bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy comparison of prostacyclin analogue and prostacyclin receptor agonist as third line treatment for pulmonary arterial hypertension
Authors: Dardi F , Guarino D , Ballerini A , Magnani I , Donato F , Bertozzi R , Martini G , Manes A , Galie' N , Palazzini M
Published: November 2023

Background

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by small pulmonary arteries remodeling that leads to increased pulmonary vascular resistance, dyspnea, fatigue, right heart failure and ultimately death. Prostacyclin analogue drugs, such as epoprostenol or treprostinil, have a vasodilator, antiproliferative and immunomodulatory effect, representing established therapies for cases of severe PAH. Both these drugs improve exercise capacity, functional class and hemodynamic parameters, while epoprostenol also improves survival among patients with PAH. Despite these therapeutic benefits, these treatments need parenteral administration. Recently, the approval of selexipag, an oral selective prostacyclin receptor agonist, may represent a possible alternative option in some PAH patients.

Methods

Patients with PAH treated as third line therapy with epoprostenol, treprostinil or selexipag, on top of inhibitor of type 5 phosphodiesterases and endothelin-1 receptor antagonists, referred to our center from February 1995 to December 2021 were retrospectively included. All patients noninvasive [6 minutes walking distance (6MWD)] and invasive [mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), right atrial pressure (RAP) and mixed venous oxygen saturation (SvO2)] parameters were first collected at the baseline right heart catheterization (prior to the beginning of prostacyclin treatment) and then 3-4 months after the beginning of third line therapy. The absolute improvements in these parameters were compared with Dunn’s test. Data are expressed as median (interquartile range).

Results

153 PAH patients treated as third line therapy with epoprostenol, treprostenil and selexipag were included (44, 73, 36 patients respectively). At 3 to 4 months after the beginning of the third line therapy, absolute improvements in the different parameters are shown in Figure 1.

Conclusions

In our study population, epoprostenol, treprostenil and selexipag improve both exercise capacity and haemodynamic parameters in PAH patients when used as third line therapy, with the highest efficacy in the first group and, possibly, the lowest efficacy in the latter. These results confirm the beneficial role of these drugs in PAH patients and may suggest a possible favorable role for selexipag in the management of PAH patients with a less severe disease reserving a more invasive treatment strategy with parenteral prostanoids in patients with a higher risk disease.Figure 1
The influence of symptom-to-reperfusion-time on left ventricular strain and extent of infarction in patients with STEMI: a 3-dimensional view on the wavefront phenomenon
Authors: Demirkiran A , Beijnink C , Kloner R A , Hopman L H G A , Van Der Hoeven N W , Van Pouderoijen N , Janssens G N , Everaars H , Van Leeuwen M A H , Van Rossum A C , Van Royen N , Robbers L F H J , Nijveldt R
Published: November 2023

Aims

Data on the relationship between time-to-reperfusion and left ventricular (LV) function and infarct characteristics after ST-segment elevation myocardial infarction (STEMI) are inconsistent and not completely understood. Therefore, we examined the association between the symptom-to-reperfusion-time and cardiovascular magnetic resonance (CMR) derived global strain parameters and infarct extent in STEMI patients.

Methods and results

The study included 108 STEMI patients who underwent successful primary percutaneous coronary intervention (PPCI). Patients were categorized according to the median symptom-to-reperfusion-time: shorter (<160min, n=54) and longer times (>160min, n=54). CMR was performed 2-7 days after PPCI and at 1-month. CMR cine imaging was performed for functional assessment and late gadolinium enhancement (LGE) to evaluate infarct extent. Myocardial feature-tracking was used for global LV strain analysis. Mean transmural extent score was quantified per patient as the average of infarct percentages for all segments containing hyperenhanced tissue. Baseline clinical and angiographic characteristics were comparable between the groups. Patients with shorter reperfusion time had more favorable baseline and follow-up LV circumferential and radial strain (p=0.049, p=0.01, p=0.047, p<0.01, respectively), while LV longitudinal strain appeared comparable for both baseline and follow-up (p>0.05 for both, Figure 1). Mean transmural extent score at follow-up was lower in patients with shorter reperfusion time (p<0.01). In multivariable regression analysis including all 3 strain directions, baseline LV circumferential strain was independently associated with mean transmural extent score at follow-up (β=1.89, p<0.001).

Conclusion

In STEMI patients, time-to-reperfusion was significantly associated with smaller extent of infarction and better LV circumferential and radial strain but not with longitudinal strain. Moreover, infarct transmurality and residual LV circumferential strain are closely linked.Comparison of BL and FU global LV strainGraphical abstract
Left atrial stiffness in patients with severe aortic stenosis: a novel approach
Authors: Alfuhied A , Steadman C , Parke K , Aslam S , Marsh A M , Sian M , Mccann G P , Singh A
Published: November 2023

Background

Left atrial (LA) stiffness index is a non-invasive transthoracic echocardiography (TTE) measure that combines left ventricle filling pressure (E/e’) and LA strain at reservoir (LAS_r)(1-3). LAS assessment using cardiac magnetic resonance feature tracking (CMR-FT) is feasible and reproducible(4, 5), and may have advantages over TTE. CMR-modelled pulmonary capillary wedge pressure (PCWP) has recently been validated and shown to be of prognostic value in heart failure(6). We investigate the feasibility of assessing LA stiffness index using novel approaches (CMR and hybrid TTE and CMR) in patients with severe aortic stenosis (AS) compared to controls.

