bluuebunny/crossref_metadata_2025 huggingface dataset:
Sacubitril-valsartan activates pAMPK and reduces NLRP3, MyD88, cytokines/growth factors and DAMPs in doxorubicin-treated mice improving longitudinal strain and ejection fraction
Authors: Maurea N , Buccolo S , Iovine M , Paccone A , Luciano A , Barbieri A , Palma G , Maurea C , Quagliariello V
Published: October 2022

Background

Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction.

Purpose

We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function

Methods

Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), LCZ-696 at 60 mg/kg (LCZ, n=6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100), pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.

Results

LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p<0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in LCZ-696-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in LCZ-696-DOXO group vs DOXO (p<0.005).

Conclusion

In this preclinical study, LCZ-696 is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of Sacubitril-valsartan in prevention of cardiomyopathies induced by anthracyclines in cancer patients.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Ricerca Corrente, Ministero della Salute
Pembrolizumab, Ipilimumab and Nivolumab reduces cardiac pAMPK and IL-10, increases vascular NF-kB expression and levels of IL-1b, IL-2 and IL-6 in myocardial tissue
Authors: Maurea N , De Lorenzo C , Passariello M , Iovine M , Buccolo S , Di Mauro A , Cipullo C , Paccone A , Maurea F , Caronna A , Quagliariello V
Published: October 2022

Background

Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality.

Purpose

We analyzed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved.

Methods

C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. pAMPK expression and vascular p65/NF-kB was analyzed through Immunohistochemistry. Cardiac levels of IL-1α, IL-1β, IL-2, IL-6 and IL-10 were quantified through ELISA method

Results

In preclinical models, all ICIs increased p65/NF-kB expression in vascular endothelial cells of mice compared to saline group. IHC analysis indicates that ICIs reduced pAMPK expression in myocardial cells. Notably, tissue levels of IL-1α, IL-1β, IL-2, IL-6 were strongly increased in ICIs group vs saline (p<0.05 vs saline). On the other hand, levels of the anti-inflammatory cytokine IL-10 were strongly reduced (overall reduction of 43.3–54.5% vs saline)

Conclusion

In preclinical models, a short treatment with ICIs is sufficient to confer a pro-inflammatory phenotype in the heart of mice. Furthermore, reductions in pAMPK indicate the inhibition of mitochondrial metabolism after ICIs. Furthermore ICIs induce chemokines involved in fibrosis, myocarditis and vascultitis. These results could indicate new therapeutic candidates aimed to prevent myocardial and vascular damages in cancer patients treated with ICIs.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Ricerca Corrente, Ministero della Salute
Berberine associated to SGLT2i Dapagliflozin synergistically reduces cardiac cell apoptosis during exposure to Trastuzumab through reduction of AGEs and IL-6 and induction of pAMPK
Authors: Maurea N , Buccolo S , Iovine M , Maurea C , Paccone A , Quagliariello V
Published: October 2022

Background

Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio-renal benefits. In the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases. Recent preclinical systematic review indicated that Berberine significantly reduces myocardial infarct size and the incidence of ventricular arrhythmia, improves cardiac function, ameliorates myocardial apoptosis.

Purpose

To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER-2 blocking agent-induced cardiotoxicity

Methods

Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co-incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes-B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL-6 was performed through ELISA method.

Results

Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p<0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal,a marker of AGEs, was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin, improving mitochondrial metabolism. No significant changes in Leukotriene B4 expression were seen. Intracellular levels of IL-6 were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group).

Conclusion

Berberine and Dapagliflozin exerts significant cardioprotective effects in cardiac cells exposed to the HER2-bloking agent Trastuzumab. Berberine and Dapagliflozin in combination induces an anti-inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Ricerca Corrente, Ministero della Salute
Dose-dependency of diclofenac's cardiovascular risks: a series of nationwide emulated trials
Authors: Schmidt M , Arendt-Nielsen L , Hauge E M , Soerensen H T , Pedersen L
Published: October 2022

Background

The dose dependency of the adverse effects of diclofenac remains poorly understood.

Purpose

To examine the dose-related cardiovascular risks associated with diclofenac initiation

Methods

We used Danish nationwide health registries (1999–2018) to conduct a series of emulated trials (n=285). Eligible adults had no recent NSAID fillings, contraindications, or conditions with low adherence. Individuals eligible for inclusion were ≥18 years with (1) ≥90 days continuous prescription records prior to diclofenac initiation (baseline); (2) no NSAID prescriptions ≤90 days before enrollment, and (3) no exclusion criteria. Exclusion criteria reflected likelihood of low adherence to treatment (dementia, schizophrenia, or antipsychotic drug use) and labeled contraindications (ulcer disease/anti-ulcer drugs, gastrointestinal bleeding, inflammatory bowel disease, thrombocytopenia, or heart failure). Initiators of diclofenac were compared to healthcare-seeking non-initiators, but also head-to-head for initiators of high (≥75 mg pills as proxy for ≥150 mg/daily) vs. low dose (≤50 mg pills as proxy for <150 mg/daily). Cox proportional-hazards regression was used to compute the intention-to-treat hazard ratio, as measure of the incidence rate ratio (IRR), of major adverse cardiac and cerebrovascular events (MACCE) within 30 days from initiation.

