bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral microvascular function is linked to cardiac involvement on CMR in systemic sclerosis-related pulmonary arterial hypertension patients
Authors: Vos J L , Lemmers J M J , El Messaoudi S , Snoeren M , Van Dijk A P J , Duijnhouwer A L , Van Leuven S I , Post M C , Vonk M C , Nijveldt R
Published: October 2022

Background

Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation and fibrosis, and carries one of the worst prognosis in patients who also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, SSc-PAH patients demonstrate disproportionately high morbidity and mortality, presumably due to cardiac involvement.

Purpose

To determine the pathophysiology of cardiac involvement in SSc, cardiovascular magnetic resonance (CMR) measures of perfusion, inflammation and fibrosis were compared between SSc-PAH and idiopathic PAH (IPAH) patients. In addition, the correlation between myocardial involvement on CMR and known markers of peripheral microvascular function was assessed.

Methods

Consecutive patients with SSc-PAH and IPAH of similar age and gender, consecutively underwent CMR imaging, and nailfold capillaroscopy (NC) with post-occlusive reactivity hyperaemia-test (PORH-test). CMR imaging included T2 mapping (inflammation), pre- and postcontrast T1 mapping to calculate the extracellular volume fraction (ECV, fibrosis), and adenosine-stress perfusion imaging to measure the relative myocardial upslope (microvascular perfusion), all measurements were performed on the left ventricle. These CMR markers were related to peripheral microvascular function by NC and PORH-test.

Results

Twenty SSc-PAH patients (71 [62–77] years, 14% male) and 5 IPAH patients (69 [47–77] years, 20% male) were included. SSc-PAH patients had higher ECV and T2 values than IPAH patients. NC showed lower average capillary density and reduced recruitment of capillaries after PORH in SSc-PAH patients, corresponding to impaired microvascular structure and function. Both higher ECV and T2 values correlated with lower average capillary density (r=−0.454 and −0.583, respectively, p<0.05 for both). Additionally, higher T2 values and lower relative myocardial upslope correlated with worse peripheral microvascular function measured by PORH-test (r=−0.471 and r=0.421, respectively, p<0.05 for both).

Conclusion

SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared to IPAH patients. These markers correlated well with worse peripheral microvascular function, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may have important therapeutic implications, for which future studies are warranted evaluating the role of anti-inflammatory/anti-fibrotic therapy.

Funding Acknowledgement

Type of funding sources: None.
Differences in coronary flow reserve and flow-mediated dilation between plaque psoriasis and psoriatic arthritis
Authors: Ikonomidis I , Pavlidis G , Katogiannis K , Kapniari I , Theodoropoulos K , Kountouri A , Kostelli G , Tsilivarakis D , Thymis J , Katsimbri P , Parissis J , Filippatos G , Lambadiari V , Papadavid E
Published: October 2022

Background/Introduction

Psoriatic disease is associated with increased cardiovascular risk through mechanisms of inflammation and oxidative stress.

Purpose

We aimed to investigate endothelial glycocalyx, coronary microcirculatory function and flow-mediated dilation in patients with plaque psoriasis and psoriatic arthritis.

Methods

In 311 patients (mean age: 52±12 years) with psoriatic disease (185 with plaque psoriasis and 126 with psoriatic arthritis) and 150 controls with similar age, sex and atherosclerotic risk factors, we assessed: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates impaired glycocalyx integrity. (2) Coronary flow reserve (CFR) in the distal left anterior descending coronary artery, (3) Flow-mediated dilation (FMD) of the brachial artery, and (4) LV global longitudinal strain (GLS) using speckle-tracking echocardiography.

Results

Compared with controls, patients with psoriatic disease had higher PBR (2.14±0.29 versus 1.78±0.25μm, p<0.001) and lower CFR (2.86±0.93 versus 3.39±0.68, p<0.001), FMD (6.97±3.9 versus 9.1±2.1, p<0.001) and GLS (−17.4±3.8 versus −21.9±1.5%, p<0.001). There was not significant difference between the two study groups (plaque psoriasis and psoriatic arthritis) in PBR (2.14±0.28 versus 2.14±0.31μm, p=0.990) and GLS (−17.2±3.9 versus −17.6±3.8%, p=0.297). Patients with psoriatic arthritis had more impaired CFR (2.75±0.85 versus 2.96±0.99, p=0.045) and FMD (5.45±3.2 versus 7.76±4, p=0.003) compared to patients with plaque psoriasis.

Conclusions

Patients with psoriatic disease have impaired endothelial, vascular and myocardial function compared with controls. Coronary microcirculatory function and flow-mediated dilation are more affected in psoriatic arthritis compared with plaque psoriasis.

Funding Acknowledgement

Type of funding sources: None.
Impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation four months after COVID-19 infection are partially improved at twelve months
Authors: Ikonomidis I , Kountouri A , Mitrakou A , Katogiannis K , Thymis J , Korakas E , Pavlidis G , Andreadou I , Chania C , Bamias A , Thomas K , Antoniadou A , Lambadiari V , Filippatos G
Published: October 2022

Introduction

COVID-19 patients present impaired subclinical markers of cardiovascular and endothelial function. Subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk.

