bluuebunny/crossref_metadata_2025 huggingface dataset:
Using coronary artery calcium to guide cardiovascular risk reduction: insights from the CAUGHT-CAD trial
Authors: Venkataraman P , Marwick T , Marwick T , Huynh Q , Huynh Q
Published: November 2020

Introduction

International guidelines now recognise the value of CT coronary artery calcium scoring (CAC) to guide statin prescribing decisions. However, evidence is conflicting on CAC's potential to reinforce clinical advice, promote adherence and facilitating positive health behavioural change.

Purpose

We sought to assess the impact of a CAC-guided statin treatment protocol on cardiovascular risk at 12 months.

Methods

The CAUGHT-CAD trial recruited 455 asymptomatic, statin-naïve individuals at intermediate risk CVD risk with a family history of premature coronary artery disease (CAD) and CAC scores between 1 and 400. Participants were randomised to visualisation of their CAC or remain blinded. Both groups were provided standard risk factor advice. We calculated the 10-year SCORE predicted risk based on participant's baseline and 12 month risk factor profile. Paired t test and regression analysis was used to assess change in predicted risk both within and between treatment group.

Results

CAC-visualisation and statin treatment resulted in a 0.45% absolute and 21% relative risk reduction in predicted SCORE risk at 1 year. The CAC exposure group demonstrated 2.78 mmHg reduction in systolic blood pressure compared to the blinded group (p<0.01); accounting for 25% of the predicted absolute risk reduction despite both groups reporting the same level of dietary and physical activity goals achieved. 9 blinded participants who were commenced on statins off-protocol showed attenuated reductions in lipids compared to the CAC exposed group (total cholesterol: m-0.5 vs. −1.5 mmol/L, p<0.01; LDL −0.6 mmol/L vs. −1.4 mmol/L, p<0.01) suggesting poorer adherence.

Conclusion

CAC visualisation can augment primary CVD prevention by improving systolic blood pressure and absolute reduction in lipids with statin treatment.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): NHMRC project grant
Echocardiographic phenogrouping by machine learning for risk stratification in the general population
Authors: Sabovcik F , Cauwenberghs N , Vens C , Kuznetsova T
Published: November 2020

Background

Improved taxonomical classification of routinely measured echocardiographic parameters is needed for better phenotypic characterisation of the asymptomatic stages of cardiac maladaptation. This would create opportunities to intervene early in the course of the heart disease and prevent progression to more advanced stages and adverse events.

Purpose

We tested the hypothesis that an unbiased clustering analysis utilizing echocardiographic indexes reflecting left heart structure and function and hemodynamic measurements could identify phenotypically distinct groups of asymptomatic individuals in the general population.

Methods

We prospectively studied 1407 community-dwelling individuals (mean age, 51.0 years; 51.5% women), in whom we performed clinical and echocardiographic examination at baseline and collected cardiac events on average 8.5 years later. Cardiac phenotypes that were correlated at r>0.8 were filtered, leaving 15 less redundant echocardiographic and hemodynamic features for phenogrouping. We employed two methods of unsupervised machine learning: agglomerative hierarchical clustering and Gaussian mixture using expectation minimization algorithm. The optimal number of phenogroups was chosen based on the combination of the cohesion/separation approach (silhouette index) and stability. Cox regression was used to demonstrate the clinical validity of phenogroups.

Results

Overall, both methods agreed with respect to cluster assignment (RI=0.75). Unbiased clustering analyses classified study participants into 3 distinct phenogroups that differed markedly in cardiac structure/function indexes and hemodynamics used for cluster analysis (Figure, left panel). Indeed, phenogroup 3 had the worst left ventricular diastolic function (ie, lowest e' velocity and left atrial reservoir strain, but highest E/e', deceleration time, and left atrial volume index), highest left ventricular mass index, as well as highest systolic blood pressure and pulse pressure (Figure, left panel). The phenogroups were also different in other clinical characteristics and incidence of cardiac events (Figure, right panel). Even after adjustment for traditional risk factors, phenogroup 3 had the highest risk of cardiac events as compared to cluster 1 (Figure, right panel).

Conclusions

Unsupervised learning algorithms integrating routinely measured cardiac imaging and hemodynamic data can provide a clinically meaningful classification of cardiac health in asymptomatic individuals. This approach might facilitate early detection of cardiac maladaptation and improve risk stratification.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders
Characteristics of cardiac rehabilitation programs in Latin America and the Caribbean, and estimation of capacity and needs in the region
Authors: Chacin A , Grace S.L , Anchique-Santos C , Supervia M , Turk-Adawi K , Britto R , Scantlebury D , Araya-Ramirez F , Gonzalez G , Burdiat G , Salmon R , Mamataz T , Medina-Inojosa J , Lopez-Jimenez F
Published: November 2020

Background

Cardiac rehabilitation (CR) is an established model of cardiovascular (CV) prevention that has proven benefits. Availability, characteristics and need of CR programs in Latin-American and Caribbean (LAC) countries remains poorly characterized. This study aims to establish the availability, capacity, density and aspects of CR delivery in LAC.

Methods

A cross-sectional survey was administered to CR programs in 24 LAC. Local CV organizations and societies identified CR programs. Characteristics of individual CR program were reviewed including: funding sources, core components, healthcare providers, and dose (number of sessions per weeks X total number of weeks) of CR. National CR capacity (median number of patients a program could serve per year X number of programs per country), density (Ischemic Heart Disease [IHD] incidence per year/ national capacity), need (IHD incidence per year- national capacity) and occupancy (median number patients program served per year/national capacity) were computed based on survey responses.

