bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of venoarterial extracorporeal membrane oxygenation in patients with acute myocardial infarction complicated by cardiogenic shock
Authors: Tao M , Gupta S , Gier C , Pastena P , Frye J , Figueira T , Price J , Bench T , Rahman T , Mann N , Tam E
Published: October 2024

Background

Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) continues to portend poor clinical prognosis and remains a major cause of morbidity and mortality. Although venoarterial (VA) extracorporeal membrane oxygenation (ECMO) is frequently used in the treatment of AMI-CS, studies evaluating its benefit compared to percutaneous ventricular assist devices (pVAD) or standard medical therapy in this patient population have yielded conflicting results.

Purpose

The goal of this meta-analysis is to evaluate the use of ECMO compared to either pVAD or medical therapy with or without intra-aortic balloon counterpulsation (IABP) in patients presenting with AMI-CS.

Methods

A database search was performed for studies reporting on the association of ECMO compared to pVAD or medical therapy with or without IABP with clinical outcomes in patients with AMI-CS. The endpoints of interest were 30-day all-cause mortality and long term all-cause mortality. The databases searched included Pubmed, Web of Science, and Embase. The search was not restricted by time or publication status. Registry studies were excluded from this analysis.

Results

A total of 8 studies with 937 participants (447 treated with ECMO, 243 treated with pVAD, 247 treated with medical therapy with or without IABP) met inclusion criteria. Mean age was 63 years old, 80.5% were men, mean left ventricular ejection fraction was 26%, mean follow-up was 6.3 months (ranging 1-12 months).

Treatment of AMI-CS patients with ECMO was not associated with lower risk of 30-day all-cause mortality compared to pVAD or standard medical therapy with or without IABP placement (OR 1.29, 95% CI 0.87-1.90; p=0.21; OR 0.58, 95% CI 0.25-1.35; p=0.13). Heterogenetic was low to moderate for each subgroup. Test for subgroup differences did not demonstrate statistically significant differences in the results for pVAD and for standard medical therapy with or without IABP (p=0.10, I2=64.1%). Compared to pVAD, ECMO was not associated lower risk of long-term mortality (OR 1.27, 95% CI 0.85-1.90; p=0.24). The heterogeneity for this analysis was low (I2=0%).

Conclusion

In patients presenting with AMI-CS, use of VA-ECMO is not associated with lower risk of mortality compared to pVAD or standard medical therapy with or without IABP placement. The risks and benefits of ECMO should be carefully considered compared to other forms of temporary mechanical circulatory support.Figure 1
Hemodynamic effects of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock waiting heart transplant
Authors: Bellini V , Fatori D , De Mateo F G , Loureiro G J F , Macatrao M F , Bernoche C , Kopel L , Lage S G
Published: October 2024

Background

The use of intra-aortic ballon pump (IABP) as a bridge therapy in patients with advanced heart failure (HF) and cardiogenic shock (CS) waiting heart transplant (HTx) remains under debate. IABP can be an available device to improve hemodynamic conditions of these patients until HTx.

Purpose

Evaluate the hemodynamic effects of IABP and its efficacy in patients with advanced HF and CS waiting HTx.

Methods

We retrospectively analyzed from a single center intensive care unit, between 2009 and 2020, patients with advanced HF with optimized intravenous drugs that required IABP placement before HTx. Changes in oxygen central venous saturation (ScvO2), arterial lactate, renal function, and use of vasoactive drugs before and 96 hours after IABP insertion were evaluated. Patients with acute myocardial infarction and implant of ventricular assist device before HTx were excluded.

Results

A total of 199 patients (mean age 46,5 ± 12 years) were included. Median time of IABP onset to HTx was 20 days. Mean left ventricle ejection fraction was 23,5 ± 5,9%, 53,7% of patients had moderate to severe right ventricular dysfunction and the most frequent etiology was Chagas disease (47,2%, n=94). Before the IABP placement, 97,47% of patients were using dobutamine, 19,29% milrinone, 58,08% nitroprusside and 17,7% norepinephrine. Clinical and laboratory data were compared before and 96 hours after IABP therapy. ScvO2 increased from 49,9% to 66,85% (p<0,001), lactate decreased from 21,91 mg/dl to 12,6 mg/dl (p<0,001), creatinine decreased from 2,04 mg/dL to 1,72 mg/dL (p=0,301) and urine output increased from 1690,12 mL/24h to 2193,12 mL/24h (p<0,001). These differences were maintained until the day before HTx. Use of nitroprusside increased from 58,08 to 63,59% (p=0,154), and the use of norepinephrine decreased from 17,7% to 6,63% (p<0,001).

Conclusion

IABP improves tissue perfusion, renal function, and hemodynamic status in patients with advanced HF and CS and can be an effective method of circulatory support as a bridge therapy to HTx.Laboratory data pre and post-IABPVasoactive Drugs pre and post-IABP
Organ perfusion pressure: a significant predictor of outcomes in cardiogenic shock
Authors: Bocchino P P , Frea S , Bertaina M , Sorini Dini C , Briani M , Garatti L , Colombo C , D'ettore N , Marini M , Pagnesi M , Sacco A , Pappalardo F , Tavazzi G , Morici N , De Ferrari G M
Published: October 2024

Background

Cardiogenic shock (CS) is an ominous condition with a high mortality rate. The diagnosis of CS relies upon signs and/or symptoms of end-organ hypoperfusion. However, the combination of hypoperfusion and systemic congestion poses a serious risk and significantly increases mortality rates in critically ill patients.

