Interventions for renal artery stenosis: Appraisal of novel physiological insights and procedural techniques to improve clinical outcome.

Randomized clinical trials failed to show additional benefit of renal artery stenting on top of medical therapy. Instead of writing an obituary on renal artery stenting, we try to explain these disappointing results. A transstenotic pressure gradient is needed to reduce renal perfusion and to activate the renin-angiotensin-aldosterone system. In only a minority of patients included in trials, a transstenotic pressure gradient is measured and reported. Like the coronary circulation, integration of physiological lesion assessment will allow to avoid stenting of non-significant lesions and select those patients that are most likely to benefit from renal artery stenting. Renal artery interventions are associated with peri-procedural complications. Contemporary techniques, including radial artery access, no-touch technique to engage the renal ostium and the use of embolic protection devices, will minimize procedural risk. Combining optimal patient selection and meticulous technique might lead to a netto clinical benefit when renal artery stenting is added to optimal medical therapy.

Double kiss mini-crush technique to treat complex recurrent renal artery in-stent restenosis.

The double-kiss mini-crush (DKMC) technique has been successfully deployed in the past for the treatment of complex coronary lesions even for left main lesions. Our case report consists of a proof-of-principle that the DKMC technique can be successfully translated as well to the field of complex renal artery lesions. Insightful thinking out-of-the "coronary" box in concert with skillful off-label application of coronary stenting procedures may open the gate for unprecedented opportunities for the treatment of difficult-to-tackle in-stent restenosis in the renal circulation.

Prediction of certainty in artificial intelligence-enabled electrocardiography.

BACKGROUND: The 12­lead ECG provides an excellent substrate for artificial intelligence (AI) enabled prediction of various cardiovascular diseases. However, a measure of prediction certainty is lacking. OBJECTIVES: To assess a novel approach for estimating certainty of AI-ECG predictions. METHODS: Two convolutional neural networks (CNN) were developed to predict patient age and sex. Model 1 applied a 5 s sliding time-window, allowing multiple CNN predictions. The consistency of the output values, expressed as interquartile range (IQR), was used to estimate prediction certainty. Model 2 was trained on the full 10s ECG signal, resulting in a single CNN point prediction value. Performance was evaluated on an internal test set and externally validated on the PTB-XL dataset. RESULTS: Both CNNs were trained on 269,979 standard 12­lead ECGs (82,477 patients). Model 1 showed higher accuracy for both age and sex prediction (mean absolute error, MAE 6.9 ± 6.3 years vs. 7.7 ± 6.3 years and AUC 0.946 vs. 0.916, respectively, P < 0.001 for both). The IQR of multiple CNN output values allowed to differentiate between high and low accuracy of ECG based predictions (P < 0.001 for both). Among 10% of patients with narrowest IQR, sex prediction accuracy increased from 65.4% to 99.2%, and MAE of age prediction decreased from 9.7 to 4.1 years compared to the 10% with widest IQR. Accuracy and estimation of prediction certainty of model 1 remained true in the external validation dataset. CONCLUSIONS: Sliding window-based approach improves ECG based prediction of age and sex and may aid in addressing the challenge of prediction certainty estimation.

The role of soluble receptor for advanced glycation end-products (sRAGE) in the general population and patients with diabetes mellitus with a focus on renal function and overall outcome.

Isoforms of the receptor for advanced glycation end-product (RAGE) protein, which lack the transmembrane and the signaling (soluble RAGE or sRAGE) domains are hypothesized to counteract the detrimental action of the full-length receptor by acting as a decoy, and they provide a potential tool to treat RAGE-associated diseases. Multiple studies have explored the relationship between sRAGE and endogenous secretory RAGE and its polymorphism and obesity, metabolic syndrome, atherosclerosis, kidney function, and increased mortality in the general population. In addition, sRAGE may be a key player in the pathogenesis of diabetes mellitus and its microvascular (e.g. kidney disease) as well as macrovascular (e.g. cardiovascular disease) complications. In this review, we focus on the role of sRAGE as a biomarker in these specific areas. As there is a lack of an underlying unifying hypothesis about how sRAGE changes according to the disease condition or risk factor, there is a call to incorporate all three players of the AGE-RAGE axis into a new universal biomarker/risk marker: (AGE + RAGE)/sRAGE. However, the measurement of RAGE in humans is not practical as it is a cell-bound receptor for which tissue is required for analysis. A high AGE/sRAGE ratio may be a valuable alternative and practical universal biomarker/risk marker for diseases associated with the AGE-RAGE axis, irrespective of low or high serum sRAGE concentrations.

Genetic Polymorphisms in the Host and COVID-19 Infection.

