non-CS Patients Research Articles

Yield of Echocardiography with Bubble Studies Among Acute Ischemic Stroke Patients.

Background: Transthoracic (TTE) and transesophageal (TEE) echocardiographic studies with agitated saline, also known as "bubble studies" (BSs), are used to diagnose patent foramen ovales (PFOs) in cryptogenic strokes (CSs). Guidelines limit PFO closure recommendations to CS patients ≤ 60 but BSs are often performed as part of standard order sets, leading to inappropriate studies in older patients with already-established stroke etiologies. Methods: This retrospective single-center study included acute ischemic stroke patients between January 2021 and June 2022 and assessed the stroke etiology and number of the echocardiographic studies performed. Results: A total of 663 patients were admitted during this period with 413 (62.3%) classified as non-CS. Overall, 390 (58.8%) TTE and 40 (6.0%) TEE with BSs were conducted. Of that, non-CS patients received 252 TTE and 17 TEE with BSs. PFOs were diagnosed in 36 CS and 18 non-CS patients and 14 of the 15 PFO closures were performed in the CS patients for primary stroke prevention. The one closure in the non-CS patient was performed in conjunction with the open excision of a mitral valve mass. Conclusions: Therefore, the majority of the BSs performed in non-CS patients yielded no change in management. Our study identifies a large volume of diagnostic studies that are not supported by current clinical guidelines and instead, may contribute to healthcare waste. A new institutional protocol should be established to improve operational efficiency and reduce the downstream implications of diagnostic overuse in ischemic stroke care.

Acute echocardiographic assessment of patients with ST-elevation myocardial infarction in detecting clinically hidden hemodynamic deterioration

Abstract Background Transthoracic echocardiography (TTE) offers an immediate non-invasive assessment of cardiac morphology and function that can be performed bedside. Acute TTE in the catheterization laboratory (cath.lab.) may be helpful to identify markers of subsequent development of cardiogenic shock (CS) in patients with ST-elevation myocardial infarction (STEMI) in addition to the previously validated ORBI risk score. This relationship has not been investigated thoroughly previously. Purpose To investigate the association between acute TTE estimates of left ventricular (LV) function prior to primary percutaneous coronary intervention (pPCI) in STEMI patients and pro-B-type natriuretic peptide (proBNP) as a proxy associated with of CS development. Method From September 2023 all non-CS STEMI patients at one tertiary heart center underwent acute bedside TTE in the cath.lab. and ORBI risk score assessing the risk of CS development aiming for inclusion of 500 patients. The 5 minutes TTE-protocol consisted of LV ejection fraction (EF), LV outflow tract velocity time integral (LVOT VTI), mitral inflow (E and E/A), mitral deceleration time, and mitral annular early diastolic velocity é lateral. The primary endpoint was proBNP measured 24 hours (h) after pPCI (12-36h) stratified in quartiles (Q4 vs. Q1-3). The correlation between proBNP and TTE measurements and proBNP and ORBI risk score was examined using univariate linear regression models. Results Until now 153 STEMI patients (mean age 64 years, 25% female) were studied. Anterior STEMI was present in 36%, and median time from cath. lab. arrival to first wire over the culprit lesion was 28 minutes (IQR 24; 37). Patients with high proBNP level (Q4 vs. Q1-3) had significantly higher heart rate (median 84 bpm vs. 72 bpm) and Killip Class>1 (16% vs. 0%) at admission, but similar lactate levels (1.8mM vs. 1.5mM), systolic blood pressure (130 mmHg vs. 137 mmHg), and out-of-hospital cardiac arrest (11% vs. 12%). Patients with high proBNP levels (Q4 vs. Q1-3) had significantly lower LVEF (35% vs. 50%), higher E/é lateral (median 11.4 vs. 7.9), and higher ORBI risk score (median 8 vs. 4). LVEF, LVOT VTI, E/é lateral, and ORBI risk score were significantly associated with proBNP (Figure 1). Two patients developed CS after the pPCI; one with high proBNP level Q4, and one deceased prior to proBNP measurement. Conclusion Acute TTE is an easy tool for assessment of the acute hemodynamic status in STEMI patients bedside in the cath.lab., and it can be without delaying time to revascularization. LVEF, LVOT VTI, E/é lateral, and ORBI were all parameters associated with increased levels of the hemodynamic biomarker proBNP, and may together with the ORBI risk score improve the assessment and risk stratification of STEMI-patients at risk of CS-development.Figure 1.

