bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits for clinical outcomes associated with dual-chamber pacing versus ventricular pacing in patients with sinus-node dysfunction: a nationwide matched control study
Authors: Fauchier L , Bodin A , Bisson A , Herbert J , Spiesser P.H , Ah-Fat V , Pierre B , Clementy N , Babuty D
Published: October 2021

Introduction

Evidence from randomized trials suggests that, in patients with sinus-node dysfunction (SND), physiologic pacing (dual-chamber, DDD) may be superior to single-chamber (ventricular, VVI) pacing because it is associated with lower risks of atrial fibrillation and stroke, better exercise capacity and lower risk of pacemaker syndrome. However, benefits on mortality and risk of heart failure have not been demonstrated and these issues have not been fully evaluated in large “real life” analyses. The aim of our study was to assess and compare clinical outcomes within the first 30 days and during a longer-term follow-up with the two types of pacing at a nationwide level for patients with SND.

Methods

Using the administrative hospital database in France 2010–2020, 52,974 patients with SND were included in the analysis: 4,069 patients had VVI pacing and 48,905 had DDD pacing. Patients with leadless VVI pacemakers were excluded of the analysis. After propensity score matching 2,213 patients with VVI pacemaker were matched 1:1 with 2,213 patients treated with DDD pacemaker.

Results

In the matched analysis, patients with DDD pacemakers had a lower rate of all-cause (hazard ratio HR 0.711, 95% CI 0.61–0.828) and cardiovascular death (HR 0.628, 95% CI 0.48–0.818) within the 30 days after implantation. There were no significant differences for incidence of tamponade (HR 0.666, 95% CI 0.11–3.992), pneumothorax (HR 1.000, 95% CI 0.32–3.105), hemothorax (HR 0.800, 95% CI 0.21–2.982), major bleeding (HR 0.824, 95% CI 0.68–1.005) and transfusion (HR 1.016, 95% CI 0.83–1.243). During subsequent follow-up (mean: 3.0±2.8 years), risk of all-cause death in the matched population was significantly lower in the DDD group than in the VVI pacemaker group (HR 0.683, 95% CI 0.60–0.784). Patients with SND treated DDD pacemakers also had a lower risk of cardiovascular death (HR 0.569, 95% CI 0.44–0.732), new-onset atrial fibrillation (HR 0.638, 95% CI 0.58–0.706), ischemic stroke (HR 0.685, 95% CI 0.53–0.887) and hospitalization for heart failure (HR 0.758, 95% CI 0.68–0.850) than those treated VVI pacemakers, whilst risk of endocarditis was not significantly different (HR 0.986, 95% CI 0.50–1.951).

Conclusion

Patients with SND treated with DDD pacemakers had better clinical outcomes compared to those treated with VVI pacemakers. DDD pacing was associated with lower risks of death, cardiovascular death, new-onset atrial fibrillation, ischemic stroke, hospitalization for heart failure. DDD pacing was neither associated with a higher risk of complication on the short-term nor of endocarditis on the longer-term.

Funding Acknowledgement

Type of funding sources: None.
Leadless pacemaker patients following cardiac valve intervention in a long-term follow-up
Authors: Martinez-Sande J.L , Gonzalez L , Garcia-Seara J , Rodriguez-Manero M , Fernandez-Lopez X.A , Vega D , Gonzalez Juanatey J.R
Published: October 2021

Introduction

Leadless pacemakers (LPM) have demonstrated adequate electrical performance and safety in patients with multiple commorbidities such as heart valve replacements at short-term follow-up.

Purpose

We present our experience in patients with LPM and heart valve replacements at long-term follow-up.

Methods

This was a prospective observational study including all consecutive LPM implantation from June 1 2005 to March 15 2021. Clinical, electrical, echocardiographic characteristics, related complications and electrical parameters were compared in 2 different groups with and with-out valve surgical procedure.

Results

A total of 255 LPM were implanted. Clinical, electrical and echocardiographic characteristics are described in table 1. Mean follow-up was of 24 months. There were no significant differences in electrical performance or related complications in between both groups (Figure 1).

Conclusions

Electrical performance and complications were no significantly different between both groups with and without heart valve replacements.

Funding Acknowledgement

Type of funding sources: None.
Impact of supervised physical training on vasovagal syncope; a randomized controlled trial
Authors: Tajdini M , Tavolinejad H , Aghajani F , Yadangi S , Niyazi S , Bozorgi A , Sadeghian S
Published: October 2021

Background

Therapeutic interventions in vasovagal syncope (VVS) are centered on lifestyle modifications aimed to counteract the recognized mechanisms that precipitate syncope. In patients with recurrent VVS, supervised training might help reduce the symptomatic burden by increasing adherence to lifestyle modifications.

Purpose

We aimed to evaluate the effect of an integrated supervised training program versus standard care on syncopal recurrence rate among patients with VVS.

Methods

This randomized, controlled, 1:1 parallel-design, open-label trial was conducted between November 2019 and February 2021. Eligible patients were those aged between 18 and 70 years with newly-diagnosed medication-naïve VVS who had experienced ≥2 syncopal episodes in the prior year. All participants received education and reassurance about the benign nature of VVS, were advised to increase salt and fluid intake, and practice counter-pressure maneuvers based on 2018 European Society of Cardiology syncope guideline (standard care). Patients were randomized to standard VVS care or the training program. The intervention program consisted of thrice-weekly four-hours-long sessions during the first month after randomization; including tilt training, aerobic exercise (with rowing ergometer, recumbent biking), and standardized counter-pressure maneuvers supervised by a team of physical medicine and rehabilitation specialist and a cardiologist. After the first month, the intervention group were planned to attend a four-hours-long session every three months. The control group were followed by phone calls after the initial visit every three months. The intended follow-up duration was one year and the primary outcome was time to first syncopal episode.

