bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of new allocation system on length of stay following heart transplantation in the US
Authors: Briasoulis A , Doulamis I , Tzani A , Rempakos A , Kampaktsis P , Alvarez P
Published: November 2023

Background

United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 in order to accommodate the increased prevalence of patients on ventricular assist device as a bridge to heart transplant and prioritize sicker people in anticipation of a heart graft.

Purpose

To assess the impact of the new allocation policy on length of stay following heart transplantation. Secondary outcomes include other risk factors for prolonged hospitalization and its effect on mortality and postoperative complications.

Methods

The UNOS Registry was queried to identify patients who solely underwent heart transplant in the US between 2000 and 2021. Patients were divided into groups according to their respective length of stay quartile.

Results

Patient demographics are summarized in Figure 1. Patients in the 4 th quartile of length of stay were more likely to be Status 1A (44% vs 37%, p<0.001), be on a left ventricular assist device (12% vs 9%, p<0.001), extracorporeal membrane oxygenator (5% vs 1%, p<0.001) and have an intra-aortic balloon pump (13% vs 8%, p<0.001) compared to the 1 st quartile. Length of stay was longer in the new allocation era (24±25 vs 20±29 days, p<0.001). Prolonged length of stay was also associated with increased 10-year mortality (HR: 1.64; 95% CI: 1.58, 1.70, p<0.001, Figure 2).

Conclusions

The longer hospital stay and the associated increased risk for mortality that is being observed in the era after the allocation criteria change reflect the rationale of this shift which was to prioritize heart transplant for sicker patients. Further studies are needed to track the progress of surgical and perioperative management of these studies over time.
Donor-derived cell-free DNA kinetics in the first year post-transplant in patients without acute cellular rejection
Authors: Jimenez-Blanco Bravo M , Crespo Leiro M , Gonzalez Sardinero E , Gomez Bueno M , Lopez Villela R , Ortiz Bautista C , Farrero M , Maestro Benedicto A , Diaz Molina B , Diez Lopez C , Rangel Sousa D , Salterain N , Garrido Bravo I , Segovia Cubero J
Published: November 2023

Background

Donor-derived cell-free DNA (dd-cfDNA) appears to be an excellent biomarker for acute cellular rejection (ACR) in heart transplant (HT) recipients. However, a significant rise in the immediate post-transplant phase probably related to direct myocardial damage during harvesting-implantation process has been described, and could potentially affect the biomarker’s performance in the first post-HT month. We sought to describe the biomarker’s kinetics in the first year post-HT in patients without ACR.

Methods

Prospective, multicentre study performed between 2019 and 2022. All patients underwent surveillance endomyocardial biopsy (EMB) at 7 pre-specified time points in the first post-HT year (0.5, 1, 2, 3, 4, 6 and 12 months). Dd-cfDNA levels were determined prior to each EMB, using Next Generation Sequencing technology.

Results

A total of 1006 pairs of EMB-dd-cfDNA from 206 patients were available for analysis (mean age 54 ±12 years, 74% male). Of these, 44 (4.3%) had clinically relevant rejection, defined as ACR grade ≥2, and 962 (95.7%) did not (562 0R and 400 1R). 15 samples that had pAMR≥1 were excluded from this analysis.

We divided the 947 samples with ACR 0-1 into three subgroups, according to the time of blood sampling: at 15 days (time point 1), at 30 days (time point 2) and 2 to 12 months post-HT (time point 3). Samples with 0R that were drawn at 15 and 30 days showed significantly higher levels of dd-cfDNA than those drawn between the second month and first year post-transplant (p <0.001) (Figure 1A). When we included patients with 1R, a similar trend was observed (p <0.001) (Figure 1B). Median dd-cfDNA levels for 0R and for 0-1R at the three time points are shown in Figure 2.

Conclusions

Dd-cfDNA levels in patients without clinically relevant rejection are significantly higher in the first month post-transplant. Further studies are needed in order to determine if a different cut-off point for ACR during the first post-HT month is useful for ACR diagnosis.Donor-derived cell-free DNA kineticsDd-cfDNA values at three time points
Reduction of cardiac allograft vasculopathy by PCI: Quantification and correlation with outcome after heart transplantation
Authors: Orban M , Kuehl A , Pechmajou L , Mueller C , Hausleiter J , Sfeir M , Bories M C , Martin A C , Ulrich S M , Dalla Pozza R , Mehilli J , Jouven X , Hagl C , Karam N , Massberg S
Published: November 2023

Background

Percutaneous coronary intervention (PCI) might improve outcome of heart transplanted (HTx) patients at severe stages of cardiac allograft vasculopathy (CAV). Yet, risk stratification of HTx patients after PCI remains challenging. The International Society for Heart and Lung Transplantation (ISHLT) provides a nomenclature for CAV classification that does not include patients after PCI (1). It is unclear how to define an individual optimal CAV reduction and how to stratify patients with CAV after PCI. Besides, whether risk-stratification tools of non-transplanted patients apply to HTx patients with CAV is uncertain.

Purpose

To assess whether the ISHLT CAV classification remains prognostic after PCI, and whether risk stratification models of non-transplanted patients can be applied to HTx patients with CAV.

