bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved heart failure screening and prevention in type 2 diabetes mellitus by cardiologist in rural areas
Authors: Klabnik A , Murin J
Published: November 2023

Purpose

Guidelines recommend screening in type 2 diabetes mellitus (T2DM) for unrecognised asymptomatic left ventricular systolic dysfunction (LVSD), reduced (HFrEF), mid-range (HFmrEF) or preserved (HFpEF) heart failure (HF) with periodic evaluation of natriuretic peptides (NTproBNP) or echocardiography (echo). Tissue doppler and speckle-tracking echo may be needed to facilitate HF diagnosis at earlier, more treatable stage.

Methods

2185 consecutive asymptomatic T2DM (age 62 ±4 years, 62% women) patients (pts) were referred from January 2015 by rural diabetologists (dia) to echolab with elevated NTproBNP (>125 pg/mL) or 5-year HF risk score WATCH-DM ≥14 points.

After exclusion of abnormal electrocardiogram or chest x-ray and significant valvular heart disease was compared continued usual care by diabetologist with randomly assigned prospective follow-up by regional cardiologist.

Results

At referral in both groups were similar baseline characteristics, 20% pts were treated with ACE-inhibitor (ACEi), 2% beta-blockers (BB). After cardiologist consultation ACEi and BB use increased significantly to 96% and 84% in both groups (all p <0.001).

Global LVSD (EF≤50%) was detected in 8% at baseline and 29% pts after 5 years in diabetologist group, respectively 9% at baseline and 13% after 5 years in cardiologist group (p <0.001).

Systolic dysfunction (S’≤6.0 cm/s) occured in 20% at baseline and 41% pts after 5 years in dia group, respectively 19% at baseline and 24% after 5 years in cardiologist group (p <0.001).

Reduced global longitudinal (GLS<16%) observed in 26% at baseline and 59% pts after 5 years in dia group, respectively 26% at baseline and 36% after 5 years in cardiologist group (p <0.001).

At baseline we found 1% pts with new-onset HF in both groups (only HFmrEF). After mean follow-up of 54 ±7 months in cardiologist group developed new HF in 4% pts (2% HFmrEF, 2% HFpEF) compared with 25% pts (3% HFrEF, 7% HFmrEF, 15% HFpEF) in diabetologist group (p <0.001).

Significant (p <0.001) predictors of incident HFmrEF were systolic dysfunction (S’≤6.0 cm/s), hazard ratio (HR) 3.6, 95% CI 2.96-4.2) and reduced GLS (HR 4.6, 95% CI 3.8-5.2), all p <0.01.

The strongest (p <0.001) predictors of incident HFpEF were new-onset atrial fibrillation (HR 2.5, 95% CI 1.2-3.7) and echo-detected left ventricular hypertrophy (septal and posterior wall thickness ≥13 mm, HR 1.7, 95% CI 1.2-2.1), all p <0.01.

Conclusions

For preventing HF progression is required additional research focused on cooperative care between diabetologists and specialised HF outpatient clinic.
Circulating beta-hydroxybutyrate levels in advanced HFrEF: the determinants and prognostic impact
Authors: Melenovsky V , Benes J , Monzo L , Kotrc M , Reichenbach A , Jurcova I , Kovar J , Jarolim P , Kautzner J
Published: November 2023

Background

Beta-hydroxybutyrate (BOHB) is the main ketone body and is generated mainly in the liver during states of exessive fatty acid (FA) utilisation, such as starvation or diabetic ketosis. BOHB serves as a metabolic substrate to heart. Mild ketosis or enahancement of BOHB utilisation may favorably affect cardiac function in preclinical HF models. Patients with HF have increased BOHB levels, but regulation of ketosis in HF is poorly understood.

Purpose

To investigate the determinants and prognostic implact of circulating BOHB levels in patients with advanced HFrEF.

Methods

We examined 847 pts with symptomatic HFrEF (age 57±11y, 50% CAD, 82% males, NYHA 2.7±0.6, LVEF 22±5%, BNP 802±850 pg/ml), referred to IKEM for TX or device (ICD/CRT/LVAD) implant. Patients underwent clinical and echocardiographic examination, MLHFQ questionnaire, circulating metabolite assessment, body composition (DEXA, n=150) and right heart catheterisation (n=383). BOHB in peripheral vein was measured in all subjects after overnight fasting by an enzymatic metod (Autokit 3-HB, Wako). Patients were followed for occurrence of an event (death/urgent Tx/LVAD).

Results

Median BOHB level was 64 (IQR: 33-161) mmol/l. BOHB was higher in DM patients (111 vs 163, <0.001) and inreased with age. Body composition, congestion status, insulin resistance (HOMA-IR), liver function tests, weight loss history, HF symptoms (NYHA, MLHFQ), gender, HF etiology or HF therapy (BB, ACE/ARB) were unrelated to BOHB levels. BOHB strongly correlated with markers of lipolysis (free FA, BNP) and GDF15, less strongly with pulmonary hypertension (PA systolic pressure, pulmonary vascular resistance-PVR), inflammation (CRP level, leukocytes%) and humoral regulators of ketogenesis in the liver (insulin/glucagon ratio). After median follow-up of 1126 days (IQR: 410; 1781), 60% patients experienced an event. In Cox analysis, Increased BOHB levels predicted worse survival (RR: 1.001, 95%CI: 1.0005-1.001, p<0.0001), particularly in the upper BOHB tercile. Impaired survival was also associated with elevated free FA (RR: 1.78 (1.23-2.51, p= 0.002). In bivariate Cox analysis of free FA and BOHB levels, only free FA, but not BOHB, remained significantly asccociated with adverse outcome.

