The Incidence, Impact, and Techniques of Commissural Alignment in Transcatheter Aortic Valve Implantation: A Review.

In current clinical practice, commissural alignment of the transcatheter heart valve (THV) during transcatheter aortic valve implantation (TAVI) is seldom achieved. Orientation of the THV within the aortic root and the subsequent influence upon leaflet haemodynamic function, coronary blood flow, and ease of access to the coronary ostia are gaining significant interest. Herein, we review the incidence and clinical implications of commissural misalignment in TAVI and offer thorough descriptions of how optimal alignment can be achieved with several different contemporary THV devices.

Soluble factors in COVID-19 mRNA vaccine-induced myocarditis causes cardiomyoblast hypertrophy and cell injury: a case report.

BACKGROUND: Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood. CASE PRESENTATION: After the first dose, we reported an mRNA vaccine-induced perimyocarditis in a young patient with a history of recurrent myocardial inflammation episodes and progressive loss of cardiac performance. We tested this possible inflammatory cytokine-mediated cardiotoxicity after vaccination in the acute phase (ten days), and we found a significant elevation of MCP-1, IL-18, and IL-8 inflammatory mediators. Still, these cytokines decreased considerably at the recovery phase (42 days later). We used the cardiomyoblasts cell line to test the effect of serum on cell viability, observing that serum from the acute phase reduced the cell viability to 75%. We did not detect this toxicity in cells when we tested serum from the patient in the recovery phase. We also tested serum-induced hypertrophy, a phenomenon in myocarditis and heart failure. We found that acute phase-serum has hypertrophy effects, increasing 25% of the treated cardiac cells' surface and significantly increasing B-type natriuretic peptide. However, we did not observe the hypertrophic effect in the recovery phase or sera from healthy controls. CONCLUSION: Our results opened the possibility of the inflammatory cytokines or serum soluble mediators as key factors for vaccine-associated myocarditis. In this regard, identifying anti-inflammatory molecules that reduce inflammatory cytokines could help avoid vaccine-induced myocardial inflammation.

Initial results of investigator initiated international database on catheter directed therapy of acute pulmonary embolism.

BACKGROUND: Catheter directed therapies (CDT) are widely used in the treatment of acute pulmonary embolism (PE). A multicenter registry was organized to evaluate their application in real life and to determine efficacy and safety of these procedures. Local experience of participating centers in percutaneous techniques for PE treatment was assessed. METHODS: An internet-based registry was designed to collect clinical, echocardiographic and laboratory data of consecutive PE patients treated with CDT in participating centers between 2017 and 2022. RESULTS: Under analysis were 145 consecutive patients with acute PE, aged 61 ± 15 years, treated with CDT in 7 centers: 50 (34.5%) patients with high-risk PE (HRPE), and 95 (65.5%) patients with intermediate-high risk PE (IHRPE). 100 (69%) patients were treated with dedicated devices, in 45 (31%) subjects a pigtail catheter was used. Total PE or CDT related in-hospital mortality in HRPE reached 14% (7 patients), while in IHRPE 3.2% (3 patients) (p = 0.032). 50% of PE or CDT related deaths occurred in patients treated with a pigtail catheter. All-cause mortality in 145 patients was 9.7%, and it was higher in HRPE than in IHRPE (18% vs. 5.3%, p = 0.019). The use of pigtail catheters compared to dedicated systems was associated with higher mortality (20% vs. 5%, p = 0.01). CONCLUSIONS: Catheter directed therapies is a real option of treating PE. It was used as primary therapy also in patients without contraindication for thrombolysis suggesting that clinical practice does not always follow current PE guidelines. Patients treated with dedicated CDT systems had a higher survival rate than subjects treated with pigtail catheters.

Risk Factors, Clinical Presentation, Therapeutic Trends, and Outcomes in Arterial Thrombosis Complicating Unvaccinated COVID-19 Patients: A Systematic Review.