Results

Among 3,177,484 diclofenac initiatiors, 31% used high and 69% used low dose. Compared with non-initiators, diclofenac initiatiors had a 70% increased rate for MACCE (IRR 1.70, 95% CI: 1.55–1.86), reflecting for the individual MACCE components an increased IRRs of 1.66 (95% CI: 1.54–1.79) for myocardial infaction, 1.32 (1.20–1.45) for ischemic stroke, and 1.69 (1.54–1.86) for cardiac death. The effect for MACCE did not differ between initiators of high (IRR 1.73, 95% CI: 1.51–1.97) and low dose (IRR 1.68, 95% CI: 1.52–1.86) (Figure 1). When comparing high and low dose diclofenac head-to-head, we found no meaningful difference in the IRR for MACCE (1.03, 95% CI: 0.89–1.19), MI (0.99, 0.87–1.11), ischemic stroke (0.95, 0.81–1.11) or cardiac death (1.04, 0.90–1.21) (Figure 2).

Conclusion

Initiation of low- and high-dose diclofenac was associated with a consistent and comparable increase in cardiovascular risk.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation
A blueprint for the continuation of comprehensive cardiac rehabilitation during the COVID-19 pandemic. An Australian single hospital experience
Authors: Zecchin R , Dickson C , Hungerford J , Leow J , Lindsay G , Mander R , Saliba I , Denniss A R
Published: October 2022

Background

The COVID-19 pandemic has disrupted cardiac rehabilitation (CR) around the world with an estimated 50–75% of CR programmes discontinuing or reducing services. Alternative models such as TeleHealth have been encouraged and adopted in place of face to face (F2F) CR. There is a paucity of published data on the continuation of F2F CR during the pandemic.

Methods

A retrospective database audit examined the CR participation rates at an Australian quaternary public hospital during the pre-COVID (2018/2019) and in-COVID (2020/2021) periods. Socio-demographic status, diagnosis at CR entry, CR modalities, and outcome measures (wait times, completion rates) were analysed.

Results

There were no COVID-19 cases or cross infections occurring in CR during the in-COVID period. An audit of 1623 consecutive patients who attended our CR programme (pre-COVID n=760: in-COVID n=863) were included in this study. No significant differences were observed in age, male sex, CR wait times and completion rates between the two groups. Participation rates of patients diagnosed with heart failure (CCF) increased (p=0.02) and those who entered CR after elective PCI decreased (p=0.03) during the in-Covid period in comparison with the pre-COVID period. Total F2F CR was maintained in the in-COVID period compared to the pre-COVID period (85%: 89%, p=not significant (NS)). A significant increase in F2F utilising home walking (p<0.0001) and a decrease in F2F utilising supervised exercise (p<0.0001) was seen. TeleHealth, introduced during the in-COVID period, only contributed to 6% of the total CR participation. More detailed results of this study are presented in Table 1 below.

Conclusions

During the COVID-19 pandemic our CR programme adhered to state health orders, recorded zero transmissions, maintained face to face services, and increased CR uptake only partially due to the introduction of TeleHealth. Our blueprint for the successful continuation of CR during COVID involves having expert nursing management, medical CR champions, dedicated CR gym, and well-established, flexible patient-centric programme modalities.

Funding Acknowledgement

Type of funding sources: None.
Cognitive impairment and low health literacy are associated with poor health outcomes in patients with heart failure
Authors: Wu J , Moser D
Published: October 2022

Background

Cognitive impairment and low health literacy are prevalent in patients with heart failure (HF). Low health literacy is associated with poor health outcomes, such as frequent re-hospitalizations and increased mortality. Little is known about the relationships among cognitive impairment, health literacy, and health outcomes (HF rehospitalization and cardiac death).

Objective

To explore the associations among cognitive impairment, health literacy, and cardiac event-free survival in patients with HF.

Methods

This was a longitudinal study of 614 rural patients with HF (male 59%, age 66±13 NYHA class III/IV: 35%). Cognitive function was measured using the Mini-Cog test. Health literacy was measured by the Short Test of Functional Health Literacy in Adults. HF hospitalizations and cardiac mortality were followed at least 2 years and obtained by patient interview, medical record review, and death certificate review. Chi-squares, t-tests, ANOVA, Kaplan-Meier with log rank tests, logistic and Cox regressions were used for data analysis.

