bluuebunny/crossref_metadata_2025 huggingface dataset:
High rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias autonomically by an ICD
Authors: Smoczynska A , Loen V , Hernandez A.A , Beekman H.D.M , Meine M , Vos M.A
Published: November 2020

Background

The anesthetized, chronic complete atrioventricular block (CAVB) dog model allows reproducible inducibility of Torsade de Pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr-blocker. High rate pacing (HRP) prevents ventricular arrhythmias, but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases prior to ventricular arrhythmias and has been proposed as a marker to guide HRP.

Purpose

A proof-of-principle study to show STV determined automatically and in real-time by an ICD can guide HRP to prevent imminent ventricular arrhythmias.

Methods

Eight CAVB dogs were implanted with an ICD (Medtronic, lead in the right ventricular (RV) apex), with software to automatically determine STV online (STV-ICD). STV was determined from the activation recovery interval (ARI) of 31 consecutive beats with the formula: STV = Σ|ARI(n+1) − ARI(n)|/(N*√2). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg i.v. in 5 minutes or until the first TdP). In the first experiment, the individual STV-ICD threshold was determined prior to the first arrhythmic event and programmed into the ICD. In a serial experiment, HRP was initiated automatically once the STV-ICD threshold was reached, by gradually increasing the heart rate to 100 bpm. Occurrence of TdPs was monitored for 10 minutes from the start of dofetilide infusion in both experiments. During HRP, STV was measured offline from RV electrograms (EGM) and left ventricular (LV) monophasic action potential durations (MAPD) (STV-offline).

Results

During the inducibility experiment, 8/8 dogs had repetitive TdPs and STV-ICD increased from 0.96±0.42 to 2.10±1.26 ms* (*p<0.05). During the prevention experiment, all dogs reached the STV threshold. HRP decreased STV-offline from 2.02±1.12 to 0.78±0.28 ms*, which was accompanied by prevention of TdPs in 7/8 dogs* (Figure 1).

Conclusion

Temporal dispersion of repolarization, quantified as STV, can guide HRP automatically by an ICD to prevent ventricular arrhythmias.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Public Private Partnership
Remote monitoring can predict lethal arrhythmic events through time-domain analysis of heart rate variability in patients with implantable cardioverter defibrillator
Authors: Shirakawa Y , Niwano S , Oikawa J , Saito D , Sato T , Matsuura G , Arakawa Y , Kobayashi S , Nishinarita R , Horiguchi A , Ishizue N , Kishihara J , Fukaya H , Ako J
Published: November 2020

Background

We prospectively collected device and heart rate data, i.e. heart rate variability (HRV), through remote monitoring (RM) of patients with implantable cardioverter defibrillator (ICD). Several studies have demonstrated usefulness of RM in implanted device patients, however, reports concerning the predictors of lethal ventricular arrhythmias are limited.

Purpose

The objective was to identify the predictors of lethal arrhythmic events (VT/VF).

Methods

Thirty-three patients (mean age: 50 years) with ICDs [with functionality of HRV analysis] were divided into 2 groups [VT/VF(+), VT/VF(−)]. Clinical, device (ventricular lead impedance; amplitude of ventricular electrogram), and HRV data were compared between the 2 groups. As the index of time-domain HRV analysis, NN intervals-index (SDNNi) was calculated for every 5 minutes, and the mean, maximum, and minimum SDNNi during the 24-hour period were used.

Results

During the observation period (median 12 months), 10 patients experienced VT/VF events. In HRV data, the mean, max, and min SDNNi were higher in VT/VF(+) than VT/VF(−) group (132.9±9.3 v.s. 93.5±6.1, p=0.0013; 214.6±10.6 v.s. 167.0±7.0, p=0.0007; 71.2±7.5 v.s. 43.9±4.9, p=0.0047). The other parameters did not exhibit significant difference. On logistic regression analysis, the mean SDNNi of 100.1, max SDNNi of 185.0 and min SDNNi of 52.0 as cut-off values for prediction of VT/VF event demonstrated significant receiver operating characteristics (ROC) curves (AUC=0.86, p=0.0007; AUC=0.84, p=0.0005; AUC=0.78, p=0.0030). Furthermore, in cases of VT/VF(+) group, the max ΔSDNNi, i.e., difference from baseline SDNNi, and min ΔSDNNi in 7 and 28 days preceding VT/VF events exhibited time course changes in comparison with baseline values. They were significant predictors of VT/VF events (max ΔSDNNi cut-off: 46.8, AUC=0.91, p=0.0002; min ΔSDNNi cut-off: −42.4, AUC=0.88, p=0.0014).

Conclusion

Time-domain analysis of HRV through RM may help identify patients at high risk of lethal arrhythmic events, and predict occurrence of such arrhythmic events.

