bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional printer guided new morphological classification of left atrial appendage -rock, paper and scissors-
Authors: Ryuzaki S , Kondo Y , Nakano M , Nakano M , Kajiyama T , Ito R , Kitagawa M , Sugawara M , Chiba T , Yoshino Y , Komai Y , Takanashi Y , Kobayashi Y
Published: November 2023

Background

Cardiogenic embolism by left atrial thrombi is one of the most important atrial fibrillation (AF)-related clinical problems. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). The WATCHMAN device was developed as a permanent implantable device to seal off the LAA to prevent cardiogenic embolism. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in JAPAN. It is known that the LAA diameter of Asians is larger than that of non-Asians. Furthermore, the LAA of the Japanese are more complicated, compared to the Western. Whereas the four classifications from previous reports are widely used in the world, the classification differs with different physicians in the real-world practice.

Purpose

We aimed to identify the relationship between morphological features of LAA and clinical events such as ischemic stroke in Japanese patients.

Methods

The LAAC database of our institution was respectively analyzed. All LAAC cases were performed between February 2020 and February 2022. The three-dimensional printing of LAA was generated from cardiovascular computed tomography imaging data. The shapes of the LAA were classified into 3 morphological types: (1) The LAA with bi lobe was defined as "Scissors" type; (2) The one with complicated erasing branches was "Paper" type; (3) The simple one was "Rock" type. We retrospectively examined the relationship between the risk of ischemic stroke and the morphological features of the LAA.

Results

The cohort consisted of 63 consecutive patients (age, 73±8 years; male gender, 73%; BMI, 24±4 kg/m²; the size of WATCHMAN device, 29±42 mm). Of those, 14 (22%), 21 (33%) and 28 (44%) patients were divided into the Scissors, Paper and Rock types, respectively. All groups were identically matched for comorbidities. Table shows the patient characteristics and the results of univariate and multivariate analysis. There were 35 (56%) patients who had a history of ischemic stroke (4 vs. 9 vs. 22; Rock vs. Scissors vs. Paper types, p-value=0.01). In the multivariate analysis, the Paper type is the potential risk factor of ischemic stroke (p-value<0.01, respectively).

Conclusions

The morphological features of LAA by three-dimensional printing may be related to cardioembolic stroke. Patients with Paper type LAA were significantly more likely to have had a history of ischemic stroke. These results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic and bleeding events and, moreover, LAAC could be the best option for these patients.Table 1Table 2
Myocardial fibrosis activity following ST-segment elevation myocardial infarction
Authors: Barton A K , Tzolos E , Waight C , Loganath K , Joshi S , Singh T , Williams M C , Van Beek E J R , Brian D , Fletcher A , Clark T , Slomka P , Dey D , Newby D E
Published: November 2023

Background

Myocardial fibrosis following myocardial infarction (MI) is a key healing mechanism and involves widespread fibroblast activation. Once activated, fibroblasts express fibroblast activation protein (FAP) (1). Hybrid positron emission tomography (PET) imaging of radiolabelled fibroblast activation protein inhibitor (FAPI) fused with cardiovascular magnetic resonance (68Ga-FAPI PET/MR) is an emerging method for assessing myocardial fibrosis activity that may provide additional insights into the recovery of the heart following MI.

Methods

Forty patients with acute (<4 weeks), 19 with recent (12 weeks), and 19 with prior established ST-segment elevation MI (>12 months), and 20 healthy volunteer participants underwent 68Ga-FAPI PET/MR. Participants were imaged 30 min after administration of 100-200 MBq 68Ga-FAPI-04. Image analysis was performed using FusionQuant (Cedars Sinai, Los Angeles, California). 68Ga-FAPI uptake was quantified by maximum standardised uptake value (SUVmax) and tissue-to-background ratio (TBRmax) correcting for blood-pool activity in the left ventricle. Comparisons between were assessed with one-way ANOVA with Tukey-Kramer post-hoc testing where significant differences were detected. A 2-sided p-value of <0.05 denoted statistical significance.

Results

Participants were predominantly middle-aged men with similar sized infarcts (peak plasma cardiac troponin concentrations and post-MI left ventricular ejection fraction) (Table). Blood pool tracer activity was also similar between groups. Focal myocardial 68Ga-FAPI uptake localised to areas of the infarct and peri-infarct zones on magnetic resonance late gadolinium enhancement imaging (Figure). Both myocardial SUVmax and TBRmax varied between infarcts of different ages, being highest in acute (TBRmax 4.1±1.2) and lowest in those with prior established MI (2.1±0.7, Table and Figure).

Conclusions

Fibrosis activity is greatest in the immediate aftermath of acute MI with a step-wise reduction in the weeks and years that follow. Fibrosis activity continues for many months and years after acute infarction.FigureTable
Increased Lipoprotein (a) and familial hypercholesterolemia: a dangerous combination.Data from a 12-year follow-up study
Authors: Andrikou I , Grigoriou K , Dima I , Skoumas I , Tsioufis K , Vlachopoulos C
Published: November 2023

Background

Lipoprotein (a)[Lp(a)] is a molecule characterized by very increased atherogenicity. Mounting evidence support the causal link between high Lp(a) concentration and atherosclerotic cardiovascular (CV) disease in the general population.

Purpose

The role of Lp (a) in specific categories of patients at high CV risk, such as patients with familial hypercholesterolaemia (FH), is also of special importance. The aim of our study was to investigate the prognostic role of Lp (a) regarding major adverse CV outcomes in subjects with heterozygous FH.

Methods

155 patients from the outpatient lipid clinic of our hospital (56 males,mean age 41.2±14.2 years, 26% smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FH criteria participated in the study. Participants were evaluated for a mean follow-up period of 12.4±7.1 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke).

