bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperaemic and non-hyperaemic pressure indices of coronary stenosis severity in patients with chronic kidney disease
Authors: Travieso A , Mejia-Renteria H , Jeronimo-Baza A , Hyun Jung J , Doh J H , Nam C W , Shin E S , Hoshino M , Sugiyama T , Kanaji Y , Gonzalo N , Lee J M , Kakuta T , Koo B K , Escaned J
Published: October 2022

Background

Evidence regarding the use of pressure indices for the assessment of coronary stenoses in patients with chronic kidney disease (CKD) is scarce.

Methods

We assessed the relation between eGFR, FFR and resting Pd/Pa in 1147 consecutive patients (1316 vessels) included in the International Collaboration of Comprehensive Physiologic Assessment Study. We also compared FFR and Pd/Pa against a standardized cut-off of coronary flow reserve (CFR<2.0). Finally, we examined the occurrence of vessel-oriented composite outcome (VOCO: cardiac death, vessel-specific revascularization, vessel-specific myocardial infarction) across negative/positive results of both FFR and CFR in patients with and without CKD.

Results

FFR increases as renal function worsens (beta −10.5, 95% CI −20.0 to −11.03, p=0.030), a relation that was not seen with resting Pd/Pa (beta −6.14, 95% CI −19.9 to 6.78, p=0.351). Both indices had similar diagnostic accuracies for the detection of a CFR<2.0 in the presence of CKD (AUC 0.629 for FFR vs 0.663 for resting Pd/Pa, p=0.192). However, CKD patients showed a higher proportion of vessels with negative FFR but low CFR (24.5% vs 13.4%, p=0.015).

CFR decreased linearly with deteriorating eGFR, and this was mainly driven by higher resting coronary flow in CKD patients (p=0.026), while hyperaemic coronary flow remained similar (p=0.403). IMR did not change significantly with eGFR (beta −0.02, 95% −0.09 to 0.05, p=0.557).

The incidence of VOCO was higher in patients with CKD and FFR>0.80 when compared to non-CKD patients and FFR>0.80 (12.7% vs 6.90%, p=0.062). Prognosis was worse for those with CKD, negative FFR and CFR<2.0 (20.59% vs. 8.44% in non-CKD, p=0.038).

Conclusions

The assessment of a given coronary stenosis in patients with CKD with either FFR or resting Pd/Pa is equivalent when compared to underlying coronary flow. In CKD, impaired CFR is caused by a state of increased resting flow. The assessment of CFR on top of standard pressure wire examination significantly improves prognostic stratification in CKD patients.

Funding Acknowledgement

Type of funding sources: None.
Ventricular-arterial coupling impairment in patients recovered from COVID-19
Authors: Lampsas S , Oikonomou E , Souvaliotis N , Anastasiou A , Katsarou O , Marathonitis A , Lysandrou A , Tzima I , Sarantos S , Kalogeras K , Tsatsaragkou A , Mystakidi V C , Siasos G , Tousoulis D , Vavuranakis M
Published: October 2022

Background

Myocardial and vascular alterations among post-COVID-19 patients are observed. The coupling between arterial stiffness with left ventricular (LV) myocardial function (ventricular-arterial coupling, VAC) is an important determinant of cardiovascular performance and cardiac energetics. The aim of the study was to investigate the spectrum of cardiac and vascular abnormalities at mid-term follow-up in post-COVID-19 patients.

Methods

We enrolled 25 hospitalized patients for COVID-19, at one and six months after hospital discharge. The ratio (PWV/GLS) of carotid-femoral pulse wave velocity (cf-PWV), as a marker of arterial stiffness, to global longitudinal strain (LV-GLS), as a marker of left ventricular performance, was estimated as a marker of arterial elastance/left ventricular elastance index the long-term. The comparison was conducted with age and sex-matched non-COVID-19 controls.

Results

There was no difference in age (56.8±11.6 y vs. 57.4±9.5 y; p=0.85) and male sex (64% vs. 68%; P=0.76) between post-COVID-19 and control subjects respectively. At one-month follow-up, significant impairment was noted between post-COVID-19 and control subjects regarding: VAC (−0.71±0.24 m/s% vs. −0.44±0.11 m/sec%; p<0.001), LV-GLS (−17.9±3.1% vs. −21.9±2.7%; p<0.001), cf-PWV (12.3±3.5 m/s vs. 9.6±1.9; p<0.001). At six-month follow-up, an improvement was observed but there still was significant difference between post-COVID-19 and control subjects in: VAC (−0.62±0.19 m/sec% vs. −0.44±0.11 m/sec%; p<0.001), LV-GLS (−19.3±2.9% vs. −21.9±2.7%; p=0.001), cf-PWV (11.7±2.7 m/s vs. 9.6±1.9 m/s; p=0.001). Moreover, it was observed at 1-month: VAC adverse correlation with the levels of IL-6 (r=−0.54; p<0.001), CRP (−0.71; p=0.011) and at 6-months: IL-6 (r=−0.47; p=0.003), CRP (−0.56; p=0.007).

Conclusion

Ventricular-arterial coupling is impaired 6 months following COVID-19 highlighting the possible effects of SARS-CoV-2 infection in left ventricular mechanics and performance.

Funding Acknowledgement

Type of funding sources: None.
Proteomics to identify biological pathways and develop prediction models of coronary microvascular dysfunction in women with angina and no obstructive coronary artery disease
Authors: Prescott E , Bove K , Suhrs H E , Bechsgaard D F , Lange T , Schroder J , Nielsen R L
Published: October 2022

Aims

Coronary microvascular dysfunction (CMD) is a major cause of angina and impaired outcome. Protein biomarkers could simplify patient selection for assessment and help uncover pathophysiologic pathways.