Results

Out of 332 patients screened, 50 (mean age: 33.5 years; 64% female, figure 1) were equally randomized. Follow-up was completed for all participants. After one year, there was a significant reduction in syncope with supervised training compared to standard care (hazard ratio: 0.28; 95% confidence interval: 0.11 to 0.68; p=0.005, figure 2). Furthermore, frequency of syncope was lower in the supervised training arm versus standard of care (median [interquartile range]: 0 [0–1] versus 1 [0–3]; p=0.017).

Conclusions

In patients with recurrent VVS, supervised training showed promising results in reducing syncopal recurrence. Future research should focus on similar approaches to alter patients' lifestyle as an effective treatment for VVS.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Tehran University of Medical Sciences Figure 1Figure 2
Gender related differences in brugada syndrome
Authors: Cardoso A , Faria B , Von Hafe P , Dias G , Pereira T , Ribeiro S , Calvo L , Oliveira M , Fernandes M , Sanfins V , Lourenco A
Published: October 2021

Background

Brugada syndrome (BS) is a heritable channelopathy with male predominance. Males (M) seem to have a higher risk of arrhythmic events, although, there is limited data regarding gender differences in BS.

Aim

To compare the differences between genders in a Portuguese sample of BS patients (pts).

Methods

Single-center retrospective study of BS pts followed by the Arrhythmology Department. Pts were divided according to gender and compared regarding baseline characteristics and electrocardiographic (ECG) parameters that possibly predict the arrhythmic risk (significative S wave in DI, R wave sign, Tpeak-Tend interval and fragmented QRS). The events during follow-up were syncope of probable arrhythmic origin, ventricular tachycardia/ventricular fibrillation (VT/VF) and sudden cardiac death (SCD).

Results

A total of 165 pts were included; 64 (39%) were female (F) and the mean age at diagnosis was 47±15 years. The diagnosis was made by family screening (FS) in 72 (44%) pts. Sixty-seven pts (41%) had spontaneous type 1 pattern, 59 (36%) had history of syncope and 5 (3%) had history of aborted SCD. A positive genetic test was identified in 41 (25%) pts. Sixty-three (38%) pts were referred for an electrophysiological study (EEF) which was positive in 17 (27%) pts. A cardioverter-defibrillator was implanted in 45 (27%) pts. Females were more often diagnosed by FS (64% vs 31%, p <.001), had less type 1 spontaneous pattern (22% vs 53%, p<.001) and had no atrial fibrillation (0% vs 7%, p=.043). They performed EEF less frequently (22% vs 49%, p<.001) and had less spontaneous pattern during treadmill stress test (8% vs 33%, p=.004).

Regarding ECG parameters, females had shorter QRS interval (104±12 vs 115±18 ms, p<0.001), less frequent aVR sign (3% vs 27%, p<0.001), less significative S wave in DI (31% vs 55%, p=0.004), and a tendency for a shorter Tp-Te interval (80 vs 100 ms, p=0.051). Corrected QT interval was longer in females (396 vs 392ms, p=0.044). During a median follow-up of 28 (IQR 16–41) months, 7 pts had VT/VF (2F, 5M) and 3 had syncope (3M), with no differences between gender (p=0.287). There were no cardiovascular deaths.

Conclusion

In BS, female pts are more often diagnosed by FS and have less spontaneous type 1 pattern. Gender appears to affect basal ECG characteristics in BS, namely in parameters that may predict arrhythmic risk. Further studies are important to clarify the role of gender in prognosis and risk stratification of BS pts.

Funding Acknowledgement

Type of funding sources: None.
It is possible to predict mortality after ICD implantation?
Authors: Carrington M , Silverio Antonio P , Nunes-Ferreira A , Rodrigues T , Couto Pereira S , Bernardes A , Lima Da Silva G , Magalhaes A , J Pinto F , De Sousa J , Marques P
Published: October 2021

Introduction

Implantable Cardioverter Defibrillators (ICD) therapy is not recommended in patients who do not have a reasonable expectation of survival for at least 1 year, although specific recommendations regarding clinical or functional status evaluation are lacking.

Purpose

To identify predictors of all-cause mortality in patients who implanted an ICD.

Methods

Prospective single-center study of patients who implanted ICD between 2015 and 2019. Clinical characteristics were evaluated at baseline and mortality was assessed using the national registry of citizens. We performed uni and multivariate analysis to compare clinical characteristics of patients who died and who survived using Cox regression and Kaplan-Meier methods. For the predictor creatinine, we assessed the discrimination power and the best cut-off using the area under the ROC curve (AUC) method.