Funding Acknowledgement

Type of funding source: None
Low-temperature electrocautery reduces lead-related complications: insights from the WRAP-IT study
Authors: Mittal S , Wilkoff B , Poole J , Kennergren C , Wright D , Berman B , Riggio D , Sholevar S , Moubarak J , Schaller R , Love J , Pickett R , Philippon F , Lande J , Tarakji K
Published: November 2020

Background

Patients with an existing cardiovascular implantable electronic device (CIED) often require a generator replacement or system upgrade/revision, during which some degree of dissection is usually necessary to free the existing lead(s). Commonly used techniques include blunt dissection, standard surgical electrocautery, or newer forms of electrocautery such as the low-temperature electrosurgical device (PlasmaBlade Soft Tissue Dissection Device) designed to minimize inadvertent thermal injury to leads.

Objective

Determine whether the dissection technique impacts the likelihood of developing a lead-related complication.

Methods

The WRAP-IT trial enrolled patients undergoing CIED replacement, upgrade, revision or de novo CRT-D implant. This analysis excluded patients undergoing a de novo procedure. All adverse events were adjudicated by an independent physician committee. Data were analyzed using Cox proportional hazard regression modeling, controlling for capsulectomies and lead dissections.

Results

5639 patients (mean [±SD] age: 70.6±12.7 years; 28.8% female) underwent a replacement/upgrade/revision. Electrocautery was used in 5203 (92.3%) patients and among these, low-temperature electrocautery was used in 1866 (35.9%) patients. Compared to standard electrocautery, low-temperature electrocautery was used more often when leads were dissected or mobilized (P<0.001) or when a partial or complete capsulectomy was performed (P<0.001). Use of low-temperature electrocautery was associated with a 31% reduction in lead-related complications (HR: 0.69, 95% CI: 0.49–0.98, P=0.037) (Figure).

Conclusion

The low-temperature electrosurgical device (PlasmaBlade) uses precise pulses of radiofrequency energy to dissect tissue with only minimal thermal damage. In this large cohort of replacement, revision, and upgrade procedures, use of low-temperature electrocautery led to significantly fewer lead-related complications.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Medtronic
Off-label combination of leadless pacemakers and subcutaneous defibrillators in bilateral venous occlusion: a new reimplantation strategy after lead extraction
Authors: Di Cori A , Viani S , Tolve S , Zucchelli G , Barletta V , Giannotti Santoro M , Parollo M , Cellamaro T , Branchitta G , Carluccio M , Segreti L , Paperini L , De Lucia R , Soldati E , Bongiorni M.G
Published: November 2020

Background

Subcutaneous implantable cardioverter-defibrillator (S-ICD) and leadless pacemakers (LPM) provide an alternative to transvenous implantable devices. Sometimes, after transvenous (TV) lead extraction, patients show a bilateral venous occlusion, resulting not eligible for TV reimplantation.

Purpose

This analysis was designed to provide preliminary data on feasibility and short-term outcome of an hybrid combination (Hyb) of s-ICD plus LPM after TV-ICD explantation, in patients without anatomical transvenous reimplantation options.

Methods

Among 2684 consecutive extracted patients, 31 (1.1%) were reimplanted with a LPM, 66 (2.4%) with a s-ICD and 6 (0.2%) patients with an Hyb combination. Hyb strategy was considered in patients with a pacing plus defibrillating indication, and an anatomical barrier, as bilateral superior venous occlusion or massive bilateral skin erosion.

Results

Hyb patients were old (72±10 years), with a prevalent ischemic disease (4/6) and a reduced ejection fraction (43±16%). Extraction indication was infection in 4 and severe venous occlusion in 2, and included 2 single chamber, 2 dual chamber and 2 biventricular ICD. After extraction, reimplantation timing was 7±6 days, LPM was implanted before and sICD the day after.

LPM reimplantation indication was sinus node dysfunction in 2 and AV block in 4. Implantation duration was 68±23 and fluoroscopy time 9.4±2.3 min. ICD reimplantation indication was primary prevention in 4 and secondary prevention in 2. Implantation duration was 118±10 min. No complications were observed. At 1 year, no complications were observed, including device related cross-talks.

Conclusions

The Hyb strategy is a potential option after TV-ICD explantation in pacemaker dependent patients, when transvenous implantation is not available.

Extraction and Reimplantation Session

Funding Acknowledgement

Type of funding source: None
Comparison of various instantaneous pulmonary arterial wedge pressure measurements with prognostic validation
Authors: Nagy A.I , Johnson J , Lund L.H , Manouras A
Published: November 2020

Background

Current recommendations on the diagnosis of pulmonary hypertension due to left heart disease (PH-LHD) emphasize the need for standardization of pulmonary arterial wedge pressure (PAWP) measurement. Instead of mean PAWP values instantaneous mid-A wave pressures or, in case of atrial fibrillation (AF), measurement 130–160 ms after the QRS onset is recommended. Recently, PAWP at the QRS onset has also been proposed. Our aim was to compare the various instantaneous PAWP measurements and assess the prognostic value of the derived diastolic pressure gradients (DPG) in heart failure (HF) patients.

