bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of impaired coupling of right ventricle to hemodynamic load in advanced HFrEF
Authors: Melenovsky V , Monzo L , Benes J , Reichenbach A , Solar N , Tupy M , Jenca D , Tykvartova T , Miklovic M , Al Hiti H , Ters J , Kautzner J
Published: October 2022

Background

The mechanisms and consequnces of impaired right ventricular (RV) dysfunction and impaired RV-pulmonary artery (PA) coupling in advanced heart failure (HF) poorely understood.

Purpose

To compare RV-PA coupling parameters in patients with advanced HFrEF, PAH and in controls to ellucidate determinants and prognostic impact of RV-PA uncoupling in HFrEF.

Methods

260 pacients with advanced HF (NYHA 3.0±0.5, 40% CAD, LVEF: 23±10%, 87% males, BMI: 28±4.5 kg/m2, BNP: 1238±982 pg/ml), 39 controls and 21 PAH patients underwent lab tests, ecocardiography, right heart catheterisation and equilibrium gated blood pool SPECT to precisely measure cardiac volumes. RV End-systolic elastance (Ees) and Effective arterial elastance (Ea) were calculated by single beat method. Patients were longitudinally followed for occurrence of adverse outcome (urgent Tx, LVAD or death without Tx/LVAD).

Results

PAH patients had higher PA pressures and more dilated RV than HFrEF and controls. Despite of that, RV-PA coupling, reflected by Ees/Ea ratio, was more profoundly reduced in HFrEF than in PAH (Figure). While RV contractility (Ees) was augmented by increased afterload in PAH, such augmentation was absent in HFrEF. At follow-up (median 258; 53–763 days), 69% of HFrEF subjects experienced adverse event (17% death, 24% urgent HTx, 28% LVAD). In HFrEF, RV-PA coupling was strongly predictive od adverse outcome, more than RV EF%, RV EDV or RV Ees. The strongest predictors of reduced RV Ees/Ea ratio in HFrEF were in descending order: RV EF, RV EDV, PA systolic/systemic systolic pressure ratio (PAs/SBP), PAWP, heart rate, PA compliance, RA mean pressure, PA mean pressure, BNP level, SBP, PAs, Tri Reg grade, Non-CAD etiology of HF, Mi Reg grade, PVR, RV dyssynchrony, absence of ACEi/ARB/S-V (GLM model, all p<0.001). RV Ees/Ea ratio correlated with PAs/SBP ratio, that reflects systolic ventricular interdependence. Invasive PAs/SBP predicted outcome and closely correlated with non-invasive estimation of PAs/SBP.

Conclusion

Despite having less PH and smaller RV, RV coupling is more impaired in HFrEF than in PAH due to absence of RV contractility enhancement. Higher RV volume, heart rate, tricuspid regurgitation, lower PA compliance, higher PAWP and systolic ventricular interdependence (PAs/SBP) are main determinants of RV PA decoupling in HFrEF. Elevated PA systolic pressure but low systemic BP (high PAs/SBP ratio) is associated with poor RV-PA coupling and prognosis.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): AZV NU20-02-00052, AZV NU21-02-00402
Cardiomyopathy associated with right ventricular apical pacing – systematic review and meta-analysis
Authors: Osiecki A , Kochman W , Witte K K , Manczak M , Olszewski R , Michalkiewicz D
Published: October 2022

Aims

Bradyarrhythmias are potentially life threatening medical conditions. The most widespread type of treatment of slow rhythms is artificial ventricular pacing. From the inception of the idea of artificial pacing, ventricular lead was located in the apex of the right ventricle. Right ventricular pacing (RVP) was thought to have deteriorating effect on left ventricular systolic function. The aim of this study was to systematically assess results of randomized controlled trials of the right ventricular pacing on left ventricular ejection fraction (LVEF).

Methods

We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases for studies evaluating the influence of the RVP on the LVEF. Pooled mean difference (MD) with a 95% confidence interval (CI) was estimated using a random effect model.

Results

15 randomized controlled trials (RCTs) comprising 951 patients were included. The mean follow-up in the included studies ranged between 6 to 24 months. In our meta-analysis, RV pacing was associated with statistically significant (MD 2.91; 95% confidence interval (CI): 1.07–4.75) left ventricular systolic function impairment measured by LVEF.

Conclusion

Our meta-analysis confirms, that the right ventricular pacing is associated with progressive deterioration of the left ventricular systolic function.

Funding Acknowledgement

Type of funding sources: None.
Baseline profile and results of atrial fibrillation ablation in patients with arrhythmia-induced cardiomyopathy
Authors: Gonzalez-Ferrero T , Minguito-Carazo C , Bergonti M , Lopez-Canoa J N , Garcia-Rodeja Arias F , Otero-Garcia O , Gonzalez-Maestro A , Martinez-Sande J L , Gonzalez-Melchor L , Garcia-Seara J , Fernandez-Lopez J A , Gonzalez-Juanatey J R , Sarkozy A , Rodriguez-Manero M
Published: October 2022

Background

Atrial fibrillation (AF) is known to trigger a reversible dilated cardiomyopathy referred as arrhythmia-induced CM (AiCM). However, it remains unclear why some patients are more prone to develop AiCM than others and there is scarce information about their clinical outcomes after AF ablation.

Purpose

We ought to find clinical and analytical predictors for the development of AiCM and recovery of LVEF in patients referred for AF ablation.

