bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnic variation in implantable cardioverter defibrillator implant trends in New Zealand 2005–2019
Authors: Foo F.S , Lee M , Stiles M.K , Poppe K.K , Jackson R , Kerr A.J 
Published: October 2021

Abstract

Background
Implantable cardioverter defibrillator (ICD) implant rates in New Zealand (NZ) have increased significantly in recent years. Previous studies in NZ have demonstrated that Māori and Pacific patients had higher rates of ischaemic heart disease compared to other ethnicities. Ethnic variation in ICD implant rates have been reported internationally, but whether this trend exists in NZ is unclear.

Purpose
This paper aims to provide the first analysis of new ICD implants by ethnicity over an extended time period.

Methods
All patients who received a new ICD implant were identified for the period of 1st January 2005 to 31st December 2019 using the National Minimum Datasets, which collects information on all public hospital admissions in NZ. Ethnicity prioritisation was performed in the following order: Māori, Pacific, Asian and European. New ICD implant rates were analysed by ethnicity and age-groups.

Results
A total of 5,514 new ICDs were implanted over the study period. New ICD implant rates increased by 137%, from 41.4/million in 2005 to 98.2/million in 2019, at an average of 5.4%/year (p&lt;0.01). Over the study period, the highest age-standardised implant rates were in Māori, followed by Pacific, European and Asian ethnicities. The largest increase was seen in Pacific patients at 8.9%/year (p&lt;0.01), followed by Māori and Asian patients at 4.7%/year (p&lt;0.01) and 4.3%/year (p&lt;0.01), respectively. In European patients, ICD implant rates initially increased by 10.3%/year (p&lt;0.01) between 2005 to 2012, but subsequently plateaued at −0.4%/year (p=0.71) between 2012 to 2019. By 2019, the age-standardised implant rates in Māori, Pacific and European patients were 3 to 4 times higher than Asian patients (Figure 1).
In the age groups of &lt;39, 40–59, 60–69 and 70–79 years, Māori and Pacific patients had higher implant rates through most of the study period. Asian patients consistently had the lowest new ICD implant rates across all age groups. The substantially higher age-specific implant rates in the age groups of 40–59 years and 60–69 years in Māori and Pacific patients resulted in higher overall age-standardised implant rates as compared to Asian and European ethnicities.

Conclusion
There is marked ethnic variation in ICD implant rates in NZ. Implant rates have increased in ethnic minorities but have plateaued in European patients in the past 7 years. The continued difference in implant rates across ethnicities warrants further investigation.

Funding Acknowledgement
Type of funding sources: None.
Implantable cardioverter-defibrillator therapy after resuscitation from cardiac arrest in vasospastic angina
Authors: Tateishi K , Kondo Y , Saito Y , Kitahara H , Kobayashi Y 
Published: October 2021

Abstract

Background
Patients with vasospastic angina (VSA) who are resuscitated from sudden cardiac arrest (SCA) are at high risk of recurrent cardiovascular events. However, there are no recommendations for implantable cardioverter-defibrillator (ICD) therapy in the VSA and SCA patient guidelines.

Purpose
This study investigated the prognostic impact of ICD therapy on patients with VSA and SCA.

Methods
The present multi-center registry included 280 patients who were resuscitated from SCA and received ICD implantation as secondary prophylaxis. The patients were divided into two groups according to the presence of VSA. The primary endpoint was a composite of all-cause death and appropriate ICD therapy, including appropriate anti-tachycardia pacing and shock for recurrent ventricular arrhythmias.

Results
Of 280 patients, 51 (18%) had VSA. Among those without VSA, ischemic cardiomyopathy was the leading cause of SCA (38%), followed by non-ischemic cardiomyopathies and Brugada syndrome (Table 1). During the median follow-up period of 3.8 years, 23 (8%) patients died, and 72 (26%) underwent appropriate ICD therapy. The incidence of the primary endpoint was not significantly different between patients with and without VSA (24% vs 33%, p=0.19). Further, the incidence of the primary endpoint was not significantly different among the etiologies (Figure 1)

Conclusions
In a cohort of patients who underwent ICD implantation as secondary prophylaxis, long-term clinical outcomes were comparable between those with VSA and those with other cardiac diseases after SCA. The results suggest that ICD therapy may be considered in patients with VSA and those with other etiologies after resuscitation from SCA.

