Prospective Registry Research Articles

Prognostic impact of systemic immune-inflammation index in patients with acute decompensated heart failure with preserved ejection fraction -PURSUIT-HFpEF Registry-

Abstract Background Systemic inflammation has been implicated in the pathophysiology of heart failure with preserved ejection fraction. Several studies have shown that systemic immune-inflammation index (SII), a novel index based on platelets, neutrophils, and lymphocytes, predicts poor prognosis in patients with cardiovascular disease. However, it remains to be elucidated whether SII could have predictive value in patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF). Purpose This study is designed to investigate the association of SII at admission or discharge with poor clinical outcome in patients with ADHF-HFpEF. Methods Patients’ data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for ADHF-HFpEF in a city. Laboratory data and body weight measurements were performed just before discharge. We analyzed 966 patients (mean age: 81 years old, male: 45%) after exclusion of patients on dialysis, missing follow-up data, or missing data to calculate SII. SII was calculated as follows: SII = platelet count × neutrophil count / lymphocyte count on admission and at discharge. The primary endpoint was the composite of all-cause death and rehospitalization for worsening heart failure. Results During a mean follow-up period of 1.8±1.3 years, the primary endpoint was observed in 435 patients (259 patients died and 176 patients underwent rehospitalization for worsening heart failure). In multivariate Cox analysis, high SII at discharge (> 536×109 determined by receiver operating characteristic curve analysis (AUC: 0.564 [0.526-0.602]) was significantly independently associated with not only the primary endpoint (hazard ratio 1.28 [1.04-1.57], p=0.020) but also all-cause death ((hazard ratio 1.39 [1.06-1.81], p=0.018) after adjustment for major confounders such as age, gender, body mass index, NYHA class, systolic blood pressure, heart rate and laboratory data including NT-proBNP and CRP. However, high SII on admission was not significantly associated with primary endpoint after multivariate adjustment. Kaplan-Meier analysis revealed that patients with high SII at discharge had significantly greater risk of both the primary endpoint (56% vs 43%, p<0.001) and all-cause mortality than those with low SII (36% vs 24%, p<0.001). Conclusion Systemic immune-inflammation index at discharge, but not on admission, would be associated with post-discharge poor outcome in patients with acute decompensated heart failure with preserved ejection fraction.

Anti-Apolipoprotein A-1 IgG, incident cardiovascular events and lipid paradox in rheumatoid arthritis

Abstract Objectives To validate the prognostic accuracy of anti-apolipoprotein A-1 IgG (AAA1) for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale. Methods Baseline AAA1 -, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1472 RA patients included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or nonfatal stroke, or myocardial infarction (MI), while elective coronary revascularisation (ECR) was the secondary endpoint. Discriminant accuracy, and incidence rate ratios (IRR) were respectively assessed by C-statistics and Poisson regression models. Results During follow-up, 2.4% (35/1472) patients experienced MACE, consisting in 6 CV deaths, 11 MI and 18 strokes. ECR occurred in 2.1% (31/1472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE (C-statistics: 0.60, 95% confidence intervals [95%CI]: 0.57-0.98, p=0.03), mostly driven by CV deaths (C-statistics:0.77; 95%CI: 0.57-0.98, p=0.01) and without predicting incident ECR. IRR indicated that for every unit increase in AAA1, incident CV death rate increased by 5-fold (95%CI:3.6-7.3), independently of various models’ adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for the MACE components. AAA1 inversely correlated with total, and HDL cholesterol, but not with atherogenic indexes. Conclusions AAA1 independently predict CV deaths in RA. Whether AAA1 could improve CV risk stratification by identifying in particular low CV risk patients remains to be demonstrated.

Prevalence of Brugada ECG pattern in psychiatric patients: a longitudinal prospective cohort of 550 patients

Abstract Background Brugada syndrome (BrS) is an inherited disorder with autosomal dominant transmission, which occurs predominantly in males in the third to fourth decade of life with resting syncope, nocturnal agonic breathing, major ventricular arrhythmias and sudden death. Arrhythmic complications can occur spontaneously or following exposure to triggers such as fever, or certain categories of medications, including psychiatric drugs. Aim of the study To evaluate the prevalence of Brugada ECG pattern in psychiatric patients. Methods from January 2023 to Decembre 2023, 550 consecutive patients who were admitted to the psychiatric department of our university hospital were enrolled. For each patient, electrocardiographic and anamnestic data including psychiatric diagnosis, current drug therapy and family history were collected. Results Twenty-one out of five-hundred and fifty patients (3.8%) presented with a Brugada ECG pattern. Mean age was 42±6 years and seventeen out of twenty-one patients (81%) were male. Two patients exhibited a Spontaneous type 1 Brugada ECG pattern meanwhile nineteen patients had a Brugada type 2 or 3 ECG pattern. When compared to the general population, those with Brugada ECG had longer P wave duration (110±7 vs 103±13 msec p<0.01) and longer QRS duration (97±14 vs 89±12 msec p=0.04). Evaluating psychiatric disorders, patients with Brugada ECG had high prevalence of mood disorders (10 out of 21, 47%). Other disorders were schizophrenia (3 out of 21, 14%), cognitive retardation (5 out of 21, 23%), and attention disorder (1 out of 21, 5%). Moreover 4 patients were drug addicted. Only 5 out of 21 (24%) patients had a family history of psychiatric and neurological disorders. Conclusions Brugada ECG pattern has a prevalence of 3.8% in a large cohort of psychiatric patients. Mood disorders was the most common diagnosis in this cohort. Large prospective registries are needed to evaluate the clinical feature and potential clinical implication of this findings.

