bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification
Authors: Yildirim M , Salbach C , Milles B R , Reich C , Biener M , Frey N , Giannitsis E , Mueller-Hennessen M
Published: October 2024

Background

The clinical chemistry score (CCS) comprising high-sensitivity (hs) cardiac troponins (cTn), glucose and estimated glomerular filtration rate has been previously validated with superior accuracy for detection and risk stratification of acute myocardial infarction (AMI) compared to hs-cTn alone.

Methods

The CCS was directly compared to other biomarker-based algorithms for rapid rule-out and prognostication of AMI including the hs-cTnT limit-of-blank (LOB, <3 ng/L) or limit-of-detection (LOD, <5 ng/L) and the dual marker strategy (DMS) (copeptin <10 pmol/L and hs-cTnT ≤14 ng/L) in 1506 patients presenting to the emergency department (ED) with symptoms suggestive of acute coronary syndrome. Negative predictive values (NPV) and sensitivities for rule-out of AMI were assessed and outcomes included rates of the combined end-point of all-cause mortality, myocardial re-infarction and stroke within 12 months.

Results

NPVs of 100% (98.3-100%) could be found for a CCS=0, hs-cTnT LoB and hs-cTnT LoD with rule-out efficacies of 11.1%, 7.6% and 18.3% as well as specificities of 13.0% (9.9-16.6%), 8.8% (7.3-10.5%) and 21.4% (19.2-23.8%), respectively. A CCS≤ 1 achieved a rule-out in 32.2% of all patients with a NPV of 99.6% (98.4-99.9%) and specificity of 37.4% (34.2-40.5%) compared to a rule-out efficacy of 51.2%, NPV of 99.0 (98.0-99.5) and specificity of 59.7% (57.0-62.4%) for the DMS. Rates of the combined end-point of death/AMI within 30 days ranged between 0.0% and 0.5% for all fast-rule-out protocols.

Conclusions

The CCS enables a reliable rule-out of AMI with low outcome rates in short and long-term follow-up for a specific population of ED patients. However, compared to a single or dual biomarker strategy, the CCS rule-out is attenuated by a loss of specificity and lower efficacy. Thus, the clinical benefit of the CCS in clinical practice seems to be negligible.
Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T
Authors: Knott J , Ola O , De Michieli L , Akula A , Slusser J , Mehta R , Crockford E , Lobo R , Hodge D , Grube E , Tak T , Cagin C , Gulati R , Sandoval Y , Jaffe A
Published: October 2024

Background

Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as these patients often have elevated baseline high-sensitivity cardiac troponin T (hs-cTnT) concentrations.

Methods

Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2- and 6-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2).

Results

The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 701 (82%) patients with myocardial injury, 64 (7.5%) with type 1, and 91 (11%) with type 2 MI. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for acute MI were 37% [95% CI 28-46], 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 64% (95% CI 50-77), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, the corresponding PPVs were 65% (95% CI 50-78), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 65% (95% CI 51-78), 73% (95% CI 57-86) and 75% (95% CI 58-88) (Figure).

Conclusion

Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in patients with CKD. It significantly improves when using higher baseline thresholds and delta values.
The prognostic utility of troponin T levels in patients undergoing PCI during initial hospitalisation for STEMI
Authors: Ediriweera T E , Nguyen T N , Jamal J J , Tam G T , Wang A W , Long M , Leung A , Yang K , Faour A K , French J K
Published: October 2024

The prognostic utility of presentation or "peak" high-sensitivity troponin T (hsTnT) levels following ST-segment elevation myocardial infarction (STEMI) has been previously reported, but hsTnT, unlike other bio-markers of myocyte damage, have a 2nd or ‘plateau-phase’ of release which lasts over a week. We have reported correlations between plateau-phase hsTnT levels, and cardiac MRI determined infarct size, though whether these levels are more highly associated with late mortality than "peak" (or highest) levels, needs clarification.

Methods

Hence we determined late mortality and the combination of cardiovascular death, myocardial infarction and cerebrovascular accident [CD/MI/CVA] among patients with STEMI, and an HsTnT level >36 hours after symptom onset (plateau phase), who underwent percutaneous coronary intervention (PCI), either primary or pharmaco-invasive, during initial hospitalisation between October 2003 and December 2021. HsTnT levels and other potential prognostic factors were determined.

Results

Amongst 1955 patients, 119 patients (6%) had died by 2 years and 192 (10%) patients experienced CD/MI/Stroke. The highest quartile of plateau phase hsTnT levels (³ 3786 ng/L ng/L), were more highly associated with 2-year mortality, than the highest quartile of "peak" hsTnT levels (³ 7687 ng/L ng/L). The Figure shows Peak and plateau hs-TnT levels in quartile groups were assessed by rank test to obtain p-values. Patients lost to follow-up or with less than 2-years of follow up were considered censored. Peak quartile 1; hs-TnT £ 1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L. Log rank mortality analyses are shown in the Figure. Peak quartile 1; hs-TnT <1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L, plateau quartile 4; hs-TnT >3786 ng/L. Multivariate Cox regression analysis incorporating age, sex, smoking status, hypertension, renal function, cardiogenic shock and heart failure hospitalisation found plateau hs-TnT levels (HR, 3.564; 95% CI, 1.674 – 7.590; P = 0.001) were an independent predictor of all-cause mortality at 2-years post-STEMI, whereas peak hs-cTnT levels (HR, 1.965; 95% CI, 0.959 – 4.025; P = 0.065) were not.

