Functional assessment in acute coronary syndrome: a systematic review of acute versus staged interventions

Federico Vergni; Silvia Buscarini; Leonardo Ciurlanti; Filippo Luca Gurgoglione; Francesco Pellone; Mario Luzi

doi:10.24875/RECICE.M25000511

. 2025 Jun 12;7(3):169–177. doi: 10.24875/RECICE.M25000511

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Functional assessment in acute coronary syndrome: a systematic review of acute versus staged interventions

Federico Vergni ^a,^*, Silvia Buscarini ^b, Leonardo Ciurlanti ^a, Filippo Luca Gurgoglione ^c, Francesco Pellone ^a, Mario Luzi ^d

PMCID: PMC12418243 PMID: 40933011

ABSTRACT

Introduction and objectives:

Several tools have been implemented to assess the functional significance of coronary lesions. Their reliability in the management of acute coronary syndrome (ACS) might be affected by alterations in the acute phase that go beyond the affected area. Our main objective was to evaluate the reliability of invasive physiological indices for non-culprit lesions (NCL) in patients with ACS.

Methods:

We conducted a systematic review across ClinicalTrials.gov, Embase, Google Scholar, PubMed, and Web of Science from inception through 5 December 2024. Additionally, a citation analysis and web searches were conducted.

Results:

A total of 20 articles, with 4379 patients were included in the analysis. The main study design is a cohort study. The following methods were compared between acute and staged interventions: a) angiography-derived; b) hyperemic; and c) non-hyperemic indices. A significant difference in fractional flow reserve, instantaneous wave-free ratio, and quantitative flow ratio was found in one or more articles. There were no articles reporting any important changes in the Murray law-based quantitative flow ratio, resting distal-to-aortic coronary pressure ratio, or vessel fractional flow reserve. However, these indices rely on retrospective and/or limited data. All significant variations were observed in cohorts of ST-segment elevation myocardial infarction. Unlike quantitative flow ratio, the fractional flow reserve and instantaneous wave-free ratio demonstrated consistent directions of change towards lower and higher values, respectively. Prospective cohorts and randomized controlled trials including non-ST-segment elevation acute coronary syndrome did not prove the existence of significant differences between acute and follow-up fractional flow reserve.

Conclusions:

Physiological methods lack complete reliability for evaluating NCL during acute ST-segment elevation myocardial infarction. However, considering directions of change, fractional flow reserve is suitable for guiding the revascularization of acute positive NCL. Conversely, instantaneous wave-free ratio can be used to defer the revascularization of negative NCL. In non-ST-segment elevation acute coronary syndrome, fractional flow reserve is appropriate for assessing NCL within the acute phase.

Keywords: Fractional flow reserve, Instantaneous wave-free ratio, Quantitative flow ratio

RESUMEN

Introducción y objetivos:

Se han implementado varias herramientas para evaluar la importancia funcional de las lesiones coronarias. Su fiabilidad en el síndrome coronario agudo (SCA) podría verse afectada por perturbaciones en la fase aguda que se extienden más allá de la zona afectada. Nuestro objetivo principal fue evaluar la fiabilidad de los índices fisiológicos invasivos para las lesiones no culpables (LNC) en pacientes con SCA.

Métodos:

Se realizó una revisión sistemática en ClinicalTrials.gov, Embase, Google Scholar, PubMed y Web of Science, desde el inicio hasta el 06/12/2024. Además, se hizo un análisis de citas y búsquedas en la web.

Resultados:

Se incluyeron en el análisis 20 estudios, que abarcaban 4.379 pacientes. El principal diseño de estudio es el de cohorte. Se compararon los siguientes métodos entre procedimientos agudos y diferidos: a) índices derivados de la angiografía; b) índices hiperémicos; y c) índices no hiperémicos. En uno o más artículos se hallaron diferencias significativas en la reserva fraccional de flujo, el índice diastólico instantáneo sin ondas y el cociente de flujo cuantitativo. Ningún artículo informó de cambios importantes en el cociente de flujo cuantitativo basado en la ley de Murray, el cociente de presión coronaria distal-aórtica en reposo o la reserva fraccional de flujo del vaso. Sin embargo, estos estudios se basan en datos retrospectivos o limitados. Todas las variaciones significativas se observaron en cohortes de pacientes con infarto de miocardio con elevación del segmento ST. A diferencia del cociente de flujo cuantitativo, la reserva fraccional de flujo y el índice diastólico instantáneo sin ondas mostraron direcciones de cambio coherentes, hacia valores más bajos y más altos, respectivamente. Las cohortes prospectivas y los ensayos controlados aleatorizados que incluyeron pacientes con infarto de miocardio sin elevación del segmento ST no encontraron diferencias importantes entre la reserva fraccional de flujo aguda y la diferida.

Conclusiones:

Los métodos fisiológicos no tienen una total fiabilidad para evaluar la gravedad de las LNC durante el infarto agudo de miocardio con elevación del segmento ST. Sin embargo, teniendo en cuenta las direcciones del cambio, la reserva fraccional de flujo es adecuada para guiar la revascularización de una LNC positiva en la fase aguda. Por el contrario, el índice diastólico instantáneo sin ondas se puede utilizar para aplazar la revascularización de una LNC con valoración negativa. En el SCA sin elevación del segmento ST, la reserva fraccional de flujo es adecuada para evaluar una LNC en la fase aguda.

Palabras clave: Reserva fraccional de flujo, Índice diastólico instantáneo sin ondas, Cociente de flujo cuantitativo

Abbreviations

ACS:: acute conary syndrome.
FFR:: fractional flow reserve.
iFR:: instantaneous wave-free ratio.
NCL:: non-culprit lesions.
QFR:: quantitative flow ratio.

INTRODUCTION

SEE RELATED CONTENT:

https://doi.org/10.1016/j.recesp.2018.11.012

The optimal strategy and timing of complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel conary artery disease remains unclear, and current recommendations are controversial.1 Accding to 2023 European Society of Cardiology (ESC) guidelines, complete revascularization, based solely on angiographic severity, is recommended in “stable”STEMI patients.2 Conversely, the 2023 Asia-Pacific Expert Consensus Document suggested a treatment strategy of non-culprit lesions (NCL) based on angiographic severity and invasive physiological assessment with fractional flow reserve (FFR) or non-hyperemic pressure ratios for patients with STEMI.3

FFR and non-hyperemic pressure ratios may be inaccurate in acute conary syndrome (ACS), as hyperemic flow may be reduced due to microcirculatory dysfunction, while the resting flow may be higher due to neurohumoral compensatory mechanisms.4

Angiography-derived indices are additional physiological tools. They need ≥ 1 angiographic projections plus frame count analysis and/or aortic pressure that may also be different in the acute setting.

Furthermore, drugs such as hypolipidemic agents may promote plaque regression, potentially impacting the results of physiological assessment after a few months into therapy.5

Our main objective was to evaluate the changes in invasive physiological measurements of NCL between the acute and staged phases of ACS.

Secondly, we aimed to evaluate the effects of different therapies on physiological measurements.

METHODS

Eligibility criteria

We included studies that evaluated the physiology of NCL during acute and staged interventions for ACS. Studies conducted on assessments following percutaneous conary interventions of non-culprit vessels, or with patients with chronic conary syndrome were excluded.

Case reports, conference abstracts, commentaries, editorials, and reviews were excluded as well. An initial protocol was registered in PROSPERO with registration No. CRD42024574683.

Search strategy, and study selection

We conducted the search across ClinicalTrials.gov, Embase (via Ovid), Google Scholar, PubMed, and Web of Science from inception through 26 April 2024 (initial search). We used the “Review articles”filter in Google Scholar and the “Topic”field in Web of Science. No language restrictions were applied.

Duplicates were removed using Deduplicator (SR-Accelerator) software. Title/abstract and full text screening was conducted independently by 2 authors using Rayyan software.

Back in July, 2 authors conducted a backward and forward citation analysis of the included articles using Citationchaser software.

The search strings were repeated in 6 December 2024 (in Embase, sources with invalid date limits were excluded). Simultaneously, we looked into any online conference news on imaging modalities and physiological measurements.6 Additionally, we looked into the “Slide Library”section using the “2024”filter on another web page.7

Finally, we manually reviewed the references of the articles included after the initial search.

All discrepancies were resolved by consensus.

Selection process was recded in sufficient detail to complete a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram.8

Data extraction

The following data were extracted from each article: a) study characteristics; b) population characteristics; c) type of physiological index(es); d) follow-up duration; e) primary endpoint.

The primary endpoint was the variation between acute and staged indices regarding statistical significance, mean difference (MD), and disagreement on revascularization decision.

One author extracted the data, and another one checked it independently. We contacted the authors of eligible studies when clarifications were needed.

Risk of bias assessment

Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools,9-11 as appropriate.

Two authors independently assessed the risk of bias for each study. We used red for high, yellow for moderate, and green for low risk of bias based on positive answers being ≤ 49%, 50%-69%, or ≥ 70%.

Data synthesis

We conducted a descriptive synthesis of the evidence. Results from data extraction were shown in separate tables based on risk of bias, or bubble charts. Some data were rounded to the nearest integer (age, diameter of stenosis of NCL, and follow-up) or 2 decimal places (MD).

Unless otherwise specified, P values < .05 were considered statistically significant. When MDs were unreported, they were estimated by calculating the difference between staged and acute mean values. When required, a formula for estimating the means was applied.12

In bubble charts, the size of the bubbles represents the number of patients or lesions if the former was not reported. Acute−/staged+ disagreement indicates an acute value above the threshold, with the staged value below the revascularization cut-off. Acute+/staged− disagreement represents the opposite.

RESULTS

Characteristics of the articles, participants, and indices

Results of the search and selection processes are shown in figure 1. Extracted data are shown in table 1 and table 2.

Table 1. Extracted data of studies with low risk of bias.

First author	Patients (No.)	Age (years)	STEMI (%)	PDS of NCL (%)	Type of index	Follow-up (days)	Comparison across measurements
First author	Patients (No.)	Age (years)	STEMI (%)	PDS of NCL (%)	Type of index	Follow-up (days)	P-value	Mean difference (staged−acute value)
Bär13	94^a	59 ± 10	53	37 ± 8	cQFR	365	NR	0.00
Bär13	99^b	58 ± 8	54	37 ± 8	cQFR	365	NR	− 0.01
Ctés14	88	68 ± 11	100	59 ± 12	cQFR	6 ± 4	S	+ 0.06
Erbay15	321	66 [58-76]	50.5^c	47 [36-57]	cQFR	49 [42-58]	NS	+ 0.01
Hou16	2256	64 ± 6	100	65 ± 9	muQFR	(7-45)	NS	0.00
Huang17	92	65 ± 10	100	(30-80)	vFFR	15 [3-30]	NS	0.00
Kirigaya18	50	63 ± 11	100	46 ± 13	cQFR	14 ± 5	NS	+ 0.01
Mensink19	150^d	64 ± 9	35.3	NR	FFR	84	NR	0.00
Musto20	50	68 ± 11	100	58 ± 12	FFR	6 ± 2	NS	0.00
Musto20	50	68 ± 11	100	58 ± 12	iFR	6 ± 2	NS	0.00
Ntalianis21	101	63 ± 12	74.2	56 ± 14	FFR	35 ± 4	NS	0.00
Sejr-hansen22	NR^e	NR	100	56 [48-66]	cQFR	13 [7-31]	NS	− 0.02
Sejr-hansen22	NR^e	NR	100	56 [48-66]	iFR	13 [7-31]	S	+ 0.02
Shenla23	31	56 ± 8	100	78 ± 9	FFR	18 ± 4	S	− 0.01
Thim24	120	66 ± 11	100	50 [41-59]	iFR	16 [5-32]	S	+ 0.03
Van der Hoeven25	73	61 ± 10	100	55 ± 13	FFR	31 ± 6	S	− 0.03
					iFR		NS	+ 0.01
					Resting P_d/P_a		NS	+ 0.01
Wang26	70	62	100	NR	QFR	30	NS	− 0.01
Wang26	70	62	100	NR	FFR	30	S	− 0.03
Zhao27	102^f	66 ± 6	100	64 ± 5	cQFR	365	NR	+ 0.01
Zhao27	253^g	65 ± 6	100	64 ± 6	cQFR	365	NR	− 0.01

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cQFR, contrast quantitative flow ratio; FFR, fractional flow reserve; iFR, instantaneous wave-free ratio; muQFR, Murray law-based QFR; NCL, non-culprit lesions; NR, not reported; NS, non-significant; P_d/P_a, distal-to-aortic conary pressure ratio; QFR, quantitative flow ratio; PDS, percent diameter stenosis; S, significant; STEMI, ST-segment elevation myocardial infarction; vFFR, vessel fractional flow reserve.