Arterial stiffness characterization of patients with different ACS-causing plaque morphologies quantified by optical coherence tomography

Abstract Background Optical coherence tomography (OCT) has refined acute coronary syndrome (ACS)-management by enabling in-depth characterization of culprit lesions. Differentiating between plaques with ruptured (RFC) and intact fibrous cap (IFC) has shaped clinical decision making. However, the systemic vascular changes associated with different plaque morphologies remain unexplored. Purpose To investigate arterial stiffness among different ACS-causing plaque morphologies (RFC vs. IFC) and its prognostic value post-ACS. Methods We conducted a secondary analysis of a prospective registry study, including patients who underwent OCT-characterization of the ACS-causing culprit lesion and received arterial stiffness assessment 90 days post-index event. The association between arterial stiffness parameters, such as pulse wave velocity (PWV), aortic pulse pressure (APP), heart rate-corrected augmentation index (AIx@75) and plaque morphologies was assessed using logistic regression, adjusted for age, sex, hypertension, presence of diabetes mellitus, smoking status, LDL-C and discharge medications (ACE-inhibitors/ARBs, beta blockers, calcium-channel blockers and diuretics). A multiparameter model additionally included intima-media-thickness and all arterial stiffness metrics. Cox regression, further adjusted for stroke history, prior percutaneous coronary intervention or stable coronary artery disease and Killip class, evaluated the link between arterial stiffness parameters and major adverse cardiovascular events plus (MACE+). Results In total, 110 patients with arterial stiffness and OCT data were included. Of these, 78 (70.9%) patients had RFC- and 32 (29.1%) IFC-ACS. The median age was 61.5 years and 80.0% of patients were male. Patients with RFC- had significantly higher PWV (8.35 vs. 7.50 m/s, p=0.015) compared to IFC-ACS. Both groups received similar regimens of antihypertensive, diuretic and lipid-lowering pharmacological therapy at discharge (p>0.1). After multivariable adjustment, increased PWV (4th Quartile [Q4] vs. 1st Quartile [Q1] Adjusted Hazard Ratio [aHR]: 1.38 [95% Confidence Interval (CI) 1.02-1.88], p=0.043) was associated with RFC- while high APP was significantly associated with IFC-ACS as the underlying plaque morphology (Q4 vs. Q1 aHR: 0.65 [95% CI 0.48-0.87], p=0.005) (Figure 1). Furthermore, per one-unit increment in APP we observed a 10% increase in risk for MACE+ in patients with RFC-ACS (aHR: 1.10 [95% CI 1.02-1.19], p=0.016) but not IFC-ACS (aHR: 0.95 [95% CI 0.82-1.11], p=0.54). No risk modification with increases in PWV and AIx@75 were observed, regardless of underlying plaque pathology (p>0.05). Conclusion There are distinct differences in arterial stiffness between patients with RFC- and IFC-ACS. These results underscore the value of a patient-specific approach that integrates invasive and non-invasive vascular characterization for identifying high-risk individuals and guiding therapy to enhance clinical outcomes.

Cardiological monitoring during BTK inhibitor, ICI, and RAF/MEK inhibitor therapy: the single-center prospective registry for cardiovascular events under new cancer therapies (RECENT)

Abstract Background The advent of novel targeted cancer therapies have revolutionized cancer treatment. However, concerns about their impact on cardiovascular health persist and current guidelines recommend cardiac monitoring. Yet, prospective data on incidence rates of cardiovascular events are lacking. The Registry for Cardiovascular Events under new cancer Therapies (RECENT) aims to systematically assess clinical as well as subclinical cardiovascular incidents in patients undergoing these novel therapies to identify baseline risk factors and derive individualized monitoring strategies. Methods This ongoing single-center prospective registry enrolls cancer patients receiving BTK inhibitors, ICI, or RAF/MEK inhibitors. Baseline cardiovascular assessment, risk stratification according to HFA-ICOS risk score, and follow up visits for 12 months at three-monthly intervals (including ECG, biomarkers and echocardiography) during treatment are conducted. Treatment-related events, in particular hypertension, arrhythmias, cancer therapy-related cardiac dysfunction (CTRCD), and (peri-) myocarditis, as defined according to current guideline recommendations, are recorded. Results We report data of the first 85 patients (60.9 ± 14.7 years, 52.9% male) included in this ongoing registry. Of those, 17/85 patients received treatment with BTK inhibitors (20%), 45/85 with ICI (53%) and 23/85 with RAF/MEK inhibitors (27%). Most common treatment indication were dermatological (39/85, 45.9%), hematologic (17/85, 20%), urological (13/85, 15.3%) and head and neck (11/85, 12.9%) cancers. Before treatment, the majority of patients were stratified as low-risk (31/85) or moderate-risk (32/85), and 22/85 (25.9%) as high-risk. 7/85 (8.2%) patients were newly diagnosed with cardiovascular disease at baseline visit, resulting in a change in risk category and subsequent initiation of cardiovascular treatment. This includes 3 patients who had been initially categorized as low-risk and would not have been referred for further cardiac workup due to current guideline recommendations. The six months follow up visit has been completed in 44/85 patients. Among these, 1/20 patients (5%) with ICI developed a perimyocarditis and 2/11 patients (18.2%) with BTK inhibitors developed atrial fibrillation. 1/13 patients (7.7%) with RAF/MEK inhibitor therapy, classified as low-risk at baseline, developed asymptomatic CTRCD, which resolved after initiation of cardioprotective drug therapy. Conclusion This interim analysis of the RECENT registry indicates benefit of a structured baseline cardiac assessment prior to cancer treatment in all patients, irrespective of the initial risk stratification. Contrary to current guidelines, which recommend routine echocardiographic monitoring in patients receiving RAF/MEK inhibitors only in high-risk patients, the current data advocate for extending this also to low-risk patients to detect subclinical deterioration of the cardiovascular status.

