Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6-8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial 'Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients' (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. METHODS: MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. SUMMARY: While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

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.

Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI).

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.

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.

Interinstitutional clinical practice guidelines for the treatment of acute myocardial infarction.

INTRODUCTION: Mexico has the highest 30-day mortality due to acute myocardial infarction (AMI), which constitutes one of the main causes of mortality in the country: 28 % versus 7.5 % on average for the Organization for Economic Co-operation and Development member countries. OBJECTIVE: To establish critical pathways and essential interinstitutional pharmacological strategies for the care of patients with AMI in Mexico, regardless of their socioeconomic status. METHOD: A group of experts in AMI diagnosis and treatment, representatives of the main public health institutions in Mexico, as well as the Mexican cardiology societies, the Mexican Red Cross and representatives of the Spanish Society of Cardiology, were brought together in order to optimize strategies based on the best existing evidence. RESULTS: An interinstitutional clinical practice guideline was designed for early diagnosis and timely treatment of AMI with ST-segment elevation, following the clinical horizon of the disease, with the proposal of algorithms that improve the prognosis of patients who attend the emergency services due to an AMI. CONCLUSION: With these clinical practice guidelines, the group of experts proposes to universalize AMI diagnosis and treatment, regardless of patient socioeconomic status. INTRODUCCIÓN: México tiene la mortalidad más alta a 30 días por infarto agudo de miocardio (IAM), el cual constituye una de las principales causas de mortalidad en el país: 28 % versus 7.5 % del promedio de los países de la Organización para la Cooperación y el Desarrollo Económicos. OBJETIVO: Establecer las rutas críticas y las estrategias farmacológicas esenciales interinstitucionales para la atención de los pacientes con IAM en México, independientemente de su condición socioeconómica. MÉTODO: Se reunió a un grupo de expertos en diagnóstico y tratamiento de IAM, representantes de las principales instituciones públicas de salud de México, así como las sociedades cardiológicas mexicanas, Cruz Roja Mexicana y representantes de la Sociedad Española de Cardiología con la finalidad de optimizar las estrategias con base en la mejor evidencia existente. RESULTADOS: Se diseñó una guía de práctica clínica interinstitucional para el diagnóstico temprano y tratamiento oportuno del IAM con elevación del segmento ST, siguiendo el horizonte clínico de la enfermedad, con la propuesta de algoritmos que mejoren el pronóstico de los pacientes que acuden por IAM a los servicios de urgencias. CONCLUSIÓN: Con la presente guía práctica, el grupo de expertos propone universalizar el diagnóstico y tratamiento en el IAM, independientemente de la condición socioeconómica del paciente.

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.

Renal impairment and outcome in Takotsubo syndrome: Insights from a national multicentric cohort.

INTRODUCTION: Data on the association between kidney function and Takotsubo syndrome (TTS) outcomes are scarce and conflictive. OBJECTIVE: To assess the impact of chronic kidney disease (CKD) and acute renal failure (ARF) in patients with TTS. MATERIAL AND METHODS: Patients from the prospective nation-wide (RETAKO) registry were included and divided into quartiles of maximum creatinine (Cr) level during hospitalization. RESULTS: The prevalence of CKD and ARF in the whole RETAKO cohort was 5.4% and 11.7%, respectively. Compared to Q1 (Cr <0.71), patients within Q4 (Cr > 1.1) had lower left ventricular ejection fraction on admission (38.5 ± 12 vs 43.3 ± 11.3, p = 0.002) and higher bleeding rates during hospitalization (6.7% vs 2%, p = 0.005). In addition, compared to Q1, Q4 patients have a greater incidence of cardiogenic shock (17.3% vs 5.6%, p < 0.001), and a higher rate of 5-year all-cause death and major adverse cardiovascular events (31.5% vs 15.8%, p < 0.001 and 22.5% vs 9.3%, p < 0.001, respectively). CONCLUSIONS: TTS patients with CKD have a higher incidence of ARF and exhibit greater Cr on admission, which were linked with higher rates of cardiogenic shock, bleeding during hospitalization as well as major adverse cardiovascular events and all-cause death during a 5-year 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.

Impact of mechanical circulatory support on outcomes in Takotsubo syndrome complicated by cardiogenic shock: Insights from the RETAKO registry.

