bluuebunny/crossref_metadata_2025 huggingface dataset:
A 7-year longitudinal association of total cholesterol with premature structural and functional cardiac damage progression in youth: the ALSPAC birth cohort study
Authors: Agbaje A O
Published: November 2023

Background

Recent evidence suggests that childhood total cholesterol was associated with midlife cardiovascular mortality. Cumulative total cholesterol has been associated with subclinical atherosclerosis during growth from mid-adolescence through young adulthood. It remains unexamined whether total cholesterol independently associates with signs of premature cardiac damage in apparently healthy youth due to the paucity of repeated measures of cardiac structure and function.

Purpose

To investigate the longitudinal association of changes in total cholesterol with structural and functional cardiac damage progression during growth from adolescence through young adulthood.

Methods

From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma total cholesterol measured at 17- and 24-year clinic visits were included. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e´ ratio (LVFP) were available at baseline and follow-up. LVMI2.7 ≥51g/m2.7, RWT ≥0.44, LVDF <1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively. Multivariable adjusted associations were examined using generalized linear mixed-effect models and generalized logit mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, sedentary time, light physical activity, and moderate to vigorous physical activity.

Results

Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) mean total cholesterol values increased in males from 3.55 mmol/L to 4.25 mmol/L and in females from 3.97 mmol/L to 4.46 mmol/L, over 7 years. The prevalence of LV hypertrophy increased in males from 3.6% to 11.9% and in females from 1.6% to 4% over 7 years. The prevalence of LVD dysfunction increased in males from 7.8% to 16.6% and in females from 10.3% to 15.4%. In a fully adjusted model, each 1 mmol increase in total cholesterol was significantly associated with higher odds of LV hypertrophy progression (odds ratio 1.18; [95% CI, 1.09 – 1.27], p<0.0001), high RWT (1.11; [1.02 – 1.21], p=0.015), and high LVFP (1.12; [1.05 – 1.20], p=0.001) but not LVD dysfunction (1.03 [0.95 – 1.13], p=0.461), over 7 years.

Conclusion

Increased total cholesterol was independently associated with progressive structural and functional cardiac damage in asymptomatic youth during growth from adolescence through young adulthood.
Cumulative accelerometer-based light physical activity from childhood through young adulthood progressively decreases left ventricular mass in British youth: a 13-year longitudinal study
Authors: Agbaje A O
Published: November 2023

Background

Several studies have reported the beneficial effect of moderate to vigorous physical activity on metabolic indices in children and adolescents. However, longitudinal evidence is lacking on the effect of objectively measured light physical activity on cardiac health in the pediatric population. An increased ventricular mass has been associated with cardiovascular events in adults.

Purpose

To investigate the longitudinal association of cumulative light physical activity from childhood through young adulthood with cardiac structural changes.

Methods

From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 766 children aged 11 years who had at least two follow-up time-points accelerometer-measured light physical activity over 13 years follow-up, and complete cardiac structural measures at age 17 years clinic visit were included. Light physical activity was assessed with ActiGraph accelerometer worn for 4-7 days at the 11-, 15-, and 24-year clinic visits. Repeated echocardiography measured left ventricular mass indexed for height2.7 (LVMI2.7) and relative wall thickness (RWT) were available at baseline and follow-up. Multivariable adjusted associations were examined using generalized linear mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sedentary time, and moderate to vigorous physical activity.

Results

Among 766 children (mean [SD] age, 11.75 [0.24] years; 422 [55.0%] females]) males spent on average 373, 288, and 146 minutes/day in light physical activity at ages 11, 15, and 24 years, respectively. Females spent an average of 373, 272, and 161 minutes/day in light physical activity at ages 11, 15, and 24 years respectively. LVMI2.7 was significantly higher among males than females with an average difference of ∼4g/m2.7 both at ages 17 and 24 years but no significant sex differences in RWT. In a fully adjusted model, every 1-minute spent in light physical activity from ages 11 – 24 years was associated with progressively decreased changes in LVMI2.7 (effect estimate -0.017g/m2.7 [CI -0.020 – -0.015] p<0.0001), and increased RWT from ages 17 – 24 years in the total cohort. Among males, each minute spent in light physical activity from ages 11 – 24 years was associated with progressively decreased changes in LVMI2.7 (-0.046g/m2.7 [CI -0.050 – -0.041] p<0.0001) and increased RWT but not in females.

Conclusion

Cumulative light physical activity during growth from childhood through young adulthood was associated with a progressive decrease in cardiac mass in the total cohort and males.
Hemodynamic profile of obesity in cardiogenic shock
Authors: Guglin M , Li B , Kanwar M , Bhimaraj A , Vallabhajosyula S , Abraham J , Kataria R , Kapur N
Published: November 2023

Background

There is a growing understanding that cardiogenic shock (CS) is a hemodynamically heterogenous condition. Hemodynamic variants within this entity are not well studied but, if recognize, may help to optimize therapies.

Purpose

We explored hemodynamics in patients with CS based on their body mass index (BMI).

Methods

The Cardiogenic Shock Working Group (CSWG) registry includes patients with CS, regardless of etiology, from 17 clinical sites across the USA. We stratified the participants into BMI quartiles (BMI≤24.4 kg/m2, 24.433.1 kg/m2), and studied the hemodynamic variables in CS depending on body mass index (BMI).