Results

From 2015–2019, 414 ICDs were implanted (81% male, 62±12 years-old), and 50 (13%) of the patients died after a median follow-up of 23 [11–41] months. Patients who died during the follow-up were older (67±9 vs 61±12, p=0.002), had more diabetes (48% vs 33%, p=0.033) and a higher creatinine (1.23 [0.84–1.86] vs 1.00 [0.84–1.22], p<0.001). The remaining comorbidities were similar between groups (Fig. 1). Patients who died had more frequently an ICD implanted after complication associated with a previous device or as a pacemaker upgrade (6% vs 2%, p=0.030). They also had a higher frequency of ischaemic cardiomyopathy (i-CMP) (82% vs 56%, p=0.002) and of ejection fraction (EF) ≤50% (96% vs 82%, p=0.040). The best cut-off value of creatinine to predict mortality with a sensitivity of 65% and a specificity of 72% was 1.2mg/dl (AUC 0.650; CI95% 0.53–0.77). After adjusting for diabetes, i-CMP, EF ≤50% and upgrade/re-implantation after complication, we found that age (HR 1.033; 95% CI 1.00–1.06, p=0.041) and creatinine ≥1.2mg/dl (HR 2.134; 95% CI 1.09–4.19, p=0.028) were independent predictors of all-cause mortality.

Conclusion

In our cohort of patients who underwent ICD implantation for primary or secondary sudden cardiac death prevention, the all-cause mortality over a median follow-up period of 23 [11–41] months was 13%. We found that in addition to age, a baseline creatinine level ≥1.2mg/dl increases by 2-fold mortality in patients who undergo ICD implantation. Decisions regarding ICD candidacy should not be based on age alone but should also consider creatinine that predisposes to mortality despite ICD implantation.

Funding Acknowledgement

Type of funding sources: None. All cause mortality
Feasibility of using his bundle pacing with boston scientific generators
Authors: Mark N , Papageorgiou N , Ramplin J , Monkhouse C , Moore P , Chow A , Hunter R , Sporton S , Providencia R , Earley M , Elliott J , Muthumala A
Published: October 2021

Introduction

His bundle pacing (HBP) aims to deliver physiological activation of the ventricles via the native His-Purkinje conduction system. A challenge of HBP is the limited market of implantation tools, pacing leads and specifically designed pacing algorithms.

Purpose

Over the last three years both Medtronic (MDT) and Boston Scientific (BSC) generators have been used for HBP in a large tertiary centre. We examined whether there was any difference between lead parameters and battery longevity depending on the type of manufacturer used.

Methods

Patients implanted with a MDT Select Secure model 3830 lead were included in this retrospective study. Data collected included HBP thresholds (analysed at 1ms pulse width) at implant and at the most recent device check, HBP percentages and battery longevity (months). Battery longevity were calculated by adding duration of follow up and estimated battery life at last follow up.

Results

A total of 31 patients were included for data analysis (58% male and mean age 72 years). 18 patients had MDT generators of which 3 were PPMs, 5 were CRT-Ps and 10 were CRT-Ds. 13 patients had BSC generators of which 5 were PPMs, 5 were CRT-Ps and 3 were CRT-Ds. Mean follow up of the cohort was 12.7±9.02 months.

Mean HBP percentages were 77±37% and 72.2±42.1% for MDT and BSC, respectively (p=0.430). Mean HBP threshold (Volts) at implant was significantly lower with BSC vs MDT (0.85±0.58 vs 1.84±1.06, p=0.01), and similar after follow up (1.01±0.91 vs 1.32±0.73, p=NS). There were no statistically significant differences between mean HBP threshold at implant compared to follow up for both manufacturers.

Interestingly, mean battery longevity for BSC vs MDT generators was significantly higher (136±29.3 vs 90.5±29.1, p<0.001). Longevity was also compared for PPM/CRT-P and CRT-D separately. For PPM/CRT-P, BSC generators had significantly higher longevity as compared to MDT (141.6±33.1 vs 91.6±34.5, p=0.009). This difference was not observed for CRT-Ds between the 2 manufacturers (p=0.068).

Conclusion

Our results suggest HBP with MDT Select Secure 3830 lead is feasible with BSC generators. There is potentially greater battery longevity with BSC compared to MDT generators. Further studies are needed with greater numbers and longer follow up to confirm this finding.

Funding Acknowledgement

Type of funding sources: None.
Survival among ischemic and non-ischemic heart failure patients with primary implantable cardioverter defibrillator therapy in Korea: a nationwide cohort study
Authors: Yang P.S , Kang Y , Sung J.H , Park H.D , Joung B
Published: October 2021

Background

Concerns still exist about the efficacy of prophylactic implantable electrocardiogram defibrillators (ICD) in patients with non-ischemic heart failure (HF). We evaluated the mortality and predictors of mortality in patients with prophylactic ICD implantation for ischemic and non-ischemic HF.

Methods

From 2008 to 2017, 1097 patients (667 non-ischemic; 430 ischemic) with prophylactic ICD implantation who were aged 19 years or older were identified from the Korean National Health Insurance Service database. We used propensity score overlap weighting to correct for differences between two groups.

Results

Compared with non-ischemic HF patients, ischemic HF patients were older (67.0±10.1 years vs. 61.8±14.2), more often male (71.4% vs. 63.7%), and had more comorbidities. During a median follow-up of 37.3 months (interquartile range (IQR), 14.2–53.8 months), all-cause death was higher in unweighted ischemic than non-ischemic HF patients (10.9 and 6.4 per 100 person-years, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.38–2.20, p<0.001). However, after weighting, annual all-cause mortality rate was similar in both groups (9.5 vs. 8.8 per 100 person-years) without difference in the risk of all-cause death (HR 1.08, 95% CI 0.68–1.71, p=0.755). Older age and chronic kidney disease were independent predictors of all-cause mortality in both groups. There was also no difference in cardiac and non-cardiac mortality between weighted non-ischemic and ischemic HF groups.