Results

The incidence of the composite endpoint of major CV events during the follow-up period was 9% (n=14). In the total population, the mean baseline Lp (a) levels were 34.9±33.7 mg/dl, while 42% had increased Lp (a) levels ≥30mg/dl. The group of FH patients with new-onset CV disease had higher levels of Lp(a) at baseline compared to those without new-onset CV disease (48.1±37.3 vs 33.6±33.1 mg/dl, p=0.01). Also, those with new-onset CV disease had higher percentage of increased Lp(a) levels (≥30mg/dl) at baseline compared to those without development of CV disease (71% vs 39%, p=0.02).Multiple Cox regression analysis revealed that during the follow-up period independent predictors of major adverse CV events were:increased baseline Lp(a) levels(≥30mg/dl)(HR 5.61, 95% CI 1.51-10.92, p=0.01), male sex (HR 8.11, 95% CI 2.02-12.48, p<0.01), baseline low-density cholesterol levels (HR 1.01, 95% CI 1.00-1.02, p=0.04) and the presence of hypertension at baseline (HR 3.59, 95% CI 1.03-12.49, p=0.04), after adjustment for confounding factors.

Conclusions

In patients with FH, increased baseline Lp(a) is an independent predictor of adverse CV events, after a 12-year follow-up period. FH patients with Lp (a)levels ≥30mg/dl have an almost 5-fold greater CV risk compared to those with lower Lp (a) levels. It seems that Lp (a) reclassifies the already increased CV risk of FH subjects into an even higher level.
The Cycle study: a prospective study on cholesterol levels during the menstrual cycle
Authors: Mulder J , Balsrud P , Schreuder M , Van Vark-Van Der Zee L C , Mulder M T , Bogsrud M P , Narverud I , Retterstol K , Langslet G , Boersma E , Holven K B , Roeters Van Lennep J E
Published: November 2023

Background

Previous studies showed fluctuating lipid levels during the menstrual cycle in healthy women with normal cholesterol (nChol). Cycle-related variations in lipid levels in women with familial hypercholesterolemia (FH) have not been studied, while these might have important consequences for lipid management.

Purpose

To investigate menstrual cycle-related fluctuations in lipid levels in women with FH compared to those with nChol.

Methods

In the Netherlands and Norway, 20 women with clinical/genetic FH and 63 healthy women with nChol were included - details are presented in the figures. Participants had to have a regular cycle between 21-35 days, while pregnant women, and those using hormone-based contraceptives without hormone free interval (HFI) were excluded. Lipid levels were measured in the follicular (visit 1), ovulation (visit 2), and luteal (visit 3) phases. In women using oral contraceptives (OC) measurements were taken during day 12-14 of the pill period (visit 1) and during day 5-7 of the HFI (visit 2).

Results

Mean (sd) age of the included subjects was 33 (9) years, BMI 23.9 (4) kg/m2, and cycle duration 28 (2) days. These characteristics were similar in FH and nChol. Women with nChol showed slight, although statistically significant, cycle-related variations in cholesterol levels (mean maximum variation total Chol 0.53, LDL-Chol 0.39 and HDL-Chol 0.22 mmol/L; figure 1). FH women who did not receive statin therapy for various reasons showed largest mean variations (total Chol 0.80, LDL-Chol 0.59 and HDL-Chol 0.23 mmol/L), with the highest lipid levels during the ovulation phase.

The women with OC had an increase in total- and LDL-cholesterol (groups combined: mean difference 0.55 and 0.51 mmol/L, respectively) between the two visits (n=9) (figure 2).

Conclusions

In women with untreated FH and normal cholesterol with a regular menstrual cycle, total- and HDL-cholesterol were highest at ovulation. These menstrual fluctuations were absent in women with FH who used statins. Women with OC showed an increase in total- and LDL-cholesterol from the contraceptive pill period to the HFI. Even though in most women the absolute variation in lipid levels during the menstrual cycle and OC are modest, the moment of measurement can be of clinical value in particular in women with untreated high lipid levels. In these women, it is recommended to measure lipid levels at a fixed time of the menstrual cycle.Figure 1Figure 2
Unrealized opportunities for cardiovascular risk reduction with optimized statin and ezetimibe in veterans with coronary artery disease
Authors: Kovach C , Mesenbring E , Gupta P , Glorioso T , Ho M , Waldo S , Schwartz G
Published: November 2023

Background

Many patients with coronary artery disease (CAD) do not achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals (1,2).

Purpose

To quantify unrealized opportunities to improve clinical outcomes of Veterans with CAD through optimized oral lipid-lowering therapy (LLT) with statins and ezetimibe within the United States Veterans Affairs healthcare system.

Methods

Veterans with CAD by coronary angiography between 2015 and 2020 were identified, the observed LLT and LDL-C were described, and the observed rates of death, myocardial infarction, stroke, and coronary revascularization were determined. Potential reductions in these events with optimized statin alone or with ezetimibe were modelled based on expected further LDL-C reductions (3).

Results

The analysis cohort comprised 111,954 Veterans (59.7% statin-treated at baseline angiography) observed for median 3.4 (IQR 2.1-4.0) years. At 6 months, statin prescription increased to 68.7%, but high-intensity statin regimens were prescribed in only 52.9%, ezetimibe use was low (1.1%), and LDL-C remained ≥70 mg/dL in 52.1% of patients. At 4 years, observed incidences (95% CI) of death, myocardial infarction, stroke, and coronary revascularization were 21.6% (21.3-21.8), 5.0% (4.9-5.2), 2.2% (2.1-2.3), and 15.4% (15.2-15.7), respectively (Figure 1). With optimized statin, projected absolute reductions in these incidences were 1.3% (0.9-1.7), 0.8% (0.7-1.0), 0.2% (0.1-0.3), and 2.3% (2.0-2.7). With optimized statin and ezetimibe, projected absolute reductions were 1.8% (1.2-2.4), 1.1% (0.9-1.3), 0.3% (0.2-0.4) and 3.1% (2.6-3.6).