BACKGROUND: Cardiogenic shock (CS) complicates Takotsubo syndrome (TTS), significantly affecting patient outcomes. Since avoiding catecholamines, particularly inotropic agents, is recommended in TTS, temporary mechanical circulatory support (MCS) shows promise as a bridge to recovery. However, there is no prospective data on its use in TTS. METHODS: Patients from the prospective nationwide RETAKO registry were included and divided based on the use and type of MCS. RESULTS: From a national TTS registry, 1591 consecutive patients were initially enrolled between 2003 and 2022. Of these, 322 patients (20.2 %) developed CS, and 31 (9.6 %) were treated with MCS [20 intra-aortic balloon pump (IABP) (64.5 %), 8 veno-arterial extracorporeal membrane oxygenation (25.8 %), and 3 Impella-CP (9.7 %)]. Compared to CS patients managed only with drugs, MCS recipients exhibited a more severe clinical profile, with worse ventricular function and more right ventricular involvement. Despite encountering more complications, such as major bleeding and atrial fibrillation, MCS did not significantly influence in-hospital mortality (19.4 % in the MCS group vs 13.1 % in the no MCS group, p = 0.33). After adjusting for other predictors of in-hospital mortality (invasive mechanical ventilation, inotropic-vasoactive score, age, and SCAI stage), MCS was not associated with higher mortality. CONCLUSION: Approximately 10 % of TTS patients complicated by CS were treated with MCS. Despite their more severe CS, patients treated with MCS had similar in-hospital mortality rates as those treated only with drugs, suggesting a potential benefit of MCS in selected cases.

Recovery of Left Ventricular Function and Long-Term Outcomes in Patients With Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a form of transient left ventricular (LV) dysfunction that usually resolves within days to weeks. OBJECTIVES: We aimed to assess the predictors and prognostic impact of time-to-LV recovery after TTS. METHODS: Prospective serial imaging data from the nationwide, multicenter RETAKO (REgistry on TAKOtsubo Syndrome) were comprehensively reviewed to assess the timing of LV recovery. Multivariable logistic regression was used to assess factors associated with late (≥10 days) vs early (<10 days) recovery. The long-term risk of all-cause mortality was compared between the late and early recovery groups using fully adjusted Cox models, and using flexible parametric survival models with recovery time included as a continuous variable. RESULTS: Of 1,463 patients included (median age 73 years, 13% men), 373 (25%) had late and 1,090 (75%) had early LV recovery. Older age, history of neurological disorders, bystander coronary artery disease, active cancer, physical triggers, elevated inflammatory biomarkers, cardiogenic shock, and lower LV ejection fraction at admission were independent predictors of late recovery. At 4-year follow-up, the adjusted risk of death was significantly higher in patients with late recovery compared with those with early recovery (16.0% vs 8.6%, adjusted HR: 1.31; 95% CI: 1.12-1.60), with the risk of death increasing by 8% for every additional 10-day delay in time-to-LV recovery (adjusted HR: 1.08; 95% CI: 1.04-1.13). CONCLUSIONS: Late recovery of LV function after TTS is associated with reduced short- and long-term survival. In TTS patients without early LV recovery, closer clinical follow-up might be considered.

Peripartum Takotsubo Cardiomyopathy: A Review and Insights from a National Registry.

Takotsubo syndrome (TTS) during the peripartum period is a relevant cause of morbidity in this population; its clinical course and prognosis, compared to the general TTS population, is yet to be elucidated. Our aim was to analyze the clinical features and prognosis of peripartum TTS in a nationwide prospective specifically oriented registry database and consider the published literature. Peripartum TTS patients from the prospective nationwide RETAKO registry-as well as peripartum TTS patients from the published literature-were included, and multiple comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between the groups. Patients with peripartum TTS exhibit a higher prevalence of secondary forms, dyspnea, atypical symptoms, and echocardiographic patterns, as well as less ST-segment elevation than the general TTS population. In the literature, patients with peripartum TTS had a higher Killip status on admission. TTS during the peripartum period has a higher prevalence of angina and dyspnea, as well as physical triggers, neither of which are related to a worse prognosis. Killip status on admission was higher in the literature for patients with TTS but with excellent mid- and long-term prognoses after the acute phase, despite mostly being secondary forms.

Echocardiographic Phenotype in Severe Aortic Stenosis With and Without Transthyretin Cardiac Amyloidosis: The AMY-TAVI Study.

