bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients with symptomatic permanent atrial fibrillation show quantitative signs of pain sensitisation
Authors: Jackson A , Frobert O , Boye Larsen D , Arendt-Nielsen L , Bjorkenheim A
Published: October 2021

Background/Introduction

Most patients with atrial fibrillation (AF) report symptoms, while around one-third are asymptomatic. We hypothesized that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF.

Purpose

To assess differences in pain sensitisation in patients with symptomatic and asymptomatic AF.

Methods

Thirty individuals with permanent AF (15 symptomatic, 15 asymptomatic) completed the AF6 and SF-36 questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalized pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP), and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to quantitative measures of pain sensitisation.

Results

The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), as well as impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared to the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=−0.50, p=0.005) and sternum (r=−0.42, p=0.02) and positively correlated to TSP of both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=−0.53, p=0.003) but not sternum.

Conclusions

Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Örebro University, Sweden PPTs tibialis anterior musclePPTs sternum
Lower heart rates and beta-blockers are associated with new-onset atrial fibrillation
Authors: Habel N , De Lavallaz J , Koehler J , Ziegler P , Infeld M , Lustgarten D.L , Meyer M
Published: October 2021

Background

Lower heart rates (HRs) prolong diastole, thereby raising filling pressures and wall stress (1,2), slowing myocardial relaxation (3), and increasing central blood pressure via superposition of reflected peripheral pressure waves onto systole (2,4). As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers (BBs) may thereby increase the risk for AF.

Purpose

Examine the relationships of HR, BNP, BB use and new-onset AF in the REVEAL-AF and SPRINT cohort of subjects at risk for developing AF.

Methods

In REVEAL-AF, 383 subjects (52% male, mean age 71.5±9.8 years) without a history of AF and a mean CHA2DS2VASC score of 4.4±1.3 received an insertable cardiac monitor and were followed up to 30 months. Baseline HRs were averaged between 8AM and 8PM for the first week post-implantation. Adjudicated AF lasting ≥6 minutes was defined as new-onset AF.

In SPRINT, 7595 patients (64% male, mean age 67.5±9.2 years) without prior history of AF and a mean CHA2DS2VASC score of 2.3±1.2 were followed for up to 60 months. Baseline average HR was derived from three seated measurements taken at the initial clinical visit. 12-lead ECG at baseline, 2 years, 4 years and close-out visit were used to determine presence of AF. Based on longitudinal medication inventories BB use was categorized into “on BB” vs “never on BB” for the duration of the trial.

Results

The median daytime HR in the REVEAL-AF cohort was 75bpm [interquartile range, IQR 68–83]. Subjects with below median HRs had 2.4-fold higher BNP levels when compared to subjects with above median HRs (median BNP [IQR]: 62pg/dl [37–112] vs. 26pg/dl [13–53], p<0.001). Below median HRs were associated with a higher incidence of AF: 37% vs. 27%, p=0.047. This was validated in the SPRINT cohort after adjusting for AF risk factors (age, HR, sex, body mass index, coronary artery disease, intensive vs standard blood pressure therapy, chronic kidney disease). Both a HR<75bpm and BB use were independently associated with a higher rate of AF: 1.9 vs 0.7%, p<0.001 and 2.5% vs. 0.6%, p<0.001, respectively. The hazard ratio for patients on BB to develop AF was 3.72 [CI 2.32, 5.96], p<0.001.

Conclusion

Lower HRs and BB use are associated with higher BNP levels and incident AF, supporting the hypothesis that lower HRs mimic and/or exacerbate the hemodynamic effects of diastolic dysfunction and promote atrial myopathy. The effects of BBs on clinical outcomes in patient populations outside the context of heart failure with reduced ejection fraction will need to be reassessed.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health
The need and duration of BB therapy in post MI patients with preserved left ventricular ejection fraction: a meta-analysis
Authors: Abdelmawgoud S , Shehata E
Published: October 2021

Background

Oral beta-blockers have beneficial effect on long-term mortality in high-risk as low left ventricular ejection fraction (LVEF) patients with MI, but the effect and duration of use of Beta-blockers in post-AMI patients with preserved LVEF is still unknown.

Methods

We performed a systematic search in Cochrane library, Embase, Medline, Pubmed, Scopus, Web of Science, clinical trial registries, and for eligible studies (26,431 patients). Data for outcomes were pooled as Hazard ratios (HRs), with 95% confidence interval, using RevMan software for windows.

Results

The pooled effect-estimate showed significant decrease in all cause mortality in beta-blocker group (HR 0.71, 95% CI 0.62–0.82). A subgroup analysis regarding duration of use of BB (≤1 year or >1 year), age (≤65 or ≥65),sex, use of CCB, presence of HTN or DM, and LVEF (≥50 or ≥40) was done. No significant subgroup differences were detected: duration of use of BB (p=0.32), age (p=0.23), sex (p=0.84), CCBs (p=0.28), HTN (p=0.32), DM (p=0.92),and LVEF (p=0.06). No significant differences between bet-blocker vs. no beta-blockers in terms of cardiac death (HR 0.69, 95% CI 0.33–1.46), re-infarction (HR1.00, 95% CI 0.68–1.48), re-hospitalization (HR1.08, 95% CI 0.32–3.68), and revascularization (HR 0.94, 95% CI 0.76–1.16).