Results

The total cohort consisted of 3,492 patients admitted with CS (mean age 62.1±14 years, 69% male), including 2,024 (58.0%) of CS related to advanced heart failure (HF-CS) and 969 (27.8%) acute myocardial infarction (AMI) related CS. IN HF-CS, more obese patients in higher BMI quartile had larger left ventricle, higher ejection fraction, and greater cardiac output (Table). Their systolic blood pressure was higher, and pulmonary artery pressure was lower than in lower BMI quartiles. Their pulmonary artery pulsatility index decreased from 2.2±1.4 in the second quartile to 1.6±1.3 in the forth (highest) quartile. Mortality in creased with the BMI increase, from 23.3% in the lowest BMI quartile to 30% in the highest BMI quartile, p=0.0128. In AMI-CS, there was no distinct hemodynamic profile related to obesity.

Conclusions

In cardiogenic shock related to heart failure, unlike in AMI-related cardiogenic shock, there is a distinct hemodynamic pattern of obesity, consistent with larger left ventricle, higher ejection fraction, higher cardiac output and systemic pressure, higher right atrial pressure, and lower pulmonary artery pulsatility index. In this subset, obesity is associated with the highest in-hospital mortality.
Association of inflammation with shock severity, 30-day mortality and therapy response in patients with cardiogenic shock
Authors: Dettling A , Weimann J , Sundermeyer J , Beer B , Besch L , Becher P , Brunner F , Kluge S , Kirchhof P , Blankenberg S , Westermann D , Schrage B
Published: November 2023

Background

Elevated concentrations of C-reactive protein (CRP) and other circulating cytokines are often found in cardiogenic shock (CS). The role of systemic inflammation in the pathogenesis of cardiogenic shock remains unclear. To address this, associations between elevated plasma CRP concentrations upon admission with shock severity, 30-day mortality, and therapy response were analysed in patients with CS.

Methods

Plasma CRP concentrations were identified in a large data base containing unselected patients admitted with cardiogenic shock. The association between plasma CRP concentrations and CS severity (SCAI stage, reference SCAI B) was analyzed using adjusted linear and logistic regression models. The association between plasma CRP concentrations and 30-day mortality was analyzed using adjusted Cox regression models. The interaction between plasma CRP concentrations and treatment response was assessed by fitting an interaction term between plasma CRP concentrations and the use of mechanical circulatory support (MCS) in the above described Cox regression models.

Results

A total of 1116 patients were analysed. Median age was 70 years [interquartile range 58-78.6 years], 71.3% were male, 47.7% presented with CS due to acute myocardial infarction, and 58.3% with prior cardiac arrest. The median plasma CRP concentration was 17 mg/dl [interquartile range 5.0-71.0 mg/dl]. Plasma CRP concentrations were equally distributed among patients with higher vs. lower shock severity (higher SCAI stage). After adjustment for CS severity and other cofounders, higher plasma CRP concentrations were associated with higher 30-day mortality [8% relative risk increase per 50 mg/dl increase in plasma CRP, range 3-13%, adjusted p<0.001]. The association of plasma CRP concentration and 30-day mortality was abolished in patients treated with MCS [HR for CRP>median: MCS use 0.92 (95%-CI: 0.67-1.26; p=0.59)], while plasma CRP concentration was associated with 30-day mortality in patients not treated with MCS [HR for CRP>median 1.50 (95%-CI: 1.21-1.86; p<0.001); p-interaction=0.01].

Conclusion

Increased concentrations of inflammatory cytokines are associated with a higher 30-day mortality regardless of shock severity. This association is abolished when mechanical circulatory support systems are used, potentially by providing sufficient end-organ perfusion. This interaction calls for further research on this topic.
Biventricular unloading with Impella on top of veno-arterial membrane oxygenation improves short- and long-term survival in refractory post-cardiac arrest cardiogenic shock
Authors: Chatzis G , Waechter C , Markus B , Luesebrink U , Divchev D , Schuett H , Karatolios K , Schieffer B , Syntila S
Published: November 2023

Background

Patients with refractory post-cardiac arrest (CA) cardiogenic shock (RCS) may present with LV-failure, biventricular failure or even combined cardiopulmonary failure. Mechanical circulatory support (MCS) with Impella or veno-arterial membrane oxygenation (vaECMO) have emerged as an alternative strategy in order to stabilize the heart function without the detrimental effects of catecholamines or to bridge these patients in definite therapies. However, the selection of the appropriate MCS device should be tailored according to the underlying pathophysiology and properties of the respective MCS device. Especially vaECMO patients may show signs of LV overloading, causing pulmonary edema, LV distension and thus compromising LV myocardial recovery. Nowadays there is no data concerning the role of biventricular unloading with an Impella on top of a vaECMO in the homogenous group of post-CA RCS.

Purpose

To report our experience from the combined use of Impella (2.5 and CP) on top of a vaECMO in the homogenous group of patients with post-CA RCS.

Methods

Single center study of consecutive patients with biventricular unloading with Impella after initial vaECMO support over a 6-year period suffering from post-CA RCS. Propensity scoring matching analysis was used to account for the differences in baseline data between the two groups.

Results

A total of 91 patients underwent vaECMO support for RCS, whereas in another 32 patients initial vaECMO support was escalated with an Impella (75% CP) (BiVent group). Mean age was 60.88 ± 9.8 and 98 (80%) patients were male. Survival rates were similar in both groups (hospital survival: BiVent 40.6% and vaECMO 33%, p=0.52; 12-month survival BiVent 37.5% and vaECMO 31.9%, p=0.67). After adjustment for baseline difference with propensity scoring matching analysis, survival rates were significantly better in the BiVent group (hospital and 12-month survival: BiVent 50% and vaECMO 17%, p=0.03 (Figure 1). Vasopressor doses and lactate levels decreased significantly more firmly in the BiVent group within 72 h on biventricular support compared to vaECMO (p<0.05). Moreover, the patients in the BiVent group demonstrated a greater functional recovery of the LV at 96 hours after admission compared to vaECMO patients (Figure 2).