Methods and results

PAWP and pulmonary arterial pressure (PAP) tracings of 116 patients with PH-LHD were manually analyzed offline. PAWP was measured in 4 different ways: 1. mean value [PAWPM]; 2.mid-A wave value in sinus, and at 10 ms intervals 130–160 ms following QRS onset in AF [PAWPR]; 3. at the onset of the QRS complex [PAWPQRS]; 4. pre C-wave point value [PAWPC]. The pre C-wave point was chosen as a reference for truly end-diastolic pressures. The corresponding DPGM, DPGR, DPGQRS and DPGC were calculated. The patients were followed for 17 (8–27) months and the prognostic value of the various DPG measurements for predicting all-cause mortality was assessed. The pre C-wave point was identifiable in 35 patients (30%); on average it occurred 171 ms after the QRS-onset whereas the A wave-onset and A-wave peak happened on average 62 and 149 ms after the QRS-onset, respectively. All three instantaneous PAWP measurements gave significantly lower values than PAWPM [19.3 (15.4–25.0)]. PAWPR did not differ from PAWPC [18.1 mmHg (14–22) vs. 19.2 mmHg (13–22.8), p=0.9], whereas PAWPQRS was lower [15.8 mmHg (12.2–19.9), p<0.001]. Accordingly, all instantaneous DPG measurements were higher than DPGM, yielding lower prevalence of negative DPG (29%, 17% and 45%, for DPGR, DPGQRS and DPGM, respectively). In AF (n=30), DPGR values at 130–140–150–160 ms demonstrated increasing scatter and progressively overestimated DPGQRS. For prognostic assessment, in case of both DPGQRS and DPGR, 6 mmHg was identified as a best cut-off value for predicting all-cause mortality, at which both indices provided superior prognostic information than DPGM [DPGR: HR 2.7; CI 1.1–6.9, p=0.029; DPGQRS: HR 2.6; CI 1.1–6.4, p=0.037, high-risk cases 17 for both; DPGM: HR 2.8; CI 1.0–7.6, p=0.045, high-risk cases 10].

Conclusions

PAWP measured at the mid-A wave provides a reliable assessment of the end-diastolic PAWP in sinus rhythm. On the other hand, ECG-gated measurements yield more robust evaluation of PAWP in AF. Finally, both approaches carry significant and similar prognostic information in PH-LHD.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIN was supported by the János Bolyai Scholarship of the Hungarian Academy of Sciences
Resting coronary blood flow velocity profile predicts coronary flow reserve in HFpEF
Authors: Svedlund S , Brodin T , Hage C , Saraste A , Tan R.S , Beussink-Nelson L , Faxen U.L , Lagerstrom Fermer M , Lam C.S.P , Shah S.J , Lund L , Gan L.M
Published: November 2020

Background

Coronary microvascular disease (CMD) is prevalent in patients with heart failure with preserved ejection fraction (HFpEF). CMD can be assessed by coronary flow reserve (CFR) using transthoracic echocardiography (TTE). We hypothesised that the coronary Doppler flow profile in LAD at rest could reveal information about the downstream resistance in the vessel, where increased resistance is a sign of CMD.

Purpose

We aimed to measure features of the acceleration and deceleration of the LAD Doppler flow profile to investigate association with coronary and cardiac function.

Methods

CFR was assessed in 202 patients by TTE in the PROMIS-HFpEF-study. Detailed flow profile measurements were possible in 169 patients (84%) who constituted the study population. The coronary Doppler flow profiles were analysed with respect to acceleration time (corAT) and slope (corAS) and deceleration pressure half time (corPHT) (figure 1).

Results

The average age was 75±9 years and 55% were female. Atrial fibrillation (AF) was present in 53% and 62% were current or previous smokers. There was no significant difference in gender, age, BMI, blood pressure or heart rate in the CMD vs non-CMD group, but AF as well as a history of smoking was more prevalent in the CMD group, p=0.022 and 0.003 respectively. Further, there were no significant differences in neither corAT nor corAS between the two groups. However, patients with CMD had shorter corPHT of 268±64 ms compared to 298±67 ms, p=0.01. A longer corPHT was associated with increased TAPSE (R=0.205, p=0.007) and higher CFR (R=0.231, p=0.002). In a multivariable analysis adjusted for age, sex, BMI, SBP, reactive hyperemia index, HR, AF, diabetes, CVD, smoking, LVM and study site*, corPHT independently predicted CFR (table 1, p=0.016).