Purpose

We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function at four and twelve months after the infection

Methods

We recruited 70 patients who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four and twelve months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. At four and twelve months we measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) malondialdehyde (MDA), an oxidative stress marker.

Results

At four months, COVID-19 patients displayed higher values of PBR5–25 compared to control group (p<0.001) which increased at twelve months (p<0.001). FMD, PWV and cSBP values were similar between 4 and 12 months (p>0.05 for all the comparisons) and higher than those in controls (p<0.001, p=0.057, p=0.003 respectively). At four months, COVID-19 patients presented impaired CFR and LVGLS values which were improved at twelve months (p=0.002, p=0.069 respectively), though remained impaired compared to controls (p=0.003 for all the comparisons). At four months, COVID-19 patients had impaired RVGLS values which were significantly improved at twelve months (p=0.001,) and showed no statistically significant difference compared to controls (p>0.05). COVID-19 patients at four months display higher myocardial wasted work and decreased myocardial efficiency compared to controls (p=0.01, p=0.006 respectively). There was a modest improvement in GWW and GWE at twelve months,(p=0.043, p=0.001, respectively); however, these markers remained impaired compared to controls (p>0.05). At four months, MDA was higher in COVID-19 patients compared to control group and significantly decreased at twelve months (p<0.001); however, these values remain higher than in controls (p=0.002) (Table 1).

Conclusions

SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at twelve months after the infection.

Funding Acknowledgement

Type of funding sources: None.
A nationwide analysis of cardiac sarcoidosis and related in-hospital outcomes
Authors: Victor V , Thakkar S , Patel H , Deshmukh A , Desimone C , Feitell S C , Blankstein R
Published: October 2022

Introduction

Sarcoidosis is a multisystem disorder characterized by an autoimmune response to an unidentified antigen in genetically susceptible persons. Despite clinically detectable cardiac manifestations of sarcoidosis occurring in approximately 5% of patients, recent studies have revealed cardiac involvement to be at 25% in patients with the disease, highlighting the fact that cardiac involvement in sarcoidosis is much more common than was once thought to be.

Purpose

With cardiac involvement in sarcoidosis being increasingly recognized due to the availability of advanced cardiac imaging, large scale data regarding in-hospital mortality and clinical outcomes of patients admitted with cardiac sarcoidosis (CS) is lacking. Our study aimed to fill this knowledge gap by analyzing demographics and in-hospital outcomes of a large cohort of patients admitted with CS across the United States (US).

Methods

We analyzed data from the national inpatient sample (NIS) database between October 2015 to December 2018 to identify patients who had been admitted with primary and secondary diagnoses of CS. The NIS is an administrative database sponsored by the Agency for Healthcare Research and Quality consisting of data from 46 participating states, representing more than 95% of the US population and providing nationwide estimates of over 35 million hospitalizations annually. The NIS uses de-identified hospital discharges as samples and hence no additional ethical committee approval was required. International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) code D86.85 was used to identify hospitalizations with CS in patients aged 18 years or older. SAS 9.4 (SAS Institute, Inc, Cary, NC) was used for statistical analyses.

Results

A total of 4275 patients were included in the analysis. A higher proportion of patients with CS were females (62.43% vs. 37.57%). Hypertension was the most common comorbidity (43.99%), followed by hyperlipidemia (39.21%) and chronic kidney disease (26.95%). All-cause in-hospital mortality was 2.57%. Atrial fibrillation (AF) was the most common arrhythmia (28.12%), followed by ventricular tachycardia (VT) (22.52%). About 16% of CS patients underwent implantable cardioverter-defibrillator (ICD) implantation during hospital stay. About 42% of patients had concurrent heart failure, out of whom 33.84% had heart failure with reduced ejection fraction (HFrEF). Mean length of hospital stay was 5 days (3–8 days), and the mean cost of hospitalization was $14,177 ($7,121–35,993).

Conclusion

Given the low prevalence of CS, most of the available studies have been retrospective in nature, based on small sample sizes. Despite being retrospective and cross-sectional, our study has the advantage of being based on a nationally representative sample population, providing key formation on the demographics and in-hospital outcomes of patients with CS.

Funding Acknowledgement

Type of funding sources: None.
Everolimus-eluting bioresorabable scaffold system in the treatment of cardiac allograft vasculopathy: the cardiac allograft reparative therapy (CART) prospective multicentre pilot study
Authors: Pighi M , Tomai F , Fezzi S , Pesarini G , Petrolini A , Spedicato L , Tarantini G , Ferlini M , Calabro P , Loi B , Tovar Forero N , Daemen J , Ribichini F T
Published: October 2022

Background

Cardiac allograft vasculopathy (CAV) is still the main drawback of heart transplantation (HTx) and percutaneous coronary intervention (PCI) is a palliative measure because of the high incidence of PCI failure. The bioresorbable scaffolds (BRS) could represent a potential novel therapeutic tool for the treatment of coronary obstructions in CAV.

Purpose

To investigates the effects of BRS implantation in CAV patients in a Nationwide prospective study.