Conclusions

Impella on top of vaECMO improves short- and long-term survival in patients with post-cardiac arrest refractory cardiogenic shock leading to a better restoration of the left ventricle and end organ function.
Relation between high-sensitivity troponin i serum levels and myocardial ischemia in patients with suspected chronic coronary syndrome: the RESET-MI study
Authors: De Vita A , Bruno I , Baroni S , Moretti G , Tempestini F , Telesca A , Tremamunno S , Felici T , Verrillo A , Lamendola P , Cambise N , Liuzzo G , Crea F , Giordano A , Lanza G A
Published: November 2023

Background

Previous studies showed that exercise may increase cardiac troponin serum levels; however, whether exercise-induced myocardial ischemia influences the exercise-induced increase of troponin levels remains debatable.

Methods

We prospectively enrolled consecutive patients undergoing an elective stress myocardial perfusion scintigraphy (MPS) because of a clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups according to the evidence and degree of stress-induced myocardial ischemia at MPS: 1) Group 1, no ischemia (≤4% of myocardium); 2) Group 2, mild ischemia (5-10%); 3) Group 3, moderate-to-severe myocardial ischemia (≥10%). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T0) and 1 hour (T1) and 4 hours (T2) after the stress test. A successive evaluation of patients was performed at 24 months.

Results

One-hundred consecutive patients (64 males; age 65.5±9.5 years) were enrolled in the study. An exercise stress test and a dipyridamole stress test were performed in 81 and 19 patients, respectively. Serum hs-cTnI concentrations significantly increased after stress test, compared to baseline, in the whole population, from (median, interquartile range) 3.9 (2.5-6.1) ng/L at T0, to 4.2 (2.8-7.3) ng/L at T1 (p<0.001) and 6.7 (3.8-14.1) ng/L at T2 (p<0.001 vs. both T0 and T1). The increase in hs-cTnI did not significantly differ between the 3 groups (p=0.35; Figure). The increase was significant after both exercise (+54.5%) and dipyridamole (+18.2%), although the increase was greater after exercise (p=0.002). Heart rate achieved during the test was the strongest determinant of cTnI increase after the stress test (p < 0.001).

Conclusions

In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and severity of myocardial ischemia and is mainly related to myocardial work, as indicated by heart rate achieved during the stress test.Figure
Phenotyping coronary plaque by computed tomography in premature coronary artery disease
Authors: Rahoual G , Zeitouni M , Charpentier E , Ritvo P G , Rouanet S , Procopi N , Boukhelifa S , Charleux P , Guedeney P , Kerneis M , Barthelemy O , Silvain J , Montalescot G , Collet J P
Published: November 2023

Background

Premature coronary artery disease (CAD) is an aggressive chronic disease with multiple recurrences mostly related to the progression or complication of new coronary lesions.

Purpose

To compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA).

Methods

106 individuals with premature CAD were matched by age, sex, smoking status, family history of CAD, and dyslipidemia with 106 controls free of overt cardiovascular disease. CCTA were standardly analyzed for CAD-RADS score, plaque composition (calcified, partially or non-calcified), and the following four high-risk plaque (HRP) features : spotty calcification, positive remodeling, napkin-ring sign, and low-attenuation plaque.

Results

At least one coronary plaque was found in 85% of individuals with premature CAD vs. 62% of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1% vs. 30.2%, p<0,001), as well as spotty calcification (42.5% vs. 17.9%, p<0.001), positive remodeling (41.5% vs. 9.4%, p<0.001), low-attenuation plaques (24.5% vs. 3.8%, p<0.001) and napkin-ring sign (1.9% vs. 0.0%) (Figure 1). Individuals with premature CAD exhibited an average of 2.2 (±2.7) HRP features per person, while the control group displayed 0.4 (±0.8) HRP per person (p<0.001). Within a median follow-up of 24 [16,34] months, 24 ischemic recurrent events occurred in 24 individuals, all in the in premature CAD group. Individuals with premature CAD and recurrent ischemic event had more high-risk plaque features (4.3±3.9) than those without ischemic recurrence (1.5±1.9). They displayed more frequently non-calcified plaques (91.7% vs. 57.3%) with positive remodeling (75.0% vs. 31.7%) and low-attenuation plaques (45.8% vs. 18.3%) as compared to those without ischemic recurrence (Figure 2).

Conclusions

Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of high-risk plaque features, contributing to disease progression with multiple recurrences in this setting.HRP features in study populationHRP according to ischemic recurrence
Acute exposure to PM2.5 promotes arterial stiffening by down-regulating serine and trans-4-hydroxyproline dependent pathways - results from an Asutralian cohort metabolomic study
Authors: Fathieh S , Kott K , Vernon S , Patrick E , Yang J , Astell-Burt T , Figtree G
Published: November 2023

Background

Exposure to air pollution is known to have both acute and chronic adverse effects on the cardiovascular system, but the pathophysiology of cardiac complications associated with air pollutants remains poorly understood; however, utilizing high-throughput omic studies can provide a better understanding of involved biomarkers, which may ultimately help identify, prevent, and discover drugs for high-risk populations.