Purpose

This study evaluated organ perfusion pressure (OPP), calculated as mean arterial pressure (MAP) minus central venous pressure (CVP), as a predictor of outcomes in CS.

Methods

All consecutive patients with CS related to acute myocardial infarction (AMI-CS) or acutely decompensated heart failure (ADHF-CS) enrolled in the multicenter Altshock-2 registry between January 2020 and November 2023 were selected. Only patients with both OPP and primary endpoint data available were included in the analysis. The primary outcome was in-hospital all-cause mortality.

Results

316 patients fulfilled the inclusion criteria (mean age: 64±13 years, 62 [20%] females, mean left ventricular ejection fraction: 24%±10%, mean MAP: 71±16 mmHg, mean CVP: 12±6 mmHg). Mean OPP was 59.1±17.3 mmHg. In-hospital all-cause death occurred in 117 (37%) patients. In univariable analysis, higher OPP was associated with a significantly lower risk of in-hospital all-cause death both as a continuous variable (HR 0.981 per mmHg [95%CI 0.969-0.993], p-value=0.003) and dichotomized (HR 0.522 [95%CI 0.354-0.770], p-value=0.001) according to the optimal cut-off value of 59.5 mmHg identified by receiver operating characteristic curve analysis (specificity 66.4%, sensitivity 53.8%, area under the curve 0.61). OPP greater than 59.5 mmHg predicted significantly reduced risk of in-hospital all-cause death among ADHF-CS patients (HR 0.315 [95%CI 0.151-0.660], p-value=0.002), but not among AMI-CS patients (HR 0.628 [95%CI 0.392-1.007], p-value=0.054). After multivariable adjustment for significant clinical data available at first bedside assessment, namely age and Sequential Organ Failure Assessment score, higher OPP still predicted significantly lower risk of in-hospital all-cause death (HR 0.984 [95%CI 0.972-0.996], p-value=0.010). In univariable analysis, OPP was also associated with significantly increased long-term overall survival (p-value<0.001), but not with worsening renal function at 24 hours after CS onset, in-hospital length of stay or the composite of left ventricular assist device implantation or heart transplantation.

Conclusions

In this multicenter, observational, prospective study of patients hospitalized for CS, higher OPP on admission was associated with a significantly reduced risk of in-hospital all-cause death.
Correlation between short-term quality of life improvement and clinical outcomes - a post-hoc ISCHEMIA trial analysis
Authors: Caldonazo T , Kim J K , Heise R H , Rahouma M R , Harik L H , Redfors B R , Sandner S S , Gaudino M G
Published: October 2024

Background

Patients with symptomatic coronary artery disease (CAD) exhibit improvement in quality of life (QoL) after invasive management (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). However, it is not clear how QoL improvements after intervention are related to clinical outcomes.

Purpose

Using the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) population, we sought to assess the relationship between short-term QoL improvement and long-term clinical outcomes.

Methods

All participants in the ISCHEMIA trial who were randomized to the invasive arm and who had QoL scores available were included in the analysis. QoL improvement was calculated using the difference between the Seattle Angina Questionnaire (SAQ) score at baseline and at six months regarding randomization. The primary outcome was the trial-defined composite outcome (cardiovascular death, myocardial infarction, cardiac arrest or hospitalization for unstable angina/heart failure) and all-cause death. The secondary outcome was all-cause mortality. Median follow-up was 3.3 years. Cox proportional hazards models included clinically relevant demographic and angiographic covariates.

Results

After the exclusion of the conservative treatment arm and patients without QoL follow-up or covariate data, 1,577 patients were selected for the final analysis (Fig.1). The median baseline SAQ score was 74 (interquartile range, IQR: 60-88), the change in score at six months was 14 (IQR: 2-26), and 76.1% of patients experienced improvement in QoL. Six-month QoL improvement was not associated with a lower risk of the primary outcome (hazard ratio [HR]: 0.961, 95% confidence interval [CI], 0.920-1.005, p=0.081 – Table 1), but was associated with all-cause mortality (HR: 0.919, 95% CI, 0.859-0.982, p=0.013 – Table 1). In this population, increased age (HR: 2.370, 95% CI, 1.710-3.287, p<0.001, per 10 years) was also associated with higher risk of all-cause mortality.

Conclusions

Among invasive treated patients in ISCHEMIA trial, six-month QoL improvement was associated with a lower risk of long-term all-cause mortality, but not with a lower risk of major adverse events.Figure 1.Study population.
Investigating the influence of possible liver fibrosis on mortality in patients with coronary artery disease - a post-hoc ISCHEMIA trial analysis
Authors: Caldonazo T , Rahouma M R , Sandner S S , Redfors B R , Harik L H , Kirov H K , Richter M R , Doenst T D , Gaudino M G
Published: October 2024

Background

There is a plethora of studies demonstrating that comorbidities (e.g., diabetes and renal dysfunction) directly influence outcomes in patients undergoing PCI or CABG for coronary artery disease (CAD). Yet, liver dysfunction is not really included in current risk assessment beyond the presence of liver cirrhosis. Retrospective single center evidence now suggests that the presence of liver fibrosis may be an indicator of elevated risk. Using the FIB-4 score, where increasing values correlate with increaseing degrees of histological liver fibrosis, liver fibrosis could already be detected with all required laboratory values (AST, ALT, platelets) within normal range. In addition, the study suggests a beneficial effect of off-pump CABG when FIB-4 is elevated. This finding contradicts current randomized evidence, negating any difference between off and on-pump CABG. Since randomized trials always suffer from strong selection of low risk patients, it is conceivable that trial patients may primarily have low FIB-4 scores.