Data are expressed as mean, mean ± standard deviation or median [interquartile range] or (range) (age, PDS of NCL, follow-up).

Statin + alirocumab subgroup.

Statin + placebo subgroup.

Percentage of ST-segment elevation acute conary syndrome.

Overall population (statin + evolocumab or placebo subgroups).

No. of lesions analyzed: 70.

Statin + evolocumab subgroup.

Statin monotherapy subgroup.

Table 2. Data drawn from studies with moderate risk of bias.

First author	Patients (No.)	Age (years)	STEMI (%)	PDS of NCL (%)	Type of index	Follow-up (days)	Comparison across measurements
First author	Patients (No.)	Age (years)	STEMI (%)	PDS of NCL (%)	Type of index	Follow-up (days)	P-value	Mean difference (staged−acute value)
Barauskas28	79	NR	100	(35-75)	QFR	≥ 91	NS^a	− 0.02
Jo29	115	60 ± 12	32.2	NR	FFR	182	NS	− 0.01
Li30	84	60 ± 11	100	(50-90)	muQFR	8 ± 2	NS	0.00
Park31	60^b	57 ± 11	30	NR	FFR	182	NS	− 0.02
Park31	60^c	59 ± 10	33.3	NR	FFR	182	NS	− 0.01
Spitaleri32	31	64 ± 12	100	59 ± 13	cQFR	(3-4)	NS	0.00

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cQFR, contrast quantitative flow ratio; FFR, fractional flow reserve; muQFR, Murray law-based QFR; NCL, non-culprit lesions; NS, non-significant; NR, not reported; PDS, percent diameter stenosis; QFR, quantitative flow ratio; STEMI, ST-segment elevation myocardial infarction.

Data are expressed as ≥ lower limit or mean or mean ± standard deviation or (range) (age, PDS of NCL, follow-up).

Level of significance was set at P < .001.

Ticagrelor subgroup.

Clopidogrel subgroup.

A total of 20 articles were included13-32 (1 article in the form of a conference presentation).19 Publication years went from 2010 through 2024. The total number of reported patients was 4379.

In every publication, the patients are predominantly men and non-diabetic. The main clinical presentation was STEMI, except for 3 studies.19,29,31

The following methods were assessed: a) angiography-derived: Murray law-based quantitative flow ratio (muQFR), quantitative flow ratio (QFR), vessel FFR (vFFR); b) hyperemic (FFR); and c) non-hyperemic indices: instantaneous wave-free ratio (iFR), resting distal-to-aortic conary pressure ratio (P_d/P_a). When reported, the FFR was obtained using adenosine.

Reported patients for each index are as follows: 2340 (muQFR), 1187 (QFR), 710 (FFR), 243 (iFR), 92 (vFFR), and 73 (resting P_d/P_a).

Risk of bias

The studies mainly used an observational (cohort) design. Cohort studies on angiography-derived methods were retrospective, except for 1 article on QFR.28 Those on FFR and non-hyperemic indices were prospective, except for 2 substudies.22,26

QFR was also evaluated by 1 quasi-experimental study27 and 1 randomized controlled trial.13

Finally, the FFR was assessed by 2 randomized controlled trials, in samples with predominance of non-ST-segment elevation myocardial infarction (NSTEMI).19,31,33

Results are shown in table 1 of the supplementary data, table 2 of the supplementary data, and table 3 of the supplementary data. There were no studies with high risk of bias.

Tabla 1. Datos extraídos de estudios con bajo riesgo de sesgo.

Autor principal	Pacientes (N)	Edad (años)	IAMCEST (%)	PED de las LNC (%)	Tipo de índice	Seguimiento (días)	Comparativa entre mediciones
							Valor p	Diferencia media (valor diferido-agudo)
							Bär13	94^a	59 ± 10	53	37 ± 8	QFRc	365	ND	0,00
99^b	58 ± 8	54	37 ± 8	ND	−0,01		Bär13					QFRc	365
Cortés14	88	68 ± 11	100	59 ± 12	QFRc	6 ± 4	S	+0,06
Erbay15	321	66 [58-76]	50,5^c	47 [36-57]	QFRc	49 [42-58]	NS	+0,01
Hou16	2.256	64 ± 6	100	65 ± 9	muQFR	(7-45)	NS	0,00
Huang17	92	65 ± 10	100	(30-80)	RFFv	15 [3-30]	NS	0,00
Kirigaya18	50	63 ± 11	100	46 ± 13	QFRc	14 ± 5	NS	+0,01
Mensink19	150^d	64 ± 9	35,3	ND	RFF	84	ND	0,00
Musto20	50	68 ± 11	100	58 ± 12	RFF	6 ± 2	NS	0,00
Musto20	50	68 ± 11	100	58 ± 12	iFR	6 ± 2	NS	0,00
Ntalianis21	101	63 ± 12	74,2	56 ± 14	RFF	35 ± 4	NS	0,00
Sejr-hansen22	ND^e	ND	100	56 [48-66]	QFRc	13 [7-31]	NS	−0,02
Sejr-hansen22	ND^e	ND	100	56 [48-66]	iFR	13 [7-31]	S	+0,02
Shukla23	31	56 ± 8	100	78 ± 9	RFF	18 ± 4	S	−0,01
Thim24	120	66 ± 11	100	50 [41-59]	iFR	16 [5-32]	S	+0,03
Van der Hoeven25	73	61 ± 10	100	55 ± 13	RFF	31 ± 6	S	−0,03
					iFR		NS	+0,01
					P_d/P_a en reposo		NS	+0,01
Wang26	70	62	100	ND	QFR	30	NS	−0,01
Wang26	70	62	100	ND	RFF	30	S	−0,03
Zhao27	102^f	66 ± 6	100	64 ± 5	QFRc	365	ND	+0,01
Zhao27	253^g	65 ± 6	100	64 ± 6	QFRc	365	ND	−0,01

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IAMCEST: infarto agudo de miocardio con elevación del segmento ST; iFR: índice diastólico instantáneo sin ondas; LNC: lesiones no culpables; muQFR: cociente de flujo cuantitativo basado en la ley de Murray; ND: no disponible; NS: no significativo; P_d/P_a: cociente de presión coronaria distal/aórtica en reposo; PED: porcentaje de estenosis por diámetro; QFR: cociente de flujo cuantitativo; QFRc: cociente de flujo cuantitativo con contraste; RFF: reserva fraccional de flujo; RFFv: reserva fraccional de flujo del vaso; S: significativo.

Los datos expresan n (%), media, media ± desviación estándar o mediana [rango intercuartílico] (edad, PED de las LNC, seguimiento).

Subgrupo estatinas + alirocumab.

Subgrupo estatinas + placebo.

Porcentaje de síndrome coronario agudo con elevación del segmento ST.

Población general (subgrupos estatina + evolocumab o placebo).

Número de lesiones analizadas: 70.

Subgrupo estatinas + evolocumab.

Subgrupo en monoterapia con estatinas.

Tabla 2. Datos obtenidos de estudios con riesgo moderado de sesgo.

Autor principal	Pacientes (N)	Edad (años)	IAMCEST (%)	PED de las LNC (%)	Tipo de índice	Seguimiento (días)	Comparativa entre mediciones
Autor principal	Pacientes (N)	Edad (años)	IAMCEST (%)	PED de las LNC (%)	Tipo de índice	Seguimiento (días)	Valor p	Diferencia media (valor diferido-agudo)
Barauskas28	79	NR	100	(35-75)	QFR	≥ 91	NS^a	−0,02
Jo29	115	60 ± 12	32,2	NR	FFR	182	NS	−0,01
Li30	84	60 ± 11	100	(50-90)	muQFR	8 ± 2	NS	0,00
Park31	60^b	57 ± 11	30	NR	FFR	182	NS	−0,02
Park31	60^c	59 ± 10	33,3	NR	FFR	182	NS	−0,01
Spitaleri32	31	64 ± 12	100	59 ± 13	cQFR	(3-4)	NS	0,00

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IAMCEST: infarto agudo de miocardio con elevación del segmento ST; LNC: lesiones no culpables; muQFR: cociente de flujo cuantitativo basado en la ley de Murray; ND: no disponible; NS: no significativo; PED: porcentaje de estenosis por diámetro; QFR: cociente de flujo cuantitativo; QFRc: cociente de flujo cuantitativo con contraste; RFF: reserva fraccional de flujo.

Los datos expresan > límite inferior o media o media ± desviación estándar o (rango) (edad, PED de las LNC, seguimiento).

El nivel de significación estadística se situó en un valor p < 0,001.

Subgrupo ticagrelor.

Subgrupo clopidrogel.

Primary endpoint

Statistical significance

There were no articles on relevant changes in muQFR,16,30 resting P_d/P_a,25 and vFFR17 at the follow-up.

A significant difference in FFR, iFR, and QFR was found in 3, 2, and 1 article(s),14,22-26 respectively. In 1 study, the difference in QFR was non-significant, with a significance threshold of .001.28

These variations were seen in cohorts of STEMI patients.14,22-26 Studies including non-ST-segment elevation acute conary syndrome (NSTEACS) did not show any relevant differences regarding the QFR15 or the FFR.19,21,29,31

A total of 4 articles20,22,25,26 evaluated > 1 method. The iFR and FFR were both stable in the study by Musto et al.,20 while the iFR was more stable than the FFR in a different article.25 The QFR was compared to both the FFR26 and the iFR.22 Unlike these indices, the QFR did not show any significant changes in staged phases.22,26

Mean differences

The most valued indices showed varying results. muQFR had MD values close to 0 in both studies.16,30

QFR variations were observed at both lower22,26,28 and higher values.14,15,18 Conversely, the FFR and the iFR varied towards smaller and greater values, respectively.22-26,29,31 Their MDs ranged from − 0.02 to + 0.06 (QFR), − 0.03 to 0.00 (FFR), and 0.00 to + 0.03 (iFR).14,19-21,24,25,28 MD values of 0.01 were observed more often.

