Search Results (15)

Embolic stroke of undetermined source (ESUS) was proposed in 2014 as a clinical category to subgroup non-lacunar cryptogenic ischemic strokes that appear embolic but lack an identifiable cause despite thorough investigation. The initial hypothesis was that anticoagulation might offer superior secondary prevention compared to antiplatelet therapy, prompting several large clinical trials. This review synthesizes current knowledge on ESUS. ESUS represents about 17% of ischemic strokes and often affects younger patients with fewer traditional risk factors. Although these patients lack major cardioembolic sources (e.g., atrial fibrillation) or significant arterial stenosis, many have covert embolic substrates. Major trials—NAVIGATE ESUS, RE-SPECT ESUS, and the atrial cardiopathy-focused ARCADIA—found no benefit of anticoagulants over aspirin, challenging the original ESUS framework. These results highlight the heterogeneity within ESUS and underscore the need for individualized diagnostic and therapeutic strategies. Full article

Left ventricular thrombosis (LVT) is one of the most feared complications of both ischemic and non-ischemic cardiopathy, and despite its incidence having decreased over the years (mostly due to novel reperfusion therapies in acute coronary syndromes), it is still not negligible. If transthoracic echocardiography, possibly with the adjunction of echo contrast, represents the cornerstone in LVT diagnosis, sometimes it is found to be nonconclusive and advanced cardiovascular imaging, namely cardiac magnetic resonance, needs to be performed to fully exclude intraventricular masses or to better characterize them. Vitamin K antagonists always represented the anticoagulant of choice for the treatment of LVT; however, the recent spread of direct oral anticoagulants (DOACs) pushed clinicians to adopt them also in this setting despite the absence of robust evidence in their favor. If the optimal duration of anticoagulation for the treatment of LVT in non-ischemic cardiopathy is still a matter of debate, an initial treatment of 3–6 months seems to be reasonable in the setting of ischemic cardiopathy, with possible extension according to the follow-up findings. High-quality randomized studies are strongly needed to evaluate the potential role of prophylactic anticoagulation in high-risk patients and provide conclusive evidence for the use of DOACs in LVT treatment. Full article

Background: Understanding the interactions between age and comorbidities is crucial for assessing COVID-19 mortality, particularly in patients with cardiac and pulmonary conditions. This study investigates the relationship between comorbidities and mortality outcomes in a cohort of hospitalized COVID-19 patients, emphasizing the interplay of age, cardiac, and pulmonary conditions. Methods: We analyzed a cohort of 3005 patients hospitalized with COVID-19 between 2020 and 2022. Key variables included age, comorbidities (diabetes, cardiac, pulmonary, and neoplasms), and clinical outcomes. Chi-square tests and logistic regression models were used to assess the association between comorbidities and mortality. Stratified analyses by age, diabetes, and pulmonary conditions were conducted to explore interaction effects. Additionally, interaction terms were included in multivariable logistic regression models to evaluate the combined impact of age, comorbidities, and mortality. Results: Cardiac conditions such as hypertension, ischemic cardiopathy, and myocardial infarction showed significant protective effects against mortality in younger patients and in those without pulmonary conditions (p < 0.001). However, these protective effects were diminished in older patients and those with pulmonary comorbidities. Age was found to be a significant modifier of the relationship between cardiac conditions and mortality, with a stronger protective effect observed in patients under the median age (p < 0.001). Pulmonary comorbidities significantly increased the risk of mortality, particularly when co-occurring with cardiac conditions (p < 0.001). Diabetes did not significantly modify the relationship between cardiac conditions and mortality. Conclusions: The findings highlight the complex interactions between age, cardiac conditions, and pulmonary conditions in predicting COVID-19 mortality. Younger patients with cardiac comorbidities show a protective effect against mortality, while pulmonary conditions increase mortality risk, especially in older patients. These insights suggest that individualized risk assessments incorporating age and comorbidities are essential for managing COVID-19 outcomes. Full article

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90–2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75–4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99–4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07–12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP. Full article