Funding Acknowledgement
Type of funding sources: None. Table 1. Patient characteristics and outcomesFigure 1. Incidence of the primary endpoint
Ventricular fibrillation amplitude analysis and comparison for transvenous ICD and extravascular ICD systems
Authors: Liu Y , Majumder S , Zhang X.S , Degroot P , Liang S 
Published: October 2021

Abstract

Background
Transvenous (TV) implantable cardioverter-defibrillator (ICD) and extravascular (EV) ICD have very different electrode configurations (Figure 1). TV ICD has direct contact with the heart via endocardial lead placement with a nominal Tip-Ring sensing vector, whereas EV ICD utilizes a lead placed substernally outside the heart, with S1-S2 sensing vector as the nominal. Different lead and electrode locations result in different electrogram (EGM) signal amplitude and variability. Small ventricular fibrillation (VF) amplitude may lead to undersensed VF.

Purpose
The purpose is to characterize the VF amplitude from nominal sensing vector for TV ICD and EV ICD.

Methods
For TV ICD, 435 VF segments from Tip-Ring vector in 80 patients were analyzed. For EV ICD, 72 VF segments from S1-S2 vector in 32 patients were analyzed. For each VF segment, 1-second moving window with 50% overlapping was used to calculate maximum rectified (MR) VF amplitude. We calculated the maximum, minimum, mean, and standard deviation of averaged MR amplitude for all the episodes for each vector. The percentage of episodes with averaged MR amplitude smaller than different amplitude thresholds was also computed for each of the two vectors.

Results
VF signals from EV ICD had smaller averaged MR amplitude than TV ICD: S1-S2 = 3.05±1.62 mV versus Tip-Ring = 6.98±2.10 mV. EV ICD had 65% of episodes above 2.00 mV vs. 96% for TV ICD. The VF amplitude for EV ICD also had a smaller range than TV ICD: 0.47–8.43 mV versus 0.88–16.00mV. Despite having smaller amplitude, recordings of all VF episodes for both systems met detection criteria with no clinically significant delay.

Conclusions
Without direct myocardial contact, mean VF EGM amplitude from EV ICD system is approximately 44% of that for the TV ICD system. But with less variability across patients, it is more likely that a single (nominal) sensitivity setting will be effective among the population with EV ICD.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Medtronic Figure 1Figure 2
Impact of atrial fibrillation and biventricular pacing percentage on long-term outcome in patients with heart failure treated with cardiac resynchronization therapy
Authors: Neves Pereira M , Leite P.V.H , Dias G , Cardoso A.F , Tinoco M , Azevedo O , Ribeiro S , Ferreira F , Sanfins V , Lourenco A 
Published: October 2021

Abstract

Introduction
A history of preoperative atrial fibrillation (AF) has been found to be associated with unfavorable outcomes, higher risks of non-response to cardiac resynchronization therapy (CRT) and loss of biventricular pacing (BivP). We aimed to assess the impact of AF and BivP on long-term outcomes in heart failure patients treated with CRT.

Methods
We retrospectively enrolled 227 patients undergoing CRT implantation between 2013 and 2020 according to the current guidelines. 118 patients were included in our analysis, from whom all data were available. Clinical, electrocardiographic and echocardiographic parameters were evaluated at baseline and 6 months after CRT. Response to CRT was defined as an increase in left ventricular ejection fraction (LVEF) &gt;10%. We considered an effective delivery of BivP &gt;98%. The primary endpoint was the composite endpoint of hospitalization due to HF or death for any cause.

Results
118 patients were included (mean age 69±11 years, 66.1% males, 39.8% ischemic etiology; baseline LVEF was 27,6±6%). Patients were divided into AF (n=42; 35,6%) and sinus rhythm (SR (n=76); 18 patients had permanent AF. AF patients had higher index left atrial volume and left ventricular mass (p&lt;0.001). Mean follow-up time was 43±18 months. BivP percentage was significantly superior in SR than in AF patients (98.1±2.1% vs 94.7±4.5%, p&lt;0.001), with 75% of SR patients having BivP&gt;98% vs 30,3% of AF patients (p&lt;0.001). There were no differences in preoperative parameters between them. The response rate to CRT was higher in SR patients when compared to AF patients (63,2% vs 40,5%, p=0.021). Indeed, the variation of LVEF was higher in SR patients (12±10% vs 7±9%, p=0.012).
During follow-up, there were significant differences between AF and SR patients in the primary endpoint (73,8% vs 42,6%, p&lt;0.001), and mortality for any cause (26,2% vs 9,2% p=0.014; p&lt;0.001). In a multivariate logistic regression analysis pre-procedural AF and BivP (%) were the only independent predictors of primary endpoint (HR 8.949, 95% CI 2.429 – 32.972, p=0.001; HR 0.719, 95% CI 0.526 – 0.982, p=0.038, respectively). Kaplan-Meier curves showed that event survival free was higher in SR patients when compared to AF (69±4 vs 24±3 months, p&lt;0.001)

Conclusion
Pre - procedural AF and BivP are independent predictors of the occurrence of a primary endpoint of hospitalization due to HF or death for any cause in HF patients submitted to CRT.