Conclusions

Suboptimal LLT was prevalent among Veterans with CAD. Meaningful improvements in their cardiovascular outcomes could be achieved with optimized statin alone. Despite lesser lipid-lowering efficacy of ezetimibe, its widespread use on a population level could contribute substantially to cardiovascular risk reduction from intensified oral LLT.Figure 1Figure 2
Statins under-treatment and mortality in patients with atrial fibrillation. Insights from the nationwide START registry
Authors: Menichelli D , Antonucci E , Pignatelli P , Violi F , Palareti G , Pastori D
Published: November 2023

Background

Statins are mainstream drugs for cardiovascular (CV) prevention, but under-prescription is an important clinical challenge. Data on the use of single statins as the rate of under-prescription in atrial fibrillation (AF) are lacking. To evaluate the association of statin underuse with mortality risk in a large AF cohort.

Methods

5,477 patients from the nationwide START registry were included. The prevalence of different statins was reported and the association with all-cause and CV mortality investigated. Mortality risk of patients with an indication to but not taking statins was also analysed.

Results

Mean age was 80.2 years, 46.4% were women. Among 2,899 patients with a clinical indication to statin, only 1,578 (54.4%) were on treatment. In a mean follow-up of 22.5±17.1 months, 491 (4.7%/year) deaths occurred (106 CV deaths, 1.0%/year). Atorvastatin and Simvastatin inversely associated with all-cause (HR 0.692, 95%CI 0.519-0.923, p=0.012 and HR 0.598, 95%CI 0.428-0.836, p=0.003, respectively). and CV death (HR 0.372, 95%CI 0.178-0.776, p=0.008 and HR 0.306, 95%CI 0.123-0.758, p=0.010, respectively).

The 1,321 untreated patients were older, more frequently women and with a higher prevalence of diabetes, previous cerebrovascular disease, peripheral artery disease compared to those on treatment. Statin undertreatment was associated with higher risk of all-cause (HR 1.565, 95%CI 1.235-1.983, p<0.001) and CV death (HR 2.057, 95%CI 1.188-3.561, p=0.010).

Conclusions

AF patients with an indication to statins but left untreated disclose a high risk of all-cause and CV mortality. Implementation of statin prescription in the AF population can help reducing the residual CV risk.
Body fat distribution, fat-free mass and cardiovascular function in the UK Biobank
Authors: Oguntade A S , Lacey B , Taylor H , Lewington S
Published: November 2023

Background

Excess adiposity and high body mass index have been associated with cardiac dysfunction and heart failure. However, the role of whole body imaging and independent associations of regional fat and fat-free mass on left ventricular and vascular function is unclear.

Purpose

This study determined the cross-sectional associations of regional fat depots and fat-free mass on left ventricular function and arterial stiffness to explain obesity-related cardiac dysfunction.

Methods

Participants who underwent whole body magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA) in an ongoing imaging study of 100,000 individuals in the UK were included in this analysis. Analyses exclude individuals with major cardiac and vascular diseases at initial baseline assessment. Regional fat distribution was quantified using MRI while body fat-free mass was quantified with DXA. Cardiac MRI was used to measure left ventricular (LV) ejection fraction and LV mass while pulse wave velocity from finger photo-plethysmography was used to measure arterial stiffness index. Associations of body fat distribution (visceral fat, abdominal subcutaneous fat, other body fat) and fat-free mass with each of LV ejection fraction, LV mass and arterial stiffness index, after mutual adjustment for one another and potential confounders were determined using multivariable linear regression.

Results

We included 31,088 individuals (mean age 63.4 years, 53% women). Among regional body fat measures, higher visceral fat was associated with lower LVEF (β=-0.43; 95% CI: -0.55, -0.31 per SD) and higher arterial stiffness index (β=0.44; 95% CI: 0.34, 0.54 per SD) while none of the regional fat and fat-free mass showed significant association with LV function or arterial stiffness. None of the fat or fat-free mass measures showed significant association with LV mass. These associations were not explained by inflammatory markers, blood pressure or glycaemic profile.

Conclusion

Visceral fat is the main driver of obesity-related cardiac and vascular dysfunction. There is need for further studies to understand the biological causal pathways of obesity-heart disease.Figure 1Figure 2
The prognostic value of high-sensitivity cardiac troponin t in diabetes patients without coronary artery disease
Authors: Deng J , Guo Q , Tu J B , He Y B , Lu X Z , Li Q , Deng J Y , Zhang Z M , Zhang J L , Wu J L , Zhou Z Y , Liu J , Chen S Q , Chen J Y , Liu Y
Published: November 2023

Background

High-Sensitivity Cardiac Troponin T (hs-cTnT) is associated with poor prognosis in patients with Diabetes mellitus (DM). However, whether it remains a valuable index for risk stratification in DM patients without coronary artery disease (CAD) is not yet determined.

Objective

To assess the association between hs-cTnT and follow-up mortality among patients with DM but without CAD in different renal function status.

Methods

2,774 patients with DM but without CAD were enrolled from the Cardiorenal Improvement II (CIN-II) Study and were divided into three groups according to tertiles of hs-cTnT levels (low, intermediate and high). The associations between hs-cTnT and all-cause mortality and Cardiovascular mortality was detected by Cox regression and Fine-Gray models, respectively. Subgroup analysis was performed in patients with different renal function status.