20 year picture of a heart failure clinic: changes in the patients profiles' and 2-year mortality

Abstract Background Heart failure (HF) is one of the most prevalent diseases. Improvements in cardiac disease management in the last two decades and in HF itself might have influenced the referral of patients with HF to a specialised HF clinic. Purpose To evaluate changes in the profile of patients referred to an outpatient HF clinic over the span of 20 years, and to analyse trends in 2-year mortality. Methods A retrospective analysis of a prospective registry of HF patients in a specialised ambulatory HF clinic was conducted, from January 1st 2002 to December 31st 2021. We divided the 20 years of the study into five periods of four years each, in order to compare the clinical characteristics of patients at admission. The variables analysed include age, sex, aetiology, HF type (preserved - HFpEF, reduced - HFrEF, mildly-reduced - HFmrEF), NYHA class, left ventricle ejection fraction (LVEF), NT-proBNP level, number of previous hospitalizations, and treatment at referral (first visit). Two-year mortality was also analysed. Results A total of 2973 patients were included (mean age 67.1± 12,9, 69.7% men). Age remained stable across the five periods, p=0.43), while the referral of women increased throughout the study period (27.7% in 2002-2005 vs 32.9% in 2018-2021, p-for-trend=0.037). Patients with HFpEF were also increasingly referred (12.3% first period vs. 27.6% last period, p-for-trend<0.001) and LVEF tended to be higher (33.09% vs. 40,9%, p<0.001). The main aetiology of the referred patients was ischaemic heart disease, although it progressively decreased in favour of other aetiologies (Table 1) (p<0.001). NYHA class tended to improve (NYHA 3-4 40.3% vs. 21.3%, p-for-trend <0.001) and NT-proBNP levels tended to decrease, predominantly in the last period (p-for-trend=0.025), as well as hospitalisation rates in the previous year (p-for-trend<0.001). Treatment with ACEi/ARB was progressively less frequent (p<0.001), at least partially due to replacement by ARNi (p<0.001). Treatment with digoxin and loop diuretics also diminished (p<0.001 and p=0.04 respectively), whereas treatment with betablockers, ARM, ivabradine and SGLT-2i increased during the study periods (all p<0.001) (Table 2); Patients carrying ICD and CRT also increased (p=0.014 and p<0.001 respectively). Adjusted 2-year mortality significantly decreased, mainly in the last period (p<0.001) (Figure 1). Conclusion The profile of HF patients referred to a tertiary HF ambulatory Clinic changed along 20 years of study. HFrEF remained the most common, but is declining in favour of HFpEF. Ischaemic aetiology also remained the most frequent but, again, showed a decreasing trend. Two-year mortality has globally decreased, markedly in the last period.Figure 1

Impact of Lp(a) on lipid control in patients with acute coronary syndrome

Abstract Background The lipoprotein(a) (Lp[a]) is a genetically determined low-density lipoprotein (LDL)-like particle. Lp(a) levels above 50mg/dl have been correlated to an increased risk of atherosclerosis and major adverse cardiovascular events. Thus, treatments designed to reduce Lp(a) levels are currently under investigation. However, it is unknown how high Lp(a) concentrations affect the control of lipid profile. Purpose The purpose of this project is to investigate how Lp(a) impacts lipid profile control in individuals with acute coronary syndromes (ACS). Methods We designed a single-center prospective registry including consecutive patients admitted for ACS. Lp(a) levels were obtained from all enrolled patients during hospitalization; lipid profile (total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides) was obtained at admission and at the 6-month follow-up (6MFU). Patients were stratified according Lp(a) concentration (low-Lp(a): Lp(a) < 50 mg/dL; high-Lp(a): Lp(a) ≥ 50 mg/dL). LDL-cholesterol (LDLcorr) levels corrected for concentration of Lp(a) were calculated as LDLcorr= LDLmeasured – 30%Lp(a). At discharge cholesterol lowering drugs were introduced or titrated as standard of care. The primary endpoint was the percentage of patients reaching target LDL and LDLcorr (<55 mg/dL) at 6MFU. The secondary endpoints were the correlations between Lp(a) levels and lipid profile, both at baseline and at 6MFU, as well as the correlation between Lp(a) levels and the total number of traditional cardiovascular risk factors in the study population. Results From February 2020 through September 2023, a total of 409 patients were included: 305 (74.6%) with Lp(a) < 50 mg/dL; 104 (25.4%) with Lp(a) ≥ 50 mg/dL (Table 1). High-Lp(a) patients showed a lower prevalence of diabetes (14.2% vs 27.87%, P = 0.0055), an overall lower number of traditional cardiovascular risk factors (>2 in 25.9% vs 38.1%, P=0.0244). High-Lp(a) patients showed higher level of LDL-cholesterol compared to the low-Lp(a) population both at baseline (124±52 mg/dL vs 110.4±44 mg/dL, P= 0.0263) and at 6MFU (70.5±21 vs 63.8±29, P= 0.0208) with fewer patients achieving the target LDL cholesterol levels (21.57% vs 40.13%, P=0.0184). Estimating the true LDL concentration (LDLcorr) the percentage of patients reaching target LDL cholesterol levels at FU significantly increased in the high-Lp(a) group (from 21.57% to 76.5%), with a minimal increase noticeable in the low-Lp(a) population (from 40.13% to 48.41%, p 0,1870). Conclusions In ACS population, patients with high Lp(a) concentrations have fewer traditional CV risk factors and a lower prevalence of diabetes. High-Lp(a) patients, furthermore, seem more challenging to meet LDL target at 6 month follow up, but not when the LDL values are adjusted for Lp(a).

