Concomitant Disease Research Articles

The Association of High Burden Premature Ventricular Contractions with Esophageal/Upper GI Diseases

Six patients in our clinical program who were diagnosed with high burden (>10%) premature ventricular contractions (PVCs) and concomitant significant upper GI disease with no other significant cardiac history demonstrated a significant reduction in the burden of PVCs following surgical or procedural interventions of the upper GI tract (68.34% reduction, p = 0.024). Furthermore, in all cases, the origin of the PVCs was from the base of the right ventricular outflow tract (RVOT). This is the first report in the literature that we are aware of that makes the unique association that we propose a dual mechanism of action of the upper GI and vagally mediated PVCs and through direct, anatomical extrinsic triggering of the right ventricular outflow tract (RVOT) of the heart. These are very preliminary findings that warrant larger clinical and mechanistic studies that if confirmed, may define a new physiologic subset of PVCs for which we propose a new term, “E-PVCs”.

Tricuspid regurgitation in the context of severe concomitant left-sided valvular heart disease: patients characteristics and long-term clinical and interventional outcomes

Abstract Background The clinical features, therapeutical management and outcome of patients with significant tricuspid regurgitation (TR) in the context of multiple valvular disease (VD) are poorly defined. Purpose To assess the characteristics, management and long-term prognosis of a large cohort of patients with multiple VD, focusing on the context of significant TR and concomitant severe mitral or aortic disease. Methods Clinical and echocardiographic data were collected in 1183 patients with ≥moderate TR diagnosed at our centers from January 2012 to June 2020: after propensity score matching for age to create matched cohort with < 10% of absolute difference, 975 patients were included in this study and divided in 4 groups as shown in Figure 1. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization+any valvular intervention. Results Patients with isolated TR (356, 37%) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). TR+ severe MR patients (466, 48%) showed higher rates of concomitant coronary artery disease, NYHA class III/IV symptoms and larger left atrial volumes. The group of TR+ severe AS (131 patients, 13%) was characterized by older age, more comorbidities and lower LVEF. Patients with TR and severe AR (22, 2%) were younger, with larger LV dimensions and higher pulmonary pressures. Overall, in 37(4%) patients tricuspid intervention was performed: no differences were found between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment (p=0.444 and p= 0.624, respectively), while left-valve only surgical treatment was more common among patients with TR and severe MR and left-valve transcatheter treatment among patients with TR and severe AS (both p<0.001). After a median follow-up of 2.8 years, the primary endpoint occured in 374 (38%) of patients, and was significantly more frequent in the group of patients with TR and severe AS (p<0.001, Figure 2). In this group, after multivariate analysis, indexed stroke volume remained independenty associated with ACD (OR 0.96, CI 0.93-0.98, p =0.040). Eventually, the secondary endpoint too was more common in patients with TR and severe AS (p<0.001, Figure 2). Conclusions In the context of significant TR, concomitant severe left-sided VD is common, and each subtype presents with different clinical features and echocardiographic phenotypes; in this scenario, TR was profoundly underteated. Long-term, patients with significant TR+ severe AS have considerable worse prognosis.Figure 1Figure 2

Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients

Abstract Background A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease. Methods This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT. Results A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT. Conclusion Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.

Clinical profile and outcomes of patients with chronic kidney disease on chronic hemodialysis hospitalized for acute coronary syndrome in a tertiary public hospital in the Philippines

Abstract Introduction Acute coronary syndrome (ACS) and end-stage renal disease (ESRD) are both prevalent globally. Of the many risk factors for ACS, chronic kidney disease (CKD) remains to be of great concern because the interplay of cardiac and renal disease is inherently complicated. Cardiovascular mortality rates are 10-30 times higher in the ESRD population. The risk for cardiovascular disease in CKD extends beyond the traditional risk factors. Purpose The guidelines for ACS may not be applicable to the ESRD population because the landmark ACS trials mostly excluded ESRD patients. Due to the gaps in knowledge regarding ACS in ESRD, our study sought to explore the clinical profile and outcomes of these patients in the our institution. Methods We did a retrospective cohort study among ESRD patients presenting with ACS in our institution from May 2021 to November 2023. The data was analyzed using univariate and bivariate statistics using PRISM software. Results A total of 48 patients with ESRD were admitted for ACS in this study - 8 with STEMI and 40 with NSTEMI. The mean age was 61 years old and 33 (68.8%) were male. The average length of hospital stay was 12 days. The most common comorbidities were hypertension (91.7%), heart failure (83.3%), and diabetes mellitus (60.4%). The most common cause of ESRD in our cohort is concomitant hypertensive and diabetic kidney disease (45.8%) with an average length of hemodialysis at 31 months. The most common chief complaints were chest pain (39.6%), dyspnea (29.2%), and decreased sensorium (10.4%). On admission, 18 (37.5%) presented with systolic BP >160mmHg, 7 (14.6%) presented with shock, and 4 (8.3%) presented with cardiac arrest. On electrocardiogram, 21 (43.8%) had left ventricular hypertrophy while 34 (70.8%) had cardiomegaly on chest radiography. On two-dimensional echocardiogram, the average left ventricular ejection fraction was 46% and 27 (90%) had segmental wall motion abnormalities. The most common angiographic finding was 3-vessel coronary artery disease (50%). Only 5 patients (10.4%) had an LDL-C greater than 55mg/dL. Among those with STEMI, 6 (75%) presented with Kilip II or more. While among those with NSTEMI, 27 (67.5%) had a TIMI risk score >2. Almost all patients received dual-antiplatelet therapy, high dose statin, and beta-blocker. The mortality rate was 43.8% with acute coronary syndrome being the most common cause of death. Conclusion Our study did not show significant associated predictors of mortality possibly due to the low sample size. Despite this, our study portrays that patients admitted for ACS with ESRD present with higher risk features reflected by derangement in vital signs, abnormal laboratories, significant imaging abnormalities, high prognostication scores, and high in-hospital morbidity.Predictors of Mortality