Conclusion

Beta-blockers might reduce mortality of post-AMI patients with preserved LVEF, but failed to prevent cardiac events. The upcoming trials (REBOOT, BETAMI, DANBLOCK, and ABYSS) will define the use of Beta-blockers in post AMI patients with preserved Left ventricular ejection fraction.

Funding Acknowledgement

Type of funding sources: None.
Low birth weight predicts impaired cardiac structure and function in mid-adulthood
Authors: Huynh Q , Magnussen C , Venn A , Marwick T
Published: October 2021

Aims

We sought to determine the relationship of low birth weight (LBW) with adult cardiac structure and function and investigate potential causal pathways.

Methods

We followed 925 Australians (41.3% male) from childhood (7–15 years) to young- (26–36 years) and mid-adulthood (36–50 years). Left ventricular (LV) global longitudinal strain (GLS, %), LV mass index (LVMi, g/m2.7), LV filling pressure (E/e') and left atrial volume index (LAVi, g/m2) were measured by echocardiography in mid-adulthood. Birth weight category was self-reported in adulthood and classified as low (≤5 pounds or ≤2270 g), normal (5–8 pounds or 2271–3630 g) and high (>8 pounds or >3630 g).

Results

7.5% (69/925) reported LBW. Compared with participants with normal birth weight, those with LBW had a 2.01-fold (1.19–3.41, p=0.009) higher risk of impaired GLS (GLS >−18%) and 2.63-fold (0.89–7.81, p=0.08) higher risk of LV hypertrophy (LVMi >48 g/m2.7 in men or >44 g/m2.7 in women) in adulthood independent of age, sex and any measures of socioeconomic status. Participants with LBW significantly increased body fat from childhood to adulthood relative to their peers, which was associated with greater levels of triglycerides, fasting blood glucose and arterial stiffness in adulthood. These factors were the strongest mediators in the association of LBW with impaired GLS in adulthood and together, explained half of the LBW effect size. The remaining half of this association was independent of any measured factors.

Conclusions

LBW was associated with impaired cardiac structure and function in mid-adulthood. This association was only partially explained by known risk factors.

Funding Acknowledgement

Type of funding sources: None.
The value of Cystatin C in the diagnosis of cardiorenal syndrome type 1
Authors: Phan H A O
Published: October 2021

Background

The presence of acute kidney injury in the setting of acute heart failure is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). In CRS1 the diagnosis of acute kidney damage is often delayed by creatinine and urine output following KDIGO standards (Kidney Disease Improving Global Outcomes). Cystatin C is one of the earliest markers of worsening renal function. We studied the value of plasma Cystatin C in the diagnosis of cardiorenal syndrome type 1.

Purpose

This study was aimed: (1) to decribe clinical, subclinical characteristics, prevalence of CRS1; (2) to evaluate the diagnostic efficacy of Cystatin C in diagnosis of CRS1.

Materials and method

There were 139 patients with acute heart failure or acute decompensated heart failure (ADHF) in the Department of cardiovascular resuscitation and Interventional cardiology at 115 Ho Chi Minh City People's Hospital from September 2018 to June 2019. This is a prospective cohort study.

Results

There were 48 cases (rate 34.5%) with CRS1, medium age 66.12±15.77, men accounted for 50.4%. The optimal cut-off Cystatin C for diagnosing CRS1 is >1.81 mg/dl, AUC is 0.787 (95% CI 0.71–0.85, p<0.001), sensitivity 75%, specificity 83.52%, positive predictive value 70.6%, negative predictive value 86.4%. Building the optimal regression model by the BMA (Bayesian Model Average) method with only one variable Cystatin C: Odds Ratio = ey, while y = −2.75 + 1.11x Cystatin C. Moreover, a nomogram with variable Cystatin C was designed to predict the likelihood of CRS1 with AUC 0.842. Ultimately, a confusion matrix was constructed to determine model accuracy 81.82%, sensitivity 78.26%, specificity 100%, positive predictive value 100%, negative predictive value 47.37%.

Conclusions

Cystatin C is quite good value in the diagnosis of CRS1 in patients with acute heart failure or ADHF. A predictive model based on Cystatin C may help early diagnose CRS1 in patients with acute heart failure or ADHF.

Funding Acknowledgement

Type of funding sources: None.
Value of combined Plasma NGAL, Cystatin C And NT-proBNP in the diagnosis of cardiorenal syndrome type 1
Authors: Phan H A O
Published: October 2021

Background

The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) in the blood and urine is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. Cystatin C is early marker of renal dysfunction. NT-proBNP is valuable in the diagnosis, prognosis and treatment of acute and chronic heart failure. This study was aimed to evaluate the diagnostic efficacy of the combination of plasma NGAL, Cystatin C and NT-proBNP in diagnosis of CRS1.

Methods

There were 139 patients with AHF or ADHF in the department of Cardiovascular resuscitation and Interventional cardiology at Ho Chi Minh City 115 People Hospital from November 2018 to May 2019. This was a prospective cohort study.

