Improved identification of left atrial enlargement in patients with obesity.

Accurate standardization of left atrium volume (LAV) in patients with obesity is challenging. The aim of this study was to investigate and to examine the relation between LAV indexed to height2 and left atrial function in patients with moderate to severe obesity. Echocardiograms of patients with moderate to severe obesity (body mass index (BMI) ≥ 35 kg/m2) without known cardiac disease were analyzed. LAV was indexed to body surface area (BSA) and height2, and patients were divided into those with or without left atrial enlargement (LAE) based on normalization using either BSA (LAEbsa) or height2 (LAEh2). Using speckle tracking echocardiography, LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were assessed as a measure of LA function. LA dysfunction was defined as LASct < 14%. A total of 142 patients were included in the analysis of whom 54.2% had LAEh2 and 18.3% LAEBSA. The LAEh2 group had significantly lower LASct (12.2% ± 3.2% vs. 13.6% ± 4.5%, p = 0.019) as compared to the patients without LAEh2. Significantly more patients with LA dysfunction would be correctly identified by LAEh2 than by LAEBSA (41.5% vs. 15.0%, p < 0.001). In patients with moderate to severe obesity, the use of LAEh2 identified significantly more patients with decreased LA function. LAVh2 should be preferred over LAVBSA in patients with moderate to severe obesity.

Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19.

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort ( n = 214 patients) was 53% and 60% in ward and ICU starters, respectively ( p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pa o2 :F io2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.

Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

AIM: Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. METHODS AND RESULTS: Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (ß coefficient -0.404, p = 0.002), and a decrease in LASct (%) (ß coefficient -0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045). CONCLUSIONS: Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease.

Potential role of left atrial strain in estimation of left atrial pressure in patients with chronic heart failure.

AIMS: In a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available. METHODS AND RESULTS: Echocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I-II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP-free survival at a median follow-up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84-0.98). An abnormal LASr (<18%) was associated with a five-fold increase in reaching the PEP. CONCLUSIONS: In HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value.

Heart failure treatment in patients with and without obesity with an ejection fraction below 50.

BACKGROUND: The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. METHODS: Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed. RESULTS: Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4 kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). CONCLUSIONS: Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

Normalization of Cardiac Function After Bariatric Surgery Is Related to Autonomic Function and Vitamin D.

PURPOSE: Subclinical cardiac dysfunction is common in patients with obesity. Bariatric surgery is associated with normalization of subclinical cardiac function in 50% of the patients with obesity. The aim of this study was to identify predictors for a lack of improvement of subclinical cardiac dysfunction 1-year post-bariatric surgery. METHODS: Patients who were referred for bariatric surgery were enrolled in a longitudinal study. Inclusion criteria were age 35-65 years and BMI ≥ 35 kg/m2. Patients with a suspicion of or known cardiovascular disease were excluded. Conventional and advanced echocardiography, Holter monitoring, and blood tests were performed pre- and 1-year post-bariatric surgery. Subclinical cardiac dysfunction was defined as either a reduced left ventricular ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, arrhythmia, or an increased BNP or hs Troponin I. RESULTS: A total of 99 patients were included of whom 59 patients had cardiac dysfunction at baseline. Seventy-two patients completed the 1-year follow-up after bariatric surgery. There was a significant reduction in weight and cardiovascular risk factors. Parameters of cardiac function, such as GLS, improved. However, in 20 patients cardiac dysfunction persisted. Multivariate analysis identified a decreased heart rate variability (which is a measure of autonomic function), and a decreased vitamin D pre-surgery as predictors for subclinical cardiac dysfunction after bariatric surgery. CONCLUSION: Although there was an overall improvement of cardiac function 1-year post-bariatric surgery, autonomic dysfunction and a decreased vitamin D pre-bariatric surgery were predictors for a lack of improvement of subclinical cardiac dysfunction.

Cardiovascular Biomarker Profiles in Obesity and Relation to Normalization of Subclinical Cardiac Dysfunction after Bariatric Surgery.

