bluuebunny/crossref_metadata_2025 huggingface dataset:
Achievement of ESC/EAS lipid treatment goals with evolocumab in patients with type 2 diabetes: analyses of the BANTING and BERSON trials
Authors: Lorenzatti A.J , Chen J , Monsalvo M.L , Wang H , Lopez J.A.G , Rosenson R.S
Published: November 2020

Background

BANTING and BERSON showed evolocumab in type 2 diabetes (T2D) effectively lowered low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and non-high-density lipoprotein-cholesterol (Non-HDL-C), all targets in cardiovascular disease (CVD) prevention.

Purpose

To evaluate the achievement of lipid treatment goals with evolocumab vs placebo in T2D.

Methods

We pooled two double-blind, randomised, phase 3 studies. In BANTING, participants received maximally-tolerated statins. In BERSON, participants began atorvastatin 20 mg post-baseline; almost half enrolled in China. LDL-C and non-HDL-C goal achievement were assessed at the mean of weeks 10 and 12; and ApoB at week 12.

Results

Of 1,402 participants analysed, 89.4% were at very high CVD risk. Treatment goals achievement was significantly greater in evolocumab vs placebo. Results were consistent in the Chinese subpopulation.

Conclusion

Evolocumab plus statins enabled most T2D patients at very-high/high CVD risk to achieve their lipid treatment goals

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Amgen Inc.
Excessive salt intake is a significant predictor for future development of metabolic syndrome in the general population
Authors: Takase H , Machii M , Nonaka D , Ohno K , Takayama S , Sugiura T , Ohte N , Dohi Y
Published: November 2020

Background/Introduction

Dietary salt consumption is one of the most important modifiable factors in our lifestyle and restriction of dietary salt results in the reduction of blood pressure in previous studies. Excessive salt intake causes cardiovascular diseases independently of its effects on blood pressure. Since metabolic syndrome also increases a risk of cardiovascular disease, there may be some association between salt intake and metabolic syndrome.

Purpose

The present study was designed to investigate a possible relationship between salt intake and future development of metabolic syndrome in the general population.

Methods

Consecutive 12,256 subjects without metabolic syndrome (male=7,053, 52.1±12.3 year-old) who visited our hospital for an annual physical check-up from April 2010 to March 2018 were enrolled. After baseline examination, subjects were followed up until March 2019 (median 1,582 days) with the endpoint being the development of metabolic syndrome. Metabolic syndrome was diagnosed according to the Japanese criteria (2005). Individual salt intake was estimated using a spot urine by a previously reported method.

Results

Salt intake was 11.9±3.0 g/day in male and 8.2±2.1 g/day in female subjects at baseline. During the follow-up period, 1,669 subjects developed metabolic syndrome (29.9 per 1,000 person-year) with the incidence being more frequent in male than female subjects (41.8 vs. 14.2 per 1,000 person-year). Non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of salt intake for the development of metabolic syndrome was 1.157 (1.142–1.173). In analysis where subjects were divided into gender-specific quartiles according to the baseline salt intake, Kaplan-Meyer curve analysis revealed that the incidence of metabolic syndrome were increased across the quartiles (20.6, 25.0, 32.4, and 42.7 per 1,000 person-years; logrank p<0.001). Multivariate Cox proportional hazard analysis adjusted for age, gender, body mass index, systolic blood pressure, heart rate, serum creatinine, uric acid, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, hemoglobin and current smoking habit at baseline revealed that salt intake predicted the new onset of metabolic syndrome (HR: 1.036, 95% CI: 1.019–1.054).

Conclusions

Excessive salt intake is significantly associated with the new development of metabolic syndrome in the general population. The results suggest that salt restriction prevents metabolic syndrome as well as hypertension leading to cardiovascular diseases.

Funding Acknowledgement

Type of funding source: None
Social status and long-term events among acute myocardial infarction patients
Authors: Kim M , Lee K.M , Moon H.Y , Jo Y.S , Jin X , Yuan S.L , Kim R.B , Hwang J.Y , Lee J.H
Published: November 2020

Background

Mood disorders, depression, and loneliness are known risk factors for thrombotic occlusions. Social relationships in general, and marital status in particular may play a role in predicting cardiovascular outcomes and survival after ST-segment elevation myocardial infarction (STEMI), but the evidence is inconclusive, especially in Asians. We sought to analyze clinical outcomes following AMI according to insurance type and living type.

Methods

From July 2016 to Sept 2018, the Korean Registry of Regional Cardiocerebrovascular Center for Acute Myocardial Infarction database collected patients over 18 years old who suffered AMI. 3 months and 1-year all-cause death, CVA and re-MI (composite endpoint) were collected by telephone interview.

Results

Overall, the total of 463 all-cause death and 113 re-MI occurred. At 3-months, each group did not any differences in all-cause death and re-MI. At 1-year, however, the single & medical aid patients exhibited significantly higher all-cause death (6.8% vs 18.3%; p=0.000) and composite endpoint (12.5% vs 20.6%; p=0.000) compared to the live together & health insurance.

Conclusion

Social and economic status may be linked to 1-year all-cause death in Korean patients with ST-segment elevation myocardial infarction.