Purpose

Utilising the targeted metabolomics in the BioHEART Discovery cohort we set to identify metabolites implicated in cardiovascular diseases in relation to acute exposure to air pollution.

Method

We included 1002 clinically stable study participants who were referred for a clinically indicated CT coronary angiogram (CTCA) between November 2015 and March 2020. Coronary artery disease (CAD) burden was assessed using coronary artery calcium scores (CACS) and the Gensini scores. We performed targeted metabolomic analysis of hydrophilic metabolites in positive and negative ionisation using Liquid chromatography–mass spectrometry (LC-MS). Acute air pollution exposure was defined as the daily average and maximum climatic (temperature and humidity) and particulate matter levels on the day of and up to 3 days prior to enrollment, based on the patient's postcode. Using K-means clustering, we grouped the population based on their overall maximum PM2.5 exposure. We also used PCA and sPLS-DA to cluster and perform variable importance selection.

Results

PCA demonstrated good separation between the high vs normal PM2.5 exposure groups in PC1-PC2 dimensions, with scores of 29.5% and 8.5% respectively [Figure 1]. All of the top five metabolites detected by sPLS-DA, including Trans-4-Hydroxyproline and Serine, demonstrated down-regulation in the high exposure cohort.Trans-4-Hydroxyproline is involved in the urea cycle and arginine and proline metabolism, while Serine is a marker of glycine, serine, and threonine metabolism. Previous studies [1] have shown that these metabolites have an inverse correlation with carotid-femoral pulse-wave velocity (PWV), an indirect measure of arterial stiffness and an indication of increased risk of all-cause mortality and cardiac morbidity [2].

Conclusion

Here we have demonstrated that acute exposure to PM2.5 can potentially result in a shift in metabolimic signature that is associated with vascular dysfunction.PCA clusters demonstrating a good separaComparing Trans-4-HYP and Serine
Predictors of coronary atherosclerosis in middle-aged and older endurance athletes
Authors: Berge K , Aengevaeren V L , Mosterd A , Velthuis B K , Eijsvogels T M H
Published: November 2023

Background

Exercise improves cardiovascular health, but emerging evidence indicates that coronary atherosclerosis is more prevalent in middle-aged and older endurance athletes than sedentary peers. It has been shown that greater lifelong exercise volumes and exercise training at a very vigorous intensity are associated with higher coronary artery calcification scores (CACS). Nevertheless, the underlying mechanisms responsible for accelerated coronary atherosclerosis in veteran athletes are unknown and largely unexplored.

Purpose

To identify predictors of CACS in middle-aged and older endurance athletes.

Methods

Cardiac CT scans were performed on 284 middle-aged and older male athletes of the MARC-2 study to assess CACS. Participants were stratified to CACS=0, CACS: 1-100, CACS: 101-400, or CACS >400. Participant characteristics, traditional cardiovascular risk factors, biomarker concentrations, nutrition characteristics, perceived stress scores, and usage of immune-modulating and performance-enhancing drugs were compared across CACS subgroups, whereas linear regression with backward elimination was used to determine associations with ln(CACS + 1).

Results

Participants were 60.0 [Q1-3 56.3-66.0] years old, had a weekly training load of 25.7 [16.9-35.2] MET-h, BMI of 24.5 [22.9-26.7] kg/m2, systolic blood pressure (SBP) of 140±18 mmHg, and reported 0.3 [0.0-8.0] smoking pack years. CACS was 31 [0-132], with 29% of athletes having CACS of 0, 40% 1-100, 18% 101-400, and 13% >400. Participants with CACS >400 were older (p<0.001), had higher SBP (p=0.004), had smoked more pack years (p=0.003), and had more often a family history of cardiovascular disease (p=0.001), compared to lower CACS groups. After backward selection, our final multivariable model (R2=0.12) revealed that alcohol intake (p=0.021), smoking pack years (p=0.027), and SBP (p=0.004) had a positive relationship with CACS, while total fat intake (p=0.005) had an inverse relationship with CACS. We also found a significant interaction effect between weekly training load with alcohol consumption (p=0.017) and SBP (p=0.028), indicating that the association of alcohol and SBP with CACS was stronger for individuals performing higher exercise volumes.

Conclusion

Alcohol consumption, smoking history, and SBP were the strongest predictors of CACS in our cohort of middle-aged and older male endurance athletes, whereas the effect size of alcohol consumption and SBP on CACS was larger for participants with higher training loads. Our findings indicate that high exercise volumes do not eliminate the cardiovascular risk associated with an unhealthy lifestyle.
Association between coronary microcirculatory resistance, left atrial strain and heart failure with preserved ejection fraction in patents with ischemia and non-obstructive coronary arteries (INOCA)
Authors: Legutko J , Szolc P , Niewiara L , Stapor M , Kleczynski P , Tekieli L , Rzeznik D , Diachyshyn M , Bernacik A , Zmudka K , Guzik B
Published: November 2023

Background

Coronary microvascular dysfunction (CMD) plays an important role in the pathogenesis of ischemia and non-obstructive coronary arteries (MINOCA) and heart failure with preserved ejection fraction (HFpEF). Left atrial strain (LAS) evaluation by transthoracic echocardiography (TTE) was proposed as a new diagnostic method to assess left ventricular dysfunction and HFpEF. However, its implementation into the diagnostic workup of INOCA has never been evaluated.