Results

During a median follow-up of 3.96 (interquartile range: 2.45 to 5.79) years, 246 (8.9%) patients died and 134 (4.8%) died from cardiovascular disease (mean age: 62.6±9.5 years; 50.4% female) among 2,774 patients. Compared to the low tertile of hs-cTnT, the high tertile of hs-cTnT increased 2.19-fold risk of all-cause mortality in DM patients without CAD (HR: 3.19, 95% CI: 2.15-4.71; P < 0.001) and increased 4.89-fold risk of cardiovascular mortality (HR: 5.89, 95% CI: 3.08-11.28; P < 0.001). Consistent results were only found in patients with eGFR >60 mL/min/1.73 m2 while the association between HS-TnI and mortality was insignificant in patients with eGFR≤60 mL/min/1.73 m2.

Conclusions

The present study demonstrates that for patients with eGFR >60 mL/min/1.73 m2, the high level of hs-cTnT is still associated with an increased risk of follow-up mortality in patients with diabetes, even without CAD.Foreset plots
Physiological and haemodynamic differences between peak exercise blood pressure and blood pressure-power output slope in healthy women
Authors: Foulkes S , Janssens K , Howden E J , Haykowsky M J , Wallace I , Climie R , La Gerche A
Published: November 2023

Background

A hypertensive response to exercise (HRE) is considered indicative of increased arterial stiffness (1). However, HRE is common in individuals with high cardiorespiratory fitness (CRF) (2), which we hypothesize is due to increased stroke volume (SV) and cardiac output (Qc).

Purpose

This study compared differences in CRF and peak-exercise SV (SVpeak) and Qc (Qcpeak) according to absolute and workload-indexed definitions of exercise hypertension in women.

Methods

Women free of overt CVD (n=142; 52±8years, BMI: 26.3±4.5kg/m2) underwent exercise cardiac magnetic resonance to quantify SVpeak and Qcpeak, and cardiopulmonary exercise testing to quantify peak VO2, power output (PO) and systolic blood pressure (SBP) responses. SBP-PO slope was determined using linear regression of SBP and PO values obtained every 2-minutes throughout exercise. HRE was defined as peak SBP ≥190mmHg (3), and elevated SBP-PO slope was defined as a slope >90th percentile for sex and age based on previously published values (4).

Results

51% and 23% of the cohort met criteria for HRE and elevated SBP-PO slope, respectively, with 16% meeting both criteria. HRE was associated with higher VO2peak (2.03±0.53 vs 1.83±0.44 L/min, P=0.015), peak PO (191±66 vs 167±51 Watts, P=0.014), SVpeak (109±27 vs 98±19 mLs, P=0.008), and Qcpeak (15.1±3.3 vs 13.9±2.8 L/min, P=0.023). In contrast, elevated SBP-PO slope was associated with lower VO2peak (1.57±0.36 vs 2.04±0.48 L/min), peak PO (135±34 vs 192±60Watts) SVpeak (88±13 vs 108±24 mLs) and Qcpeak (12.5±1.8 vs 15.1±3.1 L/min; P<0.001 for all). Overall, the group with HRE and elevated SBP-PO slope had the lowest physical capacity, VO2peak and haemodynamic response to exercise (Figure 1A-D), whilst the opposite trend was seen for those with a HRE and a normal SBP-PO slope. All results remained significant (P<0.05) after adjustment for age, BMI, resting SBP and menopausal status (pre vs peri/post-menopausal).

Conclusion

Contextualising exercise SBP responses against measures of PO better accounts for confounding from increased Qcpeak, and may improve identification of women with increased arterial stiffness.Figure 1A-D
Long-term functional cardiac changes in takotsubo syndrome
Authors: Schweiger V , Schoenberger M , Di Vece D , Wuerdinger M , Gilhofer T , Rajman K , Ghadri J R , Cammann V L , Templin C , Niederseer D
Published: November 2023

Background

Takotsubo syndrome has long been thought to be a benign condition once the acute event has been overcome. However, an increasing number of studies suggest that there might be long-term consequences. The aim of the present study was to evaluate long term functional cardiac changes in patients after Takotsubo Syndrome.

Methods

In the present study, a total of 131 TTS patients were prospectively included and age and gender matched with 131 ACS patients. Out of this cohort, a total of 66 patients (TTS: N=33, ACS: N=33) without any known respiratory diseases (e.g. Asthma or COPD) had a follow-up examination one to six months after the index event, including cardiopulmonary exercise testing (CPET) and echocardiography. CPET indices were compared between TTS and ACS patients in those who achieved an RER of at least 1.05.

Results

Mean age of patients was 65.4 in the TTS group and 65.0 in the ACS group (p=0.541). In each group, 118 (90%) patients were female. At follow-up, TTS patients had a significantly higher LVEF (%, TTS: 59 [56 to 63] vs ACS: 56.5 [51 to 60], p<0.001) and significantly lower levels of BNP (ULN, TTS: 0.5 [0.2 to 0.9] vs ACS: 1.0 [0.5 to 2.6], p<0001), compared to TTS patients. TTS patients were significantly more frequently suffering from persistent symptoms compared to ACS patients (TTS: 78 [60%] vs. ACS: 60 [45.8%], p=0.035, figure 1). Twenty-four TTS Patients (72%) had an RER over 1.05 and were age and gender matched with 24 ACS patients. VO2max was comparable between the two groups (TTS: 20.2 [±5.4] vs ACS: 18.9 [±7.6], p=0.47) as well as Peak Mets (TTS: 5.7 (±1.6) vs ACS: 5.5 (±1.9), p=0.68). However, there was a trend towards a lower oxygen pulse in TTS compared to ACS patients (TTS: 9.4 [±2.2] vs ACS: 10.9 [±3.1], p=0.055) and a significant higher oxygen cost of work (ΔV’O2/ΔW, TTS: 12.9 [11.3 to 15.5] vs ACS: 10.9 [9.7 to 12.2], p=0.019).