Results

At least one CR program was identified per LAC country (total 255 programs across 24 countries). Data was collected in 20 of the 24 countries. Responses were received from 139/255 programs (median program response rate=55%; Table 1). Over 50% (n=73) of programs were funded by multiple sources (government, hospital/clinic, private health insurance); Self-payment was reported by 63% programs, in which 24 (33.8%) patients paid over 50% of the cost. Guideline-indicated conditions were accepted in 77% or more programs. Physiotherapists (n=106, 76.3%), cardiologists (n=105, 75.5%) and dietitians (n=79, 56.8%) were the most common healthcare providers on CR teams. Regionally, programs offered 9 (IQR = 8–10) core components (patient education, exercise prescription and initial assessment delivered by nearly all programs). Median CR was 36 (IQR = 24–56) sessions/patient. Twenty-seven (20.9%) programs offered alternative CR models (e.g., home or community-based and hybrid models). Median national capacity was 500 CR spots/country (IQR= 200–2300). Regional density was 1 CR spot per 24 incident IHD patients per year. Greatest need in absolute terms for CR was observed in Brazil, Dominican Republic and Mexico (all with >150,000 spots needed per year to manage incident IHD patients; Table 1). Occupancy ranged from over 100% in Colombia to 15% in Chile (median=60%, IQR = 32%–81%), Table 1.

Conclusion

In LAC countries, there is very limited capacity to meet the need for CR. Nature of CR services varied regionally.

Funding Acknowledgement

Type of funding source: None
A predictive model of pcsk-9 inhibitors eligibility in coronary and dyslipidemic patients
Authors: Dima I , Soulis D , Terentes-Printzios D , Skoumas I , Aznaouridis K , Tousoulis D , Vlachopoulos C
Published: November 2020

Purpose

Dyslipidemia is a major cardiovascular risk factor and treatment is mostly based on statins and ezetimibe. PCSK-9 inhibitors are monoclonal antibodies that reduce LDL-c levels and have shown significant reduction of cardiovascular risk in high risk patients. Data regarding potential eligibility for PCSK-9, is limited especially when referring to the recent guidelines.

Methods

Eligibility was calculated using a proprietary adjustable software, which stores data and patient information and thus by using different criteria it can determine potential candidates for PCSK-9 inhibitors. For this purpose, 2000 patients were enrolled prospectively. Our study population was comprised of inpatients diagnosed either with acute coronary syndromes (ACS) or with chronic coronary disease (cCAD) and outpatients from Lipids' Clinic (OLC) (n=407, n=1087, n=506, respectively). In order to test eligibility, three different LDL thresholds were used in our model for high and very high risk groups: a) 70mg/dl and 55mg/dl, respectively, as recommended by the recently updated 2019 ESC/EAS Guidelines for Dyslipidaemia b) 100mg/dl and 70mg/dl, respectively, as recommended by the 2016 ESC/EAS Guidelines for Dyslipidaemias and c) 130mg/dl and 100mg/dl respectively, as mandated by our National Health Care system but also applicable in other countries.

Results

The eligible percentages for the three thresholds were 18.85%, 9.75% and 2.15%, in the total population (TP) respectively and it varied according to clinical status. Subgroup analysis of eligible population revealed the trends in each group (Figure 1). The increase toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter.

Conclusions

Our predictive model provides a realistic estimation of PCSK-9 inhibitors potential eligibility in coronary and dyslipidaemic patients and thus it can become a useful tool for the use of PCSK-9 in health care systems.

Figure 1

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Amgen Hellas LTD
Inter-individual variability in LDL-C reductions with inclisiran – data from ORION-10 and ORION-11
Authors: Wright R.S , Raal F.J , Kallend D , Stoekenbroek R , Koenig W , Leiter L.A , Landmesser U , Schwartz G.G , Wijngaard P.L.J , Kastelein J.J.P , Ray K.K
Published: November 2020

Introduction

Inclisiran, an investigational siRNA, has been shown to effectively and durably lower LDL-C in Phase 3 trials. Inter-individual variability in LDL-C reductions has been documented for statin therapy and ezetimibe.

Purpose

To evaluate the inter-individual variability in LDL-C lowering with inclisiran.

Methods

The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) who had LDL-C >70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. Co-primary endpoints were the LDL-C reduction from baseline to Day 510 and the time adjusted average % change in LDL-C reduction after Day 90 and up to Day 540. Measures of response variability were pre-specified secondary endpoints. This analysis examines the inter-individual variability of LDL-C reductions at day 510 using pooled data from both trials.

Results

The analysis included 3178 individuals (92% on statins). At Day 90, 97% of inclisiran-treated patients had an LDL-C reduction. At Day 510, the median percent reduction in LDL-C levels from baseline was 57.3% in the inclisiran group (interquartile range, 44%-70%). An LDL-C reduction ≥50% was reached by 1359 (86.6%) inclisiran-treated patients versus 97 (6.2%) placebo patients at any visit (odds ratio [OR] 97.6, 95% confidence interval [CI] 76–126). An LDL-C reduction ≥30% was reached by 1523 (97.0%) inclisiran-treated patients versus 371 (23.7%) placebo patients (OR 104.5, 95% CI 76–143). At Day 510, 921 patients (65.1%) in the inclisiran group had a reduction ≥50% in LDL-C compared to 34 patients (2.4%) in the placebo group, and 1228 (86.8%) had a reduction ≥30% compared to 148 (10.5%), respectively. Among placebo-treated patients, there was a substantial proportion with notable increases in LDL-C at Day 510 (figure).

