Innovation in interventional cardiology
Introduction and objectives: Current expert consensus guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel as antithrombotic strategy after transcatheter aortic valve implantation (TAVI) in patients without an indication for long-term oral anticoagulation. However, these recommendations have not been developed based on the results of large randomized clinical trials. The objective of this study is to compare single antiplatelet therapy (SAPT) to DAPT in patients without an indication for long-term anticoagulation after TAVI.
Methods: The PubMed, Embase, and the main international conference proceedings were reviewed in the search for randomized controlled trials comparing SAPT to DAPT after TAVI. Data were pooled using a meta-analysis and a random-effects model. The primary endpoint was life-threatening or major bleeding.
Results: Four trials enrolling 1086 patients were included. Compared to patients treated with DAPT, those treated with SAPT showed a lower risk of life-threatening or major bleeding (OR, 0.44; 95%CI, 0.27-0.70), and any bleeding (OR, 0.51; 95%CI, 0.36-0.71). No differences were observed between patients treated with SAPT compared to those treated with DAPT regarding all-cause mortality (OR, 1.01; 95%CI, 0.61-1.68), myocardial infarction (OR, 0.50; 95%CI 0.17-1.41), and stroke (OR, 0.98; 95%CI, 0.54-1.77).
Conclusions: In patients without an indication for long-term anticoagulation undergoing TAVI, single antiplatelet therapy with aspirin compared to DAPT is associated with a lower risk of life-threatening or major bleeding and a comparable risk of all-cause mortality, myocardial infarction, and stroke.
Keywords: Antithrombotic therapy. TAVI. Antiplatelet therapy. Aspirin. Bleeding.
Introducción y objetivos: Las guías de práctica clínica actuales recomiendan la terapia antiagregante plaquetaria doble con ácido acetilsalicílico y clopidogrel como estrategia antitrombótica tras el implante percutáneo de válvula aórtica (TAVI) en pacientes sin indicación de anticoagulación oral a largo plazo. Sin embargo, estas recomendaciones no se han desarrollado de acuerdo con los resultados de grandes ensayos aleatorizados. Por ello, el objetivo de esta investigación es comparar la terapia antiplaquetaria en monoterapia con el tratamiento antiagregante doble en pacientes sin indicación de anticoagulación a largo plazo después de un TAVI.
Métodos: Se realizaron búsquedas en PubMed, Embase y los principales congresos internacionales para encontrar ensayos clínicos aleatorizados que compararan el tratamiento antiagregante único con la doble terapia antiplaquetaria después de un TAVI. Los datos se agruparon en un metanálisis mediante un modelo de efectos aleatorios. El objetivo principal del estudio fue la hemorragia grave o potencialmente mortal.
Resultados: Se incluyeron cuatro ensayos que en total reclutaron 1086 pacientes. Los pacientes bajo tratamiento antiagregante en monoterapia, en comparación con aquellos con doble terapia antiplaquetaria, tuvieron menor riesgo de hemorragia grave o potencialmente mortal (odds ratio [OR] = 0,44; intervalo de confianza del 95% [IC95%], 0,27-0,70) y de cualquier sangrado (OR = 0,51; IC95%, 0,36-0,71). No se observaron diferencias entre los pacientes tratados con monoterapia y los tratados con doble terapia antiagregante en cuanto a muerte por cualquier causa (OR = 1,01; IC95%, 0,61-1,68), infarto de miocardio (OR = 0,50; IC95%: 0,17-1,41) y accidente cerebrovascular (OR = 0,98; IC95%, 0,54-1,77).
Conclusiones: En los pacientes sin indicación de anticoagulación a largo plazo sometidos a TAVI, la monoterapia con ácido acetilsalicílico en comparación con la doble terapia antiagregante se asocia con un menor riesgo de hemorragia grave o potencialmente mortal y con un riesgo comparable de muerte por cualquier causa, infarto de miocardio y accidente cerebrovascular.
Palabras clave: Tratamiento antitromb ótico. TAVI. Tratamiento antiagregante. Ácido acetilsalicílico. Sangrado.
Abbreviations DAPT: dual antiplatelet therapy. PCI: percutaneous coronary intervention. RCT: randomized clinical trial. SAPT: single antiplatelet therapy. TAVI: transcatheter aortic valve implantation.
Over the last 20 years, transcatheter aortic valve implantation (TAVI) has emerged as a successful therapeutic alternative strategy to surgery to treat aortic valve stenosis in patients of high, intermediate, and low surgical risk.1-6
Ischemic and bleeding complications are not rare after TAVI and can be life-threatening. Recently, the PARTNER 3 and Evolut Low Risk clinical trials have shown low, yet non-negligible, incidence rates of both stroke, and major bleeding within 30 days after TAVI.5,6
As of today, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is the most commonly used antithrombotic regimen after TAVI in patients without an indication for long-term oral anticoagulation enrolled in clinical studies. Indeed, the recommendations from different societal guidelines suggest 1 to 3, 3 to 6 or 6 months of therapy with clopidogrel plus low doses of aspirin. However, such recommendations have not been developed based on the results of large randomized clinical trials.7-10 Indeed, reports on course duration over the last decade have suggested a neutral or beneficial effect of single antiplatelet therapy (SAPT) compared to early DAPT followed by SAPT regarding vascular complications and major or life-threatening bleeding and no higher risk for myocardial infarction, and stroke.11-13 Recently, aspirin alone proved superior compared to a 3-month course of aspirin plus clopidogrel followed by aspirin in terms of bleeding alone and combined with thromboembolic complications at the 1-year follow-up.14
We conducted a meta-analysis of available randomized clinical studies to provide a comprehensive and quantitative assessment of the evidence available on the safety and efficacy profile of SAPT compared to DAPT after TAVI in patients with no indication for long-term oral anticoagulation.
Search strategy and selection criteria
Randomized clinical trials (RCTs) including patients undergoing TAVI were evaluated to be included in this meta-analysis. Eligible studies had to meet the following prespecified inclusion criteria: a) RCTs comparing SAPT to DAPT after TAVI, and b) availability of clinical outcome data. The exclusion criteria were these: a) RCTs including patients requiring oral anticoagulation, b) lack of randomized design, c) lack of any clinical outcome data.
The search strategy, study selection, data extraction, and data analysis were performed based on The Cochrane Collaboration and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.15
Back in August 31, 2020, we searched the PubMed and Embase databases. We also searched abstracts presented at relevant scientific meetings (American Heart Association, American College of Cardiology, European Society of Cardiology, EuroPCR, and Transcatheter Cardiovascular Therapeutics). We also used backward snowballing (ie, review of references from identified articles and pertinent reviews). The search strategy is available in the supplementary data.
Three investigators (J. Sanz-Sánchez, C. A. Pivato, and P. P. Leone) independently assessed studies with potential to be included. The senior investigator (G. G. Stefanini) resolved the discrepancies. Non-relevant articles were excluded based on title and abstract. The same investigators independently extracted data on the study design, measurements, patient characteristics, and outcomes, using a standardized data-extraction form. Data extraction conflicts were discussed and resolved with the senior investigator (G. G. Stefanini).
Data about the authors, year of publication, inclusion, and exclusion criteria, sample size, the patients’ baseline characteristics, endpoint definitions, effect estimates, and follow-up time were collected.
Outcomes of interest
The prespecified primary endpoint was life-threatening or major bleeding. The secondary clinical endpoints were all-cause mortality, myocardial infarction, stroke, and any bleeding. Each endpoint was assessed according to the definitions reported in the original study protocols as shown on table 1 of the supplementary data.
|Study||Year of publication||Study design||N of patients||Multicentre||Follow-up||DAPT duration|
|POPular TAVI14||2020||RCT||665||334||331||Yes||12 months||3 months|
|ARTE11||2017||RCT||222||111||111||Yes||3 months||3 months|
|SAT-TAVI12||2014||RCT||120||60||60||No||6 months||6 months|
|Ussia et al.13||2011||RCT||79||40||39||No||6 months||3 months|
DAPT, dual antiplatelet therapy; RCT, randomized clinical trial; SAPT, single antiplatelet therapy.
Risk of bias
The risk of bias in each study was assessed using the revised Cochrane risk-of-bias tool (RoB 2.0).16 Three investigators (J. Sanz- Sánchez, C. A. Pivato, and P. P. Leone) independently assessed 5 domains of bias in the RCTs: 1) randomization process, 2) deviations from intended interventions, 3) missing outcome data, 4) outcome measurements, and 5) selection of reported results (table 2 of the supplementary data).
|Study||Age (years)||Male||Diabetes||Hypertension||Atrial fibrillation||NYHA ≥ III||LVEF||STS-PROM score||Previous stroke||Previous MI||Transfemoral access||Valve-in-valve||TAVI indication: aortic stenosis|
|Ussia et al.13||81||46||27||84||13||62||52||7.3||8||14||97||0||100|
LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association; STS-PROM, Society of Thoracic Surgeons Predicted Risk Of Mortality; TAVI, transcatheter valve implantation.
Data are expressed as %.
The odds ratios (OR) and the 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model with the estimate of heterogeneity being taken from the Mantel-Haenszel method. The number needed to treat (NNT) to prevent 1 event was calculated from weighted estimates of pooled ORs using the random-effects meta-analytic model. The presence of heterogeneity among the studies was evaluated using Cochran Q test based on a chi-square distribution with P values ≤ .10 considered statistically significant, and the I2 test to evaluate inconsistencies. A value of 0% indicates no observed heterogeneity, and values of ≤ 25%, ≤ 50%, > 50% are indicative of low, moderate, and high heterogeneity, respectively. The presence of publication bias was investigated by visual estimation through funnel plots. We conducted a leave-one-out sensitivity analysis for the primary endpoint by iteratively removing 1 study at a time to confirm that our findings were not driven by any single study. Further sensitivity analyses were conducted by calculating the ORs with a 95%CI using a fixed-effects model with the Mantel and Haenszel method and the risk ratios with a 95%CI using both fixed-effects and random-effects models. The statistical level of significance was 2-tailed P values < .05. Statistical analyses were performed using the Stata software version 13.1 (StataCorp LP, College Station, United States).