Incidence of Compartment Syndrome Following Peri-Pandemic Intervention for Non-traumatic Acute Limb Ischemia.

During the pandemic, our institution anecdotally observed a significant proportion of acute limb ischemia (ALI) patients developing compartment syndrome (CS) following revascularization compared to pre-pandemic rates. To determine whether this perceived increase was occurring globally, we utilized the TriNetX database to evaluate the incidence of CS secondary to ALI intervention in both the pre-pandemic (2017-2019) and pandemic eras (2020-2022). We conducted a multicenter query using the TriNetX global research network for ALI patients receiving treatment. Incidence of CS diagnosis within 1 calendar day of ALI intervention was calculated for each era. Demographics and comorbidities were then compared between CS and non-CS patients within each era. Risk of adverse outcomes within 30 days of CS diagnosis was also determined for each era, including mortality, major amputation, and re-intervention. The pre-pandemic cohort contained 7736 patients while the pandemic era cohort included 8,306, for 16,042 total patients. A significant increase in CS incidence (risk ratio (RR) = 1.23, P = 0.0026) was demonstrated within the pandemic era. An increased prevalence of comorbidities such as dyslipidemia (pre-pandemic: P = 0.0022; pandemic: P = 0.0026) and peripheral vascular disease (P < 0.0001, both eras) was observed in the non-CS cohort within both eras. 30-day mortality was significantly increased in CS patients (pre-pandemic: RR = 3.057; pandemic: RR = 2.710; P < 0.0001 both eras) compared to non-CS patients. CS patients were more likely to receive major amputation (pre-pandemic: RR = 3.734; pandemic: RR = 2.809; P < 0.0001 both eras) and/or re-intervention within 30 days (pre-pandemic: RR = 1.871, P < 0.0001; pandemic: RR = 1.370, P = 0.0218) over non-CS patients. The incidence of CS following revascularization for ALI rose worldwide during the pandemic. Patients who developed CS are younger with fewer comorbidities than non-CS patients. Despite a more favorable comorbid profile, CS patients demonstrate significantly higher rates of adverse outcomes. Further investigation is necessary to determine the specific underlying mechanisms driving this increased incidence in CS among ALI patients.

Previous Cesarean Section Delivery Increases the Risk for Seroma Development in Abdominoplasty Patients: Our Experience With 746 Patients.

Complications after body-contouring surgery are a field of great interest. Recognition of patient-related characteristics contributing to a greater risk for complication is of the utmost importance in improving the quality of care and safety profile of aesthetic procedures. Previous history of cesarean section (CS) and its impact on adverse events after abdominoplasty has yet to be investigated and defined. Our objective was to evaluate the effect of previous cesarean section on the risk for adverse events in abdominoplasty. The medical records of 746 eligible patients were reviewed, and relevant information was extracted. Stratification of patients based on a previous history of CS was followed by statistical analysis of differences between the groups. Relevant regression models were implemented to further understand the data. Seven hundred forty-six patients were included in the study, of which 308 (43.1%) had history of CS delivery. The group did not differ in baseline demographic and surgical details, except for a greater hemoglobin level in the non-CS patients (P = .007). Analysis of complication rates revealed a statistically significant increase in the risk for seroma development in the group of patients with a history of CS delivery (P = .031), which correlated to a 65% increase in the risk for complications (odds ratio = 1.65, 95% CI 1.07-2.56). A medical history of CS increases the risk for seroma development in the postoperative period following abdominoplasty. Several potential pathogenic mechanisms exist, and further prospective research is needed to further characterize the association.

Role of Textural Analysis Parameters Derived from FDG PET/CT in Diagnosing Cardiac Sarcoidosis