Funding Acknowledgement
Type of funding sources: None.
Implication of sphingolipid metabolism gene dysregulation and cardiac sphingosine-1-phosphate accumulation in heart failure
Authors: Perez Carrillo L , Sanchez Lazaro I , Martinez Dolz L , Portoles M , Rosello-Lleti E , Tarazon E 
Published: October 2021

Abstract

Introduction and purpose
Abnormal levels of bioactive sphingolipids have been linked to disturbances in a variety of biological functions of several diseases, including cardiovascular diseases. However, changes in sphingolipid metabolism associated with progressive human heart failure (HF) have not been described, and S1P levels in HF tissues have not been evaluated.

Methods
We investigated changes in the transcriptome of human heart tissues using RNA sequencing technologies. We collected 26 left ventricular (LV) tissue samples from HF patients undergoing heart transplantation and 10 samples from healthy controls (CNT), and subjected these to mRNA-seq; and an additional 42 HF tissues and 8 CNT for the ncRNA-seq. In addition, we determined the bioactive sphingolipid levels in these tissues (HF, n=36; CNT, n=5) using ELISA.

Results
Most major changes were observed in expression of genes belonging to de novo (SPTSSA, −1.46±0.25; SPTSSB, −2.46±0.21; SPTLC1, −1.52±0.37; SPTLC3, −1.60±0.36; PPARA, −1.19±0.17; CERS1, 1.98±1.05; p&lt;0.05), and salvage pathways (ACER1, −1.70±0.28; ACER3, 1.19±0.26; SGPP1, −1.49±0.24; p&lt;0.05; SGPP2, −2.83±0.28; S1PR3, −1.78±0.28, p&lt;0.01). Furthermore, we observed that the tight regulation of these genes by their miRNA regulatory partners is largely dysregulated in HF. In addition, we verified that two key bioactive sphingolipids, ceramide (307±218 vs. 81±79 ng/mL, p&lt;0.01) and S1P (1908±625 vs. 963±489 ng/mL; p&lt;0.05) accumulate in cardiac tissue during HF, with the ceramide/S1P ratio increasing by as much as 57% in HF patients. Interestingly, CERS1 expression was linked to changes in LV mass (r=0.797, p&lt;0.0001), LV end-systolic (LVESD, r=0.561, p&lt;0.05) and end-diastolic diameters (LVEDD, r=0.601, p&lt;0.01), while S1P levels were inversely correlated with these parameters (LVESD, r=−0.552; LVEDD, r=−0.541; p&lt;0.05).

Conclusions
In this study, we outline the changes in the key components of the sphingolipid metabolism, mainly in the de novo and the salvage pathways, which lead to cardiac ceramide and S1P accumulation and the increase in the ceramide/S1P ratios in HF patients. Gene modulation targeting ceramide and/or S1P levels may be beneficial in the treatment of these patients. Specifically, CERS1 is linked to cardiac remodeling, making it a good candidate for the treatment of patients with HF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Carlos IIIEuropean Regional Development Fund (ERDF)
Empagliflozin in heart failure with preserved ejection fraction: decoding its molecular mechanism of action using artificial intelligence
Authors: Iborra Egea O , Spitaleri G , Domingo M , Revuelta Lopez E , Codina P , Cediel G , Santiago Vacas E , Cserkoova A , Pascual Figal D , Nunez J , Lupon J , Bayes Genis A 
Published: October 2021

Abstract

Rationale The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) to treat heart failure with preserved ejection fraction (HFpEF) is under investigation in ongoing clinical trials, but the exact mechanism of action is unclear. Here we aimed to use artificial intelligence (AI) to characterize the mechanism of action of empagliflozin in HFpEF at the molecular level.

Methods
We retrieved information regarding HFpEF pathophysiological motifs and differentially expressed genes/proteins, together with empagliflozin target information and bioflags, from specialized publicly available databases. Artificial neural networks and deep learning AI were used to model the molecular effects of empagliflozin in HFpEF.