Cardioembolic stroke accounts for over 20% of ischemic strokes and is associated with worse outcomes than other types of strokes. Atrial fibrillation (AF) is the most common risk factor for cardioembolic stroke. In this narrative review, we present an update about cardioembolic stroke mainly related to AF and atrial cardiopathy. Direct oral anticoagulants (DOACs) have revolutionized stroke prevention in patients with AF; however, their efficacy in preventing recurrent embolic stroke of unknown source remains uncertain. Various cardiac monitoring methods are used to detect AF, which is crucial for preventing stroke recurrence. DOACs are preferred over warfarin for AF-related stroke prevention; however, the timing of initiation after acute ischemic stroke is debated. Resuming anticoagulation after intracerebral hemorrhage in AF patients requires careful assessment of the risks. While catheter ablation may reduce the incidence of cardiovascular events, its effect on stroke prevention is unclear, especially in heart failure patients. Atrial cardiopathy is the emerging cause of embolic stroke of unknown source, which indicates atrial structural and functional disorders that can precede AF. Future research should focus on refining stroke risk prediction models, optimizing AF detection, understanding the roles of ablation and anticoagulation in stroke prevention, and establishing atrial cardiopathy as a therapeutic target, which could significantly reduce the burden of stroke. Full article

This comprehensive review explores the intricate aspects of left ventricular thrombus (LVT), a potential complication in both ischemic and non-ischemic cardiomyopathies. It provides a thorough understanding of left ventricular thrombus, revealing its uncommon incidence in the general population (7 cases per 10,000 patients), predominantly linked to ischemic heart diseases (ICMs) at an 80% prevalence rate. Diagnostic tools, notably transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR), demonstrate varying sensitivity but remain indispensable in specific clinical contexts related to LVT as non-invasive diagnostic modalities. A detailed comparison between ICM patients and those with non-ischemic cardiomyopathy (NICM) who have left ventricular thrombus reveals subtle distinctions with significant clinical implications. This analysis underscores the importance of these imaging techniques in distinguishing between the two conditions. Additionally, we explored the occurrence of LVT in specific non-ischemic cardiomyopathies, including Takotsubo syndrome, hypertrophic cardiomyopathy, eosinophilic myocarditis, Chagas disease, cardiac amyloidosis, and several other conditions. The article further delves into anticoagulation strategies, thoroughly examining their impact on LVT regression and patient outcomes. Pharmacological interventions, with a focus on direct oral anticoagulants, emerge as promising alternatives; however, there is insufficient information on their efficiency and safety, especially in NICM population. In conclusion, this review highlights the complex nature of LVT, incorporating a range of etiopathogenic factors, diagnostic complexities, and evolving therapeutic approaches. It emphasizes the pressing need for ongoing research in this field. Full article

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with an increased risk of major adverse cardiovascular events (MACE). The main goal was to analyze the links and associations between AF and MACE. Methods: A multicenter, observational, retrospective, community-based study of a cohort (n = 40,297) of the general population aged 65–95 years between 1 January 2015 and 31 December 2021 without a previous diagnosis of AF or MACE in the Primary Care setting. Results: 2574 people (6.39%) developed a first AF event, resulting in an overall incidence of 8.9/1000 people-years [CI95% 8.6–9.2]. The incidence of MACE among those with AF was 75.1/1000 people-years [CI95% 70.8–79.5], whereas among those without AF, it was 20.6/1000 people-years [CI 95% 20.2–21.1], resulting in a rate ratio of 3.65 [CI 95% 3.43–3.88, p < 0.001]. Besides, the incidence of HF with AF was 40.1 people-years [CI 95% 37.1–43.2], while in the group without AF, it was 8.3 people-years [CI 95% 7.9–8.6, p < 0.001], with a rate ratio of 4.85 [CI 95% 4.45–55.3, p < 0.001]. Before an AF diagnosis, there is already a higher risk of chronic kidney disease, ischemic cardiopathy, and peripheral artery disease. A higher risk of poor nutritional status was detected among those with MACE (49.7% vs. 26.6%, p < 0.001). Conclusions: AF diagnosis increases the incidence of heart failure fourfold. Additional information is required to establish the connection between AF, major adverse cardiovascular events, and nutritional status. Full article