All-cause death and Composite outcomes

Funding Acknowledgement

Type of funding source: None
Cardiovascular rehabilitation after valvular heart surgery: predictive factors of major complications
Authors: Maranta F , Pellegrino S , Bonaccorso A , Rizza V , Castiglioni A , De Bonis M , Alfieri O , Cianflone D
Published: November 2020

Background

The population of patients affected by valvular heart disease is growing and for many of them valvular surgery is still considered the gold standard treatment. Cardiovascular Rehabilitation (CR) following intervention is fundamental for the post-surgical functional recovery and for the monitoring and management of complications that may occur after surgery.

Aim of the study

We aimed at identifying predictors of major complications in patients who underwent valvular surgery and subsequently were involved in an in-patient CR program. Major complications were defined as those requiring an in-patient management: severe anemia needing transfusions, infection of the sternal surgical wound requiring an antibiotic treatment, a positive hemoculture in the presence of systemic signs of infection and pericardial effusion requiring surgical drainage.

Methods and statistical analysis

1600 patients who have been hospitalized in our CR Unit after valvular surgery were enrolled (median age 64 years; 60% males). We examined the demographic data, the cardiovascular risk factors, the main comorbidities, the type of heart surgery (type of valvular surgery and the presence of concomitant other cardiac intervention), the complications developed in Cardiac Surgery Unit and in the CR Unit, the in-hospital length of stay, the 6 minutes-walking tests and principal blood tests.

Results

At multivariate analysis we found that chronic renal dysfunction [OR 1,902 (CI 1,103–3,280), p=0,021], complex cardiac intervention [OR 1,554 (CI 1,030–2,344), p=0,036], sternal re-synthesis [OR 4,671 (CI 1,659–13,152), p=0,004], early post-surgical transfusions [OR 1,670 (CI 1,083–2,573), p=0,020] are independent risk factors for major complications, while a higher hemoglobin value at CR admission [OR 0,677 (CI 0,566–0,810), p<0,001] resulted an independent protective factor.

Conclusions

We identified predictors of major complications during CR after valvular surgery. These factors may help in defining the patients at major risk tailoring the patient management, adopting an individualized clinical and instrumental monitoring. A tailored CR period gives the possibility to optimize the use of hospital economic resources and to achieve a better final outcome.

Funding Acknowledgement

Type of funding source: None
Efficacy of neuromuscular electro stimulation on muscle strength in elderly patients with diabetes mellitus underwent cardiovascular surgery – a multicenter randomized controlled trial
Authors: Takino K , Kameshima M , Asai C , Kawamura I , Tomita S , Hirakawa A , Yamada S
Published: November 2020

Introduction

Cardiovascular surgery causes muscle weakness probably due to a postoperative increase in inflammatory cytokine production, and diabetes mellitus (DM) may promote the postoperative muscle weakness because of increased insulin resistance.

Purpose

A multicenter randomized controlled trial was conducted to examine the effects of postoperative neuromuscular electrical stimulation (NMES) on muscle strength for elderly patients with DM after cardiovascular surgery (UMIN000029940).

Methods

Patients underwent cardiovascular surgery were consecutive screened for eligibility (With DM and age ≥65 years) as study subjects. If eligible, patients were randomly assigned either to the NMES or the sham group. Both of group underwent NMES or sham stimulation (60 minutes / 5 times) and usual postoperative early mobilization program until postoperative day (POD) 7. The primary outcome was the percent change in knee extensor isometric muscle strength (%ΔKEIS) between preoperative to POD 7. Secondary outcomes were the percent change in usual (%ΔUsual walking speed) and maximum walking speed (%ΔMaximum walking speed) and grip strength (%ΔGS). Assessors for physical function were blinded to the outcomes. The statistician who was blinded to the allocation analyzed the data using preoperative value adjusted ANCOVA.

Results

Of 1151 consecutive patients screened for eligibility from February 2018 to January 2020, 158 participants (NMES group, n=79; sham group, n=79) were enrolled. NMES group demonstrated significantly lower %ΔKEIS compared with those in the sham group (Table). Among secondary outcomes, NMES group showed significantly lower %ΔMaximum walking speed and tendency of lower %ΔUsual walking speed and %ΔGS (Table).

Conclusion

NMES prevented postoperative muscle weakness in the elderly patients with DM, indicating that NMES along with early mobilization could be implicated as specific intervention to those populations.

Funding Acknowledgement

Type of funding source: None
Residential cardiac rehabilitation (rCR) derived survival predictors in patients after transcatheter aortic valve replacement (TAVR): a retrospective multicenter study
Authors: Tarro Genta F , Dalla Vecchia L , Scalvini S , Sarzi Braga S , Iannuzzi G.L , Bussotti M , Ceresa M , Rizzo C , Riboni G , Marcassa C , Giordano A , Pedretti R.F.E
Published: November 2020

Purpose

To evaluate exercise-based rCR derived outcome predictors in patients referred after TAVR.

Methods

Data of 434 patients (aged 81±6 years) admitted to an average 3-week rCR program after TAVR (walking, up to 30 minutes of cycling or treadmill session twice daily, respiratory and calistenic training) from January 2009 to December 2017 and home discharged, were retrospectively collected at 10 Italian rCR Division of Istituti Clinici Maugeri SpA. Comorbidity (cumulative illness rated state-comorbidity index) (CIRS-CI) score, echocardiography on admission, Disability (Barthel Index) (BI) score, Morse Fall Scale score (MFS), six minutes walking test distance (6MWT) on admission and discharge and maximal training session intensity (MTSI expressed in METs per minutes) were collected. The mortality was assessed up to 3 years after rCR discharge.

