bluuebunny/crossref_metadata_2025 huggingface dataset:
External validation of a heart failure risk prediction model in a remote monitoring cohort submitted to cardiac resynchronization therapy
Authors: Cardoso I , Coutinho M , Portugal G , Valentim A , Delgado A.S , Grazina A , Viegas J.M , Cunha P.S , Valente B , Oliveira M , Pereira R
Published: November 2020

Background

Patients (P) submitted to cardiac ressynchronization therapy (CRT) are at high risk of heart failure (HF) events during follow-up. Continuous analysis of various physiological parameters, as reported by remote monitoring (RM), can contribute to point out incident HF admissions. Tailored evaluation, including multi-parameter modelling, may further increase the accuracy of such algorithms.

Purpose

Independent external validation of a commercially available algorithm (“Heart Failure Risk Status” HFRS, Medtronic, MN USA) in a cohort submitted to CRT implantation in a tertiary center.

Methods

Consecutive P submitted to CRT implantation between January 2013 and September 2019 who had regular RM transmissions were included. The HFRS algorithm includes OptiVol (Medtronic Plc., MN, USA), patient activity, night heart rate (NHR), heart rate variability (HRV), percentage of CRT pacing, atrial tachycardia/atrial fibrillation (AT/AF) burden, ventricular rate during AT/AF (VRAF), and detected arrhythmia episodes/therapy delivered. P were classified as low, medium or high risk. Hospital admissions were systematically assessed by use of a national database (“Plataforma de Dados de Saúde”). Accuracy of the HFRS algorithm was evaluated by random effects logistic regression for the outcome of unplanned hospital admission for HF in the 30 days following each transmission episode.

Results

1108 transmissions of 35 CRT P, corresponding to 94 patient-years were assessed. Mean follow-up was 2.7 yrs. At implant, age was 67.6±9.8 yrs, left ventricular ejection fraction 28±7.8%, BNP 156.6±292.8 and NYHA class >II in 46% of the P. Hospital admissions for HF were observed within 30 days in 9 transmissions. Stepwise increase in HFRS was significantly associated with higher risk of HF admission (odds ratio 12.7, CI 3.2–51.5). HFRS had good discrimination for HF events with receiving-operator curve AUC 0.812.

Conclusions

HFRS was significantly associated with incident HF admissions in a high-risk cohort. Prospective use of this algorithm may help guide HF therapy in CRT recipients.

Funding Acknowledgement

Type of funding source: None
Pacemaker lead-induced progression of primary vs. secondary tricuspid regurgitation
Authors: Riesenhuber M , Spannbauer A , Pezawas T , Schukro C , Gwechenberger M , Stix G , Anvari A , Wrba T , Khazen C , Andreas M , Laufer G , Hengstenberg C , Gyongyosi M
Published: November 2020

Background

Currently no data are available whether the implantation of right ventricular (RV) pacemaker (PM) lead worsens preexisting primary or secondary (functional due to RV dilatation, RVD) tricuspid regurgitation (TR).

Purpose

The aim of the present retrospective analysis was to assess TR after PM implantation with a RV lead.

Methods

Patients with PM implantation (n=990) were enrolled if they had routine echocardiography including assessment of TR before first implantation and immediately after. RVD and severity of TR were characterized visually. Based on RVD in baseline echocardiography, patients were divided into 2 groups: with primary TR (without preexisting RVD, n=743) or secondary TR (with preexisting RVD, n=243).

Results

Lead-induced worsening of TR was present in both groups (Table 1). Progression from mild/moderate to severe TR was observed in 6.7% of patients with primary TR, compared to 25.6% of patients with secondary TR (P=0.001). Using an ordinal regression model, the probability to progress to severe TR with primary TR was 14.8% (95% CI 11.0%-19.7%), compared to 41.6% (95% CI 40.3%-42.8%) with secondary TR (P<0.001).

Conclusion

Preexisting secondary TR was associated with higher rates of lead-induced progression to severe TR compared to primary TR. Leadless pacing or tricuspid valve clipping post-PM implantation could be an option for patients with preexisting secondary TR and indication for a PM.

Table 1. Patient characteristics.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was supported by the European Union's Horizon 2020 Future and Emerging Technologies Programme [Grant number 732170].
Comparison of efficacy of different endovascular lead extraction techniques
Authors: Bracke F , Verberkmoes N , Rademakers N , Van 't Veer M , Van Gelder B.M
Published: November 2020

Background

Reports on lead extraction often concern a single technique, rendering direct comparison between techniques difficult.

Purpose

We compared efficacy and complications of consecutively used endovascular extraction techniques in a single centre.

Methods

Single centre observational study of consecutive lead extractions from 1997 to 2019. The preferential technique used over time was at first a laser sheath (LS), subsequently a femoral approach (FA) if feasible, and finally rotational mechanical sheaths (RMT). The FA remained the preferential initial technique for atrial and coronary sinus leads during the latter period. Extraction results are reported per lead for the initial technique before any alternative approach was initiated.

Results

A total of 1725 leads (including 222 ICD) leads were extracted in 775 patients. Primary endovascular extraction was attempted in 1703 leads (median implant time 6.0 yrs. [IQR 2.7–10.2]) with the remainder being surgically removed. Traction sufficed to remove 588 leads (median implant time 2.4 yrs. [IQR 1.2 - 4.7]). The table shows the radiological and procedural success of the initially used technique per lead. Including use as backup technique there were 7.4%, 0.5% and 1.2% major complications with respectively LS, FA, and RMT. Including backup approaches, clinical success (lead completely removed or only lead fragment <4cm left behind without mayor complication) for endovascular extraction of the 1703 leads was 94.8%.