Methods

At two European academic centers, 203 patients were stratified according to CAV severity and PCI history, and patients were assigned to only one cohort: cohort 1 (ISHLT CAV grade 1, without PCI, n=126) or cohort 2 (ISHLT CAV grades 2&3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I and SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). A rSXS-I>0 defined incomplete revascularization (IR). Five-year mortality was assessed. For cohort 2, first reintervention was a secondary outcome. Baseline parameters were also included into analysis.

Results

SXS-II predicted mortality in cohort 1 (Hazard ratio [HR] 2.5 [1.4–4.8], p=0.004), whereas SXS-I (HR 4.2 [1.4–12.2], p=0.009) and SXS-II (HR 7.1 [2.0–24.5], p=0.002) predicted mortality in cohort 2. Post-PCI, IR (HR 5.4 [1.7–17.0], p=0.004), high rISHLT (HR 3.6 [1.3–10.2], p=0.02) and highest tertile of rSXS-II (HR 5.1 [1.6–15.9], p=0.006) were associated with higher mortality. In cohort 2, post-transplant interval and KDIGO category of renal function at timepoint 0 were also predictors of 5-year mortality after first PCI (HR 1.1 [1.0 – 1.2], p=0.004 and HR 4.5 [1.8–11.3], p=0.01, respectively). In bivariable Cox analysis, baseline SXS-II, IR, rSXS-II, post-transplant interval and KDIGO category of renal function remained predictors of 5-year mortality. The interval to first reintervention was inversely related to baseline SXS-I (r=-0.55, p<0.001) and rSXS-I (r=-0.50, p=0.003).

Conclusion

A higher reduction of stenotic CAV was associated with improved 5-year survival rate after first PCI. ISHLT CAV classification could apply for risk stratification after PCI and SYNTAX-scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV.Figure 1.Study flow chart.Figure 2.Kaplan-Meier curves (cohort 2)
Imbalance of iron needs and supply in patients with acute and chronic heart failure
Authors: Lanser L , Poelzl G , Messner M , Ungericht M , Zaruba M M , Hirsch J , Hechenberger S , Obersteiner S , Koller B , Ulmer H , Weiss G
Published: November 2023

Background

Iron deficiency (ID) is frequent in patients with chronic and acute heart failure (CHF, AHF) associated with morbidity and mortality. ID can be absolute, defined as depleted iron stores (also named true ID), or functional describing hypoferremia despite adequate iron stores as a result of inflammation-related reduced iron mobilization and restriction in mononuclear cells. Empty iron stores can also be found simultaneously to inflammation-related reduced iron mobilization (combined ID).

Purpose

We aimed to better characterize ID and iron homeostasis in HF patients applying different biomarkers and to evaluate the accuracy of current ID definition by the ESC to indicate actual tissue iron needs and supply.

Methods

We performed a retrospective cohort study including 277 AHF and 476 CHF patients treated between 02/2021–05/2022 at the Medical University of Innsbruck.

Results

AHF patients had higher iron needs and lower iron supply than CHF patients, reflected by increased soluble transferrin receptor (sTfR) and sTfR-Ferritin (sTfR-F) index, and lower ferritin, serum iron, transferrin saturation (TfS), hepcidin and reticulocyte hemoglobin (Ret-Hb). Only 28.0% of CHF and 81.4% of AHF patients with absolute ID as well as 10.5% of CHF and 50.0% of AHF patients with combined ID based on the current ESC definition presented with an elevated sTfR-F index (>2.0 without and >3.2 with inflammation) and/or reduced Ret-Hb (<28pg), being indicative for tissue iron needs. Suppressed hepcidin expression (≤8.6ng/mL) as early marker of iron depletion was found in 80% of CHF and 91% of AHF patients with absolute ID and only in 19% of CHF and 32% of AHF patients with combined ID based on the current ESC definition.

When breaking down the ID definition into ferritin and TfS, in AHF an elevated sTfR-F index was found in patients with inflammation and associated with lower ferritin (<200 ng/mL), while a reduced Ret-Hb was primarily found in patients with inflammation, TfS <20% and ferritin <100 ng/mL. In CHF an elevated sTfR-F index and a reduced Ret-Hb were primarily present in patients with ferritin <30 ng/mL and TfS <20% as well as in patients with inflammation, TfS <20% and ferritin <100 ng/mL. (Figure 1) Specificity for defining true ID based on iron needs was increased when including inflammation for defining true ID and reducing the upper limit of ferritin for defining true ID in the setting of inflammation (Figure 2).

Conclusion

A substantial proportion of patients with ID defined by the current ESC definition, had normal tissue iron supply with no increased tissue iron needs. In accordance with previous studies, results from our study suggest that the current ESC definition might overestimate true ID especially in CHF. A more accurate definition of ID may help to identify those patients with AHF and CHF who truly benefit from intravenous iron supplementation.
Prognostic impact of improvement in quality of life after discharge in patients with ADHF with preserved ejection fraction regardless of the course of HF -PURSUIT-HFpEF registry
Authors: Kondo T , Watanabe T , Yamada T , Seo M , Yano M , Hayashi T , Nakagawa A , Nakagawa Y , Tamaki S , Yasumura Y , Sotomi Y , Hikoso S , Nakatani D , Fukunami M , Sakata Y
Published: November 2023

Background

Lower quality of life (QOL) is associated with poor clinical outcome in patients with heart failure (HF). However, there is not fully clarified whether the changes in QOL could have prognostic value in patients with HF with preserved ejection fraction (HFpEF).