Methods and results

We quantified 184 protein biomarkers in 1471 women with angina and no obstructive coronary artery disease on angiography characterized for CMD by coronary flow velocity reserve (CFVR) by Doppler Echocardiography. Sixty-one biomarkers were significantly associated with CFVR (Figure 1). The strongest correlations were seen for renin, growth differentiation factor 15 (GDF15), brain natriuretic protein (BNP), NT-proBNP and adrenomedullin (ADM) (all p<1e-06). To identify pathophysiological patterns, we applied principal components (PC) analyses and weighted protein co-abundance network analyses. Two PCs with the highest loading on BNP/ NTproBNP and interleukin 6 (IL-6), respectively, were strongly associated with low CFVR. The weighted protein co-abundance network analyses identified two clusters associated with low CFVR reflecting involvement of hypertension/vascular function and immune modulation. For prediction of CMD (CFVR <2.25, n=646), data was split into model and validation cohorts. The best model using only clinical data had area under the receiver operating characteristic curve (ROC-AUC) of 0.61 (95% CI 0.56–0.66). ROC-AUC improved to 0.66 (95% CI: 0.62–0.71) with addition of biomarkers. Stringent two-layer cross-validated machine learning models had ROC-AUC ranging from 0.58 to 0.66 (Figure 2); the most predictive biomarkers were renin, BNP, NT-proBNP, GDF15 and ADM.

Conclusion

CMD was associated with biological pathways, particularly involving inflammation (IL-6), blood pressure (renin, ADM) and ventricular remodelling (BNP/NTproBNP). The identified biomarker pathways may prove potential treatment targets for CMD. Diagnostic models improved significantly when adding protein biomarkers to clinical information.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Heart Foundation
Angiography derived index of microvascular resistance (IMR) in Takotsubo syndrome
Authors: Castaldi G , Fezzi S , Widmann M , Lia M , Rizzetto F , Mammone C , Galli V , Piccolo S , Pazzi S , Pighi M , Pesarini G , Prati D , Scarsini R , Tavella D , Ribichini F L
Published: October 2022

Background and purpose

Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an “adrenergic storm” upon a susceptible microvascular circulation. The aim of our manuscript was to assess and quantify CMD in patients with TTS through angiography-derived index of microcirculation (IMR) and evaluate its correlation with clinical presentation.

Methods

Coronary angiograms of 41 consecutive TTS patients were retrospectively offline analyzed to derive angiography-based indices of CMD. Three recently developed indices (NH-IMRangio, AngioIMR and A-IMR) were calculated and compared based on Quantitative Flow Reserve (QFR) analysis. CMD was defined as an IMRangio ≥25 units. The correlation between CMD and clinical presentation and outcomes was then assessed.

Results

Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in Left Anterior Descending artery (LAD) than Circumflex artery (LCX) and Right Coronary artery (RCA) with either NH-IMRangio (52.7 vs 35.3 vs 41.4), AngioIMR (47.2 vs 31.8 vs 37.3) or A-IMR (52.7 vs 36.1 vs 41.8). All patients presented CMD with angiography-derived IMR ≥25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 vs 46.3, p. value=0.030; AngioIMR: 52.9 vs 41.4, p-value=0.037; A-IMR: 59.2 vs 46.3, p-value=0.035).

Conclusion

CMD, assessed with angiography-derived IMR, is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.

Funding Acknowledgement

Type of funding sources: None.
Ventricular fibrillation complicating acute myocardial infarction in women
Authors: Weizman O , Marijon E , Narayanan K , Garcia R , Puymirat E , Simon T , Danchin N
Published: October 2022

Background

Very little data is available in women presenting with ventricular fibrillation in the setting of acute myocardial infarction.

Purpose

To investigate sex-discrepancies in the incidence, characteristics and outcomes of acute myocardial infarction complicated by ventricular fibrillation.

Methods

Data were analyzed from the FAST-MI registry, which prospectively included 14,406 patients with acute myocardial infarction (mean age 66±14 years, 72% male, mean left ventricular ejection fraction 52±12%, 59% with ST elevation myocardial infarction). All consecutive patients admitted to French cardiac intensive care units ≤48 hours from acute myocardial infarction onset during a 1-month period every five years during 1995 and 2015 were included. This analysis focused on ventricular fibrillation occurring during the initial in-hospital stay for acute myocardial infarction in women compared to men.

Results

A total of 359 patients developed ventricular fibrillation during acute myocardial infarction, including 81 women (2.0% of 4,091 women overall) and 278 men (2.7% of 10,315) (p=0.02). ST-elevation myocardial infarction (OR 2.29, 95% CI 1.75–2.99, p<0.001) was independently associated with occurrence of ventricular fibrillation, while female gender (OR 0.73, 95% CI 0.56–0.95, p=0.02), hypertension (OR 0.75, 95% CI 0.60–0.94, p=0.01) and prior MI (OR 0.69, 95% CI 0.50–0.96, p=0.03) were protective factors. Women were less likely to have percutaneous coronary intervention during hospitalization than men (48.1% vs. 69.1%, OR 0.48, 95% CI 0.29–0.80, p<0.001). One-year mortality was higher in women compared to men (23.1% vs. 7.0%, HR 5.5, 95% CI 1.7–17.2, p=0.001). However, after adjustment for age, type of myocardial infarction and percutaneous coronary intervention, female gender was no longer associated with a worse one-year mortality (adjusted HR 1.04, 95% CI 0.71–1.51, p=0.85).