Conclusion

Increased BOHB levels in HFrEF correlate with free FA levels, likely due to sympatetic activation-driven and BNP-driven lipolysis. The association of increased BOHB with adverse outcome dissapears after adjustment to free FA level. Other notable associations of BOHB were diabetic status, GDF15 level, systemic inflammation and pulmonary hypertension.
The prognostic value of right ventricular longitudinal strain in predicting incident atrial fibrillation and ischemic stroke in the general population
Authors: Saed Alhakak A , Hauser R , Skaarup K G , Lassen M C H , Johansen N D , Jensen G B , Schnohr P , Mogelvang R , Biering-Sorensen T
Published: November 2023

Background

Right ventricular (RV) longitudinal strain (RVLS) is a predictor of many cardiovascular outcomes including ventricular arrhythmias. However, the prognostic value of RVLS in predicting incident atrial fibrillation (AF) in participants from the general population is currently unknown.

Purpose

The aim of this study was to investigate if RVLS can be used to predict AF and ischemic stroke in the general population.

Methods

A total of 2794 participants (mean age 54±17 years, 42% male) from the general population underwent a health examination including two-dimensional speckle tracking echocardiography. RVLS was measured in the apical four-chamber projection optimized for a view of the RV. The RV free wall was divided into three segments, and the strain values of the three segments were averaged to obtain RVLS.

The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n=175). The secondary endpoint consisted of the composite of AF and ischemic stroke.

Results

During a median follow-up of 5 years (interquartile range, 4.5-6.2 years), 110 participants (4%) were diagnosed with incident AF and 59 (2%) experienced an ischemic stroke, resulting in 169 (6%) experiencing the composite outcome. The risk of AF increased incrementally with decreasing tertile of RVLS, being approximately 3-fold higher in the 1st tertile as compared to the 3rd tertile (HR 2.71; 95% CI (1.64-4.46), p<0.001; figure).

RVLS was a univariable predictor of AF with 9% increased risk per 1% decrease in RVLS (per 1% decrease: HR 1.09; 95% CI (1.06-1.13), p<0.001). The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 1% decrease: HR 1.06; 95% CI (1.01-1.11), p=0.015).

RVLS was also a univariable predictor of the composite outcome of AF and ischemic stroke (per 1% decrease: HR 1.08; 95% CI (1.05-1.12), p<0.001). After multivariable adjustment for the same clinical and echocardiographic parameters, RVLS remained an independent predictor of the composite outcome (per 1% decrease: HR 1.04; 95% CI (1.00-1.09), p=0.032)

Additionally, RVLS provided incremental prognostic information with regard to predicting AF as assessed by a significant increase in the net reclassification improvement (NRI) index beyond the CHARGE-AF score (continuous NRI, 0.232; 95% CI, 0.011-0.570).

Conclusion

In a low-risk general population, RVLS provides novel prognostic information on the long-term risk of AF and ischemic stroke. In addition, RVLS provides incremental prognostic information beyond the CHARGE-AF score in predicting AF in the general population.
Exosomal preconditioning of human iPSC-derived cardiomyocytes beneficially alter cardiac electrophysiology during hypoxia
Authors: Rosand O , Scrimgeour N , Marwarha G , Hoydal M
Published: November 2023

Introduction and purpose

Cardiac-Exosomes (EXO) are nano-sized extracellular vesicles, continuously secreted by the myocardium. Despite previous misconceptions, cardiac-EXO are not just a way for the cell to dispatch waste, but functions as carriers of signaling molecules. Furthermore, the effects of cardiac-EXO signaling during hypoxic stress is not well understood. The present study aimed to determine the biological effects of EXO released from hypoxic cardiomyocytes, focusing on whether the EXO-cargo can benefit recipient cells during hypoxic stress. We hypothesize that cardiomyocytes exposed to hypoxic stress would display advantageous electrophysiological properties after preconditional treatment with isolated cardiac-EXO secreted from cardiomyocytes exposed to hypoxic stress.

Methods

For preconditional treatment we isolated EXO from human iPSC-derived cardiomyocytes (CM) exposed to hypoxia (1% O2) for 16 h (H-EXO). H-EXO was thereafter administrated as preconditional treatment to a secondary population of CM 24 h before subjection to 16 h of hypoxia. Electrophysiological effects of H-EXO precondition treatment were assessed with a multiwell microelectrode array (MEA) system. Using the MEA-system; field potential, beat period, spike slope, spike amplitude, excitation-contraction (EC) coupling, and cardiac action potentials were recorded and analyzed.

Results

We found that CM exposed to hypoxic stress conditions (16 hours) displayed significant increase in beat period when preconditioned with H-EXO compared to non-treated CM (+15.7%, p<0.05). Furthermore, precondition with H-EXO resulted in faster EC coupling compared with non-treated CM after 16 h of hypoxia (-25.3%, p<0.05). More efficient EC coupling indicates that the H-EXO recipient cells are less affected by the hypoxic stress. There were no significant changes in field potential, spike slope, spike amplitude and cardiac action potential between the two groups after 16 h of hypoxia.

