bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of age on the diagnosis of type 1 myocardial infarction using high-sensitivity cardiac troponin
Authors: Lowry M T H , Doudesis D , Kimenai D , Anand A , Mills N L
Published: October 2021

Background

Cardiac troponin concentrations are influenced by age and comorbidities with values above the 99th centile diagnostic threshold more common in older patients without myocardial infarction. Despite this, rule-in thresholds for myocardial infarction are applied universally regardless of age or comorbidities.

Purpose

We sought to evaluate how age and cardiovascular comorbidities influence the diagnostic performance of high-sensitivity cardiac troponin I for myocardial infarction.

Methods

In a secondary analysis of a multi-centre randomised controlled trial, we identified 45,991 consecutive patients with suspected acute coronary syndrome without ST-segment elevation myocardial infarction. The diagnostic performance of high-sensitivity cardiac troponin I measured at presentation for type 1 myocardial infarction was evaluated for the sex-specific 99th centile and thresholds three and five times this value in patients stratified by age (under 50 years, between 50 and 75 years, and over 75 years). The effect of comorbidities on diagnostic accuracy was evaluated using regression modelling.

Results

Of the 45,991 patients, 8,187 (18%) had myocardial injury of which 7,677 (94%) had a presentation troponin above the sex-specific 99th centile. Mean age of those with myocardial injury was 74 years (range 18–108). The positive predictive value (PPV) of the 99th centile was 54.6% (95% confidence interval [CI] 50.6–58.8%), 58.8% (56.9–60.6%) and 36.6% (35.1–38.2%) in patients under 50 years, between 50 and 75 years, and over 75 years, respectively. Rule-in thresholds three and five-times the 99th centile gave a higher PPV in all age groups with a PPV of 45.5% (43.1–47.8%) and 50.4% (47.6–53.2%), respectively in those aged over 75 years (Table 1). Regardless of threshold, specificity and PPV was lowest in patients over 75 years and decreased with advancing age (Figure 1). Across all age groups, the presence of heart failure resulted in the greatest decrease in PPV (36.9% [34.6–39.2%] versus 50.6% [49.3–51.8%]). Adjusting for cardiovascular comorbidities resulted in modest change in the discrimination of cardiac troponin for myocardial infarction (area under curve 0.89 vs 0.90) and did not prevent a decline in diagnostic accuracy in older patients.

Conclusion

The specificity and PPV of high-sensitivity cardiac troponin I for myocardial infarction decreases with advancing age. Cardiovascular comorbidities impact the PPV of troponin, but do not explain the decline in diagnostic accuracy with age. Clinicians should be aware of these important differences in performance by age of the diagnostic and rule-in thresholds for myocardial infarction when interpreting troponin results in older patients.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): University of Edinburgh Figure 1
Non-ST elevation myocardial infarction in patients with previous CABG: what is the best treatment option?
Authors: Oliveira L , Machado C , Almeida C , Fatima Loureiro M , Martins D ,   the Portuguese Registry of Acute Coronary Syndromes
Published: October 2021

Background

Current European Society of Cardiology guidelines recommend an invasive strategy (IS) for the treatment of non-ST elevation myocardial infarction (NSTEMI) patients, but the clinical trials that support this recommendations included only a few patients with previous coronary artery bypass graft (CABG).

Purpose

To characterize NSTEMI patients with previous CABG who underwent medical and invasive management and to evaluate the prognostic impact of the type of strategy used.

Methods

Retrospective analysis of a cohort of patients from a multicenter national registry diagnosed with NSTEMI with a previous history of CABG between 2010 and 2021. Patient's baseline demographics, medical history and in-hospital management data was collected. Outcomes of in-hospital and six months follow-up all-cause mortality were accessed.

Results

A total of 890 patients were included in the analysis. Of these, 470 were medically managed (MM) – this group included 249 patients (53.1%) who underwent coronary angiography but did not perform any further revascularization. The remaining 420 underwent an invasive strategy (IS) and performed additional revascularization, mainly percutaneous (only 1 patient submitted to reCABG). Mean age was similar (MM 72±10 vs IS 71±10 years, p=0.147) and most patients were male (MM 81.5% vs IS 83.8%, p=0.362). MM patients had more chronic kidney disease (16.7% vs 9.9%, p=0.003), peripheral artery disease (20.5% vs 15.0%, p=0.003) and heart failure (20.5% vs 11.9%, p<0.001). Main presenting symptom was chest pain in both groups, however it was more frequent in the IS group (89.4% vs 94.5%, p=0.006) and dyspnea in the MM patients (6.3% vs 3.1%). Mean left ventricle ejection fraction was similar between groups (MM 49±12% vs IS 50±11%, p=0.290). Although the GRACE risk score was available for only 124 patients, high risk patients (GRACE score >140) were equally distributed among the two groups (55.9% vs 48.2%, p=0.395). An IS was associated with significant lower in-hospital mortality (4.5% vs 1.7%, OR 0.37, 95% CI 0.15–0.87, p=0.018). At six months follow-up an IS was also associated with lower mortality (6.6% vs 2.4%, HR 0.18, 95% CI 0.06–0.52, p=0.002), even after adjusting for the baseline differences (HR 0.41, 95% CI 0.20–0.85, p=0.016).

Conclusions

In this cohort of patients with NSTEMI and previous CABG, an IS was linked to better outcomes during hospitalization and during six months follow-up. Randomized clinical trials are needed to address this issue.