Invasive testing leads to significantly altered (surgical) management strategy in coronary anomalies with interarterial course: 3 year interim analysis of MuSCAT

Abstract Introduction Diagnostic work-up of patients with an anomalous aortic origin of a coronary artery (AAOCA) includes an anatomical and functional assessment. The approach to functional evaluation currently varies widely and mainly includes noninvasive assessment. Intracoronary hemodynamic assessment can potentially enhance risk assessment for myocardial ischemia and sudden cardiac death and guide management of AAOCA patients. Hence, this study aims to evaluate invasive detection of ischemia on top of the standard of care diagnostic work-up for interarterial or intraseptal AAOCA and the impact on patient management. We report the first clinical outcomes. Methods In this multicenter prospective cohort study on AAOCA, all consecutive patients of 16 years and older with AAOCA with a newly diagnosed interarterial or intraseptal course in whom diagnostic work-up according to the protocol of the MuSCAT trial was performed between January 2021 and January 2024, were included for analysis. Exclusion comprised incomplete diagnostic evaluation, hemodynamically significant concomitant congenital heart disease or obstructive coronary artery disease in the AAOCA effluence. The work-up included invasive ischemia testing using fractional flow reserve (FFR) and or instantaneous wave-free ratio (iFR)/resting full-cycle ratio (RFR) at baseline and during pharmacological stress using adenosine, adrenaline and dobutamine. Results Fifty-eight patients (50% female, median age at AAOCA diagnosis 51.5 years (IQR 44.0-59.0)) were included, Table 1. The right coronary artery was anomalous in 88%, 93% patients had an interarterial and 69% an intramural course. Non-invasive ischemia detection was positive in 12%, negative in 84% and inconclusive in 4%. Invasive hemodynamic assessment was positive for ischemia in 22%, negative in 74% and inconclusive in 3%. Class of recommendation for surgery based on ESC guidelines was I or IIa in 28% patients and IIb, III or unclassified in 72%. Invasive hemodynamic assessment changed the treatment decision in 24% of the patients; 50% with initially recommended surgical treatment and 14% with initially a conservative treatment adjudication, Figure 1. Median follow-up after initial diagnosis was 20 [IQR 10-28] months and in 56% of all patients who completed 6 months follow-up the initial symptoms alleviated. One (2%) patient underwent a percutaneous re-intervention of the operated AAOCA. Conclusions This national prospective study of invasive hemodynamic assessment in patients with AAOCA showed clinically significant impact on the adjustment of initial management strategy in 24% of the patients. No cardiac death of myocardial infarction in the AAOCA supply area occurred during follow-up. Analysis of the complete follow-up of the MuSCAT trial can further substantiate the role of additional invasive functional imaging in AAOCA.

Demographics and clinical outcomes of flow-gradient patterns of aortic stenosis: an analysis of the CURRENT AS Registry-2