Cardiopulmonary long-term effects 6, 18 and 30 months after severe COVID-19 infection

Abstract Background SARS-CoV-2 infection affects the cardiopulmonary system in both the acute and long-term phase. This study aimed to comprehensively assess symptoms and potential longterm impairments 6, 18 and 30 months in patients previously hospitalized for severe Covid-19 infection. Methods This prospective registry included patients hospitalized for PCR-confirmed Covid-19 infection. Approximately 6 months post-discharge, follow-up examination included patient history, clinical examination, echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel. Patients with pathologic findings during the first visit underwent a second (at 18 months) and third (at 30 months) follow-up examination. Those without pathologic findings or who refused further medical examinations were contacted via phone to inquire about symptoms. Results Between July 2020 and April 2022, 200 patients (91% general ward, 9% intensive care unit) were recruited. Due to dropouts, the second visit was conducted in 170 patients and the third visit in 139 (74 in person, 65 via telephone). Long Covid criteria were fulfilled by 73% at 6 months, 52% at 18 months and 49% at 30 months post-discharge, with fatigue being the most common symptom (Figure 1). Echocardiography at 6 months showed impaired left ventricular function in 15 patients, with normalization in 80% at 18 months and further 66% at 30 months (Figure 2). cMRI revealed pericardial effusions in 28 patients at 6 months, which resolved in 47% at 18 months and in further 60% at 30 months. Signs of peri- or myocarditis were present in 7 patients at 6 months and were resolved in all 4 patients who attended control studies at 18 months. PFT at 6 months detected reduced vital capacity in 17 patients, of whom 10% returned to normal at 18 months and a further 66% showed normalization at 30 months. Chest CT scans at 6 months identified post-infectious residues in 41 patients, with full recovery in 20% at 18 months without further normalization after 30 months. The length of in-hospital stay was identified as a significant predictor for persisting Long Covid 6 months after discharge (95% CI: 1.005 - 1.12, p=0.03). No predictors have been found for Long Covid at 18 and 30 months. Conclusion While the prevalence of Long Covid decreased over time, a significant symptom burden persisted at 6, 18 and even 30 months after severe Covid-19 infection. Structural and functional abnormalities were less frequent compared to reported symptoms, posing a challenge in substantiating the causes of these symptoms.

Association between in-hospital haemoglobin drop with or without overt bleeding and long-term clinical outcomes after percutaneous coronary intervention

Abstract Background Periprocedural bleeding complications remain a significant issue in patients undergoing percutaneous coronary intervention (PCI). Although most bleeding complications are defined by the degree of haemoglobin drop, prognostic implications of haemoglobin drop without clinically overt bleeding remain unclear. Purpose We aimed to investigate the association between haemoglobin drop after PCI and long-term prognosis, stratified by the occurrence of clinically overt bleeding. Methods Consecutive patients discharged after PCI between September 2008 to June 2018 from Keio Cardiovascular PCI multicenter prospective registry in Japan were analyzed. Patients were categorized into four groups: those with overt bleeding with haemoglobin drop, those with overt bleeding without haemoglobin drop, those without overt bleeding with haemoglobin drop, and those without overt bleeding nor haemoglobin drop. The pre- and post-PCI haemoglobin were defined as the lowest value within 72 hours before and after PCI. We defined the haemoglobin drop as the value obtained by subtracting the pre-PCI haemoglobin value from the post-PCI haemoglobin value equal to or greater than 3.0 g/dL. The primary outcome was the 2-year composite of major adverse cardiovascular events (MACE): all-cause mortality, acute coronary syndrome, heart failure hospitalization, or stroke. Cox proportional models were used to assess the association between the haemoglobin drop and the clinical outcomes. Results Among the 6,013 patients [mean age 68 years and 78% male], 52 (0.9%) had overt bleeding with haemoglobin drop, 45 (0.7%) had overt bleeding without haemoglobin drop, 497 (8.3%) had haemoglobin drop without overt bleeding, and 5,419 (90.1%) had neither. At the two-year follow-up, patients with overt bleeding, both with and without haemoglobin drop had higher rates of MACE compared to those without overt bleeding, with and without haemoglobin drop (28.8% vs. 20.0% vs. 11.8% vs. 10.5%, respectively). Patients with overt bleeding with haemoglobin drop were associated with increased risks of MACE compare to those without overt bleeding without haemoglobin drop (HR: 2.19, 95% CI: 1.26-3.81, P=0.01). Conversely, patients without overt bleeding with haemoglobin drop and patients with overt bleeding without haemoglobin drop were not associated with increased risk of MACE (HR:1.19, 95% CI: 0.88-1.63, P=0.26, and HR: 0.62, 95% CI: 0.29-1.31, P=0.21, respectively). The spline curve showed a significant correlation between haemoglobin drop and MACE in patients with overt bleeding. However, for patients without overt bleeding, the correlation was attenuated. Conclusions Patients with haemoglobin drop with overt bleeding were significantly associated with long-term prognosis, but no association was observed among those with haemoglobin drop without overt bleeding. Our findings prompt a reevaluation of the current criteria for classifying bleeding complications.Figure

Echocardiographic pulmonary vascular resistance in patients undergoing tricuspid annuloplasty: prognostic implications and reversibility

