bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart rate response during cardiopulmonary exercise in heart transplant recipients
Authors: Nygaard S , Rolid K , Nytroen K , Fiane A , Wyller V.B.B , Gullestad L , Broch K
Published: November 2020

Background

Denervation at heart transplant (HTx) results in attenuated heart rate (HR) control and limited exercise tolerance.

Purpose

The aim of this study was to assess longitudinal changes in the HR response to exercise in HTx recipients. We compared the results with those of healthy controls.

Methods

Seventy-four HTx recipients were enrolled in a cardiopulmonary exercise trial. The HR response to maximal exercise was tested at 11 weeks and at 1- and 3-years follow-up post HTx, and compared with the HR response in 50 age and gender matched controls. The HR was measured at rest, at 25-, 50-, 75-, and 100% of VO2peak, and 30 sec, 1, 2, and 4 min after peak exercise on a treadmill or bicycle ergometer. We also assessed the HR reserve and the chronotropic response index (CRI).

Results

Elleven weeks after HTx, the HR response to exercise was blunted, but improved significantly during follow-up. The change in HR from rest to peak exercise increased by 53% (41 bpm vs 62 bpm; p<0.001) from inclusion to 12 months follow-up, but levelled off between 12- and 36 months (62 bpm vs 65 bpm; p=0.59) (Figure 1). In comparison, the exercise-induced increase in HR in healthy controls was 117 bpm. In HTx recipients, approximately 40% of the total increase in HR occurred between rest and 25% of VO2peak at inclusion (Figure). In contrast, only 31% of the increase in HR in healthy controls occurred between rest and 25% of VO2peak (p<0.001). The fall in HR during the first 4 minutes after exercise increased over the duration of the study (p<0.001 for all comparisons between inclusion and 12 months, and 12- and 36 months at 30 sec, 1, 2, 3 and 4 min after exercise). During the first minute after the end of exercise, the HR rose 2 bpm at baseline, but fell 10 bpm at 12 months (p for difference <0.001). However, even at 36 months, the decline in HR after exercise remained less rapid than in healthy controls (p<0.001) (Figure). CRI increased between baseline and 12 months, but levelled off between the 12-month visit and 36 months (0.50±0.2 vs 0.79±0.3; p<0.001 and 0.79±0.3 vs 0.81±0.3; p=0.51). The chronotropic response was normalized (>0.85) in 44% of the HTx recipients at 1 year and in 51% at 3 year after HTx.

Conclusion

The increase and decrease in HR during exercise are considerably muted in de novo HTx recipients. The HR response improves during the first year after surgery, and thereafter levels off. In contrast the decline in HR after exercise seems to increase with time, which may be related to the effect of exercise. This suggests that partial re-innervation takes place. Whether this response continues to improve in the longer term remains to be determined.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority
Effectiveness of nurse-led hospital-based heart failure programmes in octagenarians and nonagenarians: is age important?
Authors: Guerrero G , Alcoberro L , Vime J , Calero E , Hidalgo E , Marin R , Enjuanes C , Garay A , Yun S , Jimenez S , Moliner P , Delso C , Fernandez I , Rosenfeld L , Comin J
Published: November 2020

Background

Efficacy of HF programmes in oldest old (octogenarians and nonagenarians) has not been fully explored.

Methods

We conducted a natural experiment evaluating all patients after hospitalization for heart failure as primary diagnosis between January 2017 and January 2019. We compared outcomes between patients discharged during Period #1, before the implementation of the program with patients discharged during Period #2, after the implementation of the 7-step bundle of interventions. We explored the interaction between age group (<80 vs. ≥80 years old) by the intervention modality (HF programme vs. usual care). Primary end-point was the combined end-point of all-cause death or all-cause hospitalization at 6 months after discharge from the index hospitalization.

Results

The study enroled 440 patients. Mean age of the whole cohort was 75±9 years. In the oldest old subgroup (n=160), mean age was 84±3. No differences were found in baseline characteristics of patients between usual care and HF program. 30-day all-cause readmission was significantly reduced in patients in the HF programme group compared to patients in the usual care group in both age strata. In unadjusted Cox regression analyses in the oldest old group, management of patients in the HF programme was significanty associated with a reduction in the risk of the primary end-point (HR: 0.50; 95% CI [0.29–0.85]; p=0.011).

Conclusions

Management of patients in a nurse-led integrated care-based heart failure programme results in reduction of all-cause death or all-cause hospitalizations in oldest old patients.

Event-free survival cumulative curves.

Funding Acknowledgement

Type of funding source: None
Increased incidence of heart failure in patients with severe obstructive sleep apnoea: a long-term prospective cohort study
Authors: Liang V , Holtstrand-Hjalm H , Peker Y , Thunstrom E
Published: November 2020

Background

Obstructive sleep apnoea (OSA) is highly prevalent among patients with heart failure. Accumulating research data suggest that this association is bidirectional. Less is known regarding the long-term impact of OSA and continuous positive airway pressure (CPAP) treatment on incident heart failure.

Purpose

We addressed the association of severe OSA with development of heart failure, and consequently addressed the impact of efficient CPAP treatment in a sleep clinic cohort.