Conclusion

In Phase 3 trials, inclisiran on top of maximally tolerated statins provided reliable, consistent and durable reductions in LDL-C. A large percentage of subjects randomized to inclisiran achieved substantial reductions (>50%) in LDL-C and nearly all achieved at least a 30% reduction suggesting inclisiran is potentially a promising novel therapy for patients needing sustained LDL-C reductions.

Waterfall plot of pooled trials

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): The Medicines Company
The current LDL-C target <1.4mmol/l of the ESC is achieved in less than 16% of patients with Coronary Heart Disease despite effective lipid-lowering therapy: data from the LLT-R registry
Authors: Noack F , Schwaab B , Voeller H , Eckrich K , Guha M , Bongarth C , Heinze V , Schlitt A
Published: November 2020

Background

In the current guideline of the ESC, in patients with very high cardiovascular risk such as coronary heart disease (CHD) a treatment target for LDL-C <1.4mmol/l and/or a halving of the initial value are defined. It is unclear whether these treatment targets are achievable with standard therapy including statins and/or ezetemibe.

Methods

The primary objective of this prospective, multi-centre register study was the question of the guidance-based adaptation and adherence to lipid-lowering therapy during and after a cardiac rehabilitation in 1,100 patients with CHD up to 12 months after discharge from the six rehabilitation clinics involved. Patients were included from 2016 to 2018.

Results

The median age of the 1,100 patients was 63.4±10.4 years, the mean BMI was 28.5±4.7kg/m2, and 24.1% of patients were female. 12.2% were active smokers, 91.6% reported dyslipoproteinemia, 33.9% suffered from diabetes mellitus and 86.5% from hypertension.

The majority of patients were included with the main indications NSTEMI (31.6%), STEMI (29.6%) and after CABG surgery (26.4%).

The proportion of patients treated with statins was more than 94% when admitted and discharged from the rehabilitation clinic, as well as in 3- and 12-months follow-ups.

Approximately 9% of patients were treated with ezetemibe at baseline. On discharge from the rehabilitation clinic 23% of patients were treated with ezetemibe, which remains stable at 3 and 12 months.

PCSK9 inhibitors were used in 0.1–0.3% of patients at all times.

The adjustment of LLT during three week cardiac rehabilitation resulted in median LDL-C values of 2.27mmol/l (1.80/2.84) at baseline, 1.97mmol/l (1.57/2.47) on discharge (p<0.001 compared to baseline), 1.94mmol/l (1.57/2.49) after three months and 1.94mmol/l (1.53/2.40) after 12 months.

The proportion of patients with LDL-C <1.4mmol/l was 9% at baseline, 15.7% on discharge (p<0.001 compared to baseline), 15.6% at three-month follow-up and 15.1% at 12-month follow-up (Figure 1).

Discussion

In the context of cardiac rehabilitation, an effective adjustment of LLT is carried out, which resulted in a significant reduction of LDL-C. However, despite a high percentage of patients on statins and ezetemibe, the proportion of patients in the new target range <1.4mmol/l was only achievable in a small percentage and the question arises whether these treatment targets can be achieved without additional administration of PCSK9 inhibitors in majority of patients with CHD.

Figure 1

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): This study was supported by an unrestricted grant from Sanofi-Aventis Germany.
Carotid artery temperature reduction with statin therapy in patients with familial hyperlipidemia syndromes
Authors: Benetos G , Galanakos S , Koutagiar I , Skoumas I , Oikonomou G , Karanasos A , Drakopoulou M , Stathogiannis K , Plytaria S , Xanthopoulou M , Latsios G , Synetos A , Tousoulis D , Toutouzas K
Published: November 2020

Background

Familial hypercholesterolemia (FH) syndromes constitute an important risk factor for premature atherosclerosis. Microwave radiometry (MWR) assess non-invasively carotid artery temperatures reflecting inflammation. Recent data support that statin therapy, that constitutes the cornerstone for the treatment of FH, reduces systemic inflammation.

Purpose

To investigate the impact of statin therapy either with simvastatin or with combination simvastatin plus ezetimibe on carotid artery temperatures.

Methods

Consecutive patients with diagnosis of either heterozygous hypercholesterolemia (hFH) or combined hyperlipidemia (FCH) not under statin therapy for at least 6 months were included in the study. FH pts were assigned to either simvastatin 40 mg or simvastatin 40 mg plus ezetimibe 10mg according to the discretion of the physician. FH patients who refused statin therapy were used as control group for the assessment of statins effect. In all subjects, common carotid intima-media thickness (ccIMT) was measured in the last 2 cm of the far wall of both common carotids close to the carotid bifurcation and ΔT (maximum-minimum) temperature measurements were performed across each carotid during MWR evaluation. Examinations were performed at baseline and after 6 months. Blood's lipid profile was also obtained in all patients.