Funding Acknowledgement

Type of funding sources: None.
Ticagrelor or prasugrel in patients with acute coronary syndrome in relation to glomerular filtration rate
Authors: Wohrle J , Seeger J , Lahr S , Mayer K , Bernlochner I , Gewalt S , Hochholzer W , Hemetsberger R , Hapfelmeier A , Sager H , Joner M , Richardt G , Neumann F J , Schunkert H , Kastrati A ,   ISAR-REACT V
Published: October 2021

Objectives

The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their glomerular filtration rate (GFR).

Background

The outcomes of ticagrelor versus prasugrel in patients with ACS according to GFR have not been defined.

Methods

Patients (n=3985) with GFR available were categorized in three groups according to the tertiles of GFR. The primary endpoint was a composite of all-cause death, myocardial infarction and stroke at 1 year.

Results

The primary endpoint occurred significantly more often in patients with low GFR compared to high GFR as well as in patients with low GFR compared to intermediate GFR (picture 1). Patients in the lowest GFR group had significantly higher ischemic and bleeding risks than patients in the intermediate (hazard ratio [HR] 1.93 and 1.68) or high GFR groups (HR 3.52 and 2.96). In the group with low GFR, the primary endpoint occurred in 103 of 677 ticagrelor patients (15.4%) and in 72 of 652 prasugrel patients (11.2%; (HR=1.45, [1.07–1.96], p=.016, picture 2). In addition, each single component of the primary endpoint and stent thrombosis were numerically lower with prasugrel compared with ticagrelor. Occurrence of myocardial infarction was 3.7% with prasugrel compared to 6.6% with ticagrelor (p=0.019). BARC 3–5 bleeding events were similar with ticagrelor and prasugrel (8.8% versus 7.1%, p=0.278). In the intermediate and high GFR group the primary endpoint and bleeding events were similar between prasugrel and ticagrelor.

Conclusions

The incidence of a composite endpoint (all-cause death, myocardial infarction or stroke) occurred less frequently in patients who received prasugrel compared to patients who received ticagrelor in the low GFR population, whereas rate of bleeding events was similar.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Supported by a grant (FKZ 81X1600501) from the German Center for Cardiovascular Research and the Deutsches Herzzentrum München, Germany. Primary endpoint according to GFRLow GFR: Prasugrel versus Ticagrelor
Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes
Authors: Lahu S , Behnes M , Ndrepepa G , Neumann F J , Sibbing D , Bernlochner I , Menichelli M , Mayer K , Richardt G , Angiolillo D J , Laugwitz K L , Schunkert H , Schuepke S , Kastrati A , Akin I
Published: October 2021

Background

The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unknown.

Purpose

To assess the efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to BMI.

Methods

This post-hoc analysis of the ISAR-REACT 5 trial included 3987 patients with BMI data available. BMI was grouped in 3 categories: low (BMI<25 kg/m2, n=1084), intermediate (BMI ≥25 to <30 kg/m2, n=1890) and high (BMI≥30 kg/m2, n=1013). The primary endpoint was the 12-month incidence of all-cause death, myocardial infarction, or stroke. The secondary endpoint was the 12-month incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding.

Results

There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=0.578). However, the primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the low BMI group (11.7% vs. 7.5%; hazard ratio [HR]=1.62; 95% confidence interval [CI], 1.09–2.42; P=0.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the intermediate BMI group (8.3% vs. 6.2%; HR=1.36 [0.97–1.91]; P=0.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the high BMI group (8.6% vs. 7.3%; HR=1.18 [0.76–1.84]; P=0.451). BARC type 3 to 5 bleeding events did not differ between ticagrelor and prasugrel in patients with low (6.5% vs. 6.6%), intermediate (5.6% vs. 5.0%), or high (4.4% vs. 2.8%) BMI.

Conclusions

BMI of patients with ACS did not impact significantly on the treatment effect of ticagrelor vs. prasugrel in terms of both efficacy and safety.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research;Deutsches Herzzentrum München, Germany
Indirect effects of COVID-19 Pandemic in ST-segment elevation myocardial infarction: insights from a multicentric national survey
Authors: Pereira H , Cale R , Farto-Abreu P , Pereira E , On Behalf Of Stent Save A Life Initiative S S L ,   Stent Save a Life
Published: October 2021

Objective

Coronavirus disease 2019 (COVID-19) pandemic may have indirect consequences in ST-segment elevation myocardial infarction (STEMI) outcomes due to difficulties in healthcare access, but also due to reperfusion delays. The objective of this study was to evaluate the performance indicators in STEMI during the early phase of the lockdown following the COVID-19 pandemic.

Methods

The “patient delay” and the “system delay” were evaluated in 312 patients with suspected STEMI, in the period of the first State of Emergency in Portugal, through a survey called “Moment COVID” implemented within 18th March to 2 May 2020, in 18 national centers of Interventional Cardiology where PPCI is carried out 24/7. These patients were compared with a historical cohort of 267 patients from the 5th year after integration of SFL Initiative in Portugal (Moment 2015) in which the same survey was applied. Patients with late presentation of STEMI (>12 hours of symptoms onset) were excluded from this analysis.

Results

In “Moment COVID” there was a trend towards a longer “patient delay” (incremental median 20 min; p=0.059) and a significant longer system-delay (incremental median 17 min; p=0.033) compared to the historical cohort of “Moment 2015”. Consequently, times to revascularization tended to be longer (incremental median 26 min; p=0.074). Indeed, in “Moment COVID” patients were less compliant with the times recommended by the European guidelines: door-to-balloon time <60 min was achieved in 47.6% of patients compared to 57.0% (p=0.052) in “Moment 2015” and system-delay <90 min in 13.9% compared to 21.8% (p=0.033).

Conclusion

These results from a multicentric national analysis demonstrated a trend to longer time from symptom onset to request healthcare system assistance and a significantly longer time from first medical contact to revascularization among patients with STEMI during COVID-19 pandemic. This delay for treatment could negatively impact the STEMI prognosis at the long-term.