In STEMI patients, the MDs of the FFR, the iFR, and the QFR were close to 0 only in studies with mean follow-ups of < 1 week.20,32 In studies including NSTEACS, the FFR MDs were close to 0 after longer mean follow-ups (> 1 month).19,21 Furthermore, Ntalianis et al. showed a greater stability of FFR in patients with NSTEMI (MD, 0.00) vs those with STEMI (MD, − 0.02).21

Disagreement

Disagreement in the indication for revascularization is shown in figure 2. MDs of 0.01 resulted in variable disagreements: 5%-18%.15,18,23,25

Unlike the QFR, the FFR and the iFR consistently showed a higher frequency of one type of disagreement: acute−/staged+ for FFR,21,23,25 and acute+/staged− for iFR.24,25

Secondary endpoint

A total of 4 studies compared the effects of different drugs on the physiological parameters.13,19,27,31

Ticagrelor (which can increase the levels of adenosine) was compared to clopidogrel and no significant differences were found in the FFR of non-culprit vessels after 6 months of treatment.31

Another 3 studies compared a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (eg, alirocumab or evolocumab) plus high-intensity statin (HIST) (eg, rosuvastatin 20 mg/day) vs statin-only therapy.13,19,27

In a nonrandomized study, the QFR values were significantly higher in the evolucumab group at 12 months.27 However, in 2 randomized studies, no significant differences were observed across the 2 treatment groups in the QFR at 12 months or in the FFR at 3 months, respectively.13,19

DISCUSSION

The main findings of this systematic review are these: firstly, in STEMI patients, the muQFR, resting P_d/P_a, and vFFR indices remained relatively stable in retrospective and/or small studies. The FFR, iFR, and QFR showed variability between acute and staged phases. Secondly, the FFR did not change significantly in prospective cohorts or randomized controlled trials including NSTEACS. Thirdly, the QFR was more stable than both the FFR and the iFR in direct comparisons, although only the FFR and the iFR exhibited consistent directions of change. Fourthly, PCSK9 inhibitors added to HIST did not influence physiological measurements compared with HIST in randomized controlled trials.

The muQFR demonstrated stability in a large sample of patients. This index is based on a single angiographic view, unlike other angiography-based methods that require 2 angiographic projections. This characteristic might reduce observer variability and enhance reliability. Future prospective and comparative studies are needed to confirm the validity of this method.

Although low variations for FFR, iFR, and QFR were observed in cohorts of STEMI patients,20,32 these studies were limited by short-term follow-ups. Thim et al. found a non-significant change in the iFR with 5-day follow-ups, whereas there were significant changes with ≥ 5 day follow-ups.24 Therefore, physiological disarrangements initiated at the acute moment of STEMI might still exist if a staged procedure is conducted close to the index event.24,25

Angiographic, hemodynamic, and microcirculatory variables may alter acute physiologic assessment and account for the higher reliability of the FFR in NSTEACS vs STEMI.

In patients with microvascular dysfunction, epicardial blood flow cannot increase sufficiently during maximal hyperemia, thus causing a reduced pressure gradient across the stenotic lesion,29 and higher FFR values.

In STEMI patients, microcirculatory indices (conary flow reserve and index of microcirculatory resistance) were significantly worse during the acute phase, along with a higher FFR.25 Conversely, studies including NSTEACS did not show any significant differences in the conary flow reserve and/or index of microcirculatory resistance at the follow-up.21,29,31

Furthermore, STEMI patients showed greater acute angiographic severity, along with lower QFR or iFR values,14,22 which may be attributed to vasoconstriction typically occurring during the acute phase.

Consequently, the FFR seems more reliable in NSTEACS vs STEMI due to reduced acute microcirculatory impairment and/or vasoconstriction.

Literature trials support the use of the FFR in NCL of NSTEMI during the acute phase (eg, within the index hospitalization).34,35 In contrast, acute FFR-guided complete revascularization did not show any significant benefits in terms of death or myocardial infarction in STEMI patients.36-39

The higher stability of QFR when directly compared to the FFR or the iFR was limited to a small number of patients in post-hoc substudies.22,26 A MD of 0.01 sometimes led to non-trivial disagreement on revascularization decision,25 likely due to baseline values being near the cut-off. Therefore, it is essential to have an index which remains stable or demonstrates consistent changes, such as the FFR and the iFR. Similarly, these indices demonstrated a greater frequency of a specific type of disagreement (methodological variations–wire positioning–may explain the less frequent cases of disagreement).24

Therefore, the FFR and the iFR could be considered in the acute STEMI as an alternative to delayed assessments,25 considering that the FFR tends to decrease and the iFR tends to increase. The FFR could guide the revascularization of positive lesions (FFR ≤ 0.80).25 In patients with a FFR > 0.80, acute iFR assessment can be used to delay the revascularization of negative NCL (iFR > 0.89).24 In the remaining cases (iFR ≤ 0.89), some authors suggested a staged reevaluation.24 At least 5 days after the index procedure should go by. This was the minimum time needed to observe the initial resolution of acute physiological disturbances.24

Finally, when plaques are crectly identified as functionally negative, they may still be vulnerable and associated with adverse events. NCL exhibiting thin-cap fibroatheromas as defined by optical coherence tomography, and having a muQFR ≤ 0.80, showed the highest event rate,40 which suggests that imaging can offer additional prognostic information.

PCSK9 inhibitors have shown minimal impact on conary physiology, despite greatly reducing low-density lipoprotein-cholesterol (LDL-C) levels. A large treatment effect on HIST only,19 minor flow limitation at baseline, and microvascular compensation may account for this finding.13

However, combining alirocumab with HIST resulted in a greater increase in cap thickness of fibroatheromas vs statin monotherapy as assessed by optical coherence tomography.41 Moreover, lower LDL-C levels after an ACS are associated with the occurrence of fewer cardiovascular events.2 Therefore, PCSK9 inhibitor treatment is recommended in patients who do not reach their LDL-C target despite maximum tolerated statin and ezetimibe therapy.2

Limitations

The wide variety of indices to assess conary physiology has led to a lack of evidence on some of them; similarly, few studies made direct comparisons among such indices.

Our evaluations are mainly based on observational studies with a very different follow-ups.

Angiography-based methods frequently exhibited bias due to their retrospective analysis. Some patients were excluded because of the poor quality of angiographies or anatomic issues, such as ostial lesion or severe vascular tortuosity. Some angiographies were not obtained optimally accding to the specific acquisition guide.

CONCLUSIONS

The assessment of functional indices for NCL during the initial procedure for STEMI is not absolutely reliable. This evidence is due to potential variability of the FFR, the iFR, and the QFR outside the acute phase. Although variation was not significant for muQFR, resting Pd/Pa, and vFFR, retrospective and/or limited data limit the generalizability of these findings.

Both the FFR and the iFR showed consistent directions of change. Therefore, during an acute STEMI, the FFR can guide the revascularization of positive NCL, while the iFR can help defer revascularization of negative NCL. A negative FFR with a positive iFR should be reevaluated.

The FFR shows robust data supporting its use in NLC of NSTEMI during the acute phase, meaning that it is a more reliable index for initial ACS procedures.

DATA AVAILABILITY

ETHICAL CONSIDERATIONS

Ethical committee and patient’s informed consent: not applicable. We followed the SAGER guidelines with respect to possible sex/gender bias.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Microsoft Copilot was used to help edit the English version of the text.

AUTHORS’ CONTRIBUTIONS

F. Vergni designed the work. F. Vergni, S. Buscarini, L. Ciurlanti, and F.L. Gurgoglione contributed to data acquisition (screening, and/or extraction). F. Vergni, and L. Ciurlanti conducted the critical appraisal. F. Vergni, and S. Buscarini contributed to data interpretation. F. Vergni, and F.L. Gurgoglione drafted, edited and reviewed the work. F. Vergni, S. Buscarini, L. Ciurlanti, F.L. Gurgoglione, F. Pellone, and M. Luzi approved the final version for publication.

SUPPLEMENTARY DATA

Supplementary data associated with this article can be found in the online version available at https://doi.org/10.24875/RECICE.M25000511.

WHAT IS KNOWN ABOUT THE TOPIC?

– The role of physiological assessment of NCL in patients with ACS is still under discussion because its reliability might be flawed due to alterations of both the hyperemic and resting flow in the acute phase.

WHAT DOES THIS STUDY ADD?

– In NSTEACS, it is appropriate to use the FFR for the acute evaluation of NCL. Regarding STEMI, a hybrid approach with both acute FFR and iFR can be considered, with delayed reassessment for doubtful NCL.

Footnotes

FUNDING: None declared.