Abstract Background Low-gradient (LG) severe aortic stenosis (AS) has not been fully characterized compared with high-gradient (HG) AS. Methods Among 3369 patients with severe AS enrolled in the CURRENT AS Registry-2, the current study population consisted of 3363 patients with data on left ventricular ejection fraction (LVEF) after excluding patients with LG AS without indexed stroke volume data. Patients were divided into 4 groups (LG AS with reduced LVEF: N=285, paradoxical low-flow low-gradient [LFLG] AS: N=220, normal-flow low-gradient [NFLG] AS: N=872, and HG AS: N=1986). Results Compared to HG AS, LG AS with reduced LVEF more often had cardiovascular comorbidities, advanced cardiac damage stages, and frailty with less extensive aortic valve (AV) calcification by computed tomography (CT), and paradoxical LFLG AS more often had atrial fibrillation, concomitant valvular disease, advanced cardiac damage stages, and frailty with less extensive AV calcification, while NFLG AS were less often symptomatic, and had comparable cardiac damage stages, and frailty with less extensive AV calcification. Patients with the 3 types of LG AS less often underwent surgical or transcatheter aortic valve replacement than those with HG AS (cumulative 3-year incidence: LG AS with reduced LVEF: 64.5%, paradoxical LFLG AS: 59.1%, NFLG AS: 54.2%, and HG AS: 87.3%, P<0.001). Cumulative 3-year incidence of death or heart failure hospitalization was much higher in patients with LG AS with reduced LVEF and paradoxical LFLG AS than in those with HG AS (cumulative 3-year incidence: LG AS with reduced LVEF: 65.9%, paradoxical LFLG: 51.1%, NFLG: 35.5%, and HG: 30.5%, P<0.001). After adjusting confounders, LG AS with reduced LVEF and paradoxical LFLG AS compared with HG AS were independently associated with higher risk for death or heart failure hospitalization (HR: 1.82, 95%CI: 1.49-2.23, P<0.001; HR 1.43, 95%CI: 1.13-1.82, P=0.003, respectively), but not NFLG AS (HR 1.03, 95%CI: 0.88-1.21, P=0.68). Conclusions Aortic stenosis might be less severe in LG AS than in HG AS when assessed by the CT calcium score of the aortic valve, and each of the 3 hemodynamic types of LG AS had distinct clinical, and echocardiographic characteristics as well as clinical outcomes that were different from HG AS.Different patterns of severe AS

Characteristics and outcomes of patients with moderate multivalvular disease in the context of tricuspid regurgitation

Abstract Background The clinical features and the long-term prognosis of patients with moderate tricuspid regurgitation (TR) in the context of concomitant moderate left-sided valvular disease (VD) are poorly characterized. Purpose This study sought to describe the characteristics and the outcomes of patients with combined moderate TR and moderate mitral or aortic VD. Methods Baseline clinical and follow-up data were collected from 2110 patients with moderate TR in combination with a moderate left-sided VD diagnosed at our centers from January 2012 to July 2020; the final cohort was divided in 4 groups as shown in Figure 1. The primary endpoint was all-cause death; secondary EP was the first occurrence of heart failure (HF) hospitalization. Results Group 1 patients (1529, 72.5%) had the highest prevalence of chronic kidney disease (897, 66%) and lowest left ventricular systolic function (LVEF <50%, 298, 21%), as detailed in Table 1. Coronary artery disease was most prevalent in Group 2 patients (43, 41%), which also presented with the lowest average Charlson Index scores (3.95±1.87) and most prevalent dyspnea symptoms (44, 41%). Group 3 patients (41, 1.9%) were the oldest (82±7 years), had the highest rate of comorbidities (mean Charlson score 5.2±1.6), atrial fibrillation (20, 54%) and pulmonary hypertension (17, 46%). Eventually, Group 4 patients (422, 20%) were the youngest (74±13 years), more commonly female (279, 66%) and with the highest right ventricular dysfunction rate (TAPSE < 17 mm, 114, 40%). After a median follow-up of 2.1 years, the primary endpoint occurred in 895 (42.4%) patients, with a significantly higher incidence in Group 3 patients (p<0.001) (Figure 1). The secondary endpoint occurred in 316 (15.0%) patients and, similarly, significantly more frequently in Group 3 patients (p=0.01). Subgroup analysis for the primary and secondary endpoint in patients with preserved ejection fraction (LVEF > 50%) confirmed the results of the primary analysis, with Group 3 as the cohort with the most adverse outcomes. Conclusions Patients with significant TR frequently exhibit concurrent left-sided VD, identifying distinct patient subgroups with varying clinical profiles. Notably, TR combined with moderate AS is associated with the most severe clinical presentation and the poorest long-term prognosis, even in patients with preserved LVEF.Figure 1.