Conclusion

The laser sheath has an inferior procedural outcome compared to rotational mechanical sheaths or a femoral approach which is largely the results of a higher complication rate. The femoral approach and mechanical rotational sheaths are seemingly equally effective, but the femoral approach is not suitable for many ICD leads and technically more demanding for ventricular leads. In current practice, the combination of a femoral approach and rotational mechanical sheaths yields optimal results.

Funding Acknowledgement

Type of funding source: None
The role of cardiac surgery in transvenous lead extraction (TLE) – experience from high volume center and 3207 procedures
Authors: Tulecki L , Czajkowski M , Targonska S , Tomkow K , Nowosielecka D , Jachec W , Polewczyk A , Stazka J , Kutarski A
Published: November 2020

Background

The guidelines suggest close co-operation between TLE operating team and cardiac surgery and its key role in the management of life-threatening complications remains unquestionable. But the role of cardiac surgeon seems to be much more extended.

Purpose

We have analysed the role of cardiac surgery in treatment of patients undergoing TLE procedures.

Methods

Using standard non-powered mechanical systems we have extracted ingrown PM/ICD leads from 3207 pts (38,7% female, average age 65,7-y) during the last 14 years. Non-infectious TLE indications were in 66,4% of patients. 46% had PM DDD system, 19% PM SSI, 22% ICD, 9% CRT, 4% other systems. In 12% of patients abandoned leads were found. 8% of patients had one lead, 54% - two, 15% - three and 4% - 4–6 leads in the heart. An average dwell time of all leads was 91,5 mth. The lead entry side was left in 96% of patients, right in 3% and both – 4%.

Results

Procedural success 96,1%, clinical success - 97,8%, procedure-related death 0,2%. Major complications appeared in 1,9% (cardiac tamponade 1,2%, haemothorax 0,2%, tricuspid valve damage 0,3%, stroke, pulmonary embolism <1%).

Conclusions

Rescue cardiac surgery (for severe haemorrhagic complications) is still the most frequent reason of surgical intervention (1,1%). The second area of co-operation includes supplementary cardiac surgery after (incomplete) TLE (0,8%). The third one is connected with reconstruction or replacement of tricuspid valve, which can be affected by ingrown lead or damaged during TLE procedure (0,5%). Implantation of the complete epicardial system during any surgical intervention (rescue or delayed) should be considered as a supplementation of the operation (0,65%). Some of patients after TLE need implantation of epicardial leads for permanent epicardial pacing (0,6%) and some only left ventricular lead to rebuild permanent cardiac resynchronisation (0,5%). The single experience of large TLE centre indicates the necessity of close co-operation with cardiac surgeon, whose role seems to be more comprehensive than a surgical stand-by itself.

Table 1

Funding Acknowledgement

Type of funding source: None
Transvenous removal of pacing and ICD leads: single italian referral center experience
Authors: Segreti L , Giannotti Santoro M , Di Cori A , Fiorentini F , Zucchelli G , De Lucia R , Viani S , Paperini L , Barletta V , Soldati E , Bongiorni M.G
Published: November 2020

Introduction

Device related complications are rising the need of Transvenous Lead Removal (TLR). Transvenous extraction of Pacing (PL) and Defibrillating Leads (DL) is a highly effective technique. Aim of this report is to analyse the longstanding experience performed in a single Italian Referral Center.

Methods

Since January 1997 to December 2019, we managed 2769 consecutive patients (2100 men, mean age 65.5 years) with 5086 leads (mean pacing period 73.6 months, range 1–576). PL were 3998 (1828 ventricular, 1704 atrial, 466 coronary sinus leads), DL were 1088 (1067 ventricular, 6 atrial, 15 superior vena cava leads). Indications to TLR were infection in 79% (systemic 27%, local 52%) of leads. We performed mechanical dilatation using a single polypropylene sheath technique and if necessary, other intravascular tools; an Approach through the Internal Jugular Vein (JA) was performed in case of free-floating leads or failure of the standard approach.

Results

Removal was attempted in 5076 leads because the technique was not applicable in 10 PL. Among these, 4952 leads were completely removed (97.6%), 49 (1.0%) partially removed, 75 (1.4%) not removed. Among 4989 exposed leads, 818 were removed by manual traction (16.4%), 3664 by mechanical dilatation using the venous entry site (73.4%), 48 by femoral approach (FA) (1.0%) and 335 by JA (6.7%). All the free-floating leads were completely removed, 25.3% by FA and 74.7% by JA. Major complications occurred in 20 cases (0.72%): cardiac tamponade (19 cases, 4 deaths), hemotorax (1 death).

Conclusions

Our experience shows that in centers with wide experience, TLR using single sheath mechanical dilatation has a high success rate and a very low incidence of serious complications. TLR through the Internal Jugular Vein increases the effectiveness and safety of the procedure also in case of free-floating or challenging leads.