Methods

A prospective multicenter study of consecutive patients undergoing point-by-point radiofrequency (RF) catheter ablation between September 2016 and November 2021 was conducted. The low voltage areas and left atrial (LA) volume were analyzed offline on high density electroanatomical maps collected prior to RF ablation. Peripheral blood sample for biomarker analysis (Gal-3, FABP4 and sRAGE) were obtained at the time of the procedure.

Results

803 consecutive patients were included, median age was 61 and 240 (30,81%) were women. AF pattern was paroxysmal in 254 (32,60%) and persistent in 534 (68,55%; of whom, long-standing persistent in 113 (14,51%) patients). The median follow-up period was 23.83 months [IQR 9 to 36]. The multivariate analysis revealed LA area, width of QRS segment, persistent AF and chronic kidney disease (CKD) as independent predictors for AiCM. Recurrence-free survival was not different amog both cohorts (Figure 1).

The median increase in LVEF from baseline to the 6-month follow-up visit in patients with AiCM was 16% (CI 14.31–18.47) without changes in the non-AiCM group. The median LVEF previously to CA from patients in the AiCM group was 38% (IQR 30–45%) and after the procedure 57% (IQR 50–60%) [see figure 2].

Conclusions

AiCM is characterized to have a particularly complex pathophysiology not fully understood thus far. Pulmonary vein isolation in patients is safe and suitable for patients that suffered from tachycardiomyopathy. We found that persistent AF and chronic kidney disease play a key role in its development. Neither peripheral blood biomarkers nor left atrial samples showed relevant association with its occurrence.

Funding Acknowledgement

Type of funding sources: None.
Liver fibrosis might drive fibrogenesis in the heart in early alcoholic liver disease
Authors: Grander W , Grander C , Wenter C , Aysar Y , Riederer M , Zagitzer-Hofer S , Tilg H , Graziadei I , Marksteiner J
Published: October 2022

Background/Introduction

Alcohol use disorder (AUD) is associated with the development of psychiatric conditions as well as alcoholic liver disease (ALD). Ethanol toxicity but also the intestinal microbiota are important drivers of fibrogenesis in the liver and eventually also of the myocardium.

Purpose

The aim of our study was the investigation of simultaneous development of fibrosis in liver and heart in patients with early ALD.

Methods

The HALFWAY-Study is a cohort study, recruiting patients with ALD during a detoxification program. Liver stiffness was measured by non-invasive elastography (ARFI, Acoustic Radiation Force Impulse). Echocardiographic measured E/e' (early ventricle filling velocity, E / mitral annular early diastolic velocity, e') and left atrial volume (LaVol) were used as surrogate markers for atrial filling pressure, which in case of normal de-loading of the left ventricle, correlates with diastolic dysfunction.

Results

50 patients were included into the study (females n=27, males n=23). Participants were young (mean age 43.3 years ± 7.3), non-obese (body mass index; BMI 23.9 kg/m2 ±3.9) and non-diabetic (HbA1c 5.1% ± 0.3), ruling out metabolic disease. All patients displayed normal ejection fraction (EF; 61.3% ± 9.1) a global longitudinal strain (4 chamber view) of −15.03±3.7 and NTproBNP (50 pg/ml; IQR 46.5). 95% of patients reported alcohol consumption more than four times a week, with 65% drinking 7–8 drinks per day and 25% consuming more than daily 10 drinks. The mean liver stiffness was 6.5 kPa ± 4.2, whereby in 18% of participants a significant liver fibrosis was diagnosed. We could observe a significant correlation between non-invasive liver stiffness measurements (ARFI) and E/e' (p=0.019, R=0.338) as well as LaVol (p=0.043, R=0.29). In a multivariate linear regression model using ARFI, EF, LaVol and global strain as independent variables, using the backward selection method (R2=0.114, p=0.022 for the final model), we identified ARFI as the only significant predictor of E/e' (B=0,337; p=0.022).

Conclusion

In patients with early ALD liver stiffness (measured by ARFI) independently predicts E/e' which might indicate simultaneous fibrogenesis of liver and heart.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): ÖGGH
Left ventricular dysfunction in a cohort of new onset idiopathic inflammatory myopathy without known heart disease
Authors: Lindstedt M , Andreasson K , Da Silva C , Manouras A , Alexanderson H , Andersson D C
Published: October 2022

Impaired myocardial function is linked to inflammatory mechanisms. Indeed, many systemic inflammatory diseases are associated to risk of developing heart disease. Idiopathic inflammatory myopathy (IIM; here Dermato- or polymyositis) are rare systemic inflammatory diseases, characterised by immune infiltration in muscle, presence of autoantibodies and cytokines in circulation leading to weakness and disability. IIM can involve extra-muscular tissues, e.g. heart, and is associ-ated with elevated risk for cardiovascular disease. Heart function in IIM is little investigated and has mostly been studied in patients at a chronic IIM stage or with a concomitant heart disease.

To our knowledge, heart function has not been characterized at the early stage in IIM when the risk of inflammatory associated cardiomyopathy may be high. Our hypothesis is that patients at early-stage IIM may present with subclinical myocardial dysfunction that can be detected by echocardiography.

We used echocardiography (echo) following clinical standards to investigate heart function in a cohort of 18 patients (61% females; age 46±12 years) with recent onset IIM (mean diagnosis time 5 month). Patients were recruited from the rheumatology clinic at Karolinska University Hospital, Stockholm, and had given written consent. None had previous heart disease. Echo parameters were compared to normal reference limits as established by the American Society for Echocardiography. Heart failure association (HFA)-PEFF score (≥2 p) was used to define left ventricular diastolic dysfunction (LVDD).