Conclusion

TTS patients were more frequently suffering from persistent symptoms compared to ACS patients. Moreover, TTS patients demonstrated long-term functional cardiac changes reflected in impaired CPET parameters comparable to or worse than those of ACS patients. These findings highlight the long-term consequences of TTS and further challenge the concept that TTS is a benign disease.
Effectiveness of hybrid comprehensive telerehabilitation in heart failure patients with permanent atrial fibrillation - subanalysis of the TELEREH-HF RCT
Authors: Piotrowicz E , Kowalik I , Opolski G , Banach M , Zareba W , Orzechowski P , Pluta S , Szalewska D , Glowczynska R , Mierzynska A , Kalarus Z , Irzmanski R , Piotrowicz R
Published: November 2023

Background

Atrial fibrillation (AF) negatively impacts physical fitness and quality of life (QoL). Little is known about efficacy of hybrid comprehensive telerehabilitation (HCTR) in heart failure (HF) patients with AF.

Purpose

The purpose of this study was to assess safety and effectiveness of HCTR in HF patients with permanent AF.

Methods

The present analysis formed part of TELEREH-HF multicenter, randomized trial that enrolled 850 HF patients (NYHA I-III, LVEF ≤ 40%). Patients were randomized 1:1 to HCTR plus usual care (UC) or UC alone. Patients underwent either an HCTR (1 week in hospital and 8 weeks at home, five times weekly) or UC with observation.

The effectiveness of HCTR was assessed by changes in peak oxygen consumption (VO2 peak), workload duration (t) in cardiopulmonary exercise test and quality of life (QoL) based on Medical Outcome Survey Short Form 36 Questionnaire (SF-36). Measurements were made before and after intervention/observation.

Results

There were 73 patients with permanent AF in HCTR group and 72 patients with permanent AF in UC group. HCTR resulted in a significant improvement in VO2peak and workload duration. We did not observe these favorable results in the UC group. In the HCTR group, there was a significantly greater improvement in physical component of QoL than in the UC group. All results are presented in Table 1. In neither group were there deaths nor major adverse events.

Conclusion

In HF patients with permanent AF, hybrid comprehensive telerehabilitation is safe and resulted in a significant improvement in physical capacity and physical component of QoL.
Submaximal in addition to peak stress echocardiogram differentiates pathological LV dilatation from physiological dilatation and could help facilitate early heart failure diagnosis
Authors: Marwaha S , Fanton Z , Bulleros P , Simmons R , Bhatia R , Chatrath N , Fyyaz S , Tome M , Finocchiaro G , Ghati S , Prasad S , Papadakis M , Sharma S
Published: November 2023

Background

Left ventricular dimensions in athletes overlap with those observed in patients with dilated cardiomyopathy (DCM). Among athletes with concomitant baseline low left ventricular ejection fraction (LVEF), the differentiation between the two entities may be difficult.

Purpose

We compared the role of changes in left ventricular ejection fraction (LVEF) during submaximal and maximal stress exercise echocardiography to facilitate the differentiation between athlete’s heart and DCM individuals with asymptomatic exercising individuals with a dilated left ventricle (LV) and borderline/low LVEF (48-54%).

Methods

47 highly active asymptomatic individuals with DCM and mildly impaired LVEF, 52 athletes with borderline/low LVEF (grey zone athletes) and 44 athletes with a normal EF (healthy athletes) underwent a stress echocardiography on a semi-recumbent bike with an incremental ramp protocol of 25watt/min.Echocardiographic images were obtained at rest, submaximal (80% of predicted heart rate) and maximal exercise. Maximal exercise was classified as a heart rate 90-100% of the calculated maximum heart rate for their age.

Results

Both grey zone and healthy athletes achieved a greater increase in peak LVEF compared with DCM individuals (20.4% and 20.2% vs 4.6% respectively). The mean increase in LVEF from submaximal exercise to maximal exercise in healthy athletes and grey zone athletes was 7.0% and 3.4% (p<0.001) respectively whereas individuals with DCM showed a mean reduction in LVEF of -4.3% during this period. 8 (17%) of DCM individuals were able to increase LVEF ≥10% from rest to peak exercise, however most (96%) revealed a drop in LVEF as effort progressed from submaximal to maximal exercise.97.7% of control athletes were able to augment an EF ≥10% from rest to maximum exercise and continued to show an increase in LVEF from submaximal to maximal exercise. Whereas 47 (90.4%) grey zone athletes also showed an increase in LVEF >10% from rest to peak exercise, the remaining 5 (9.6%) were unable to augment this response and revealed a drop in contractile reserve from submaximal to maximal exercise, suggesting the possibility of an underlying diagnosis of DCM.

Conclusion

Healthy athletes and grey zone athletes show a greater contractile reserve compared to DCM athletes during exercise.Over 90% athletes and 10% DCM patients reveal an increase in LVEF >10% from baseline to peak exercise.Comparison of changes in LVEF between submaximal and maximal exercise reveals that 96% DCM patients and 9.6% grey zone athletes show a drop in in LVEF during this period. Failure to augment LVEF between submaximal and maximal exercise may identify grey zone athletes with DCM.
Increased risk of decompensated heart failure, acute coronary syndrome, arrythmias and ischemic stroke following exacerbation of COPD: results from a multi-database cohort study
Authors: Hawkins N M , Vogelmeier C F , Simons S O , Garbe E , Manito N , Swart K , Ekwaru P , Kossack N , Hernandez I , Mullerova H , Randhawa A , Van Burk L , Sanchez-Covisa J , Rhodes K , Nordon C
Published: November 2023

Introduction

The risk of acute coronary syndrome (ACS), stroke or death is increased following an exacerbation of chronic obstructive pulmonary disease (COPD). However, little is known about the risk of decompensated heart failure (HF) or acute arrhythmias.

