The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices.

BACKGROUND: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2-I) in patients with left ventricular assist devices (LVAD) are unknown. METHODS: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2-I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2-I. RESULTS: SGLT2-I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2-I initiation was 108 days, IQR (26-477). Following SGLT2-I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2-38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7-4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23-11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2-I initiation (p > 0.2 for all). No adverse events were recorded during median follow-up of 354 days, IQR (206-786). CONCLUSION: SGLT2-I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.

Society of thoracic surgeons risk score and left atrial pressure for predicting clinical outcomes among transcatheter mitral edge-to-edge repair patients.

BACKGROUND: Limited data exist regarding the performance of the Society of Thoracic Surgeons (STS) risk score among transcatheter mitral edge-to-edge repair (TEER) patients. OBJECTIVE: Evaluate STS score accuracy, and the incremental value of post-procedural left atrial pressure (LAP). METHODS: A retrospective analysis of TEER patients between 2013 and 2020. Patients were allocated into 3 groups: high (≥8% [n = 298, 31%]), intermediate (4%-8% [n = 318, 33%]), and low (<4% [n = 344, 36%]). Primary outcomes included 1-year mortality or cardiovascular hospitalizations. Cox proportional hazards regression modeling was used to determine the hazard ratio of the primary outcome, and STS score accuracy was assessed by receiver operating characteristic. A spline curve was used to display the relationship between LAP and the primary endpoint. Continuous net reclassification improvement (NRI) was used to determine the incremental value of LAP. RESULTS: We included 960 patients, primarily elderly (79 [70-85]), with a median STS risk of 5.6 (3-9). High-risk patients were older (83 [75-89], 81 [74-87], 72 [64-79], p < 0.001), and had more comorbidities compared to intermediate and low-risk groups. Upon Cox regression, STS score (high vs. low: HR 2.5 [1.7-3.8]; Intermediate vs. low: HR 1.8 [1.2-2.7] and LAP HR 1.03 [1.01-1.06], p = 0.007) were associated with the outcome. C statistics analysis revealed low accuracy of the STS score (AUC-0.61 [0.58-0.65, p < 0.001]). Continuous NRI analysis indicated an improvement in risk prediction of 17% (6.9-26.2), p < 0.001. CONCLUSION: STS risk score has low accuracy in predicting clinical outcomes after TEER. Adding LAP measurements can improve reclassification and identify those prone to adverse outcomes.

BNT162b2-vaccine-induced neutralization responses are immune correlates of clinical protection against SARS-CoV-2 in heart transplant recipients.

BACKGROUND: Defining immune correlates of protection against COVID-19 is pivotal for optimizing the use of COVID-19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next-generation vaccines. We aimed to identify vaccine-induced immune correlates of protection against COVID-19-related hospitalizations in a highly vaccinated heart transplant (HT) cohort. METHODS: In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine-induced neutralization of the wild-type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID-19 hospitalization. ROC analyses were performed. Primary outcomes were COVID-19 hospitalizations and severity of SARS-CoV-2 breakthrough infection. RESULTS: The study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty-six (61%) patients with COVID-19 were hospitalized; most cases were non-severe (58, 98%). For hospitalized (vs. non-hospitalized) COVID-19 patients, vaccine-induced neutralization titers were significantly lower against all SARS-CoV-2 variants (p < .005). Vaccine-induced neutralization of the wild-type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID-19-related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID-19 hospitalizations were 96 (wild-type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5). CONCLUSIONS: BNT162b2-vaccine-induced neutralization responses are immune correlates of protection and confer clinical protection against COVID-19 hospitalizations.

PESI score for predicting clinical outcomes in PE patients with right ventricular involvement.