The risk factors for in-stent restenosis following drug-eluting stent implantation in end-stage renal disease patients receiving renal replacement therapy

Abstract Background Chronic renal disease is a recognized risk factor for in-stent restenosis (ISR) following percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). However, the specific risk of ISR among individuals with end-stage renal disease (ESRD) remains unclear or insufficiently studied. Purpose It is imperative to identify the risk factors associated with ISR among patients with ESRD and coronary artery disease following the implantation of DES. This identification is crucial for generating evidence-based strategies aimed at preventing ISR. Methods ESRD patients undergoing renal replacement therapy with concomitant coronary artery disease who underwent PCI with their initial DES implantation at our hospital between January 2013 and December 2022 were included in the study cohort. Clinical data, laboratory test results, and PCI specifics were compared between patients with and without ISR. Univariate and multivariate analyses utilizing Cox proportional hazard regression were employed to identify independent risk factors for DES-ISR. Results Among the 321 patients with ESRD who underwent PCI with DES implantation, totaling 874.5 patient-years of follow-up, 53 cases of ISR occurred during this period, yielding an incidence rate of 6.1 per 100 patient-years. Several baseline characteristics, angiographic findings, and procedural details were found to elevate the risk of ISR significantly. These included underlying diabetes mellitus, peripheral artery disease (PAD), high serum parathyroid hormone levels, LDL-C levels, acute coronary syndrome as the clinical presentation, the presence of triple vessel disease, duration of dual antiplatelet therapy less than 1 year, target lesion involving the left main (LM) or left anterior descending (LAD) artery, target vessel size less than 3 mm, ostial lesion, bifurcation lesion, number of stents implanted equal to or more than 3, and stent size less than 3 mm. In the multivariate Cox proportional hazard model, bifurcation lesion (HR 14.70, 95% CI 4.66-46.38), PCI of LM or LAD (HR 5.29, 95% CI 1.14-24.60), target vessel size less than 3 mm (HR 4.10, 95% CI 1.77-9.50), PAD (HR 3.92, 95% CI 1.52-10.08), and ostial lesion (HR 2.92, 95% CI 1.16-7.38) were identified as independent risk factors for ISR (all p-values < 0.05). Conclusions Among ESRD patients with coronary artery disease, bifurcation lesion, PCI involving the LM or LAD, target vessel size less than 3 mm, PAD, and ostial lesion are identified as independent risk factors for ISR. These findings hold significance in enhancing risk stratification and decision-making concerning treatment planning for this population.Univariate analysis risk factors for ISR

Electronic nudge letters to increase influenza vaccination uptake in younger and middle-aged individuals with diabetes: a prespecified analysis of the NUDGE-FLU-CHRONIC trial

Abstract Background Despite evidence demonstrating that influenza vaccination is associated with reduced risk of adverse cardiovascular events and all-cause mortality, influenza vaccine uptake remains suboptimal in persons with diabetes mellitus (DM). Purpose In this prespecified analysis of the NUDGE-FLU-CHRONIC trial we assessed the effectiveness of electronically delivered nudges on influenza vaccine uptake according to DM status. Methods NUDGE-FLU-CHRONIC was a nationwide, randomized, pragmatic implementation trial among younger and middle-aged (18-64 years) Danish citizens with chronic disease during the 2023/2024 influenza season. All trial participants were eligible for a free influenza vaccination through the Danish governmental vaccine program. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care (no electronic letter) or one of 6 different electronic nudge letters delivered on Sep 26, 2023. Baseline and outcome data were obtained using the Danish nationwide registries. The endpoint was receipt of a seasonal influenza vaccine on or before Jan 1, 2024. Results Of 299,881 NUDGE-FLU-CHRONIC participants, 57,666 (19.2%) had DM at baseline. Participants with DM had a median age of 51.6 years, 43.0% were female, median Hba1c of 53 mmol/mol, median DM duration of 10.0 years, and 51.2% were insulin dependent. During follow-up, 43.0% of those with DM vs. 34.6% of those without DM received the seasonal influenza vaccine (p<0.001). Any electronic letter vs. usual care was highly effective in increasing vaccine uptake in participants with DM at baseline (45.6% vs. 36.5%, difference: +9.1 percentage points [99.29%CI: 7.9-10.3], relative risk ratio [RR]: 1.42, 99.29%CI: [1.39-1.44]). However, DM status modified the effect of any electronic letter such that participants without DM at baseline experienced a slightly greater effect than those with DM (37.3% vs. 25.9%, difference: +12.3 percentage points [11.7-12.8], RR: 1.47 [1.45-1.50]; p-interaction <0.001). For each individual electronic nudge letter, the effect of the intervention was slightly lower in participants with DM compared to those without (Figure 1; all p-interaction < 0.015). When assessing DM subgroups, the effect of any electronic letter vs. usual care was greater in participants with DM and concomitant cardiovascular disease than in those without, greater in non-insulin treated than in insulin-treated individuals, and greater in those with shorter diabetes duration. Effectiveness of nudges were consistent across all other DM subgroups including HbA1c level (Figure 2). Conclusions Electronic nudge letters significantly boosted vaccine uptake in a broad range of individuals with DM, but the effect was slightly lower compared to those without DM. Future studies should test whether behaviorally designed nudges may positively influence other health behaviors in people with diabetes.

