Intravenous antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention : A report from the INVEST-STEMI group.

The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2-5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30-0.53). The risk of BARC 2-5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92-1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Postprocedural trans-mitral gradient in patients with degenerative mitral regurgitation undergoing mitral valve transcatheter edge-to-edge repair.

BACKGROUND: The relationship between high postprocedural mean gradient (ppMG) and clinical events following mitral valve transcatheter edge-to-edge repair (MV-TEER) in patients with degenerative mitral regurgitation (DMR) is still debated. AIM: The purpose of this study was to evaluate the effect of elevated ppMG after MV-TEER on clinical events in patients with DMR at 1-year follow-up. METHODS: The study included 371 patients with DMR treated with MV-TEER enrolled in the "Multi-center Italian Society of Interventional Cardiology (GISE) registry of trans-catheter treatment of mitral valve regurgitation" (GIOTTO) registry. Patients were stratified in tertiles according to ppMG. Primary endpoint was a composite of all-cause death and hospitalization due to heart failure at 1-year follow-up. RESULTS: Patients were stratified as follows: 187 with a ppMG ≤ 3 mmHg, 77 with a ppMG > 3/=4 mmHg, and 107 with a ppMG > 4 mmHg. Clinical follow-up was available in all subjects. At multivariate analysis, neither a ppMG > 4 mmHg nor a ppMG ≥ 5 mmHg were independently associated with the outcome. Notably, the risk of elevated residual MR (rMR > 2+) was significantly higher in patients belonging to the highest tertile of ppMG (p = 0.009). The association of ppMG > 4 mmHg and rMR ≥ 2+ was strongly and independently associated with adverse events (hazard ratio: 1.98; 95% confidence interval: [1.10-3.58]). CONCLUSIONS: In a real-world cohort of patients suffering DMR and treated with MV-TEER, isolated ppMG was not associated with the outcome at 1-year follow-up. A high proportion of patients showed both elevated ppMG and rMR and their combination appeared to be a strong predictor of adverse events.

Clinical outcome of patients with ST-elevation myocardial infarction and angiographic evidence of coronary artery ectasia.

OBJECTIVES: The aim of this study was to describe the prevalence of coronary artery ectasia (CAE) in patients with ST-elevation myocardial infarction (STEMI) and to compare the long-term outcome of subjects with and without CAE undergoing emergent coronary angiography. BACKGROUND: The prognostic impact of CAE in STEMI patients has been poorly investigated. METHODS: This retrospective, single-center, study included consecutive patients with STEMI undergoing emergent coronary angiography from January 2012 to December 2017. The primary endpoint was the assessment of recurrent myocardial infarction (MI) in patients with versus those without CAE at the longest available follow-up. The propensity score weighting technique was employed to account for potential selection bias between groups. RESULTS: From 1,674 patients with STEMI, 154 (9.2%) had an angiographic evidence of CAE; 380 patients were included in the no CAE group. CAE patients were more often males and smokers, and showed a lower prevalence of diabetes than no CAE patients. After percutaneous coronary intervention, the corrected thrombolysis in MI frame count (p < .001) and the myocardial blush grade (p < .001) were significantly lower in CAE than in no CAE patients. The mean follow-up was 1,218.3 ± 574.8 days. The adjusted risk for the primary outcome resulted significantly higher in patients with CAE compared to those without (adjusted HR: 1.84; p = .017). No differences in terms of all-cause and cardiac death were found between groups. CONCLUSIONS: In this study, STEMI patients with CAE had a distinct clinical and angiographic profile, and showed a significantly higher risk of recurrent MI than those without CAE.

Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients.

BACKGROUND: A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19. METHODS: MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death. RESULTS: The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9-15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04-1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02-1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01-1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01-1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99-1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models. CONCLUSIONS: This meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.

ANMCO POSITION PAPER: Role of intra-aortic balloon pump in patients with acute advanced heart failure and cardiogenic shock.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

Transcatheter Repair of Functional Mitral Regurgitation in Heart Failure Patients　- A Meta-Analysis of 23 Studies on MitraClip Implantation.

BACKGROUND: The aim of this study was to investigate long-term survival, clinical status, and echocardiographic findings of patients with severe functional mitral regurgitation (FMR) undergoing MitraClip (MC) treatment and to explore the role of baseline features on outcome. Methods and Results: Randomized and observational studies of FMR patients undergoing MC treatment were collected to evaluate the overall survival, New York Heart Association (NYHA) class and echocardiographic changes after MC treatment. Baseline parameters associated with mortality and echocardiographic changes were also investigated. Across 23 studies enrolling 3,253 patients, the inhospital death rate was 2.31%, whereas the mortality rate was 5.37% at 1 month, 11.87% at 6 months, 18.47% at 1 year and 31.08% at 2 years. Mitral regurgitation Grade <3+ was observed in 92.76% patients at discharge and in 83.36% patients at follow-up. At follow-up, 76.63% of patients NYHA Class I-II and there were significant improvements in left ventricular (LV) volume, ejection fraction, and pulmonary pressure. Atrial fibrillation (AF) had a significant negative effect on 1-year survival (ß=0.18±0.06; P=0.0047) and on the reduction in LV end-diastolic and end-systolic volumes (ß=-1.05±0.47 [P=0.0248] and ß=-2.60±0.53 [P=0.0024], respectively). CONCLUSIONS: MC results in durable reductions in mitral regurgitation associated with significant clinical and echocardiographic improvements in heart failure patients. AF negatively affects LV reverse remodeling and 1-year survival after MC treatment.