Purpose

The purpose of this study is to investigate the prognostic impact of changes in QOL in patients with HFpEF in relation to the changes in condition of heart failure.

Methods

We prospectively studied 435 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome within 1 year after the discharge. The patients’ QOL was evaluated at discharge and 1 year after the discharge using EuroQol 5 dimensions 5-level (EQ-5D-5L) and the difference in the EQ-5D-5L index at these two time points was used to assess the change in QOL. The primary outcome was all-cause death.

Results

The median EQ-5D-5L index were 0.753 (0.562-0.875) at discharge and 0.784 (0.646-0.895) at 1 year after the discharge. During a mean follow-up period of 1.6±1.2 years, primary outcome occurred in 92 patients. Patients with improved QOL (defined as equal to or greater than the EQ-5D-5L index at discharge) were significantly younger, had lower volume load on echocardiography and higher level of hemoglobin and serum sodium than those without improved QOL. Both the improved QOL and the improvement of HF (defined as more than -0.035 in the difference in Log NTproBNP value within 1 year after discharge by ROC analysis: AUC 0.570 [0.506-0.635]) were associated with primary outcome at univariate Cox proportional hazard analysis and the improved QOL was significantly independently associated with primary outcome after multivariable adjustment. Kaplan-Meier analysis revealed that patients with improved QOL had significantly lower risk for primary outcome than those without improved QOL not only in the whole study patients (14% vs 27%, p=0.0007) but also both in the group with improving HF (11% vs 22% p=0.0129) and in those with worsening HF (17% vs 31% p=0.0468).

Conclusion(s)

The improvement in QOL had the prognostic impact in patients with ADHF-HFpEF regardless of the course of heart failure.
Evidence-based heart failure therapies at discharge of patients with acute coronary syndromes and reduced ejection fraction: Data from the ACSIS survey
Authors: Zafrir B , Ovdat T , Abu Akel M , Bahouth F , Orvin K , Beigel R , Amir O , Elbaz-Greener G
Published: November 2023

Background

Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS), even in the absence of overt HF. Few real-world data are available regarding early implementation of HF therapies in patients with ACS and reduced LVEF.

Methods

Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). Utilization of HF therapies at discharge or 90-days following ACS was analyzed in relation to LVEF [reduced ≤40% (n=406) or mildly-reduced 41-49% (n=255)] and short-term adverse outcomes.

Results

History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p<0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and BBC were used by >85% of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF≤40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41-49%, respectively, and SGLT2I in a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p=0.084. No association was observed between the number of HF drug classes, or the use of ARNI and/or SGLT2I with adverse clinical outcomes.

Conclusions

In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.Drug therapies for heart failure
Impact of in-hospital initiation of sodium-glucose cotransporter-2 inhibitors in patients with heart failure and reduced ejection fraction
Authors: Burgos L , Ballari F , Spaccavento A , Ricciardi B , Suarez L , Baro Vila R , Campos Cevera L , Chicote F , Fasan M , Fescina J , Arias R , Santos Gallego C , Diez M
Published: November 2023

Introduction

Safety and early clinical benefit make sodium-glucose cotransporter-2 inhibitor (SGLT-2i) therapy suitable for in-hospital initiation in patients with heart failure and reduced ejection fraction (HFrEF). Despite randomized controlled trials and guideline recommendations, they are underused and clinical inertia may play a role.

Objectives

Primary: To assess the impact of initiating SGLT-2i at discharge on 90-day prescription rates in patients with HFrEF during hospitalization for acute heart failure (AHF). Secondary: To evaluate the presence of contraindications at discharge and the independent factors associated with in-hospital prescription, and to assess clinical outcomes at 90 days.

Methods

Retrospective analysis of a consecutive prospective single-center cohort. Adult patients hospitalized between January 2021 and October 2022 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) <40% were included. Patients who underwent heart transplantation during hospitalization, used SGLT2i before admission, died or were referred during the index hospitalization were excluded. Those who started SGLT-2i before or at discharge were compared with those who did not. The primary outcome was SGLT-2i prescription rate at 90 days, and the exploratory secondary endpoints was the composite of hospitalization or urgent visit for AHF or all-cause mortality at 90 days. Independent factors associated with inpatient SGLT-2i prescription were analyzed using a logistic regression model.

Results

Among 378 patients with documented HFrEF, 240 (64%) met the inclusion criteria. Mean age was 76±11 years, 75.4% were male and the mean LVEF was 25±13%. SGLT-2i was indicated during hospitalization in 31.6% of patients. A total of 86% of the cohort had a 90-day follow-up, and the SGLT2i prescription rate was 94.2% in those with in-hospital initiation and 14.4% in those without (p<0.001). Among those without contraindications at discharge (n=141), the independent factor associated with inpatient prescription was lower age, OR 0.96 (0.93-0.99) for each year. There were no statistically significant differences between the two groups for the combined endpoint of all-cause death, HF rehospitalisation or unplanned HF visit at 90 days (p=0.3).

