Incidence and Predictors of Cerebrovascular Accidents in Patients Who Underwent Transcatheter Mitral Valve Repair With MitraClip.

Transcatheter mitral edge-to-edge repair (TEER) with transcatheter devices has become a mainstay in the minimally invasive treatment of patients with severe mitral regurgitation at increased surgical risk. Despite its apparently favorable risk profile, there is uncertainty on the risk and features of cerebrovascular accidents (CVAs) early and long after transcatheter mitral valve repair. We aimed to appraise the incidence and predictors of CVA in patients who underwent TEER. We explicitly queried the data set of an ongoing multicenter prospective observational study dedicated to TEER with MitraClip (Abbott Vascular, Santa Clara, California). The incidence of CVAs after TEER was formally appraised, and we explored potential predictors of such events. Descriptive, bivariate, and diagnostic accuracy analyses were performed. Of 2,238 patients who underwent TEER, CVAs occurred in 33 patients (1.47% [95% confidence interval 1.02% to 2.06%]), including 6 (0.27% [0.10% to 0.58%]) in-hospital strokes and 27 events after discharge (0.99% [0.66% to 1.44%]), over a median follow-up of 14 months. Most CVAs were major ischemic strokes during and after the in-hospital phase. Overall, CVAs were more common in patients with atrial fibrillation (p = 0.018), renal dysfunction (p = 0.032), higher EuroSCORE II (p = 0.033), and, as expected, higher CHA2DS2-VASc score (p = 0.033), despite the limited prognostic accuracy of the score. Notably, the occurrence of CVA did not confer a significantly increased risk of long-term (p = 0.136) or cardiac death (p = 0.397). The incidence of CVA in patients who underwent TEER is low, with most events occurring after discharge and being associated with preexisting risk features. These findings, although reassuring on the safety of TEER, call for proactive antithrombotic therapy whenever CVA risk is increased before and after TEER.

Acute Hyperglycemia-Induced Injury in Myocardial Infarction.

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate.

Missense and Non-Missense Lamin A/C Gene Mutations Are Similarly Associated with Major Arrhythmic Cardiac Events: A 20-Year Single-Centre Experience.

Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene-phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.

A 25-year-long journey into interventional cardiology: looking back, and rushing forward.

Cardiovascular disease remains decade after decade a leading cause of mortality, morbidity and resource use globally as well as locally. We have had the opportunity of being involved in several iterative breakthroughs in invasive cardiovascular procedures, ranging from the advent of coronary stents to transcatheter mitral valve repair. Building up such extensive clinical and research experience, we hereby present 25 years of cardiovascular interventions at Pineta Grande Hospital and Casa di Salute S. Lucia, respectively in Castel Volturno, and S. Giuseppe Vesuviano, both in the Italian Campania region, where the same team of interventional cardiologists has managed to adopt and master several cardiovascular innovations for the benefit of thousands of patients. Our experience showcases the evolution of invasive cardiology, especially in diagnostic and therapeutic practices. Key highlights include advancements in coronary procedures, with the introduction of bare-metal stents, drug-eluting stents and drug-coated balloons, despite the setback of bioresorbable vascular scaffolds, as well as transcatheter aortic valve implantation and innovative approaches to mitral regurgitation. Furthermore, this overview scrutinizes procedural challenges, patient outcomes, and quality of life improvements, providing a rich tapestry of clinical experiences and research insights. It serves as a testament to the dynamic nature of interventional cardiology, offering a forward-looking perspective on future trends and technologies. We hope that this overview will prove an informative and insightful read for those seeking to understand the intricate journey of invasive cardiovascular care over the past decades and its trajectory into the future.

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.

Aortic valve fibroelastoma presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA): A case report and review of the literature.