Conclusions

All-cause, cardiac and non-cardiac mortality were similar between non-ischemic and ischemic HF patients undergoing prophylactic ICD implantation. Our findings support the current guidelines recommendation for primary-prevention ICD in HFrEF patients with ischemic and non-ischemic HF.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Korean Healthcare Technology R&D project funded by the Ministry of Health and Welfare
Prognostic effect of the electrocardiographic pattern following cardiac resincronization
Authors: Asensio Nogueira J , Salgado-Aranda R , Garcia-Fernandez F.J , Martin-Gonzalez F.J , Villagraz-Tecedor L , Alvarez-Calderon M , Gomez-Llorente M , Sanchez-Corral E , Fernandez-Gonzalez B , Perez-Rivera J.A
Published: October 2021

Introduction

Following cardiac resincronization therapy (CRT), QRS duration is the most important prognostic factor in the 12-lead electrocardiogram (ECG). However, there is little evidence regarding if the electrocardiographic pattern following CRT has impact on morbidity and mortality.

Purpose

In this historical cohort study we analysed if a certain pattern in three leads of the ECG (Rs in V1, Qr in aVL or rS in I) is associated with lower incidence of adverse outcomes in a population of CRT patients within 1 year of implant. Other variables previously associated with success or failure of CRT were analysed.

Methods

Patients with CRT devices (pacemaker or defibrillator) with left ventricle lead in the coronary sinus were included from January 2012 to April 2019. One year clinical follow-up was performed. The primary endpoint was a composite of death of any cause and heart failure hospitalization. Differences in categorical data were reported as frequencies then compared using χ2 tests. Continuous variables were reported as means ± standard deviation with differences between groups tested using independent samples t-tests. Survival analysis was performed using Kaplan-Meier test, comparing survival graphics through Log-Rank test. For multivariate analysis, Cox regression was performed. Variables that showed significance in the univariate analysis were included.

Results

111 patients were included. Sample was divided into 2 groups according to the presence of the pattern in any of the three ECG leads. Two patients (1.8%) presented Rs in V1 and Qr in aVL simultanously and two patients (1.8%) presented Rs in V1 and rS in I. None of the patients presented all three patterns simultaneously. Baseline characteristics are reported in Table 1. Presence of any of the three patterns was independently associated with a lower incidence of the primary endpoint (2.3% vs. 17.6%, hazard ratio 0.1, 95% confidence interval 0.013–0.774, p=0.016). Previous atrial fibrillation was also independently associated with a higher incidence of the primary endpoint. QRS duration postimplantation did not showed prognostic value.

Conclusion

The presence of the patterns Rs in V1, Qr in aVL or rS in I is an independent predictor of good prognosis in patients with CRT.

Funding Acknowledgement

Type of funding sources: None. Baseline characteristicsKaplan Meier survival curves
Empagliflozin reduces TNFa-induced reactive oxygen species through inhibition of the human endothelial Na+/H+ exchanger 1
Authors: Uthman L , Baumgart P , Baartscheer A , Schumacher C.A , Li X , Hermanides J , Preckel B , Hollmann M.W , Coronel R.C , Zuurbier C.J , Weber N.C
Published: October 2021

Background

Chronic low-grade inflammation, endothelial dysfunction and oxidative stress are major interactive pathways contributing to the pathogenesis of HFpEF. The sodium/glucose cotransporter 2 (SGLT2) inhibitor Empagliflozin (EMPA) inhibits inflammation-induced ROS generation in endothelial cells. EMPA also lowers Na+/H+ exchanger 1 (NHE1) activity and cytoplasmatic Na+ levels ([Na+]c) in cardiomyocytes.

Purpose

It is unknown how inflammation causes oxidative stress in endothelial cells and how EMPA can mitigate this. Here we examined for human endothelial cells whether 1) inflammatory mediators activate NHE1 activity, 2) increased [Na+]c mediates the inflammation-induced ROS production, and 3) EMPA reduces inflammation-induced ROS through NHE1 inhibition.

Methods

Human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) were incubated with vehicle (V), 10ng/mL TNFα, 1μM EMPA or the canonical NHE1 inhibitor 10μM Cariporide. NHE1 activity was measured using the intracellular pH sensitive seminaphtharhodafluor fluorescence, by the pH recovery rate after an ammonium pulse. Intracellular ROS were detected by fluorescent live cell imaging in the presence of 10ng/mL TNFα or under increased Na+ conditions using 100nM ouabain (partial inhibition of the Na+/K+ pump). [Na+]c was measured using the sodium-binding benzofuran isophthalate 1 fluorescent probe.

Results

TNFα enhanced NHE1 activity in HCAECs (Fig a, in Δ[H+]/sec, V 0.81±0.14, TNFα 1.86±0.35 p<0.05). Increasing [Na+]c by ouabain elevated ROS generation (Fig b, in mM, HUVECs; V 5.6±1.3, ouabain 25.2±1.6 p<0.001, HCAECs; V 18.5±2.4, ouabain 91.2±32.6 p<0.05). EMPA reduced NHE1 activity in HUVECs (in Δ[H+]/sec, V 3.55±0.54, EMPA 1.66±0.25 p<0.01 vs V, Cariporide 0.95±0.11 p<0.001 vs V). HCAECs showed similar results. EMPA lowered [Na+]c (HUVECs; from 8.8±0.9 to 6.0±0.5 mM, p<0.05, HCAECs; from 7.8±0.7 to 4.0±0.8 mM, p<0.001). ROS generation was reversed in the presence of EMPA and/or Cariporide indicating that the effect was mediated by NHE inhibition (Fig c).