Funding Acknowledgement

Type of funding source: None
The prevalence and prognosis of tricuspid regurgitation in stage A to C heart failure with preserved ejection fraction
Authors: Ren Q.W , Chen Y , Wu M.Z , Yu Y.J , Yiu K.H
Published: November 2020

Background

Previous studies have demonstrated that the presence of moderate and severe degree of tricuspid regurgitation (TR) is associated with adverse outcome in patients with heart failure with reduced ejection fraction. However, little is known about the prevalence and prognostic value of TR in patients with stage A, B and C heart failure with preserved ejection fraction (HFpEF).

Purpose

The aims of this study is to investigate the prevalence and prognostic value of TR in patients with stage A, B and C HFpEF.

Methods

A total of 2882 patients with stage A (n=904), B (n=1305) and C (n=673) HFpEF from 2013 to 2017 were enrolled. Detailed transthoracic echocardiogram was performed and the severity of TR was graded according to the latest recommendation. Patients were prospectively followed up at our heart failure clinic.

Results

The average age of the study population was 65 and 47% were male. Hypertension was presence in 58% and diabetes in 33% and the mean left ventricular ejection fraction was 62%. The prevalence of moderate and severe TR increased from stage A to C heart failure (HF) (4.2%, 5.9% and 16.5%, respectively, P<0.01). Kaplan-Meier curve revealed that the presence of moderate and severe degree of TR was associated with all-cause mortality and heart failure hospitalization (Log-rank test P<0.01) (Figure). Multivariable analysis demonstrated that moderate (hazard ratio=1.57, P<0.01) and severe TR (hazard ratio=2.53, P<0.01) was associated with mortality and heart failure hospitalization after adjusting for age, gender, ejection fraction, atrial fibrillation and HF stage.

Conclusions

The presence of moderate and severe TR is not uncommon in patients with stage A, B and C HFpEF. Importantly, moderate and severe TR was independently associated with mortality and heart failure hospitalization.

Kaplan-Meier curve for the impact of TR

Funding Acknowledgement

Type of funding source: None
Correlation of coronary microvascular function and diastolic dysfunction
Authors: Kim I.C , Hwang J , Lee C.H , Cho Y.K , Park H.S , Chung J.W , Yoon H.J , Kim H , Han S , Hur S.H , Koo B.K , Doh J.H , Shin E.S , Lee J.M , Nam C.W
Published: November 2020

Background

Coronary microvascular dysfunction (CMD) is an important mechanism for heart failure with preserved ejection fraction (HFpEF) which is closely related with diastolic dysfunction on transthoracic echocardiography (TTE).

Purpose

The aim of this study was to evaluate the association of CMD with echocardiographic parameters of diastolic dysfunction.

Methods

Total 385 patients with chest discomfort in the absence of significant coronary artery obstruction were enrolled to this study and underwent invasive coronary physiologic assessment including index of microcirculatory resistance (IMR), and coronary flow reserve (CFR). Echocardiographic parameters for diastolic dysfunction - left atrial volume index (LAVI) and left ventricular filling pressure (E over e') were compared in patients with true CMD (CFR<2.5 with IMR ≥20), mismatched CMD (CFR≥2.5 with IMR ≥20 or CFR<2.5 with IMR <20), and no CMD (CFR≥2.5 with IMR <20).

Results

Among the study population, 55 patients (14.3%) were true CMD, 162 patients (42.1%) were mismatched CMD and 168 patients (43.6%) were no CMD. Age (62.9±10.5 vs. 61.1±9.9 vs. 61.7±10.5, p=0.522) and left ventricular ejection fraction (63.9±8.1 vs. 63.9±6.2 vs. 63.0±6.7, p=0.414) was not different between groups. Patients with true CMD showed significantly larger left atrial size (LAVI: 34.7±18.2 mL/m2 vs. 26.8±10.7 mL/m2, p=0.005) and trend towards higher LV filling pressure (E/e': 10.8±3.5 vs. 9.9±3.5, p=0.073) compared with no CMD. In subgroup analysis, younger patients showed more pronounced increase of LAVI (Age <65: 39.6±22.6 vs. 26.1±11.6, p=0.003; Age ≥65: 28.0±9.13 vs. 28.8±8.2, p=0.266; p for interaction 0.043) in true CMD compared to no CMD. Non-diabetic patients also showed more pronounced increase of E/e' in true CMD (Non-diabetes: 10.2±2.7 vs. 9.2±2.6, p=0.002; Diabetes: 12.1±4.5 vs. 11.9±5.1, p=0.197; p for interaction 0.015).

Conclusions

Coronary microvascular dysfunction is significantly related with echocardiographic parameters of diastolic dysfunction. The effect of CMD on diastolic dysfunction is more prominent in low-risk patients.

Figure 1

Funding Acknowledgement

Type of funding source: None
Effect of infarct stiffness on non-infarcted left and right ventricular tissue remodeling: a computational study based on myocardial mechano-transduction
Authors: Koopsen T , Van Osta N , Willemen E , Van Nieuwenhoven F.A , Gorcsan J , Prinzen F.W , Arts T , Delhaas T , Lumens J
Published: November 2020

Background/Introduction

The mechanical properties of infarcted myocardium are important determinants of cardiac pump function and risk of developing heart failure following myocardial infarction (MI).

Purpose

To better understand the effects of infarct stiffness on compensatory hypertrophy and dilation of non-infarcted tissue in the left (LV) and right ventricle (RV), by using a computational model.