A total of 541 patients treated with aspirin and 545 patients treated with DAPT after TAVI were included.
The main baseline characteristics of the patients included are shown on table 2. Most patients underwent TAVI due to aortic stenosis. The Society of Thoracic Surgeons mean predicted risk of mortality was 4.4% and most of the procedures were performed via transfemoral access.
Publication bias and asymmetry
The funnel-plot distributions of the prespecified outcomes are indicative of lack of publication bias for all the outcomes (figures 1-5 of the supplementary data).
Compared to patients treated with DAPT, those treated with SAPT had a lower risk of life-threatening or major bleeding (OR, 0.44; 95%CI, 0.27-0.70; I2 = 0%), and any bleeding (OR, 0.51; 95%CI, 0.36-0.71; I2 = 0%) (figure 2). No differences were seen between patients treated with SAPT compared to those treated with DAPT in terms of all-cause mortality (OR, 1.01; 95%CI, 0.61-1.68; I2 = 0%), myocardial infarction (OR, 0.50; 95%CI, 0.17-1.41; I2 = 0%), and stroke (OR, 0.98; 95%CI, 0.54-1.77; I2 = 0%) (figure 3). The NNT to prevent 1 life-threatening or major bleeding was 17 patients and the NNT to prevent any bleeding was 11 patients.
Risk of bias assessment
Table 2 of the supplementary data shows the results of the risk of bias assessment using the RoB 2.0 tool. Two trials were considered at a low overall risk of bias11,14 and 2 presented some concerns.12,13
Findings remained consistent with the main analysis after calculating the ORs using a fixed effects model and risk ratios with both fixed and random-effects models (table 3 of the supplementary data).
The leave-one-out sensitivity analysis results remained consistent with the primary analysis (table 4 of the supplementary data).
The current meta-analysis evaluated available RCTs comparing SAPT with aspirin to DAPT in patients undergoing TAVI with no indication for long-term oral anticoagulation. The main findings were these:
1) The risk of life-threatening or major bleeding, and any bleeding is reduced in patients treated with SAPT compared to DAPT.
2) The risk of all-cause mortality, myocardial infarction, and stroke did not differ between the 2 treatment strategies.
Currently, the clinical practice guidelines recommend DAPT for 1 to 6 months after TAVI in patients with no indication for long-term oral anticoagulation.7-9 However, this regimen is not supported by actual evidence available. This practice is derived from the percutaneous coronary intervention field where the addition of a P2Y12 inhibitor to aspirin compared to aspirin monotherapy proved to reduce the risk of ischemic complications especially stent thrombosis.17 The addition of clopidogrel to aspirin after TAVI has the theorical rationale of reducing the rate of ischemic cerebrovascular events, myocardial infarction, and valve thrombosis.
Ischemic stroke is one of the worst complications after TAVI. Its highest incidence rate occurs within the first 24 hours after the procedure. It seems to be mainly associated with embolized tissue waste during TAVI due to dilation of the calcified valve or navigation through the aortic arch.18-20 Instead, subacute stroke (between 1 to 30 days after the procedure)—representative of a quarter of the total number events at 2 years—4,21 are often associated with new-onset atrial fibrillation,22-24 against which DAPT is known to perform poorly.
Another motivation to prescribe DAPT after TAVI is to limit the rate of myocardial infarction. Nevertheless, the reported rate of myocardial infarction after TAVI is relatively low,4,21 and concomitant coronary artery disease is often treated percutaneously before TAVI. Therefore, the addition of a P2Y12 inhibitor to aspirin after TAVI does not seem to offer any additional advantages compared to aspirin monotherapy regarding the reduction of the risk of myocardial infarction as our results showed.
Finally, while symptomatic valve thrombosis is a rare condition (< 1%), subclinical thrombosis has a higher incidence rate (from 10% to 40% according to different series).25-27 The clinical impact of this phenomenon is still unknown: it could not only impact valve durability due to pannus formation, but it also has been associated with a higher rate of transient ischemic attack.25,26 In this setting, the pathophysiology of thrombus formation after TAVI is also still under discussion as the relative weight of primary and secondary hemostasis is still to be established. On the one hand, the endothelial injury and high shear stress environment present all around the valve stent frame before re-endothelialization may favour platelet aggregation, thus leading to the formation of a platelet-rich thrombus. This is somehow similar to what happens during coronary stent thrombosis against which the most effective treatment has proven to be DAPT.17 On the other hand, the bioprosthetic sinus of the valve leaflets could favour a condition of low shear stress and flow turbulence, thus predisposing to the development of a thrombin-rich thrombus. DAPT seems to offer no benefit over SAPT in terms of reducing bioprosthetic valve thrombosis while oral anticoagulants have proven to both prevent and resolve this complication.25-27 However, so far the only trial to assess the role of anticoagulant therapy following TAVI in patients with no indication for long-term oral anticoagulation is the Global study comparing a rivaroxaban-based antithrombotic strategy to an antiplatelet-based strategy after transcatheter aortic valve replacement to optimize clinical outcomes (GALILEO). It was stopped following relevant safety issues seen on the interim analyses revealing higher rates of complications with low doses of rivaroxaban/aspirin compared to DAPT including hard endpoints like mortality (6.8% vs 3.3%).28
Overall, ischemic events post-TAVI seem to elude the antiplatelet action provided by thienopyridines added to aspirin. A current meta-analysis confirms that the addition of a P2Y12 inhibitor does not reduce the risk of ischemic events (ie, myocardial infarction, and stroke), but most importantly predisposes patients to a higher risk of life-threatening or major bleeding. The bleeding risk reduction seen with SAPT compared to DAPT shown by this meta-analysis is of great clinical relevance, with a NNT of only 11 patients to prevent any bleeding and a NNT of 17 patients to prevent 1 life-threatening or major bleeding. Moreover, since most of the bleeding events occur within 30 days after the procedure, likely due to periprocedural antithrombotic therapy and access site bleeding complications,1-4,29 even a short-term DAPT course raises safety issues in term of bleeding events.
Based on the evidence published so far and the results of this research, in patients with no indication for long-term anticoagulation undergoing TAVI, aspirin monotherapy should be preferred over DAPT. However, larger trials are still needed to determine whether antiplatelet strategies should be tailored and based on the valve implanted (balloon-expandable vs self-expandable) or on the particular valve-in-valve implantation setting; also, to elucidate the role of alternative antiplatelet regimens (ie, P2Y12i monotherapy), and oral anticoagulants.
The results of our study should be interpreted considering some limitations. First, this was a study-level meta-analysis that provided average treatment effects. Also, the lack of patient-level data from the studies included data prevents us from assessing the impact baseline clinical and procedural characteristics had on treatment effects. Secondly, minor differences in the definition used were present in the ischemic endpoints, thus limiting the reliability of the effect estimates. However, in terms of the bleeding endpoints, the VARC definition was used in all the studies included, which adds to the robustness of our findings. Finally, the limited number of studies and patients as well as the small event rate for certain endpoints such as myocardial infarction may have reduced the statistical power to detect any significant inter-group differences.
Additional evidence will be provided by ongoing randomized trials: the Antithrombotic strategy after trans-aortic valve implantation for aortic stenosis (ATLANTIS, NCT02664649) trial will evaluate the benefit of apixaban therapy (standard dose) vs standard of care; the Anticoagulant versus dual antiplatelet therapy for preventing leaflet thrombosis and cerebral embolization after transcatheter aortic valve replacement (ADAPT-TAVR, NCT03284827) trial will compare edoxaban (standard dose) vs DAPT. Finally, the Dual antiplatelet therapy versus oral anticoagulation for a short time to prevent cerebral embolism after TAVI (AUREA, NCT01642134) trial will study a strategy of vitamin K antagonist vs a 3-month course of DAPT.
In patients without an indication for long-term anticoagulation undergoing TAVI, monotherapy with aspirin compared to DAPT is associated with a lower risk of life-threatening or major bleeding, and a comparable risk of all-cause mortality, myocardial infarction, and stroke.
J. Sanz-Sánchez, C. A. Pivato, P. P. Leone, and M. Chiarito con- tributed to the design, analysis, and writing of this manuscript. D. Regazzoli, and G. Petriello contributed to the design, and writing of this manuscript too. B. Reimers, G. Condorelli, and G. G. Stefanini contributed to the study design, writing, and supervision.
CONFLICTS OF INTEREST
G. G. Stefanini reported a research grant from Boston Scientific, and speaker/consulting fees from B. Braun, Biosensors, and Boston Scientific. D. Regazzoli reported speaker fees from Amgen, and Boehringer. The remaining authors declared no conflicts of interest whatsoever.
What is known about the topic?
- Ischemic and bleeding complications are not rare after TAVI and can be life-threatening. To reduce the rate of stroke, myocardial infarction, and valve thrombosis, the clinical practice guidelines recommend a 1 to 6 month DAPT course after TAVI in patients with no indication for long-term oral anticoagulation. However, this regimen is not supported by the current evidence and overall, ischemic events post-TAVI seem to elude the antiplatelet action provided by thienopyridines added to aspirin. Indeed, reports on therapy duration over the last decade have suggested a neutral or beneficial effect of aspirin monotherapy compared to early DAPT followed by aspirin regarding vascular complications, and major or life-threatening bleedings.
What does this study add?