Purpose

To quantify the risk of decompensated HF, ACS, acute arrhythmias and ischemic stroke following an exacerbation of COPD.

Methods

Individuals living with COPD were identified in electronic healthcare and claims databases between 2014 and 2018 in Canada (n=142,787), Germany (n=126,795), the Netherlands (NL, n=8,020) and Spain (n=24,393) and followed until a first non-fatal severe CV event of interest (defined as a hospitalisation for ACS, decompensated HF, arrythmias and ischemic stroke), death or censoring. For each non-fatal severe CV event, a multivariable time-dependent Cox model compared the risk of outcome in the 12 months following the onset of a COPD exacerbation (exposed period, split into granular sub-periods of time) with the risk of outcome during periods outside an exacerbation (unexposed period), providing adjusted hazard ratios (HR) and 95% confidence intervals.

Results

Mean age ranged between 65-68 years old and more than 50% of patients were male, in all countries (Table 1). Cardiovascular risk factors and diseases were common, with 47% to 91% of patients prescribed cardiovascular medications. During follow-up a non-fatal severe CV event occurred in 11% of patients in Canada, 23% in Germany, 8% in NL and 24% in Spain. Decompensated HF was the most frequent event of interest and accounted for 35% to 47% of non-fatal CV events, except in Canada where ACS accounted for 37% of events. In the first 7 days following an exacerbation, the HR ranged between 2.59 (95% CI, 2.32 - 2.89) and 72.34 (64.43 - 81.22) for decompensated HF; 5.59 (5.09 - 6.15) and 24.57 (21.70 - 27.83) for ACS; 9.16 (8.36 - 10.03) and 31.18 (26.84 - 36.21) for arrythmia (mainly driven by atrial fibrillation); and between 2.22 (1.88 - 2.63) and 16.12 (13.39 - 19.41) for ischemic stroke (Table 2). The risks remained elevated for 6 months for decompensated HF and 30 days for ACS in all countries except NL.

Conclusion

The risk of all severe CV events, including decompensated HF and arrhythmias, was increased following an exacerbation of COPD. Despite heterogeneity of findings across countries, our results indicate that an exacerbation of COPD should be considered as an important risk factor for cardiopulmonary events, emphasizing the need for optimized COPD management across specialties.
Age at menopause and the risk of stroke: observational and mendelian randomisation analysis in 204,244 postmenopausal women
Authors: Tschiderer L , Peters S A E , Van Der Schouw Y T , Van Westing A C , Seekircher L , Willeit P , Onland-Moret N C
Published: November 2023

Background

Observational studies have shown that women with an early menopause are at higher risk of stroke compared to women with a later menopause. However, associations with stroke subtypes are inconsistent and the causality is unclear.

Purpose

We conducted a large-scale analysis to investigate the observational association between age at menopause and different types of stroke accompanied by a Mendelian Randomisation analysis to evaluate causality.

Methods

We analysed data of the UK Biobank and EPIC-CVD study. Postmenopausal women without a history of stroke at baseline were eligible for inclusion. The study endpoints were total stroke and stroke subtypes (i.e., ischaemic stroke, haemorrhagic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage). We investigated the observational association between age at menopause and risk of stroke using Cox-regression analysis in each study separately before combining effect sizes using random-effects meta-analysis. Cox-regression analyses were progressively adjusted for (1) age, (2) smoking status, body mass index, glycated haemoglobin, total cholesterol, and hypertension, and (3) ever use of hormone replacement therapy and age at menarche. We used two-sample Mendelian Randomisation analysis to study whether there is a causal relationship between genetically proxied age at menopause and risk of stroke.

Results

A total of 204,244 women were included (7,883 from EPIC-CVD [5,292 from the sub-cohort]; 196,361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD 5.8) and pooled mean age at menopause was 47.8 years (SD 6.2). Natural menopause occurred in 77.6% of all women. Over a median follow-up of 12.6 years (IQR 11.8, 13.3), 6,770 women experienced a stroke. In multivariable adjusted observational analyses, the pooled hazard ratios per five years younger age at menopause were 1.09 (95% CI: 1.07, 1.12) for stroke, 1.09 (1.06, 1.13) for ischaemic stroke, 1.10 (1.04, 1.16) for haemorrhagic stroke, 1.14 (1.08, 1.20) for intracerebral haemorrhage, and 1.00 (0.84, 1.20) for subarachnoid haemorrhage. The Mendelian Randomization analysis found no evidence for a causal relationship between genetically proxied age at menopause and risk of any type of stroke.

Conclusion

Earlier age at menopause is associated with, but no causally related to the risk of stroke.
Menopausal vasomotor symptoms and subclinical atherosclerotic cardiovascular disease
Authors: Nilsson S , Qvick A , Henriksson M , Sederholm Lawesson S , Spetz Holm A C , Leander K
Published: November 2023

Background

Menopausal vasomotor symptoms (VMS) have been associated with subclinical and manifest atherosclerotic cardiovascular disease (ASCVD) but the scientific basis is limited and VMS have not been studied in relation to image-detected coronary atherosclerosis.

PURPOSE

To assess, in peri- and postmenopausal women, associations between VMS and subclinical ASCVD detected through computed tomography angiography (CCTA), coronary artery calcium score (CACS) or carotid ultrasound, and if potentially determined associations are modified by menopausal hormone therapy (MHT) or regular physical activity (PA).