Results

In total 115 patients were included in the study. Of them 40 patients received simvastatin (19 hFH and 11 FCH), 41 simvastatin + ezetimibe (31hFH and 10 FCH) and 34 (21 hFH and 13 FCH) no statin. There was no difference at baseline in ccIMT and ΔT measurements between hFH and FCH patients (0.10±0.03 vs 0.10±0.02, p=0.74 and 0.88±0.38 vs 0.84±0.32, p=0.52, respectively). Patients who refused statin therapy did not show any reduction in ccIMT and ΔT measurements between baseline and follow up (ccIMT: 0.10±0.02 vs 0.09±0.02, p=0.06 and ΔT: 0.72±0.26 vs 0.70±0.26). In contrast, there was a significant reduction in ccIMT and ΔT for patients under both simvastatin (0.10±0.03 vs 0.09±0.01, p=0.004 for ccIMT and 0.83±0.34 vs 0.63±0.24, p=0.04 for ΔT) and simvastatin + ezetimibe therapy (0.11±0.03 vs 0.09±0.02, p<0.001 and 1.00±0.38 vs 0.69±0.23, p<0.001 for ΔT). Patients under combination therapy reduced more significantly their carotid artery temperatures compared to patients under simvastatin monotherapy or patients without statin (−0.31±0.46 vs −0.2±0.40 vs −0.01±0.37, ANOVA p=0.04, Figure 1).

Conclusions

Both simvastatin and simvastatin + ezetimibe therapy among the beneficial effect on IMT, reduced carotid wall inflammation in FH pts.

Figure 1

Funding Acknowledgement

Type of funding source: None
Role of physical fitness in the obesity paradox. Long-term major adverse cardiovascular events in the Women's Ischemia Syndrome Evaluation (WISE)
Authors: Quesada O , Wei J , Suppogu N , Kelsey S.F , Reis S , Shaw L , Sopko G , Handberg E.M , Pepine C.J , Bairey Merz C.N
Published: November 2020

Background

Emerging data suggests there is an “obesity paradox” where obesity may be protective against cardiovascular morbidity and mortality in patients with cardiovascular disease. However, weight status primarily assessed through body mass index (BMI) is limited in its ability to discern contributions from fat vs. lean muscle mass. Most studies on BMI have not accounted for physical fitness, which is a known modifier of weight status and a potential mediator of effects of obesity on major adverse cardiovascular events (MACE).

Purpose

To investigate the relationship between BMI and physical fitness, measured by self-reported Duke Activity Status Index (DASI) score, with long-term MACE in women evaluated for suspected myocardial ischemia.

Methods

The National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation (WISE) study is a multicenter prospective cohort study. From 1996–2000, 936 women were enrolled at the time of clinically indicated coronary angiography and assessed with a median follow up of 5.8 (range 0–9 years) for MACE. MACE was defined as a composite of death, nonfatal myocardial infarction, stroke, or congestive heart failure. Proportional hazards regression was used to estimate adjusted hazard ratios of MACE in relation to metabolic status and physical fitness. DASI scores ≥25, equivalent to ≥7 metabolic equivalents [METs]) was used as cut point to define high physical fitness, in our prior studies DASI >25 approximates completion of the second stage of a Bruce treadmill protocol.

Results

Among the 899 women with complete data, 69.5% had low physical fitness (DASI scores <25), 34.9% overweight (BMl ≥25 to 30), 40.5% obese (BMI ≥30). In fit women, obesity was associated with lower hazard ratio for MACE (HR 0.64, p=0.01); while low fitness in normal weight women was associated with 60% excess risk of MACE (HR 1.61, p=0.01) (Figure 1).

Conclusions

Among women undergoing coronary angiography for suspected myocardial ischemia, obesity was inversely related with long-term MACE in physically fit women. Our findings suggest that physical fitness may play a role in the obesity paradox. These results support the inclusion of fitness in understanding the relations between body weight and long-term MACE. The DASI is a simple, self reported tool that can identify higher-risk symptomatic women and should be considered in future investigations and routine examination of normal, overweight and obese women.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): U01 HL064829
Is metabolically healthy obesity indeed healthy at the microvascular level?
Authors: Tibirica E , Huguenin G , Rodrigues-Junior L , Pecanha D , Duque M , Escobar S , Duque A , Araujo C , Mediano M , Lorenzo A
Published: November 2020

Background

In the current “obesity epidemic”, obese individuals without insulin resistance, lipid disorders, or hypertension, have been called “metabolically healthy” (MHO) and considered to have intermediate cardiovascular risk, between that of healthy nonobese (HNO) individuals and of metabolically unhealthy obese (MUO). Nonetheless, this is controversial, as MHO may have subclinical abnormalities, and indeed may be a transitory state in the way to the unhealthy phenotype.

Purpose

To evaluate systemic microvascular reactivity in MHO, MUO and HNO.

Methods

Ten MHO, 10 MUO and 20 HNO individuals were studied. Obesity was considered as a BMI ≥30 kg/m2. The NCEP/ATPIII criteria, excluding waist circumference, were used to define the metabolically healthy phenotype (absence of all criteria) or unhealthy phenotype (presence of any of the criteria). Laser speckle contrast imaging coupled with skin acetylcholine (Ach) iontophoresis was employed to study cutaneous microvascular reactivity (endothelial-dependent vasodilatation), as a surrogate for systemic microvascular function, and cutaneous vascular conductance [CVC in arbitrary perfusion units of microvascular flow (APU)/mean arterial pressure (mmHg)] was measured.