Methods

The CircAdapt computational model of the human heart and circulation was applied to simulate an acute MI involving 20% of LV wall mass. The simulation was validated using previously published experimental data. Subsequently, two degrees of increased infarct stiffness were simulated. In all three simulations, a model of structural myocardial adaptation of the non-infarcted tissue was applied, based on sensing of mechanical loading of myocytes and extracellular matrix (ECM).

Results

Mild and severe stiffening of the infarct reduced the increase of LV end-diastolic volume (EDV) from +23 mL to +17 mL and +16 mL, respectively, and the increase of LV non-infarcted tissue mass from +31% to +21% and +18%. RV EDV decreased after adaptation, and mild and severe infarct stiffening reduced the decrease of RV EDV from −21 mL to −12 mL and −10 mL, respectively. Increase of RV tissue mass was reduced from +13% to +8% and +7% with mild and severe infarct stiffening. In the LV, reduced dilation and hypertrophy were driven mainly by a reduction of maximum stress in the ECM and a higher stress between the myocytes and ECM following infarct stiffening. The decreased RV hypertrophy, but not EDV reduction, was caused by a reduction of maximum RV ECM stress and maximum RV active myofiber stress.

Conclusions

Model simulations predicted that a stiffened LV infarct reduces both LV and RV non-infarcted tissue hypertrophy as well as LV dilation. In LV remodeling, maximum ECM stress and stress between myocyte and ECM played a more prominent role than in RV remodeling, while maximum active stress was more important in the RV.

Overview of all model simulations

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.
Neutrophil neprilysin expression correlates with inflammatory activation in chronic HFrEF patients
Authors: Prausmueller S , Pavo N , Stasek S , Arfsten H , Spinka G , Goliasch G , Bartko P.E , Huelsmann M
Published: November 2020

Background

Inhibition of neprilysin by the angiotensin receptor-neprilysin inhibitor has shown remarkable success in the treatment of heart failure with reduced ejection fraction (HFrEF). However, the exact mechanism of action is still a matter of debate. Neprilysin (NEP) is a ubiquitous transmembrane endopeptidase markedly expressed on the cell surface of neutrophils, in this context also known as CD10. Originally, CD10 has been identified as a cell surface marker to discriminate mature from immature neutrophils. Other inflammatory neutrophil surface markers such as CD11b, CD64 and CD66b are commonly used to determine the activation status of neutrophils. In our previous explorative study, NEP expression on neutrophils correlated inversely with HF severity and mortality. This study aimed to explore the relationship between NEP expression and typical neutrophil activation markers and to confirm its relation to HF severity reflected by NT-proBNP and NYHA class in a bigger cohort of HFrEF patients.

Methods

We prospectively enrolled 208 consecutive patients with stable HFrEF. Mean fluorescence intensity (MFI) of CD10 expression on peripheral blood neutrophils was determined by flow cytometry of whole blood samples. In addition, for a subset of 117 patients the expression of CD11b, CD64 and CD66b was measured. EDTA anticoagulated blood (100 μl) was stained using a combination of six antibodies with fluorescence minus one sample as control [CD10 (#332777), CD45 (#560178), CD16 (#335035), CD11b (#555388), CD64 (#561191), CD66b (#562254); BD Biosciences, San Jose, CA, USA].

Results

Median age was 64 years (IQR 54–72), 57 (27%) patients were female. Median NT-proBNP values were 1819 pg/ml (IQR 740–4264). Approximately half of the study population with 115 (55.3%) patients had a non-ischemic etiology of HF. Median MFI of NEP (CD10) on neutrophils was 5542 (IQR 4168–6903). Neutrophil NEP expression decreased with HF severity reflected by NYHA stage (p=0.006) and tertiles of NT-proBNP (p=0.003). Interestingly, non-ischemic HFrEF was characterized by higher neutrophil NEP expression compared to ischemic HFrEF [5703 (IQR 4548–7235) vs 4994 (IQR 3844–6718), p=0.018]. Neutrophil NEP expression correlated highly significant with CD11b expression (r=0.61, p<0.001) but not with CD64 and CD66b [p=ns] (Figure 1).

Conclusion

These data support the evidence for an inverse correlation of neutrophil NEP expression with HF severity in stable HFrEF patients and for NEP upregulation on neutrophils in patients with non-ischemic cardiomyopathy. There was a strong relationship between neutrophil NEP regulation and the activation marker CD11b, proposing a link between the neutrophil NEP compartment and systemic inflammatory response.

Figure 1

Funding Acknowledgement

Type of funding source: None
Prevalence and prognostic impact of somatic mutations in patients with heart failure and reduced ejection fraction
Authors: Vazquez Andres D.J , Hernandez Vicente A , Diez Diez M , Gomez Molina M , Quintas A , Vazquez E , Dopazo A , Asensio Lopez M.C , Lax A , Sanchez Perez M.C , Fer E , De La Barrera J , Sanchez Cabo F , Fuster J.J , Pascual Figal D.A
Published: November 2020

Introduction

Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis.

Purpose

To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis.

Methods

We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF<45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF.

Results

A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556).

Conclusions

Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings.

Figure 1

Funding Acknowledgement

Type of funding source: None
Rehospitalization as a predictor of mortality in Polish population of heart failure patients-national registry
Authors: Zaleska-Kociecka M , Witczak K , Bartolik K , Was D , Kleinork A , Maruszewski B , Brukalo K , Rolska-Wojcik P , Leszek P
Published: November 2020

Background

High mortality risk in heart failure (HF) is related to repeat HF hospitalizations but also individual patient characteristics.