Results

There were 48 cases (rate 34.5%) with CRS1, mean age 66.12±15.77, men accounted for 50.4%. There were no significant differences of vital signs on admission, diagnosis, type of heart failure between CRS1 and Non-CRS1 groups. The urea, creatinin on first day (creatininD1) and third day (creatininD3), NT-proBNP, Cystatin C, NGAL levels were higher in the group with CRS1 than Non-CRS1, the difference was statistically significant p<0.05. The optimal cut-off NGAL for diagnosing CRS1 was >353.23 ng/ml, Area Under Curve (AUC) was 0.732 (95% CI 0.65–0.80, p<0.001), sensitivity 74.47%, specificity 68.48%, positive predictive value 54.7%, negative predictive value 84%. The optimal cut-off Cystatin C for diagnosing CRS1 was >1.81 mg/dl, AUC was 0.787 (95% CI 0.71–0.85, p<0.001), sensitivity 75%, specificity 83.52%, positive predictive value 70.6%, negative predictive value 86.4%. The optimal cut-off NT-proBNP for diagnosing CRS1 was 17681 pg/ml, AUC was 0.683 (95% CI 0.59 – 0.76, p<0.001), sensitivity 53.19%, specificity 77.17%, positive predictive value 54.3%, negative predictive value 76.3%. Combined three biomarker plasma NGAL, Cystatin C and NTproBNP, the specificity of the diagnosis was the highest 95.6%, the positive predictive value was the highest 84.62% in diagnosing CRS1.

Conclusions

The combined plasma NGAL, Cystatin C and NT-proBNP is high value in the diagnosis of CRS1 in patients with AHF or ADHF.

Funding Acknowledgement

Type of funding sources: None.
Trends and outcomes in opioid related cardiac arrest in a contemporary US population from 2012–18
Authors: Malik S , Aronow W S
Published: October 2021

Background

Opioid abuse is a significant problem and has been associated in patients presenting with cardiac arrest. We aimed to investigate and compare the contemporary trends of cardiac arrest in patients with and without opioid abuse.

Methods

All hospitalizations for primary diagnosis of Cardiac arrest between 2012 and 2018 identified in the Nationwide Readmissions Database were categorized into those with or without a secondary diagnosis of opioid disease. Cardiac arrest hospitalizations with opioid use using the year of admission, discharge quarter, age, sex, and elixhauser comorbidity index. Primary outcomes were inpatient mortality. Survey techniques were used to do comparative analyses using Stata 16.0.

Results

Of 1,410,475 cardiac arrest hospitalizations that met inclusion criteria, 43,090 (3.1%) had cardiac arrest with a secondary diagnosis of opioid use. In hospital mortality in cardiac arrest patients with and without opioid use was 56.7% vs 61.2%. Hospitalizations for cardiac arrest with opioid use were associated with higher prevalence of alcohol (16.9% vs. 7.1%; p<0.05), depression (18.8% vs. 9%; p<0.05), and smoking (37.0% vs. 21.8%; p<0.05) as compared with cardiac arrest without opioid use. Hospitalizations for cardiac arrest with opioid use was seen less likely in patients with heart failure (21.2% vs. 40.6%; p<0.05), diabetes mellitus (19.5% vs. 35.4%; p<0.05), hypertension (43.4% vs. 64.9%; p<0.05) and renal failure (14.3% vs. 30.2%; p<0.05). Over the last 7 years, there has been a significant increasing trend in opioid associated cardiac arrest (p for trend <0.05) see figure.

Conclusions

Opioid remains a significant cause of cardiac arrests in the contemporary US population with an increase in its incidence over last 7 years. Lifestyle choices is most attributing to this increasing trend. Opioid users that presented with cardiac arrest were twice as more likely to have depression.

Funding Acknowledgement

Type of funding sources: None. Trends of opioid related cardiac arrest
Real world experience with coronary sinus reducer implantation for the treatment of refractory angina: a single-centre experience
Authors: Dias Ferreira Reis J P , Ramos R , Rio P , Fiarresga A , Cacela D , Cruz Ferreira R
Published: October 2021

Background

Coronary sinus Reducer device (CSF) implantation is a novel therapeutic option to relieve symptoms in patients with refractory angina (RA). There is limited real-world data describing its use outside of clinical trials.

Aim

To assess the safety and efficacy of this procedure in a real-world setting.

Methods

This is a report of a single centre prospective registry of consecutive patients with RA (CCS II-IV) deemed unsuitable for revascularization. Between May 2017 and August 2019, 17 patients were referred to CSF implantation. Baseline and follow-up evaluation consisted of clinical assessment, including completion of the short version of the Seattle Angina Questionnaire (SAQ-7) and CCS class evaluation and objective evaluation by transthoracic echocardiography and cardiopulmonary exercise test (CPET).

Results

A total of 13 patients (70,6±6,5 years, 76,9% male) underwent CSF implantation with a procedural success of 84.6%. No cases of periprocedural serious adverse events were reported. At 12-month follow-up, any reduction in CCS Class was achieved in 72.7% of cases, with 27.2% reducing 2 CCS classes. Baseline CCS score was reduced from 2.8±0.4 to 1.7±0.8 (p=0.009). Quality of life (QoL) was significantly improved as assessed by the improvement seen in all items of SAQ-7 (p<0.017 for all). CPET duration was significantly increased (p=0.034), but no change was noted in the remainder CPET variables. During follow-up, 3 patients suffered myocardial infarction, resulting in 1 death.

Conclusion

CSF implantation in patients with RA was safe and led to a significant reduction of the angina burden and improvement of QoL at 12-month follow-up.