Abstract Background Pulmonary vascular resistance (PVR) intimately connects with right ventricular afterload and the development of secondary tricuspid regurgitation (sTR). Objectives We sought to investigate the prognostic roles of PVR derived from echocardiography in patients who underwent tricuspid annuloplasty (TA) for sTR. Methods Data from 322 patients who underwent TA [median age (interquartile range): 65.0 (59.0-70.0) years; 35.7% males] were obtained from a prospective registry to determine the impact of PVR on the composite outcome (including all-cause mortality and heart failure hospitalization). PVR was calculated by dividing the peak TR velocity by time-velocity integral of the right ventricular outflow tract and then adding 0.16. Results During a median follow-up of 5.2 (interquartile range: 2.2-8.2) years, 108 adverse events occurred including 48 deaths and 60 heart failure readmissions. Baseline PVR ≥ 2.0WU was independently associated with a higher risk of composite outcome (adjusted HR[KY1] [u2] :1.674, 95% CI: 1.028-2.726, P=0.038). Baseline PVR outperforms pulmonary artery systolic pressure (PASP) and the ratio of tricuspid annulus plane systolic excursion to PASP in terms of outcome prediction, with pronounced improvement of global model fit, reclassification, and discrimination. In 150 patients who received echocardiograms after surgery, the presence of post-operative PVR ≥ 2.0WU (n=20, 13.3%) was independently associated with the composite outcome (adjusted HR: 2.621, 95% CI: 1.292-5.319, P=0.008). Conclusion PVR measured on echocardiography is an independent determinant of clinical outcomes in patients undergoing TA. The inclusion of echocardiographic PVR assessment may provide valuable additional information for patient selection and risk stratification in this population.Kaplan-Meier CurveChange of PVR after Surgery

Prognostic impact of SGLT2-inhibitor therapy on survival in patients with transthyretin amyloid cardiomyopathy

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) significantly improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction. Recently published data indicates the safety and tolerability of SGLT2i therapy in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, there is a lack of evidence regarding the impact of SGLT2i therapy on clinical outcomes in those patients. Purpose This study aims to investigate the association between SGLT2i therapy and clinical outcomes in patients with ATTR-CM. Methods This is an analysis of a prospective registry conducted at an expert center for hypertrophic cardiomyopathies. We included all participants with a confirmed diagnosis of ATTR-CM, who were enrolled until December 2022. Prior and concomitant SGLT2i treatment was systemically assessed according to the patient interview and medical records. Patients’ outcomes were retrieved from local medical and health insurance records. Results We enrolled 116 patients, of whom 7 patients (6%) were treated with SGLT2i at inclusion and 44 patients (38%) were started on SGLT2i therapy during the observational period while 65 patients (56%) were SGLT2i-naïve. There were no significant differences in baseline characteristics between groups, as shown in the table. Median (interquartile range) age was 80 (76-82) years with 15% females. Median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 2844 (1519-5033) pg/ml, median estimated glomerular filtration rate (eGFR) 58 (46-69) ml/min/1,73m2, and median troponin T 56 (34-83) pg/ml. During a median follow-up of 2.6 (1.8-3.7) years, 28 patients (24%) died, of whom 6 patients (5%) were in the treatment group and 22 patients (19%) in the control group. In univariate Cox-regression analysis, SGLT2i treatment was significantly associated with a lower mortality (HR 0.325, 95%CI 0.132-0.802, p=0.015). This association persisted after adjusting for age and sex (HR 0.347, 95%CI 0.139-0.867, p=0.023). However, when treatment initiation time was considered, the benefit did not remain statistically significant. No significant associations between SGLT2i treatment and worsening heart failure hospitalizations or cardiovascular death were observed. Conclusion In a prospective registry-based cohort of patients with ATTR-CM, SGLT2i therapy was associated with significantly better survival, with a potential treatment initiation time bias. These results suggest that SGLT2i may exert beneficial effects in patients with ATTR-CM and warrant a randomized controlled trial.

Prognostic implications of N-terminal pro-brain natriuretic peptide in patients with Non-ST segment elevation myocardial infarction

Abstract Background Limited data exist regarding prognostic implications of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with non-ST segment elevation myocardial infarction (NSTEMI) who underwent percutaneous coronary intervention (PCI). Objectives The current study sought to evaluate the prognostic implications of NT-proBNP in patients with NSTEMI who underwent PCI. Methods Among a total of 13,104 patients from a nationwide, multicenter, and prospective registry of the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH), a total of 3,083 patients with NSTEMI who underwent PCI were selected. The selected patients were classified according to the initial NT-proBNP value (cut-off value of NT-proBNP, 700 pg/ml). Primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction (MI), unplanned repeat revascularization, and admission for heart failure. Results Among the study population, 1,813 patients (58.8%) were in the low NT-proBNP group (<700 pg/ml) and 1,270 patients (41.2%) were in the high NT-proBNP group (≥700 pg/ml). The high NT-proBNP group showed significantly higher risk of MACE than the low NT-proBNP group (29.5% vs 12.3%; adjusted hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.39-2.07; P<0.001), mainly driven by higher risk of cardiac death or admission for heart failure (15.6% vs. 2.2%; adjusted HR, 2.98; 95% CI, 2.03-4.40; P<0.001). These results were consistent after confounder adjustment by propensity score matching (HR, 1.56; 95% CI, 1.21-2.02; P=0.001) and inverse probability weighting analysis (HR, 1.54; 95% CI, 1.19-2.00; P=0.001). Conclusion In patients with NSTEMI who underwent PCI, elevated initial NT-proBNP level was associated with higher risk of MACE at 3 years, mainly driven by the higher risk of cardiac death or admission for heart failure. The current results suggest that the initial NT-proBNP level may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Sinus rhythm restoration as an independent predictor of left ventricular ejection fraction improvement in patients with the first hospitalization for heart failure and reduced ejection fraction

