bluuebunny/crossref_metadata_2025 huggingface dataset:
P1029Catheter ablation outcome and heart failure hospitalization in atrial fibrillation patients: insights from the Kansai plus atrial fibrillation (KPAF) registry
Authors: Tanaka N , Inoue K , Kobori A , Kaitani K , Morimoto T , Morishima I , Yamaji H , Nakazawa Y , Kusano K , Tanaka K , Hirao Y , Iwakura K , Fujii K , Kimura T , Shizuta S
Published: October 2019

Background

Heart failure (HF) is the leading cause of death in patients with atrial fibrillation (AF). Radiofrequency catheter ablation (RFCA) for AF is effective to maintain sinus rhythm.

Purpose

We sought to clarify whether AF ablation outcome influenced incidence of HF hospitalization after the procedures.

Methods

We conducted a large-scale, prospective, multicenter, observational study. A total of 5010 consecutive patients who underwent an initial RFCA for AF in 26 centers were enrolled (average age, 64±10 years; non-paroxysmal AF, 35.6%). The median follow-up duration was 2.9 years.

Results

The 3-year cumulative incidence of AF recurrence after a single procedure was 40.2%. The 3-year incidence of hospitalization for HF was observed in 92 patients (1.8%) and was significantly higher in patients with AF recurrence than those without it (3.3% vs 0.84%, log-rank p<0.001). After adjustment by advanced age,(≥65 years), reduced left ventricular ejection fraction (≤50%), low estimated glomerular filtration rate (≤60ml/min), and history of HF, all of which were statistically associated with a risk of HF hospitalization (p<0.1, respectively), AF recurrence after the index RFCA was an independent predictor of HF hospitalization (hazard ratio [HR]; 3.17, 95% confidence interval [CI]; 2.06–5.04, p<0.001).Even after multiple procedures (1425 re-ablation sessions in 1274 patients [25.4%]), AF recurrence after the last procedure was an independent predictor of HF hospitalization (HR; 2.83, 95% CI; 1.89–4.24, p<0.001).

Conclusions

Among AF patients receiving RFCA, those with AF recurrence were at greater risk of heart failure hospitalization than were patients without AF recurrence. These differences should be noted when treating AF patients in actual clinical practice.

Acknowledgement/Funding

This study was supported by the Research Institute for Production Development in Kyoto, Japan.
P1033Impact of workflow modifications in atrial fibrillation ablation for reducing the incidence of silent cerebral lesions with a new multi-electrode radiofrequency balloon catheter
Authors: Grimaldi M , Tondo C , Riva S , Neuzil P , Ghaly N , Bishara M , Schilling R , Reddy V
Published: October 2019

Background

Silent cerebral lesions (SCL) often occur after invasive cardiac procedures. Reported SCL incidence with AF ablation varies (incidence, up to 50%), depending on technology used, procedural workflow, and detection method.

Objective

To evaluate the impact of ablation workflow modifications on SCL incidence following pulmonary vein isolation radiofrequency (RF) ablation with a novel multi-electrode RF balloon catheter in patients with symptomatic paroxysmal AF (PAF).

Methods

In the RADIANCE feasibility study of the balloon catheter, all enrolled patients who underwent ablation were screened for SCL using pre- and post-procedural diffusion-weighted MRI. Several modifications were made to the ablation workflow in a subsequent European registration study (SHINE) of the same catheter: eliminating dual transseptal access, using an over-the-wire mini lasso, continuously irrigating all side ports, bolus dosing with heparin before transseptal puncture, maintaining activated clotting time (ACT) at 350–400 sec, and setting a maximum temperature limit of 55°C (previously, 60–65°C). Interim data are presented for SHINE (data cutoff, 22 Oct 2018).

Results

In the neurological assessment evaluable (NAE) populations of RADIANCE (n=38) and SHINE (n=30), respectively, mean ages were 60.8±10.04 and 59.7±7.83 years, and 57.9% and 70.0% were male. One patient in each study had a history of TIAs. SCL incidences were 23.7% (10 lesions in 9 patients) in RADIANCE and 7.1% (2 lesions in 2 patients) in SHINE (excluding 1 SCL that occurred in a patient who failed to meet inclusion criteria [age>75] and 1 SCL that occurred after data cut-off). SHINE NAE enrollment has since completed with no further SCL occurrences. Overall, mean ACTs were 344.3±24.55 sec in RADIANCE and 381.6±73.31 sec in SHINE (p=0.01); in patients with SCL, mean ACTs were 349.3±25.65 and 417.8±87.33 sec, respectively.

Conclusion(s)

Modifications to the workflow led to a decrease in the SCL incidence for PAF ablation using the novel RF balloon catheter.

Acknowledgement/Funding

These studies were sponsored by Biosense Webster, Inc.
1108Effectiveness of nursing counseling for patients with cardiovascular risk factors: controlled clinical trial with a 24 months post-intervention follow-up
Authors: Salazar A , Vilchez-Barboza V , Saez K , Paravic T
Published: October 2019

Objective

To establish the effect after 24 months of a face-to-face and telephone nursing counseling intervention, aimed at controlling cardiovascular risk factors (hypertension, dyslipidemia and overweight) and improving health-related quality of life (HRQoL) in patients of the cardiovascular health program of family health centers of Concepciόn, Chile.