Pulmonary embolism (PE) patients with right ventricular (RV) involvement are a heterogenous group who mandate further risk stratification. Our objective was to evaluate the efficacy of the PE severity index (PESI) for predicting adverse clinical outcomes among PE patients with RV involvement. Consecutive normotensive PE patients with RV involvement were allocated according to admission PESI score (PESI ≤ III vs. PESI ≥ IV). The primary outcome included hemodynamic instability and in-hospital mortality. Secondary outcomes included each component of the primary outcome as well as mechanical ventilation, thrombolytic therapy, acute kidney injury, and major bleeding. Multivariable logistic regression model was performed to assess the independent association between the PESI score and primary outcome. C-Statistic was used to compare the PESI with the BOVA score. A total of 253 patients were evaluated: 95 (38%) with a PESI ≥ IV. Of them, 82 (32%) patients were classified as intermediate-low risk and 171 (68%) as intermediate-high risk. Fifty (20%) patients had at least 1 adverse event. Multivariate analysis demonstrated the PESI to be an independent predictor for the primary outcome (HR 4.81, CI 95%, 1.15-20.09, p = 0.031), which was increased with a concomitant increase of the PESI score (PESI I 4.2%, PESI II 3.4%, PESI III 12%, PESI IV 16.3%, PESI V 23.1%, p for trend < 0.001). C-Statistic analysis for the PESI score yielded an AUC-0.746 (0.637-0.854), p = 0.001, compared to the BOVA score: AUC-0.679 (0.584-0.775), p = 0.011. PESI score was found to predict adverse outcomes among normotensive PE patients with RV involvement.

Outcomes among patients admitted for non-ST-segment myocardial infarction in the pre-pandemic and pandemic COVID-19 era: Israel Nationwide study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI). OBJECTIVE: We aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey. METHOD: A prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period). RESULTS: There were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5-46.7) vs. 2.9 h (IQR 1.7-6.8), respectively, P < 0.001]. Nevertheless, the time from hospital admission to reperfusion was similar in both groups. The rate of coronary angiography was also similar in both groups. The in-hospital mortality rate was similar in both the COVID-19 era and the control period groups (2.3% vs. 4.7%, respectively, P = 0.149) as was the 30-day mortality rate (3.7% vs. 5.1%, respectively, P = 0.238). CONCLUSION: In contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

Complications of retained pacemaker hardware in heart transplant recipients: case series and review of the literature.

Heart transplantation (HT) in patients with prior cardiovascular implantable electronic devices (CIEDs) is becoming more common, in parallel with the increased use of CIEDs for patients with advanced heart failure. Complete removal of CIED components during HT is not always feasible, and it is thus surprising that the literature addressing the implications of retained CIED components is limited. Indeed, there are neither guidelines nor consensus regarding the need for removal of these CIED fragments. This issue is nonetheless becoming important in light of the increase in the percentage of HT candidates having CIEDs, on the one hand, and newer therapeutic immunosuppressive protocols with higher bacterial infection potential, on the other. Thus, with the aim to study the implications of retained CIED fragments as a step towards establishing a therapeutic approach for the unique population of HT recipients with CIED remnants, we present here a case series of HT patients with retained CIED fragments who developed complications of infections together with a review of the available literature.

The prevalence and clinical effect of immunogenicity of TNF-α blockers in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the prevalence of immunogenicity of TNF-α blockers in axial spondyloarthritis (SpA) patients and to assess the effect of immunogenicity on drug levels and clinical response. METHPDS: Patients with axial SpA treated with either infliximab (INF), adalimumab (ADA) or etanercept (ETN) were recruited to our observational cross-sectional study. Demographic and clinical data were collected and disease activity scores were assessed. Drug trough levels and anti-drug antibodies were measured in serum samples and collected before the next administration. RESULTS: Thirty-nine patients with axial SpA with a mean age of 46.3±12.7 (10 women) were recruited to the study (14 receiving INF, 16 ADA and 9 ETN). Patients' mean therapy duration was 50.6 months (±46.4) and 6 (15%) of them were using MTX concomitantly with the TNF-α blockers. Anti-drug antibodies were found in 6 (15%) patients (4 with INF and 2 with ADA), all of which had undetectable drug level. No anti-drug antibodies were detected in patients treated with ETN. Immunogenicity was associated with higher BASDAI (Bath Ankylosing Spondylitis Disease Index), ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) and ASDAS-ESR. CONCLUSIONS: Axial SpA patients failure to respond to TNF-α blockers may be at least partially related to immunogenicity. Measurement of anti-drug antibodies and drug levels in these patients may assist in determining further treatment strategies.