Methods

Multicentre, single-arm, prospective, open-label study that included patients affected by advanced CAV treated with PCI and second-generation ABSORB BRS. The primary endpoint was the incidence of 12-month angiographic in-segment scaffold restenosis (ISSR). Secondary endpoints were the composite of cardiac death, myocardial infarction, and target lesion revascularisation at 12-and 36-month follow-up and the incidence of ISSR at 36 months. A paired analysis of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) at baseline and follow-up was also performed.

Results

Between 2015–2017 35 HTx patients were enrolled and treated on 44 coronary lesions with 51 BRS. The primary endpoint occurred in 13.5% of the lesions (5/37), with a cumulative ISSR rate up to 3 years of 16.2% (6/37).Angiographic lumen loss was 0.40±0.62mm at 12 months and 0.53±0.57mm at 36 months. Overall survival was 91.4% and 74.3%, and MACEs 14.2% and 31.4% at 12 and 36 months, respectively. At the paired intracoronary imaging analysis a significant increase of the vessel external elastic membrane area in the treated segment of the BRS was described at the OCT, while some progression of CAV was detected proximally at the IVUS assessment.

Conclusions

BRS in CAV was feasible and safe, with an ISSR incidence similar to drug-eluting stents. For the first time, a positive remodeling was observed in HTx patients after PCI. Vessel enlargement and the lack of metallic stents may allow repeated PCI avoiding the vessel shrinkage caused by the addition of multiple metal layers, being CAV a complex clinical scenario with a high incidence of MACEs, mainly driven by PCI failure.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Partial funding by Abbott Vascular Italy
Impact of cannabis use in patients with implantable cardiac defibrillators admitted with acute heart failure: a national perspective
Authors: Mathew D , Hasin F , Bumrah K , Kosuru B , Singh V , Bedi P
Published: October 2022

Background

Cannabis is the most popular recreational drug in the United States but knowledge about its health implications remain limited. Cannabis use has been linked to acute myocardial infarction and congestive heart failure. The effect of cannabis use in acute decompensated heart failure in patients with Implantable Cardiac Defibrillators (ICDs) is not known.

Objective

In this study, we sought to explore the impact of cannabis use in patients with Implantable Cardiac Defibrillators (ICDs) admitted with acute decompensated heart failure.

Methods

We queried the 2019 National Inpatient Sample (NIS) database for all patients aged ≥18 with ICD devices admitted with acute heart failure. Patients were stratified into two groups based on Cannabis use. We excluded patients with opioid, amphetamine, psychostimulants, cocaine, sedative, and hallucinogen abuse disorders to eliminate the effect of polysubstance use.

Results

Of the 174,295 hospitalization events for acute decompensated heart failure with ICDs, 1824 were noted to have diagnosis of cannabis use (CU). Patients with CU were younger (mean age 52.4y vs 68.5y) and mostly male (81.1% vs 18.9%). CU group had lower prevalence rates for anemia, atrial fibrillation, coronary artery disease, diabetes, cirrhosis, chronic kidney disease and hypothyroidism. They had higher rates of alcoholism, tobacco use and depression. The primary outcome studied was inpatient mortality. Secondary outcomes include cardiac arrest, myocardial infarction, cardiogenic shock, ventricular tachycardia, ventricular fibrillation, stroke, respiratory failure, pleural effusion, acute kidney injury, length of stay (LoS) and hospital charges. Patients in CU group were noted to have decreased length of stay (reduction in adjusted mean LoS: 2.14 days, P=0.000), mortality (adjusted OR: 0.14, P=0.006) and respiratory failure (adjusted OR: 0.53, P=0.009).

Conclusion

Among patients with implantable cardiac defibrillator admitted for acute decompensated heart failure, cannabis users were younger and mostly male. These patients were noted to have decreased length of stay, inpatient mortality, and respiratory failure.

Funding Acknowledgement

Type of funding sources: None.
Sex-specific disparities in predictive factors of smoking cessation among smokers at high cardiovascular risk. Findings from a nationwide smoking cessation services cohort
Authors: Allagbe I , Zeller M , Chague F , Thomas D , Limosin F , Le Faou A L
Published: October 2022

Background

Tobacco use is a major risk factor for cardiovascular diseases (CVD), but smoking cessation (SC) reduces or even cancels the risk of CVD for both sex. Using data from the French national “Consultations de Dépendance Tabagique” (CDTnet) cohort, we aimed to determine the predictive factors of SC in men and women smokers at high cardiovascular (CV) risk (i.e. with a CV disease or risk factor).

Material and methods

Retrospective study from the French SC services CDT-net database. Inclusion criteria were age ≥18 years, and ≥1 CV risk factor (BMI ≥25 kg/m2, hypercholesterolemia, diabetes, arterial hypertension) or CVD (history of stroke, myocardial infarction or angina pectoris, peripheral arterial disease (PAD)). Smoking abstinence (≥28 consecutive days) was self-reported and confirmed by exhaled carbon monoxide <10 ppm. Logistic regression assessed the association between SC and sociodemographic factors, medical characteristics and patients' smoking profile.

