bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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) >10%. We considered an effective delivery of BivP >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<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<0.001), with 75% of SR patients having BivP>98% vs 30,3% of AF patients (p<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<0.001), and mortality for any cause (26,2% vs 9,2% p=0.014; p<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<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

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<0.05), and salvage pathways (ACER1, −1.70±0.28; ACER3, 1.19±0.26; SGPP1, −1.49±0.24; p<0.05; SGPP2, −2.83±0.28; S1PR3, −1.78±0.28, p<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<0.01) and S1P (1908±625 vs. 963±489 ng/mL; p<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<0.0001), LV end-systolic (LVESD, r=0.561, p<0.05) and end-diastolic diameters (LVEDD, r=0.601, p<0.01), while S1P levels were inversely correlated with these parameters (LVESD, r=−0.552; LVEDD, r=−0.541; p<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

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

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

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

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
In hospital mortality and outcomes of patients with acute decompensated diastolic heart failure with and without amyloidosis
Authors: Murthi M , Sharma B , Velagapudi S , Atluri R , Velazquez G , Wahab A
Published: October 2021

Introduction

The incidence of heart failure has exponentially increased over the last few decades and acute decompensated diastolic heart failure is one of the leading causes of hospitalization and readmission. Cardiac amyloidosis is one of the rapidly progressing heart conditions. It occurs due to amorphous proteinaceous material called amyloid into the extracellular space of the heart. The infiltration of the heart from amyloid protein has a broad spectrum of presentation, including diastolic heart failure.

Purpose

Heart failure due to amyloidosis is characterized by diastolic dysfunction resulting from restrictive cardiomyopathy. The outcomes of hospitalized patient with acute decompensated diastolic heart failure in amyloidosis patients compared to those without amyloidosis is not well defined.

Methods

We conducted a retrospective cohort study by utilizing the National Inpatient sample database from 2017. Using International Classification of disease (ICD)-10 codes, patients with the diagnosis of acute and acute on chronic diastolic heart failure were enrolled in the study. They were further stratified based on the presence of amyloidosis. The primary outcome was to measure in-hospital mortality, while secondary outcomes included development of acute kidney injury (AKI), Acute respiratory failure (ARF), shock and arrhythmias.

Results

Out of the 915,694 patients with Acute Decompensated diastolic heart failure, about 2270 had amyloidosis as secondary diagnosis. 6.1% of ADHF and amyloidosis died in hospital, compared to 4.2% in those without amyloidosis (aOR=1.35 CI=0.89–2.05, p=0.197). On multivariate analysis, patients with Amyloidosis had increased odds of developing AKI (aOR=1.40 CI 1.13–1.72, p=0.001), Cardiogenic shock (aOR=2.67 CI 1.56–4.55, p<0.001) and arrhythmias (aOR=1.34, CI 1.10–1.64, p=0.004). The incidence of ARF was however lower in patients without amyloidosis compared to those with it (aOR=0.60, CI 0.47–0.75, p<0.001).

Conclusion

Amyloidosis is one of the underappreciated and underdiagnosed causes of heart failure. Our study shows an increased risk of complications in acute decompensated heart failure with the presence of amyloidosis. Thus, physicians must be aware of this clinical entity for early diagnosis as patients with advanced disease are likely to have poor prognoses.

Funding Acknowledgement

Type of funding sources: None.
Vericiguat and health status outcomes in heart failure with reduced ejection fraction: insights from the VICTORIA trial
Authors: Butler J , Stebbins A , Melenovsky V , Sweitzer N , Cowie M.R , Stehlik J , Ezekowitz J.A , Hernandez A.F , Lam C.S.P , Nkulikiyinka R , O'Connor C.M , Pieske B , Ponikowski P , Voors A.A , Armstrong P.W ,   the VICTORIA Study Group
Published: October 2021

Background

In the VICTORIA trial, vericiguat compared with placebo reduced the risk of the primary endpoint of cardiovascular death (CVD) or hospitalization for heart failure (HFH) among 5050 patients with worsening HF with reduced ejection fraction (HFrEF).

Purpose

We evaluated whether the efficacy of vericiguat on clinical outcomes varied according to participants' baseline health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ)-23, and how vericiguat affected health status post-randomization.