AIMS: We aimed to gain insight into the underlying pathophysiology of cardiac dysfunction in obesity patients and the improvement of cardiac function after weight loss. METHODS: This is a longitudinal study in which 92 cardiovascular biomarkers were measured by multiplex immunoassays in obesity patients without known cardiovascular disease, before and one year after bariatric surgery. RESULTS: Out of 100 eligible patients, 72 patients completed the follow-up. A total of 72 (78%) biomarkers changed significantly. The biomarkers with the highest relative changes represented processes linked mainly to insulin resistance and inflammation. In the patients with persistent subclinical cardiac dysfunction, the baseline values of 10 biomarkers were different from values in patients with normalization of cardiac function. Most of these biomarkers were linked to inflammation or atherosclerosis. Finally, a model was developed to investigate the relationship between changes in the biomarkers and persistent subclinical cardiac dysfunction. Seven biomarkers were retained in this model, mainly linked to inflammation, atherosclerosis, and hypercoagulability. CONCLUSION: The majority (78%) of cardiovascular biomarkers changed, pointing mainly to modulation of insulin resistance and inflammation. The baseline levels of 10 biomarkers, as well as pre- to post-bariatric surgery changes in seven biomarkers, were related to persistent subclinical cardiac dysfunction after bariatric surgery.

Prognostic value of temporal patterns of global longitudinal strain in patients with chronic heart failure.

Background: We investigated whether repeatedly measured global longitudinal strain (GLS) has incremental prognostic value over repeatedly measured left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and a single "baseline" GLS value, in chronic heart failure (HF) patients. Methods: In this prospective observational study, echocardiography was performed in 173 clinically stable chronic HF patients every six months during follow up. During a median follow-up of 2.7 years, a median of 3 (25th-75th percentile:2-4) echocardiograms were obtained per patient. The endpoint was a composite of HF hospitalization, left ventricular assist device, heart transplantation, cardiovascular death. We compared hazard ratios (HRs) for the endpoint from Cox models (used to analyze the first available GLS measurements) with HRs from joint models (which links repeated measurements to the time-to-event data). Results: Mean age was 58 ± 11 years, 76% were men, 81% were in New York Heart Association functional class I/II, and all had LVEF < 50% (mean ± SD: 27 ± 9%). The endpoint was reached by 53 patients. GLS was persistently decreased over time in patients with the endpoint. However, temporal GLS trajectories did not further diverge in patients with versus without the endpoint and remained stable during follow-up. Both single measurements and temporal trajectories of GLS were significantly associated with the endpoint [HR per SD change (95%CI): 2.15(1.34-3.46), 3.54 (2.01-6.20)]. In a multivariable model, repeatedly measured GLS maintained its prognostic value while repeatedly measured LVEF did not [HR per SD change (95%CI): GLS:4.38 (1.49-14.70), LVEF:1.14 (0.41-3.23)]. The association disappeared when correcting for repeatedly measured NT-proBNP. Conclusion: Temporal evolution of GLS was associated with adverse events, independent of LVEF but not independent of NT-proBNP. Since GLS showed decreased but stable values in patients with adverse prognosis, single measurements of GLS provide sufficient information for determining prognosis in clinical practice compared to repeated measurements, and temporal GLS patterns do not add prognostic information to NT-proBNP.

Biomarker profiles in obesity patients and their relation to cardiac dysfunction.

Aim: Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient. Several biomarkers reflecting biological processes that may play a role in the occurrence of cardiac dysfunction in obesity patients are available. Purpose: To compare cardiovascular biomarker profiles between obesity patients and nonobese controls, and between obesity patients with and without cardiac dysfunction, in order to better understand the underlying pathophysiology of cardiac dysfunction in obesity patients. Materials & methods: Blood samples were obtained from 100 obesity patients (BMI ≥35 kg/m2) without known cardiovascular disease, and from 50 age- and gender-matched nonobese controls (BMI ≤30 kg/m2). The third cardiovascular panel of the Olink Multiplex platform was used for the measurement of 92 biomarkers. Results: The majority (53%) of biomarkers were elevated in obesity patients compared with nonobese controls. Only 5% of the biomarkers were elevated in obesity patients with cardiac dysfunction compared with those without. Biomarkers discriminating cardiac dysfunction from no cardiac dysfunction in obesity patients differed from those discriminating obese from nonobese patients. An elastic net model for the prediction of cardiac dysfunction in obesity patients had a high area under the receiver operating curve of 0.87 (95% CI: 0.79-0.94; p < 0.001). The sensitivity of this model was 84% and the specificity was 79%. Conclusion: A multiplex immunoassay was used for the first time in obesity patients without known cardiovascular disease. These patients have cardiovascular biomarker profiles that are clearly different from nonobese controls. Comparison of obesity patients with and without cardiac dysfunction suggested an important role for inflammation, atherosclerosis and insulin resistance in the underlying pathophysiology of cardiac dysfunction in obesity patients.

Conduction dynamics after transcatheter aortic valve implantation and implications for permanent pacemaker implantation and early discharge: the CONDUCT-study.