BIBLIOGRAFÍA

1.Benatti G, Gragnano F, Vignali L, CalabròP, Gurgoglione FL, Niccoli G. Timing and modality of complete revascularization in patients presenting with ST-segment elevation myocardial infarction and multivessel coronary artery disease. Int J Cardiol. 2023;380:6-11. [DOI] [PubMed]; Benatti G, Gragnano F, Vignali L, Calabrò P, Gurgoglione FL, Niccoli G. Timing and modality of complete revascularization in patients presenting with ST-segment elevation myocardial infarction and multivessel coronary artery disease. Int J Cardiol. 2023;380:6–11. doi: 10.1016/j.ijcard.2023.03.022. [DOI] [PubMed] [Google Scholar]
2.Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44:3720-3826. Published correction appears in Eur Heart J. 2024;45:1145. [DOI] [PubMed]; Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44:3720–3826. doi: 10.1093/eurheartj/ehad191. Published correction appears in Eur Heart J. 2024:45.1145. [DOI] [PubMed] [Google Scholar]
3.Koo BK, Hwang D, Park S, et al. Practical Application of Coronary Physiologic Assessment:Asia-Pacific Expert Consensus Document:Part 2. JACC Asia. 2023;3:825-842. [DOI] [PMC free article] [PubMed]; Koo BK, Hwang D, Park S, et al. Practical Application of Coronary Physiologic Assessment:Asia-Pacific Expert Consensus Document:Part 2. JACC Asia. 2023;3:825–842. doi: 10.1016/j.jacasi.2023.07.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Mejía-Rentería H, Lee JM, van der Hoeven NW, et al. Coronary Microcirculation Downstream Non-Infarct-Related Arteries in the Subacute Phase of Myocardial Infarction:Implications for Physiology-Guided Revascularization. J Am Heart Assoc. 2019;8:e011534. [DOI] [PMC free article] [PubMed]; Mejía-Rentería H, Lee JM, van der Hoeven NW, et al. Coronary Microcirculation Downstream Non-Infarct-Related Arteries in the Subacute Phase of Myocardial Infarction:Implications for Physiology-Guided Revascularization. J Am Heart Assoc. 2019;8:e011534. doi: 10.1161/JAHA.118.011534. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Takenaka H, Okamura T, Miyazaki Y, et al. Serial changes in the quantitative flow ratio in patients with intermediate residual stenosis after percutaneous coronary intervention. Heart Vessels. 2022;37:363-373. [DOI] [PubMed]; Takenaka H, Okamura T, Miyazaki Y, et al. Serial changes in the quantitative flow ratio in patients with intermediate residual stenosis after percutaneous coronary intervention. Heart Vessels. 2022;37:363–373. doi: 10.1007/s00380-021-01923-x. [DOI] [PubMed] [Google Scholar]
6.Cardiovascular Research Foundation. Conference News. Disponible en:https://www.tctmd.com. Consultado 30 Mar 2025.; Cardiovascular Research Foundation Conference News. [Consultado 30 Mar 2025]. Disponible en: https://www.tctmd.com.
7.Clinical Trial Results. Slide Library. Disponible en:https://clinicaltrialresults.org. Consultado 30 Mar 2025.; Clinical Trial Results Slide Library. [Consultado 30 Mar 2025]. Disponible en: https://clinicaltrialresults.org.
8.Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement:an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PMC free article] [PubMed]; Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement:an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
9.Moola S, Munn Z, Tufanaru C, et al. Chapter 7:systematic reviews of etiology and risk. In:Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide:JBI;2020.; Moola S, Munn Z, Tufanaru C, et al. Chapter 7:systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide: JBI; 2020. [Google Scholar]
10.Barker TH, Habibi N, Aromataris E, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for quasi-experimental studies. JBI Evid Synth. 2024;22:378-388. [DOI] [PubMed]; Barker TH, Habibi N, Aromataris E, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for quasi-experimental studies. JBI Evid Synth. 2024;22:378–388. doi: 10.11124/JBIES-23-00268. [DOI] [PubMed] [Google Scholar]
11.Barker TH, Stone JC, Sears K, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21:494-506. [DOI] [PubMed]; Barker TH, Stone JC, Sears K, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21:494–506. doi: 10.11124/JBIES-22-00430. [DOI] [PubMed] [Google Scholar]
12.Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. [DOI] [PMC free article] [PubMed]; Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. doi: 10.1186/1471-2288-14-135. [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Bär S, Kavaliauskaite R, Otsuka T, et al. Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction:a prespecified substudy of the PACMAN-AMI trial. EuroIntervention. 2023;19:e286-e296. [DOI] [PMC free article] [PubMed]; Bär S, Kavaliauskaite R, Otsuka T, et al. Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction:a prespecified substudy of the PACMAN-AMI trial. EuroIntervention. 2023;19:e286–e296. doi: 10.4244/EIJ-D-23-00201. [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Cortés C, Rodríguez-Gabella T, Gutiérrez H, et al. Quantitative flow ratio in myocardial infarction for the evaluation of non-infarct-related arteries. The QIMERA pilot study. REC Interv Cardiol. 2019;1:13-20.; Cortés C, Rodríguez-Gabella T, Gutiérrez H, et al. Quantitative flow ratio in myocardial infarction for the evaluation of non-infarct-related arteries. The QIMERA pilot study. REC Interv Cardiol. 2019;1:13–20. [Google Scholar]
15.Erbay A, Penzel L, Abdelwahed YS, et al. Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome. Int J Cardiovasc Imaging. 2021;37:1815-1823. [DOI] [PMC free article] [PubMed]; Erbay A, Penzel L, Abdelwahed YS, et al. Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome. Int J Cardiovasc Imaging. 2021;37:1815–1823. doi: 10.1007/s10554-021-02195-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Hou S, Zhu X, Zhao Q, et al. Quantitative flow ratio-guided staged percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Heliyon. 2024;10:e39335. [DOI] [PMC free article] [PubMed]; Hou S, Zhu X, Zhao Q, et al. Quantitative flow ratio-guided staged percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Heliyon. 2024;10:e39335. doi: 10.1016/j.heliyon.2024.e39335. [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Huang J, Groenland FTW, Scoccia A, et al. Acute-setting vs. staged-setting vessel fractional flow reserve of intermediate non-culprit lesions in patients with ST-segment elevation myocardial infarction (FAST STAGED study). Int J Cardiol Heart Vasc. 2023;45:101192. [DOI] [PMC free article] [PubMed]; Huang J, Groenland FTW, Scoccia A, et al. Acute-setting vs. staged-setting vessel fractional flow reserve of intermediate non-culprit lesions in patients with ST-segment elevation myocardial infarction (FAST STAGED study) Int J Cardiol Heart Vasc. 2023;45:101192. doi: 10.1016/j.ijcha.2023.101192. [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Kirigaya H, Okada K, Hibi K, et al. Diagnostic performance and limitation of quantitative flow ratio for functional assessment of intermediate coronary stenosis. J Cardiol. 2021;77:492-499. [DOI] [PubMed]; Kirigaya H, Okada K, Hibi K, et al. Diagnostic performance and limitation of quantitative flow ratio for functional assessment of intermediate coronary stenosis. J Cardiol. 2021;77:492–499. doi: 10.1016/j.jjcc.2020.11.002. [DOI] [PubMed] [Google Scholar]
19.Mensink F, Los J, van Geuns RJ. Functional and morphological changes of significant non-culprit coronary artery stenosis by extensive LDL-C reduction with PCSK9 inhibitors. Results of the randomized, placebo-controlled FITTER trial. En:ESC Congress 2024;2024 30 agosto - 2 septiembre;Londres, Reino Unido. Disponible en:https://clinicaltrialresults.org/slide-library/.; Mensink F, Los J, van Geuns RJ. Results of the randomized, placebo-controlled FITTER trial. En:ESC Congress. Vol. 2024. Londres: Reino Unido; 2024. Functional and morphological changes of significant non-culprit coronary artery stenosis by extensive LDL-C reduction with PCSK9 inhibitors. 30 agosto - 2 septiembre. Disponible en: https://clinicaltrialresults.org/slide-library/ [Google Scholar]
20.Musto C, De Felice F, Rigattieri S, et al. Instantaneous wave-free ratio and fractional flow reserve for the assessment of nonculprit lesions during the index procedure in patients with ST-segment elevation myocardial infarction:The WAVE study. Am Heart J. 2017;193:63-69. [DOI] [PubMed]; Musto C, De Felice F, Rigattieri S, et al. Instantaneous wave-free ratio and fractional flow reserve for the assessment of nonculprit lesions during the index procedure in patients with ST-segment elevation myocardial infarction:The WAVE study. Am Heart J. 2017;193:63–69. doi: 10.1016/j.ahj.2017.07.017. [DOI] [PubMed] [Google Scholar]
21.Ntalianis A, Sels JW, Davidavicius G, et al. Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction. JACC Cardiovasc Interv. 2010;3:1274-1281. [DOI] [PubMed]; Ntalianis A, Sels JW, Davidavicius G, et al. Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction. JACC Cardiovasc Interv. 2010;3:1274–1281. doi: 10.1016/j.jcin.2010.08.025. [DOI] [PubMed] [Google Scholar]
22.Sejr-Hansen M, Westra J, Thim T, et al. Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction-An iSTEMI substudy. Catheter Cardiovasc Interv. 2019;94:686-692. [DOI] [PubMed]; Sejr-Hansen M, Westra J, Thim T, et al. Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction-An iSTEMI substudy. Catheter Cardiovasc Interv. 2019;94:686–692. doi: 10.1002/ccd.28208. [DOI] [PubMed] [Google Scholar]
23.Shukla A, Dwivedi SK, Chandra S, et al. Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach. Cureus. 2024;16:e52668. [DOI] [PMC free article] [PubMed]; Shukla A, Dwivedi SK, Chandra S, et al. Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach. Cureus. 2024;16:e52668. doi: 10.7759/cureus.52668. [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Thim T, Götberg M, Fröbert O, et al. Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2017;10:2528-2535. [DOI] [PubMed]; Thim T, Götberg M, Fröbert O, et al. Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2017;10:2528–2535. doi: 10.1016/j.jcin.2017.07.021. [DOI] [PubMed] [Google Scholar]
25.van der Hoeven NW, Janssens GN, de Waard GA, et al. Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction. JAMA Cardiol. 2019;4:736-744. [DOI] [PMC free article] [PubMed]; van der Hoeven NW, Janssens GN, de Waard GA, et al. Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction. JAMA Cardiol. 2019;4:736–744. doi: 10.1001/jamacardio.2019.2138. [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Wang L, Travieso A, van der Hoeven N, et al. Improved Nonculprit Stenosis Assessment in Patients With ST-Segment Elevation Myocardial Infarction Using Quantitative Flow Ratio. JACC Cardiovasc Interv. 2023;16:1828-1830. [DOI] [PubMed]; Wang L, Travieso A, van der Hoeven N, et al. Improved Nonculprit Stenosis Assessment in Patients With ST-Segment Elevation Myocardial Infarction Using Quantitative Flow Ratio. JACC Cardiovasc Interv. 2023;16:1828–1830. doi: 10.1016/j.jcin.2023.04.045. [DOI] [PubMed] [Google Scholar]
27.Zhao Q, Sun S, Zhou F, Yue J, Luo X, Qu X. The Inhibition of Evolocumab on Non-Infarct-Related Artery Disease in Patients with ST-Elevation Myocardial Infarction. Int J Gen Med. 2023;16:2771-2781. [DOI] [PMC free article] [PubMed]; Zhao Q, Sun S, Zhou F, Yue J, Luo X, Qu X. The Inhibition of Evolocumab on Non-Infarct-Related Artery Disease in Patients with ST-Elevation Myocardial Infarction. Int J Gen Med. 2023;16:2771–2781. doi: 10.2147/IJGM.S417481. [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Barauskas M, Žiubryte G, Jodka N, Unikas R. Quantitative Flow Ratio for Assessment of Non-Culprit Coronary Artery Lesions During Percutaneous Coronary Intervention (PCI) in 79 Patients Diagnosed with ST-Elevation Myocardial Infarction (STEMI):A Study from a Single Center in Lithuania. Med Sci Monit. 2023;29:e939360. [DOI] [PMC free article] [PubMed]; Barauskas M, Žiubryte G, Jodka N, Unikas R. Quantitative Flow Ratio for Assessment of Non-Culprit Coronary Artery Lesions During Percutaneous Coronary Intervention (PCI) in 79 Patients Diagnosed with ST-Elevation Myocardial Infarction (STEMI):A Study from a Single Center in Lithuania. Med Sci Monit. 2023;29:e939360. doi: 10.12659/MSM.939360. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Jo YS, Moon H, Park K. Different Microcirculation Response Between Culprit and Non-Culprit Vessels in Patients With Acute Coronary Syndrome. J Am Heart Assoc. 2020;9:e015507. [DOI] [PMC free article] [PubMed]; Jo YS, Moon H, Park K. Different Microcirculation Response Between Culprit and Non-Culprit Vessels in Patients With Acute Coronary Syndrome. J Am Heart Assoc. 2020;9:e015507. doi: 10.1161/JAHA.119.015507. [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Li X, Mi L, Duan J, Tao L, Xu X, Wang G. Murray law-based quantitative flow ratio for assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction. Cardiol J. 2024;31:522-527. [DOI] [PMC free article] [PubMed]; Li X, Mi L, Duan J, Tao L, Xu X, Wang G. Murray law-based quantitative flow ratio for assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction. Cardiol J. 2024;31:522–527. doi: 10.5603/cj.93499. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Park K, Cho YR, Park JS, Park TH, Kim MH, Kim YD. Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices. Circ Cardiovasc Interv. 2019;12:e008105. [DOI] [PubMed]; Park K, Cho YR, Park JS, Park TH, Kim MH, Kim YD. Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices. Circ Cardiovasc Interv. 2019;12:e008105. doi: 10.1161/CIRCINTERVENTIONS.119.008105. [DOI] [PubMed] [Google Scholar]
32.Spitaleri G, Tebaldi M, Biscaglia S, et al. Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease. Circ Cardiovasc Interv. 2018;11:e006023. [DOI] [PubMed]; Spitaleri G, Tebaldi M, Biscaglia S, et al. Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease. Circ Cardiovasc Interv. 2018;11:e006023. doi: 10.1161/CIRCINTERVENTIONS.117.006023. [DOI] [PubMed] [Google Scholar]
33.Mensink FB, Los J, Oemrawsingh RM, et al. Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody:Rationale and design of the randomized FITTER trial. Heliyon. 2024;10:e38077. [DOI] [PMC free article] [PubMed]; Mensink FB, Los J, Oemrawsingh RM, et al. Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody:Rationale and design of the randomized FITTER trial. Heliyon. 2024;10:e38077. doi: 10.1016/j.heliyon.2024.e38077. [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Biscaglia S, Guiducci V, Escaned J, et al. Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction. N Engl J Med. 2023;389:889-898. [DOI] [PubMed]; Biscaglia S, Guiducci V, Escaned J, et al. Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction. N Engl J Med. 2023;389:889–898. doi: 10.1056/NEJMoa2300468. [DOI] [PubMed] [Google Scholar]
35.Lee JM, Kim HK, Park KH, et al. Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease:a randomized trial. Eur Heart J. 2023;44:473-484. [DOI] [PubMed]; Lee JM, Kim HK, Park KH, et al. Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease:a randomized trial. Eur Heart J. 2023;44:473–484. doi: 10.1093/eurheartj/ehac763. [DOI] [PubMed] [Google Scholar]
36.Böhm F, Mogensen B, Engstrøm T, et al. FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction. N Engl J Med. 2024;390:1481-1492. [DOI] [PubMed]; Böhm F, Mogensen B, Engstrøm T, et al. FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction. N Engl J Med. 2024;390:1481–1492. doi: 10.1056/NEJMoa2314149. [DOI] [PubMed] [Google Scholar]
37.Smits PC, Abdel-Wahab M, Neumann FJ, et al. Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction. N Engl J Med. 2017;376:1234-1244. [DOI] [PubMed]; Smits PC, Abdel-Wahab M, Neumann FJ, et al. Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction. N Engl J Med. 2017;376:1234–1244. doi: 10.1056/NEJMoa1701067. [DOI] [PubMed] [Google Scholar]
38.Engstrøm T, Kelbæk H, Helqvist S, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI):an open-label, randomised controlled trial. Lancet. 2015;386:665-671. [DOI] [PubMed]; Engstrøm T, Kelbæk H, Helqvist S, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI):an open-label, randomised controlled trial. Lancet. 2015;386:665–671. doi: 10.1016/s0140-6736(15)60648-1. [DOI] [PubMed] [Google Scholar]
39.Puymirat E, Cayla G, Simon T, et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021;385:297-308. [DOI] [PubMed]; Puymirat E, Cayla G, Simon T, et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021;385:297–308. doi: 10.1056/NEJMoa2104650. [DOI] [PubMed] [Google Scholar]
40.Xu X, Fang C, Jiang S, et al. Functional or anatomical assessment of non-culprit lesions in acute myocardial infarction. EuroIntervention. 2025;21:e217-e228. [DOI] [PMC free article] [PubMed]; Xu X, Fang C, Jiang S, et al. Functional or anatomical assessment of non-culprit lesions in acute myocardial infarction. EuroIntervention. 2025;21:e217–e228. doi: 10.4244/EIJ-D-24-00720. [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Räber L, Ueki Y, Otsuka T, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction:The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022;327:1771-1781. [DOI] [PMC free article] [PubMed]; Räber L, Ueki Y, Otsuka T, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction:The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022;327:1771–1781. doi: 10.1001/jama.2022.5218. [DOI] [PMC free article] [PubMed] [Google Scholar]

