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.

Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.

The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.

Hospital-Acquired Anemia in Patients with Acute Coronary Syndrome: Epidemiology and Potential Impact on Long-Term Outcome.

BACKGROUND: Anemia (either pre-existing or hospital-acquired) is considered an independent predictor of mortality in acute coronary syndromes. However, it is still not clear whether anemia should be considered as a marker of worse health status or a therapeutic target. We sought to investigate the relationship between hospital-acquired anemia and clinical and laboratory findings and to assess the association with mortality and major cardiovascular events at long-term follow-up. METHODS: Patients consecutively admitted at Niguarda Hospital between February 2014 and November 2020 for an acute coronary syndrome were included in this cohort analysis and classified as anemic at admission (group A), with normal hemoglobin at admission but developing anemia during hospitalization (hospital-acquired anemia) (group B); and with normal hemoglobin levels throughout admission (group C). RESULTS: Among 1294 patients included, group A included 353 (27%) patients, group B 468 (36%), and group C 473 patients (37%). In terms of cardiovascular burden and incidence of death, major cardiovascular events and bleeding at 4.9-year median follow-up, group B had an intermediate risk profile as compared with A and C. Baseline anemia was an independent predictor of death (hazard ratio 1.51; 95% confidence interval, 1.02-2.25; P = .04) along with frailty, Charlson comorbidity Index, estimated glomerular filtration rate, previous myocardial infarction, and left ventricular ejection fraction. Conversely, hospital-acquired anemia was not associated with increased mortality (hazard ratio 1.18; 95% confidence interval, 0.8-1.75; P = .4). CONCLUSIONS: Hospital-acquired anemia affects one-third of patients hospitalized for acute coronary syndrome and is associated with age, frailty, and comorbidity burden, but was not found to be an independent predictor of long-term mortality.

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.

Natural history and clinical burden of moderate aortic stenosis: a systematic review and explorative meta-analysis.

AIMS: The mortality risk of patients with moderate aortic stenosis is not well known, but recent studies suggested that it might negatively affect prognosis. We aimed to assess the natural history and clinical burden of moderate aortic stenosis and to investigate the interaction of patients' baseline characteristics with prognosis. METHODS: Systematic research was conducted on PubMed. The inclusion criteria were inclusion of patients with moderate aortic stenosis; and report of the survival at 1-year follow-up (minimum). Incidence ratios related to all-cause mortality in patients and controls of each study were estimated and then pooled using a fixed effects model. All patients with mild aortic stenosis or without aortic stenosis were considered controls. Meta-regression analysis was performed to assess the impact of left ventricular ejection fraction and age on the prognosis of patients with moderate aortic stenosis. RESULTS: Fifteen studies and 11 596 patients with moderate aortic stenosis were included. All-cause mortality was significantly higher among patients with moderate aortic stenosis than in controls in all timeframes analysed (all P  < 0.0001). Left ventricular ejection fraction and sex did not significantly impact on the prognosis of patients with moderate aortic stenosis ( P  = 0.4584 and P  = 0.5792), while increasing age showed a significant interaction with mortality (estimate = 0.0067; 95% confidence interval: 0.0007-0.0127; P  = 0.0323). CONCLUSION: Moderate aortic stenosis is associated with reduced survival. Further studies are necessary to confirm the prognostic impact of this valvulopathy and the possible benefit of aortic valve replacement.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

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.

The long-term clinical course of moderate tricuspid regurgitation.

BACKGROUND: To evaluate the long-term clinical outcome of a cohort of patients suffering from moderate tricuspid regurgitation (TR), regardless of its etiology. METHODS: Clinical and echocardiographic follow-up were assessed in 250 patients diagnosed with moderate TR between January 2016 and July 2020. TR progression at follow-up was defined as TR grade increase to at least severe. The primary endpoint was all-cause death; secondary endpoints were cardiovascular (CV) death and the composite of heart failure (HF) hospitalization plus tricuspid valve (TV) intervention. RESULTS: After a median follow-up of 3.6 years, TR progression occurred in 84 patients (34%). At multivariate analyses, atrial fibrillation (AF, OR 1.81, CI 1.01-3.29, p = 0.045) and right ventricular end-diastolic diameter (RVEDD, OR 2.19, CI 1.26-3.78, p = 0.005) were independent predictors of TR progression. The primary endpoint occurred in 59 patients (24%) and was significantly more frequent in the group with TR progression (p = 0.009). At multivariate analyses, chronic kideney disease (OR 2.80, CI 1.30-6.03, p = 0.009), left ventricular ejection fraction (OR 0.97, CI 0.94-0.99, p = 0.041) and TR progression (OR 2.32, CI 1.31-4.12, p = 0.004) were independent predictors of the primary outcome. Moreover, both the secondary endpoints of CV death and HF hospitalization plus TV intervention were more frequent in the TR progression group (p = 0.001 and p < 0.001, respectively). CONCLUSIONS: Moderate TR progresses in a significant proportion of patients over a long-term follow-up, leading to a worse prognosis. TR progression is an independent determinant of hard clinical events and AF and RVEDD are associated with TR progression.