Conclusion and relevance

Women have lower risk of developing ventricular fibrillation during acute myocardial infarction compared to men. However, they are less likely to receive early coronary interventions than men, possibly contributing to worse outcomes.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): French Society of Cardiology
Association of air pollutants, weather variables, and myocardial infarction incidence in Berlin. A study of the Berlin Brandenburg Myocardial Infarction Registry (B2HIR) based on 17873 cases
Authors: De Buhr-Stockburger I , Theres H , Bruch L , Dreger H , Ebbinghaus J , Fried A , Maier B , Roehnisch J U , Schuehlen H , Stockburger M
Published: October 2022

Background

Harmful health effects of air pollutants have long been assumed. Respective associations with respiratory diseases have frequently been reported. Recently, studies also pointed at possible links between air pollution and cardiovascular disease. Currently, nitric oxide (NOx) and particulate matter are of concern in Germany.

Purpose

To investigate the association of NOx, particulate matter (PM10), and weather variables with the incidence of myocardial infarction (MI) in Berlin.

Methods

The Berlin Brandenburg myocardial infarction registry (B2HIR) is documenting symptom onset, patient characteristics, comorbidity, procedural data, and outcome of patients with acute MI (onset ≤24h before admission) in Berlin and Brandenburg. From 2008 to 2014 (study period) the stable number of enrolling cardiology departments enabled epidemiologic analyses. Daily (aggregate and variable-specific) MI incidence was assessed for the study period. The government of Berlin provides detailed regional air pollution data (BLUME network). Daily and local NOx and PM10 concentrations were assessed and grouped according to regions (downtown, main roads, suburbs). Preceding days (single and 3 day average) values were also assorted to every single day. Ambient temperature, precipitation, and sunshine duration were assessed from the Berlin-Tempelhof weather station. Bivariate correlations and Poisson regression were calculated to examine associations between air pollutants, weather parameters, and MI incidence.

Results

17873 MI cases were included over 7 years. Bivariate correlations and the Poisson regression model revealed a highly significant independent association of the overall MI incidence with same day NOx concentrations (mean values across all measuring stations) and with average PM10 concentration over three preceding days. Based on regression coefficient and interquartile range of pollutant concentrations, MI incidence variation with same day NOx was 3.2% (p<0.001) and variation with three preceding days PM10 was 4.8% (p<0.001). Daily peak ambient temperature was inversely related to MI incidence (p<0.001), whereas for sunshine duration and precipitations no independent association could be identified. Interestingly, the MI incidence in current smokers was unaffected (p=0.145 and p=0.104, respectively) by NOx and PM10 pollution.

Conclusion

This study is the first to show significant associations between the air pollutants NOx (same day level) and PM10 (3 day preceding average level) and MI incidence in Berlin. MI incidence varied with these pollutants at single digit percentage points. A causal relationship appears likely, as continuously self-intoxicating smokers did not exhibit this association.

Funding Acknowledgement

Type of funding sources: None.
Impact of pre-existing vascular disease on clinical outcomes in patients with non-ST-segment myocardial infarction: a nationwide cohort study
Authors: Weight N , Moledina S , Zoccai G B , Zaman S , Smith T , Siller-Matula J , Dafaalla M , Rashid M , Nolan J , Mamas M A
Published: October 2022

Aims

Little is known about the outcomes and processes of care of patients with non ST-segment myocardial infarction (NSTEMI) who present with “polyvascular” disease.

Methods

We analysed 287,279 NSTEMI patients using the Myocardial Infarction National Audit Project (MINAP) registry. Clinical characteristics and outcomes were analysed according to history of affected vascular bed; coronary artery disease (CAD), cerebrovascular disease (CeVD) and peripheral vascular disease (PVD), with comparison to a historically disease-free control group; comprising 167,947 patients (59%). Further analyses compared cumulative number of affected beds with our control.

Results

After adjusting for demographics and management, vascular bed disease was associated with increased likelihood of MACE (CAD OR: 1.06, 95% CI: 1.01–1.12, P=0.02) (CeVD OR: 1.19, 95% CI: 1.12–1.27, P<0.001) (PVD OR: 1.22, 95% CI: 1.13–1.33, P<0.001) and in-hospital mortality (CeVD OR: 1.24, 95% CI: 1.16–1.32, P<0.001) (PVD OR: 1.33, 95% CI: 1.21–1.46, P<0.001). Patients with no vascular disease were less likely to be discharged on statins (PVD 88%, CeVD 86%, CAD 90% and control 78%), and those with moderate (EF 30–49%) or severe left ventricular systolic dysfunction (LVSD) (EF<30%) were less likely to be discharged on ACE inhibitors (CAD 82%, CeVD 77%, PVD 77%, control 74%). Patients with polyvascular disease were less likely to be discharged on DAPT (PVD 78%, CeVD 77%, CAD 80%, control 87%).

Conclusion

Polyvascular disease patients had a higher adjusted incidence of in-hospital mortality and MACE. Patients with no history of vascular disease were less likely to receive statins or ACE inhibitors/ARBs, but more likely to receive DAPT.

Funding Acknowledgement

Type of funding sources: None.
Hemoglobin A1c and long-term mortality in patients undergoing coronary angiography: the ECAD registry
Authors: Dykun I , Hendricks S , Babinets O , Al-Rashid F , Totzeck M , Rassaf T , Mahabadi A A
Published: October 2022

Background

Hemoglobin A1c (HbA1c) reflects long-time glycemic control and is associated with an increased risk of cardiovascular events among diabetic and non-diabetic patients. The precise impact of HbA1c itself on the all-cause mortality in addition to the control of other cardiovascular risk factors remains uncertain.

Purpose

We tested the hypothesis that HbA1c levels associate with long-term mortality.