[NOVELTIES IN PERICARDIAL DISEASES: A FOCUSED REVIEW OF THE LATEST EUROPEAN GUIDELINES].

INTRODUCTION: More than a decade has elapsed since the first international guidelines on the diagnosis and management of pericardial diseases were issued by the European Society of Cardiology (ESC) in 2004. Since then, significant advances have been made in this field due to several randomized double blinded controlled trials and also retrospective, as well as prospective, cohort studies that were conducted during this time frame. However, despite the amount of knowledge that has been accumulated, only Spanish and Brazilian national societies of cardiology have so far published national guidelines on the management of pericardial diseases. No official guidelines were issued by the American College of Cardiology/American Heart Association. Therefore, a demand for an updated document has become inevitable in order to summarize all new data and translate them into a set of recommendations which could be implemented in clinical practice. For this purpose, the new guidelines, focused on the clinical management of patients with pericardial diseases were issued by the ESC in 2015. The full text of the 2015 guidelines reflects the progress that has been made so far: the manuscript contains 9 sections (excluding appendix and references), nearly 30 second-level subsections and covers 44 pages. Several new chapters are introduced for the first time in the current guidelines, as compared with the previous version. Therefore, the aim of this review is to summarize and emphasize the most clinically relevant new aspects of the current guidelines as compared with its previous version published in 2004.

Postoperative versus Spontaneous Intracranial Abscess: Diagnostic Value of the Apparent Diffusion Coefficient for Accurate Assessment.

Purpose To assess the diagnostic value of apparent diffusion coefficients (ADCs) in spontaneous intracranial abscesses compared with those occurring after primary neurosurgery. Materials and Methods This retrospective comparative study was approved by the local institutional review board. The requirement to obtain written informed consent was waived. A total of 73 consecutive patients who underwent preoperative diffusion-weighted magnetic resonance (MR) imaging from February 2005 to May 2015 were divided into two cohorts depending on whether the abscess was identified after a primary neurosurgical procedure (n = 43) or was a spontaneous abscess (n = 30). Abscesses were assessed for ADC by two readers independently. ADCs were described as medians with interquartile range. The Mann-Whitney and χ(2) tests were used to compare ADCs between the two cohorts, and χ(2) automatic interaction detection analysis was used to classify the ADCs into categories according to the cohorts. Results The median ADC of postoperative abscesses was 1.34 × 10(-3) mm(2)/sec (interquartile range, 1.00-1.62 × 10(-3) mm(2)/sec), which was significantly higher than the median ADC of spontaneous abscesses, 0.68 × 10(-3) mm(2)/sec (interquartile range, 0.58-0.79 × 10(-3) mm(2)/sec; P < .001). Twenty four (83%) of the abscesses with ADCs less than 0.79 × 10(-3) mm(2)/sec were found to be spontaneous, while only six (27%) abscesses with ADCs between 0.79 and 1.33 × 10(-3) mm(2)/sec and no abscesses with ADCs greater than 1.33 × 10(-3) mm(2)/sec were spontaneous (P < .001). Conclusion Significantly higher ADCs were found in postoperative abscesses compared with those in spontaneous abscesses. Diffusion-weighted imaging with ADC mapping is not sufficient for excluding postoperative intracranial abscess and should not be used as the key diagnostic modality in this situation. (©) RSNA, 2016.

European Guidelines on Pericardial Diseases: a Focused Review of Novel Aspects.