Results

During a 3-years follow up there were 120 (28%) deaths. At t-test analysis non survivors compared to survivors had significantly higher CIRS CI (p=0.000), MFS score on admission (p=0.008) and discharge (p=0.017), serum creatinine level on admission (p=0.000) and discharge (p=0.000); moreover they had significantly lower BI score on admission (p=0.000) and discharge (P=0.000), left ventricle ejection fraction (p=0.008),6MWT on admission (p=0.001) and discharge (p=0.000) and MTSI (p=0.022) in comparison to survivors.

At multivariate logistic stepwise analysis, BI score on admission and serum creatinine level at discharge were the only independent predictors of mortality (Table 1); the AUC of the final logistic model was 0.72.

Conclusions

Patients attending rCR after TAVR seem to be very old; overall mortality at 3 years follow up in patients discharged home after rCR is substantial. Disability profile on admission (measured by Barthel Index) and impaired renal function on discharge (measured by creatinine levels) are independently correlated to death at long term follow up.

Funding Acknowledgement

Type of funding source: None
Left atrial performance during exercise in endurance athletes: the impact of gender
Authors: Simard F , Sanz-De La Garza M , Vaquer-Segui A , Blanco I , Prat-Gonzalez S , Bijnens B , Sitges M
Published: November 2020

Background

High-intensity endurance training is associated with an increased risk of atrial fibrillation (AF) in male athletes while it seems to have a protective effect for the development of atrial arrhythmias in female athletes. Mechanisms underlying this fact are unknown but a differential atrial adaptation to exercise may be involved.

Aim

To evaluate left atrial (LA) performance during exercise in endurance athletes (EAs) of both sexes.

Methods

Highly-trained (>10 hours training/week) EAs performed a maximal cardiopulmonary exercise test. LA evaluation was performed at rest and immediately after exercise. LA analysis consisted of standard and speckle-tracking assessment: atrial contractile, reservoir and conduction strain.

Results

80 EAs (55% women, 34.8±5.8 years) were enrolled. Baseline LA size and functional parameters were similar in both sexes (Table 1). Compared to men, women achieved a higher predicted VO2max (Δchange+11.9%, p<0.01) but a similar increase of systolic blood pressure (Δ+63 vs +66%, p=0.58). Exercise induced a mild decrease in LA size but of similar amplitude for both sexes. LA strain parameters of EAs improved with exercise, but a significantly greater improvement in LA reservoir and conduit function was noted in women compared to men. In EAs with marked atrial remodelling (LA ≥35ml/m2), the same trend of greater improvement of LA reservoir and conduit function in women persisted.

Conclusion

In highly-trained EAs, premenopausal women have better LA function profile during exercise compared to men, even when the LA is significantly dilated. This discriminatory LA adaptation in female EAs could at least partly explain the dichotomous relationship between AF and exercise regarding sexes and warrants further studies to clarify the underlying mechanism.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Government of Spain - Plan Nacional I+D, Ministerio de Economia y Competitividad
You've got to be in it to win it: the importance of including female athletes in screening ECG cohorts
Authors: Janssens K , Paratz E , Brosnan M , Lindqvist A , Mitchell A , Afridi A , Orchard J , Prior D , La Gerche A
Published: November 2020

Background

ECG screening is widely employed in athletic populations with the aim of identifying cardiac conditions associated with sudden death. Recommendations for athlete ECG interpretation are disproportionately reliant on data from male athletes and sex-specific differences have not been adequately elucidated.

Purpose

The aim of this study is to identify any different patterns in female athletic training response on ECG screening.

Methods

444 elite athletes (156 male rowers, 135 female rowers, 117 male cricketers, 36 female cricketers) underwent electrocardiogram (ECG) screening. Standard definitions were used to characterize abnormalities identified on ECG. Comparisons were made according to sex and endurance (rowing) vs skill-based (cricket) athletes (EA and SBA respectively).

Results

“Potentially pathological” T-wave inversion extending to V3 was more prevalent in female athletes (9.9% vs. 2.9%, P=0.002), especially amongst endurance athletes (11.9% female EA vs. 2.8% female SBA, P=0.004) (Figure 1). As compared with males, the QTc interval was longer in female athletes (418 vs. 402ms), the QRS duration was shorter (90 vs. 100 ms) and left ventricular hypertrophy on voltage criteria were less prevalent (9.9% vs. 33.3%, P<0.001 for all). First-degree heart block and incomplete right bundle branch block were more prevalent amongst male athletes.

Conclusion

Female athletes exhibit different training-related cardiac remodelling responses to exercise compared to males. A greater proportion of ostensibly healthy female athletes, especially female endurance athletes, have ECG changes that would be deemed “potentially pathological” according to current sex-agnostic guidelines.

Figure 1

Funding Acknowledgement

Type of funding source: None
Serum uric acid possibly associated with abnormal left ventricular diastolic function in healthy individuals
Authors: Liu C.W , Tu C.M
Published: November 2020

Background

Elevated serum uric acid (SUA) is reportedly associated with the traditional left ventricular diastolic dysfunction (LVDD).

Purpose

We aimed to investigate the association between SUA and the contemporarily defined LV diastolic function (LVDF).

Methods

We prospectively enrolled healthy individuals who underwent echocardiography to evaluate electrocardiographic abnormalities at the health exam between 1st Jan 2018 and 31th Dec 2019. The evaluation for LVDF includes four criteria: (1) septal E' velocity <7 cm/s or lateral E' <10 cm/s. (2) average E/e' ≥14, (3) left atrial volume index (LAVI) >34 ml/m2, (4) tricuspid regurgitation (TR) velocity >2.8 m/s. The study interest were the presence of the LVDF criteria for each or combined.

