Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy.

BACKGROUND: Enzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may still progress despite ERT over a long-term follow-up is still unclear. METHODS: Consecutive patients with AFD from the Independent Swiss-Fabry Cohort receiving ERT who were at least followed up for 5 years were included. Cardiac progression was defined as an increase of >10 g/m2 in left ventricular mass index (LVMI) between the first and the last available follow-up transthoracic echocardiography. RESULTS: 60 patients (35 (23-48) years, 39 (65%) men) were followed up for 10.5 (7.2-12.2) years. 22 had LVH at ERT start (LVMI of 150±38 g/m2). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7-17.6) g/m2 per 100 patient-years, of these 7 (11%, 29±13 years) with no LVH at baseline. Three of them progressed to LVH. LVMI progression occurred mostly in men (17 of 39 (43%) vs 5 of 21 (24%), p<0.01) and after the age of 30 years (17 of 22 (77%)). LVH at ERT start was associated with LVMI progression (OR 1.3, 95% CI 1.1 to 2.6; p=0.02). A total of 19 (31%) patients experienced a major AFD-related event. They were predominantly men (17 of 19, 89%), older (45±11 vs 32±9 years) with baseline LVH (12 of 19, 63%), and 10 of 19 (52%) presented with LVMI progression. CONCLUSIONS: Over a median follow-up of >10 years under ERT, 36% of the patients still had LVMI cardiac progression, and 32%, predominantly older men, experienced major AFD-related events. LVH at treatment initiation was a strong predictor of LVMI progression and adverse events on ERT.

[Cardiac amyloidosis : simplifying the diagnosis of a complex disease]. / Amyloïdose cardiaque : simplifier le diagnostic d'une maladie complexe.

Amyloidosis is a systemic infiltrative disease characterized by deposition of misfolded proteins in tissues, notably affecting the heart. According to type of protein, various types are known with the most prevalent being light-chain and transthyretin amyloidosis. Prognosis is dismal with progression to severe heart failure without disease-modifying treatment. Latter having dramatically improved over the last decade, prompt diagnosis is of paramount importance. Recognition of early signs followed by multidisciplinary approach is essential for optimal patient management.

L'amyloïdose est une maladie infiltrative systémique caractérisée par le dépôt intratissulaire de protéines. Selon l'origine de la protéine on distingue différents types d'amyloïdose, mais ce sont essentiellement l'amyloïdose à chaînes légères et celle associée à la transthyrétine qui affectent le myocarde. Le pronostic de l'amyloïdose cardiaque est sombre, évoluant vers une insuffisance cardiaque terminale en absence de traitement spécifique. Avec l'arrivée récente de thérapies pouvant ralentir l'évolution de la maladie, un diagnostic précoce est devenu primordial. La reconnaissance des signes précurseurs de la maladie et la mise en place rapide de traitements dans un centre de référence de l'amyloïdose sont essentielles pour une gestion optimale des patients.

[Cardiac CT in 2024]. / CT cardiaque en 2024.

Coronary Computed Tomography Angiography (CCTA) has now become an established tool in the diagnostic process for patients suspected of coronary artery disease. In light of rapid technological development, CCTA has evolved into an imaging modality providing both anatomical and functional information to guide patient management. In this article, we describe the role of cardiac CT in assessing atherosclerotic plaque, chest pain evaluation, cardiovascular risk stratification, planning and guiding coronary intervention, as well as structural heart diseases.

Le scanner coronarien est actuellement un outil reconnu dans le processus diagnostique des patients chez qui on suspecte une maladie coronarienne. Bénéficiant d'un développement technologique rapide et procurant des informations tant morphologiques que fonctionnelles, le CT cardiaque devient une modalité d'imagerie incontournable pour orienter la prise en charge des patients. Dans cet article, nous décrivons le rôle du CT cardiaque dans l'évaluation de la plaque d'athérosclérose, des douleurs thoraciques, de la stratification du risque cardiovasculaire, de la planification et du guidage de l'intervention coronarienne, ainsi que des maladies cardiaques structurelles.

Outcomes and Safety of Transcaval Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis.

