bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity accelerates cardiac senescence in heart failure with preserved ejection fraction
Authors: Verbrugge F.H , Reddy Y.N.V , Kapa S , Borlaug B.A
Published: November 2020

Background

Diastolic reserve decreases with aging. A recently developed artificial intelligence (AI) algorithm can predict age based on 12-lead electrocardiogram (ECG) analysis.

Purpose

This study aims to use a validated AI algorithm to assess cardiac senescence and investigate the impact of obesity on cardiac aging in heart failure with preserved ejection fraction (HFpEF).

Methods

This retrospective cohort study includes 403 patients with HFpEF, admitted for treatment with intravenous diuretics. ECG age was assessed by a convolutional neural network as previously validated. Patients were stratified according to the presence of obesity (body mass index >30 kg/m2) and ECG age was compared between groups. The relationship between ECG versus calendar age and structural/functional alterations on echocardiography, as well as the risk of atrial fibrillation (AF) development, was evaluated.

Results

In 253 (63%) obese patients with HFpEF, calendar age was 8 years younger compared with their non-obese counterparts, but ECG age was only 3 years younger. ECG minus calendar age was higher in obese patients (P-value <0.001; figure) and correlated moderately strong with weight, fat free, and fat mass (r=0.35–0.41; P-value <0.001). Older ECG age was correlated with worse diastolic function, but not with left ventricular afterload (table). Calendar age correlated less strongly with diastolic dysfunction (table). ECG age did predict AF development, independently of calendar age, gender, and presence of obesity [HR (95% CI) = 1.31 (1.06–1.63) per 5-year; P-value=0.015].

Conclusions

Obesity accelerates cardiac senescence in HFpEF as reflected by more pronounced diastolic dysfunction and a higher AF risk, which was identified from ECG analysis by a validated AI algorithm.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Belgian American Educational Foundation (B.A.E.F.); Special Research Fund (BOF) of Hasselt University (Hasselt, Belgium).
Interatrial Block Predicts Atrial Fibrillation and Total Mortality in Patients with Cardiac Resynchronization Therapy
Authors: Jacobsson J , Carlson J , Reitan C , Borgquist R , Platonov P.G
Published: November 2020

Background

Interatrial block (IAB) and abnormal P-wave terminal force in lead V1 (PTFV1) are electrocardiographic (ECG) abnormalities associated with new-onset atrial fibrillation (AF) and death. However, their prognostic importance has not been proven in CRT recipients with advanced heart failure (HF).

Purpose

To assess if IAB and abnormal PTFV1 are associated with new-onset AF or death in CRT recipients.

Methods

CRT recipients without AF history before CRT implantation were included (n=210, median age 67 years, 80% male, 55% ischemic heart disease, 70% NYHA Class III/IV, median LVEF 25%, 51% CRT-P). Automated analysis of P-wave duration (PWD) and morphology classified patients as having either No IAB (PWD <120ms), Partial IAB (pIAB: PWD ≥120 ms, positive P waves in leads II and aVF) or Advanced IAB (aIAB: PWD ≥120 ms and biphasic or negative P wave in leads II or aVF). PTFV1 >0.04 mm·s was considered abnormal. Cox regression analyses adjusted for age, NYHA Class, ischemic etiology of HF, LBBB, LVEF and CRT-P vs. CRT-D were performed to assess the impact of IAB and abnormal PTFV1 on the primary endpoint new-onset AF, death or heart transplant (HTx) and the secondary endpoint death or HTx at 5 years of follow up.

Results

IAB was found in 45% (34% pIAB and 11% aIAB) and was associated with both the primary (HR 1.9, 95% CI 1.2–2.9, p=0.004) and the secondary (HR 2.1, 95% CI 1.2–3.4, p=0.006) endpoints. Abnormal PTFV1 was not associated with outcome. See Forest plot for adjusted HRs for individual P-wave indices.

Conclusions

IAB is associated with new-onset AF and death in CRT recipients and may be helpful in risk stratification in the context of HF management. Abnormal PTFV1 did not demonstrate any prognostic value in the setting of CRT-treated patients with advanced HF.

Forest plot

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swedish Heart and Lung Foundation
Central and obstructive apneas prevalence in heart failure with reduced, mid-range and preserved ejection fraction
Authors: Borrelli C , Sciarrone P , Gentile F , Ghionzoli N , Mirizzi G , Passino C , Emdin M , Giannoni A
Published: November 2020

Background

Central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF) both with reduced and preserved systolic function. However, a comprehensive evaluation of apnea prevalence across HF according to ejection fraction (i.e HF with patients with reduced, mid-range and preserved ejection fraction- HFrEf, HFmrEF and HFpEF, respectively) throughout the 24 hours has never been done before.

Materials and methods

700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring.

Results

In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40%, 51%, and 9%, respectively, while at nighttime 15%, 55%, and 30%, respectively.

When stratified according to left ventricular EF, CA prevalence decreased from HFrEF to HFmrEF and HFpEF: (daytime CA: 57% vs. 43% vs. 42%, respectively, p=0.001; nighttime CA: 66% vs. 48% vs. 34%, respectively, p<0.0001), while OA prevalence increased (daytime OA: 5% vs. 8% vs. 18%, respectively, p<0.0001; nighttime OA: 20 vs. 29 vs. 53%, respectively, p<0.0001).