Results
The model predicted that empagliflozin could reverse 59% of the protein alterations found in HFpEF. The effects of empagliflozin in HFpEF appeared to be predominantly mediated by inhibition of NHE1 (Na+/H+ exchanger 1), with SGLT2 playing a less prominent role. The elucidated molecular mechanism of action had an accuracy of 94%. Empagliflozin's pharmacological action mainly affected cardiomyocyte oxidative stress modulation, and greatly influenced cardiomyocyte stiffness, myocardial extracellular matrix remodelling, heart concentric hypertrophy, and systemic inflammation. Validation of these in silico data was performed in vivo in patients with HFpEF by measuring the declining plasma concentrations of NOS2, the NLPR3 inflammasome, and TGF-β1 during 12 months of empagliflozin treatment.

Conclusion
Using AI modelling, we identified that the main effect of empagliflozin in HFpEF treatment is exerted via NHE1 and is focused on cardiomyocyte oxidative stress modulation. These results support the potential use of empagliflozin in HFpEF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos IIICentro de investigaciόn biomédica en red cardiovascular (CIBERCV) Summary figureTable 1
Hospitalization and mortality in heart failure with preserved ejection fraction: real-world data from a US integrated healthcare delivery system
Authors: Nichols G.A , Qiao Q , Deruaz-Luyet A , Kraus B.J 
Published: October 2021

Abstract

Introduction
Heart Failure with preserved ejection fraction (HFpEF) is a major public health and economic burden, but large real-world incident rates of clinical outcomes are scarce.

Purpose
Calculate adjusted incidence rates of hospitalization and mortality in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) using an integrated healthcare delivery System in the United States.

Methods
Non-interventional longitudinal cohort analysis between 2005 and 2017 of existing data of adult patients with a HF diagnosis (ICD9/ICD10) in the electronic medical record of Kaiser Permanent Northwest. Clinical outcomes of interest were all-cause hospitalizations, heart failure hospitalization (HHF, defined as a discharge diagnosis of HF in the primary position) and all-cause mortality. Age/sex adjusted incidence rates were assessed generalized estimating equations over 15 years of follow-up (2005–2019).

Results
Of the 37,773 patients with HF diagnosis, 36% had no EF available. 46.4% were categorized as HFpEF, 7.2% HFmrEF and 10.4% HFrEF. Compared with patients with HFrEF, those with HFpEF were older (72.1 vs. 68.3 years), more likely to be female (55% vs. 33.2%), had higher BMI (31.9 vs. 29.3 kg/m2), higher SBP (130 vs. 121mmHg) and were less likely to have a history of myocardial infarction (26.1% vs. 43.8%). Patients with HFpEF were less likely to receive RAAS blockade compared with HFrEF (66.0% vs. 86.7%) but use of any HF-related medication (ACE/ARB, diuretics, β-blockers, or aldosterone agonists) was similarly high (89.6% vs 88.8%). As shown in Figure 1, adjusted mortality rates per 1,000 person-years, [95% CI] were lower in HFpEF (107.9 [105.5, 110.3]) vs. HFrEF (143.0 [136.5, 149.7]). Also, HHF were lower in HFpEF (41.6 [40.1, 43.2]) compared to HFrEF (72.6 [67.7, 77.9]). All-cause hospitalization rates were about 12% lower in HFpEF (197.3 [193.9, 200.7]) compared with HFrEF (222.8 [214.1, 231.7]). Nonetheless, due to the much larger size of the HFpEF group, these patients generated 1,982 more HHF, 10,427 more hospitalizations for any reason, and 6,723 more deaths during follow-up.

Conclusions
In a large real-world dataset of HF patients, incidence rates for hospitalization and mortality were relatively lower in HFpEF vs. HFrEF. However, given the greater prevalence of HFpEF (46.4% vs. 10.4% for HFrEF), this diagnosis posed a much higher public health burden.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim
Empagliflozin improves prognosis and energetic properties through modulating mitochondrial function in failing murine hearts
Authors: Shiraki A , Oyama J , Shimizu T , Nakajima T , Yokota T , Node K 
Published: October 2021

Abstract

Background/Introduction
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to have beneficial effects on heart failure in large clinical trials; however, the underlying mechanism is still unclear.

Purpose
The purpose of this study is to elucidate the mechanism of cardioprotective effect of empagliflozin in heart failure.