Funding Acknowledgement

Type of funding sources: None.
Long-term follow-up of patients with MINOCA (myocardial infarction with unobstructed coronary arteries) undergoing intracoronary spasm provocation testing
Authors: Pirozzolo G , Seitz A , Sechtem U , Bekeredjian R , Ong P
Published: October 2021

Background

Up to 30% of patients presenting with acute coronary syndrome undergoing coronary angiography are found to have no culprit lesion. Among them, epicardial or microvascular spasm can be diagnosed in ∼50% of patients undergoing provocative testing. While prognostic data in patients with coronary spasm and stable angina are abundant, the outcome of patients with myocardial infarction and unobstructed coronaries (MINOCA) and coronary spasm is not clear.

Purpose

The aim of this study was to investigate the prognosis of a cohort of patients presenting with MINOCA undergoing intracoronary acetylcholine (ACH) spasm testing.

Methods

We evaluated consecutive patients with MINOCA undergoing acetylcholine testing to detect epicardial or microvascular spasm from 2014 to 2017. Other aetiologies for MINOCA such as myocarditis, supraventricular tachycardia, pulmonary embolism etc. were excluded. Data regarding mortality (cardiac/non-cardiac), nonfatal myocardial infarction (MI), repeated coronary angiography and percutaneous coronary intervention (PCI) were recorded.

Results

Of 112 patients in our study, follow-up data were available for 96 patients (86%, 51% women, mean age 63±13 years). Acetylcholine testing was positive in 51 (53%) patients. Among patients with a positive test, epicardial spasm was detected in 26 (51%) and microvascular spasm in 25 (49%) patients. After a median follow-up of 5±3.5 years, 7 deaths (7%) and 20 nonfatal myocardial infarctions (21%) occurred. Moreover, 19 patients (20%) underwent coronary angiography and 9 patients (9%) received a PCI. Comparisons of the Kaplan–Meier curves by log-rank test showed that patients with positive acetylcholine test had a worse outcome compared to those with a negative test in terms of death from any cause (p=0.01), myocardial infarction (p=0.03) and repeated coronary angiography (p=0.05).

Conclusion

This follow-up study shows that prognosis of MINOCA patients with coronary spasm on provocative testing is worse compared to patients with an uneventful test. The results underline the potential prognostic value of spasm testing in MINOCA patients.

Funding Acknowledgement

Type of funding sources: None.
Long-term prognostic factors of coronary artery disease patients after out-of-hospital cardiac arrest
Authors: Nitta G , Matsuda J , Lee T , Kato S , Hada Y , Inaba O , Matsumura Y , Nozato T , Ashikaga T , Sasano T
Published: October 2021

Background

The long-term prognosis of survival in patients with out-of-hospital cardiac arrest (OHCA) with coronary artery disease (CAD) remains poor.

Methods

There were 2391 out-of-hospital cardiac arrest (OHCA) patients transferred to 2 hospitals. We included 405 cardiovascular arrest patients, who got return of spontaneous circulation (ROSC) from January 2015 to December 2018. Among them, 204 patients had CAD that caused OHCA (39%: multi-vessel disease, 19%: chronic total occlusion (CTO), 13%: vasospastic angina (VSA)). To predict mortality, we investigated patients' characteristics, pre-hospital information and findings of CAG.

Results

At 1-year later, 104 patients (51%) survived. Younger age (P<0.001), VF survivor (P<0.001), pre-hospital ROSC (P<0.001), bystander CPR (P=0.013), without ECMO (P<0.001), lower lactate level on admission (P<0.001), and higher geriatric nutritional risk index score (P<0.001) were associated with low 1-year mortality, while with ST-segment elevation (P=0.778), BMI level (P=0.344), and sex (0.401) were not. And in the findings of CAG, the past history of CAD (P=0.049), the higher number of coronary vessel disease (P=0.003) such as multi-vessel disease (P=0.022), higher SYNAX score (P=0.016), and larger infarct size (max CK level; P=0.013, max CK-MB level; P<0.001) were associated with high 1-year mortality. On the other hand, acute coronary syndrome (P=0.300), any coronary lesion (RCA (P=0.447), LAD (P=0.089), LCX (P=0.096), or LMT (P=0.842)), and with CTO lesion (P=0.140) were not associated. Zero-vessel disease (VSA, P=0.001) had lower mortality among the CAD patients. In the multivariate Cox proportional hazards model, age (hazards ratio; HR: 1.03, 95%confidence interval (CI) 1.00–1.06, P<0.001) and bystander CPR (HR: 0.36, 95% CI 0.20–0.65, P<0.001) were the independent predictors of mortality.

Conclusions

Younger age and pre-hospital support after OHCA with CAD were the predictors of low mortality. Pre-hospital information, systemic condition on arrival, or anatomical coronary complexity were important to predict low mortality.

Funding Acknowledgement

Type of funding sources: None.
Phenotypic characterization of rabbit model for aortic valve stenosis: a novel medial calcification paradigm
Authors: Anousakis-Vlachochristou N , Mavroidis M , Makridakis M , Miliou A , Kontostathi G , Agapaki A , Mouchtouri E , Zigouri L , Konstantinou G , Lampas E , Kalogera S , Vlahou A , Cokkinos D , Tsioufis K , Toutouzas K
Published: October 2021

Introduction

Calcific aortic valve stenosis (CAVS) is the result of subtle, chronic inflammation and osteoblastic differentiation. As we lack human specimens of the early stages, reliable and reproducible animal models are needed to facilitate research. We previously demonstrated the ability of a novel rabbit CAVS vitamin D2 toxicity protocol to produce calcification and valve stenosis (1). We sought to characterize the phenotype of the model at the final stage.