Prognostic value of exercise right ventricular-pulmonary arterial coupling in primary mitral regurgitation

Abstract Background Exercise-induced pulmonary hypertension (mPAP/CO slope >3mmHg/L/min) was recently associated with worse outcome in >moderate PMR. However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods Cohort study including consecutive pts submitted to CPET-echo with >moderate PMR, no/discordant symptoms, preserved LV function and without >moderate concomitant valvular disease or atrial fibrillation (AF). Thorough assessment of RV systolic function and RVPAc (TAPSE/sPAP ratio) was obtained by echocardiography using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of all-cause mortality, cardiovascular hospitalization (CVH), new-onset AF and valvular intervention; secondary outcome was the composite of CVH and new-onset AF. Results A total of 128 consecutive pts (64±11 years, 61% men) underwent CPET-echo. Event-free survival rate was 55% and 46% at 1 and 2 years. Pts that reached the primary combined endpoint were significantly older, had larger left atrium indexed volumes (LAVi), higher proportion of grade 4 MR, lower absolute and normalized peak VO2, and a significantly higher mPAP/CO slope (2,1±0,8 vs.3,7±2,6). They had a significantly lower rest and exercise TAPSE/sPAP, RV global and free wall longitudinal strain, rest and exercise TAPSE and exercise RV free wall S’. Rest and low exercise TAPSE/sPAP scored the highest accuracy in predicting the primary combined endpoint among variables statistically significant in the univariate analysis and therefore were used in the multivariate model. Sequentially adding rest and low exercise TAPSE/sPAP significantly improved the baseline predictive model (age, LAVi and MR grade). Low exercise TAPSE/sPAP and LAVi remained as significant independent variables in the multivariate model. They also correlated with new-onset AF and CVH; with rest and low exercise TAPSE/sPAP constituting significant steps (Fig 2). Replacing low exercise TAPSE/sPAP for mPAP/CO slope in the proposed model only slightly improved its accuracy in predicting the primary and secondary composite outcomes. Adding predicted peak VO2 (≥80% vs <80%) did not significantly improve the accuracy of any of the multivariate models. Low exercise TAPSE/sPAP and mPAP/CO slope both correlated well with peak VO2 and VE/VCO2 slope. Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in pts with >moderate PMR and no/discordant symptoms. Low exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Low exercise TAPSE/sPAP is a potential alternative to mPAP/CO slope in this population and it may be simpler to adopt in clinical practice.Central Illustration

Sex differences in severe aortic stenosis undergoing surgical replacement

Abstract Background Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Sex differences have been described in AS pathophysiology and left ventricular (LV) remodelling, as well as clinical presentation and response to therapies (1). However, sex differences in LV function parameters, namely global longitudinal strain (GLS), have been scarcely explored so far. Purpose To investigate sex differences, taking into account GLS, in patients with severe AS referred to surgical aortic valve replacement (SAVR). Methods The study population was from a single centre, prospective registry of patients with severe native valve AS who were referred for SAVR between June 2020 to October 2022. Severe AS was defined by standard guideline criteria (2). All patients underwent an echocardiogram immediately before and at least 3 months after surgery. Results Table 1 recapitulates sex differences in our population (n=119, 43% women). No differences in age or cardiovascular (CV) risk factors were noted. Clinical presentation and AS etiology were also similar. At baseline, women had lower EuroSCORE (p=0.039), creatinine (p <0.001), and haemoglobin levels (p=0.001). The echocardiogram showed a higher mean aortic valve gradient in women (Gmean, 62 vs. 50 mmHg, p=0.002). Women also had higher relative wall thickness (RWT, 0.49 vs. 0.42, p=0.037), despite lower LV mass index (124.9 vs. 136.6 g/m², p=0.037). Regarding LV function, women showed higher EF (64% vs. 60%, p=0.002) and GLS (16.5% vs. 14.6%, p=0.006) values. This is partially explained by the higher prevalence of concomitant coronary artery disease (CAD) in men, more frequently subjected to a concomitant coronary artery bypass graft than women (CABG, 38% vs. 8%, p <0.001). Post-operative complications had similar rates in men and women. After a median follow-up of 16 (6-18) months, death from any cause (6.0% vs. 1.5%, p=0.186) and rehospitalization for CV causes (14.0% vs. 4.0%, p=0.055) tended to be more frequent among women. When considering patients with severe AS alone (n=89), women had higher Gmean (64 vs. 53 mmHg, p=0.035) and EF (65% vs. 62%, p=0.045) but similar GLS (16.9% vs. 16.6%, p=0.230) as compared to men (Figure 2). At follow-up, EF and GLS failed to improve in both sexes and no differences were noted between women and men (EF 60% vs. 60%, p=0.476; GLS 15.9% vs. 16.0%, p=0.976). Conclusions In a population of all-comers patients with severe AS undergoing SAVR, women showed higher Gmean, EF, and GLS values. This is partially due to the higher prevalence of a concomitant CAD in men. When considering patients with AS alone, women still had higher EF and Gmean than men, despite a similar GLS. Future larger prospective studies with longer follow-up are needed in order to further characterize such differences and correlate them with specific outcomes.