Data on characteristics and outcomes of coronavirus (COVID)-19 patients complicated with arterial thrombosis (AT) are scarce. Therefore, we carried out a systematic review (PRISMA, PROSPERO statements; PubMed, Scopus, and Web of Science) to identify risk factors, clinical presentation, treatment, and outcomes. We included publications from December 2019 to October 2020. Groups: (a) ischemic stroke, (b) thrombotic storm, (c) peripheral vascular thrombosis, (d) myocardial infarction, and (e) left cardiac thrombus or in-transit thrombus (venous system thrombus floating or attaching to the right heart). We considered 131 studies. The most frequent cardiovascular risk factors were: hypertension, diabetes, and dyslipidemia. A high proportion presented with asymptomatic, mild, or moderate COVID-19 (n = 91, 41.4%). We identified a high percentage of isolated ischemic stroke and thrombotic storm. Groups with higher mortality rate: intracardiac thrombus (1/2, 50.0%), thrombotic storm (18/49, 36.7%), and ischemic stroke (48/131, 36.6%). A small number received thromboprophylaxis. Most patients received antithrombotic treatment. The most frequent bleeding complication was intracranial hemorrhage, primarily with isolated stroke. Overall mortality was 33.6% (74/220). Despite a wide range of COVID-19 severity, a high proportion had AT as a complication of non-severe disease. AT can affect different vascular territories; mortality is associated with stroke, intensive care unit stay, and severe COVID-19.

Comprehensive Assessment of Myocardial Ischemia Mechanisms in the Catheterization Laboratory: Design and Rationale of the Advanced Invasive Diagnosis Strategy for Patients with Stable Coronary Syndromes Undergoing Coronary ANGIOgraphy - the AID-ANGIO Study.

BACKGROUND: The diagnostic yield of invasive coronary angiography (ICA) to identify obstructive coronary artery disease in the context of chronic coronary syndromes (CCS) is very low. Furthermore, myocardial ischemia may have a non-obstructive origin, which cannot be detected by ICA. METHODS: AID-ANGIO is an observational, prospective, single-cohort, multicenter study, intended to evaluate the diagnostic yield of adopting a hierarchical strategy to assess obstructive and non-obstructive causes of myocardial ischemia in an all-comers population of patients with CCS at the time of ICA. The primary endpoint will investigate the additional diagnostic value of such strategy over angiography alone regarding the identification of ischemia-generating mechanisms. SUMMARY: An estimated sample of consecutive 260 patients with CCS referred by their clinicians to ICA, will be enrolled. In a stepwise manner, a conventional ICA will be performed as the initial diagnostic tool. Those patients with severe-grade stenosis will not undergo further assessment and an obstructive origin for myocardial ischemia will be assumed. Subsequently, the remainder with intermediate-grade stenosis will be assessed with pressure guidewires. Those with a negative result from physiological evaluation and those without epicardial coronary stenosis will be further studied for ischemia of non-obstructive origin, including microvascular dysfunction and vasomotor disorders. The study will be conducted in two steps. Firstly, ICA images will be displayed to patient's referring clinicians, who will be asked to identify the existent epicardial stenosis, their angiographic severity and probable physiological relevance, together with a tentative therapeutic approach. Then, the diagnostic algorithm will continue to be applied and, considering the whole gathered information, a definite therapeutic plan will be consensually established by the interventional cardiologist and patient's referring clinicians. CONCLUSION: The AID-ANGIO study will assess the additional diagnostic yield of a hierarchical strategy over ICA alone to identify ischemia-generating mechanisms in patients with CCS and its impact on therapeutic approach. Positive results of the study might support a streamlined invasive diagnostic process for patients with CCS.

Killip-Kimball classification in octogenarians with acute coronary syndrome: an 11-year experience / Clasificación de Killip-Kimball en octogenarios con síndrome coronario agudo: 11 años de experiencia

Abstract Objective: The objective of the study is to validate the use of the Killip-Kimball classification (KC) as a predictor of outcomes in an octogenarian cohort with acute coronary syndrome. Methods: A retrospective analysis of patients who underwent a catheterization procedure for acute coronary syndrome (ACS) was performed. ACS was defined as per the American Heart Association guidelines, and included ST-elevation myocardial infarction (STEMI), non-STEMI and Unstable Angina. We determined factors associated with the KC upon admission to the emergency room. Likewise, we compared in-hospital mortality, length of stay, and other outcomes dividing the patients by KC. Results: A total of 133 patients with a mean age of 83 years were analyzed and assigned a KC from 1 to 4 according to clinical presentation. Each group included 86, 9, 23, and 15 patients, respectively. In-hospital mortality was 12%, 5% in KC-I, 11% in KC-II, 22% in KC-III, and 40% in KC-IV with a significant difference between classes (p = 0.002). In addition, we found higher KC groups to be associated with acute kidney injury during the hospitalization (p < 0.01). Conclusion: Despite a strong reduction in mortality for elderly patients with ACS in recent decades, patients presenting with ACS and higher KC have a high mortality rate, as described in younger cohorts. KC remains a reliable prognostic tool, with applicability in octogenarian patients.