Methods

Twelve New Zealand Rabbits were randomized 1:1 to control (normal chaw) and experimental group (normal chaw+1% cholesterol+3.500 I.U.s Vitamin D2, in oil in a biscuit) for 7 weeks. Animals were sacrificed and aortic valve cusps were snap frozen or formalin-fixed paraffin embedded. Cusps were then mechanically homogenized in buffer optimized for protein extraction and total protein measured with Bradford method. Part of the extract was subjected to trypsinization, in-gel digestion and untargeted LC-MS/MS. The rest was used to quantitate BMP-2 with total protein-normalized sandwitch competitive ELISA. Thin tissue sections were stained with Masson's trichrome, Von Kossa and H&E. Osteopontin, Bone sialoprotein II (BSPII), tissue non-specific alkaline phosphatase (TNAP) and osteocalcin (OCN) were detected on tissue with immunohistochemistry. Femoral bones from the same animals served as positive controls.

Results

Aortic valve cusp demonstrate large areas of collagen degradation and calcification in the medial layer, almost sparing the intima. Osteopontin deposits were colocalized with the calcification area in the media, whereas BSPII, TNAP and OCN were not expressed in the lesion, although present in bones. Similarly, BMP-2 levels were not significantly different between groups (experimental = 43.45 vs controls = 62.75 pg/ml, Mann-Whitney U test p=0.496). Proteomic analysis revealed a set of 96 differentially expressed proteins between cases and controls, interestingly including sortilin, osteonectin, beta-crystallin A2, Matrix Gla protein, Na/H exchanger 3, V-type H ATPase subunit D, Y-box binding protein.

Conclusion

The novel rabbit vitamin D2 toxicity protocol leads to excessive medial calcification of the aortic valve, with overexpression of osteopontin but without other classic markers of CAVS. Proteomics analysis reveals novel pathways with pathophysiological implications for the model and medial calcification.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Hellenic Cardiology Society, Hellenic Heart Foundation
Trends in incidence and mortality from non-rheumatic degenerative mitral valve disease across europe, over the past three decades
Authors: Al-Khayatt B , Crawley C , Salciccioli J , Marshall D , Hartley A , Hammond-Haley M , Sikkel M , Shalhoub J ,   Medical Research Collaborative
Published: October 2021

Background

Valvular heart disease is common globally; mitral regurgitation is the most common valve pathology in the general population and subsequently the second most frequent indication for valve surgery in Europe. Whilst the European epidemiology of aortic stenosis is well elucidated in the literature, no Europe-wide study has been undertaken to identify trends in incidence and mortality secondary to non-rheumatic degenerative mitral valve disease.

Purpose

Our aim is to describe trends in degenerative mitral valve disease incidence and mortality throughout Europe from 1990 to 2019.

Methods

We performed a temporal analysis of data deposited in the Global Burden of Disease Study Database across the European Union. We extracted age-standardised incidence and age-standardised mortality rates for 20 member states from the database. We graphically inspected the data and performed Joinpoint regression analysis to detect and summarise periods of significant change. These periods were described using estimated annual percentage change (EAPC).

Results

Trends in age-standardised incidence and mortality rates were heterogenous amongst the 20 member states included. A gender disparity in mortality rates favouring males were present in Austria, Belgium, Greece, Hungary and the Netherlands throughout the time period studied. Except for Hungary, this disparity was not reflected in the incidence rates for the aforementioned countries. Incidence rates of degenerative mitral valve disease in 2019 were highest in Italy for both males and females with 90.6 and 140.1 cases per 100,000 respectively. Mortality rates in 2019 were highest in the Netherlands for both males in females with 1.7 and 2.0 cases per 100,000 respectively; this was preceded by a downwards trend in mortality with an EAPC of −7.3% and −8.5% respectively. Other notable inflection points in incidence trends were observed in Italy, with an EAPC of −4.9% females between 1994 to 2004 followed by an EAPC of 0.8% between 2009 to 2019.

Conclusion

No overall trends in non-rheumatic mitral valve disease were observed throughout Europe, but gender disparities and some notable deviations in incidence and mortality rates from the European median were identified. Overall, however, incidence rates remained static in most countries studied despite the ubiquity of colour flow doppler echocardiography. Further analysis of the burden of mitral valve disease can help elucidate this geographical variation.

Funding Acknowledgement

Type of funding sources: None.
TAVI via alternative access routes: patient selection and 10-year center experience
Authors: Rocha B , Nolasco T , Teles R , Madeira S , Vale N , Madeira M , Brito J , Raposo L , Goncalves P , Gabriel H M , Sousa-Uva M , Abecasis M , Almeida M , Neves J P , Mendes M
Published: October 2021

Background

Femoral access is considered the gold standard for transcatheter aortic valve implantation (TAVI). However, this route might be precluded due to the presence of tortuosity, small vessel diameter and/or peripheral artery disease. We aimed to investigate TAVI through an alternative access (AA), focusing on the selection criteria and clinical outcomes compared to the femoral route (TF).

Methods

We conducted an all-comers longitudinal single-centre prospective registry in whom a TAVI was performed. The feasibility, safety and efficacy of TAVI by means of an access route other than standard TF was assessed, according to the VARC-2 criteria. The prospective surgical criteria used at our institution to accept an AA route were: a) TF deemed inappropriate; b) acceptable haemorrhagic risk; c) acceptable general anaesthesia risk; and d) adequate anatomy and diameter within acceptable range (subclavian, axillar, transaortic) or e) age <85 years and non-frail patient (transapical). The primary endpoint was all-cause death at 1-year.