Pericardial diseases are not uncommon in daily clinical practice. The spectrum of these syndromes includes acute and chronic pericarditis, pericardial effusion, constrictive pericarditis, congenital defects, and neoplasms. The extent of the high-quality evidence on pericardial diseases has expanded significantly since the first international guidelines on pericardial disease management were published by the European Society of Cardiology in 2004. The clinical practice guidelines provide a useful reference for physicians in selecting the best management strategy for an individual patient by summarizing the current state of knowledge in a particular field. The new clinical guidelines on the diagnosis and management of pericardial diseases that have been published by the European Society of Cardiology in 2015 represent such a tool and focus on assisting the physicians in their daily clinical practice. The aim of this review is to outline and emphasize the most clinically relevant new aspects of the current guidelines as compared with its previous version published in 2004.

Single arterial access technique for simultaneous dual mechanical circulatory support in cardiogenic shock.

Temporary mechanical circulatory support is a treatment of choice for patients in severe cardiogenic shock. Combining veno-arterial extracorporeal life support (ECLS) with devices that enable left ventricular unloading emerges as a promising strategy to diminish detrimental effect of elevated left ventricular afterload and to improve survival. However, the need to establish multiple arterial access sites remains a major drawback of this approach due to a significant rate of vascular complications. We describe herein a case of a single arterial access for ECLS and intra-aortic balloon pump using axillary artery that may provide a simple, modular and flexible approach for escalation or de-escalation of mechanical circulatory support.

Heart failure with improved ejection fraction: patient characteristics, clinical outcomes and predictors for improvement.

Background: Heart failure with improved ejection fraction (HFimpEF) is a recently recognized entity presenting a diagnostic and therapeutic challenge. Our aim was to characterize the profile of HFimpEF patients and evaluate predictors for EF lack of improvement among heart failure with reduced ejection fraction (HFrEF) patients. Methods: We included ambulatory HFrEF patients (EF≤40%) between January 1, 2015, and September 1, 2022, with two consecutive echocardiography exams at least 6 months apart. HFimpEF was defined as improved EF from ≤40%->40% and by ≥10%. Results: A total of 567 HFrEF patients (72% male, 54.3 ± 14.4 years old) were analyzed. Patients without EF improvement were more likely to be male, had more comorbidities, ischemic cardiomyopathy (ICMP), markers of adverse cardiac remodeling (lower EF and higher left and right ventricular diameters) and presence of late gadolinium enhancement (LGE) in MRI (P < 0.05 for all). In a multivariate analysis, male sex, ICMP, lower EF, larger ventricular size and LGE remained independent predictors for lack of EF improvement. A prediction model for lack of EF improvement including LVEF, LV diameter, diastolic blood pressure and ischemic etiology exhibited an area under the ROC curve of 0.77 (95% CI 0.73-0.81; P < 0.001). HFimpEF patients had better prognosis with lower hospitalizations and mortality rates. Guideline directed medical therapy (GDMT) were associated with improved outcomes in both groups regardless of EF improvement. Conclusions: Lack of improvement in EF among HFrEF patients may be predicted by HF etiology and imaging parameters of adverse cardiac remodeling, and is associated with worse prognosis. GDMT were associated with improved outcomes in both HFimpEF and HFrEF patients.

Sixth monovalent XBB.1.5 vaccine elicits robust immune response against emerging SARS-CoV-2 variants in heart transplant recipients.

Continued circulation of severe acute respiratory syndrome coronavirus 2 has driven the selection of variants with improved ability to escape preexisting vaccine-induced responses, posing a persistent threat to heart transplant recipients (HTRs). The immunogenicity and safety of the updated XBB.1.5-containing monovalent vaccines are unknown. We prospectively enrolled 52 HTRs who had previously received a 5-dose ancestral-derived monovalent and bivalent messenger RNA (mRNA) vaccination schedule to receive the monovalent XBB.1.5 vaccine. Immunogenicity was evaluated using live virus microneutralization assays. The XBB.1.5 monovalent vaccine elicited potent and diverse neutralizing responses and broadened the reactivity spectrum to encompass newer strains, with the highest increase in neutralization activity being more pronounced against XBB.1.5 (15.8-fold) and JN.1 (13.3-fold) than against BA.5 (6.7-fold) and wild-type (4-fold). Notably, XBB.1.5 and JN.1 were resistant to neutralization by prevaccination sera. There were no safety concerns. Our findings support the updating of coronavirus disease 2019 vaccines to match antigenically divergent variants and exclude ancestral spike-antigen to protect HTRs.