Results

The study consisted of 275 healthy individuals (89% male) with the mean age of 32.9±7.6 years and SUA of 6.1±1.3 mg/dl. The hyperuricemic (N=77) vs. normouricemic (N=198) groups had greater ratio of septal e' <7 (18.2% vs. 5.6%, P=0.002), lateral e' <10 (26% vs. 10.8%, P=0.003), the composite of septal e' <7 or lateral e' <10 (31.6% vs. 13.3%, P=0.001), and average E/e' >14 (3.9% vs. 0%, P=0.021). SUA remained significantly associated with septal e' <7 cm/s (adjusted HR: 1.704, 95% CI: 1.093–2.655, P=0.019) and the presence of any LVDF criteria (adjusted HR: 1.342, 95% CI: 1.044–1.724, P=0.022); Trends toward significant association were found between SUA and average E/e' >14 (adjusted HR: 1.330, 95% CI: 0.981–1.804, P=0.066) and between SUA and lateral e' <10cm/s (adjusted HR: 1.342, 95% CI: 0.970–1.857, P=0.076).

Conclusions

Elevated SUA was associated with abnormal LVDF in the healthy individuals with normal kidney function. Maintaining SUA level within a normal limit may prevent from the development of abnormal LVDF and LVH.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Tri-service General Hospital, Songshan branch
Sex differences in patients with ischemia and no obstructive coronary disease subjected to intracoronary acetylcholine test in a multicenter registry
Authors: Grigorian L , Gutierrez E , Oteo J.F , Abdul-Jawad O , Amat Santos I , Gutierrez Barrios A , Fernandez Cisnal A , Jimenez Mazuecos J , Roa J , Vazquez M.E , Sanz R , Diez-Delhoyo F , Rivera A , Elizaga J , Fernandez-Aviles F
Published: November 2020

Background

Ischemia with no obstructive coronary disease (INOCA) is increasingly diagnosed because of wide performance of coronary angiography. Prevalence of INOCA is higher in women than in men, however the exact pathophysiological mechanisms which may explain this phenomenon are still not very well understood.

Objective

To evaluate differences in clinical and procedural characteristics between men and women with INOCA subjected to intracoronary acetylcholine test (Ach).

Methods

A total of 210 women and 148 men with INOCA diagnosed with coronary angiography, were prospectively enrolled in a multicenter, observational registry. Ach test was performed according to clinical indications in all included patients. After 1-year patients were re-evaluated for major cardiovascular events, angina symptoms and prescribed medical treatment.

Results

Mean age of 60.6±13.6 years old was similar in both populations, but differences were observed in the prevalence of risk factors: active smoking was more frequent among men (43% vs. 17%, p<0.001), who had also a higher number of associated risk factors (≥3 risk factors were present in 31.2% of men vs. 20.2% of women, p<0.01) and more frequent history of percutaneous coronary revascularization (14.2% vs. 6.7%, p=0.03). Women were more prone to have dyspnea than men (35.5% vs. 20.8%, p=0.01). Men had more coronary atherosclerosis in angiography (57.9% vs. 43.7%, p=0.01) and more slow flow in the left anterior descending artery (21.6% vs. 9.0%, p=0.001). Ach was positive in 36.5% of patients, similar in both sexes, with no differences in the type of induced coronary spasm. Among those with a positive Ach test, at one-year, 36% of women vs. 43.6% of men were on optimal medical treatment for vasospasm although the difference was not statistically significant. Importantly, 41.5% of women and 38.1% of men experienced severe symptoms of angina during follow-up.

Conclusions

Although men with INOCA have a higher risk profile than women and more coronary atherosclerosis, one third of patients present endothelial dysfunction, similar in both groups, indicating that probably other pathophysiological mechanisms are responsible for it in females. Treatment in these patients remains suboptimal and associated with highly impaired quality of life.

Funding Acknowledgement

Type of funding source: None
Antithrombotic drugs do not increase the risk of laparotomy for gastrointestinal cancer
Authors: Okino S
Published: November 2020

Background

Some patients with gastrointestinal cancer requiring laparotomy take antithrombotic drugs (AT). However, safety of continuing or withdrawing AT before surgery is controversial.

Purpose

To investigate whether the use of AT increases intraoperative blood loss, perioperative thromboembolic event and mortality in patients undergoing laparotomy for gastrointestinal cancer.

Methods

In this retrospective study carried out from January 2016 to July 2019, we took a survey of laparotomy for gastrointestinal cancer in our hospital. AT was defined as aspirin, Adenosine-diphosphate receptor antagonists (ADPi), direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA). Patients were stratified into three groups; non-AT (group N), continuing AT (group C) and withdrawing AT before surgery (group W). We investigated differences in risks of events, including intraoperative blood loss, thromboembolic events within 60 days including acute coronary syndrome, cerebral infarction and venous thromboembolism, and long-term mortality. We also compared between continuing and withdrawing AT after propensity score matching.