Application of anticoagulants in the perioperative period of pci for patients with a history of atrial fibrillation and NSTEMI: a real-world, large multicenter retrospective clinical study

Abstract Backgrounds The optimal management for patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) remains unclear, particularly regarding anticoagulants use and ischemia-bleeding balance risks. This study aims to investigate the impact of perioperative anticoagulant use on patients with AF and acute non-ST-segment elevation myocardial infarction (NSTEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 150,530 patients were enrolled, including 74,373 NSTEMI patients. Patients were divided into anticoagulants and non-anticoagulants groups. A total of 1,358 patients were included in the non-anticoagulant group, and 3,541 patients were included in the anticoagulant group. Patients in each group were one-to-one matched based on propensity scores using the nearest available pair matching (PSM) method with a caliper width equal to 0.01. The primary endpoints were major adverse cardiovascular and cerebrovascular adverse events (MACCE), including cardiovascular death, recurrent myocardial infarction, and stroke. Secondary endpoints included cardiovascular death, recurrent myocardial infarction, BARC type 3 bleeding, and cerebral hemorrhage. Follow-up time points were set at 1 month,3 months, and 6 months. Multivariate Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results After PSM matching, each group consisted of 809 patients. The anticoagulant group had a higher proportion of males, a higher prevalence of patients with a history of Percutaneous Coronary Intervention, and hyperlipidemia, while proportions of patients with Killips classification of III/IV and history of chronic kidney disease were lower. Anticoagulant use during the perioperative period significantly reduced the occurrence of MACCE at the primary endpoint at 1 month (aHR 0.57; P < 0.001), 3 months (aHR 0.57; P = 0.023), and 6 months (aHR 0.57; P < 0.001). At the secondary endpoint, anticoagulants use was associated with a lower incidence of cardiogenic death at 1 month,3 months, and 6 months (aHR 0.55; P <0.001), (aHR 0.55; P <0.001), (aHR 0.56; P <0.001), lower risk of myocardial infarction recurrence at 3 months and 6 months (aHR 0.47; P = 0.02), (aHR 0.44; P <0.001), without increasing the risk of bleeding events, including BARC type 3 bleeding and cerebral hemorrhage. Conclusion Perioperative anticoagulant use during PCI can reduce the occurrence of cardiac death, myocardial infarction, and stroke recurrence within 6 months post-surgery without increasing bleeding events in AF and NSTEMI patients. Therefore, for patients with AF, it is recommended to consider combining anticoagulant therapy with dual antiplatelet therapy during the perioperative period, if no contraindications.

Adherence to treatment in patients with arterial hypertension at the wartime conditions in Ukrainian population

Abstract Background Adherence to therapy significantly affects the course and prognosis of the disease. However, the impact of military operations and related factors on adherence to therapy has not been studied. Purpose The aim of the study was to evaluate additional factors influencing adherence to antihypertensive treatment in wartime. Materials and Methods A total of 1299 patients with arterial hypertension from different regions of Ukraine included into the study. All regions were divided into 3 zones: active hostilities; regions with moderate intensity; relatively calm regions. Besides traditional factors (age, education, concomitant pathology, type of therapy), the individual patients’ status was included to analysis as being a resident of a given region, an immigrant from an occupied territory or from a region of hostilities, or a person temporarily displaced. Analysis was performed in 4 treatment groups: 1 – fixed three-component combination olmesartan medoxomil/ amlodipine/ hydrochlorothiazide, 2 – fixed two-component combination olmesartan/ hydrochlorothiazide, 3 – fixed two-component therapy with olmesartan/ amlodipine, 4 - other antihypertensive therapy. Adherence was assessed at 1, 2 and 3 treatment months. Uni- and multivariate statistical analyses was performed to identify factors independently associated with treatment adherence. Results In total, 50 patients stopped the drug during the first month (3.8%), 9.8% stopped medication after 2 months, and 19.1% after 3 months. When analyzing patients' adherence depending on whether or not the doctor arrived from another region, we found that the percentage of patients who stopped treatment was almost twice higher if the doctor was displaced (32%), compared to doctors who remained in the places (18%). Based on results of comparative analysis, adherence to therapy was influenced by several factors: age, presence of concomitant coronary artery disease, staying in a high-risk region, number of pills, and prescribed drug. After 3 months adherence was 89% in patients who received 1 tablet per day, 84% - 2 tablets, 82% - 3-5 tablets, and 52% - more than 5 pills. The highest adherence was observed with the three-component pill and with combination of olmesartan and amlodipine. These combinations showed higher adherence compared to other types of therapy. Patient's level of education had no effect on adherence to therapy. Multivariate regression analysis showed, that age over 55 years (p=0.01) and patient’s being in dangerous area (p<0.0001) had significant independent negative influence on adherence. The use of two-component combination olmesartan/amlodipine or three-component therapy significantly increased adherence (p<0.0001). Conclusion In the wartime adherence to antihypertensive treatment depends both on previously known and specific factors - activity of hostilities in the region, as well as relocation of both patients and prescribing physicians to another region.