Purpose

The primary objective of the study was to evaluate the frequency of HFpEF in patents with INOCA using LAS as a marker of left ventricular dysfunction. The secondary objective was to assess the association between coronary microcirculatory resistance, LAS and HFpEF.

Methods

MOSAIC-COR is a single-center, prospective, observational registry of patents with INOCA diagnosed with pressure wire-based comprehensive coronary physiology assessment and provocative test with acetylcholine. In the absence of significant coronary artery stenosis CFR and IMR was calculated in LAD using thermodilution to assess CMD. Serum levels of NT-proBNP and LAS indexes (LA reservoir strain, LA contraction strain, LA conduit strain) were calculated to diagnose HFpEF according to EACVI consensus document published in the year 2022.

Results

We assessed 63 patients with INOCA, 35% male. Median age was 67 years. Baseline clinical characteristics of the study group is presented in Table. Coronary microvascular dysfunction was diagnosed in 37 patents (59%) and HFpEF was diagnosed in 15 patents (24%) . Worse left atrium reservoir strain was connected with higher value of IMR (P < 0.001) and higher level of NT-proBNP (P < 0.001). Worse left atrium conduit strain was connected with higher value of IMR (P = 0.04). Left atrium contraction strain was connected with higher level of NT-proBNP (P < 0.001) (Figure).

Conclusions

Confirmation of HFpEF in 24% of INOCA opens new therapeutic option for this group of patents. Association between microvascular resistance and left atrium strain may reflect pathophysiological connection between INOCA and HFpEF. Implementation of SGLT-2 inhibitors in the treatment of CMD with and without INOCA require further evaluation.
PSRC1 rs599839 G allele may promote protection from coronary artery disease in a Madeira Island population
Authors: Sousa F , Mendonca M , Sa D , Temtem M , Santos M , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Drumond A , Sousa A C , Dos Reis R P
Published: November 2023

Previous research associates the PSRC1 gene on the chromosomal locus 1p13.3 with coronary artery disease (CAD). Specifically, the A wild allele of the PSRC1 rs599539 A>G was identified as a risk allele for CAD, and the mutated G minor allele with a reduced risk of CAD. However, the underlying genetic mechanism is not yet fully understood and is controversial in other populations.

Aim

To investigate the association of rs599839 A>G variant with CAD risk and lipid profile in a Portuguese population from Madeira Island.

Materials and Methods

We performed a case-control study including 3161 participants, 1724 patients with CAD (78.7% male) and 1437 controls (76.3% male). Coronary patients were recruited from the Madeira Central Hospital, and controls were from the normal population. PSRC1 was genotyped by TaqMan allelic discrimination assay (Applied Biosystems, 7300 Real-Time PCR). Pearson´s Chi-squared test evaluated the association between CAD-genotypes and the t Student test for genotypes-lipid levels.

Results

PSRC1 rs599839 A>G variant was within Hardy -Weinberg equilibrium. The wild dominant model (AA+AG) conferred a trend for CAD risk (OR=1.16; p=0.414), and the mutated dominant model (GG+GA) presented slight protection for CAD susceptibility. However, the minor G (protector) allele was associated with low levels of total cholesterol (p=0.003) and LDL-cholesterol (p=0.004).

Conclusions

This finding is consistent with previous reports indicating a decrease in LDL-C and total cholesterol levels in carriers of the minor allele G of rs599839. Recent research refers that this allele could affect PSRC1 expression, resulting in lower levels of LDL cholesterol and reduced risk of CAD. In contrast, the A wild allele is associated with high LDL levels. PSRC1, lipid, and CAD risk is a complex topic involving genetic, epigenetic and environmental factors.
Optimal medical management vs. percutaneous coronary intervention for patients with stable angina: from nation-wide Korean Insurance data
Authors: Jo S H
Published: November 2023

Background

To investigate whether percutaneous coronary intervention (PCI) on top of optimal medical therapy (OMT) is superior to OMT only in patients with stable angina.

Methods

We enrolled patients with stable angina from 2005-2010 using the Korean national Insurance data. 68621 patients were candidate with stable angina and finally 5673 patients in PCI plus OMT and 5673 in OMT were selected with 1:1 propensity matching.

Results

Primary endpoint, a composite of myocardial infarction (MI), stroke, cardiac death and revascularization was significantly more common in PCI than in OMT group, 13.5/1000 vs. 11.5/1000 person year with HR, 1.182(1.059-1.319) (P=0.0027). Individual outcome rate of MI, revascularization and cardiac death was higher in PCI group then in OMT group , 2.9 vs. 2. (HR [1.376 1.085-1.744], p=0.0085), 30.3 vs. 8.1 (HR 3.638 [3.269-4.049], p<0.001) and 4.8 vs 3.4/1000 person year (HR 1.397 [1.155-1.69], p=0.0006) respectively. No difference was found in stroke rate. In subgroup analysis same trend of more rate of event in PCI group was detected.

Conclusions

PCI was associated with higher rate of primary endpoint of MI, stroke, cardiac death as compared to OMT only in patients with stable angina.Primary endpoint between PCI vs. OMT
A predictors for 10-year mortality and clinical events in patients with chronic coronary total occlusion lesion
Authors: Kim K , Choi B G , Rha S W
Published: November 2023

Background

Despite advances in cardiovascular intervention techniques and devices, the treatment of patients with chronic coronary total occlusion CTO lesions is challenging yet. We evaluated predictors of 10-year mortality and clinical events in patients with CTO lesions in this study.