Methods

KCCQ-23 was completed at randomization and at 4, 16, and 32 weeks. Patients were grouped based on tertiles of baseline KCCQ total symptom score (TSS; <55.2, 55.2–79.2, and >79.2), clinical summary score (CSS; <52.1, 52.1–76.0, and >76.2) and overall summary score (OSS; <48.5, 48.5–70.8, and >70.8) across tertiles 1–3, respectively. Cox proportional hazard models were performed for the tertiles to evaluate the effects of vericiguat on the primary outcomes.

Results

Overall 4741, 4664, and 4470 participants had KCCQ-TSS (median 68.8 [interquartile range 47.9, 85.4]), KCCQ-CSS (65.6 [45.8, 81.8]) and KCCQ-OSS (59.9 [42.0, 77.1]) available at baseline. Vericiguat reduced CVD or HFH risk across baseline KCCQ-TSS (P=0.21), KCCQ-CSS (P=0.13) and KCCQ-OSS (P=0.65) tertiles (Table). The effect of vericiguat on HFH alone was also not modified by baseline KCCQ-TSS, CSS and OSS (all P>0.05) scores. At 4 weeks after randomization, improvement in both vericiguat and placebo arms was seen in KCCQ-TSS (vericiguat 6.3 vs. placebo 6.3; P=0.85), KCCQ-CSS (vericiguat: 5.7 vs. placebo 5.7, P=0.54), and KCCQ-OSS (vericiguat 6.3 vs. placebo 5.7, P=0.36). Similar results were seen at weeks 16 and 32.

Conclusion

Vericiguat reduced the risk of the composite outcome of CVD or HFH as well as HFH alone across the range of baseline health status. Addition of vericiguat to best standard of care did not significantly improve health status compared with standard of care alone in HF patients with a recent worsening event. The early improvement in KCCQ seen in both randomized groups underscore the need to assess trajectory of health status changes in the spectrum of patients with HFrEF.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Merck & Co., Inc. and Bayer
Resting and exercise hemodynamic determinants of daily activity measured by accelerometer in stable heart failure patients
Authors: Omar M , Jensen J , Frederiksen P , Videbaek L , Kjaer Poulsen M , Christian Broend J , Gustafsson F , Borlaug B , Schou M , Eifer Moeller J
Published: October 2021

Background

Patient-worn accelerometer is increasingly used in patients with heart failure and reduced ejection fraction (HFrEF) to assess daily activity and and as surrogate endpoint. We examined the association between cardiac physiology and daily activity by patient-worn accelerometer recordings in stable HFrEF patients.

Methods

In this descriptive study, physical average daily accelerometer units (PADA) and total average daily accelerometer unit (TADA) were assessed by a accelerometer recordings. Sixty three stable ambulatory patients with HFrEF, mainly men (92%), mean age 58±10 years, and ejection-fraction 26±4% underwent hemodynamic exercise testing, and accelerometry (Table 1). Patients were divided by PADA in a low and high activity level groups based on counts per minute physical activity.

Results

Patients in the low activity group were older and more frequently treated with diuretics. At rest, the low activity group was characterized by a lower cardiac index (CI) (2.2±0.4 vs. 2.4±0.4 l/min/m2, p=0.01), Stroke volume (SV) (70±19 vs. 81±17 ml, p=0.02) but not pulmonary capillary wedge pressure (PCWP) (12±5 vs. 11±5 mmHg, p=0.3) (Figure 1). Low activity group reached a lower CI (4.8±1.7 vs. 6.6±1.7 l/min/m2, p<0.001) and SV (94±32 vs. 121±29 ml, p<0.001), but not in PCWP (31±12 vs. 27±8 mmHg, p=0.2) or arterial-venous O2 content difference (A-VO2 diff) (13.00±2.32 vs. 12.96±1.65 ml O2/dl, p=0.9) at peak exercise. The attenuated increase was associated with attenuated increase in SV rther than increase in heart rate (42±23 vs. 52±21 bpm, p=0.07). Finally, CI at peak exercise was the only independent variable associated with PADA after adjusting for age, gender, and BMI (p<0.0001). The PADA and TADA were associated to functional assessments using Kansas City Cardiomyopathy Questionnaire, but not with New York Heart Association class or N-terminal pro brain natriuretic peptide (NT-proBNP) (Table 1).