Methods

This cross-sectional population-based study was conducted on a subset of participants from the Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-65 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive questionnaire, which included questions about current and previous menopause-related symptoms. VMS was assessed on a 4-point scale and analyzed in relation to subclinical ASCVD, detected via CCTA, CACS and carotid ultrasound using multivariate logistic regression analyses.

Results

Of 2995 women included, 14.2% reported severe VMS (n= 425), 18.1% moderate VMS (n=543), and 67.7% no or mild VMS (n=2027). Women with severe, but not those with moderate, VMS had higher prevalence of CCTA detected atherosclerosis (34.1% vs 27.8%, p<0.05), but not CACS >100 (5.8% vs 6.6% p >0.05) or any carotid plaque (47.6% vs 46.6%, p>0.05) than women with no or mild VMS. Using the same reference category, severe but not moderate VMS was significantly associated with CCTA-detected atherosclerosis, odds ratio (OR) before and after multivariable adjustment 1.36, 95% confidence interval (CI) 1.08 – 1.72 and 1.33, 95% CI 1.02 – 1.72, respectively. This association became stronger when requiring an over 5-year duration of severe VMS, multivariable adjusted OR 1.53, 95% CI 1.09 – 2.14. Additional adjustment for MHT strengthened the association (OR 1.64, 95% CI 1.16 – 2.32). No significant association with CACS >100 or with the presence of any carotid plaque was observed. Additional adjustment for PA did not change any associations.

Conclusions

Severe but not moderate VMS were significantly associated with CCTA detected atherosclerosis, independent of a broad range of cardiovascular risk factors. Further research is required to determine the eventual causality of this relationship.Figure 1.Forest plots
Sex differences and survival after TAVI for severe aortic stenosis
Authors: Santos Ferreira D A , Diaz S , Guerreiro C , Silva G , Silva M , Brandao M , Nunes F , Teixeira R , Pereira E , Pires-Morais G , Melica B , Santos L , Rodrigues A , Braga P , Fontes-Carvalho R
Published: November 2023

Background

There is still controversy about survival rates and clinical response of women versus men who undergo transcatheter aortic valve implantation (TAVI) for the treatment of severe aortic stenosis (SAS).

Purpose

Assess mortality and heart failure (HF) symptoms following TAVI for SAS, according to sex.

Methods

A retrospective analysis of a single-center database including all TAVI performed in 2011-2019 was performed. Clinical, echocardiographic, and blood-analysis data were determined, and all-cause mortality over the five years after the procedure was compared based on sex. A reduction of at least one New York Heart Association (NYHA) class after TAVI was the secondary endpoint.

Results

Of the 488 cases analyzed, 252 (51.6%) were women. They were older (84 vs. 80 years-old, p<0.001), had a lower body surface area, and had a higher estimated surgical risk, as determined by EuroSCORE II (4.5 vs. 3.8, p=0.011) and STS-mortality (4.46 vs. 3.44, p<0.001). However, they had a lower prevalence of diabetes mellitus, coronary artery disease, and peripheral artery disease, a lower estimated creatinine clearance, and a lower frequency of previous pacemaker implantation. Women had more frequently a phenotype of high gradient severe aortic stenosis, with lower functional aortic valve areas. While there was no difference in TAVI design, smaller valves were implanted in women. Median follow-up was 46 months and there was a 40% mortality rate over the five years after treatment, with no statistically significant differences according to sex in both univariate and multivariate analysis, after adjusting for estimated surgical risk. EuroSCORE II had a statistically significant association with the primary endpoint (hazard ratio 1.03 (1.01-1.05), p=0.004). Despite having a similar NYHA class before TAVI, women experienced a lower frequency of functional class improvement (61% vs. 72%, p=0.034).

Conclusions

Although women had a higher estimated surgical risk, no differences were found regarding survival after TAVI for SAS. However, improvement in HF symptoms was less frequent in this subset.Table 1Figure 1
Maternal hypertensive disorders of pregnancy and electrocardiographic findings in newborns
Authors: Noerskov E H , Paerregaard M M , Raja A A , Sillesen A S , Christiansen A H , Boyd H A , Bundgaard H , Iversen K K , Voegg R O B
Published: November 2023

Background

Hypertensive disorders of pregnancy (HDP) - preeclampsia in particular - are important causes of pregnancy complications and death for both the mother and her offspring. Preeclampsia is also associated with both congenital heart defects (CHDs) in the offspring and subtle changes in left ventricular structure and function in the offspring. However, whether preeclampsia also affects the newborn’s cardiac conduction system is unknown.

Purpose

To assess whether newborns born after pregnancies complicated by HDP exhibit changes in their electrocardiogram (ECG) compared with newborns born after pregnancies without HDP.

Methods

This population-based cohort study included newborns, who had ECG data obtained within 30 days of birth. Information on maternal preeclampsia (ICD-10 codes DO14-14.2 and DO15-15.9) and maternal gestational hypertension (ICD-10 codes DO13-13.9) was retrieved from an obstetric database. ECG parameters of interest included heart rate, PR interval, QRS axis, QRS duration, uncorrected and corrected QT intervals, maximum R- and S-wave amplitudes in V1 and V6, respectively. ECG parameters of exposed and non-exposed newborns were compared using summary statistics and linear regression, adjusting for sex, gestational age at delivery and length, weight and age at examination. Sensitivity analyses were conducted with adjustments for maternal smoking, parity, age, and multiple pregnancies and the analyses were repeated after excluding neonates and mothers with CHD, newborns exposed to pre-gestational diabetes and children born preterm (<37 weeks’ gestation).