Purpose

To evaluate the impact of HF re-/hospitalizations and patient-related factors (sex, HF etiology, age, comorbidity) on all-cause mortality.

Methods

Our study represents one of the most extensive retrospective cohort analyses consisting of 1,686,861 adult Polish HF patients who presented into public health system in years 2013–2018. It is a part of a nationwide National Health Fund registry covering out- and in-patient data for the entire Polish population (38,495,659 in 2013) since 2009. HF hospitalizations were extracted using ICD-10 coding, whereas the comorbidity was evaluated by means of Charlson Comorbidity Index (CCI).

Results

In years 2013–2018 the absolute number of HF hospitalizations in Poland grew by 33% to 264,808 in 2018, whereas the number of rehospitalizations increased 1.5-fold to reach 137,708 in 2018.

In fact, nearly half of HF patients (n=817,432; 48.5%) experienced at least one hospitalization, while 15.4% (n=259,868) were rehospitalized during the study period. After initial hospitalization the readmission rate due to HF/all circulatory diseases at 30, 60, 180, 360, and 720 days was 10.4%/15.1%, 21.2%/28.3%, 43.9%/52.8%, 62%/70.4%, and 81%/87%, respectively.

As compared to patients who were hospitalized just once, those who underwent at least one rehospitalization were more often female (p<0.001), slightly older (p<0.001), and with higher burden of comorbidities based on CCI (p<0.001).

Patient survival was highly dependent on hospitalization frequency (Fig. 1). Mean survival rate at day 720 was 66.4%, 59.8%, 54.9%, 51%, and 43.9% for 1st, 2nd, 3rd, 4th, and ≥5th hospitalization, respectively.

After adjusting for age, sex, etiology (ischemic/non-ischemic) and CCI using a multivariate stratified Cox regression model, the estimated hazard ratios (HR) for all-cause mortality amounted to 1.22 (95% CI: 1.21–1.23, p<0.001) for 2nd, 1.4 (95% CI: 1.39–1.42, p<0.001) for 3rd, 1.58 (95% CI: 1.56–1.6, p<0.001) for 4th, and 1.97 (95% CI: 1.95–1.98 p<0.001) for 5th and subsequent hospitalizations, as compared to the first hospitalization.

Conclusions

Hospitalization rate in Poland is alarmingly high. Repeat HF hospitalizations strongly predict mortality rate for HF patients even after adjustment for age, sex, etiology, and comorbidity burden.

Figure 1. Kaplan-Meier for survival post hosp.

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.
Risk for stroke and systemic embolism in patients with atrial fibrillation and heart failure according to heart failure type
Authors: Uhm J.S , Yu H.T , Kim T.H , Pak H.N , Lee M.H , Joung B
Published: November 2020

Introduction

Risk for stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) and heart failure (HF) with mid-range (mr) ejection fraction (EF) is not well known.

Methods

Total 10,780 patients (age, 66.8±11.1 years; men, 64.7%) with AF were included in a prospective, multicenter AF registry. The patients were grouped into four according to HF type: no-HF, HF with preserved EF (HFpEF), HFmrEF, and HF with reduced EF (HFrEF). Baseline characteristics, cumulative incidence and hazard ratios for stroke/SE, major bleeding, and mortality were compared among the four groups.

Results

Proportion of patients with HF was 10.3%: HFpEF, 43.7%; HFmrEF, 23.6%; HFrEF, 32.7%. CHA2DS2-VASc score was significantly higher in the HFpEF, HFmrEF, and HFrEF groups than the no-HF group (4.0±1.7, 3.8±1.8, 3.5±1.8, and 2.5±1.6, respectively). Oral anticoagulants were administered in 83.6% of patients with CHA2DS2-VASc score ≥1. Annual incidence of stroke/SE was 2.0% in HFpEF group, 0.6% in HFmrEF group, 1.1% in HFrEF group, and 0.7% in no-HF group for 23.0±9.5 months of follow-up period. Cumulative incidence of stroke/SE was significantly higher in the HFpEF group than the no-HF and HFmrEF groups (p<0.001 and p=0.042, respectively; Figure). Risk for stroke/SE was significantly higher in the HFpEF group than the no-HF group [hazard ratio, 1.929; 95% confidence interval, 1.171–3.179, p=0.010]. There were no significant differences in risk for stroke/SE in the HFmrEF and HFrEF groups, compared with the no-HF group. There were no significant differences in major bleeding and mortality among the groups.

Conclusions

Risk for stroke/SE is highest in HFpEF and lowest in HFmrEF in patients with AF and HF.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Research Foundation of Korea
The expression of NKT like cells and NK cells in the peripheral blood among patients with idiopathic dilated cardiomyopathy (IDCM)
Authors: Stettner-Leonkiewicz D , Grywalska E , Zhang Z.Y , Rolinski J , Wysokinski A
Published: November 2020

Introduction

Dilated cardiomyopathy is associated with various immunological abnormalities, such as decreases in the activity and subsets of suppressor T cells and in the activity of natural killer cells, suggesting the involvement of immunological mechanisms in the pathogenesis of this disease. However, the role of NKT like cells and NK cells in the pathogenesis of idiopathic dilated cardiomyopathy remains still uncertain.

