Use of cangrelor for complex percutaneous coronary intervention in the context of concomitant severe aortic stenosis: a case series.

Background: There is a growing need for percutaneous coronary intervention (PCI) to be performed within the same transcatheter aortic valve implantation (TAVI) procedure. In such cases, cangrelor, a fast-acting intravenous P2Y12-inhibitor with a short offset, is potential clinical utility to minimize bleeding and vascular complications during large-bore arterial access (LBAA) as well as the thrombotic risk associated with concomitant PCI. Case summary: We report two cases of TAVI with an indication to concomitant, high-risk PCI. In the first one, cangrelor was started only after LBAA was secured and TAVI completed, just before the initiation of complex PCI. In the second case, due to predicted complex coronary cannulation after TAVI, complex PCI was performed before TAVI and cangrelor started just after LBAA. In both cases, use of cangrelor (vs. pre-treatment with oral P2Y12-i) allowed for a tailored minimization of the risk of bleeding and vascular complications during LBAA while offering full platelet inhibition during a complex/high-risk PCI. Discussion: In this case series, we illustrate a possible approach to the use of cangrelor for patients undergoing TAVI and complex/high-risk PCI. In such complex cases, thorough pre-procedural planning might include a cangrelor to minimize vascular, bleeding, and ischaemic complications.

Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry.

BACKGROUND: In patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). METHODS: The JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. RESULTS: A total of 1095 patients were included: median age was 67 (58-75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5-137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58-65) of cases. At 1-month LDL-C levels dropped to 53 (38-70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49-57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55-62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. CONCLUSIONS: In this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

Mitral valve transcatheter edge-to-edge repair with PASCAL Vs MitraClip: A aystematic teview and meta-analysis.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) using the MitraClip (Abbott Vascular) system has emerged as a standard treatment for patients with symptomatic severe secondary or inoperable primary mitral regurgitation (MR). The relatively recent approval of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences) has expanded the options of TEER devices. However, evidence comparing PASCAL with MitraClip systems is still limited. METHODS: We conducted a systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies comparing PASCAL and MitraClip systems. RESULTS: Four observational studies and 1 randomized controlled trial, involving 1315 patients total, were eligible for inclusion. All patients exhibited symptomatic (NYHA II-IV) MR grades 3+ or 4+. Baseline characteristics were comparable across all included studies. The clinical outcomes were assessed according to the Mitral Valve Academic Research Consortium consensus. The procedural success rates for the 2 devices were comparable in terms of achieving post-procedural MR grades of less than or equal to 2+ and less than or equal to 1+. Furthermore, most patients improved their clinical status, with no significant differences between patients treated with PASCAL and those treated with MitraClip. In terms of safety, both procedures exhibited low overall mortality rates and occurrence of major adverse events (MAE), without significant difference between the 2 devices. These findings remained consistent in both short- and long-term follow-up assessments. CONCLUSIONS: Our study revealed similar effectiveness and safety profiles between the PASCAL and MitraClip devices in patients experiencing significant symptomatic MR.

Fighting Cardiac Thromboembolism during Transcatheter Procedures: An Update on the Use of Cerebral Protection Devices in Cath Labs and EP Labs.

Intraprocedural stroke is a well-documented and feared potential risk of cardiovascular transcatheter procedures (TPs). Moreover, subclinical neurological events or covert central nervous system infarctions are concerns related to the development of dementia, future stroke, cognitive decline, and increased risk of mortality. Cerebral protection devices (CPDs) were developed to mitigate the risk of cardioembolic embolism during TPs. They are mechanical barriers designed to cover the ostium of the supra-aortic branches in the aortic arch, but newer devices are able to protect the descending aorta. CPDs have been mainly designed and tested to provide cerebral protection during transcatheter aortic valve replacement (TAVR), but their use in both Catheterization and Electrophysiology laboratories is rapidly increasing. CPDs have allowed us to perform procedures that were previously contraindicated due to high thromboembolic risk, such as in cases of intracardiac thrombosis identified at preprocedural assessment. However, several concerns related to their employment have to be defined. The selection of patients at high risk of thromboembolism is still a subjective choice of each center. The aim of this review is to update the evidence on the use of CPDs in either Cath labs or EP labs, providing an overview of their structural characteristics. Future perspectives focusing on their possible future employment are also discussed.