Conclusions

Plateau phase hsTnT levels were of prognostic significance in STEMI patients treated with PCI. Thus, measurement of plateau hs-cTnT levels following STEMI could be an accurate, inexpensive method of long-term prognostic risk stratification.
Comparison of rapid test for high-sensitivity troponin I with laboratory high-sensitivity troponin T in patients with acute chest pain - a prospective monocentric study
Authors: Han E , Anwari E , Kokabi V , Gyongyosi M , Bergler-Klein J
Published: October 2024

Background and purpose

High-sensitivity troponin (hs-Tn) assays are recommended for routine clinical use for diagnosis of acute coronary syndrome (ACS). However, laboratory hs-TnT can be elevated due to non-cardiac conditions, such as pulmonary embolism, skeletal muscle injury or chronic kidney disease. The aim of our study was to compare the diagnostic accuracy of the bed-side rapid hs-troponin I (hs-TnI) assay with hs-TnT measured by routine laboratory.

Methods

This prospective monocentric study was conducted at a tertiary hospital outpatient cardiac unit with an emergency clinic for patients with acute symptoms. A total of 129 patients were included between May 2021 and August 2022. Hs-TnI was measured via a bed-side test from whole blood directly in the emergency room, while hs-TnT was measured from plasma through the routine laboratory. Definite ACS was confirmed by coronary angiography. Patients were compared by grouping them into definitive diagnosis of ACS or no ACS. Hs-TnI as well as hs-TnT values were compared for accuracy and predictive values. Routine clinical parameters and comorbidities were documented and compared as well. Agreement between hs-TnI and hs-TnT was assessed by likelihood ratios and Bland Altman plot.

Results

Overall, 129 patients (65.1% male, 61.8 ± 15.6 years) with acute chest pain were analysed. Median hs-TnI was 7.0 ng/L (IQR: 2.7-15.8), while median hs-TnT was 14 ng/L (IQR: 7.0-31.0). Results for TnI were available faster (average: 1:14 h ± 0:54) compared to TnT. Coronary angiography confirmed ACS in 17 patients (13.2%) displaying significant coronary stenoses requiring intervention. The relative risk of ACS patients to have an elevated hs-TnI result was 6.59 compared to that of 2.29 for the hs-TnT test, meaning that a positive hs-TnI test was a better classifier for validated ACS than that of hs-TnT. Hs-TnI exhibited equivalent negative predictive value to hs-TnT (99%) for definite ACS diagnosis, but had comparatively higher positive predictive value (50.0 vs. 25.8%). Bland Altman plot of hs-TnI versus hs-TnT showed an average difference of -4.6 ng/L (95% CI: -12.4 to 3.2) between the tests. In 39 patients with chronic kidney disease (minimum stage 3a CKD) median hs-TnT (27.0 ng/L, IQR: 16.0-55.0) values were higher than hs-TnI (11.2 ng/L, IQR: 7.5-30.7).

Conclusion

Bed-side hs-TnI is comparable to hs-TnT with a high degree of agreement. Measurement of troponin I using the rapid bed-side hs-TnI assay possesses a shorter blood-draw-to-result-time than routine troponin T measurement.
Comparing combined testing of cMyBP-C and hs-cTnT with other algorithms for rapid rule-out of acute myocardial infarction in suspected acute coronary syndrome patients
Authors: Yildirim M , Salbach C , Milles B R , Biener M , Frey N , Mueller-Hennessen M , Giannitsis E
Published: October 2024

Background

We aimed to compare the diagnostic accuracy of a dual-marker strategy (DMS), incorporating cardiac myosin-binding protein C (cMyBP-C) and high-sensitivity cardiac troponin T (hs-cTnT) testing, against other rapid rule-out algorithms for acute myocardial infarction (AMI).

Methods

We enrolled 2059 patients presenting to the emergency department with suspected AMI and compared diagnostic measures using the DMS (cMyBP-C <10 ng/L and hs-cTnT≤14 ng/L), serial hs-cTnT sampling (hs-cTnT<14ng/L at different time points within 1-3h), modified European Society of Cardiology (ESC) 0/1h- or 0/3h-protocol (hs-cTnT<5ng/L or <12ng/L & ∆hs-cTnT<3ng/L at 1h or <7ng/L at 3h if hs-cTnT at 1h was not available), as well as the hs-cTnT limit-of-blank (LoB, <3ng/L) and -detection (LoD, <5ng/L) were compared. Negative predictive values (NPV) and sensitivities for AMI rule-out were assessed.

Results

True-negative rule-out rates using the DMS ranged from 38.1% to 51.6% across all patients, surpassing rates of 6.2%, 17.4%, 45%, and 50.8% achieved by LoB, LoD, serial hs-cTnT sampling, and ESC 0/1h or 0/3h algorithms, respectively. The DMS demonstrated an NPV of 99.7%, similar to serial hs-cTnT sampling and ESC 0/1h or 0/3h algorithms, and 100% for both LoB and LoD. Sensitivities were 98.9%, 98.9%, 100%, and 100%, respectively.

Conclusions

The DMS - incorporating cMyBP-C and hs-cTnT - effectively rules out AMI, showing non-inferiority to hs-cTnT-only-based rapid rule-out algorithms and offers a promising alternative, potentially enhancing clinical decision-making in emergency settings.
Relationship between lipoprotein(a) and endogenous fibrinolytic status in patients with STEMI
Authors: Leader J H , Farag M , Viljoen A , Kanji R , Gorog D A
Published: October 2024

Background

The risk of myocardial infarction is at least doubled in individuals with lipoprotein(a) (Lp[a]) levels >90th percentile.[1] Lp(a) may exert pro-thrombotic effects by impairing fibrinolysis. Lp(a) has a high degree of homology to plasminogen and can competitively inhibit tissue plasminogen activator (tPA)-mediated plasminogen activation and tPA-mediated clot lysis.[2] Furthermore, Lp(a) stimulates the activity of plasminogen activator inhibitor-1, the major inhibitor of the fibrinolytic system.

