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.

SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion.

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older (P = .002), less often active smokers (P = .002), and hypercholesterolemic (P = .006), they presented more often later than 12 h (P = .037), more often to the hub and were more often in cardiogenic shock (P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow (P = .029) and more thrombectomy (P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

BACKGROUND AND AIMS: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. RESULTS: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. CONCLUSIONS: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI.

BACKGROUND: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. OBJECTIVES: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment. METHODS: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic. CONCLUSIONS: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655).

Primary prophylaxis in children with haemophilia.

Starting from the clinical observations that moderate haemophiliacs experienced only few bleeding episodes and rarely developed significant joint deterioration (haemophilic arthropathy), and the pioneer experience in Sweden, prophylaxis (i.e. the regular and long-term administration of clotting factor concentrate in order to prevent bleeding) has been practiced for more than forty years in severe haemophilia and is currently recommended as the first choice of treatment by the World Health Organisation and World Federation of Hemophilia and by many national medical/scientific organizations. Observational studies clearly established the superiority of prophylaxis over on-demand treatment in reducing the risk of arthropathy, also showing that starting prophylaxis earlier in life and after very few joint bleeds was associated with better joint outcomes, and led to the current definitions of primary (started before the age of 2 yrs and after no more than one joint bleed) and secondary prophylaxis. More recently, evidences from randomized trials, which were previously lacking in this setting, were also provided. This review summarizes available data from which current clinical practice of primary (and early secondary) prophylaxis in children with severe haemophilia was drawn. Open issues concerning optimal regimens and barriers to the implementation of prophylaxis are also discussed.

Predictive parameters of left ventricular reverse remodeling in response to cardiac resynchronization therapy in patients with severe congestive heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) is useful for the treatment of severe congestive heart failure. Unfortunately up to 30% of patients could be non-responders. The aim of our study was to find parameters to predict responsiveness to CRT. METHODS: Fifteen patients (9 males, 6 females, mean age 67.3 +/- 7.8 years, range 52-83 years) with dilated cardiomyopathy, NYHA functional class III-IV, left ventricular (LV) ejection fraction < 35% and QRS > or = 110 ms, underwent CRT. All the patients had echocardiographic evidence of systolic dys-synchrony. RESULTS: One patient died of electromechanical dissociation. The remaining 14 patients maintained biventricular stimulation at 6 months; mean QRS width decreased from 156 to 132 ms (p < 0.001). Ten patients (71%) were considered responders because of a reduction in LV end-systolic volume > 15%. In non-responders (4 patients, 29%) LV end-systolic volume was stable in 3 patients and increased in 1. LV ejection fraction significantly increased only in responders (p < 0.001). Responders had more severe pre-pacing dyssynchrony than non-responders (p < 0.001). Inter- (p = 0.002) and intraventricular dyssynchrony (p = 0.003) did significantly reduce after CRT only in responders. On multiple regression analysis there were two independent predictors of reverse remodeling after pacing: the baseline mitral QS-tricuspid QS (QSm-QSt) time (B = -1.7, p = 0.005) and the intraventricular dyssynchrony index (B = -1.55, p = 0.007). Pre-implant QSm-QSt of 38 ms correctly identified the two groups: responders had a value > 38 ms and non-responders < 38 ms. The pre-implant intraventricular dyssynchrony index of 28 ms was the cut-off value: responders had an index > 28 ms, non-responders < 28 ms. CONCLUSIONS: In the literature a tissue Doppler imaging index of intraventricular dyssynchrony evaluated before implantation is used to select responders to CRT. In our work we studied interventricular and intraventricular dyssynchrony, and both the QSm-QSt time and the standard deviation of the 12 LV segment QS time were correctly able to identify responders.

Usefulness of transthoracic color Doppler echocardiography for the identification of left anterior descending coronary artery stenosis.

We briefly describe our experience with transthoracic Doppler echocardiography for the direct evaluation of mid-distal left anterior descending coronary artery (LAD) stenosis. Three patients with previous myocardial infarction, scheduled for coronary flow reserve evaluation, underwent Doppler analysis of the mid-distal LAD. In all 3 cases, the mid-distal LAD stenosis was accurately quantified by the Doppler spectrum as confirmed by quantitative coronary angiography. Our study demonstrated the feasibility of transthoracic Doppler echocardiography in the discrimination of significant and non-significant mid-distal LAD stenosis. Limitations of such a technique could be related to the variable coronary anatomy and to the severity of the atherosclerotic process.