-up, 89 patients (79%) had a diagnosis of AF. In 11/19 incident AF cases (i.e., 58%), AF was solely detected on the ILR. Yearly 12-lead ECG detected six incident AF cases and four of these cases were also detected on two yearly 24 h Holter monitors. Two incident AF cases were detected on an unplanned ECG/Holter. CONCLUSIONS: Atrial fibrillation is extremely common in heart failure with HFmrEF/HFpEF and may inform on symptom evaluation and treatment options. AF screening with an ILR had a much higher diagnostic yield than conventional modalities.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure.

AIMS: Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. METHODS AND RESULTS: In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan-Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 µg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). CONCLUSION: This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

Connecting epicardial adipose tissue and heart failure with preserved ejection fraction: mechanisms, management and modern perspectives.

Obesity is very common in patients with heart failure with preserved ejection fraction (HFpEF) and it has been suggested that obesity plays an important role in the pathophysiology of this disease. While body mass index defines the presence of obesity, this measure provides limited information on visceral adiposity, which is probably more relevant in the pathophysiology of HFpEF. Epicardial adipose tissue is the visceral fat situated directly adjacent to the heart and recent data demonstrate that accumulation of epicardial adipose tissue is associated with the onset, symptomatology and outcome of HFpEF. However, the mechanisms by which epicardial adipose tissue may be involved in HFpEF remain unclear. It is also questioned whether epicardial adipose tissue may be a specific target for therapy for this disease. In the present review, we describe the physiology of epicardial adipose tissue and the pathophysiological transformation of epicardial adipose tissue in response to chronic inflammatory diseases, and we postulate conceptual mechanisms on how epicardial adipose tissue may be involved in HFpEF pathophysiology. Lastly, we outline potential treatment strategies, knowledge gaps and directions for further research.

Right ventricular dysfunction in patients with new-onset heart failure: longitudinal follow-up during guideline-directed medical therapy.

AIMS: Improvement in left ventricular ejection fraction (LVEF) after up-titration of guideline-directed medical therapy (GDMT) has been well described in heart failure (HF) patients. Less is known about the prevalence and clinical course of right ventricular dysfunction (RVD) in patients with new-onset HF. METHODS AND RESULTS: From 2012 to 2018, 625 patients with a recent (<3 months) diagnosis of HF were referred to a specialized nurse-led HF clinic for protocolized up-titration of GDMT. RVD, defined as tricuspid annular plane systolic excursion (TAPSE) <17 mm, was assessed at baseline and at the follow-up visit. Patients were followed for the combined endpoint of all-cause mortality and HF hospitalization for a mean of 3.3 ± 1.9 years. Of the 625 patients, 241 (38.6%) patients had RVD at baseline. Patients with RVD were older, more symptomatic, had a lower LVEF, and more often had a history of cardiothoracic surgery and atrial fibrillation. After a median follow-up of 9 months, right ventricular function normalized in 49% of the patients with baseline RVD. RVD at baseline was associated with a higher risk of the combined endpoint (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.21-2.18). Right ventricular function normalization was associated with a lower risk for the combined endpoint (HR 0.56, 95% CI 0.31-0.99), independent of baseline TAPSE, age, sex, and LVEF. CONCLUSION: More than one-third of patients with new-onset HF have RVD. RVD is associated with a higher risk of all-cause mortality and HF hospitalization. Recovery of RVD regularly occurs during up-titration of GDMT and is associated with improved clinical outcomes.

Bariatric surgery and cardiovascular disease: a systematic review and meta-analysis.

AIMS: Obesity is a global health problem, associated with significant morbidity and mortality, often due to cardiovascular (CV) diseases. While bariatric surgery is increasingly performed in patients with obesity and reduces CV risk factors, its effect on CV disease is not established. We conducted a systematic review and meta-analysis to evaluate the effect of bariatric surgery on CV outcomes, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. METHODS AND RESULTS: PubMed and Embase were searched for literature until August 2021 which compared bariatric surgery patients to non-surgical controls. Outcomes of interest were all-cause and CV mortality, atrial fibrillation (AF), heart failure (HF), myocardial infarction, and stroke. We included 39 studies, all prospective or retrospective cohort studies, but randomized outcome trials were not available. Bariatric surgery was associated with a beneficial effect on all-cause mortality [pooled hazard ratio (HR) of 0.55; 95% confidence interval (CI) 0.49-0.62, P < 0.001 vs. controls], and CV mortality (HR 0.59, 95% CI 0.47-0.73, P < 0.001). In addition, bariatric surgery was also associated with a reduced incidence of HF (HR 0.50, 95% CI 0.38-0.66, P < 0.001), myocardial infarction (HR 0.58, 95% CI 0.43-0.76, P < 0.001), and stroke (HR 0.64, 95% CI 0.53-0.77, P < 0.001), while its association with AF was not statistically significant (HR 0.82, 95% CI 0.64-1.06, P = 0.12). CONCLUSION: The present systematic review and meta-analysis suggests that bariatric surgery is associated with reduced all-cause and CV mortality, and lowered incidence of several CV diseases in patients with obesity. Bariatric surgery should therefore be considered in these patients.

Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure.

BACKGROUND: In REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure), implantation of an atrial shunt device did not provide overall clinical benefit for patients with heart failure with preserved or mildly reduced ejection fraction. However, prespecified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial volume, and sex. Shunt implantation reduces left atrial pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). On the basis of these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. METHODS: REDUCE LAP-HF II enrolled 626 patients with heart failure, ejection fraction ≥40%, exercise pulmonary capillary wedge pressure ≥25 mm Hg, and resting pulmonary vascular resistance <3.5 Wood units who were randomized 1:1 to atrial shunt device or sham control. The primary outcome-a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status-was analyzed using the win ratio. Latent PVD was defined as pulmonary vascular resistance ≥1.74 Wood units (highest tertile) at peak exercise, measured before randomization. RESULTS: Compared with patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated left atrial pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio, 0.60 [95% CI, 0.42, 0.86]; P=0.005) and signal of clinical benefit in patients without PVD (win ratio, 1.31 [95% CI, 1.02, 1.68]; P=0.038). Patients with larger right atrial volumes and men had worse outcomes with the device and both groups were more likely to have pacemakers, heart failure with mildly reduced ejection fraction, and increased left atrial volume. For patients without latent PVD or pacemaker (n=313; 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio, 1.51 [95% CI, 1.14, 2.00]; P=0.004). CONCLUSIONS: In patients with heart failure with preserved or mildly reduced ejection fraction, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

The value of echocardiographic measurement of epicardial adipose tissue in heart failure patients.

AIMS: Epicardial adipose tissue (EAT) is increasingly recognized as an important factor in the pathophysiology of heart failure (HF). Cardiac magnetic resonance (CMR) imaging is the gold-standard imaging modality to evaluate EAT size, but in contrast to echocardiography, CMR is costly and not widely available. We investigated EAT thickness on echocardiography in relation to EAT volume on CMR, and we assessed the agreement between observers for measuring echocardiographic EAT. METHODS AND RESULTS: Patients with HF and left ventricular ejection fraction >40% were enrolled. All patients underwent CMR imaging and transthoracic-echocardiography. EAT volume was quantified on CMR short-axis cine-stacks. Echocardiographic EAT thickness was measured on parasternal long-axis and short-axis views. Linear regression analyses were used to assess the association between EAT volume on CMR and EAT thickness on echocardiography. Intraclass correlation coefficient (ICC) was used to assess the interobserver agreement as well as the intraobserver agreement. EAT on CMR and echocardiography was evaluated in 117 patients (mean age 71 ± 10 years, 49% women and mean left ventricular ejection fraction 54 ± 7%). Mean EAT volume on CMR was 202 ± 64 mL and ranged from 80 to 373 mL. Mean EAT thickness on echocardiography was 3.8 ± 1.5 mm and ranged from 1.7 to 10.2 mm. EAT volume on CMR and EAT thickness on echocardiography were significantly correlated (junior-observer: r = 0.62, P < 0.001, senior-observer: r = 0.33, P < 0.001), and up to one-third of the variance in EAT volume was explained by EAT thickness (R2  = 0.38, P < 0.001). The interobserver agreement between junior and senior observers for measuring echocardiographic EAT was modest [ICC, 0.65 (95% confidence interval (CI) 0.47-0.77], whereas the intraobserver agreement was good (ICC 0.98, 95% CI 0.84-0.99). CONCLUSIONS: There was a modest correlation between EAT volume on CMR and EAT thickness on echocardiography. Limited agreement between junior and senior observers for measuring echocardiographic EAT was observed. EAT thickness on echocardiography is limited in estimating EAT volume.

Relative fat mass, a new index of adiposity, is strongly associated with incident heart failure: data from PREVEND.