Conclusion

The present study report that EXO secreted by CM under hypoxia alter electrophysiological properties in recipient cells exposed to 16 h hypoxic stress. The alterations indicate more efficient cardiomyocyte EC coupling and longer beat period.
Right ventricular uncoupling in heart failure with preserved ejection fraction: a simple parameter to predict long-term mortality?
Authors: Burgos L , Campos Cevera L , De Bortoli A , Ballari F , Spaccavento A , Baro Vila R , Ricciardi B , Fasan M , Suarez L , Chicote F , Diez M
Published: November 2023

Introduction

Several prognostic models have been developed for risk stratification of mortality in patients with acute heart failure (AHF). eRecent evidence suggests that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcomes in heart failure. Patients with heart failure and preserved ejection fraction (HFpEF) are a heterogeneous population with a wide range of clinical outcomes. However, the prognostic utility of RV-PA uncoupling for predicting long-term mortality in these patients remains elusive.

Objective

To assess the prognostic value of right ventricle-pulmonary artery coupling for long-term mortality in hospitalized patients with HFpEF.

Methods

Retrospective analysis of a consecutive, prospective, single-center cohort. Adult patients hospitalized between 2015 and 2020 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) >40% were included. The primary endpoint was long-term all-cause mortality. Ventricular uncoupling was assessed as the ratio of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) estimated from an echocardiogram performed within 3 months of the index hospitalization. Univariable Cox proportional hazards regression models were used to calculate hazard ratios (HR), and multivariable Cox regression was performed with previously analyzed covariates: age, sex, atrial fibrillation, renal dysfunction and E/e'.

Results

Of 465 patients with HFpEF, 361 (77%) PASP and TAPSE could be estimated simultaneously. During a mean follow-up of 20.9 months, the primary outcome event occurred in 100 patients (27.7%). The optimal cut-off for the primary endpoint was TAPSE/PASP=0.38. Univariable Cox regression showed that RV-PA uncoupling was associated with the primary endpoint of long-term mortality (hazard ratio [HR] 1.96 [95% CI, 1.32-2.92], P=0.001). Kaplan-Meier analysis showed that patients with a ratio <0.38 were at high risk of all-cause mortality (Figure 1). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with long term mortality independent of age, sex, atrial fibrillation, renal dysfunction and E/e' (HR 2.21 [95% CI, 1.26-3.81], P=0.005).

Conclusions

In patients hospitalized for AHF with preserved ejection fraction, RV-PA uncoupling as determined by the TAPSE/PASP ratio was independently associated with long-term all-cause mortality. TAPSE/PASP was associated with mortality independently of age, sex, renal function, atrial fibrillation and diastolic dysfunction. This simple echocardiographic parameter may identify a population at higher risk for events during follow-up.Kaplan-Meier for all-cause mortality
In-hospital Prognostic Value of TAPSE/sPAP in Patients Hospitalized for Acute Heart Failure
Authors: Fauvel C , Pezel T , Rossanaly Vasram R , Charbonnel C , Bouleti C , Logeart D , Roubille F , Meune C , Nhan P , Ohlmann P , Bonnefoy-Cudraz E , Albert F , Andrieu S , Dillinger J G , Henry P
Published: November 2023

Background

Tricuspid annular plane systolic excursion over systolic pulmonary artery pressure (TAPSE/sPAP) assessed by echocardiography appears to be a good noninvasive approach for right ventricular to pulmonary artery coupling assessment. Yet, the in-hospital prognostic value of TAPSE/sPAP in patients hospitalized for acute heart failure (AHF) has never been explored.

Purpose

To assess TAPSE/sPAP prognostic value among patients hospitalized for AHF.

Methods

All consecutive major patients hospitalized for AHF across 39 French cardiology department, with TAPSE/sPAP measured by echocardiography within the 24 first hours of hospitalization were included in this prospective study. The primary outcome was in-hospital major cardiac adverse events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock.

Results

Three hundred and thirty-three patients with both AHF and TAPSE/sPAP measurement were included (mean age 68±14 years, 70% of male, 40% HFpEF, 18% HFmrEF, 42% HFrEF). In-hospital MACEs occurred in 50 (15%) of the patients. Using receiver operating characteristics curves analysis, the best threshold for in-hospital MACEs was 0.40 mm/mmHg. Patients with TAPSE/sPAP <0.40 mm/mmHg had more frequently atrial fibrillation (p=0.024), chronic kidney disease (p=0.001), higher NTproBNP level (p<0.001), and worse left and right ventricular function (p<0.01). TAPSE/sPAP <0.40 mm/mmHg was independently associated with in-hospital MACEs, even after adjustment with comorbidities (OR=3.75, 95%CI[1.87-7.93], p<0.001), clinical severity (OR=2.80, 95%CI[1.36-5.95], p=0.006), or using a propensity matched population analysis (OR=2.98, 95%CI[1.53-6.12], p=0.002, figure 1). Finally, TAPSE/sPAP showed incremental prognostic value for in-hospital MACEs over traditional risk factors, including left ventricular ejection fraction (figure 2).