Conclusion

Short pressure half time, indicating a steep deceleration of the coronary Doppler signal at rest, may provide useful information for prediction of CFR determined by transthoracic ultrasound by reflecting the increased resistance in the coronary microvasculature associated with CMD.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Sahlgrenska University Hospital, Sponsor AstraZeneca
Sex-specific effect of obesity on exercise capacity and diastolic function
Authors: Jung M , Ihm S.H , Han S , Jung H.O , Youn H.J , Ryu K.H
Published: November 2020

Background

Obese women are overrepresented in heart failure with preserved ejection fraction (HFpEF). We sought to 1) characterize the sex-specific effect of obesity on exercise capacity and diastolic function and 2) identify the determinant of exercise intolerance and diastolic dysfunction in each sex.

Methods

A total of 736 healthy participants, who underwent comprehensive health check-ups, were included in this study. All individuals were divided into 4 groups according to sex and presence of obesity (BMI ≥23kg/m2).

Results

The exercise capacity (peak VO2) was greatly affected by sex, which was worse in women. In addition, exercise capacity significantly differed according to obesity in women (23.5±7.3 vs. 21.3±5.4ml/kg/min, p<0.05), whereas there was no such difference in men (28.2±7.8 vs. 28.0±6.6ml/kg/min, p>0.10). Overall, women had an elevated E/e' ratio. Even non-obese women had a similar E/e' ratio to obese men (8.2±1.8 vs. 8.4±2.1, p>0.10) and obese women exhibited the highest E/e' ratio over any other group (Fig 1). Among 5 parameters (aging, obesity, elevated blood pressure, elevated heart rate, and elevated fasting glucose), obesity was a significant determinant of exercise intolerance for women, but not for men (women, HR 1.87 [95% CI 1.12–3.11], p=0.016; men, HR 1.22 [95% CI 0.63–2.38], p=0.558). Furthermore, obesity confers a greater risk of diastolic dysfunction in women than men (women, HR 4.03 [95% CI 2.24–7.25], p<0.001; men, HR 2.82 [95% CI 1.37–5.79], p=0.005).

Conclusions

Women had a more deleterious effect on exercise capacity and diastolic function in response to obesity than men. These sex-specific effects might explain the female predominance of HFpEF, particularly for the obese phenotype.

Figure 1

Funding Acknowledgement

Type of funding source: None
Stabilin-1+/SMA- macrophages in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction
Authors: Gombozhapova A , Rogovskaya Y , Rebenkova M , Kzhyshkowska J , Ryabov V
Published: November 2020

Introduction

Molecular biomarkers of monocytes/macrophages identified to date have provided advanced diagnostic capabilities. We have accumulated a large amount of knowledge related to the role of innate immune response in the development of postinfarction cardiac remodeling. However, there is no significant advancement in clinical studies.

Purpose

The purpose was to assess prospects of macrophage biomarkers in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction (MI).

Methods

The study included 41 patients with MI type 1, died in 2013–2014. We used a biobank of tissue samples for analysis. Group 1 (n=24) comprised patients who died within 72 hours of MI (the inflammatory phase), group 2 (n=17) comprised patients who died 4–28 days after MI (the regenerative phase). Macrophage infiltration in the heart was assessed by double immunofluorescence. We used stabilin-1 as a marker of M2 macrophages, while α-smooth muscle actin (α-SMA) was considered as a marker of cell transdifferentiation. Cells were counted in the infarct (IA) and non-infarct area (NIA). Morphological determination of adverse cardiac remodeling was based on the ratio of heart size, in particular, length/width ratio that was <1.1.

Results

We identified subpopulations of stabilin-1+/α-SMA− and stabilin-1+/α-SMA+ macrophages. In the IA the number of stabilin-1+/α-SMA− macrophages was lower during the inflammatory phase than during the regenerative phase (Table 1). The calculation of sensitivity and specificity of stabilin-1+/α-SMA− macrophages in the NIA for predicting of adverse cardiac remodeling has shown following: AUC=0.96, p<0.001. The cut-off value was 18 cells/mm2. The ROC curve is presented in Figure 1.

Conclusions

We identified that number of stabilin-1+/α-SMA− macrophages in the NIA ranged from 0 to 18 cells/mm2 was associated with adverse cardiac remodeling. The presence of stabilin-1+/α-SMA+ macrophages could indicate persistent tissue inflammation and possibility of macrophage transdifferentiation and plasticity. Our study supports prospects for implementation of macrophage biomarkers in clinical practice that might become a breakthrough in the development of new methods for management of MI and following complications.

Figure 1

Funding Acknowledgement

Type of funding source: None
Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction
Authors: Yoshida T , Shibata A , Tanihata A , Hayashi H , Ichikawa Y , Ishikawa H , Yamaguchi Y , Kitada R , Ehara S , Izumiya Y , Yoshiyama M
Published: November 2020

Background

Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy.

Purpose

We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy.

Methods

We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission.

Results

During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p<0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004).

Conclusions

In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events.