Abstract Introduction Texture and radiomic analysis characterize the lesion's phenotype and evaluate its microenvironment in quantitative terms. The aim of this study was to investigate the role of textural features of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT) images in differentiating patients with cardiac sarcoidosis (CS) from patients with physiologic myocardial uptake. Methods This is a retrospective, single-center study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients. These patients underwent FDG PET/CT for the diagnosis of CS. The non-CS group underwent 18F-FDG PET/CT for other oncological indications. The PET/CT images were then processed in a commercially available textural analysis software. Region of interest was drawn over primary tumor with a 40% threshold and was processed further to derive 92 textural and radiomic parameters. These parameters were then compared between the CS group and the non-CS group. Receiver operating characteristics (ROC) curves were used to identify cutoff values for textural features with a p-value &lt; 0.05 for statistical significance. These parameters were then passed through a principle component analysis algorithm. Five different machine learning classifiers were then tested on the derived parameters. Results A retrospective study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients, was done. Twelve textural analysis parameters were significant in differentiating between the CS group and the non-CS group. Cutoff values were calculated for these parameters according to the ROC curves. The parameters were Discretized_HISTO_Entropy, GLCM_Homogeneity, GLCM_Energy, GLRLM_LRE, GLRLM_LGRE, GLRLM_SRLGE, GLRLM_LRLGE, NGLDM_Coarseness, GLZLM_LZE, GLZLM_LGZE, GLZLM_SZLGE, and GLZLM_LZLGE. The gradient boosting classifier gave best results on these parameters with 85.71% accuracy and an F1 score of 0.86 (max 1.0) on both classes, indicating the classifier is performing well on both classes. Conclusion Textural analysis parameters could successfully differentiate between the CS and non-CS groups noninvasively. Larger multicenter studies are needed for better clinical prognostication of these parameters.

Radiomic analysis reveals diverse prognostic and molecular insights into the response of breast cancer to neoadjuvant chemotherapy: a multicohort study

BackgroundBreast cancer patients exhibit various response patterns to neoadjuvant chemotherapy (NAC). However, it is uncertain whether diverse tumor response patterns to NAC in breast cancer patients can predict survival outcomes. We aimed to develop and validate radiomic signatures indicative of tumor shrinkage and therapeutic response for improved survival analysis.MethodsThis retrospective, multicohort study included three datasets. The development dataset, consisting of preoperative and early NAC DCE-MRI data from 255 patients, was used to create an imaging signature-based multitask model for predicting tumor shrinkage patterns and pathological complete response (pCR). Patients were categorized as pCR, nonpCR with concentric shrinkage (CS), or nonpCR with non-CS, with prediction performance measured by the area under the curve (AUC). The prognostic validation dataset (n = 174) was used to assess the prognostic value of the imaging signatures for overall survival (OS) and recurrence-free survival (RFS) using a multivariate Cox model. The gene expression data (genomic validation dataset, n = 112) were analyzed to determine the biological basis of the response patterns.ResultsThe multitask learning model, utilizing 17 radiomic signatures, achieved AUCs of 0.886 for predicting tumor shrinkage and 0.760 for predicting pCR. Patients who achieved pCR had the best survival outcomes, while nonpCR patients with a CS pattern had better survival than non-CS patients did, with significant differences in OS and RFS (p = 0.00012 and p = 0.00063, respectively). Gene expression analysis highlighted the involvement of the IL-17 and estrogen signaling pathways in response variability.ConclusionsRadiomic signatures effectively predict NAC response patterns in breast cancer patients and are associated with specific survival outcomes. The CS pattern in nonpCR patients indicates better survival.

MiR-619-5p and cardiogenic shock in patients with ST-segment elevation myocardial infarction.

Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients. STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes. Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003). Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.

The 2023 Türkiye-Syria earthquakes: analysis of pediatric victims with crush syndrome and acute kidney Injury

BackgroundOn February 6th, 2023, two consecutive earthquakes struck southeastern Türkiye with magnitudes of 7.7 and 7.6, respectively. This study aimed to analyze the clinical and laboratory findings, as well as management of pediatric victims with Crush Syndrome (CS) and Acute Kidney Injury (AKI).MethodsThe study included pediatric earthquake victims who were presented to Mersin University Hospital. Clinical and laboratory characteristics of the patients were collected retrospectively.ResultsAmong 649 patients, Crush injury (CI), CS and AKI was observed in 157, 59, and 17 patients, respectively. White blood cell count (12,870 [IQR: 9910–18700] vs. 10,545 [IQR: 8355–14057] /µL, P < 0.001), C-reactive protein (51.27 [IQR: 14.80–88.78] vs. 4.59 [1.04–18.25] mg/L, P < 0.001) and myoglobin levels (443.00 [IQR: 198.5–1759.35] vs. 17 [11.8–30.43] ng/ml) were higher in patients with CS, while their sodium (IQR: 134 [131–137] vs. 136 [134–138] mEq/L, P < 0.001) levels were lower compared to non-CS patients. An increase in myoglobin levels was identified as an independent risk factor for developing CS (OR = 1.017 [1.006–1.027]). Intravenous fluid replacement was administered to the patients with CS at a dose of 4000 cc/m2/day. Hypokalemia was observed in 51.9% of the CS patients on the third day. All patients with AKI showed improvement and no deaths were reported.ConclusionsHyponatremia and increase in inflammation markers associated with CS may be observed. An increase in myoglobin levels was identified as a risk factor for CS. Hypokalemia may be seen as a complication of vigorous fluid therapy during hospitalization.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Abstract 13760: Systematic Review and Meta-Analysis of Clinical Outcomes in Cardiac Sarcoidosis: A Comprehensive Review