Methods

The “Sleep Apnea Patients in Skaraborg (SAPIS)” project was a single center (two sites), open-label, prospective cohort study, conducted in Sweden between 2005 and 2018. All consecutive adults admitted to the Skaraborg Hospital between 2005 and 2011 were registered in a local database, and the follow-up ended in May 2018. Anthropomorphic and clinical characteristics as well as results of the diagnostic cardiorespiratory recordings were documented. Treatment of OSA was based on the clinical routines. OSA was defined as an apnoea-hypopnoea index (AHI) of at least 5 events/hr, and severe OSA consisted of patients with an AHI ≥30 events/hr. Median follow-up for the entire cohort was 8.8 years (interquartile range 7.5–10.1 years). Data regarding incident heart failure were obtained from the medical records and the Swedish Hospital Discharge Register. CPAP use (downloaded reports from the devices) of at least 4 hrs/night was defined as efficient treatment.

Results

Among 4239 patients with diagnostic sleep recordings, 3185 were free of a known cardiac disease at baseline. Severe OSA was observed among 953 (29.9%). Severe OSA significantly predicted incident heart failure (hazard ratio [HR] 2.42; 95% confidence interval [CI] 1.44–4.06) compared to adults with AHI <30 events/hr, adjusted for age, gender, obesity, hypertension and diabetes mellitus. The adjusted HR for severe OSA was 2.82 (95% CI 1.33–5.99) among inefficiently treated/untreated patients whereas the risk was lower but still meaningful among the individuals who were adherent to CPAP (HR 2.25; 95% CI 0.99–5.15)

Conclusion

Our results suggest that severe OSA is associated with increased risk for development of heart failure. More than 4 hours of CPAP use per night may be necessary for OSA patients in the primary prevention models.

CHF-free survival

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): ALF
Axial muscle size quantification by cardiac mri as a strong predictor of major cv events in hf
Authors: Lopes Da Cunha G.J , Rocha B.M.L , Freitas P.N , Lopes P.M.D , Guerreiro S , Andrade M.J , Aguiar C.M.T , Abecasis J , Saraiva C , Mendes M , Ferreira A
Published: November 2020

Background

Clinical overt cardiac cachexia is a late and ominous sign in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Low muscle mass could serve as a surrogate of subclinical cardiac cachexia and has already been shown to predict major adverse events in HF patients. The main goal of this study was to assess the feasibility and prognostic significance of a simplified muscle mass quantification by cardiac magnetic resonance (CMR) in HF with reduced LVEF.

Methods

HF patients with LVEF <40% referred for a clinically indicated CMR (1.5T scanner) were retrospectively identified in a single center. The main exclusion criteria were known primary muscle disease, diagnosed or suspected infiltrative myocardial disease and implanted device. The area of both pectoralis major muscles was measured on standard axial images at the level of the carina using manual outlining. To account for the effect of age and gender, pectoralis major muscle area was expressed as the difference in standard deviations in relation to the mean pectoralis major muscle area of a healthy cohort of 32 females and 37 males aged between 50 and 80 years old. The primary endpoint was a composite of all-cause mortality or HF hospitalization. Survival analysis was performed with Cox-regression hazards model and Kaplan-Meier.

Results

A total of 184 HF patients were included (mean age 65±12 years; 78% male; LVEF 30±8%). Lower pectoralis major area was significantly correlated with older age (r=−0.36, p<0.001), lower LVEF (r=0.14, p=0.050) and higher NT-proBNP (r=−0.44, p<0.001). During a median follow-up of 22 months (IQR: 14–29) there were 44 (23.9%) patients who met the primary endpoint (a total of 15 patients died and 29 had at least one HF hospitalization). In multivariate analysis, LVEF (HR per 1%: 0.95; CI: 0.91–0.98; p=0.004), creatinine (HR per 1mg/dL: 2.12; CI: 1.09–4.11; p=0.026) and pectoralis major area (HR per 1 SD below the mean: 1.40; CI: 1.01–1-1.95; p=0.047) were independent primary endpoint predictors.

Conclusions

Pectoralis major size measured by CMR in HFrEF was independently associated with a higher risk of death or HF hospitalization. Further studies need to be undertaken to establish appropriate age and gender-adjusted cut-offs of muscle areas that identify high-risk subgroups.

Figure 1

Funding Acknowledgement

Type of funding source: None
TAC induced cardiac hypertrophy leads to increased levels of circulating microvesicles
Authors: Pfeifer P , Hoelscher M , Werner N , Nickenig G , Jansen F
Published: November 2020

Introduction

Cardiac hypertrophy and heart failure are wide spread diseases of elderly patients in the industrialised world and drive a majority of healthcare costs in these countries. Therefore, there is a high urgency to understand the development and progress of heart failure to find new therapeutic strategies especially in early stages. Microvesicles are involved in the development and propagation of almost all cardiac diseases and increased levels of circulating microvesicles can be found in blood of patients with chronic heart failure. To point out the underlying mechanisms and to provide a new animal model based approach, we investigated microvesicle (MV)-release in mice that underwent Transverse Aortic Constriction (TAC). TAC is a common method to induce cardiac hypertrophy and heart failure in mice by inducing pressure overload. We hypothesized that TAC leads to upregulation of total MV and MV of specific origin.