The aim of the study was to compare the frequencies of peripheral NKT like cells and NK cells among patients with IDCM to healthy controls.

Methods

The frequencies of NKT like cells and NK cells were measured by flow of cytometry among 50 patients with IDCM from Cardiology Clinic in Lublin. The control group consisted of 50 healthy sex- and age- matched volunteers. The diagnosis of IDCM was based on the common known ESC Guidenlines 2018 criteria. Statistical analysis of the results was conducted using IBM program. A value of p less than 0.05 was considered statistically significant.

Results

The frequency (%) (mean ± SD) of NK cells (CD3+/CD16+CD56+) was significantly lower (p≤0.001) in IDCM group (12.0±4.5) when compared to control group (15.6±3.4). The frequency (%) (mean ± SD) of NK T like cells (CD3+/CD16+CD56+) was significantly elevated (p≤0,04) in IDCM group (4,66±3,4) in comparison to the control group (3,23±1,7).

Conclusions

Our findings of the abnormalities in immune cells distribution in peripheral blood of IDCM patients suggest that IDCM development and progression is related to the dysregulation of the immune system. The decreases in the activity in the NK cells among patients with IDCM might indicate chronic myocarditis and lymphocyte infiltration in the myocardium. Moreover, the elevation of NKT like cells could be a result of prolonged exposure to pathogen in which TCD3+ cells become involved more than less mature NK cells in engaging specific immunity response.

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Medical University in Lublin, Grant for Young Reserchers
Estimated population prevalence of cardiac transthyretin amyloidosis in elderly men derived from incidental cardiac uptake from routine bone scans – “we're going to need a bigger boat”
Authors: Manning D , Butler T , Butler M , Majeed Y , Gordon R , Qadir G , Kazi S , Beynon R , Appaji A , Patwala A , Bailey D , Satchithananda D
Published: November 2020

Background/Introduction

Transthyretin amyloidosis (TTR) is a cause of restrictive cardiomyopathy and heart failure predominantly in elderly men. Two main factors have moved TTR amyloidosis from super-specialist centres into mainstream cardiology:

We aimed to determine the potential magnitude of referrals to our embryonic cardiac TTR service from patients having routine bone scans for non-cardiac reasons. We planned to estimate the prevalence of cardiac TTR in our local over 65 male population to plan service provision.

Methods

All HDP bone scans performed at a teaching and research hospital in the UK from the 2017/18 financial year were reviewed (n=1530). Our hospital is the only provider of these scans locally. Of these, 1399 were for oncological and musculoskeletal (oncology/MSK) indications and 37 were referred to specifically “exclude amyloidosis”. We excluded paediatric and duplicate follow-up imaging. There are approximately 140,000 people over aged 65 living within our catchment region. We have assumed approximately 50% are male.

Results

Myocardial uptake was present in 7/1399 of the oncology/MSK group and 3/7 (43%) of these already had features of heart failure. In these 7 patients bone scans were performed to investigate bony metastases in 6 (1 oesophageal cancer and 5 for prostate cancer) and 1 following an orthopaedic procedure. Cardiac uptake was present in 10/37 of the “exclude amyloid” group. In those with cardiac uptake across both groups (17) 94% were male with a mean age of 83 (sd ±6.59) and 41% were from the oncology/musculoskeletal group. Incidental cardiac uptake was seen in 1:200 routine HDP scans. When looking at males >65 specifically the uptake rate increases to (6 out of 701 scans) i.e. 1:117. Assuming there is no increased risk of TTR in patients with prostate or oesophageal cancer, then an estimate of cardiac TTR in the 75,000 males over the age of 65 locally would be approximately 640 men.

Conclusions

Bone scans account for 41% of all HDP scans with incidental cardiac uptake and therefore represents a significant potential referral source for a cardiac amyloid service. Our data suggests a potential prevalence of cardiac amyloidosis in 1:117 men over 65 with 43% already having heart failure symptoms and signs. Our age and sex specific prevalence suggests cardiac TTR is neither a rare nor unusual diagnosis. We will use our prevalence estimate to ensure our cardiac TTR service is resourced appropriately. We suggest that cardiac amyloid and cardio-oncology services should include pathways incorporating rapid access routes for suitable patients with incidental cardiac uptake on bone scans performed by non-cardiologists.

Funding Acknowledgement

Type of funding source: None
Risk of volume reduction associated with sodium-glucose cotransporter-2 inhibitors treatment: a meta-analysis of randomized controlled trials
Authors: Rong X.I , Li X , Gou Q , Chen X.P
Published: November 2020

Introduction

Sodium-glucose cotransporter-2 (SGLT2) inhibitors is a newly class of drug which improving glycemia by enhancing glycosuria, subsequently reducing blood pressure by osmotic diuresis and natriuresis. There are multiple large-scale randomized control trials demonstrating that SGLT2 inhibitors had salutary effect on cardiovascular-renal outcome, especially on heart failure. Although SGLT2 inhibitors exhibited promising potential value on treatment for type 2 diabetes mellitus (T2DM) with cardiovascular-renal comorbidities, the potential adverse events (AEs) related to osmotic diuresis such as volume reduction should not be neglected. Moreover, older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies are susceptible to adverse events related to volume reduction.