- The present study confirms that the addition of thienopyridines added to aspirin does not reduce the risk of ischemic events (namely myocardial infarction, and stroke). Instead it predisposes patients to an increased risk of life-threatening or major bleeding. The bleeding risk reduction with aspirin compared to DAPT is of great clinical relevance, with a NNT of only 11 patients to prevent any bleeding and a NNT of 17 patients to prevent 1 life-threatening or major bleeding. Based on the evidence published so far and the results of this study, in patients without an indication for long-term anticoagulation undergoing TAVI, aspirin monotherapy should be preferred over DAPT.
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Introduction and objectives: The objective of this study was to describe our experience with coronary physiology assessment using the instantaneous wave-free ratio (iFR) and/or a Syncvision-guided iFR-pullback study [Syncvision version 188.8.131.52, Philips Volcano, Belgium] in all-comer patients.
Methods: Consecutive patients undergoing coronary physiology assessment with the iFR (and/or a Syncvision-guided iFR-pullback study) at our center between January 2017 and December 2019 were included. The iFR cut-off value was 0.89. The primary endpoint was a composite of cardiac death, myocardial infarction, probable or definitive stent thrombosis, and target lesion revascularization.
Results: A total of 277 patients with 433 lesions evaluated were included. The mean age was 65 ± 10 years and 74% were men. Personal history of diabetes mellitus was present in 41% of patients. Clinical presentation was stable angina in 160 patients (58%), and acute coronary syndrome in 117 patients (42%). iFRs > 0.89 were obtained in 266 lesions (61.4%) on which the PCI was postponed. The remaining lesions were revascularized. The Syncvision software was used to guide the iFR-pullback study in 155 lesions (36%) and the decision-making process, mainly in long, diffuse or sequential lesions (91 lesions, 58.7%), and intermediate lesions (52 lesions, 33.5%). After a median follow-up of 18 months, the primary endpoint occurred in 17 patients (6.1%) without differences regarding the baseline iFR (≤ 0.89 or > 0.89) (4.2% vs 3.8%; P = .9) or the clinical presentation (stable angina or acute coronary syndrome) (4.4% vs 8.5%; P = .1)
Conclusions: The use of coronary physiology assessment with the iFR and the Syncvision-guided iFR-pullback study in the routine daily practice and in all-comer patients seems safe with a low percentage of major adverse cardiovascular events at the mid-term follow-up.
Keywords: Physiological assessment. All-comer patients. Syncvision-guided iFR-pullback study.
Introducción y objetivos: El propósito del estudio fue describir nuestra experiencia con el uso del índice diastólico instantáneo sin ondas (iFR) para la evaluación fisiológica coronaria o el uso del software Syncvision/iFR (Syncvision versión 184.108.40.206, Philips Volcano, Bélgica) en todo tipo de pacientes.
Métodos: Se incluyeron todos los pacientes consecutivos a quienes, entre enero de 2017 y diciembre de 2019, se realizó en nuestro centro una evaluación fisiológica coronaria con iFR o con Syncvision/iFR. El valor de corte establecido para el iFR fue 0,89. El objetivo primario fue un compuesto de muerte cardiaca, infarto de miocardio, trombosis de stent probable o definitiva y nueva revascularización de la lesión evaluada.
Resultados: Se incluyeron 277 pacientes con 433 lesiones evaluadas. La edad media fue de 65 ± 10 años y el 74% eran varones. El 41% tenía antecedente personal de diabetes mellitus. La presentación clínica fue angina estable en 160 pacientes (58%) y síndrome coronario agudo en 117 pacientes (42%). Se obtuvo un iFR > 0,89 en 266 lesiones (61,4%), en las cuales la intervención coronaria percutánea fue diferida. Las lesiones restantes se revascularizaron. El software Syncvision/iFR se usó en 155 lesiones (36%) para guiar la toma de decisiones, principalmente lesiones largas, difusas o secuenciales (91 lesiones, 58,7%) y lesiones intermedias (52 lesiones, 33,5%). Tras un periodo de seguimiento de 18 meses, el objetivo primario se observó en 17 pacientes (6,1%), sin diferencias en función del iFR basal (≤ 0,89 o > 0,89) (4,2 frente a 3,8%; p = 0,9) ni de la presentación clínica (angina estable o síndrome coronario agudo) (4,4 frente a 8,5%; p = 0,1).
Conclusiones: La evaluación fisiológica coronaria con iFR y el software Syncvision/iFR en la práctica diaria y en todo tipo de pacientes parece ser segura, con un bajo porcentaje de eventos cardiacos adversos mayores a medio plazo.
Palabras clave: Evaluacion fisiologica. Todo tipo de pacientes. Software Syncvision/iFR.
Abbreviations iFR: instantaneous wave-free ratio. PCI: percutaneous coronary intervention. MACE: major adverse cardiovascular events.
Physiological assessment using the fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR) is strongly recommended by the European guidelines to the guide percutaneous coronary intervention (PCI) decision-making process to treat intermediate coronary stenosis (indication I, level of evidence A) and multivessel disease (indication IIa, level of evidence B).1-7
The established cut-off values based on landmark trials to safely postpone treatment of a coronary lesion are FFRs > 0.80 and iFRs > 0.89.2-7 Unlike the FFR, the new iFR resting index allows us to analyze the physiological significance of each segment in the presence of coronary arteries with several lesions. Syncvision is a new software that analyzes the specific contribution of each coronary segment allowing us to predict physiological improvement after percutaneous treatment.8,9 It’s not necessary to use any vasodilators either, thus reducing any potential side effects.3,4
However, the evidence supporting the use of coronary physiology assessment with both indices and the use of the Syncvision software in other type of lesions and other clinical scenarios is scarce.8-10 For this reason, it is not quite clear whether the same cut-off value established in the landmark trials should be used; or if safety, utility, and efficacy will be the same.
The objective of this study is to describe our experience with coronary physiology assessment using the iFR (and/or the Syncvision- guided iFR-pullback study) in all-comer patients undergoing invasive coronary angiography.
We performed a single-center retrospective study including all patients who underwent functional assessments (using the iFR) and/or the Syncvision software at our center between January 2017 and December 2019 on a PCI decision-making process. The cut-off value to consider the need for revascularization was the same one established by the landmark clinical trials (iFR ≤ 0.89).3,4 The pressure guidewires used for the functional assessment were the Volcano Verrata, and the Volcano Verrata Plus (Philips Volcano, Belgium). The use of the Syncvision software to guide the iFR study as well as the lesions assessed were left to the operator’s discretion.
All subjects included in the study gave their informed consent to undergo the procedure and for data analysis and publication. Additionally, the study received the proper ethical oversight and was approved by our center ethics committee.
Inclusion and exclusion criteria
Patients with the following criteria were included: a) consecutive patients in whom an invasive coronary angiography was performed due to stable or unstable symptoms or silent ischemia; b) presence of, at least, a lesion or vessel physiologically assessed with the iFR during the index procedure. The following exclusion criteria were stablished: a) impossibility to understand the informed consent during the index procedure; b) written informed consent to use data for research purposes not provided.
The lesions physiologically assessed were classified based on their angiographic characteristics and/or clinical setting: a) intermediate lesions: lesions with a 40% to 80% angiographic stenosis as seen on the quantitative coronary angiography (QCA); b) sequential or diffuse coronary lesions: presence of, at least, 2 sequential lesions or a coronary segment with diffuse disease (coronary vessel with multiple plaques in most of the epicardial territory) with a total length of 25 mm; c) bifurcation lesions: presence of a coronary stenosis at bifurcation level with a side branch size large enough to be protected; d) in-stent restenosis: presence of focal or diffuse in-stent restenosis with a a 40% to 80% angiographic stenosis as seen on the QCA; e) coronary bypass lesion, defined as, at least, a lesion in the coronary artery bypass grafting or native vessel presenting with proximal total occlusion.
The primary endpoint of the study was the rate of major adverse cardiovascular events (MACE) at the follow-up. The MACE were defined as a composite of cardiac death, myocardial infarction (MI), definitive or probable stent thrombosis, and new target lesion revascularization (TLR). All deaths were considered cardiovascular unless unequivocal non-cardiac causes would be established. Myocardial infarction included spontaneous ST-segment elevation MI or non-ST-segment elevation acute myocardial infarction. The TLR was defined as a new revascularization of a baseline physiologically negative lesion at the follow-up or as a repeat revascularization of a baseline physiologically positive lesion percutaneously treated during the index procedure.
The secondary endpoints established were: a) analysis of the primary endpoint components separately; b) rate of MACE based on the clinical setting (stable angina or acute coronary syndrome), non-ST-segment elevation acute myocardial infarction (NSTEMI), and ST segment elevation myocardial infarction (STEMI); c) rate of MACE based on the baseline iFR; d) to determine the type of lesions where the Syncvision software was used for the iFR-pullback study.
The patients’ follow-up was performed through phone calls, hospital record reviews or outpatient visits.
Quantitative coronary measurements
Quantitative coronary measurements were performed using a validated system (CAAS system, Pied Medica Imaging, The Netherlands). These were the measurements analyzed: reference vessel diameter, minimum lumen diameter, percent diameter stenosis, and lesion length. All measurements were performed at baseline and after the PCI.
Continuous variables were expressed as mean ± standard deviation, and the Student t test was used to establish comparisons. The categorical variables were expressed as frequency and percentage, and compared using the chi-square test. The univariate analysis was performed with the following covariates: age, male sex, current smoking status, dyslipidemia, left ventricular ejection fraction, acute coronary syndrome, multivessel disease, clopidogrel, ticagrelor, right coronary artery as the study vessel, other vessels analyzed, and baseline iFRs ≤ 0.89. Results were reported using odds ratios (OR), and two-sided 95% confidence intervals. In all the cases, P values < .05 were considered statistically significant. The statistical analysis was performed using the IBM-SPSS statistical software package (version 24.0 for Macintosh, SPSS Corp., United States).