Cardiac papillary fibroelastomas (CPFs) are rare benign cardiac tumors more often involving the left-sided valves and related with threatening embolic complications. We report the case of a 35-year-old woman presenting with relapsing-remitting chest pain and elevated cardiac troponins. After a negative coronary angiography, an integrated imaging assessment based on echocardiography and cardiac magnetic resonance showed a pedunculated mass on the aortic valve causing an intermittent obstructive engagement of the right coronary ostium. A tailored surgical treatment was performed and the histopathological examination of the specimen revealed mesenchymal tissue with the characteristics of CPF.

Long-term outcomes following transcatheter aortic valve implantation with the Portico self-expanding valve.

AIM: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic valve stenosis in elderly patients, but there is uncertainty on their long-term effectiveness. We aimed to assess the long-term outcome of patients undergoing TAVI with the Portico valve. METHODS: We retrospectively collected the data on patients in whom TAVI with Portico was attempted from 7 high-volume centres. Only patients theoretically eligible for 3 or more years of follow-up were included. Clinical outcomes, including death, stroke, myocardial infarction, reintervention for valve degeneration and hemodynamic valve performance were systematically assessed. RESULTS: A total of 803 patients were included, with 504 (62.8%) women, mean age of 82 years, median EuroSCORE II of 3.1%, and 386 (48.1%) subjects at low/moderate risk. The median follow-up was 3.0 years (3.0; 4.0). The composite of death, stroke, myocardial infarction, and reintervention for valve degeneration occurred in 37.5% (95% confidence interval: 34.1-40.9%), with all-cause death in 35.1% (31.8-38.4%), stroke in 3.4% (1.3-3.4%), myocardial infarction in 1.0% (0.3-1.5%), and reintervention for valve degeneration in 1.1% (0.6-2.1%). The mean aortic valve gradient at follow-up was 8.1 ± 4.6 mmHg, and at least moderate aortic regurgitation was present in 9.1% (6.7-12.3%). Independent predictors of major adverse events or death were: peripheral artery disease, chronic obstructive pulmonary disease, estimated glomerular filtration rate, atrial fibrillation, prior pacemaker implantation, EuroSCORE II, and reduced left ventricular ejection fraction (all p < 0.05). CONCLUSIONS: Portico use is associated with favorable long-term clinical outcomes. Clinical outcomes were largely impacted by baseline risk factors and surgical risk.

Features and outcomes of bailout repeat transcatheter aortic valve implantation (TAVI): the Bailout Acute TAVI-in-TAVI to Lessen Events (BATTLE) international registry.

AIM: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic stenosis in patients with intermediate to prohibitive surgical risk. When a single TAVI device fails and cannot be retrieved, TAVI-in-TAVI must be performed acutely, but outcomes of bailout TAVI-in-TAVI have been incompletely appraised. We aimed at analyzing patient, procedural and outcome features of patients undergoing bailout TAVI-in-TAVI in a multicenter registry. METHODS: Details of patients undergoing bailout TAVI-in-TAVI, performed acutely or within 24 h of index TAVI, in 6 international high-volume institutions, were collected. For every case provided, 2 same-week consecutive controls (prior TAVI, and subsequent TAVI) were provided. Outcomes of interest were procedural and long-term events, including death, myocardial infarction, stroke, access site complication, major bleeding, and reintervention, and their composite (i.e. major adverse events [MAE]). RESULTS: A total of 106 patients undergoing bailout TAVI-in-TAVI were included, as well as 212 controls, for a total of 318 individuals. Bailout TAVI-in-TAVI was less common in younger patients, those with higher body mass index, or treated with Portico/Navitor or Sapien devices (all p < 0.05). Bailout TAVI-in-TAVI was associated with higher in-hospital rates of death, emergency surgery, MAE, and permanent pacemaker implantation (all p < 0.05). Long-term follow-up showed that bailout TAVI-in-TAVI was associated with higher rates of death and MAE (both < 0.05). Similar findings were obtained at adjusted analyses (all p < 0.05). However, censoring early events, outlook was not significantly different when comparing the two groups (p = 0.897 for death, and p = 0.645 for MAE). CONCLUSIONS: Bail-out TAVI-in-TAVI is associated with significant early and long-term mortality and morbidity. Thus, meticulous preprocedural planning and sophisticated intraprocedural techniques are of paramount importance to avoid these emergency procedures.