Methods

The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography with percutaneous coronary intervention at the West German Heart and Vascular Center between 2004 and 2019. HbA1c was quantified at hospital admission using standardized enzymatic methods. The incidence of death due to any cause was evaluated during follow-up. Cox regression analysis was used to determine the association of HbA1c with incident mortality, adjusting for age, sex, systolic blood pressure, low-density lipoprotein cholesterol, smoking status, and family history of premature cardiovascular disease. In addition to the analysis on HbA1c as continuous variable, the association of HbA1c-groups (≤10th percentile, >10th-<25th percentile, 25th-<50th percentile, 50th-<75th percentile, 75th-<90th percentile, and ≥90thpercentile) with incident mortality was determined using HbA1c >10th-<25th percentile as reference.

Results

Among 4700 patients, mean age was 66.1±11.4 years and 77.1% were men. Mean HbA1c was 6.3±1.2%. During a median follow-up of 3.0 years, 558 patients (8.4%) died. In multivariable analysis, higher HbA1c levels were independently associated with all-cause mortality (hazard ratio [95% confidence interval]: 1.15 [1.06, 1.25] per 1 standard deviation change in HbA1c, p<0.001). Using HbA1c >5.3–5.6% as reference, we observed a U-shaped event rate for different HbA1c groups (≤5.3%: 1.69 [1.20; 2.37], p=0.003; >5.6–5.9%: 0.95 [0.68; 1.63], p=0.8, >5.9–6.6%: 1.19 [0.87; 1.61], p=0.3, >6.6–7.8: 1.66 [1.18; 2.35], p=0.004, >7.8%: 2.04 [1.43; 2.9], p<0.001).

Conclusions

In a large longitudinal registry cohort of patients following percutaneous coronary intervention, we observe a U-shaped association of HbA1c levels with long-term mortality with best prognosis of patients in the range of HbA1c levels between 5.3 and 5.9%.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only.
Coronary artery disease is a stronger predictor of mortality than left ventricular ejection fraction among newly diagnosed patients with heart failure
Authors: Pryds K , Nielsen R R , Olesen K K W , Mortensen M B , Nielsen J C , Maeng M
Published: October 2022

Background

Heart failure (HF) prevalence remains high and prognosis is poor despite improvements in both medical treatment and implantation of primary prophylactic implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT) devices. At present, classification of HF and treatment algorithms are determined by the left ventricular ejection fraction (LVEF). However, in patients with LVEF <50% and newly diagnosed HF, evidence remains sparse as to whether LVEF per se or presence of CAD provide independent prognostic information on mortality.

Methods

Using the Western Denmark Heart Registry, we identified newly diagnosed patients with HF and LVEF 10–49% undergoing first-time coronary angiography (CAG) from 2003 to 2016 referred due to HF. Patients were stratified by LVEF (10–35% vs. 36–49%, according as to whether primary prophylactic ICD and CRT treatment should be considered) and presence of coronary artery disease (CAD). Maximum follow-up was 10 years. We estimated 10-year cumulative incidence of death and calculated hazard ratios (HR) adjusted for relevant comorbidities and risk factors.

Results

Of 154,186 Western Danish residents undergoing CAG, 3,620 patients had HF and LVEF 10–49%. Among these, 2,780 (77%) patients had LVEF 10–35% and 840 (23%) patients had LVEF 36–49%. CAD was present in 1,592 (44%) patients.

There was a potential association in 10-year mortality when comparing patients with HF and LVEF 36–49% to those with LVEF 10–35% (37.3% vs. 42.1%, HR 1.15; 95% CI 0.99–1.34) (Figure 1A), with point estimates of mortality ranging from being 1% reduced to 24% increased. This result was not strongly influenced by the presence of CAD (HR 1.11; 95% CI 0.91–1.35) or absence of CAD (HR 1.24; 95% CI 0.97–1.57) (Figure 1B). There was no trend between LVEF categorized by 5-percentiles and mortality (p for trend = 0.24) (Table 1). In contrast, CAD was more strongly associated with increased 10-year mortality (55.0% vs. 31.5%, HR 1.43; 95% CI 1.25–1.64) irrespective of LVEF (Figure 1B).

Conclusion

Among newly diagnosed patients with HF and LVEF 10–49%, presence of CAD impacts mortality substantially more than LVEF per se. These results emphasize that assessment of CAD is pivotal for prognostication of newly diagnosed patients with HF and LVEF 10–49%.

Funding Acknowledgement

Type of funding sources: None.
Infarction of the papillary muscle is an independent predictor of heart failure, ventricular tachycardia, and consequent mortality
Authors: Beijnink C , Raessens S , Ortiz-Perez J T , Bodi V , Rodwell L , Valente F , Alamar M , Marcos-Garces V , Lorenzatti D , Rios-Navarro C , Gavara J , Ferreira I , Barrabes J A , Rodriguez Palomares J , Nijveldt R
Published: October 2022

Background

Previous studies have assessed the effect of papillary muscle infarction (papMI) as seen with Late Gadolinium Enhancement (LGE) Cardiac Magnetic Resonance imaging (CMR) after ST-segment elevation myocardial infarction (STEMI) on patient prognosis. As these studies delivered inconclusive results due to limited sample size and follow-up, we set out to assess whether STEMI patients with papMI are at an increased risk of cardiovascular mortality, heart failure, and arrhythmic events.

Methods

This is a 3-center observational study in n=1,055 consecutive STEMI patients who underwent CMR at a median of 6 (4–9) days, with a mean follow-up of 6.0 years (IQR 3.1–9.1 years). Any presence of papMI, be it supero-lateral, infero-medial, or double, was evaluated visually on the LGE images and checked on the matched cine images. The primary outcomes are time to cardiovascular mortality, heart-failure events defined as heart failure death and hospital admission for heart failure, and arrhythmic events, defined as arrhythmic death and ventricular tachycardia (VT).