RETRACTED: De Vecchis et al. An Admission-to-Discharge BNP Increase Is a Predictor of Six-Month All-Cause Death in ADHF Patients: Inferences from Multivariate Analysis Including Admission BNP and Various Clinical Measures of Congestion. J. Clin. Med. 2016, 5, 99.

The Journal of Clinical Medicine retracts the article "An Admission-to-Discharge BNP Increase Is a Predictor of Six-Month All-Cause Death in ADHF Patients: Inferences from Multivariate Analysis Including Admission BNP and Various Clinical Measures of Congestion" [...].

RETRACTED: De Vecchis et al. Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice? J. Clin. Med. 2016, 5, 86.

The Journal of Clinical Medicine retracts the article "Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice [...].

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study.

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

Transcatheter mitral valve repair with MitraClip: comparison of NT, NTr, and XTr Devices.

OBJECTIVES: Transcatheter edge-to-edge repair (TEER) has become an established minimally invasive treatment for significant mitral regurgitation. Ongoing refinements and the availability of different clipping devices have expanded the indications for and effectiveness of TEER, but comprehensive comparative data on this issue are lacking. In this study, we compared NT, NTr, and XTr MitraClip devices (Abbot) for TEER. METHODS: Details on patient, imaging, and procedural details, as well as short- and long-term outcomes, were sought from a national prospective clinical registry on TEER with MitraClip. The primary outcome of interest was discharge after procedural success without major clinical complications. RESULTS: A total of 2236 patients were included, 1228 (54.9%) in whom NT implantation only was attempted, 233 (10.4%) in whom NTr but not XTr implantation was attempted, and 775 (34.7%) in whom XTr implantation was attempted. Clinical and imaging features differed substantially across the groups, reflecting expanding indications with NTr and XTr devices. In-hospital outcomes were largely similar among the 3 groups, including death. Long-term unadjusted estimates of effect showed significant differences in several outcomes, including death, rehospitalization, and their composite, which demonstrated that NT was associated with more unfavorable outcomes compared with the other devices (all P less than .05). However, most differences depended on baseline features, as adjusted analysis showed no significant differences for early as well as long-term outcomes, including long-term death, rehospitalization, and their composite (all P greater than .05). CONCLUSIONS: New-generation MitraClip devices are associated with favorable procedural and clinical outcomes, despite being used in patients with more adverse features, when compared with patients treated with previous devices.

Prognostic Impact of Mitral Regurgitation Before and After Transcatheter Aortic Valve Replacement in Patients With Severe Low-Flow, Low-Gradient Aortic Stenosis.

Background There is little evidence about the prognostic role of mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the prevalence and outcome implications of MR severity in patients with low-flow, low-gradient aortic stenosis undergoing TAVR, and to evaluate whether MR improvement after TAVR could influence clinical outcome. Methods and Results This study included consecutive patients with low-flow, low-gradient aortic stenosis undergoing TAVR at 2 Italian high-volume centers. The study population was categorized according to the baseline MR severity and to the presence of MR improvement at discharge. The primary outcome was the composite of all-cause death and hospitalization for worsening heart failure up to 1 year. The study included 268 patients; 57 (21%) patients showed MR >2+. Patients with MR >2+ showed a lower 1-year survival free from the primary outcome (P<0.001), all-cause death (P<0.001), and heart failure hospitalization (P<0.001) compared with patients with MR ≤2+. At multivariable analysis, baseline MR >2+ was an independent predictor of the primary outcome (P<0.001). Among patients with baseline MR >2+, MR improvement was reported in 24 (44%) cases after TAVR. The persistence of MR was associated with a significantly reduced survival free from the primary outcome, all-cause death, and heart failure hospitalization up to 1 year. Conclusions In this study, the presence of moderately severe to severe MR in patients with low-flow, low-gradient aortic stenosis undergoing TAVR portends a worse clinical outcome at 1 year. TAVR may improve MR severity in nearly half of the patients, resulting in a potential outcome benefit after discharge.

Impact of coronary artery disease on outcome after transcatheter edge-to-edge mitral valve repair with the MitraClip system.

