Development and first results of a dedicated chronic total occlusion programme

Objective To describe the development and first results of a dedicated chronic total occlusion (CTO) programme in a tertiary medical centre. Background Because of the complexity and the increased risk of complications during percutaneous coronary intervention (PCI) for CTO, it is essential that less experienced and evolving CTO centres perform regular quality analyses. Methods We therefore performed analyses to describe the results during the first 3 years of a dedicated CTO programme at a high-volume PCI centre. In addition, we discuss the strategies employed to develop such a programme. Results A total of 179 consecutive patients undergoing 187 CTO procedures were included in the study. The complexity of the CTO lesions increased from a mean J-CTO (Japanese Multicentre CTO Registry) score of 1.3 in 2015 to 2.1 in 2017. In the majority of cases, the antegrade wire escalation technique was performed. Final technical success rate was 78.5% in 175 patients with a single CTO and 80.2% of all 187 CTO procedures. No peri-procedural or in-hospital deaths occurred. One peri-procedural myocardial infarction occurred. Cardiac tamponade occurred in 2 cases, both managed by pericardiocentesis. No urgent cardiac surgery was necessary. Survival and revascularisation rates at 30 days and 1 year were excellent. Conclusion Following initiation of a dedicated CTO programme, using up-to-date techniques and strategies, procedural and clinical outcome were comparable with current standards in established centres

Translational insights from single-cell technologies across the cardiovascular disease continuum

Cardiovascular disease is the leading cause of death worldwide. The societal health burden it represents can be reduced by taking preventive measures and developing more effective therapies. Reaching these goals, however, requires a better understanding of the pathophysiological processes leading to and occurring in the diseased heart. In the last 5 years, several biological advances applying single-cell technologies have enabled researchers to study cardiovascular diseases with unprecedented resolution. This has produced many new insights into how specific cell types change their gene expression level, activation status and potential cellular interactions with the development of cardiovascular disease, but a comprehensive overview of the clinical implications of these findings is lacking. In this review, we summarize and discuss these recent advances and the promise of single-cell technologies from a translational perspective across the cardiovascular disease continuum, covering both animal and human studies, and explore the future directions of the field

Effects of caffeine intake prior to stress cardiac magnetic resonance perfusion imaging on regadenoson- versus adenosine-induced hyperemia as measured by T1 mapping

The antagonistic effects of caffeine on adenosine receptors are a possible cause of false-negative stress perfusion imaging. The purpose of this study was to determine the effects of coffee intake <4 h prior to stress perfusion cardiac magnetic resonance imaging (CMR) in regadenoson- versus adenosine-induced hyperemia as measured with T1-mapping. 98 consecutive patients with suspected coronary artery disease referred for either adenosine or regadenoson perfusion CMR were included in this analysis. Twenty-four patients reported coffee consumption <4 h before CMR (15 patients with adenosine, and 9 patients with regadenoson); 74 patients reported no coffee intake (50 patients with adenosine, and 24 patients with regadenoson). T1 mapping was performed using a modified look-locker inversion recovery sequence. T1 reactivity was determined by subtracting T1(rest) from T1(stress). T1(rest), T1(stress), and T1 reactivity in patients referred for regadenoson perfusion CMR were not significantly different when comparing patients with <4 h coffee intake and patients who reported no coffee intake (976 +/- 4 ms, 1019 +/- 48 ms, and 4.4 +/- 3.2% vs 971 +/- 33 ms, 1023 +/- 43 ms, and 5.4 +/- 2.4%) (p = 0.70, 0.79, and 0.40), and similar to values in patients without coffee intake undergoing adenosine CMR. In patients with <4 h coffee intake, T1(stress), and T1 reactivity were significantly lower for adenosine (898 +/- 51 ms, and -7.8 +/- 5.0%) compared to regadenoson perfusion CMR (p <0.001). Coffee intake <4 h prior to regadenoson perfusion CMR has no effect on stress-induced hyperemia as measured with T1 mapping