Method

Patients with severe AS and matched controls were prospectively recruited. CMR and TTE scans were performed on the same day. LAS_r was assessed on 4- and 2-chamber long-axis images, and average value was calculated. Images were analysed using TomTec-ARENA (v2.4) for speckle tracking echocardiography (STE), whereas Medis Suite (v3.1) was used for FT-CMR by a blinded single observer. CMR-modelled PCWP was calculated as: 6.1352 + (0.07204 ∗ LAV) + (0.02256 ∗ LVM), where LAV=left atrial maximum volume and LVM=left ventricle mass by CMR(6). LA stiffness index calculated by (i) TTE: E/e’/LAS_r, using LAS by STE; (ii) TTE-CMR hybrid: E/e’/LAS_r, using LAS by FT-CMR; (iii) CMR: CMR PCWP/LAS_r, using LAS by FT-CMR (Figure).

Result

Patients with severe AS (n=78, mean age 67.1±9.4 years; 74% males) were well matched to the controls (n=19) for demographics and body size. Patients demonstrated significantly higher filling pressures, lower LAS, higher LAV and LVM. All measures of LA stiffness were significantly higher in patients with AS than matched controls (Table). The correlation between TTE and CMR measured LA stiffness was fair (r=0.46, p-value <0.001), moderate between CMR and TTE-CMR hybrid (r=0.71, p-value <0.001) and strong correlation between TTE and TTE-CMR hybrid (r=0.86, p-value <0.001).

Conclusion

Non-invasively estimated LA stiffness obtained by TTE, CMR or hybrid are feasible in patients with severe AS, and demonstrates higher stiffness index compared to matched controls.Table 1Figure 1
Reduced right ventricular outflow tract strain at cardiac magnetic resonance correlates with low-voltage areas at unipolar electroanatomic mapping in patients with brugada syndrome
Authors: Ciabatti M , Zocchi C , Pieroni M , Notarstefano P , Tavanti V , Nesti M , Sisti N , Fumagalli C , Malatesti L , Raimondi F , Pedrizzetti G , Chan R H , Olivotto I , Bolognese L
Published: November 2023

Background

Brugada Syndrome (BrS) was initially described as a channelopathy without underlying structural substrate, but pathological and electroanatomic abnormalities of the right ventricular outflow tract (RVOT), are increasingly recognized, suggesting a possible role of electroanatomic mapping (EAM) in risk stratification of these patients. New echocardiographic and cardiac magnetic resonance (CMR) tools are able to identify subtle structural and functional myocardial abnormalities associated with an increased arrhythmic risk.

Purpose

We aimed to assess the presence of structural and functional abnormalities of RVOT by CMR-derived RV and RVOT feature tracking in BrS patients. We also sought to evaluate the relationship between RVOT functional abnormalities and the presence and extension of RVOT abnormal voltage areas at EAM.

Methods

we retrospectively enrolled BrS patients submitted to CMR comprehensive of RVOT sequences and bipolar and unipolar endocardial EAM. Abnormal voltage areas were defined by the presence of signal amplitude <4mV at unipolar mapping and signal amplitude <1.5mV at bipolar mapping. We included a control group of 15 healthy volunteers submitted to CMR including RVOT sequences.

Results

We studied 16 patients, 12/16 males, mean age 42±9 years. In all cases CMR showed normal left and right ventricular ejection fraction (LVEF 57±4%, RVEF 56±6%). RVOT peak strain values were significantly impaired in BrS patients compared to controls (-17.9±8.6% vs -26.4±9.5%, p=0.011), while RV-GLS did not differ between the two groups (-22.2±4.0% vs 24.6±2.5%, p=0.061). EAM showed the presence of pathological voltages at both unipolar and bipolar mapping in 12 patients, abnormal unipolar and normal bipolar maps in 1 case and both unipolar and bipolar normal maps in 3 patients. Median extent of abnormal voltage areas was 5.3 cm2 [IQ 1-4 = 0.6-9.3 cm2] at unipolar and 4.1 cm2 [IQ 1-4 = 0.7-7.5 cm2] at bipolar map. RVOT peak strain showed a significant correlation with abnormal voltage areas at unipolar EAM (r=0.546, r2=0.525, p=0.029). Patients with both unipolar and bipolar normal maps (n=3) had normal RVOT strain values compared to controls (-25.7±3.9 vs -26.4±9.5%, p=0.90).

Conclusions

In patients with BrS, RVOT peak strain is significantly reduced compared to controls and is associated with abnormal voltage areas at endocardial unipolar EAM. Noninvasive evaluation of BrS patients with CMR-derived RVOT feature tracking may help to identify patients requiring invasive evaluation with EAM. Prospective studies evaluating the prognostic role of RVOT strain and EAM in BrS patients are needed.
Incremental prognostic value of fully-automatic machine-learning based global circumferential strain during a stress CMR exam
Authors: Pezel T , Garot P , Toupin S , Sanguineti F , Hovasse T , Unterseeh T , Chitiboi T , Jacob A J , Borgohain I , Sharma P , Champagne S , Garot J
Published: November 2023

Background

Left ventricular global circumferential strain using cardiovascular magnetic resonance (CMR) is an accurate indicator to predict cardiovascular events. Although several studies have shown the excellent prognostic value of stress CMR, the prognostic value of stress global circumferential strain (sGCS) remains unknown.

Purpose

To investigate the prognostic value of sGCS for predicting cardiovascular events using a fully automatic machine learning algorithm without human correction in consecutive patients referred for stress CMR.