Results

A total of 335 patients (123 females, mean age 72.5±9.5 years) were enrolled and stratified into group C (n=24), W (n=45) and N (n=266). Mean follow-up period was 684±400 days. Aspirin was taken in twenty of group C and twenty-six of group W. ADPi was taken in ten and nine of each group respectively. DOAC was taken in three and six of each group respectively. And VKA was taken in one and eleven of each group respectively. Patients of group C had more coronary artery disease (75.0% of group C, 33.3% of group W and 2.3% of group N, p<0.001) and prior coronary stent implantation (54.2%, 20.0% and 0% of each group respectively, p<0.001). There was no significant difference in cancer site and cancer stage. There was no significant difference in intraoperative blood loss (median [interquartile] (mL): 102 [8, 154] in group C, 140 [50, 310] in group W, and 150 [53, 324] in group N (p=0.095). Thromboembolic event had occurred in 4.4% of group W and 1.9% of group N (p=NS). Long term mortality was 33.3% of group C, 20% of group W and 22.9% of group N (p=NS). Kaplan-Meier analysis showed there was also no significant difference of long-term mortality (Log-rank p=NS). In patients with AT, after propensity score matching, there was no significant difference in intraoperative blood loss (102 [8,154] vs. 88 [18,217], p=NS), thromboembolic event (none in both group) and long-term mortality (33.3% vs. 12.5%, p=0.168) between continuing AT and withdrawing AT. Kaplan-Meier analysis revealed there was a tendency of higher mortality in group C but not significant difference (Log-rank p=0.0643).

Conclusion

This study suggests that patients taking AT do not have significant higher risk of intraoperative blood loss, thromboembolic event and mortality in laparotomy of gastrointestinal cancer.

Funding Acknowledgement

Type of funding source: None
Transcatheter aortic valve replacement in elderly population. Do we have reliable scores to predict prognosis?
Authors: Ribas Barquet N , Giralt Borrell T.G.B , Caldentey Adrover G.C.A , Millan Segovia R.M.S , Sanchez Carpintero A.S.C , Roqueta Guillen C.R.G , Herrero Torrus M.H.T , Izquierdo Marquisa A.I.M , Quiroga Arbones X.Q.A , Vaquerizo Montilla B.V.M
Published: November 2020

Background

Aortic stenosis (AS) is the most common valvulopathy in the western world and its prevalence is rising due to an ageing population. Transcatheter aortic valve replacement (TAVR) is the procedure of choice for severe AS in intermediate and high-risk patients and for very elderly population. Geriatric evaluation can be crucial to identify those subjects in which TAVR will not provide a prognosis benefit.

Purpose

The aims of this study were to compare clinical outcomes of patients that were evaluated by a Heart Team and were treated with conservative treatment or by TAVR and to identify geriatric scales that could predict worse prognosis during follow-up.

Methods

From November 2015 to April 2019, 154 consecutive patients with severe aortic stenosis assessed for suitability of TAVR were included in the analysis. A complete geriatric evaluation were performed at inclusion.

Results

Seventy-six patients (51%, median age 82.9±0.7) were allocated to medical treatment (MT) and the remainder (n=78, 49%, median age 83.7±0.6) to TAVR. Median follow up period was 17.8±13.8 months. Basal and echocardiographic features were similar in both groups except for Euroscore and geriatric evaluation (table 1). In a multivariate analysis including treatment and geriatric scales, conservative treatment was an independent predictor of all-cause and cardiovascular mortality (HR 3.92, 95% CI 1.47–10.48, p=0.015 and HR 4.12, 95% CI 0.98–17.28, p=0.0023 respectively). TAVR was also a protective factor for cardiovascular hospitalizations (OR 0.21, 95% CI 0.08–0.52, p<0.001). A Lawton scale score <4 was associated with a higher cardiovascular mortality (HR 9.97, 95% CI 1.18–84.42, p=0.0023) and cardiovascular hospitalizations (OR 3.5, 95% CI 1.30–9.43 p<0.0001). None of the other scores were associated to outcomes.

Conclusion

TAVR confers a survival benefit in the elderly population with severe aortic stenosis compared to conservative treatment. Lawton scale could be a useful tool to identify high risk patients with poorer prognosis during follow-up independently of the therapy performed.

Funding Acknowledgement

Type of funding source: None
Utilization of an electronic health record derived elder risk assessment score and outcome in patients undergoing aortic valve replacement
Authors: Gharacholou S , Ball C.B , Del-Carpio Munoz F.D.C , Takahashi P.Y.T , Pellikka P.A.P , Pollak P.M.P , El Sabbagh A.E.S , Chaudhry R.C , Borgman P.G.B , Singh M.S
Published: November 2020

Background

Older adults with severe aortic stenosis (AS) are at high risk of mortality unless surgical or transcatheter aortic valve replacement (AVR) is performed. Risk stratification often becomes complicated in frail elders with multi-morbidity, and time constraints limit thorough evaluation of geriatric comorbidities in the outpatient clinic setting.

Purpose

Utilization of an automated administratively-derived electronic health record (EHR) tool may aid in risk stratification of AS patients undergoing AVR.

Methods

We reviewed patients with severe AS undergoing AVR at our hospital program and cross-referenced with the Elder Risk Assessment (ERA) score. The ERA score is an administratively abstracted score derived on adults >60 years old followed by general medicine clinic. It contains the following variables: marital status, age, hospitalized days in preceding 2 years, diabetes, coronary disease, heart failure, stroke, pulmonary disease, cancer, and dementia; higher scores indicate greater risk for adverse outcomes. Kaplan-Meier method was used to estimate survival by ERA score tertile. Cox regression was used to test the association of ERA with survival.