Results

Mean age was 34.8, 36.7 and 32.3 years (P=0.17, ANOVA) and BMI was 20.7, 32.2 and 33.3 kg/m2 (P<0.0001) for HNO, MHO and MUO, respectively. Both MHO and MUO had significantly decreased microvascular vasodilation in comparison to HNO (Figure 1). Of note, there was no significant difference between MHO and MUO regarding CVC (both similarly decreased when compared to the healthy controls).

Conclusions

This study underscores that MHO is not a “benign” condition, as it has adverse effects on microvascular function, similarly to those found in MUO. The study of cutaneous microvascular function may be useful to identify subclinical abnormalities in obese individuals who might deserve more intensive management.

Figure 1

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): FAPERJ - Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - Brazil
Gender-specific relationship between abdominal obesity and prevalence of new-onset atrial fibrillation in the general Japanese population
Authors: Ninomiya Y , Kawasoe S , Ichiki H , Kubozono T , Miyahara H , Tokushige K , Ohishi M
Published: November 2020

Background

The number of incidences of atrial fibrillation (AF) is expected to rise rapidly in the near future because of the increased number of geriatric patients in Japanese society. In addition, obesity is increasing in the general Japanese population. Although a higher body mass index is associated with a higher risk of AF, the relationship between abdominal obesity (large waist circumference) and new-onset AF is unclear.

Methods and results

We performed a longitudinal retrospective observational study from January 2007 to October 2018 using the annual health checkup data. Data from 58,844 adults (29,572 males, age 54±13 years) without baseline AF, who underwent routine health checkups, were analyzed. We performed logistic regression analyses to determine the strength of the association between abdominal obesity and new-onset AF. We also examined the effect of abdominal obesity on the incidences of AF stratified by gender. During a median follow-up of 4 years, we recorded new cases of AF in 322 (0.5%) individuals. In univariate analysis, a large waist circumference was significantly associated with new-onset AF, both in males [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.02 to 1.05, p<0.001] and in females (HR 1.04, 95% CI 1.01 to 1.06, p=0.002), respectively. In multivariate analysis adjusted for clinical variables (age, hypertension, dyslipidemia, estimated glomerular filtration rate, habitual drinking and diabetes), a large waist circumference was significantly and independently associated with new-onset AF in males (HR 1.04, 95% CI 1.03 to 1.06, p<0.001), but not in females (HR 1.01, 95% CI 0.99 to 1.04, p=0.269).

Conclusion

Abdominal obesity is independently associated with an increased risk of new-onset AF in males. This association in males might imply some sex-specific mechanisms. There might be a gender difference in the effectiveness of interventions to decrease abdominal obesity to prevent AF.

Funding Acknowledgement

Type of funding source: None
Night heart rate variability identifies cardiovascular risk in community dwelling people with uncomplicated type 2 diabetes mellitus
Authors: Hadad R , Larsen B.S , Fenger A.S , Stavnem D , Mattsson N , Kristiansen O.P , Nielsen O.W , Sajadieh A
Published: November 2020

Introduction

Low Heart rate variability (HRV) reflects cardiac autonomic neuropathy, associated with increased cardiovascular mortality in type 2 diabetes (T2DM) patients. Measuring HRV is challenged by environmental noise, mental stress and physical activity during the day-time. Thus, measuring night-time HRV during sleep may be a better tool to predict cardiovascular (CV) events in low risk T2DM patients without previous cardiovascular disease.

Methods

Copenhagen Holter Study included 678 community dwelling subjects aged 55–75 years free of previous cardiovascular disease. Day- and night-time HRV were available for 653. The population included 133 well-controlled T2DM patients (mean HbA1c 7.2%). Median follow- up was 14.4 years. HRV is defined as standard deviation for the mean value of normal-to-normal complexes (SDNN). Night-time HRV measurements were pre-defined from 2:00 to 2:15 AM. CV events were defined as CV death, myocardial infarction, stroke, or coronary revascularization.

Results

The rate of CV events was 17 and 31 per 1000 patient-year in patients without and with T2DM, respectively (p=0.015). Night-time SDNN was inversely associated with CV events in T2DM patients with a HR of 0.74 (0.61–0.89), P=0.001, for each 10 ms increment in SDNN, after adjustment for sex, age, LDL, smoking, systolic BP, glucose, CRP and NT pro-BNP (table 1). Twenty-four-hours HRV was not associated with cardiovascular events (table 1). Conventional risk factors had an AUC of 0.704 (95% CI 0.602–0.806) to predict CV events in T2DM. Prediction was improved by the addition of night-time SDNN; AUC 0.765 (95% CI 0.669–0.862), P=0.037, but not by CRP or NT-proBNP (Figure 1). In subjects with well-controlled T2DM and night-time SDNN ≤30 ms, the 10-year risk of CV death and CV even-rate were 12% and 45%, respectively. This allocates these T2DM patients in a “very high-risk” group, and more aggressive targets for blood-pressure and lipids according to the current guidelines.

Conclusion

Reduced night-time HRV associates with increased risk of CV events in persons with well-controlled T2DM. We observed improved risk prediction of cardiovascular events in T2DM by night-time HRV, which may have therapeutic consequences.

