The VENERE Study: EffectiVenEss of a Rehabilitation Treatment With Nordic Walking in ObEse or OveRweight Diabetic PatiEnts With Cardiovascular Disease.

Background: Nordic walking (NW) has several potential benefits for individuals with cardiovascular (CV) disease, type 2 diabetes, and obesity and/or overweight. NW improves cardiovascular health, including exercise capacity and blood pressure control. NW enhances glycemic control and insulin sensitivity in diabetes, and aids in weight management and body composition improvement. NW offers additional advantages, such as improvement in muscular strength, joint mobility, physical activity levels, and psychological well-being. Methods: This open-label study with 3 arms will aim to evaluate the efficacy, safety, and adherence to exercise prescription in obese and/or overweight diabetic patients with CV complications. The primary objective will be to assess the CV performance of participants after a 6-month and a 12-month follow-up period, following a 3-month NW intervention, compared with standard rehabilitation, and with cardiological counseling (control group) training lasting 3 months. Results: The results of the study will provide valuable insights into the comparative effectiveness of a NW intervention vs standard rehabilitation and control group training in improving CV performance in obese and/or overweight diabetic patients with CV complications. Additionally, safety and adherence data will help inform the feasibility and sustainability of the exercise prescription over an extended period. Conclusions: These findings may have implications for the development of tailored exercise programs for this specific patient population, with the aim of optimizing CV health outcomes. Clinical Trials Registration: NCT05987410.

Contexte: La marche nordique offre plusieurs bienfaits potentiels aux personnes atteintes d'une maladie cardiovasculaire (CV), de diabète de type 2, de surpoids ou d'obésité. Elle améliore la santé cardiovasculaire, notamment l'endurance à l'effort et la régulation de la pression artérielle, en plus de favoriser l'équilibre glycémique et d'accroître la sensibilité à l'insuline chez les personnes diabétiques. Elle facilite également la gestion du poids et l'amélioration de la composition corporelle. Par ailleurs, la marche nordique présente d'autres avantages, comme l'augmentation de la force musculaire, de la mobilité articulaire, du niveau d'activité physique et du bien-être psychologique. Méthodologie: Cette étude ouverte à 3 groupes vise à évaluer l'efficacité, la sécurité et l'observance des exercices prescrits chez des sujets diabétiques obèses ou en surpoids présentant des complications CV. Le principal objectif consistera à évaluer la performance CV des participants au cours d'une période de suivi de 6 et 12 mois après un programme de marche nordique de 3 mois, comparativement à un programme de réadaptation standard et à un programme d'encadrement en soins CV (groupe témoin) de 3 mois. Résultats: Les résultats de l'étude fourniront de précieux renseignements sur l'efficacité d'un programme de marche rapide comparativement à un programme de réadaptation standard et à un programme d'encadrement (groupe témoin) pour améliorer la performance CV chez des sujets diabétiques obèses ou en surpoids présentant des complications CV. Les données relatives à la sécurité et à l'observance permettront également d'évaluer la faisabilité et la viabilité de la prescription d'exercices sur une longue période. Conclusions: Ces résultats pourraient s'avérer utiles dans l'élaboration de programmes d'exercices spécifiquement conçus pour cette population de patients, afin d'optimiser les résultats en santé CV. Numéro d'inscription de l'essai clinique: NCT05987410.

Relationships, Current Issues, Safety and Efficacy of Oral Anticoagulation in Cancer Patients with Atrial Fibrillation.

A relationship between malignancy and impaired hemostasis has been proven, and balancing clotting and bleeding risks can be challenging. Half of cancer patients with atrial fibrillation (AF) do not receive any oral anticoagulation (OAC). Using PubMed on the relationship between cancer and AF and their association with hemostasis, targeting studies comparing vitamin K antagonists (VKAs) and direct OAC (DOAC) strategies in AF cancer patients, three RCTs (>3000 patients) and eight observational studies (>250,000 patients) comparing different OACs were retrieved. The VKA prescribed was always warfarin. Dabigatran was the only DOAC not analyzed in the RCTs but the most used in non-randomized studies, whereas edoxaban-treated patients were the majority in the RCTs. Overall, the DOAC patients showed similar or lower rates of efficacy (thromboembolic) and safety (bleeding) outcomes compared to the VKA patients. DOACs are subject to fewer interactions with antineoplastic agents. DOACs may be preferable to VKAs as a thromboembolic prophylaxis in cancer patients with non-valvular AF.