Results

There were 97 patients with severe AS undergoing AVR with ERA scores. Mean age was 80.6 (±6.6) years, 37% were female, average Society of Thoracic Surgery (STS) score was 3.6% (± 2.6), and 7% had transcatheter AVR. Co-morbidities were prevalent and included atrial fibrillation (41%), chronic renal failure (16%), stroke (14%), and diabetes (35%). Over a mean follow-up of 68 months (± 37.9 months), there were 62 deaths. Elevated ERA score was associated with worse long term survival (p=0.016 by log-rank) (Figure 1), with only 49% surviving at 5 years in the highest ERA tertile vs 68% in the lowest ERA tertile. Cox regression demonstrated that the relative risk of death per 6 unit increase in ERA score was 1.54 (95% CI 1.21–1.96, P<0.001) in single variable analysis and 1.43 (95% CI 1.11–1.84, P=0.006) after adjusting for STS score.

Conclusions

Patients undergoing AVR for severe AS are often co-morbid older adults. An automated EHR derived ERA score was independently associated with survival after accounting for STS score and may streamline and improve risk assessment in these patients.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Mayo Clinic
Cardioprotective effects of PCSK9 inhibitor evolocumab against doxorubicin-trastuzumab sequential treatments and ipilimumab-induced cardiotoxicity: the role of MyD88/NF-KB/mTORC1 pathways
Authors: Quagliariello V , Caronna A , Lombari C , Bonelli A , Conforti G , Botti G , Maurea N
Published: November 2020

Introduction

Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapy to treat hypercholesterolaemia and related cardiovascular diseases. Evolocumab, a PCSK9 inhibitor, reduced the risk of cardiovascular events in patients with atherosclerotic cardiovascular diseases when added to maximally tolerated statin therapy (± ezetimibe), and recent data from the ODYSSEY OUTCOMES trial indicate that alirocumab added to maximally tolerated statin therapy (± other lipid-lowering drugs) reduces the risk of cardiovascular events in patients with a recent acute coronary syndrome.

Purpose

Considering the expression of PCSK9 in heart tissue, we aimed to study for the first time the direct biochemical effects of evolocumab in cardiomyocytes during exposure to doxorubicin, trastuzumab, their sequential treatments, and immune checkpoint inhibitor ipilmumab.

Methods

Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin, trastuzumab, sequential treatment of both ( all 100 nM), alone or in combination with evolocumab (50 nM) for 48h. In another experiment, in co-coltures of human fetal cardiomyocytes and lymphocytes, we incubated ipilimumab (200 nM) alone or in combination with evolocumab for 48h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6).

Results

Evolocumab co-incubated with doxorubicin alone or in sequence with trastuzumab exerts cardioprotective effects, enhancing cell viability of 35–43% compared to untreated cells (p<0,05 for all); Cardiomyocytes co-incubated withevolocumab and ipilimumab (in co-colture of cardiomyocytes and lymphocytes) reduces significantly the cardiotoxicity phenomena through MyD88/NF-KB/cytokines axis and mTORC1 Fox01/3α mediated mechanisms.

Conclusion

We demonstrated, for the firts time, that PCSK9 inhibitor evolocumab exerts direct effects in cardiomyocytes during doxorubicin, trastuzumab and ipilimumab mediated cardiotoxicity turning on a new light on its possible use in the management of the cardiotoxic effects of antineoplastic drugs in cancer patients

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the “Ricerca Corrente” grant from the Italian Ministry of Health
Could diastolic perfomance parameters be earlier markers for cardiotoxicity in high risk cancer patients?
Authors: Farcas A.D , Anton F.P , Mocan-Hognogi D.L , Cainap C
Published: November 2020

Introduction

Survival after chemotherapy in cancer patients can be affected by several factors, including cardiotoxicity. Identification of high-risk patients and early diagnosis of cardiotoxicity would allow preventive therapies that would mitigate its effect. Although troponin I (hsTnI) and NT-proBNP have shown their usefulness, there still is incomplete data regarding the time and frequency of their testing.

Aims

The goal of our study was to identify new diagnostic biomarkers for early diagnosis of cardiotoxicity and analyze their predictive value for outcome.

Methods

We included 68 female patients with breast cancer treated with trastuzumab, who underwent clinical, biological and echocardiographic evaluation and signed informed consent. We performed biomarker testing (NT-proBNP, hsTnI, Gal 3 and GDF-15) and echocardiography at inclusion and on the day of the first chemotherapy course (after trastuzumab was administered).The patients was follow for 1 years and cardiovascular events was noted.

Results

The study group included middle-aged women (34.5±8.4). Although changes in the biomarker levels after the first chemotherapy course were found, these were not statistically significant. The more interesting aspect is that we found some markers increased (NTproBNP 11.12±2.9 vs 16.25±3.17, p=0.12, hsTnI 147.75±32.88 vs 151.09±34.67, p=0.74,) while other decreased (Gal-3 2300.92±982.26 vs 2193.53±377.69, p=0.78, GDF-15- 1014.09±1689 vs 1006±1662, p=0.76). Echocardiography showed no significant differences in systolic performance parameters – ejection fraction (EF) and global longitudinal strain (GLS) – but a significant change in left ventricular end-diastolic filling pressure (LVEDP) estimated by the e/e' ratio (5.68±5.63 vs 10.05±4.42, p=0.000. The LVEDP increase was correlated to NTproBNp (r=0.712, p=0.000) and Gal3 (r=0.44, p=0.009) variability. Univariate analysis showed that only NTproBNP variability predicts 16.3% of the LVEDP variability between the two moments, but the NTproBNP and LVEDP could predict the cardiovascular events during the 1-year follow-up.