Methods

Randomized controlled clinical trial with a 24 months post-intervention follow-up. 120 patients with cardiovascular risk factors under the cardiovascular health program were recruited from 6 family health centers and randomized into a control group (60) and an intervention group (60). The intervention group received the regular care in addition to face-to-face and telephone nursing counseling. Baseline measurements were taken and also at the end of the intervention (7 months). Participants returned then after 12 and 24 months for follow-up evaluations. A total of 109 subjects completed the intervention at 7 months and 45 returned at 24 months. During follow-up evaluations both groups continued to receive regular care given in the health centers. The measurements consisted of HRQoL (physical and mental health), systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), abdominal circumference (AC), total cholesterol (TC), low density lipoproteins (LDL-Chol), high density lipoprotein (HDL-Chol), atherogenicity index (LDL/HDL), cardiovascular risk factor (TC/HDL), 10-year coronary risk. Ethical requirements were considered and statistical analysis was carried out using MANCOVA and d-Cohen repeated measurements.

Results

The analysis of the effects of the intervention in the 24-month follow-up showed that subjects in the intervention group only maintained significant improvement of AC over time (F=3.18; p=0.03), compared to the control group.

Conclusion

Although participants in the intervention group only maintained the AC improvement over time, this can be regarded as an indirect indicator of the presence of intra-abdominal fat that makes it possible to predict and classify the risk of cardiovascular disease. Long-term follow-up studies are required to investigate behaviors and mechanisms that contribute to maintaining improvements in this indicator. Additionally, future research should include reinforcement activities, either face-to-face or by telephone, to help maintain the positive results of interventions.

Acknowledgement/Funding

Universidad de Concepciόn 214.082.049-1.0
1181Role of rho-mdia1 signaling to maintain cardiac function in response to pressure overload in mice
Authors: Abe I , Terabayashi T , Teshima Y , Ishii Y , Miyoshi M , Kira S , Kondo H , Saito S , Yufu K , Takahashi N , Ishizaki T
Published: October 2019

Background

Cardiac hypertrophy is a compensatory response to pressure overload that leads to heart failure. Recent studies have shown that Rho signaling has crucial regulatory roles in actin cytoskeleton rearrangement during cardiac hypertrophic responses. Rho is rapidly activated in response to pressure overload, but the mechanisms by which Rho and its downstream proteins control actin dynamics during hypertrophic responses remain unclear.

Objective

To identify the essential roles of mDia1 (Rho-effector molecule) in pressure overload-induced ventricular hypertrophy.

Methods and results

Male wild-type (WT) and mDia1-knockout (mDia1KO) mice (10–12 weeks old) were subjected to transverse aortic constriction (TAC) or a sham operation. The heart weight/tibia length ratio, cardiomyocyte cross-sectional area, left ventricular wall thickness, and expression of hypertrophy-specific genes were significantly decreased in mDia1KO mice 3 weeks after TAC, and the mortality rate was higher at 12 weeks. Echocardiography and the pressure-volume loop indicated that mDia1 deletion increased the severity of heart failure 8 weeks after TAC. Microarray gene expression profiling showed that the induction of immediate early genes due to the TAC operation was significantly lower in mDia1KO mice than WT mice, as was the activation of extracellular signal-regulated kinase (ERK) and focal adhesion kinase (FAK). We examined the role of mDia1 in neonatal rat ventricular cardiomyocytes (NRVMs) exposed to mechanical stress. The siRNA-mediated silencing of mDia1 attenuated stretch-induced ERK and FAK phosphorylation, and gene expression of c-fos. Importantly, loss of mDia1 suppressed an increase in the F/G-actin ratio in response to pressure overload in the mice. In addition, increases in nuclear myocardin-related transcription factors (MRTFs) and serum response factor (SRF) were perturbed in response to pressure overload in mDia1KO mice and to mechanical stretch in mDia1 depleted NRVMs.

Conclusions

Rho-mDia1, through actin dynamics, plays critical roles in pressure overload-induced hypertrophy by regulating ERK and FAK phosphorylation and the transcriptional activity of MRTF-SRF.
1199Reduction in blood pressure following renal denervation for patients with differing baseline cardiovascular risk
Authors: Mahfoud F , Mancia G , Schmieder R , Narkiewicz K , Ruilope L , Schlaich M , Williams B , Fahy M , Bohm M
Published: October 2019

Background

Lowering blood pressure (BP) reduces clinical events. Renal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent a particularly attractive option for patients with high cardiovascular (CV) risk. To evaluate this proposal, it is important to determine whether baseline CV risk impacts the efficacy of RDN in lowering BP.

Purpose

We evaluated whether BP changes after RDN were dependent on baseline CV risk.

Methods

AHA/ACC Atherosclerosis CV Disease (ASCVD) risk score was calculated for patients in the Global Symplicity Registry (GSR; NCT01534299), a global registry of RDN in patients with uncontrolled hypertension, using baseline office systolic BP, total/HDL cholesterol measurements, diabetic and smoking status, gender, age, and number of baseline anti-hypertensive medications. Patients were separated into 3 groups based on ASCVD risk scores: <10%, ≥10% and <20% and ≥20%. Baseline demographics and 24-hour systolic BP changes at 6 months and 1, 2 and 3 years were compared between groups, as well as rates of adverse events at 3 years.

Results

Individual ASCVD risk scores were calculated for 1,434 patients in GSR. The median ASCVD risk score was 19.4% and 403 patients had a risk score of <10%, 326 a risk score of ≥10 and <20%, and 705 a risk score ≥20%. Patients with ASCVD risk score ≥20% had a higher baseline office systolic BP, were significantly older, and had higher rates of prior myocardial infarction and/or diabetes (all p<0.0001 compared to patients with lower risk scores). RDN reduced BP similarly across all groups of patients. Changes in 24-hour systolic BP at 6 months and 1, 2 and 3 years are shown in Figure 1. Adverse events at 3 years are shown in Table 1.