BACKGROUND: The transcaval (TCv) vascular approach is increasingly utilized in transcatheter aortic valve replacement (TAVR), in patients unsuitable for the gold-standard transfemoral approach. We aimed to evaluate the efficacy, safety, and clinical outcomes associated with TCv-TAVR. METHODS: A systematic review and meta-analysis was conducted by searching PubMed/MEDLINE, EMBASE and the Cochrane Library for all articles assessing the TCv approach published until December 2023. Outcomes included 30-day and 1-year all-cause mortality (ACM), 30-day rehospitalization, peri-operative and post-operative complications at 30 days. The meta-analysis was registered on the PROSPERO database with the identifier CRD42024501921. RESULTS: A total of eight studies with 467 patients were included. TCv-TAVR procedures achieved a success rate of 98.5%. TCv-TAVR was associated with a 30-day ACM rate of 6.4% (95% confidence interval [CI]: 3.9-8.2%), a one-year ACM rate of 14.4% (95% CI: 2.3- 27.6%) and a 30-day rehospitalization rate at of 4.4% (95% CI: 2.2-10.6%). Postoperative stroke or transient ischemic attack, major vascular complications and major or life-threatening bleeding occurred in 3.9%, 8.5% and 10.1% of cases, respectively. Cumulative meta-analyses showed a trend of decreasing rates of vascular complications. CONCLUSIONS: The TCv approach in TAVR demonstrated a reassuring efficacy and safety profile, with mortality and post-operative complication rates comparable to those reported for supra-aortic alternative TAVR access routes. The temporal decrease in vascular complications suggests potential improvements in procedural techniques and device technology. These findings further support the TCv approach as a viable option in patients ineligible for the transfemoral access.

Prevention of esophageal lesions during atrial fibrillation catheter ablation using esophageal temperature monitoring: A systematic review and meta-analysis.

INTRODUCTION: The use of esophageal temperature monitoring (ETM) for the prevention of esophageal injury during atrial fibrillation (AF) ablation is often advocated. However, evidence supporting its use is scarce and controversial. We therefore aimed to review the evidence assessing the efficacy of ETM for the prevention of esophageal injury. METHODS: We performed a meta-analysis and systematic review of the available literature from inception to December 31, 2022. All studies comparing the use of ETM, versus no ETM, during radiofrequency (RF) AF ablation and which reported the incidence of endoscopically detected esophageal lesions (EDELs) were included. RESULTS: Eleven studies with a total of 1112 patients undergoing RF AF ablation were identified. Of those patients, 627 were assigned to ETM (56%). The overall incidence of EDELs was 9.8%. The use of ETM during AF ablation was associated with a non significant increase in the incidence of EDELs (12.3% with ETM, vs. 6.6 % without ETM, odds ratio, 1.44, 95%CI, 0.49, 4.22, p = .51, I2 = 72%). The use of ETM was associated with a significant increase in the energy delivered specifically on the posterior wall compared to patients without ETM (mean power difference: 5.13 Watts, 95% CI, 1.52, 8.74, p = .005). CONCLUSIONS: The use of ETM does not reduce the incidence of EDELs during RF AF ablation. The higher energy delivered on the posterior wall is likely attributable to a false sense of safety that may explain the lack of benefit of ETM. Further randomized controlled trials are needed to provide conclusive results.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Thrombocytopenia among Patients Undergoing Aortic Valve Replacement Using the Sutureless Perceval S Bioprosthesis: A Retrospective Study.

BACKGROUND: The sutureless Perceval S bioprosthesis is associated with postoperative thrombocytopenia. Our objectives were to compare the incidence, severity, and clinical implications of thrombocytopenia after aortic valve replacement (AVR) using the Perceval S or the Trifecta bioprosthesis. METHODS: Patients who underwent AVR between March 2016 and August 2019 using the Perceval or Trifecta were retrospectively included. The primary endpoint was the nadir in platelet counts within 15 days after surgery. Secondary endpoints included postoperative hemolysis and inflammatory parameters, as well as clinical and echocardiographic outcomes. RESULTS: Overall, 156 patients were included (Perceval, n = 103; Trifecta, n = 53). Preoperatively, there was no difference in platelet counts between the two groups. Postoperatively, the Perceval S bioprosthesis was associated with a greater decrease in platelet counts. The nadir was reached at Day 3 for both groups, but thrombocytopenia was more severe for the Perceval S (Perceval S vs. Trifecta, 89.2 ± 37.7 × 109/L vs. 106.5 ± 34.1 × 109/L, p = 0.01). No difference regarding lactate dehydrogenase, C-reactive protein, and white blood cells count was found. All-cause 30-day mortality rates (both valves, 2%, p = 0.98), hospital lengths of stay, and re-operation rates were similar. CONCLUSION: The Perceval S bioprosthesis was associated with more severe postoperative thrombocytopenia. This did not translate into higher short-term morbidity or mortality.