Funding Acknowledgement

Type of funding sources: None.
Abnormal hb-levels associate differently with type 1 and type 2 myocardial infarction in patients visiting the emergency department with chest pain
Authors: Forsell S , Najeb A , Habel H , Jerberg T , Hofmann R , Svensson P
Published: October 2021

Background

Previous studies have found an association between myocardial infarction (MI) and abnormal haemoglobin (Hb) but it is unknown whether Hb-levels are associated with type 1 and type 2 MI in unselected patients with chest pain visiting the emergency department (ED).

Purpose

To investigate the association between abnormal Hb-levels and type 1 and type 2 MI in patientens visiting the ED with chest pain.

Methods

The study population comprised all consecutive patients visiting four urban ED:s for chest pain between 2013–2016 with available data on Hb. Clinical data from the ED visit were cross-referenced to compulsory national registries retrieving information on previous diagnoses and treatments to identify history of cardiovascular disease (defined as previous MI, stroke or peripheral vascular disease), hypertension, hyperlipidaemia and diabetes mellitus. Patients were categorized depending on the exposure (Hb-level) to anaemia, normal and polycythaemia. The primary outcome (type 1 and type 2 MI) was identified in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Relative risk ratio (RRR) was calculated using multinomial logistic regression, with 95% confidence interval (CI) using no infarction as reference. The robust sandwich estimator was used to estimate standard errors. Adjustments were made for risk factors according to HEART-score.

Results

A total of 64 606 patient with chest pain were included with a mean (SD) age of 56 (19) years and 48% were women. Anaemia was present in 10 204 (15.8%) and polycythaemia in 1598 (2.5%). Overall, type 1 MI occurred in 2 296 patients and type 2 MI in 145. The risk for type 1 MI was higher in both anaemia (RRR 1.8, 95% CI 1.6–2.0) and polycythaemia (RRR 1.6, 95% CI 1.3–2.0) compared to normal Hb. For type 2 MI the risk was markedly higher for both low and high Hb compared to normal (RRR 4.0, 95% CI 2.8–5.6) and (RRR 3.0, 95% CI 1.4–6.9). Taking age, gender and risk factors into account, patients with anaemia had a lower risk (RRR 0.8, 95% CI 0.7–0.9) for type 1 MI compared to patients with normal Hb whereas patients with polycythaemia still had a higher risk (RRR 1.6, CI 1.2–2.0). For type 2 MI, the risk remained higher for both low (RRR 1.9, 95% CI 1.3–2.8) and high Hb (RRR 2.8, 95% CI 1.3–6.2) compared to normal.

Conclusion

Abnormal Hb-levels in chest pain patients in the ED were significantly associated with an increased risk of type 1 or type 2 MI, however when accounting for risk factors, in a differential pattern. These novel findings indicate that Hb-level may be important when assessing patients for MI symptoms in the ED, however, further investigations are needed to establish the definite predictive value.

Funding Acknowledgement

Type of funding sources: None. Adjusted results type 1 and type 2 MI
ECG markers of atrial abnormalities are not associated with new onset atrial fibrillation in patients with acute ST-segment elevation myocardial infarction
Authors: Baturova M , Demidova M M , Carlson J , Erlinge D , Platonov P G
Published: October 2021

Introduction

New onset AF is a known complication in patients with acute ST-segment elevation myocardial infarction (STEMI). However, whether new-onset AF is linked to atrial structural abnormalities or has different underlying mechanisms is not fully clarified.

Purpose

We aimed to assess the association of P wave indices as ECG markers of atrial structural abnormalities with new-onset AF in STEMI patients undergoing primary percutaneous intervention (PCI).

Methods

Study sample comprised of 2277 consecutive patients with STEMI admitted to a tertiary care hospital for primary PCI from 2007 to 2010. SWEDEHEART registry was used as the source of information regarding clinical characteristics and events during index admission, including new-onset AF. The closest available ECGs prior to STEMI (median 448, interquartile rate 25–75% 112–1390 days before STEMI) were extracted from the regional electronic ECG databases and automatically processed using Glasgow algorithm. Patients with sinus rhythm ECGs were included in the current analysis (n=1481, mean age 68±12 years, 33% females). P-wave duration, PR interval, P-wave frontal axis and P terminal force in lead V1 (PTF-V1) were assessed. PTF-V1 >40 mm*ms was considered abnormal.

Results

Paroxysmal AF prior to STEMI was known in 77 patients (5.2%). Among patients without pre-existing AF (n=1404), new-onset AF during hospital admission was identified in 102 patients (6.9%). Patients with new-onset AF were older than those without AF history (74±9 vs 67±12 years, p<0.001), but did not differ in regard to other clinical characteristics. In univariate logistic regression analysis P wave duration as continuous variable, P wave duration >120 ms and PR interval were significantly associated with new onset AF (Table 1). However, after adjustment for age both, P wave duration >120 ms (odds ratio (OR) 1.20, 95% CI 0.77–1.89, p=0.418) and PR interval (OR 1.01, 95% CI 1.00–1.01, p=0.068), failed to demonstrate the significant association with new onset AF while age (OR 1.06, 95% CI 1.04–1.08, p<0.001) remained an independent risk factor for AF development.