Adverse events at 3 years ASCVD risk score <10% ASCVD risk score ≥10% & <20% ASCVD risk score ≥20% p-value (N=265) (N=224) (N=468) Death 3 (1.1) 5 (2.2) 41 (8.8) <0.0001 Cardiovascular death 3 (1.1) 2 (0.9) 23 (4.9) 0.0017 Myocardial infarction 6 (2.3) 6 (2.7) 11 (2.4) 0.9513 Stroke 8 (3.0) 9 (4.0) 24 (5.1) 0.3894 Hospitalization for new onset heart failure 4 (1.5) 7 (3.1) 26 (5.6) 0.0194 Values are proportions reported as n (%).

Conclusions

BP changes after RDN were similar for patients with varying baseline ASCVD risk scores, suggesting uniform BP-lowering efficacy of RDN regardless of patients' baseline CV risk. The impact of baseline risk on clinical event reduction by RDN-induced BP reduction will need to be evaluated in further studies.

Acknowledgement/Funding

The Global SYMPLICITY Registry is funded by Medtronic.
1410Clinical predictors of NT-proBNP response to early initiation of sacubitril/valsartan after hospitalisation for decompensated heart failure: An analysis of the TRANSITION study
Authors: Pascual-Figal D , Bao W , Senni M , Wachter R , Behlolavek J , Chakrabarti A , Noe A , Schwende H , Butylin D , Prescott M
Published: October 2019

Background

NT-proBNP has diagnostic and prognostic value in patients with heart failure (HF). Compared with enalapril, sacubitril/valsartan (S/V) significantly reduced NT-proBNP within 1 week (wk) of administration and reduced HF re-hospitalisation in patients with acute decompensated HF (ADHF) in PIONEER-HF. Identification of predictors of NT-proBNP reduction with S/V could aid prognostication following hospitalisation.

Methods

TRANSITION (NCT02661217) is an open label study in stabilised ADHF patients with HFrEF that compared S/V initiation pre- versus post-discharge (within 2 wk of discharge). Baseline NT-proBNP was measured at randomisation in both S/V groups (n=950). Clinical predictors of favourable response of NT-proBNP to S/V therapy (defined as reduction to <1000 pg/ml or >30% reduction vs. baseline) were studied at discharge, 4 wk and 10 wk post-randomisation.

Results

Median NT-proBNP at randomisation was similar in patients with S/V started pre- and post-discharge (1919 vs 1659 pg/ml). In patients receiving S/V in-hospital, NT-proBNP was reduced by 28% at discharge, compared to a 3% reduction in patients receiving optimised standard of care (between group p<0.001). A favorable response was reached in 46% vs 18% patients at discharge, 46% vs 42% at 4 weeks and 51% vs 48% at 10 weeks in pre- vs post-discharge groups. (Figure 1). Predictors of favourable NT-proBNP response to S/V at discharge were hypertension and shorter time from admission to first S/V dose. At 4 wk after randomisation, NT-proBNP was reduced similarly in patients started on S/V pre- and post-discharge. When the two S/V initiation groups were combined, predictors of favorable NT-proBNP response at 4 wk were higher initial dose of S/V (≥49/51 mg b.i.d.), higher baseline levels of NT-proBNP, de novo HF hospitalisation, ACEI/ARB naïve, lower baseline creatinine, no atrial fibrillation (AFib), no prior myocardial infarction (MI). A further reduction in NT-proBNP was seen at 10 wk post-randomisation in patients started on S/V pre- and post-discharge (38% vs 34%, between group p=0.250). Predictors of favourable NT-proBNP response to S/V were similar at 4 wk and 10 wk post-randomisation.

Conclusion

In-hospital initiation of sacubitril/valsartan shortly after stabilisation was associated with a prompt improvement of NT-proBNP already at discharge, whereas higher baseline levels of NT-proBNP, higher starting dose, absence of AFib and MI history, de novo HF and ACEI/ARB naïve status were associated with favourable NT-proBNP response in the vulnerable phase after discharge.

Acknowledgement/Funding

The TRANSITION study was funded by Novartis
1411The effect of eplerenone on fibrosis in hypertrophic cardiomyopathy. A randomised controlled trial assessed using cardiopulmonary exercise testing and cardiovascular magnetic resonance
Authors: Bhatti Y J , O'hanlon R , Ismail T F , Pennell D , Vassiliou V , Prasad S
Published: October 2019

Background

Recent studies have implicated aldosterone, a hormone of the renin-angiotensin-aldosterone system to cardiac hypertrophy, and cardiac and vascular fibrosis in cardiomyopathy. High levels of circulating aldosterone have been shown to cause myocardial and aortic fibrosis in animal models. In humans, high aldosterone concentrations have been associated with endothelial dysfunction, myocardial infarction, left ventricular hypertrophy and death. Aldosterone antagonism with spironolactone or eplerenone reverses the process of fibrosis in animal models.

Purpose

Left ventricular dysfunction due to hypertrophic cardiomyopathy (HCM) is a disorder associated with an increased risk of morbidity and premature mortality. An important pathological feature seen in cardiomyopathy is the development of fibrosis and its association with functional impairment and arrhythmia, including predisposition to sudden cardiac death. This trial observes the effect of eplerenone on myocardial fibrosis and exercise tolerance in patients with HCM.

Methods

42 patients were recruited into a double-blinded, placebo-controlled randomised study. Each patient had an established diagnosis of HCM without exclusion criteria (figure 1). 2 patients withdrew before enrolment. Enrolled patients were established on maximally tolerated doses of standard drugs used in the treatment of HCM and the doses of these drugs remained unchanged in the 2 months preceding enrolment to the trial. Patients were randomised to receive a maximal dose of 50mg eplerenone (n=21) or placebo (n=19). The patients underwent cardiopulmonary exercise testing and cardiovascular magnetic resonance (CMR) scan at baseline and 52 week follow up.