Conclusion

Emphasizing the prognostic value of TAPSE/sPAP <0.40 mm/mmHg for in-hospital MACEs, over traditional risk factors, these results suggest embedding this parameter into clinical decision-making and risk stratification in patients hospitalized for AHF.
Validation of a new CPET multivariable score to predict cardiovascular events in heart failure patients
Authors: Borges-Rosa J , Fernandes R , Ar G O M E S , Campos G O , Monteiro E , Almeida Fernandes D , Ferraz Costa G , Guimaraes J , Milner J , Oliveira-Santos M , Goncalves L
Published: November 2023

Introduction

Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Recently, a new multivariable score (MVS) was proposed as a powerful method to predict HF events with an optimal cut-off value of 120.

Purpose

We aimed to evaluate the prognostic value of this tool in patients with HF.

Methods

We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), partial pressure of end-tidal CO2 at the anaerobic threshold (PETCO2L), circulatory power (CP=pVO2 x peak SBP), and ventilatory power (VP=peak SBP/(VE/VCO2) slope). The score was calculated as follows: (pVO2 × 2.194) + (PETCO2L × 1.545) + (LVEF × 1.134) + (HR × 1.055; 0 if AF, 1 if sinus rhythm). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality.

Results

We included 212 patients 76.9% male and with a mean age of 55.4±10.9 years-old. The most frequent aetiology was dilated cardiomyopathy (43.9%) followed by ischaemic heart disease (38.7%). Accordingly, the mean left ventricle ejection fraction was 29±13%. Additionally, 39.8% had atrial fibrillation. The most used exercise protocol was the modified Naughton (76.6%). Mean pVO2 was 16.7±5.9mL O2·kg−1·min−1, median VE/VCO2 slope was 37.5 [32.7-44.3], and PETCO2L 33.5±5.2mmHg. Mean VP was 3.46±1.31mmHg while the median CP was 1927 [1427-2697]mmHg·min/mL/kg. The mean MVS was 116.2±23.1. Despite weak, there were significant positive correlations between the MVS and both VP (r=0.59, p<0.01) and CP (rs=0.64, p<0.01). After a median follow-up of 71 [49-81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). The new CPET MVS was associated with the primary outcome (p<0.01). Additionally, patients with MVS <120 had a higher rate of the primary outcome (83.2% vs. 39.1%, p<0.01). Kaplan-Meier estimates of tthe primary outcome according to the optimal cut-off value of 120 are shown in Figure 1A. Receiver operating characteristic curve revealed that the MVS has higher discriminative power for the primary endpoint (AUC 0.80, p<0.01) compared to pVVO2, VP, and CP (Figure 1B).

Conclusion

The novel multivariable score is associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification.
Clinical characteristics of patients with cardiac sarcoidosis who were hospitalized for heart failure
Authors: Sakamoto T , Kitai T , Yoshii T , Yaku H , Kato T , Nakagawa S , Irie Y , Moriuchi K , Amano M , Amaki M , Kanzaki H , Kimura T , Izumi C
Published: November 2023

Background

Cardiac sarcoidosis (CS) often leads cardiac dysfunction and exacerbates heart failure. However, there are limited data regarding CS patients who were hospitalized for acute heart failure (AHF).

Purpose

We aimed to compare the patient characteristics and outcomes between patients with CS who were hospitalized for AHF (CS-AHF) and patients with AHF of other etiology.

Methods

A total of 4,556 hospitalized patients with CS were identified from the Japanese Diagnosis Procedure Combination database from 2012 to 2020. Among them, we analyzed 254 patients who were hospitalized due to AHF. Patient characteristics, prior medical history, medical therapy for heart failure, intensive care management during hospitalization, in-hospital outcomes and rehospitalization within one year after the index hospitalization were compared with general 4,056 hospitalized AHF patients who were enrolled in the Kyoto Congestive Heart Failure registry.

Results

Patients with CS-AHF were younger (71 [63-78] vs 80 [72-86]) and more women (69% vs 45%; p < 0.001) than general AHF patients. In addition, CS-AHF were associated with lower prevalence of hypertension, diabetes and dyslipidemia (46% vs 72%, p < 0.001; 28% vs 37%, p = 0.005; and 21% vs 38%, p < 0.001), and lower prescription of angiotensin converting enzyme inhibitors or angiotensin II receptor blocker (28 % vs 46%; p < 0.001) while prescription of beta-blockers were similar between the groups. The length of hospital stay was significantly longer in CS-AHF (23 [14-39] days vs 16 [11-25] days), more patients were treated by intensive respiratory care (32% vs 25%; p = 0.05) and cardiac resynchronization therapy defibrillator (CRTD) implantation (6% vs. 0.5%; p < 0.001) Although in-hospital mortality was similar between the groups, the rate of rehospitalization within one year was higher in CS-AHF (51% vs 39%; p = 0.001).

Conclusions

Patients with CS-AHF were younger, more women and had lower cardiovascular risk factors than those with AHF in general. CS-AHF were associated with longer hospital stay, higher rate of CRTD implantation and higher rehospitalization rates. More attention might be needed for this distinct group of patients.
Is a change of the current echocardiographic red flag for left ventricular wall thickness useful in cardiac amyloidosis screening?
Authors: Ungericht M , Messner M , Sappler N , Zaruba M M , Poelzl G
Published: November 2023

Background

Cardiac amyloidosis (CA) is a serious and progressive infiltrative cardiomyopathy caused by the extracellular deposition of amyloid fibrils in the myocardium. As new disease-modifying therapies are increasingly emerging, prompt and specific diagnosis is fundamental to avoid treatment delay. Echocardiography is the most often used first-line imaging tool for amyloidosis screening. Left ventricular (LV) wall thickness ≥12 mm and age ≥65 years are major criteria for the suspicion of CA. However, it is very likely that many patients, especially in the early stages of the disease, will not be detected. Reducing the diagnostic wall thickness threshold will certainly increase the sensitivity of the amyloidosis screening. It is to be feared, however, that reduction of the cut-off will lead to a large number of patients being unnecessarily subjected to further testing, and substantially increase costs.