The study flowchart is shown on figure 1. During the study period, a total of 2951 patients underwent coronary angiography at our center. The iFR-based physiological assessment was performed in 277 patients (9.4%) with 433 lesions. The baseline clinical data are shown on table 1. The mean age was 65 ± 10 years, and 74% of the patients (204) were men. The prevalence of comorbidities was high (diabetes mellitus, 41%; previous MI, 32%; peripheral arterial disease, 4%; cerebrovascular disease, 6%; chronic kidney disease, 13%). The clinical presentation included stable angina in 160 patients (58%), NSTEMI in 91 patients (33%), and STEMI in 26 patients (9%).
|Patients||Total (N = 277)||Stable angina (N = 160)||ACS (N = 117)||P|
|Age, years||65 ± 10||65 ± 10||64 ± 11||.071|
|Sex, male, N (%)||204 (74)||116 (72)||94 (80)||.112|
|Hypertension, N (%)||175 (63)||101 (63)||77 (66)||.645|
|Diabetes mellitus, N (%)||114 (41)||58 (36)||52 (44)||.169|
|Dyslipidemia, N (%)||157 (57)||101 (63)||58 (50)||.024|
|Current smoker, N (%)||72 (26)||29 (18)||42 (36)||.001|
|Previous myocardial infarction, N (%)||89 (32)||53 (33)||37 (32)||.792|
|Previous revascularization, N (%)||94 (34)||50 (31)||32 (27)||.518|
|Percutaneous, N (%)||80 (85)||50 (31)||30 (26)||.336|
|Surgical, N (%)||14 (15)||8 (16)||6 (19)||.095|
|Atrial fibrillation, N (%)||39 (14)||19 (12)||13 (11)||.844|
|Heart failure, N (%)||8 (3)||7 (4)||2 (2)||.216|
|Prior ACE, N (%)||17 (6)||11 (7)||9 (8)||.795|
|Peripheral arterial disease, N (%)||11 (4)||7 (4)||5 (4)||.967|
|Previous bleeding, N (%)||3 (1)||2 (1)||2 (2)||.752|
|Chronic kidney disease, N (%)||36 (13)||19 (12)||17 (15)||.486|
|Hemoglobin, g/dL||13.96 ± 1.7||13.87 ± 1.8||14.13 ± 1.8||.365|
|Creatinine, g/dL||0.98 ± 0.47||1 ± 0.63||1 ± 0.37||.584|
|Left fentricular ejection fraction, %||59 ± 15||57 ± 16||60 ± 13||.098|
ACE, acute cerebrovascular event; ACS, acute coronary syndrome. Data are expressed as number (N) and percentage (%).
Angiographic and procedural data
Angiographic and procedural data are shown on table 2. Radial access was the access of choice in most of the cases (392 lesions, 91%). A total of 186 patients (67%) showed angiographic multivessel disease. Regarding the angiographic Syntax I score, 232 patients (84%) had Syntax scores < 22, 41 patients (15%) between 22 and 32, and only 4 patients (1%) > 32 without any differences being reported between stable and unstable patients. The vessel most frequently analyzed was the left anterior descending coronary artery (180, 42%) followed by the right coronary artery (99, 23%). The left main coronary artery was evaluated in 23 patients (5%).
|Patients||Total (N = 277)||Stable angina (N = 160)||ACS (N = 117)||P|
|Radial access, N (%)||251 (90)||147 (92)||104 (89)||.329|
|Multivessel disease, N (%)||165 (59)||84 (52)||81 (69)||.004|
|Syntax score||11 ± 8||10 ± 8||12 ± 8||.885|
|Low risk (< 22)||45 (16)||25 (16)||20 (17)||.184|
|Intermediate risk (22-32)||6 (2)||1 (1)||5 (4)||.066|
|High risk (> 32)||1 (1)||1 (1)||0||.331|
|Acetylsalicylic acid, N (%)||245 (88)||142 (88)||103 (88)||.740|
|P2Y12 inhibitor, N (%)||195 (71)||98 (61)||97 (83)|
|Clopidogrel||63 (23)||40 (25)||23 (20)||.011|
|Ticagrelor||127 (46)||56 (35)||71 (61)||.019|
|Prasugrel||65 (2)||2 (1)||3 (3)||.642|
|Vessel analyzed, N (%)|
|LAD||121 (44)||66 (41)||55 (47)||.318|
|LCx||40 (14)||26 (16)||14 (12)||.327|
|RCA||75 (27)||50 (31)||25 (21)||.072|
|LMCA||15 (5)||8 (5)||7 (6)||.712|
|Other||27 (10)||11 (7)||16 (14)||.057|
|Reference vessel diameter (mm)||3.3 ± 3||3.3 ± 3||3.3 ± 3||.971|
|Vessel stenosis (%)||49 ± 16||49 ± 17||49 ± 16||.816|
|Vessel minimal lumen diameter (mm)||1.6 ± 0.6||1.5 ± 0.6||1.5 ± 0.5||.203|
|Vessel lesion length (mm)||21 ± 12||21 ± 13||20 ± 11||.174|
|Vessel stent diameter (mm)||2.8 ± 0.4||2.8 ± 0.4||2.8 ± 0.4||.581|
|Type of stent implanted (%)|
|Immediate angiographic optimal result (%)||100|
|Contrast used (mL)||142 ± 91||151 ± 110||164 ± 72||.166|
|Intracoronary imaging, N (%)||6 (2)||6 (4)||0||.034|
|Procedural complications, N (%)||3 (1)||2 (1)||1 (1)||.754|
|Baseline iFR||0.88 ± 0.12||0.89 ± 0.12||0.86 ± 0.14||.097|
|Final iFR||0.93 ± 0.04||0.93 ± 0.04||0.93 ± 0.04||.951|
|Syncvision-guided iFR-pullback study, N (%)||155 lesions (36)||94 lesions (36)||61 lesions (35)||.4|
|Lesions evaluated||Total (N = 433)||Stable angina (N = 258)||ACS (N = 175)||P|
|Angiographically moderate lesions, N (%)||244 (56.4)||149 (58)||95 (54)||.475|
|Sequential/diffuse coronary lesions, N (%)||118 (27.3)||64 (25)||53 (30)||.208|
|Bifurcation lesions, N (%)||51 (11.8)||31 (12)||20 (11)||.853|
|In-stent restenosis, N (%)||15 (3.5)||11 (4.3)||4 (2.3)||.269|
|Coronary artery bypass grafting, N (%)||2 (0.5)||0 (0)||2 (1.1)||.085|
|Other lesions, N (%)||3 (0.75)||2 (0.8)||1 (0.6)||.802|
ACS, acute coronary syndrome; BMS, bare metal stent; DES, drug-eluting stent; iFR, instantaneous wave-free ratio; LAD, left anterior descending coronary artery; LCx, left circumflex artery; LMCA, left main coronary artery; RCA, right coronary artery. Data are expressed as number (N) and percentage (%).
The mean reference diameter was 3.3 mm ± 3 mm with a mean vessel stenosis of 49% ± 16%, and a mean lesion length of 21 mm ± 12 mm. The mean diameter of the stent implanted was 2.8 ± 0.4. All the stents implanted were drug-eluting stents (100%). Intracoronary imaging was used in 14 patients (3%).
The instantaneous wave-free ratio was obtained in 433 lesions, with a baseline value of 0.89 ± 0.12. The physiological assessment results after the PCI were obtained in 129 lesions (29.8%) with a final iFR of 0.93 ± 0.04.
The lesions physiologically assessed are shown on table 2. The most common type of lesions undergoing physiological assessment were angiographically moderate lesions (244, 56.4%) followed by sequential and diffuse lesions (118, 27.3%). Physiological assessment was used in 51 bifurcation lesions (11.8%) basically to guide the intervention over the side branch while using a provisional stenting strategy.
The Syncvision software for the iFR-pullback study was used in 155 lesions to guide the decision-making process (35.8%). Sequential and diffuse coronary lesions were the most common lesions analyzed by the iFR-pullback study (91 vessels, 58.7%, figure 2) followed by angiographically moderate lesions (52 vessels, 33.5%). This software was used in 5 bifurcation lesions (3.2%) to establish a baseline physiological classification or confirm an optimal physiological result after the PCI in both branches. The remaining lesions assessed by the iFR-pullback study were 6 focal or diffuse in-stent restenoses (3.9%) and 1 saphenous vein bypass graft with diffuse disease (0.6%).
Follow-up data were available for 274 out of 277 patients (99%). After a mean 18 ± 10-month follow-up, 17 patients (6.1 %) presented with a major adverse cardiovascular events (table 3), 7 patients (2.5 %) with TLR, 2 of them over a lesion treated during the index procedure (0.7%) and 5 (1.8%) due to disease progression of a baseline physiologically negative lesion; 6 patients (2.2 %) suffered from acute myocardial infarction (1 patient due to acute stent thrombosis, another to a new lesion not evaluated at the index procedure, another to a baseline physiologically non-significant lesion, and the remaining 3 patients due to failed previously revascularized lesions); also, 4 patients (1.4%) presented with unclear or cardiac death. There were no differences regarding MACE between baseline physiologically negative and positive lesions (table 3).
|MACE (277 patients, 433 lesions)||iFR ≤ 0.89 (N = 167 lesions)||iFR > 0.89 (N = 266 lesions)||P||Stable angina (N = 160)||ACS (N = 117)||P|
|Overall, N (%)||17 (6.1)||7 (4.2)||10 (3.8)||.9||7 (4.4)||10 (8.5)||.1|
|Unclear or cardiac death, N (%)||4 (1.4)||2 (1.2)||2 (0.8)||.2||3 (1.9)||1 (0.8)||.9|
|Myocardial infarction, N (%)||6 (2.2)||1 (0.6)||5 (1.9)||.46||1 (0.6)||5 (4.3)||< .05|
|Target lesion revascularization, N (%)||7 (2.5)||4 (2.4)||3 (1.1)||.09||3 (1.9)||4 (3.4)||.2|
ACS, acute coronary syndrome; iFR, instantaneous wave-free ratio; MACE, major adverse cardiovascular events. Data are expressed as number (N) and percentage (%).