Introduction: Cardiac sarcoidosis (CS), often overlooked due to its myriad and non-specific presentation, is mainly understood through small studies. Hypothesis: What comprehensive evidence exists regarding the cumulative clinical outcomes in CS patients? Methods: A literature search in PubMed and EMBASE was conducted until September 8, 2022. Data from Kaplan-Meier curves were reconstructed using WebPlotDigitizer, with subsequent analysis was conducted via Cox proportional hazards models and non-parametric methods. Results: We reviewed 183 studies with 29,830 CS-diagnosed patients, and CS predominantly affected middle-aged, White, and Black individuals, with data primarily derived from Europe, North America, and Japan. The prevalent arrhythmias were ventricular arrhythmias (25%) and conduction block (low-degree, 21%; high-degree, 15%). Steroids were the primary treatment, with implantable cardioverter-defibrillators (ICD) used in 20% of cases (Image 1) . Survival meta-analysis showed that immunosuppressants significantly lower mortality risk in CS patients (HR: 0.52, 95% CI: 0.38-0.7, p &lt; 0.0001) compared with the general CS population. ICD implanted for primary prevention in CS patients was associated with lower risk of inappropriate ICD therapy compared with ICD for secondary prevention (HR: 0.29, 95% CI: 0.19-0.44, p &lt; 0.0001). Post-transplant survival was superior in CS patients than non-CS patients (HR: 0.58, 95% CI: 0.46-0.72, p &lt; 0.0001) (Image 2) . Conclusions: This study is the first to provide comprehensive outcomes in CS patients. We encourage global research efforts to include underrepresented population in order to better understand CS.

Comparison of Direct and Extraction Immunoassay Methods With Liquid Chromatography-Tandem Mass Spectrometry Measurement of Urinary Free Cortisol for the Diagnosis of Cushing's Syndrome.

Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing's syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected. A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing-Bablok regression and Bland-Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r=0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r=0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LC-MS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8-1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Low-dose dobutamine infusion and single-dose tocilizumab in acute myocardial infarction patients with high risk of cardiogenic shock development - rationale and design of the DOBERMANN trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Fonden Background Cardiogenic shock (CS) is seen in up to 10% of patients with ST-elevation myocardial infarction (STEMI) and is associated with a high mortality rate of up to 50%. Approximately 1/3 of STEMI-patients developing CS are not in overt shock at time of hospital admission but will develop hemodynamical instability within the following hours to days. Patients at risk of CS development may be clinically stable but with normal lactate levels (Society for Cardiovascular Angiography and Interventions classification, SCAI A/B). The Observatoire Régional Breton sur l'Infarctus (ORBI) clinical risk score has recently been developed and validated for predicting the risk of in-hospital (late) CS. STEMI-patients with an ORBI score &amp;gt;=10 have a risk of in-hospital CS development of more than 8-10%. NTproBNP is a biomarker released from the myocardium reflecting neurohormonal activation which is strongly correlated with hemodynamic parameters. Neurohormonal activation as well as a systemic inflammatory response are present acutely at hospital admission in STEMI patients developing late CS compared to non-CS patients suggesting an early subclinical hemodynamic deterioration. Dobutamine induces significant positive inotropic- and dose-dependent chronotropic effects and decreases afterload by peripheral vasodilatation, which increases cardiac output and organ perfusion. The interleukin-6 receptor antagonist Tocilizumab has been shown to reduce troponin leakage and increase myocardial salvage in acute MI patients. The effects of Dobutamine and Tocilizumab in a high-risk population have not previously been investigated. Methods DOBERMANN is an investigator-initiated, double blinded randomized clinical trial. Consecutive patients with acute MI admitted for acute coronary angiography and treated with percutaneous coronary intervention are screened with the ORBI risk score in the catheterization laboratory. One hundred adult patients presenting without CS at hospital admission with an intermediate-high risk of CS development (ORBI risk score of &amp;gt;=10) will be randomized 2x2 to receive a continuous intravenous infusion of dobutamine (5 micrograms/kg/minute, 24h) vs. placebo, and a single dose of Tocilizumab (280 mg, 1h) vs. placebo. NTproBNP as a proxy for development of CS and hemodynamic instability will be sampled for primary endpoint analysis. Effects on clinical parameters, mortality, morbidity as well as specific indicators of inflammation, cardiac function, and infarct size will secondarily be assessed noninvasively at 48h and at three months follow-up. Enrollment began in March 2022 and is commencing as planned. Discussion We hypothesize that inflammatory and neurohormonal responses are associated with subclinical hemodynamic instability in patients with AMI with intermediate/high risk of CS. The potentially unstable condition may be targeted pharmacologically as an add-on to existing therapy.