Satisfactory self-rated health is associated with better clinical outcomes in patients with ST-segment elevation myocardial infarction

Abstract Background It is well known that health status is a risk factor for cardiovascular diseases, but its specific impact on the prognosis of patients with acute myocardial infarction remains unclear. Purpose This study was aimed to investigate the impact of varying health self-evaluation on the long-term outcomes of patients diagnosed with ST-elevation myocardial infarction (STEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospital from 2010 to 2023. Patients were divided into satisfied group and dissatisfied group based on their responses to a self-assessment health questionnaire. Baseline data of the two groups were compared, and the relationship between health status and major cardiovascular and cerebrovascular adverse events (MACCE) was analyzed using multivariate cox regression. MACCE, defined as the composite endpoint of cardiac death, recurrent myocardial infarction, stroke and revascularization, was the primary endpoint, with each component considered a secondary endpoint. Results Among STEMI patients, 25214 patients reported satisfaction with their health, while 375 patients expressed dissatisfaction. The satisfied group exhibited a younger age, fewer females, a higher rate of primary percutaneous coronary intervention (PPCI) and PCI during hospitalization, a better Killips classification and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, and cerebrovascular disease. After a median follow-up of 1626 days, the satisfied group demonstrated significantly lower proportions of total death, cardiac death, recurrent myocardial infarction and stroke compared to dissatisfied group. Multivariate COX regression showed that satisfactory health self-rating was associated with a decreased risk of MACCE (HR 0.813, 95%CI 0.704-0.939, P=0.005), stroke (HR 0.670, 95%CI 0.511-0.878, P=0.003), and recurrent myocardial infarction (HR 0.732, 95%CI 0.548-0.979, P=0.035). Conclusions Satisfactory self-rated health is associated with better clinical outcomes in STEMI patients.

Correlation analysis of self-rated health and net adverse clinical events in patients with acute myocardial infarction

Abstract Backgrounds Self-rated health (SRH） is a recognized standard risk factor for myocardial infarction, but its impact on prognosis remains uncertain. Purpose This study aims to investigate the impact of self-rated health on the long-term clinical outcomes of myocardial infarction patients. Methods The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023, Patients were divided into satisfied and unsatisfied groups based on their responses to an SRH questionnaire. Propensity score matching (PSM) was utilized to balance covariates between the two groups and analyze the relationship between SRH and clinical outcomes. The primary endpoint was net adverse clinical events (NACE), comprising cardiac death, recurrent myocardial infarction, revascularization, ischemic stroke, and bleeding events (BARC ≥3). The secondary endpoint comprised the individual components of the primary endpoint. Results The study included a total of 55,054 AMI patients, with 54,049 rating their health as satisfactory and 1,005 patients as unsatisfactory. In the satisfactory group, patients tended to be younger, had fewer females, better Killip classification, a higher proportion of STEMI cases, a higher rate of undergoing PCI, and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, cerebrovascular disease, peripheral vascular disease, thyroid disease, and chronic lung disease. Additionally, patients in the satisfactory group had a higher proportion of antiplatelet therapy use (aspirin, ticagrelor). 1,005 pairs were well matched after PSM. After a median follow-up of 1626 days, the proportion of all-cause death, cardiac death, and recurrent myocardial infarction in the satisfied group was significantly lower than that in the unsatisfied group. Multivariable Cox regression analysis revealed that satisfactory SRH was associated with a reduced risk of NACE (aHR 0.809, 95%CI 0.704-0.930, P=0.002), cardiac death (aHR 0.790, 95%CI 0.665-0.939, P=0.007), and recurrent myocardial infarction (aHR 0.734, 95%CI 0.563-0.955, P=0.021). Conclusions Good SRH can decrease the risk of NACE in myocardial infarction patients, underscoring the importance of considering SRH in clinical assessment.

Correlation of exercise blood pressure levels with concomitant cardiovascular disease.