Results

Two hundred and seven patients (34%) had cognitive impairment. Compared to those without cognitive impairment, patients with cognitive impairment were 2.77 times more likely to have low health literacy (P<0.001). Patients were divided into 4 groups based on cognitive impairment or not and adequate/low health literacy: (1) No cognitive impairment with adequate health literacy; (2) cognitive impairment with adequate health literacy; (3) no cognitive impairment with low health literacy; and (4) cognitive impairment with low health literacy. Both cognitive impairment and health literacy independently predicted cardiac event-free survival. Cardiac event-free survival was worst in those with both cognitive impairment and low health literacy compared to patients in any of the other three groups. Patients with cognitive impairment and low health literacy had 3.5 times higher risk of a cardiac event compared to those without cognitive impairment or low health literacy (P<0.001, Figure). Age, income, angiotensin converting enzyme inhibitor use, beta-blocker use, New York Heart Association functional class, left ventricular ejection fraction, BNP level were significantly different among the four cognitive and literacy groups.

Conclusion

Patients with cognitive impairment with low health literacy were at high risk of experiencing a cardiac event. Interventions need to be developed to target high risk patients with cognitive impairment and low health literacy, such as older, low-income patients, to alleviate poor outcomes in patients with HF.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH/NHLBI
Patients and healthcare professionals views on injectables for cardiovascular disease
Authors: Lee G , Durante A , Vellone E , Dellafiore F , Cagginelli G , Khan M , Baker E E , Khatib R
Published: October 2022

Introduction

Injectable medicines are increasingly used to manage risk factors for cardiovascular (CV) events, such as PCSK-9 inhibitors in dyslipidaemia and GLP-1 agonists in diabetes. However, there is a paucity of data around the administrative and clinical practicalities when using these injectables, and limited information on patient and healthcare professionals' perceptions.

Purpose

To identify the facilitators and barriers on the use of injectable therapies with CV benefits by undertaking interviews with patients, caregivers and healthcare professionals (HCPs).

Methods

Interviews were conducted via telephone and using MS Teams due to Covid-19 restrictions in the United Kingdom (London and Leeds) and Italy (Rome and Milan) in 2021. Coding was undertaken using NVivo and thematic analysis performed.

Results

A total of 56 patients were interviewed: 30 in the U.K. (mean age 66 yrs, 60% male) and 26 patients in Italy (mean age 63 yrs, 80% male) and 11 caregivers (mean age 59 yrs, 73% female). A total of 38 HCPs were interviewed, 19 in each country and composed of physicians (n=18), pharmacists (n=10), nurses (n=9) and pharmacy technician (n=1). Three distinct themes were identified: (i) Organisational and governance issues - relating to prescribing restrictions and availability of the drugs locally (PCSK9i are initiated and supplied from hospitals) and lack of communication between hospital and primary care setting; (ii) Clinical issues around HCPs' skills and experience - including: lack of experience with these injectables, lack of time to provide education to patients and caregivers, therapeutic inertia (HCPs not adopting a change in practice despite the evidence or due to bureaucratic restrictions) as well as lack of knowledge on long-term effects, and finally (iii) Patient-related issues - relating to behaviours and beliefs such as reluctance about using injectable therapies, and lack of education about these injectables in terms of indications/clinical benefits for use. Despite some differences in the prescribing of these injectables in the two countries, the analysis captured similar facilitators and barriers. Facilitators included prior use of injectables (e.g. insulin), and the ability to reach a clinical target of lower cholesterol by having just a “one shot”. HCPs stated that access to rapid pathology tests would aid uptake of injectables with CV benefit as well as having educational tools on these injectables in practice.

Conclusion

This qualitative study identified barriers to initiation, continuation, and adherence with injectable therapies with CV benefits but also highlighted areas where changes can be made especially around education and support for patients and HCPs.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): ACNAP education grant. Sponsored by Amgem and Novo Nordisk
Changes in self-care maintenance during quarantine in patients with heart failure
Authors: Klompstra L , Almenar L , Deka P , Munoz-Gomez E , Lopez-Vilella R , Pathak D , Westas M , Marques-Sule E
Published: October 2022

Background

Patients with heart failure (HF) experience challenges in self-care that contribute to poor quality of life and high health care utilization. The COVID-19 pandemic required HF patients, especially living in countries with strict lockdowns and quarantines, to change their lifestyle including health promoting behaviors.

Purpose

To assess changes in self-care maintenance in patients with HF changed during quarantine compared to before quarantine. We hypothesized that the self-care maintenance behavior physical activity was most effected during quarantine.

Method

This is a cross-sectional survey study. From the medical chart, patients' disease severity (NYHA-class), ejection fraction and comorbidities were collected. Self-care maintenance was assessed using subscale Self-Care of Heart Failure Index 6.2. The total score ranges from 0–100, where 70 or higher is seen as having good self-care maintenance. With all the questions in the self-care maintenance scale a question was added: Did this change due to the COVID-19 pandemic? Patients could answer yes or no. When patients answered yes, they were asked the elaborate. Patients self-reported physical activity, before and during the pandemic, using the International Physical Activity Questionnaire (short form). Descriptive analyses were used for self-care maintenance, content analysis was applied for the qualitative data. Paired sample t-test were performed to assess the change in the total physical activity.