When assessing moderte-severe apneas, defined with an apnea/hypopnea index >15 events/hour, prevalence of CA was again higher in HFrEF than HFmrEF and HFpEF both at daytime (daytime moderate-severe CA: 28% vs. 19% and 23%, respectively, p<0.05) and at nighttime (nighttime moderate-severe CA: 50% vs. 39% and 28%, respectively, p<0.05). Conversely, moderate-severe OA decreased from HFrEF to HFmrEF to HFpEF both at daytime (daytime moderate-severe OA: 1% vs. 3% and 8%, respectively, p<0.05) and nighttime (noghttime moderate-severe OA: 10% vs. 11% and 30%, respectively, p<0.05).

Conclusions

Daytime and nighttime apneas, both central and obstructive in nature, are highly prevalent in HF regardless of EF. Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses, both during daytime and nighttime.

Funding Acknowledgement

Type of funding source: None
Temporal characteristics of an integrated diagnostics risk score before and after heart failure hospitalizations in a large real-world population of patients with implantable devices
Authors: Koehler J , Ippolito E , Warman E.N , Sarkar S
Published: November 2020

Background

Diagnostic parameters measured in implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy defibrillators (CRTD) have been shown to change before and after heart failure (HF) events with fluid overload.

Purpose

We investigated the temporal characteristics of an integrated diagnostic risk score before and after HF events in a large real-world cohort of patients with ICD/CRTD devices.

Methods

We linked a de-identified database of aggregated electronic health record (EHR) data (2007–2017) to a manufacturer's device database with continuous diagnostic monitoring data. Patients with ICD/CRTD implants with intra-thoracic impedance diagnostic feature were included for this study. The previously defined integrated diagnostic risk score was derived by combining daily diagnostic data, including intra-thoracic impedance, night-time heart rate, activity, heart rate variability, and atrial fibrillation (AF) burden, ventricular rate during AF, CRT pacing, ventricular tachycardia episodes and shocks, in a Bayesian Belief Network framework. HF event was defined as an inpatient, emergency department, or observation unit stay in a hospital with primary diagnosis of HF and intravenous diuretic administration. Temporal average of daily risk score across all patients in the 60 days pre and post HF events were compared in HF events with and without readmission within 60 days and with no HF event during pre and post follow-up days.

Results

A total of 17,886 patients with 1.8±1.2 years of follow-up met inclusion criteria. The average age of patients was 66.6±12.3 years, with 72% being males, and 51% with ICD devices. The average integrated diagnostics risk score in HF events with and without readmission and with no events is shown in Figure. A total of 1174 patients had 1425 HF events with no readmission for HF within 60 days and 282 patients had 295 HF events which were followed by readmission for HF within 60 days. A total of 17,839 patients had no HF events over 86,858 follow-up months. The average daily risk score across all patients was higher on all 60 days pre and post HF event with readmission compared to HF events with no readmission (p<0.001) and both were higher compared to follow-up period with no events (p<0.001). The risk score recovers less often after HF events which are followed by readmission within 60 days compared to HF events with no readmission.

Conclusions

In a large real-world population of patients with ICD/CRTD devices, the average integrated diagnostics risk score was higher before and after HF events with readmission compared to HF events with no readmission. Re-admissions are more likely in patients with smaller risk score recovery after HF events.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Medtronic Plc
Strong independent association between hospital bleeding and death in acute coronary syndromes: causal relationship or coexistence of two phenomena?
Authors: Melo M.H.V.M , Pontes B , Bagano G.O.B , Azevedo T.E.A.S , Filgueiras P.H.C.F , Lopes P.O.A.L , Meireles A.C.M , Porto J.V.M.P.O , Oliveira A.L.F.O.J.R , Viana M.S.V , Noya-Rabelo M.M.N.R , Correia L.C.L.C
Published: November 2020

Background

Bleeding and hospital death have an independent association in observational records of acute coronary syndromes (ACS), leading to interpretation of this relationship as causal. However, association does not guarantee causality, and better exploitation of this phenomenon is necessary.

Purpose

To describe the association between bleeding and death of patients with ACS, exploring causality through the cascade of events that separate these two phenomena.

Methods

Patients consecutively admitted to Coronary Unit by objective criteria of ACS were included prospectively. Major bleeding during hospitalization was defined according to types 3 and 5 of the Universal Bleeding Classification. Logistic regression and sequence analysis of events were used to evaluate the association between bleeding and death.

Results

A total of 1104 patients were studied, age 65±14 years, 58% male, 23% with ST elevation. The incidence of major bleeding was 4.7% (52 cases). Bleeding patients presented mortality of 31% (16 deaths), compared to 4.7% death in the non-bleeding group (RR=6.6, 95% CI: 4.0–11). Those who bled had a GRACE score significantly higher than those free of bleeding (157±39 versus 121±38, P<0.001). After adjustment for this score, bleeding remained strongly associated with death (OR=4.5, 95% CI: 2.1–9.7, P<0.001). However, among the 16 deaths that occurred after bleeding, in 56% of the patients the death was due to hemorrhage, while the remainder was a consequence of the myocardial injury of the infarct or natural evolution of noncardiac morbidities.

Conclusion

The independent association between major bleeding and death in acute coronary syndromes is only partially mediated by causality. In the same proportion, deaths coexist with bleeding without a causal relationship.