Methods

Between 2016 and 2018, all consecutive patients referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction (MI). A fully automatic machine learning algorithm was trained and validated on unseen CMR studies (MAGNETOM Aera and Skyra, Siemens Healthcare, Erlangen, Germany) to assess the sGCS from short-axis cine images at stress. The algorithm combines multiple deep learning networks for detection and segmentation with an active contours approach. Cox regressions were performed to determine the prognostic value of sGCS.

Results

Among 2,906 consecutive patients who underwent stress CMR, the automatic sGCS was successfully computed in 2,859 (98.4%) patients (68% male, mean age 64±12 years). A total of 256 (8.8%) MACEs were observed during a median (IQR) follow-up period of 4.5 (3.7-5.3) years. Using Kaplan-Meier analysis, sGCS and the presence of inducible ischemia were significantly associated with the occurrence of MACE (hazard ratio, HR: 1.12 [95% CI, 1.08-1.17]; and HR: 8.48 [95% CI, 6.05-11.91], both p<0.001; respectively). After adjustment for traditional risk factors, inducible ischemia and late gadolinium enhancement (LGE), sGCS was an independent predictor of a higher incidence of MACE (adjusted HR: 1.12 [95% CI, 1.05-1.20]). Finally, sGCS showed an incremental prognostic value to predict MACE compared to a multivariable model including traditional risk factors, the presence of inducible ischemia and LGE (C-statistic improvement: 0.05, p=0.007; NRI= 0.169; IDI= 0.097; both p<0.001).

Conclusions

Automatic sGCS has an incremental prognostic value to predict MACE above traditional risk factors, and other stress CMR parameters.Survival curvesIncremental prognostic value
Hemodynamic forces from 4D flow magnetic resonance imaging for optimised prediction of cardiac resynchronisation therapy outcome
Authors: Pola K , Roijer A , Borgquist R , Ostenfeld E , Carlsson M , Bakos Z , Arheden H , Arvidsson P M
Published: November 2023

Background

Patients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronisation therapy (CRT), but many patients have limited treatment response (1). The use of imaging to optimise patient selection has been repeatedly attempted with some success (2), and scar detected on late gadolinium enhancement (LGE) imaging has been associated with reduced response rates (3). Intraventricular hemodynamic force (HDF) analysis has been suggested as a novel marker for assessment of patients eligible for CRT (4). The aim of this study was therefore to investigate if septal scar from LGE or left ventricular HDF computed from cardiac magnetic resonance (CMR) imaging can improve prediction of CRT outcome.

Methods

Patients with heart failure, EF<35% and LBBB (n=22) underwent CMR with 4D flow at 1.5T or 3T (Achieva, Philips Healthcare) prior to CRT (Figure 1). Scar was assessed by LGE. Left ventricular HDF were computed based on the Navier-Stokes equations, using a validated module in the software Segment v3.3 R10057 (Medviso, Lund, Sweden) (5). Forces (N) were analysed in three orthogonal directions as root mean square (RMS) and peak values, reported in median [interquartile range]. Transversal/longitudinal HDF ratio was calculated for systole and diastole. Echocardiography was performed before and six months after CRT, and patients with end-systolic volume reduction ≥15% at follow-up were defined as responders. The Mann-Whitney U test was used for group comparisons, Fisher’s exact test for binary categorical data, Wilcoxon test for paired comparisons, and receiver operating characteristic analysis for prediction of CRT response.

Results

There was no difference between responders and non-responders in LGE (Table 1). Non-responders had smaller HDF than responders in the inferior-anterior direction in systole (RMS: 0.055 [0.027] vs 0.070 [0.032], p=0.04; peak: 0.11 [0.069] vs 0.15 [0.083], p=0.03), and in the apex-base direction in diastole (RMS: 0.087 [0.018] vs 0.11 [0.046], p=0.047). Non-responders had larger diastolic HDF ratio than responders (RMS: 0.89 [0.45] vs 0.67 [0.20], p=0.004; peak: 1.1 [0.51] vs 0.57 [0.40], p=0.01) (Figure 1). Receiver operating characteristic analysis of diastolic HDF ratio found an area under the curve of 0.88 (p=0.005). Identification of non-responders using diastolic HDF ratio with a specificity of 100%, resulted in a ratio of >0.87 for non-responders, with a sensitivity of 57%. Intragroup comparison found higher HDF ratio in systole than diastole for responders but not for non-responders (Figure 1).

Conclusions

Prediction of left ventricular remodelling following CRT may be optimized by hemodynamic force analysis from 4D flow CMR, while septal scar from LGE was not found indicative of CRT outcome in this pilot study. Larger-scale studies are required before clinical implementation of HDF analysis.Table 1Figure 1
Enhancing the diagnostic performance of CZT SPECT myocardial perfusion imaging with myocardial blood flow information
Authors: Kadoya Y , Al-Harbi J A , Small G S , Wells G W , Ruddy T R
Published: November 2023

Background

The use of cadmium-zinc-telluride (CZT) single photon emission computed tomography (SPECT) for measuring myocardial blood flow (MBF) has been established as a valuable tool for improving diagnostic accuracy. However, the clinical significance of incorporating MBF into the interpretation of stress SPECT myocardial perfusion imaging (MPI) remains largely unknown.

Purpose

The objective of this study is to determine the effect of MBF information on the interpretation of CZT SPECT MPI.