Objective

We investigated the distribution of interventricular septum thickness (IVS) in patients referred for routine echocardiography with the aim of establishing a wall thickness cut-off value that is assumed to be suitable for targeted amyloidosis screening.

Methods

We retrospectively analysed the echocardiographic reports from August 2021 to December 2021 at our department. Individual IVS values were documented and categorised. This was to give an idea of how many patients were potentially eligible for further amyloidosis screening solely due to changes in the echocardiographic IVS cut-off value.

Results

1.007 echocardiographic reports were analysed. Of these, 900 included a valid IVS value, while 107 (mainly exclusions of pericardial effusion) did not. From IVS ≥15 mm (5.4%), to ≥14 mm (10.0%), to ≥13 mm (18.6%), to ≥12 mm (32.0%) an increase in patient number was recorded (Figure 1). With regard to CA diagnosis, it can be assumed that systematic screening of patients with IVS ≥12 mm will certainly result in increasing sensitivity but in turn decreasing specificity. On the basis of the patient number within each IVS category we conclude that amyloidosis screening of patients with an IVS ≥13 mm is feasible and reasonable.

Conclusion

We herein conclude that an IVS ≥13 mm should result in targeted amyloidosis screening. In case of IVS <13 mm the use of further red flags is recommended to avoid unnecessary amyloidosis screening and disproportionate increase in costs.
A review of current landscape and definition of septic cardiomyopathy
Authors: Sivapathan S , Gehardy B , Pathan F , Orde S , Negishi K
Published: November 2023

Background

Septic cardiomyopathy (SCM) is a reversible myocardial dysfunction that is increasingly recognised in critically-ill septic patients. SCM and sepsis cause significant morbidity and mortality. However, the lack of consensus on the diagnostic criteria for SCM makes it difficult to understand how sepsis can impact cardiac function.

Purpose

To review the current literature regarding SCM and compare the various proposed diagnostic criteria and imaging parameters utilised.

Method

This literature review comprised of a three-part research method: patient population, imaging modality, and outcomes. Our patient population included critically ill patients diagnosed with sepsis or septic shock. We analysed all cardiac imaging modalities, including TTE, TOE, CT, and CMR. Our outcome was mortality or any related terms. We conducted a comprehensive search of PubMed, EMBASE, and SCOPUS and manually searched for past reviews on the subject. We excluded conference abstracts, review articles, and duplicates using Covidence. Only English-language, adult-audience articles were considered, and the last search update was in November 2022.

Result

This study analysed 77 papers on SCM, of which 55 were prospective and 18 were retrospective (figure 1). The majority of research was conducted in the ICU, and 61 studies used TTE as the primary imaging modality for assessing SCM. Approximately 44% of the studies evaluated cardiac dysfunction in septic patients using systolic function as the primary metric. About half of the research lacked a clear definition of SCM, and 49% did not provide a definitive LVEF cut-off point (figure 2). 78% of the studies determined the reversibility period to be between 7 and 10 days. The majority of studies required that SCM be diagnosed within 24 hours. However, 66% of the studies did not include any type of imaging follow-up for septic patients with cardiac dysfunction.

Conclusion

The heterogeneity inherent among these studies points toward the lack of standardisation in measurements and use of various parameters to assesses cardiac dysfunction in septic patients. There is a need for a new definition of SCM that may be better suited to describing the spectrum of cardiac dysfunction in patients with severe sepsis. Further work is required to establish a consensus definition of SCM and a standardised diagnostic approach.Figure 1Figure 2
Fractional excretion of urea nitrogen can identify true worsening renal function in patients with acute heart failure
Authors: Watanabe Y , Kubota Y , Nishino T , Tara S , Kato K , Hayashi D , Tachibana T , Mozawa K , Matsuda J , Miyachi H , Tokita Y , Iwasaki Y , Yasutake M , Asai K
Published: November 2023

Background

Worsening renal function (WRF) often occurs during decongestive treatment in acute heart failure (AHF). Although WRF has previously been associated with worse prognosis, recent studies have revealed that it may not contribute to an unfavorable outcome in the setting of adequate decongestion achieved. Therefore, there is growing interest to identify patients who develop "true WRF" with poor outcomes.

Purpose

Fractional excretion of urea nitrogen (FEUN), which is used to differentiate causes of renal failure, has emerged as a surrogate marker of volume status in patients with AHF complicated by renal dysfunction. Recent study has reported that a low FEUN value (FEUN ≤32.1%) represents intravascular dehydration, whereas a high FEUN value (FEUN >38.0%) reflects intravascular congestion, both being independent adverse prognostic factors. Therefore, we hypothesized that FEUN could identify "true WRF" in patients with AHF.