Conclusions

In-hospital initiation of SGLT-2-i was associated with significantly higher prescription rates 90 days after discharge, without differences in death from all causes and hospitalization or urgent visit for AHF at 90 days. This study reflects the presence of medical inertia, particularly in older patients. It also highlights the hospitalization period as an optimal time to start SGLT-2i and achieve the proven clinical benefits that accumulate rapidly over weeks, with solid safety and tolerability.
Early versus delayed introduction of renin angiotensin aldosterone system inhibitors in cardiogenic shock
Authors: Sulman D , Zeitouni M , Beaupre F , Devos P , Procopi N , Kerneis M , Guedeney P , Hammoudi N , Rouanet S , Brugier D , Combes A , Hekimian G , Collet J P , Montalescot G , Silvain J
Published: November 2023

Background

There is currently no recommendation on the appropriate timing of introduction of renin angiotensin aldosterone system inhibitors (RAASi) in patients admitted with cardiogenic shock.

Purpose

To describe the timing of introduction of RAASi during cardiogenic shock and its association with mortality.

Methods

We analyzed patients admitted with cardiogenic shock and treated with RAASi between January 1st, 2010, and December 31st, 2020, in our tertiary shock center. The characteristics and outcomes of patients with early RAASi introduction (≤ 3 days from admission) were compared with those who had a delayed RAASi introduction (> 3 days). Inverse propensity score was used to compare the primary outcome of in-hospital mortality. All-cause death or readmission for heart failure/cardiogenic shock was evaluated up to June 1st, 2022.

Results

The study population included 406 shock patients, 53% (n=215 patients) with early RAASi introduction and 47% (n=191 patients) in the delayed introduction group. Patients treated with early RAASi (vs. delayed introduction) were more frequently admitted for an acute myocardial infarction (53 % vs. 35 %) (p<0.01), had a better left ventricular fraction (LVEF 22% vs. 20 %) (P=0.001) and had less frequently chronic kidney disease (3.2 % vs. 9.4%) (p<0.01). Early RAASi introduction was associated with a higher in-hospital mortality (OR 6.47 (95% CI) 3.4 - 13.4, p<0.001) as compared with delayed introduction (figure 1). Each day of delay before introduction of RAASi was associated with a reduction of in-hospital mortality OR 0.80 95 % CI (0.69 - 0.89) (p<0.01). After a median follow up of 11 (2 – 48) months, there was no difference in the risk of death or heart failure between both strategies (p=0.89) (figure 2).

Conclusion

Early RAASi introduction during cardiogenic shock was associated with a higher in-hospital mortality, without apparent benefits during the year after discharge. Randomized studies are needed to evaluate the optimal time and dose management of RAAS inhibitors in cardiogenic shock.
Stress echocardiography: application of the ABCDE protocol in patients with permanent atrial fibrillation
Authors: Barbieri A , Bursi F , Ciampi Q , Cortigiani L , Zanella H , Wierzbowska-Drabik K , Kasprszak J D , Arbucci R , Zagatina A , Mantovani F , Bartolacelli Y , Carerj S , Pepi M , Pellika P A , Picano E
Published: November 2023

Objectives

A new standard of practice in stress echocardiography (SE) was founded with the development of the ABCDE protocol, which added functional information to conventional ischemia diagnosis. Each step showed to provide incremental prognostic information: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. However, the utility of SE and ABCDE protocol in patients with atrial fibrillation (AF) has never been tested.

Background

A growing body of evidence suggests that AF patients have a significant residual risk of myocardial infarction despite anticoagulant treatment; furthermore, they have an increased risk of heart failure and all-cause death. However, ABCDE-SE has never been applied in this population.

Methods

Of the 3965 patients who completed clinically indicated ABCDE-SE and with available information on rhythm stored in the shared data bank and enrolled from 13 certified centers, 3891 were in sinus rhythm (SR, Group 1) and 50 in permanent AF (Group 2) at the time of the test. ABCDE-SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). The employed stress was an exercise in 1626 (41%), vasodilator in 1864 (47%), and dobutamine in 475 (12%).

Results

Group 2 pts were older than Group 1 patients, more frequently hypertensives and diabetics, with lower ejection fraction, and with more signs of pulmonary congestion at rest. During stress, differences were magnified, and Group 2 patients showed more peak stress B-lines and higher values of peak WMSI compared with Group 1 (see Table). In addition, patients with AF had higher ABCDE scores (Group 1= 1.5 ±1.4 vs. Group 2= 2.6±1.6, p<0.0001). The distribution of the score in patients in SR and AF is shown in Figure.

Conclusions

Patients with AF are scarcely represented among patients undergoing SE. Patients with AF showed a higher prevalence of positivity in each step and a higher ABCDE score. More specifically, AF patients are more vulnerable than patients in SR to coronary microvascular dysfunction and chronotropic incompetence during stress.TableFigure
Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial (final results)
Authors: D'amario D , Restivo A , Merkin D , Crea F , Ince H , Sievert H , Schaefer U , Trani C , Di Mario C , Anker S , Perl L
Published: November 2023

Background

In heart failure (HF), implantable hemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided hemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure (PAP) monitoring systems.