Methods and results

Wildtype C57BL/6 mice underwent TAC to induce cardiac hypertrophy and heart failure. After TAC, mice developed cardiac hypertrophy as determined by altered heart weight/ bodyweight ratio, end-diastolic and end-systolic diameter and decreased fractional shortening. Total numbers of circulating microvesicles were detected 1, 4 and 12 weeks after TAC. We found that total numbers of circulating macrovesicles raised in a time dependent manner. Similar observations could be done with samples stained for annexin V, although results were not significant. Moreover, microvesicles were stained with specific surface markers for lymphocyte (CD3), monocyte (CD14), endothelial cells (CD31), thrombocytes (CD41), B-cells (CD45) and neutrophils (Lys6). One week after TAC increased numbers of specific microvesicles could be detected which in the course declined rapidly. Only microvesicles subgroup of lymphocyte origin showed significant increase one week after TAC-OP.

Conclusion

In this study, we show that total number of circulating microvesicles raise after TAC over an observation period of 12 weeks. Furthermore, we found that increased numbers of circulating microvesicles of specific origin like lymphocytes, monocytes, endothelial cells, thrombocytes, B-cells and neutrophils showed a trend towards increased levels one week after TAC with a rapid decline in subsequent detection. To our knowledge this is the first time that the impact of TAC on number of circulating microvesicles in mice was investigated. Future studies should characterize the content and effects of these MV on recipient cells to elucidate possible contributions to heart failure progression or protective effects. Detecting new harmful or protective effects of heart failure triggered by circulating microvesicles could offer new highly needed approaches to suppress heart failure development or deliver the possibility to develop new drugs for heart failure treatment.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Else Kröner-Fresenius
Do Rockwood frailty score and Charlson comorbidity index help to risk stratify outpatient versus inpatient management of acute decompensated heart failure?
Authors: Neoh K.A.I , Sevdynidis L , Hatherley J , Tay J , Douglas H , Akpan A , Sankaranarayanan R
Published: November 2020

Introduction

Acute decompensated heart failure (ADHF) is associated with frailty and co-morbidities which influence prognosis. The Rockwood Frailty Score (RFS) and age-adjusted Charlson co-morbidity index (CCI) have been used to predict outcomes in hospitalised ADHF patients.

Purpose

To describe the relationship of CCI, RFS and clinical risk score -Get With The Guidelines Score (GWTG) with mortality in ADHF treated as outpatients (OP) versus hospitalised inpatients (IP).

Methods

This retrospective analysis compared 2 cohorts of consecutive ADHF patients - hospitalised in-patients (IP) versus outpatients (OP) who were treated with bolus intravenous diuretics in a specialist heart failure nurse delivered OP HF unit (Ambulatory HF Unit -AHFU) with input from various specialties (renal, palliative, ascitic, pleural teams) from Nov 16 to Dec 17. Mean follow-up duration was similar for both groups (IP=19.5±4.1 months; OP=19.3±3.9 months, p=0.6). Mortality was compared at 1, 3 and 12 months based on RFS (no frailty <5, mild to moderate frailty 5/6, severe frailty - 7 to 9). Results were expressed as mean±SD and analysed using One-Way ANOVA and Chi-squared with Fisher's exact test test.

Results

410 consecutive patients (482 admissions) were hospitalised (inpatients -IP) and 231 OP (289 OP visits) were treated in the AHFU. IP group had significantly higher mean CCI (IP=6.55±2; OP=6.10±1.9; p=0.006) and mean RFS (IP 5.2±1.2; OP 4.9±1.1; p=0.002). Mean Clinical Risk Score GWTG was similar (IP=38.9±7.2; OP=38.4±6.6; p=0.44). Mean survival was significantly lower in IP (IP=378±270 days; OP=437±228; P=0.003). As shown in the table higher RFS predicts increased mortality risk (1 month, 3 month and 12 month).

Conclusions

Rockwood Frailty Score predicts mortality in ADHF and assessment of RFS can play an important role in risk stratifying and decision-making in addition to clinical risk-scores, with regards to suitability for outpatient treatment of ADHF.

Funding Acknowledgement

Type of funding source: None
The association between acute-to-chronic glycemic ratio and outcome in acute heart failure
Authors: Teraguchi I , Imanishi T , Komukai K , Tamaki T , Imamura S , Kataiwa H
Published: November 2020

Introduction

Elevated blood glucose level on admission worsen outcome in acute heart failure (AHF). The admission blood glucose (ABG)/ the estimated average glucose (eAG) ratio which combines both acute and chronic glucose levels is attracting attention as a newly introduced glycemic index. It may be accepted as indicating the true acute glycemic rise in critically in all patients.

Purpose

The aim of this study was to assess the association between acute-to-chronic glycemic ratio and outcome in AHF.

Methods

This study assessed consecutive patients with AHF. The ABG/ eAG ratio was determined as ABG divided by eAG. We examined the relationship between ABG/ eAG ratio and all-cause mortality and readmission for heart failure within 30 days.

Results

A total of 249 patients with AHF (mean age; 81 years, 50% male and 37% DM) were studied. 31 (12.4%) patients had events within 30 days [18 (7.2%) died and 13 (5.2%) readmitted for HF]. We divided into three tertiles [T1 (<0.93), T2 (0.93–1.21) and T3 (>1.21)] based on the ABG/ eAG ratio. There was a stepwise worsening of the 30 days outcome [1 patient (0.4%) vs 7 patients (2.8%) vs 23 patients (9.2%), p<0.0001]. In multiple variable analysis, ABG/ eAG ratio was an independent predictor of the events (p=0.002). A cut-off value of the ABG/ eAG ratio <1.11 had a sensitivity of 94% and specificity of 67% for the increase of events within 30 days. In full model, the ABG/ eAG ratio was independent predictor of 30 days outcome in AHF (odds ratio: 11.7; 95% confidence interval: 3.65–37.5; p<0.0001).