Abstract Background and Purpose Tachycardiomyopathy (TCM) is prevalent in heart failure with reduced ejection fraction (HFrEF). Despite its significance, a comprehensive understanding of its evolutionary trajectory and prognosis remains limited. This study aims to investigate the prognosis and left ventricular ejection fraction (LVEF) trajectory in patients with TCM compared to other etiologies within a cohort initially admitted for "de novo" HFrEF (LVEF < 40%). Methods A prospective registry was conducted across two University Hospitals, incorporating patients hospitalized with a diagnosis of HFrEF. The study encompassed 370 patients admitted between March 2021 and October 2023, with a median follow-up of 15 months (IQR 7-22). Two distinct groups were delineated based on etiology (TCM vs other etiologies). Within the TCM cohort, subgroups were established concerning LVEF improvement, following the criteria outlined in the "Universal Definition and Classification of Heart Failure" report. Categorical variables were presented as absolute frequencies and percentages, analyzed using the chi-square test. Continuous variables were expressed as mean +/- SD and compared through Student's t-test or Mann-Whitney U test. Hazard functions were estimated using the Kaplan-Meier method. Data analysis was executed using SPSS Statistics. Results In our cohort, both TCM and other etiologies groups exhibited improved LVEF post-neurohumoral blockage titration. Nonetheless, the TCM cohort demonstrated notably higher LVEF (49.1% vs. 43.5%, p = 0.005) [Figure 1]. Moreover, overall mortality, cardiovascular mortality, and the composite of CV mortality and hospitalizations for CV causes were notably lower in the TCM group compared to other etiologies [Figure 2]. Among TCM patients, those with improved LVEF during follow-up were younger (66 vs. 72), with no differences in treatment at discharge or after neurohumoral blockage titration. While achieving sinus rhythm before discharge did not correlate with LVEF improvement, attaining sinus rhythm during follow-up (at titration completion) significantly correlated with LVEF improvement [Table 1]. Multivariate analysis revealed that sinus rhythm restoration after up-titration emerged as an independent predictor of LVEF improvement, irrespective of sinus rhythm restoration at discharge or the attainment of quadruple therapy during follow-up, among other variables (Table 2). Conclusions Among patients initially admitted for "de novo" HFrEF, TCM presents a potentially more favorable clinical trajectory compared to other HF causes, showcasing reduced total and cardiovascular mortality, as well as combined cardiovascular mortality and hospitalizations for cardiovascular causes. Notably, in this patient subset, sinus rhythm restoration during follow-up emerged as an independent predictor of improved LVEF, irrespective of pre-discharge sinus rhythm restoration or adherence to comprehensive four-pillar HF management.

Cardiovascular etiologies and risk factors of survival outcomes after resuscitation for out-of-hospital cardiac arrest: data from the KoCARC registry

Abstract Background The outcomes and characteristics of out-of-hospital cardiac arrest (OHCA) vary across geographic regions. The etiologies and prognoses of OHCA in Asian populations remain less established. This study aimed to investigate the etiologies and clinical characteristics of patients successfully resuscitated after OHCA and identify predictors of survival outcomes. Methods Data were extracted from a South Korean multicenter prospective registry of OHCA that included 64 tertiary hospitals from 2015 to 2018 (n=7577). The primary outcome was in-hospital mortality, and secondary outcome was the grade-1 cerebral performance category (CPC) score at discharge. Results Of the 7577 patients, 2066 achieved return of spontaneous circulation (ROSC) and were hospitalized and 915 (44·2%) presented with ventricular arrhythmia (VA) as their initial rhythm or on admission. The leading cause was obstructive coronary artery disease (n=413; 20·0%). Sudden unexplained death syndrome (SUDS) accounted for 67·5% of survivors, which were significantly lower with VA (82·7% vs. 48·3%, p<0.001). VA was an independent predictor of in-hospital mortality (adjusted hazard ratio [aHR] 0·72, 95% confidence interval 0·60–0·87) and the grade-1 CPC score at discharge (aHR 3·63, 95% CI 2·56–5·15). Other predictors of the primary outcome included age, ROSC on arrival, total arrest time, alertness on admission, extracorporeal membrane oxygenation use, targeted temperature management, implantable cardioverter defibrillator use, and coronary vasospasm. Conclusions SUDS was common in patients with ROSC after OHCA and thus needs to be evaluated comprehensively. VA was independently associated with favorable survival outcomes at discharge. Further management may improve clinical outcomes in patients with OHCA, particularly those with VA.

Association between average glucose concentration or glucose variability and acute kidney injury among CAD patients with prediabetes