Mitochondrial Rieske iron-sulfur protein is a crucial molecule in COPD-associated pulmonary hypertension

Pulmonary hypertension (PH) often occurs in chronic obstructive pulmonary disease (COPD) and is the major cause of death in COPD patients. Molecular mechanisms for PH in COPD remain poorly understood, and clinical treatments are neither specific nor effective. Cigarette and e-cigarette smoking (CS) account for up to 90% of COPD cases, in which nicotine is the major active component and causes COPD-like cellular responses; moreover, hypoxia is a known key factor in the development of PH. In this study, we aim to develop a PH in COPD animal model and determine the underlying molecular mechanisms. Our findings revealed that co-exposure of nicotine (or CS) and hypoxia synergistically elevated PH (i.e., right ventricular pressure and weight) compared to nicotine, CS, or hypoxia alone. We also found that mitochondrial reactive oxygen species ([ROS] m ), assessed using mitochondrial-specific ROS indicator MitoSOX, was significantly increased in pulmonary artery smooth muscle cells (PASMCs) from CS patients with COPD compared to normal PASMCs from non-CS patients. The increased [ROS] m was blocked by lentiviral short hairpin RNA (shRNA)-mediated knockdown of Rieske iron-sulfur protein (RISP) in mitochondrial complex III. More importantly, SMC-specific RISP gene knockout blocked nicotine/hypoxia exposure-induced PA remodeling and hypertension, whereas SMC-specific RISP overexpression exacerbated PH in mice. We further discovered that RISP regulated DNA damage following nicotine/hypoxia co-exposure via ataxia telangiectasia-mutated (ATM) signaling. RISP also mediated nuclear factor (NF)-κB inflammatory signaling. Together, our studies for the first time demonstrate that nicotine/hypoxia co-exposure leads to RISP-dependent [ROS] m , ATM-mediated DNA damage-dependent NF-κB-associated inflammation, PA vasoremodeling and PH in COPD in a sex-dependent manner. Moreover, RISP, ATM, and NF-κB may serve as novel and effective molecular targets in treating COPD and its associated PH. NIH R01 HL122865, NIH R03AG070784, and NIH R01 HL108232 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Morphometric characteristics of interatrial septum in patients with patent foramen ovale and cryptogenic stroke

High-risk morphometric characteristics of patent foramen ovale (PFO), as observed by transesophageal echocardiography (TEE), are associated with cryptogenic stroke (CS) and crucial for selecting optimal treatment. This study aimed to evaluate the pathogenic characteristics and mobility of the interatrial septum (IAS) in patients with PFO and CS. The PFO parameters of 69 patients, including 32 patients with CS and 37 without CS, were assessed using TEE to determine the degree of mobility and pathogenic characteristics. CS patients had more significant IAS mobility, shorter PFO length and thinner septum primum thickness than non-CS patients. Multivariate analysis showed that age, IAS mobility, PFO length and septum primum thickness were independently associated with CS. No correlation was found in the mobility of the middle and edge of the septum primum and septum secundum in both groups of patients. TEE could accurately identify the morphometric characteristics of PFO. CS was associated with PFO characteristics, including age, IAS mobility, PFO length and septum primum thickness.