Results

Our study cohort included 11,826 newborns; 441 were exposed to maternal preeclampsia and 320 were exposed to maternal gestational hypertension (table). Newborns born to mothers with preeclampsia had significantly prolonged QRS duration compared to neonates born after pregnancies without HDP (adjusted mean difference of 0.6 ms, 95% CI [0.04 – 1.16], p=0.04). The maximum amplitude of the R-wave in the V1-recording was significantly lower in newborns born to mothers with preeclampsia by 5% (linear scale: 0.95, 95% CI [0.9 – 0.996], p=0.03). These associations persisted after adjustment for additional covariates and restrictions on the study population. Gestational hypertension was not associated with significant differences in any of the investigated ECG parameters.

Conclusion

The cardiac conduction was affected in children born to mothers with preeclampsia compared with newborns born after pregnancies without HDP, including prolonged QRS duration and lower amplitude of the R-wave in V1 in the ECG. These findings could be an indicator of thickening of the left ventricular myocardium in newborns of mothers with preeclampsia. The potential clinical implications of these changes – short or long-term – are unknown and require further investigation.Table
The effect of tafamidis treatment on cardiovascular aging in patients with Transthyretin cardiomyopathy. An observational study
Authors: Bampatsias D , Georgiopoulos G , Delialis D , Angelidakis L , Theodorakakou F , Petropoulos I , Tselegkidi M E , Zervas G , Dimoula A , Patras R , Kyriazopoulou A , Trougakos I , Briasoulis A , Kastritis E , Stamatelopoulos K
Published: November 2023

Background

Sporadic cardiac transthyretin amyloidosis (wtATTR) is a degenerative age-related disease with dismal prognosis and continuously increasing incidence. ATTR may have adverse effects also on vascular function and accelerate vascular aging. Tafamidis, a new agent that stabilizes the TTR tetramer improves wtATTR prognosis; however, whether tafamidis exerts any effect on vascular aging processes is unknown.

Purpose

To evaluate the effect of tafamidis treatment on markers of vascular aging.

Methods

This is an observational, non-interventional longitudinal study. wtATTR patients receiving tafamidis were evaluated prospectively at baseline, 3 months, 6 months and 1 year for non-invasive markers of vascular aging including arterial stiffness by pulse wave velocity (PWV, primary outcome measure), and markers derived from pulse wave analysis and compared to non-amyloidosis elderly controls (N=30, age>70 years) who were re-assessed for vascular function 1 year after their baseline visit.

Results

Twenty-one patients with wtATTR and were receiving tafamidis completed all 4 visits. Linear mixed model analysis revealed that PWV progressively decreased compared to baseline, during follow-up visits in patients receiving tafamidis [baseline vs a) 3 months: -0.95 mean difference (95%CI -1.73, -0.159) p-value=0.0121, b) 6 months: -1.36 mean difference (95%CI -2.19, -0.54) p-value=0.0002, c) 1 year: -1.08 mean difference (95%CI -2.03, -0.12) p-value=0.002]. The non-amyloidosis elderly control group presented a significant increase in PWV after 1 year compared to baseline (13.63 m/s vs 11.99 m/s, p =0.001 respectively, Wilcoxon rank test), while PWV was significantly lower in wtATTR group after 1 year compared to the control group despite younger mean age of the latter (p for interaction=0.0089). Central systolic blood pressure was decreased after 6 months of treatment, while it returned to baseline levels after 1 year [mixed model analysis, baseline vs 6 months -5.95 mean difference (95%CI -10.31, -1.60) p-value=0.007, baseline vs 1 year -0.47 mean difference (95%CI -5.42, 4.49) p-value=0.854]. A similar trend was observed for central diastolic blood pressure, although not achieving statistical significance (mixed model analysis, baseline vs 6 months -2.66 mean difference (95%CI -5.72, 0.40) p-value=0.088, baseline vs 1 year 0.005 mean difference (95%CI -3.47, 3.48) p-value=0.998].

Conclusion

The results of this prospective study suggest that tafamidis may delay vascular aging in addition to cardiac aging in patients with wtATTR.
Anti-diabetic medication adherence and cardiovascular outcomes in patients with cancer: a nationwide population-based cohort study
Authors: Jung M , Jung M , Kim J , Lee S , Kim K , Kang D , Kyoung D , Chung W , Jung H , Youn H , Kim H , Youn J
Published: November 2023

Background

Diabetes is an important cause of morbidity, which predisposes patients to major cardiovascular (CV) events and mortality. However, clinical implications of anti-diabetic medication adherence for cancer patients have not been well studied in the real clinical practice.

Purpose

This study aimed to evaluate the association between anti-diabetic medication adherence and clinical outcomes in adult patients with cancer.

Methods

Using the prospective nationwide cohort (Korean NHIS-NSC), we extracted adult cancer patients treated with anti-diabetic medications. Based on the medication possession ratio (MPR) value, participants were divided into 3 groups: good (MPR ≥0.8), moderate (0.5 ≤ MPR < 0.8), and poor (MPR<0.5) adherence groups. The primary outcomes were overall and CV mortality. The secondary outcome was CV events requiring hospitalization due to major CV diseases.

Results

Among 8,052 cancer patients with concomitant diabetes, 59.4% were nonadherence group (21.5% were moderate and 37.9% were poor adherence group). Over a median of 8.4 years of follow-up, 1,475 deaths and 2,931 CV events occurred. Compared to the good adherence group, the moderate and poor adherence groups had a 1.61-fold and 2.00-fold increased risk for overall mortality; and 1.66-fold and 1.98-fold elevated risk for CV mortality, respectively, after adjustment for possible confounders. Furthermore, moderate and poor adherence groups had a 1.29-fold and 1.38-fold elevated risk for new-onset CV events. These trends were consistent across CV event subtypes.

Conclusions

Nonadherence to anti-diabetic medication is common in cancer patients and is associated with worse clinical outcomes in adult cancer patients with diabetes. More attention should be paid to improve adherence to anti-diabetic medication among patients with cancer.