Prevalence of Infective Endocarditis among Patients with Staphylococcus aureus Bacteraemia and Bone and Joint Infections.

We aimed to evaluate the occurrence of infective endocarditis (IE) among patients with bone and joint infections (BJIs) and Staphylococcus aureus bacteraemia. This observational study was conducted at Lausanne University Hospital, Switzerland, from 2014 to 2023, and included episodes involving BJI, S. aureus bacteraemia, and cardiac imaging studies. The endocarditis team defined IE. Among the 384 included episodes, 289 (75%) involved native BJI (NBJI; 118 septic arthritis, 105 acute vertebral or non-vertebral osteomyelitis, 101 chronic osteitis), and 112 (29%) involved orthopedic implant-associated infection (OIAI; 78 prosthetic joint infection and 35 osteosynthesis/spondylodesis infection). Fifty-one episodes involved two or more types of BJI, with 17 episodes exhibiting both NBJI and OIAI. IE was diagnosed in 102 (27%) episodes. IE prevalence was 31% among patients with NBJI and 13% among patients with OIAI (p < 0.001). The study revealed a high prevalence of IE among S. aureus bacteraemic patients with NBJI, with notably lower prevalence among those with OIAI.

Eyes Wide Shut: A Cohort Study Questioning the Role of Fundoscopy in Infective Endocarditis Diagnosis.

In this retrospective/prospective study, we assessed the role of fundoscopy in 711 episodes with suspected infective endocarditis (IE); 238 (33%) had IE. Ocular embolic events (retinal emboli or chorioretinitis/endophthalmitis) and Roth spots were found in 37 (5%) and 34 (5%) episodes, respectively, but had no impact on IE diagnosis.

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis.

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.

[Cardiology: what's new in 2023]. / Cardiologie: ce qui a changé en 2023.

The year 2023 has been extremely rich in new publications in the various subfields of cardiology. Furthermore, the European Society of Cardiology (ESC) has issued revised guidelines focused on the management of acute coronary syndrome (ACS) and endocarditis, as well as an update on the recommendations for the management of heart failure and cardiovascular prevention. The most significant updates according to the Cardiology Department of CHUV are summarized in this review article.

L'année 2023 a été extrêmement riche en nouvelles publications dans les différents sous-domaines de la cardiologie. De plus, la Société européenne de cardiologie (ESC) a formulé des directives révisées axées sur le management du syndrome coronarien aigu (SCA) et de l'endocardite ainsi qu'une mise à jour des recommandations sur la prise en charge de l'insuffisance cardiaque et la prévention cardiovasculaire. Les nouveautés les plus importantes selon l'équipe du Service de cardiologie du CHUV sont résumées dans cet article de synthèse.

Transcaval versus Supra-Aortic Vascular Accesses for Transcatheter Aortic Valve Replacement: A Systematic Review with Meta-Analysis.

A growing body of evidence suggests that extrathoracic vascular accesses for transcatheter aortic valve replacement (TAVR) yield favorable outcomes and can be considered as primary alternatives when the gold-standard transfemoral access is contraindicated. Data comparing the transcaval (TCv) to supra-aortic (SAo) approaches (transcarotid, transsubclavian, and transaxillary) for TAVR are lacking. We aimed to compare the outcomes and safety of TCv and SAo accesses for TAVR as alternatives to transfemoral TAVR. A systematic review with meta-analysis was performed by searching PubMed/MEDLINE and EMBASE databases for all articles comparing TCv-TAVR against SAo-TAVR published until September 2023. Outcomes included in-hospital or 30-day all-cause mortality (ACM) and postoperative complications. A total of three studies with 318 TCv-TAVR and 179 SAo-TAVR patients were included. No statistically significant difference was found regarding in-hospital or 30-day ACM (relative risk [RR] 1.04, 95% confidence interval [CI] 0.47-2.34, p = 0.91), major bleeding, the need for blood transfusions, major vascular complications, and acute kidney injury. TCv-TAVR was associated with a non-statistically significant lower rate of neurovascular complications (RR 0.39, 95%CI 0.14-1.09, p = 0.07). These results suggest that both approaches may be considered as first-line alternatives to transfemoral TAVR, depending on local expertise and patients' anatomy. Additional data from long-term cohort studies are needed.