Aims

We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients (V-LAP).

Methods and Results

The VECTOR-HF study was a first-in-human, prospective, multicenter, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After three months, a right heart catheterization (RHC) was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute Major Adverse Cardiac and Neurological Events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22±4.92mmHg, the correlation coefficient and the Lin’s Concordance Correlation Coefficient values were equal to 0.79 (P<0.0001) and 0.776 (95%CI=0.582-0.886), respectively. Preliminary experience with VLAP-based HF management was associated with significant improvements in NYHA functional class (32% of patients reached NYHA II class at 6 months, P<0.005; 60% of patients at 12 months, P<0.005) and 6-minute walk-test distance (from 244.59±119.59m at baseline to 311.78±129.88m after 6 months, P<0.05, and 343.95±146.15m after 12 months, P<0.05).

Conclusion

The V-LAP™ monitoring system proved to be safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms that could be associated to a better outcome. Further studies are needed to test the efficacy of the device in heart failure patients.
Myocarditis after vaccination against COVID-19: an umbrella review of systematic review and meta-analysis
Authors: Bouchlarhem A , Boulouiz S , Ismaili N , El Ouafi N
Published: November 2023

Introduction

A few months after the beginning of the COVID-19 vaccination, several reports of myocarditis secondary to the vaccines were published, sometimes with fulminant cases, but until today there is no proven causal link between these two events, but with many hypotheses proposed.

Purpose

We conducted an umbrella review of all systematic reviews with meta-analyses published in this sense, in order to carry out a critical review to be able to draw relevant conclusions for our practice.

Methods

A systematic review of current evidence regarding myocarditis after COVID-19 vaccination was performed by searching several databases including PubMed/Medline and Web of Science. The quality of MAs was assessed using the AMSTAR-2 tool as well as other qualitative criteria. The evidence was graded from convincing (Class I) to weak (Class IV), according to the type of studies included (prospective or retrospective), p-value of the overall effect, level of heterogenicity, sample size, or inclusion or not of the null value in the 95% confidence interval.

Results

Our umbrella review appraised 4 MAs of retrospective studies (range: 5–12), The number of vaccine doses included ranged from 12 to 179 million, with the number of myocarditis cases observed ranging from 343 to 1489. All types of vaccines were evaluated, with no exclusions. The overall incidence ranged from 0.89 to 2.36 cases of myocarditis per 100,000 doses of vaccine received (Figure 1). Heterogeny was assessed in 3 of the MAs, and was highly significant (>75%) in all included studies, and with a significant p-value (p <0.05). Regarding publication bias, three of the MAs conducted the egger and begg regression, with a significant result in only one. Of the 4 MAs included, only one was not registered in the PROSPERO database. Writing guidelines and reporting, including Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), were used in all included Mas. Regarding the assessment of the methodology by the AMSTAR-2 scale indicating that the quality was very critical in one, low in 2 MAs, and moderate in one MA. All MAs were classified as level IV evidence except one, which was classified as level III, and this was due to the retrospective nature of the included studies and the failure to report the p-value of the overall effect.

Conclusion

Despite the power of meta-analysis to increase sampling and precision, the quality of current non-randomized evidence on real causality and real incidence of myocarditis after COVID-19 vaccine is still low.
Coronary flow velocity reserve during exercise stress echocardiography in hypertrophic cardiomyopathy
Authors: Palinkas E D , Palinkas A , Zagatina A , Wierzbowska-Drabik K , D'Andrea A , Ciampi Q , Sepp R , Nagy V , Olivotto I , Picano E
Published: November 2023

Background

Coronary flow velocity reserve (CFVR) can be assessed with transthoracic echocardiography (TTE) as the stress/rest ratio of coronary flow velocity (CFV). Reduced CFVR during vasodilator stress (adenosine or dipyridamole) is a powerful predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the feasibility and correlates of CFVR during the more physiological - and recommended - exercise stress echocardiography (ESE) is unresolved.

Aim

To assess the feasibility and functional correlates of CFVR during exercise in HCM.

Methods

We studied 56 HCM patients (age=49±13 years, 33 [59%] males) and 44 age- and sex-matched healthy subjects with symptom-limited semi-supine ESE. ESE assessment included CFVR (stress/rest diastolic CFV) in the mid-distal left anterior descending coronary artery, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate reserve (HRR, peak/rest heart rate).

Results

CFVR was feasible in 46/56 HCM patients and in 41/44 controls (82% vs 93%, p=0.138). Median CFVR was significantly lower in patients with HCM compared to controls (1.72 [1.48; 2.10] vs 2.57 [2.25; 3.30], p<0.001), see Figure 1. In HCM patients, among resting parameters, CFVR was inversely correlated with left ventricular maximal septal thickness (r= -0.308, p=0.038), end-systolic diameter (r= -0.393, p=0.007), resting DBP (r= -0.398, p=0.006) and resting SBP (r= -0.321, p=0.030), while in controls CFVR correlated only with resting DBP (r= -0.322, p=0.040). During exercise, HCM patients with lower CFVR (<1.72, i.e. 1.72) showed lower peak CFV (78±20 vs 96±24 cm/s, p=0.003) and lower HRR (1.55±0.29 vs 1.76±0.25, p=0.020), see Figure 2. Exercise duration, peak stress workload or metabolic equivalents were not related to CFVR. In multivariable analysis, resting CFV (b=-0.034, 95% CI -0.037 and -0.030, p<0.001), resting DBP (b=-0.003, 95% CI -0.005 and -0.001, p=0.020), peak stress CFV (b=0.019, 95% CI 0.017 and 0.021, p<0.001) and HRR (b=0.126, 95% CI 0.005 and 0.247, p=0.041) were independently associated with CFVR.