Background: Checkpoint inhibitors, such as PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab), are widely used in metastatic melanoma, and most immune-related adverse events are known. Several cardiovascular AEs (CVAEs) associated with immune checkpoint inhibitor exposure have been reported in post-marketing surveillance studies and represent major issues for patients with melanoma during and after cancer treatment. Data on CVAES induced by immune checkpoint inhibitors in melanoma, especially incidence and risk factors, are lacking. Methods: A systematic review of the literature up to 31 August 2020 was performed in Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov register according to prespecified selection criteria from inception to 7 April 2020. Statistics were performed on 3289 patients from five randomized clinical trials on melanoma. Results: Patients with melanoma treated with immune checkpoint inhibitors had a significant risk of presenting dyslipidemia (Peto OR: 4.74, 95% CI: 2.16–10.41, p < 0.01, I2 = 0%, p = 0.94). The Peto OR was numerically significant for pericarditis, myocarditis, heart failure, myocardial infarction, cerebral ischemia, high pulmonary pressure, blood high pressure, arrhythmias, endocarditis, and conduction disturbances, but the confidence interval was not significant. The risk of CVAEs was not statistically different between melanoma treated with immune checkpoint inhibitors and other tumors treated with immune checkpoint inhibitors (range of p-value from 0.13 to 0.95). No interaction between follow-up length and CVAE reporting was found. Conclusions: Our study underlines that checkpoint inhibitors used for melanoma increase CVAEs, especially dyslipidemia, which could pave the way to chronic inflammatory processes, atherosclerosis, and, finally, ischemic cardiopathy. These cardiovascular adverse events could be acute or delayed, justifying the monitoring of lipidic biology and a baseline cardiology consultation. Full article

(1) Introduction: Cardiovascular disease is associated with high mortality, especially in older people. This study aimed to characterize the evolution of combined multimorbidity and polypharmacy patterns in older people with different cardiovascular disease profiles. (2) Material and methods: This longitudinal study drew data from the Information System for Research in Primary Care in people aged 65 to 99 years with profiles of cardiovascular multimorbidity. Combined patterns of multimorbidity and polypharmacy were analysed using fuzzy c-means clustering techniques and hidden Markov models. The prevalence, observed/expected ratio, and exclusivity of chronic diseases and/or groups of these with the corresponding medication were described. (3) Results: The study included 114,516 people, mostly men (59.6%) with a mean age of 78.8 years and a high prevalence of polypharmacy (83.5%). The following patterns were identified: Mental, behavioural, digestive and cerebrovascular; Neuropathy, autoimmune and musculoskeletal; Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological; Non-specific; Multisystemic; Respiratory, cardiovascular, behavioural and genitourinary; Diabetes and ischemic cardiopathy; and Cardiac. The prevalence of overrepresented health problems and drugs remained stable over the years, although by study end, cohort survivors had more polypharmacy and multimorbidity. Most people followed the same pattern over time; the most frequent transitions were from Non-specific to Mental, behavioural, digestive and cerebrovascular and from Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological to Non-specific. (4) Conclusions: Eight combined multimorbidity and polypharmacy patterns, differentiated by sex, remained stable over follow-up. Understanding the behaviour of different diseases and drugs can help design individualised interventions in populations with clinical complexity. Full article

Background. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected >160 million people around the world. Hypertension (HT), chronic heart disease (CHD), and diabetes mellitus (DM) increase susceptibility to SARS-CoV-2 infection. Aims. We designed this retrospective study to assess the gender differences in hypertensive diabetic SARS-CoV-2 patients. We reported data, by gender differences, on the inflammatory status, on the hospital stays, intensive care unit (ICU) admission, Rx and CT report, and therapy. Methods. We enrolled 1014 patients with confirmed COVID-19 admitted into different Hospitals of Campania from 26 March to 30 June, 2020. All patients were allocated into two groups: diabetic-hypertensive group (DM-HT group) that includes 556 patients affected by diabetes mellitus and arterial hypertension and the non-diabetic- non-hypertensive group (non-DM, non-HT group) comprising 458 patients. The clinical outcomes (i.e., discharges, mortality, length of stay, therapy, and admission to intensive care) were monitored up to June 30, 2020. Results. We described, in the DM-HT group, higher proportion of cardiopathy ischemic (CHD) (47.5% vs. 14.8%, respectively; p < 0.0001) and lung diseases in females compared to male subjects (34.8% vs. 18.5%, respectively; p < 0.0001). In male subjects, we observed higher proportion of kidney diseases (CKD) (11% vs. 0.01%, respectively; p < 0.0001), a higher hospital stay compared to female subjects (22 days vs. 17 days, respectively, p < 0.0001), a higher admission in ICU (66.9% vs. 12.8%, respectively, p < 0.0001), and higher death rate (17.3% vs. 10.7%, respectively, p < 0.0001). Conclusion. These data confirm that male subjects, compared to female subjects, have a higher hospital stay, a higher admission to ICU, and higher death rate. Full article