Figure 1. ROC Curve

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Heart Foundation
The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study
Authors: Siao W.-Z , Jong G.P
Published: November 2020

Background/Introduction

Clinical trials have shown the cardiovascular protective effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias.

Purpose

To evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors.

Methods

This was a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA.

Results

A total of 399,810 patients newly diagnosed with type 2 diabetes mellitus (T2DM) were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.547; 95% confidence interval [CI] 0.482–0.621; P=0.0001) and NOA (aHR 0.830; 95% CI 0.751–0.916; P=0.0002). Subgroup analysis revealed that the SGLT2 inhibitor group was associated with a lower risk of all-cause mortality in all age and severity of the adapted Diabetes Complication Severity Index (aDCSI) subgroups. Furthermore, NOA and atrial fibrillation were associated with a lower risk in subgroups with an aDCSI score of between 1 and 2.

Conclusions

Patients with T2DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice. The potential protective effect of NOA and atrial fibrillation is observed, especially in individuals with T2DM and an aDCSI score of between 1 and 2.

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): This study was supported in parts by grants from Chung Shan Medical University Hospital.
Effect of air pollution on acute heart failure hospitalization differ across specific heart failure populations
Authors: Takei M , Harada K , Miyazaki T , Kohsaka S , Matsushita K , Shiraishi Y , Shinme T , Shindo A , Miyamoto T , Kitano D , Kodera S , Nakano H , Yamamoto T , Takayama M
Published: November 2020

Introduction

Several report showed the association between ambient air pollution including particular matter under 2.5um (PM2.5) and increasing rate of hospitalization for heart failure. However, these report analyzed mainly cross-sectional, epidemiological data, thus the reports regarding association between vulnerability to PM2.5 and specific populations in acute heart failure (AHF) were scarce.

Purpose

1. To analyze the association between air pollution and rate of hospitalization for AHF

2. To analyze whether the vulnerability to air pollution differ between specific populations in AHF. Methods

A case-cross over analysis was conducted to 4980 consecutive patients registered for multicenter acute heart failure registry in 2017 in our city Japan. This registry enrolled patients transferred to cardiovascular care unit (80 institutions) via emergency medical services across our city area. Logistic regression analysis were conducted to estimate percentage changes in the rate of acute heart failure hospitalization associated with per 1μg/m3 PM2.5 concentration increase. We also conducted subgroup analysis for patients stratified by age, gender, comorbidities, left ventricular ejection fraction, and clinical scenario.

Results

An increase in 1 μg/m3 PM2.5 concentration corresponded to 2.9% (95% CI 1.2–4.6%) increase in AHF hospitalization. Patients with age younger than 75, without prior heart failure hospitalization, without history of hypertension, without anemia, and with reduced ejection fraction were more susceptible to increase in PM2.5 concentration (Figure).

Conclusions

Increase in PM2.5 concentration was associated with increased rate of AHF hospitalization. Effect of PM2.5 may differ across specific AHF subpopulations.

Figure 1

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Tokyo Metropolitan Government
Subacute post-operative atrial fibrillation after valvular surgery in patients undergoing cardiac rehabilitation: predictive factors
Authors: Maranta F , Bonaccorso A , Rizza V , Pellegrino S , Meloni C , Avitabile M , De Bonis M , Alfieri O , Cianflone D
Published: November 2020

Background

Postoperative atrial fibrillation (POAF) is the most frequent arrhythmic complication following cardiac surgery (occurring in up to one third of patients). It may develop between the second and fourth postoperative days (acute POAF) as well as later, within 30 days after surgery (subacute). Episodes of atrial fibrillation in the subacute phase (sPOAF) are associated with an increase in morbidity, length of hospital stay and several complications both in the mid- and long- term. Therefore, POAF is not just an acute event but it may impact on long term clinical outcomes.

Aim of the study

The aim of this study was to identify the clinical predictors of postoperative atrial fibrillation in the subacute phase (sPOAF) in patients performing Cardiovascular Rehabilitation (CR) after cardiac surgery.

Materials and methods

A retrospective study was conducted on 737 post-surgical valvular patients (median age 62 years; 55,4% male) hospitalised in our Unit for in-patient CR program. During all the hospital stay patients received continuous monitoring with 12-lead ECG telemetry. We evaluated the predictive value of anamnestic data, the type of cardiac surgery intervention, the clinical course in the Cardiac Surgery Unit and in the CR Unit, the 6 minutes-walking tests (6MWT) parameters and main blood tests on sPOAF onset.

Results

SPOAF was documented in 170 patients (23,1%). Those who developed sPOAF were older [median 66 (56–74) years vs median 61 (50–70) years; p<0,001), had a history of atrial fibrillation prior to surgery (29,4% vs 16,2%; p<0,001), had a worse functional result at the 6MWT at the admission in CR Unit [median 250 (180–320) vs median 275 (210–370); p=0,015], had higher values of neutrophil-lymphocite ratio at baseline [median 2,33 (1,84–3,27) vs median 2,17 (1,64 - 2,87); p=0,027] when compared to those who did not develop POAF. At the multivariable logistic regression analysis, the occurrence of POAF in the acute phase (OR 2,916; 95% CI 2,011–4,228; p<0,001), advanced age (OR 1,027; 95% CI 1,01–1,044; p=0,002), previous history of atrial fibrillation (OR 1,652; 95% CI 1,068–2,555; p=0,024), higher values of NLR at baseline (OR 1,144; 95% CI 1,028–1,272; p=0,013) and mitral valve surgery (OR 1,632, 95% CI 1,075–2,480; p=0,022) were found to be independent predictors of sPOAF after cardiac surgery.