Methods

A cohort of 411 patients underwent a rest/stress gated perfusion and MBF imaging procedure using full-dose 99mTc-tetrofosmin. MBF and flow reserve were calculated using the Corridor4DM v2018 software (INVIA, Ann Arbor, MI). The SPECT data were analyzed twice, once without and once with MBF results. The criteria for abnormal myocardial flow reserve were set at 2.0, while stress flow was set at 1.8 ml/min/g. The interpretations were categorized into normal, equivocal, or abnormal and interpretive certainty was classified into five groups: definitely normal/abnormal, probably normal/abnormal, or equivocal. The overall results were evaluated, along with differences between men and women. Statistical significance was determined using contingency table analysis and chi-squared testing.

Results

The study cohort had a mean age of 62.5 ± 9.8 years, with 71% of the participants being male. The addition of MBF altered the MPI interpretation in 10.7% of patients (44/411), with a change from abnormal or equivocal to normal in 45.5% (20/44) of cases. The frequency of equivocal MPI interpretations dropped significantly from 4.6% without MBF to 1.5% with MBF (P=0.008). Interpretive certainty improved with a significant decrease in equivocal scans (P=0.006). 89.1% of MPI with MBF were reported as definitely normal or abnormal, compared to 83.0% without MBF (P=0.012) (Figure 1). Further analysis by gender showed similar results for men, while no significant changes were observed in women's MPI interpretation and certainty (Figure 2).

Conclusion

The inclusion of MBF had a significant impact on the interpretation of CZT SPECT MPI scans, with changes observed in 10.7% of cases. Interpretative certainty improved with fewer equivocal scans and a higher proportion of definitely normal or definitely abnormal interpretations. These findings were evident in men, but not in women (possible due to smaller sample size).Figure 1Figure 2
Speckle tracking echocardiography allows for the detection of subclinical myocardial dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement
Authors: Cygulska K M , Blaszczyk M B , Kasprzak J D K , Wejner-Mik P W M , Szymczyk E S , Wdowiak-Okrojek K W O , Frynas-Jonczyk K F J , Plachcinska A P , Kusmierek J K , Lipiec P L
Published: November 2023

Background

Speckle tracking echocardiography (STE) is helpful for the detection of subclinical systolic function abnormalities. Coronary flow reserve (CFR) measured by dynamic 99mTc-MIBI SPECT-CZT gamma camera allows the diagnosis of myocardial perfusion defects in patients with suspected coronary artery disease (CAD).

Purpose

The aim of our study is to assess the diagnostic value of STE and SPECT-based CFR in patients with suspected coronary artery disease (CAD).

Methods

85 patients (pts) (37.6% females, mean age 65.4 ± 8.5 years) with suspected CAD underwent 2D and 3D STE, as well as myocardial perfusion study with novel solid-state CZT nuclear camera (dipyridamole stress protocol). We calculated global longitudinal left ventricular strain (GLS), as well as LS of individual coronary artery territories (LAD LS, Cx LS and RCA LS). Total CFR and CFR in three coronary territories were also measured. The presence of CAD (coronary artery stenosis > 70%) was assessed by coronary angiography.

Results

Significant CAD was confirmed in 50 patients. Mean total CFR (1.71 ± 0.61 vs 2.1 ± 0.52, p = 0.002), as well as CFR in LAD territories (1.54 ± 0.68 vs 1.91 ± 0.56, p = 0.02), RCA territories (1.58 ± 0.82 vs 1.95 ± 0.68, p = 0.048) and Cx territories (1.58 ± 0.78 vs 2.08 ±0.76, p = 0.01) were lower in pts with CAD. In the ROC curve analysis of total CFR for the diagnosis of CAD the AUC was found to be 0.7 (p = 0.001).

Mean absolute 2D GLS in pts with total CFR < 2.0 was significantly lower than in pts with CFR >= 2.0 (-14.5 ± 4.3 vs -16.9 ± 3.4, p = 0.005). Similar differences were observed in all three coronary territories (p ≤ 0.05). The same results were not observed in case of 3D GLS . Modest but significant correlations were detected between total CFR and 2D GLS values (r = -0.38; p < 0.001), LAD CFR and 2D LAD LS (r = -0.33; p = 0.002), LCx CFR and 2 D LCx LS (r = -0.39; p < 0.001), total CFR and EF (r = 0.36; p < 0.001). GLS at rest had good diagnostic value for detecting total CFR < 2 (AUC= 0.7; p = 0.004). The criterion with the highest diagnostic accuracy was GLS > (- 18.5) – its sensitivity was 84%, specificity 42%, positive predictive value 0.7, negative predictive value 0.7 and overall accuracy 66%.

Conclusions

CFR assessed by SPECT provides acceptable diagnostic accuracy for the detection of significant CAD. STE allows for identification of patients with subclinical dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement.
Quantitative myocardial perfusion should be interpreted in the light of sex and comorbidities in patients with suspected chronic coronary syndrome - a cardiac positron emission tomography study
Authors: Szekely A , Steding-Ehrenborg K , Ryd D , Hedeer F , Valind K , Akil S , Hindorf C , Hedstrom E , Erlinge D , Arheden H , Engblom H
Published: November 2023

Background and aim

Diagnosis and treatment of patients with suspected chronic coronary syndrome (CCS) currently relies on the degree of coronary artery stenosis and its significance for myocardial perfusion (1). However, myocardial perfusion can be affected by factors other than coronary stenosis (2-6). The aim of this study was to investigate to what extent sex, age, diabetes, hypertension and smoking affect quantitative myocardial perfusion, beyond the degree of coronary artery stenosis, in patients with suspected CCS.