In patients with ST-segment elevation myocardial infarction (STEMI), impaired endogenous fibrinolysis is a strong, independent risk factor for recurrent cardiovascular events,[3] but the drivers of this are not fully understood. Whether impaired endogenous fibrinolysis is related to increased Lp(a) levels in patients with STEMI, is not known.

Purpose

We aimed to assess the relationship between Lp(a) and endogenous fibrinolysis in patients with STEMI.

Methods

In a prospective, observational study, venous blood samples were drawn from patients presenting with STEMI immediately before revascularisation, after dual antiplatelet therapy but before heparin administration. Endogenous fibrinolysis was measured immediately in non-anticoagulated whole blood using the point-of-care Global Thrombosis Test, which measures the time for occlusive thrombus formation under high shear (occlusion time) and the time for spontaneous lysis of the thrombus (lysis time).[3] Assessment of Lp(a) levels, measured by particle enhanced immunoturbidimetric assay, was performed with paired plasma samples, standardized against the International Federation of Clinical Chemistry reference material SRM2B for nmol/L. Lp(a) >32 nmol/L is associated with increased risk of ischaemic heart disease.

Results

A total of 80 patients were included (age 64±14y, 25% females and 86% Caucasian). There was a positive correlation between Lp(a) level and lysis time (r = 0.330, P = 0.003) (Figure 1). Lysis time was significantly longer in patients with Lp(a) >32 nmol/L (2782 [1626-3683] vs. 1725 [1259-2955] s, P = 0.044). Using a cut-point of lysis time ≥2500 s previously associated with a significantly increased cardiovascular risk in patients with STEMI, we showed that Lp(a) was significantly higher in patients with lysis time ≥2500 s (40 (22-111) vs. 18 (7-73) nmol/L, P = 0.045). Table 1 shows the relationship between clinical characteristics and Lp(a) and lysis time. Lp(a) level was higher in non-Caucasian patients. There was no correlation between Lp(a) and occlusion time (r = 0.156, P = 0.168).

Conclusion

In patients with STEMI, longer endogenous fibrinolysis time is related to higher Lp(a) level. Raised Lp(a) levels may, in part, contribute to impaired endogenous fibrinolysis. Future studies are required to assess whether reduction in Lp(a) with novel therapies currently in phase 3 trials can favourably modulate fibrinolysis and improve clinical outcomes.Figure 1
Effect of alirocumab on coronary plaque stratified by atherothrombotic risks
Authors: Ueki Y , Otsuka T , Kakizaki R , Losdat S , Shibutani H , Haner J , Bar S , Iglesias J , Geuns R , Spirk D , Daemen J , Engstrom T , Lang I , Koskinas K , Raber L
Published: October 2024

Background

Previous clinical studies have shown that high-risk subgroups including patients with major atherosclerotic cardiovascular disease (ASCVD) events and multiple atherothrombotic risk factors derive enhanced cardiovascular benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. To date, the effect of alirocumab on coronary plaque regression stratified by the number of atherothrombotic risk factors remains unknown.

Purpose

To investigate the utility of atherothrombotic risk stratification to identify patients with acute myocardial infarction (AMI) who have the greatest potential for benefit on plaque regression as assessed by intracoronary imaging from the addition of alirocumab to high-intensity statin therapy.

Methods

This was a substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Intravascular ultrasound (IVUS) was serially performed in non-infarct-related coronary arteries at baseline and after 52 weeks. Atherothrombotic risk factors defined in the 2018 ACC/AHA cholesterol guidelines include myocardial infarction, ischemic stroke, peripheral artery disease, age ≥65 years, familial hypercholesterolemia, coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, LDL-C ≥100 mg/dL despite maximum tolerated statin therapy, and history of heart failure. The key endpoint was the change in IVUS-derived percent atheroma volume (PAV) from baseline to 52 weeks.

Results

A total of 263 patients available for serial IVUS data were analyzed for the current study. The most prevalent atherothrombotic risk factors were current smoking (49%), hypertension (43%), and age ≥65 years (24%). Patients were divided into 3 groups according to the number of risk factors (0 risk factor: n=52, 1 risk factor: n=101, ≥2 risk factors: n=100). Patients with risk factors had greater PAV at baseline compared with those with 0 risk factor (39.0% vs. 42.6% vs. 42.8%, P=0.008). The addition of Alirocumab to high-intensity statin therapy demonstrated a significant reduction in PAV among patients with 0 risk factor (-2.66% vs. -1.02%, P=0.009) and those with 1 risk factor (-2.36% vs. -0.76%, P<0.001) (Figure 1). In contrast, patients with ≥2 risk factors had no significant PAV reduction by alirocumab (-1.72% vs. -1.12%, P=0.076, P for interaction=0.009).