Systematic Review and Meta-Analysis of Oral Anticoagulant Therapy in Atrial Fibrillation Cancer Patients.

(1) Introduction: Cancer and atrial fibrillation (AF) are increasingly coexisting medical challenges. These two conditions share an increased thrombotic and bleeding risk. Although optimal regimens of the most suitable anti-thrombotic therapy are now affirmed in the general population, cancer patients are still particularly understudied on the matter; (2) Aims And Methodology: This metanalysis (11 studies (incl. 266,865 patients)) aims at evaluating the ischemic-hemorrhagic risk profile of oncologic patients with AF treated with oral anticoagulants (vitamin K antagonists vs. direct oral anticoagulants); (3) Results: In the oncological population, DOACs confer a benefit in terms of the reduction in ischemic, hemorrhagic and venous thromboembolic events. However, ischemic prevention has a non-insignificant bleeding risk, lower than Warfarin but significant and higher than the non-oncological patients; (4) Conclusions: Anticoagulation with DOACs provides a higher safety profile with respect to VKAs in terms of stroke reduction and a relative bleeding reduction risk. Further studies are needed to better assess the optimal anticoagulation strategy in cancer patients with AF.

New Onset Atrial Fibrillation in STEMI Patients: Main Prognostic Factors and Clinical Outcome.

The indications for the treatment of patients with known atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are clear, while less is available about the management of new-onset AF (NOAF) during ST-segment elevation myocardial infarction (STEMI). The aim of this study is to evaluate mortality and clinical outcome of this high-risk subgroup of patients. We analyzed 1455 consecutive patients undergoing PCI for STEMI. NOAF was detected in 102 subjects, 62.7% males, with a mean age of 74.8 ± 10.6 years. The mean ejection fraction (EF) was 43.5 ± 12.1% and the mean atrial volume was increased (58 ± 20.9 mL). NOAF occurred mainly in the peri-acute phase and had a very variable duration (8.1 ± 12.5 min). During hospitalization, all the patients were treated with enoxaparin, but only 21.6% of them were discharged with long term oral anticoagulation. The majority of patients had a CHA2DS2-VASc score >2 and a HAS-BLED score of 2 or 3. The in-hospital mortality was 14.2%, while the 1-year mortality was 17.2% and long-term mortality 32.1% (median follow-up 1820 days). We identified age as an independent predictor of mortality both at short- and long-term follow-ups, while EF was the only independent predictor for in-hospital mortality and arrhythmia duration for 1-year mortality. At the 1-year follow-up, we recorded three ischemic strokes and no bleeding complications.

Uric acid associated with acute heart failure presentation in Acute Coronary Syndrome patients.

We focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcomes were acute HF and cardiogenic shock at admission, secondary outcomes were the use of Non Invasive Ventilation (NIV) and the admission Left Ventricular Ejection Fraction (LVEF). We consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Median age was 68 (first-third quartile 59-77) years and males were 970 (76%). All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (UA higher than 6 mg/dL for females and 7 mg/dL for males, n = 292): acute HF 35.8 vs 11.1% (p < 0.0001), cardiogenic shock 10 vs 3.1% (p < 0.0001), NIV 24.1 vs 5.1% (p < 0.0001) and lower admission LVEF (42.9±12.8 vs 49.6±9.9, p < 0.0001). By multivariable analyses, UA was confirmed to be significantly associated with all the outcomes with the following Odds Ratio (OR): acute HF OR = 1.119; 95% CI 1.019;1.229; cardiogenic shock OR = 1.157; 95% CI 1.001;1.337; NIV use OR = 1.208; 95% CI 1.078;1.354; LVEF ß = -0.999; 95% CI -1.413;-0.586. We found a significant association between UA and acute HF, cardiogenic shock, NIV use and LVEF. Due to the cross-sectional nature of our study no definite answer on the direction of these relationship can be drawn and further longitudinal study on UA changes over time during an ACS hospitalization are needed.

Access-site hematoma in distal and conventional transradial access: a randomized trial.