902 INCIDENCE, CHARACTERISTICS AND CLINICAL OUTCOMES OF PATIENTS PRESENTING WITH VERSUS WITHOUT CARDIOGENIC SHOCK AND RECEIVING CANGRELOR: AN EXPLORATORY SUBANALYSIS OF THE ICARUS REGISTRY

Abstract Aims To assess the frequency, clinical characteristics, and clinical outcomes of patients presenting with and without cardiogenic shock (CS) among those receiving cangrelor in the peri-percutaneous coronary intervention (PCI) phase. Methods Consecutive patients treated with cangrelor in 7 Italian institutions were retrospectively enrolled in the ICARUS (“Intravenous CAngrelor in high-bleeding Risk patients Undergoing percutaneouS coronary intervention”, NCT05505591) registry. Cardiogenic shock was defined as system hypotension (systolic blood pressure &amp;lt; 90 mmHg) despite adequate volume in presence of clinical or laboratory signs of hypoperfusion. The primary endpoint was net adverse clinical events (NACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis and Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding, at 48 hours. Secondary endpoints were assessed at 48 hours. Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, and definite or probable stent thrombosis were evaluated at discharge. Results Out of 551 patients undergoing PCI with cangrelor between January 2019 and August 2022, cardiogenic shock status was available in 550 (99.9%). Among those, 25 (4.5%) presented with CS. Median age was 67 (59-78) vs. 68 (59-77) years in CS vs. non-CS patients (p=0.767). Female sex (44% vs. 24%, p=0.038), presentation with ST-elevation myocardial infarction (84% vs. 42%, p&amp;lt;0.001) and cardiac arrest (46% vs. 4%, p&amp;lt;0.001) were more frequent in the CS group. Likewise, CS patients had higher rates of femoral access (36% vs. 10%, p&amp;lt;0.001), three-vessel PCI (17% vs. 3%, p=0.007), intra-aortic balloon pump implantation (50% vs. 3%, p&amp;lt;0.001) and Gp IIb/IIIa inhibitors use (16% vs. 3%, p=0.005). At 48 hours, CS patients had higher rates of NACE (44% vs. 7%, p&amp;lt;0.001), MACE (12% vs. 1%, p=0.008), cardiovascular death (12% vs. 0.4%, p=0.001), BARC 2, 3 or 5 bleeding (32% vs. 6%, p&amp;lt;0.001), and BARC 3 or 5 bleeding (16% vs. 1%, p=0.001). At multivariable logistic regression, CS independently predicted the occurrence of NACE (odds ratio [OR] 1.29, 95% CI 1.14-1.45, p&amp;lt;0.001) and BARC 3 or 5 bleeding (OR 1.14, 95% CI 1.08-1.21, p&amp;lt;0.001). In-hospital MACE were available in all but one patient, with an event rate that was higher among CS patients (32% vs. 1.3%, log-rank p&amp;lt;0.001). At Cox multivariable analysis, cardiogenic shock was the only independent predictor of in-hospital MACE (hazard ratio [HR] 7.13, 95% CI 1.37-36.8). Conclusions Approximately 5% of patients receiving cangrelor in real-world clinical practice presented with CS. These patients were at higher risk of both ischemic and bleeding events. CS independently predicted the occurrence of 48-hour NACE and major bleeding, as well as in-hospital MACE.

Change in patent foramen ovale height is associated with cryptogenic stroke and the construction of a morphology-based scoring system.

Current guidelines recommended patent foramen ovale (PFO) occlusion as the preferred treatment for PFO-related cryptogenic stroke (CS); however, finding the causative foramen ovale remains challenging. This study aimed to identify predictors and establish a scoring system by assessing PFO morphology and stroke-related factors. Based on a prospective multicenter registered clinical trial, we compared data mainly derived from transesophageal echocardiography (TEE) and clinical history in patients with PFO-related CS and those without CS (non-CS) with incidental PFO. Subsequently, we explored independent predictors using logistic analysis, established a scoring system based on the results, and finally evaluated the scoring system using receiver operating characteristic (ROC) analysis and internal validation. 75 patients with PFO-related CS and 147 non-CS patients were enrolled. Multivariate logistic analysis showed that the change in PFO height, large PFO, atrial septal aneurysm (ASA), and sustained right-to-left shunt (RLS) had independent relationships with CS. Based on the odds ratio value of each independent factor, a scoring system was built: change in PFO height ≥ 1.85 mm (3 points), large PFO (2 points), ASA (5 points), sustained RLS (2 points). 0-2 points correspond to low-risk PFO, 3-5 points medium-risk PFO, and 7-12 points high-risk PFO. ROC analysis showed an area under the curve of 0.80 to predict CS. The proportion of patients with CS is increasing based on these points. Our study screened out the change in PFO height as an independent predictor of CS. A simple and convenient scoring system can provide constructive guidance for identifying whether the PFO is causal and consequently selecting patients more likely to benefit from closure.