Conclusions

Atrial fibrillation is a common complication after cardiac surgery with great clinical relevance. Advanced age, previous history of AF, higher values of NLR at baseline, mitral valve surgery and the occurrence of POAF in the acute phase were shown to be predictors of sPOAF in a cardiac surgery population during the rehabilitation period.

Funding Acknowledgement

Type of funding source: None
High-intensity interval training improves interventricular synchrony and strain under hypoxic stress in sedentary males
Authors: Huang Y.C , Wang J.S
Published: November 2020

Background

Interventricular interactions in increased RV afterload such as hypoxia stress, which affects both synchrony and function in an in-series effect as well as a parallel effect arising from leftward septal shift. Improved myocardial contractility is a critical circulatory adaptation to exercise training, however, the types of exercise that can improve interventricular synchrony under hypoxic environment have not yet been established.

Purpose

This study investigates how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) influence on the interventricular synchrony in response to normobaric hypoxia in sedentary men.

Methods

Fifty-four sedentary males were randomized to perform HIIT (3-minute intervals at 40% and 80% VO2peak, n=18), MICT (sustained 60% VO2peak, n=18) for 30 minutes/day, 5 days/week for 6 weeks and the control group (CTL, n=18). Synchrony measurements at apical 4-chamber view including (1) intra-delay, the difference in time to peak strain (TS) between segmental septal-to-lateral ventricular or atrial walls, and (2) inter-delay, the difference in TS between RV or RA free wall and LV or LA lateral wall. The data were acquired by 2-dimensional speckle tracking echocardiography at rest under hypoxic condition (12% FIO2, simulated an altitude of 4,500 m) before and after the interventions.

Results

HIIT had significantly elevated radial and longitudinal strains in both LA and LV (p<0.05). As the results showed, HIIT was superior than MICT in improvement of longitudinal intra-delay of LV; furthermore, only HIIT simultaneously ameliorated both radial and longitudinal synchrony at apex. Although the HIIT enhanced intraventricular synchrony in both motions, whereas the interventricular synchrony deteriorated at radial motion. In atrium synchrony, although both groups augmented the intra-LA synchrony, however, only HIIT reduced the inter-delay between LA and RA at the roof motion. LV end-systolic volume (ESV) significantly correlated with the longitudinal inter-delay of ventricle (r=−0.53, p<0.05), whereas the LV end-diastolic volume (EDV) correlated with the inter-delay of atrium in roof motion (r=0.40, p<0.05).

Conclusion

We found differences between HIIT and MICT in segmental intra- and inter- synchrony. HIIT enhanced both ventricular or atrial synchrony, and further increased the EDV coupled with decreased ESV. These findings give new insight into cardiac adaptation to difference endurance training and the long-term impact of such changes warrants future study in cardiac diseases.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science Council of Taiwan
Better outcome of exercise-related out-of-hospital cardiac arrest in men and in the young
Authors: Frisk Torell M , Stromsoe A , Herlitz J , Claesson A , Rawshani A , Borjesson M
Published: November 2020

Background

Survival from out-of-hospital cardiac arrest (OHCA) is higher if the arrest occurs in relation to physical activity,however there is contradicting data on prognosis with regards to gender and age. The purpose of the study was to compare prognosis and circumstances of exercise-related OHCA in different age-groups as well as between genders in a large unselected population.

Methods

Observational data from exercise-related OHCA occurring outside of home reported to the Swedish Register of Cardiopulmonary Resuscitation (SRCR) from 2011 to 2014 and from 2016 to 2018 was analyzed. Comparing analyses were made for three different age-groups (0–35, 36–65 and >65 years) and for males versus females.

Results

A total number of 9607 cases of OHCA outside of home where resuscitation was attempted occurred during the study period, 635 (6.6%) were exercise-related. Mean age was similar between males and females (59.1 years in both groups). The 30-day survival rate was significantly higher among exercise-related OHCAs compared to non-exercise-related OHCAs (44.5% vs 18.8%, p<0.0001). The highest survival rate was observed in the age-group 0–35 years, compared to 36–65 years and >65 years respectively (59.6% vs 46.0% and 40.4% respectively, p=0.01). A sub-group analysis of victims aged 0–25 years (n=32) showed a survival rate of 68.8%. Exercise-related OHCA in women (9.1% of total) were bystander witnessed to a lower extent than in men (66.7% vs 79.6%, p=0.03). Both men and women received bystander CPR at the same extent but median time to CPR was 1min longer for women (2.0 vs 1.0 min, p=0.001). Women had lower rates of ventricular fibrillation as initial rhythm (43.4% vs 64.7%, p=0.003) and 30-day survival was lower among women (29.3% vs 46.0%, p=0.02).