Based on their clinical signs, patients who presented with ACS had an increased rate of new myocardial infarction at the follow-up (5.3% vs 0.6%; P < .05), although no differences were found regarding unclear or cardiac death (0.9% vs 1.8%; P = .9) and the overall MACE (8.5% vs 4.4%; OR, 2.056, 0.759-5.572; P = .156 (table 3).
Finally, we performed a univariate analysis and found no risk or protective factors for MACE in this cohort of patients (table 4).
|Current smoker||1.23 (0.42-3.60)||.713|
|Left ventricular ejection fraction (%)||0.99 (0.95-1.04)||.684|
|Acute coronary syndrome||2.06 (0.76-5.57)||.156|
|Multivessel disease||0.90 (0.33-2.45)||.842|
|Right coronary artery as examined vessel||1.52 (0.54-4.26)||.428|
|Other vessel analyzed||1.26 (0.27-5.82)||.769|
|Baseline iFR ≤ 0.89||1.43 (0.88-2.32)||.152|
95%CI, confidence interval; iFR, instantaneous wave-free ratio; OR, odds ratio.
This study tried to describe our experience using the physiological assessment and the Syncvision software in all-comer patients who underwent percutaneous coronary evaluations. The main findings of our study are: a) the use of the iFR in lesions of all-comer patients with the same cut-off values than established in the main trials showed a low percentage of MACE at the mid-term follow-up (6.1%); b) patients who presented with acute coronary syndrome showed an increased rate of myocardial infarction at the mid-term follow-up, and a trend towards a higher rate of MACE (OR, 2.056, 0.759-5.572; P = .156); c) The Syncvision-guided iFR-pullback study provided additional information to guide the PCI decision-making process, especially in complex lesions like sequential lesions and diffuse coronary artery disease.
The fractional flow reserve was the first physiological index that demonstrated its utility, safety, and efficacy guiding the revascularization decision-making process.2,5-7 To obtain it, the use of a hyperemic agent to reduce vascular resistance is mandatory. Adenosine is the most commonly used drug, but it presents a series of side effects and contraindications.3,4,11,12 The more recent resting index (the instantaneous wave-free ratio) has demonstrated similar utility, safety, and efficacy to the FFR.3,4 Furthermore, it has 2 main advantages: first, it is not necessary to use vasodilators, thus reducing side effects, contraindications for use, and procedural time; secondly, it allows us to assess the contribution of each lesion when the vessel presents several lesions, with the specific Syncvision-guided iFR-pullback study.8,9
For these reasons, the coronary physiology assessment is already the routine practice at the cath lab for the assessment of intermediate lesions,2-5 and multivessel disease.6,7 The main clinical setting included in these studies was stable angina. Patients with NSTEMI could be included if the lesion evaluated was identified as a non-culprit lesion. However, patients with STEMI, left main coronary artery lesions, and coronary artery bypass grafting lesions were not represented in the trials; also, the percentage of bifurcation lesions and sequential or diffuse coronary lesions is tiny. The cut-off value for the FFR and the iFR is well defined in those trials, being safe to postpone a lesion with a FFR > 0.80 or an iFR > 0.89. However, information is scarce on the utility and efficacy of physiological assessment and the same cut-off values in other types of lesions and clinical presentations.13 A multicenter registry that used the iFR to guide revascularization in patients with left main coronary artery stenosis has just been published. Using a cut-off value of 0.89, the authors conclude that postponing a left main coronary artery lesion with a iFR > 0.89 seems to be safe.10
Our study results suggest that the use of physiological assessment and the Syncvision software to guide the PCI decision-making process in all-comer patients with the same cut-off values as established by the landmark trials seems useful and safe regardless of the lesion and clinical presentation undergoing evaluation. Also, the MACE rates are similar to those reported by the landmark trials with selected lesions and patients.3,4 The iFR was the index used more often. The reasons are the faster and more comfortable use,3,4 and the possibility of lesion assessment with the Syncvision software.8,9
An important point of the study was to evaluate the rate of MACE based on the clinical presentation. Although no significant differences in the overall rate of MACE were found, patients who presented with acute coronary syndrome showed a significantly higher rate of MI at the follow-up, and a trend towards a higher rate of overall MACE. We think that this absence of statistical significance could be associated with a lack of statistical power.
A type of lesion included in the study was bifurcation lesions. Physiological assessment was used mainly to guide the side branch results during a provisional stenting strategy, thus keeping the pressure wire jailed as previously described.14,15 However, another interesting use of the iFR-pullback study with the Syncvision software was to stablish the baseline physiological contribution of every segment included in the most accepted classification.16
Finally, the Syncvision-guided iFR-pullback study was used in 155 lesions (36%). The main type of lesions where this software was used were diffuse and tandem lesions. This software can predict the physiological contribution of each lesion or coronary segment, which is why we believe that it is a very useful tool to avoid treating lesions without any physiological contribution and probably without clinical benefits. That is why this software seems to reduce the total stent length implanted regarding angiographically-guided revascularization with potential benefits at long-term follow-up.17,18 A clinical trial is currently in the recruitment phase to demonstrate the efficacy of this software reducing the length of the stent implanted in this type of lesions without detriment to the adverse events.19
In our experience, the key aspects to properly perform this technique are: a) a perfect aortic pressure curve allows the accurate detection of diastole through the software; b) passing the pressure sensor as distally as possible; c) finding a projection where the artery can be seen completely and with the least foreshortening possible; d) withdrawing the pressure guidewire very slowly so that the software can perfectly recognize the length of each arterial segment; e) checking that there is not drift when the pressure guidewire reaches the coronary ostium (iFR different to 1 ± 0.02) to avoid erroneous results; f) performing the coronary angiography in the same position as the guidewire withdrawal without any modifications to the height of the table or the C-arm, and with a higher flow and volume of contrast to facilitate the software recognition of all the lesions. The main problem when using this technique is the presence of lesions with complicated wiring. The pressure wire has a hydrophilic non-polymeric coating that is useful in most lesions. However, it may be very challenging to reach the distal part of the artery in very complex lesions (calcified, angled lesions…), and our experience with previous normalization, wire disconnection, the microcatheter exchange technique, and reconnection is very limited, but still there is a significant level of drift.
The study presents several limitations. It is a retrospective, single-center analysis with a low number of patients and lesions. Therefore, the results should be interpreted with caution, although it could be a hypothesis-generating study for future larger scale randomized clinical trials.
The use of coronary physiology assessment using the iFR and the Syncvision-guided iFR-pullback study in the routine daily practice and in all-comer patients seems safe with a low percentage of MACE at the mid-term follow-up. The Syncvision-guided iFR-pullback study provides additional information to guide the PCI decision-making process.
The study has not had funding.
F.J. Hidalgo-Lesmes prepared the main draft of the manuscript. S. Ojeda-Pineda participated in the drafting of the manuscript. C. Pericet-Rodríguez, R. González-Manzanares, A. Fernández-Ruiz, and M.G. Flores-Vergara all contributed to the analysis and interpretation of data. A. Luque-Moreno, J. Suárez de Lezo, and F. Mazuelos-Bellido participated in the conception and design of the study. M.A. Romero-Moreno, and J.M. Segura Saint-Gerons revised the manuscript critically for important intellectual content. M. Pan Álvarez-Ossorio approved the final version of the manuscript.
CONFLICTS OF INTEREST
F.J. Hidalgo-Lesmes received minor fees from Philips Volcano Europe unrelated to the manuscript; S. Ojeda-Pineda received minor fees from Terumo and Philips Volcano Europe unrelated to the manuscript; M. Pan Álvarez-Ossorio received minor fees from Terumo, Abbott Vascular, and Philips Volcano Europe unrelated to the manuscript. The remaining authors declared no conflicts of interest.
WHAT IS KNOWN ABOUT THE TOPIC?
- Physiological assessments with the iFR are strongly recommended by the European guidelines on coronary revascularization to guide the PCI decision-making process in intermediate coronary stenosis.
- However, the evidence supporting the use of coronary physiology assessment, and the new Syncvision-iFR software in other type of lesions and clinical settings is scarce.
WHAT DOES THIS STUDY ADD?
- This study describes our experience with the iFR and the Syncvision-iFR software in all-comer patients and demonstrates an acceptable percentage of MACE at the mid-term follow-up.
- Furthermore, the study shows that the Syncvision-guided iFR-pullback study provides additional information to guide the PCI decision-making process, particularly in complex lesions like sequential lesions and diffuse coronary artery disease.
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4. Götberg M, Christiansen EH, Gudmundsdottir IJ, et al. Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI. N Engl J Med. 2017;376:1813-1823.
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6. Tonino AL, Bruyne B De, Pijls NHJ, et al. Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention Pim. N Engl J Med. 2015:687-696.
7. Van Nunen LX, Zimmermann FM, Tonino PAL, et al. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME):5-year follow-up of a randomised controlled trial. Lancet. 2015;386:1853-1860.
8. Nijjer SS, Sen S, Petraco R, Mayet J, Francis DP, Davies JER. The Instantaneous wave-Free Ratio (iFR) pullback:A novel innovation using baseline physiology to optimise coronary angioplasty in tandem lesions. Cardiovasc Revasc Med. 2015;16:167-171.