Abstract 9382: Reperfusion Delays and Outcomes Among ST-Segment-Elevation Myocardial Infarction Patients With and Without Cardiogenic Shock

Introduction: Mortality remains high among STEMI patients with cardiogenic shock (CS), and rapid reperfusion has been shown to improve outcomes. However, the comparative benefits of shorter reperfusion times among STEMI patients with and without CS is unclear. Hypothesis: STEMI patients presenting with CS would have significantly greater increases in mortality and MACE as FMC-to-device time increased compared to non-CS patients. We hoped to identify a FMC-to-device time threshold below which outcomes were optimized for CS and non-CS patients. Methods: We performed a retrospective analysis using prospective data from the Vancouver Coastal Health Authority STEMI registry. We included all patients with STEMI who received PCI between January 1, 2010, and December 31, 2020. Patients were stratified based the presence of CS at the time of admission and assessed for the primary outcome of in-hospital mortality and the secondary outcome of an in-hospital major adverse cardiovascular event (MACE), defined as a composite of the first occurrence of mortality, cardiac arrest, heart failure, ICH/CVA/Stroke or reinfarction. Logistic regression was used to estimate the relationships between FMC-to-device time and the primary and secondary outcomes in the CS and non-CS groups. Results: 2929 consecutive STEMI patients were included, of whom 9.4% (n= 275) had CS. Median FMC-to-device time was 113.5 (IQR 93.0-145.0) minutes for CS patients and 103.0 (IQR 85.0- 130.0) minutes for non-CS patients. CS patients were more likely to have FMC-to-device times above guideline recommendations (76.6% vs. 54.1%, p &lt;0.001) compared to non-CS patients. Between 60 and 90 minutes, for each 10-minute increase in FMC-to-device time, mortality for STEMI patients with CS increased by 5-8%, while for non-CS patients it increased by less than 0.5%. Compared to non-CS patients, those with CS had higher incidences of mortality (41.1% vs. 1.9%, p &lt;0.001) and MACE (81.1% vs. 19.4%, p &lt;0.001). Conclusions: Among STEMI patients undergoing primary PCI, reperfusion delays among CS patients are associated with significantly worse outcomes compared to non-CS patients. Strategies to reduce FMC-to-device times for STEMI patients specifically presenting with CS are needed.

Cardiogenic Shock Does Not Portend Poor Long-Term Survival in Patients Undergoing Primary Percutaneous Coronary Intervention.

Although a strong association of cardiogenic shock (CS) with in-hospital mortality in patients with acute coronary syndrome (ACS) is well established, less attention has been paid to its prognostic influence on long-term outcome. We evaluated the impact of CS in 1173 patients undergoing primary percutaneous coronary interventions between 1997 and 2009. Patients were followed up until the primary study endpoint (cardiovascular mortality) was reached. Within the entire study population, 112 (10.4%) patients presented with CS at admission. After initial survival, CS had no impact on mortality (non-CS: 23.5% vs. CS: 24.0%; p = 0.923), with an adjusted hazard ratio of 1.18 (95% CI: 0.77–1.81; p = 0.457). CS patients ≥ 55 years (p = 0.021) with moderately or severely impaired left ventricular function (LVF; p = 0.039) and chronic kidney disease (CKD; p = 0.013) had increased risk of cardiovascular mortality during follow-up. The present investigation extends currently available evidence that cardiovascular survival in CS is comparable with non-CS patients after the acute event. CS patients over 55 years presenting with impaired LVF and CKD at the time of ACS are at increased risk for long-term mortality and could benefit from personalized secondary prevention.

Prognostic Risk Factors for the Development of Compartment Syndrome in Acute Lower Limb Ischemia Patients Treated With Catheter-Directed Thrombolysis