Kaplan-Meier curves

Funding Acknowledgement

Type of funding source: None
Sacubitril/valsartan improves ventilation stability in patients with chronic heart failure
Authors: Sciarrone P , Borrelli C , Giannoni A , Gentile F , Aimo A , Vergaro G , Emdin M , Passino C
Published: November 2020

Background

Sacubitril/valsartan (SV) ameliorates symptoms and prognosis in patients with heart failure and reduced ejection fraction (HFrEF), but the reasons for such effects are unclear. The impact of SV on ventilation has never been investigated. In HFrEF, apneas are highly prevalent both at daytime and nighttime and are associated with increased mortality.

Purpose

We hypothesize that treatment with SV could favourably stabilize ventilation by reducing the severity of central apneas in patients with HFrEF.

Methods

51 patients with HFrEF (mean age 67±9 years, mean left ventricular ejection fraction, LVEF 27±7%) and apneas defined by an apnea-hypopnea index, AHI≥5 (median 16, interquartile range 8–28) events/hour, eligible to treatment with SV and previously on optimal medical therapy for HFrEF, were enrolled. An extensive evaluation including cardiac ultrasound and a 24-hour cardiorespiratory monitoring was performed.

Results

After six months of treatment with SV, left ventricle systolic and diastolic function, mitral regurgitation (MR), left atrial volume (LAVI) and systolic pulmonary artery pressure (sPAP) were improved. Severity of apneas was reduced by 50%, 65% and 36% throughout the 24-hour, at daytime and nighttime, respectively.

Conclusion

Besides its known efficacy on cardiac remodeling, SV positively decreases the apneic burden in patients with HFrEF.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Roche Diagnostics unrestricted grant
U-shaped association of sphingosine-1-phosphate level with mortality in chronic systolic heart failure
Authors: Xue Y , Ma Q , Chen S , Wang X , Ma A
Published: November 2020

Background

The immunomodulatory molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. Until now, it has been unclear what is the normal range of S1P in chronic heart failure patients and whether it is related to long term prognosis.

Purpose

The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis.

Methods

We recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described a U-shaped association between S1P and all cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death. Survival curves were using the Kaplan-Meier method and the log-rank test was used for comparison.

Results

Compared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 μmol/L vs 1.122 μmol/L, P=0.006) and a larger standard deviation (0.441 vs 0.316, P=0.022). After a follow-up period of 31.7±10.3 months, the second quartile (0.967–1.192μml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (HR=3.87, 95% CI 1.504–9.960, P=0.005, adjusted HR=3.134, 95% CI 1.211–8.111, P=0.019) or a decrease (HR=3.271, 95% CI 1.277–8.381, P=0.014, adjusted HR=1.90, 95% CI 0.711–5.083, P=0.200) predicted a worse prognosis.

Conclusions

Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation. Through restoring abnormal levels to a normal range instead of simply up regulation or down regulation, S1P may have the potential to be a therapeutic target for reducing the risk of death in patients with heart failure in the future.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Science and Technology of the People's Republic of China. Ministry of Finance of the People's Republic of China.
Head-to-head comparison of MAGGIC-HF, SHFM and BCN-Bio HF scores
Authors: Codina P , De Antonio M , Domingo M , Santiago-Vacas E , Zamora E , Santesmases J , Subirana I , Buchaca D , Diez-Quevedo C , Boldo M , Rivas C , Velayos P , Nunez J , Lupon J , Bayes-Genis A
Published: November 2020

Background

Three heart failure (HF) web-based risk scores are currently used in clinical practice. Two only include clinical variables; one adds biomarkers, known to refine pathophysiological pathways in HF and to improve mortality prediction.

Objective

To assess inter-score agreement and to compare mortality prediction discrimination between MAGGIC-HF risk score, Seattle HF Model (SHFM) and Barcelona Bio-HF Risk Calculator (BCN Bio-HF), which includes both clinical and biomarker variables (NTproBNP).

Methods

Out of 1745 consecutive patients with HF from different etiologies admitted at our Unit from May 2006 to November 2018, 1689 with NTproBNP measurement at first visit were included. Absolute and consistency intraclass correlation coefficient (ICC) at individual level among the three risk estimation tools was assessed. Bland Altman graphics were used to illustrate the differences between scores across the broad spectrum of mortality risk. Discrimination of the three prediction tools was compared by AUC of the ROC curves for 1-, 3- and 5-year all-cause mortality. Patients used previously to derivate the BCN Bio-HF were excluded.

Results

Patients age 66.3±13.3 years, 70.4% men, LVEF 36.4%±14.4, ischemic etiology 43.7%. Absolute ICC was poor for the three tools (from 0.18 [–0.006 to 0.35] to 0.53 [0.42 to 0.62], while consistency ICC was slightly better (from 0.28 [0.24 to 0.33] to 0.57 [0.53 to 0.60], being highest the ICC of MAGGIC-HF and BCN Bio-HF. Correlation was better among scores in low-mortality risk profile patients but clinical scores tended to infraestimate the risk in comparison with the BCN Bio-HF in high-risk patients (Figure). Discrimination was numerically better with the BCN Bio-HF at every time risk (Table), significantly better when compared with SHFM.