Methods

Eighty-six patients (median age 69, range 46-86 years, 24 females) planned for elective coronary angiography due to suspected CCS were included. All patients underwent cardiac positron emission tomography (PET) using 13N-NH3 to quantify myocardial perfusion at rest and at adenosine stress. The stenosis degree of the culprit lesion for each main coronary artery was related to the myocardial segment with lowest myocardial perfusion (perfusionmin) at stress and lowest myocardial perfusion reserve (MPRmin) for its corresponding myocardial territory.

Results

Degree of coronary artery stenosis, male sex, increasing age, diabetes and smoking were independently associated with myocardial perfusionmin at stress (Table 1). Degree of coronary artery stenosis, age, diabetes and hypertension were independently associated with MPRmin (Table 1). Male sex was independently associated with a significantly lower myocardial perfusionmin at stress at 0-50% coronary artery stenosis but not for higher degree of stenosis (>50%) or MPRmin (Figure 1).

Conclusion

Sex, increasing age, diabetes, hypertension and smoking affect myocardial perfusion independently of coronary artery stenosis in patients with suspected CCS. Thus, these factors need to be considered when assessing the significance of reduced quantitative myocardial perfusion of patients with suspected CCS.

Fig. 1 Myocardial perfusionmin at stress (A) and lowest myocardial perfusion reserve (B) in males and females with 0-50% and 51-100% stenoses. Solid lines indicate mean perfusion in each group. Dashed lines indicate the lower boundary of the current reference interval for myocardial perfusion at 2.0 ml/min/g. Univariable linear mixed model analyses were performed to compare the groups and obtain the p-values.
In patients with atrial cardiomyopathy long-lasting atrial fibrillation is associated with unfavorable structural changes in right chambers and worse outcome
Authors: Ilieva R , Slavchev B , Georgieva N , Spasova N , Kalaydzhiev P , Somleva D , Kinova E , Goudev A
Published: November 2023

Background

The main factor responsible for atrial cardiomyopathy (ACM) is atrial fibrillation (AF). It is known that AF causes remodeling of the left atrium but its effects on the right heart chambers and mortality are not well studied.

Purpose

To assess the echocardiographic characteristics of patients with atrial cardiomyopathy with long-standing and paroxysmal AF and their impact on survival.

Methods

From 624 consecutive patients with AF only 173 met the inclusion criteria for atrial cardiomyopathy, defined as severely dilated left atrium with indexed left atrial volume (LAVI) >48 ml/m2, preserved left ventricular systolic function, without significant valvular disease or left ventricular hypertrophy. The mean age of the studied population was 73,7 ± 9,5 years, 59% women. The patients were divided into two groups according to the presence of persistent or permanent AF (long-standing AF) - Group 1 (n = 87) or paroxysmal AF - Group 2 (n = 86). All patients underwent a comprehensive echocardiography with volumetric and speckle tracking analysis on enrollment and were followed for cardiovascular outcomes, including mortality 24 months.

Results

The group with long-standing AF had more dilated right atrium (indexed right atrial volume- RAVI 41.9 ± 24.4 vs. 33 ± 13.5 ml/m2; P=0.003), lower reservoir strain of the right atrium (13.1% ± 8.6 vs. 19.7% ± 10.6; P<0.001) and lower right ventricular free wall strain (18.1% ±7.3 vs. 21.2% ± 7.1; P=0.006). Over a median follow up of 18 months (7-29) 16 patients (18%) from Group 1 died compared to 6 patients (7%) from Group 2 (P=0.022). The presence of more than mild tricuspid regurgitation (OR 4.53; CI: 2.37-8.67; P<0.001), heart failure (OR 3.44; 95% CI: 1.83-6.48; P<0.001), and long-standing AF (OR 3.00, 95% CI: 1.41-8.09; P=0.028) were associated with worse mid-term survival.

Conclusion

Patients with ACM and long-standing AF have more advanced structural changes of the right atrium and the right ventricle and worse prognosis. The presence of more than mild tricuspid regurgitation, heart failure, and long-standing AF are predictors of poor outcome.
The relation between fractional flow reserve and vascular dilation ration in predicting myocardial ischemia
Authors: Lin P L , Liu Y M , Lee Y H , Tsai C T , Hsu C
Published: November 2023

Introduction

Fractional flow reserve (FFR) is the gold standard for evaluation of myocardial ischemia but requires invasive pressure wire. Laplace’s Law states that the tension in the wall if a vessel is proportional to the pressure inside the vessel and its radius. The vascular dilation ratio (VDR) is the degree of dilation in the vessel proximal to the stenosis. Our aim was to test VDR using routine angiographic images and its correlation with FFR.

Method

Patients who performed coronary angiography with FFR were enrolled. After the images were reconstructed using ciunterpint and binarization analysis, VDR was calculated using the ratio of the maximal diameter minus the minimal diameter divided by the minimal diameter after contrast injection. Lesion’s characteristics, including adenosine dose and FFR were collected. The lesions were divided into two groups based on their FFR values: FFR≤ 0.8 and FFR >0.8.

Result

A total of 31 patients were enrolled, with a mean age 62.0 ± 13.3 years, and 19 of them were male). Of the 31 de-novo lesions analyzed, 23 were located in the left anterior descending artery, 4 in left circumflex artery, and 4 in right coronary artery. VDR was significantly higher in the group of lesions with FFR≤ 0.8, compared to the group with FFR >0.8 (P<0.01) (Table 1). The negative correlation coefficient between VDR and FFR was -0.92 (Figure 1).