REC Interv Cardiol. 2025 Jun 12;7(3):169–177. [Article in Spanish]

Evaluación funcional en el síndrome coronario agudo: una revisión sistemática del escenario agudo frente al diferido

Abreviaturas

iFR:: índice diastólico instantáneo sin ondas.
LNC:: lesiones no culpables.
QFR:: cociente de flujo cuantitativo.
RFF:: reserva fraccional de flujo.
SCA:: síndrome coronario agudo.

INTRODUCCIÓN

La estrategia y momento óptimos para realizar una revascularización completa en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) y enfermedad coronaria multivaso siguen sin estar claros y las recomendaciones actuales siguen siendo objeto de debate1. Según las guías de práctica clínica de la European Society of Cardiology (ESC) de 2023, se recomienda la revascularización completa en base, solo, a la gravedad angiográfica en pacientes “estables”con IAMCEST2. Sin embargo, el Documento de Consenso de Expertos de Asia-Pacífico 2023 sugiere una estrategia de tratamiento de las lesiones no culpables (LNC) basada tanto en la gravedad angiográfica como en un estudio fisiológico invasivo empleando la reserva fraccional de flujo (RFF) o los índices de presión no hiperémicos en pacientes con IAMCEST3.

Tanto la RFF como los índices de presión no hiperémicos pueden dar resultados inexactos en el síndrome coronario agudo (SCA) por un menor flujo hiperémico secundario a la disfunción microcirculatoria; por su parte, el flujo en reposo puede verse aumentado por mecanismos neurohumorales compensatorios4.

Los índices angiográficos son herramientas fisiológicas adicionales. Requieren ≥ 1 proyección angiográfica más un análisis de recuento de fotogramas o de la presión aórtica que también son susceptibles de variación en el contexto agudo.

Por su parte, fármacos como los agentes hipolipemiantes pueden fomentar el avance de la placa con posible afectación de los resultados del estudio fisiológico tras unos meses en tratamiento5.

Nuestro objetivo principal fue evaluar los cambios en las mediciones fisiológicas invasivas de LNC entre las fases aguda y diferida del SCA.

En segundo lugar, se intentó evaluar los efectos de diferentes tratamientos sobre las mediciones fisiológicas.

MÉTODOS

Criterios de elegibilidad

Se incluyeron estudios que evaluaran la fisiología de las LNC durante intervenciones agudas y diferidas en el contexto del SCA. Se excluyeron todos los estudios sobre valoración de vasos no culpables tras intervenciones coronarias percutáneas o pacientes con síndrome coronario crónico.

También se excluyeron todos aquellos casos clínicos, resúmenes de congresos, comentarios, editoriales y revisiones. El protocolo inicial fue registrado en PROSPERO con el número de registro CRD42024574683.

Estrategia de búsqueda y selección de estudios

La búsqueda se realizó a través de ClinicalTrials.gov, Embase (vía Ovid), Google Scholar, PubMed y Web of Science desde el principio hasta el 26 de abril de 2024 (búsqueda inicial). Se utilizó el filtro “Artículos de revisión”en Google Scholar y el campo “Asunto”en Web of Science. No se aplicaron restricciones idiomáticas.

Los duplicados se eliminaron mediante el software Deduplicator (SR-Accelerator). La revisión de títulos/resúmenes y textos completos la realizaron, de manera independiente, 2 autores con ayuda del software Rayyan.

En julio, 2 autores realizaron un análisis de citas hacia atrás y hacia adelante de los artículos incluidos con ayuda del software Citationchaser.

Las cadenas de búsqueda se repitieron el 6 de diciembre de 2024 (en Embase, se excluyeron fuentes con límites de fecha inválidos). Al mismo tiempo, se revisaron noticias de congresos sobre técnicas de imagen y mediciones fisiológicas online6. También se exploró la sección «Slide Library» empleando el filtro «2024» en otra página web7.

Por último, se revisaron manualmente las bibliografías de los artículos incluidos tras la búsqueda inicial.

Todas las discrepancias se resolvieron mediante consenso.

El proceso de selección se documentó detalladamente para completar un diagrama de flujo PRISMA (Elementos de reporte preferidos para revisiones sistemáticas y metanálisis)8.

Extracción de datos

De cada artículo se extrajeron los siguientes datos: a) características del estudio; b) características de la población; c) tipo(s) de índice(s) fisiológico(s); d) duración del seguimiento; e) objetivo primario.

El objetivo primario fue la variación entre las fases aguda y diferida en términos de significación estadística, diferencia media (DM) y discrepancias en la decisión de revascularizar.

Un autor extrajo los datos y otro los verificó de forma independiente. Cuando se hizo necesaria alguna aclaración al respecto, nos pusimos en contacto con los autores de estudios elegibles.

Valoración del riesgo de sesgo

El riesgo de sesgo se valoró empleando las herramientas de evaluación crítica del Joanna Briggs Institute (JBI)9-11, según correspondiera.

Dos autores evaluaron, de forma independiente, el riesgo de sesgo de cada estudio. Se utilizó el color rojo para riesgo alto, amarillo para moderado y verde para riesgo bajo de sesgo según los porcentajes de respuestas positivas: ≤ 49%, 50-69% o ≥ 70%.

Síntesis de datos

Se realizó una síntesis descriptiva de la evidencia. Los resultados de la extracción de datos se presentaron en tablas aisladas según el riesgo de sesgo o bien en gráficos de burbujas. Algunos datos se redondearon al número entero más cercano como, por ejemplo, la edad, el diámetro de estenosis de la LNC y el seguimiento o a 2 decimales (DM).

A menos que se especificase lo contrario, se consideraron estadísticamente significativos aquellos valores de p < 0,05. Cuando no se informaron las DM, estas se calcularon mediante la diferencia entre los valores medios de las fases aguda y diferida. Siempre que fuese necesario, se aplicó una fórmula para calcular las medias12.

En los gráficos de burbujas, el tamaño representa el número de pacientes o lesiones en ausencia del primero. La discrepancia agudo−/diferido+ indica un valor agudo por encima del umbral con el valor diferido por debajo del punto de corte para la revascularización. La discrepancia agudo+/diferido− representa justo lo contrario.

RESULTADOS

Características de los artículos, participantes e índices

Los resultados de los procesos de búsqueda y selección se muestran en la figura 1. Los datos extraídos se ilustran en la tabla 1 y tabla 2.

Se incluyó un total de 20 artículos13-32 (1 artículo en forma de presentación de conferencia)19. Los años de publicación fueron de 2010 a 2024. El número total de pacientes informados fue de 4.379.

En todas las publicaciones, los pacientes eran predominantemente varones no diabéticos. Salvo en 3 estudios, la principal presentación clínica fue IAMCEST19,29,31.

Se analizaron los siguientes métodos: a) derivados de la angiografía: cociente de flujo cuantitativo basado en la ley de Murray (muQFR), cociente de flujo cuantitativo (QFR), RFF del vaso (RFFv); b) hiperémicos (RFF); e c) índices no hiperémicos: índice diastólico instantáneo sin ondas (iFR), cociente de presión coronaria distal/aórtica en reposo (P_d/P_a). En aquellos casos en los que se participó la RFF, esta se obtuvo mediante la utilización de adenosina intracoronaria.

A continuación se muestran los pacientes informados para cada índice: 2.340 (muQFR), 1.187 (QFR), 710 (RFF), 243 (iFR), 92 (RFFv) y 73 (P_d/P_a en reposo).

Riesgo de sesgo

En los estudios se empleó un diseño observacional (de cohorte). Los estudios de cohortes sobre métodos angiográficos fueron retrospectivos, excepto 1 artículo sobre el QFR28. Salvo 2 subestudios, los estudios sobre la RFF y los índices no hiperémicos fueron, todos ellos, prospectivos22,26.

El QFR también se valoró en 1 estudio cuasiexperimental27 y 1 ensayo clínico aleatorizado13.