Conclusion

In patients with acute STEMI new onset AF developed during hospital admission is common and strongly associated with age. P wave indices failed to demonstrate the significant association with new onset AF thus indicating that atrial structural abnormalities are unlikely the underlying cause of AF development in acute STEMI.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Scholarship grant from Swedish Institute. Table 1
Short-Term outcomes using contemporary balloon-expandable valves in transcatheter aortic valve implantation
Authors: Medranda G , Schwartz R K , Green S J
Published: October 2021

Background/Introduction

Advancements in balloon-expandable transcatheter heart valves (THV) have improved outcomes in transcatheter aortic valve implantation (TAVI). The most recent iteration, the SAPIEN 3 Ultra THV, offers a taller paravalvular skirt which has demonstrated similar short-term outcomes while reducing mild paravalvular leak in high- and intermediate-risk patients.

Purpose

We sought to describe a real-world experience comparing short-term outcomes in the SAPIEN 3 THV to the SAPIEN 3 Ultra THV in patients across the risk spectrum (including low-risk).

Methods

We conducted a retrospective, observational study of patients who underwent TAVI using either the SAPIEN 3 or SAPIEN 3 Ultra THV between 2019–2020. In-hospital, 30-day and 1-year Valve Academic Research Consortium-2–defined outcomes were examined.

Results

We screened a total of 457 patients who underwent TAVI at our institution between 2019–2020. Included were 254 patients who received either the SAPIEN 3 THV or the SAPIEN 3 Ultra THV. Baseline clinical characteristics were similar in both cohorts (Table 1). Procedural success was similar in both cohorts (97.2% vs. 97.3%; p=1.ehab724.1647) with similar rates of >mild paravalvular leak (7.7% vs. 10.7%; p=0.3796). Mortality and rates of stroke were extremely low and similar in both cohorts at 30 days and 1 year (Table 2). There was a trend towards lower rates of permanent pacemaker implantation in the SAPIEN 3 Ultra cohort (In-Hospital: 9.2% vs.4.5%, p=0.2177; 30-Day: 11.3% vs.4.5%, p=0.0658; 1-Year: 12.7% 5.4%, p=0.0536).

Conclusions

In this real-world analysis of contemporary TAVI patients across the risk spectrum, the SAPIEN 3 Ultra THV demonstrated excellent short-term outcomes comparable to the SAPIEN 3 THV with a trend towards lower rates of permanent pacemaker implantation.

Funding Acknowledgement

Type of funding sources: None.
18F-Sodium fluoride positron emission tomography, aortic disease activity and ischaemic stroke risk
Authors: Fletcher A , Tzolos E , Joshi S , Kwiecinski J , Bing R , Doris M K , Moss A J , Van Beek E J , Joshi N , Adamson P , Whiteley W , Wardlaw J , Slomka P , Newby D E , Dweck M R
Published: October 2021

Background

Arterial 18F-sodium fluoride (18F-NaF) activity on positron emission tomography (PET) is a marker of active microcalcification and atherosclerosis. Coronary 18F-NaF activity (CMA) predicts coronary artery disease progression and subsequent myocardial infarction.

Objective

To investigate whether aortic 18F-NaF activity (AMA) predicts thoracic aortic atherosclerotic disease progression and subsequent ischaemic stroke or myocardial infarction in patients with established cardiovascular disease.

Methods

In a post-hoc observational cohort study, we evaluated AMA and CMA in patients with stable coronary artery disease (n=239) or aortic stenosis (n=158) who had underwent thoracic 18F-NaF PET and computed tomography (CT). We assessed the associations between AMA or CMA and progression of calcified atherosclerotic plaque in both thoracic aortic and coronary territories on follow up CT, as well as subsequent ischaemic stroke or myocardial infarction.

Results

In 141 and 231 patients with repeat aortic and coronary CT imaging respectively at 12.7±2.7 months, AMA correlated with log progression of thoracic aortic calcium scores (r=0.21, p=0.011), volume (r=0.29, p<0.01) and mass (r=0.29, P<0.01) as well as log coronary calcium score progression (r=0.21, p=0.03). CMA correlated with log coronary (r=0.42, p<0.01), but not log aortic (p>0.80) calcium score progression. In 397 patients, 16 had an ischaemic stroke and 25 had a myocardial infarction after 4.7±1.6 years. After adjusting for clinical risk factors, CMA and calcium scoring, AMA was associated with stroke (hazard ratio, 1.71 [95% confidence interval 1.00–2.90], p=0.048]). AMA was superior to clinical risk and calcium scores in identifying patients with stroke (c-statistic 0.76 versus 0.58 versus 0.63 respectively, p<0.05). Survival analysis demonstrated that AMA was associated with ischaemic stroke (p<0.001) but not myocardial infarction (p=0.45), whereas CMA was associated with myocardial infarction (p<0.001) but not stroke (p=0.39).

Conclusions

In patients with established cardiovascular disease, AMA is associated with progression of aortic atherosclerosis and future ischaemic stroke. Arterial 18F-NaF identifies localised areas of atherosclerotic disease activity that relate to regional atherothrombotic events.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): British Heart Foundation AMA, disease progression and outcomesVariables associated with stroke
B- mode ultrasound- guided balloon angioplasty of occluded artery accompanied by combined focused ultrasound sonodynamic therapy and catheter- based 192Ir- mediated brachytherapy
Authors: Mehrad H
Published: October 2021

Background and aims

Three mechanisms are responsible for the development of restenosis: elastic recoil, intimal hyperplasia and late vascular constriction, all grouped under the catch phrase “negative remodeling”. Neointimal hyperplasia is usually defined in an artery as thickening of the intimal layer after an injury such as balloon angioplasty methods. The aim of this study was to evaluate the effect of combined ultrasound sonodynamic therapy and catheter- based 192Ir-mediated β-brachytherapy on restenosis reduction after balloon angioplasty.