The outbreak of the COVID-19 pandemic shows a marked geographical variation in its prevalence and mortality. The question arises if the host genetic variation may (partly) affect the prevalence and mortality of COVID-19. We postulated that the geographical variation of human polymorphisms might partly explain the variable prevalence of the infection. We investigated some candidate genes that have the potential to play a role in the immune defense against COVID-19: complement component 3 (C3), galactoside 2-alpha-L-fucosyltransferase 2 (FUT2), haptoglobin (Hp), vitamin D binding protein (DBP), human homeostatic iron regulator protein (HFE), cystic fibrosis transmembrane conductance regulator (CFTR), and angiotensin-converting enzyme 1 (ACE1). In a univariate approach, ACE1 D/I, C3, CFTR, and HFE polymorphisms correlated significantly with COVID-19 prevalence/mortality, whereas Hp and FUT2 polymorphism did not show any significant correlations. In a multivariate analysis, only ACE1 D/I and C3 polymorphisms were determinants for COVID-19 prevalence/mortality. The other polymorphisms (CFTR, DBP, FUT2, HFE, and Hp) did not correlate with COVID-19 prevalence/mortality. Whereas ACE1 D/I polymorphism shows functional links with ACE2 (which is the receptor for the virus) in COVID-19, C3 can act as a critical step in the virus-induced inflammation. Our findings plead against a bystander role of the polymorphisms as a marker for historical migrations, which comigrate with causal genes involved in COVID-19 infection. Further studies are required to assess the clinical outcome of COVID-19 in C3S and ACE1 D allele carriers and to study the role of C3 and ACE1 D/I polymorphisms in COVID-19 and their potential effects on treatment response.

Progression of incomplete toward complete left bundle branch block: A clinical and electrocardiographic analysis.

BACKGROUND: Complete left bundle branch block (cLBBB) is associated with increased cardiovascular mortality and heart failure. On the contrary, the clinical relevance of incomplete left bundle branch block (iLBBB) is less known. This study investigated the profile and outcome of iLBBB patients and assessed the risk of progression to cLBBB. METHODS: Patients diagnosed with iLBBB between July 2013 and April 2018 were retrospectively included. Subsequently, echo- and electrocardiographic examinations at time of iLBBB diagnosis and during follow-up, as well as progression to non-strict cLBBB and strict cLBBB, were evaluated. RESULTS: The study enrolled 321 patients (33% female, age 74 ± 11 years). During the follow-up of 21 (8;34) months, 33% of iLBBB patients evolved to non-strict cLBBB and 27% to strict cLBBB. iLBBB patients who evolved to non-strict or strict cLBBB were older, had more frequently reduced left ventricular ejection fraction, and had more often QRS notching/slurring in the lateral leads and inferior leads, compared to patients without progression to cLBBB. In multivariate analysis, only QRS notching/slurring in the lateral leads was independently associated with progression to non-strict cLBBB (odds ratio 4.64, p < .001) and strict cLBBB (odds ratio 9.6, p < .001). iLBBB patients with QRS notching/slurring had a progression rate to non-strict cLBBB of 52% and 49% to strict cLBBB. CONCLUSION: Among patients with iLBBB, up to one third of the patients progress to cLBBB within a period of 2 years. The presence of QRS notching/slurring in the lateral leads during iLBBB was the strongest predictor for progression toward cLBBB.

Outcome of degenerative nonprolapse mitral regurgitation using the average pixel intensity method.

BACKGROUND: Primary mitral valve regurgitation (MR) is a comprehensive term that mostly comprises mitral valve prolapse (MVP), while other causes of degenerative MR are often not considered. We describe the echocardiographic characteristics of degenerative nonprolapse mitral regurgitation (DMR) and assess the outcome at medium-term follow-up using the novel average pixel intensity (API) method. METHODS: Of 126 patients with any nonprolapse DMR were consecutively included. MR was graded according to all guideline-recommended parameters and with the API method. MR flow dynamics in DMR were compared to MVP-MR and functional MR (FMR). RESULTS: DMR is associated with moderate-to-severe calcifications of the mitral valve apparatus, and a low event rate was observed at a mean follow-up of 27 months. The API grading method had a higher feasibility (94%) compared to proximal isovelocity surface area (PISA) (60%) method and vena contracta width (VCW) (71%) for assessing MR. The API method was predictive for events. The API method also provides insights into DMR flow dynamics: A triphasic pattern was observed with a midsystolic nadir for both API and PISA-EROA, which is similar to the dynamic flow pattern described in FMR, but distinct from holosystolic MVP-MR. Compared to FMR and MVP-MR patients, DMR is less severe and patients with DMR are generally older than MVP-MR patients. CONCLUSIONS: DMR is a distinct MR pathology and conveys a relatively low event rate. MR grading was feasible with the API method, and flow dynamics demonstrated a similar triphasic pattern compared to FMR but distinct from holosystolic MVP-MR.