9. Nijjer SS, Sen S, Petraco R, et al. Pre-angioplasty instantaneous wave-free ratio pullback provides virtual intervention and predicts hemodynamic outcome for serial lesions and diffuse coronary artery disease. JACC Cardiovasc Interv. 2014;7:1386-1396.
10. Warisawa T, Cook CM, Rajkumar C, et al. Safety of Revascularization Deferral of Left Main Stenosis Based on Instantaneous Wave-Free Ratio Evaluation. JACC Cardiovasc Interv. 2020;13:1655-1664.
11. Gili S, Barbero U, Errigo D, et al. Intracoronary versus intravenous adenosine to assess fractional flow reserve:A systematic review and meta-analysis. J Cardiovasc Med. 2018;19:274-283.
12. Patel HR, Shah P, Bajaj S, Virk H, Bikkina M, Shamoon F. Intracoronary adenosine-induced ventricular arrhythmias during fractional flow reserve (FFR) measurement:case series and literature review. Cardiovasc Interv Ther. 2017;32:374-380.
13. Ihdayhid AR, Koh JS, Ramzy J, et al. The Role of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Measurements in Patients with Acute Coronary Syndrome. Curr Cardiol Rep. 2019;21.
14. Burzotta F, Lassen JF, Banning AP, et al. Percutaneous coronary intervention in left main coronary artery disease:The 13th consensus document from the European Bifurcation Club. EuroIntervention. 2018;14:112-120.
15. Hidalgo F, Pan M, Ojeda S, et al. Feasibility and Efficacy of the Jailed Pressure Wire Technique for Coronary Bifurcation Lesions. JACC Cardiovasc Interv. 2019;12:109-111.
16. Medina A, Suárez de Lezo J, Pan M. A New Classification of Coronary Bifurcation Lesions. Rev Esp Cardiol. 2006;59:183.
17. Mauri L, O'Malley AJ, Popma JJ, et al. Comparison of thrombosis and restenosis risk from stent length of sirolimus-eluting stents versus bare metal stents. Am J Cardiol. 2005;95:1140-1145.
18. Kikuta Y, Cook CM, Sharp ASP, et al. Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease:Primary Results of the International Multicenter iFR GRADIENT Registry. JACC Cardiovasc Interv. 2018;11:757-767.
19. Hidalgo F, Ojeda S, de Lezo JS, et al. Usefulness of a co-registration strategy with iFR in long and/or diffuse coronary lesions (iLARDI):study protocol. REC Interv Cardiol. 2020. https://doi.org/10.24875/RECICE.M20000143.
Introduction and objectives: Transcatheter aortic valve implantation (TAVI) has proven safe and effective in low-to-high risk patients, but emergency procedures have been excluded from the landmark trials. We aimed to assess the current outcomes and main factors conditioning the prognosis during emergency TAVI.
Methods: A systematic search in PubMed and Google Scholar was conducted for all studies comparing elective vs emergency TAVI. Searched terms were “emergency” and/or “urgent”, “elective”, and “transcatheter valve replacement” and/or “heart failure” and/or “cardiogenic shock”. Emergency TAVI was considered as any unscheduled TAVI performed to treat refractory heart failure or cardiogenic shock. A random-effects model was used.
Results: A total of 7 studies with 84 427 TAVI patients were included (14 241 emergency procedures; 70 186 elective TAVIs). Emergency cases presented higher risk scores (logistic EuroSCORE 65.9% ± 21% vs 29.4% ± 18%, P < .001; Society of Thoracic Surgeons Risk Score 29.4% ± 27.4% vs 13.7% ± 11.6%, P < .001). More advanced heart disease was observed with deterioration of left ventricular (LV) function (39.5% ± 17.8% vs 52.5% ± 12.8%; P < .001) and larger LV end-diastolic diameters (55 ± 9 mm vs 48 ± 7 mm; P < .001) despite similar aortic valve areas and gradients. Elective TAVIs presented a greater success rate (93.6% vs 92.5%; odds ratio [OR] = 0.84; 95%CI, 0.74-0.95; P = .005), less acute kidney injury, and a lower need for dialysis and mechanical circulatory support. Overall, non-emergency cases had lower in-hospital (3.3% vs 5.7%; P < .001), 30-day (4.4% vs 8.8%; P < .001) and 1-year mortality rates (19.7% vs 34.75%; P = .0001). The main determinants of mortality were need for new dialysis (OR = 2.26; 95%CI, 1.84-2.76; P < .001) or mechanical circulatory support (OR = 2.55; 95%CI, 1.14-5.67; P < .001).
Conclusions: Emergency TAVI recipients presented worse baseline risk and more advanced cardiac disease that determined greater in-hospital, 30-day, and 1-year mortality rates. The early identification of patients at risk for requiring mechanical circulatory support or dialysis may contribute to a better indication of TAVI in emergency scenarios.
Keywords: Cardiogenic shock. Heart failure. Transcatheter aortic valve replacement. Aortic stenosis.
Introducción y objetivos: El implante percutáneo de válvula aórtica (TAVI) ha demostrado ser seguro y eficaz en pacientes tanto de bajo como de alto riesgo, pero los procedimientos emergentes se han excluido en los principales estudios. El objetivo fue determinar los resultados actuales y los condicionantes del pronóstico durante el TAVI emergente.
Métodos: Se realizó una búsqueda sistemática en PubMed y Google Scholar de cualquier estudio que comparara el TAVI electivo frente al emergente. Los términos empleados fueron «emergent» y/o «urgent», «elective», y «transcatheter valve replacement» y/o «heart failure» y/o «cardiogenic shock». Se consideró TAVI emergente todo procedimiento no programado realizado para tratar la insuficiencia cardiaca refractaria o el shock cardiogénico. Se utilizó un modelo de efectos aleatorios.
Resultados: Se incluyeron 7 estudios (84.427 pacientes) tratados con TAVI (14.241 emergentes y 70.186 electivos). Los casos electivos presentaron una mayor puntuación de riesgo (EuroSCORE logístico 65,9 ± 21 frente a 29,4 ± 18%, p < 0,001; Society of Thoracic Surgeons Risk Score 29,4 ± 27,4 frente a 13,7 ± 11,6%, p < 0,001). Presentaron una enfermedad cardiaca más avanzada, con peor función ventricular izquierda (39,5 ± 17,8 frente a 52,5 ± 12,8%; p < 0,001) y mayor diámetro telediastólico del ventrículo izquierdo (55 ± 9 frente a 48 ± 7 mm; p < 0,001), pese a tener similar área valvular aórtica y gradientes. El TAVI electivo tuvo mayor tasa de éxito (93,6 frente a 92,5%; odds ratio [OR] = 0,84; IC95%, 0,74-0,95; p = 0,005), con menor tasa de fallo renal agudo y menos necesidad de diálisis y de soporte circulatorio mecánico. En conjunto, los casos no emergentes tuvieron menor mortalidad intrahospitalaria (3,3 frente a 5,7%; p < 0,001), a 30 días (4,4 frente a 8,8%; p < 0,001) y a 1 año (19,7 frente a 34,75%; p = 0,0001). Los principales determinantes de mortalidad fueron la nueva necesidad de diálisis (OR = 2.26; IC95%, 1,84-2,76; p < 0,001) o requerir soporte circulatorio mecánico (OR = 2,55; IC95%, 1,14-5,67; p < 0,001).
Conclusiones: Los receptores de TAVI emergente presentaron peor riesgo basal y enfermedad cardiaca más avanzada, que determinaron una mayor mortalidad intrahospitalaria, a 30 días y a 1 año. La identificación precoz del riesgo de precisar soporte circulatorio mecánico o diálisis podría ayudar a una optimización de la indicación de TAVI emergente.
Palabras clave: Shock cardiogenico. Insuficiencia cardiaca. Implante percutaneo de valvula aortica. Estenosis aortica
Abbreviations AS: aortic stenosis. CKD: chronic kidney disease. CS: cardiogenic shock. HF: heart failure. SAVR: surgical aortic valve replacement. TAVI: transcatheter aortic valve implantation.
Aortic stenosis (AS) is the most commonly treated valvular heart disease in Western countries.1 In a relatively small but growing proportion of patients (from 3.5% to 12%), AS may present as cardiogenic shock (CS) with an estimated short-term mortality as high as 70% if definitive surgical or percutaneous treatment is not provided.2 CS is characterized by an inadequate tissue perfusion as a result of a decompensated cardiac disease that translates into a low-output state. Early management is directed toward keeping a steady hemodynamic profile and ensuring tissue oxygenation through medication or advanced support.3 However, specific therapies are required to ensure a complete resolution, yet conventional surgical aortic valve replacement (SAVR) is often associated with a very high risk of mortality.2
Several trials have shown that transcatheter valve implantation (TAVI) is a safe alternative to SAVR in low-to-high risk patients in stable situations and it is currently considered the preferred alternative in those of high prohibitive surgical risk.4-7 Nevertheless, the risk scores for the main studies that settled the evidence for TAVI procedures were estimated after excluding patients with CS. As a consequence, the main outcomes in this challenging scenario have not been randomly compared to surgery. Actually, such a comparison is unlikely to be performed due to the highly variable baseline profile and differential availability of resources such as mechanic circulatory assist devices. In addition, the different outcomes in emergency TAVIs and planned interventions have been scarcely researched; still, they are key to improve results in what stands as the worst possible clinical scenario. We aimed to assess the current outcomes of emergency/urgent TAVI and the main factors conditioning its prognosis through a systematic review and meta-analysis.
