Stroke risk after transcatheter aortic valve replacement in patients with carotid stenosis: A systematic review and meta-analysis.

BACKGROUND: Stroke is a feared complication of transcatheter aortic valve replacement (TAVR). Patients undergoing TAVR typically have multiple comorbidities, such as carotid artery stenosis (CAS). We conducted the present meta-analysis to determine the risk of stroke and mortality following TAVR in patients with CAS. METHODS: We searched PubMed/Medline, Scopus, ScienceDirect, and Cochrane Clinical Trials databases for clinical studies that compared CAS ≥50% and CAS ≥70% versus non-CAS TAVR population. The endpoints included the 30-day incidence of stroke or transient ischemic attack (TIA) and 30-day all-cause of mortality. RESULTS: We identified seven studies that included 12,418 patients in the CAS group and 102,316 in the control group. CAS ≥50% was not associated with an increased risk of 30-day stroke or TIA after TAVR [risk ratio (RR): 1.38; 95% confidence interval (95% CI): 0.95-2.02; p = 0.09]. However, patients with CAS ≥70% had an increased risk of stroke or TIA (RR: 1.43; 95% CI: 1.02-2.01; p = 0.04). No difference in 30-day all-cause mortality was observed between CAS ≥50% or CAS ≥70% and control groups (RR: 1.09; 95% CI: 0.79-1.52; p = 0.59 and RR: 1.11; 95% CI: 0.85-1.45; p = 0.43, respectively). CONCLUSIONS: CAS ≥70% was associated with an increased risk of stroke or TIA following TAVR compared with patients without CAS.

Three-Year Clinical Impact of Murray Law-Based Quantitative Flow Ratio and OCT- or FFR-Guidance in Angiographically Intermediate Coronary Lesions.

BACKGROUND: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (µQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of µQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up. METHODS: µQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline µQFR was considered the final µQFR for deferred lesions, and post-PCI µQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up. RESULTS: A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. µQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI µQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P=0.023), and the post-PCI µQFR improvement was greater in FFR-group (0.14 versus 0.08; P<0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P=0.617). Final µQFR was the only predictor of TVF. µQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P=0.004). PCI was a predictor of higher final µQFR (odds ratio, 0.22 [95% CI, 0.14-0.34]; P<0.001). CONCLUSIONS: In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. µQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01824030.

Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis.

AIMS: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF. METHODS AND RESULTS: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P < 0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P = 0.04]. CONCLUSIONS: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization.

Ischaemic heart disease in patients with cancer.

Cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD). Several factors account for the interrelationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential. Furthermore, experimental work indicates that IHD and cancer can promote one another, and the CV or metabolic toxicity of anticancer therapies can lead to IHD. The connections between IHD and cancer are reinforced by social determinants of health, non-medical factors that modify health outcomes and comprise individual and societal domains, including economic stability, educational and healthcare access and quality, neighbourhood and built environment, and social and community context. Management of IHD in cancer patients is often challenging, due to atypical presentation, increased bleeding and ischaemic risk, and worse outcomes as compared to patients without cancer. The decision to proceed with coronary revascularization and the choice of antithrombotic therapy can be difficult, particularly in patients with chronic coronary syndromes, necessitating multidisciplinary discussion that considers both general guidelines and specific features on a case by case basis. Randomized controlled trial evidence in cancer patients is very limited and there is urgent need for more data to inform clinical practice. Therefore, coexistence of IHD and cancer raises important scientific and practical questions that call for collaborative efforts from the cardio-oncology, cardiology, and oncology communities.

Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction.

Despite prompt epicardial recanalization in patients presenting with ST-segment elevation myocardial infarction (STEMI), coronary microvascular obstruction and dysfunction (CMVO) is still fairly common and is associated with poor prognosis. Various pharmacological and mechanical strategies to treat CMVO have been proposed, but the positive results reported in preclinical and small proof-of-concept studies have not translated into benefits in large clinical trials conducted in the modern treatment setting of patients with STEMI. Therefore, the optimal management of these patients remains a topic of debate. In this Review, we appraise the pathophysiological mechanisms of CMVO, explore the evidence and provide future perspectives on strategies to be implemented to reduce the incidence of CMVO and improve prognosis in patients with STEMI.

Prognostic value of combined fractional flow reserve and pressure-bounded coronary flow reserve: outcomes in FFR and Pb-CFR assessment.