Results

At 52 weeks follow up there was no difference between placebo and treatment groups in peak oxygen consumption (−1.05 vs 0.63, p=0.32), anaerobic threshold (0.4 vs 1.45, p=0.31) or ventilatory efficiency slope (−0.77 vs 1.76, p=0.065). In addition, there was no significant difference observed in LV mass or fibrosis as assessed by CMR.

Inclusion and Exclusion Criteria

Conclusion

In the first randomised controlled trial using eplerenone in humans with HCM, we report no effect of treatment after 52 weeks on exercise capacity compared with placebo. In addition, we report no effect of treatment on the presence of fibrosis detected by CMR. Interpretation of these results are limited by small sample size and further studies will require a multi-centre recruitment process. The data presented here support the feasibility of eplerenone treatment in patients with HCM and provide statistical power calculation for future trials.
1440Anti-inflammatory adipokine, omentin, attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein-E knockout mice
Authors: Fang L , Ohashi K , Otaka N , Kawanishi H , Takikawa T , Murohara T , Ouchi N
Published: October 2019

Background

Abdominal aortic aneurysm (AAA) is an increasing and life-threatening disease. Obesity is associated with an increased risk of AAA. Omentin is a circulating adipokine, which is downregulated by obesity. Recently we have demonstrated that omentin is an anti-inflammatory adipokine that prevents the development of atherosclerosis in apolipoprotein-E knockout (apoE-KO) mice. Here we examined whether omentin could modulate angiotensin II-induced AAA formation in apoE-KO mice.

Methods and results

To overexpress human omentin in apoE-KO mice, apoE-KO mice were crossed with transgenic mice expressing the human omentin gene in fat tissue under the control of AP2 promoter (OMT-Tg mice). Circulating levels of human omentin in apoE-KO/OMT-Tg mice were approximately threefold higher than those in healthy human subjects, whereas human omentin was undetectable in apoE-KO mice. There were no differences in body weight, blood pressure and heart rate between apoE-KO/OMT-Tg and apoE-KO mice. We also subjected apoE-KO/OMT-Tg and apoE-KO mice at 24 weeks of age to continuous angiotensin II-infusion by using osmotic mini pumps for 4 weeks, which is a widely-accepted model of experimental AAA. ApoE-KO/OMT-Tg mice exhibited a lower incidence of AAA formation and a reduced maximal diameter of AAA determined by direct measurement and ultrasound imaging as compared with apo-E KO mice. In histological analyses with van Gieson staining, apoE-KO/OMT-Tg mice showed attenuated disruption of medial elastic fibers in response to angiotensin II compared with apo-E KO mice. ApoE-KO/OMT-Tg mice also displayed reduced mRNA levels of matrix metalloproteinase (MMP) 2 and MMP9 as well as pro-inflammation genes including interleukin (IL)-6 in aortic walls compared with apo-E KO mice. Treatment of human monocyte-derived macrophages with human omentin protein attenuated LPS-stimulated expression of MMP9, TNF-α and IL-6. Omentin treatment also reduced LPS-induced activation of MMP9 in cultured media of human macrophages as evaluated by gelatinolytic zymography. Omentin treatment increased phosphorylation levels of Akt in human macrophages. The suppressive effects of omentin on inflammatory response in macrophages were reversed by treatment with LY294002, which is an inhibitor of PI3 kinase/Akt signaling.

Conclusion

These data suggest that omentin acts as an adipokine that can attenuate angiotensin II-induced development of AAA through suppression of MMP activation and inflammatory response in the vascular wall.
2130The patient in clinical research: disposable guinea pig or involved actor?
Authors: Cosmi D , Mariottoni B , Cosmi F
Published: October 2019

Background

The request for informed consent to join a clinical trial often creates mistrust and hesitation in the patient who should be enrolled.

Methods

In the last ten years of cardiovascular clinical research we asked an informed consent to 2,586 patients. 59% agreed to join clinical trials, 40% refused. The 1% initially accepted and then withdrew the consent. We asked all the patients who refused the consent to answer a brief interview about the reasons for rejection. Patients who refused to join clinical trials were relatively young (mean age 62±5) and had a high level of education; 619 (60%) had a high school diploma or a degree.

Results

Of 1031 patients, 629 (61%), accepted to answer the interview; 176 (28%) answered they refused on relatives', friends' or other doctors' advices, or after Internet searches; 157 (25%) answered they didn't agree about how the trials were carried out (double blind control procedure, use of placebo, ecc); 126 (20%) didn't trust official medicine. 63 (10%) couldn't guarantee their presence at the controls. 69 (11%) didn't want to undergo additional medical examinations. 31 (5%) had previous bad research experiences (feeling like a guinea pig, ecc). 7 (about 1%) refused for other reasons.