Conclusion

CFVR assessment by TTE in the left anterior descending coronary artery is feasible during semi-supine exercise in most HCM patients. CFVR is markedly reduced in HCM patients on effort, particularly in the presence of high resting CFV and low HRR.Figure 1Figure 2
Cardiac energetics and end-organ perfusion with veno-arterial extracorporeal membrane oxygenation versus ecmella for cardiogenic shock in a large animal model
Authors: Hartmund Frederiksen P , Linde L , Gregers E , Udesen N L J , Helgestad O K , Banke A , Dahl J S , Jensen L O , Lassen J F , Larsen J P , Povelsen A L , Schmidt H , Ravn H B , Moller J E
Published: November 2023

Background

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is in severe cases of left ventricular (LV) failure associated with pulmonary edema due to inadequate LV emptying. In clinical practice VA-ECMO may be combined with Impella CP (ECMELLA), to unload the LV. We hypothesized that ECMELLA improves cardiac energetics without compromising end-organ perfusion compared to VA-ECMO alone in a porcine model of cardiogenic shock (CS).

Methods

Land-race pigs (weight 70 kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. Arterial blood samples were analyzed for lactate level. CS was induced with embolization in the left main coronary artery and was defined as a reduction of 50% or more in cardiac output (CO) or mixed oxygen saturation (SvO2) or a SvO2 < 30%. VA-ECMO was initiated at CS and embolization was continued until arterial pulse pressure was below 10 mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for four hours.

Results

CS was induced in 15 pigs (VA-ECMO n=7, ECMELLA n=8) and at CS the CO declined from 6.1 L/min (0.8) to 2.5 L/min (1.1) in the VA-ECMO arm and from 5.2 L/min (SD: 0.6) to 2.0 L/min (SD: 0.7) in the ECMELLA arm. The pressure-volume area (PVA) was comparable at CS, but significantly higher with VA-ECMO compared to ECMELLA after four hours (9567 SD: 1733 versus 6921 SD: 0536 mmHg*mL, p=0.014).

Carotid blood flow increased from CS and was similar in VA-ECMO and ECMELLA (239 mL/min SD: 97 versus 213mL/min SD: 133) at four hours p=0.6. Arterial lactate was equally elevated in both groups at four hours (VA-ECMO 5.2 SD: 3.4 versus 4.2 SD: 2.9 mmol/l for ECMELLA), p=0.5).

Conclusion

In a porcine model of CS, we found lower PVA with the ECMELLA configuration compared to VA-ECMO, yet similar lactate levels after four hours of mechanical circulation. These findings indicate that ECMELLA better cardiac energetics without compromising systemic perfusion.Central hemodynamicsEnd-organ perfusion
Impact of worsening renal function (WRF) and baseline chronic kidney disease (CKD) on clinical outcomes in patients with chronic coronary syndromes (CCS); insights from the REAL-CAD study
Authors: Ozaki Y , Yoshiki Y , Abe M , Takahashi H , Muramatsu T , Ismail T F , Ohota M , Takatsu H , Miyajima K , Shiki Y , Niwa Y , Harada M , Izawa H , Kimura T , Nagai R
Published: November 2023

Background

The impact of worsening renal function (WRF) and baseline chronic kidney disease (CKD) on clinical outcomes in patients with chronic coronary syndromes (CCS) in the era of modern PCI and optimal medical therapy is still unknown.

Methods

The REAL-CAD study is a prospective, multicenter, randomized trial either high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12,118 patients with CCS. The primary endpoint was composite of cardiovascular-death, nonfatal myocardial infarction and stroke, or unstable angina requiring emergency hospitalization (MACCE). CKD was defined as estimated glomerular filtration rate [eGFR]<60mL/min/1.73m2. WRF was defined as an annual decrease in eGFR >20% in the first year and Pre-WRF was defined as decrease in eGFR <20%. After excluding 1,247 patients who had MACCE, censored or missing eGFR within 1-year, 10,871 patients were examined. P < 0.05 was considered as statistically significant.

Results

Of the 12,118 baseline-patients, 4,340 had baseline-CKD (estimated glomerular filtration rate [eGFR]<60mL/min/1.73m2) and the remaining 7,778 had baseline-non-CKD (eGFR≥60mL/min/1.73m2). Five-year MACCE significantly deteriorated from 5.5% in non-CKD to 9.5% in CKD (p<0.0001). Of the 10,871 patients, 577 patients had WRF, 6014 patients showed Pre-WRF and the remaining 4280 patients maintained Non-WRF. In CKD patients, WRF was independent predictor for 4-year MACCE as compared to Non-WRF (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.03 to 2.73; P=0.039). In Non-CKD patients, Pre-WRF was significant predictor for 4-year MACCE as compared to Non-WRF (HR,1.40; 95%-CI,1.03-to-1.91; P=0.032).