Conclusions

In comparison with other clinical scores, the BCN Bio-HF calculator predicted better higher mortality risk. Correlation was globally poor for the three tools at individual level, although improved in the low risk patients. Discrimination tended to be numerically better with the BCN Bio-HF calculator, reaching statistical significance when compared with the SHFM.

Bland Altman agreement among tools

Funding Acknowledgement

Type of funding source: None
The impact of frailty and aging on prognosis in patients with heart failure with preserved ejection fraction – insights from PURSUIT-HFpEF registry
Authors: Okada M , Inoue K , Onishi T , Iwakura K , Yamada T , Yasumura Y , Tamaki S , Hayashi T , Yano M , Hikoso S , Sakata Y
Published: November 2020

Introduction

Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes.

Purpose

To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF).

Methods

Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: <76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: >87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident.

Results

The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p<0.001). The prevalence of frailty, defined as a CFS rating >4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p<0.001). During the median follow-up period 396 days (interquartile range, 344–698) after discharge, the clinical endpoint was observed in 172 patients. The incidence was higher in patients with frailty than those without it (49.6% vs. 30.4%, log-rank p<0.001). It was also correlated with age quartiles (Q1: 23.0%, Q2: 34.2%, Q3: 36.2%, Q4: 48.8%, log-rank p=0.001). Multivariate Cox regression analysis revealed that frailty (hazard ratio, 1.52; 95% confidence interval, 1.09–2.10; p=0.013) and age (hazard ratio per quartile increase, 1.24; 95% confidence interval, 1.07–1.43; p=0.004) were both associated with the clinical endpoint. Subgroup analysis in 352 patients without frailty also revealed the significant impact of age on the endpoint (1.26; 1.06–1.51; p=0.008). However, in 131 patients with frailty, there was no significant impact of age on the endpoint (1.16; 0.90–1.51; p=0.25).

Conclusions

Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.
Real world heart failure epidemiology and outcome: a population-based analysis of 1,990,162 heart failure patients
Authors: Leszek P , Zaleska-Kociecka M , Was D , Witczak K , Bartolik K , Rolska-Wojcik P , Brukalo K , Maruszewski B , Kleinork A
Published: November 2020

Background

Heart failure (HF) is the leading cause of death and hospitalization in developed countries. Most of the information about HF is based on selected cohorts, the real epidemiology of HF is scarce.

Purpose

To assess trends in the real world incidence, prevalence and mortality of all in-and outpatients with HF who presented in public health system in 2009–2018 in Poland.

Methods

It is a retrospective analysis of 1,990,162 patients who presented with HF in Poland in years 2009–2018. It is a part of nationwide Polish Ministry of Health registry that collects detailed information for the entire Polish population (38,495,659 in 2013) since 2009. Detailed data within the registry were collected since 2013. HF was recorded if HF diagnosis was coded (ICD-10).

Results

The incidence of HF in Poland fell down from 2013 to reach 127,036 newly diagnosed cases (330 per 100,000 population) in 2018 that equals to 43.6% drop. This decrease was mainly driven by marked reduction in females (p<0.001; Fig. 1A) and HF of ischaemic etiology (HF-IE vs HF-nonIE, Fig. 1B. p<0.001). The HF incidence per 100,000 population decreased across all age groups with the greatest drop in the youngest (Table 1).

The prevalence rose by 11.6% to reach 1,242,129 (3233 per 100,000 population) in 2018 with significantly greater increase in females and HF-IE (both p<0.0001, Fig. 1C and D, respectively). The HF prevalence per 100,000 population increased across all age groups except for the 70–79 years old. (Table 1).

Mortality increased by 28.5% to reach 142,379 cases (370 per 100,000 population) in 2018. The rise was more pronounced among females (p=0.015, Fig. 1E) and in HF-IE (p<0.001, Fig. 1F). The HF mortality per 100 000 population increased across all age groups, except for the 50–59 subgroup (Table 1).

Conclusions

Heart failure incidence plummeted in years 2013–2018 in Poland due to drop in newly diagnosed HF-IE. Despite that fact, the prevalence and mortality increased with rising trends in HF-IE.

Figure 1. Incidence, prevalence, mortality trends

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): The project is co-financed by the European Union from the European Social Fund under the Operational Programme Knowledge Education Development and it is being carried out by the Analyses and Strategies Department of the Polish Ministry of Health
Increasing home-time for patients with heart failure in Sweden 1992–2008
Authors: Ekestubbe S , Fu M , Giang K.W , Lindgren M , Rosengren A , Schioler L , Schaufelberger M
Published: November 2020

Background

Heart failure (HF) reduces survival and is one of the most common causes of hospitalizations in the elderly, imposing a major economic burden on the health care system, with frequency of rehospitalizations often used in interventional and observational studies in patients with HF. Home-time is a novel end-point measuring time spent alive and out of hospital and is easier for both clinicians and patients to relate to. Given the advances in treatment of HF over the last decades we postulated that an increase in home-time would follow.