Literature search strategy
A systematic review of all published articles in PubMed and Google Scholar databases between January 2014 and January 2020 regarding emergency/urgent versus elective TAVI in severe AS was independently performed by 2 of the authors (A. Aparisi and M. Carrasco-Moraleja). Searched terms were “emergency” and/or “urgent”, “elective”, AND “transcatheter valve replacement” or “TAVR” (transcatheter aortic valve replacement) or “heart failure” and/or “cardiogenic shock”. Definition of emergency/urgent procedures was variable, but the consensus reached for this article was to include patients who required an unscheduled TAVI procedure to treat their refractory heart failure or CS to correct this condition within the next 72 hours after admission. A total of 7 studies8-14 were chosen, and the inclusion criteria established by our group were: a) the study population included patients with aortic stenosis who underwent TAVI; b) only cohort studies that compared emergency or urgent to elective TAVI were included; c) only full English peer-reviewed papers with enough data of outcomes were chosen. The selected exclusion criteria were: a) abstracts; b) case reports; c) editorials; d) experts’ opinions; and e) repetitive studies. Discrepancies between reviewers were resolved through discussion, and consensus was reached. Flowchart is shown on figure 1 and the main features of the studies included are shown on table 1 of the supplementary data.
|Variable||No. of patients||Overall TAVI population N = 84 427||Elective TAVI N = 70 186 (83.1%)||Emergency/urgent TAVI N = 14 241 (16.9%)||P|
|Sex (male) (%)||84 427||43 735/84 427 (51.8%)||36 576/70 186 (52.11%)||7 159/14 241 (50.27%)||< .001|
|Age (years)||44 385||81.12 ± 8.47||81.16 ± 8.27||80.96 ± 9.08||.041|
|EuroSCORE (%)||1387||31.24 ± 18.15||29.42 ± 17.99||68.88 ± 20.97||< .001|
|STS score (%)||985||14.76 ± 13.34||13.66 ± 11.61||29.39 ± 27.39||< .001|
|Anemia (%)||42 524||11 415/42 524 (26.84%)||8004/32 382 (24.71%)||3411/10 142 (33.63%)||< .001|
|Atrial fibrillation (%)||41 185||17 373/41 885 (41.47%)||15 304/37 780 (40.51%)||2069/4105 (50.40%)||< .001|
|CAD (%)||41 329||25 723/41 329 (62.24%)||23 178/37 308 (62.13%)||2545/4021 (63.29%)||.147|
|CKD (%)||83 308||17 948 /83 308 (21.54%)||13 368/69 187 (19.32%)||4580/14 121 (32.43%)||< .001|
|COPD (%)||84 398||25 081/84 398 (29.72%)||20 315/70 157 (28.96%)||4766/14 241 (33.47%)||< .001|
|Diabetes (%)||84 040||29 670/84 040 (35.30%)||24 571/69 820 (35.19%)||5099/14 220 (35.86%)||.130|
|Hypertension (%)||83 308||70 608/83 308 (84.75%)||59 117/69 187 (85.44%)||11 491/14 121 (81.38%)||< .001|
|NYHA III-IV (%)||41 143||33 056/41 143 (80.34%)||29 297/37 065 (79.04%)||3759/4078 (92.17%)||< .001|
|PAD (%)||84 069||25 236/84 069 (30.02%)||20 933/69 849 (29.96%)||4303/14 220 (30.26%)||.490|
|Porcelain aorta (%)||40 669||2158/40 669 (5.3%)||1914/36 669 (5.22%)||244/4000 (6.1%)||.018|
|Previous AVR (%)||40 658||1599/40 658 (3.93%)||1292/36 664 (3.53%)||307/3994 (7.69%)||< .001|
|Previous CABG (%)||83 656||20 924/83 656 (25.01%)||18 000/69 442 (25.92%)||2924/14 214 (20.57%)||< .001|
|Previous MI (%)||83 040||15 173/83 040 (18.27%)||12 597/68 868 (18.29%)||2576/14 172 (18.18%)||.747|
|Previous PCI (%)||83 029||22 118/83 029 (26.64%)||18 979/68 863 (27.56%)||3139/14 166 (22.16%)||< .001|
|Previous PM/ICD||40 774||8304/40 774 (20.36%)||7401/36 723 (20.15%)||903/4051 (22.29%)||.001|
|Previous stroke/TIA (%)||42 244||8815/42 244 (20.87%)||7884/38 118 (20.68%)||931/4126 (22.57%)||.005|
|Aortic valve area (cm²)||2 230||0.7 ± 0.23||0.7 ± 0.23||0.66 ± 0.21||.308|
|LVEDD (mm)||616||48.98 ± 7.34||48.53 ± 7.20||55.05 ± 9.03||< .001|
|LVEF (%)||1861||51.51 ± 13.24||52.23 ± 12.71||29.58 ± 14.89||< .001|
|Mean gradient (mmHg)||1398||43.71 ± 16.42||43.91 ± 16.31||40.26 ± 18.29||.061|
|AR III-IV (%)||41 032||8156/41 032 (19.88%)||7159/37 033 (19.33%)||997/3999 (24.93%)||< .001|
|PHT (%)||43 251||2003/43 251 (4.63%)||1536/33 088 (4.64%)||467/10 163 (4.6%)||.843|
AR, aortic regurgitation; AVR, aortic valve replacement; CABG, coronary artery bypass graft; CAD, coronary artery disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; ICD, implantable cardioverter defibrillator; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA; New York Heart Association; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention; PHT; pulmonary hypertension; PM, pacemaker; STS, Society of Thoracic Surgeons score; TIA, transient ischemic attack; TAVI, transcatheter aortic valve implantation.
Primary endpoints were short-term mortality and procedural success. Secondary outcomes were perioperative complications. Complications were mostly reported by using the definitions established by the Valve Academic Research Consortium-2.15
Qualitative variables were expressed as absolute frequency and percentage. Continuous variables were expressed as mean ± standard deviation unless specified otherwise. To compare the demographic variables and the risk factors between thew groups, the chi-square test or Fisher’s exact test were used for the categorical variables. The Student t test was used for the continuous variables, when applicable.
As a measure of the combined effect, the studies included the odds ratio (OR), a 95% confidence interval, and statistical significance. The homogeneity among the studies was compared using the QH statistic. With regard to the low sensitivity of this test, P values < .10 were considered significant. To somehow overcome this limitation, the I2 statistic was estimated as well, which measures the percentage of the overall variation of the studies explained by the heterogeneity and its 95%CI. A random effects model was used for cases in which the I2 statistic was > 50% and a fixed effects model was used for the opposite cases. The potential publication bias was assessed using a funnel plot, Egger’s test, and Begg and Mazumdar rank correlation test. In the presence of publication bias, the trim-and-fill method was used to reassess the pooled OR. Sensitivity analyses sequentially eliminating dissimilar studies were also conducted.
All P values were 2-tailed. Statistical analyses were conducted using the R software, version 3.6.1 (R Project for Statistical Computing) and Review Manager 5.3.
Patient distribution and baseline characteristics
Seven studies were selected including a total of 84 427 patients who underwent TAVIs, with 70 186 elective procedures (83.1%) and 14 241 emergency ones (16.9%). The main baseline characteristics according to the elective or emergency character of the intervention are shown on table 1 and sensitivity and asymmetry analyses are shown on table 2 of the supplementary data and figure 1 of the supplementary data. Asymmetry was detected for acute kidney injury and, therefore, the trim-and-fill method had to be used to reassess the odds ratio. The percentage of men who underwent elective procedures (52.1%) was higher compared to emergency interventions (50.27%, P < .001). Overall, patients treated urgently showed more comorbidities as summarized by the logistic EuroSCORE (65.9% ± 21% vs 29.4% ± 18%, P < .001) and the Society of Thoracic Surgeons Risk Score (STS) (29.4 ± 27.4 vs 13.7 ± 11.6, P < .001). However, the classical cardiovascular risk factors did not differ among groups (hypertension and diabetes mellitus) and the rates of myocardial infarction and percutaneous coronary intervention were similar. On the contrary, those treated urgently more often had undergone a previous aortic valve replacement. Regarding the main echocardiographic characteristics, emergency procedures were performed in patients with left ventricular (LV) function deterioration (39.5% ± 17.8% vs 52.5% ± 12.8%; P < .001), larger LV end-diastolic diameters (55 ± 9 vs 48 ± 7; P < .001), but similar aortic valve areas (0.66 ± 0.21 vs 0.70 ± 0.23; P = .308), and transaortic mean gradients (40.3 ± 18.3 vs 43.9 ± 16.3; P = .061).
|Variable||No. of patients||Overall TAVI population||Elective TAVI||Emergency/urgent TAVI||P|
|Success rate (%)||41 140||38 765/41 440 (93.54%)||35 038/37 413 (93.65%)||3727/4027 (92.55%)||.007|
|Device migration (%)||40 042||105/40 042 (0.26%)||90/36 090 (0.25%)||15/3952 (0.38%)||.129|
|General anesthesia (%)||40 669||34 419/40 669 (84.6%)||31 004/36 669 (84.55%)||3415/4000 (85.37%)||.170|
|Transapical (%)||83 953||14 742/83 953 (17.56%)||12 194/69 790 (17.47%)||2548/14 163 (18%)||.139|
|Transfemoral (%)||83 811||66 526/83 811 (79.38%)||55 196/69 612 (79.29%)||11 330/14 199 (79.79%)||.177|
|Transsubclavian (%)||40 813||643/40 813 (1.57%)||573/36 834 (1.55%)||70/3979 (1.76%)||.327|
|Mechanical circulatory support (%)||83 326||1858/83 326 (2.29%)||1355/69 211 (1.96%)||503/14 115 (3.56%)||< .001|
TAVI, transcatheter aortic valve implantation.