Evaluation of the 2023 Duke-ISCVID and 2023 Duke-ESC Clinical Criteria for the Diagnosis of Infective Endocarditis in a Multicenter Cohort of Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB). METHODS: This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018-23) or IE expert clinicians (2014-17). RESULTS: Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% vs 7%, P = .026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% vs 5%, P = .461). CONCLUSIONS: The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria.

European Society of Cardiology guidelines and 1 year outcomes of acute heart failure treatment in Central Asia and Europe.

AIMS: Outcomes reported for patients with hospitalization for acute heart failure (AHF) treatment vary worldwide. Ethnicity-associated characteristics may explain this observation. This observational study compares characteristics and 1-year outcomes of Kyrgyz and Swiss AHF patients against the background of European Society of Cardiology guidelines-based cardiovascular care established in both countries. METHODS AND RESULTS: The primary endpoint was 1 year all-cause mortality (ACM); the secondary endpoint was 1 year ACM or HF-related rehospitalization. A total of 538 Kyrgyz and 537 Swiss AHF patients were included. Kyrgyz patients were younger (64.0 vs. 83.0 years, P < 0.001); ischaemic or rheumatic heart disease and chronic obstructive pulmonary disease were more prevalent (always P < 0.001). In Swiss patients, smoking, dyslipidaemia, hypertension, and atrial flutter/fibrillation were more frequent (always P ≤ 0.035); moreover, left ventricular ejection fraction (LVEF) was higher (47% vs. 36%; P < 0.001), and >mild aortic stenosis was more prevalent (P < 0.001). Other valvular pathologies were more prevalent in Kyrgyz patients (P < 0.001). At discharge, more Swiss patients were on vasodilatory treatment (P < 0.006), while mineralocorticoid receptor antagonists (P = 0.001), beta-blockers (P = 0.001), or loop diuretics (P < 0.001) were less often prescribed. In Kyrgyz patients, unadjusted odds for the primary and secondary endpoints were lower [odds ratio (OR) 0.68, 95% confidence interval (CI): 0.51-0.90, P = 0.008; OR 0.72, 95% CI: 0.56-0.91, P = 0.006, respectively]. After adjustment for age and LVEF, no difference remained (primary endpoint: OR 1.03, 95% CI: 0.71-1.49, P = 0.894; secondary endpoint: OR 0.82, 95% CI: 0.60-1.12, P = 0.206). CONCLUSIONS: On the background of identical guidelines, age- and LVEF-adjusted outcomes were not different between Central Asian and Western European AHF patients despite of large ethnical disparity.

Risk of embolic events before and after antibiotic treatment initiation among patients with left-side infective endocarditis.

PURPOSE: Embolic events (EEs) are a common complication of left-side infective endocarditis (IE). The aim of the present study was to identify risk factors for the occurrence of EEs before or after antibiotic treatment instauration among patients with definite or possible IE. METHODS: This retro-prospective study was conducted at the Lausanne University Hospital, Lausanne, Switzerland, from January 2014 to June 2022. EEs and IE were defined according to modified Duke criteria. RESULTS: A total of 441 left-side IE episodes were included (334: 76% were definite and 107; 24% possible IE). EE were diagnosed in 260 (59%) episodes; in 190 (43%) before antibiotic treatment initiation and 148 (34%) after. Central nervous system (184; 42%) was the most common site of EE. Multivariable analysis identified S. aureus (P 0.022), immunological phenomena (P < 0.001), sepsis (P 0.027), vegetation size ≥ 10 mm (P 0.003) and intracardiac abscess (P 0.022) as predictors of EEs before antibiotic treatment initiation. For EEs after antibiotic treatment initiation, multivariable analysis revealed vegetation size ≥ 10 mm (P < 0.001), intracardiac abscess (P 0.035) and prior EE (P 0.042), as independent predictors of EEs, while valve surgery (P < 0.001) was associated with lower risk for EEs. CONCLUSIONS: We reported a high percentage of EEs among patients with left-side IE; vegetation size, intracardiac abscess, S. aureus and sepsis were independently associated with the occurrence of EEs. In addition to antibiotic treatment, early surgery led to further decrease in EEs incidence.

[Management of aortic disease: the importance of an organized care network]. / Prise en charge de la maladie aortique : l'importance d'une filière des soins.