Results

Among the 246,364 subjects in the database, 15% (36,864) fulfilled the inclusion criteria. One month-abstinence was lower in women (52.6% (n=8,102) vs 55% (n=11,848) in men, p<0.001). For both sex, smokers with the lowest abstinence rates were those with respiratory diseases (47% among women vs. 50% among men respectively), depression history (48% vs. 48%), anxiety or depression symptoms (49% vs 50%) use of anxiolytics/antidepressants, use of opioid substitution treatment, use of cannabis (42% vs 41%) and benefit less than 3 follow-up visits (36% vs 41%). Factors positively associated with SC in both sex were age >65 years, having a degree, being employed, coming by self-initiation or by one's relatives, being overweight, having previous quit attempts, presenting with low nicotine dependence and being confident in achieving abstinence. Factors negatively associated with abstinence only in women but not in men was alcohol disorder. Finally, factors negatively associated with abstinence only in men but not in women were PAD, and tobacco-related cancers.

Conclusion

Our results from a large nationwide database suggest the relevance of differentiated management according to sex in smokers at high CV risk, given the major sex-specific disparities in factors associated with abstinence rates.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): This work was supported by IReSP and INCa through a call for doctoral grants launched in 2019.
Prevalence of illicit drug use in young sudden cardiac death patients; an Australian prospective cohort study
Authors: Trytell A , Paratz E D , Van Heusden A , Zentner D , Morgan N , Smith K , Thompson T , James P , Connell V , Pflaumer A , Semsarian C , Ingles J , Stub D , Parsons S , La Gerche A
Published: October 2022

Background

Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young sudden cardiac death (SCD) patients are uncertain.

Purpose

To identify rates of illicit drug use in young SCD patients in Australia.

Methods

A prospective multi-centre registry identified out of hospital cardiac arrest (OHCA) patients aged 1–50 years between April 2019 and April 2020. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included stimulants such as amphetamine-type substances and cocaine, or non-stimulants such as heroin, cannabis and novel psychoactive substances (cathinones and synthetic cannabinoids).

Results

770 OHCAs occurred, with 555 patients undergoing forensic assessment. 287 patients had confirmed cardiac cause of OHCA, with 274 undergoing toxicological assessment and 79 (28.8%) having positive toxicology for illicit drugs (n=60) or reported regular drug use (n=19). An additional 121 patients experienced non-cardiac SCD due to illicit drug toxicity, resulting in a total of 200 patients (36.0% of OHCAs) with illicit drug use. Patients with SCD and illicit drug use were more commonly male (86.1% vs 72.3%, p=0.015), regular smokers (36.7% vs 21.5%, p=0.009), had cardiomegaly (76.5% vs 57.5%, p=0.007), and higher rates of coronary disease and cardiomyopathy (coronary disease 44.3% vs 33.3%, cardiomyopathy 30.4% vs 18.5%, p=0.003). Methamphetamines (n=42, 53.1%) were the most common illicit drug identified and polysubstance abuse occurred frequently (n=15, 19.0%).

Conclusion

Approximately one-third of young SCD patients use illicit drugs, with high rates of polysubstance abuse. Illicit drug use in SCD patients is associated with coronary disease and cardiomyopathy.

Funding Acknowledgement

Type of funding sources: None.
Drucebo effect in statin therapy: more attributable to the patient, the doctor, or the mass media?
Authors: Cosmi D , D'Orazio S , Mariottoni B , Tarquini B , Cosmi F
Published: October 2022

In recent years, the term “drucebo effect” (drug + nocebo) has been coined to mean the nocebo effect attributable more to the patient's expectations, the doctor's preferences and the interference of the mass media rather than the actual pharmacological effect [1,2]. We evaluated this effect over the last 10 years in 9,605 outpatients treated with statins, in primary (27%) and secondary (73%) prevention. Statin intolerance was reported in 1,729 patients (18%) with discontinuation of therapy for 5 days to 4 weeks. The table shows the causes of the presumed intolerance. In patients with muscular symptoms we calculated the related SMIS (Statin Myalgia Index Score) [3].

Patients with myalgia with or without CPK elevation and probable or possible SMIS were advised to halve the statin dose and reassess after 2–4 weeks. With persisting symptoms, the statin was changed. If symptoms persisted also with the second statin, the patient was advised to take the drug every other day. In case of unlikely SMIS, the decision to resume statin therapy was shared with the patients, with an accurate counseling, informing them of the important benefits of statins regarding mortality and morbidity.

Probable true statin intolerance was found in 576 patients (6% of the overall statin therapy population: 332 with myalgia with or without CPK elevation and SMIS probable, 152 with myalgia and CPK elevation with SMIS possible, 46 with asymptomatic elevation of CPK, 15 transaminases increase, 21 with general malaise, 10 with severe depression). In 12% of patients, on the other hand, the interruption is attributable to a nocebo effect due both to the patient and both to the treating physician or other specialist, inclined to attribute the unwanted symptoms more to the drug than to other factors or to consider it non-modifiable by changing statin or doses. The Influence of the mass media is significant, too, and it is difficult to distinguish a greater responsibility of one or the other.