Body-mass index (BMI), waist circumference, and waist-hip ratio are commonly used anthropometric indices of adiposity. However, over the past 10 years, several new anthropometric indices were developed, that more accurately correlated with body fat distribution and total fat mass. They include relative fat mass (RFM), body-roundness index (BRI), weight-adjusted-waist index and body-shape index (BSI). In the current study, we included 8295 adults from the PREVEND (Prevention of Renal and Vascular End-Stage Disease) observational cohort (the Netherlands), and sought to examine associations of novel as well as established adiposity indices with incident heart failure (HF). The mean age of study population was 50 ± 13 years, and approximately 50% (n = 4134) were women. Over a 11 year period, 363 HF events occurred, resulting in an overall incidence rate of 3.88 per 1000 person-years. We found that all indices of adiposity (except BSI) were significantly associated with incident HF in the total population (P < 0.001); these associations were not modified by sex (P interaction > 0.1). Amongst adiposity indices, the strongest association was observed with RFM [hazard ratio (HR) 1.67 per 1 SD increase; 95% confidence interval (CI) 1.37-2.04]. This trend persisted across multiple age groups and BMI categories, and across HF subtypes [HR: 1.76, 95% CI 1.26-2.45 for HF with preserved ejection fraction; HR 1.61, 95% CI 1.25-2.06 for HF with reduced ejection fraction]. We also found that all adiposity indices (except BSI) improved the fit of a clinical HF model; improvements were, however, most evident after adding RFM and BRI (reduction in Akaike information criteria: 24.4 and 26.5 respectively). In conclusion, we report that amongst multiple anthropometric indicators of adiposity, RFM displayed the strongest association with HF risk in Dutch community dwellers. Future studies should examine the value of including RFM in HF risk prediction models.

The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction.

Heart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 ± 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07-19.31, p = 0.001 and 1.68 (1.03-2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5-18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk.

Epicardial Adipose Tissue and Outcome in Heart Failure With Mid-Range and Preserved Ejection Fraction.

BACKGROUND: Epicardial adipose tissue (EAT) accumulation is thought to play a role in the pathophysiology of heart failure (HF) with mid-range and preserved ejection fraction, but its effect on outcome is unknown. We evaluated the prognostic value of EAT volume measured with cardiac magnetic resonance in patients with HF with mid-range ejection fraction and HF with preserved ejection fraction. METHODS: Patients enrolled in a prospective multicenter study that investigated the value of implantable loop-recorders in HF with mid-range ejection fraction and HF with preserved ejection fraction were analyzed. EAT volume was quantified with cardiac magnetic resonance. Main outcome was the composite of all-cause mortality and first HF hospitalizations. Hazard ratios (HR) and 95% CI are described per SD increase in EAT. RESULTS: We studied 105 patients (mean age 72±8 years, 50% women, and mean left ventricular ejection fraction 53±8%). During median follow-up of 24 (17-25) months, 31 patients (30%) died or were hospitalized for HF. In univariable analysis, EAT was significantly associated with a higher risk of the composite outcome (HR, 1.76 [95% CI, 1.24-2.50], P=0.001), and EAT remained associated with outcome after adjustment for age, sex, and body mass index (HR, 1.61 [95% CI, 1.13-2.31], P=0.009), and after adjustment for New York Heart Association functional class and N-terminal of pro-brain natriuretic peptide (HR, 1.53 [95% CI, 1.04-2.24], P=0.03). Furthermore, EAT was associated with all-cause mortality alone (HR, 2.06 [95% CI, 1.26-3.37], P=0.004) and HF hospitalizations alone (HR, 1.54 [95% CI, 1.04-2.30], P=0.03). CONCLUSIONS: EAT accumulation is associated with adverse prognosis in patients with HF with mid-range ejection fraction and HF with preserved ejection fraction. This finding supports the importance of EAT in these patients with HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01989299.

Importance of epicardial adipose tissue localization using cardiac magnetic resonance imaging in patients with heart failure with mid-range and preserved ejection fraction.

BACKGROUND: Epicardial adipose tissue (EAT) has been implicated in the pathophysiology of heart failure (HF) with left ventricular ejection fraction (LVEF) >40%, but whether this is due to a regional or global effect of EAT remains unclear. HYPOTHESIS: Regional EAT is associated with alterations in local cardiac structure and function. METHODS: Patients with HF and LVEF >40% were studied. Cardiac Magnetic Resonance imaging was used to localize EAT surrounding the right ventricle (RV) and LV separately, using anterior- and posterior interventricular grooves as boundaries. Atrial- and ventricular EAT were differentiated using the mitral-valve position. All EAT depots were related to the adjacent myocardial structure. RESULTS: 102 consecutive HF patients were enrolled. The majority of EAT was present around the RV (42% of total EAT, p < .001). RV-EAT showed a strong association with increased RV mass (ß = 0.60, p < .001) and remained associated with RV mass after adjusting for total EAT, sex, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renal function and blood glucose. LV-EAT showed a similar association with LV mass in univariable analysis, albeit less pronounced (ß = 0.24, p = .02). Atrial EAT was increased in patients with atrial fibrillation compared to those without atrial fibrillation (30 vs. 26 ml/m2 , p = .04), whereas ventricular EAT was similar (74 vs. 75 ml/m2 , p = .9). CONCLUSIONS: Regional EAT is strongly associated with local cardiac structure and function in HF patients with LVEF >40%. These data support the hypothesis that regional EAT is involved in the pathophysiology of HF with LVEF >40%.