Pathologies of the aorta are a complex cardiovascular diseases requiring multidisciplinary management coordinated by specialized centers able to ensure adequate patient volume. This article describes the care pathways, based on the most recent data of the literature, to optimize the management of aortic diseases).

Les pathologies de l'aorte sont des maladies cardiovasculaires complexes nécessitant une prise en charge multidisciplinaire et cordonnée par des centres spécialisés pouvant assurer un volume adéquat de patients. Cet article décrit la filière des soins, basée sur les données les plus récentes de la littérature, pour optimiser la prise en charge de la maladie aortique.

Prevalence of Pericardial Late Gadolinium Enhancement in Patients After Cardiac Surgery: Clinical and Histological Correlations.

BACKGROUND: Pericardial late gadolinium enhancement (LGE) is usually associated with active pericarditis, but it is not infrequently found in patients after cardiac surgery even a long time after the intervention. The clinical relevance of this finding and its histological correlates are unknown. We sought to determine the prevalence of chronic pericardial LGE in patients after cardiac surgery. METHODS: All consecutive patients with previous cardiac surgery, who were referred to cardiovascular magnetic resonance between January 2017 and December 2021 were enrolled in the study. Cardiovascular magnetic resonance examination protocol was adapted to clinical indication but always included standard LGE acquisitions. Two independent observers blinded to clinical data assessed the presence of pericardial enhancement on LGE sequences. Fifteen patients underwent cardiac reintervention and pericardial biopsies were obtained. The primary study end point was to assess the prevalence of pericardial enhancement after cardiac surgery and identify possible determinants. The secondary end point was to correlate pericardial enhancement with clinical symptoms and histopathology. RESULTS: Two hundred four patients were included in the study. The median time between surgery and cardiovascular magnetic resonance was 160 months (35-226 months). Pericardial LGE was observed in 90 patients (44%). All patients were asymptomatic, and no specific treatment for pericarditis was started. All patients remained asymptomatic at a 1-year clinical follow-up. Pericardial LGE was significantly correlated with the number of previous surgeries (P=0.03). Pericardial fibrosis was detected in all 15 pericardial biopsy specimens; pericardial LGE was present in 7 patients (47%) who underwent biopsy. Histological signs of low-grade inflammation were detected in 6 patients (40%) with severe, circumferential pericardial LGE but in no patient without pericardial enhancement. CONCLUSIONS: Pericardial LGE is a frequent finding even several years after cardiac surgery. Its histological correlate is a chronic subclinical post-pericardiotomy inflammation.

Extrathoracic Against Intrathoracic Vascular Accesses for Transcatheter Aortic Valve Replacement: A Systematic Review With Meta-Analysis.

Alternative vascular accesses to transfemoral access for transcatheter aortic valve replacement (TAVR) can be divided into intrathoracic (IT)-transapical and transaortic- and extrathoracic (ET)-transcarotid, transsubclavian, and transaxillary. This study aimed to compare the outcomes and safety of IT and ET accesses for TAVR as alternatives to transfemoral access. A systematic review with meta-analysis was performed by searching PubMed/MEDLINE and EMBASE databases for all studies comparing IT-TAVR with ET-TAVR published until April 2023. Outcomes included in-hospital or 30-day all-cause mortality (ACM), 1-year ACM, postoperative and 30-day complications. A total of 18 studies with 6,800 IT-TAVR patients and 5,032 ET-TAVR patients were included. IT accesses were associated with a significantly higher risk of in-hospital or 30-day ACM (relative risk 1.99, 95% confidence interval 1.67 to 2.36, p <0.001), and 1-year ACM (relative risk 1.31, 95% confidence interval 1.21 to 1.42, p <0.001). IT-TAVR patients presented more often with postoperative life-threatening bleeding, 30-day new-onset atrial fibrillation or flutter, and 30-day acute kidney injury needing renal replacement therapy. The risks of postoperative permanent pacemaker implantation and significant paravalvular leak were lower with IT-TAVR. ET-TAVR patients were more likely to be directly discharged home. There was no statistically significant difference regarding the 30-day risk of stroke. Compared with ET-TAVR, IT-TAVR was associated with higher risks of in-hospital or 30-day ACM, 1-year ACM and higher risks for some critical postprocedural and 30-day complications. Our results suggest that ET-TAVR could be considered as the first-choice alternative approach when transfemoral access is contraindicated.