External validity of the PRECISE-DAPT score in patients undergoing PCI: a systematic review and meta-analysis.

AIMS: To summarize the totality of evidence validating the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, ascertaining its aggregate discrimination and validation power in multiple population subsets. METHODS AND RESULTS: We searched electronic databases from 2017 (PRECISE-DAPT proposal) up to March 2023 for studies that reported the occurrence of out-of-hospital bleedings according to the PRECISE-DAPT score in patients receiving DAPT following percutaneous coronary intervention (PCI). Pooled odds ratios (OR) with 95% confidence interval (CI) were used as summary statistics and were calculated using a random-effects model. Primary and secondary endpoints were the occurrence of any and major bleeding, respectively. A total of 21 studies and 67 283 patients were included; 24.7% of patients (N = 16 603) were at high bleeding risk (PRECISE-DAPT score ≥25), and when compared to those at low bleeding risk, they experienced a significantly higher rate of any out-of-hospital bleeding (OR: 2.71; 95% CI: 2.24-3.29; P-value <0.001) and major bleedings (OR: 3.51; 95% CI: 2.71-4.55; P-value <0.001). Pooling data on c-stat whenever available, the PRECISE-DAPT score showed a moderate discriminative power in predicting major bleeding events at 1 year (pooled c-stat: 0.71; 95% CI: 0.64-0.77). CONCLUSION: This systematic review and meta-analysis confirms the external validity of the PRECISE-DAPT score in predicting out-of-hospital bleeding outcomes in patients on DAPT following PCI. The moderate discriminative ability highlights the need for future improved risk prediction tools in the field.

Prognostic Significance of Flail Mitral Leaflet in Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation.

Despite the growing experience with MitraClip in the broad spectrum of mitral regurgitation (MR), limited data are available regarding the independent prognostic role on survival of different mitral regurgitation etiology subtypes. We sought to evaluate the impact of flail leaflet etiology in a large series of patients with primary MR (PMR) who underwent MitraClip treatment. The study included 588 patients with significant PMR from the multicenter GIOTTO (Italian Society of Interventional Cardiology [GIse] registry Of Transcatheter treatment of mitral valve regurgitaTiOn), stratified into 2 groups according to MR etiology: flail+ (n = 300) and flail- (n = 288). The primary end point was a composite of cardiac death and first rehospitalization for heart failure (HF). To account for the baseline differences, patients were propensity score-matched 1:1. Flail leaflet etiology was present in about a half of the patients. Acute technical success was achieved in 98% of the overall cohort, with no significant differences between the study groups (p = 0.789). At the 2-year Kaplan-Meier analysis, the primary end point occurred in 13% of flail+ patients compared with 23% in flail- (p = 0.009). The flail+ group presented lower rates of both cardiac death and rehospitalization for HF, whereas a similar overall death rate was observed between the groups. A multivariate Cox regression analysis identified flail leaflet etiology as an independent predictor of favorable outcome in terms of the primary end point (hazard ratio 0.141, 95% confidence interval 0.049 to 0.401, p <0.001). After propensity score matching, flail+ patients had confirmed lower rates of cardiac mortality and rehospitalization for HF but similar rates of overall death. In conclusion, flail leaflet-related etiology was common in patients with PMR who underwent MitraClip treatment and was an independent predictor of midterm favorable clinical outcomes.

2-year outcomes of MitraClip as a bridge to heart transplantation: The international MitraBridge registry.

BACKGROUND: In the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years. METHODS: By the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation. RESULTS: Procedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9-52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement. CONCLUSIONS: After 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases.

First- Versus New-Generation Drug-Eluting Stents in Patients With Heart Transplant With Cardiac Allograft Vasculopathy.