Results

PapMI was diagnosed in 351 patients (33%). PapMI is an independent predictor of cardiovascular mortality after correction for clinically relevant parameters such as infarct size and left ventricular ejection fraction (Multivariate Cox Regression Hazard Ratio (HR)=2.46, 95% confidence interval (CI) 1.23–4.92). Secondly, papMI independently predicts the combined endpoints of heart failure death/heart failure (HR=1.72, 95% CI 1.12–2.63) and arrhythmic death/ VT (HR=4.52, 95% CI 2.18–9.36).

Conclusions

PapMI predicts cardiovascular mortality, arrhythmic death and heart failure. PapMI should be taken into account, especially when conducting new prognosis studies after STEMI and as a stratification factor in studies for secondary prevention of VT and arrhythmic death.

Funding Acknowledgement

Type of funding sources: Other.
Noninvasive evaluation of coronary velocity reserve: need for correction of the sympathetic tone
Authors: Armenis I , Hatzigeorgiou G , Marinou M , Kyrzopoulos S , Tsiapras D , Athanassopoulos G
Published: October 2022

Introduction

Noninvasively Doppler estimated coronary velocity (as a surrogate of flow) reserve (CVR) by adenosine is a useful parameter for risk stratification in chronic coronary syndromes (CAD). However, baseline velocity fluctuation due to sympathetic drive, as in mental stress, may affect the evaluation of the actual CVR.

Aim

Aim of the study was to assess the effect of b blocker administration following adenosine infusion in the coronary velocity and thus the consequences in the estimated CVR.

Patients and methods

Sixty (females 8) patients (pts) with stable CAD (mean/SD: age 64/10, ejection fraction % 55/8) were studied before the performance of a dobutamine stress echo. Distal left anterior descending (LAD) velocity was estimated at rest (CVrest), at maximal adenosine infusion (140γ/kg/min: CVaden) and following esmolol infusion 3–5 min later (CVbbl). CVR was estimated using as baseline velocity either CVrest (CVRrest) or CVbbl (CVRbbl). Respective changes of heart rate (HR) and systolic blood pressure (SBP) were also estimated.

Results

CVbbl was smaller than CVrest (23/7 vs 29/13, p<0.0.01). Thus, CVRbbl was greater than CVRrest (3/0.9 vs 2.7/0.6, p<0.001) with an absolute difference (dCVR) of 0.46/0.84, a % difference (%dCVR) of 23/34%, with a modest linear relationship (R2=0.08, p=0.02 figure). The %dCVR was also linearly related to CVRrest (R2=0.13, p=0.003 figure) and it was independent from age, HR/BP changes and the dobutamine stress echo outcome.

Differences between CVRbbl and CVRrest were greater in females (females/males: dCVR 1.2/0.9 vs 0.36/0.8, %dCVR 0.67/0.56 vs 0.36/0.26, both p<0.001).

Conclusions

Noninvasively estimated CVR is affected by the baseline sympathetic tone, irrespectively from the age in stable CAD. A gender effect is evident, reiterating the microvascular susceptibility in females. Thus, potential mental stress background must be considered, and b-blockade subsequently might be applied during CVR evaluation to overcome any sympathetic effect.

Funding Acknowledgement

Type of funding sources: None.
Cardiovascular risk factors and underlying pathology and prevalence of lipid plaques in women with acute coronary syndromes in different age groups
Authors: Seegers L M , Araki M , Nakajima A , Yuki H , Yonetsu T , Soeda T , Kurihara O , Higuma T , Minami Y , Adriaenssens T , Nef H , Lee H , Sugiyama T , Kakuta T , Jang I K
Published: October 2022

Background

An incidence of cardiovascular events increases with age in women. The relationship between cardiovascular risk factors, and the underlying pathology and the prevalence of lipid plaques has not been systematically studied in different age groups in women presented with acute coronary syndromes (ACS).

Purpose

We investigated the underlying pathology and the prevalence of lipid plaques in culprit lesions by optical coherence tomography (OCT) in women with different risk factors.

Methods

A total of 382 women who underwent pre-intervention OCT imaging were included. The underlying pathology and the prevalence of lipid plaques in the culprit lesion was compared between women with and without cardiovascular risk factors (i.e. hypertension, smoking, hyperlipidemia, diabetes mellitus, family history and chronic kidney disease) in three different age groups (<60 yr, 60–70 yr, >70 yr).

Results

The relative prevalence of plaque erosion was higher in younger women (<60 yr) and decreased with age (from 51% to 28%, p<0.001). There was no significant difference in the prevalence of lipid plaques between women with and without risk factors, except a higher prevalence of lipid plaques in current smokers compared to non-smokers (79% vs. 63%, p=0.003). In women with hyperlipidemia, the prevalence of lipid plaques was modest in young ages (<60 yr), but increased steeply with age (p<0.001). The increasing age trend for lipid plaque was also observed in women with hypertension (p=0.03) and current smokers (p=0.01). In women with diabetes mellitus and family history, the prevalence of lipid plaques was high even in young ages (<60 yr) and did not increase with age.

Conclusion

The prevalence of plaque erosion was higher in younger women (<60 yr) and decreased with age. Current smokers had significantly higher prevalence of lipid plaque. Patients with diabetes and positive family history had a higher prevalence of lipid plaque at young age. The prevalence of lipid plaques increased with age particularly in women with hyperlipidemia and hypertension.