Ejection fraction (EF) was generally preserved in the cohort with no patient displaying EF<55% (Table 1). Yet, 4 patients (22%) displayed reduced global strain (LVGLS; >−20%) suggesting presence of impaired myocardial contraction. In contrast, diastolic dysfunction was seen in several patients as indicated by one or more diastolic parameters outside normal rage (table 1). Moreover, when calculating HAVA-PEFF score 9 patients (50%) fulfilled criteria for LVDD. None of the patients displayed hypertension (>140/90 mmHg), or left ventricular hypertrophy.

In a cohort of patients with recent onset IIM without known heart disease, we have found that diastolic dysfunction is prevalent with 50% of the patients fulfilling criteria for LVDD according to the HFA-PEFF score. This gives a high likelihood of fulfilling criteria for the diagnosis heart failure with preserved EF (HFpEF). We conclude that clinical echocardiography is important in the initial work up of IIM to screen for LVDD as the risk of heart failure is likely to be high.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation
Circulating microRNA-122-5p is associated with a lack of improvement in left-ventricular function after TAVR and regulates viability of cardiomyocytes via extracellular vesicles
Authors: Hosen D R
Published: October 2022

Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis (AVS). However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Herein, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EV-miRNAs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes.

Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in aortic stenosis patients at day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=−0.264 and p=0.015) and at six months (r=−0.328 and p=0.0018) after TAVR. At the three-year follow-up, patients with a higher level of miR-122-5p displayed significantly increased cardiovascular mortality (p=0.03). By utilization of patient-derived samples and a murine aortic-stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced aortic-valve-stenotic mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocytes dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells in comparison to cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes and regulates the viability of cardiomyocytes. Mechanistically, miR pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation confirmed that miR-122-5p interacts with the RNA-binding protein, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling into recipient cells, miR-122-5p reduces the expression of the anti-apoptotic gene BCL2, by binding to its 3' untranslated region to inhibit its translation, and thereby decreasing the viability of target cardiomyocytes.

Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. Extracellular vesicular shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): German Research Foundation (DFG)German Society of Cardiology (DGK)
Optimization of biventricular cardiac resynchronization improves cardiac power and atrial kinetics in patients with systolic heart failure with often hospitalizations for decompensation
Authors: Magkas N , Xydis P , Konstantinou K , Antoniou C , Chrysohoou C , Manolakou P , Dilaveris P , Tsioufis K
Published: October 2022

Cardiac resynchronization therapy (CRT) reduces symptoms and improves left ventricular function in patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. In this work the biochemical, clinical and echocardiographic outcome of optimizing CRT (optCRT) function by the optimal VTI value of left ventricular outflow track.

Methods

80 NYHA III patients (68±10 years; 75% men; 53% ischemic cardiomyopathy-ICM), under optimal tolerated medical therapy, with standard BVP indication, having been implanted with a CRT system. Echocardiographic measurements, including aortoventricular coupling (VAC) calculation, 6-min-walking-test and quality of life (MLHF questionnaire) were measured at baseline, 6 months on optCRT. Cardiac power (CP) was calculated according the equation: CP=Cardiac Output x Mean Aortic Pressure/451.

Results

End-systolic volume of left ventricle was reduced (p=0.001) in both ischemic and non-ICM; while max left atrial volume was reduced only in non-ICM patients (72.1±32 to 65.8±30, p=0.04). Global longitudinal strain was improved in non ICM patients (p=0.015). Systolic strain of right ventricle was improved in non-ICM (9.4±2.2 to 10.7±2.3 vs. 8.7±3 to 8.9±3.2, p=0.03 for non-ICM); while left atrial function and the ratio E to E TDI of mitral annulus were not improved in either group. Non-ICM patients improved VAC (baseline: 1,36±0,3; CRT: 1.11±0.2; p=0.01) and CP (baseline 660±160 to 782±260, p=0.001); while no significant improvement was detected to ICM patients. 6-min-walk test was improved up to 30% (p=0.05). NtproBNP levels were decreased only in non-ICM patients (1759±1060.9 to 1015±650 vs. 2063,8±1800 to 1950.7±2342, p=0.001). MLHFQ improved in non-ICM patients (p=0.015); while non-significant improvement was detected in ICM patients.

Conclusion

Optimization of cardiac resynchronization therapy based on stroke volume maximization benefits quality of life and exercise tolerance, mainly in non-ICM. GLPS and aorto-ventricular coupling was improved in non-ischemic patients, reflecting the better adaptation of CRT in this population. Thus, CRT optimization by echocardiographic evaluation may be useful in improve clinical status and quality of life in CRT non-responder patients.

Funding Acknowledgement

Type of funding sources: None.
Definition of left ventricular dilation in heart failure using cardiovascular magnetic resonance: prognostic implications of end-diastolic diameter and volume assessment
Authors: Kasa Yaglici G , Teis Soley A , Aimo A , Junca Puig G , Lupon Roses J , Domingo Teixidor M , Ferrer Sistach E , Vallejo Camazon N , Lopez Ayerbe J , Cediel Calderon G , Codina Verdaguer P , Bayes Genis A , Delgado Garcia V
Published: October 2022

Background

Patients with heart failure (HF) and reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) display variable grades of left ventricular (LV) dilation. LV end-diastolic diameter (LVEDD) and volume (LVEDV) may not be concomitantly increased. The respective prognostic implications of LV dilation have not been explored.