Results

In total, 120 patients with HF were included in this study (mean age was 79±13, 39% female, 78% NYHA-class I/II). Patients had a mean self-care maintenance of 32 (±6). No participant had good self-care maintenance (score of 70 or higher). Patients were non-adherent to regular physical activity (77%, n=92), keeping weight down (74%, n=89) and weighing themselves (66%, n=79) during quarantine (Figure). Behaviors which changed the most included keeping medical appointments (81%) and regular exercise (82%). Significantly higher levels of physically active was noticed before quarantine (776 Mets-minutes) compared to during quarantine (106 Mets-minutes) (p<0.01). The change in self-care maintenance was explained by change in motivation and self-confidence. Because of the pandemic and the quarantine, patients reported not being able to rely on health care and their usual social support system. Patients tried to create new habits when trying to maintain their self-care.

Conclusion

Patients with HF reported experiencing low self-care maintenance during quarantine due to not being able to go to medical appointments and decrease in physical activity. Public health policies during crisis events such as a pandemic should strive to provide support in coping with these changes and offer alternative ways of maintaining their self-care maintenance, especially with physical activity.

Funding Acknowledgement

Type of funding sources: None.
A service evaluation of patch technology compared with traditional holter monitoring in a stroke pathway
Authors: Orava S , Chauhan M , Stain N
Published: October 2022

Background

Atrial fibrillation (AF) is a known risk factor for embolic stroke. Establishing a diagnosis of AF will guide clinical decision making and help with downstream secondary stroke prevention. Patch technology is increasingly used for long-term cardiac monitoring for arrhythmia detection, as healthcare organisations look for new innovative ways to streamline service delivery. We were selected as a host site to evaluate the service and patient benefits of Zio XT in AF detection for cryptogenic stroke, as part a Artificial Intelligence Award.

Purpose

To evaluate the service and patient benefits of patch technology versus traditional Holter in a Stroke / TIA pathway.

Methods

The Zio XT data were collected between March and December 2021. A total of 778 patients were included. We only selected patients who were referred for a long-term ambulatory monitoring following a recent diagnosis of stroke or transient ischaemic attack (TIA) of an unknown cause (cryptogenic). The stroke pathway operates across three sites and all were included. We undertook a retrospective analysis of our previous pathway using Holter monitoring and sampled 100 stroke / TIA patients who underwent 24–72 hours of monitoring between January to June 2019. In order to obtain the requisite data a variety of sources were scrutinised: referral letters, test reports, patient medical records, internal clinical systems and third-provider platforms.

Results

The comparison of the ECG technologies showed the Zio XT used less staff time. We found a 50% reduction in-clinic monitor fitting when compared with Holter. Zio XT were all analysed by the provider staff resulting in significant savings in service resource time for analysis. The Zio XT had a faster test turnaround time (referral to report available), 19 days (inclusive of 14 days wear time) for Zio compared with 60 days for Holters. The rapid Zio turnaround led to a 27.5% reduction in repeat clinic appointments, due to results being unavailable for the consultation (table 1). Zio XT also had fewer repeat testing due to inconclusive results, 1% for Zio versus 16% for Holter. AF yield did not vary significantly between technologies, 3% yield for both Holter and Zio, which could be due to the young mean age of the stroke/ TIA the patient cohort: 63.8 years for Holter versus 62.9 years for Zio XT.

Conclusion

Introducing new ECG technologies such as Zio XT could increase outpatient and diagnostic capacity due to patches being more readily available than Holters, reduced reliance on clinical staff for fitting and analysis as well as fewer repeat clinic appointments. Overall, access to rapid long term cardiac monitoring has benefits over traditional Holter monitoring for TIA/stroke patients and service delivery.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): AI award from the Accelerated Access Collaborative (ACC) in partnership with NHSX and National Institute for Health Research
Referrals to palliative care for cardiovascular patients: a 10-year longitudinal retrospective study
Authors: Ecarnot F , Giffard M , Seydou Sall F , Van Bulck L , Becoulet N , Seronde M F
Published: October 2022

Background

Patients with cardiovascular diseases have a significant symptom burden and often have a progressive course towards end-stage disease and ultimately, death. For this reason, consensus guidelines advocate early integration of palliative care into the care for cardiovascular patients, especially those with heart failure. However, palliative care involvement in the care of cardiovascular patients remains suboptimal, whereby only a small proportion of patients are referred to palliative care specialists, and often too late in the disease course. We aimed to examine the current situation and describe the profile, circumstances of death, and time of referral to palliative care of cardiovascular patients over a 10 year period in our unit.

Methods

This retrospective study included all patients with cardiovascular disease who were referred to the mobile palliative care team by the cardiology unit, in a single, large University Hospital in France between 2010 and 2020. All data were extracted from the medical hospital files. We recorded vital status, day of birth, time of referral to palliative care, day of death, and medical diagnoses. We noted whether patients had advance directives (AD).