Abstract Background Prediabetes, impacting approximately 10% of adults, lacks comprehensive attention, and there is limited data on effective glycemic control strategies. Meta-analysis suggests that intensive glycemic control is linked to a lower incidence of major adverse cardiovascular events, mainly driven by decreased reinfarction and reduced microvascular complications in coronary artery disease (CAD) patients. However, despite these associations, existing evidence does not conclusively establish the efficacy of intensive glycemic control in enhancing cardio-renal outcomes. Purpose In the present study, we aimed to validate the utility of intensive glycaemic control on acute kidney injury (AKI) prevention using a prospective, pragmatic clinical data of patients with CAD. Methods This study utilized data from the Prospective Registry of the Current Status of Care for Patients with Coronary Artery Disease database, a nationwide and pragmatic registry project initiated on January 17th, 2022. Data, including demographics, medical history, and lab results, were collected from electronic medical records. The time-weighted average glucose (TWAG) and glucose variability (CV) for each patient to assess glycaemic control, and outcomes including AKI were assessed. Statistical analysis involved logistic models and sensitivity analyses. SAS 9.4 and R software were used, with p<0.05 considered significant. Results Between January 2022 and June 2023, 2,454 CAD patients with prediabetes were included for final analysis. Among them, the average age was 62.6 ± 10.3 years, of whom 27.1% were females. In univariate model, the incidence of AKI was 1.51 (1.36,1.68) times higher in patients with an increasing TWAG per mmol/L. After the stepwise adjusting of covariates, the OR was 1.50 (1.35,1.67). CV of glucose also had positive association with AKI. An increasing of 0.1 unit of CV increased the risk of about 44%. When adjusting the TWAG and CV of glucose at the same time, both still had positive association with AKI. A restricted cubic splines plot showed an increasing trend of the ORs for AKI as both TWAG and CV of glucose increased. Subgroups analyses also showed stable positive association between TWAG, CV and AKI. Conclusions Our study reveals an association between TWAG or CV and AKI in individuals with both CAD and prediabetes. These findings underscore the importance of continuous glucose monitoring and the implementation of intensive glycaemic control for CAD patients coexistence of prediabetes.Restricted cubic splines function

Aortic stenosis and the evolution of cardiac damage after transcatheter aortic valve replacement

Abstract Aims Cardiac damage staging has been postulated as a prognostic tool in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of our study is to show the echocardiographic and clinical outcome of patients one-year after TAVR. Methods and results Patients undergoing TAVR from 2017 to 2021 were included in a single-centre prospective registry. Transthoracic echocardiography was performed in all patients before TAVR and at one-year. Patients were classified according to a previously published staging model.1 496 patients (mean age 82.1±5.9 years, 53% female) were included. At baseline, Stage 0 included 24.5% of patients, Stage 1 included 42.8%, Stage 2 included 16.5%, and Stage 3 included 16.2% of patients. One-year overall mortality was 17.7% (n=88). Among patients who survived, after one-year of follow-up, the higher the baseline stage of cardiac damage, patients showed larger LVEDV (p= 0.223), LV mass (p= 0.207) and LAVI (p= <0.001); higher E/e’ ratio (p= 0.284) and PASP (p= <0.001). As for LVEF, at one-year; it was significantly lower the higher the baseline stage of cardiac damage (p= 0.005); the same was observed with GLS (p= <0.001) and right ventricle-arterial coupling (p= <0.001), Table 1. Conclusions The higher the stage of initial cardiac damage, the lower the possibility of morphological and functional improvement, despite undergoing TAVR. The use of staging systems and earlier intervention could help improve the prognosis of these patients.

Prognostic impact of left ventricular ejection fraction improvement after transcatheter aortic valve replacement

Abstract Introduction Transcatheter aortic valve replacement (TAVR) has become an efficient and save alternative to surgical aortic valve replacement (SAVR). While severe aortic stenosis as well as severe aortic regurgitation (AR) is known to negatively impact left ventricular ejection fraction (LVEF), prior studies have shown that TAVR can lead to improvement in LVEF. So far, little is known about the prognostic implication of LVEF-improvement as a sole predictor of outcomes. Purpose The aim of this study was to assess the prognostic significance of early LVEF improvement in patients undergoing TAVR. Materials and Methods Patients undergoing TAVR in a large tertiary university hospital have been consecutively included in a large prospective registry. Transthoracic echocardiography (TTE) was performed at baseline, after TAVR before discharge, at 1 month and annually thereafter. Significant LVEF improvement was defined as >10% relative increase of LVEF at 30 days compared to baseline LVEF. Primary outcome was all-cause mortality at 5 years. Secondary outcome were major adverse cardiovascular events (MACE), including death, non-fatal myocardial infarction, stroke, bleeding and unplanned re-interventions of the aortic valve. Results Among 1481 patients undergoing TAVR between September 2011 and June 2023, LVEF at baseline and at 30 days was available in 1013 patients. 665 patients (65.6%) had normal LVEF at baseline, whereas 348 patients (34.4%) had a reduced LVEF. Of these, 137 patients (13.5%) showed significant improvement of LVEF ≥10%) after 30 days, while 266 patients (26.3%) showed no significant LVEF-improvement (<10%). The combined patients with persevered LVEF at baseline had significantly better outcomes than those with impaired EF (p=<0.001). LVEF improvement was not associated with mortality at 5 years (p= 0.51), however with lower MACE rate at 5 years (p=0,024). Conclusion Normal LVEF before TAVR is an independent predictor for improved outcomes. In addition, early improvement of LVEF is associated with beneficial outcomes in patients undergoing TAVR.Course of LVEF after TAVROutcomes after TAVR