Conclusion

Women seem to be protected from exercise-related OHCA but in case of occurrence the prognosis is actually worse compared to men. This may partly be explained by lower grade of bystander witnesses and longer time to CPR, but the results indicate the need for further studies on additional factors, such as variances in underlying disease pattern and exercise habits of women. In addition, this study presents an exceptionally high survival rate for exercise-related OHCA in the youngest age-groups, especially in victims 0–25 years of age which is a novel finding.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Swedish Heart-Lung Foundation, Laerdal Foundation
Characteristics and health status of patients with and without confirmed HFpEF
Authors: Deaton C , Forsyth F , Mant J , Edwards D , Hobbs R , Taylor C , Aziz A , Schiff R , Odone J , Zaman J
Published: November 2020

Aims

Patients with heart failure with preserved ejection fraction (HFpEF) are usually older and multi-morbid and diagnosis can be challenging. The aims of this cohort study were to confirm diagnosis of HFpEF in patients with possible HFpEF recruited from primary care, to compare characteristics and health status between those with and without HFpEF, and to determine factors associated with health status in patients with HFpEF.

Methods

Patients with presumed HFpEF were recruited from primary care practices and underwent clinical assessment and diagnostic evaluation as part of a longitudinal cohort study. Health status was measured by Montreal Cognitive Assessment (MOCA), 6-minute walk test, symptoms, and the Kansas City Cardiomyopathy Questionnaire (KCCQ), and quality of life (QoL) by EQ-5D-5L visual analogue scale (VAS).

Results

151 patients (mean age 78.5±8.6 years, 40% women, mean EF 56% + 9.4) were recruited and 93 (61.6%) were confirmed HFpEF (those without HFpEF had other HF and cardiac diagnoses). Patients with and without HFpEF did not differ by age, MOCA, blood pressure, heart rate, NYHA class, proportion with atrial fibrillation, Charlson Comorbidity Index, or NT-ProBNP levels. Patients with HFpEF were more likely to be women, overweight or obese, frail, and to be more functionally impaired by 6 minute walk distance and gait speed than those without. Although not statistically significant, patients with HFpEF had clinically significant differences (>5 points) on the physical limitations, symptom burden and clinical summary subscales of the KCCQ, but did not differ by other subscales or by EQ-5D-5L VAS (70±17 vs 73±19, p=0.385). More patients with HFpEF reported daytime dyspnoea (63% vs 46%, p=0.035) and fatigue (81% vs 61%, p=0.008), but not other symptoms compared to those without HFpEF. For both groups BMI was moderately negatively correlated with KCCQ subscale scores, and 6 minute walk distance was positively correlated with KCCQ subscales.

Conclusions

Nearly 40% were not confirmed as HFpEF indicating the challenges of diagnosis. Patients with confirmed HFpEF differed by sex, overweight/obesity, frailty, functional impairment, and symptoms but not by age or comorbidities from those without HFpEF. These differences were reflected in some subscale scores of the KCCQ, but not how patients reported their quality of life on the KCCQ QoL subscale and EQ-5D-5L VAS. Older patients with HFpEF reported relatively high QoL despite poor health status by functional impairment, frailty and symptoms.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research School of Primary Care Research
Ictal ECG changes and antiepileptic drug therapy
Authors: Teryan R.A , Drapkina O.M
Published: November 2020

Purpose

Epileptic seizures may cause severe cardiac arrhythmias. Most people with epilepsy die suddenly and whose death is recognized to a sudden unexpected death in epilepsy (SUDEP). There are controversial reports on the association between polytherapy using antiepileptic drugs and SUDEP. First-line drugs include, in particular, carbamazepine, oxcarbazepine, and lamotrigine, which are sodium channel blockers that may impair heart function. Often a patient requires a combination of antiepileptic drugs

Methods

204 patients with epilepsy and were on antiepileptic drugs therapy. The ECG cardiac monitor was implanted in all patients (n=204) and was analyzed together with the preclinical data including age, sex, family history, cardiac risk factors (hypertension, dyslipidemia, diabetes mellitus), heart disease, antiepileptic drug type.

Results

After a follow-up of 12-month ictal ECG changes (rhythm and conduction disturbances, ST segment abnormalities) were observed in 134 (66%) patients, and only in 70 (34%) – without ictal ECG changes, the average age in these groups was 34,4±9,9 and 36,7±11,8 years (p>0,05). In the group with ictal ECG changes among patients receiving as monotherapy antiepileptic drugs, ictal ECG changes were found in 53.7% of cases, with polytherapy antiepileptic drugs significantly more often – in 71.5% of cases (p<0.05). a reliable association between carbamazepine and changes in sinoatrial and atrioventricular conduction (p=0.01) was significant. In the analyzed group of patients, carbamazepine therapy was also associated with the presence of ictal ST-segment abnormalities (depression/elevation) (p=0.013). A positive association was observed between the administration of oxcarbazepine and development of ictal tachycardia (p=0.04) and ictal right and left bundle branch block, which was observed in 71.4% of cases against the background of oxcarbazepine, significantly more often than with other drugs (p=0.005).

Conclusion

In agreement with previous publications available in the literature, our results confirm the risk of high-frequency rhythm and conduction disturbances, ST segment abnormalities related to antiepileptic drugs, in particular, carbamazepine and oxcarbazepine and indicates the need of not only cardiological examination before prescribing an antiepileptic drugs, but also a thorough follow-up during the therapy. Patients with ictal ECG changes, primarily rhythm and conduction disturbances, should be under the dynamic control of not only neurologists but also cardiologists and require regular cardiological check-up (ECG, Holter monitoring of the electrocardiogram, echocardiography).

Funding Acknowledgement

Type of funding source: None