Funding Acknowledgement

Type of funding source: None
External validation of the PRECISE-DAPT score in a large nationwide population of myocardial infarction patients: a SWEDEHEART study
Authors: Wester A , Mohammad M.A , Erlinge D , Koul S
Published: November 2020

Background/Introduction

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with stent placement in myocardial infarction (MI) patients has improved ischemic outcomes but increased the risk of bleeding. The PRECISE-DAPT (Predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy) score has been implemented in recent guidelines to tailor the duration of DAPT based on each patient's individual risk profile. However, to date it has only been externally validated on small data samples or exclusively for subgroups of PCI treated MI patients.

Purpose

To assess the performance of the PRECISE-DAPT score in a nationwide cohort of MI patients undergoing PCI with subsequent DAPT. This will be the world's largest validation of the PRECISE-DAPT score in approximately 20.000 unique real-world MI patients.

Methods

Data from the Swedish Websystem for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry on MI patients treated with DAPT after PCI between 2008 and 2016 in Sweden were obtained and merged with the Swedish Patient Registry as well as the Prescribed Drugs Registry that holds data from all Swedish pharmacies. The ability of PRECISE-DAPT to predict bleeding and ischemic outcomes in relation to DAPT duration was determined.

Results

Results are to be announced.

Conclusions

Whether the PRECISE-DAPT score can be validated or not in a large nationwide cohort of MI patients in relation to DAPT duration, has the potential to impact current DAPT guidelines and clinical decision making in everyday practice. Further results and conclusions are to be announced.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Märta Winkler's research foundation and Thorsten Westerström's research foundation
Left ventricle unloading and valvular integrity following microaxial mechanical circulatory support: a two year follow-up study
Authors: Hatzis G , Ahrens H , Karatolios K , Markus B , Divchev D , Syntila S , Schuett H , Schieffer B , Luesebrink U
Published: November 2020

Background

Although the use of mechanical circulatory support (MCS) systems may improve the outcome of patients with cardiogenic shock (CS) due to myocardial infarction, little is known about its effect on the long-term structural integrity of left-ventricular (LV) valves as well as on the development of LV- architecture.

Methods

84 consecutive patients were monitored over 2 years having received microaxillar MCS device (ImpellaTM CP or 2.5) for complete coronary revascularization followed by optimal medical treatment.

Results

62 patients were treated for severe cardiogenic shock and compared with 22 patients receiving short-term microaxillar MCS for high risk percutaneous coronary interventions (PCI). 24 patients of the total population received Impella CP (14F motor pump) and the remaining 60 patients received Impella 2.5 (12F motor pump). Beside a significant increase in LV-ejection fraction after 2 years (p≤0.03 vs. pre implantation) in total cohort, we observed a statistically significant decrease in LV-dilation (p<0.001) and the severity of mitral valve regurgitation (p=0.007) in the 2 year follow-up period suggesting an improved LV-architecture. Neither the duration of support, nor the size of the MCS device or the indication for its use revealed any devastating impact on aortic or mitral valve integrity.

Conclusions

These findings indicate that beside complete revascularization and optimal medical treatment, microaxillar transvalvular MCS device supports the restoration of LV-architecture without detrimental long-term effects on the structural integrity of LV valves regardless of the size of the device or the duration of support.

Funding Acknowledgement

Type of funding source: None
The impact of coronary heart disease on productivity in Australia over ten years
Authors: Savira F , Wang B.H , Kompa A.R , Ademi Z , Owen A , Liew D , Zomer E
Published: November 2020

Background

Coronary heart disease (CHD) is the highest individual disease burden in Australia and associated with productivity losses through unplanned absence from work, reduced output while at work and early labour force withdrawal. Approximately eighty per cent of CHD cases in Australia are preventable, suggesting the potential benefit of employing preventive strategies addressing populations at risk of CHD.

Purpose

To determine the preventable productivity burden attributable to CHD over the next ten years, using the novel productivity measure: the “productivity-adjusted life year” (PALY).

Methods

A dynamic life table model was constructed for the total Australian population, separated by CHD status. Analysis was limited to the Australian working-age population (15–69 years) over ten years (2020–2029). Australian age- and sex-specific prevalence, incidence, migration and mortality data was employed, and productivity estimates were sourced from the literature. The PALY was ascribed a financial value in terms of gross domestic product (GDP) per equivalent full-time worker. The total number of years lived, total PALYs, and total economic burden (in terms of cost of PALYs) were estimated for each year. The model simulation was repeated assuming incidence was reduced, and the differences represented the preventable productivity burden attributable to CHD. All outcomes beyond the first year were discounted by 5% per annum.

Results

Over the next ten years, the total projected years lived and PALYs among the Australian working-age population (with and without CHD) were approximately 132 million and 83 million, respectively, amounting to A$17.2 trillion (€10.5 trillion) in GDP. We predicted nearly 40,000 new (incident) CHD cases over this ten-year period. If, however, we could prevent these new cases of CHD, a total of 14,000 deaths could be averted, resulting in more than 8,000 years of life saved and 100,000 PALYs gained, equivalent to A$21 billion (€12.9 billion) in GDP.

Conclusion

Prevention of CHD will prolong both years of life lived and productive life years, resulting in substantial economic benefit. Policy makers and employers are encouraged to engage in preventive measures addressing CHD.