Results

From 2008 to 2018, there were 548 patients submitted to TAVI [median age 84 (79–87) years, males 45.4%]. An AA route was used in 100 patients (79 trans-apical, 9 trans-aortic, and 12 trans-subclavian), with a decreasing rate over follow-up (−11% per year). Compared to TF, these patients were younger [80 (77–84) vs. 85 (80–87) years; p<0.001) with a similar baseline surgical risk as per EuroSCORE II [5.1 (3.3–9.0) vs. 4.7 (3.3–7.0); p=0.410). AA patients presented a higher burden of atherosclerotic disease, namely coronary (54.0 vs. 41.3%; p<0.001) and peripheral artery disease (35.0 vs. 16.5%, p<0.001) despite a lower number of other comorbidities (e.g. glomerular filtration rate <50mL/min: 53.1 vs. 64.8%; p=0.030). Left ventricular ejection fraction (56±13 vs 55±12%; p=0.203) and aortic stenosis severity (e.g. valve area: 0.70±0.19 vs. 0.67±0.18cm2; p=0.302) were similar between groups. Haemorrhagic events (minor or major) following TAVI were less often documented in the AA group (11.0 vs 21.7%; p=0.015), contrasting with de novo atrial fibrillation (18.5 vs 7.6%; p=0.048). Overall, 67 patients met the primary endpoint (18.8 vs 16.2%; p=0.584). After adjusted multivariate analysis, the independent predictors of one-year mortality did not include the TAVI access route.

Conclusion

In the first 10 years of experience, 1 in every 6 patients was treated with a TAVI by means of an AA, most often trans-apically initially and, nowadays, via a trans-subclavian approach. The use of meticulous prospective selection criteria seems to explain the one-year similar results, regardless of the access route.

Funding Acknowledgement

Type of funding sources: None.
Multilayer global longitudinal strain assessment of subclinical myocardial dysfunction related to insulin resistance
Authors: Atici A , Asoglu R , Ali Barman H
Published: October 2021

Myocardial tissue is sensitive to insulin resistance (IR) due to its interactions with insulin levels. Previous studies demonstrated that heart failure prevalence was higher in IR patients. Evaluation of myocardial deformation by multilayer global longitudinal strain (MGLS) might provide more information about IR related left ventricular dysfunction. In this study, we aimed to investigate subclinical LV dysfunction with MGLS in patients with IR. The study was designed as a prospective cross-sectional study. The present study included 64 patients with IR(+), and 54 subjects without IR(−) prospectively. The homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. Specific analysis for endocardial, mid-myocardial and epicardial layers were performed by two-dimensional (2D) speckle tracking echocardiography (STE) for multilayer global longitudinal strain. MGLS (Endocard-Mid-myocard-Epicard) values were significantly lower in the IR(+) group compared to IR(−) group ((GLS-endocard; −15.1±1.5 vs. −18.7±1.3, p<0.001), (GLS-mid-myocard; −16.0±2.0 vs. −18.0±2.0, p<0.001), (GLS-epicard; −17.0±1.7 vs. −18.01±1.94, p=0.004)). GLS-endocard levels were significantly and positively correlated with HOMA-IR levels (r=0.643, p<0.001). HOMA-IR and age were found to be independent factors in detecting a decrease in GLS-endocard level in regression analysis. In conclusion, our data reveal that IR(+) patients had significantly lower strain values compared to IR(−) group. Besides, we presented that the HOMAIR value was an independent predictor of subclinical left ventricular dysfunction.

Funding Acknowledgement

Type of funding sources: None.
Survival analysis in hypertrophic cardiomyopathy caused by the three most common pathogenic TPM1 variants
Authors: Lamounier Junior A , Alonso Garcia D , Fernandez Ferro G , Cardenas Reyes I J , Noel Brogger M , Valverde Gomez M , Garcia Hernandez S , Fernandez X , Ortiz M , Barriales-Villa R , McKenna W , Monserrat Iglesias L
Published: October 2021

Purpose

To evaluate survival free of cardiovascular events in carriers of the three most frequent TPM1 pathogenic hypertrophic cardiomyopathy (HCM) variants.

Methods

Clinical and genetic data on families carrying TPM1 variants in the literature and identified in our center were systematically revised and collected in a database. Classification of variant's pathogenicity was in accordance with ACMG criteria. We evaluated available follow-up data and constructed Kaplan-Meier survival curves to cardiovascular death (sudden death, appropriate cardiodefibrillator shock, heart failure death, and stroke-related death) or heart transplant. Long-rank test was used to compare event-free survival time.

Results

562 carriers (343 HCM-probands and 219 relatives; 51.3% male carriers) were identified carrying 73 missense variants considered disease causing. TPM1 p.Asp175Asn (87 probands, 109 relatives, 6 unaffected), p.Arg21Leu (52 probands, 25 relatives, 16 unaffected), and p.Met281Val (37 probands, 8 relatives, 9 unaffected) were the most prevalent HCM-variants. Among these three variants, survival data was reported for 508 individuals. Eight-nine carriers had suffered events: 74 sudden deaths (55% males), nine heart failure deaths (44% males), two transplants (50% males), and five stroke-related death (25% males). Incidence of cardiovascular death or transplant was similar between TPM1 p.Arg21Leu and p.Met281Val (p=0.75) and different than p.Asp175Asn (p=0.03 and p=0.06, respectively) and all TPM1 variants (p=0.004 and p=0.04). Analysis by sex showed TPM1 p.Arg21Leu female carriers had better prognosis than p.Asp175Asn male carriers (p=0.048) and all TPM1 male and female carriers (p=0.02 and p=0.04) (curves not showed in the graph).