Conclusion

ABG/ eAG ratio was one of the strong predictors 30 days outcome in AHF. Elevated blood glucose in the acute phase evaluated using the ABG/ eAG ratiocan enhance affect outcome and it could be a potential therapeutic target in patients of AHF.

Funding Acknowledgement

Type of funding source: None
Artificial intelligence in echocardiography diagnostics – detection of takotsubo syndrome
Authors: Di Vece D , Laumer F , Schwyzer M , Burkholz R , Corinzia L , Cammann V.L , Citro R , Bax J , Ghadri J.R , Buhmann J.M , Templin C
Published: November 2020

Background

Machine learning allows classifying diseases based only on raw echocardiographic imaging data and is therefore a landmark in the development of computer-assisted decision support systems in echocardiography.

Purpose

The present study sought to determine the value of deep (machine) learning systems for automatic discrimination of takotsubo syndrome and acute myocardial infarction.

Methods

Apical 2- and 4-chamber echocardiographic views of 110 patients with takotsubo syndrome and 110 patients with acute myocardial infarction were used in the development, training and validation of a deep learning approach, i.e. a convolutional autoencoder (CAE) for feature extraction followed by classical machine learning models for classification of the diseases.

Results

The deep learning model achieved an area under the receiver operating curve (AUC) of 0.801 with an overall accuracy of 74.5% for 5-fold cross validation evaluated on a clinically relevant dataset. In comparison, experienced cardiologists achieved AUCs in the range 0.678–0.740 and an average accuracy of 64.5% on the same dataset.

Conclusions

A real-time system for fully automated interpretation of echocardiographic videos was established and trained to differentiate takotsubo syndrome from acute myocardial infarction. The framework provides insight into the algorithms' decision process for physicians and yields new and valuable information on the manifestation of disease patterns in echocardiographic data. While our system was superior to cardiologists in echocardiography-based disease classification, further studies should be conducted in a larger patient population to prove its clinical application.

Funding Acknowledgement

Type of funding source: None
Selective beta-3 adrenergic receptor blockade increases contractility of human ventricular trabeculae from HFrEF donors
Authors: Nguyen N , Page G , Abi-Gerges N , Miller P.E , Adams J.W
Published: November 2020

Background

Alterations of the beta-adrenergic system have been extensively described in the setting of heart failure (HF). Upregulation of beta-3 adrenergic receptor (β3-AdrR) expression in human failing hearts depresses myocardial contractility and, during an acute decompensation event, can be considered a maladaptive compensatory mechanism that exacerbates cardiac dysfunction. APD418 is a selective β3-AdrR antagonist currently in development for patients who have acute heart failure with reduced ejection fraction (HFrEF). APD418 is designed to improve myocardial contractility by selectively antagonizing the β3-AdrR and thereby avoiding the cAMP/Ca2+ signaling pathway stimulated by current inotropes.

Purpose

This study evaluated the effect of a selective β3-AdrR antagonist (APD418) on contractile responses in explanted human ventricular trabeculae obtained from normal and HFrEF hearts.

Methods

Left ventricular trabeculae from normal and HFrEF donors were electrically stimulated (1 Hz) ex-vivo to analyze force generated during contractions. First, BRL37344, a selective β3-AdrR agonist, was applied at increasing concentrations (0.01–10 μM) to confirm β3-AdrR mediated negative inotropy in human myocardial tissue. To test the effect of a selective β3-AdrR antagonist on contractile force, myocardial tissue was pre-treated with APD418 or vehicle for 5 minutes, followed by treatment with non-selective β-AdrR agonists isoproterenol (10 nM) or norepinephrine (5 μM).

Results

In heart tissue from normal donors, the β3-AdrR agonist BRL37344 did not affect contractile function at 0.01 and 0.1 μM. However, in heart tissue from HFrEF donors, BRL37344 induced a significant decrease in contractility at 0.01, 0.1 and 1 μM (85.9±1.8% with 0.1 μM BRL37344 vs 104.1±2.9% with vehicle). Selective blockade of β3-AdrR with APD418 had no effect on force of contraction induced by norepinephrine in cardiac tissue from normal donors. In contrast, APD418 potentiated the force of contraction induced by either isoproterenol (49.1±20.6% increase with 0.1 μM APD418 compared to baseline) or norepinephrine (26.5±4.9% increase with 0.01 μM APD418 compared to baseline) in cardiac tissue from HFrEF patients.

Conclusion

This is, to our knowledge, the first evidence showing that selective blockade of β3-AdrR increases contractility of human ventricular trabeculae from HFrEF donors and suggests that further studies evaluating the therapeutic benefit of APD418 in patients with HFrEF are warranted.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Arena Pharmaceuticals
Temporary assist devices in France 2014–2018: intra-aortic balloon pump: is the technique really outdated?
Authors: Roubille F , Akodad M , Delmas C , Bonnefoy-Cudraz E , Huet F , Leclercq F , Gaudard P , Rouviere P , Gandet T , Duflos C , Delseny D , Battistella P , Agullo A , Aguilhon S , Puymirat E
Published: November 2020

Aims

Intra-aortic balloon pump (IABP) utilization was expected to be quickly abandoned following the IABP-shock trial and its class III, level B of recommendation in the 2016 ESC guidelines. The aim of this study was to evaluate the use of IABP compared to other mechanical support devices in a nationwide approach.