Por último, la RFF fue analizada en 2 ensayos controlados aleatorizados, en muestras con predominio de infarto agudo de miocardio sin elevación del segmento ST (IAMSEST)19,31,33.

Los resultados se muestran en la tabla 1 del material adicional, la tabla 2 del material adicional y la tabla 3 del material adicional. No se identificó ningún estudio con riesgo alto de sesgo.

Objetivo primario

Significación estadística

No se encontró ningún artículo que informase de cambios significativos en el muQFR16,30, el P_d/P_a en reposo25 ni en la RFFv17 durante el seguimiento.

Se observó una diferencia significativa en la RFF, iFR y QFR en 3, 2 y 1 artículo(s), respectivamente14,22-26. En 1 estudio, la diferencia en el QFR no fue significativa, con un umbral de significación estadística de 0,00128.

Estas variaciones se observaron en cohortes de pacientes con IAMCEST14,22-26.

Los estudios que incluyeron pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) no mostraron ninguna diferencia importante en el QFR15 ni en la RFF19,21,29,31.

Cuatro artículos20,22,25,26 evaluaron > 1 método. Tanto el iFR y como la RFF se mantuvieron estables en el estudio de Musto et al.20; por su parte, el iFR se mostró más estable que la RFF en otro artículo25. El QFR se comparó tanto con la RFF26 como con el iFR22. A diferencia de estos índices, el QFR no mostró cambios significativos en las fases diferidas22,26.

Diferencias medias

Los índices más valorados mostraron resultados distintos. El muQFR mostró DM cercanas a 0 en los 2 estudios16,30.

Se observaron variaciones del QFR hacia valores más bajos22,26,28 y más altos14,15,18. En cambio, tanto la RFF como el iFR se inclinaron hacia valores más bajos y altos, respectivamente22-26,29,31. Sus DM se situaron entre −0,02 y +0,06 (QFR), −0,03 y 0,00 (RFF), y 0,00 y +0,03 (iFR)14,19-21,24,25,28. Las DM igual a 0,01 fueron las que se observaron con mayor frecuencia.

En pacientes con IAMCEST, las DM de la RFF, iFR y QFR estuvieron cercanas a 0 solo en estudios con seguimientos medios < 1 semana20,32. En estudios del SCASEST, las DM de la RFF estuvieron cercanas a 0 en seguimientos medios más largos (> 1 mes)19,21. Por si esto fuera poco, Ntalianis et al. demostraron una mayor estabilidad de la RFF en pacientes con IAMSEST (DM = 0,00) que en aquellos con IAMCEST (DM = −0,02)21.

Discordancia

La discordancia en la indicación de revascularización se muestra en la figura 2. Las DM iguales a 0,01 provocaron diferentes discordancias de entre el 5 y el 18%15,18,23,25.

A diferencia del QFR, la RFF y el iFR mostraron con mayor frecuencia un tipo específico de discordancia: agudo−/diferido+ para la RFF21,23,25 y agudo+/diferido− para el iFR24,25.

Objetivo secundario

Cuatro estudios compararon los efectos de diferentes fármacos sobre los parámetros fisiológicos13,19,27,31.

Se comparó ticagrelor (capaz de aumentar los niveles de adenosina) con clopidogrel, pero no se hallaron diferencias significativas en la RFF de vasos no culpables tras 6 meses de tratamiento31.

Otros 3 estudios compararon un inhibidor de la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9) (como alirocumab o evolocumab) más estatinas de alta intensidad (EAI) (como rosuvastatina 20 mg/día) frente a tratamiento, solo, con estatinas13,19,27.

En un estudio no aleatorizado, los valores del QFR fueron mucho mayores en el grupo a tratamiento con evolocumab a los 12 meses27. No obstante, 2 estudios aleatorizados no mostraron diferencias significativas entre los 2 grupos a tratamiento en el QFR a 12 meses ni en la RFF a 3 meses13,19.

DISCUSIÓN

Los principales hallazgos de esta revisión sistemática son los siguientes: en primer lugar, en pacientes con STEMI, los índices muQFR, P_d/P_a en reposo y RFFv se mantuvieron relativamente estables en estudios retrospectivos o de pequeño tamaño. En cambio, la RFF, el iFR y el QFR sí variaron entre las fases aguda y diferida. En segundo lugar, la RFF no mostró cambios significativos en cohortes prospectivas ni en ensayos controlados aleatorizados de pacientes con SCASEST. En tercer lugar, el QFR fue más estable que la RFF y el iFR en comparativas directas, aunque solo la RFF y el iFR mostraron direcciones de cambio consistentes En cuarto y último lugar, los inhibidores de PCSK9 añadidos a las EAI no influyeron en las mediciones fisiológicas frente a, solo, las EAI en ensayos controlados aleatorizados.

El muQFR se mostró estable en una gran muestra de pacientes. Este índice se basa en una única proyección angiográfica, a diferencia de otros métodos angiográficos que precisan 2. Una característica que podría llegar a reducir la variabilidad entre observadores y mejorar la fiabilidad. Se necesitan, no obstante, estudios prospectivos y comparativos que confirmen la validez de este método.

Aunque se observaron pocas variaciones en la RFF, iFR y QFR en cohortes de pacientes con IAMCEST20,32, estos estudios se vieron limitados por seguimientos a corto plazo. Thim et al. no hallaron cambios significativos en el iFR en seguimientos de 5 días, pero sí en seguimientos ≥ 5 días24. En este sentido, las alteraciones fisiológicas iniciadas en el momento agudo del IAMCEST podrían persistir cuando la intervención diferida se realiza poco después del evento índice24,25.

Las variables angiográficas, hemodinámicas y microcirculatorias pueden alterar un estudio fisiológico agudo y explicarían la mayor fiabilidad de la RFF descrita en el SCASEST frente al IAMCEST.

En pacientes con disfunción microvascular, el flujo sanguíneo epicárdico no aumenta lo suficiente en hiperemia máxima, lo cual provoca un menor gradiente de presión a través de la lesión estenótica29 y valores más altos de la RFF.

En pacientes con IAMCEST, los índices microcirculatorios (reserva de flujo coronario e índice de resistencia microcirculatoria) fueron muchos peores durante la fase aguda y los valores de la RFF fueron más altos25. En cambio, los estudios que incluyeron el SCASEST no mostraron diferencias significativas en la reserva de flujo coronario ni en el índice de resistencia microcirculatoria durante el seguimiento21,29,31.

Además, los pacientes con STEMI mostraron una mayor gravedad angiográfica aguda y valores más bajos de QFR o iFR14,22, lo cual podría atribuirse a la vasoconstricción típica de la fase aguda.

En consecuencia, la RFF parece ser más fiable en el SCASEST que en el IAMCEST por la menor alteración microcirculatoria aguda o vasoconstricción.

En la literatura, los ensayos avalan el uso de la RFF en LNC de IAMSEST durante la fase aguda (por ejemplo, en la primera hospitalización)34,35. En cambio, la revascularización completa guiada por la RFF en la fase aguda no mostró beneficios significativos en términos de mortalidad o infarto de miocardio en pacientes con IAMCEST36-39.

Comparado con la RFF o el iFR, la mayor estabilidad observada en el QFR se limitó a un pequeño número de pacientes en subestudios post-hoc22,26. En ocasiones, una DM de 0,01 provocó importantes desacuerdos en la decisión de revascularización25, probablemente por los valores basales cercanos al punto de corte. En este sentido, resulta esencial disponer de un índice que se mantenga estable o muestre cambios consistentes, como la RFF y el iFR. Asimismo, estos índices mostraron con mayor frecuencia un tipo específico de desacuerdo (variaciones metodológicas como la posición de la guía podrían explicar los casos menos frecuentes de desacuerdo)24.

En este sentido, tanto la RFF como el iFR podrían tenerse en cuenta en el IAMCEST agudo como alternativa a evaluaciones diferidas25, teniendo en cuenta que los valores de la RFF tienden a caer y los del iFR a subir. La RFF podría guiar la revascularización de lesiones positivas (RFF ≤ 0,80)25. En pacientes con RFF > 0,80, la evaluación aguda con iFR podría usarse para diferir la revascularización de LNC negativas (iFR > 0,89)24. En los demás casos (iFR ≤ 0,89), algunos autores sugieren un nuevo estudio diferido24. Deben pasar un mínimo de 5 días tras la intervención índice, es decir, el tiempo mínimo necesario para observar la resolución inicial de las alteraciones fisiológicas agudas24.

Por último, aunque las placas se identifiquen correctamente como funcionalmente negativas, podrían seguir siendo vulnerables y asociarse a la ocurrencia de eventos adversos. Las LNC con fibroateromas de capa fina según la tomografía de coherencia óptica y un muQFR ≤ 0,80 tuvieron la tasa de eventos más alta de todas40, lo cual sugiere que las imágenes proporcionan información pronóstica adicional.

Los inhibidores de PCSK9 han tenido un impacto mínimo en la fisiología coronaria, a pesar de que reducen significativamente los niveles de colesterol unido a lipoproteínas de baja densidad (cLDL). El efecto importante del tratamiento con, solo, EAI19, una limitación menor del flujo a nivel basal y la compensación microvascular podrían explicar este hallazgo13.

No obstante, la combinación alirocumab + EAI aumentó el grosor de la capa fibrosa de los fibroateromas frente al monotratamiento con estatinas, según la tomografía de coherencia óptica41. Por si esto fuera poco, los niveles más bajos de cLDL tras un SCA se asocian a una menor incidencia de eventos cardiovasculares2. En consecuencia, se recomienda tratamiento con inhibidores de PCSK9 en pacientes que no alcanzan su diana de cLDL a pesar de tratamiento con estatinas a dosis máximas toleradas y ezetimiba2.

Limitaciones

La amplia variedad de índices para estudiar la fisiología coronaria ha provocado una falta de evidencia sobre algunos de ellos; al mismo tiempo, son pocos los estudios que han realizado comparativas directas entre estos índices.

Nuestras evaluaciones se basan, principalmente, en estudios observacionales con seguimientos muy heterogéneos.

Con frecuencia, los métodos angiográficos presentaron sesgos debido a su análisis retrospectivo. Algunos pacientes fueron excluidos debido a la mala calidad de las angiografías o por problemas anatómicos tales como lesiones ostiales o una marcada tortuosidad vascular. Algunas angiografías no se obtuvieron de forma óptima de conformidad con la guía de adquisición específica.

CONCLUSIONES

El estudio de los índices funcionales para LNC durante la intervención índice en el contexto de un IAMCEST no es del todo fiable. Esta evidencia se debe a la posible variabilidad entre la RFF, el iFR y el QFR fuera de la fase aguda. Aunque no se observaron variaciones significativas en el muQFR, el P_d/P_a en reposo ni en la RFFv, los datos retrospectivos o limitados impiden la extrapolación de estos hallazgos.

Tanto la RFF como el iFR mostraron direcciones de cambio consistentes. En este sentido, durante un IAMCEST agudo, la RFF podría guiar la revascularización de las LNC positivas y el iFR ayudar a diferir la revascularización de las LNC negativas. Ante una RFF negativa con un iFR positivo, se recomienda hacer una nueva valoración.

La RFF cuenta con evidencias sólidas que avalan su uso en LCN de pacientes con IAMSEST durante la fase aguda, lo cual quiere decir que nos encontramos ante índice más fiable durante la realización de intervenciones índices en el context del SCA.