Conclusions

TNFα induces oxidative stress in EC through NHE1 activation and the consequently increased [Na+]c. EMPA acutely inhibits TNFα-induced ROS generation by inhibiting NHE1 and lowering [Na+]c in human cardiac and non-cardiac endothelial cells. Our data suggest that the previously reported cardiac effects of EMPA on NHE1 and [Na+]c are also present in endothelial cells. Endothelial ion homeostasis may be a valuable target to reduce inflammation-induced ROS generation and can constitute the pathway through which SGLT2 inhibitors offer protection in HFpEF patients, as examined in the EMPEROR-Preserved trial.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Prevalence of heart failure with preserved ejection fraction in antiphospholipid antibodies syndrome. The multicenter ATHERO-APS study
Authors: Pastori D , Ames P.R , Triggiani M , Cammisotto V , Carnevale R , Pignatelli P , Bucci T
Published: October 2021

Background

The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown.

Methods

Prospective multicenter cohort study including 125 patients: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP >220 pg/ml, left atrial (LA) enlargement, increased left ventricular filling pressure.

Results

Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE (Figure). Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG >40 GPL (odds ratio [OR] 3.43, 95% Confidence Interval [CI] 1.09–10.77, p=0.035), anti β-2-glycoprotein-I IgG >40 GPL (OR 5.28, 1.53–18.27, p=0.009), lupus anticoagulants DRVVT >1.25 (OR 5.20, 95% CI 1.10–24.68, p=0.038), (OR 3.56, 95% CI 1.11–11.47, p=0.033) and triple positivity (OR 3.56, 95% CI 1.11–11.47, p=0.033) were associated with HFpEF after adjustment for age and sex.

Discussion

HFpEF has a clinically relevant prevalence in patients with APS. The role of antiphospholipid antibodies in the pathogenesis and prognosis of HFpEF needs to be investigated.

Funding Acknowledgement

Type of funding sources: None.
Clinical significance of spleen size in patients with heart failure
Authors: Hiraiwa H , Okumura T , Sawamura A , Kondo T , Araki T , Mizutani T , Kazama S , Kimura Y , Shibata N , Oishi H , Kuwayama T , Furusawa K , Morimoto R , Murohara T
Published: October 2021

Background

The spleen is an important organ that stores blood, releases erythrocytes or monocytes, and destroys no-longer-needed platelets. It can reserve 20–30% of the total blood volume, and its size is reduced in hypovolemic shock. However, the clinical significance of the spleen size in patients with heart failure (HF) remains unclear.

Purpose

The purpose of this study was to investigate the relationship between spleen size, hemodynamic parameters, and prognosis in patients with HF.

Methods

A total of 219 patients with clinically stable HF were enrolled. All patients underwent right heart catheterisation and computed tomography. The spleen size was measured using computed tomography volumetry. In addition, spleen volume was assessed using the spleen volume index (SVI), corrected for body surface area. Cardiac events were composite endpoints of cardiac death, hospitalisation for worsening HF, fatal arrhythmias, implantation of cardiac devices, implantation of left ventricular assist devices, and unexpected percutaneous coronary intervention or cardiac surgery. Spearman's rank correlation coefficient was used to examine the relationship between spleen volume and hemodynamic parameters. Multivariate Cox hazard regression models were used to investigate whether SVI was an independent determinant of cardiac events.

Results

Of the 219 patients (median age, 54 [interquartile range] 46–64 years), 145 (66%) were males. The median (interquartile range) spleen volume and SVI was 118.0 (91.5–156.0) mL and 67.8 (54.9–87.2) mL/m2, respectively. SVI was positively correlated with cardiac output (r=0.269, P<0.001), and negatively correlated with systemic vascular resistance (r=−0.302, P<0.001) (Figure 1). A total of 70 cardiac events were observed, and the optimal cut-off value of SVI for cardiac events was 68.9 mL/m2 in the receiver operating characteristic analysis. Patients were divided into two groups: low-SVI (n=107, <68.9 mL/m2) and high-SVI groups (n=112, ≥68.9 mL/m2). Blood adrenaline concentration was higher in the low-SVI group than in the high-SVI group (0.039 [0.020–0.057] ng/mL vs 0.026 [0.014–0.044] ng/mL, P=0.004). The low-SVI group had more cardiac events than the high-SVI group (log-rank test, P<0.001) (Figure 2). In the multivariate Cox proportional hazard model, the low-SVI group was an independent predictor of cardiac events, even when adjusted for the conventional validated HF risk score, blood catecholamine levels, and hemodynamic parameters.

Conclusion

The spleen size may affect the prognosis in patients with HF, reflecting haemodynamics, including systemic circulating blood volume status and sympathetic nerve activity.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Features of chronic heart failure in COVID-19 pandemic
Authors: Grigoricheva E , Gessen G.R
Published: October 2021

Relevance

Current and past coronavirus infection can provoke and aggravate the course of previous chronic heart failure by initiating the processes of thrombus formation, inflammation and fibrinogen synthesis, affecting the pleuropericardial space, increasing the load on the right heart due to pulmonary hypertension.

Purpose of the study

To identify the features of chronic heart failure after COVID-19 infection with lung damage.

Material

An open cohort prospective study of 50 patients was carried out. Inclusion criteria: the presence of a positive brain natriuretic peptide and echocardiographic changes corresponding to systolic or diastolic dysfunction before the onset of the pandemic, signed informed consent. The diagnosis of COVID - 19 was confirmed by a positive PCR test and the presence of M and G antibodies, lung damage - by the results of computed tomography of the lungs.