Aging, telomeres and heart failure

During normal aging, the heart undergoes functional, morphological and cellular changes. Although aging per se does not lead to the expression of heart failure, it is likely that age-associated changes lower the threshold for the manifestation of signs and symptoms of heart failure. In patients, the susceptibility, age of onset and pace of progression of heart failure are highly variable. The presence of conventional risk factors cannot completely explain this variability. Accumulation of DNA damage and telomere attrition results in an increase in cellular senescence and apoptosis, resulting in a decrease in the number and function of cells, contributing to the overall tissue and organ dysfunction. Biological aging, characterized by reduced telomere length, provides an explanation for the highly interindividual variable threshold to express the clinical syndrome of heart failure at some stage during life. In this review, we will elaborate on the current knowledge of aging of the heart, telomere biology and its potential role in the development of heart failure

Validation of a cerebral hemodynamic model with personalized calibration in patients with aneurysmal subarachnoid hemorrhage

This study aims to validate a numerical model developed for assessing personalized circle of Willis (CoW) hemodynamics under pathological conditions. Based on 66 computed tomography angiography images, investigations were obtained from 43 acute aneurysmal subarachnoid hemorrhage (aSAH) patients from a local neurovascular center. The mean flow velocity of each artery in the CoW measured using transcranial Doppler (TCD) and simulated by the numerical model was obtained for comparison. The intraclass correlation coefficient (ICC) over all cerebral arteries for TCD and the numerical model was 0.88 (N = 561; 95% CI 0.84–0.90). In a subgroup of patients who had developed delayed cerebral ischemia (DCI), the ICC had decreased to 0.72 but remained constant with respect to changes in blood pressure, Fisher grade, and location of ruptured aneurysm. Our numerical model showed good agreement with TCD in assessing the flow velocity in the CoW of patients with aSAH. In conclusion, the proposed model can satisfactorily reproduce the cerebral hemodynamics under aSAH conditions by personalizing the numerical model with TCD measurements. Clinical trial registration: [http://www.trialregister.nl/], identifier [NL8114]

Discovering and Visualizing Disease-Specific Electrocardiogram Features Using Deep Learning: Proof-of-Concept in Phospholamban Gene Mutation Carriers

BACKGROUND: ECG interpretation requires expertise and is mostly based on physician recognition of specific patterns, which may be challenging in rare cardiac diseases. Deep neural networks (DNNs) can discover complex features in ECGs and may facilitate the detection of novel features which possibly play a pathophysiological role in relatively unknown diseases. Using a cohort of PLN (phospholamban) p.Arg14del mutation carriers, we aimed to investigate whether a novel DNN-based approach can identify established ECG features, but moreover, we aimed to expand our knowledge on novel ECG features in these patients. METHODS: A DNN was developed on 12-lead median beat ECGs of 69 patients and 1380 matched controls and independently evaluated on 17 patients and 340 controls. Differentiating features were visualized using Guided Gradient Class Activation Mapping++. Novel ECG features were tested for their diagnostic value by adding them to a logistic regression model including established ECG features. RESULTS: The DNN showed excellent discriminatory performance with a c-statistic of 0.95 (95% CI, 0.91-0.99) and sensitivity and specificity of 0.82 and 0.93, respectively. Visualizations revealed established ECG features (low QRS voltages and T-wave inversions), specified these features (eg, R- and T-wave attenuation in V2/V3) and identified novel PLN-specific ECG features (eg, increased PR-duration). The logistic regression baseline model improved significantly when augmented with the identified features (P<0.001). CONCLUSIONS: A DNN-based feature detection approach was able to discover and visualize disease-specific ECG features in PLN mutation carriers and revealed yet unidentified features. This novel approach may help advance diagnostic capabilities in daily practice

Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10$^{-8}$); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10$^{-7}$) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.This research was conducted using the UK Biobank Resource. This project is supported by the Netherlands organization for health research and development (ZonMw grant 90.700.441). S.B. is supported by the Wellcome Trust (grant 100114). P.B.M. acknowledges support from the NIHR Cardiovascular Biomedical Research Unit at Barts and the London School of Medicine and Dentistry, Queen Mary University of London. N.V. is supported by Netherlands Heart Institute and Marie Sklodowska-Curie Global Fellowship (grant 661395)