Hypertension is a fatal but preventable risk factor for cardiovascular disease and an important cause of death from cardiovascular disease. Exercise training has a definite clinical effect on blood pressure control. However, inappropriate exercise is ineffective and may also cause disease. The aim of this study was to evaluate the possible factors influencing blood pressure level in an exercise treadmill test and its relationship with accompanying clinical diseases. Five hundred sixty-four patients who underwent exercise treadmill test were selected and divided into the abnormal exercise blood pressure group (n = 156, age 60.46 ± 9.2 years) and normal exercise blood pressure group (n = 408, age 56.57 ± 8.8 years) according to whether the peak exercise systolic blood pressure was more than or equal to 180 mm Hg. General clinical data and associated clinical diseases were collected from both groups. The prevalence of hypertension and coronary atherosclerotic heart disease in the abnormal exercise blood pressure group was significantly higher than that in the normal exercise blood pressure group (all P < .05). At the same time, the smoking rate and glycohemoglobin level of the patients with abnormal exercise blood pressure were significantly increased (all P < .05), but there was no statistically significant difference in age, sex, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other indicators between the 2 groups (all P > .05). Patients with abnormal exercise blood pressure response have a higher prevalence of hypertension and coronary heart disease. Exercise blood pressure level may be an important factor affecting patients' cardiovascular prognosis.

Delineating three distinct spatiotemporal patterns of brain atrophy in Parkinson's disease.

The clinical manifestation of Parkinson's disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson's disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration. We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning algorithm that combined disease progression modelling with clustering methods, to cortical and subcortical neurodegeneration visible on 3 T structural MRI of a large cross-sectional sample of 504 patients and 279 healthy controls. Serial longitudinal data were available for a subset of 178 patients at the 2-year follow-up and for 140 patients at the 4-year follow-up. In a subset of 210 patients, concomitant Alzheimer's disease pathology was assessed by evaluating amyloid-β concentrations in the CSF or via the amyloid-specific radiotracer 18F-flutemetamol with PET. The SuStaIn analysis revealed three distinct subtypes, each characterized by unique patterns of spatiotemporal evolution of brain atrophy: neocortical, limbic and brainstem. In the neocortical subtype, a reduction in brain volume occurred in the frontal and parietal cortices in the earliest disease stage and progressed across the entire neocortex during the early stage, although with relative sparing of the striatum, pallidum, accumbens area and brainstem. The limbic subtype represented comparative regional vulnerability, which was characterized by early volume loss in the amygdala, accumbens area, striatum and temporal cortex, subsequently spreading to the parietal and frontal cortices across disease stage. The brainstem subtype showed gradual rostral progression from the brainstem extending to the amygdala and hippocampus, followed by the temporal and other cortices. Longitudinal MRI data confirmed that 77.8% of participants at the 2-year follow-up and 84.0% at the 4-year follow-up were assigned to subtypes consistent with estimates from the cross-sectional data. This three-subtype model aligned with empirically proposed subtypes based on age at onset, because the neocortical subtype demonstrated characteristics similar to those found in the old-onset phenotype, including older onset and cognitive decline symptoms (P < 0.05). Moreover, the subtypes correspond to the three categories of the neuropathological consensus criteria for symptomatic patients with Lewy pathology, proposing neocortex-, limbic- and brainstem-predominant patterns as different subgroups of α-synuclein distributions. Among the subtypes, the prevalence of biomarker evidence of amyloid-β pathology was comparable. Upon validation, the subtype model might be applied to individual cases, potentially serving as a biomarker to track disease progression and predict temporal evolution.

Prognosis and factors related to anti-VEGF therapy in patients with retinal vein occlusion and concomitant carotid artery disease

To evaluate the prognosis and influencing factors of retinal vein occlusion (RVO) in patients with concomitant carotid artery disease receiving anti-vascular endothelial growth factor (VEGF) treatment. Patients diagnosed with RVO and receiving anti-VEGF treatment were included. Eye and clinical data were collected. The patients were divided into a group with concomitant carotid artery disease (Group A) and a group without concomitant carotid artery disease (Group B). The risk factors affecting the visual prognosis of RVO patients with concomitant carotid artery disease were analyzed. Among 177 eligible patients with RVO, 101 had concomitant carotid artery disease (Group A), while 76 did not (Group B). Group A had a significantly lower treatment effectiveness rate than Group B (P < 0.001). The age and platelet distribution width of Group A were significantly higher than Group B (P < 0.001). Multivariate logistic regression analysis showed that baseline best-corrected visual acuity (BCVA), disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) disruption, and red blood cell distribution width (RDW) were significantly associated with the posttreatment visual prognosis of RVO patients with concomitant carotid artery disease(P < 0.05). RVO patients with concomitant carotid artery disease had a significantly lower treatment effectiveness rate than RVO patients without carotid artery disease. The poor baseline BCVA, DRIL, ELM disruption, and a greater RDW are risk factors for low anti-VEGF treatment efficacy among RVO patients with concomitant carotid artery disease.

Aspirin Hypersensitivity in Patients with Coronary Artery Disease: An Updated Review and Practical Recommendations.

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity.

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impactsintrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.