Resumen Objetivo: Validar el uso de la clasificación de Killip- Kimball como predictor de desenlaces en una cohorte de pacientes octogenarios con síndrome coronario agudo. Métodos: Se realizó un análisis retrospectivo de pacientes sometidos a cateterismo por síndrome coronario agudo (ACS). Se incluyeron infarto al miocardio con y sin elevación del segment ST, así como angina inestable, utilizando las definiciones de la American Heart Association (AHA). Se determinaron los factores que influyeron en la clasificación de Killip-Kimball (KC) al momento de ingreso al hospital. Se comparó la mortalidad, la estancia intrahospitalaria y otros desenlaces, dividiendo a los pacientes por su KC. Resultados: Un total de 133 pacientes se incluyeron en el análisis y se clasificaron dependiendo de su KC (I-IV). Cada grupo incluyó 86, 9, 23 y 15 pacientes, respectivamente. La edad media fue de 83 años. La mortalidad intrahospitalaria fue de 5, 11, 22 y 40%, respectivamente para cada KC, y 12% global. Hubo una diferencia significativa en la mortalidad por clase (p = 0.002). Adicionalmente, se encontró que a mayor KC, mayor riesgo de lesión renal aguda durante la hospitalización (p < 0.01). Conclusión: A pesar de una reducción en la mortalidad de adultos mayores con ACS en décadas recients, pacientes con ACS y mayor KC tienen riesgo aumentado de morir, igual que pacientes en grupos de edad menores. La KC continñua siendo una herramienta confiable para la clasificación y con utilidad pronóstica, con aplicabilidad en pacientes mayores de 80 años.

Killip-Kimball classification in octogenarians with acute coronary syndrome: An 11-year experience.

Objective: The objective of the study is to validate the use of the Killip-Kimball classification (KC) as a predictor of outcomes in an octogenarian cohort with acute coronary syndrome. Methods: A retrospective analysis of patients who underwent a catheterization procedure for acute coronary syndrome (ACS) was performed. ACS was defined as per the American Heart Association guidelines, and included ST-elevation myocardial infarction (STEMI), non-STEMI and Unstable Angina. We determined factors associated with the KC upon admission to the emergency room. Likewise, we compared in-hospital mortality, length of stay, and other outcomes dividing the patients by KC. Results: A total of 133 patients with a mean age of 83 years were analyzed and assigned a KC from 1 to 4 according to clinical presentation. Each group included 86, 9, 23, and 15 patients, respectively. In-hospital mortality was 12%, 5% in KC-I, 11% in KC-II, 22% in KC-III, and 40% in KC-IV with a significant difference between classes (p = 0.002). In addition, we found higher KC groups to be associated with acute kidney injury during the hospitalization (p < 0.01). Conclusion: Despite a strong reduction in mortality for elderly patients with ACS in recent decades, patients presenting with ACS and higher KC have a high mortality rate, as described in younger cohorts. KC remains a reliable prognostic tool, with applicability in octogenarian patients.

Objetivo: Validar el uso de la clasificación de Killip- Kimball como predictor de desenlaces en una cohorte de pacientes octogenarios con síndrome coronario agudo. Métodos: Se realizó un análisis retrospectivo de pacientes sometidos a cateterismo por síndrome coronario agudo (ACS). Se incluyeron infarto al miocardio con y sin elevación del segment ST, así como angina inestable, utilizando las definiciones de la American Heart Association (AHA). Se determinaron los factores que influyeron en la clasificación de Killip-Kimball (KC) al momento de ingreso al hospital. Se comparó la mortalidad, la estancia intrahospitalaria y otros desenlaces, dividiendo a los pacientes por su KC. Resultados: Un total de 133 pacientes se incluyeron en el análisis y se clasificaron dependiendo de su KC (I-IV). Cada grupo incluyó 86, 9, 23 y 15 pacientes, respectivamente. La edad media fue de 83 años. La mortalidad intrahospitalaria fue de 5, 11, 22 y 40%, respectivamente para cada KC, y 12% global. Hubo una diferencia significativa en la mortalidad por clase (p = 0.002). Adicionalmente, se encontró que a mayor KC, mayor riesgo de lesión renal aguda durante la hospitalización (p < 0.01). Conclusión: A pesar de una reducción en la mortalidad de adultos mayores con ACS en décadas recients, pacientes con ACS y mayor KC tienen riesgo aumentado de morir, igual que pacientes en grupos de edad menores. La KC continñua siendo una herramienta confiable para la clasificación y con utilidad pronóstica, con aplicabilidad en pacientes mayores de 80 años.