Methods

Briefly, golden Syrian hamsters were submitted to common carotid artery advanced atherosclerotic occlusion by primary perivascular Co2 laser-mediated far-infrared injury followed by a 2% cholesterol-rich diet for six weeks. Histopathology results showed the formation of a thick-cap fibroatheromatic plaque, resulted to occlusion in all of the hamsters' arteries. Then treatment group (n=10) underwent B-mode ultrasound-guided balloon angioplasty followed by combined pulsed low level focused ultrasound (F=750 KHz, I=1.5 W/cm2, PD=120 ms)-mediated sonosensitizer protoporphyrin-IX-loaded PESDA (Perfluorocarbon Exposed Sonicated Dextrose Albumin) microbubbles (100ml/kg, 2–5×105 bubbles/ml) sonodynamic therapy and catheter- based β-brachytherapy (125I−, 18 Gy).

Results

Results from ultrasonography and histopathology showed a significant reduction in the mean value for macrophages and smooth muscle hyperplasia cells density after balloon angioplasty in the treated group compared with the other groups (p<0.05).

Conclusions

Enhanced anti-inflammatory effect of sonodynamic therapy, induced by collapsed microbubbles accompanied by apoptotic effect of β-brachytherapy, can cause to reduce the inflammation and smooth muscle hyperplasia cells in the intimal layer.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab
Combined verteporfin- mediated photodynamic therapy and catheter- based 192Ir- mediated brachytherapy for neoatherosclerosis inhibition after laser angioplasty
Authors: Mehrad H
Published: October 2021

Background and aims

The laser atherectomy methods that are currently in use, cause to inflammation and subsequent restenosis. The aim of this study was to evaluate the effect of combined verteporfin photodynamic therapy and catheter-based 192Ir-mediated β-brachytherapy on inflammation and neoatherosclerosis reduction after laser angioplasty of the animal occluded femoral artery, wherein diagnostic ultrasound is adjuncted with laser angioplasty system and combination therapy system, with a goal of increased safety.

Methods

Briefly, New Zealand white rabbits were submitted to femoral artery advanced atherosclerotic occlusion by primary perivascular severe cold injury followed by a 2% cholesterol- rich diet for fourteen weeks. Histopathology results showed the formation of stable advanced atherosclerosis with lipid and neovessel-rich plaque, resulted in occlusion in all of the rabbits' arteries. Then treatment group underwent B- mode ultrasound-guided argon laser (488 nm) angioplasty followed by catheter- based β-brachytherapy (192Ir, 15 Gy) in combination with verteporfin (10mg/kg)-mediated low level red laser (λ=635 nm, E=130 J/cm2) photodynamic therapy.

Results

Results from ultrasonography and histopathology showed a significant reduction in the mean value for immune cells and smooth muscle hyperplasia cells density after angioplasty in the treatment group compared with the other groups (p<0.05).

Conclusions

Apoptotic effect of catheter-based 192Ir-mediated β-brachytherapy in combination with toxicity effect of verteporfin, can cause to reduce the density of macrophage cells and smooth muscle hyperplasia cells in the intimal layer. These findings provide the basis for developing of combined β-brachytherapy and verteporfin- mediated photodynamic therapy for a successful clinical application in the treatment of neoatherosclerosis after laser angioplasty.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab
Evaluation of global left ventricular systolic function in dipper and newly diagnosed nondipper hypertensive patients
Authors: Cakal S , Cakal B
Published: October 2021

Objective

Nondipper hypertension has been associated with enhanced target organ damage and adverse cardiovascular outcomes. The effect of dipper and non-dipper status on cardiac target organ damage has not been comprehensively investigated by two-dimensional strain echocardiography. We aimed to investigate myocardial deformational strain parameters in dipper and non-dipper untreated hypertensive patients.

Material and methods

We included 42 newly diagnosed hypertensive patients without previous history of cardiovascular disease and coexisting chronic disease. Study population consisted of two groups of patients, 23 dipper patients and 19 non dipper patients. Global longitudinal strain (GLS), radial strain and circumferential strain analysis were measured by two-dimensional (2-D) speckle tracking method.

Results

The study population included 42 patients (15 male) with a mean age of 54.5±9 years. The assessment of LV systolic function by GLS showed decreased values in nondippers compared with dippers (−18.13±2.07 vs. −13.7±1.95; p=0.001). But no significant intergroup differences were observed in circumferential and radial strain. The analysis showed that night-time mean arterial pressure (MAP), night-time systolic and diastolic blood pressures (BP), 24-hr SBP, dipping rate and nocturnal reduction rate of MAP were the parameters that correlated with GLS. Only dipping rate was independently associated with left ventricular GLS.

Conclusion

An isolated non-dipper BP was found to cause impaired LV systolic function detected by myocardial strain.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Effect of physical activity on mortality and hospitalization for lower respiratory tract infection in patients with cardiovascular disease
Authors: Jung M
Published: October 2021

Background

Despite the well-validated benefit of physical activity on various health outcomes, little is known about its effect on lower respiratory tract infection. We explored the dose-response associations between physical activity and lower respiratory tract infection outcomes in patients with cardiovascular disease.