Conclusions

Among AMI patients with no or 1 atherothrombotic risk factor, the addition of alirocumab to high-intensity statin therapy demonstrated greater coronary plaque regression. Patients with fewer risk factors thus appear to be more susceptible for atheroma regression.Change in PAV stratified by risk factors
The sooner the better? What is the optimal timing for coronary angiography in high-risk non-ST-elevation acute coronary syndrome
Authors: Carvalho C , Bernardo M , Moreira I , Azevedo L , Fernandes I , Mateus P , Baptista A , Moreira I
Published: October 2024

Introduction

current guidelines recommend an early invasive coronary angiography (ICA), in the first 24 hours, for high-risk non-ST elevation acute coronary syndrome (NSTE-ACS) patients. However, several studies have failed to demonstrate a significant improvement in all-cause mortality, with controversial results regarding recurrent ischemia and myocardial infarction.

Purpose

to evaluate the optimal timing of ICA in high-risk NSTE-ACS.

Methods

this was a national multicentre retrospective study of patients hospitalized for NSTE-ACS between October 2010 and October 2023. Patients presenting in Killip class IV, mechanical complications, life-threatening arrhythmias or cardiac arrest were excluded. Participants were divided into three groups, according to the timing of ICA: in the first 24 hours (D0), between 24 and 48 hours (D1) and between 48 and 72 hours (D2). The incidence of in-hospital complications and mortality, as well as 1-year mortality rate and cardiovascular rehospitalization, was compared for the three groups.

Results

a total of 9949 patients was included, 98.2% with non-ST elevation myocardial infarction (NSTEMI) and 1.8% with unstable angina with high-risk criteria (GRACE risk score >140 or transient ST-segment elevation).

Most patients were submitted to early ICA (46.7%), with 26.7% and 26.6% in D1 and D2, respectively. Interestingly, patients in higher Killip class (II or III) were referred for ICA latter than patients in Killip class I (9.0% in D0 vs. 11.3% in D1 vs. 13.5% in D2, p<0.001).

Regarding in-hospital complications, early ICA was associated with a lower incidence of acute heart failure (8.5% vs. 11.1% vs. 11.5%, p<0.001) and shorter length of stay (7 vs. 6 vs. 10 days, p=0.01). However, it did not reduce in-hospital mortality (1.2% vs. 0.7% vs. 0.8%, p=0.07), recurrent myocardial infarction (0.9% vs. 1.5% vs. 1.3%, p=0.09), cardiogenic shock (7.9% vs. 5.7% vs. 5.4%, p=0.19), mechanical complications (0.1% vs. 0.2% vs. 0.1%, p=0.50) or sustained ventricular tachycardia (0.8% vs. 0.6% vs. 0.4%, p=0.12). Left ventricular ejection fraction was also similar between groups (54%±12, p=0.97).

There were also no significant differences between groups regarding 1-year mortality or cardiovascular rehospitalization (15.1% vs. 15.9% vs. 15.7%, p=0.89).

Conclusion

in high-risk NSTE-ACS patients, early ICA resulted in lower incidence of acute heart failure and shorter length of stay. However, timing of ICA didn’t show a significant impact on in-hospital mortality or complications, nor in 1-year mortality rate or cardiovascular rehospitalization.
Real-life impact of complete revascularization of non-ST elevation myocardial infarction during index hospitalization
Authors: Carvalho C , Bernardo M , Moreira I , Azevedo L , Fernandes I , Mateus P , Baptista A , Moreira I
Published: October 2024

Introduction

patients with non-ST elevation acute myocardial infarction (NSTEMI) frequently present multivessel disease (MVD) with significant stenosis in non-infarct-related arteries (non-IRA). Unlike for ST elevation acute myocardial infarction, there is a paucity of studies evaluating the prognostic impact of complete revascularization in these patients. In fact, recommendation for complete revascularization is based in observational and non-randomized studies suggesting a possible benefit regarding mortality and major cardiovascular events.

Purpose

to evaluate the prognostic impact of complete revascularization during the index hospitalization in the Portuguese patients with NSTEMI and MVD.

Methods

patients hospitalized for NSTEMI with MVD included in a national multicentre retrospective study between October 2010 and December 2022 were divided into two groups: group 1 was submitted to complete percutaneous revascularization during the index hospitalization (IRA and non-IRA with diameter stenosis ≥50% on angiography), and group 2 performed IRA-only revascularization. The impact of complete revascularization on the probability of cardiovascular re-hospitalization, as well as on in-hospital and one-year mortality rates was evaluated.

Results

a total of 3084 patients was included, 74.8% were males, with a mean age of 67.8±11.9 years. Most patients were submitted to IRA-only revascularization (72.9%). From the remaining, 81.4% performed complete revascularization during the index procedure and 18.6% staged during index hospitalization.

Group 1 patients were younger (65.5±11.8 vs. 68.6±11.8 years, p<0.001), with fewer comorbidities and slightly higher left ventricular ejection fraction (55±11 vs. 51±11%, p<0.001). On the other hand, group 2 patients revealed a significantly higher percentage of previous, revascularization (14.8% vs. 1.6%), mostly surgical.

Besides overall similar incidence of in-hospital complications, including recurrence of acute myocardial infarction, patients submitted to complete revascularization showed a non-significant trend to an inferior in-hospital mortality rate (0.7 vs. 1.6%, p=0.06). Also, 1-year mortality rate was similar between groups (4.2 vs. 5.0%, p=0.54). However, complete revascularization appeared to result in a long-term prognostic benefit, halving the incidence of unplanned cardiovascular re-hospitalizations at one year of follow-up (9.3 vs. 18.8%, p<0.001).