Although several studies have previously reported on the efficacy of percutaneous coronary intervention (PCI) with first-generation drug-eluting stents (DES) in heart transplant patients with cardiac allograft vasculopathy, few data regarding new-generation DES are currently available. We sought to compare the efficacy of new-generation versus first-generation DES in 90 consecutive patients with heart transplant (113 de novo coronary lesions) who underwent urgent or elective PCI with first-generation (28 patients) or new-generation (62 patients) DES. For each patient, the severity of cardiac allograft vasculopathy and postprocedural extent of revascularization were quantified calculating baseline and residual SYNTAX score, respectively. The primary end point was a composite of major adverse cardiac events-myocardial infarction, cardiovascular death, or target vessel revascularization-at 3 years. Overall, the median baseline SYNTAX score was 8 (5 to 15), and a total number of stents per patient of 1.6 ± 0.9 was implanted. Post-PCI residual SYNTAX score was 1.5 (0 to 4), with 13 patients having a score >8. At 3 years, the Kaplan-Meier estimate of freedom from major adverse cardiac events was 64%, with no differences between first-generation and new-generation DES groups (log-rank test p = 0.269). Nevertheless, patients treated with new-generation DES experienced a lower rate of target vessel revascularization (15% vs 31%, log-rank test p = 0.058). In the multivariate Cox regression analysis, a post-PCI residual SYNTAX score >8 (hazard ratio 2.37, confidence interval 0.98 to 5.73, p = 0.054) was identified as an independent predictor of the primary end point.

Changes in Right Ventricular-to-Pulmonary Artery Coupling After Transcatheter Edge-to-Edge Repair in Secondary Mitral Regurgitation.

BACKGROUND: Preprocedural right ventricular-to-pulmonary artery (RV-PA) coupling is a major predictor of outcome in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). However, clinical significance of changes in RV-PA coupling after M-TEER is unknown. OBJECTIVES: The aim of this study was to evaluate changes in RV-PA coupling after M-TEER, their prognostic value, and predictors of improvement. METHODS: This was a retrospective observational study, including patients undergoing successful M-TEER (residual mitral regurgitation ≤2+ at discharge) for SMR at 13 European centers and with complete echocardiographic data at baseline and short-term follow-up (30-180 days). RV-PA coupling was assessed with the use of echocardiography as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). All-cause death was assessed at the longest available follow-up starting from the time of the echocardiographic reassessment. RESULTS: Among 501 patients included, 331 (66%) improved their TAPSE/PASP after M-TEER (responders) at short-term follow-up (median: 89 days; IQR: 43-159 days), whereas 170 (34%) did not (nonresponders). Lack of previous cardiac surgery, low postprocedural mitral mean gradient, low baseline TAPSE, high baseline PASP, and baseline tricuspid regurgitation were independently associated with TAPSE/PASP improvement after M-TEER. Compared with nonresponders, responders had lower New York Heart Association functional class and less heart failure hospitalizations at short-term follow-up. Improvement in TAPSE/PASP was independently associated with reduced risk of mortality at long-term follow-up (584 days; IQR: 191-1,243 days) (HR: 0.65 [95% CI: 0.42-0.92]; P = 0.017). CONCLUSIONS: In patients with SMR, improvement in TAPSE/PASP after successful M-TEER is predicted by baseline clinical and echocardiographic variables and postprocedural mitral gradient, and is associated with a better outcome.

Evolution of tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair for secondary mitral regurgitation and its impact on mortality.

AIM: To evaluate short-term changes in tricuspid regurgitation (TR) after transcatheter edge-to-edge mitral valve repair (M-TEER) in secondary mitral regurgitation (SMR), their predictors and impact on mortality. METHODS AND RESULTS: This is a retrospective analysis of SMR patients undergoing successful M-TEER (post-procedural mitral regurgitation ≤2+) at 13 European centres. Among 503 patients evaluated 79 (interquartile range [IQR] 40-152) days after M-TEER, 173 (35%) showed ≥1 degree of TR improvement, 97 (19%) had worsening of TR, and 233 (46%) remained unchanged. Smaller baseline left atrial diameter and residual mitral regurgitation 0/1+ were independent predictors of TR ≤2+ after M-TEER. There was a significant association between TR changes and New York Heart Association class and pulmonary artery systolic pressure decrease at echocardiographic re-assessment. At a median follow-up of 590 (IQR 209-1103) days from short-term echocardiographic re-assessment, all-cause mortality was lower in patients with improved compared to those with unchanged/worsened TR (29.6% vs. 42.3% at 3 years; log-rank p = 0.034). Baseline TR severity was not associated with mortality, whereas TR 0/1+ and 2+ at short-term follow-up was associated with lower all-cause mortality compared to TR 3/4+ (30.6% and 35.6% vs. 55.6% at 3 years; p < 0.001). A TR ≤2+ after M-TEER was independently associated with a 42% decreased risk of mortality (p = 0.011). CONCLUSION: More than one third of patients with SMR undergoing successful M-TEER experienced an improvement in TR. Pre-procedural TR was not associated with outcome, but a TR ≤2+ at short-term follow-up was independently associated with long-term mortality. Optimal M-TEER result and a small left atrium were associated with a higher likelihood of TR ≤2+ after M-TEER.