Methods

Standard clinical examination, quality of life questionnaire, echocardiography with measurement of cavity volume, indicators of left ventricular systolic and diastolic function, size and function of the right ventricle. The second examination was carried out one month after hospitalization.

Results

The features of the clinical picture were an increase in shortness of breath (38 people, 86%), a decrease in exercise tolerance (40 people, 90%), an increase in chest pain (25 people, 60%), palpitations (40 people, 90%). On echocardiography, the most frequent dynamics compared to the 2019 echocardiography indicators were an increase in pressure in the pulmonary artery (44 people, 100%), the size of the right (38 people, 86%) and left ventricles (30 people, 68%), left atrium (38 people, 86%), an increase in the severity of valvular regurgitation (44 people, 100%) and a decrease in the ejection fraction within the “gray zone” (38 people, 86%). The newly emerging decrease in EF below 45% was recorded much less frequently, in 13 people (30%). In 40 (80%) patients, certain signs of deterioration of left ventricular diastolic function were revealed: dilatation of the left atrium, decrease in the mean e, increase in E/e' according to tissue Doppler ultrasonography. The TAPSE index, which characterizes the global function of the right ventricle, practically did not decrease. Frequent findings during echocardiography one month after the disease were a small amount of fluid in the pericardial cavity (30 people, 68%) and pleuropericardial adhesions.

Conclusion

The clinical condition of patients with CHF in the first month after a previous infection with COVID-19 with lung involvement corresponded to a worsening of CHF with rhythm disturbances and instability of blood pressure, which on echocardiographic examination was manifested by dilatation of the heart cavities, valvular regurgitation, diastolic dysfunction of the left ventricle and increased pressure in the arteries.

Funding Acknowledgement

Type of funding sources: None. Dynamics of echocardiography in patients
Predictive value of NT-proBNP in non-obstructive hypertrophic cardiomyopathy
Authors: Hutt E.H , Mentias A.M , Alashi A.A , Fava A.F , Popovic Z.P , Thamilarasan M.T , Lever H.L , Desai M.Y.D
Published: October 2021

Background

We studied the prognostic value of serum NT-proBNP in nonobstructive hypertrophic cardiomyopathy (nHCM) patients.

Methods

We studied 777 nHCM patients (55±13 years, 54% men, maximal left ventricular outflow tract gradient [LVOTG] <30 mm Hg) with serum NT-proBNP measured at baseline. We excluded patients with prior septal myectomy (SM) & LV ejection fraction (LVEF) <55%. NT-proBNP was adjusted for age & sex & converted to a log NT-proBNP ratio. Clinical & echo variables were recorded. Primary endpoint was death, appropriate implantable defibrillator (ICD) discharge or heart transplant.

Results

NT-proBNP ratio was high in 473 and low in 304 patients. Median [interquartile range] LVEF, LVOTG & NT-proBNP were 61% [59, 66], 7 [4, 12] mm Hg & 481 [137–1361] pg/dl. 31% had functional class ≥II & 32% had ≥1 sudden cardiac death risk factor. At 5.3 [3–9] years, 139 (18%) met the primary endpoint (107 deaths). On spline analysis, log NT-proBNP ratio >2.75 was associated with higher events. Cox & Kaplan-Meier survival analyses showed that high NT-proBNP ratio was independently associated with events (Figures 1A-B). In the subgroup of asymptomatic patients, NT-proBNP ratio remained associated with the primary outcome (adjusted HR 1.45, 95% CI 1.10–1.93, P=0.009).

Conclusions

Higher NT-proBNP ratio (>2.75) is independently associated with adverse outcomes in nHCM, including asymptomatic patients, suggesting risk stratification even in earlier disease stages.

Funding Acknowledgement

Type of funding sources: None.
Cardiac reverse remodelling by 2D and 3D echocardiography in heart failure patients treated with sacubitril/valsartan: a prospective study
Authors: Mantegazza V , Volpato V , Mapelli M , Sassi V , Salvioni E , Mattavelli I , Tamborini G , Agostoni P , Pepi M
Published: October 2021

Background

Left ventricular (LV) reverse remodelling induced by sacubitril/valsartan (S/V) has been shown in heart failure patients with reduced ejection fraction (HFrEF) by two-dimensional (2D) transthoracic echocardiography (TTE). Data about S/V effect on the right ventricle (RV) are scarce.

Aims

We aimed to evaluate S/V-induced changes in NT-proBNP levels, and cardiac remodelling indices by 2D and three-dimensional (3D) TTE in HFrEF patients, classifying patients according to aetiology.

Methods

We prospectively enrolled 51 HFrEF patients (24 ischaemic, 27 non-ischaemic). At baseline and at 6-months follow-up (6MFU) after S/V treatment optimization, we i) assessed NT-proBNP; ii) performed 2D TTE according to guidelines for the assessment of biventricular size and function, mitral regurgitation grade and LV diastolic function; and iii) performed 3D TTE, using the Dynamic HeartModel software for the evaluation of LV volumes and function, the 4D LV-Analysis software for the assessment of LV longitudinal strain, and the 4D RV-Analysis software for the assessment of RV volumes and function (Figure 1).