Methods

We examined 801 hospitalized patients with AHF and renal dysfunction (defined as discharge estimated glomerular filtration rate <60 mL/min/1.73 m²) whose FEUN was measured at discharge. The patients were divided into four groups as follows: no WRF (n=683); WRF with low FEUN (≤32.1%) (n=36); WRF with medium FEUN (>32.1% and ≤38.0%) (n=25); and WRF with high FEUN (>38.0%) (n=57). WRF was defined as an increase in serum creatinine ≥0.3 mg from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100 / (serum urea × urinary creatinine). The primary endpoint was the composite of all-cause death and heart failure (HF) readmission within 1-year after discharge.

Results

Regarding baseline characteristics, the WRF with low FEUN group had lower left ventricular ejection fraction, whereas the WRF with high FEUN group had poorer renal function. During the median follow-up period of 300 days, 18 all-cause deaths and 165 HF readmissions occurred. Kaplan–Meier analysis showed that patients without WRF had a significantly higher event-free survival rate than those with WRF. In addition, the WRF with medium FEUN group had a significantly higher event-free survival rate similar to that of the no WRF group, whereas the WRF with low FEUN and WRF with high FEUN groups had lower event-free survival rates. In multivariable Cox regression analysis, the WRF with low FEUN (hazard ratio, 1.91; 95% confidence interval, 1.02–3.57; P=0.043) and WRF with high FEUN (hazard ratio, 1.71; 95% confidence interval, 1.02–2.89; P=0.043) groups were independently associated with poor outcomes, even after adjusting for confounders.

Conclusion

Our study suggests that FEUN can identify prognostically relevant WRF and may be a useful marker for guiding decongestive therapy in patients with AHF complicated by WRF.Table 1Figure 1
Clinical effect of renal dysfunction on diagnostic and prognostic accuracy of B-type Natriuretic Peptide and N-terminal Pro-B-type Natriuretic Peptide for acute heart failure
Authors: Wussler D , Balkin M , Michou E , Sabti Z , Kozhuharov N , Strebel I , Nowak A , Von Eckardstein A , Pfister O , Breidthardt T , Mueller C
Published: November 2023

Background

Acute heart failure (AHF) continues to have unacceptable high rates of mortality and morbidity. Therefore, accurate and rapid diagnosis of AHF is crucial for the early initiation of effective treatment. Previous studies have shown that plasma concentrations of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) increase with declining renal function and that renal dysfunction seems to decrease the accuracy of BNP and NT-proBNP in the diagnosis of AHF.

Purpose

We aimed to directly compare the diagnostic and prognostic accuracy of BNP and NT-proBNP in patients presenting with acute dyspnea, including the effect of renal function.

Methods

This prospective diagnostic study enrolled unselected patients presenting with acute dyspnea to the emergency department. The final diagnosis was centrally adjudicated by two independent cardiologists using all information including imaging and follow-up. BNP and NT-proBNP plasma levels were determined at presentation. 360 days all-cause mortality was the primary prognostic end point.

Results

Among 1579 patients, acute heart failure (AHF) was the adjudicated final diagnosis in 865 patients (54.8%). Plasma concentrations of both BNP and NT-proBNP were significantly higher in AHF as compared to other causes of acute dyspnea (both p<0.001). Diagnostic accuracy as quantified by the area under the receiver-operating-characteristics curve (AUC) was 0.948 (95% CI 0.938-0.958) for BNP as compared to 0.921 (95% CI 0.908-0.935) for NT-proBNP, p<0.001. The diagnostic superiority of BNP was consistent among predefined subgroups according to renal function and increased with the extent of renal dysfunction (Figure 1: all patients (A), patients with eGFR≥ 60 ml/min/1,73 m² (B), patients with eGFR 30-59 ml/min/1,73 m² (C), patients with eGFR <30ml/min/1,73 m² (D)).

In contrast, prognostic accuracy for the prediction of death at 360 days was higher for NT-proBNP (AUC 0.731, 95% CI 0.702-0.760 versus 0.706, 95%CI 0.676-0.736 for BNP; p<0.001). The diagnostic superiority of NTproBNP was consistent among predefined subgroups according to renal function but decreased with the extent of renal dysfunction.

Conclusion

In patients with acute dyspnea, BNP and NT-proBNP at presentation both have very high diagnostic accuracy for AHF and moderate prognostic accuracy for death. There is a numerically small, but statistically and possibly also clinically significant diagnostic superiority of BNP and prognostic superiority of NT-proBNP.Diagnostic accuracy for AHF
Hepatic venous stasis index reflects hepatic congestion and predicts adverse outcomes in patients with heart failure
Authors: Ohara H , Yoshihisa A , Sugawara Y , Ichijo Y , Sato Y , Misaka T , Sato T , Oikawa M , Kobayashi A , Takeishi Y
Published: November 2023

Background

It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in heart failure (HF) patients. However, the parameter which quantifies hepatic vein waveforms has not been established. We suggest hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in HF patients, we aimed to clarify the associations of HVSI with parameters of cardiac function and right heart catheterization (RHC), as well as that with prognosis, in patients with HF.

Methods

We performed abdominal ultrasonography, echocardiography and RHC in patients with HF (N = 513). The patients were divided into three groups based on HVSI as follows; HVSI 0 (HVSI = 0, N = 253), low HVSI (HVSI 0.01–0.20, N = 132) and high HVSI (HVSI > 0.20, N = 128) as shown in Figure 1. We examined the associations of HVSI with parameters of cardiac function and RHC, and followed up for cardiac events defined as cardiac death or worsening HF.