Funding Acknowledgement

Type of funding source: None
Proteomic profiling of acute stent thrombi reveals critical involvement of the complement system
Authors: Hofbauer T.M , Distelmaier K , Bileck A , Ondracek A.S , Seidl V , Frueh A , Neuditschko B , Mangold A , Pils D , Gerner C , Lang I.M
Published: November 2020

Background

Stent thrombosis (ST) is a severe complication after primary percutaneous coronary intervention (pPCI) and associated with significant morbidity and mortality. Apart from procedure- and lesion-related parameters and patient-related factors. However, the underlying molecular and cellular mechanisms of ST are still not fully understood.

Purpose

We aimed to perform in-depth proteomic analysis of ST to understand its pathogenesis.

Methods

We recruited 77 patients suffering from ST after pPCI for myocardial infarction (MI). As controls, we included matched patients suffering from native vessel acute myocardial infarction (NT, n=154). Five cases of acute ST (within 24 h) and six cases of NT thrombi aspirated from the culprit site were subjected to shotgun proteomic analysis. Gene-set analysis was employed to screen for pathways differing between ST and NT. All-cause mortality was assessed using Kaplan-Meier analysis.

Results

9 patients presented with acute ST (<24 h, 11.7%), 18 patients with subacute ST (24 h to 30 days, 23.4%), 11 patients with late ST (30 days to 1 year, 14.3%) and 39 patients with very late ST (>1 year, 50.6%). ST was associated with increased all-cause mortality compared to NT (mean survival 129 vs. 109 months, log-rank p=0.032). We identified a total of 2438 proteins to be expressed in both ST and NT thrombi. Gene set analysis revealed the complement system to be highly active in acute ST compared to NT. Specifically, we found factors of both the classical (complement factor [C]1q, C1s) and alternative pathway (complement factor B) to be increased in ST, along with higher levels of C2, C3, C4a, C4b, C5, C8a and C9.

Conclusion

This hypothesis-generating study highlights a crucial role of the complement system in the pathogenesis of acute ST. Further studies are required to validate these findings in a larger cohort.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund
Cardiac magnetic resonance T1 mapping allows for predicting adverse left ventricular remodeling post-reperfused st-elevation myocardial infarction
Authors: Zhang L , Guo Y.K , Yang Z.G , Yang M.X , Diao K.Y , Zhou X.Y
Published: November 2020

Background

Cardiac magnet resonance (CMR) T1 mapping allows the quantitative characterization of the severity of tissue injury and predict functional recovery in acute myocardial infarction (AMI).

Purpose

The study aimed to investigate whether native T1 and ECV of infarct myocardium are influenced by microvascular obstruction (MVO) and have predictive value for adverse left ventricular (LV) remodeling post-infarction.

Method

A cohort of 54 patients with successfully reperfused STEMI underwent CMR imaging at a 3T scanner in AMI and 3 months post-infarction. Native T1 data was acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, and ECV maps were calculated using blood sampled hematocrit. Manual regions-of-interest were drawn within the infarct myocardium to measure native T1 and ECV (native T1infarct and ECVinfarct, respectively). MVO identified as a low-intensity area within the infarct zone on LGE was eliminated.

Results

MVO was present in 36 patients (66.67%) in AMI. ECVinfarct in patients with MVO was different from those without (58.66±8.71% vs. 49.64±8.82%, P=0.001), while no significant difference in T1infarct was observed between patients with and without MVO (1474.7±63.5ms vs. 1495.4±98.0ms, P=0.352). ECV correlated well with the change in end-diastolic volume (all patients: r=0.564, P<0.001) and predicted LV remodeling in patients with and without MVO (rMVO absent = 0.626, P=0.005; rMVO present = 0.686, P<0.001; all patients: r=0.622, P<0.001); Native T1 was only associated with a 3-month change in LV end-diastolic volume (rMVO absent= 0.483, P=0.042) and predicted LV remodeling in patients without MVO (rMVO absent = 0.659, P=0.003). Furthermore, ECV had an association with LV remodeling (β=0.312, P=0.007) in multivariable logistic analysis.

Conclusion

Absolute native T1 in infarct myocardium might be affected by MVO but ECV isn't. ECV could predict LV remodeling in MI patients with and without MVO, while native T1 predict it in MI with MVO absent.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University
Lower levels of high-density lipoprotein cholesterol are associated with increased cardiovascular events in patients with acute coronary syndrome receiving contemporary lipid-lowering therapy
Authors: Nakazawa M , Arashi H , Inagaki Y , Otsuki H , Yamaguchi J , Ogawa H , Hagiwara N
Published: November 2020

Background

This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events.

Methods

The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. For the present analysis, the entire cohort was divided into three groups according to HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, 43–53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and the incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups.

Results

The primary endpoint was reported in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively. The incidence of the primary endpoint was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19–1.9; p=0.001). Irrespective of the treatment regimen, Group 1 had a significantly higher rate of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12–2.22; p=0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05–1.98; p=0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles.

Conclusions

Lower levels of HDL-C at 3-month follow-up are associated with higher incidence of the cardiovascular events in patients with acute coronary syndrome receiving contemporary lipid-lowering therapy.

HDL-C levels and Cardiovascular events

Funding Acknowledgement

Type of funding source: None
Time for a new paradigm shift from STE/non-STEMI to ACO/non-ACOMI?
Authors: Aslanger E , Yildirimturk O.Y , Simsek B , Bozbeyoglu E , Simsek M , Karabay C.Y , Degertekin M
Published: November 2020

Introduction

Although ST-segment elevation (STE) has been used synonymously with acute coronary occlusion (ACO), current STE criteria miss nearly one-third of ACO and cause a substantial amount of false catheterization laboratory activations.