Conclusion

TPM1 p.Arg21Leu and p.Met281Val could have a better prognosis than p.Asn175Asn and all other TPM1 missense variants in HCM. No marked difference was observed between male and female carriers. More than 80% of the events were arrhythmic deaths.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): HEALTH IN CODE SL
Characterization of left atrial geometry and function in patients with non-obstructive hypertrophic cardiomyopathy: a cardiac magnetic resonance imaging study
Authors: Agoston Coldea L , Muresan I , Zlibut A , Cojan-Minzat B O , Cionca C , Horvat D
Published: October 2021

Background

Left atrial (LA) function and geometry are important predictors of cardiac dysfunction and prognosis in cardiovascular disease, however studies that evaluate their role in patients with hypertrophic cardiomyopathy (HCM) are scarce. Furthermore, altered LA phasic functions might become predictors for disease progression, even in these patients. This study sought to assess the use of cardiac magnetic resonance imaging (CMR) in the assessment of LA function and geometry in patients with HCM.

Methods

We conducted a prospective case-control study on eighty-six patients with first non-obstructive HCM (NO-HCM) diagnosis. They underwent standard cardiovascular examinations and CMR. LA geometry was assessed using LA maximum, minimum and pre-A volumes (LAVmax, LAVmin, LAVpre-A), LA sphericity index (LASI), and LA late gadolinium enhancement (LA-LGE). LA phasic functions were assessed using LA total emptying fraction (LATF), LA passive emptying fraction (LAPF) and LA active emptying fraction (LAAF). LA strain parameters of all three phasic functions were quantified by total strain (et); passive strain (ep), active strain (ea).

Results

86 HCM patients (51±13.7) and 86 healthy volunteers (51±13.6) were enrolled. LA volumes parameters were significantly increased in NO-HCM group (LAVmax: 39.7 vs 33.9 mL/m2; LAVmin: 20.4 vs 13.9 mL/m2; LAVpre-A31.7 vs 24.1 mL/m2, all p<0.001). LA geometry was significantly altered by an increased LASI (56.3 vs 39.7, p<0.001). All three LA phasic functions and strain were impaired in those withHCM (LATF: 49.2±6.5% vs. 58.8±3.1%, et 30.9% vs 39.8%; LAPF: 19.9±5.9% vs. 29.1±8.4%, ep 15.9% vs 18.1%; LAAF: 36.3±8.8% vs. 41.2±8.2%, ea: 20.5% vs 29.1%; all p<0.001). Last but not least, LA replacement fibrosis was present in 39.5% (n=34) of patients with NO-HCM. In multivariable analysis, increased LA-LGE was associated with lower LAPF, peak global longitudinal LA strain (p<0.001).

Conclusion

LA function, strain and geometry are significantly impaired in patients with NO-HCM, even before left ventricular outflow tract obstruction occurs. These parameters might have predictive ability, however further studies are required.

Funding Acknowledgement

Type of funding sources: None.
Cause of death in adult patients with congenital heart disease: experiences of a tertiary centre
Authors: Kecskemeti D , Szegedi M , Temesvari A , Andreka P , Balint H
Published: October 2021

Background

We are currently facing a growing and aging population of adults with complex congenital heart disease. However, long-term survival in these patients remained reduced.

Purpose

To identify the main causes of death and compare mortality based on the complexity of the underlying congenital heart defect.

Methods

Patients with at least one visit in our adult congenital heart disease (ACHD) clinic between 2010 and 2020 were reviewed. Clinical data were obtained from digital medical records. Based on the complexity of the underlying heart defect patients were classified as mild, moderate, and severe. Data about the median age at death in the general population was collected from the National Statistical Office. Survival difference between the groups was analysed using the Kaplan-Meier method along with the log rank test.

Results

We included 2658 patients (53% female, overall median age of 35.6 years) with severe (21.2%), moderate (46.2%), and mild (32.6%) lesions. Over the median follow-up of 8.5 years (IQR 5.2–12.2) 125 patients (4.7%) died with an incidence of 0.51 deaths/100 patient years. The median age at death was 39.1 years (severe: 37.2 years, moderate: 50.3 years, mild: 83.1 years, p<0.001) Heart failure was the leading cause of death (35.2%) followed by non-cardiac causes (12.8%), perioperative/periprocedural death (11.2%), arrhythmia (7.4%), sudden cardiac death (4.1%) and endocarditis (2.4%). Heart failure related death was the most likely present in severely complex lesions (mild: 2.3%, moderate: 13.6%, severe: 84.1%). Underlying CHD with the highest mortality were univentricular heart (26.3%), pulmonary atresia (24.3%), Eisenmenger syndrome (22.7%), Ebstein anomaly (15.2%), and transposition of the great arteries after Senning procedure (13.4%).

Conclusions

Adult patients with moderately to severely complex congenital heart disease die at a relatively young age. The highest mortality rates were observed in patients with severely complex defects, with heart failure being the most common cause of death.

Funding Acknowledgement

Type of funding sources: None. Kaplan-Meier survival curve
Exercise stress echocardiography in children and teenagers with congenital heart diseases
Authors: Avesani M , Calvo G , Sirico D , Castaldi B , Reffo E , Cerutti A , Biffanti R , Di Candia A , Sabatino J , Borrelli N , Piccinelli E , Fraisse A , Padalino M , Vida V , Di Salvo G
Published: October 2021

Background

Exercise Stress Echocardiography (ESE) is currently applied to paediatric patients mainly to detect myocardial ischemia and few data is available for congenital heart diseases (CHDs).

Purpose

The aim of this study is to describe the current application of ESE in our Departments.

Methods

Data from patients who underwent ESE in our two centres were retrospectively analysed, as well as clinical management plans formulated based on ESEs results.