Conclusion

complete revascularization led to an overall long-term benefit, mainly due to a reduction in cardiovascular re-hospitalizations, without a significant impact on 1-year mortality rate.
dPdT >1200ms predicts greater and sustained drop in ejection fraction post mitral TEER
Authors: Lander K , Higgins M , Lau K , Murdoch D , Raffel C , Walters D , Scalia G
Published: October 2024

Background

The maximum rate of left ventricular pressure rise (dP/dTmax) using a CW Doppler from a mitral regurgitation (MR) curve is a simple technique which can estimate myocardial contractility, with "normal" values >1200ms. This technique has not been applied to patients undergoing mitral transcatheter edge-to-edge repairs (M-TEER).

Purpose

Assess if dP/dT can predict post-procedural ejection fraction (EF).

Methods

A retrospective review of all M-TEER's performed from January 2011 – February 2023 at a single cardiac centre with an adequate MR CW Doppler to calculate the dP/dT as well as a subsequent TTE at the institution were included. An early TTE (performed day 1-50, average 34.9) and late TTE (goal 1 year, average 354 days) were recorded.

Results

A total of 155 M-TEER procedures were performed; 66 for degenerative MR (DMR), 11 for atrial functional MR (AFMR) and 78 for ventricular functional MR (VFMR). Baseline characteristics: overall EF 47.9% (DMR 61%, AFMR 52% and VFMR 32%). Age DMR 75.8y, AMFR 78.9y, VFMR 75.6y), overall 31.6% female (DMR 34.6%, AFMR 45.5%, VFMR 25.8%). Surprisingly the DMR cohort demonstrated a significant drop in EF post M-TEER of 5.1% (p<0.001, figure 1). This was most marked in the group with "normal" dP/dT of >1200ms (figure 2, DMR EF drop 7.8% p<0.001). This cohort remained at the new, lower value on follow up (figure 2). The EF in the VFMR remained severely impaired despite M-TEER (figure 1). There was no significant difference between EF pre or early post (p= 0.86). When divided into groups according to baseline dP/dT. The greatest drop in EF was again seen with an apparently normal dP/dT of >1200ms (figure 2).

Conclusion

"Normal" dP/dT of >1200ms in patients undergoing M-TEER is likely a marker of hyper-contractile LV function as a compensatory mechanism, and may predict a greater fall in EF post correction of MR.
Impact of inhaled nitric oxide therapy in patients with cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation combined with Impella
Authors: Ueno M , Yamada N , Kakehi K , Fujita K , Nakazawa G
Published: October 2024

Background

Mortality rates remain high in patients with cardiogenic shock (CS) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) combined with Impella (ECPELLA) support. Early weaning from VA-ECMO may be the first step in reducing mortality in these patients. Inhaled nitric oxide (iNO) therapy improves right ventricular function by decreasing pulmonary arterial resistance, resulting in increased Impella flow rate, which may facilitate early withdrawal of VA-ECMO and improve survival.

Purpose

The purpose of this study was to investigate the prognostic impact of iNO therapy on ECPELLA patients.

Methods

We retrospectively studied consecutive patients with CS due to acute myocardial infarction (AMI-CS) or decompensated heart failure (ADHF-CS) supported with ECPELLA from September 2019 to January 2024 at our hospital. The VA-ECMO withdrawal rate, time to withdrawal, and 30-day survival were compared for ECPELLA patients with and without iNO therapy.

Results

A total of 47 patients were included (AMI-CS, n=26, and ADHF-CS, n=21). Of these, 21 patients (44.7%) were treated with iNO therapy. Patient characteristics were not significantly different between those with and without iNO therapy, including age, gender, percentage of cardiopulmonary arrest or acute coronary syndrome, and lactate levels at mechanical circulatory support induction. Patients receiving iNO therapy had significantly higher VA-ECMO withdrawal rates (90% vs. 50%, P=0.003) and shorter time to VA-ECMO withdrawal (5.0±1.3 vs. 7.8±5.6 days, P=0.04) than those not receiving iNO therapy. Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was significantly higher in patients receiving iNO therapy than those without (P=0.003, Figure).

Conclusion

Adjuvant iNO therapy for CS patients supported by ECPELLA facilitates early withdrawal of VA-ECMO and improve survival representing a useful therapeutic option.Figure
Evaluation of repeated machine learning-based phenotyping in patients with cardiogenic shock
Authors: Zweck E , Kanwar M , Li S , Sinha S S , Garan A R , Hernandez-Montfort J , Abraham J , Polzin A , Kelm M , Burkhoff D , Kapur N K
Published: October 2024

Background

Cardiogenic shock (CS) is a highly mortal disease with variable clinical manifestations, severity, and in-hospital trajectories. Multiple clinical trials have failed to show an impact of therapies on outcomes, partly because they focus on etiology as a classifier, failing to capture the clinical heterogeneity. A phenotype-based approach to CS allows for a dynamic risk stratification based on disease severity. We have previously presented three CS phenotypes at baseline using machine learning-based algorithms: phenotype I (non-congested), II (cardiorenal), and III (cardiometabolic). However, little is known about the clinical course of these CS phenotypes during hospitalization and whether repeated phenotyping may provide additional insights.

Purpose

To assess relevance and prognostic impact of repetitive reassessment of CS phenotypes and their trajectories during the first 72h after CS diagnosis.

Methods

We included all-cause CS patients from the multi-center, multinational Cardiogenic Shock Working Group (CSWG) V3 and V4 registries (Yr. 2022-2023). Phenotypes were assigned by nearest centroid classification based on the centroids from the initial CSWG V1 (Yr. 2019) registry derivation cohort. Missing values required for phenotype assignment were imputed for all patients, but imputed values were only used for phenotype assignment and not reported as outcomes.