Conclusions

in patients treated with statins a drucebo effect is attributable in part to the patient, in part to the doctor and to the mass media, which tend to attribute the symptoms (especially of muscle origin) to the treatment and to interrupt the therapy without take into account the clear benefits regarding reduction of mortality and morbidity [4]. In our study, a probable true intolerance to statins is found in about one third of patients who report symptoms of a presumed intolerance.

Funding Acknowledgement

Type of funding sources: None.
Low-density lipoprotein cholesterol target attainment among statin-naive Chinese atherosclerotic vascular disease patients
Authors: Sun H , Lai A , Yan B
Published: October 2022

Background

Low-density lipoprotein cholesterol (LDL-C) of patients with atherosclerotic vascular disease (ASCVD) is expected to be lowered by ≥50% and <1.4 mmol/L. Despite the use of lipid-lowering therapies, most of Chinese patients failed to meet the treatment target.

Purpose

We aimed to evaluate the potential of different statin intensities on LDL-C target attainment among statin-naïve Chinese ASCVD patients.

Methods

We retrospectively analyzed statin-naïve ASCVD patients who were initiated with statin therapy between January and July 2020 from 43 public hospitals or clinics in Hong Kong. Patients were divided into high-intensity (HI-S, atorvastatin 40–80 mg, rosuvastatin 20–40 mg), moderate-intensity (MI-S, atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg) and low-intensity (LI-S, simvastatin 10 mg) statin groups. With baseline and follow-up LDL-C, percentage reduction was calculated and the distance to LDL-C target was investigated within groups.

Results

Of 7,241 patients (mean age 61.8±12.4 years and 64.2% male), 4,451 (61.5%) had coronary artery disease, 109 (1.5%) peripheral artery disease, and 2,879 (39.8%) cerebrovascular disease. HI-S, MI-S and LI-S were prescribed in 20% (n=1,450), 61.1% (n=4,421) and 18.9% (n=1,370) patients, respectively. Mean baseline LDL-C was 2.9±1.0 mmol/L and mean follow-up value was 1.9±0.8 mmol/L with median LDL-C reduction of 46.1%, 40.4%, and 32.0% by HI-S, MI-S, and LI-S, respectively. 42.1%, 31.8%, and 14.7% of patients on HI-S, MI-S, and LI-S achieved ≥50% LDL-C reduction and only 23.5%, 18.2%, and 8.8% reached both ≥50% LDL-C reduction and <1.4 mmol/L. One in ten patients require further ≥50% LDL-C reduction to reach <1.4 mmol/L.

Conclusion

In statin-naïve Chinese ASCVD patients, most patients did not reach guidelines recommended LDL-C target even with high-intensity statin. Early statin up-titration or addition of non-statin lipid-lowering therapy may be required in majority of patients.

Funding Acknowledgement

Type of funding sources: None.
PCSK-9-inhibitor therapy improves endothelial function in high-risk patients with cardiovascular disease
Authors: Kannenkeril D , Bosch A , Kolwelter J , Striepe K , Pietschner R , Ott C , Schiffer M , Achenbach S , Schmieder R E
Published: October 2022

Background

Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyse the effect of evolocumab on endothelial function in patients with cardiovascular disease and on obligatory statin therapy.

Methods

This was a prospective, double-blinded, randomized, controlled, single center study including patients with cardiovascular disease (diagnosis of coronary artery disease, non-hemorrhagic stroke, transient ischemic attack or symptomatic peripheral artery disease) and treated with statins, similar to the inclusion criteria of the FOURIER study. Patients were consecutively randomized (1:1) to either evolocumab treatment (420mg was administrated in monthly intervals, twice during the study) or placebo. All patients underwent examination of endothelial function at baseline, and after 1, 4 and 8 weeks of treatment by a semi-automatic high-resolution ultrasound system (UNEX EF 18G; Unex Co., Nagoya, Japan). Endothelial function parameter such as flow-mediated vasodilation (FMD; vasodilator responsiveness), low flow-mediated vasocontriction (L-FMC; vasoconstrictor responsiveness) and vasoactive range (VAR; total vasomotor responsiveness) were measured.

Results

103 patients with a mean age of 66.2 (±7.7) years and a mean LDL-cholesterol of 98.2 (±19.1) mg/dl completed the study. 83.5% of the study population was known to have coronary artery disease. Endothelial function parameter (VAR) increased after 8 weeks of treatment with evolocumab compared to baseline (p=0.034), whereas there was no significant change at 1 and 4 weeks after treatment. Moreover, an improvement in VAR from baseline at week 8 was found with evolocumab compared to placebo (p=0.045).

In a subgroup analysis, in patients with age ≤67 years, lower systolic blood pressure (≤125 mmHg) or higher baseline LDL-cholesterol (>95 mg/dl), significant evolocumab treatment effect was found in VAR improvement (p=0.006, p=0.049 and p=0.042, respectively) from baseline at week 8. No serious adverse event related to study medication occurred during the study.