Table 1. Acceptance or refusal to join cardiological intervention or observational clinical trials in the last 10 years Informed consent Immediately after reading and Principal Investigator's explanation After discussion with family, GP or Internet searches Total Accepted 914 (35%) 608 (24%) 1522 (29%) Initially accepted with subsequent withdrawal before randomization 1 (0.03%) 30 (1.2%) 31 (1%) Initially accepted with subsequent withdrawal after randomization 0 2 (0.07%) 2 (0.07%) Refused 151 (6%) 880 (34%) 1.031 (40%) Total 1.066 (41%) 1.520 (59%) 2.586 (100%)

Conclusions

Recruitment into clinical research studies is still a major challenge; patients are not fully aware of the importance of participation in clinical research studies for the development and implementation of medical advances. Paradoxically, people who refuse to participate in a trial are young and have a high level of education. Researcher's duty is to involve the patient in the trial and clarify the benefits of join the research.
2154Apolipoprotein B/apolipoprotein A-I ratio is comparable with C-reactive protein in predicting cancer mortality: results from two multi-ethnic US populations
Authors: Mazidi M , Mikhailidis D P , Katsiki N , Sniderman A , Banach M
Published: October 2019

Background

There is a lack of evidence regarding the link between apolipoproteins and cancer mortality.

Purpose

By using two nationally representative samples of US adults, we prospectively evaluated the associations between apolipoprotein B (apoB) levels and apoB/apolipoprotein A-I (apoA-I) ratio with cancer mortality. We also examined the role of C-reactive protein (CRP) in these associations.

Method

Adults aged ≥20 years, enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III, 1988–1994) and continuous NHANES (2005–2010), and followed up to December 31st 2011, were included in the present analysis. Multiple Cox regressionswere applied to evaluate the associations between the variables of interest and cancer mortality.

Results

Overall, 7,695 participants were included (mean age: 49.2 years; 50.4% men, median follow-up: 19.1 years). In the fully adjusted (for age, gender, race, poverty to income ratio, educational status, body mass index, alcohol and dietary intake, smoking, dyslipidemia, hypertension and diabetes) model, participants in the highest quartile (Q4) of apoB/apoA-I had a significantly greater risk for cancer mortality [hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.25–1.93] compared with those in the first quartile (Q1) (Figure). In the same model, a positive and significant association between apoB levels and fatal cancer was observed for individuals in the Q3 (HR: 1.12, 95% CI: 1.09–1.16) and Q4 (HR: 1.17, 95% CI: 1.09–1.25) compared with those in the Q1. When CRP levels were added in the analysis, the apoB/apoA-I ratio, but not apoB levels, remained significantly related to cancer mortality (Q4= HR: 1.17, 95% CI 1.09–1.25). In contrast, CRP levels were not able to predict cancer death after correction for apoB/apoA-I ratio.

Cancer death and quartiles of ApoB/ApoA1

Conclusions

In a large representative sample of the US adult population, the apoB/apoA-I ratio and apoB levels significantly predicted cancer mortality, independently of several cardiometabolic risk factors. The predictive value of apoB/apoA-I, but not apoB levels, remained significant after taking into account CRP, whereas CRP was not associated with cancer mortality after adjustment for apoB/apoA-I ratio. If further evidence supports our findings, apoA-I and apoB measurements could be considered in general health-care policies.

Acknowledgement/Funding

None
2209Oxygen therapy in suspected acute myocardial infarction and concurrent chronic obstructive pulmonary disease: a prespecified subgroup analysis from the DETO2X-AMI trial
Authors: Andell P , James S K , Ostlund O , Yndigegn T , Sparv D , Pernow J , Jernberg T , Lindahl B , Herlitz J , Erlinge D , Hofmann R
Published: October 2019

Background

The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction (AMI). Patients with chronic obstructive pulmonary disease (COPD) may both benefit and be harmed by supplemental oxygen. Thus, we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic COPD patients with suspected AMI.

Methods and results

A total of 6629 patients with suspected AMI were randomized in the DETO2X-AMI trial to oxygen or ambient air. In the oxygen group (n=3311) and the ambient air group (n=3318), 155 and 141 patients, respectively, had COPD (prevalence of 4.5%). Patients with COPD were older, had more comorbid conditions and experienced a two-fold higher risk of death at one year (COPD: 32/296 [10.8%] vs. non-COPD 302/6333 [4.8%]). Oxygen therapy compared to ambient air was not associated with improved outcomes at 365 days (COPD: all-cause mortality HR 0.99 [95% CI 0.50–1.99, interaction-p=0.96]; cardiovascular death HR 0.80 [0.32–2.04, interaction-p=0.59]; rehospitalization with AMI or death HR 1.27 [0.71–2.28, interaction-p=0.46]; hospitalization for heart failure or death HR 1.08 [0.61–1.91, interaction-p=0.77]); there were no significant treatment-by-COPD interactions.

Outcome

Conclusions

Although COPD patients had twice the mortality rate compared to non-COPD patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic COPD patients with suspected AMI revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings.
2214Prevalence and severity of coronary disease in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: data from the RICO survey
Authors: Farnier M , Mouhat B , Pommier T , Yao H , Maza M , Chague F , Bichat F , Cottin Y , Zeller M
Published: October 2019

Aim

Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described. From a large database of a regional registry of acute MI, we aimed to address prevalence of FH and severity of CAD.

Methods

Consecutive patients hospitalized with MI in a multicentre database from 2001–2017 were considered. An algorithm, adapted from Dutch Lipid Clinic Network criteria, was built upon 4 variables (LDL-cholesterol (LDL-C) and lipid lowering agents, premature and family history of CAD) to identify FH probabilities.

Results

Among the 11624 patients included in the survey, 249 (2.1%) had probable/definite FH (score ≥6), and 2405 (20.7%) had possible FH (score 3–5). When compared with patients without FH (score 0–2), FH patients (score ≥6) were 20y younger (51 (46–57) vs 71 (61–80) y, p<0.001), with a lower rate of hypertension (47 vs 59%, p<0.001), diabetes (17 vs 25%, p<0.001) and prior stroke (4 vs 8%, p=0.016), but a higher prevalence of smokers (56 vs 23%, p<0.001), personal (20 vs 15%, p=0.02) or familial history of CAD (78 vs 18%, p<0.001). Chronic statin treatment was only used in 48% of FH patients and ezetimibe in 8%. After adjustment for age, sex and diabetes, FH patients were characterized by increased extent of CAD (syntax score 11 (4–19) vs 7 (1–13), p<0.001) and multivessel disease (55 vs 40%, p<0.001).