Purpose

To address the distribution of FIB-4 scores in a selected trial population with CAD (from the ISCHEMIA trial) and relate the degree of liver fibrosis reflected by the score to mortality.

Methods

The FIB-4 score was calculated for all patients. According to the standard classification, a value of greater than 1.2 reflects a 90% chance of the presence of histological liver fibrosis. The imapct of FIB-4 on late all-cause mortality was assessed as a continuous and categorical variable using maximally selected rank statistics determined FIB-4 cutoff. Cox regression model was peformed including the adjustment for the main CAD risk factors.

Results

Among 3735 included patients, 58.8% had a FIB-4 value above 1.2. Patients with higher FIB-4 score (cutoff= 1.64) were slighly older, presented higher prevalence of male sex, prior PCI and CABG, and prior history of atrial fibrillation and cerebrovascular disease. FIB-4 score was directly associated with higher risk of mortality when addressed as a continouos variable and as a categorical variable (Fig. 1). This relationship was evident in the overall population and in all subsets (PCI, CABG and no revascularization; Fig. 2).

Conclusions

The use of Fib-4 to determine the degree of liver fibrosis may be powerful to predict mortality in CAD populations which may not show any evident clinical signs of liver dysfunction. The Fib-4 distribution in this trial population, considered as selected and low risk, warrants investigating randomized trial populations having compared on- and off-pump CABG.Figure 1.Mortality: overall population.Figure 2.Mortality: by therapy subsets.
Coronary flow characteristics in cases with discordance between coronary flow reserve and the index of microvascular resistance in the assessment of coronary microvascular dysfunction
Authors: Shiono Y , Taniguchi M , Takeda J , Hikida R , Higashimoto N , Taruya A , Takahata M , Wada T , Ozaki Y , Kitabata H , Tanaka A
Published: October 2024

Background/Introduction

Coronary flow reserve (CFR) and the index of microvascular resistance (IMR) are commonly used for the diagnosis of coronary microvascular dysfunction, but the two indices can reveal discordance.

Purpose

The aim of this study was to investigate the mechanisms of the discordance between CFR and IMR.

Methods

Haemodynamic data from patients who underwent invasive coronary functional assessment using a guidewire equipped with pressure and temperature sensors was analysed. We performed vessel-based analysis, and classified vessels with reference to the criteria of IMR ≥25 and CFR <2.0 as pathological into four groups: normal IMR/normal CFR (Group 1: G1), abnormal IMR/normal CFR (Group 2: G2), normal IMR/abnormal CFR (Group 3: G3), and abnormal IMR/abnormal CFR (Group 4: G4).

Results

Of 249 vessels form 176 patients, 82 (33%) were classified into G1, 28 (11%) into G2, 94 (38%) into G3, and 45 (18%) into G4. Median and interquartile ranges of IMR of the four groups were 14.3 [10.7–18.9], 34.2 [29.8–45.1], 16.9 [12.7–19.7], and 30.7 [28.4–43.5] (P <0.001), respectively, and those of CFR were 3.21 [2.48–4.29], 2.73 [2.34–3.03], 1.27 [1.06–1.55], and 1.28 [1.07–1.67] (P <0.001), respectively (Figure).

In G2, hyperemic flow velocity was as low as G4 (1.97 [1.47–2.29] vs. 1.95 [1.41–2.50] sec-1, P=1.00), and the baseline flow velocity was lower than G4 (0.71 [0.49–0.85] vs. 1.44 [0.93–1.96] sec-1, P <0.001), leading to apparently normal CFR despite the diminished hyperemic flow.

In G3, the hyperemic (3.60 [2.77–4.73] vs. 1.95 [1.41–2.50] sec-1, P <0.001) and the baseline flow velocity (2.85 [2.19–3.92] vs. 1.44 [0.93–1.96] sec-1, P <0.001) were higher than G4, leading to apparently decreased CFR despite the maintained hyperemic flow.

Conclusion(s)

The discordance between IMR and CFR can be explained by decreased coronary flow in abnormal IMR/normal CFR, and by increased baseline coronary flow in normal IMR/abnormal CFR.
Comparison of fully angiography-derived versus a hybrid of angiography and pressure-wire-derived approach to assess coronary microvascular resistance: the OxAMI-Hybrid study
Authors: Chai J , Kotronias R , Benenati S , Chu M , Couch L S , Marin F , Langrish J , Channon K , Banning A , De Maria G L
Published: October 2024

Background

Despite growing evidence of its clinical implications, assessment of coronary microvascular dysfunction (CMD) remains limited in routine clinical practice. Hence, there is an increasing interest in angiography-derived indices to encourage assessment of CMD in the cardiac catheterisation laboratory. We investigate here a novel approach, IMRhybrid, using a combination of pressure-wire-based assessment of distal coronary pressure (Pd) and an angiography-derived surrogate of coronary flow.

Methods

Patients were enrolled to the OxAMI-Hybrid study. The accuracy of IMRhybrid was assessed in diagnosing CMD using fully pressure wire and bolus thermodilution Index of Microcirculatory Resistance (IMR) as a reference. The accuracy of IMRhybrid was then compared against a fully angiography-derived index of microvascular resistance (IMRangio).

Based on previous work, angiography-derived IMR, IMRangio, was calculated as IMRangio = Quantitative Flow Ratio (QFR) ado x Pahyperaemia x TIMI Frame Count (TFC) hyperaemia / Frame Rate. Conversely, IMRhybrid was expressed as IMRhybrid = Pdhyperaemia x TFChyperaemia / Frame Rate, where frame rate was fixed at 15 frame per second for both indices. In both cases, TFC/frame rate represented angiography-derived mean transit time, mTt in hyperaemia.