Conclusion

Our data indicate that endothelial function could be improved with evolocumab treatment in high-risk patients with preexisting cardiovascular disease and on statin therapy. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AMGEN GmbH
Regional strain score as prognostic marker of cardiovascular events. from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Pezel T , Bluemke D , Wu C , Lima J , Ambale Venkatesh B
Published: October 2022

Background

Left ventricular (LV) circumferential strain (Ecc) is an accurate indicator of regional myocardial function, particularly using the regional Ecc or layer-specific strain.

Purpose

To investigate the prognostic value of a regional strain score (RSS) for predicting the incident of heart failure (HF) and coronary heart disease (CHD) in a population without a history of cardiovascular disease at baseline.

Methods

In Multi-Ethnic Study of Atherosclerosis (MESA), 1,506 study participants (63.3±9.4 years, 54.6% men) underwent tagged magnetic resonance imaging for left ventricular circumferential strain (Ecc) analysis. Using −17% and −10% as Ecc cut-offs, each segment was rated from 0–2 points according to the Ecc value of each layer. The endo-Ecc, mid-Ecc, and epi-Ecc values from the 16-segment model were used to calculate three RSS: Endo-, Mid-, and Epi-RSS, respectively, which were defined as a percentage of good LV regional function. The Intramyocardial-RSS was the sum of these three RSS. Cox proportional models were used to evaluate the association between RSS and cardiovascular outcomes.

Results

After a median [IQR] follow-up of 15.9 [12.9–16.6] years, 122 hard CHD and 91 HF were observed. After adjustment, Mid-, Epi-, and Intramyocardial-RSS values <50% were independently associated with HF (HR 1.43; 95% CI [1.08–2.87], p=0.004; HR 1.80; 95% CI [1.12–3.07], p<0.001; and HR 2.01; 95% CI [1.19–3.20], p<0.001). After adjustment, Endo-, Mid-, Epi-, and Intramyocardial-RSS <50% were also independently associated with hard CHD (HR 1.31; 95% CI [1.03–1.51], p=0.04; HR 1.79; 95% CI [1.26–2.57], p<0.001; HR 2.03; 95% CI [1.45–3.40], p<0.001; and HR 2.28; 95% CI [1.51–3.53], p<0.001).

Conclusion

Layer-specific regional Ecc, assessed by RSS, provides a robust, independent predictive value for incident HF and hard CHD in asymptomatic participants without any cardiovascular disease at baseline.

Funding Acknowledgement

Type of funding sources: None.
Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus
Authors: Ikonomidis I , Kountouri A , Pavlidis G , Katogiannis K , Thymis J , Pliouta L , Korakas E , Balampanis K , Bamias A , Lambadiari V
Published: October 2022

Background/Introduction

Patients with type 1 diabetes mellitus (T1DM) present signs of vascular and endothelial dysfunction earlier compared to healthy individuals. According to clinical studies, SGLT-2i favorably affect cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the data regarding the efficacy of SGLT-2i on cardiovascular markers in patients with T1DM are scarce.

Purpose

We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM.

Methods

We recruited in total 30 patients with T1DM and pour glycemic control who were under medication with insulin and received dapagliflozin (n=15) or intensification of insulin treatment (n=15) (control group). We measured at baseline and at four months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography.

Results

At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p>0.05). After four months treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−41%, p<0.05), in PWV (−10%, p<0.05), in cSBP (−6%, p<0.05) and in GLS (+5%, P<0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +3%, PWV: +2%, cSBP: −2%, GLS: −3% at 4 months, P>0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after four months treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P<0.05).

Conclusions

Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

Funding Acknowledgement

Type of funding sources: None.
Unmasking systolic impairment in HFpEF by cardiovascular magnetic resonance derived hemodynamic force assessment: insights from the HFpEF stress trial
Authors: Backhaus S J , Uzun H , Roesel S F , Schulz A , Lange T , Evertz R , Kutty S , Hasenfus G , Schuster A
Published: October 2022

Background

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Exercise-stress testing is recommended in case of uncertainty; however, this approach is time-consuming and costly. Since preserved EF does not represent normal systolic function, we evaluated cardiovascular magnetic resonance (CMR) comprehensive cardiac hemodynamic forces (HDF) analyses for an in-depth characterisation of cardiac function at rest.

Methods

The HFpEF Stress Trial (DZHK-17) prospectively recruited 75 patients with exertional dyspnea, preserved EF (≥50%) and signs of diastolic dysfunction (E/e' ≥8) on echocardiography. Patients underwent right heart catheterisation, echocardiography and CMR. 68 patients entered the final study cohort (HFpEF n=34 and non-cardiac dyspnea n=34 according to pulmonary capillary wedge pressure (PCWP)). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, E-wave deceleration as well as A-wave acceleration forces. Two patients were lost to 24 months follow-up evaluating cardiovascular mortality and hospitalisation (CVH).