Methods

We conducted a retrospective study based on the French national hospital discharge database. All patients implanted by an assist device either by IABP, extracorporeal membrane oxygenation (ECMO) or IMPELLA® from 2014 to 2018 (2 years before/2 years after the 2016 guidelines) were included. The primary endpoint was the incidence of IABP implantation over the years. Secondary endpoints were incidence of total assist devices implantations, ECMO and IMPELLA® implantation.

Results

From 2014 to 2018, a total of 18,872 patients benefited from mechanical support by IABP (n=6,637, 35.2%), ECMO (n=11,833, 62.7%) or IMPELLA® (n=402, 2.1%) in France. The incidence of total mechanical support implantations (ECMO and IABP) was constant over the years. IABP implantation decreased progressively from 1,725 implantations in 2014 to 976 in 2018 (−44%). By contrast, ECMO implantation increased progressively from 1,919 implantations in 2014 to 2,715 implantations in 2018 (+42%). IMPELLA® implantations remained stable over the years from 63 (1.7%) implantations in 2014 to 83 (2.1%) in 2018.

Conclusion

In this nationwide real-life study, despite a significant decline in IABP implantations over the years since the ESC guidelines, this device remained used in clinical practice with around 1,000 implantations in 2018. The size of the centers is not strictly correlated with this use, suggesting differential uses depending of the local background.

Funding Acknowledgement

Type of funding source: None
Mechanical circulatory support with impella in patients with non-acute myocardial infarction related cardiogenic shock
Authors: Haurand J , Bueter S , Jung C , Kelm M , Westenfeld R , Horn P
Published: November 2020

Background

Percutaneous left ventricular assist devices such as the Impella pump, are used to hemodynamically stabilize patients with cardiogenic shock (CS) caused by acute myocardial infarction (AMI) until cardiac function has recovered after revascularization. Whether Impella mechanical circulatory support (MCS) is effective in stabilizing patients with CS not caused by AMI has so far not been thoroughly investigated.

Purpose

The aim of this study is to analyze whether MCS with Impella is effective to stabilize patients with non-AMI related CS compared to patients with AMI related CS.

Method

We retrospectively analyzed 106 patients with CS and Impella support in the years from 2011 to 2018. Efficacy to stabilize the patient was assessed by laboratory values such as lactate, hemodynamic parameters and clinical scores. The difference in mortality was calculated with the Log-Rank-Test, comparing Kaplan-Meier curves.

Results

36 patients suffered from non-AMI CS and in 70 patients CS was caused by AMI. Regarding the clinical scores and hemodynamic parameters, both groups were severely ill, with no significant difference in APACHE II score, with a mean score of 17.9 in the non-AMI group compared to 20.5 in the AMI-group (p=0.103), the SOFA score (mean score of 6.3 in non-AMI group vs 6.8 in AMI group, p=0.467) and cardiac index (mean CI of 1.9 l/min/m2 in non-AMI group vs 2.2 l/min/m2 in AMI group, p=0.176). There was a comparable mean decrease in lactate levels in both groups 48 hours after initiation of MCS, from initially 4.1 mmol/l to 1.7 mmol/l (p<0.001) in the non-AMI group and from initially 3.6 mmol/l to 2.2 mmol/l (p=0.025) in the AMI group. The non-ACS group exhibited a trend of lower mortality compared to the AMI group, with 47% in the non-AMI group and 57% in the AMI group (p=0.067). In multivariate analysis, age, lactate levels, cardiopulmonary resuscitation, low platelets and higher doses of inotropes and vasopressors were independent predictors for mortality. An upgrade to LVAD was performed for 22% of the non-AMI group and for 6% of the AMI group (p=0.020).

Conclusion

Impella support is effective to hemodynamically stabilize patients with non-AMI related CS. Therefore, MCS can be used as bridge to recovery or enables further treatment options as upgrade to longterm mechanical support devices.

Funding Acknowledgement

Type of funding source: None
Intra-aortic balloon pump as a bridge therapy to heart transplant in refractory heart failure
Authors: Boros G.A.B , Bellini V.S.C , Fatori D , Bernoche C , Macatrao-Costa M.F , Lopes L.N.G.D , Bacal F , Hueb W , Kopel L , Lage S.G
Published: November 2020

Background

The role of intra-aortic balloon pump (IABP) in advanced heart failure (HF) treatment is still under debate. Some heart transplant (HTx) candidates on the waiting list require mechanical support, and IABP may be the simple and most available device.

Purpose

Describe the impact of IABP treatment in advanced HF patients who underwent HTx.

Methods

We retrospectively analysis patients who underwent HTx from a single center intensive care unit (ICU), between 2009 and 2018, to evaluate the use of IABP as bridge therapy. Selection included decompensated chronic HF patients that required intensive care with optimized intravenous drugs before IABP placement. Exclusion criteria were acute myocardial infarction or cardiac surgery 90 days prior to admission, and implant of ventricular assist device before HTx.