Preliminary data on short-term outcomes within the cardio-obstetrics registry

Abstract Background Pregnancy leads to physiological changes within the cardiovascular system such as increased plasma volume and cardiac output or hypercoagulability. These changes can be challenging for women with pre-existing cardiovascular disease with higher risks of complications. The guidelines of the European Society of Cardiology recommend treating high-risk patients in specialized centres by an interdisciplinary pregnancy heart team. In a team-based approach, the Pregnancy Heart Team was founded at our university hospital, in order to establish specific structures of communication and responsibility. Methods A prospective registry of all patients treated by the Pregnancy Heart Team between November 2022 and March 2024 was established. Patients consisted of women with pre-existing cardiovascular disease undergoing pregnancy as well as women who developed pregnancy-associated cardiovascular disease. Patients were evaluated throughout pregnancy by lab work and echocardiography during each trimester as well as in the postpartum period. Results In total 39 women (mean age 34±5 years) were prospectively included in the registry. 17 patients (43.5%) were classified as mWHO ≥ III. 17 patients (43.5 %) with pre-existing (pregnancy-associated) cardiovascular disease were managed throughout pregnancy and delivery. 9 patients (18.4 %) developed pregnancy-associated cardiovascular diseases such as peripartum cardiomyopathy or spontaneous coronary artery dissection. Preliminary data shows that mean left-ventricular ejection fraction remained stable during pregnancy with a non-significant trend towards lower values postpartum. Cardiac biomarkers such as high-sensitivity troponin T and NT-pro-BNP showed a non-significant trend towards increased values in the third trimester and postpartum. Adverse maternal outcomes occurred in 14 patients (35.9 %), including preterm premature rupture of membranes (12.2%), gestational hypertension (7.6%), gestational diabetes (5.1%), preeclampsia/eclampsia (7.6%) and delivery-associated complications (10.2%). Fetal complications included macrosomia (10.2%) or intrauterine growth retardation (5.1%). Discussion These preliminary data of a real-world patient collectivedemonstrate that a significant number of patients experienced adverse pregnancy outcomes which was associated with a trend towards increased cardiac biomarkers throughout pregnancy and postpartum. As recent studies have shown, interpretation of standard parameters such as cardiac biomarkers is not fully understood during pregnancy, especially in women with pre-existing cardiovascular disease. Our data may aid to understand prognostic implications of cardiac biomarkers during pregnancy.

Significant reduction of complications applying an optimized vascular access and post-interventional groin-site management during electrophysiology procedures

Abstract Background Catheter ablation of cardiac arrhythmias is an established treatment strategy. However, the optimal femoral vascular access strategy and post-interventional management in the electrophysiology (EP) setting is still under debate. Purpose To assess the impact of ultrasound-guided versus conventional femoral vascular puncture and of a modified post-interventional groin-site management strategy on complication rates. Method Patients undergoing EP procedures at the our university heart and vascular center are included in an institutional prospective registry. Conventional vascular access as well as post-interventional groin site pressure-bandage and bed rest of 6 hours (group I) was compared to a new strategy including ultrasound-guided vascular access, venous closure by a Z-suture and groin site pressure-bandage for only 2 hours plus additional 4 hours bed rest (group II). Incidences of minor and major groin site complications for both groups were compared. Hematoma, bleeding, arteriovenous fistula or pseudoaneurysm of the femoral artery without need for intervention (e.g. transfusion, thrombin injection, surgery) were classified as minor complications. Complications requiring intervention or retroperitoneal hematoma were defined as major complications. Results A total of 1535 procedures in 1381 patients (779 (51 %) procedures in 705 (51%) patients in group I and 756 (49%) procedures in 676 (49%) patients in group II) were analyzed. In group I and group II, respectively, 39%/44% procedures were index pulmonary vein isolations, 30%/29% repeat atrial fibrillation, 16 %/15% supraventricular tachycardia, 12%/11% PVC or VT ablations, and 4%/2% left atrial appendage occlusions. The total groin site complication rate was 9% (70/779 procedures) for group I, and 5% (38/756 procedures) for group II (OR 0.54 [95%-CI 0.35-0.82], p=0.003). Major groin site complications occurred in 2% (19/779 procedures) in group I and were reduced to 1% (10/756 procedures) in group II (OR 0.53 [95%-CI 0.22-1.22], p=0.156). Conclusion The overall groin site complication rate in EP-procedures was significantly reduced by implementing a novel institutional standard for vascular access management including ultrasound-guided puncture and a modified post-interventional groin site management.

Different impact of chronic kidney disease in older patients with heart failure according to frailty

Abstract Introduction Chronic kidney disease (CKD) and frailty are often present in older patients with heart failure (HF). Our aim was to evaluate the impact of CKD and frailty in one-year mortality in a cohort of older (≥75 years) outpatients with HF. Methods Our data come from the FRAGIC study ("Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of older outpatients with heart failure"), a multicenter prospective registry conducted in 16 cardiology services in Spain which included ≥75 years outpatients with HF. Results We included 499 patients, mean age 81.4 ± 4.3 years, 38% women. Mean estimated glomerular filtration rate (eGFR) was 52.1±17.5 ml/min/1.72 m2. Patients were classified in three groups: eGFR ≥60 ml/min/1.72m2 (normal: 182 patients, 36%), eGFR 30-59 ml/min/1.72m2 (moderately impaired: 261 patients, 52.7%), and eGFR < 30 ml/min/1.72m2 (severely impaired: 56 patients, 11.3%). Patients with severe renal dysfunction were older, more often female, and presented a worse clinical profile, with higher comorbidity burden and frailty. Baseline variables according to eGFR group are depicted in Table 1. After a median follow up of 371 days, 58 patients (11.6%) died. One year mortality was higher in patients with worse renal function (8.8%, 11% and 21% according to normal, moderate and severe renal dysfunction respectively, p=0.036) and in frail patients (Figure 1). In multivariate analysis, frailty, but not severe renal dysfunction, was associated with one year mortality (frailty HR 2.05 95%CI 1.11-3.78 p 0.021, eGFR < 30 and 30-60 ml/min/1.72m2 HR 1.39 95%CI 0.62-3.09 p0.424 and 1.09 95%CI 0.58-2.09 p0.793 respectively). Conclusions Most HF patients ≥75 years have renal dysfunction. The association between renal function and clinical outcomes is different according to frailty status. CKD is related to worse prognosis only in non-frail patientsCumulative incidence of 1-year mortalityTable 1.Baseline characteristics