Evidence shows that objectives for detecting and controlling cardiovascular risk factors are not being effectively met, and moreover, outcomes differ between men and women. This study will assess the gender-related differences in diagnostic inertia around the three most prevalent cardiovascular risk factors: dyslipidemia, arterial hypertension, and diabetes mellitus, and to evaluate the consequences on cardiovascular disease incidence. This is an epidemiological and cohort study. Eligible patients will be adults who presented to public primary health care centers in a Spanish region from 2008 to 2011, with hypertension, dyslipidemia, or/and diabetes and without cardiovascular disease. Participants’ electronic health records will be used to collect the study variables in a window of six months from inclusion. Diagnostic inertia of hypertension, dyslipidemia, and/or diabetes is defined as the registry of abnormal diagnostic parameters—but no diagnosis—on the person’s health record. The cohort will be followed from the date of inclusion until the end of 2019. Outcomes will be cardiovascular events, defined as hospital admission due to ischemic cardiopathy, stroke, and death from any cause. The results of this study could inform actions to rectify the structure, organization and training of health care teams in order to correct the inequality. Full article

(1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; p < 0.001). The multivariate study identified age, gender (male), body mass index (BMI), arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic cardiopathy, chronic heart failure, chronic hepatopathy, Charlson’s index, heart rate and respiratory rate upon admission >20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes. Full article

Chagas disease is an important infection in Latin America but it is also reported in non-endemic countries all over the world. Around 30% of infected patients develop chronic Chagas cardiopathy, which is responsible for most poor outcomes, mainly heart failure, arrhythmias and thromboembolic events. Of all thromboembolic events, stroke is the most feared, due to the high probability of evolution to death or disability. Despite its importance, the actual incidence of cardioembolic ischemic stroke in Chagas disease is not completely known. The Instituto de Pesquisa Evandro Chagas/Fundação Oswaldo Cruz (IPEC-FIOCRUZ) score aims to propose prophylaxis strategies against cardioembolic ischemic stroke in Chagas disease based on clinical risk–benefit. To date, the IPEC-FIOCRUZ score is considered the best tool to identify patients for stroke prophylaxis in Chagas disease according the Latin American guideline and Brazilian consensus. It can prevent many cardioembolic strokes that would not be predicted, by applying the current recommendations to other cardiopathies. However, the IPEC-FIOCRUZ score still requires external validation to be used in different Chagas disease populations with an appropriate study design. Full article

The investigation of the potential association between ischemic stroke and subclinical atrial fibrillation (SCAF) is important for secondary prevention. We aimed to determine whether SCAF can be predicted by atrial substrate measurement with P wave signal-averaged electrocardiography (SAECG). We recruited 125 consecutive patients with embolic stroke of undetermined source (ESUS) and 125 patients with paroxysmal atrial fibrillation as controls. All participants underwent P wave SAECG at baseline, and patients with ESUS were followed up with Holter monitoring and electrocardiography at baseline, 3, 6, and 12 months after discharge and every 6 months thereafter. In the ESUS group, 32 (25.6%) patients were diagnosed with SCAF during follow-up. There were no significant differences between the groups regarding atrial substrate. P wave duration (PWD) was a significant predictor of SCAF. Stroke recurrence occurred in 22 patients (17.6%), and prolonged PWD (≥ 135 ms) predicted stroke recurrence more robustly than SCAF detection. In ESUS patients, PWD can be a useful biomarker to predict SCAF and to identify patients who are more likely to have a recurrent embolic stroke associated with an atrial cardiopathy. Further research is needed for supporting the utility and applicability of PWD. Full article

Thrombotic material retrieved from acute ischemic stroke (AIS) patients represents a valuable source of biological information. In this study, we have developed a clinical proteomics workflow to characterize the protein cargo of thrombi derived from AIS patients. To analyze the thrombus proteome in a large-scale format, we developed a workflow that combines the isolation of thrombus by endovascular thrombectomy and peptide chromatographic fractionation coupled to mass-spectrometry. Using this workflow, we have characterized a specific proteomic expression profile derived from four AIS patients included in this study. Around 1600 protein species were unambiguously identified in the analyzed material. Functional bioinformatics analyses were performed, emphasizing a clustering of proteins with immunological functions as well as cardiopathy-related proteins with blood-cell dependent functions and peripheral vascular processes. In addition, we established a reference proteomic fingerprint of 341 proteins commonly detected in all patients. Protein interactome network of this subproteome revealed protein clusters involved in the interaction of fibronectin with 14-3-3 proteins, TGFβ signaling, and TCP complex network. Taken together, our data contributes to the repertoire of the human thrombus proteome, serving as a reference library to increase our knowledge about the molecular basis of thrombus derived from AIS patients, paving the way toward the establishment of a quantitative approach necessary to detect and characterize potential novel biomarkers in the stroke field. Full article