Results

HDF assessment revealed impairment of LV longitudinal force in HFpEF (15.8 vs. 18.3, p=0.035) attributable to impairment of systolic peak (38.6 vs 51.6, p=0.003) and impulse (20.8 vs. 24.5, p=0.009) forces as well as late diastolic filling (−3.8 vs −5.4, p=0.029). Impairment of early diastolic filling could be observed in HFpEF patients identified at rest only but not stress (7.7 vs. 9.9, p=0.004). Impaired systolic peak was associated to CVH (HR 0.95, p=0.016) and superior for CVH prediction compared to LV global longitudinal strain (AUC 0.76 vs. 0.61, p=0.048).

Conclusions

Assessment of HDF reveals impairment of LV systolic and diastolic function in HFpEF. The value of systolic HDF assessment exceeded that of conventional deformation imaging for CVH prediction.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research
The association of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers with renal protection in patients with SARS-CoV-2
Authors: Douen A D , Tan S T , Sukoo-Pertab M S , Bowser C B , Busari O B , Siu W S , Panetti P R , Kedarisetti S K , Romney W R , Ramdass R P , Lee W L , Juang G J , Toreli A T , Soni A S
Published: October 2022

Background

Kidney dysfunction is a prevalent disease that leads to many complications over time, such as hypertension, heart disease, and death. ACEI/ARBs are known to be renoprotective. However, few studies describe the association between ACEI/ARB use and kidney dysfunction in patients with SARS-CoV-2 infection.

Purpose

To explore the association between patients with SARS-CoV-2 and kidney dysfunction in patients taking an ACEI/ARB. We hypothesize a negative association between patients with SARS-CoV-2 taking an ACEI/ARB and kidney dysfunction.

Methods

A retrospective query between March 2020 and April 2021 was performed in patients 18 years and older who tested positive for SARS-CoV-2 using a polymerase chain reaction test. Patients were divided into two groups: kidney dysfunction and no kidney dysfunction. Kidney dysfunction was defined as any diagnosis of chronic kidney disease or acute kidney injury. Primary outcomes were all-cause mortality and hospitalization rate. Secondary outcomes included myocardial infarction (MI), hypotension, intubation, vasopressor use, ventricular tachycardia, and ventricular fibrillation. We used multivariate logistic regression to adjust for baseline characteristics.

Results

We identified 996 patients with kidney dysfunction and 22,106 without kidney dysfunction who tested positive for SARS-CoV-2. The incidence was 258 (25.9%) for ACEI/ARB use in patients with kidney dysfunction. Adjusted odds ratio (OR) for patients with kidney dysfunction was 5.705 (95% Confidence Interval [CI]: 4.554–7.146; p<0.001) for hospitalization, 0.895 (95% CI: 0.707–1.135; p<0.361) for patients taking ACEI/ARB, and 0.529 (95% CI: 0.333–0.838; <0.007) for mortality in patients with kidney dysfunction who took ACEI/ARB. All secondary outcomes had significantly greater adjusted OR (p<0.001), except for MI (p<0.339), ventricular tachycardia (p<0.697), and ventricular fibrillation (p<0.060).

Conclusion

To date, the benefits of ACEI/ARB in SARS-CoV-2 patients have been controversial. While ACEI/ARB is known to have renoprotective properties, we did not find a significant association between ACEI/ARB and kidney dysfunction in patients with SARS-CoV-2. However, we found the use of ACEI/ARB in patients with kidney dysfunction to be associated with lower mortality. Therefore, clinicians should continue using this medication for its mortality benefits in patients with kidney dysfunction and its cardioprotective effects.

Funding Acknowledgement

Type of funding sources: None.
Trends in oral anticoagulant use in patients with atrial fibrillation in Belgium from 2013 to 2019: a nationwide cohort study
Authors: Grymonprez M , De Backer T L , Capiau A , Vauterin D , Mehuys E , Boussery K , Steurbaut S , Lahousse L
Published: October 2022

Background

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly preferred over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management. However, differences in oral anticoagulant (OAC) prescribing according to patient's age, patient's sex and physician's specialty may be present.

Purpose

To investigate the incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC on a full-population scale.

Methods

Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between January 1st, 2013 and December 31st, 2019 were identified. OAC use was investigated per half-year with a repeated cross-sectional design, based on medication prescription claims on a day-to-day basis. Incident use was defined as the first OAC use during the study period in OAC-naïve AF patients, whereas prevalent OAC use was defined as at least 1 OAC dispensing during a specific half-year. Factors influencing NOAC versus VKA initiation were identified by multivariable logistic regression models.

Results

Among 448,661 included OAC-treated AF patients (260,184 prevalent NOAC and 188,477 prevalent VKA users), 297,818 were newly-treated (232,739 incident NOAC and 65,079 incident VKA users). The mean age of incident NOAC and VKA users was 76±10 and 71±12 years, and 48% and 47% were female, respectively. Incident OAC use ranged from 45–49 to 42–44 users/10,000 persons between 2013–2019, whereas prevalent OAC use increased from 337 to 435 users/10,000 persons. Incident and prevalent NOAC use exceeded VKA use since 2013 and 2015 respectively, and NOACs represented 92% of incident and 81% of prevalent OAC users in 2019. Apixaban was the most frequently used NOAC since 2016. NOACs were significantly more prescribed by cardiologists and to older patients, whereas VKAs were more initiated in patients with cardiovascular, renal and hepatic comorbidities. Prevalent OAC use increased less in women than men (+25% versus +33% between 2013–2019) and female subjects had a 5% significantly lower odds of NOAC versus VKA initiation than men after multivariable adjustment.