Results

We included 134 HF patients with IABP therapy before HTx. Insertion site was exclusively femoral. Mean time of IABP onset to HTx were 26±21 days, and hospital admission to HTx 65±45 days. The main cardiomyopathy etiology was Chagas Disease (46%) and mean LVEF was 23±6% (TABLE 1). Clinical and laboratory data were compared before and 96 hours after IABP therapy. Mean central venous oxygen saturation (SvO2) increased from 49.7±14.6% to 67.4±11.3% (p<0.001), creatinine decreased from 1.77±0.9 mg/dL to 1.40±0.6 mg/dL (p<0.001), and urine output increased from 1552±886 mL/24h to 2189±1029 mL/24h (p<0.001). These differences were sustained or improved until the day before HTx (FIGURE 1). After 96 hours dobutamine was maintained in 98% of patients, nitroprusside increased from 56% to 67%, milrinone decreased from 26% to 20%, and norepinephrine decreased from 18% to 3%. Significant IABP complications were few (5.2%; n=7: 3 infections, 2 major bleeding, 2 arterial injury).

Conclusion

In this single center ICU sample, IABP improved hemodynamic status and renal function in refractory HF patients waiting for HTx. IABP can be a reasonable, available and effective bridging therapy.

Figure 1

Funding Acknowledgement

Type of funding source: None
Coronary flow velocity reserve predicts adverse outcome in patients with angina and no obstructive coronary artery disease
Authors: Schroder J , Michelsen M.M , Mygind N.D , Frestad D , Suhrs H.E , Bove K.B , Aziz A , Hansen H.S , Hansen P.R , Gustafsson I , Kastrup J , Prescott E
Published: November 2020

Background

Many patients with angina do not have obstructive coronary artery disease (CAD) when evaluated with coronary angiography. It is unknown whether echocardiographic coronary flow velocity reserve (CFVR) predicts an adverse outcome in these subjects. Previous CFVR studies have included heterogeneous patient subtypes both with and without CAD.

Purpose

To assess whether reduced CFVR predicts adverse outcome in women with angina and no CAD.

Methods

We evaluated 1853 women with angina and a coronary angiogram without stenosis. Exclusion criteria were previous myocardial infarction, coronary revascularisation, heart failure or valvular disease. Coronary microvascular function was assessed by echocardiographic CFVR. All patients were followed up for major adverse cardiovascular events.

Results

CFVR was obtained in 1681 patients (91%), median CFVR was 2.33 (IQR 2.00–2.74). During a median follow-up of 4.48 years, 96 adverse events occurred (acute myocardial infarction: 25; heart failure: 21; revascularisation: 8; stroke: 32; cardiovascular death: 10). In univariate Cox regression, CFVR (hazard ratio [HR] 2.04 [95% CI 1.39–2.94] per unit decrease in CFVR; p<0.001), hypertension (HR 2.29 [95% CI 1.46–3.59]; p<0.001) and diabetes (HR 2.13 [95% CI 1.31–3.45]; p=0.002) were associated with adverse outcome. These associations remained in age-adjusted multivariable regression. Exploratory analyses identified CFVR=2.24 as the optimal discriminating threshold. Stratification according to reduced CFVR and hypertension identified subgroups with better, intermediate and worse outcome (Figure 1). Outcome analyses excluding stroke yielded similar results.

Conclusion

Impaired CFVR predicts adverse outcome in women with angina and no CAD. Integrating CFVR and hypertension identifies high-risk patients.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Danish Heart Foundation
Distinct circulating cytokine levels in patients with angiography-proven coronary artery disease compared to disease-free controls
Authors: Maaniitty E , Sinisilta S , Jalkanen J , Hollmen M , Biancari F , Gunn J , Jalkanen S , Airaksinen K.E.J , Kiviniemi T.O
Published: November 2020

Background

Systemic inflammation has a critical role in the development of coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches.

Purpose

We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls.

Methods

Study population consisted of 458 patients who underwent diagnostic invasive coronary angiography for clinical indications. Altogether 312 patients had angiographically significant CAD whereas 146 had no angiographically-detected coronary atherosclerosis. We measured the serum concentrations of 48 circulating cytokines.

Results

Patients with CAD had increased levels of interleukin-1 receptor antagonist (IL-1-RA), interleukin-2 receptor alpha (IL-2Rα), IL-3, IL-4, IL-6, IL-9, IL-10, IL-16, IL-17, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), macrophage inflammatory protein-1-beta (MIP-1-β), tumor necrosis factor-alpha (TNF-α), TNF-β, cutaneous T-cell-attracting chemokine (CTACK), growth regulated oncogene alpha (GRO-α), hepatocyte growth factor (HGF), interferon alpha-2 (IFNα-2), leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), monokine induced by gamma interferon (MIG), beta-nerve growth factor (β-NGF), stem cell factor (SCF) and stromal cell-derived factor 1 alfa (SDF1α). On a logistic multivariate regression model adjusted with age, sex, hypertension and treatment for diabetes, increased levels of IL-4 (p=0.027, OR 1.090), IL-9 (p=0.000, OR 1.013), IL-17 (p=0.011, OR 1.005), CTACK (p=0.008, OR 1.001), MIP-1-β (p=0.004, OR 1.006), GRO-α (p=0.008, OR 1.004), TNF-α (p=0.019, OR 1.011) were independently associated with atherosclerosis.

Conclusions

Patients with CAD have distinct circulating cytokine profiles compared to disease-free controls. Based on these findings, certain cytokines may have a pivotal role in the development of atherosclerotic cardiovascular disease and cytokine-mediated pathway appear as a promising target for cardiovascular drug development.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Finnish Medical Foundation, Helsinki, Finland; The Finnish Foundation for Cardiovascular Research, Helsinki, Finland
Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention
Authors: He C , Lin K , Chen H , He H , Yang J , Zhang S , Guo Y , Chen J
Published: November 2020

Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention.