BACKGROUND: Distal transradial access (dTRA) has been recently proposed as an innovative access for coronary procedures and a valuable alternative to conventional transradial access (cTRA). The aim of this study was to assess the safety of dTRA versus cTRA in patients undergoing percutaneous coronary angiography and intervention. METHODS: In this single-center randomized trial, consecutive patients admitted for stable cardiac condition or acute coronary syndrome (ACS) were assigned to dTRA or cTRA. The primary endpoint was an early discharge after transradial stenting of coronary arteries (EASY) grade ≥II access-site hematoma (ASH). Vascular access failure, radial artery occlusion (RAO) at hospital discharge, 30-day rates of death, myocardial infarction, stroke and bleeding not related to coronary artery bypass grafting were considered as secondary endpoints. RESULTS: A total of 204 patients were included and randomized to dTRA (N.=100) or cTRA (N.=104). The two populations were similar, except for a higher percentage of ACS in the dTRA than in the cTRA group (38% versus 24%, P=0.022). The rate of EASY grade ≥II ASH was lower in dTRA than in cTRA patients, but the difference was not statistically significant (4% versus 8.4%, respectively, P=0.25). Vascular access failure was more frequent in dTRA patients than in cTRA patients (34% versus 8.7%, P<0.0001). We detected no case of RAO at hospital discharge and similar rates of 30-day adverse events in both groups. CONCLUSIONS: DTRA is safe and feasible. When compared to cTRA, dTRA is technically more demanding and limited by more frequent crossover to an alternative vascular access.

Influence of Different COVID-19 Pandemic Phases on STEMI: Experience From an Italian Hub Centre.

INTRODUCTION: During Coronavirus disease 2019 (COVID-19) pandemic a reduction in ST-elevation acute myocardial infarction with an increase in in-hospital mortality has been observed. In our region the pandemic temporal trend was sinusoidal with peaks and valleys. A first outbreak was in March 2020, a reduction in May 2020 and a second outbreak in November 2020. MATHERIALS & METHODS: Our hospital was reorganized as one of the 13 Macro-Hubs identified in Lombardy and we retrospectively analysed consecutive STEMI patients hospitalized in the three different phases of COVID-19 pandemic. RESULTS: We did not register any difference in the number of STEMI hospitalized in the three phases. At multivariate analysis for the entire population COVID-19 infection was the strongest independent predictor of in-hospital mortality. Focusing on COVID-19 patients they experienced a 5-time increased incidence of in-hospital mortality (COVID-19pos vs COVID-19neg, 47.1% vs 8.6%; p < 0.0001) mainly driven by a higher incidence of respiratory complications (COVID-19pos vs COVID-19neg, 41.2% vs 6.2%; p < 0.0001) with a similar incidence of cardiac death. DISCUSSION: Among STEMI admitted during different phases of pandemic, this study found an increased mortality in patients affected by COVID-19; the co-presence of COVID-19 infection leads to an increase of mortality mostly related to respiratory complications. Interestingly the different incidence in the general population of COVID-19 did not influence the incidence of STEMI. CONCLUSION: In conclusion our data suggest the crucial need for an early and precise diagnosis of COVID-19 infection in STEMI to establish a correct management of these very high-risk patients.

Predictors of Mortality and Long-Term Outcome in Patients with Anterior STEMI: Results from a Single Center Study.

Anterior ST segment elevation myocardial infarction (A-STEMI) has the worst prognosis among all infarct sites due to larger infarct size and the higher cardiac enzyme release. We retrospectively analyzed 584 A-STEMI undergoing urgent coronary angiography from October 2008 to April 2019. The median follow-up time was 1774 days with a minimum of a 1-year follow-up for 498 patients. In-hospital mortality was 8.6%, while long-term, all-cause mortality and 1-year mortality were 18.8% and 6.8%, respectively. The main predictors for in-hospital mortality were ejection fraction (LV-EF), baseline estimated glomerular filtration rate (eGFR), female gender and cardiogenic shock (CS) at admission, while long-term predictors of mortality were age, coronary artery disease (CAD) extension and LV-EF. Patients presenting with CS (6.5%) showed a higher mortality rate (in-hospital 68.4%, long term 41.7%). Among 245 patients (42%) with multivessel disease (MVD), complete revascularization (CR) during the index procedure was performed in 42.8% of patients and more often in patients with CS at admission (19.1% vs. 6.1%, p = 0.008). Short- and long-term mortality were not significantly influenced by the revascularization strategy (CR/culprit only). Our study confirmed the extreme fragility of A-STEMI patients, especially in case of CS at admission. LV-EF is a powerful predictor of a poor outcome. In MVD, CR during p-PCI did not show any advantage for either long- or short-term mortality compared to the culprit-only strategy.

Meta-Analysis of Placebo-Controlled Trials of Levosimendan in Acute Myocardial Infarction.