Results

60 patients were enrolled prospectively, of which 28 with acute coronary syndrome and 32 with stable coronary artery disease. A total of 66 vessel analyses were performed. Both IMRhybrid and IMRangio correlated with IMR (rho=0.51, p <0.001 and rho=0.51, p <0.001 respectively) and showed good and comparable overall diagnostic accuracy in predicting IMR ≥ 25 (83.3% and 75.4% respectively) with a receiver operator curve (ROC) analyses showing an AUC of 0.82 and 0.81 respectively (p for comparison= 0.97).

Conclusion

Both approaches, IMRhybrid and IMRangio provide viable and comparable methods of assessing CMD which correlate with bolus thermodilution-based IMR, retaining good diagnostic accuracy. IMRhybrid is a simple alternative to conventional bolus thermodilution-based IMR, offering the advantage of being suitable with any pressure wire system.A: IMR, B: QFR, C: TFCA+C: IMRhybrid, B+D: IMRangio
Early coronary artery atherosclerosis in humans is associated with attenuated coronary retention of klotho
Authors: Akhiyat N , Ozcan I , Lerman L , Lerman A
Published: October 2024

Background

Vascular aging is a key feature of cardiovascular disease. α-klotho (klotho) is a protein inversely associated with aging and may contribute to vascular repair. Lower levels of systemic klotho have been identified in humans with features of early and advanced coronary atherosclerosis. It remains unknown if circulating klotho is present within human coronary circulation and whether cardiovascular klotho retention correlates with atherosclerosis.

Purpose

The current study aimed to assess the presence of klotho within coronary circulation compared to systemic circulation and hypothesized that net coronary klotho retention is attenuated in patients with early age-related features of coronary artery disease (CAD).

Methods

A total of 42 patients that underwent clinically indicated coronary angiogram for chest pain that had no obstructive CAD underwent intravascular ultrasound (IVUS) assessment were retrospectively examined. Virtual histology assessed coronary plaque characteristics. Blood samples simultaneously collected from the proximal aorta and coronary sinus were used for klotho detection using enzyme-linked immunosorbent assay. The net gradient of klotho across cardiovascular circulation was calculated by multiplying the arteriovenous klotho gradient by basal coronary blood flow. A net positive gradient indicated less cardiovascular klotho retention; a net negative gradient indicated greater cardiovascular klotho retention.

Results

Overall, participants were age 54±10 years old and 76% were female. There were overall higher levels of klotho within the coronary sinus (median 0.49 ng/mL [0.15; 1.69]) compared to systemic circulation (median 0.30 ng/mL [0.16; 1.14]). Participant groups were determined by those with positive (n = 20) or negative (n = 22) cardiovascular retention of klotho. Both groups were similar in age (56 ±2 vs. 51 ±2 years old, p = 0.080), gender (72% vs. 80% female, p = 0.580), and had similar occurrences of traditional cardiovascular comorbidities. Those with less cardiovascular klotho retention in the coronary vascular bed had significantly greater degree of non-obstructive coronary artery plaque (Gensini score 3.5 vs. 0, p < 0.001) and had higher percent plaque burden (46% [35; 53] vs. 34% [28; 46], p = 0.044) than those with greater cardiovascular klotho retention.

Conclusions

Patients with early coronary atherosclerosis may be characterized by attenuated retention of klotho within coronary circulation. Moreover, humans appear to have higher circulating klotho in coronary circulation than in systemic circulation. The current study may support a role for mechanism or potential therapeutic target for klotho in coronary atherosclerosis in humans.
Myocardial Bridging: a bridge to spasm?
Authors: O H-Ici D , Kubik S , Manstein M , Joshi S , Paul C , Baerisch A , Kische S
Published: October 2024

Introduction

Myocardial bridges (MBs) represent a congenital anomaly where a segment of a coronary artery passes through the myocardium, resulting in systolic compression. The role of MBs in causing chest pain has been debated, as coronary blood flow occurs primarily in diastole. MBs are generally considered benign, there is growing evidence implicating them in the pathogenesis of coronary artery spasm (CAS). However, the prevalence of CAS in patients in Europe with MBs, particularly assessed through acetylcholine (ACh) testing, remains poorly defined.

Methods

We conducted a retrospective analysis of consecutive patients with angina with no obstructive CAD (ANOCA), ischemia with no obstructive CAD (INOCA), or myocardial infarction with no obstructive coronary arteries (MINOCA) undergoing ACh testing between 2021 and 2024 at our centre. Patients with documented MBs on coronary angiography were included. The presence of epicardial CAS, defined as >90% reduction in coronary diameter with symptoms and/or ischemic electrocardiographic changes, was assessed during ACh provocation testing. Clinical characteristics, Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were also analyzed.

Results

From a total of 299 patients who underwent ACh Testing, 21 patients were identified with MBs, (17 Male, 4 Female). The prevalence of focal CAS in the MB among these patients was 90%. None of these patients had abnormal hyperemic (FFR) or non-hyperemic (RFR) measurements. 9 of the 21 patients with MB had increased IMR, and only 1 had a CFR < 2. 1 Patient had both microvascular CAS in addition to focal epicardial CAS.