Methods

This study is a single-center, prospective, all-comer registry designed to reflect "real world" practice since 2001. Of a total of 1,672 consecutive patients were diagnosed with CTO lesions by coronary angiogram. The primary endpoints were all-cause death or major adverse cerebral, and cardiac events (MACCE) defined as the composite of all-cause death, myocardial infarction (MI), any coronary revascularization, and stroke up to 10 years. We derived for final results, from survival analysis by Kaplan-Meier and Cox-proportional regression analysis.

Results

In this study, males were 1,255 (75.1%), and the mean age was 65.2±10.9. Also, a total of 660 patients had received a successful PCI for CTO lesions at enrollment. A total of 267 patients was heart failure. Ten years of clinical follow, MACCE occurs in 407 cases (56.6%), all-cause death in 152 cases (18.5%), cardiac death in 87 cases (9.9%), myocardial infarction (MI) in 54 cases (7.7%), any revascularization of 251 cases (30.7%), and stroke of 41 cases (6.3%) by Kaplan-Meier analysis. In a multiple Cox-proportional regression analysis, a prior myocardial infarction, reduced LV ejection fraction less than 50%, chronic kidney disease, multi-vessel disease had increased a risk of MACCE and the use of statin, and aspirin had reduced a risk of MACCE. Also, an aging, prior MI, reduced LV ejection fraction less than 40%, and multi-vessel disease had increased a risk of all-cause death and the use of statin, and renin-angiotensin system inhibitors, nitrates, statin, and aspirin had reduced a risk of risk of all-cause death. However, PCI for CTO lesions could not reduce both of MACCE and all-cause death.

Conclusions

The study found that a prior myocardial infarction, reduced LV ejection fraction, chronic kidney disease, and multi-vessel disease were associated with an increased risk of MACCE, while the use of statins and aspirin reduced the risk of MACCE. Furthermore, PCI for CTO lesions did not reduce the incidence of MACCE or all-cause death. These findings highlight the need for further research and development of more effective treatment strategies for patients with CTO lesions.
Anatomic vs ischemia-driven strategies for percutaneous coronary revascularization in chronic coronary syndrome: a network meta-analysis
Authors: Giacobbe F , Valente E , Giannino G , Yip H C , Di Vita U , Carmagnola L , De Filippo O , Bruno F , Iannaccone M , Biondi Zoccai G , Gasparini M , Pocock S , Escaned J , De Ferrari G M , D'ascenzo F
Published: November 2023

Background

In patients with chronic coronary syndrome (CCS), percutaneous coronary intervention (PCI) stands out as an alternative to optimal medical therapy (OMT). The decision to perform a PCI may be driven either by angiographic evaluation or ischemia assessment, thus depicting different potential strategies which have not yet been compared.

Purpose

To compare different strategies of percutaneous revascularization (angiography, non-invasive ischemia and coronary physiology (FFR or iFR) guided) in order to identify a potential benefit of PCI depending on the guidance chosen in CCS.

Methods

Randomized controlled trials (RCTs) comparing OMT vs. PCI-angio guided or vs. PCI guided by non-invasive or invasive ischemia assessment were included and compared via network metanalysis. Major adverse clinical events (MACE), as defined by each included trial, were the primary end point, while cardiovascular (CV) death, myocardial infarction and subsequent revascularization the secondary ones.

Results

18 studies, encompassing 17512 patients, were included followed up for a weighted mean of 3,5 years. PCI guided by non-invasive assessment of ischemia entailed a reduced risk of myocardial infarction compared with OMT (HR 0.61:0.37-0.94, CI 95%). This strategy ranked best in preventing CV death. In addition, PCI guided by ischemia defined either invasively or not was associated with a reduced risk of MACE as compared with OMT. iFR and FFR guided approaches showed the highest probability of performing best. Finally, physiology guided PCI ranked best in reducing subsequent urgent revascularizations.

Conclusions

For patients with CCS, ischemia-guided PCI, either by invasive or noninvasive assessment, resulted in a reduced risk of MACE as compared with OMT. PCI guided by a non-invasive assessment of ischemia reduced risk of myocardial infarction compared to OMT, while PCI guided by iFR or FFR showed the highest probability of reducing the need of subsequent revascularization. These strategies showed the highest probability of reducing MACE and CV death.Bar plot of best treatmentPRISMA diagram and Network Plot
Association between quantitative flow ratio and non-target-vessel-related events before planned staged percutaneous coronary intervention in patients with acute coronary syndrome
Authors: Baer S , Kavaliauskaite R , Otsuka T , Ueki Y , Haener J D , Siontis G C M , Lanz J , Praz F , Pilgrim T , Stortecky S , Losdat S , Windecker S , Raeber L
Published: November 2023

Introduction

The optimal timepoint of non-target-vessel (non-TV) percutaneous coronary intervention (PCI) among patients with acute coronary syndrome (ACS) remains a matter of debate. Quantitative Flow Ratio (QFR) is a novel, non-invasive, vasodilator-free method to assess the hemodynamic significance of coronary stenoses.

Purpose

We aimed to investigate the association between non-TV QFR and non-TV-related events occurring prior to planned staged PCI (sPCI), to derive first conceptual knowledge, whether QFR could be useful to determine the optimal timepoint of sPCI.

Methods

Between 2009-2017, all ACS patients scheduled to undergo out-of-hospital sPCI within 6 months from index PCI at Bern University Hospital, Switzerland, were eligible for QFR measurement. The primary endpoint was non-TV myocardial infarction (MI) and urgent (unplanned) non-target-vessel PCI occurring before planned sPCI. QFR was measured using the index presentation angiogram in the non-TV planned for sPCI. The association between lowest QFR per patient (per 0.1) and the occurrence of the primary endpoint was assessed with a multivariable Cox proportional hazards regression including a penalized spline term for QFR and the variables age, sex, diabetes mellitus, renal failure, and diameter stenosis (DS%) (per 5%).