Purpose

To assess the prognostic implications of LVEDD and LVEDV index (LVEDVi) in HFrEF/HFmrEF.

Methods

Data from consecutive HF outpatients undergoing cardiovascular magnetic resonance (CMR) and with LV ejection fraction <50% were analyzed. LVEDD was measured in a basal short axis slice. Established age- and gender-specific cut-offs for LVEDVi and a cut-off of 58 mm for LVEDD were used to define LV dilation. Patients were followed for the occurrence of the combined endpoint of cardiovascular death or HF hospitalization.

Results

A total of 564 patients (79% men, median age 65 years [56–73], ischaemic aetiology in 32%) were included. HFrEF was present in 85% of patients, and HFmrEF in 15%. Median values for LVEDD and LVEDVi were 63 mm (58–69) and 124 mL/m2 (104–149) respectively. LVEDD was significantly correlated with LVEDVi (r=0.804, p<0.001). Sixty-nine percent of patients had concomitant dilation of LV based on LVEDD and LVEDVi. In contrast, 18% of patients did not have concordant definition of LV dilation based on LVEDVi and LVEDD, including 14% with small LVEDD and large LVEDVi. LV dilation based on LVEDVi was associated with a shorter survival free from CV death or HF hospitalization (log-rank 4.6, p=0.032), while LVEDD >58 mm was not (p=0.278). There was a trend toward an independent association between LV dilation based on LVEDVi and outcome adjusting for HFrEF/HFmrEF status and ischaemic aetiology (hazard ratio 2.10, 95% confidence interval 1.00–4.41, p=0.050). An independent association was not found for LV dilation based on LVEDD. An LVEDD >66 mm was associated with increased risk of CV death or HF hospitalization on spline curve analysis (Figure 11). All patients with an LVEDD >66 mm had also LV dilation based on LVEDVi.

Conclusions

In patients with HFrEF and HFmrEF, LV dilation based on LVEDVi does not always coincide with a dilated LVEDD. The cut-off value of LVEDD associated with an excess of the combined endpoint is much larger than the value used in clinical practice. However, in patients with dilated LV based on LVEDVi, LVEDD does not add to the risk stratification.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of left ventricular contractile reserve and heart rate reserve in dilated cardiomyopathy
Authors: Ciampi Q , Cortigiani L , Zagatina A , Wierzbowska-Drabik K , Rigo F , Djordjevic-Dikic A , Amor M , Merli E , Arbucci R , Celutkiene J , Gaibazzi N , Bartolacelli Y , De Nes M , Pepi M , Picano E
Published: October 2022

Background

Stress echocardiography (SE) allows to assess simultaneously left ventricular contractile reserve (LVCR) and heart rate reserve (HRR) in dilated cardiomyopathy (DCM).

Aim

To assess the prognostic value of LVCR and HRR in DCM patients

Methods

We prospectively enrolled 395 DCM patients with ejection fraction ≤40% (age 62±27 years, 270 males, 68%; ejection fraction 35±9%) referred from 9 certified laboratories, 264 with nonischemic DCM (67%) and 131 (33%) with ischemic DCM. All patients underwent clinically indicated SE. The employed stress modality was exercise (n=63), or pharmacological stress (n=332, with vasodilator, n=232; or dobutamine, n=100). LVCR was present with a rest-stress decrease ≥0.20 in wall motion score index. HRR was normal with a peak-rest value ≥1.80 with exercise or dobutamine and ≥1.22 with dipyridamole or adenosine stress.

Results

New regional wall motion abnormality was present in 46 (12%), LVCR in 131 (33%) and abnormal HRR in 275 (70%) DCM patients. During a median follow-up of 950 days (interquartile range: 360–1187 days) 71 deaths occurred. Annual mortality was 10.5%/year in DCM patients with abnormal HRR (HRR−) and absence of LVCR (LVCR−), 5.4%/year in patients with either abnormal HRR or absent LVCR, and 2.5%/year in patients with normal HRR and presence of LVCR (Figure 1). At multivariable analysis, only abnormal HRR (HR: 2.952, 95% CI: 1.547–5.630, p=0.001) but not absence of LVCR (HR: 1.545, 95% CI: 0.929–2.568, p=0.094), was independent predictors of survival.

Conclusion

Abnormal HRR predicts adverse prognosis in DCM patients, in addition to the presence of LV CR.

Funding Acknowledgement

Type of funding sources: None.
Impact of age on the utility of CardioMEMs device to guide heart failure therapy: analysis of the National Readmissions Database
Authors: Malik A , Gupta R , Maitz T , Bandyopadhyay D , Lanier G , Briasoulis A
Published: October 2022

Background

Weeks before patients exhibit signs and symptoms of HF, intracardiac and pulmonary artery pressures increase, offering a potential target for early intervention. The CardioMEMs device is an implantable hemodynamic device placed directly into a branch of the pulmonary artery (PA) which allows remote PA pressure monitoring. The aim of our analysis is to compare outcomes of patients admitted with HF receiving implanted CardioMEMs based on their age.

Methods

Data from the National Inpatient Sample (NIS) database from 2014–2019 was used to identify hospitalizations with International Classification of diseases – 9th Revision and International classification of Diseases – 10th Revision procedural codes of patients with heart failure and CardioMEMs implantation. The outcome of interest was readmission rates at 30 days and complications associated with device implantation.