Methods

Using the Korean National Health Insurance data, we identified more than 1 million individuals with cardiovascular diseases who had data on self-reported physical activity (baseline 2009–2012). Participants were followed up until 2018–2019 regarding the risk of death or hospitalization due to lower respiratory tract infection according to their physical activity level.

Results

Age- and sex-adjusted hazard ratios (95% confidence interval) for lower respiratory tract infection mortality were 1.00 (reference), 0.70 (0.67–0.74), 0.63 (0.59–0.66), 0.48 (0.43–0.53), and 0.51 (0.45–0.56) for those engaging in physical activity of 0, <500, 500–999, 1000–1499, and ≥1500 MET min/week, respectively. This was similarly applied to hospitalization due to lower respiratory tract infection. Generally, the association was stronger in the elderly population than in the younger population. Restricted cubic spline curve showed a non-linear association, that is, gradual risk reduction with a steeper slope between 0 and 500 MET min/week, reaching a plateau for 1500–1800 MET/min, and the curve flattened out thereafter.

Conclusions

In patients with cardiovascular disease, engaging in even low level of physical activity was associated decreased risk for lower respiratory tract infection outcomes and incremental risk reduction was shown with an increasing physical activity.

Funding Acknowledgement

Type of funding sources: None.
Impact of diabetes on coronary severity and cardiovascular outcomes in patients with heterozygous familial hypercholesterolemia: an analysis of genotype and phenotype
Authors: Liu M M , Li J J
Published: October 2021

Aims

Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular disease. However, the association between T2DM and coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (HeFH) has not been thoroughly evaluated. Our study aimed to assess the effect of T2DM on CAD severity and hard cardiovascular endpoints in a HeFH cohort.

Methods

A total of 432 patients with HeFH with a molecular and/or clinical Dutch Lipid Clinic Network score ≥6 (definite and probable) were enrolled. Patients were divided into a T2DM group (n=99) and a non-T2DM group (n=333). Hard endpoints included a composite of non-fatal myocardial infarction, stroke, and cardiac death.

Results

No differences were observed regarding genetic mutations in patients with and without T2DM. Patients with T2DM demonstrated a greater number of diseased vessels (p=0.029) and more severe coronary lesions with high Gensini, SYNTAX, and Jeopardy score tertiles. Compared with patients without T2DM, patients with T2DM were at a significantly greater risk of hard endpoints (multivariate adjusted hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.02–4.84, p=0.025). Additionally, patients with T2DM and good glucose control (HbA1c <7.0%) were at a lower risk of hard endpoints compared with those with poor glucose control (HbA1c ≥7.0%, HR 0.08, 95% CI 0.01–0.56, p=0.011).

Conclusions

We conclude that T2DM is an independent predictor of CAD severity when assessed by four different tests and worse cardiovascular outcomes, suggesting that T2DM could be further used for risk stratification of patients with HeFH.

Funding Acknowledgement

Type of funding sources: None. Graphical abstract
Impact of early initiation of SGLT2 inhibitor on cardiovascular outcomes in diabetic patients with known atherosclerotic cardiovascular disease or risk factors: propensity score matched analysis
Authors: Sun W , Yan B
Published: October 2021

Purpose

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular benefits in patients with diabetes and atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the impact of early initiation of SGLT2 inhibitor on cardiovascular outcomes in diabetic patients with known and at risk of ASCVD.

Methods

We retrospectively analyzed 29,309 consecutive patients with type 2 diabetes prescribed empagliflozin (N=18,979, 64.8%) and dapagliflozin (N=10,330, 35.2%) between August 2015 and August 2020 in 16 public hospitals in Hong Kong. Patients with diagnosis of diabetes to first prescription of SGLT2 inhibitors (Dx-to-Rx time) ≤12 months were matched with >12 months using propensity score derived from logistic regression. 3,370 matched patients were divided into 4 groups: (i) patients with known ASCVD involving 1 territory (coronary artery, peripheral artery or cerebrovascular disease); (ii) known ASCVD involving >1 territories; (iii) CV risk factor(s) other than diabetes and (iv) no known ASCVD or additional CV risk factors. Incidence rates of 3-point major adverse cardiovascular events (MACE, including non-fatal stroke, non-fatal myocardial infarction and cardiovascular death) were compared between Dx-to-Rx time ≤12 months and >12 months across 4 subgroups during a median follow-up of 2.8 years (IQR 2.2 to 3.4).

Results

Of 29,309 patients (mean age 54.9±11.6 years, female 41.0%), 22.9% had single territory and 6.1% multi-territories ASCVD, 53.3% with additional CV risk factors and 17.7% neither risk factor nor ASCVD. Overall, 19.0% of patients had Dx-to-Rx time ≤12 month; 19.3%, 15.7%, 17.6% and 30.0% in each group, respectively. Overall, Dx-to-Rx time ≤12 months was associated with lower rates of MACE (hazard ratio (HR) =0.27, 95% CI: 0.17–0.42). Subgroup analysis showed similar results in patients with CV risk factors of or known ASCVD but not in patients with neither risk factor nor ASCVD (P for interaction=0.001, Table 1).

Conclusion

Early initiation of SGLT2 inhibitor was associated with significant lower MACE rates in diabetic patients with known ASCVD or additional CV risk factors. The impact was more marked in patients with additional CV risk factors. Our findings suggested early initiation in diabetic patients with known ASCVD and additional CV risk factors.