Conclusions

Prevalent anticoagulant use increased with 29% in Belgium between 2013 and 2019. However, potential (N)OAC underuse among female AF patients was observed.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO)
Antithrombotic strategies in antiphospholipid syndrome with arterial thrombosis: a systematic review and network meta-analysis
Authors: Attachaipanich T , Aungsusiripong A , Piriyakhuntorn P , Hantrakool S , Rattarittamrong E , Rattanathammethee T , Tantiworawit A , Norrasethada L , Chai-Adisaksopha C
Published: October 2022

Background

There was still a lack of consensus regarding optimal antithrombotic strategies in Antiphospholipid syndrome (APS) with arterial thrombosis.

Purpose

This Systematic review and Network meta-analysis (NMA) were conducted to evaluate the relative efficacy and safety of secondary thromboprophylaxis strategies in this setting.

Methods

We searched OVID MEDLINE, Web of Science and the Cochrane Controlled Register of Trials (CENTRAL) from inception to the March 1, 2022 without language restriction. Eligible studies were: i) included APS with arterial thrombosis; ii) treated with any of antiplatelet, warfarin, direct oral anticoagulants (DOACs) or a combination of those treatments, and iii) reported recurrent thrombotic events. Case reports or small studies which included less than 5 patients in each arm were excluded. Two investigators independently abstracted data and assessed risk of bias of included studies. A frequentist random-effects network meta-analysis was performed. All results were analyzed using the netmeta package in R, version 3.6.2.

Results

The database search resulted in 4076 results. After screening, 3998 studies were excluded. A total of 78 studies were included in full-text reviews. Finally, there were 12 studies (6 randomized and 6 non-randomized studies) included in this network meta-analysis, comprising 681 participants. Dual antiplatelet therapy (DAPT) and combined antiplatelet with warfarin were associated with lower risk of recurrent thrombosis with odds ratio (OR) 0.16 (95% CI 0.03 to 0.90) and 0.25 (95% CI 0.08 to 0.78) respectively comparing to single antiplatelet therapy (SAPT). DOACs and moderate-intensity warfarin were associated with higher recurrent arterial thrombosis with OR 12.59 (95% CI 2.03 to 78.19) and 5.25 (95% CI 1.17 to 23.48) respectively. There was no significant different major bleeding risk among antithrombotic regimens. The certainty of the evidences was very-low for all outcomes.

Conclusion

This network meta-analysis shows that a combination of antiplatelet with warfarin and DAPT were relatively effective antithrombotic strategies secondary prevention of recurrent thrombosis in arterial-thrombotic APS as compared to SAPT. However, there was still limited quality of evidence.

Funding Acknowledgement

Type of funding sources: None.
Thirty-days versus standard duration of dual antiplatelet treatment after percutaneous coronary interventions: a systematic review and meta-analysis
Authors: Apostolos A , Trigka A , Chlorogiannis D , Vasilagkos G , Chamakioti M , Spyropoulou P , Karamasis G , Dimitriadis K , Moulias A , Katsanos K , Tsioufis C , Toutouzas K , Alexopoulos D , Davlouros P , Tsigkas G
Published: October 2022

Background/Introduction

Abbreviation of duration of dual antiplatelet therapy (DAPT) (one or three months) has been recently proposed, especially for high-bleeding risk patients, after percutaneous coronary intervention (PCI) with drug-eluting stent (DES).

Purpose

The purpose of the specific systematic review and meta-analysis was to compare 30-days versus longer duration (≥3 months) of DAPT in patients undergoing PCI with DES, focusing on ischemic and bleeding events.

Methods

Three databases were screened for eligible randomized-control trials. The primary endpoint was the incidence of net adverse clinical events (NACE), as they were defined in each trial. Secondary endpoints consisted of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality, myocardial infraction, stroke, stent-thrombosis, repeat revascularization and major bleeding.

Results

We included 4 RCTs with a total of 26,576 patients; 13,282 patients were grouped in 30-days DAPT, while the remaining 13,294 were allocated in longer period of DAPT. One-month of DAPT did not significantly reduce NACE (odds ratio [OR]: 0.87, 95% confidence intervals [Cl]: 0.74–1.03); however major bleedings were significantly reduced by 22% (OR: 0.78, 95% Cl: 0.65–0.94). Mortality or ischemic events (stroke, myocardial infraction, revascularization and stent thrombosis) were not affected.

Conclusions

Thirty-days DAPT did not significantly affect NACEs. However, odds of major bleedings were reduced significantly by 22%. Mortality and ischemic events did not differ between the two arms. Thus, 30-days DAPT could be considered as a safe and feasible after PCI with DES in selected patients, especially those in high-bleeding risk. Forthcoming RCTs could shed light on the optimal duration of DAPT.

Funding Acknowledgement

Type of funding sources: None.