Conclusion

Accelerometer-assessed activity in patients with HFrEF are associated with impairments in LV performance, SV reserve and cardiac output during exercise, to a greater extent than changes in arterial-venous O2 content difference or pulmonary vascular pressures. Accelerometer data may provide information about the functional status that we do not nessecary find in the widely used tools in both research and daily clinical practice.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the Danish Heart Foundation [grant numbers 17-R116-A7714-22076, 18-R124-A8573-22107]; Steno Diabetes Center Odense, Denmark [grant number 3363] and A.P. Møller Foundation for the Advancement of Medical Science [grant number 17-L-0339]. Table 1. Baseline and regression analysisFigure 1. Change in PCWP and CI by exercise
Chronic ischemic heart failure in humans is associated with changes in expression of antigen processing HLA types and activation of T-cells
Authors: Merten M , Rasper T , Schuhmacher B , Cremer S , Zeiher A.M , Hoffmann J , Abplanalp W , Dimmeler S
Published: October 2021

Background

Sustained pathological inflammation is a hallmark of chronic ischemic heart failure (HF). The short term response to myocardial ischemia has found a protective phenotype for T regulatory cells, yet the extent and consequence of prolonged T-cell activation in chronic ischemic heart failure is unclear.

Methods and results

Single cell RNA sequencing of circulating immune cells (n=181,712 cells) from healthy (n=8) and heart failure donors (n=8) revealed a relative increase in the proportion of activated T cells in heart failure patients relative to healthy controls. T cell activation molecules of the HLA-DR series genes on antigen presenting cells were found to be strongly associated with heart failure patients in the sequencing data, with decreases in antigen processing genes (HLA-DM series) in heart failure patients. Validation via flow cytometry in 27 healthy controls and 43 heart failure patients showed relative decreases of greater than 30% for HLA-DM to HLA-DRB molecule ratios in HF patients (p=0.0082), suggesting an aberrant antigen presentation to T cells linked to autoimmunity in heart failure patients. Additionally, costimulatory molecules such as ICAM-1 (p=0.004) and activation markers like TREM-1 (p=0.04) were elevated in circulating monocytes cells, which may potentiate T cell activation. Correspondingly, a significant and striking decrease in CD4+ and CD8+ naïve T cells along with increases in combined effector memory and TEMRA cells could be evidenced in heart failure patients. Levels of the T-cell homing marker CCR5 were elevated in patients with heart failure. To gain additional insights into potential functional consequences in the heart, supernatants from 3h LPS stimulated immune cells (peripheral blood mononuclear cells or T cells) were applied to various vascular cell types (endothelial cells, pericytes) and with cardiac organoids for 48h. Apoptosis was increased more than 3 fold following incubation with media derived from peripheral blood cells of HF patients, suggesting that immune cells from heart failure patients can directly and indirectly impair cardiovascular cells.

Conclusion

Heart failure is marked by sustained increases in relative proportions of effector T cell and TEMRA populations and homing markers suggesting these cells may undergo extravasation to tissues and deteriorate inflamed myocardium - hastening heart failure progression, worsening prognosis. Further research is required to assess how these cells may migrate to myocardial tissues and what interventions could be useful for blocking myocardial damage.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DZHK, DGK, SFB
Examination about more realistic prognosis evaluation method, how long the patients with congestive heart failure can spend at home
Authors: Takaishi A , Iida T , Kishinoue T , Mori H , Yamaji T , Tanimoto M , Onishi N , Hirohata S , Ueeda M , Ito H
Published: October 2021

Background

From August 2015, for efficient medical care in congestive heart failure (CHF) cases, we had introduced a unique clinical pathway (PATH) provided the immediate use of Tolvaptan and comprehensive education by multi-disciplinary staff after admission. And by introduction of PATH, we confirmed the shortening effect of hospitalization period with CHF and the suppressive effect of readmission with CHF after discharge. But since almost CHF patients repeat hospitalization and discharge due to change of their medical condition, the investigation for only first readmission rate after discharge is not enough to assess the entire long clinical course of CHF. Recently we found one report about evaluation method for CHF clinical prognosis, how long CHF patients can stay healthy at their own home after discharge within a certain period. This evaluation method is considered to take into account the long clinical course of CHF.