AIM: The relative apical sparing pattern of left ventricular (LV) longitudinal strain (RELAPS]>1) has been described as a typical sign of cardiac amyloidosis (CA). The objective was to validate this pattern in concomitant CA and aortic stenosis (AS) and to identify new echocardiographic variables suggestive of CA in the presence of AS. METHODS AND RESULTS: 324 consecutive patients (age 81.5±5.8 years, 51% women) with AS who underwent transcatheter aortic valve implantation (TAVI) were prospectively included. 2D-Speckle-tracking echocardiography was performed. Following TAVI, 99mTc-DPD-scintigraphy and protein electrophoresis were performed to screen for CA. 38 patients (11.7%) showed cardiac uptake in scintigraphy: 14 patients (4.3%) with grade 1, 13 (4%) with grade 2, and 11 (3.4%) with grade 3. Patients with grades 2 and 3 (AS-CA group) had more LV hypertrophy (LV mass index: 188 vs.172 g/m2, p=0.032), lower transvalvular aortic pressure gradient (p<0.003), and higher prevalence of low-gradient AS (50% vs.19%, p=0.001), as well as greater diastolic and systolic dysfunction. Strain analysis was limited to 243 patients due to poor acoustic window and COVID-19 restrictions (81 lost: 79 in AS alone, 1 each in AS-DPD1 and AS-CA groups). RELAPS>1 was more prevalent in AS-CA group (74% vs.44%, p=0.006). An echocardiographic prediction model (GRAM score) for CA in the presence of AS, that is more sensitive and specific than RELAPS>1 alone, is proposed using the LV mass, maximum aortic gradient, and RELAPS>1, in addition to age (AUC:0.85, 95%CI: 0.77-0.93). CONCLUSIONS: RELAPS>1 is more prevalent in AS-CA but can occur in almost half of AS patients without CA, which reduces its value as a screening tool. A more sensitive and specific prediction score for CA in patients with severe AS is proposed.

[Heart rate disorders in patients with Tako-tsubo syndrome]. / Trastornos del ritmo cardiaco en pacientes con síndrome de Tako-tsubo.

OBJECTIVES: This study sought to evaluate the incidence, prognosis and treatment of heart rhythm disorders (HRD) in Tako-tsubo syndrome (TTS). BACKGROUND: TTS is associated with HRD. The HRD prognostic value is not well characterized in TTS yet. METHODS: The HRD of patients included in the National Registry of Tako-tsubo syndrome, admitted between 2002 and 2018 and coming from 38 hospitals throughout the country, was analyzed. We analyzed any heart rhythm disorder in patients presented before admission, at admission and in long-term follow-up. RESULTS: All types of HRD were described in 259 (23.5%) cases, from a cohort of 1,097 consecutive patients with TTS. HRD was more associated with diabetes mellitus, smoking, hyperuricemia, sleep apnea, anemia with a worse LVEF on admission. The most frequent HRD was a new onset of atrial fibrillation. During hospitalization, patients with HRD showed more complications such as shock on admission, major bleeding, acute renal failure, and combined infections. At follow-up, they presented higher mortality and more major adverse cardiac events, but with a non-significant correlation. CONCLUSIONS: The incidence of HRD in patients with TTS is not infrequent. TTS, when associated with HRD, presents more complications and a worse prognosis both in hospital and in the long term.

Takotsubo Syndrome, Stressful Triggers, and Risk of Recurrence.

The risk of recurrence in takotsubo syndrome (TTS) appears to be low, although previous studies have shown conflicting results and factors associated with recurrences are unclear. The aim of this study is to evaluate the incidence and predictors of TTS recurrences. Adult patients included in the Spanish Multicenter REgistry of TAKOtsubo syndrome (RETAKO) between January 2003 and September 2019 were identified. Patients were categorized based on recurrences during follow-up and a multivariate logistic regression model was used to identify factors associated with recurrences. A total of 1097 patients (mean age 71.0±11.9 years, 87% females) were included, repeated TTS events were documented in 44 patients (4.0%), including 13 patients with prior TTS and 31 patients with recurrent TTS during a median follow-up of 279 days. Two patients (0.02%) had two episodes of recurrence. Compared to patients who had no recurrence of TTS, those with recurrent TTS more frequently had no identifiable stressful trigger in the index admission (20 [64.5%] vs 352 [33.0%], p <0.001). Primary TTS, defined as TTS without physical trigger, was also more common in the recurrence group (93.5% vs 68.3%, p <0.001). The only factor independently associated with recurrences was the absence of an identifiable trigger (odds ratio 3.7 [95% confidence interval 1.8-7.8], p=0.001). In conclusion, our data indicate that for patients presenting with TTS, the rate of early recurrent TTS is approximately 4% per year. Among TTS patients, those who have no identifiable trigger events appear to have a higher rate of recurrence.

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.

Very long-term efficacy and safety of paclitaxel-eluting balloon after a bare-metal stent for the treatment of ST-elevation myocardial infarction: 8-year results of a randomized clinical trial (PEBSI study).