Results

A total of 4308 patients were included, of which 928 had CS due to myocardial infarction (MI-CS) and 2164 had CS due to heart failure (HF-CS). At time of diagnosis/ baseline, 1627 (37.8%), 1832 (42.5%), and 849 (19.7%) of patients were in phenotype I (non-congested), II (cardiorenal) and III (cardiometabolic), respectively. In MI-CS, patients were evenly distributed between the three phenotypes (35.5%, 34.4%, and 30.2%, respectively), whereas in HF-CS, non-congested and cardiorenal CS were more common than cardiometabolic shock (38.8%, 48.9%, and 12.3%, respectively). Within the first 12 hours, most patients in cardiorenal and cardiometabolic CS shifted to non-congested CS (Figure 1). In-hospital mortality in admission phenotype I, II, and III was 21.7%, 32.1%, and 50.1% (p<0.0001 for difference), respectively, in concordance with previous reports. When assessed at different time points, phenotypes II and III were associated with higher odds of mortality than phenotype I at 24h, 48h, and 72h after initial shock diagnosis (p≤0.03 for all, Figure 2).

Conclusion

Beyond baseline, re-assessment of machine learning-based CS phenotypes within the first 72h after CS diagnosis may provide additional prognostic insights. These data may inform future clinical trial design to tailor interventions to specific CS phenotypes.Figure 1Figure 2
Validation of quantitative aortic valve calcification assessment by photon-counting computed tomography from contrast-enhanced data sets using virtual non-contrast reconstructions
Authors: Jung S , Weidinger F , Ammon F , Smolka S , Moshage M , Janka R , Marwan M , Achenbach S
Published: October 2024

Background

The spectral information of photon-counting computed tomography (PCCT) permits the reconstruction of energy-selective images.

Purpose

We evaluated two methods for the reconstruction of virtual non-contrast-enhanced images from contrast-enhanced CT angiographic data sets regarding their ability to quantify aortic valve calcification. Results were validated by comparison to non-enhanced computed tomography.

Methods

A total of 100 subjects with severe aortic valve stenosis who underwent ECG-synchronized cardiac photon-counting CT for diagnostic workup prior to transcatheter aortic valve implantation (TAVI) were included in the current analysis. A standard true non-contrast acquisition was performed for aortic valve calcium quantification in each subject. In addition, two virtual non-enhanced data sets were reconstructed from contrast-enhanced CT angiographic data: a calcium-specific image ("pure calcium scan", PCS) and a virtual non-contrast (VNC) scan by subtraction of iodine. The PCS algorithm separates calcium and iodine in spectral PCCT images, creating a non-calcium mask for denoised spectral input and preserving calcium contrast in final material decomposition. Iodine extraction is achieved by measurement of the iodine content and its differentiation from native soft tissue attenuation. The Agatston Score was assessed in each of the three image data sets using semi-automated software.

Results

The mean age of the subjects was 78 ± 7 years, 66% were male. Mean EUROSCORE II was 4 ± 4%, mean STS Score for morbidity and mortality was 16 ± 11%. In the true non-contrast scan used for validation, the mean Agatston Score was 3028 ± 1820. The mean Agatston Score obtained from the PCS data set was 3004 ± 2042 and did not differ significantly from true non—contrast image sets (p=0.716). In the VNC data sets, the mean Agatston score was 1726 ± 1288, significantly lower than in the true non-contrast and the PCS data sets (both <0.001). Both, PCS and VNC data showed a significant correlation with true non-contrast scans (correlation coefficient PCS: 0.978, VNC scan: 0.975, both p<0.001).

Conclusion

In conclusion, the current results show the possibility to reliably quantify the Agatston Score of larger cardiac calcifications in virtual non-contrast data sets – however, there is substantial influence of the algorithm that is used so that validation of new techniques is of key importance.
Volume-outcome relationships for intra-aortic balloon pump in acute myocardial infarction
Authors: Saito Y , Tateishi K , Kanda M , Shiko Y , Kawasaki Y , Kobayashi Y , Inoue T
Published: October 2024

Background

Acute myocardial infarction (MI) is one of the major scenarios of intra-aortic balloon pump (IABP) use, particularly when complicated by cardiogenic shock. The utilization of mechanical circulatory support devices including IABP varies widely per hospital, while whether a higher IABP volume at each hospital is translated into better outcomes in acute MI is unclear.

Purpose

To evaluate the relationship between the volume of IABP use and mortality at the hospital level in patients with acute MI undergoing percutaneous coronary intervention (PCI).

Methods

Using a Japanese nationwide administrative database, a total of 26,490 patients with acute MI undergoing primary PCI from 154 hospitals were included. The primary endpoint was the observed/predicted in-hospital mortality ratio. The predicted mortality per patient was calculated using baseline variables and was averaged for each hospital. The associations among PCI volume for acute MI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed at the hospital level.

Results

Of the 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of IABP use per hospital in acute MI was 4.5 [2.4-10.7]. In lower primary PCI volume centers, IABP was more likely to be underused than expected, and the observed/predicted in-hospital mortality ratio was higher than in higher volume centers (Figure). The observed/predicted mortality ratio seemed lowest in hospitals where the observed/predicted IABP use ratio was around one.