Aims: To correlate dynamics in electrical conduction after transcatheter aortic valve implantation (TAVI) with need for permanent pacemaker implantation (PPM) and assess implications for early discharge. Methods and results: Daily electrocardiograms after TAVI were analysed for rhythm and conduction times and were correlated with PPM. Transcatheter aortic valve implantation was performed in 291 consecutive patients with three contemporary transcatheter heart valve designs: Medtronic CoreValve (n = 111), Edwards Sapien XT (n = 29) and Sapien 3 (n = 72), and Boston Lotus (n = 79). We considered two cohorts: (A) Patients with normal baseline conduction; and (B) patients with pre-existent conduction disturbances. Based on QRS dynamics, three patterns were discerned: stable normal QRS duration, transient QRS prolongation, and persistent QRS prolongation. In Cohort B, QRS dynamics did not correlate with PPM. In contrast, in Cohort A, QRS dynamics and PPM appeared highly correlated. Neither patients with stable normal QRS duration (0/47), nor patients with transient QRS prolongation required PPM (0/26). All PPMs occurred in patients with persistent QRS prolongation until discharge (27/85). Persistent QRS prolongation was typically seen with Lotus and CoreValve, whereas stable normal QRS duration was typically seen with Sapien XT and Sapien 3. Conclusion: Three distinct patterns of QRS dynamics can be discerned after TAVI and their predictive probabilities for PPM strongly relate to the baseline conduction status. Patients with normal conduction at baseline and stable QRS duration after TAVI are potentially eligible for early discharge.

Current decision making and short-term outcome in patients with degenerative aortic stenosis: the Pooled-RotterdAm-Milano-Toulouse In Collaboration Aortic Stenosis survey.

AIMS: The aim of this study was to provide a real-world snapshot of contemporary Heart Team decision making on patients with aortic stenosis (AS) and the consequent short-term clinical outcome. METHODS AND RESULTS: This was an international multicentre prospective registry encompassing 390 patients with symptomatic severe AS who were prospectively enrolled. Clinical endpoints and the decisive arguments to opt for surgical or transcatheter aortic valve replacement, or medical therapy were recorded separately. The mean age was 76.4±11.6 years, 55% were male and the STS score was 2.9% (IQR 1.6-6.9). The local Heart Teams considered 43%, 25% and 23% to be at low, intermediate and high operative risk with a calculated STS score of 2.18±1.72, 5.08±2.76 and 13.15±9.43, respectively. Overall, 7% were deemed inoperable. Ninety-four percent of patients at low operative risk were sent for SAVR whereas 64% and 92% of intermediate and high-risk patients underwent TAVI. Only 6% of patients did not receive any kind of aortic valve replacement. Overall, 30-day all-cause mortality was 2.8%. TAVI was associated with more major vascular complications, need for permanent pacemakers and post-procedural aortic regurgitation. SAVR had more life-threatening bleedings and new-onset atrial fibrillation. CONCLUSIONS: The PRAGMATIC AS survey offers a snapshot of the contemporary management of patients with symptomatic severe AS. Multidisciplinary Heart Teams select an optimal strategy based on age, frailty and comorbidities. Nearly half of all patients are sent for TAVI. Only a small minority of patients will not receive valve replacement therapy.

Thrombus formation following transcatheter aortic valve replacement.

OBJECTIVES: This paper reviews the published data and reports 3 cases of thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1 involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three of these cases had pathological findings at autopsy. BACKGROUND: Only a limited number of cases of valve dysfunction with rapid increase of transvalvular aortic gradients or aortic insufficiency post-transcatheter aortic valve replacement (TAVR) have been described. This nonstructural valvular dysfunction has been presumed to be because of early pannus formation or thrombosis. METHODS: Through reviews of the published reports and 4 clinical cases, pathological and clinical findings of early valve thrombosis are examined to elucidate methods for recognition and identifying potential causes and treatments. RESULTS: This paper presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology cases showed presence of a valve thrombosis in at least 2 TAV leaflets on autopsy, but were not visualized by transthoracic echocardiogram or transesophageal echocardiogram. One case was medically treated with oral anti coagulation with normalization of gradients. The consequence of valve thrombosis in all 3 pathology patients either directly or indirectly played a role in their early demise. At least 18 case reports of early valve thrombosis have been published. In 12 of these cases, the early treatment with anticoagulation therapy resolved the thrombus formation and normalized aortic pressures gradients successfully. CONCLUSIONS: These 4 cases elucidate the occurrence of valve thrombosis post-TAVR. Consideration should be given to treatment with dual antiplatelet therapy and oral anticoagulation in patients post-TAVR with increasing mean pressure gradients and maximum aortic valve velocity. Further research should be conducted to create guidelines for antithrombotic therapy following TAVR procedure.