Funding Acknowledgement

Type of funding sources: None.
Statin use can attenuate the decline in left ventricular ejection fraction during the cardiotoxic chemotherapy: a systemic review and meta-analysis
Authors: Kim J , Miyazaki K
Published: October 2021

Background

Antineoplastic medications such as anthracyclines and trastuzumab are effective in treating various hematologic and solid organ malignancies, however an increased risk of cardiotoxicity in patients has been reported. A decline in left ventricular ejection fraction (LVEF) is a common finding in chemotherapy-induced cardiomyopathy and is sometimes irreversible and lethal. Several agents such as beta blockers and angiotensin-converting enzyme (ACE) inhibitors have shown to reduce the chemotherapy-induced cardiotoxicity in cancer patients. The use of statins, however, to prevent chemotherapy-related cardiotoxicity is not as well studied as other cardioprotective agents. In this study, we aimed to investigate the difference in the degree of decline in the LVEF in patients who received concurrent statin during the chemotherapy compared to those who received chemotherapy alone.

Methods

A systematic search of MEDLINE and EMBASE databases was performed from inception to March 2021 for studies that reported the mean LVEF before and after chemotherapy in patients who received concurrent statin therapy and those who did not receive statin along with the chemotherapy. A random effects meta-analysis was performed to obtain the pooled WMD of LVEF between the intervention (statin with chemotherapy) and the control group (chemotherapy alone) before and after chemotherapy treatments using STATA 16.

Results

Four studies with a total of 297 patients were included in this meta-analysis. Of the 297 patients, 115 patients were in the intervention group and received statin with chemotherapy, while 182 patients were in the control group and received chemotherapy alone. Baseline mean LVEF had no statistically significant difference between the intervention (statin) and the control (no statin) group, and the WMD was −0.38% (95% CI: −1.27 to 0.51, p=0.342). Upon follow-up, the control group patients showed a significantly greater decline in LVEF, with WMD of −6.08% (95% CI: −8.55 to −3.61, p=0.013), compared to the intervention group.

Conclusion

Patients who did not receive statin during the chemotherapy period had a greater mean decline in LVEF from baseline compared to that of the control group after the chemotherapy treatments.

Funding Acknowledgement

Type of funding sources: None.
Increased CaMKII-dependent pro-arrhythmic activity in a novel mouse model of obstructive sleep apnoea
Authors: Schaner B , Lebek S , Hegner P , Maier L S , Arzt M , Wagner S
Published: October 2021

Background

Obstructive sleep apnoea (OSA) is frequently associated with atrial arrhythmias, but detailed mechanisms remain elusive. Most recently, we found an increased CaMKII-dependent pro-arrhythmic activity in patients with sleep apnoea. Since patients suffer from various confounding comorbidities, we have developed a novel mouse model of OSA by tongue enlargement.

Purpose

We tested if mice with OSA exhibit increased atrial CaMKII-dependent pro-arrhythmic activity.

Methods

Polytetrafluorethylene (PTFE) was injected into the tongue of 12 wild-type (WT) and 10 CaMKII knock-out (CKO) mice. 9 WT and 9 CKO mice were used as control without PTFE injection. Inspiratory flow limitations and apnoeas were monitored during murine sleep phases by whole-body plethysmography (Buxco). After eight weeks, isolated atrial cardiomyocytes were incubated with the Ca-sensitive dye FURA-2 AM for 15 min. Regular Ca transients were elicited by electrical field stimulation (1 Hz, 20 V for 4 ms) using epifluorescence microscopy. Pro-arrhythmic non-stimulated events were defined as deviations from diastolic Ca baseline between two stimulated Ca transients.

Results

Sonographic measurements revealed a significant increase in mean tongue diameter from (in mm) 3.7±0.1 to 5.1±0.1 after PTFE injection (n=23, p<0.0001). There was a significant correlation between magnitude of tongue diameter and frequency of apnoeas in OSA mice (p=0.046, r2=0.19, Fig. 1A). Interestingly, we observed a significantly increased frequency of pro-arrhythmic events of (in s–1) 0.06±0.01 in WT OSA mice compared to 0.02±0.01 in WT control mice (p=0.047, Fig. 1B). Similar results were observed at higher stimulation frequencies (2 and 4 Hz). There was a significant correlation of pro-arrhythmic events with inspiratory flow limitations (p=0.03, r2=0.24, Fig. 1C) and with the frequency of apnoeas by strong trend (p=0.06, r2=0.18). In contrast, no increase in atrial pro-arrhythmic events was observed in CKO mice after PTFE injection (for CKO mice after PTFE vs. CKO mice without PTFE, 0.03±0.01 s–1 vs. 0.03±0.01 s–1, p=0.89, Fig. 1B). Accordingly, the correlations between pro-arrhythmic events and both inspiratory flow limitations (p=0.36, r2=0.05, Fig. 1C) and apnoeas (p=0.82, r2=0.004) were completely abolished in CKO mice.

Conclusion

In a novel mouse model of obstructive sleep apnoea, atrial pro-arrhythmic activity was increased in a CaMKII-dependent fashion, which may have therapeutic implications.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Benedikt Schaner / Mr., this work is supported by a research grant of the German Cardiac Society (DGK); Stefan Wagner / Professor, was funded by DFG grants Figure 1