Results

In non-ischaemic patients, both 2D and 3D TTE showed an improvement in LV volumes and biventricular function, whereas only 3D detected a reduction in RV size at 6MFU vs baseline (Table 1). In ischaemic patients, only 3D TTE showed an improvement in biventricular size and LV function (Table 1). Finally, S/V induced a significant improvement in NT-proBNP (Table 1) and diastolic function both in ischaemic and non-ischaemic groups: patients with elevated left atrial pressure (as assessed by 2D parameters of diastolic function) decreased from 45% to 20% in ischaemic and from 40% to 10% in non-ischaemic patients (p<0.05).

Conclusions

S/V induced a significant improvement in NTproBNP and diastolic function in both aetiologic groups. A clinically significant improvement in biventricular function was shown only in non-ischaemic patients. 3D TTE may be advantageous to ascertain subtle changes in LV size and function, undetected by 2D imaging, and to evaluate RV dimensions and function, which have a major impact on HFrEF prognosis.

Funding Acknowledgement

Type of funding sources: None. Figure 1Table 1
Impact of decreased lymphocyte, total cholesterol, and albumin levels at discharge on all-cause death in patients with acute heart failure
Authors: Kato T , Yaku H , Yamamoto E , Inuzuka Y , Tamaki Y , Ozasa N , Kimura T
Published: October 2021

Background

Lymphocyte, total cholesterol, and albumin levels consist of Controlling Nutritional Status (CONUT) score, which has been reported to prognosticate patients with acute heart failure (AHF). However, the influence of each component of CONUT score on outcomes in patients with AHF was not fully elucidated.

Purpose

We aimed to evaluate the prognostic implication of the decrease in lymphocyte, total cholesterol, and albumin levels in patients with AHF.

Methods

We analyzed 1812 AHF patients in whom data at discharge were available from a multicenter registry. The decrease of lymphocyte (Ly) count was assigned with Ly≥1600/mL (31.0%), 1200≤ Ly <1600 (26.9%), 800≤ Ly <1200 (28.6%), Ly <800 (13.5% of patients). The decrease of total cholesterol (TC) was assigned with TC≥180mg/dL (28.9%), 140≤ TC <180 (42.2%), 100≤ TC <140 (26.7%), TC <100 (2.1% of patients). The decrease of albumin (Alb) was assigned and doubled with Alb≥3.5g/dL (45.7%), 3≤ Alb <3.5 (35.1%), 2.5≤ Alb <3 (15.2%), Alb <2.5 (3.9% of patients). The primary outcome measure was all-cause death after discharge from the index hospitalization. Cumulative incidences were estimated by the Kaplan-Meier method and differences were assessed with the log-rank test. We constructed multivariable Cox proportional hazard models to estimate the risk of the decrease in each value per grade, with the results expressed as the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Cumulative one-year incidence of the all-cause death was higher with decreasing Ly, TC, and Alb levels (P<0.0001, P<0.0001, and P=0.02, respectively) (Figure 1). The adjusted hazard ratio for all-case death per grade decrease is most prominent in albumin (HR: 1.36, 95% CI: 1.20–1.54), followed by lymphocyte count (HR: 1,23, 95% CI: 1.10–1.38), whereas it became insignificant in total cholesterol (HR: 1.05, 95% CI: 0.91–1.21).

Conclusions

The prognostic implications after discharge were different in albumin, lymphocyte count, and total cholesterol in patients with AHF.

Funding Acknowledgement

Type of funding sources: None. Figure 1
How predict right ventricular-pulmonary circulation coupling improvement in chronic heart failure
Authors: Santiago-Vacas E , Domingo M , Codina P , Cediel G , Spitaleri G , Zamora E , Gual F , Teis A , Santesmases J , Velayos P , Pulido A , Crespo E , Nunez J , Lupon J , Bayes-Genis A
Published: October 2021

Background

Right ventricular-pulmonary circulation coupling (RVPAC), which can be measured by the relation between tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) by echocardiography, has been postulated as an independent prognostic factor of hospitalizations and mortality in heart failure (HF) patients.

Purpose

Our aim was to know the predictors of RVPAC improvement in a chronic HF cohort.

Methods

Retrospective analysis of a prospectively studied cohort of HF outpatients of different aetiologies attended in a multidisciplinary HF Unit. Prospectively scheduled echo-Doppler studies were performed at first visit and 1 year. A TAPSE/SPAP ratio <0.36 mm/mmHg was identified as the most deleterious. Significant RVPAC improvement at 1 year was defined as TAPSE/SPAP ratio ≥0.36 mm/mmHg together with a ≥10% improvement from baseline RVPAC. Multivariable logistic regression analysis (conditional backward stepwise) was performed to select variables independently associated with significant RVPAC improvement. A predictive model including age and the previously selected variables was created.

Results

From August 2001 to July 2017, 554 patients with TAPSE and SPAP data in the initial visit were included. Mean follow-up time was 4.6±3.7 years. At first visit 252 (45.5%) patients had RVPAC <0.36 mm/mmHg. Out of them, RVPAC at 1 year improved in 55 (21.8%). In multivariable analysis, the presence of baseline atrial fibrillation/flutter (OR 0.12 [95% CI 0.05–0.28], p<0.001), SPAP (OR 0.96 [95% CI 0.92–0.99], p=0.014) and female gender (OR 0.34 [95% CI 0.12–0.91], p=0.03) were related to lesser probability of RVPAC improvement at 1 year. A model with such variables, together with age, showed an AUC of 0.824 to predict significant RVPAC improvement.