Results

We identified 1841 hospitalizations: 708 (38.5%) for patients <65 years-old (mean age 53.6) and 1,113 (60.1%) for patients >65 years-old (mean age 79.5). Gender was similar between the two age cohorts with females representing 36.6% vs 37.7% of the patients (<65 and >65 years old respectively). The cohort of patients >65 years of age had a higher rate of comorbidities including hypertension (87.9% vs 80.2%; p=0.003), prior CABG (20.3% vs 8.5%; p = <0.001), atrial fibrillation (59.2% vs 38.4%; p = <0.001), PPM (10.9%% vs 2.3%; p = <0.001), and ESRD (56.1% vs 47.3%; p=0.015. The presence of LVAD prior to device implantation was higher in the <65-year-old group at 2.8% vs 1.2% (p=0.065). Diabetes, prior PCI, PVD, pulmonary disease, anemia, cancer, and oxygen dependence were similar among the two cohorts and not statistically significant. Complications including acute kidney injury requiring dialysis, stroke, and transplant post CardioMEMs implantation were similar among the two groups. The patients who survived the index hospitalization, readmission rates were significantly improved in the cardioMEMs arm patients who were <65 years of age (13.8% vs 21.9%) compared to those 65 and above (19.6% vs 20.5%), p for interaction <0.001, Figure 1.

Conclusion

The CardioMEMS device is more effective in a younger patient population to reduce HF admissions.

Funding Acknowledgement

Type of funding sources: None.
Differences in chronic heart failure treatment between patients with and without obesity in a large real-world heart failure population
Authors: Aga Y , Radhoe S P , Aydin D , Linssen G C M , Moons A H M , Pronk A C B , Engelen D J M , Van Tooren R M , Brunner-La-Rocca H P , Dalen B M , Brugts J J
Published: October 2022

Background

Obesity is a well-established risk factor for the development of heart failure (HF). Numerous studies have demonstrated that HF patients with obesity have better prognosis and clinical outcomes compared to non-obese HF patients, a phenomenon commonly known as the obesity paradox. One of the proposed reasons for this paradox is that HF patients with obesity use more cardioprotective medication for the treatment of HF compared to HF patients without obesity. However, studies investigating treatment differences between HF patients with and without obesity are lacking.

Purpose

The aim of this study was to assess differences in HF treatment between patients with and without obesity in a large contemporary real-world cohort.

Methods

Patients with chronic HF with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry, which included chronic heart failure patients between 2013 and 2016 in 34 Dutch outpatient HF clinics. Patients were divided into those with BMI ≥30 kg/m2 and those with BMI <30 kg/m2. Detailed information on heart failure therapy prescription and dosage were recorded.

Results

A total of 7671 patients, of whom 1899 were obese (24.8%), were included in this analysis. Patients with obesity were younger, more often female and in NYHA class III/IV, and hypertension and diabetes were more prevalent in the obesity group. HF patients with obesity more often received beta-blockers (83.1% vs. 79.6%, p=0.001), renin-angiotensin system (RAS) inhibitors (84.8% vs. 80.8%, p<0.001), mineralocorticoid receptor antagonists (MRAs) (56.9% vs. 51.5%, p<0.001), and diuretics (87.4% vs. 82.8%, p<0.001) compared to HF patients without obesity. Furthermore, guideline-recommended doses of beta-blockers (23.5% vs. 16.4%, p<0.001), RAS-inhibitors (51.5% vs. 40.9%, p<0.001), and MRAs (57.9% vs. 49.2%, p<0.001) were significantly more often prescribed in patients with obesity (Figure 1). In multivariable logistic regression analysis, obesity was significantly associated with a higher likelihood to receive beta-blockers (OR 1.18 (1.02–1.38)), RAS-inhibitors (OR 1.25 (1.06–1.47)), MRAs (OR 1.15 (1.02–1.29)), and diuretics (OR 1.59 (1.34–1.89)).

Conclusion

In this large real-world HF registry, guideline recommended HF drugs were more frequently prescribed and at higher dose in patients with obesity as compared to HF patients without obesity.

Funding Acknowledgement

Type of funding sources: None.
Effects of sacubitril-valsartan on clinical, echocardiographic and polygraphic parameters in patients affected by heart failure with reduced ejection fraction and sleep apnea
Authors: Armentaro G , Pelaia C , Volpentesta M , Mancuso L , Cassano V , Severini G , Pastura C A , Francica M , Barbara K , Miceli S , Maio R , Caroleo B , Perticone M , Sesti G , Sciacqua A
Published: October 2022

Background

Heart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity.

Purpose

The aim of this work is to evaluate the effects of a 6-month therapy with sac/val on hemodynamic and metabolic parameters, as well as on the occurrence of apnea/hypopnea and oxygen saturation in patients with HFrEF and SA, already treated with CPAP.

Methods

We recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 hours before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val.

Results

After 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p<0.0001), central AHI (p<0.0001), obstructive AHI (p<0.0001), oxygen desaturation index (ODI) (p<0.0001), and percentage time of saturation below 90% (TC90) (p<0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP and tricuspid annular plane excursion (TAPSE) contributed to 23.6%, 7.6%, 7.3% and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation.

Conclusions

Our results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA.