Conclusion

The high negative correlation between VDR and FFR suggests that VDR could be a useful pre-FFR test for evaluating the severity of myocardial ischemia. Further studies with larger sample sized are warranted to confirm these finding.Table 1Figure 1
LDL cholesterol target attainment in a representative German cohort of high- and very-high-CV risk patients with statin intolerance: a simulation study
Authors: Katzmann J , Stuerzebecher P E , Kruppert S , Laufs U
Published: November 2023

Background

The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. Reasons include the inability to tolerate sufficient doses of statins. To reduce cardiovascular risk in these patients, alternative lipid-lowering therapies (LLT) are required.

Purpose

Simulation of LDL-C target attainment and achievable LDL-C reductions with oral LLT including ezetimibe and bempedoic acid in patients with statin intolerance (SI) using electronic health records.

Methods

Data were obtained from the IQVIATM Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high cardiovascular risk based on ESC/EAS guidelines and diagnosed hypercholesterolaemia. Within this cohort, statin-intolerant patients were classified by applying the following literature-informed definitions pointing towards SI with high confidence (among others): patients with LLT only consisting of non-statins, long-term discontinuation of statin therapy, down-titration of statins, and documented side effects in the electronic health records. We used a Monte Carlo approach to simulate sequentially escalating oral LLT, by adding ezetimibe and bempedoic acid in patients with uncontrolled LDL-C in this population.

Results

Of the total study population (n=130,778 patients), 33.9% had high and 66.1% had very-high cardiovascular risk. Within this cohort, 11,286 patients (8.6%) met the criteria of SI. Compared to the total study population, in the SI group, there were higher proportions of patients who exhibited atherosclerotic manifestations and who were classified as "very-high cardiovascular risk" (73.7% vs. 66.1%). Their LDL-C levels were slightly higher (105.6 vs. 103.6 mg/dL). 46.5% received a low-intensity statin monotherapy. Ezetimibe, both as monotherapy or in combination, was more frequently prescribed. 12.3% did not receive any LLT (Table).

Patients classified as statin-intolerant entered into the simulation model. At baseline, 7.7% were at LDL-C target. In patients without ezetimibe, consecutive treatment with ezetimibe and bempedoic acid increased the calculated proportion of patients at goal to 22.6% and 52.0%. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1% vs. 49.9%). The median LDL-C (IQR) after simulation of ezetimibe and bempedoic acid treatment was 62 (48–84) mg/dL (Figure).

Conclusions

Patients meeting the definition of SI based on their electronic health records represented 8.6% of the total cohort of the patients with high or very-high cardiovascular risk. In this population, oral combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.
Impact of ESC Guidelines implementation on lipid lowering strategy in a tertiary hospital cohort of STEMI patients: Can we aspire to do better than the EUROASPIRE V registry?
Authors: Ferrer M , Gonzalez C , Santalo M , Taroncher C , Gual M , Duran A , Barros A J , Bragagnini W , Garcia-Moll X , Lopez L , Rodriguez L , Vila M , Sionis A
Published: November 2023

Background

Treatment with LDL-C-lowering-drug therapy (LLT) is essential in the management of patients who have suffered an acute coronary syndrome. The latest 2019 ESC/EAS Guidelines for the management of dyslipidaemias recommend an LDL-C target of <55mg/dL and 50% reduction in these very high risk patients. However, the impact of these recommendations on contemporary LLT prescription is uncertain.

Purpose

To analyse the impact of the publication of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias on the prescription of LLT in our centre in patients who have suffered a ST elevation myocardial infarct (STEMI) and its impact on the achievement of treatment objectives and major adverse cardiovascular events (MACEs) in the first year of treatment.

Methods

All patients who suffered a STEMI at our centre in 2018 and 2021 were retrospectively registered. We compared baseline characteristics, ESC Guidelines objectives achievement at first follow-up visit and MACE in the first 1 year of treatment in both groups. The 2016 ESC Guidelines objective was defined as an LDL-C <70mg/dL and the 2019 ESC Guidelines objective was defined as an LDL-C <55 mg/dL. MACEs were defined as a combination of mortality, acute coronary syndrome, stroke, peripheral ischemia and need for revascularization. Those patients whose follow-up time until LDL-C after discharge was greater than 1 year were excluded from the final analysis.

Results

Of a total 726 STEMI patients, 520 patients were included in the final analysis. 239 in 2018 and 281 in 2021. No significant differences were found in baseline characteristics. LDL-C at admission was 115.7±39.3 mg/dL in 2018 and 110.6±38.6 mg/dL in 2021 (p 0.11). The prescription of ezetimibe in association with a high potency statin at discharge was significantly higher in 2021 (125 patients; 33.6%) compared to 2018 (17 patients; 5.07%) (p<0.001) and it was independently associated with the presence of prior lipid-lowering treatment (p < 0.011) and higher LDL-C at admission (p < 0.001). In 2018 there were 105 patients (50.24%) with LDL-C <70mg/dL and 52 patients (24.88%) with LDL-C <55mg/dL. This was significantly lower than in 2021, with 178 patients (66.67%) with LDL-C <70mg/dL and 112 patients (41.95%) with LDL-C <55mg/dL (p<0.001). MACEs after 1 year of treatment occurred in 27 patients (8.88%) in 2018 and in 31 patients (9.06%) in 2021 (p 0.935).