Conclusion

In this large real world population of acute MI, a high prevalence of FH was found. FH patients were characterized by their young age associated with the severity of CAD burden and limited use of preventive lipid lowering therapy.

Acknowledgement/Funding

University Hospital Center Dijon Bourgogne, Agence Régionale de Santé Bourgogne Franche Comté, France
2401Cardiac resinchronization therapy for the systemic right ventricle: a single center experience
Authors: Barracano R , Guarguagli S , Kavouras C , Brida M , Griffith S , Wong T , Gatzoulis M A
Published: October 2019

Introduction

Cardiac resynchronization therapy (CRT) has become a treatment of choice in patients with chronic heart failure (HF). About 25% of patients with systemic right ventricle (SRV) progress to symptomatic HF, which may be refractory to drug therapy and is commonly associated with significant morbidity and mortality. For these reasons, CRT has been emerging as an effective treatment strategy for patients with SRV failure and electrocardiographic signs of ventricular dyssynchrony. Few studies have reported the acute and long - term effects of CRT in SRV subjects, with different findings. Our study aimed to describe the experience with CRT in SRV patients in a single tertiary centre.

Purpose

Assess the long term efficacy of CRT in patient with SRV

Materials and methods

All consecutive SRV patients who underwent CRT implantation and/or upgrading between 1994 and 2018 at our tertiary centre were included. Clinical and echocardiographic parameters before and after CRT implantation were collected and analyzed.

Results

A total of 21 patients (mean age 47.8±14.8 years, 13 M) were implanted with CRT-P (12, 57%) or CRT-D (9,43%) during the study period. 90% of patients showed an anatomy of congenitally corrected transposition of the great arteries (CCTGA), whereas 9.5% underwent Mustard procedure for transposition of the great arteries (TGA). Among CCTGAs, 11 (52.5%) subjects underwent previous surgical procedures, including implant of a conduit between the left ventricle (LV) and the pulmonary artery (PA) in 8 (38%) patients, tricuspid valve repair in 2 (9.5%) and surgical closure of atrial septal defect in 1 (5%). Before CRT implant/upgrading, 10 (48%) patients had a moderate to severe reduction in the SRV ejection fraction (EF) and 7 (33%) had a moderate to severe tricuspid regurgitation (TR). Overall, 15 (71%) patients referred a NYHA II or III. After a median follow up of 57 months (IQR 35–83), 43% of patients showed an improvement in their functional status, which was associated with an improvement of SRV EF and TR only in 22% and 33% of these patients. On the contrary, no patient reported a worsening in NYHA class, while SRV EF decreased in 28.5% and the grade of TR worsen in 23.8% of patients.

Conclusions

CRT is emerging as an effective treatment for SRV dysfunction. However, criteria for implantation are not well defined and the deterioration of SRV function related to subpulmonary univentricular pacing should be considered. Moreover, TR did not improve in this study, suggesting that concurrent tricuspid valve interventions may be necessary in patients with severe TR and may facilitate the improvement in RV function achieved with CRT. Proper planning, tertiary expertise and international collaborations are all paramount in this field.
P1222Intensification of lipid lowering therapy before and after publication of the IMPROVE-IT trial: A temporal analysis from the SPUM-ACS cohort
Authors: Gencer B , Carballo D , Nanchen D , Koskinas K , Klingenberg R , Raeber L , Auer R , Carballo S , Heg D , Windecker S , Luscher T F , Matter C M , Rodondi N , Mach F
Published: October 2019

Background

The gradual implementation of evidence-based treatment strategies has improved outcomes in patients with acute coronary syndromes (ACS). The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) was published on June 3rd, 2015, but its relevance on real life practice has not been explored.

Methods

We analyzed a prospective Swiss cohort of 6266 patients hospitalized for ACS between 2009 and 2017. The primary endpoints were the ezetimibe use overall or in combination with high-intensity statin at discharge and at one year after ACS. Secondary endpoint was LDL-C target achievement at one year in a subsample of 2984 patients. Relative Ratios (RR) were used to assess changes in primary endpoints before and after the publication of IMPROVE-IT, adjusting for age, sex, pre-existing diabetes, history of myocardial infarction, baseline low-density lipoprotein cholesterol (LDL-C) and attendance to cardiac rehabilitation.

Results

The period following the publication of the IMPROVE-IT trial was associated with an overall increase in the use of ezetimibe at discharge (from 1.8% to 3.8%, P<0.001, adjusted RR 2.85, 95% CI 1.90–4.25) and at one year (from 5.0% to 13.8%, P<0.001, adjusted RR 3.00, 95% CI 2.40–3.75). Before IMPROVE-IT trial, ezetimibe use at one year was stable around 5%, then steadily increased after its publication until 20% for patients included in 2017. The combination of high-intensity statin and ezetimibe increased from 0.9% to 2.1% at discharge (P<0.001, adjusted RR 3.35, 95% CI 1.90–5.89) and from 2.1% to 7.8% at one year (P<0.001, adjusted RR 3.98, 95% CI 2.90–5.47). The period following the publication of the IMPROVE-IT trial was associated with an improvement of LDL-C target <1.8 mmol/L (adjusted RR 1.37, 95% CI 1.12–1.68).