Conclusion

This analysis provides valuable insights into the prevalence of CAS in patients with MBs undergoing ACh testing. The findings underscore the importance of considering CAS in the evaluation and management of patients with MBs, particularly during provocative testing. Further prospective studies are warranted to validate these findings and elucidate the clinical implications for risk stratification and treatment strategies in this patient population.
Predictive factors and gender insights into abnormal myocardial flow reserve in non-obstructive coronary artery disease: a CZT-SPECT analysis
Authors: Wang Y J , Li J M , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Background

Dynamic myocardial perfusion imaging (D-MPI) using cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT has emerged as a valuable method for assessing coronary microcirculation, particularly compared to conventional SPECT. Additionally, gender-specific disparities in microvascular dysfunction require further investigation.

Objective

This study aims to identify predictive factors for abnormal myocardial flow reserve (MFR) in non-obstructive coronary artery disease (CAD) using CZT-SPECT, with a focus on gender differences in MFR dysfunction.

Methods

A retrospective analysis was conducted on clinical data from 393 patients presenting with symptoms of "chest pain and/or tightness," all of whom were confirmed to lack obstructive CAD by coronary angiography or CT angiography. MFR was measured using CZT-SPECT, with values ≥2.5 considered normal and values <2.5 considered abnormal.

Results

Of the patients, 49.1% (193/393) demonstrated abnormal MFR, with females representing 56.7% (223/393). Females with abnormal MFR exhibited higher averages in age, total cholesterol, LDL-C, creatinine, left atrial diameter, left ventricular posterior wall (LVPW) thickness in diastole, and E/e’ ratio (P < 0.05). Additionally, MDRD-eGFR and mitral annular septal velocity e’ were lower in the abnormal MFR cohort (P < 0.05). Multivariate logistic regression analysis identified elevated LDL-C levels (OR = 1.513, 95%CI: 1.122–2.041, P = 0.007) and increased LVPW thickness (OR = 1.717, 95%CI: 1.140–2.585, P = 0.010) as independent predictors of abnormal MFR in females. ROC analysis suggested optimal cutoff for LDL-C at 3.68 mmol/L (sensitivity 31%, specificity 84%, AUC = 0.586; 95%CI: 0.511–0.661) and LVPW thickness at 9.5 mm (sensitivity 62%, specificity 52%, AUC = 0.576; 95%CI: 0.501–0.652). A combined ROC analysis of LDL-C and LVPW thickness showed a sensitivity of 50% and specificity of 73% (AUC = 0.632, 95%CI: 0.559–0.705). In males, greater left ventricular end-diastolic diameter (LVEDD) was significantly associated with abnormal MFR (P = 0.014), with LVEDD identified as a predictor (OR = 1.130, 95%CI: 1.016–1.258, P = 0.025) and an optimal cutoff at 44.5 mm (sensitivity 88%, specificity 37%, AUC = 0.609; 95%CI: 0.524–0.694). No significant gender differences were observed in overall left ventricular resting myocardial blood flow (MBF) among patients with abnormal MFR (P = 0.072); however, female patients exhibited higher resting MBF in specific territories supplied by the left circumflex and right coronary arteries, and higher E/e’ ratios (P < 0.05). Furthermore, a negative correlation was found between resting MBF in the territory supplied by the right coronary artery and E/e’ in females (r = -0.210, P = 0.030).

Conclusion

Predictors of abnormal MFR in non-obstructive CAD show gender disparities, implicating an association with left ventricular diastolic function.
Minimal coronary microvascular resistance: agreement between continuous and bolus thermodilution
Authors: Mahendiran T , Keulards D , Pijls N , Viscusi M , Gallinoro E , Bertolone D , Van Royen N , Collet C , Knaapen P , De Bruyne B
Published: October 2024

Background

Continuous thermodilution quantifies absolute microvascular resistance (Rµ, Woods units), the quintessential metric of microvascular function. Rµ is minimal during hyperaemia (Rµ,hyper) with increased Rµ,hyper suggestive of microvascular dysfunction. Bolus thermodilution measures the index of microcirculatory resistance (IMR), a dimensionless surrogate of Rµ,hyper.

Purpose

We compared Rµ,hyper measured by continuous thermodilution (invasive Rµ,hyper) with the gold standard [15O]H2O positron emission tomography (PET Rµ,hyper), and explored the correlation between invasive Rµ,hyper and uncorrected IMR.

Methods

The accuracy of invasive Rµ,hyper was assessed in a cohort of 24 patients in which both invasive and PET Rµ,hyper were measured (cohort 1). For both techniques, Rµ,hyper was assessed in both the left anterior descending artery (LAD) and the circumflex artery (LCX), corresponding to 46 measurement of Rµ,hyper in total (LAD=24, LCX=22). Agreement between invasive Rµ,hyper and IMR was evaluated in a cohort of 250 patients with angina and non-obstructive coronary arteries (ANOCA) evaluated in 3 European centres (cohort 2). All measurements in this cohort were performed in the LAD, with patients randomly assigned in a 1:1 ratio to undergo either bolus or continuous thermodilution first. Both techniques were performed by the same operator during the same procedure with a strict interval of 5 minutes between techniques.

Results

In cohort 1, invasive Rµ,hyper exhibited a strong correlation with PET Rµ,hyper (r=0.86 [95% CI 0.76-0.92], p<0.001), with excellent absolute agreement (ICC 0.82 [95% CI 0.70-0.90], p<0.001) (Figure 1). Furthermore, Passing-Bablok regression analysis found no significant systematic (intercept A: 54.53 [95% CI -18.95 to 120.96]) or proportional (slope B: 0.90 [95% CI 0.71 to 1.15]) bias between invasive Rµ,hyper and PET Rµ,hyper. However, in cohort 2, invasive Rµ,hyper exhibited no significant correlation with IMR (r=0.11 [95% CI -0.01 to 0.23], p=0.08) (Figure 2).