Comparative effectiveness of Cangrelor in patients with acute coronary syndrome undergoing percutaneous coronary intervention: an observational investigation from the M.O.Ca. registry.

Cangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes, and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention. The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the cath lab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p = 0.03). Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.

Outcomes of Transcatheter Aortic Valve Replacement in Patients With Severely Reduced Left Ventricular Systolic Function in the Low Systolic Function and Transcatheter Aortic Valve Implantation (LOSTAVI) International Registry.

Transcatheter aortic valve replacement (TAVR) is an established therapy for severe, symptomatic aortic valve stenosis even in patients with impaired left ventricular systolic function. However, there is uncertainty on the clinical effectiveness of the currently available TAVR devices in patients with reduced left ventricular ejection fraction (LVEF). The LOSTAVI (Low Systolic function and Transcatheter Aortic Valve Implantation) registry is a retrospective observational study using baseline, procedural, discharge, and long-term follow-up details. A total of 3 groups of interest were distinguished: extremely reduced LVEF (<25%), severely reduced LVEF (25% to 30%), and reduced LVEF (31% to 35%). Unadjusted and adjusted analyses were carried out for in-hospital and follow-up outcomes. A total of 923 patients were included from 12 centers, with 146 patients (16%) with LVEF <25%, 425 (46%) with LVEF 25% to 30%, and 352 (38%) with LVEF 31% to 35%. Several baseline and procedural features were different across groups, including age, risk, functional class, and prevalence of bicuspid disease (all p <0.05). In-hospital mortality was similar in the 3 groups (7 [4.8%], 18 [4.2%], and 7 [2.0%], respectively, p = 0.661), but major adverse events were more common in those with extremely reduced and severely reduced LVEF (19 [13%], 53 [13%], and 25 [7.1%], respectively, p = 0.024). The 12-month follow-up confirmed the significant detrimental impact of reduced LVEF on both death (21 [14%], 49 [12%], and 25 [7.1%], respectively, p = 0.024) and major adverse events (37 [25%], 89 [21%], and 53 [15%], respectively, p = 0.016). The adjusted analysis confirmed the significant prognostic role of LVEF on both outcomes, whereas TAVR device type was not associated with death or major adverse events (all p >0.05). In conclusion, TAVR yields favorable early and 1-year results in patients with reduced LVEF, including those with extremely depressed systolic dysfunction. However, reduced LVEF still represents a major adverse prognostic factor for both short- and mid-term outcomes.

Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study.

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital "P. Giaccone" Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox's regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student's t test for continuous variables and the Mantel-Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox's regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43-48%). Patients with anemia were significantly older (p < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59-4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65-3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.

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.

Appraising features and outlook of women and men discharged after an acute coronary syndrome: evidence from the 23,700-patient PRAISE International Registry.

BACKGROUND: Acute coronary syndromes (ACS) are a common cause of morbidity and mortality. Several studies have focused on ACS at admission, but limited evidence is available on sex-based comparison of patients discharged after ACS. We appraised the outlook of women and men discharged after ACS. METHODS: Details on women enrolled in the PRAISE registry, an international cohort study spanning 23,700 patients included between 2003 and 2019, were systematically collected. We focused on patient and procedural features, medications at discharge, and 1-year outcomes. The primary endpoint was the composite of death, myocardial infarction, or major bleeding after discharge. RESULTS: A total of 17,804 (76.5%) men and 5466 (23.5%) women were included. Several baseline differences were found, including risk factors and prior revascularization (all P<0.05). Men underwent more frequently radial access, and at discharge they received more commonly dual antiplatelet therapy and guideline-directed medical therapy (P<0.001). At 1-year follow-up, risks of death, reinfarction, major bleeding, and non-fatal major bleeding, jointly or individually, were all significantly higher in women (all P≤0.01). All such differences however did not hold true at multivariable analysis, with the exception of major bleeding, which appeared surprisingly less common in females at fully adjusted analysis (P=0.017). CONCLUSIONS: Women, albeit only apparently, had worse outcomes 1 year after discharge for ACS, but adjusted analysis suggested instead that they faced a lower risk of major bleeding after discharge. These findings support the call for more aggressive management of women after ACS.