Funding Acknowledgement

Type of funding sources: Foundation.
Heterogeneous plaque geometry is associated with major adverse cardiovascular events
Authors: Gu Z S , Huang Y , Costopoulos C , Jessney B , Bourantas C , Teng Z , Maehara A , Raber L , Stone G , Bennett M R
Published: October 2022

Objectives

To determine whether coronary artery plaque-lumen geometry predicts major adverse cardiovascular events (MACE), and incorporating geometric measures enhances risk stratification from intravascular imaging.

Background

Prospective studies show that only a minority of plaques with higher-risk features result in future MACE, indicating the need for more predictive markers of plaque vulnerability. Plaques show heterogeneous structures and plaque-lumen geometry, both of which can promote high plaque structural stress (PSS); however, the relationships between geometric heterogeneity and MACE or PSS are unknown.

Methods

We examined plaque-lumen curvature, irregularity, lumen aspect ratio (LAR), roughness, PSS and their longitudinal heterogeneity (Figure 1A) in 35 non-culprit lesions (NCL) associated with MACE and 66 propensity-matched no-MACE NCL from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Causes of heterogeneous geometry and PSS were examined using a separate group of co-registered virtual histology-intravascular ultrasound (VH-IVUS) and optical coherence tomography (OCT) images (n=53 plaques).

Results

Plaque geometry heterogeneity indices (HI) were increased in NCL MACE vs. no-MACE lesions across the whole plaque and peri-minimal luminal area (MLA) segments (HI curvature: p=0.002; HI irregularity: p<0.001; HI LAR: p=0.001; HI roughness: p=0.002). Peri-MLA HI roughness was an independent predictor of future MACE (hazard ratio: 3.69, p<0.001) (Figure 1B). Inclusion of HI roughness improved identification of NCLs leading to MACE in VH-defined thin-cap fibroatheromas (VH-TCFA, p=0.005), MLA ≤4mm2 (p=0.001), and plaque burden (PB) ≥70% (p<0.001) (Figure 1C–E), and further improved the ability of PSS to identify MACE NCLs in VH-TCFA (p=0.041), MLA ≤4mm2 (p=0.033), and PB ≥70% (p<0.001). HI roughness generally corresponded with HI PSS, but was also increased at sites of local calcification and multilayering.

Conclusions

Plaque-lumen geometric heterogeneity is increased across whole plaque and peri-MLA segments of NCLs causing MACE. Inclusion of geometric heterogeneity may improve the ability of intravascular imaging to predict MACE.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): British Heart Foundation
The effects of smoking on cardiac structure and function in a general population
Authors: Holt E , Skaarup K G , Lassen M C H , Johansen N D , Joergensen P G , Hauser R , Lind J N , Jensen G , Schnor P , Prescott E , Soegaard P , Moegelvang R , Biering-Soerensen T
Published: October 2022

Background

Cigarette smoking is the leading preventable cause of death worldwide. Smoking is known to cause coronary artery disease, but studies have also shown that smoking independently is associated with higher risk of heart failure. However, the link between smoking and cardiac structure and function is not yet fully examined.

Purpose

The aim of the study was to investigate the independent effect of cigarette smoking on cardiac structure and function in a general population using echocardiographic measures.

Methods

A prospective cohort of 3,874 participants from a general population free of prevalent heart disease underwent an echocardiographic examination including two-dimensional speckle-tracking analysis. Smoking history was obtained through a self-administered questionnaire, that generated three groups; current smokers (18.6%), former smokers (40.9%) and never smokers (40.5%). Pack-years were estimated from the questionnaire.

Results

After multivariable adjustment for age, sex, body mass index, hypertension, hypercholesterolemia, diabetes and lung function, current smokers had significantly alterations in septal thickness (1.1±0.2 cm, P=0.018) and relative wall thickness (0.4±0.1 cm, P=0.016) compared to never smokers. Furthermore, left ventricular mass index (LVMi) was increased in current smokers compared to never smokers (85.8±19.3 g/cm2, P=0.048). Reduced left ventricle systolic function as assessed by global longitudinal strain (GLS) was evident in current smokers compared to never smokers (19.1±2.3%, P<0.001). Additionally, after multivariable adjustment increasing pack-years was associated with decreases in left ventricular ejection fraction (LVEF) (β=−0.04, P=0.031), E/A ratio (β=−0.06, P<0.001) and GLS (β=−0.04, P=0.008). Comparing cardiac structure and function in never smokers, continuous smokers and former smokers after 10 years, showed that continuous smokers developed increased LVMi (Δ=3.97±17.48 g/cm2, P<0.001) and decreased GLS (Δ=−0.77±3.84%, P=0.04) and LVEF (Δ=−4.23±5.7, P<0.001) compared to never and former smokers.

Conclusion

In a large general population study without known heart disease, current smoking and accumulated pack-years were independently associated with alterations in cardiac structure and reduced systolic function. Furthermore, we found that continuous smokers over a 10-year period developed relatively worse systolic function and increased LV structure alterations compared to never smokers and to participants that stopped smoking during that period.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Copenhagen City Heart Study is funded by The Danish Heart Foundation andThe Metropolitan Region of Denmark.
Prognostic implications of fractional flow reserve and coronary flow reserve after newer-generation drug-eluting stent implantation
Authors: Ueno H , Hoshino M , Sugiyama T , Kanaji Y , Hada M , Misawa T , Nagamine T , Nogami K , Sayama K , Matsuda K , Yonetsu T , Sasano T , Kakuta T
Published: October 2022

Background

FFR after percutaneous coronary intervention (PCI) has been reported to provide prognostic information. However, limited data are available regarding the prognostication by CFR in patients treated with elective PCI using newer generation DES.