Conclusions

The adoption of the 2019 ESC/EAS Dyslipidaemia Guidelines recommendations has fostered a change in the LLT strategy in our centre leading to a greater number of patients reaching the LDL-C goal. Unfortunately, nearly 60% of them still have an LDL-C >55 mg/dL. This should prompt us to seek structured clinical pathways in order to improve our results.Figure 1
Treatment patterns and adherence to lipid-lowering drugs during 8 years of follow-up after a cardiovascular event
Authors: Engebretsen I , Bugge C , Husebye E , Stovring H , Halvorsen S , Sverre E , Munkhaugen J
Published: November 2023

Introduction

In previous research using nationwide prescription data we demonstrated that a considerable proportion of statin users in Norway had treatment gaps or discontinuation in treatment, with 20% of patients having gaps exceeding 180 days. Yet, evidence for treatment practice and long-term adherence to lipid lowering drugs among patients with atherosclerotic cardiovascular disease is limited.

Purpose

To investigate long-term treatment patterns and adherence to lipid lowering drugs following hospitalization for an acute cardiovascular event. Secondary, to investigate the association between patient characteristics and adherence.

Methods

Consecutive patients admitted to two hospitals in Norway with acute myocardial infarction or angina undergoing revascularization from 2011-2014 (N=1094) were included in this study. Data on clinical and psychosocial factors were linked to prescription registry data from 2010 to the date of death or end-of follow-up (2020). We evaluated treatment adherence from time of hospital admission to end of follow-up by estimating proportion of days covered (PDC) and gaps in statin treatment. Risk of gaps in statin treatment of >180 days were evaluated across different patient subgroups. Treatment practice after hospital discharge was assessed by the proportion of patients with atorvastatin 40/80 mg or rosuvastatin 20/40 mg, and the proportion of patients with a subsequent ezetimibe prescription.

Results

Median age was 63 years (SD 9.6) at time of hospital admission. 96% of the patients were discharged with a statin at the index event. During a median of 8 years (SD 2.5) of follow-up, 16% had a gap in their statin treatment exceeding 180 days, and 22% had a PDC < 0.8. LDL-cholesterol target achievement at follow-up was poor and psychosocial distress was prevalent (Table 1). The proportion of patients with gaps ≥180 days was quite similar in all patient subgroups, however somewhat more prevalent among patients who reported statin side-effects (Figure 1). Less than two out of three patients were prescribed high intensity statin therapy during follow-up, while 25% received additional treatment with ezetimibe (Figure 1). Mean number of milligrams redeemed during follow-up was 43 for atorvastatin, 36 for simvastatin and 18 for rosuvastatin.

Conclusion

In this study of patients hospitalized for an atherosclerotic cardiovascular event, long-term follow-up over 8 years showed that a considerable proportion of patients have poor statin adherence, with gaps in treatment exceeding 180 days. Furthermore, many patients are treated with suboptimal statin therapy, and only 1 out of 4 patients were prescribed ezetimibe. There is a considerable potential for improving long-term adherence and optimizing lipid lowering therapy in secondary prevention.Patient characteristics (N=1094)Proportion of patients with gap>180 days
DOACs or warfarin use in morbidly obese patients (BMI > 40 kg/m2) on anticoagulant therapy? : a systematic review and meta-analysis
Authors: Sagris M , Ktenopoulos N , Pamporis K , Theofilis P , Oikonomou E , Tsioufis K , Tousoulis D
Published: November 2023

Introduction

Current guidelines and consensus statements have advised against the use of direct oral anticoagulants (DOACs) for morbidly obese patients (BMI > 40 kg/m2), indicating warfarin as the first-line treatment.

Purpose

Our aim was to systematically review and examine the effectiveness and safety of DOACs compared to warfarin in patients with BMI > 40 kg/m2 and atrial fibrillation (AF) or venous thromboembolism (VTE).

Methods

This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies comparing the effectiveness and safety of DOACs and Warfarin in extremely obese patients. The primary outcome was the incidence of the composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), ii) stroke/systematic embolism (SE) and, iii) VTE. Secondary endpoints referred to major and minor bleeding events.

Results

This meta-analysis comprised 16 studies and 114,999 morbidly obese patients with AF or VTE on oral anticoagulation therapy (48,937 on DOACs vs. 65,080 on Warfarin). The DOAC use was significantly associated with lower all-cause mortality and major bleeding rates compared to the warfarin group [risk ratio= 0.66; 95% confidence interval: 0.53, 0.81; p = 0.03; I2 = 60%, RR: 0.78 (95% CI: 0.6-1.01, p <0.01, I2 = 85%)]. Although the rates of composite endpoint, stroke/SE and VTE were lower in the DOAC group, no statistically significant difference was observed [RR: 0.88 (95% CI: 0.7-1.12, p <0.01, I2 = 86%), RR: 0.92; (95% CI: 0.63-1.35, p <0.01, I2 = 86%), RR: 0.72; (95% CI: 0.46-1.15, p <0.01, I2 = 91%)], indicating no-superiority of Warfarin compared to DOAC use. The rates of minor bleeding events, hemorrhagic stroke and ischemic stroke were lower in the DOAC compared to warfarin groups [RR: 0.78 (95% CI: 0.56-1.10, p <0.01, I2 = 80%), RR: 0.56 (95% CI: 0.26-1.21, p <0.01, I2 = 86%), RR: 0.87; (95% CI: 0.6-1.24, p <0.01, I2 = 81%)]. The same trend favoring DOACs over Warfarin in all the assessed endpoints was observed in the subgroup analysis when results adjusted for the anticoagulation indication (AF or VTE).

