Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry.

Background: Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods: Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results: 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion: Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399.

Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry.

BACKGROUND: The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. METHODS: HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. RESULTS: We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure. CONCLUSION: RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.

Anticoagulation Therapy in Patients With Coronavirus Disease 2019: Results From a Multicenter International Prospective Registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 [HOPE-COVID19]).

OBJECTIVES: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival. DESIGN: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019). SETTING: Hospitalized patients with coronavirus disease 2019. PATIENTS: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients. INTERVENTIONS: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient. MEASUREMENTS AND MAIN RESULTS: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49-0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49-0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51-1.01) in noninvasive ventilation. CONCLUSIONS: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation.

Clinical profile and prognosis in patients on oral anticoagulation before admission for COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) shows high morbidity and mortality, particularly in patients with concomitant cardiovascular diseases. Some of these patients are under oral anticoagulation (OAC) at admission, but to date, there are no data on the clinical profile, prognosis and risk factors of such patients during hospitalization for COVID-19. DESIGN: Subanalysis of the international 'real-world' HOPE COVID-19 registry. All patients with prior OAC at hospital admission for COVID-19 were suitable for the study. All-cause mortality was the primary endpoint. RESULTS: From 1002 patients included, 110 (60.9% male, median age of 81.5 [IQR 75-87] years, median Short-Form Charlson Comorbidity Index [CCI] of 1 [IQR 1-3]) were on OAC at admission, mainly for atrial fibrillation and venous thromboembolism. After propensity score matching, 67.9% of these patients died during hospitalization, which translated into a significantly higher mortality risk compared to patients without prior OAC (HR 1.53, 95% CI 1.08-2.16). After multivariate Cox regression analysis, respiratory insufficiency during hospitalization (HR 6.02, 95% CI 2.18-16.62), systemic inflammatory response syndrome (SIRS) during hospitalization (HR 2.29, 95% CI 1.34-3.91) and the Short-Form CCI (HR 1.24, 95% CI 1.03-1.49) were the main risk factors for mortality in patients on prior OAC. CONCLUSIONS: Compared to patients without prior OAC, COVID-19 patients on OAC therapy at hospital admission showed lower survival and higher mortality risk. In these patients on OAC therapy, the prevalence of several comorbidities is high. Respiratory insufficiency and SIRS during hospitalization, as well as higher comorbidity, pointed out those anticoagulated patients with increased mortality risk.

COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

COVID-19 anosmia and gustatory symptoms as a prognosis factor: a subanalysis of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry.

Olfactory and gustatory dysfunctions (OGD) are a frequent symptom of coronavirus disease 2019 (COVID-19). It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2 could be due to olfactory bulb invasion, conversely studies suggest it could be a good prognostic factor. The aim of the current study was to investigate the prognosis value of OGD in COVID-19. These symptoms were recorded on admission from a cohort study of 5868 patients with confirmed or highly suspected COVID-19 infection included in the multicenter international HOPE Registry (NCT04334291). There was statistical relation in multivariate analysis for OGD in gender, more frequent in female 12.41% vs 8.67% in male, related to age, more frequent under 65 years, presence of hypertension, dyslipidemia, diabetes, smoke, renal insufficiency, lung, heart, cancer and neurological disease. We did not find statistical differences in pregnant (p = 0.505), patient suffering cognitive (p = 0.484), liver (p = 0.1) or immune disease (p = 0.32). There was inverse relation (protective) between OGD and prone positioning (0.005) and death (< 0.0001), but no with ICU (0.165) or mechanical ventilation (0.292). On univariable logistic regression, OGD was found to be inversely related to death in COVID-19 patients. The odds ratio was 0.26 (0.15-0.44) (p < 0.001) and Z was - 5.05. The presence of anosmia is fundamental in the diagnosis of SARS.CoV-2 infection, but also could be important in classifying patients and in therapeutic decisions. Even more knowing that it is an early symptom of the disease. Knowing that other situations as being Afro-American or Latino-American, hypertension, renal insufficiency, or increase of C-reactive protein (CRP) imply a worse prognosis we can make a clinical score to estimate the vital prognosis of the patient. The exact pathogenesis of SARS-CoV-2 that causes olfactory and gustative disorders remains unknown but seems related to the prognosis. This point is fundamental, insomuch as could be a plausible way to find a treatment.

Clinical profile and predictors of in-hospital mortality among older patients hospitalised for COVID-19.

BACKGROUND: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. METHODS: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. RESULTS: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality. CONCLUSION: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population.

Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry.

BACKGROUND: The COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF). METHODS: We conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated. RESULTS: 1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2 saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint. CONCLUSION: NIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis. TRIAL REGISTRATION NUMBERS: NCT04334291/EUPAS34399.

Outcomes of Isolated Tricuspid Valve Surgery.

BACKGROUND: Isolated tricuspid valve surgery is a rarely performed procedure and traditionally is associated with a bad prognosis, although its clinical outcomes still are little known. The aim of this study was to assess the short- and long-term clinical outcomes obtained at our center after isolated tricuspid valve surgery as treatment for severe tricuspid regurgitation. METHODS: This retrospective study included 71 consecutive patients with severe tricuspid regurgitation who underwent isolated tricuspid valve surgery between December 1996 and December 2017. Perioperative and long-term mortality, tricuspid valve reoperation, and functional class were analyzed after follow up. RESULTS: Regarding surgery, 7% of patients received a De Vega annuloplasty, 14.1% an annuloplasty ring, 11.3% a mechanical prosthesis, and 67.6% a biological prosthesis. Perioperative mortality was 12.7% and no variable was shown to be predictive of this event. After a median follow up of 45.5 months, long-term mortality was 36.6%, and the multivariate analysis identified atrial fibrillation as the only predictor (Hazard Ratio 3.014, 95% confidence interval 1.06-8.566; P = 0.038). At the end of follow up, 63.6% of survivors had functional class I. CONCLUSIONS: Isolated tricuspid valve surgery was infrequent in our center. Perioperative mortality was high, as was long-term mortality. However, a high percentage of survivors were barely symptomatic after follow up.

Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study.

Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.

Infective endocarditis in patients with bicuspid aortic valve: Clinical characteristics, complications, and prognosis. / Endocarditis infecciosa sobre válvula aórtica bicúspide: características clínicas, complicaciones y pronóstico.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE). METHODS: Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV). RESULTS: Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048). CONCLUSIONS: Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher.

The importance of data in Pulmonary Arterial Hypertension: from international registries to Machine Learning. / La importancia de los datos en la hipertensión arterial pulmonar: de los registros internacionales al machine learning.

Real-world registries have been critical to building the scientific knowledge of rare diseases, including Pulmonary Arterial Hypertension (PAH). In the past 4 decades, a considerable number of registries on this condition have allowed to improve the pathology and its subgroups definition, to advance in the understanding of its pathophysiology, to elaborate prognostic scales and to check the transferability of the results from clinical trials to clinical practice. However, in a moment where a huge amount of data from multiple sources is available, they are not always taken into account by the registries. For that reason, Machine Learning (ML) offer a unique opportunity to manage all these data and, finally, to obtain tools that may help to get an earlier diagnose, to help to deduce the prognosis and, in the end, to advance in Personalized Medicine. Thus, we present a narrative revision with the aims of, in one hand, summing up the aspects in which data extraction is important in rare diseases -focusing on the knowledge gained from PAH real-world registries- and, on the other hand, describing some of the achievements and the potential use of the ML techniques on PAH.

Effectiveness of a Prostacyclin IP Receptor Agonist in Patients With Pulmonary Arterial Hypertension in the Real-world Andalusian Setting: The RAMPHA Study.

PURPOSE: The pillar for therapeutic decisions in the evolution of pulmonary arterial hypertension (PAH) is the patients' prognostic stratification. METHODS: A retrospective cohort study was conducted in a Spanish real-world setting to assess the clinical improvement of PAH patients treated with selexipag measured as changes in the risk profile. Secondary objectives were to describe their baseline characteristics, initial risk status, and variables used to assess patient survival and adverse events. FINDINGS: Total 42 patients (mean age 52.36 [SD: 15.09] years) were included. All had received initial endothelin receptor antagonist treatment and 95.2% dual therapy with phosphodiesterase-5 inhibitor or riociguat. At 6 to 12 months from baseline, patients risk stratification tripled the percentage of patients with low risk, and a trend towards improved risk stratification (P = 0.122). World Health Organization functional class changed, with more patients in milder classes (P = 0.003), and symptom progression slowed down (P < 0.0001). At 3-years, survival was 85.7% and the estimated median survival time was 2.73 years (SD: 1.351; 95% CI: 2.51-2.95). IMPLICATIONS: Selexipag did not achieve a significant improvement in risk profile, although it did show an excellent survival rate, effectively improved functional class, and delayed symptom progression in real life. Selexipag was well tolerated and showed a favorable safety profile, supporting a clinical benefit for PAH patients.