Conclusions

Atrial fibrillation/flutter, increasing SPAP and female gender hamper RVPAC improvement at 1 year in HF patients with baseline TAPSE/SPAP ratio <0.36.

Funding Acknowledgement

Type of funding sources: None. Multivariate regression analysis
Cysteine-rich angiogenic inducer 61 (CCN1) independently predicts all-cause mortality in patients with dilated cardiomyopathy
Authors: Klingenberg R , Gross S , Lehnert K , Wegner D , Hamm C.W , Felix S , Keller T , Doerr M
Published: October 2021

Introduction

Cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) is a member of the CCN family of matricellular proteins exerting key functions in inflammation and fibrotic turnover. Recently it has been shown that CCN1 improves risk stratification for all-cause mortality in ACS patients.

Purpose

Since both inflammation and fibrosis are key processes involved in the pathogenesis of dilated cardiomyopathy (DCM), we aimed to investigate the prognostic value of CCN1 serum levels for survival in a large cohort of DCM patients.

Methods

The cohort compromised patients with a primary diagnosis of DCM, defined as a reduced left ventricular ejection fraction (LVEF <45%) and an increased left ventricular enddiastolic diameter according to the HENRY score (LVEDD according to HENRY >117%) at the time of diagnosis. Exclusion criteria were primary valvular diseases (≥ second degree), acute myocarditis, active infectious diseases, pulmonary diseases, cancer, chronic alcoholism and heart failure of other origins. CCN1 levels were determined in human serum using an enzyme-linked immunosorbent assay (R&D Systems, USA). Multivariable cox regression models for the association between CCN1 and all-cause mortality were adjusted for age, sex, disease duration, LVEF, estimated glomerular filtration rate (eGFR) measured based on the CKD-EPI formula, high-sensitivity C-reactive protein (hs-CRP) and aminoterminal-proB-type natriuretic peptide (NT-proBNP) levels.

Results

306 DCM patients had available biomarker and clinico-demographic data in this single-center cohort (79.3% males) with a mean age of 55.2 years [interquartile range [IQR] 47.9, 64.8]). On average, disease duration was 0.3 years (IQR 0.9, 1.9), LVEF 31% (IQR 25, 37), LVEDD 67.7 mm (IQR 63, 72), and eGFR 91.5 ml/min (IQR 74.1, 102.4). During a median follow-up of 12.5 years (IQR 10.5, 14.1), a total of 114 (37.3%) patients died. Multivariable-adjusted cox regression models revealed an increasing all-cause mortality risk across CCN1 tertiles (p for trend = 0.03), with the highest incidence in the highest tertile (hazard ratio [HR] 1.75; 95%-CI 1.04, 2.94; P=0.034) as compared to the lowest tertile (Figure 1).

Conclusion

CCN1 predicts long-term survival in DCM patients independent of NT-pro-BNP and other risk determinants. Further research needs to evaluate whether this novel biomarker also plays a causal role in the pathogenesis of DCM.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Kerckhoff Foundation Figure 1
Reassessing the NYHA classification for heart failure: a comparison between classes I and II using cardiopulmonary exercise testing
Authors: Zimerman A , Cardoso De Souza G , Engster P , Spier Borges M , Ulrich Schaan T , Pilar I , Stein R , Fonteles Ritt L.E , Donelli Da Silveira A , Rohde L.E
Published: October 2021

Background

The New York Heart Association (NYHA) functional classification has evolved to become a major determinant of eligibility to medical interventions and clinical trials, but its reliability to discriminate patients with mild heart failure (HF) has been questioned by studies that demonstrated a major overlap in self-reported symptoms and laboratory markers between NYHA classes I and II.

Purpose

To assess the reliability of NYHA classification by comparing cardio-pulmonary exercise test (CPET) results and its overlap between HF patients classified as NYHA I and II.

Methods

We retrospectively analyzed data from HF patients who underwent CPET in 3 medical centers in Brazil. NYHA class was defined as recorded on CPET day or during the previous clinical visit. Inclusion criteria were diagnosis of HF, age ≥16, and NYHA class I or II. We analyzed overlap between kernel density estimations for the percent-predicted peak VO2, minute ventilation/carbon dioxide production (VE/VCO2) slope, and oxygen uptake efficiency slope (OUES) in patients in NYHA classes I and II. Categorical variables were compared using chi-square tests.

Results

We included 684 patients, of which 42% (284) were classified as NYHA I. Mean age was 56.1 years; 44% (303) were female and mean left ventricular ejection fraction was 36% (±14.2%). Regarding CPET measures, mean global percent-predicted peak VO2 was 56.6% (±26.1%), VE/VCO2 slope was 38.8 (±10.2), and OUES was 1.50 (±0.59). Kernel density overlap between NYHA classes I and II was considerable: 83% for percent-predicted peak VO2, 89% for VE/VCO2 slope, and 85% for OUES (Figure 1). There was no significant difference between NHYA I and II in CPET indicators of poor prognosis: percent-predicted peak VO2 <50% was present in 53% vs. 48% of patients classified as NYHA I and II, respectively (p=0.15); VE/VCO2 slope >36 in 54% vs. 57% (p=0.39); and OUES <1.4 in 46% vs. 48% (p=0.51).

Conclusions

HF patients classified as NYHA I and II overlap substantially in objective measures of functional capacity assessed by CPET. These findings suggest that NYHA classification is a poor discriminator of cardiopulmonary capacity among patients with mild HF, and raise questions about its use as a benchmark to guide HF therapy.

Funding Acknowledgement

Type of funding sources: None. Figure 1