Conclusion

After the publication of the IMPROVE-IT trial, the use of ezetimibe was increased by three-fold in a large contemporary cohort of ACS patients, concomitant with an improved LDL-C target achievement.
P1231Loss of function in cytoskeletal genes associates with early onset atrial fibrillation
Authors: Vad O , Ahlberg G , Refsgaard L , Svendsen J H , Tveit A , Christophersen I E , Olesen M S
Published: October 2019

Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It carries an increased risk of serious complications and an increased mortality. Genome Wide Association Studies have demonstrated that variants in several structural genes are associated with AF, and recently two landmark papers have implicated loss of function (LoF) variants in titin (TTN), a gene associated with dilated cardiomyopathy (DCM), in patients with early onset AF. An atrial cardiomyopathy syndrome has been proposed as a mechanism in the development of AF.

Purpose

We hypothesized that genes encoding structural proteins that were associated with DCM, could also be involved in atrial cardiomyopathy and contribute to AF.

Materials and methods

We performed targeted deep sequencing of structural genes associated with DCM. The genes were grouped by cellular function, and the burden of LoF variants was examined in a cohort of 540 early onset AF patients and compared to a control group (n=383). The patients were below age 49 with normal echo, and no other cardiovascular disease at onset of AF. Patient inclusion in the cohort is still ongoing, and we are working on obtaining a CRISPR/CAS9 modified zebra fish model with LoF variants in cytoskeletal proteins.

Results

We identified a total of 6 carriers of LoF variants in 3 genes thought to encode cytoskeletal proteins (DMD, PDLIM3 and FKTN). The burden of variants in cytoskeletal genes was significantly increased in patients with early onset AF compared with controls (p=0.0385). Four carriers had LoF variants in the dystrophin gene (DMD), while there was 1 carrier of LoF variants in PDLIM3 and FKTN respectively. All carriers with LoF variants in DMD developed persistent AF before age 30.

Conclusion

Our data suggest that rare mutations in cytoskeletal genes previously associated with DCM, may also play a role in the development of early onset AF. The data supports that AF is a part of an atrial cardiomyopathy syndrome.

Acknowledgement/Funding

Novo Nordisk Fonden Pre-Graduate Scholarships
P1236Revealing cardiac mechanics with CMR whilst CRT is active: the first step
Authors: Koshy A , Gierula J , Paton M , Swoboda P , Toms A , Saunderson C , Shelley D , Plein D , Cubbon R , Kearney M , Witte K
Published: October 2019

Introduction

Cardiac resynchronisation therapy (CRT) is a routine treatment for heart failure with reduced ejection fraction and conduction delay to improve symptoms and prognosis. Technological advancements both in cardiac magnetic resonance (CMR) and devices (MRI-conditional modes) now enable investigation of the haemodynamic response to CRT over a range of heart rates.

Methods

Patients with a CRT-D device were enrolled from heart failure clinics at a single tertiary centre. A complete device system assessment and baseline device check was conducted to ensure MRI compatibility and suitability. Left ventricular (LV) volumes and systolic blood pressure were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 bpm (randomised order) with CRT active and intrinsic conduction (AOO). MRI conditional mode parameters were replicated through standard parameter modification to ensure biventricular pacing during CRT active scans. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner with analysis on commercially available software. Contractility was derived from the systolic blood pressure and left ventricular end systolic volume. A post scan device and lead assessment was conducted to assess for scanning safety.

Results

Scanning was conducted in 22 patients (safety cohort). Post scan battery voltage reduced by 2.9±1.0%. Mean change in atrial, right ventricular and left ventricular lead impedance was 0.5±0.06%, 3.0±0.04% and −1.7±0.05% respectively. Mean change in atrial, right ventricular and left ventricular pacing threshold was 0.0±0.3%, 8.3±0.3% and 5.6±0.3%. No patient experienced symptoms related to scanning or device failure.

Preliminary data for patients with CRT on and off have been analysed (paired analysis cohort, n=8, 6 men). Mean age was 71.1±8.2, aetiology was primarily ischaemic (62.5%) with the remainder dilated cardiomyopathy. The mean LV ejection fraction at baseline was 29.4±12.9%. Biventricular pacing led to acute improvements in ejection fraction (p=0.005), left ventricular cardiac output (p<0.0001) and contractility (p=0.05) over the entire range of heart rates studied. We also noted an improvement in the force frequency relationship during biventricular pacing with a higher peak contractility (p=0.05), a higher heart rate at which this occurred (HR=130) and a generally up sloping relationship when compared with intrinsic conduction.

Conclusion

We have demonstrated for the first time, the mechanistic improvements in cardiac contractility consequent to CRT using CMR and also that MRI scans of conditional devices can be safe with CRT active.

Acknowledgement/Funding

Dr A Koshy is conducting a PhD supported by grant from Medtronic. Dr Klaus Witte has received honoraria from Medtronic
P1240Is resynchronization therapy really efficient in laminopathy?
Authors: Burdeau J , Viart G , Gandjbakhch E , Savoure A , Godin B , Maury P , Pasquie J L , Wahbi K , Eltchaninoff H , Anselme F
Published: October 2019

Introduction

Laminopathy (LMNA) is a group of rare disease caused by a mutation of lamin A/C genes. Heart transplantation (HT) is often required. Cardiac resynchronization therapy (CRT) may be an option to postpone HT.

Purpose

To describe characteristics and outcome of LMNA patients receiving CRT.

Methods

All consecutive LMNA patients implanted with a CRT device for conventional indications were included in the study. Clinical and echocardiographic (TTE) data were collected during the follow-up period.