BACKGROUND: The clinical impact of coronary artery disease (CAD) on the prognosis of patients undergoing MitraClip implantation is still unclear. METHODS: One thousand nine hundred fifty-three patients undergoing MitraClip implantation included in the multicenter GIOTTO Registry were stratified according to CAD. Endpoints were all-cause death, cardiac death, and re-hospitalization for heart failure at follow-up (median 15.8 months). RESULTS: Although younger, CAD patients were more symptomatic, had worse cardiovascular risk profile, higher burden of comorbidities, more frequently affected by functional MR, with higher left ventricle (LV) diameters and lower ejection fraction (EF). At follow-up, CAD patients showed higher rates of all-cause death (25.4% vs. 19.6%; P=0.002), cardiovascular death (14.0% vs. 10.1%; P=0.007) and re-hospitalization for heart failure (13.9% vs. 10.2%; P=0.011). Dividing the population according to mitral regurgitation (MR) etiology (functional vs. non-functional MR), no differences were observed between CAD and no-CAD patients. At multivariate logistic regression, NYHA III/IV class, prior heart failure hospitalization, severe chronic kidney disease, atrial fibrillation, LV end-diastolic diameter and LVEF<30% but not CAD resulted independent predictors of all-cause death. The same finding was confirmed even after propensity score adjustment. CONCLUSIONS: CAD did not show a relevant impact on mid-term prognosis per se, but seemed to identify a more complex and diseased cohort of patients with worse clinical and functional status.

Bioprosthetic Valve Fracture After TAVR Complicated by Balloon Rupture: Bail-Out TAVR in TAVR in SAVR.

Transcatheter aortic valve replacement in surgical aortic valve is a safe and effective procedure to treat patients with failed bioprosthetic surgical valves at high risk for reoperation. Performing bioprosthetic valve fracture has been shown to improve postprocedural hemodynamics of TAVR in surgical aortic valve replacement. However, specific complications related to valve fracture are becoming more common. (Level of Difficulty: Advanced.).

Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome.

OBJECTIVE: The advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population. METHODS: This was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death. RESULTS: The study population included 825 patients (median age: 72.0 (63.0-78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047). CONCLUSIONS: In this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.

Implantation of one, two or multiple MitraClip™ for transcatheter mitral valve repair: insights from a 1824-patient multicenter study.

BACKGROUND: Transcatheter mitral valve repair (TMVR) with MitraClip™ (Abbott Laboratories; Abbott Park, IL, USA) is an established treatment for mitral regurgitation (MR). More than one MitraClip™ may be implanted if a single one does not reduce MR adequately. We aimed to appraise the outlook of patients undergoing implantation of one, two or multiple MitraClip™ for TMVR. METHODS: Exploiting the ongoing prospective GISE Registry of Transcatheter Treatment of Mitral Valve Regurgitation (GIOTTO) Study dataset, we compared patients, procedural details and outcomes distinguishing those receiving one, two or multiple MitraClip™. The primary endpoint was the composite of 1-year cardiac death or rehospitalization for heart failure. Additional endpoints included all cause death, surgical mitral repair, and functional class. Multivariable adjusted Cox proportional hazard analysis was used for confirmatory purposes. RESULTS: As many as 1824 patients were included: 718 (39.4%) treated with a single MitraClip™, and 940 (51.5%) receiving two MitraClip™, and 166 (9.1%) receiving three or more. Significant differences were found for baseline features, including age, female gender, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, atrial fibrillation, permanent pacemaker, cardiac resynchronization therapy, implantable cardioverter defibrillator, and prior mitral valve repair (all P<0.05). Several imaging features were also different, including left ventricular dimensions, MR severity and proportionality, mitral valve area, flail leaflet, and pulmonary vein flow (all P<0.05). Among procedural features, significant differences were found for anesthesia type, MitraClip™ type, fluoroscopy, device, and operating room times, postprocedural mitral gradient, residual MR, smoke-like effect, device success partial detachment and surgical conversion (all P<0.05). In-hospital death occurred more frequently in patients receiving multiple MitraClip™, and the same applied severe residual MR (all P<0.05). Mid-term follow-up (15±13 months) showed significant differences in the risk of death, cardiac death, rehospitalization for heart failure, and their composites, mainly, but not solely, associated with multiple MitraClip™ (all P<0.05). Adjusted analysis confirmed the significantly increased risk of composite adverse events when comparing the multiple vs. single MitraClip™ groups (P=0.014 for death and rehospitalization, P=0.013 for cardiac death or rehospitalization). CONCLUSIONS: Implantation of one or two MitraClip™ is associated with favorable clinical outcomes. Conversely, bail-out implantation of three or more MitraClip™ may portend a worse long-term prognosis.

Retraction: De Vecchis, R., et al. Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea. J. Clin. Med. 2016, 5, 85.

The journal retracts the article "Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea" by De Vecchis, R [...].