Conclusions

Our findings are of paramount importance indicating, firstly, the non-superiority of Warfarin compared to DOAC use, and secondly, a significantly better profile of DOACs in terms of safety and effectiveness in morbidly obese patients with BMI > 40 kg/m2 in all the assessed endpoints. The findings may aid in the endeavor to enhance the upcoming recommendations for the management of this subgroup.
Effect of diabetes duration on subclinical target organ damage in young diabetic adults with type 1 diabetes mellitus
Authors: Kowalczyk E , Wejner - Mik P , Wierzbowska-Drabik K , Wdowiak-Okrojek K , Lipiec P , Szadkowska A , Trzos E , Kurpesa M , Kasprzak J D
Published: November 2023

Objective and aim

Cardiovascular disease is a key cause of premature mortality in type 1 diabetes mellitus (DMt1). According to ESC guidelines, 10-year risk of death from cardiovascular disease in 35-year-old patients with diabetes lasting ≤10 years is estimated as moderate, however studies based on the young adult patients with DMt1 are limited. The aim of this study is to identify the relationship between the duration of DMt1 and occurrence of subclinical cardiovascular target organ damage among adult patients before the age of thirty.

Material and methods

We included patients aged from 18 to 30 years old with childhood- or juvenile-onset diabetes mellitus type 1. In all patients 24-hour blood pressure measurement was performed and a daily pressure profile (dipper or non-dipper) was defined. Non-invasive diagnostics of subclinical cardiovascular damage included:

• 2-dimensional echocardiographic examination with the assessment of global longitudinal strain (GLS),

• ultrasound of the carotid arteries with the assessment of intima media thickness (IMT),

• assessment of the pulse wave velocity (PWV),

• assessment of flow-dependent brachial artery vasodilation (FMD),

• assessment of the ankle-brachial index (ABI).

Results

Obtained from non-invasive examination were compared between two groups depending on duration of DMt1: group 1 ( DMt1 lasting ≤10 years) vs group 2 (DMt1 lasting >10 years).

Results

The study population consist of 56 patients (48% male). Group consist of 25 patients and group 2 consist of 31 patients. Statistical analysis showed that received values of GLS (P=0.04) and PWV (P=0.01) differ significantly between group 1 and group 2. Interestingly the GLS, but not PWV, showed a significant negative linear correlation with the duration of diabetes (r=0.28; P=0.03). A post-hoc analysis showed that among patients with a DMt1 duration of ≤10 years absolute GLS values were significantly lower in patients with non-dipper profile than those with a dipper profile (P=0.04) (Fig. 1). Also a post-hoc analysis demonstrated significant difference in IMT thickness among non-dipping patients according to time of DMt1 duration (P=0.01) (Fig. 1).

Conclusions

Subclinical target organ damage can be detected even in young adults with DMt1 (aged 18-30 years). Patients with DMt1 lasting >10 years had a significantly lower absolute GLS value and GLS value correlate with the duration of diabetes. Patients with DMt1 lasting >10 years had a significantly higher PWV value.Fig 1. Post-hoc analysis of GLS and IMT
The impact of glycated hemoglobin A1c on cardiovascular risk in patients with and without coronary artery disease
Authors: Olesen K K W , Thrane P G , Hansen M K , Gyldenkerne C , Maeng M
Published: November 2023

Background

Diabetes is defined according to the level of glycated hemoglobin (HbA1c) based on the risk of microvascular complications. However, HbA1c has been associated with increased risk of macrovascular complications at lower HbA1c levels than the conventional cut-off for "microvascular" diabetes. In patients without known diabetes, it is unsettled when HbA1c becomes a marker of macrovascular complications in non-diabetes patients with and without coronary artery disease (CAD).

Purpose

We tested the hypothesis that the HbA1c cut-off for macrovascular complications differ for patients with versus without CAD.

Methods

We included every patient undergoing coronary angiography in Western Denmark from 2011-2021 without known diabetes prior to examination. Follow-up was censored if it exceeded 10 years. We examined the risk of atherosclerotic cardiovascular disease (ASCVD, a composite of myocardial infarction and ischemic stroke) and HbA1c using Cox regression. We modeled the relation between ASCVD and HbA1c using restricted cubic splines with 38 mmol/mol as reference. In a separate analysis, we stratified patients by HbA1c levels (<30 mmol/mol, 31-38 mmol/mol (reference), 39-47 mmol/mol, and ≥48 mmol/mol) and CAD.

Results

We included 56,927 patients without known diabetes at the time of angiography, of whom 1,225 (2.2%) had undiagnosed, untreated diabetes, i.e. HbA1c ≥48 mmol/mol. Mean HbA1c was 38 mmol/mol. In patients without CAD we did not observe any association between HbA1c and ASCVD (Figure 1). In contrast, we observed a U-shaped relationship between HbA1c and ASCVD in patients with CAD. The lowest risk of ASCVD was observed at HbA1c 35 mmol/mol, which was followed by a steady incline with higher HbA1c levels. When categorizing HbA1c, the adjusted ASCVD risk was significantly increased in patients with CAD and HbA1c 39-47 mmol/mol (aHR 1.09, 95% CI 1.01-1.19), with HbA1c ≥48 mmol/mol (aHR 1.60, 95% CI 1.32-1.94) having the highest ASCVD risk (Figure 2).

Conclusions

The current study provides two novel findings. Firstly, HbA1c provides no prognostic information concerning risk of ASCVD when CAD is absent. Secondly, a U-shaped relationship between HbA1c and ASCVD was found in patients where CAD is present. The lowest risk of ASCVD was observed at HbA1c 35 mmol/mol and the risk steadily increased with higher (and lower) HbA1c levels. Thus, the risk of ASCVD associated with HbA1c starts much earlier than the conventional 48 mmol/mol HbA1c cut-off for diabetes, but the relationship exists only when CAD is present.Figure 1Figure 2