Purpose

To investigate whether home-time for patients with HF has changed over the last decades in Sweden and if home-time differs between patients of working age and those retired, or between men and women.

Methods

Patients aged 18–84 years with a first hospitalization for HF in Sweden between 1992 and 2008 were identified using the National Inpatient Register which was linked to the Swedish Cause of Death Register. Information on rehospitalizations and mortality was collected and followed over a time period of 4 years. The patients were divided into two age groups: (i) <65 years and (ii) >65 years. The cut off 65 years was chosen being the official age of retirement over the study period in Sweden.

Results

A total of 324,907 patients were included in this study, mean age 73.5 years (standard deviation 9.3). Only 15.6% were <65 and 45.1% were women. In total, average home-time was 70.1% of the total follow up time, 2.1% of time was spent in hospital while, during a mean of 27.9% of the 4 year-period, patients were no longer alive. A small increase in home-time was observed over the study period. The older age group spent 67.7% at home compared with 83% in the younger group. After taking differences in mortality into account, the difference in home-time was no longer significant, with 92.7 and 95.8% home-time for the older and younger age groups, respectively. Over the entire study period older men had less home-time compared with older women. Since 1998 the reverse was true in younger men and women, where younger men had more home-time than younger women. Home-time increased for all subgroups over the study period with the most pronounced increase for younger men (see figure 1).

Conclusion

Home-time for patients in Sweden increased over the study period and the increase was more marked for younger patients, where men spent more time at home than women.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish state (ALF), The Swedish Heart and Lung Foundation, Västra Götaland Region, The Göteborg Medical Society
Coronary sinus oxidative stress markers allow for accurate assessment of the prognosis in patients with advanced heart failure awaiting transplantation
Authors: Szczurek W , Gasior M , Skrzypek M , Antonczyk K , Bielka A , Dziobek B , Zembala M , Szygula Jurkiewicz B
Published: November 2020

Background

Oxidative stress is a cause of cardiac diseases and contribute to apoptosis, cardiac remodeling, cardiac growth and repair. The end-stage heart failure (HF) is associated with ischemia-reperfusion, increased neurohumoral activity, cytokine stimulation and presence of inflammatory cells. Above factors are stimuli which generate free radicals and can induce oxidative stress in the heart and cause damage to essential myocardial structures and function. However, the role of oxidative stress in end-stage HF has not been fully understood.

Purpose

This study aimed to evaluate the prognostic value of the oxidative stress markers in ambulatory patients with end-stage HF awaiting heart transplantation (HT) during a 1.5 year follow-up period.

Method

The study was a prospective analysis of 85 optimally treated adult patients with end-stage HF, who were added to the HT waiting list at the Cardiology Department between 2015 and 2016. At the time of enrollment to the study routine laboratory tests, cardiopulmonary exercise test, echocardiography, spirometry and right heart catheterization were performed in all patients. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine total oxidant status (TOS) and total antioxidant capacity (TAC) levels. TOS and TAC were measured by Erel's method. The endpoint was all-cause mortality during a 1.5 years follow-up. The Medical University of Silesia's local Institutional Review Board approved the study protocol, and all patients provided informed consent.

Results

Median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. During the observation period, the mortality rate was 40%. The area under the receiver operating characteristics (ROC) curves indicated an acceptable discriminatory power of TAC (AUC: 0.780 [CI: 0.677–0.883]; sensitivity 56%, and specificity 90%); and excellent power of TOS (AUC: 0.9530 [CI: 0.9279–0.9781]; sensitivity 88%, and specificity 94%) for 1.5 years mortality. Patients with a low TAC level (≤1.10) had a significantly worse 1.5-year survival compared to the group with a high TAC level (>1.10) (1.5 year survival: 20.8% versus 75.4%; (long rank p<0.001). Similarly, patients with a high TOS level (≥3.11) had a significantly worse survival compared to the group with a low TOS level (<3.11) (1.5- year survival: 9.1% versus 92.3%; p<0.001).

Conclusion

TAC with acceptable prognostic power and TOS with excellent prognostic power allows assessment of the prognosis in end-stage HF during a 1.5 year follow-up period.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice, Poland
Predictors of relapse after improved ejection fraction in patients with heart failure
Authors: Esteves A.F , Marinheiro R , Fonseca M , Farinha J.M , Pinheiro A , Ferreira J , Goncalves S , Duarte T , Fonseca N , Caria R
Published: November 2020

Background

Patients with systolic dysfunction with improvement in left ventricular ejection fraction (LVEF) present a more favorable clinical profile when compared to those that maintain dysfunction. However, little is known about the characteristics of patients who “relapse” after LVEF improvement.