Comparison between invasive cardiac output and left ventricular assist device flow parameter.

OBJECTIVES: Evaluate the correlation between left ventricular assist device flow parameter and invasive cardiac output measurements. METHODS: We retrospectively evaluated right heart catheterization examinations performed in left ventricular assist device patients from 2 tertiary medical centers. We evaluated the correlation between cardiac output measurement methods (indirect Fick and thermodilution) and pump flow parameter using linear regression, agreement was graphically displayed using Bland-Altman plot technique. Clinical, echocardiographic, pump and haemodynamic parameters were compared between patients with and without discordance, defined as at least 20% difference between measurements. RESULTS: The study population consisted of 102 patients (median age 58 [51-64], 86% males, 17 ± 12 months post left ventricular assist device implantation) with a total of 544 measurement compared. Discordance between measurements were present in 102 of 226 (45%) comparisons between indirect Fick and pump flow and in 72 of 161 (48%) between thermodilution and pump flow. A comparison of indirect Fick and left ventricular assist device exhibited a statistical correlation of R = 0.751, and that of thermodilution and left ventricular assist device of R = 0.789. Parameters associated with the presence of discordance between cardiac output measurements included a higher rate of aortic valve opening, lower indirect Fick and higher thermodilution cardiac output. After excluding the lowest tertile of indirect Fick cardiac output values, the correlation between measurements improved (thermodilution: R = 0.879 and indirect Fick: R = 0.843, p < 0.001). CONCLUSIONS: The current left ventricular assist device flow parameter provides an estimation of cardiac output that correlates well with indirect Fick and exhibits the strongest correlation with thermodilution. This correlation was stronger after excluding lower cardiac output values.

International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.

Keep the Right in Mind-A Focused Approach to Right Ventricle-Predominant Cardiogenic Shock.

Cardiogenic shock (CS) remains a highly lethal condition despite many efforts and new interventions. Patients presenting with a rapid onset of hemodynamic instability and subsequent collapse require prompt and appropriate multimodality treatment. Multiple etiologies can lead to heart failure and subsequent shock. As the case prevalence of heart failure increases worldwide, it is of great importance to explore all manners and protocols of presentation and treatment present. With research primarily focusing on CS due to cardiac left-sided pathology, few assessments of right-sided pathology and the subsequent clinical state and treatment have been conducted. This review aims to present an in-depth assessment of the currently available literature, assessing the pathophysiology, presentation and management of CS patients due to right heart failure.

Sex differences of patients with acute chest pain evaluated through a chest pain unit.

BACKGROUND: Although sex disparities between patients with acute myocardial infarction are well known, the data regarding sex differences among symptomatic patients with acute chest pain (ACP) are limited. METHODS: We retrospectively evaluated the records of 1000 consecutive patients with ACP and hospitalized in a tertiary medical center chest pain unit (CPU). Patients were divided according to sex. The primary outcome was defined as a composite end point of readmission because of chest pain, incidence of acute coronary syndrome, revascularization, and death at 90 days and 1 year. RESULTS: Overall, 673 men and 327 women were included in the current analysis. There was no difference in regard to sex for patients who underwent noninvasive evaluation, (87.8 vs. 87.3%, P  = 0.85, for female vs. male, respectively). Among patients who underwent coronary computed tomography angiography, women were less likely to have significant coronary artery disease (CAD) (4.2 vs. 11.3%, P  = 0.005). Similarly, women had fewer significant findings (4.4 vs. 7.6%, P  = 0.007) on myocardial perfusion imaging. Consequently, fewer women underwent angiography (8 vs. 14%, P  = 0.006) and revascularization (2.8 vs. 7.3%, P  = 0.004). During follow-up, sex was not associated with the development of the primary composite outcome [odds ratio (OR) 0.91, 95% confidence interval (CI) 0.39-2.09, P -value = 0.82 and OR 1.16, 95% CI 0.65-2.06, P -value = 0.59 for 90-day and 1-year follow-up, respectively]. CONCLUSION: Evaluation of patients through a CPU enables comparable noninvasive evaluation, appropriate utilization of invasive assessment with similar outcomes during the short and intermediate follow-up period regardless of patients' sex.