Purpose

This study aimed to assess the prognostic value of post-procedural fractional flow reserve (FFR) and coronary flow reserve (CFR) after newer-generation drug-eluting stent implantation (DES).

Methods

A total of 466 stenoses in 466 patients underwent FFR-guided PCI. FFR and CFR measurements before and after PCI by a pressure-temperature sensor-tipped wire were performed. Follow-up data were studied to determine the predictors of target vessel failure (TVF), defined as death, target vessel-related nonfatal myocardial infarction, and unplanned clinically driven target vessel late revascularization. Prognostic value of post-PCI CFR was compared with that of FFR or FFR/CFR combination.

Results

After PCI completion, 13.7% showed post-PCI FFR ≤0.80 and 44.2% exhibited post-PCI CFR <2.5. Discordant results were observed in 42.5% (198/466). During 2.7 (1.8–3.3) years follow-up, 57 (12.2%) TVF were documented. The multivariable Cox proportional hazard regression analysis revealed that post-PCI FFR and post-PCI CFR were independent prognostic factors. ROC analysis revealed that the optimal cut-off values of post-PCI FFR and CFR values were 0.85 and 2.26, respectively. Significant differences in TVF were detected according to post-PCI FFR (≤0.85 vs >0.85: 17.8% vs 8.9%, P<0.05) and post-PCI CFR (≤2.26 vs >2.26: 20.5% vs 7.2%, P<0.01), although the reclassification ability for TVF was improved only with post-PCI CFR (net reclassification index 0.598; P<0.01; integrated discrimination index 0.038; P<0.01), but not with post-PCI FFR, in comparison with the clinical model. Compared with patients with FFR >0.85, those with post-PCI FFR ≤0.85 and CFR ≤2.26 showed significantly higher risk of TVF (8.9% vs 28.9%, P<0.01, HR 4.24, 95% CI 2.40–7.50, P<0.01), whereas those with post-PCI FFR <0.85 and CFR >2.26 had similar TVF risk (8.9% vs 9.2%, P=1.00, HR 1.01, 95% CI 0.47–2.16, P=0.97).

Conclusions

After PCI completion with newer-generation DES, discordant results between FFR and CFR were observed in 42.5%. Compared with post-PCI CFR, post-PCI FFR provided limited reclassification ability for TVF. Among patients with lower post-PCI FFR, only patients with lower post-PCI CFR showed significantly higher risk of TVF than those with higher post-PCI FFR.

Funding Acknowledgement

Type of funding sources: None.
Direct cost analysis of genetic testing for CYP2C19*2 and *3 loss of function variants in percutaneous coronary intervention patients
Authors: Huxley S , Pereira N , Borah B , Lennon R , Moriarty J
Published: October 2022

Background/Introduction

Patients with CYP2C19*2 or *3 loss of function (LOF) variants who undergo percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel.

Purpose

A subgroup of patients who were included in the TAILOR-PCI trial were also enrolled in this study to determine if a genotype-guided (GG) approach based on CYP2C19*2 or *3 LOF variants is cost-effective.

Methods

Patients were randomized to the conventional therapy group with clopidogrel and to the GG group who underwent point of care genotype testing for CYP2C19*2 or *3 LOF variants. In the GG group, therapy was based on genotype results. Those identified as LOF carriers were prescribed ticagrelor while non-carriers were prescribed clopidogrel.

Results

There were no significant differences in direct medical costs between the conventional therapy group and GG group (mean $19,747 versus $20,682, p=0.11), however total costs were significantly greater in the GG group which was primarily driven by the outpatient cost of ticagrelor. Furthermore, there was no significant cost difference between ticagrelor treated LOF carriers and clopidogrel treated non-carriers.

Conclusion

These findings suggest that a GG approach with point of care testing for CYP2C19*2 or *3 LOF variants in patients undergoing PCI may be a cost-effective practice.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): NIH grants
Effects of CYP3A4*22 carrier and CYP3A5 expressor status on clinical outcome in patients treated with ticagrelor for acute coronary syndrome
Authors: Azzahhafi J , Bergmeijer T O , Van Den Broek W W A , Chan Pin Yin D R P P , Rayhi S , Peper J , Bor W L , Van Schaik R H N , Ten Berg J M
Published: October 2022

Background

Current guidelines recommend using ticagrelor in patients with acute coronary syndrome. Ticagrelor is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5. CYP3A4*22 allele and the CYP3A5 expressor status influence the metabolization of ticagrelor, increasing plasma concentration and platelet inhibition. Nevertheless, little is known about the impact of the CYP3A4*22 allele or CYP3A5 expressor status on clinical outcomes in ticagrelor treated patients.

Purpose

Our study aims to assess the effects of the CYP3A4*22 allele and CYP3A5 expressor status in patients with STEMI and treated with ticagrelor, with regards to clinical outcomes and the clinical side-effect dyspnea.

Methods

Patients from the POPular Genetics trial treated with ticagrelor were genotyped for the CYP3A4*22 and CYP3A5*3 alleles. Patients were divided into two groups based on their CYP3A4 (*22 carriers vs. *22 non carriers) and CYP3A5 status (expressor vs. non-expressors). The primary thrombotic endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis and stroke. The primary bleeding outcome consisted of PLATO major and minor bleeding. The key secondary endpoint was clinically relevant dyspnea. The follow-up duration was one year.