Purpose

We investigated whether the CHF patients introduced PATH on admission could stay longer at their home than CHF patients without PATH.

Methods

Between April 2014 and July 2019, 471 CHF cases, who ware admitted in our hospital at first and could be followed up for at least 1 month after discharge, ware enrolled. We divided them to two groups, PATH- group before introducing PATH (until July 2015, 142 cases), and PATH+ group applied PATH (after August 2015, 329 cases). Between both groups, we investigated the readmission rate (RR) with CHF and the total period (TP) that patients could spend at home within1, 3, 6 and 12month after discharge.

Results

There were no significant differences in mean age, pre-hospital living status, or clinical status at admission between the two groups. On the other hand, due to efficient CHF care, the average length of hospital stay was significantly shorter (figure1). RR within 1, 3, 6 and 12 months after discharge ware all lower in PATH+ group. And TP within 1, 3, 6 and 12 months after discharge ware all longer in PATH+ group (figure2).

Conclusion

By introducing our unique clinical pathway for congestive heart failure cases requiring hospitalization, we could confirm not only the improvement of their conventional clinical prognosis index but also the improvement of their new and more realistic clinical prognosis index after discharge.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Cognitive impairment is a determinant of patient response to disease management programs to reduce readmission in heart failure
Authors: Huynh Q , Negishi K , Depasquale C , Hare J , Leung D , Stanton T , Marwick T
Published: October 2021

Background

Cognitive impairment (CI) is highly prevalent in heart failure (HF), and increases patients' risks of readmission.

Purpose

This study sought to determine whether the presence and degree of CI could identify patients most likely to benefit from a HF disease management program (DMP) to reduce readmissions.

Methods

1152 consecutive Australian patients admitted with HF (2014–17) were prospectively followed-up for 12 months. Of these, 324 patients who received DMP (1-month duration, including post-discharge home visits, medication reconciliation, exercise guidance and early clinical review) were matched (1:2 ratio) with 648 usual care patients. Cognitive function was assessed either on the day of or one day before discharge using the Montreal Cognitive Assessment (MoCA). Outcomes included readmission or death at 1-, 3- and 12-months, and days-at-home within 12 months, from discharge.

Results

Poorer cognitive function was associated with all adverse outcomes. Compared with usual care, DMP was associated with lower odds of 30-day (OR=0.60 [0.40, 0.91]) and 90-day (OR=0.53 [0.36, 0.77]) readmission or death, and with 19 more days-at-home within 12 months, independent of HF therapy. The effect sizes of these associations were greater for patients with diminished cognition than those with normal cognition (interaction p=0.036), and might have been more pronounced among those with mild CI compared with those with more severe CI (MoCA score 17–22, OR=0.42 [0.21, 0.87] at 30-day, OR=0.31 [0.16, 0.60] at 90-day). Patients with normal cognition had fewer events, irrespective of DMP.

Conclusions

Cognitive function may determine how HF patients respond to a DMP. Cognitive screening before implementation of a DMP may allow personalized plans for patients with different levels of cognitive function

Funding Acknowledgement

Type of funding sources: None.
Risk stratification and survival in patients with HFmrEF: the role of cardiopulmonary exercise testing
Authors: Westphal J.G , Schulze P.C
Published: October 2021

Background

The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Since the introduction of HF with mid-range ejection fraction (HFmrEF) as an additional category in 2016, optimal management strategy and risk stratification for these patients is a field of ongoing research.

Purpose

Left ventricular ejection fraction (LVEF) is only one part of the picture when planning treatment and estimating long time risk for patients with HF. We planned to investigate the predictive long-term value of exercise intolerance as measured by CPET in patients with HFmrEF in comparison to HFrEF.

Methods

We performed a single-center retrospective cohort study of ambulatory consecutive patients that showed signs of heart failure (NYHA functional class II or III) and had a LVEF of 49% or below as measured by echocardiography at the time of CPET. All patients underwent CPET evaluation with an upright bicycle between 2015–2017. The primary endpoint of all-cause mortality as well as the secondary composite endpoint of all-cause mortality or heart transplant/ventricular assist device implantation (transplant/VAD free survival) were assessed.