Serum uric acid significantly improves the accuracy of cardiovascular risk score models.

AIMS: This study evaluated the impact of serum uric acid (sUA) on the accuracy of pooled cohort equations (PCE) model, Systematic COronary Risk Evaluation 2 (SCORE2), and SCORE2-older persons. METHODS AND RESULTS: We evaluated 19 769 asymptomatic self-referred adults aged 40-79 years free of cardiovascular disease and diabetes who were screened annually in a preventive healthcare setting. sUA levels were expressed as a continuous as well as a dichotomous variable (upper sex-specific tertiles defined as high sUA). The primary endpoint was the composite of death, acute coronary syndrome, or stroke, after excluding subjects diagnosed with metastatic cancer during follow-up. Mean age was 50 ± 8 years and 69% were men. During the median follow-up of 6 years, 1658 (8%) subjects reached the study endpoint. PCE, SCORE2, and high sUA were independently associated with the study endpoint in a multivariable model (P < 0.001 for all). Continuous net reclassification improvement analysis showed a 13% improvement in the accuracy of classification when high sUA was added to either PCE or SCORE2 model (P < 0.001 for both). sUA remained independently associated with the study endpoint among normal-weight subjects in the SCORE2 model (HR 1.3, 95% CI 1.1-1.6) but not among overweight individuals (P for interaction = 0.01). Subgroup analysis resulted in a significant 16-20% improvement in the model performance among normal-weight and low-risk subjects (P < 0.001 for PCE; P = 0.026 and P < 0.001 for SCORE2, respectively). CONCLUSION: sUA significantly improves the classification accuracy of PCE and SCORE2 models. This effect is especially pronounced among normal-weight and low-risk subjects.

Fifth bivalent omicron BA.4/BA.5 vaccination neutralization of SARS-CoV-2 in heart transplant recipients.

In 2022, the antigenically divergent SARS-CoV-2 omicron variants (BA.1, BA.2, BA.4, BA.5) outcompeted previous variants and continued to cause substantial numbers of illnesses and deaths. We evaluated the safety and immunogenicity of the bivalent original/omicron BA.4/BA.5 Pfizer/BioNTech vaccine administered as a fifth dose to heart transplant recipients (HTxRs). We compared neutralization (using live virus assays) of SARS-CoV-2-infected cells in serum samples from HTxRs who had previously received 4 doses of the monovalent BNT162b2 vaccine with samples from HTxRs with breakthrough infection after 4 monovalent BNT162b2 doses. The fifth vaccination induced high neutralization efficiency against the wild-type virus and omicron BA.1, BA.2, BA.4, and BA.5 variants, with significantly higher neutralization efficiency being induced in HTxRs with breakthrough infection than in those without. Neutralizing titers in those with breakthrough infection were sustained above the level induced by the fifth dose in the uninfected. We conclude that the fifth bivalent vaccine is immunogenic, including to variants, with higher vaccine immunogenicity conferred by breakthrough infection. Nevertheless, the clinical protection conferred by the fifth dose is yet to be determined. The sustained neutralization responses in those with breakthrough infection support the notion of delaying booster in those with natural breakthrough infection.