Conclusion

Invasive Rµ,hyper derived from continuous thermodilution exhibited excellent agreement with non-invasive Rµ,hyper measured by [15O]H2O PET, the current standard of reference. However, IMR exhibited no significant correlation with invasive Rµ,hyper in patients with stable coronary syndromes.Figure 1.PET vs invasive Rµ,hyperFigure 2.Invasive Rµ,hyper vs IMR
The correlation between angio-IMR and thermodilution-based IMR in patients with ischemia and non obstructive coronary arteries
Authors: Diachyshyn M , Niewiara L , Szolc P , Kleczynski P , Guzik B , Judzialo P , Zmudka K , Legutko J
Published: October 2024

Background

The diagnostic dilemma of angina with no obstructive coronary lesions (INOCA) poses remarkable challenges in clinical practice, and presents as a significant disease burden affecting up to 4 million people annually. Additionally, standard diagnostic tests such as angiography, do not reveal microvascular dysfunction despite clinical symptoms being present. Since the current Gold Standard of functional assessment is based on guidewire dependent measurements (i.e. CFR, IMR). As an invasive method, it is associated with an increased risk of adverse events such as arterial damage. Therefore new modalities are being introduced to improve patient safety, specifically, an angio-IMR (QMR, calculated based on angiography), shows a substantial promise as a potential diagnostic tool for INOCA patients.

Purpose

The aim of this study is to assess correlation between angio-IMR and thermodilution-based invasively measured IMR in INOCA patients.

Methods

In a group of INOCA patients who had undergone coronary angiography with concomitant thermodilution-based assessment of index of microcirculatory resistance (IMR) an additional angio-based IMR calculation was performed.

The INOCA group consisted of 92 patients ranging in age from 49 to 80 years old, with a median age of 66 years. The majority of the patients were female (59.3%), predominantly with arterial hypertension (87%) and dyslipidemia (100%). Diabetes was present in 27% of cases.

Angio-IMR (QMR) was determined by a qualitative angiography software using information about aortic pressures registered during angiography. Coronary microcirculatory dysfunction (CMD) was diagnosed according to current guidelines when IMR ≥ 25 or CFR < 2.0 were present.

Results

Increased IMR values were detected in 26% of patients. Median calculated value of angio-IMR value was 29 [IQR: 22,46], whereas the invasively measured IMR median value was 17 [IQR: 13,26]. A significant correlation between angio-IMR and invasive-IMR values was observed, Spearman Rho 0.29, p<0.001. Detailed scatterplot with histograms is presented in the figure.

Conclusions

Noninvasive methods, such as the Angio-IMR, represent a shift towards reducing the need for additional invasive procedures while still providing valuable diagnostic insights. Angio-IMR is significantly correlated with invasively measured IMR. When evaluated along with the clinical presentation, noninvasive approaches may therefore help mitigate certain risks and healthcare costs associated with invasive techniques.Figure.Correlation angio-IMR vs MR
Role of Galectin-3 in resident macrophages and effects on atherosclerosis
Authors: Li Y , Duan R D , Blanchet X , Jahantigh M N , Su R , Schulz C , Schober A , Weber C , Von Hundelshausen P
Published: October 2024

Background

Arterial macrophages play an important role in atherosclerosis, exhibiting heterogeneity in their origins as either resident or inflammatory monocyte-derived macrophages. Resident macrophages originate predominantly from the yolk sac, and they are endowed with homeostatic functions and can have anti-inflammatory properties under inflammation [1]. Resident macrophages pre-existing within the tissue differentiate into foamy macrophages before monocytes appear in early atherosclerotic lesions [2]. Galectin-3 (Gal-3) encoded by the gene Lgals3, is a crucial effector molecule that is prominently expressed by macrophages [3]. Studies have provided conflicting evidence regarding the role of Gal-3 in atherosclerosis by affecting macrophage functions and monocyte recruitment [4,5].

Purpose

This study aims to investigate the role of Gal-3 in arterial resident macrophages for atherosclerosis and reveal the underlying mechanisms.

Methods

General Lgals3 knockout (Lgals3-/-) and resident macrophage specific knockout (Lgals3-/-Rank-Cretg) mice on the Apoe-deficient background were generated and atherosclerotic lesion development (8 weeks of western diet) was compared.

Results

Our study revealed that Lgals3-/- mice exhibited increased numbers of monocytes and neutrophils in the blood, which was associated with the development of larger atherosclerotic plaques. Plasma Gal-3 concentration from Lgals3-/-Rank-Cretg mice was decreased by 60%, indicating that the majority of circulating Gal-3 is derived from resident macrophages. Surprisingly, Lgals3-/-Rank-Cretg mice did not show the observed increase in blood monocytes and neutrophils, suggesting that this effect was independent of circulating Gal-3. Consistent with a causal role of monocytosis and leukocytosis in atherogenesis, plaque formation in Lgals3-/-Rank-Cretg was not significantly affected. Additionally, Gal-3 deficiency promoted M1 polarization and reduced efferocytosis, phagocytosis and chemokine receptor expression in BMDMs, and the addition of exogenous Gal-3 restored the effect on phagocytosis and blocked CXCL12 and CCL5-induced leukocyte migration.