Results

For the primary analysis, 253 patients (mean age 61.2±13.0 years, 82.6% male) were included. 68 patients showed an LVEF between 40 and 49% (HFmrEF) whereas 185 patients had an LVEF of below 40% (HFrEF). HF etiology was in 31.3% ischemic. Mean BNP values were 788±1061 pg/ml while HFmrEF patients had on average lower values than HFrEF (322±676 vs. 945±1121, p<0.001). Patients were followed up for a median of 4.2 years (IQR: 3.5–5.0 years). Over this period, the primary and secondary end-point occurred in 22.5%/30.8% of patients.

Patients in the HFmrEF group showed a higher mean peak oxygen uptake compared to HFrEF (pVO2; 17.3±4.6 vs 14.2±3.7 ml/min/kg, p<0.001), peak exercise power (Pmax; 111±49 vs 91±38 Watt, p=0.02) and peak oxygen pulse (pO2/HR; 12.6±4.2 vs 10.4±4.1 ml/min/kg, p<0.001). The Kaplan-Meier-Estimate showed a significant difference in survival for both HFmrEF and HFrEF who had pVO2 below 14 ml/min/kg (Log Rank: Chi2: 4.45, p=0.035 and Chi2: 10.05, p=0.02). In univariate Cox regression, pVO2 was predictive of the primary endpoint (HR per +1 mL/kg/min: 0.81; CI: 0.71–0.93; p=0.002 and HR per +1 mL/kg/min: 0.84; CI: 0.77–0.92; p<0.001) in both groups as was Pmax and pO2/HR (p<0.05 for both variables in both groups).

Conclusion

As in HFrEF, CPET is a useful tool to stratify risk in HFmrEF as well. Our findings support the prognostic role of pVO2 as well as pO2/HR and Pmax in HF with mid-range LVEF. Using a cut off of pVO2 14 ml/min/kg selected patients at risk with similar long-term prognosis as in the HFrEF cohort. Further research to identify subgroups at risk within the heterogeneous group of HFmrEF is warranted for optimal risk stratification.

Funding Acknowledgement

Type of funding sources: None.
The validity of heart failure diagnoses at hospital-discharge and ambulatory evaluation visits: insights from two Norwegian local hospitals
Authors: Ofstad A.P , Johansen O.E , Brunborg C , Morkedal B , Fagerland M.W , Laugsand L.E , Gullestad L , Dalen H
Published: October 2021

Background

The validity of heart failure (HF) diagnoses made in hospitals has been debated and low positive predictive values (PPV) may represent a bias in epidemiological research.

Purpose

To validate primary and secondary HF diagnoses at discharge or during ambulatory evaluation in general hospitals aiming to obtain confirmed HF diagnoses to develop a HF-prediction risk score.

Methods

We extracted data on all patients with a HF diagnosis by ICD-10 codes (I50 HF, I42 cardiomyopathy and I11 hypertension with HF) in any position from the hospitals' electronic medical records from Oct. 2006 to Dec. 2018. One experienced cardiologist scrutinized all journals for events being either a valid HF event, unlikely, or uncertain due to lacking information, according to the 2016 ESC HF guidelines. In cases where first event was unlikely or uncertain subsequent events were judged for valid HF.

Results

A total of 3411 patients with at least one HF diagnosis were assessed (mean age 79.7±10.6 yrs, 49.1% men); 3089 after in-hospital stays and 322 after ambulatory consultations. Overall, 2174 were deemed as valid HF diagnosis with a PPV of 63.7%; PPV was higher when HF diagnosis was based on in-hospital diagnoses and when HF was the primary diagnosis (Table).