Conclusions

Baseline-CKD was independent predictor for 5-year MACCE in patients with CCS. While WRF was independent predictor for 4-year MACCE in CKD patients, Pre-WRF was also predictor for 4-year MACCE in Non-CKD patients (NCT01042730).
Intracoronary ECG ST-segment shift remission time during reactive coronary hyperemia (tau-icECG): a new approach to assess hemodynamic coronary stenosis severity
Authors: Kieninger-Graefitsch A , Bigler M R , Waldmann F , Wildhaber R , Seiler C
Published: November 2023

Background

Coronary pressure-derived fractional flow reserve (FFR) measurements are recommended for hemodynamic coronary stenosis assessment. Given temporary paralysis of the coronary microcirculation during hyperemia, pressure is, in theory, directly related to coronary flow. Pressure drop during hyperemia across a coronary stenosis, thus, provides an estimate of its restrictive effect on flow. FFR during reactive hyperemia induced by a proximal, 1-minute coronary artery balloon occlusion has been shown non-inferior to FFR as obtained by adenosine-induced hyperemia. Intracoronary ECG (icECG) is more sensitive in detecting myocardial ischemia than the surface ECG, and can be easily obtained.

Purpose

The present study evaluated a novel diagnostic approach based on icECG ST-segment shift remission time for hemodynamic stenosis severity assessment.

Methods

This was a retrospective observational trial in patients with chronic coronary syndrome, who underwent hemodynamic measurements during a brief coronary occlusion with simultaneous icECG recording during coronary angiography. The icECG recording was used for a beat-to-beat analysis of the ST-segment elevation performed by a previously developed fully autonomous algorithm. The time after release of the 1-minute ostial coronary balloon occlusion when the ST elevation reached 50% of the pre-occlusion (baseline) isoelectric line, i.e., icECG remission half time (τ-icECG; τ=tau), was obtained by the algorithm (Figure1). τ-icECG was evaluated using the simultaneously obtained FFR at a threshold of 0.80 as reference parameter.

Results

139 icECGs from 119 patients were analysed, 23 had to be excluded in advance, due to incomplete icECG recording or algorithm failure. A ROC-analysis of τ at a threshold of >8s found it significantly accurate for detecting a hemodynamically relevant coronary stenosis at FFR≤0.80 (area under the ROC-curve 0.618, 95% CI 0.507-0.735, sensitivity 60%, specificity 67%, p=0.037) (Figure2).

Conclusion

Τ-icECG, a measure of icECG ST-elevation remission time to isoelectricity as obtained during reactive hyperemia FFR accurately detects hemodynamically relevant coronary artery stenoses at a threshold of ≥ 8 seconds.
TDE-derived impaired post-PCI Coronary flow velocity reserve predicts MACE in patients who underwent LAD PCI
Authors: Hanyu Y , Usui E , Hoshino M , Hada M , Nagamine T , Nogami K , Ueno H , Sayama K , Matsuda K , Sakamoto T , Yonetsu T , Sasano T , Kakuta T
Published: November 2023

Background

Coronary flow velocity reserve (CFVR) can be obtained noninvasively by stress transthoracic Doppler echocardiography (S-TDE). However, prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown.

Purpose

This study aimed to investigate the relationship between post-PCI CFVR and major adverse cardiac event (MACE).

Methods

This study prospectively included 200 patients with stable coronary artery disease who were scheduled for elective PCI of de novo, single, functionally significant left anterior descending (LAD) lesions at a single tertiary-care center between April 2019 and November 2022. All patients underwent fractional flow reserve (FFR)-guided elective PCI.

Exclusion criteria were patients with previous coronary artery bypass graft surgery, left main coronary artery disease and periprocedural myocardial infarction as defined by the fourth universal definition of myocardial infarction. Eligible patients underwent pre- (1 day before) and post-procedural (3 days after) LAD coronary flow assessments by stress-TDE. CFVR was calculated as the ratio of the hyperemic peak diastolic flow velocity to the basal peak diastolic flow velocity. We also excluded the patients with suboptimal S-TDE imaging. Association between post-PCI physiological parameters and MACE (composite of cardiac death, myocardial infarction, heart failure and target vessel revascularization) were evaluated.

Results

A total of 174 patients were included in the final analysis after successful LAD PCI. MACE occurred in twenty-one (12.0%) patients during the follow-up (1.9 [0.9-2.5] years). Clinical demographics were similar in patients with versus without MACE. Post-PCI S-TDE-derived CFVR was lower in patients with versus without MACE (P = 0.023), while post-PCI FFR values tended to be lower in patients with versus without MACE, albeit not significant (P = 0.077).

Receiver-operating characteristic curve analysis revealed that the optimal cut-off values of post-PCI FFR and post-PCI CFVR values to predict MACE were 0.83 and 1.70, respectively. Significant differences in the MACE were detected according to post-PCI FFR (≤ 0.83 versus > 0,83: 17.9 % versus 6.7 %, P = 0.035) and post-PCI CFVR (< 1.70 versus ≥ 1.70: 33.3% versus 8.2%, P = 0.001).