Results

Out of 8657 ACS patients, 1432 were scheduled to undergo sPCI, and 1093 patients (1262 vessels) were analyzed by QFR. At baseline, mean QFR was 0.73±0.17 and mean DS% 54.8±11.2%. sPCI was planned with median 28 days after the index PCI. In multivariable analysis (1018 patients, 51 events), there was no independent association between QFR and the primary endpoint (HR 0.87, 95% CI 0.69-1.05, p=0.125; QFR non-linear p=0.648).

Conclusions

In this cohort study of ACS patients scheduled to undergo out-of-hospital sPCI within median 28 days, QFR did not emerge as a predictor of non-TV events prior to planned sPCI. Thus, this study does not support the concept, that QFR would be helpful to determine the optimal timepoint of sPCI.Figure 1.Primary endpointTable 1.Cox model primary endpoint
Clinical outcomes of deferred lesions by IVUS versus FFR-guided treatment decision: the FLAVOUR trial substudy
Authors: Lee J M , Kim H , Hong D , Nam C W , Doh J H , Lee B K , Kim W , Kang J , Ahn S G , Yoon M H , Kim U , Shin E S , Koo B K , Wang J , Hahn J Y
Published: November 2023

Background

There is limited data regarding the safety of deferral of percutaneous coronary intervention (PCI) based on intravascular ultrasound (IVUS) findings. Current study sought to compare the prognosis between deferred lesions based on IVUS and FFR (fractional flow reserve)-guided treatment decision.

Methods

Study population was derived from FLAVOUR trial which is a multinational, open-label, randomized, and non-inferiority trial that compared 2-year clinical outcomes between IVUS and FFR-guided treatment decision using predefined criteria. In both IVUS and FFR groups, vessels were classified into deferred or revascularized vessels, and patients into those with or without deferred lesion. Vessel-oriented composite outcomes (VOCO) (cardiac death, target-vessel myocardial infarction, or target-vessel revascularization) in deferred vessels and patient-oriented composite outcomes (POCO) (death, myocardial infarction, or any revascularization) in patients with deferred lesion were compared between IVUS and FFR group.

Results

A total of 1682 patients and 1820 vessels were analyzed. At 2 years, there is no difference in cumulative incidence of VOCO in deferred vessels between IVUS and FFR groups (3.8% vs. 4.1%; hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.47-1.75; P=0.771). The risk of VOCO was comparable between deferred and revascularized vessels following both IVUS (3.8% vs. 3.5%; HR 1.09; 95% CI 0.54-2.19; P=0.813) and FFR-guided treatment decision (4.1% vs. 3.6%; HR 1.14; 95% CI 0.56-2.32; P=0.715). In comparison of POCO in patients with deferred lesion, there was no significant difference between IVUS and FFR groups (6.2% vs. 5.9%; HR 1.05; 95% CI 0.61-1.80; P=0.856).

Conclusion

In patients with intermediate coronary artery stenosis, deferral of PCI based on IVUS-guided treatment decision showed comparable risk of clinical events with FFR-guided treatment decision.
High resting coronary flow velocity and reduced coronary flow velocity reserve independently predict worse survival in diabetic patients without inducible ischemia and normal left ventricular function
Authors: Meola L , Cortigiani L , Ciampi Q , Gaibazzi N , Rigo F , Wierzbowska-Drabik K , Rodriguez-Zanella H , Bovenzi F M , Picano E
Published: November 2023

Background

High resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery (LAD) can be easily assessed with transthoracic echocardiography (TTE) and is a predictor of worse survival.

Purpose

In this study, we sought to assess the relationship between resting CFV, coronary flow velocity reserve (CFVR), and outcome in patients without inducible regional wall motion abnormality during stress echo (SE).

Methods

In a prospective multicenter study design, we enrolled 6,887 patients (age 65±11 years, 3,838 men, 1,963 diabetics), with left ventricular ejection fraction (LVEF) ≥50% referred for SE. Recruitment (years 2004-2022) involved 7 accredited laboratories, with inter-observer variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV (abnormal value >32 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. Coronary flow velocity reserve (CFVR, abnormal value ≤2.0) was assessed with dipyridamole. All-cause death was the only end-point.

Results

The mean CFV of LAD was 30±11 cm/s. The mean CFVR was 2.37±0.58. During a median follow-up of 6.0±4.2, 1,015 (15%) patients died. At Cox analysis, resting CFV >32 cm/s independently predicted mortality together with CFVR <2, age, diabetes, previous myocardial infarction, history of coronary surgery and LVEF. Resting CFV allowed effective risk stratification either in diabetics and nondiabetics although the difference in survival based on resting CFV was more marked in the former (Figure). In addition, it added significant (p<0.0001) prognostic information to CFVR result in the diabetic, but not in the non-diabetic population (Figure).