DISPONIBILIDAD DE LOS DATOS

CONSIDERACIONES ÉTICAS

Comité de ética y consentimiento informado del paciente: no aplicable. Se siguieron las directrices SAGER respecto a un posible sesgo por sexo/género.

DECLARACIÓN SOBRE EL USO DE INTELIGENCIA ARTIFICIAL

Se utilizó Microsoft Copilot para ayudar en la edición de la versión en inglés del manuscrito.

CONTRIBUCIÓN DE LOS AUTORES

F. Vergni diseñó el estudio. F. Vergni, S. Buscarini, L. Ciurlanti y F.L. Gurgoglione participaron en la obtención de datos (cribado o extracción). F. Vergni y L. Ciurlanti realizaron la evaluación crítica. F. Vergni y S. Buscarini contribuyeron a la interpretación de los datos. F. Vergni y F.L. Gurgoglione redactaron, editaron y revisaron el manuscrito. F. Vergni, S. Buscarini, L. Ciurlanti, F.L. Gurgoglione, F. Pellone y M. Luzi aprobaron la versión final del manuscrito para su publicación.

¿QUÉ SE SABE DEL TEMA?

– El papel que desempeña el estudio fisiológico de las LNC en pacientes con SCA sigue siendo objeto de debate porque su fiabilidad podría verse afectada por alteraciones tanto del flujo hiperémico como del flujo en reposo durante la fase aguda.

¿QUÉ APORTA DE NUEVO?

– En los SCASEST, resulta apropiado utilizar la RFF para el estudio agudo de las LNC. En el caso del IAMCEST, se puede emplear un abordaje híbrido RFF + iFR agudos y un nuevo estudio diferido en casos de LNC dudosas.

MATERIAL ADICIONAL

Se puede consultar material adicional a este artículo en su versión electrónica disponible en https://doi.org/10.24875/RECIC.M25000520.

Footnotes

FINANCIACIÓN: Ninguna.

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

[B1] 1.Benatti G, Gragnano F, Vignali L, CalabròP, Gurgoglione FL, Niccoli G. Timing and modality of complete revascularization in patients presenting with ST-segment elevation myocardial infarction and multivessel coronary artery disease. Int J Cardiol. 2023;380:6-11. [DOI] [PubMed]; Benatti G, Gragnano F, Vignali L, Calabrò P, Gurgoglione FL, Niccoli G. Timing and modality of complete revascularization in patients presenting with ST-segment elevation myocardial infarction and multivessel coronary artery disease. Int J Cardiol. 2023;380:6–11. doi: 10.1016/j.ijcard.2023.03.022. [DOI] [PubMed] [Google Scholar]

[B2] 2.Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44:3720-3826. Published correction appears in Eur Heart J. 2024;45:1145. [DOI] [PubMed]; Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44:3720–3826. doi: 10.1093/eurheartj/ehad191. Published correction appears in Eur Heart J. 2024:45.1145. [DOI] [PubMed] [Google Scholar]

[B3] 3.Koo BK, Hwang D, Park S, et al. Practical Application of Coronary Physiologic Assessment:Asia-Pacific Expert Consensus Document:Part 2. JACC Asia. 2023;3:825-842. [DOI] [PMC free article] [PubMed]; Koo BK, Hwang D, Park S, et al. Practical Application of Coronary Physiologic Assessment:Asia-Pacific Expert Consensus Document:Part 2. JACC Asia. 2023;3:825–842. doi: 10.1016/j.jacasi.2023.07.004. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B4] 4.Mejía-Rentería H, Lee JM, van der Hoeven NW, et al. Coronary Microcirculation Downstream Non-Infarct-Related Arteries in the Subacute Phase of Myocardial Infarction:Implications for Physiology-Guided Revascularization. J Am Heart Assoc. 2019;8:e011534. [DOI] [PMC free article] [PubMed]; Mejía-Rentería H, Lee JM, van der Hoeven NW, et al. Coronary Microcirculation Downstream Non-Infarct-Related Arteries in the Subacute Phase of Myocardial Infarction:Implications for Physiology-Guided Revascularization. J Am Heart Assoc. 2019;8:e011534. doi: 10.1161/JAHA.118.011534. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B5] 5.Takenaka H, Okamura T, Miyazaki Y, et al. Serial changes in the quantitative flow ratio in patients with intermediate residual stenosis after percutaneous coronary intervention. Heart Vessels. 2022;37:363-373. [DOI] [PubMed]; Takenaka H, Okamura T, Miyazaki Y, et al. Serial changes in the quantitative flow ratio in patients with intermediate residual stenosis after percutaneous coronary intervention. Heart Vessels. 2022;37:363–373. doi: 10.1007/s00380-021-01923-x. [DOI] [PubMed] [Google Scholar]

[B6] 6.Cardiovascular Research Foundation. Conference News. Disponible en:https://www.tctmd.com. Consultado 30 Mar 2025.; Cardiovascular Research Foundation Conference News. [Consultado 30 Mar 2025]. Disponible en: https://www.tctmd.com.

[B7] 7.Clinical Trial Results. Slide Library. Disponible en:https://clinicaltrialresults.org. Consultado 30 Mar 2025.; Clinical Trial Results Slide Library. [Consultado 30 Mar 2025]. Disponible en: https://clinicaltrialresults.org.

[B8] 8.Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement:an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PMC free article] [PubMed]; Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement:an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B9] 9.Moola S, Munn Z, Tufanaru C, et al. Chapter 7:systematic reviews of etiology and risk. In:Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide:JBI;2020.; Moola S, Munn Z, Tufanaru C, et al. Chapter 7:systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide: JBI; 2020. [Google Scholar]

[B10] 10.Barker TH, Habibi N, Aromataris E, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for quasi-experimental studies. JBI Evid Synth. 2024;22:378-388. [DOI] [PubMed]; Barker TH, Habibi N, Aromataris E, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for quasi-experimental studies. JBI Evid Synth. 2024;22:378–388. doi: 10.11124/JBIES-23-00268. [DOI] [PubMed] [Google Scholar]

[B11] 11.Barker TH, Stone JC, Sears K, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21:494-506. [DOI] [PubMed]; Barker TH, Stone JC, Sears K, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21:494–506. doi: 10.11124/JBIES-22-00430. [DOI] [PubMed] [Google Scholar]

[B12] 12.Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. [DOI] [PMC free article] [PubMed]; Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. doi: 10.1186/1471-2288-14-135. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B13] 13.Bär S, Kavaliauskaite R, Otsuka T, et al. Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction:a prespecified substudy of the PACMAN-AMI trial. EuroIntervention. 2023;19:e286-e296. [DOI] [PMC free article] [PubMed]; Bär S, Kavaliauskaite R, Otsuka T, et al. Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction:a prespecified substudy of the PACMAN-AMI trial. EuroIntervention. 2023;19:e286–e296. doi: 10.4244/EIJ-D-23-00201. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B14] 14.Cortés C, Rodríguez-Gabella T, Gutiérrez H, et al. Quantitative flow ratio in myocardial infarction for the evaluation of non-infarct-related arteries. The QIMERA pilot study. REC Interv Cardiol. 2019;1:13-20.; Cortés C, Rodríguez-Gabella T, Gutiérrez H, et al. Quantitative flow ratio in myocardial infarction for the evaluation of non-infarct-related arteries. The QIMERA pilot study. REC Interv Cardiol. 2019;1:13–20. [Google Scholar]

[B15] 15.Erbay A, Penzel L, Abdelwahed YS, et al. Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome. Int J Cardiovasc Imaging. 2021;37:1815-1823. [DOI] [PMC free article] [PubMed]; Erbay A, Penzel L, Abdelwahed YS, et al. Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome. Int J Cardiovasc Imaging. 2021;37:1815–1823. doi: 10.1007/s10554-021-02195-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B16] 16.Hou S, Zhu X, Zhao Q, et al. Quantitative flow ratio-guided staged percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Heliyon. 2024;10:e39335. [DOI] [PMC free article] [PubMed]; Hou S, Zhu X, Zhao Q, et al. Quantitative flow ratio-guided staged percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Heliyon. 2024;10:e39335. doi: 10.1016/j.heliyon.2024.e39335. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B17] 17.Huang J, Groenland FTW, Scoccia A, et al. Acute-setting vs. staged-setting vessel fractional flow reserve of intermediate non-culprit lesions in patients with ST-segment elevation myocardial infarction (FAST STAGED study). Int J Cardiol Heart Vasc. 2023;45:101192. [DOI] [PMC free article] [PubMed]; Huang J, Groenland FTW, Scoccia A, et al. Acute-setting vs. staged-setting vessel fractional flow reserve of intermediate non-culprit lesions in patients with ST-segment elevation myocardial infarction (FAST STAGED study) Int J Cardiol Heart Vasc. 2023;45:101192. doi: 10.1016/j.ijcha.2023.101192. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B18] 18.Kirigaya H, Okada K, Hibi K, et al. Diagnostic performance and limitation of quantitative flow ratio for functional assessment of intermediate coronary stenosis. J Cardiol. 2021;77:492-499. [DOI] [PubMed]; Kirigaya H, Okada K, Hibi K, et al. Diagnostic performance and limitation of quantitative flow ratio for functional assessment of intermediate coronary stenosis. J Cardiol. 2021;77:492–499. doi: 10.1016/j.jjcc.2020.11.002. [DOI] [PubMed] [Google Scholar]

[B19] 19.Mensink F, Los J, van Geuns RJ. Functional and morphological changes of significant non-culprit coronary artery stenosis by extensive LDL-C reduction with PCSK9 inhibitors. Results of the randomized, placebo-controlled FITTER trial. En:ESC Congress 2024;2024 30 agosto - 2 septiembre;Londres, Reino Unido. Disponible en:https://clinicaltrialresults.org/slide-library/.; Mensink F, Los J, van Geuns RJ. Results of the randomized, placebo-controlled FITTER trial. En:ESC Congress. Vol. 2024. Londres: Reino Unido; 2024. Functional and morphological changes of significant non-culprit coronary artery stenosis by extensive LDL-C reduction with PCSK9 inhibitors. 30 agosto - 2 septiembre. Disponible en: https://clinicaltrialresults.org/slide-library/ [Google Scholar]

[B20] 20.Musto C, De Felice F, Rigattieri S, et al. Instantaneous wave-free ratio and fractional flow reserve for the assessment of nonculprit lesions during the index procedure in patients with ST-segment elevation myocardial infarction:The WAVE study. Am Heart J. 2017;193:63-69. [DOI] [PubMed]; Musto C, De Felice F, Rigattieri S, et al. Instantaneous wave-free ratio and fractional flow reserve for the assessment of nonculprit lesions during the index procedure in patients with ST-segment elevation myocardial infarction:The WAVE study. Am Heart J. 2017;193:63–69. doi: 10.1016/j.ahj.2017.07.017. [DOI] [PubMed] [Google Scholar]

[B21] 21.Ntalianis A, Sels JW, Davidavicius G, et al. Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction. JACC Cardiovasc Interv. 2010;3:1274-1281. [DOI] [PubMed]; Ntalianis A, Sels JW, Davidavicius G, et al. Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction. JACC Cardiovasc Interv. 2010;3:1274–1281. doi: 10.1016/j.jcin.2010.08.025. [DOI] [PubMed] [Google Scholar]