Funding Acknowledgement

Type of funding sources: None.
Predictors of ICU admission in patients with peripartum cardiomyopathy
Authors: Shahin O , Shahin H , Heineke H , Biswas M
Published: October 2022

Background

Peripartum cardiomyopathy (PPCM) is a dilated cardiomyopathy that affects women in the peripartum period. The incidence of PPCM in the United States is 1,100 women per year. We studied the admission of women diagnosed with PPCM to the intensive care unit (ICU) with the goal of identifying factors that increase risk for adverse outcomes.

Methods

This was a retrospective study of 2,286 patients with a diagnosis of PPCM admitted to a private hospital system across the United States between the years 2017 and 2021. Logistical regression analysis was utilized to identify specific patient characteristics and risk factors that were associated with admission to the ICU.

Results

The average age of patients was 32.13 years. The patient cohort was 39.76% black, 39.15% white, and 13.12% Hispanic. The average length of stay was 3.35 days. Preeclampsia was present in 342 (14.96%) patients, cerebral infarction in 31 (1.36%) patients, eclampsia in 48 (2.10%) patients, myocardial infarction (MI) in 52 (2.27%) patients, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in 24 (1.05%) patients. There was a total of 504 (22.05%) patients admitted to the ICU. Preeclampsia (adjusted odds ratio [adj. OR] 1.588, 95% confidence interval [CI] 1.215–2.074, p<0.001), eclampsia (adj. OR 3.131, 95% CI 1.718–5.708, p<0.001), cerebral infarction (adj. OR 4.381, 95% CI 2.028–9.463, p<0.001), age (adj. OR 0.967, 95% CI 0.953–0.982, p<0.001), MI (adj. OR 2.961, 95% CI 1.608–5.455, p<0.001), and HELLP syndrome (adj. OR 4.655, 95% CI 1.926–11.256, p<0.001) were all associated with increased odds of requiring ICU level of care. However, hypertension, d-dimer level, troponin level, active tobacco smoking, alcohol use, and diabetes mellitus were not associated with increased likelihood of admission to the ICU.

Conclusion

In our study of 2,286 women with PPCM, we found statistically significant predictors of ICU admission included age, HELLP syndrome, eclampsia, preeclampsia, MI, and cerebral infarction. This data may be useful for the early identification and triaging of patients with PPCM that require higher level of care. These results can be utilized in developing a risk score to assist in this goal.

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): HCA-Riverside Community Hospital
The comparison of composite end-points between SGLT-2 inhibitors and placebo in diabetic patients with heart failure with mildly reduced ejection fraction: a meta-analysis of the literature
Authors: Saylik F , Cinar T , Selcuk M , Cicek V , Hayiroglu M I , Orhan A L
Published: October 2022

Background

Sodium–glucose cotransporter 2 (SGLT-2) inhibitors have been found to decrease the incidence and progression of heart failure (HF) with reduced ejection fraction (EF). In the classification of HF, there is a gray zone between HF with reduced EF (EF <40%) and HF with preserved EF (EF >50%), which is named as HF with mildly reduced EF (EF between 40–50%). The effect of SGLT-2 inhibitors in mildly reduced EF HF patients have not yet been well established. We aimed to compare the composite outcomes, including cardiac death and re-hospitalization, between SGLT-2 inhibitors and placebo in this meta-analysis.

Methods

We searched MEDLINE, Scopus, EMBASE, Google Scholar, and the Cochrane Library for eligible studies. Of 167 eligible studies, three studies that compared the outcomes between SGLT-2 inhibitors and placebo in mildly reduced EF HF diabetic patients were included in this meta-analysis (n=928) (Table 1). Heterogeneity was assessed using High's I2, Egger's test and prediction intervals. The pooled effect size was calculated with a fixed-effect model. Due to the total number of studies was lower than 10, we did not report publication bias by drawing Funnel plot.

Results

Two studies were randomized controlled trial compared Sotagliflozin and placebo, and one study was an observational study with propensity score matched that compared SGLT-2 inhibitors with placebo. Patients using SGLT-2 inhibitors had lower primary composite end-points, such as cardiac death and re-hospitalization, than patients using placebo (HR= 0.69, 95% confidence intervals = 0.49–0.98, p value = 0.03) (Figure 1). There was no heterogeneity between studies, which was determined with High's I2 (0%) and Egger's test (p>0.05). Prediction interval was detected as a relatively wide that ranged between 0.30 and 1.58, which concluded that it could be expected to get the results within this range in future studies.

Conclusion

This meta-analysis indicated that the composite outcomes, including cardiac death and re-hospitalization, were lower in mildly reduced EF HF diabetic patients using SGLT-2 inhibitors when compared to placebo in such patients.

Funding Acknowledgement

Type of funding sources: None.
Heart failure with mildly reduced ejection fraction: not a mid-range prognosis
Authors: Borges-Rosa J , Almeida J P L , Martinho S , Marques-Alves P , Oliveira-Santos M , Goncalves L
Published: October 2022

Introduction

Heart failure with mildly reduced ejection fraction (HFmrEF) has been recognized in the last heart failure guidelines of the European Society of Cardiology, replacing the concept of “midrange ejection fraction”. There is limited data regarding mortality outcomes of HFmrEF compared to heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction.

Purpose

We aimed to evaluate whether HFmrEF has a different prognosis after an acute heart failure (AHF) episode, in a real-world contemporaneous southern European population.