Conclusion

High resting CFV with TTE in mid-distal LAD predicts worse survival in patients without inducible ischemia. The value is independent and additive to CFVR in diabetic patients. The combination of high resting CFV-low CFVR is associated with worse survival.
Functional Syntax score based on quantitative flow ratio vs. anatomical Syntax score
Authors: Gkini K P , Terentes-Printzios D , Oikonomou D , Dima I , Gardikioti V , Aznaouridis K , Tsioufis K , Vlachopoulos C
Published: November 2023

Background/Introduction

Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score takes into consideration only the anatomy of the coronary network, while the Functional Syntax Score based on Quantitative Flow Ratio (FSSQFR) combines all the information derived from both anatomy and physiology of coronary arteries.

Purpose

To investigate the level of agreement between anatomical SYNTAX Score I (SS) and FSSQFR and its possible impact on risk re-stratification of patients and on revascularization options.

Methods

We performed an offline QFR analysis in consecutive patients who underwent coronary angiography in a single Greek center. A total of 410 patients with accountable FSSQFR were included. The latter was counted by summing the individual points only of physiologically signiﬁcant lesions (vessel QFR ≤0.8). Patients were divided into low-, intermediate- and high risk according to SS and FSS with the same cutoff. The primary endpoint was the estimation of the predictive value of FSSQFR for the composite outcome of cardiovascular death, myocardial infarction and ischemia-driven revascularization at follow-up.

Results

FSSQFR and SS were estimated for all patients. After calculating the FSSQFR, 12% (48/410) of study patients changed the risk group. Most of them moved from higher-risk group by SS to lower-risk group and only three of them presented the opposite movement. Moreover, 5.9% (24/410) of patients, for whom coronary artery bypass grafting would be recommended according to SS, converted to favor percutaneous coronary intervention after FSSQFR calculation. After a median 30.2 (25.7-33.7) months follow-up period, the cumulative incidence of a composite of cardiac death, myocardial infarction or ischemia-driven revascularization was 4.6%, 10.7%, and 24.1%, in the low, intermediate, and high FSSQFR group correspondingly (log-rank P<0.001) (Figure 1). After multivariate regression analysis, FSSQFR was an independent predictor of the primary endpoint after adjustment for age, gender, smoking, and hypertension (adjusted OR: 1.08 [95% CI, 1.05–1.12]; P<0.001). The area under the curve for FSSQFR to predict the 2-year composite endpoint was higher than that of the classic anatomic SYNTAX score (0.711 vs. 0.706; p<0.001) (Figure 2).

Conclusions

In our study, FSSQFR found to be an independent predictor of higher cardiovascular adverse events. Also, compared with SS, FSSQFR signiﬁcantly improved risk classiﬁcation of patients with coronary disease widening the possible therapeutic options.
Cost-effectiveness analysis of PCI in focal and diffuse coronary artery disease
Authors: Munhoz D M , Hlatky M , Collison D , Berry C , Oldroy K , Mizukami T , Sakai K , Storozhenko T , Seki R , Bouisset F , Sonck J , De Bruyne B , Collet C
Published: November 2023

Aims

The pattern of CAD predicts angina relief after PCI. Our aim was to evaluate the cost-effectiveness of PCI in diffuse coronary artery disease (CAD) to deferral from PCI in these patients.

Methods

This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The pullback pressure gradient (PPG) was calculated to differentiate focal from diffuse CAD.

Healthcare resource use associated with the index hospitalization and with follow-up outpatient visits, medications, was recorded prospectively. We did not discount costs because of the limited follow-up period. Costs of procedures and follow-up consultations were derived from Healthcare Resource Group reference costs and drug costs from the National Health Service (NHS).

Quality-adjusted life-years (QALYs) were derived from health-related quality of life and survival during the 3-month time horizon of the trial. Quality-of-life indexes (utilities) were evaluated at baseline and 3 months with the European Quality of Life–5 Dimensions (EQ-5D) instrument with UK weights scaled from 0 (death) to 1 (perfect health). The overall QALYs for each patient were estimated as the area under the curve determined by the utility values at baseline and 3 months. We computed confidence intervals for differences in costs and QALYs and in the incremental cost-effectiveness rate (ICER) using the bootstrap technique with the percentile method with 10 000 replications. A Markov model was used to simulate deferral of diffuse disease from PCI and not using PPG to select treatment. Probabilistic sensitivity analysis was undertaken to test the robustness of results to parameter uncertainty.

Results

Patients who underwent PCI for focal CAD had higher EQ-5D index values at follow-up (0.89 ± 0.18 vs 0.76 ± 0.28, p=0.004) and higher QALYs after 3 months follow-up (0.19 ± 0.06 vs 0.21 ± 0.04, p=0.022). Mean cumulative costs were £1574.3 ± 230.5 and significantly higher in patients treated for diffuse CAD as compared to patients treated for focal CAD (£1697 ± 293.4 vs £1393 ± 264.3; p<0.001). The ICER was £7746/QALY (95% CI 5024 – 11007). PCI in focal CAD saved £1522.2/QALY when compared to PCI in diffuse CAD (£7009.2 ± 1919.4 /QALY vs. £8531.4±2753.4 /QALY, p< 0.001). Deferring 30% of the diffuse CAD patients from PCI to optimized medical therapy would save £673.8/QALY (£7072.2 ± 1730.147 /QALY vs. £7746 ± 1943.5/QALY, p< 0.001).

Conclusion

PCI is more cost-effective in focal than diffuse CAD. Treatment of diffuse CAD results in worst QALYs and costlier procedures. Every 5% of the diffuse CAD patients that were deferred from PCI saved aproximately £100/QALY. Further trials are needed to determine if the cost-effectiveness of PCI can be improved by deferring patients with diffuse CAD.Quality of life in focal and diffuse CADCost-effectiveness focal vs diffuse CAD