Conclusions

The present study showed that the lower annual number of IABP use was associated with an increased mortality risk at the hospital level, and suggested that standardized IABP use can be an institutional quality indicator in a setting of acute MI.
Diastolic shock index: a novel prognostic parameter unveiling insights into vasodilatory cardiogenic shock
Authors: Paiva M , Carvalho R A , Brizido C , Bello A R , Lima M R , Domingues M , Pereira J C , Azevedo S , Presume J , Strong C , Ferreira J , Tralhao A
Published: October 2024

Introduction

Systemic vasodilation is an increasingly acknowledged feature in cardiogenic shock (CS), defining a subset of patients with low systemic vascular resistances and higher vasopressor requirements. While a diastolic shock index (DSI) above 2.0 predicts vasoplegia and mortality in septic shock, its cut-off and prognostic significance in CS remain unclear. Our study aimed to characterize vasoplegia in CS using the DSI and assess its impact on prognosis.

Methods

Single-center retrospective cohort study on Cardiac Intensive Care Unit (CICU) admissions for CS from January 2017 to October 2023. Data included patient variables, CS features, vasoactive drugs, mechanical circulatory support, and 30-day mortality. DSI (heart rate (HR) to invasive diastolic blood pressure (DBP) ratio) impact on 30-day all-cause mortality was assessed with univariate Cox regression. Optimal DSI cut-off for adverse outcomes was determined through ROC curve analysis, and survival based on this cut-off was analyzed using Kaplan-Meier curves.

Results

185 patients (mean age 59 ± 12 years, 63% male) were included. Acute myocardial infarction-related CS (47%) and heart failure-related CS (29%) were predominant. According to SCAI classification, 86% were class C, 22% class D, and 4% class E, with 26% experiencing previous cardiac arrest. Median Vasoactive-Inotropic Score (VIS) was 48 (IQR 21-85), and 25% used mechanical circulatory support. At admission, median HR was 105 bpm (IQR 90-125), DBP was 60 mmHg (IQR 55-65), and DSI was 1.71 (IQR 1.31-2.18).

Thirty-day all-cause mortality was 36% (n=67), with median time to death of 4 days (IQR 1-10). DSI at 30 days predicted mortality (OR 1.42, 95%CI 1.06-1.91, p=0.020). DSI showed fair discriminative power for 30-day mortality (C-Statistic 0.60, 95% CI 0.51-0.68, p=0.031) with a cut-off of 2.2. Patients with DSI >2.2 exhibited heightened likelihood of prior cardiac arrest (38% vs. 20%, p=0.032), and higher serum lactate (5.5 vs. 3.9 mmol/L, p=0.008), and serum creatinine (2.64 vs. 1.88 mg/dL, p=0.003) at admission. Despite higher VIS at 48 hours (120±136 vs. 65±93.9, p=0.04), MCS need did not significantly differ. This group had superior 30-day mortality risk (log-rank p=0.011).

Conclusion

In our cohort, the admission Diastolic Shock Index (DSI) emerged as a promising identifier for CS vasoplegic patients and was a predictor of a higher risk for mortality. A DSI above 2.2 identified a subset of patients with previous cardiac arrest and higher lactate levels, enlightening possible risk factors associated with vasoplegia. Further studies are warranted to establish the robustness of this novel prognostic parameter in CS patients and its therapeutic implications.
Sex differences in outcomes of patients with cardiogenic shock due to acute myocardial infarction: a systematic review and epidemiological meta-analysis
Authors: Hill N , Fisher T , Kalakoutas A , Warren A , Proudfoot A G , Rathod K S , Lahlou A
Published: October 2024

Background

Women are at higher risk of mortality from ST-elevation myocardial infarction (1) when compared to men. There is a lack of consensus among studies examining the effect of sex on outcomes from cardiogenic shock due to acute myocardial infarction (AMI-CS) (2-5). In this systematic review and meta-analysis, we sought to assess the relationship between outcomes of AMI-CS and sex.

Purpose

To examine sex-related differences in mortality in patients with cardiogenic shock secondary to acute myocardial infarction (AMI-CS).

Methods

Cochrane Central, PubMed, MEDLINE and EMBASE were searched in February 2023 for studies reporting in-hospital or 30-day sex-specific mortality in patients with cardiogenic shock. Inclusion criteria consisted of observational or randomised controlled trials of adult patients with cardiogenic shock that reported unadjusted or adjusted (by odds or risk ratio) mortality rates by sex. In-hospital or 30-day mortality were treated as equivalent. Data were extracted for study size, number of men and women, unadjusted and adjusted mortality rates, and factors used in multivariable analysis. Studies were assessed for risk of bias and publication bias. Meta-analysis was performed using DerSimonian-Laird random effects model with inverse variant weighting, due to predicted high heterogeneity of included studies. Data are reported as odds ratios (ORs) with 95% confidence interval (CI). P values were adjusted for multiple comparison using Holm-Bonferonni correction. The primary outcomes were unadjusted and adjusted sex-specific mortality rates due to AMI-cardiogenic shock.

Results

4,286 studies were identified and 37 met inclusion criteria, pooling a total of 630,890 patients. Raw 30-day/in-hospital mortality of females with AMI-cardiogenic shock was 41.2% compared to 32.3% in males. Unadjusted OR for mortality in females was 1.42 (95% CI 1.31–1.55, p <0.001, t2 = 0.02, I2 = 70.3%), and the adjusted OR was 1.11 (95% CI 1.04–1.20, p <0.001, t2 = 0.01, I2 = 76.8%). Eight studies included data on use of mechanical circulatory support (MCS), which was used in 31.2% of females compared to 39.9% of males. OR for use of MCS in females compared to males was 0.71 (95% CI 0.66–0.77, p < 0.001, t2 = 0.003, I2 = 35.2%).