Unexpected arterial thrombosis and acute limb ischemia in COVID-19 patients. Results from the Ibero-Latin American acute arterial thrombosis registry in COVID-19: (ARTICO-19).

OBJECTIVE: Few studies have focused on arterial thrombosis and acute limb ischemia in COVID-19. This international registry intended to study the spectrum of clinical characteristics, therapeutic trends, and outcomes in a cohort of Ibero-Latin American patients with arterial thrombosis or acute limb ischemia and COVID-19. METHODS: Data were retrospectively obtained from 21 centers in 9 countries. Patients with proven COVID-19 and asymptomatic or symptomatic arterial thrombosis were included. COVID-19 diagnosis was established by RT-PCR assay or IgM serology plus suggestive clinical/radiographical findings. We recorded and analyzed variables related to demography, clinical presentation, therapeutic trends, and outcomes. RESULTS: Eighty one patients were included in the registry. In 38.3%, acute limb ischemia symptoms were the first manifestation of COVID-19. Non-surgical management was more frequent in severe cases than surgical interventions, 11.1% vs. 88.9%, respectively (p = 0.004). Amputation rates were similar between all COVID severity groups (p = 0.807). Treatment was classified as non-surgical, open surgical, and endovascular treatment. Further analysis revealed an equal frequency of major leg amputation between treatment groups and increased mortality in patients with non-surgical management. However, multivariate regression analysis showed that treatment choices are associated with disease severity, with significant non-surgical treatment in critical patients; thus, mortality is related to the severity and confounds treatment analysis. CONCLUSION: Arterial thrombosis can be the initial symptom of a patient presenting with COVID-19. Physicians and health workers should potentially suspect COVID-19 in acute ischemia cases without a known risk factor or embolic cause. More experimental and clinical research is required to understand the complex phenomenon of arterial COVID-19 induced coagulopathy fully.

Venous Thromboembolism in Hospitalized COVID-19 Patients Treated in a Single Academic Center in Mexico: A Case Series Study.

BACKGROUND: The increasing prevalence of venous thromboembolism (VTE) among patients with coronavirus disease 2019 (COVID-19) is a matter of concern as it contributes significantly to patients' morbidity and mortality. Data regarding the optimal anticoagulation regimen for VTE prevention and treatment remain scarce. This study describes the characteristics, treatment, and outcomes of COVID-19 patients with VTE treated in a single academic center in Mexico. METHODS: We conducted a retrospective study of all patients with a positive PCR test for SARS-CoV-2 hospitalized in a single academic center in Monterrey, Mexico, between March 2020 and February 2021, with a radiologically confirmed VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE). Informed consent was obtained from each patient before reviewing their medical records. RESULTS: Of the 2000 COVID-19 hospitalized patients, 36 (1.8%) developed VTE and were included in the analysis. The median age was 60 years (range 32-88 years), and up to 78% (n = 28) were males. Most patients (n = 34, 94%) had an underlying comorbidity and 47% (n = 17) had a BMI ≥ 30 kg/m2. In most cases (n=28, 78%), VTE presented as a PE, whereas the remaining 22% (n = 8) had a DVT. The median time between hospital admission and VTE was 8 days (range 0-33 days). Regarding the thromboprophylaxis regimen, 35/36 patients received low molecular weight heparin enoxaparin on admission, most commonly at a dose of 60 mg daily (n = 19, 53%). Other complications presented were superinfection (n = 19, 53%), acute kidney injury (n = 11, 31%), and septic shock (n = 5, 14%). A total of 69% of patients (n = 25) required intensive care unit admission, and patients' overall mortality was 55.6%. CONCLUSION: VTE remains a significant cause of increased morbidity and mortality among patients with COVID-19. The strikingly high mortality among patients with VTE highlights the need for further investigation regarding the best preventive, diagnostic, and treatment approaches.

Differences between surviving and non-surviving venous thromboembolism COVID-19 patients: a systematic review.