Purpose

We sought whether a new ACO/non-ACO myocardial infarction (MI) paradigm would result in better identification of the patients who need acute reperfusion therapy.

Methods

A total of 3000 patients were enrolled in STEMI, non-STEMI and control groups. A combined ACO endpoint was composed of peak troponin level, troponin rise within the first 24 hours and angiographic appearance.

Results

In non-STEMI group, 282 patients were re-classified as having ACO. This subgroup had a higher ACO frequency and myocardial damage compared to NSTEMI group. More importantly, in-hospital and long-term mortality rates was similar to STEMI patients. The ECG reviewers prospectively classified 35.6% of ECGs as STEMI and 35.5% of ECGs as ACOMI; 25.6% being shared in the both definitions. Both unweighted and weighted diagnostic accuracy of STEMI/non-STEMI and ACOMI/non-ACOMI approaches for ACO and long-term mortality were presented in Table 1. The diagnostic accuracy of the ACOMI/non-ACOMI approach was superior to the STEMI/non-STEMI approach in three out of four comparisons. We also sought to compare ECG subtypes according to early (ECG-to-PCI time<120 min) and late (ECG-to-PCI time over 120 min) coronary intervention (Figure 1).

Conclusions

We believe that it is time for a new paradigm shift from the STEMI/non-STEMI to the ACOMI/non-ACOMI in the acute management of MI.

Figure 1

Funding Acknowledgement

Type of funding source: None
Left atrial dynamics in the hemodynamic response during exercise in patients with asymptomatic severe aortic stenosis: a cardiopulmonary imaging study
Authors: Sugimoto T , Bandera F , Barletta M , Alfonzetti E , Guazzi M
Published: November 2020

Background

The hemodynamic impact of left atrial (LA) dynamics in aortic stenosis (AS) in relation to cardiopulmonary response to exercise has never been studied. We aimed at investigating the link between LA function vs valvulo-arterial impedance (Zva) and right ventricular (RV)-to-pulmonary circulation (PC) coupling in asymptomatic severe AS patients.

Methods

A total of 94 patients: 64 asymptomatic severe AS patients (aortic valve area (AVA) <1.0 cm2 or AVA index <0.6 cm2/m2) with ejection fraction >50% and 30 gender-matched control subjects underwent cardiopulmonary exercise testing combined with Echo-Doppler with assessment of LA strain and RV-to-PC coupling (tricuspid annular peak systolic excursion (TAPSE)/ pulmonary arterial systolic pressure (PASP) ratio). AS patients were divided into 3 groups according to peak aortic jet velocity (PV), mean pressure gradient (MPG) and stroke volume index (SVI). Zva was assessed using (MPG + systolic blood pressure)/ SVI ratio.

Results

Paradoxical low-flow low-gradient AS (PLFLG: PV <4 m/s and MPG <40 mmHg, SVI ≤35ml/m2, N=18, AVA 0.77±0.16 cm2), Normal-flow low-gradient AS (NFLG: PV <4 m/s and MPG <40 mmHg, SVI >35ml/m2, N=23, AVA 0.85±0.16 cm2) and High-gradient AS (HG: PV ≥4 m/s or MPG ≥40 mmHg, N=20, AVA 0.62±0.17 cm2) had a higher LA volume index than Control (Control 22±6, PLFLG 33±11*, NFLG 38±12* and HG 33±9* ml/m2, *P<0.05 vs Control). There was no significant difference in peak VO2 (17±5 ml/min/kg) and VE/VCO2 slope (28±3) among 3 AS groups although PLFLG had lower peak cardiac output (7.0±2.4 L/min) compared to NFLG (9.0±2.3 L/min) and HG (9.2±3.3 L/min). In PLFLG and NFLG AS, LA strain at rest (21±9 and 26±13%) and during exercise (26±12 and 31±14%) were decreased compared to Control (37±8% at rest, 43±11% during exercise) but maintained some reserve during exercise (P<0.001). HG AS had no increase in LA strain (31±15% at rest, 28±15% during exercise) (Figure A). In AS groups, no significant correlation at rest was observed between LA strain and Zva, whereas a negative correlation was observed during exercise (R=−0.4, P=0.003, Figure B). LA strain was also correlated with TAPSE/PASP at rest and exercise (R=0.44 and 0.47, P<0.01, respectively, Figure C).

Conclusions

In asymptomatic severe AS, the study of LA functional adaptation to exercise plays a key role in the hemodynamic unfavorable cascade from AS-related left ventricular afterload to RV-to-PC uncoupling.

Funding Acknowledgement

Type of funding source: None
Effect of hypokintic transformation on the clinical phenotype and functional capacity in hypertrophic cardiomyopathy
Authors: Wasserstrum Y , Itelman E , Barriales-Villa R , Fernandez-Fernandez X , Adler Y , Lotan D , Klempfner R , Shlomo N , Sabbag A , Freimark D , Monserrat L , Arad M
Published: November 2020

Background

Advanced hypertrophic cardiomyopathy (HCM) may be complicated by a dilated hypokinetic transformation. Reduced left ventricular ejection fraction (HFrEF) has been described in terms of specific risks of morbidity and mortality, and specifically in terms of increased risk for fatal arrhythmias. Nevertheless, recent publications have casted doubt regarding the role of arrhythmia in non-ischemic HFrEF and questioned the role of primary prevention strategies in these cases.