Conclusions

Women with AMI-related cardiogenic shock are at greater risk of death compared to male patients and are less often treated with MCS. Potential explanations include residual confounding factors, differences in AMI-cardiogenic shock pathophysiology between men and women, and sex-related differences in healthcare behaviours, but we cannot exclude the effect of systemic bias on outcomes. Further research is required to address the causes of sex disparities in outcomes and ensure equitable management of AMI-cardiogenic shock in women.Unadjusted sex outcomes from AMI-CSAdjusted sex outcomes from AMI-CS
new insights into the pathophysiology of rheumatic valve disease based on different genetic and proteomics profiles
Authors: Almeida Valadares A , Martins A , Castelli J , Melechco V , Tarasoutchi F , Aiello V , Laurindo F , Gaiotto F , Almeida Brandao C M , Orismar Sampaio R
Published: October 2024

Introduction

Rheumatic heart disease (RHD) pathogenesis is not fully understood. Purpose The protein profile in rheumatic heart disease may have a different fingerprint in the aortic and mitral valves, which results in different evolution in terms of valve damage.

Methods

To evaluate the genetic profile in symptomatic RHD, 4 simultaneous mitral and aortic valves were obtained during valve replacement, as well as 4 "normal" valves from cadavers (Control Group). The expression of 90 genes was evaluated using a customized RT-PCR array kit. A second experiment was carried out to evaluate proteomics. Then, 7 mitral and aortic valves, from the same patient, were also collected during valve surgery. The Control Group consisted of 6 mitral and aortic valves obtained from explanted hearts during heart transplantation due to non-valvular pathologies. Additionally, histopathological and sectoral proteomic analysis of amyloid deposits, found in some mitral and aortic valves, from the second experiment, were also reported.

Results

Mitral rheumatic valves exhibited higher expression of genes linked to calcification and immuno-inflammation compared to aortic rheumatic valves (Figure 1). Proteomic analysis, visualized through PCA graphs, highlighted differences in proteomic patterns. Despite having the same genetic pattern, control valves exhibited different proteomic profiles (Figure 1) Rheumatic mitral and aortic valves, even from the same individual, showed distinct proteomic fingerprint (Figure 1). A total of 49 significant proteins were identified in distinguishing healthy mitral and aortic valves from the same individual (Figure 1). The aortic valve displayed a richer extracellular matrix and higher levels of housekeeping proteins that maintain valve homeostasis compared to the mitral valve (Figure 1). The dominant proteomic pattern in valvular rheumatic disease was identified as alterations in critical mitochondrial metabolic activities related to proteostasis. (Figure 2). Particularly notable was the upregulation of pathways associated with lipid metabolism (Figure 2). Finally, amyloid deposits suggested APOA1 as a potential deposit protein in RHD (Figure 2).

Conclusion

The study confirms distinct constitutional differences between mitral and aortic valves affecting rheumatic disease progression. It emphasizes the role of altered proteostasis and altered proteins deposit, mitochondrial metabolic changes, and inflammatory responses in the disease's pathophysiology, highlighting the complexity of valvular rheumatic disease involvement.For the first time amyloid deposition has been reported as a likely consequence of significant disruption in valvular proteostasis and the proteins potentially comprising this deposit within a rheumatic valve.Genomic and proteomic overviewproteomic fingerprint of RHD and amyloid
The effect of the LPA gene on aortic valve calcification in a Portuguese population
Authors: Sousa F , Mendonca M I , Serrao M , Sa D , Abreu G , Freitas S , Rodrigues M , Henriques E , Borges S , Guerra G , Ornelas I , Drumond A , Sousa A C , Palma Dos Reis R
Published: October 2024

Introduction

Aortic valve calcium (AVC) deposition is one of the mechanisms behind aortic sclerosis and stenosis. There is a known association between LPA gene rs3798220 T>C polymorphism and the development of severe aortic stenosis. However, it is still unknown if it has been a driving factor since the early stages of the disease.

Objective

Investigate, in our population, the association between the LPA gene variant rs3798220 T>C and aortic valve calcification.

Methods

AVC was measured in 451 consecutive individuals from the prospective arm of the GENEMACOR study with a mean age of 63.4±9.7 years, 58.8% male. AVC score was performed by cardiac computed tomography and reported as Agatston units. Results were separated into two groups (Group A: AVC=0; Group B: AVC>0). Lp(a) levels were analyzed in the different groups. Each individual was genotyped for LPA rs3798220 T>C. This variant has a minor allele frequency (MAF)<2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. The bivariate and multivariate logistic regression analysis evaluated the presence of AVC adjusting to traditional risk factors (TRFs) and the LPA heterozygous genotype (CT).

Results

LP(a) levels were higher in the CT allele versus the homozygous TT, but this difference did not reach a statistical significance. After multivariate analysis, the heterozygous LPA rs3798220 T>C polymorphism remained an independent risk factor for the presence of aortic valve calcification (OR=12.14, p=0.002) together with age (OR=1.13, p<0.0001), arterial hypertension (AHT) (OR=1.96, p=0.006) and alcohol consumption (OR=2.46, p=0.016).

Conclusion

The LPA gene variant rs3798220 T>C is associated with the presence of aortic valve calcification in a Portuguese population. In such an age-dependent disease as aortic stenosis, the inversion in the age pyramid will see a dramatic increase in the prevalence of aortic stenosis. The early identification of high-risk individuals might enable prompt traditional risk factors control and disease prevention. Larger population studies may help to determine if this difference is driven by Lp(a) levels.