Relation between electrical and mechanical dyssynchrony in patients with left bundle branch block: An electro- and vectorcardiographic study.

BACKGROUND: Current guidelines select patients for cardiac resynchronization therapy (CRT) mainly on electrocardiographic parameters like QRS duration and left bundle branch block (LBBB). However, among those LBBB patients, heterogeneity in mechanical dyssynchrony occurs and might be a reason for nonresponse to CRT. This study assesses the relation between electrocardiographic characteristics and presence of mechanical dyssynchrony among LBBB patients. METHODS: The study included patients with true LBBB (including mid-QRS notching) on standard 12-lead electrocardiograms. Left bundle branch block-induced mechanical dyssynchrony was assessed by the presence of septal flash on two-dimensional echocardiography. Previously reported electro- and vectorcardiographic dyssynchrony markers were analyzed: global QRS duration (QRSDLBBB ), left ventricular activation time (QRSDLVAT ), time to intrinsicoid deflection (QRSDID ), and vectorcardiographic QRS areas in the 3D vector loop (QRSA3D ). RESULTS: The study enrolled 545 LBBB patients. Septal flash (SF) is present in 52% of patients presenting with true LBBB. Patients with SF are more frequent female, have less ischemic heart disease and smaller left ventricular dimensions. In multivariate analysis longer QRSDLBBB , QRSDLVAT and larger QRSA3D were independently associated with SF. Of all parameters, QRSA3D has the best accuracy to predict SF, although overall accuracy remains moderate (59% sensitivity, 58% specificity). The predictive value of QRSA3D remained constant in both sexes, irrespective of ischemic heart disease, ejection fraction and even when categorizing for QRSDLBBB . CONCLUSION: In LBBB patients, large QRS areas correlate better with mechanical dyssynchrony compared to wide QRSD intervals. However, the overall accuracy to predict mechanical dyssynchrony by electrocardiographic dyssynchrony markers, even when using complex vectorcardiographic parameters, remains low.

Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than QRS Duration or QRS Amplitudes.

INTRODUCTION: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). METHODS AND RESULTS: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XAmpl , YAmpl , ZAmpl , and 3DAmp ) and QRS areas (XArea , YArea , ZArea , and 3DArea ) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Δ) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large ZArea (109 µVs, interquartile range [IQR]:75;135), significantly larger than XArea (22 µVs, IQR:10;57) and YArea (44 µVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters, 3DAmpl , Δ3DAmpl , ZArea, ΔZArea , Δ3DArea , and ΔQRSD differentiate AHR response from nonresponse (P < 0.05). ΔZArea predicted best positive AHR (area under the curve = 0.813) and outperformed any other VCG parameter or QRSD measurement. CONCLUSION: Of all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method might be an easy, noninvasive tool to guide CRT implantation and optimization.

Diagnostic accuracy of a novel method for detection of acute transmural myocardial ischemia based upon a self-applicable 3-lead configuration.

BACKGROUND: Delayed medical attendance is a leading cause of death in patients with ST elevation myocardial infarction (STEMI). METHODS: We aimed to introduce, develop, and validate a novel method (RELF method) for detection of transmural ischemia based on a new and easy-to-use 3-lead configuration and orthonormalization of ST reference vectors (STDVN). The study included 60 patients undergoing coronary artery occlusion (CAO) during balloon inflation and 30 healthy subjects. RESULTS: STDVN was significantly different and an optimal discriminator between CAO patients and healthy subjects (respectively 8.00±4.50 vs. 1.90±0.86 normalized units, p<0.001). Compared to the 12-lead ECG, the RELF method was sensitive (90 vs. 73%, p=0.13) and more specific (91 vs. 75%, p<0.001). CONCLUSIONS: The RELF method is highly accurate for early detection of acute occlusion related ischemia and it outperforms the conventional 12-lead ECG criteria for STEMI. This method provides a platform for self-detection of CAO with handheld devices or smart phones.

MRI Assessment of Diastolic and Systolic Intraventricular Pressure Gradients in Heart Failure.

A deep phenotypic characterization of heart failure (HF) is important for a better understanding of its pathophysiology. In particular, novel noninvasive techniques for the characterization of functional abnormalities in HF with preserved ejection fraction are currently needed. While echocardiography is widely used to assess ventricular function, standard echocardiographic techniques provide a limited understanding of ventricular filling. The application of fluid dynamics theory, along with assessments of flow velocity fields in multiple dimensions in the ventricle, can be used to assess intraventricular pressure gradients (IVPGs), which in turn may provide valuable insights into ventricular diastolic and systolic function. Advances in imaging techniques now allow for accurate estimations of systolic and diastolic IVPGs, using noninvasive methods that are easily applicable in clinical research. In this review, we describe the basic concepts regarding intraventricular flow measurements and the derivation of IVPGs. We also review existing literature exploring the role of IVPGs in HF.