Methods

We retrospectively studied 1026 patients admitted to our emergency department between November 2016 and December 2017 with discharge diagnosis of AHF. Median follow up was 5 months (IQR 3–11 months). Incidence of rehospitalization, cardiovascular (CV) and all-cause mortality were evaluated through multivariable logistic regression models and by Kaplan-Meyer survival curves.

Results

From all patients, 782 were categorized in HFrEF (34.1%), HFmrEF (19.4%) and HFpEF (46.4%). There was heterogeneity between groups. Compared to HFrEF, HFmrEF patients were older (80 [74–84] vs. 76 [67–82] years, p<0.001), with lower prevalence of males (61.2% vs. 76.4%, p=0.004) and coronary artery disease (CAD) (35.5% vs. 47.6%, p=0.024), but higher rates of valvular heart disease (VHD) (48.0% vs. 29.6%, p<0.001). Compared to HFpEF, HFmrEF subjects had higher prevalence of males (61.2% vs. 40.8%, p<0.001) and CAD (35.5% vs. 13.2%, p<0.001). At admission, patients with HFmrEF and HFrEF had similar serum creatinine e B-type natriuretic peptide values, but higher than the HFpEF group: 1.38±0.7 vs. 1.45±0.7 vs. 1.28±0.8mg/dL, p=0.019 and 701 [385–1191] vs. 1000 [494–1776] vs. 360 [214–717]pg/mL, p<0.001, respectively. HFmrEF patients had higher rates of hospitalization (71.7% vs. 43.8%, p<0.001), follow-up readmissions (27.6% vs. 18.7%, p=0.034), CV (11.8% vs. 5.0%, p=0.025) and all-cause mortality (25.7% vs. 14.9%, p=0.015), compared to HFpEF; no differences comparatively to HFrEF. There was no difference between groups regarding the length of hospitalization (9 [5–15] vs. 8 [5–15] vs. 10 [6–17] days, p=0.302). In multivariate logistic regression model adjusted for age, sex, SBP, CAD, VHD, creatinine, and BNP, HFmrEF increased the risk of CV (OR 2.9, 95% CI 1.2–6.7, p=0.016) and all-cause mortality (OR 2.1, 95% CI 1.2–3.9, p=0.011), but not follow-up readmissions (OR 1.7, 95% CI 0.9–2.9, p=0.059). Kaplan-Meier estimates of CV, and all-cause mortality are shown in Figure 1.

Conclusions

HFmrEF have a similar prognosis to HFrEF and worse than HFpEF, with more readmissions, CV and all-cause mortality, after an AHF episode.

Funding Acknowledgement

Type of funding sources: None.
Association between use of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors and beta-blockers and outcome in real-world heart failure and mildly reduced ejection fraction
Authors: Stolfo D , Lindberg F , Lund L , Sinagra G , Dahlstrom U , Rosano G , Savarese G
Published: October 2022

Background

In heart failure with mildly reduced ejection fraction (HFmrEF) European guidelines recommend the use of antineurohormonal therapies with a low level of evidence (IIb C) based on data from subgroup and post-hoc analyses of randomized clinical trials (RCTs). Data from large and unselected real-world HFmrEF populations are lacking.

Purpose

To assess the association between renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers and outcomes in HFmrEF.

Methods

Data from patients with HFmrEF (EF: 40–49%) from the Swedish HF Registry during 2000–2018 were considered. The association between each of RASI/ARNI and beta-blockers treatment and cardiovascular (CV)mortality/heart failure hospitalization (HFH) and all-cause mortality was assessed by Cox proportional hazard models in a 1:1 propensity score-matched cohort. Since propensity score (PS) matching might lead to a selection of the study population and reduction of the sample size, as consistency analysis Cox proportional hazard models were also fitted in the overall cohort adjusting rather than matching for PS.

Results

Of 12421 patients with HFmrEF (mean age 74±12 years, 64% males), 10419 (84%) received RASI/ARNI, 10941 (88%) received beta-blockers. Patients treated with both RASI/ARNI and beta-blockers were 9332 (75%), 2696 (22%) patients received one drug (9% RASI/ARNI, 13% beta-blockers) and 393 (3%) none. Main predictors of treatments use were younger age, female sex (only for beta-blockers), outpatient setting, referral to specialty care and nurse-led HF clinic. Lower NT-proBNP levels were associated with more use of RASI/ARNI but less use of beta-blockers. Better renal function was predictive of RASI/ARNI use. Comorbidities were associated with less use of treatments, in particular atrial fibrillation for RASI/ARNI, and COPD for RASI/ARNI and beta-blockers. In the matched cohorts including 3854 for RASI/ARNI analyses and 2940 patients for beta-blockers, RASI/ARNI (HR=0.90, 95% CI: 0.83–0.97) and beta-blocker (HR=0.82, 95% CI: 0.75–0.91) use were associated with a statistically significant lower risk of CV mortality/HF hospitalization (Figure 1) and of all-cause mortality (HR=0.72, 95% CI: 0.67–0.78 and HR=0.77, 95% CI: 0.70–0.85, respectively). Consistency analysis confirmed results.

Conclusions

RASI/ARNI and beta-blockers were largely used in this large real-world cohort of patients with HFmrEF to treat comorbidities. Their use was associated with lower risk of mortality/morbidity and the magnitude of the associations was somehow similar to what observed in subgroup/post-hoc analyses of RCTs. Our findings call for a fast implementation of guidelines recommendations on HFmrEF treatment.