Methods

We've reviewed clinical characteristics of 883 patients age ≥40, diagnosed with HCM who were evaluated in the cardiomyopathy clinic in two tertiary medical centers in Israel and Spain.

Results

Forty-five patients (5%) suffered from hypokinetic transformation. They were younger at diagnosis (median 32 [IQR 24–55] vs. 49 [35–60], p<0.001), had a lower body-mass index (28.4 [±4.7] vs. 26.0 [±3.9], p<0.001), and suffered more from strokes (19% vs 6%, p<0.001). They had lower had a lower NYHA class (p=0.001) and lower exercise capacity (7.3 [4.5–10.8] vs. 9.6 [6.7–12.0] METS, p<0.001). Patients with hypokinetic HCM had higher rates of pacemaker and implanted defibrillator (ICD) implantations (41% vs 11%, p<0.001) and (43% vs 13%, p<0.001) respectively. These patients had a higher incidence of sustained ventricular tachyarrhythmias (14% vs 2%, p<0.001). Among patients who had an ICD, patients suffering from hypokinetic transformation had received more appropriate ICD therapy (27% vs 12%, p<0.001). These patients received more heart transplantations (13% vs 1%, p<0.001), and had a trend for higher incidence rate of Sudden cardiac death (6% vs 2% p=0.06) and a higher 5-year mortality rates (21% vs. 5%, p<0.001).

Conclusions

HCM patients suffering from hypokinetic transformation have lower functional and exercise capacities, are more likely to suffer from ventricular tachyarrhythmias and experience appropriate ICD therapy, and undergo heart transplantation. They also have a significantly lower 5-year survival.

Five-year survival

Funding Acknowledgement

Type of funding source: None
Hereditary transthyretin amyloidosis: predictors of conduction disease
Authors: Dias De Frias A.F , Rodrigues P , Trepa M , Fontes-Oliveira M , Costa R , Campinas A , Hipolito-Reis A , Torres S
Published: November 2020

Introduction

Pacemakers are frequently needed due to a high prevalence of conduction disease in mutated ATTR amyloidosis (mATTR). We aimed to identify the variables associated with the need of pacemaker implantation in this population.

Methods

We retrospectively studied 255 patients with suspicion of heart involvement of mATTR observed at our cardiology clinic during the last year. Clinical and outcome data were retrieved by chart review. We have defined the need for pacemaker implantation as: 1) the formal guidelines indications or 2) Ventricular pacing >10% in patients who had prophylactic pacemaker implantation prior to liver transplantation (LT). This way, we have defined 3 different groups: group 1: patients with no evidence of conduction disease; group 2: patients with conduction disease, but no formal indication for pacemaker implantation; and group 3: patients with formal indication for pacemaker implantation or ventricular pacing >10% in patients who had prophylactic pacemaker implantation prior to hepatic transplantation.

Results

We included 255 patients (50±14 years, 53% male, 52.5% treated with tafamidis and 27% had prior LT, and 10% with atrial fibrillation), 43.3% with no evidence of conduction disease, 32.3% with conduction disease, but no formal indication for pacemaker implantation and 24.4% with formal indication for pacemaker implantation. Patients with formal indication for pacemaker implantation were older, with longer duration of neurologic manifestations, with higher concentration of both Troponin T and NT-proBNP and with higher number of organs affected. In multivariate analysis, longer duration of neurologic manifestations (OR 1.090 – 95% IC: 1.036–1.145, p-value 0.001), Left ventricular (LV) maximal wall thickness (OR 1.230 – 95% CI: 1.070–1.414, p-value 0.004), neurologic staging (OR 3.420 – 95% CI: 1.443–8.104, p-value 0.005) and higher number of organs affected (OR 1.719 – 95% CI: 1.218–2.424, p-value 0.002) all showed to be independent predictors of the need for pacemaker implantation, in contrast to LV ejection fraction and serum concentration of Troponin T and NT-proBNP. We've also found a statistical significant association between conduction disease and ophthalmic manifestations.

Conclusions

Our findings suggest that the need for pacemaker implantation in patients with mATTR is closer linked to the duration, severity and affected number of organs than to cardiac biomarkers or echocardiographic findings.

Funding Acknowledgement

Type of funding source: None
Progressive electrocardiographic changes in parallel with cardiac magnetic resonance findings in fabry disease
Authors: Figliozzi S , Camporeale A , Pieroni M , Pieruzzi F , Namdar M , Lusardi P , Spada M , Mignani R , Burlina A , Scolari F , Carrubbi F , Battaglia Y , Graziani F , Boveri S , Lombardi M
Published: November 2020

Background

Cardiac Magnetic Resonance (CMR) allows to detect progressive stages of cardiac involvement in Fabry Disease (FD). A systematic description of electrocardiographic (ECG) alterations occurring in FD is currently missing.

Purpose

To explore ECG changes in progressive stages of FD cardiomyopathy.

Methods

71 FD patients and 17 healthy controls underwent CMR with T1 mapping and 12-lead ECG. ECG analysis included the duration of the P-wave and the interval between the end of P-wave and the beginning of QRS (PendQ). FD patients in the test cohort were divided into 3 groups with increasing severity of cardiac involvement: A) normal T1, no LVH; B) low T1, no LVH; C) low T1, LVH.