Conclusion

This study reveals a prominent protective role of Gal-3, primarily through inflammatory macrophages rather than resident macrophages for the development of atherosclerotic lesions. This protective effect is attributed to its homeostatic effects on monocyte and neutrophil numbers, as well as its influence on macrophage functions.
Antibodies against phosphorylcholine in prediction of cardiovascular disease among women: a population-based prospective cohort study
Authors: Frostegard J , Agneta Akesson A A , Emilie Helte E H , Fredrik Soderlund F S , Jun Su J S , Xiang Hua X H , Susanne Rautiainen S R , Alicja Wolk A W
Published: October 2024

Background and aims

Antibodies against phosphorylcholine (anti-PC) have been reported as associated with protection against atherosclerosis, cardiovascular disease (CVD) and other chronic inflammatory diseases. Underlying potential mechanisms have been demonstrated and include anti-inflammatory, clearance of dead cells and inhibition of oxidized low-density lipoprotein-effects. The aim is to study the role of IgM anti-PC and incident CVD among women, where less is known than among men in the general population.

Methods

In a total of 932 women, 66 ± 6 years old at baseline, from the population-based Swedish Mammography Cohort IgM anti-PC levels of sera were measured using ELISA. Prospective associations with any first CVD, ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke were assessed using Cox proportional hazard regression, generating hazard ratios (HR) and 95% confidence intervals (CI). The model was adjusted for potential confounding factors.

Results

Over the course of 16 years (14,900 person-years), we identified 113 cases of composite CVD, - 69 cases of ischemic heart disease (IHD), 44 cases of myocardial infarction (MI) and 50 cases of ischemic stroke. IgM antiPC was statistically significantly inversely associated with risk of CVD, IHD and MI, but not with ischemic stroke. Comparing the highest tertile with lowest, we observed multivariable-adjusted HR of 0.26 (95% CI: 0.10–0.66; p-trend <0.01) for MI.

Conclusions

IgM anti-PC may play an active role in inhibition of CVD development in women, especially MI. Elevating anti-PC concentration through immunization, may be a future development in CVD prevention.
Circulating levels of neutrophil extracellular traps reflects local neutrophil activity but not fibrinolytic activity in coronary thrombi from patients with ST-elevation myocardial infarction
Authors: Kindberg K , Nordeng J , Langseth M , Solheim S , Seljeflot I , Stokke M K , Helseth R
Published: October 2024

Introduction

Neutrophil extracellular traps (NETs) are associated with impaired fibrinolysis in ischemic stroke, while NETs degradation enhances lysis of coronary thrombi in ex vivo experiments. Whether circulating NET markers are associated with local fibrinolytic activity in patients with ST-elevation myocardial infarction (STEMI) has not been reported.

Purpose

We investigated associations between circulating NET markers and gene expression of fibrinolytic markers in aspirated coronary thrombi from patients with STEMI. Furthermore, we explored whether local upregulation of NET formation by peptidylarginine deiminase 4 (PAD4) was reflected in the circulation.

Methods

Coronary thrombi from 35 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were aspirated and promptly snap-frozen to -80°C. Peripheral blood samples were collected simultaneously. Median time from start of symptoms to PCI was 152 min. Thrombus gene expression of tissue Plasminogen Activator (tPA), urinary-type Plasminogen Activator (uPA), plasminogen-activation inhibitor type 1 (PAI-1) and PAD4 were quantified with RT-PCR. Gene expression of PAD4 was also measured in circulating leukocytes. Circulating NET markers were measured by a fluorescent nucleic acid stain using fluorometry (dsDNA), an in-house ELISA technique (MPO-DNA) and commercial ELISA (H3Cit). Correlations were tested using Spearman’s rho.

Results

There were no correlations between any of the circulating NET markers and gene expression of the fibrinolytic markers tPA, uPA and PAI-1 in the thrombus. Of the circulating NET markers, dsDNA correlated with thrombus gene expression of PAD4 (rs=0.491 p=0.006), whereas none of the NET markers correlated with gene expression of PAD4 in circulating leukocytes.

Conclusion

Circulating NET markers were not associated with gene expression of fibrinolytic activity in thrombi from patients with STEMI. Local NET formation in the thrombi, measured as PAD4 expression, was associated with the circulating NET marker dsDNA. These findings suggest that circulating NET markers have limited utility for assessing local fibrinolytic activity, but might reflect PAD4-dependent NET formation in coronary thrombi.
Predictors of 1-year follow-up period MACE in patients with NSTEMI
Authors: Popovici I , Munteanu M , Ivanov V , Popovici I , Ciobanu L , Cobet V , Popovici M
Published: October 2024

Background

Identifying viable predictors of MACE in NSTEMI continues to pose a challenge in the field of cardiology. Unraveling these factors will elucidate crucial mechanisms underlying adverse post-infarction outcomes and identify key strategies for optimizing treatment.

Aim

Evaluation by using the multi-marker panel the biomarkers having a high predictive value regarding the risk of MACE developing in patients with NSTEMI.

Methods

The study embraced 550 patients with NSTEMI treated by angioplasty. A panel of 67 biomarkers was quantitatively determined by ELISA, immune assay and flow cytometry on admission in the blood linked to the most important mechanisms conceptually involved in post-infarction evolution (inflammation, endothelial dysfunction, hemostasis disorders, oxidative stress, NETosis, Ang 1-7/Ang II axis etc.) The rate of MACE (cardiac death, stroke, myocardial reinfarction) was estimated in a follow-up period of 18 months. In order to underline the overt predictors, the hazard ratio CI (95%) was assayed. 60 healthy persona formed control series.