On a multivariable Cox-proportional hazard analysis, patients with post-PCI CFVR < 1.70 had an increased risk for MACE (adjusted hazard ratio [HR] 4.75, 95% confidence interval [CI] 1.98-11.38, P < 0.001), along with post-PCI FFR ≤ 0.83 (adjusted HR 2.78, 95% CI 1.07-7.20, P=0.035).

Conclusions

In patients who underwent successful elective PCI for LAD, S-TDE-derived impaired post-PCI CFVR and post-PCI FFR were independently associated with MACE.
Longitudinal assessment of coronary microvascular dysfunction in an all-comer patient population detects the highly dynamic natural history of this condition
Authors: Milzi A , Lubberich R , Reith S , Burgmaier K , Marx N , Dettori R , Burgmaier M
Published: November 2023

Introduction

Coronary microvascular dysfunction (CMD) is a common condition contributing to heterogenous cardiac diseases, such as myocardial ischemia and heart failure. However, little is known regarding the natural history of CMD, as most studies assessing this condition were performed cross-sectionally. Therefore, we investigated the evolution over time of microvascular function in an all-comer population, to assess the natural history of CMD.

Methods

273 patients undergoing elective coronary angiography at two timepoints at least 6 months apart were included; average time between the two coronary angiographies was 34±21 months. Microvascular function was measured retrospectively by means of angiography-based index of microvascular resistance (aIMR) at both timepoints in the same vessel (LAD in 93.4% of cases, LCx in 1.5%, RCA in 4.8%), in order to assess variation of microvascular function over time. An aIMR ≥25 was considered indicative of CMD.

Results

Of the included 273 patients, 107 presented CMD at inclusion (39.2%); average aIMR at baseline was 23.2±8.0. At the second timepoint, after an average of 34±21 months, average aIMR was significantly increased compared to baseline (24.4±8.6, p=0.013).

Interestingly, in spite of an overall increased average aIMR expressing a tendentially worsening microvascular function over time, of the 107 patients with CMD at inclusion only 61 (22.3% of the total population) still presented CMD at follow-up. On the contrary, 46 patients with CMD at inclusion (16.8%) showed an improved coronary microvascular function with an aIMR<25. On the other hand, 60 patients (22.0%) with initially normal aIMR developed de novo CMD at control angiography.

Conclusion

In our study longitudinally assessing CMD in an all-comer population, we could show that average microvascular function shows a mild overall worsening over time. However, our data show that CMD is a highly dynamic condition with high rates of improvement and worsening over time. The assessment of the clinical predictors of these variations may shed further light on the still incompletely understood pathogenesis of CMD and mainly on its natural history.
Combined assessment of coronary microvascular dysfunction and left ventricular diastolic dysfunction can stratify prognosis of patients with nonobstructive coronary artery disease
Authors: Ito A , Murai T , Hikita H , Watanabe T , Takahashi K , Ikeda H , Cho S , Yano H , Hishikari K , Takahashi A , Yonetsu T , Sasano T
Published: November 2023

Background

Previous studies reported that coronary microvascular dysfunction (CMD) and left ventricular diastolic dysfunction (LVDD) were associated with adverse cardiovascular events. To date, the relationship between coronary flow reserve (CFR), left ventricular diastolic function and future cardiovascular risk is unknown.

Methods and results

This study included 214 patients undergoing intracoronary physiological assessment with CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery at Yokosuka Kyosai Hospital from December 2019 to June 2021. Of 214 patients (female: N=55 [29%], age: 72±9 years), 94 (44%) had CMD (CFR<2.5) and 75 (35%) had LVDD (E/e’>14). Patients were classified into 4 groups based on the cut-off values of CFR and E/e’: group 1 (no CMD nor LVDD, n=88); group 2 (only LVDD, n=39); group 3 (only CMD, n=51) and group 4 (both CMD and LVDD, n=36).

The primary endpoint was major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction, any revascularization, hospitalization for heart failure or arrhythmia. The secondary endpoint was all cause hospitalization including cerebrovascular events and infectious diseases.

During a median follow-up of 572 days, the cumulative MACE-free survival rate at 1 year were 97.5%, 97.2%, 91.3% and 72.8% in groups 1 to 4. Group 4 showed significantly higher risk of MACE and all cause hospitalization at 1 year compared with group 1 (hazard ratio [HR] 5.17; 95% confidence interval [CI] 1.91-13.98; p<0.001, and HR 5.49; 95% CI 2.35-12.85; p=0.001, respectively). Group 2 and 3 had significantly higher risk of all cause hospitalization than Group1 (HR 3.10; 95% CI 1.25-7.72; p=0.010 and HR 2.53; 95% CI 1.04-6.11; p=0.033, respectively).

Notably, Group 4 showed the highest incidence of hospitalization due to heart failure (6 [16.7%]) than other 3 groups (1 [1.1%] p<0.001, 0 [0%] p<0.001 and 0 [0%] p<0.001, Group 1 to 3 respectively).

Conclusion

Patients with both CMD and LVDD showed significantly higher risk for MACE, especially for heart failure requiring hospitalization. The combined classification based on CFR and diastolic function would identify the high-risk patients for MACE as well as all cause hospitalization.