Reduced right ventricular function on cardiovascular magnetic resonance imaging is associated with uteroplacental impairment in tetralogy of Fallot.

BACKGROUND: Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). METHODS: Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. RESULTS: We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF; P = 0.037 and P = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 and P = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%, p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. CONCLUSIONS: Reduced RV function before pregnancy is associated with abnormal uteroplacental Doppler flow parameters. It could be postulated that reduced RV function on pre-pregnancy CMR (≤2 years) is a predisposing factor for impaired placental function in women with repaired ToF.

Epicardial Adipose Tissue and Invasive Hemodynamics in Heart Failure With Preserved Ejection Fraction.

OBJECTIVES: This study examined associations between epicardial adipose tissue (EAT), invasive hemodynamics, and exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: EAT is increased in patients with HFpEF and may play a role in the pathophysiology of this disorder. METHODS: Patients with heart failure and a left ventricular ejection fraction >45% who underwent right and left heart catheterization with simultaneous echocardiography were included. Pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP), right ventricular end-diastolic pressure (RVEDP), and pulmonary vascular resistance (PVR) were invasively measured. Obesity was defined as body mass index (BMI) ≥30 kg/m2. EAT thickness alongside the right ventricle was measured on echocardiographic long- and short-axis views. Cardiopulmonary exercise testing was performed to obtain maximal oxygen uptake (VO2-max). RESULTS: This study examined 75 patients, mean age 74 ± 9 years; 68% were women, mean BMI was 29 ± 6 kg/m2, and 36% were obese. Higher BMI was strongly associated with increased EAT (r = 0.74; p < 0.001). Increased EAT was associated with higher RVEDP, independent of PVR (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.02 to 1.34; p = 0.03), but not independent of obesity (p = 0.10). Increased EAT and higher RVEDP were both associated with lower VO2-max (r = -0.43; p < 0.001 and r = -0.43; p = 0.001, respectively). Increased EAT remained associated with lower VO2-max after adjustment for PVR (OR: 0.64; 95% CI: 0.49 to 0.84; p = 0.002) and obesity (OR: 0.69; 95% CI: 0.53 to 0.92; p = 0.01). EAT thickness was not associated with left-sided filling pressures (i.e., PCWP and LVEDP). CONCLUSIONS: In HFpEF, obesity and increased EAT were associated with higher right-sided filling pressures and with reduced exercise capacity.

Ventricular tachyarrhythmia detection by implantable loop recording in patients with heart failure and preserved ejection fraction: the VIP-HF study.

AIMS: The primary aim of the VIP-HF study was to examine the incidence of sustained ventricular tachyarrhythmias (VTs) in heart failure (HF) with mid-range (HFmrEF) or preserved ejection fraction (HFpEF). Secondary aims were to examine the incidence of non-sustained VTs, bradyarrhythmias, HF hospitalizations and mortality. METHODS AND RESULTS: This was an investigator-initiated, prospective, multicentre, observational study of patients with HF and left ventricular ejection fraction (LVEF) >40%. Patients underwent extensive phenotyping, after which an implantable loop recorder was implanted. We enrolled 113 of the planned 250 patients [mean age 73 ± 8 years, 51% women, New York Heart Association class II/III 54%/46%, median N-terminal pro B-type natriuretic peptide 1367 (710-2452) pg/mL and mean LVEF 54 ± 6%; 75% had LVEF >50%]. Eighteen percent had non-sustained VTs and 37% had atrial fibrillation on Holter monitoring. During a median follow-up of 657 (219-748) days, the primary endpoint of sustained VT was observed in one patient. The incidence of the primary endpoint was 0.6 (95% confidence interval 0.2-3.5) per 100 person-years. The incidence of the secondary endpoint of non-sustained VT was 11.5 (7.1-18.7) per 100 person-years. Five patients developed bradyarrhythmias [3.2 (1.4-7.5) per 100 person-years], three were implanted with a pacemaker. In total, 23 patients (20%) were hospitalized for HF [16.3 (10.9-24.4) per 100 person-years]. Fourteen patients (12%) died [8.7 (5.2-14.7) per 100 person-years]; 10 due to cardiovascular causes, and four sudden deaths, one with implantable loop recorder-confirmed bradyarrhythmias as terminal event, three others undetermined. CONCLUSION: Despite the lower than expected number of included patients, the incidence of sustained VTs in HFmrEF/HFpEF was low. Clinically relevant bradyarrhythmias were more often observed than expected.