Results

Upon admission, the circulating levels of 62 out of 67 biomarkers in patients with NSTEMI significantly deviated from control values. The MACE rate during 1-st year after revascularization was 28% (154 pts). According to hazard ratio (HR) the maximal predictive power regarding MACE risk of 1-year follow-up period was unraveled for 3 markers: endothelial microparticles (EMs), platelet-derived microvesicles (PMVs) and von Willebrand/ADAMTS13 ratio. For EMs – HR 2.21 CI (1.19-3.84; p<0.01); for PMVs - HR 2.56 CI (1.43-3.96; p<0.01); for von Willebrand/ADAMTS13 ratio - HR 2.94 CI (1.77-4.73; p<0.01). EMs-CD62E exceeded control level by 77,6% (325.6±101.5 vs 183.2±67.7 Ms/µL); PMVs-CD62P by 129% (378.6±87.4 vs 165.5±59.6 MVs/µL) and von Willebrand/ADAMTS13 ratio by 88% (2.52±1.88 vs 1.34±1.11). These predictors have not been adjusted to age, gender and cardiovascular risk factors.

Conclusion

Considering the pathophysiological significance of the highlighted predictors of MACE (EMs, PMPs and the von Willebrand/ADAMTS13 ratio) endothelial dysfunction and an activated prothrombotic state emerge as pivotal mechanism in the adverse progression of NSTEMI. THUS, these predictors should indicate a focus on corrective therspy targets.
Young female acute myocardial infarction patients have worse all-cause mortality compared to males: insights from a national myocardial infarction registry
Authors: Teo Y N , Yau C , Low C E , Wong H J , Chai P , Chan M Y , Teo Y H , Sia C H
Published: October 2024

Introduction

Existing studies have examined the differences in presentation and outcomes between male and female patients with acute myocardial infarction (AMI). However, the translatability of these findings to young AMI patients is uncertain. In this study, we aimed to investigate sex differences in young AMI patients.

Methods

Retrospective data for all patients ≤50 years of age with a first-time AMI occurring between 2007 and 2020 were analysed from a national myocardial infarction registry. We examined the outcomes of overall survival and cardiovascular-related survival. Cox proportional hazards regression was used to assess the association of survival with various covariates. Effect estimates were summarized using hazard ratios (HRs) and 95%-confidence intervals (95%CI).

Results

A total of 12435 patients was analyzed, of which 1699 (13.7%) were female. Onset age of first-time AMI was not significantly different between males (46.0 interquartile range (42.0, 48.0)) and females (46.0 interquartile range (42.0, 48.0)). Compared to males, more females had atypical symptoms (26% vs 22%, p<0.001), hypertension (54% vs 43%, p<0.001), diabetes mellitus (47% vs 32%, p<0.001). Fewer females had hyperlipidemia (53% vs 62%, p<0.001). The median follow-up time was 7.71 years (IQR (4.34, 11.22)). When adjusted for race, age of onset, heart failure status at admission, hyperlipidemia, diabetes mellitus, hypertension, previous percutaneous coronary intervention and chest pain at presentation, females had significantly higher all-cause mortality (adjusted HR: 1.30 (95%CI: 1.18, 1.45)) (Figure 1).

Conclusion

In conclusion, females who had first-time AMI under 50 years old were more likely to present atypically and have worse all-cause mortality.Figure 1
Symptomatic patients without coronary artery disease do not have excess cardiovascular risk compared to the general population
Authors: Olesen K K W , Andersen M H , Gyldenkerne C , Hansen M K , Stodkilde-Jorgensen N , Thrane P G , Norgaard B L , Mortensen M B , Maeng M
Published: October 2024

Background

Patients with stable angina with no coronary atherosclerosis by coronary computed tomography angiography (CCTA) have a lower cardiovascular risk compared to CCTA patients with greater atherosclerotic burden. However, it remains unknown whether these symptomatic patients have excess cardiovascular risk when compared to the general population and if any excess risk is sex or age dependent.

Purpose

To examine the 10-year cardiovascular risk and mortality in patients with no coronary atherosclerosis by CCTA compared to a matched general population comparison cohort.

Methods

We included every symptomatic CCTA patient with no coronary artery disease (CAD), defined as no coronary plaques and Agatston calcium score of 0, in Western Denmark from 2008-2021. Each patient was matched by age and sex with 5 individuals with no previous history of ischemic heart disease from the Western Danish general population. Maximum follow-up was 10 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated 10-year risk difference (RD) and incidence rate ratios (IRR) using a conditional Poisson regression, comparing patients with no CAD to the general population cohort. Additionally, we performed age- (<45 year, 45-65 years, and ≥65 years) and sex stratified analyses.

Results

We included 39,223 patients with no CAD who were matched with 196,115 individuals from the general population. Median age was 54 and 60% were women. Baseline use of anti-thrombotic agents, statins, and anti-hypertensive drugs was higher in patients with no CAD than the general population. Median follow-up was 6.1 years. CCTA patients with no CAD had lower risk of myocardial infarction [RD -0.2%, IRR 0.75 (95% CI 0.65-0.85)] and death [RD -3.3%, IRR 0.51 (95% CI 0.48-0.55)], but similar risk of ischemic stroke [RD 0.0%, IRR 0.93 (95% CI 0.84-1.02)] compared to the general population (Figure 1). However, patients <45 years had higher 10-year risk of both myocardial infarction and ischemic stroke despite absence of CAD by CCTA compared the general population (Figure 2).

Conclusions

Symptomatic patients without CAD by CCTA do not have excess cardiovascular risk when compared to a general population cohort without known ischemic heart disease. Future cardiovascular risk management of these patients should therefore follow primary prevention guidelines. However, patients <45 years did exhibit higher risk of ischemic outcomes and may require intensified preventative treatment.Figure 1Figure 2