Conclusion

Changes in diastolic performance – e/e' ratio – occur early after chemotherapy and correlate with the variability of serum natriuretic peptides.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): Partnership for the transfer of knowledge in biogenomics applications in oncology and related fields - BIOGENONCO, Project co-financed by FEDR through Competitiveness Operational Programme 2014–2020, contract no. 10/01.09.2016.
Impact of HIV on treatment and outcome after acute myocardial infarction: a Swedish nationwide observational cohort study
Authors: Vingerling M , Andell P , Jernberg T , Marrone G
Published: November 2020

Background

People living with HIV (PLHIV) on antiretroviral therapy (ART) have a higher risk of developing cardiovascular diseases (CVD) at a younger age due to chronic inflammation, higher prevalence of traditional cardiovascular risk factors and side-effects of ART – although the last is controversial. Moreover, recent studies have shown that PLHIV have unfavorable CVD outcomes compared to HIV-negative people. A potential explanation could be differences in acute treatment and in-hospital management.

Purpose

This study is aimed at investigating patients with and without HIV experiencing an acute myocardial infarction (AMI) in relation to baseline characteristics, in-hospital management and short-term outcomes.

Methods

The nationwide SWEDEHEART (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry and Swedish National HIV Registry (InfCareHIV) were used to identify patients with and without HIV experiencing AMI. Primary outcome was the occurrence of a combined composite endpoint of major adverse cardiovascular events (MACE: all-cause mortality, new myocardial infarction or stroke) at 1 year in PLHIV versus HIV-negative people presenting with acute MI. Secondary outcomes were the occurrence of any of the individual components of the above composite endpoint. Kaplan-Meier survival curves and multivariable Cox regression models were used to compare the populations.

Results

We identified all PLHIV (n=319; 85% male) and HIV-negative people (n=711,506; 59% male) who experienced an AMI during 1996–2017 in Sweden. PLHIV presented with AMI more than ten years younger (median age 54.7 vs 67.1 years), had a higher prevalence of smoking and chewing tobacco use and a lower prevalence of hypertension. PLHIV with AMI had higher risks of MACE (adjusted hazard ratio (adjHR) for age, sex, traditional risk factors, comorbidities, in-hospital treatment and discharge medication = 1.60, 95% confidence interval (CI) 0.98–2.61) and mortality (adjHR = 2.37, 95% CI 1.34–4.16) at 1 year compared to HIV-negative people with AMI.

Conclusion

PLHIV suffer AMI more than 10 years earlier than HIV-negative people. HIV was independently associated with higher risk of MACE and more than doubled all-cause mortality at 1 year after AMI. Improved primary and secondary prevention (e.g. smoking cessation) may improve outcomes.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Fellowship Gilead Science, Public Health Agency of Sweden
Long-term outcomes and determinants of restenosis after renal artery angioplasty in hypertensive patients with renovascular disease
Authors: Roslawiecka A , Kablak-Ziembicka A , Badacz R , Pieniazek P , Rzeznik D , Trystula M , Przewlocki T
Published: November 2020

Introduction

Restenosis (RS) following percutaneous angioplasty (PTA) of renal artery stenosis (RAS) might have an unfavorable impact on renal function and blood pressure (BP) outcomes.

Aim

To evaluate prevalence and predictors of RS in patients treated with PTA for RAS, and relationship between BP and renal function (RF) changes with RS.

Material and methods

We analyzed freedom from RS in 210 patients (64.6±12.8; range:20–85y.o.), who underwent 248 successful stent-assisted PTAs in RAS. The change in levels of serum creatinine (SCC), eGFR, systolic/diastolic BPs (SBP/DBP) were analyzed prior to PTA, at 6-, 12-months and final follow-up visits, and whenever RS was diagnosed.

Results

RS was identified in 30 (14.3%) patients and 36 (14.5%) lesions. The Kaplan-Meier RS-free survival curves in fibromuscular dysplasia, atherosclerosis and vasculitis were: 100% and 100%; 95.6 and 83.9%, while 71.4 and 39.7% at 1 and 7-years, respectively. Patients with RS, as compared to RS-free patients, presented with lesser response in changes of: SBP (1.4±17.6 vs −15.8±25.8mmHg; p=0.01), DBP (2.64±10.1 vs. −6.5±14.1mmHg; p=0.002), SCC (22.4±55.2 vs −3.6±43.9μmol/L; p=0.002) and eGFR (−1.85±18 vs. −5.34±19.5mmHg; p=0.045).

In multivariate Cox regression analysis, independent predictors of RS occurred: lack of BP decrease (HR: 4.19, 95% CI: 1.67–10.3; p=0.002), lack of eGFR increase of less than ≤0.17 ml/min/1.73m2 (HR: 2.93, 95% CI: 1.08–7.91; p=0.033), stent diameter ≤5mm (HR: 2.76, 95% CI: 1.09–6.97; p=0.031) and vasculitis (HR: 5.61, 95% CI: 1.83–17.2; p=0.003). RS was treated in 24 patients with RS recurrence in 20%.

Conclusions

RS rate differs depending on RAS etiology. Lack of SBP/DBP and eGFR improvement, vasculitis, and stent diameter are associated with RS risk. Repeated PTA is effective, but recurrent RS occurs in 20% of cases.