The treatment of acute myocardial infarction is early revascularization. Heart failure and cardiogenic shock may complicate acute myocardial infarction despite applying the best available strategy. Levosimendan is a relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channel's opening, it also has a vasodilator effect which may participate concretely in the global effects of the drug. The focus of the literature is on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in acute myocardial infarction. The aim of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials. Based on the eight studies selected, we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction. With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischemic heart disease. Further studies specifically designed to investigate the early role in the treatment of ischemic heart failure are needed.

Safety and efficacy of rotational atherectomy in heavily calcified lesions involving coronary aneurysms.

Percutaneous transluminal rotational atherectomy (PTRA) is one of the most used techniques to facilitate percutaneous coronary intervention in heavily calcified coronary lesion (CCL). Coronary aneurysms (CAs) are detected in 1.2-4.9% of coronary angiogram. The presence of CA and CCL is infrequent but not rare, where the use of PTRA may be mandatory despite the high risk. After a complex procedure of PTRA in a CCL with CA we decided to investigate about this particular condition. We identified a total of six patients among 174 consecutive percutaneous coronary intervention (3.4%). All the procedures showed good stent expansion in the absence of major complications, such as no-reflow or coronary perforation. Cardiovascular death, rehospitalization for myocardial infarction and target lesion failure were not reported at follow-up (252 ± 152 days).

Takotsubo syndrome in COVID-19 era: Is psychological distress the key?

Covid-19 pandemic, starting from Wuhan, China spread all over the world and Italy was one of the most affected countries, especially in Lombardy, where, on February 20, the first confirmed case was detected. Italian Government ordered a national lockdown on the 9 th March 2020, forcing the population to severe restrictive isolation measures. The burden on mental health of the medical emergency related to COVID19 is progressively been revealed. Takotsubo syndrome (TTS), is estimated to represent 1-3% of patients admitted with suspected STEMI, mostly affecting elderly women with emotional stress and/or acute illness preceding the presentation. Comparing patients hospitalised from February to May 2020 with those of the corresponding period in 2019 we observed a significantly increased number of TTS diagnosis in 2020 (11 patients vs 3 in 2019), especially during the first period of lockdown. The only two males were patients with COVID-19 and were the only two who died in hospital. At psychological examination all patients enrolled report to have lived a particularly stressful experience at IES-R in the last year, without presenting the symptoms of a post-traumatic stress disorder. Most patients were positive to the allostatic overload. Only one patient showed a clinical cut-off for HADS and no one for the Fear COVID-19 scale. We finally concluded that subjects with pre-pandemic psychological distress may have experienced additional psychological overload, opening the door to TTS by a series of physiological alterations as the secretion of cortisol and catecholamines, making the subject more vulnerable to the onset of TTS.

Impact of COVID-19 on STEMI: Second youth for fibrinolysis or time to centralized approach?

On March 11th 2020 the World Health Organization declared the pandemic infection of SARS-CoV-2 (COVID-19) and Italy was one of the most affected country. The regional Emergency Medical System (EMS) founded itself facing an exponential increase in hospitalizations with a consequent organizational system crisis. Experts from Cina, UK and US suggested to reconsider thrombolysis as the best treatment in term of balance between time consumption and operators safety for ST-segment elevation myocardial infarction (STEMI) patients respect to primary PCI (pPCI). The system reorganization consisted in a centralization of all the emergency nets: from 55 hospitals with cardiac catheterization laboratories distributed within our region offering a 24/7 service we passed to 13 Hub and 42 Spoke centres. Dedicated in-hospital paths for patients COVID positive or suspected (pCOV+) and COVID negative (pCOV-) were instituted. We analysed all consecutive patients undergoing emergency coronary angiogram from March 14 to April 14, 2020 at San Carlo Hospital in Milan comparing the two different in-hospital paths. We collected 30 STEMI patients. Eighteen patients (60%) were treated in pCOV-, while twelve patients (40%) in pCOV+. No significant differences were found among the two groups regarding key time points of STEMI care and interestingly we didn't find any treatment delay in pCOV+. In conclusion, a focused overhaul of the EMS may allow to maintain pPCI as the treatment of choice for patients and operators.

Impact of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome.