Procedural results from the studies included are shown on table 2. Transfemoral access (79.3% vs 76.8%; P = .177) and use of general anesthesia (84.5% vs 85.4%; P = .17) were the preferred approaches in both groups. Elective TAVIs showed a higher procedural success rate (93.6% vs 92.5%; P = .007) and a lower need for mechanical circulatory support (1.96% vs 3.56 %; P < .001). Other procedural outcomes were comparable between both cohorts.
The main postoperative outcomes are shown on table 3 and figure 2. The ORs for perioperative myocardial infarction, life-threatening bleedings, need for permanent pacemaker implantation, and stroke were similar regardless of the planned or emergency setting. On the contrary, the elective cohort showed a smaller rate of acute kidney injury (9.6% vs 22.4%; OR = 2.26; 95%CI, 1.84-2.76; P < .001), and need for dialysis (1.1% vs 2.8%; OR = 2.37; 95%CI, 2.09-2.68; P < .001). Overall, this translated into shorter hospital stays for elective cases, lower in-hospital (3.3% vs 5.75%; OR = 1.32; 95%CI, 1.32-2.83; P < .001), 30-day (4.43% vs 8.84%; OR = 3.13; 95%CI, 1.68-5.80; P < .001), and 1-year mortality rates (19.7% vs 34.47%; OR = 2.87; 95%CI, 1.67-4.94; P = .0001) for elective TAVI (figure 3).
|Variable||No. of patients||Overall TAVI population||Elective TAVI||Emergency/urgent TAVI||P|
|Life-threatening bleeding (%)||83 811||13 170/83 811 (15.71%)||9903/69 612 (14.22%)||3267/14 199 (23.01%)||< .001|
|Major bleeding (%)||43 400||14 725/43 400 (33.93%)||11 065/33 180 (33.35%)||3660/10 220 (35.81%)||< .001|
|Major vascular complications (%)||41 656||513/41 656 (1.23%)||460/37 572 (1.22%)||53/4084 (1.29%)||.686|
|Myocardial infarction (%)||82 671||1299/82 671 (1.57%)||557/68 526 (0.81%)||742/14 145 (5.24%)||< .001|
|Acute kidney injury (%)||83 811||9856/83 811 (11.75%)||6678/69 612 (9.59%)||3178/14 199 (22.38%)||< .001|
|Need for dialysis (%)||82 197||1178/82 197 (1.43%)||782/68 130 (1.15%)||396/14 067 (2.81%)||< .001|
|PPMI (%)||84 069||8786/84 069 (10.45%)||7188/69 849 (10.29%)||1598/14 220 (11.24%)||< .001|
|Stroke (%)||83 442||2242/83 442 (2.69%)||1824/69 270 (2.63%)||418/14 172 (2.94%)||.034|
|In-hospital mortality rate||83 427||3099/83 427 (3.71%)||2284/69 255 (3.3%)||815/14 172 (5.75%)||< .001|
|30-day mortality rate||46 228||2268/46 228 (4.9%)||1830/41 274 (4.43%)||430/4954 (8.84%)||< .001|
|1-year mortality rate||41 156||8706/41 156 (21 15%)||7327/37 156 (19.72%)||1379/4000 (34.75%)||< .001|
|Mean gradient (mmHg)||369||7.75 ± 4.15||7.82 ± 4.22||6.9 ± 3.2||.269|
|AR III-IV (%)||17 977||1465/17 977 (8.15%)||1299/16 125 (8.05%)||166/1852 (8.96%)||.176|
AR, aortic regurgitation; PPMI, permanent pacemaker implantation; TAVI, transcatheter aortic valve implantation.
When patients with AS present with severe acute heart failure (HF) or CS the 5-year all-cause mortality is above 60% despite the implementation of therapies to treat valvular heart disease, which poorly compares to this rate in patients free of HF (~20%) or with chronic HF symptoms (~30%) in this setting (16). Determining the factors that condition such a high mortality rate is the key to improve the management of this growing group of patients. The main findings of this study are: a) patients who required emergency TAVIs had a higher baseline risk compared to planned procedures, not only due to the emergency setting, but also to a high burden of comorbidities and deterioration of LV function; b) although procedural success rate was significantly higher in planned cases, this difference was small (93.6% vs 92.5%; P = .007) suggestive that the higher short- and mid-term mortality rates seen in emergency cases were mainly due to postoperative complications, not to the intervention per se; c) need for mechanical circulatory support and dialysis was higher after emergency cases. The early identification of patients at risk who may require these therapies might be useful for a better indication of TAVI in emergency settings.
Baseline characteristics and predicted mortality
In our study, emergency/urgent TAVI patients had a more significant number of comorbid conditions compared to those who underwent elective procedures. We should mention that the Society of Thoracic Surgeons (STS) score has been widely used to assess mortality risk in SAVR patients.17 Nevertheless, the score developed by the Transcatheter Valve Therapy (TVT) group to evaluate in-hospital and 30-day mortality rates18 may be more accurate. According to that score, the prognosis is strongly influenced by the presence of chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and need for emergency TAVI. Of note, AS with concomitant CKD has been linked to higher all-cause and cardiovascular mortality rates compared to patients with AS and without this condition; indeed, the increase of all-cause mortality exponentially correlates with a decline in the glomerular filtration rate.19 In addition, the higher rate of anemia20 and increased bleeding risk in CKD patients is well-known, which conditions a higher need for red blood cell transfusion21 parallel to a deterioration of renal function and survival rate.
The LV function is a well-known prognostic factor of valvular heart disease and its deterioration conditions surgical or transcatheter aortic valve treatment even in asymptomatic patients.22 We should mention that the similar transaortic gradient, despite a reduced LV function in the emerging baseline cases, suggests a more severe valve disease, probable more calcified and degenerated native valves, as also suggested by the higher rate of aortic regurgitation of this cohort. Therefore, the multidisciplinary and multi-imaging approach might be particularly useful for procedural planning and outcome improvement.23
Procedural complications and mortality
Most procedural complications were similar in elective and emergency TAVIs. Although this may be partially explained by the growing operators’ experience worldwide and the lack of differences in the rate of transfemoral approach,24 the greater use of mechanical circulatory support devices may have been particularly relevant in emergency/urgent cohorts. Indeed, the more limited LV contractile reserve of this group of patients can lead to rapid deterioration in the presence of complications like periannular shunts, severe aortic regurgitation or coronary obstruction. Therefore, the presence of risk factors for these complications may suggest the need for circulatory support devices in certain cases before valve implantation as a potential strategy to avoid dreadful prognoses if they occur in the emergency setting.25-27 Prior experience with the Impella device and extracorporeal membrane oxygenation is shown on table 3 of the supplementary data; however, whether there are mortality differences between those with and without mechanical support requires further research. Since procedural success was similar to that of the standard setting, the clinical translation of this is that, even if these cases can be performed successfully in all centers by implanting TAVI, this profile of patients should only be treated in centers with mechanical circulatory support devices available (particularly ECMO), which would exclude low volume or non-surgical centers.
In the present meta-analysis, the cases treated with isolated balloon aortic valvuloplasty were not included. This strategy bears a class IIb-C level of evidence in the last iteration of the guidelines, but it is often used as a bridging therapy to definitive TAVI in hemodynamically unstable patients.28,29 A single-center retrospective study found that TAVI may be superior to a stand-alone balloon aortic valvuloplasty and medical therapy in patients with severe AS and CS, since the isolated balloon aortic valvuloplasty is not free of complications (~25%) and has higher mortality rates.30 Despite of this, large randomized controlled trials exploring this scenario with TAVI are lacking.
Postoperative complications associated with a higher mortality rate
In this systematic review and meta-analysis, we found that emergency/urgent TAVIs had a significantly higher rate of AKI, hemodialysis, and mortality. This is consistent with previous reports that found that patients with post-TAVI AKI were more likely to die. Besides, AKI is a predictor of sepsis, which is also an independent predictor of mortality. The main factors increasing the risk of AKI include CKD, peripheral artery disease, diabetes mellitus, and deterioration of LV function.31,32 A prophylactic strategy may vary from simple hydration with a normal saline solution to forced diuresis with early supportive measures;33 indeed, the use of prophylactic dialysis has been explored in TAVI patients with a high risk of AKI and may be particularly useful in the emergency setting.
There are several limitations related to this systematic review and meta-analysis. First, the studies included were observational since no multicenter randomized studies specifically addressing this topic could be found. Secondly, the definition of emergency/urgent procedures was variable in the studies although an inclusive definition was reached by the study team. Finally, the results may not be generalizable and should be interpreted with caution due to the high heterogenicity reported, which may relate to variability in the study samples and designs.
In conclusion, the association between emergency/urgent TAVIs and a higher short-to-mid-term mortality rate is mainly due to a high-risk baseline profile, advanced stage of the cardiac disease, and higher rate of acute renal failure. The early identification and referral of patients at high risk for circulatory collapse or AKI need to be properly identified to reduce the TAVI related mortality rate. Further research is needed to elucidate the role of TAVI in emergency or urgent scenarios.
No funding to declare.
CONFLICTS OF INTEREST
Dr. Amat-Santos is a proctor for Boston Scientific.
WHAT IS KNOWN ABOUT THE TOPIC?
- TAVI is performed mainly in hemodynamically stable patients, otherwise aortic balloon valvuloplasty is empirically preferred as a bridging therapy to TAVI. However, few studies have addressed TAVI in life-threatening scenarios and multicenter randomized controlled trials are still lacking.
WHAT DOES THIS STUDY ADD?
- In this large pooled meta-analysis (n = 84 427) emergency TAVI was not rare but associated with higher in-hospital, 30-day, and 1-year mortality rates compared to elective procedures. The need for dialysis or mechanical circulatory support conditioned the mortality rate following emergency TAVIs. The early identification of patients at risk of circulatory collapse or acute kidney injury may help to determine if TAVI is futile in this setting.
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