Results

A total of 148 patients were identified; full data were available for 144 (97.3%). Of these, 136 (94.4%) died, while 8 (5.6%) were still alive in March 2022. The mean age at the time of death was 75±14 years. The median time between referral to palliative care and death was 9 days (interquartiles, 2, 41.5). We noted the following underlying diseases (patients could have more than one diagnosis): 111 (77%) had heart failure, 58 (40.2%) had ischemic heart disease, 55 (38.2%) had valvular heart disease, 39 (27%) had diabetes, 37 (25.7%) had chronic kidney disease, 30 (20.8%) had pulmonary hypertension, 17 (11.8%) had chronic obstructive pulmonary disease. In addition, 78 (54%) had at least one documented episode of atrial fibrillation, 27 (18.7%) had had a stroke. Place of death was available for 119 patients (82.6%) (Figure): The majority (73, 61.4%) died in the Cardiology department of our hospital; only 17 (14.3%) died at home (see Figure 1). Only 4 patients (2.7%) had documented AD.

Conclusion

This study suggests that palliative care is still widely under-used in cardiology patients, and is often initiated very close to the time of death, and mainly for heart failure patients. A large proportion of patients still die in the hospital setting. Further, prospective studies are warranted to investigate whether these dispositions corresponds to patients' wishes, and whether earlier initiation of palliative care could improve quality of life for cardiology patients with end-stage disease.

Funding Acknowledgement

Type of funding sources: None.
Estimation of Cardiorespiratory fitness using a using a chest mounted accelerometer
Authors: Schmidt S E , Hansen M T , Roemer T , Soegaard P , Helge J W
Published: October 2022

Cardiorespiratory fitness expressed as maximal oxygen consumption (V̇O2 max) is a strong predictor of cardiovascular health. However, quantification of cardiorespiratory fitness by cardiopulmonary exercise (CPX) assessment is complex and costly and therefore not suitable in most clinical settings. In the current study we develop and validate an algorithm for estimation of V̇O2 max using seismocardiography (SCG-V̇O2 max). SCG is measurement of precordial vibrations using an accelerometer.

Methods

SCG recordings and results from ergometer CPX testing of V̇O2 max in 300 subjects from six clinical studies were combined in a database. 83 subjects underwent repeated measurements sessions across several days. SCG was obtained using a sensitive accelerometer, located on the lower sternum at the Xiphoid protrusion and subjects were placed in a supine position. 5 subjects were excluded due to cardiovascular disease, or missing data. A machine learning algorithm was devolved for estimation of V̇O2 max in a training set including 221 subjects. The remaining 74 subjects were included in a test set for validation. Correlation and accuracy between SCG-V̇O2 max and ergometer CPX V̇O2 max assessed and day to day variation was assessed in subjects who underwent multiple ergometer CPX sessions.

Results

In 144 recordings from 74 test set subjects SCG-V̇O2 max was 45.0±9.3 ml/min/kg which was comparable to the ergometer CPX V̇O2 max at 44.3±10.1 ml/min/kg (p=0.09) and correlation between ergometer CPX V̇O2 max and SCG-V̇O2 max was r=0.875. Mean average percentage error was 8.7%. Day to day variation measured as the within-subjects-standard-deviation was 1.2 ml/min/kg for SCG-V̇O2 max and 1.7 ml/min/kg for ergometer CPX.

Conclusions

SCG based estimation of VV̇O2 max is a novel, low cost, easy to use and accurate estimation method of CRF with a high level of reproducibility. SCG-V̇O2 max can potentially facilitate that cardiorespiratory fitness becomes an integrated part of modern health assessment.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): VentriJect A/S DK
Effects of lockdown on physical activity and arrhythmia burden in patients with an implantable cardioverter-defibrillator: the COVID-19 Lockdown ICD-Carelink (CLIC) study
Authors: Ghossein M A , Linz D , Van Kraaij D J W , Van Stipdonk A M W , De Melis M , Vernooy K , Heijman J
Published: October 2022

Background

Both COVID-19 and the measures taken to control the pandemic may significantly affect cardiovascular health. The effects of a lockdown on physical activity and its potential consequences for arrhythmia burden remain largely unknown.

Purpose

In this study, we investigated the effect of the lockdown during the first COVID-19 wave on patients' physical activity and arrhythmia burden.

Methods

All patients with an ICD connected to a Carelink home-monitoring system from two Dutch hospitals were included. Anonymized data on physical activity, heart rate, and occurrence of ventricular tachycardia/fibrillation (VT/VF), and atrial fibrillation/tachycardia (AF/AT) were obtained and were compared between March-April 2020 (lockdown) and March-April 2019 (reference) within each patient. The study was approved by the local ethics committee.