BACKGROUND: Coronary flow reserve (CFR) has an emerging role to predict outcome in patients with and without flow-limiting stenoses. However, the role of its surrogate pressure bounded-CFR (Pb-CFR) is controversial. We investigated the usefulness of combined use of fractional flow reserve (FFR) and Pb-CFR to predict outcomes. METHODS: This is a sub-study of the PROPHET-FFR Trial, including patients with chronic coronary syndrome and functionally tested coronary lesions. Patients were divided into four groups based on positive or negative FFR (cut-off 0.80) and preserved (lower boundary ≥2) or reduced (upper boundary <2) Pb-CFR: Group1 FFR≤0.80/ Pb-CFR <2; Group 2 FFR≤0.80/Pb-CFR≥2; Group 3 FFR >0.80/Pb-CFR<2; Group 4 FFR>0.80/Pb-CFR≥2. Lesions with positive FFR were treated with PCI. Primary endpoint was the rate of major adverse cardiac events (MACEs), defined as a composite of death from any cause, myocardial infarction, target vessel revascularization, unplanned cardiac hospitalization at 36-months. RESULTS: A total of 609 patients and 816 lesions were available for the analysis. At Kaplan-Meier analysis MACEs rate was significantly different between groups (36.7% Group 1, 27.4% Group 2, 19.2% Group 3, 22.6% Group 4, P=0.019) and more prevalent in groups with FFR≤0.80 irrespective of Pb-CFR. In case of discrepancy, no difference in MACEs were observed between groups stratified by Pb-CFR. FFR≤0.80 was associated with an increased MACEs rate (30.2% vs. 21.5%, P<0.01) while Pb-CFR<2 was not (24.5% vs. 24.2% Pb-CFR≥2 P=0.67). CONCLUSIONS: FFR confirms its ability to predict outcomes in patients with intermediate coronary stenoses. Pb-CFR does not add any relevant prognostic information.

Impact of thrombus aspiration on left ventricular remodeling and function in patients with ST-segment elevation myocardial infarction: A meta-analysis of randomized controlled trials.

BACKGROUND: Routine thrombus aspiration (TA) does not improve clinical outcomes in patients with ST-segment-elevation myocardial infarction (STEMI), although data from meta-analyses suggest that patients with high thrombus burden may benefit from it. The impact of TA on left ventricular (LV) functional recovery and remodeling after STEMI remains controversial. We aimed to pool data from randomized controlled trials (RCTs) on the impact of TA on LV function and remodeling after primary percutaneous coronary intervention (pPCI). METHODS: PubMed and CENTRAL databases were scanned for eligible studies. Primary outcome measures were: LV ejection fraction (LVEF), LV end diastolic volume (LVEDV), LV end systolic volume (LVESV) and wall motion score index (WMSI). A primary pre-specified subgroup analysis was performed comparing manual TA with mechanical TA. RESULTS: A total of 28 studies enrolling 4990 patients were included. WMSI was lower in TA group than in control (mean difference [MD] -0.11, 95% confidence interval [CI] -0.19 to -0.03). A greater LVEF (MD 1.91, 95% CI 0.76 to 3) and a smaller LVESV (MD -6.19, 95% CI -8.7 to -3.6) were observed in manual TA group compared to control. Meta regressions including patients with left anterior descending artery (LAD) involvement showed an association between TA use and the reduction of both LVEDV and LVESV (z = -2.13, p = 0.03; z = -3.7, p < 0.01) and the improvement in myocardial salvage index (z = 2.04, p = 0.04). CONCLUSION: TA is associated with improved LV function. TA technique, total ischemic time and LAD involvement appears to influence TA benefit on post-infarction LV remodeling.

Ticagrelor Enhances the Cardioprotective Effects of Ischemic Preconditioning in Stable Patients Undergoing Percutaneous Coronary Intervention: the TAPER-S Randomized Study.

BACKGROUND: Ticagrelor improves clinical outcomes in patients with acute coronary syndrome compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve (FFR)-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary (IC)-ECG during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning. The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by intracoronary-ECG during two-step sequential coronary balloon inflations. RESULTS: Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (p<0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel. CONCLUSIONS: Ticagrelor enhances the cardioprotective effects of ischemic preconditioning compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique Identifier: NCT02701140.

Chronic systemic glucocorticoid therapy is associated with increased risk of major vascular complications and cardiac tamponade after transcatheter aortic valve implantation: a systematic review and meta-analysis.

INTRODUCTION: TAVI-related complications, such as conduction disturbances, vascular complications or death may be related to increased inflammatory response. The aim of this study was to elucidate the efficacy and safety of the systemic glucocorticoid therapy regarding the adverse events after TAVI deployment. EVIDENCE ACQUISITION: We conducted a systemic search of PubMed, a reference list of relevant articles, and Medline. The main efficacy outcomes of interest were all-cause death, cardiac and non-cardiac death, permanent pacemaker implantation (PPM), new left bundle branch block (LBBB), stroke, and myocardial infarction (MI). Safety endpoints were major vascular complications, major bleeding events, and cardiac tamponade. EVIDENCE SYNTHESIS: A total of 7 studies including data from 3439 patients with a median follow-up was 30 days. Systemic glucocorticoid compared to the control group were associated with an increased risk of non-cardiac death (Relative Risk [RR] 5.90 95%CI [2.95; 11.80], P<0.001) major vascular complications (RR 1.78, 95%CI [1.22 - 2.61], P=0.003) and cardiac tamponade (RR 3.42, 95%CI [1.69 - 6.92], P<0.001). However, there were no differences in all-cause death, cardiac death, new LBBB, stroke, MI, or major bleeding events (all P values >0.05). CONCLUSIONS: Glucocorticoid therapy before the TAVI procedure was associated with an increase in non-cardiac death, major vascular events and cardiac tamponade. There were no differences in the risk of all-cause death, cardiac death, PPM or LBBB, stroke, or MI.