Kaplan-Meier RS-free survival curves

Funding Acknowledgement

Type of funding source: None
Impact of polyvascular disease and renal dysfunction on cardiovascular outcomes in diabetes: post hoc analyses from EMPA-REG OUTCOME
Authors: Verma S , Mazer C.D , Inzucchi S.E , Wanner C , Ofstad A.P , Johansen O.E , Zwiener I , George J.T , Butler J , Zinman B
Published: November 2020

Background

Individuals with polyvascular disease and impaired renal function are at high risk of cardiovascular (CV) events, but this relationship is not well investigated in people with type 2 diabetes (T2D). Furthermore, the impact of polyvascular disease plus renal dysfunction on the risk for hospitalisation for heart failure (HHF) remains unclear.

Purpose

We investigated this in a post hoc analysis of the EMPA-REG OUTCOME trial in which empagliflozin reduced risk of CV death and HHF versus placebo in people with T2D and vascular disease. In addition, we explored the treatment effect of empagliflozin on CV, HF and mortality outcomes across the spectrum of baseline polyvascular disease and impaired renal function.

Methods

Patients with T2D, CV disease and estimated glomerular filtration rate (eGFR) of ≥30 ml/min/1.73 m2 received empagliflozin 10 mg, 25 mg, or placebo. Vascular beds (VBs) were defined as coronary artery disease, peripheral artery disease, and cerebrovascular disease (Fig). By use of Cox regression, we explored the association between baseline eGFR < or ≥60 ml/min/1.73 m2, with or without polyvascular disease (1 vs ≥2 VBs involved), and CV death, HHF, CV death (excl. fatal stroke)/HHF, and all-cause mortality (ACM), as well as the treatment effect of empagliflozin versus placebo on these outcomes.

Results

Patients with ≥2 VBs involved and eGFR <60 ml/min/1.73 m2 [n=463], were slightly older (mean age 68.2 vs. 64.3 or 62.6 years), had T2D duration >10 years more often (73.4% vs. 63.2% or 54.9%), and a higher HF prevalence at baseline (19.4% vs. 11.1% or 9.2%) versus those with ≥2 VBs involved and eGFR ≥60 ml/min/1.73 m2 [n=866], or those with only 1 VB involved regardless of eGFR [n=5630], respectively. However, characteristics were generally balanced between treatment groups. Notably, co-existing polyvascular disease and eGFR <60 ml/min/1.73 m2 was strongly associated with increased risk of all outcomes. The placebo incidence rates per 1000 patient-years for CV death were 14.4 (95% CI 10.9, 18.3) and 19.6 (12.8, 27.8) in those with 1 VB involved and eGFR ≥60 or eGFR <60, respectively, and 32.7 (21.7, 45.8), and 52.4 (32.9, 76.5) in those with 2 VBs and eGFR ≥60 or eGFR <60 ml/min/1.73 m2, respectively. Importantly, empagliflozin reduced the risk for all outcomes regardless of number of VBs affected and kidney function (Fig).

Conclusions

Co-existing polyvascular disease and eGFR <60 ml/min/1.73 m2 confer an extremely high risk of CV and all-cause mortality, and HHF. Empagliflozin lowered this risk consistently compared with placebo, regardless of polyvascular disease and impaired kidney function.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance
Effects of linagliptin vs glimepiride stratified by prior insulin secretagogue use in the cardiovascular outcome study of linagliptin versus glimepiride in type 2 diabetes (CAROLINA) trial
Authors: McGuire D.K , Rosenstock J , Johansen O.E , Zinman B.J , Khunti K , Mattheus M , Lund S.S , Espeland M.A , Marx N
Published: November 2020

Background/Introduction

The cardiovascular outcome study of linagliptin versus glimepiride in type 2 diabetes (CAROLINA) was designed to compare the effects on cardiovascular (CV) events, and other outcomes, of linagliptin with glimepiride in patients with relatively early type 2 diabetes with elevated CV risk

Purpose

These post hoc analyses of the CAROLINA randomized controlled trial explore outcomes in subgroups stratified by prior sulfonylurea (SU) or glinide use.

Methods

Participants with relatively early type 2 diabetes, high CV risk and HbA1c 6.5–8.5% were randomized to linagliptin 5 mg or glimepiride 1–4 mg once daily with standard of care. 29.5% of patients had prior SU/glinide use. SU/glinides were discontinued at trial entry. Outcomes included time to first CV death/MI/stroke (3P-MACE), time to all-cause mortality, HbA1c change from baseline and time to first hypoglycaemia event.

Results

6033 participants received ≥1 study drug dose (mean [SD] age 64.0 [9.5] yrs, HbA1c 7.2 [0.6] %, median diabetes duration 6.3 yrs, 42% with CV disease); 897 linagliptin and 884 glimepiride participants had prior SU/glinide use. Results for 3P-MACE and all-cause mortality were consistent across subgroups with/without prior SU/glinide use (interaction p>0.05; Fig). After some initial differences, there was no meaningful difference in HbA1c between linagliptin vs glimepiride across SU/glinide subgroups and overall. Hypoglycaemia rates were lower with linagliptin vs glimepiride overall and across SU/glinide subgroups, with some heterogeneity for prior SU/glinide use (interaction p<0.01; Fig).

Conclusion

There was no difference in linagliptin versus glimepiride on 3P-MACE and all-cause mortality, with consistent results across subgroups irrespective of prior SU/glinide use. Hypoglycaemia rates were consistently lower with linagliptin vs glimepiride, regardless of prior SU/glinide use.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company