Index and Repeat Ablation for Atrial Fibrillation in Older versus Younger Patients: A Propensity-Score Matching Analysis.

Catheter ablation is a well-established rhythm control therapy in atrial fibrillation (AF). Although the prevalence of AF increases dramatically with age, the prognosis and safety profile of index and repeat ablation procedures remain unclear in the older population. The primary endpoint of this study was to assess the arrhythmia recurrence, reablation and complication rates in older patients. Secondary endpoints were the identification of independent predictors of arrhythmia recurrence and reablation, including information on pulmonary vein (PV) reconnection and other atrial foci. Older (n=129, ≥70 years) and younger (n=129, <70 years) patients were compared using a propensity-score matching analysis based on age, gender, obesity, hypertension, dyslipidemia, diabetes mellitus, dilated left atrium, severe obstructive sleep apnea, cardiac disease, left systolic ventricular function, AF pattern and ablation technique. Arrhythmia recurrence and reablation were evaluated in both groups using a Cox regression analysis in order to identify predictors. During a 30-month follow-up period, there were no significant differences between older and younger patients in the arrhythmia-free survival (65.1% and 59.7%; log-rank test p=0.403) and complication (10.1% and 10.9%; p>0.999) rates after the index ablation. However, the reablation rate was significantly different (46.7% and 69.2%; p<0.05, respectively). In those patients who underwent reablation procedure (redo subgroups), there were no differences in the incidence of PV reconnection (38.1% redo-older and 27.8% redo-younger patients; p=0.556). However, the redo-older patients had lower reconnected PVs per patient (p<0.01) and lower atrial foci (2.3 and 3.7; p<0.01) than the redo-younger patients. A further important finding was that age was not an independent predictor of arrhythmia recurrence or reablation. Our data reveal that the AF index ablation in older patients had a similar efficacy and safety profile to younger patients. Therefore, age alone must not be considered a prognostic factor for AF ablation but the presence of limiting factors such as frailty and multiple comorbidities.

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score.

BACKGROUND: Long-term consequences of COVID-19 are still partly known. AIM OF THE STUDY: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. METHODS: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. RESULTS: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1-4 points for age class (<65 years, 65-74, 75-84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (<3, 3-6, >6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). CONCLUSIONS: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Spontaneous coronary artery dissection and ST-segment elevation myocardial infarction: Does clinical presentation matter?

BACKGROUND: Some patients with spontaneous coronary artery dissection (SCAD) present as ST-segment-elevation myocardial infarction (STEMI). This study evaluates the characteristics, management and outcomes of SCAD patients presenting as STEMI compared to non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We analysed data from consecutive patients included in the prospective Spanish Registry on SCAD. All coronary angiograms were centrally reviewed. All adverse events were adjudicated by an independent Clinical Events Committee. RESULTS: Between June 2015 to December 2020, 389 patients were included. Forty-two percent presented with STEMI and 56% with NSTEMI. STEMI patients showed a worse distal flow (TIMI flow 0-1 38% vs 19%, p < 0.001) and more severe (% diameter stenosis 85 ± 18 vs 75 ± 21, p < 0.001) and longer (42 ± 23 mm vs 35 ± 24 mm, p = 0.006) lesions. Patients with STEMI were more frequently treated with percutaneous coronary intervention (PCI) (31% vs 16%, p < 0.001) and developed more frequently left ventricular systolic dysfunction (21% vs 8%, p < 0.001). No differences were found in combined major adverse events during admission (7% vs 5%, p = 0.463), but in-hospital reinfarctions (5% vs 1.4%, p = 0.039) and cardiogenic shock (2.6% vs 0%, p = 0.019) were more frequently seen in the STEMI group. At late follow-up (median 29 months) no differences were found in the incidence of major adverse cardiac and cerebrovascular events (13% vs 13%, p-value = 0.882) between groups. CONCLUSIONS: Patients with SCAD and STEMI had a worse angiographic profile and were more frequently referred to PCI compared to NSTEMI patients. Despite these disparities, both short and long-term prognosis were similar in STEMI and NSTEMI SCAD patients.

Post-COVID-19 Symptoms and Heart Disease: Incidence, Prognostic Factors, Outcomes and Vaccination: Results from a Multi-Center International Prospective Registry (HOPE 2).

BACKGROUND: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. METHODS: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. RESULTS: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81-3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04-0.19). CONCLUSIONS: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.

Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice.

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.