Results

The ICDs of 531 patients registered significantly less activity during de lockdown period compared to the reference period (210±104 min vs 182±103 min, p<0.0001, Figure 1, panels A and B), while weather conditions improved (1A). Daytime and nighttime heart rates were significantly lower during lockdown compared to the reference period (71.3±9 bpm vs 72.6±9 bpm, p<0.0001 and 63.4±9 vs 63.8±9, p=0.02, respectively). AF/AT burden increased (Figure 2A) while number of VT/VF episodes decreased (2B). There was no significant difference in number of NSVT episodes.

Conclusion

During the lockdown in the first COVID-19 wave, the Carelink system revealed significantly less activity, increase in AF/AT burden and decrease in VT/VF episodes. Further investigation is needed to understand the relationship between physical activity and the occurrence of arrhythmias in ICD patients.

Funding Acknowledgement

Type of funding sources: None.
Multi-category classification of left ventricle ejection fraction using a convolutional neural network
Authors: Carter R , Hardway H , Johnson P , Douglass E , Adedinsewo D
Published: October 2022

Background

Screening for left ventricular (LV) systolic dysfunction (defined as ejection fraction ≤35%) based on data from a standard 12-lead electrocardiogram (ECG) has become well established when standard digital ECGs are available–8 independent leads sampled at least 250 hertz for 10 seconds. As the algorithm has been incorporated into various clinical scenarios and ancillary research projects, a limitation of the binary classification at 35% has become apparent.

Purpose

The objective of this study was to develop and validate a deep learning-based algorithm that would classify LVEF into three categories based on only the digital ECG input.

Methods

After IRB approval, native digital resting ECGs acquired between 1/1/2010 and 12/31/2021 on patients seen in Mayo Clinic in Jacksonville were extracted from the institutional electronic ECG database management system (MUSE, GE Healthcare). These ECGs were matched with transthoracic echocardiograms obtained up to four days prior or 30 days after the ECGs acquisition. A convolutional neural network consisting of 8 layers of convolutions, batch normalization and pooling was trained using Keras and Tensorflow with hyper-parameter optimization for L1 and L2 regularization, learning rate adjustments, and class weights to predict three classes of LVEF: ≤35%, 36–51%, and ≥52% based on clinical relevance. The primary measure of overall performance was the detection of LVEF ≤35%; however, the triad of model predictions was also considered in translating the model output to human interpretable findings.

Results

A total of 30,153 patients (60,169 ECG pairings; mean age 63 years; 48% male) were randomly split at the patient level into training (24,172 patients), validation (2,973 patients) and testing (3,008 patients). The trained model provided robust discrimination in the withheld testing data – AUROC of 0.941 (95% CI: 0.931 to 0.950). Using the optimal model threshold based on Youden's index from the validation data (0.186), sensitivity and specificity were estimated to be 87.9% (95% CI: 83.8% to 91.2%) and 86.3% (95% CI: 85.4% to 87.2%) in the testing data. In instances where discordant predictions were observed, the posterior distribution of model probabilities provide additional insights into the possible underlying value of LVEF (Figure 1).

Conclusions

The utilization of a multi-category deep learning classification model for the detection of reduced ejection fraction adds new dimensions to the use of AI technologies on digital ECGs. This work shows high discrimination can still be obtained when using three classes of LVEF.

Funding Acknowledgement

Type of funding sources: None.
Prognostic yield of stress CMR to evaluate chronic coronary syndromes: a systematic review and meta-analysis
Authors: Bisaccia G , Khanji M Y , Gallina S , Petersen S E , Bucciarelli-Ducci C , Ricci F
Published: October 2022

Background

Assessment of ischemia with stress cardiovascular magnetic resonance (CMR) imaging is recommended in patients with stable chest pain and intermediate or high pre-test probability of coronary artery disease (CAD).

Purpose

To provide an updated synthesis on prognostic significance of stress CMR imaging in patients with stable chest pain and suspected or known CAD.

Methods

After prospective registration and approval of the study protocol, we performed a systematic review and meta-analysis of studies published between 2000 through 2021, enrolling ≥100 patients, and reporting outcome data of CAD patients undergoing stress CMR. Odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause death, cardiovascular (CV) death and major adverse cardiac events (MACE: CV death and myocardial infarction), were pooled through inverse variance random-effects meta-analysis to compute summary effect size. Annualized event rates (AERs) were extracted from each study and compared by χ2-statistic. A warranty period was defined as the time interval with an AER <1%.

Results

We identified a total of 33 studies pooling an overall tested population of 68920 patients (mean age 62 years; 56% males; known CAD 32%; 386117 person-years). Ischemia was found in 13617 (20%). Mean follow-up was 3.5±2.1 years. Presence of ischemia was associated with increased risk of all-cause death (OR 2.0 95% CI: 1.7–2.3), CV death (OR 6.4 95% CI: 4.5–9.1), and MACE (OR 5.0 95% CI: 3.6–6.8). Cumulative AERs for all-cause death, CV death and MACE were 2.97%, 2.51%, and 3.99% in patients with ischemia, and 1.40%, 0.59%, and 0.98% in patients without ischemia, respectively (p<0.0001 for all comparisons).