Results

Fifty-five patients (median age 15 years) were included. Among them, 19 had been previously treated surgically, 6 percutaneously and 30 were under follow-up.

Indications for ESE were: hypertension and/or evaluation of aortic arch gradient in patients treated surgically (5) or percutaneously (1) for aortic coarctation (ACo); aortic/subaortic gradient in bicuspid aortic valve (BAV) after balloon valvuloplasty (4), Ross (1), or under follow up (1); right ventricular and pulmonary valve function in Tetralogy of Fallot (3) and after percutaneous treatment of pulmonary atresia (1); atrio-ventricular valves gradient (1 for tricuspid dysplasia and 1 for left cor triatriatum); single ventricle function (1); pulmonary artery gradient (2) and myocardial ischemia (6) after Arterial Switch; rule out myocardial ischemia in coronary anomalies (4), chest pain (9), Kawasaki disease (KD 9), syncope (1) and in patients with ectopic beats under exercise (2); rule out dynamic obstruction in hypertrophic cardiomyopathy (HCM, 3).

The exercise was maximal in 28 patients, with 2 of them having symptoms at the peak of exercise. In the other patients, peak heart rate ranged from 52% to 84% of targeted values. Mean exercise duration and reached Watts were 10 minutes and 112, respectively. Reasons for ending exercise were muscle fatigue in 25 patients and dyspnoea in 2 patients. No arrhythmia was detected.

Clinical management changed in 10 of patients after ESE (20%), all having CHDs. Three patients underwent percutaneous interventions; 1 aortic balloon valvuloplasty, 1 stent dilation and 1 pulmonary valve replacement; 2 underwent surgery (1 aortic valve replacement and 1 subaortic membrane resection), 4 underwent further imaging including cardiac computed tomography (1), cardiac magnetic resonance (2) and cardiac catheterization (1); 1 received indication for restriction from intense physical activities.

Conclusions

ESE has an important clinical role in patients with congenital heart diseases, impacting clinical management.

Funding Acknowledgement

Type of funding sources: None. Indications for ESEChangements in clinical management
Percutaneous transluminal pulmonary angioplasty for hypertensive pulmonary Takayasu's arteritis
Authors: Zhou Y.-P , Jiang X , Zhu Y.-J , Xu X.-Q , Wu T , Wei Y.-P , Peng F.-H , Wang H.-P , Sun K , Wang Y.-N , Li M.-T , Jing Z.-C
Published: October 2021

Background

Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to patients with hypertensive pulmonary Takayasu's arteritis (PTA), another chronic obstructive pulmonary vascular disease, remains unclear.

Purpose

To investigate the potential efficacy and safety of PTPA for hypertensive PTA.

Methods

All consecutive patients with hypertensive PTA who completed PTPA in our center between January 1, 2016 and December 31, 2019 were prospectively enrolled. Hemodynamics, exercise capacity and oxygen saturation were measured at baseline and at least 3 months after the last PTPA session. PTPA procedure related complications, restenosis and all-cause deaths during follow-up were recorded.

Results

A total of 50 patients were enrolled, with the median age of 41 (IQR, 30–49) years and female predominance (82.0%). After PTPA, significant improvements in hemodynamics including mean pulmonary artery pressure (from median 48 [39–60] to 37 [31–42] mm Hg, p<0.001) and pulmonary vascular resistance (from 9.6 [7.0–11.8] to 4.8 [3.6–6.4] Wood U, p<0.001) were achieved. Furthermore, PTPA also significantly improved the WHO functional class (p<0.001), six-minute walking distance (from 412 [313–470] to 492 [430–539] meters, p<0.001) and arterial oxygen saturation (from 91.3 [86.9–94.1] to 93.9 [91.8–95.3] %, p<0.001). No peri-procedural death occurred. The most common complication was pulmonary artery injury (27/150 PTPA sessions, 18.0%), which was always asymptomatic and without further clinical sequelae. Pulmonary angiography during follow-up revealed complete self-healing in 26 out of 27 (96.3%) vessels. Restenosis occurred in 5 out of 360 treated vessels (1.4%). Three patients died during follow-up, and the 1-year, 2-year and 3-year survival rates were 98.0%, 95.7% and 92.8%, respectively.

Conclusion

PTPA appears to be a promising therapeutic option for patients with hypertensive PTA.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Key Research and Development Program of China Efficacy of PTPA
Current use of catheter directed treatment of acute PE in Europe: results of survey of EAPCI and ESC Working Group on Pulmonary Circulation and Right Ventricular Function
Authors: Roik M , Pruszczyk P , Klok F A , Barco S , Jermakow M , Dudek D
Published: October 2021

Aims

This survey conducted by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and ESC Working Group on Pulmonary Circulation & Right Ventricular Functioncollected information on current practices in catheter-directed treatment (CDT) of acute pulmonary embolism (PE) among cardiology intervention centers in European countries.

Methods and results

Responses from 157 Catheterization laboratories (Cath Lab) representing European countries were collated and analyzed.Sixty seven centers (43%) centers reported application of CDT in PE patients. Almost all centers performing CDT (96%) provided 24/7 service and had experience with a wide spectrum of percutaneous interventions including those for the treatment of structural heart diseases; 53% of the Cath labs utilizing CDT were located in teaching hospitals, and involved 5 to 10 interventional cardiologists performing more than 600 coronary procedures per year. The survey showed a rapid increase in CDT use in European countries after 2015 (45 out of 67 centers). Over 60% of responding centers performed 5–10 CDT procedures per year. It was estimated that 24 patients were treated with CDT per center on a yearly base. The majority of centers (80.3%) indicated that CDT is used in high-risk PE patients, while 38% also apply CDT to intermediate high risk PE.