BACKGROUND: To our knowledge, the treatment, outcome, clinical presentation, risk stratification of patients with venous thromboembolism and COVID-19 have not been well characterized. METHODS: We searched for systematic reviews, cohorts, case series, case reports, editor letters, and venous thromboembolism COVID-19 patients' abstracts following PRISMA and PROSPERO statements. We analyzed therapeutic approaches and clinical outcomes of venous thromboembolism COVID-19 patients. Inclusion: COVID-19 patients with venous thromboembolism confirmed by an imaging method (venous doppler ultrasound, ventilation-perfusion lung scan, computed tomography pulmonary angiogram, pulmonary angiography). We assessed and reported the original Pulmonary Embolism Severity Index for each pulmonary embolism patient. In addition, we defined major bleedings according to the International Society of Thrombosis and Haemostasis criteria. RESULTS: We performed a systematic review from August 9 to August 30, 2020. We collected 1,535 papers from PubMed, Scopus, Web of Science, Wiley, and Opengrey. We extracted data from 89 studies that describe 143 patients. Unfractionated and low-molecular-weight heparin was used as parenteral anticoagulation in 85/143 (59%) cases. The Food and Drug Administration-approved alteplase regimen guided the advanced treatment in 39/143 (27%) patients. The mortality was high (21.6%, CI 95% 15.2-29.3). The incidence of major bleeding complications was 1 (0.9%) in the survival group and 1 (3.2%) in the death group. Pulmonary Embolism Severity Index was class I in 11.6% and II in 22.3% in survivors compared to 0% and 6.5% in non-survivors, respectively. Patients who experienced venous thromboembolism events at home were more likely to live than in-hospital events. CONCLUSIONS: We determined a high mortality incidence of pulmonary embolism and a low rate of bleeding. Unfractionated and low-molecular-weight heparin drove parenteral anticoagulation and alteplase the advanced treatment in both groups. The original Pulmonary Embolism Severity Index could be helpful in the risk stratification.

Clinical outcomes of very elderly patients treated with ultrasound-assisted catheter-directed thrombolysis for pulmonary embolism: a systematic review.

Pulmonary embolism (PE) is a significant cause of death in the very elderly (≥ 75 years) population. Ultrasound-assisted catheter-directed thrombolysis (USCDT) emerges to improve thrombolysis safety and efficacy. However, outcomes in very elderly patients are unknown, as randomized controlled trials exclude this population. Recently, we demonstrated acute kidney injury (AKI) and ischemic hepatitis in an octogenarian intermediate-risk PE patient treated with USCDT. Considering the lack of evidence, we undertook a systematic review to evaluate the clinical outcomes in very elderly PE patients treated with USCDT. We searched for very elderly PE patients treated with USCDT from 2008 to 2019. Additionally, we conducted another systematic review without age restriction to update previous evidence and compare both populations. We also did an exploratory analysis to determine if thrombolysis was followed based on current guidelines or impending clinical deterioration factors. We identified 18 very elderly patients (age 79.2, 75-86), mostly female and with intermediate-risk PE. We found an intracranial hemorrhage (ICH), and a right pulmonary artery rupture. Additionally, two significant bleedings complicated with transient AKI, and one case of AKI and ischemic hepatic injury. The patients who survived all had clinical and echocardiographic in-hospital improvement. Despite low rt-PA doses, ICH and major bleeding remain as feared complications. Thrombolysis decision was driven by impending clinical deterioration factors instead of international guideline recommendations. Our data do not suggest prohibitive risk associated with USCDT in very elderly intermediate and high-risk PE patients. Despite long-term infusions and right ventricular dysfunction, AKI and ischemic hepatic injury were infrequent.

Systemic thrombolysis and anticoagulation improved biomarker measurements in massive-like pulmonary embolism and severe COVID-19 pneumonia: a case report.

BACKGROUND: From asymptomatic patients to severe acute respiratory distress syndrome, COVID-19 has a wide range of clinical presentations, and venous thromboembolism has emerged as a critical and frequent complication. CASE SUMMARY: We present a case of a 69-year-old man with a clinical presentation of massive-like pulmonary embolism (PE) overlapping with severe COVID-19 pneumonia. The diagnosis was made based on hypotension, severe oxygen desaturation (33%), and right ventricular dysfunction (RVD). We used alteplase and low-molecular-weight heparin, obtaining immediate clinical improvement. Also, we identified an extremely elevated D-dimer (31.2 mcg/mL), and computed tomography pulmonary angiography (CTPA) revealed an unexpected low thrombus burden and a crazy-paving pattern. Considering this, we decided to discontinue the alteplase. Therefore, the mechanisms of pulmonary hypertension and RVD could be multifactorial. Despite the patient's respiratory status worsening and ongoing mechanical ventilation, biomarkers kept lowering to normal ranges. It appears a favourable outcome was related to early PE diagnosis and a multimodal therapeutic approach. DISCUSSION: Physicians in the ER should be warned about extremely high D-dimer measurements and severe oxygen desaturation as possible markers of severe COVID-19 pneumonia in patients with high-clinical suspicion of PE. Although ESC guidelines recommend immediate reperfusion in cardiogenic shock secondary to PE, we suggest initial CTPA in patients with high-clinical suspicion of severe COVID-19.