Background: Drug-eluting stents (DES) are considered the therapy of choice in ST-segment elevation myocardial infarction (STEMI); however, a low persistent rate of revascularizations and stent thrombosis exist over the time. We have previously shown that a paclitaxel (PTX)-drug-coated balloon (DCB) after a bare-metal stent (BMS) implantation (DCB-combined strategy) yields superior angiographic and clinical results compared to BMS in the short term. However, the long-term safety and efficacy of this approach remain uncertain. Methods: An 8-year clinical follow-up was conducted on patients enrolled in the randomized PEBSI-1 trial (NCT01839890). The original trial included patients who suffered a STEMI, patients were randomly assigned to receive a DCB-combined strategy or BMS only and the primary endpoint was in-stent late luminal loss (LLL) at 9-month follow-up. After the completion of this study, death, myocardial re-infarction, ischemia-driven repeated revascularizations included target lesion revascularization (TLR) and target vessel revascularization (TVR), and stent thrombosis, were assessed by yearly contact by a clinical visit, telephone or by electronic records. These outcomes were adhered to ARC-2 criteria. Results: The rate of incomplete follow-up was very low, with only 3 out of 111 patients (2.7%) in the DCB-combined strategy group and 1 out of 112 patients (0.9%) in the BMS group. At 8 years there were a lower rate of TVR [3.7% vs. 14.3%; hazard ratio (HR): 0.243; 95% confidence interval (CI): 0.081-0.727; P=0.006], and a trend towards lower TLR (2.8% vs. 8.9%; HR: 0.300; 95% CI: 0.083-1.090; P=0.052) in the DCB-combined strategy group. No statistical difference between the DCB-combined strategy and BMS groups were found for all causes of death, deaths from cardiovascular disease, reinfarctions or stent thrombosis. Notably in the DCB-combined strategy group, no episode of stent thrombosis occurred after the first year. Similarly, there were no cardiovascular deaths, TVR and TLR in the DCB-combined strategy group after 5 years. In contrast, during the period from year 5 to 8, the BMS group experienced an additional cardiovascular death, as well as one case of TVR, one case of TLR, and one case of stent thrombosis. Conclusions: In STEMI patients, the DCB-combined strategy maintains its safety and clinical efficacy over time. Our rates of TVR, TLR, and very late stent thrombosis (VLST) at very long-term are the lowest ever found in a STEMI trial. Further studies are warranted to assess the potential superiority of this novel strategy as compared with new-generation DES to prevent very late events in these patients. Trial Registration: ClinicalTrials.gov; identifier: NCT01839890.

Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry.

Background: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited. Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs. Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005). Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM.

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

Prevalence and prognosis of anxiety, insomnia, and type D personality in patients with myocardial infarction: A Spanish cohort.

BACKGROUND: It has been suggested that patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) have more psycho-emotional disorders than patients with obstructive coronary artery disease (MICAD). The aim of this study is to compare the prevalence of anxiety, insomnia, and type D personality between MINOCA and MICAD and their impact on prognosis. METHODS: Patients with myocardial infarction undergoing coronary angiography were prospectively enrolled. Psychological questionnaires were completed by each patient during admission. RESULTS: Among a total of 533 patients, 56 had MINOCA and 477 had MICAD. There were no differences in the prevalence of anxiety and insomnia between both groups: trait anxiety median value (M) MINOCA = 18 (11-34) vs. MICAD M = 19 (12-27), p = 0.8; state anxiety MINOCA M = 19 (11-29) vs. MICAD M = 19 (12.2-26), p = 0.6; and insomnia MINOCA M = 7 (3-11) vs. MICAD M = 7 (3-12), p = 0.95. More MINOCA patients had type D personality (45.0% vs. 28.5%, p = 0.03). At 3-year follow-up, there were no differences in mortality between MINOCA and MICAD (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.28-2.17) in major adverse cerebral or cardiovascular events (MACCE) (HR 0.71, 95% CI 0.38-1.31). Scores of trait anxiety and negative affectivity were significantly associated with MACCE (HR 1.65, 95% CI [1.05-2.57]; HR 1.75, 95% CI [1.11-2.77], respectively). High insomnia levels were associated with greater mortality (HR 2.72, 95% CI [1.12-6.61]). CONCLUSIONS: Anxiety and insomnia levels were similar between patients with MINOCA and those with MICAD, whilst the prevalence of type D personality was higher in the MINOCA than in the MICAD group. Higher scores in trait anxiety, insomnia, and negative affectivity were related to a worse prognosis at 3-year follow-up.