The survey revealed that pigtail catheters are most commonly used for CDT (49%), while dedicated systems such as AngioJet, Indigo and EKOS were reported to be used in 25%, 23.81% and 20.24% of the centers, respectively. Local thrombolysis during CDT was used in 71% of the procedures. More than 60% of the responders indicated that according to their expert opinion CDT will be routinely used in PE patients in the future. However, they stressed the need for randomized trials to evaluate the safety and efficacy of CDT and determine the patients that would benefit most.

Conclusions

According to the survey, use of CDT in patients with PE is increasing over time. Currently, it is mostly but not exclusively applied to patients with high-risk PE. The respondents indicated the need for high-quality randomized trials to establish the optimal indication for CDT and further standardize the use of the available techniques.

Funding Acknowledgement

Type of funding sources: None.
Efficacy and safety of percutaneous pulmonary artery subtotal occlusion and CTO intervention in chronic thromboembolic pulmonary hypertension
Authors: Gerges C , Friewald R , Gerges M , Shafran I , Sadushi-Kolici R , Skoro-Sajer N , Moser B , Taghavi S , Klepetko W , Lang I M
Published: October 2021

Background

Balloon pulmonary angioplasty (BPA) is an emerging percutaneous therapy for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), and patients with mean pulmonary artery pressure (mPAP) ≤30mmHg have an excellent survival. Common vascular lesion types are ring-like stenoses (type A), web lesions (type B), subtotal occlusions (type C), chronic total occlusions (CTO, type D) and tortuous lesions (type E). Occlusive lesions (i.e. subtotal occlusions and CTOs) are most challenging. While the CTO intervention the coronary arteries remains controversial, risk and benefit of pulmonary artery occlusive lesion intervention in CTEPH has not been studied yet. We evaluated the impact of percutaneous pulmonary artery subtotal occlusion and CTO intervention on BPA treatment response.

Methods

120 patients underwent 712 BPA procedures between April 2014 and October 2019. Clinical features and hemodynamics were assessed at baseline and 6–12 months after the last BPA session.

Results

A total of 2542 lesions were targeted; 720 occlusions (28.3%; 352 CTOs and 368 subtotal occlusions) and 1822 non-occlusion lesions (71.7%). Complications occurred in 6.0% of all procedures (severe complications in 0.4% of all procedures). 45 patients completed BPA treatment after a median of 6 (4; 10) procedures per patient. In these patients, mPAP dropped from 40.1±10.8 to 25.6±5.1mmHg (p<0.001), without significant change in cardiac output (5.2±1.4 to 5.5±3.1L/min, p=0.409). In the overall cohort, success rate for recanalization of occlusions was 81% (subtotal occlusions (type C lesions): 98%; CTOs (type D lesions) 50%). Number of successfully treated lesions of any type (β −0.86 [−1.19; −0.53]; p<0.001), number of successfully treated occlusions (β −2.17 [−3.38; −0.97]; p=0.001) and number of successfully treated non-occlusion lesions (β −0.81 [−1.25; −0.37]; p<0.001) emerged as predictors of relative change in mPAP. The impact on relative change in mPAP was higher for CTOs (β −5.88 [−10.49; −1.26]; p=0.014) than for subtotal occlusions (β −2.51 [−4.18; −0.83]; p=0.004).

Conclusions

The number of successfully treated vascular lesions predicts treatment response to BPA. The number of successfully recanalized occlusions (particularly CTOs) appears to have the strongest impact on change in mPAP, highlighting the importance of advanced BPA technique.

Funding Acknowledgement

Type of funding sources: None. Visual overview
A network meta-analysis on the vasomodulators for portopulmonary hypertension
Authors: Chew N , Tan E X , Tan C H , Lim W H , Xiao J L , Chin Y H , Syn N , Low T T , Wong R , Yip J , Siddiqui M S , Muthiah M
Published: October 2021

Background

In patients with portopulmonary hypertension (PoPH) who are eligible and awaiting liver transplant, guidelines recommend lowering pulmonary pressures with vasomodulators as a bridge to transplant. However, efficacy of each vasomodulator class as a bridge to transplant remains unknown.

Purpose

This review compares the use of endothelin receptor antagonists (ERA), phosphodiesterase type-5 inhibitors (PDE5-I), prostacyclin (PC) and combination therapy in its pulmonary pressure-lowering effects and pre-transplant mortality in this strictly selected subset of patients.

Methods

A search conducted on Medline and Embase on articles relating to vasomodulator use in PoPH for pulmonary pressure-lowering effects and mortality. Network analysis was conducted to summarize the evidence. Surface under the cumulative ranking curve (SUCRA) was used to rank treatments.

Results

Ten studies with 180 patients were included. SUCRA analysis demonstrated largest mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) lowering effects in ERA and combination therapy, followed by PDE5-I and PC. mPAP-lowering effects were largest in ERA (MD −19.440, CI: −62.280 to 23.400) and combination therapy (MD −18.223, CI: −29.677 to −6.770) when compared to PDE5-I (table 1). Pre-transplant mortality were comparable between ERA, PDE5-I and combination therapy. Both ERA (RR:0.349. CI: 0.137–0.891) and PDE5-I (RR: 0.279, CI: 0.091–0.854) had significantly lower mortality than PC (table 2).

Conclusion

This meta-analysis provides preliminary evidence that ERA have shown larger pulmonary pressure-lowering effects than PDE5-I in PoPH patients who were eligible for LT. Both ERA and PDE5-I have comparable mortality outcomes, with unfavorable outcomes in PC users.

Funding Acknowledgement

Type of funding sources: None.