BACKGROUND: To assess the association between admission serum uric acid (SUA) levels and in-hospital outcomes in a real-world patients population with acute coronary syndrome (ACS) and to investigate the potential incremental prognostic value of SUA added to GRACE score (GRACE-SUA score). METHODS: The data of consecutive ACS patients admitted to Coronary Care Unit of San Paolo and Niguarda hospitals in Milan (Italy) were retrospectively analyzed. RESULTS: 1088 patients (24% female) were enrolled. Mean age was 68 years (IQR 60-78). STEMI and NSTE-ACS patients were 504 (46%) and 584 (54%) respectively. SUA (OR 1.72 95%CI 1.33-2.22, p < 0.0001) and GRACE score (OR 1.04 95%CI 1.02-1.06, p < 0.0001) were significantly associated with an increased risk of in-hospital death at the multivariate analysis. Admission values of SUA were stratified in four quartiles. Rates of acute kidney injury, implantation of intra-aortic balloon pump and non-invasive ventilation use were significantly higher in the last quartile compared to Q1, Q2 and Q3 (p < 0.01). The areas under the ROC curve (AUC) for GRACE score and for SUA were 0.91 (95% CI 0.89-0.93, p < 0.0001) and 0.79 (95% CI 0.76-0.81, p < 0.0001) respectively. The AUC was larger for predicting in-hospital mortality with the GRACE-SUA score (0.94; 95% CI 0.93-0.95). CONCLUSIONS: High admission levels of SUA are independently associated with in-hospital adverse outcomes and mortality in a contemporary population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality in this study population.

Predictors of procedural and clinical outcome in rotational atherectomy: analysis of a single center registry.

BACKGROUND: Heavy calcified lesions can decrease effectiveness of drug eluted stents in preventing restenosis. Rotational atherectomy (RA) demonstrated to improve outcomes in patients with severely calcified lesions pretreated with debulking. However, its feasibility and its safety are continuously on stage. Our aim has been to identify predictors of clinical and procedural outcome in RA. METHODS: We retrospectively analyzed a population of patients referred to our cath lab for urgent or elective coronary catheterization treated with RA. The associations between clinical variables and clinical or procedural events were evaluated using logistic regression. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE) from procedure date to last day of follow-up. MACE have been defined as follows: cardiovascular death, heart failure hospitalization and target lesion revascularization. RESULTS: The registry included 68 of the 1908 (3.6%) patients that underwent percutaneous coronary intervention. Procedural success was as high as 94% and more than 90% of cases were treated without any complication. The most common complication during PCI with RA was vessel dissection (8.8%) and no procedural death occurred. None of the clinical nor procedural characteristics were associated with burr entrapment or vascular access hematoma. We identified as independent predictor of treated vessel dissection the female sex (OR 16.9, 95% CI 1.55-183.77, P<0.05). Logistic regression revealed age (OR 1.17, 95% CI: 1.02-1.33, P<0.02) as the only independent predictor of MACE. We therefore calculated the ROC curve on age in predicting MACE, that showed a C-statistics of 0.75 (95% CI 0.628 to 0.852, P=0.02), with 80 years old as the best threshold in defining high risk population. CONCLUSIONS: RA is a feasible and safe procedure. Females and elderly patients must be carefully selected in order to balance the risk/benefit ratio in these high-risk populations.

Comparison of CRUSADE and ACUITY-HORIZONS Bleeding Risk Scores in Patients With Acute Coronary Syndromes.

BACKGROUND: Compare the discriminative performance of two validated bleeding risk models for in-hospital bleeding events in a non-selected cohort of acute coronary syndrome (ACS) patients. METHODS: CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) and ACUITY-HORIZONS (Acute Catheterization and Urgent Intervention Triage strategY-Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) scores were calculated in 501 consecutive patients (median age 68 years (IQR 57-77), 31% female) admitted for ACS to the coronary care unit (CCU) of San Paolo Hospital in Milan (Italy). In-hospital haemorrhagic events and mortality were recorded and calibration and discrimination of the two risk models were evaluated using the Hosmer-Lemeshow test and the C-statistic, respectively. RESULTS: Overall bleeding events were observed in 32 patients and major bleedings in 11 (with an incidence of 6.4% and 2.2%, respectively). In-hospital mortality was 2.6%. Regarding major bleedings both risk scores demonstrated an adequate calibration (H-L test p>0.20) and a moderate discrimination with no significant difference in predictive accuracy between the two models (C-statistic 0.69 for CRUSADE and 0.73 for ACUITY-HORIZONS). We also tested the performance of the two risk models in predicting in-hospital mortality, showing an adequate calibration and a very good discrimination (C-statistic 0.88 and 0.89 for the CRUSADE and ACUITY-HORIZONS scores, respectively), with no significant difference in predictive accuracy. CONCLUSIONS: In our ACS population the CRUSADE and the ACUITY-HORIZONS risk scores showed a fairly good and comparable predictive accuracy regarding in-hospital bleeding events and they appeared to be very good predictors of in-hospital mortality.