Objective

Contrast-induced nephropathy (CIN) remains a common complication of coronary procedure and increases poor outcomes, especially in patients with heart failure. Plasma volume expansion relates to worsening prognosis of heart failure. We hypothesised that calculated plasma volume status (PVS) might provide predictive utility for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention (PCI).

Methods

We enrolled 441 patients with heart failure undergoing PCI from 2012 to 2018. Pre-procedural PVS was calculated by comparing actual plasma volume (aPV) derived from the Hakim formula to ideal plasma volume (iPV). CIN was defined as an absolute SCr increase ≥0.5 mg/dl within 72h of contrast medium exposure. We assessed the association between PVS and risk of contrast-induced nephropathy in patients with heart failure undergoing elective PCI.

Results

In 441 patients, 28 (6.3%) patients developed CIN. The median pre-procedural PVS was −0.02 (−0.09–0.05). The best cutoff value of PVS for predicting CIN was 0.04 with 64.5% sensitivity and 75.5% specificity according to the ROC analysis (C statistic = 0.718; 95% CI: 0.674–0.760),of which predictive value is similar to NT-proBNP (C statistics 0.721 vs. 0.773, P=0.355). After adjusting for potential confounding risk factors, multivariable analysis demonstrated that PVS >0.04 (OR=3.142, 95% CI: 1.185–8.332, P<0.05) and NT-proBNP >4518pg/ml (OR=7.591, 95% CI: 2.886–19.968, P<0.05)were strong independent predictors of CIN.

Conclusion

Pre-procedural PVS is an independent risk factor for predicting CIN markedly, of which predictive value is comparable to BNP and also independent of BNP. The best cutoff point of PVS for predicting CIN was 0.04.

ROC for PVS and NT-proBNP to predict CIN

Funding Acknowledgement

Type of funding source: None
Association of Lipoprotein(a) levels with intrinsic and on-clopidogrel platelet reactivity
Authors: Kille A , Nuehrenberg T , Valina C.M , Neumann F.J , Hochholzer W
Published: November 2020

Background

Lipoprotein(a) [Lp(a)] is an independent, genetic, and causal risk factor for premature cardiovascular disease (CVD). Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its structural similarity to plasminogen. So far, the potential association of Lp(a) with platelet activation and reactivity has not been well established in larger clinical cohorts.

Methods

This secondary analysis of the EXCELSIOR study analyzed intrinsic platelet reactivity before loading with clopidogrel 600mg and on-treatment platelet reactivity tested 24 hours following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry as final aggregation after 5 min following stimulation with 5μM ADP. Platelet reactivity was also assessed by flow cytometry (expression of CD62P and PAC1) following stimulation with ADP and TRAP. Levels of Lp(a) on admission of each patient were immediately measured from fresh samples in a central laboratory.

Results

The present analysis included 2046 patients. Levels of Lp(a) ranged between 0 and 332 mg/dl. Results for intrinsic (p=0.80) and on-clopidogrel platelet reactivity (p=0.81) did not differ between quartiles of Lp(a) levels (Figure). Flow cytometry analyses confirmed these findings.

Conclusion

The present data do not support the hypothesis of an interaction of Lp(a) with platelet function. This finding might be important to define the safety of evolving therapeutic options for lowering Lp(a).

Funding Acknowledgement

Type of funding source: None
The prognostic impact of coronary calcium score in low risk patients presenting with chest pain; a 6-year follow-up single center study
Authors: Thalamus J , Gibbs C.C , Topper M.E , Oestvold C , Heldal K , Solli J.D , Motswakadikgwa T , Tobiasson K.A , Aasegard H , Hysing J , Haugaa K.H
Published: November 2020

Background

Evaluation and risk stratification of patients with chest pain is a frequent task in cardiology. Coronary artery calcium is an established risk marker and is in wide clinical use. However, less is known about the long-term prognostic implications of coronary calcium score values in low risk individuals.

Purpose

We wanted to investigate the long-term outcome related to coronary artery calcium score (CAC).

Methods

We included patients who were examined with coronary CT angiography or GT SPECT from August 2011 to August 2015. The coronary calcium score percentile was calculated using the MESA Coronary Artery Calcium (CAC) Score Reference Values web tool. We excluded patients already stratified as high risk due to previous myocardial infarction or coronary revascularization. The primary endpoint was a composite of 5 point MACE (death, myocardial infarction, PCI, CABG and stroke) and was extracted from the electronic medical records. We censored follow up on the 31st December 2018.

Results

We included 1975 patients (958 (48.5%) male, age 60.3±12.0). The average CAC was 288±701. After median follow up of 6.0 (5.3–6.5 IQR) years, 372 patients fulfilled a primary endpoint. Event rate increased significantly with higher percentiles of CAC score (log rank 0.001, Figure 1). A total of 687 patients had a CAC score of 0. In this group we observed only 21 events during 6 years follow up, giving an annual event rate of 0.6%. Annual event rate in the patients with CAC percentile 1–75 was 3.2% and in the patients with CAC percentile 75–99 annual event rate was 5.6%. Death occurred in 10% of patients in the two upper percentiles compared to only 2% in the lowest percentile (p<0.001)

Conclusion

Our findings support that CAC is a powerful predictor of coronary artery events. Furthermore, our study confirms excellent long term prognosis regarding cardiac events in patients with 0 CAC, which is helpful in risk stratification of patients with chest pain.

