Machine learning prediction of progressive subclinical myocardial dysfunction in moderate aortic stenosis.

Background: Moderate severity aortic stenosis (AS) is poorly understood, is associated with subclinical myocardial dysfunction, and can lead to adverse outcome rates that are comparable to severe AS. Factors associated with progressive myocardial dysfunction in moderate AS are not well described. Artificial neural networks (ANNs) can identify patterns, inform clinical risk, and identify features of importance in clinical datasets. Methods: We conducted ANN analyses on longitudinal echocardiographic data collected from 66 individuals with moderate AS who underwent serial echocardiography at our institution. Image phenotyping involved left ventricular global longitudinal strain (GLS) and valve stenosis severity (including energetics) analysis. ANNs were constructed using two multilayer perceptron models. The first model was developed to predict change in GLS from baseline echocardiography alone and the second to predict change in GLS using data from baseline and serial echocardiography. ANNs used a single hidden layer architecture and a 70%:30% training/testing split. Results: Over a median follow-up interval of 1.3 years, change in GLS (≤ or >median change) could be predicted with accuracy rates of 95% in training and 93% in testing using ANN with inputs from baseline echocardiogram data alone (AUC: 0.997). The four most important predictive baseline features (reported as normalized % importance relative to most important feature) were peak gradient (100%), energy loss (93%), GLS (80%), and DI < 0.25 (50%). When a further model was run including inputs from both baseline and serial echocardiography (AUC 0.844), the top four features of importance were change in dimensionless index between index and follow-up studies (100%), baseline peak gradient (79%), baseline energy loss (72%), and baseline GLS (63%). Conclusions: Artificial neural networks can predict progressive subclinical myocardial dysfunction with high accuracy in moderate AS and identify features of importance. Key features associated with classifying progression in subclinical myocardial dysfunction included peak gradient, dimensionless index, GLS, and hydraulic load (energy loss), suggesting that these features should be closely evaluated and monitored in AS.

Does geographical variability influence five-year MACCE rates in the multicentre SYNTAX revascularisation trial?

AIMS: The use of multiple geographical sites for randomised cardiovascular trials may lead to important heterogeneity in treatment effects. This study aimed to determine whether treatment effects from different geographical recruitment regions impacted significantly on five-year MACCE rates in the SYNTAX trial. METHODS AND RESULTS: Five-year SYNTAX results (n=1,800) were analysed for geographical variability by site and country for the effect of treatment (CABG vs. PCI) on MACCE rates. Fixed, random, and linear mixed models were used to test clinical covariate effects, such as diabetes, lesion characteristics, and procedural factors. Comparing five-year MACCE rates, the pooled odds ratio (OR) between study sites was 0.58 (95% CI: 0.47-0.71), and countries 0.59 (95% CI: 0.45-0.73). By homogeneity testing, no individual site (X2=93.8, p=0.051) or country differences (X2=25.7, p=0.080) were observed. For random effects models, the intraclass correlation was minimal (ICC site=5.1%, ICC country=1.5%, p<0.001), indicating minimal geographical heterogeneity, with a hazard ratio of 0.70 (95% CI: 0.59-0.83). Baseline risk (smoking, diabetes, PAD) did not influence regional five-year MACCE outcomes (ICC 1.3%-5.2%), nor did revascularisation of the left main vs. three-vessel disease (p=0.241), across site or country subgroups. For CABG patients, the number of arterial (p=0.49) or venous (p=0.38) conduits used also made no difference. CONCLUSIONS: Geographic variability has no significant treatment effect on MACCE rates at five years. These findings highlight the generalisability of the five-year outcomes of the SYNTAX study.

Incidence and predictors of coronary obstruction following transcatheter aortic valve implantation in the real world.