Methods
Eight-week-old mice deficient in cardiac and skeletal muscle-specific manganese superoxide dismutase, a mouse model of dilated cardiomyopathy (MnSOD-cKO mice), were given food mixed with or without 10 mg/kg empagliflozin for seven weeks and evaluated. Mitochondrial function in the cardiac muscle were measured by a high-resolution respirometer, Oxygraph-2K. Respiratory gas analysis were performed by indirect calorimetry (ARCO 2000) to estimate the energy consumption and energetic substrates.

Results
The survival rate (P=0.015) and cardiac fibrosis (P=0.036) were significantly improved in the empagliflozin group. The capacity of oxidative phosphorylation in cardiac mitochondria was significantly improved by empagliflozin. Blood lactate levels were decreased in the empagliflozin group, indicating that energy such as ATP could be produced without resorting to anaerobic metabolism.
Respiratory gas analysis revealed significant improvement in energy expenditure along with increase in food intake. Respiratory quotient was not different between the two groups, showing the consumption of the carbohydrate to fat rate was not changed by empagliflozin in this study. Ketone levels in blood and HbA1c were neither significantly different between the two groups. Although a moderate amount glucose was excreted in urine in the empagliflozin group (128.3±20.4 mg/day, 0.51±0.08 kcal/day), the available energy substrates in the whole body nonetheless expanded because of the increased caloric intake (10.58±0.72 in control group vs. 13.55±0.08 kcal/day in empagliflozin group, P=0.018).

Conclusion(s)
We have shown that empagliflozin improved myocardial mitochondrial function and increased energy metabolism, which was accompanied by adequate energy intake and uptake, even in heart failure. Empagliflozin decreased myocardial fibrosis and improved prognosis in failing murine hearts through positive energetical properties including mitochondrial function. The finding that empagliflozin modulates cardiac metabolism in a positive way provides a novel mechanism for the cardioprotective effect of SGLT2 inhibitors in heart failure.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boehringer Ingelheim Empa improved prognosis in HFEmpa improved mitochondrial function
Examination of the acute efficacy and safety about aggressive use of tolvaptan for early rising after admission in super-elder patients with congestive heart failure
Authors: Takaishi A , Iida T , Kishinoue T , Mori H , Yamaji T , Tanimoto M , Onishi N , Hirohata S , Ueeda M , Ito H 
Published: October 2021

Abstract

Background
From August 2015, for shortening of hospitalization period through efficient medical care in acute phase, we had introduced a unique clinical pathway (PATH) for congestive heart failure (CHF) cases. In PATH, since immediate taking of Tolvaptan, which is an strong oral diuretic and approver for use in the treatment of CHF cases since 2010 in Japan, after admission is specified, early diuresis makes it possible to achieve early rising from bed and streamline each medical care such as oxygen inhalation, continuous infusion, and urethral catheterization. Early rising from bed is particularly important for super-elder CHF patients who merge often frail. On the other hand, for super-elder CHF patients, it is feared that aggressive use of Tolvaptan may frequently cause dehydration, renal damage caused by it, or hypernatremia, which is a peculiar side effect about the drug.

Purpose
In this study, we examined the usefulness and safety of active use of Tolvaptan by introducing PATH in patients with super-elder CHF patients.

Methods
We set up three groups, NE group consist of 37 CHF cases (90 years old or over) who admitted in our hospital before (without) introduction of PATH between April 2014 and July 2015, PE group consist of 130 CHF cases (90 years old or over) and PY group consist of 466 CHF cases (under 90 years old) who ware admitted with introduction of PATH between August 2015 and July 2020. And in each group, we investigated various medical conditions in their acute phase after admission and the incidence of adverse events related to oral administration of tolvaptan, and examined the differences between three groups.

Results
Between NE group and PE group, there were no significant differences in mean age, pre-hospital living status, or clinical status at admission (Figure 1). But due to lean and efficient CHF care, the average length of hospitalization period was significantly shorter in PE group. And, in PE group, each medical care was performed as efficiently as in PY group, but the progression of renal damage or hypernatremia that required unscheduled discontinuation of tolvaptan use occurred more frequently in PE group (Figure 2).

Conclusions
Aggressive Tolvaptan use through our unique clinical pathway for congestive heart failure cases seemed to be useful even in super-elder patients. Although we thought that the safety of active use of tolvaptan for super-elder patients was well tolerated considering the results of this study, the incidence of adverse events such as hypernatremia was clearly higher in super-elder patients than in non-super-elder patients. It seemed that we should pay close attention to the clinical data of super-elder patients after introduction of tolvaptan.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2