Impact of coronary artery disease on outcome after transcatheter edge-to-edge mitral valve repair with the MitraClip system.

BACKGROUND: The clinical impact of coronary artery disease (CAD) on the prognosis of patients undergoing MitraClip implantation is still unclear. METHODS: One thousand nine hundred fifty-three patients undergoing MitraClip implantation included in the multicenter GIOTTO Registry were stratified according to CAD. Endpoints were all-cause death, cardiac death, and re-hospitalization for heart failure at follow-up (median 15.8 months). RESULTS: Although younger, CAD patients were more symptomatic, had worse cardiovascular risk profile, higher burden of comorbidities, more frequently affected by functional MR, with higher left ventricle (LV) diameters and lower ejection fraction (EF). At follow-up, CAD patients showed higher rates of all-cause death (25.4% vs. 19.6%; P=0.002), cardiovascular death (14.0% vs. 10.1%; P=0.007) and re-hospitalization for heart failure (13.9% vs. 10.2%; P=0.011). Dividing the population according to mitral regurgitation (MR) etiology (functional vs. non-functional MR), no differences were observed between CAD and no-CAD patients. At multivariate logistic regression, NYHA III/IV class, prior heart failure hospitalization, severe chronic kidney disease, atrial fibrillation, LV end-diastolic diameter and LVEF<30% but not CAD resulted independent predictors of all-cause death. The same finding was confirmed even after propensity score adjustment. CONCLUSIONS: CAD did not show a relevant impact on mid-term prognosis per se, but seemed to identify a more complex and diseased cohort of patients with worse clinical and functional status.

A Young Patient Presenting with Dilated Cardiomyopathy and Renal Infarction during Treatment with Isotretinoin: Mere Coincidence or Serious Side Effect of a Drug Commonly Used in Adolescence?

Isotretinoin or 13-cis-retinoic acid (RA) is one of the most effective and widely used drugs for the treatment of severe acne vulgaris. Despite being deemed safe, no definite consensus has been reached on the cardiovascular risk of RA derivatives. We report a case of heart failure due to dilated cardiomyopathy (DCM) and concomitant renal infarction occurring after 5 months of isotretinoin use in a previously healthy 18-year-old male. The patient, with a history of acne vulgaris, presented to our emergency department with left iliac fossa pain and effort dyspnea. A trans-thoracic echocardiogram showed DCM and severely reduced left ventricle ejection fraction (LVEF: 29%). During hospitalization, a total body computed tomography (CT) showed an ischemic lesion in the left kidney. Ischemic, autoimmune, infective, and heritable causes of DCM were ruled out. Cardiac magnetic resonance (CMR) evidenced LV circumferential mid-wall late gadolinium enhancement. Heart failure therapy was promptly started and up-titrated, but only poor LVEF improvement was detected overtime. Our case aims to raise awareness on rare life-threatening cardiovascular events possibly associated with isotretinoin use. To the best of our knowledge, this is the first described case of renal thromboembolism and severe DCM leading to implantable cardioverter-defibrillator (ICD) implantation occurring during isotretinoin treatment.

Targeting unfolded protein response reverts ER stress and ER Ca2+ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/C R321X.