Funding Acknowledgement

Type of funding sources: None.
Exercise oscillatory ventilation disturbances: finding order amongst chaos
Authors: Lopes Da Cunha G J , Rocha B , Rocha B , Maltes S , Maltes S , Freitas P , Freitas P , Gama F , Gama F , Andrade M J , Andrade M J , Aguiar C , Aguiar C , Moreno L , Moreno L , Durazzo A , Durazzo A , Mendes M , Mendes M
Published: October 2022

Background

Exercise Oscillatory Ventilation (EOV) during Cardiopulmonary Exercise Test (CPET) predicts prognosis in patients with Heart Failure (HF). In these patients, O2 consumption (VO2) oscillations have also been described, possibly secondary to circulatory delay. We hypothesize that in clinically meaningful EOV, cardiac output variation is mirrored by VO2 oscillation, which is then chronologically followed by a similar oscillation in minute ventilation (VE) (Figure 1). Accordingly, we aimed to assess whether this new definition surpassed that of classical EOV.

Methods

This is a single-centre cohort study of consecutive patients undergoing CPET from 2016 to 2018. Patients with LVEF >50% were excluded. CPET was performed on a treadmill to the limit of tolerance. Data was collected as a rolling average of 20 seconds and a composite VE/time and VO2/time plot was created. Classical EOV was defined as three or more regular oscillations of the VE graph with a minimal average amplitude of five litters. The addition of exercise VO2-to-VE peak-to-peak ventilation asynchrony (EVA) to the previous criteria fulfilled the new definition. The primary endpoint was a composite of time to all-cause death, heart transplantation or HF hospitalization.

Results

Overall, 177 patients were enrolled (mean age 58±11 years, LVEF 34±9%), of whom 35 had EOV and 17 had EVA. Compared to those without EVA, patients with EVA had markers of more severe HF. During a median follow-up of 32 (21–42) months, 55 patients met the primary outcome (32 all-cause deaths, 15 heart transplants, 47 HF hospitalizations). In multivariate analysis, EVA was associated with a 2.5-fold increased risk of events (HR 2.489; 95% CI: 1.302–4.759; p=0.006), adjusted for peak VO2, VE to CO2 production ratio (VE/VCO2 slope) and LVEF. EVA outperformed EOV in predicting the primary endpoint at 1 year, with a similar sensitivity and higher specificity (96.2 vs. 83.2%). The rate of events between the subgroup of patients without EVA was similar regardless of presence of EOV, contrasting with a higher rate in the EVA subgroup (Figure 2).

Conclusion

EVA is a strong predictor of hard outcomes in a broad population with HF. The new definition may outperform that of classical EOV. The incidence and prognostic value of EVA in the management algorithm and risk stratification of patients with HF is worth being further explored.

Funding Acknowledgement

Type of funding sources: None.
A new cardiopulmonary exercise testing score for predicting heart failure events
Authors: Dias Ferreira Reis J P , Bras P , Goncalves A , Moreira R , Pereira Silva T , Timoteo A , Cruz Ferreira R
Published: October 2022

Background

Cardiopulmonary exercise test (CPET) provides several variables (V) that are strong predictors of events in patients (pts) with heart failure (HF).

Purpose

Our aim was to develop and evaluate the predictive power (PP) of a CPET-based score, comparing to that of the Heart Failure Survival Score – HFSS.

Methods

Retrospective evaluation of adult pts with HF submitted to CPET in a tertiary center. Pts were followed up for at least 1 year for the primary endpoint of cardiac death and urgent heart transplantation/ ventricular assist device implantation (MTV). The PP of several CPET V's was assessed using ROC curve analysis, which was used to define optimal threshold values for each V. A multiple regression analysis was performed to identify independent prognostic predictors and to determine the regression coefficient (β) for the Vs included in the model, each expressed dichotomously using the threshold value. According to β, a weight was assigned to each V and summed to calculate the composite score. ROC curves were compared using the Hanley and McNeil test.

Results

CPET was performed in 487 HF pts, with a mean age of 56±13 years, 79% were male. 46% of pts were of ischemic etiology, with a mean LVEF of 30±8%, a mean HFSS of 8.6±1.1 and a mean BNP value of 509±668pg/ml. The mortality rate during a mean follow-up of 21 months, was 19% (93pts) with 23 pts (5%) undergoing HT. The primary endpoint was reached by 55 (11%) pts. The variables with higher predictive power were OUES (AUC 0.796), ventilatory power (AUC 0.790), the partial pressure of end-tidal CO2 at the anaerobic threshold (PETCO2L – AUC of 0.787), the pVO2 (AUC 0.767) and heart rhythm (HR) during the test (AUC – 0.640). LVEF also presented a high predictive power with AUC of 0.755. The multivariate analysis revealed that pVO2, PETCO2L, AF, and LVEF were independent prognostic predictors. According to the β of these Vs, the equation was calculated as follows: (pVO2 × 2.194) + (PETCO2L × 1.545) + (LVEF × 1.134) + (HR × 1.055; 0 if AF, 1 if sinus rhythm). The score presented a high PP with an AUC of 0.866. A cut-off of 120 had an 83.6% sensitivity and a 75% specificity for MTV, and pts with a score value of <120 had a markedly lower rate of MTV (log-rank p<0.001). When compared to HFSS, our score presented a higher PP (0.866 vs 0.774, p=0.011).

Conclusion

A multivariable score based on readily available CPET Vs provides a simple, integrated and powerful method to predict HF events.

Funding Acknowledgement

Type of funding sources: None.