Results

From 2002 to 2017, 68 LMNA patients had CRT implantation. Despite CRT, 30/68 patients (44%) had HT. Population divided into two groups according to response to CRT. Patients were considered without benefit (WHOB-CRT group) if they experienced severe events (inscription on heart transplantation list or death) within two years after CRT implantation. Other patients were in the WB-CRT group. TTE and clinical parameters are described in Table 1.

Table 1 Parameters WB-CRT (n=33) WHOB-CRT (n=35) P-value At implantation   Age (years) 52.3±9.7 50.6±9.5 0.27   Women 9 (27%) 13 (37%) 0.45   NYHA class 2.7±0.6 2.8±0.7 0.45   LVEF (%) 33.2±8.8 31.3±7 0.64   LVEDD (mm) 60±6.9 60±6.9 0.96   TAPSE (mm) 23±3.7 14±4.8 0.002 At last follow up   NYHA class 2.2±0.6 2.9±0.7 <0.001   LVEF (%) 36.4±11 27±9 <0.001   LVEDD (mm) 59±5.5 59±7.7 0.98   TAPSE (mm) 19.9±5.5 12.3±3.3 0.003 Left ventricular ejection fraction (LVEF); Left ventricular end diastolic diameter (LVEDD); Tricuspid annular plane systolic excursion (TAPSE).

Conclusion

Cardiac resynchronization therapy is less efficient in LMNA patients. An impaired right ventricular stroke function seems to be the only predictive factor leading to poor response to CRT.
P1242ECG predictors of outcome in non-left bundle branch block cardiac resynchronization therapy patients
Authors: Van Stipdonk A M W , Dural M , Salden F , Ter Horst I A H , Crijns H J G M , Prinzen F W , Meine M , Maass A H , Vernooy K
Published: October 2019

Background

The effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited, compared to those with LBBB. Still, a substantial part of these patients can benefit from therapy and additional selection criteria are needed to identify these patients.

Purpose

To evaluate the association of additional baseline 12-lead ECG features; with clinical and echocardiographic outcomes in CRT-treated non-LBBB patients.

Methods

Pre-implantation 12-lead ECGs from 790 consecutive non-LBBB CRT patients from 3 implanting centres in the Netherlands were evaluated for the presence of predefined ECG parameters. QRS morphology (right bundle branch block and intraventricular conduction delay), QRS duration (≥/<150ms), QRS area (≥/<109μVs), left ventricular activation time ((≥/<125ms), and the presence of fragmented QRS (fQRS). The association with the primary endpoint, the combination of left ventricular assist device implantation, cardiac transplantation and all-cause mortality, was evaluated.

Results

There was a significantly lower occurrence of the primary endpoint in non-LBBB patients with QRS area ≥109 μVs (p<0.001) and in those without fQRS present (p=0.004) (figure 1).

Figure 1

Conclusion

A large QRS area and the absence of fQRS are positively associated to event free survival in non-LBBB patients treated with CRT. Whereas currently used patient selection cut-off QRS duration is not associated to outcome in these patients. These data may provide additional value for the non-LBBB patient selection for CRT and warrant prospective evaluation of these ECG features.

Acknowledgement/Funding

None
P1248Characteristics and clinical significance of right ventricular involvement in patients with hypertrophic cardiomyopathy
Authors: Seo J W , Choi K U , Choi J Y , Lkhagvasuren P J , Shim C Y , Hong G R , Ha J W
Published: October 2019

Background

A few studies have demonstrated bi-ventricular hypertrophy in hypertrophic cardiomyopathy (HCM). However, clinical significance of HCM with right ventricular (RV) involvement has not been fully established. Therefore, we aimed to investigate the structural characteristics and clinical significance of RV hypertrophy in patients with HCM.

Methods

In a single center, large HCM registry, 256 patients with HCM who underwent both cardiac magnetic resonance (CMR) and transthoracic echocardiography within 6 months were retrospectively analyzed. RV involvement was defined as increased RV wall thickness >7 mm on CMR in any segments of RV free wall and apex. Patients who had evidence of significant RV pressure overload (RV systolic pressure >50mmHg) or had undergone septal myectomy were excluded. Cardiovascular outcomes were defined as the composite of cardiovascular death and hospitalization for cardiovascular disease.

Results

Among 256 patients, 41 (16%) showed RV involvement. During follow-up period (median 1099 days), 32 cardiovascular outcomes (3 cardiovascular death and 29 cardiovascular hospitalization) were occurred. Patients with RV involvement showed a significantly higher left ventricular (LV) thickness (23.8±5.8 vs. 21.2±5.0 mm, p=0.004), more advanced diastolic dysfunction, and larger left atrial volume index (LAVI, 48.5±20.3 vs. 40.2±14.9 mm/m2, p=0.016) compared to those without RV involvement. In multivariate cox regression analysis, presence of RV involvement (HR: 4.21, 95% CI: 1.99–8.90, p<0.001) and LV ejection fraction <50% (HR: 4.29, 95% CI: 1.37–13.43, p=0.012) were independently associated with cardiovascular outcomes. The Kapan-Meier curve showed that there was a significant decrease in probability of cardiovascular outcomes-free survival in patients with RV involvement (p=0.007) after using 1:1 propensity score matching (n=82) to adjust for age, sex, LV ejection fraction, LV maximal wall thickness, LAVI, and RV systolic pressure than patients without RV involvement (Figure 1).

Figure 1

Conclusion

RV involvement in patients with HCM were not rare (16%). Patients with RV involvement showed more advanced LV structure and dysfunction, suggesting an indicator of severe HCM. RV involvement in HCM has clinical significance related to cardiovascular outcomes.