Large-bore arterial access closure after transcatheter aortic valve replacement: a systematic review and network meta-analysis.

Aims: As the indications to transcatheter aortic valve replacement (TAVR) expand to patients at increasingly lower risk, procedure-related vascular and bleeding complications events must be minimized. We aimed to evaluate the impact of different large-bore arterial access closure devices on clinical outcomes after TAVR. Methods and results: We searched for papers that reported outcomes according to the type of vascular closure device/technique used after TAVR and performed a Bayesian network meta-analysis (NMA). Fifteen studies involving 9259 patients who underwent access site closure using PROSTAR™ XL percutaneous vascular surgical system (Abbott Vascular, Santa Clara, CA, USA), Perclose ProGlide™ suture-mediated closure system (Abbott), or MANTATM vascular closure device (Teleflex, Morrisville, NC, USA) were included. NMA showed MANTA to have the highest likelihood of reducing a primary composite endpoint of intra-hospital death, major vascular complications, and major or life-threatening bleedings [surface under the cumulative ranking curve analysis (SUCRA) 94.8%], but this was mitigated when only randomized clinical trials and propensity-matched cohorts were included (SUCRA 56.1%). The ProGlide showed the highest likelihood to reduce major or life-threatening bleedings, especially with increasing procedural complexity, and the MANTA device to reduce major and minor vascular complications. The ProStar XL device performed poorly in all explored endpoints. Conclusion: Available evidence summarized through a NMA shows that ProGlide and MANTA devices appear to be both valid vascular closure devices globally and to be the best options to minimize vascular complications and reduce bleeding in patients undergoing TAVR, respectively.

Edge-to-edge percutaneous mitral repair for functional ischaemic and non-ischaemic mitral regurgitation: a systematic review and meta-analysis.

AIM: Randomized controlled trials comparing the use of the MitraClip device in addition to guideline directed medical therapy (GDMT) to GDMT alone in patients with secondary mitral regurgitation (MR) have shown conflicting results. However, if these differences could be due to the underlying MR aetiology is still unknown. Therefore, we aimed to evaluate if the effects of percutaneous edge-to-edge repair with MitraClip implantation could differ in patients with ischaemic (I-MR) and non-ischaemic mitral regurgitation (NI-MR). METHODS AND RESULTS: PubMed, Embase, BioMed Central, and the Cochrane Central Register of Controlled Trials were searched for all studies including patients with secondary MR treated with the MitraClip device. Data were pooled using a random-effects model. Primary endpoint was the composite of all-cause death and heart failure-related hospitalization. Secondary endpoints were the single components of the primary endpoint, New York Heart Association functional Classes III and IV, and mitral valve re-intervention. Seven studies enrolling 2501 patients were included. Patients with I-MR compared with patients with NI-MR had a similar risk of the primary endpoint (odds ratio: 1.17; 95% confidence interval: 0.93 to 1.46; I2 : 0%). The risk of all-cause death was increased in patients with I-MR (odds ratio: 1.31; 95% confidence interval: 1.07 to 1.62; I2 : 0%), while no differences were observed between the two groups in terms of the other secondary endpoints. CONCLUSIONS: The risk of mortality after MitraClip implantation is lower in patients with NI-MR than in those with I-MR. No absolute differences in the risk of heart failure related hospitalization were observed between groups.

Validation of the ARC-HBR criteria in 68,874 patients undergoing PCI: A systematic review and meta-analysis.

The Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria aims to stratify patients undergoing percutaneous coronary intervention (PCI) and are now recommended by international guidelines to stratify bleeding risk in clinical practice. We searched electronic databases from 2019 (ARC-HBR proposal) up to February 2021 for studies that reported the occurrence of major bleedings according to ARC-HBR status in patients undergoing PCI and pooled them as relative risk (RR) in a random-effect analysis. Only studies that reported events according to the number of times the ARC-HBR definition was met were included in a sensitivity analysis and RR for each stratum was calculated. Nine studies and 68,874 subjects were included in our analysis; 39.2% of them were at HBR and they had a significantly higher risk of major bleedings (RR: 2.70; 95% CI: 2.35-3.10; p < 0.0001). The ARC-HBR definition also had a moderate discriminative power (pooled c-stat: 0.69; 95% CI: 0.61-0.75) while calibration was suboptimal with a tendency toward underpredicting bleeding events (pooled observed:expected ratio: 1.47; 95% CI: 0.82-2.60). Our sensitivity analysis included 5 studies and 46,712 patients and confirmed the incremental, additive power of the ARC-HBR when it is met multiple times. Finally, among baseline characteristics explored, only presenting with an acute coronary syndrome had a significant impact on the ARC-HBR predictive ability. The ARC-HBR definition is a useful clinical tool, but with a tendency towards underpredicting major bleedings and its predictive ability might be optimized by including the number of times the definition is met.

Meta-Analysis of Relation Between Left Ventricular Dysfunction and Outcomes After Transcatheter Mitral Edge-to-Edge Repair.

Randomized controlled trials (RCTs) and observational studies provided conflicting results regarding the role of left ventricular (LV) function on outcomes after transcatheter edge-to-edge repair (TEER). The study aimed to provide a comprehensive assessment of the interplay between severe LV dysfunction and TEER outcomes. Multiple electronic databases, including PubMed, EMBASE, Scopus, Web of Science, and CENTRAL, were searched to identify studies on TEER for secondary mitral regurgitation reporting outcomes stratified for LV ejection fraction <30% and ≥30%. The prespecified primary end points were the composite of all-cause death or heart failure (HF) hospitalization and New York Heart Association (NYHA) class III/IV. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by random-effects models. Multiple sensitivity analyses accounting for baseline characteristics and study design were applied. A total of 6 studies (1,957 patients) with 1 year or 2 years of follow-up were available. Severe LV dysfunction was associated with an increased risk of death or HF hospitalization (OR 1.71, 95% CI 1.14 to 2.57). Conversely, comparable rates of NYHA class III/IV (OR 1.06, 95% CI 0.82 to 1.38) or secondary end points (reinterventions, recurrence of significant secondary mitral regurgitation) were found regardless of the baseline LV function. Subgroup meta-analysis found no difference in the composite primary end point between patients with LV ejection fraction <30% and ≥30% enrolled in RCTs. In conclusion, TEER seems to be associated with higher mortality or HF hospitalization rates in patients with severe LV dysfunction. However, RCTs found no differences between groups. No impact of LV function was found on the risk of NYHA class III/IV or other clinical outcomes.

Response to acute vasodilator challenge and haemodynamic modifications after MitraClip in patients with functional mitral regurgitation and pulmonary hypertension.

The effectiveness of transcatheter edge-to-edge repair (TEER) in patients with functional mitral regurgitation (FMR) and pulmonary hypertension (PH) is still debated and pre-procedural predictors of haemodynamic improvement after TEER in this setting are currently unknown. We investigated whether normalization of pulmonary artery wedge pressure (PAWP) in response to sodium nitroprusside (SNP) during baseline right heart catheterization might be predictive of a favourable haemodynamic response to MitraClip in patients with FMR and PH. Among 22 patients enrolled, 13 had a positive response to SNP (responders), nine were non-responders. At 6-months follow-up, responders showed a 33% reduction in PAWP and a 25% reduction in mean pulmonary artery pressure (PAP) (P = 0.002 and 0.004, respectively); no significant change occurred in non-responders. In patients with FMR and PH, pre-procedural vasodilator challenge with SNP may help define patients who may have haemodynamic improvement after TEER.

Contrast-Associated Acute Kidney Injury.

Contrast-associated acute kidney injury (CA-AKI) is an impairment of renal function, which occurs within days of intravascular administration of iodinated contrast media. Taking into account that minimally invasive cardiac interventions are becoming increasingly popular, compared to traditional surgery, given their impact on prognosis and costs, CA-AKI remains a subject of increasing interest for patients and physicians. This review summarizes the epidemiology and risk stratification, diagnostic criteria, pathophysiology and clinical implications of CA-AKI, providing evidence for the most studied preventive strategies.