Purpose

To assess the association between sodium-glucose cotransporter-2 inhibitors and risk of volume reduction in patients with type 2 diabetes mellitus.

Methods

A systematic literature retrieval was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception up to 10 December 2019, Data for study characteristics and outcomes of interest were extracted from each eligible study. Pooled risk ratios (RRs) with 95% confidence interval (CI) for volume reduction was calculated using random-effects model.

Result

A total of 51 studies (n=56,866) were included in our meta-analysis, with a result of 1,337 incident volume reduction cases (814 in the SGLT2 inhibitors group, 523 in the control group). The pooled RR was 1.15 (95% CI: 1.03–1.28). It is evident that receiving SGLT2 inhibitors had increased the risk of volume reduction, when stratified by placebo-control or active-control the result was consistent.

Conclusion

Our meta-analysis has demonstrated that SGLT2 inhibitors increase the risk of volume reduction in patients with T2DM. It is necessary to attention for the risk of volume reduction associated with SGLT2 inhibitors, especially in older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies.

SGLT2 inhibitors vs control

Funding Acknowledgement

Type of funding source: None
Potantial clinical application of potassium binders in patients with chronic heart failure in real life clinical practice: results from TREAT HF study
Authors: Cavusoglu Y , Kaya H , Murat S , Yilmaz B
Published: November 2020

Purpose

Hyperkalemia is increasingly prevalent and life-threatening condition in heart failure (HF). In clinical practice, hyperkalemia is also an important barrier to optimal application of RAASi. New potassium binders, sodium zirconium cyclosilicate and patiromer, were developed for the treatment of hyperkalemia. TREAT HF data were analyzed for the evaluation of potential clinical application of potassium binders in real life clinical care in HF patients.

Methods

TREAT HF is a network which undertakes multicenter, national, observational studies designed to evaluate HF patients' clinical characteristics and current treatment modalities. 1028 patients with the diagnosis of chronic HF, median age 64 years and median LVEF 30% who had potassium and GFR data were included in this analysis. In this patient population, 847 patients (82.6%) were receiving beta blockers, 739 (71.9%) were receiving ACE inhibitors or ARBs and 518 (50.4%) were receiving MRA. Patients with hyperkalemia (serum potassium ≥5.1 mEq/L) were considered candidate for potassium binders based on the criteria of HARMONIZE study. According to eGFR (mL/min) level, renal dysfunction was subclassified as: stage-1 (eGFR ≥90) (n=211), stage-2 (eGFR 60-<90) (n=398), stage-3 (eGFR 30-<60) (n=306) and stage 4–5 (eGFR <30) (n=113).

Results

In study population, median potassium level was 4.5 mEq/L, median creatinin level was 1.1 mg/dL and median eGFR was 65.5 mL/min. Overall, 82.9% of patients had normal serum potassium levels (≥3.5–5 mEq/l) and 14.3% of patients (n=147) were found to have hyperkalemia (≥5.1 mEq/L) and, hypokalemia was found in 2.8% of patients (n=30). Hyperkalemia was present in 10.9% (n=23) of patients with stage-1, 12.6% (n=50) of patients with stage-2, 17.0% (n=52) of patients with stage-3 and 19.5% (n=22) of patients with stage 4–5 renal dysfunction. In patients with eGFR <60 ml/min (n=419), hyperkalemia was much more prevalent than those with eGFR ≥60 ml/min (n=609) (17.6% and 11.9% respectively, p=0.011). In patients with stage 4–5 renal dysfunction who were receiving ACEI/ARB or combination of ACEI/ARB and MRA (RAASi), more patients had hyperkalemia than those not receiving RAASi therapy (23.4%, 20.0% and 12.5%, respectively).

Conclusions

This study suggested that in real life clinical practice, 14.3% of HF patients have hyperkalemia and seem to be eligible for the treatment of potassium binders. The risk of hyperkalemia increases with advanced stages of renal dysfunction and the use of RAASi, showing an increased clinical need for potassium binders in HF patients with renal dysfunction and in those receiving RAASi.

Funding Acknowledgement

Type of funding source: None
Left atrial mechanics improvement after initiation of sacubitril-valsartan
Authors: Ferreira Fonseca M , Farinha J.M , Goncalves S , Marinheiro R , Esteves A , Pinheiro A , Ferreira J , Caria R
Published: November 2020

Introduction

Heart failure with reduced ejection fraction (HFrEF) is associated with significant morbidity and mortality. Recently, in the PARADIGM-HF, sacubitrilvalsartan was superior to enalapril in reducing death and hospitalization for heart failure, and there is a growing interest in determining the structural changes besides reverse left ventricular remodelling.

Purpose

To determine if, in patients treated with sacubitril-valsartan, there was a change in left atrial (LA) mechanics quantified by two-dimensional strain echocardiography (2D-STE).

Methods

A total of 38 consecutive patients with HFrEF, followed in an outpatient heart failure clinic, were recruited. Population characteristics are summarized in Table 1. 2D-STE was used to measure left atrial strain in the reservoir phase (LASr) (Figure 1) and strain rate (LA-SR) before and 3 months after initiation of sacubitril-valsartan.