Results

There were significant correlations between HVSI and mean right atrial pressure (R = 0.244, P < 0.001), right ventricular fractional area change (R = -0.195, P < 0.001) and inferior vena cava diameter (R = 0.318, P < 0.001). During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan–Meier analysis, cardiac event rate increased across increasing HVSI (log-lank, P = 0.002, Figure 2). In the multivariate Cox proportional hazard analysis, high HVSI was independently associated with cardiac events (high HVSI group vs. HVSI 0 group: hazard ratio, 1.746; 95% confidence interval, 1.053–2.894, P = 0.031).

Conclusions

HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF, and is associated with adverse prognosis in HF patients.Figure 1Figure 2
Association between speckle tracking echocardiography and pressure-volume loop derived parameters at increasing levels of myocardial damage in a porcine model of acute cardiogenic shock
Authors: Hartmund Frederiksen P , Linde L , Gregers E , Udesen N L J , Helgestad O K L , Banke A B S , Dahl J S , Jensen L O , Lassen J F , Povlsen A L , Larsen J P , Schmidt H , Ravn H B , Moller J E
Published: November 2023

Background

Echocardiography is a diagnostic cornerstone in acute cardiovascular care. However, the relationship between speckle tracking assessed global longitudinal strain (LS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops remains poorly elucidated, especially with increasing levels of myocardial damage.

Objectives

We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central hemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction.

Methods

Twelve Danish landrace pigs weighing 75-80 kg were used. All instrumentations were performed percutaneously, including placement of a conductance catheter in the LV. Progressive LV dysfunction was induced by stepwise embolization trough the left main coronary artery every three minutes until a 50% reduction in cardiac output or mixed venous saturation, compared to baseline, or a mixed venous saturation <30%. Echocardiography was performed through a subxiphoid midline incision, and was done at baseline and 90 seconds after each injection.

Results

With progressive LV dysfunction, mean cardiac output decreased from 5.6 l/min (SD: 0.9) to 2.1 l/min (SD: 0.9) and mean mixed venous saturation deteriorated from 61.1%(SD: 7.9) to 35.3% (SD: 6.1). Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8% (SD 3.0) to -6.1% (SD: 2.0) and 16.9 cm (SD: 2.6) to 7.8 cm (SD: 1.8), respectively (Figure 1). LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted univariate regression (r2=0.53 and r2=0.49, respectively. p<0.01 for both). LS correlated significantly, but modest, with stroke volume (r2=0.46, p<0.01), end-systolic elastance (r2=0.32, p<0.01), systolic blood pressure (r2=0.37, p<0.01), ventriculo-arterial coupling(r2=0.34, p<0.01), and arterial elastance (r2=0.23, p<0.01) (Figure 2). In a multivariate regression analysis, LS showed significant correlation with stroke work, systolic blood pressure, and end-diastolic wall stress (r2=0.60, p<0.01).

Conclusion

In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and LS showed moderate correlations with contractility, arterial elastance and ventriculo-arterial coupling. This indicates that LS is a marker of overall ventricular performance.Echocardiographic changes from baselineScatter plot of LS and hemodynamics
MCS current practice and weaning: CCCTN survey of CICU directors at academic medical centers
Authors: Balgobind A , Pierce M , Alvarez Villela M
Published: November 2023

Background/Introduction

As the treatment of cardiogenic shock evolves, temporary mechanical circulatory support (MCS) use is increasing. Few studies have examined Cardiac Intensive Care Unit (CICU) practices for management and weaning of MCS.

Purpose

We aimed to describe current management and weaning practices for patients supported with an intra-aortic balloon pump (IABP) or Impella in CICUs.

Methods

During December 2022, a 45-question survey was electronically distributed by the Critical Care Cardiology Trials Network (CCCTN) to the CICU directors of 44 academic medical centers in North America. Descriptive statistics were used to summarize the results.

Results

A response rate of 84% was achieved. Among respondents, CICU bed capacity ranged from 8-32 (Mean of 17). Staffing was primarily by cardiologists without board certification in heart failure or critical care (38%). One-in-four centers reported staffing by a multi-disciplinary team consisting of cardiologists and intensivists. Most centers use heparin anticoagulation for both IABP (32, 87%) and Impella (32, 91%) and primarily used PTT to monitor anticoagulation (23, 62%) with a target of 50-70 seconds (27, 73%). While using Impella support, daily TTE (29%), plasma free hemoglobin measurements (34%) and prophylactic antibiotics (3%) were uncommon. Most institutions did not have a formal weaning protocol for IABP (78%) or Impella (66%). The majority of centers reported IABP weaning to be a subjective decision led by the CICU attending (65%), while Impella weaning was commonly a decision made by a multi-disciplinary team including the CICU attending (57%). PACs are used routinely when weaning Impella (83%) but not IABP (46%). IABP removal is most commonly done at bedside by CICU team (70%), whereas Impella removal is most commonly done in the catheterization laboratory (43%).