Conclusion

Stress CMR imaging yields robust prognostic information in patients with suspected or known CAD. Presence of ischemia is associated with increased risk of all-cause death, CV death and MACE. Patients with negative stress CMR have a very low risk (<1%) of CV death and MACE with a warranty period of at least 3.5 years.

Funding Acknowledgement

Type of funding sources: None.
Predicting cardiovascular risk factors from facial & full body photography using deep learning
Authors: Knorr M S , Neyazi M , Bremer J P , Brederecke J , Ojeda F M , Ohm F , Augustin M , Blankenberg S , Kirsten N , Schnabel R B
Published: October 2022

Introduction

The early and easy detection of pathological cardiovascular phenotypes can lead to an early medical intervention and thus slow or limit the development of cardiovascular diseases. As full body photographs are easily obtainable without the need of medical expertise, this modality holds the potential to be viable for screening of populations.

Purpose

Utilizing data from a population-based study, we examined the possibility to detect cardiovascular risk factors from total body photographs using deep learning.

Methods

A population-based cohort study was utilized. The first data release provides facial and full body photographs in dermatologic standard poses of 6500 participants (median age 62.0 years, 49.6% men) and corresponding cardiovascular risk factors. Here, we focus on the most prevalent ones: smoking status (prevalence: 19.0%), hypertension (35.3%) and diabetes (8.2%). Here we employ a 2D-Convolutional Resnet-18 Neural Network for predicting the risk factors. It receives the full body image, the facial image and age and sex as input. We compare this to a logistic regression model only including sex and age. Logistic Regression and Neural Network are employed in a 5-fold validation scheme and t-tested for significance.

Results

Our model provided a good detection of arterial hypertension (AUC 0.711, CI 0.684–0.739), while a logistic regression on age and sex yielded a significantly worse prediction (AUC 0.681, CI 0.679– 0.683, p<0.05). Additionally, it made a good detection of a positive smoking status (AUC 0.733, CI 0.711–0.754), being significantly better than a respective logistic regression on age and sex (AUC 0.598, CI 0.597–0.6, p<0.001). Lastly, it classified diabetes well (AUC 0.744, CI 0.724–0.764, p<0.001) in comparison to the logistic regression (AUC 0.681, CI 0.679–0.683, p<0.001).

Conclusion

The presence of cardiovascular risk factors can be detected from a total body photograph. As total body photographs can be easily obtained with a majority of digital cameras, including smart phones, this model represents a potentially widely applicable diagnostic tool to easily screen large parts of the population for relevant cardiovascular risk factors, making an early medical intervention possible.

Funding Acknowledgement

Type of funding sources: None.
Cardiovascular disease risk prediction via machine learning using mental health data
Authors: Dorraki M , Liao Z , Abbott D , Psaltis P J , Baker E , Bidargaddi N , Van Den Hengel A , Narula J , Verjans J W
Published: October 2022

Background

Robust and accurate risk prediction models are much needed in cardiovascular disease. It is well-known that mental health is associated with the risk of developing cardiovascular disease. It is unknown whether mental health markers can enhance existing risk prediction models for cardiovascular disease.

Purpose

The main purpose of this study was to assess capability of mental health factors along with traditional risk factors to be used in cardiovascular predictive machine learning models, and to develop a combined machine learning approach using both traditional risk and psychological factors in 375,145 participants of the UK Biobank.

Methods

A comprehensive Pearson correlation analysis is carried out on UK Biobank data. Subsequently, an ensemble model containing decision tree, random forest, XGBoost, support vector machine (SVM), and deep neural network (DNN) classification approaches was built to predict cardiovascular diseases (CVD) in UK Biobank participants. The model was first trained using traditional cardiovascular risk factors, and subsequently trained using a combination of cardiovascular risk and psychological factors.

Results

The correlation analysis revealed that there is a correlation between CVD and mental health factors suggesting the potential of mental health application for machine learning models. Our ensemble machine learning model was able to predict CVD with an accuracy of 73.49% using CVD risk factors alone. However, by combining psychological factors with CVD risk factors in the training data, an improved accuracy of 95.70% was achieved. The accuracy and robustness of ensemble machine learning model outperformed any of five constituent learning algorithms alone.

Conclusions

Our results suggest that mental health assessment data along with traditional risk factors provides a powerful, safe and affordable machine learning model enrichment that can be used for state-of-the-art prediction of CVD.

Funding Acknowledgement

Type of funding sources: None.
Diagnostic accuracy of stress CMR to evaluate chronic coronary syndromes: an updated meta-analysis
Authors: Bisaccia G , Khanji M Y , Gallina S , Petersen S E , Bucciarelli-Ducci C , Ricci F
Published: October 2022

Background

Stress cardiovascular magnetic resonance (CMR) imaging is utilised for the evaluation of patients with stable chest pain and intermediate or high pre-test likelihood of coronary artery disease (CAD).