Results

An increase of Pwave/PendQ ratio was observed in Group A compared to Controls (1.08 vs. 0.75, p<0.0001). Higher Pwave/PendQ ratio (1.50 vs. 1.08, p<0.0001), shorter PQc interval (127.9 vs. 159.5, p=0.0007), increased Sokolow-Lyon Index (SLI) (3.2 vs. 2.4, p<0,001) and T wave amplitude (0.6 vs. 0.4 mV, p=0.002) characterized Group B in comparison with Group A. A higher prevalence of left bundle branch blocks (13.6% vs. 0%, p=0.03) and repolarization abnormalities (77.3% vs. 5.7%), wider QRS (120 vs 95 msec, p<0.0001) and QT (460 vs 400 msec, p=0.003) intervals were found in Group C compared to Group B. SLI (AUC 0.769), Pwave/PendQ (AUC 0.778), QRS (AUC 0.703) and QT (AUC 0.769) durations resulted to be independent predictors of low T1 values on CMR at stepwise multivariate analysis.

Conclusion

FD is characterized by progressive ECG changes. The identification of ECG parameters able to predict a lowering of myocardial T1 values on CMR may promote early detection of cardiac involvement, helping to target the therapeutic approach.

Progressive ECG and CMR changes in FD

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): This study was partially supported by Ricerca Corrente funding from the Italian Ministry of Health to IRCCS Policlinico San Donato.
Suppression of myocardial HIF-1 by pubertal insulin resistance compromises metabolic adaptation and impairs cardiac function in patients with cyanotic congenital heart disease
Authors: Liu Y , Luo Q , Su Z , Xing J , Wu J , Xiang L , Huang Y , Pan H , Wu X , Zhang X , Li J , Yan F , Zhang H
Published: November 2020

Background

Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). A proportion of CCHD patients are unoperated due to various reasons. These patients remain CH all their lives and are at increased risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulation of hypoxia-inducible factor 1α (HIF-1α).

Purpose

The aim of this study was to determine the effect of CH on cardiac metabolism and function in CCHD patients and how it relates with age. The mechanistic role of HIF-1α in this process was investigated and potential therapeutic targets were explored.

Methods

CCHD patients (n=20) were evaluated for cardiac metabolism and function by positron-emission tomography/computed tomography and magnetic resonance imaging. Heart tissues collected during surgical intervention were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated using genetically modified animals and isotope-labeled metabolomic-pathway tracing studies.

Results

Prepubertal CCHD patients had glucose-dominant cardiac metabolism and normal cardiac function. By comparison, among patients who had entered puberty, the level of myocardial glucose uptake and glycolytic intermediates were significantly lower, but fatty acids were significantly higher, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients and animals with CH, myocardial HIF-1α was upregulated prior to puberty, but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α-knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, leading to inhibition of ATP production and impairment of cardiac function. Increased insulin resistance (IR) suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation under CH during puberty. Pioglitazone significantly reduced myocardial IR, restored glucose metabolism, and improved cardiac function in pubertal animals.

Conclusions

In CCHD patients, maladaptation of cardiac metabolism occurred during puberty, impairing cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation under CH but its expression was suppressed by pubertal IR. The use of pioglitazone during puberty might help improve cardiac function in these patients.

Metabolic maladaptation in CCHD patients

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China (81525002, 31971048) and Shanghai Outstanding Medical Academic Leader
Validation of serial echocardiographic versus mri functional assessments in patients with a systemic right ventricle
Authors: Zandstra T.E , Jongbloed M.R.M , Widya R.L , Ten Harkel A.D.J , Holman E.R , Vliegen H.W , Egorova A.D , Schalij M.J , Kies P
Published: November 2020

Background

Inherent to its geometry, echocardiographic imaging of the systemic right ventricle (sRV) may not always be feasible and/or reproducible in daily clinical practice. Here, we aim to validate the usefulness of all published echocardiographic measurements of systemic RV function in a longitudinal cohort by serial assessment of their correlations with cardiac magnetic resonance (CMR)-derived sRV ejection fraction (sRVEF).

Methods

A single-center, retrospective cohort study was performed. Adult patients with a sRV who underwent both CMR and echocardiography, at two different points in time, were included. Offline analysis of echocardiographic images was blinded to offline CMR analysis and vice versa. Measurements were repeated by a second observer blinded to the results of the first observer. Correlations between echocardiographic and CMR measures were assessed with Pearson's correlation coefficient and inter-observer variability was quantified with intraclass-correlation coefficients.

Results

Fourteen patients were included, of which 4 with congenitally corrected transposition of the great arteries (TGA) and 10 patients with TGA late after atrial switch. Eight patients (57%) were female. There was a mean of 8 years between the first and second imaging assessment. The average CMR-derived sRVEF was 39±6% at t=1. Only global systemic RV function (r=−0.77, p=0.002 at t=1, r=−0.63, p=0.024 at t=2), fractional area change (FAC; r=0.79, p=0.001 at t=1, r=0.67 and p=0.018 at t=2) and global longitudinal strain (GLS; r=−0.73 and p=0.005 at t=1 and r=−0.70 and p=0.011 at t=2) correlated consistently with CMR-sRVEF at both time points. The intraclass-correlation coefficient of GLS was consistently more favorable than that of FAC.