Conclusions

In this survey of academic CICUs, IABP and Impella management showed substantial variability across centers. Use of invasive hemodynamic monitoring was common but its use during weaning was not uniform. Multidisciplinary involvement was more common with Impella support and weaning when compared to IABP. These heterogeneous results highlight the need for further investigation to guide best practices in MCS management.
Validating the association between a composite metric of guideline-directed medical therapy (GDMT) and clinical outcomes for patients with heart failure with reduced ejection fraction (HFrEF)
Authors: Calma J , Hsiao S , Varshney A S , Azizi Z , Golbus J R , Heidenreich P A , Sandhu A T
Published: November 2023

Introduction

A composite metric to characterize the overall quality of GDMT for patients with HFrEF is important to evaluate quality-of-care and for clinical research.

Purpose

We sought to evaluate the associations between GDMT scores and cardiovascular outcomes amongst patients with recently-diagnosed HFrEF within a large national integrated health system within the United States.

Methods

We identified a cohort of patients with recent-onset HFrEF who received care within the Veterans Affairs system between January 2013 and June 2019. We excluded patients with systolic blood pressure <100mmHg or glomerular filtration rate <30 mL/min/1.73m2. We identified active medical therapy based on the last medication fill 90-180 days after the index date (first date with documented HF diagnosis and EF≤40%). We calculated three different GDMT scores: the original Heart Failure Collaboratory Score, the 4-Pillar Intensification Score, and a modified 4-Pillar Intensification Score that included continuous scoring to further incentivize dose uptitration (Figure 1). Using a landmark analysis, we evaluated the association between a 1 standard deviation (SD) change in the GDMT scores at 6 months with the following outcomes: all-cause death, cardiovascular death, and the composite of cardiovascular death/heart failure hospitalization. We repeated the analyses with adjustment for comorbidities and vital signs.

Results

Among 108,752 patients with recent-onset HFrEF, the mean age was 70.0 years (SD: 11.1) and 97.6% were men. Treatment rates were the following: evidence-based beta-blockers – 55.2%, renin-angiotensin system inhibitors – 60.2%, angiotensin neprilysin inhibitors – 2.9%, mineralocorticoid receptor antagonists – 17.6%, sodium glucose transporter 2 inhibitors – 0.7%, hydralazine/nitrates – 4.9%, and ivabradine – 0.1%. A one standard deviation increase in each of the GDMT scores was associated with improved clinical outcomes (Table 1). Figure 1 illustrates the association between the modified 4-Pillar Intensification Score and the composite of cardiovascular death/heart failure hospitalization. These associations were attenuated but remained significant with comorbidity adjustment. Results also remained consistent when the study period was restricted to 2016 or later and with inclusion of the last prescription fill between 1-180 days post-index date.

Conclusion

Our study suggests that GDMT scores are consistently associated with clinical outcomes among patients with HFrEF.
Transcatheter edge to edge repair of functional mitral regurgitation as bridge to heart transplantation: 2-years follow up results from MitraBridge international registry
Authors: Marcelli C , Munafo' A R , Estevez-Loureiro R , Adamo M , Guerin P , Arzamendi D , Ho E C , Asgar A , Petronio A S , Grasso C , Van Mieghem N M , Tarantini G , Potena L , Saia F , Godino C
Published: November 2023

Background

Chronic severe functional mitral regurgitation (FMR) is a common finding in patients with advanced heart failure (AHF) who undergo evaluation for heart transplantation (HTx). Nevertheless, access to surgical strategies for AHF could be limited by scarce availability of donors and by temporary or definitive contraindications. MitraBridge registry already proved that transcatheter edge to edge repair (TEER) of FMR performed as a bridge to HTx is an effective and safe treatment strategy at 1-year follow up with 64% of patients free from composite primary endpoint of all-cause death, new admission for HF, urgent HTx or LVAD implantation.

Purpose

The aim of this study is to determine whether 1-year results of MitraBridge registry were maintained at 2-years follow up.

Methods

Mitrabridge is a retrospective, multicenter observational study that enrolled 153 adult patients with AHF and moderate-to-severe or severe FMR and considered candidates for HTx who underwent TEER between 2018 and 2021. Depending on the strategy TEER was performed for, patients were classified in bridge to transplant, candidacy or decision. Primary endpoint of the current analysis was the 2-year composite rate of all-cause death, new admission for HF, urgent HTx or LVAD implantation.

Results

Median age was 59 years old [53-63], most patients were in INTERMACS class 5-6 (47.5%) and mean left ventricle ejection fraction (LVEF) was 26.9±7.7%. Baseline right heart catheterization was available for 112 (73%) patients, of them 87.5% had pulmonary hypertension with mean pulmonary artery pressure (mPAP) of 33±10 mmHg. Procedural success was achieved in 89.5% of cases and no deaths at 30 days were reported. At 2-years follow up, freedom from primary endpoint was maintained in 47% of patients. A significant reduction of echocardiographic systolic pulmonary artery pressure (sPAP) was observed (from 50 [40-61] mmHg to 43 [33-53] mmHg, p-value<0.001). At the end of follow-up (median time of 26 months, IQR 9-52), elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) had no longer indication for HTx, due to clinical improvement. Nine patients underwent LVAD implantation for clinical worsening and nine (8%) urgent HTx (15% of already listed population).

Conclusions

MitraBridge 2-years follow up confirms that TEER is a safe option in AHF population with FMR and shows that haemodynamic and clinical benefits following the procedure are maintained at long term. In particular, it allowed 21% of patients to receive elective HTx reducing need for urgent organ transplantation and helped to expand the candidacy for HTx.