Results

There was a significant improvement in LASr (11.3±6.5% vs 14.2±7.4%, p=0.006) and LA-SR (0.55±0.25 s-1 vs 0.69±0.31 s-1, p=0.008) after initiation of sacubitril-valsartan. There was also a significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (1443.5 pg/ml (Interquartile range [IQR], 772–2912) vs 1112.0 pg/ml (IQR, 510–1455), p=0.016) and a tendency towards reduction in left atrial volume index (LAVI) (54.6±17.0 ml/m2 vs 51.4±18.8 ml/m2, p=0.053). The change in LASr and LA-SR was not related with the dose of sacubitril-valsartan (p=0.089).

Conclusion

In this population of HFrEF patients LA mechanics, as determined by 2D-STE, as well as NT-proBNP levels, significantly improved after treatment with sacubitril-valsartan.

Figure 1. Left atrial strain

Funding Acknowledgement

Type of funding source: None
A different cardiac resynchronization therapy technique might be needed in some patients with nonspecific intraventricular conduction disturbance pattern-final results
Authors: Vereckei A , Katona G , Szelenyi Z , Kozman B , Szenasi G
Published: November 2020

Background

Current cardiac resynchronization therapy (CRT) works by pacing the latest activated left ventricular (LV) site. We hypothesized that the greater nonresponse rate of patients with nonspecific intraventricular conduction disturbance (NICD) than with left bundle branch block (LBBB) pattern to CRT might be due, besides less dyssynchrony, to the inability of the current CRT technique, devised to eliminate dyssynchrony caused by LBBB pattern, to eliminate dyssynchrony in some patients with NICD pattern, because their latest activated LV site is far away from that in LBBB.

Methods

We devised a novel surface ECG method to estimate the approximate location of the latest activated LV site based on the principle that the resultant ST vector of secondary ST segment alterations associated with wide QRS complexes is directed 180o away from the latest activated LV site. By measuring the amplitude and polarity of secondary ST segment alterations in two optional frontal and horizontal plane ECG leads and using a software, we determined the resultant 3D spatial secondary ST vector in 88 patients with LBBB and 57 patients with NICD patterns and heart failure. To validate the ECG method, we also estimated the latest activated LV region by echocardiography using 3D parametric imaging and 2D speckle tracking in 16 LBBB and 13 NICD patients. Patients with NICD pattern were subdivided according to their non-overlapping frontal plane resultant secondary ST vector ranges to NICD-1 (n=35) and NICD-2 (n=22) subgroups.

Results

The resultant 3D spatial secondary ST vector coordinates in the LBBB group were: (x axis: −0.228 mV, y axis: −0.062 mV, z axis: 0.63 mV); in the NICD-1 and NICD-2 subgroups: (x: 0.154 and 0.198 mV, y: −0.198 and 0.162 mV, z: 0.422 and 0.398 mV respectively). Consequently the latest activated LV sites were located leftward, posterosuperior in the LBBB group, right, posterosuperior in the NICD-1 and right, posteroinferior in the NICD-2 subgroups. The latest activated LV region determined by ECG and echocardiography matched in all patients, except 1.

Conclusions

The latest activated LV site was at the expected position in the LBBB group, while it was at an almost opposite site in the NICD-2 group [22/57 (39%)]. Thus, one potential reason for the unfavorable response to CRT, occurring in approx. 40% of patients with NICD pattern with a QRS duration of 120–149 ms in randomized studies, is that the current CRT technique using a left posterolateral LV electrode position may not be able to eliminate dyssynchrony in these patients.

Funding Acknowledgement

Type of funding source: None
Lateral left ventricular lead position is superior to posterior position in long-term outcome of patients underwent cardiac resynchronization therapy
Authors: Behon A , Schwertner W.R , Merkel E.D , Kovacs A , Lakatos B.K , Zima E , Geller L , Kutyifa V , Kosztin A , Merkely B
Published: November 2020

Background

Preferring side branch of coronary sinus during cardiac resynchronization therapy (CRT) implantation is empirical due to the limited data on the association of left ventricular (LV) lead position and long-term clinical outcome.

Purpose

We evaluated the long-term all-cause mortality by LV lead non-apical positions and further characterized them by interlead electrical delay (IED).

Methods

In our retrospective database 2087 patients were registered between 2000 and 2018. Those with non-apical LV lead locations were classified into anterior (n=108), posterior (n=643), and lateral (n=1336) groups. All-cause mortality was assessed by Kaplan-Meier and Cox analyses. Echocardiographic response was measured 6 months after CRT implantation.

Results

During the median follow-up time of 3.7 years, 1150 (55.1%) patients died, 710 (53.1%) with lateral, 78 (72.2%) with anterior and 362 (56.3%) with posterior positions. Patients with lateral position had significantly better outcome in all-cause mortality compared to others (HR 0.80; 95% CI: 0.71–0.90; p<0.0001), which was also confirmed by multivariate analysis after adjusting for relevant clinical covariates (HR 0.81; 95% CI: 0.72–0.91; p<0.0001). When echocardiographic response was evaluated in the lateral group, patients with an IED longer than 110 ms (ROC AUC 0.63; 95% CI: 0.53–0.73; p=0.012) showed 2.1 times higher odds of improvement in echocardiographic response 6 months after the implantation.

Conclusions

In this study we proved that after CRT implantation only the lateral LV lead location was associated with long-term mortality benefit. Moreover, patients with this position showed the greatest echocardiographic response over 110 ms IED.

Survival of total patient cohort

Funding Acknowledgement

Type of funding source: None