Antiplatelet Strategies for Older Patients with Acute Coronary Syndromes: Finding Directions in a Low-Evidence Field.

Patients ≥ 75 years of age account for about one third of hospitalizations for acute coronary syndromes (ACS). Since the latest European Society of Cardiology guidelines recommend that older ACS patients use the same diagnostic and interventional strategies used by the younger ones, most elderly patients are currently treated invasively. Therefore, an appropriate dual antiplatelet therapy (DAPT) is indicated as part of the secondary prevention strategy to be implemented in such patients. The choice of the composition and duration of DAPT should be tailored on an individual basis, after careful assessment of the thrombotic and bleeding risk of each patient. Advanced age is a main risk factor for bleeding. Recent data show that in patients of high bleeding risk short DAPT (1 to 3 months) is associated with decreased bleeding complications and similar thrombotic events, as compared to standard 12-month DAPT. Clopidogrel seems the preferable P2Y12 inhibitor, due to a better safety profile than ticagrelor. When the bleeding risk is associated with a high thrombotic risk (a circumstance present in about two thirds of older ACS patients) it is important to tailor the treatment by taking into account the fact that the thrombotic risk is high during the first months after the index event and then wanes gradually over time, whereas the bleeding risk remains constant. Under these circumstances, a de-escalation strategy seems reasonable, starting with DAPT that includes aspirin and low-dose prasugrel (a more potent and reliable P2Y12 inhibitor than clopidogrel) then switching after 2-3 months to DAPT with aspirin and clopidogrel for up to 12 months.

Bi-Caval Valve Implantation to Palliate Symptoms in a Case of Massive Tricuspid Regurgitation.

Severe tricuspid regurgitation is associated with the occurrence of right failure and increased morbidity and mortality. Transcatheter heterotopic bi-caval valve implantation might offer symptom relief in these patients that are often at prohibitive surgical risk.

Dual antiplatelet therapy duration after percutaneous coronary intervention in patients with indication to oral anticoagulant therapy. A systematic review and meta-analysis of randomized controlled trials.

AIMS: Optimal duration of dual antiplatelet therapy (DAPT) in patients with concomitant indication to oral anticoagulation (OAC) is still debated. METHODS AND RESULTS: A systematic review was performed on electronic databases to search for randomized controlled trials comparing an abbreviated or prolonged (≥3 months) DAPT regimen in patients with OAC and they were analysed in the framework of standard and network meta-analyses. Co-primary endpoints were major or clinically relevant non-major bleedings (MCRB) and major bleeding, while the composite of major adverse cardiovascular events (MACE) was the key safety endpoint. Five studies and 7 665 patients (abbreviated DAPT n = 3 843; prolonged DAPT n = 3 822) were included. Both MCRB and major bleeding were lower with abbreviated DAPT [risk ratio (RR) 0.69 (0.52-0.91); P = 0.01 and 0.70 (0.52-0.95); P = 0.01, respectively] while MACE [RR: 0.96 (0.70-1.33); P = 0.6], all-cause death, cardiovascular death, stent thrombosis, or myocardial infarction did not differ. Network meta-analysis showed that peri-procedural DAPT had the highest probability to prevent MCRB and major bleeding (97.1 and 92.0% respectively) when compared with both short (4-6 weeks) and longer (≥3 months) DAPT regimens. Sensitivity analyses and meta-regressions showed consistency in different clinical scenarios and suggested a larger bleeding reduction with P2Y12 inhibitors vs. aspirin after DAPT discontinuation. CONCLUSION: In patients undergoing PCI with concomitant OAC indication, an abbreviated DAPT regimen reduced MCRB and major bleeding without increasing MACE or other ischaemic events. Peri-procedural DAPT and P2Y12 inhibitor monotherapy after DAPT withdrawal appear to be the best strategies to optimize the bleeding and ischaemic risk tradeoff. Trial registration. PROSPERO CRD284001.

Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice.

The assessment of bleeding and ischemic risk is a crucial step in establishing appropriate composition and duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) treated with percutaneous coronary angioplasty. Evidence from recent randomized clinical trials led to some paradigm shifts in current guidelines recommendations. Options alternative to the standard 12-month DAPT duration include shorter periods of DAPT followed by single antiplatelet treatment with either aspirin or P2Y12 monotherapy, guided or unguided de-escalation DAPT, prolonged DAPT beyond the 12-month treatment period. Although DAPT composition and duration should be selected for each ACS patient on an individual basis weighing clinical and procedural variables, data from latest trials and meta-analyses may permit suggesting the most appropriate DAPT strategy according to the ischemic and bleeding risk assessed using validated tools and scores.

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry.

BACKGROUND: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. METHODS AND RESULTS: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively). CONCLUSIONS: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.