Purpose

Evaluate prevalence, clinical characteristics and outcomes of patients in whom ejection fraction declined after previous improvement.

Methods

We retrospectively studied patients followed at a heart failure (HF) clinic with LVEF improvement after an initial diagnosis of HF with reduced ejection fraction (EF), which was defined as having an LVEF >40% on follow-up. We then evaluated the presence of LVEF “relapse” in these patients – a decline in LVEF to <50% or <40%, in cases where it recovered to preserved EF or to mid-range EF, respectively. We analysed patient demographics, clinical parameters and outcomes and used logistic regression to assess the predictors of LVEF “relapse”.

Results

98 patients were studied, 70 (71%) male, median age 69 (58–76) years.

Fifty-four (55%) patients had recovered EF (>50%) and in 44 (45%) it had improved to mid-range values. In 36 (37%) occurred LVEF “relapse”: in 10 (10%) patients to an EF 40–50% and in 88 (90%) to an EF<40%.

Ischemic cardiomyopathy and non-ischemic dilated cardiomyopathy were the main HF aetiologies (38% and 35%, respectively).

During a median follow-up of 7 years, 39 (40%) patients had at least one HF hospitalization. Global mortality was 30%, with no significant statistical difference between the two groups.

In univariate analysis, HF duration, type 2 diabetes mellitus (T2DM), left main or left anterior descending coronary (LAD) disease, valvular heart disease (VHD) and chronic kidney disease (CKD) predicted LVEF “relapse”.

In multivariate analysis, T2DM, left main or LAD disease and VHD were the only predictors of LVEF “relapse” (Table).

Conclusion

In this group of patients, LVEF “relapse” after it had initially improved was frequent and was predicted by the presence of T2DM, left main or LAD disease and VHD. Despite improved systolic function, these patients remain at high risk, thus the need to maintain treatment.

Funding Acknowledgement

Type of funding source: None
Impact of right ventricular contractile reserve on exercise capacity in patients with heart failure: clinical application of low-load exercise stress echocardiography
Authors: Kinoshita M , Inoue K , Akazawa Y , Nakagawa H , Sasaki Y , Higashi H , Fujii A , Uetani T , Aono J , Nagai T , Nishimura K , Ikeda S , Yamaguchi O
Published: November 2020

Background

The peak oxygen uptake (VO2) evaluated by the cardiopulmonary exercise test (CPX) is an established marker of exercise capacity in patients with heart failure (HF). In particular, peak VO2 <14 ml/kg/min is used to be one of the criteria for heart transplantation. However, given exercise intolerance in patients with HF, it is difficult for refractory HF patients to reach sufficient exercise load. A recent report has highlighted significant impact of right ventricular (RV) function on mortality and urgent heart transplantation. Taken together, we hypothesized that the assessment of RV function was helpful to predict exercise capacity by using low-load exercise stress echocardiography (low-load ESE) in patients with HF.

Purpose

We evaluated whether RV dysfunction assessed by the low-load ESE determined a low peak VO2 <14 ml/kg/min in patients with HF.

Methods

We studied 67 consecutive hospitalized patients with HF (mean age, 65 years; 75% male; mean LV ejection fraction, 36%) who underwent ESE and CPX after stabilized HF condition, and the time interval of CPX and ESE tests was within 48 hours. CPX was performed using an upright cycle ergometer by a ramp protocol, while ESE was performed using ergometer in semi-supine position and the workload was generally increased by 25 watts every 3 minutes. The low-load ESE was defined as the 25 watts exercise. The increments of RV s' velocity at tricuspid annulus and RV strain in the free wall were considered as a preservation of RV contractile reserve. Among the study population, 26 patients were performed right heart catheterization and RV dP/dt/Pmax was estimated as an invasive marker of RV contractility.

Results

The achieved intensity of exercise was 50.4±21.0 watts, and all patients completed the low-load ESE. The invasive study showed that the change of RV s' velocity during the low-load ESE significantly correlated with RV dP/dt/Pmax (r=0.706, p<0.001). As shown in Figure, the non-invasive parameters of RV contractile reserve during the low-load ESE were significantly correlated with peak VO2 (RV s' velocity: r=0.787, p<0.001; RV strain: r=0.244, p=0.047). ROC analysis showed that the change of RV s' velocity during the low-load ESE correctly identified patients with peak VO2 <14 ml/kg/min (AUC=0.95, sensitivity 92.3%, specificity 85.2%). In terms of inter- and intra-observer variabilities, ICCs of the change of RV s' velocity were 0.86 and 0.96, and ICCs of the changes of RV strain were 0.63 and 0.70, respectively.

Conclusion

The change of RV s' velocity during the low-load ESE could determine exercise tolerance in patients with HF. The assessment of RV contractile reserve might be clinically useful to discriminate high risk HF patients.

Figure 1

Funding Acknowledgement

Type of funding source: None