Figure 1

Funding Acknowledgement

Type of funding source: None
Impact of copeptin, miRNA-499 and miRNA-208 as new biomarkers for early detection of acute coronary syndrome
Authors: El-Deek S , Meki A.R , Hassan A , Gaber M , Mohamed O
Published: November 2020

Introduction

Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission.

Aim of the work

To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR.

Results

Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P<0.001 each). Also these biomarkers were significantly increased in NSTEMT compared to UA (P<0.001 each). They also significantly elevated in UA and NSTEMI patient in the first 3 hours who had negative cardiac troponin (p<0.001 each). ROC curve analysis revealed that the area under curve (AUC) for prediction of ACS was 0.96 for copeptin, 0.97 for miRNA-499 and 0.0.97 for miRNA-208. Interestingly, combining copeptin with miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.98, P<0.001. The sensitivity and specificity within the first 3 hours were 90%, 86% for copeptin, 95%, 94% for miRNA-499 and 93%, 98% for miRNA-208. The sensitivity and specificity were 81% and 86% for cardiac troponin within 6 hours. There was a positive correlation between copeptin and miRNA-499 and miRNA-208 (r=0.75, P<0.001 and r=0.76, P<0.001 respectively) Also, there was a positive correlation between these biomarkers and cTn (r=0.7. P<0.001, r=0.64, P<0.001 and r=0.68, P<0.001 respectively).

Conclusions

Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation.

Funding Acknowledgement

Type of funding source: None
Influence of caffeine intake on intravenous adenosine-induced fractional flow reserve
Authors: Ishibuchi K , Fujii K , Otsuji S , Takiuchi S , Hasegawa K , Tamaru H , Ishii R , Yasuda S , Nakabayashi S , Yamamoto W , Kusumoto H , Taniguchi Y , Kakishita M , Shimatani Y , Higashino Y
Published: November 2020

Background

This study evaluated whether caffeine abstention is required before fractional flow reserve (FFR) measurement by intravenous adenosine triphosphate (ATP) administration in Japanese patients.

Methods and results

This study was a subanalysis of a previously published study and a total of 208 intermediate lesions that underwent FFR measurements were enrolled for this analysis. Hyperemia was induced by continuous intravenous ATP infusion at 150μg/kg/min (IVATP150) and 210μg/kg/min (IVATP210), and by intracoronary administration of nicorandil 2mg (ICNIC2mg) as a reference standard. The degree of change in the FFR value both after IVATP150 and after IVATP210, as compared with the FFR value after ICNIC2mg was similar between the caffeine and non-caffeine groups (−0.04±0.05 vs. −0.04±0.07, and 0.00±0.02 vs. 0.01±0.02, respectively). In patients who consumed caffeine before the FFR measurement, the degree of FFR change was independent of the time interval (<12 hours, 12–24 hours, and 24–48 hours) between caffeine intake and catheterization both after IVATP150 and ICNIC2mg and after IVATP210 and ICNIC2mg.

Conclusion

When compared with the FFR value after ICNIC2mg, the degree of change in the FFR value both after IVATP150 and after IVATP210 remained similar regardless of caffeine intake. Strict caffeine abstention before intravenous ATP-induced FFR measurement may not be required in clinical practice.

Funding Acknowledgement

Type of funding source: None
Coronary artery echo-attenuated plaques in acute coronary syndromes: a serial intravascular ultrasound imaging study
Authors: Scherer D.J , Shishikura D , Andrews J , Di Giovanni G , Jones S , Honda S , Butters J , Kataoka Y , Nicholls S.J
Published: November 2020

Background

Echo attenuation of atherosclerotic plaque (EAP) identified with intravascular ultrasound (IVUS) has been shown to correlate with vulnerable plaque morphologies and their presence is predictive of future cardiovascular events. EAP have predominantly been assessed at a single time point and their natural history in the immediate post acute coronary syndrome (ACS) period remains unknown. We aimed to assess this and whether their presence correlated with a more modifiable plaque composition in the immediate post-ACS setting.

Methods

Serial IVUS imaging was performed in non-culprit vessels of 270 patients undergoing angiogram for ACS and at 3 month follow up. IVUS analysis of plaque burden and EAP was performed.

Results

Baseline characteristics are described in Table 1. EAP were present at baseline in 62 patients (23%) with these patients more likely to be male (89.1% vs. 76.7%, p=0.03) but no differences in other atherosclerotic risk factors. There was no difference in baseline plaque burden between patients with EAP and those without (Percent atheroma volume [PAV] 38.9% vs. 37.8%, p=0.32). At follow up IVUS change in PAV was not statistically significantly different between patients with baseline EAP and those without (ΔPAV 0.09% vs. −0.36%, p=0.43), and neither was there a difference in the frequency of plaque regressors (42.7% vs 50%, p=0.31). EAP had resolved in 25 patients (40%) within 3 months at the follow up IVUS. Despite contemporary post-ACS therapy 18 patients who had not had EAP present at baseline (9%) developed new EAP at the follow up IVUS.

Conclusion

EAP were present in a quarter of ACS patients and were not associated with baseline plaque burden or a more modifiable plaque phenotype. In the setting of contemporary ACS treatments the natural history of high risk IVUS plaque characteristics such as EAP is dynamic with significant change even over a 3 month period in the post ACS setting.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Royal Adelaide Hospital Research Fund AR Clarkson Scholarship