Conclusions

Only 64% of all HF diagnoses were likely HF according to present guidelines, with higher precision for in-hospital diagnoses and HF in the primary position. This underscores the importance to use validated HF-diagnoses for HF prediction risk score development.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Boehringer Ingelheim Norway KS
Correlation between invasive and non-invasive quantification of myocardial amyloid load in cardiac transthyretin amyloidosis
Authors: Ungericht M , Groaz V , Messner M , Zaruba M.-M , Doerler J , Lener D , Stocker E.-M , Mayr A , Kroiss A , Poelzl G
Published: October 2021

Background

Cardiac transthyretin (ATTR) amyloidosis is an infiltrative disease caused by the extracellular deposition of misfolded ATTR protein in the myocardium. Early disease recognition and accurate description of cardiac involvement are fundamental, as cardiac ATTR amyloidosis is associated with poor prognosis. Although endomyocardial biopsy (EMB) remains the gold standard in amyloid detection and typing, non-invasive imaging can provide an accurate diagnostic tool. Bone scintigraphy enables early disease detection with high accuracy. However, it remains to be determined whether the degree of cardiac tracer uptake on bone scintigraphy correlates with the extent of histologic amyloid burden in EMB.

Aim

This single center observational study aimed to compare the histological amyloid load in endomyocardial biopsies with the quantification of cardiac tracer uptake on 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy in cardiac ATTR amyloidosis.

Methods

23 patients with cardiac ATTR amyloidosis were enrolled. Diagnosis was obtained with a combination of invasive and non-invasive methods. Perugini score, mean left ventricular tracer uptake (LV uptake) and left ventricular to corpus sterni uptake ratio (LV/CS ratio) on 99mTc-DPD-scintigraphy were measured, while histological amyloid load was quantified as percentage of the analysed myocardial tissue using Sulfated Alcian Blue staining and the Fiji-ImageJ programme. Bivariate correlation and Pearson correlation coefficient were used to study the relationship between EMB and 99mTc-DPD-scintigraphy findings.

Results

We found a statistically significant correlation between histological amyloid load and Perugini score (r=0.47 p=0.02), as well as between Perugini score and LV/CS ratio (r=0.31 p=0.046). Mean LV tracer uptake showed a trend for correlation with histological amyloid load (r=0.37 p=0.08), without reaching statistical significance.

Conclusion

We found a correlation between the extent of histologic amyloid burden in EMB and the degree of cardiac tracer uptake on 99mTc-DPD-scintigraphy. Our results underline the reliability of 99mTc-DPD-scintigraphy as a surrogate of histological amyloid load in the diagnosis of cardiac ATTR amyloidosis. Possible implications for the assessment of prognosis are subject to future studies with a larger number of patients.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer
MicroRNA-223 might be a predictive biomarker for major adverse cardiovascular events prognosis in patients undergoing transcatheter aortic valve implantation procedure
Authors: Eyileten C , Fitas A , Jarosz-Popek J , Adem T , Jakubik D , Wolska M , Czajka P , Postula M , Nowak A , Gasecka A ,   I-COMET
Published: October 2021

Background

Transcatheter aortic valve implantation (TAVI) is an emerging invasive therapeutic strategy for patients with severe aortic stenosis (AS) significantly enhancing not only quality-of-life measures but also improving short-and long-term survival rates.

Purpose

For these purposes we aimed to analyze correlation between expression levels of platelet-derived microRNAs in patients with heart failure (HF) due to AS who underwent TAVI procedure and assess their association with primary major adverse cardiac events (MACE) defined by all cause mortality and secondary MACE defined as cardiovascular mortality, ischemic stroke, and non-fatal myocardial infarction.

Methods

61 patients before and after the TAVI procedure were included. PlasmaRNA was extracted by mirVANA PARIS Kit and quality of RNA was assessed by fluorometric assay. GEP analysis was performed using the Clariom D pico chips, analyzed on the Affymetrix platform. RT-PCR was performed in order to validate the miRNAs in 61 patients by using the Taqman advanced protocol. MiRNA related to platelet function/antiplatelet treatment were chosen among those with the most relevant modulation between the groups. Wilcoxon test was performed for miRNAs comparison before and after TAVI. Calculations were performed using SPSS version 22.0, p<0.05 (IBM Corporation, Chicago, USA).

Results

We have found that miR-223, miR-125b and miR-125a were significantly increased in patients after the TAVI procedure. ROC analysis showed that increased miR-223 expression after the TAVI procedure might slightly have protective value against MACE outcome.

Conclusions

Our analysis showed alteration of circulating miRNAs after the TAVI procedure and miR-223 might have a predictive value for MACE prognosis in patients with HF due to AS who underwent TAVI procedure.

Acknowledgment

I-COMET research team

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2