[B22] 22.Sejr-Hansen M, Westra J, Thim T, et al. Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction-An iSTEMI substudy. Catheter Cardiovasc Interv. 2019;94:686-692. [DOI] [PubMed]; Sejr-Hansen M, Westra J, Thim T, et al. Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction-An iSTEMI substudy. Catheter Cardiovasc Interv. 2019;94:686–692. doi: 10.1002/ccd.28208. [DOI] [PubMed] [Google Scholar]

[B23] 23.Shukla A, Dwivedi SK, Chandra S, et al. Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach. Cureus. 2024;16:e52668. [DOI] [PMC free article] [PubMed]; Shukla A, Dwivedi SK, Chandra S, et al. Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach. Cureus. 2024;16:e52668. doi: 10.7759/cureus.52668. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B24] 24.Thim T, Götberg M, Fröbert O, et al. Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2017;10:2528-2535. [DOI] [PubMed]; Thim T, Götberg M, Fröbert O, et al. Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2017;10:2528–2535. doi: 10.1016/j.jcin.2017.07.021. [DOI] [PubMed] [Google Scholar]

[B25] 25.van der Hoeven NW, Janssens GN, de Waard GA, et al. Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction. JAMA Cardiol. 2019;4:736-744. [DOI] [PMC free article] [PubMed]; van der Hoeven NW, Janssens GN, de Waard GA, et al. Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction. JAMA Cardiol. 2019;4:736–744. doi: 10.1001/jamacardio.2019.2138. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B26] 26.Wang L, Travieso A, van der Hoeven N, et al. Improved Nonculprit Stenosis Assessment in Patients With ST-Segment Elevation Myocardial Infarction Using Quantitative Flow Ratio. JACC Cardiovasc Interv. 2023;16:1828-1830. [DOI] [PubMed]; Wang L, Travieso A, van der Hoeven N, et al. Improved Nonculprit Stenosis Assessment in Patients With ST-Segment Elevation Myocardial Infarction Using Quantitative Flow Ratio. JACC Cardiovasc Interv. 2023;16:1828–1830. doi: 10.1016/j.jcin.2023.04.045. [DOI] [PubMed] [Google Scholar]

[B27] 27.Zhao Q, Sun S, Zhou F, Yue J, Luo X, Qu X. The Inhibition of Evolocumab on Non-Infarct-Related Artery Disease in Patients with ST-Elevation Myocardial Infarction. Int J Gen Med. 2023;16:2771-2781. [DOI] [PMC free article] [PubMed]; Zhao Q, Sun S, Zhou F, Yue J, Luo X, Qu X. The Inhibition of Evolocumab on Non-Infarct-Related Artery Disease in Patients with ST-Elevation Myocardial Infarction. Int J Gen Med. 2023;16:2771–2781. doi: 10.2147/IJGM.S417481. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B28] 28.Barauskas M, Žiubryte G, Jodka N, Unikas R. Quantitative Flow Ratio for Assessment of Non-Culprit Coronary Artery Lesions During Percutaneous Coronary Intervention (PCI) in 79 Patients Diagnosed with ST-Elevation Myocardial Infarction (STEMI):A Study from a Single Center in Lithuania. Med Sci Monit. 2023;29:e939360. [DOI] [PMC free article] [PubMed]; Barauskas M, Žiubryte G, Jodka N, Unikas R. Quantitative Flow Ratio for Assessment of Non-Culprit Coronary Artery Lesions During Percutaneous Coronary Intervention (PCI) in 79 Patients Diagnosed with ST-Elevation Myocardial Infarction (STEMI):A Study from a Single Center in Lithuania. Med Sci Monit. 2023;29:e939360. doi: 10.12659/MSM.939360. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B29] 29.Jo YS, Moon H, Park K. Different Microcirculation Response Between Culprit and Non-Culprit Vessels in Patients With Acute Coronary Syndrome. J Am Heart Assoc. 2020;9:e015507. [DOI] [PMC free article] [PubMed]; Jo YS, Moon H, Park K. Different Microcirculation Response Between Culprit and Non-Culprit Vessels in Patients With Acute Coronary Syndrome. J Am Heart Assoc. 2020;9:e015507. doi: 10.1161/JAHA.119.015507. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B30] 30.Li X, Mi L, Duan J, Tao L, Xu X, Wang G. Murray law-based quantitative flow ratio for assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction. Cardiol J. 2024;31:522-527. [DOI] [PMC free article] [PubMed]; Li X, Mi L, Duan J, Tao L, Xu X, Wang G. Murray law-based quantitative flow ratio for assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction. Cardiol J. 2024;31:522–527. doi: 10.5603/cj.93499. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B31] 31.Park K, Cho YR, Park JS, Park TH, Kim MH, Kim YD. Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices. Circ Cardiovasc Interv. 2019;12:e008105. [DOI] [PubMed]; Park K, Cho YR, Park JS, Park TH, Kim MH, Kim YD. Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices. Circ Cardiovasc Interv. 2019;12:e008105. doi: 10.1161/CIRCINTERVENTIONS.119.008105. [DOI] [PubMed] [Google Scholar]

[B32] 32.Spitaleri G, Tebaldi M, Biscaglia S, et al. Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease. Circ Cardiovasc Interv. 2018;11:e006023. [DOI] [PubMed]; Spitaleri G, Tebaldi M, Biscaglia S, et al. Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease. Circ Cardiovasc Interv. 2018;11:e006023. doi: 10.1161/CIRCINTERVENTIONS.117.006023. [DOI] [PubMed] [Google Scholar]

[B33] 33.Mensink FB, Los J, Oemrawsingh RM, et al. Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody:Rationale and design of the randomized FITTER trial. Heliyon. 2024;10:e38077. [DOI] [PMC free article] [PubMed]; Mensink FB, Los J, Oemrawsingh RM, et al. Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody:Rationale and design of the randomized FITTER trial. Heliyon. 2024;10:e38077. doi: 10.1016/j.heliyon.2024.e38077. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B34] 34.Biscaglia S, Guiducci V, Escaned J, et al. Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction. N Engl J Med. 2023;389:889-898. [DOI] [PubMed]; Biscaglia S, Guiducci V, Escaned J, et al. Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction. N Engl J Med. 2023;389:889–898. doi: 10.1056/NEJMoa2300468. [DOI] [PubMed] [Google Scholar]

[B35] 35.Lee JM, Kim HK, Park KH, et al. Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease:a randomized trial. Eur Heart J. 2023;44:473-484. [DOI] [PubMed]; Lee JM, Kim HK, Park KH, et al. Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease:a randomized trial. Eur Heart J. 2023;44:473–484. doi: 10.1093/eurheartj/ehac763. [DOI] [PubMed] [Google Scholar]

[B36] 36.Böhm F, Mogensen B, Engstrøm T, et al. FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction. N Engl J Med. 2024;390:1481-1492. [DOI] [PubMed]; Böhm F, Mogensen B, Engstrøm T, et al. FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction. N Engl J Med. 2024;390:1481–1492. doi: 10.1056/NEJMoa2314149. [DOI] [PubMed] [Google Scholar]

[B37] 37.Smits PC, Abdel-Wahab M, Neumann FJ, et al. Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction. N Engl J Med. 2017;376:1234-1244. [DOI] [PubMed]; Smits PC, Abdel-Wahab M, Neumann FJ, et al. Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction. N Engl J Med. 2017;376:1234–1244. doi: 10.1056/NEJMoa1701067. [DOI] [PubMed] [Google Scholar]

[B38] 38.Engstrøm T, Kelbæk H, Helqvist S, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI):an open-label, randomised controlled trial. Lancet. 2015;386:665-671. [DOI] [PubMed]; Engstrøm T, Kelbæk H, Helqvist S, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI):an open-label, randomised controlled trial. Lancet. 2015;386:665–671. doi: 10.1016/s0140-6736(15)60648-1. [DOI] [PubMed] [Google Scholar]

[B39] 39.Puymirat E, Cayla G, Simon T, et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021;385:297-308. [DOI] [PubMed]; Puymirat E, Cayla G, Simon T, et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021;385:297–308. doi: 10.1056/NEJMoa2104650. [DOI] [PubMed] [Google Scholar]

[B40] 40.Xu X, Fang C, Jiang S, et al. Functional or anatomical assessment of non-culprit lesions in acute myocardial infarction. EuroIntervention. 2025;21:e217-e228. [DOI] [PMC free article] [PubMed]; Xu X, Fang C, Jiang S, et al. Functional or anatomical assessment of non-culprit lesions in acute myocardial infarction. EuroIntervention. 2025;21:e217–e228. doi: 10.4244/EIJ-D-24-00720. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B41] 41.Räber L, Ueki Y, Otsuka T, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction:The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022;327:1771-1781. [DOI] [PMC free article] [PubMed]; Räber L, Ueki Y, Otsuka T, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction:The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022;327:1771–1781. doi: 10.1001/jama.2022.5218. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Functional assessment in acute coronary syndrome: a systematic review of acute versus staged interventions

Evaluación funcional en el síndrome coronario agudo: una revisión sistemática del escenario agudo frente al diferido

Federico Vergni

Silvia Buscarini

Leonardo Ciurlanti

Filippo Luca Gurgoglione

Francesco Pellone

Mario Luzi

ABSTRACT

Introduction and objectives:

Methods:

Results:

Conclusions:

RESUMEN

Introducción y objetivos:

Métodos:

Resultados:

Conclusiones:

Abbreviations

INTRODUCTION

METHODS

Eligibility criteria

Search strategy, and study selection

Data extraction

Risk of bias assessment

Data synthesis

RESULTS

Characteristics of the articles, participants, and indices

Figure 1. PRISMA flow diagram. PRISMA, preferred reporting items for systematic reviews and meta-analyses.

Table 1. Extracted data of studies with low risk of bias.

Table 2. Data drawn from studies with moderate risk of bias.

Risk of bias

Tabla 1. Datos extraídos de estudios con bajo riesgo de sesgo.

Tabla 2. Datos obtenidos de estudios con riesgo moderado de sesgo.

Primary endpoint

Statistical significance

Mean differences

Disagreement

Secondary endpoint

DISCUSSION

Limitations

CONCLUSIONS

DATA AVAILABILITY

ETHICAL CONSIDERATIONS

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

AUTHORS’ CONTRIBUTIONS

SUPPLEMENTARY DATA

Footnotes

BIBLIOGRAFÍA

Evaluación funcional en el síndrome coronario agudo: una revisión sistemática del escenario agudo frente al diferido

Abreviaturas

INTRODUCCIÓN

MÉTODOS

Criterios de elegibilidad

Estrategia de búsqueda y selección de estudios

Extracción de datos

Valoración del riesgo de sesgo

Síntesis de datos

RESULTADOS

Características de los artículos, participantes e índices

Figura 1. Diagrama de flujo PRISMA. Declaración PRISMA: elementos de reporte preferidos para revisiones sistemáticas y metanálisis.

Riesgo de sesgo

Objetivo primario

Significación estadística

Diferencias medias

Discordancia

Objetivo secundario

DISCUSIÓN

Limitaciones

CONCLUSIONES

DISPONIBILIDAD DE LOS DATOS

CONSIDERACIONES ÉTICAS

DECLARACIÓN SOBRE EL USO DE INTELIGENCIA ARTIFICIAL

CONTRIBUCIÓN DE LOS AUTORES

MATERIAL ADICIONAL

Footnotes

Associated Data

Data Availability Statement

ACTIONS