Purpose

To provide an updated synthesis of diagnostic accuracy of stress CMR imaging for the diagnosis of anatomically and functionally significant CAD in patients with stable chest pain and suspected or known CAD.

Methods

After prospective registration and approval of the study protocol, we performed a systematic review and meta-analysis of studies published between 2000 through 2021, enrolling ≥100 patients, and reporting on the diagnostic accuracy of stress CMR imaging to diagnose anatomically and functionally significant CAD with invasive coronary angiography (ICA) or ICA and fractional flow reserve (FFR <0.80) as the reference standard. The novel split component synthesis method was used through the SCSmeta function in R. The meta-analysis yielded pooled diagnostic indicators including diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (pLR), negative likelihood ratio (nLR) and area under the curve (AUC).

Results

We identified a total of 32 studies pooling an overall population of 7,678 individuals (mean age 62 years, 70% males, CAD prevalence 52%). Compared with ICA (29 studies, 7,360 patients), stress CMR yielded a pooled DOR of 19.2 (95% CI: 12.5–29.4), a sensitivity of 84% (95% CI: 79–88%), a specificity of 79% (95% CI: 73–84%), a pLR of 3.9 (95% CI: 3.0–5.3), a nLR of 0.2 (95% CI: 0.2–0.3), and an AUC of 0.81 (95% CI: 0.78–0.84) for the detection of anatomically obstructive CAD. Compared with ICA and FFR (8 studies, 1,196 patients), stress CMR yielded a pooled DOR of 26.4 (95% CI: 10.6–65.9), a sensitivity of 81% (95% CI: 68–89), a specificity of 86% (95% CI: 75–93%), a pLR of 5.8 (95% CI: 3.0–11.4), a nLR of 0.2 (95% CI: 0.1–0.4), and an AUC of 0.84 (0.77–0.89) for the detection of functionally obstructive CAD. Higher diagnostic accuracy was observed for 3 Tesla myocardial perfusion imaging studies to detect both anatomically and functionally obstructive CAD, with pooled DORs of 24.3 and 33.2, respectively.

Conclusions

In patients with stable chest pain and known or suspected CAD, stress CMR imaging yields high diagnostic accuracy to detect both anatomically and functionally obstructive CAD. Stress CMR perfusion imaging at 3 Tesla is to be associated with overall greater diagnostic accuracy.

Funding Acknowledgement

Type of funding sources: None.
The use of handheld ultrasound device in cardiac examination of patients with history of COVID-19
Authors: Filipiak D , Kasprzak J D , Lipiec P
Published: October 2022

Background

Clinical usefulness of Handheld Ultrasound Device [HUD] was previously confirmed in numerous clinical scenarios. During the previous two years Covid-19 patients become a focal point of healthcare worldwide. The assessment of long term consequences of this infection is bound to overload already burdened healthcare system.

Purpose

To assess clinical usefulness of HUD as an adjunct to physical cardiac examination of patients with history of COVID-19.

Methods

Study population consisted of randomly selected patients with no symptoms of cardiovascular pathology, who had been hospitalized due to COVID-19 one year prior to examination. Physical examination and clinical assessment was augmented with short examination with the use of HUD, which included: visual evaluation of the global and regional LV function, measurement of RV size, screening for the significant valve defects and the presence of pericardial effusion. Subsequently full echocardiographic examination with the use of high-end workstation was performed, which results were treated as reference.

Results

54 patients (35 men, mean age 63±13 years) were enrolled into the study. In clinical examination no significant cardiovascular abnormalities were discovered. In 30 [56%] of patients cardiac abnormalities in HUD examination were detected. In 18 patients [33%] LV function assessment was not performed, due to insufficient quality of registered view. In the remaining group significant impairment of LV ejection fraction (<50%) was detected in HUD examination in 3 [6%] patients (2 confirmed in full examination, positive predictive value [PPV] 57%, negative predictive value [NPV] 97%, AUC 0,82±0,17, P 0,057). WMA were diagnosed in 6 [11%] patients (4 confirmed in full examination, PPV 84% NPV 78%, AUC 0,69±0,17, P 0,02). RV enlargement was identified in 21 [39%] patients (PPV 57%, NPV 97%, AUC 0,85±0,05, P<0,0001), mild pericardial effusion in 3 [6%] patient (1 confirmed in full echocardiographic examination; 2 false positive, no false negative), at least moderate mitral/tricuspid/aortic valve insufficiency in 7 [13%] patients (3 confirmed, 4 false positive cases, no false negative). A total mean time of the heart and lungs HUD examination was 2,1±0,6 minute.

Conclusion

Cardiac abnormalities exposed in brief assessment with the use HUD are a relatively common finding in asymptomatic patients previously hospitalized due to COVID infection in a 1-year follow-up, despite normal physical examination. Normal HUD examination excludes the presence of significant cardiac abnormalities with high probability. However one should keep in mind a relatively high percentage of false positive results, which may lead to an exceeding number of patients referred for a full echocardiographic examination.

Funding Acknowledgement

Type of funding sources: None.