Conclusion

Out of the published echocardiographic parameters, GLS is the most robust measurement of sRV function in terms of feasibility, interobserver variability and correlation with CMR sRVEF.

Figure 1. Echocardiographic assessment

Funding Acknowledgement

Type of funding source: None
Sacubitil/valsartan in systemic right ventricular failure
Authors: Nederend M , Zandstra T.E , Kies P , Vliegen H.W , Jongbloed M.R.M , Schalij M.J , Egorova A.D
Published: November 2020

Background

In patients with heart failure with low ejection fraction (EF) (≤35%) sacubitril/valsartan is proven to be beneficial. We aimed to assess the effects of sacubitril/valsartan in adult congenital heart disease patients with failing systemic right ventricle (sRV) in the setting of congenitally corrected transposition of the great arteries (TGA) or TGA after atrial switch.

Purpose

To evaluate the feasibility and effect of treatment with sacubitril/valsartan in patients with heart failure in the setting of a sRV on optimal medical heart failure treatment.

Methods

Data of patients with sRV failure (estimated RVEF ≤35%) treated with sacubitril/valsartan were analyzed. Patients were clinically evaluated at baseline and at six months after initiation of the highest tolerated dose.

Results

Fourteen patients completed six-month follow-up thus far, of which 6 female (42.8%) and 2 (14.3%) with congenitally corrected transposition of the great arteries (TGA). After 6 months, 9 patients (64.3%) were using the highest dose (97/103 mg twice daily) of sacubitril/valsartan. NT-proBNP was significantly lower after 3 months and after 6 months compared with baseline (64% of baseline, p=0.006 and 53% of baseline, p=0.001, respectively). The kidney function did not change significantly (creatinine at baseline 83.6±12.0 and at 6 months 88.5±13.87, p=0.141) and serum potassium remained within normal limits (4.28±0.36 and 4.49±0.30, p=0.007). There was no significant decrease in systolic blood pressure (p=0.960). The echocardiographic sRV fractional area change (FAC) improved (p=0.002) and Global Longitudinal Strain (GLS) showed a trend towards improvement (p=0.058). During the 6 months of treatment, the exercise capacity remained stable, there was no increase in diuretic use, no serious adverse events and no heart failure related admissions occurred.

Conclusion

Treatment of sRV heart failure patients with sacubitril/valsartan leads to a significant reduction in NT-proBNP and significant increase in FAC. All patients remained clinically stable and no heart failure related admissions or serious adverse events occurred.

Changes after 6 months

Funding Acknowledgement

Type of funding source: None
Nerve growth factor receptor is involved in maintaining homeostasis of pulmonary arterial hypertension
Authors: Goten C , Usui S , Inoue O , Okada H , Takashima S , Sakata K , Kawashiri M , Takamura M
Published: November 2020

Introduction

Pulmonary arterial hypertension (PAH), characterized by vascular remodeling, is still disease with poor prognosis although many pulmonary vasodilators have been developed, and new mechanism of treatment for PAH is desired. Nerve growth factor receptor (Ngfr) is known to relate to inflammatory reaction and repair process in the damaged tissue. We have reported that Ngfr is associated to vascular remodeling in patients with acute coronary syndrome. However, it is unclear how Ngfr is involved in the pathogenesis of PAH.

Purpose

In this study, we investigated whether Ngfr relate to pathophysiology in PAH.

Methods

We estimated the frequency of Ngfr positive cells (% Ngfr+) in peripheral blood mononuclear cells obtained from PAH and non-PAH patients using flowcytometric analysis. In PAH patients, the hemodynamic parameters such as mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI) were obtained by right heart catheterization, and evaluated for correlation with the % Ngfr+.

Next, adult 8-week-old C57BL/6 (WT) mice and Ngfr knock out (KO) mice were exposed to chronic hypoxia (10% O2) or normoxia for 6 weeks. Then, mice were anesthetized and performed echocardiography and right heart catheterization. Then, mice were exsanguinated and blood sample was collected to evaluate the % Ngfr+ by flow cytometry. Right ventricular weight was measured and lung tissue was also collected for histological assessment and molecular pathway profiling.

Results

PAH (n=24) patients and non-PAH patients (n=17) were enrolled. The % Ngfr+ was significantly higher in PAH patients than that in non-PAH patients (0.056% versus 0.019%, p<0.0001). In PAH patients, the % Ngfr+ was correlated with severity of hemodynamic parameters such as mPAP (R=0.64 p<0.001), PVR (R=0.62 p<0.005), and CI (R=−0.48 p<0.05).

In WT mice, chronic hypoxia significantly increased the right ventricular systolic pressure and induced vascular medial thickness and fibrosis around the pulmonary artery. Flow cytometry analysis revealed that the % Ngfr+ was significantly increased in the hypoxia compared to that in the normoxia. Under hypoxic conditions, the right ventricular systolic pressure was significantly increased in Ngfr KO mice compared to that in WT mice. In histological analysis, hypoxia-induced peripheral vascular fibrosis and medial thickness was more severe in Ngfr KO than that in WT mice.

Conclusion

Circulating Ngfr-positive cells are associated with severity of PAH in patients. In the hypoxia-induced PH model, gene deletion of Ngfr shows the progression of the pathogenesis of PAH. These results suggest that circulating Ngfr-positive cells have an important role in the pathogenesis of PAH and may be a novel target for PAH therapy.

Funding Acknowledgement

Type of funding source: None