BACKGROUND: We previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DCM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/C protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-CHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac cells. METHODS: HL-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targeting the UPR, salubrinal, guanabenz and empagliflozin to rescue ER stress and dysfunction. In these cells, the state of activation of both the UPR and the pro-apoptotic pathway were analyzed monitoring the expression levels of phospho-PERK, phospho-eIF2α, ATF4, CHOP and PARP-CL. In addition, we measured ER-dependent intracellular Ca2+ dynamics as indicator of proper ER functionality. RESULTS: We found that salubrinal and guanabenz increased the expression levels of phospho-eIF2α and downregulated the apoptosis markers CHOP and PARP-CL in LMNA R321X-cardiomyocytes, maintaining the so-called adaptive UPR. These drugs also restored ER ability to handle Ca2+ in these cardiomyocytes. Interestingly, we found that empagliflozin downregulated the apoptosis markers CHOP and PARP-CL shutting down the UPR itself through the inhibition of PERK phosphorylation in LMNA R321X-cardiomyocytes. Furthermore, upon empagliflozin treatment, ER homeostasis, in terms of ER ability to store and release intracellular Ca2+ was also restored in these cardiomyocytes. CONCLUSIONS: We provided evidence that the different drugs, although interfering with different steps of the UPR, were able to counteract pro-apoptotic processes and to preserve the ER homeostasis in R321X LMNA-cardiomyocytes. Of note, two of the tested drugs, guanabenz and empagliflozin, are already used in the clinical practice, thus providing preclinical evidence for ready-to-use therapies in patients affected by the LMNA R321X associated cardiomyocytes.

Role of pre-operative embolization in carotid body tumor surgery according to Shamblin classification: A systematic review and meta-analysis.

BACKGROUND: Pre-operative embolization prior to surgical resection of carotid body tumors was meant to decrease intraoperative blood loss and operative time. Yet, potential confounders such as different Shamblin classes have never been analyzed. Aim of our meta-analysis was to investigate effectiveness of a pre-operative embolization according to different Shamblin classes. METHODS: Five studies comprising 245 patients were included. A random effects model meta-analysis was conducted, and the I2 statistic was used to assessment for heterogeneity. RESULTS: Pre-operative embolization was associated with a significant reduction in blood loss (WM: 276.4 mL; 95% CI, 201.9-378.3, p < 0.01); an absolute mean reduction, though not statistically significant, was observed in both Shamblin 2 and 3 classes. No difference in operative time was found between the two strategies (WM: 192.0 min; 95% CI, 157.7-234.1, p = 1.0). CONCLUSIONS: Embolization proved an overall significant reduction in perioperative bleeding, which did not reach threshold for statistical significance when Shamblin classes were singularly considered.

Unsupervised Machine Learning with Cluster Analysis in Patients Discharged after an Acute Coronary Syndrome: Insights from a 23,270-Patient Study.

Characterization and management of patients admitted for acute coronary syndromes (ACS) remain challenging, and it is unclear whether currently available clinical and procedural features can suffice to inform adequate decision making. We aimed to explore the presence of specific subsets among patients with ACS. The details on patients discharged after ACS were obtained by querying an extensive multicenter registry and detailing patient features, as well as management details. The clinical outcomes included fatal and nonfatal cardiovascular events at 1-year follow-up. After missing data imputation, 2 unsupervised machine learning approaches (k-means and Clustering Large Applications [CLARA]) were used to generate separate clusters with different features. Bivariate- and multivariable-adjusted analyses were performed to compare the different clusters for clinical outcomes. A total of 23,270 patients were included, with 12,930 cases (56%) of ST-elevation myocardial infarction (STEMI). K-means clustering identified 2 main clusters: a first 1 including 21,998 patients (95%) and a second 1 including 1,282 subjects (5%), with equal distribution for STEMI. CLARA generated 2 main clusters: a first 1 including 11,268 patients (48%) and a second 1 with 12,002 subjects (52%). Notably, the STEMI distribution was significantly different in the CLARA-generated clusters. The clinical outcomes were significantly different across clusters, irrespective of the originating algorithm, including death reinfarction and major bleeding, as well as their composite. In conclusion, unsupervised machine learning can be leveraged to explore the patterns in ACS, potentially highlighting specific patient subsets to improve risk stratification and management.

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.