Results

A total of 1,281 patients with ST-elevation myocardial infarction (STEMI) were used for the analyses. In the first analysis, CYP3A4*22 carriers (n=152) versus CYP3A4*22 non-carriers (n=1,129) were not found to have a significant correlation with the primary thrombotic outcome (1.3% vs. 2.5% adjusted hazard ratio 1.81 [0.43–7.62]) or the primary bleeding outcome (13.2% vs. 11.3% adjusted hazard ratio 0.93 [0.58–1.50]) (See Figure 1 and 2). CYP3A5 expressors (n=196) versus non-expressors (n=926) did not show a significant difference for the primary thrombotic outcome (2.6% versus 2.5% adjusted hazard ratio 1.03 [0.39–2.71] or the primary bleeding outcome (12.8% versus 10.9% adjusted hazard ratio 1.13 [0.73–1.76]). With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers 44.0% vs. 45.0%, risk ratio 1.04 [0.45–2.42] or CYP3A5 expressors versus CYP3A5 non-expressors 35.3% versus 47.8% risk ratio 0.60 [0.27–1.30].

Conclusions

In STEMI patients treated with ticagrelor, CYP3A4*22 carriers and CYP3A5 expressors did not affect clinical outcomes with regards to thrombotic events, bleeding rate, or the side-effect dyspnea.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organization for Health Research and Development (ZonMW). The authors are solely responsible for designing and conducting this study, conducting all study analyses, and drafting and editing the manuscript and its final contents.
At the outer edge of STEMI time: even after 12 hours, the clock keeps ticking
Authors: Martinho M , Cale R , Nabais S , Briosa A , Pereira E , Pereira A R , Grade Santos J , Ferreira B , Santos Cunha D , Santos P , Vitorino S , Eusebio C , Morgado G , Martins C , Pereira H
Published: October 2022

Introduction

Although primary percutaneous coronary intervention (pPCI) is not a class I recommendation in all patients (pts) presenting within 12 to 48h of symptom onset (late ST-segment Elevation Myocardial Infarction, STEMI), there is increasing evidence supporting its routine use in this population. Data on long-term clinical outcomes is sparse.

Objective

To evaluate long-term MACE in late-STEMI pts submitted to pPCI and compare with clinical outcomes of early reperfusion groups.

Methods

Retrospective analysis of consecutive pts submitted to pPCI due to STEMI between 2010 and 2015 in a pPCI centre. Included pts were stratified in 5 groups according to symptom-to-balloon time (SBT): <3h; 3–6h; 6–12h; 12–24h; 24–48h. Of a total of 903 pts, 19 pts were excluded due to SBT >48h. Long-term events were established as 5y mortality and 5y-MACE (a composite endpoint of death, re-infarction, heart failure hospital admission and ischemic stroke). The cumulative incidence of long-term outcomes was calculated by the Cox regression analysis and presented according to the Kaplan-Meier method.

Results

Of the 884 pts included in the study, stratification according to SBT was: pPCI<3h (47.4%), pPCI 3–6h (24.9%), pPCI 6–12h (16.5%), pPCI 12–24h (8.0%), and pPCI 24–48h (3.2%). These groups showed no significant difference in terms of demographic characteristics (age, CV risk factors, previous coronary disease or heart failure), clinical severity (systolic arterial pressure, Killip-Kimball class, left ventricle ejection fraction) and angiography findings (multivessel disease, complete revascularization and PCI success). After a median follow-up of 76 (56; 98) months, 5-year mortality was 20.6% (182 pts) and 5-year MACE was 23.3% (206 pts). MACE was associated with increased median SBT: 5.0 (2.0; 9.0) hours vs 4.0 (2.0; 6.5) hours, p<0.001. Of the MACE components, the only that showed a significant association with higher median SBT was mortality: 5.0 (2.0; 10.0) hours vs 4.0 (2.0; 6.0), p<0.001. Differences in long-term outcomes were significant when considering SBT stratified by revascularization time (Figure 1).

Conclusions

As expected, there is a clinical benefit of early reperfusion for long-term cardiovascular events. Within the late-STEMI group, there seems to be a clear distinction between pPCI<24h and >24h, although the clinical benefit of pPCI timing most probably acts a continuum.

Funding Acknowledgement

Type of funding sources: None.
Evolution of functional mitral regurgitation and left atrial function in patients receiving cardiac resynchronization therapy
Authors: Stassen J , Galloo X , Hirasawa K , Van Der Bijl P , Marsan N A , Bax J J
Published: October 2022

Background

Left atrial (LA) function is a strong prognostic marker in patients with heart failure and patients with functional mitral regurgitation (MR). Although cardiac resynchronization therapy (CRT) has shown to improve MR severity, the interaction between a reduction in MR severity and an improvement in LA function, as well as their association with outcomes, has not been investigated.

Purpose

To investigate the association between a reduction in MR severity and an improvement in LA function, as well as their association with outcomes.

Methods

LA reservoir strain (RS) was evaluated with speckle tracking echocardiography in patients with moderate and severe functional MR. MR improvement was defined as at least 1 grade improvement in MR severity at 6 months after CRT implantation. The association between MR improvement and change in LARS was evaluated using multivariable logistic regression analysis. Patients were dividing into 3 groups: MR non-improvers; MR improvers with no LARS improvement; and MR improvers with LARS improvement. The primary endpoint was all-cause mortality.

Results

A total of 340 patients (mean age 66±10 years, 73% male) were included, of whom 200 (59%) showed MR improvement after CRT implantation. On multivariable analysis, an improvement in MR was independently associated with an improvement in LARS (OR 1.008; 95% CI 1.003–1.013; p=0.002) (Table 1). MR improvers showing LARS improvement had the lowest mortality rate, whereas outcomes were not significantly different between MR non-improvers and MR improvers showing no LARS improvement (p=0.236) (Figure 1).

Conclusion

In patients with HF and significant functional MR, an improvement in MR after CRT implantation is independently associated with an improvement in LARS, which in turn, is associated with better survival.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): ESC Training Grant App000064741