To determine predisposing factors that may lead to the development of compartment syndrome (CS) in patients with acute lower limb ischemia (ALLI) managed with intra-arterial catheter-directed thrombolysis (CDT). This is a retrospective study of patients admitted between 01/2002 and 12/2015 to three university hospitals in Tampere, Turku, and Oulu, Finland, with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb). Patients managed with CDT and aspiration thrombectomies (AT) as an adjunct to CDT were included in the study. Multivariable binary logistic regression models were used to detect possible risk factors for the development of CS and its impact on the limb salvage and survival. Amputation-free survival (AFS) rates of CS and non-CS patients were compared using Kaplan-Meier survival analysis. The length of hospitalization was calculated and compared between the CS and non-CS groups. A total of 292 CDTs with or without ATs were performed on patients with a mean age of 71 years (standard deviation 13 years), 151 (51.7%) being male. Altogether, 12/292 (4.1%) treatment-related CS cases were registered. Renal insufficiency (odds ratio [OR] 4.27, P=0.07) was associated with an increased risk of CS. All CS cases were managed with fasciotomies. Treatment with fasciotomy was associated with a prolonged hospitalization of a median of 7 days versus the 4 days for non-CS patients, P < 0.001. During the median follow-up of 51 months (interquartile range 72 months), 152/292 (52.1%) patients died and 51/292 (17.5%) underwent major amputations. CS was not associated with an increased risk of mortality, but it was associated with a higher risk of major amputation (OR 3.87, P=0.027). The AFS rates of patients with or without CS did not significantly differ from each other in the long term. CS after CDT for the treatment of ALLI is uncommon. Renal insufficiency is associated with an increased risk of CS. Fasciotomy prolongs the hospitalization. Patients with CS are exposed to an increased risk of major amputation.

Abstract 10868: Risk Factors and Long-Term Outcomes of Cardiogenic Shock in Young Patients with Myocardial Infarction - The Mass General Brigham Young-MI Registry

Introduction: Cardiogenic shock complicating acute myocardial infarction (CS-AMI) is associated with high morbidity and mortality, yet data among younger individuals are limited. Methods: Retrospective cohort study of consecutive AMI patients aged 18-50 years admitted to 2 tertiary care academic centers from 2000-2016. CS was determined by physician review of electronic health records (EHR) using the SCAI CS classification system. Baseline characteristics, treatment and outcomes including all-cause mortality (ACM), cardiovascular mortality (CVM) and 1-year hospitalization for heart failure (HHF) were adjudicated by physicians using EHR and death records. Mahalanobis distance matching was used to define a comparator group in the non-CS cohort. Results: The study included 2097 AMI patients (mean age 44 ± 5.1 years, 74% white, 81% male), with CS-AMI identified in 148 (7%) patients. There were no significant differences in age, sex or race between groups, although CS-AMI patients were more likely to have public or no insurance (p=0.02). Independent factors associated with CS-AMI included female sex, STEMI at presentation, out of hospital cardiac arrest, left main coronary disease, diabetes and peripheral artery disease. Over a median follow up of 11.2 years, compared to 461 matched non-CS-AMI patients and controlling for relevant covariates, CS-AMI patients had significantly higher ACM (aHR 2.84, p&lt;0.001), CVM (aHR 4.09, p&lt;0.001), and 1-year HHF (aHR 6.18, p=0.001) (Figure 1). In landmark analyses, CS-AMI patients who survived to discharge continued to have significantly higher risk of CVM (aHR 2.76, p=0.016) compared with matched non-CS AMI patients. All results were similar in the full cohort comparison. Conclusion: Cardiogenic shock is infrequent amongst young AMI patients, but associated with substantially higher overall and post-discharge mortality, and 1-year heart failure hospitalizations after AMI compared to those without cardiogenic shock.

Heart transplantation outcomes in cardiac sarcoidosis

Cardiac sarcoidosis (CS) is a progressive inflammatory cardiomyopathy that can lead to heart failure, arrhythmia, and death. There is limited data on Orthotopic Heart Transplantation (OHT) outcomes in patients with CS. Here we examine outcomes in patients with CS who have undergone OHT at centers throughout the United States from 1987 to 2019. This was an analysis of 63,947 adult patients undergoing OHT captured in the United Network for Organ Sharing (UNOS) registry. Patients were characterized as cardiac sarcoidosis (CS) or Non-CS. Baseline characteristics were compared using chi-square and Kruskal-Wallis Tests. Outcomes of interest included primary graft failure, patient survival, treated graft rejection, hospitalization for infection, and post-transplant malignancy. During the study period 227 patients with CS underwent OHT. Patients with CS were younger, had higher proportion of non-white patients, and received transplants at more urgent statuses. After multivariable modeling there was no difference in survival (HR 0.86, CI 0.59-1.3, p = 0.446) or graft failure (HR 0.849, CI 0.58-1.23, p = 0.394) between patients with CS and Non-CS. Patients with CS had lower odds of rejection (OR 0.558, CI 0.315- 0.985, p = 0.0444). Patients with CS had similar odds of hospitalization for infection and post-transplant malignancy, as Non-CS patients. Patients with CS and Non-CS had similar post OHT survival, odds of graft failure, hospitalizations for infection, and post-transplant malignancy. Results of this study confirm the role of heart transplantation as a viable option for patients with CS.