OBJECTIVES: Coronary obstruction (CO) is a rare but serious complication of transcatheter aortic valve implantation (TAVI). There are very limited data regarding CO following TAVI. The aim of this study was to evaluate the incidence and outcomes of CO after TAVI and identify the predictors including the valve type. METHODS: Between October 2006 and March 2015, 1,203 TAVI cases were performed in our institution. Of them, 814 cases whose coronary height was measured using computed tomography for screening were analyzed in this study. RESULTS: The Edwards SAPIEN/SAPIEN XT (S/XT) was used in 427 (52.4%) cases, the CoreValve in 265 (32.6%), and the S3 in 122 (15.0%). CO occurred in 8 (1.0%) cases, 1.6% with S/XT, 0.4% with CoreValve, and 0% with S3. All instances of CO occurred at the left coronary artery. The 30-day mortality was significantly higher in cases of CO (37.5% vs. 5.8%, P = 0.010). The frequency of CO tended to be lower in recipients of the CoreValve (0.4%) and S3 (0%) compared with the S/XT (1.6%) (P = 0.188 for CoreValve vs. S/XT, P = 0.022 for S3 vs. S/XT). CONCLUSIONS: CO has poor outcomes and identification of patients at risk of CO to take preventive measures is crucial. The preliminary data showing that the occurrence of CO is low in patients receiving the S3 despite increased prosthesis height need further confirmation. © 2017 Wiley Periodicals, Inc.

Platypnea-Orthodeoxia Syndrome after Transcatheter Aortic Valve Implantation.

Progressive dyspnea and hypoxaemia in the subacute phase after transcatheter aortic valve implantation (TAVI) are uncommon and warrant immediate assessment of valve and prosthesis leaflet function to exclude thrombosis, as well as investigation for other causes related to the procedure, such as left ventricular dysfunction, pulmonary embolism, and respiratory sepsis. In this case, we report the observation of a patient presenting two weeks after TAVI with arterial hypoxaemia in an upright position, relieved by lying flat, and coupled with an intracardiac shunt detected on echocardiography in the absence of pulmonary hypertension, raising the suspicion of Platypnea-Orthodeoxia Syndrome (POS). Invasive intracardiac haemodynamic assessment showed a significant right-to-left shunt (Qp/Qs = 0.74), which confirmed the diagnosis, with subsequent closure of the intracardiac defect resulting in immediate relief of symptoms and hypoxaemia. To our knowledge, this is the first reported case of an interatrial defect and shunt causing Platypnea-Orthodeoxia Syndrome after transcatheter aortic valve implantation, resolved by percutaneous device closure.

Comparison of Transradial vs Transfemoral Access for Aortoiliac and Femoropopliteal Interventions: A Single-Center Experience.

PURPOSE: To compare the procedure and safety outcomes of the transradial approach (TRA) with the femoral approach (FA) for treating aortoiliac and femoropopliteal stenoses and occlusions. METHODS: A single-center retrospective study was conducted involving 188 patients (mean age 66.4±10.8 years; 116 men) with lower limb claudication or critical limb ischemia who underwent aortoiliac (131, 62.4%) or femoropopliteal (79, 37.6%) interventions on 210 lesions over a 3-year period. Operator discretion determined TRA suitability; exclusions included Raynaud's disease, upper limb occlusive disease, previous TRA difficulties, or planned hemodialysis. Lesion characteristics, clinical endpoints, and access site complications were compared. RESULTS: FA was used primarily in 123 patients and the TRA (12 left and 53 right radial arteries) in 65 procedures. Eleven (16.9%) TRAs failed vs 9 (7.3%) FAs (p=0.42). Crossover to FA was due to occlusive lesions requiring alternative equipment in 9 cases and to tortuosity of the aortic arch vessels in 2 patients. The 134 FA interventions (balloon angioplasty, stents) were retrograde (112, 83.6%) or antegrade (22, 16.4%). There were significantly more TASC C/D lesions in the FA group (p=0.02). Sheath sizes (5-F to 8-F) did not differ between groups, and no significant differences were found between FA vs TRA in terms of procedure time (50.0±28.9 vs 46.8±25.1 minutes, p=0.50) or length of stay (2.2±0.6 vs 2.1±0.3 days, p=0.24). While there were no strokes, access site complications occurred in 6.0% of the FA patients vs 3.7% of the TRA patients (p=0.12). CONCLUSION: The transradial approach for aortoiliac and femoropopliteal interventions is safe and efficacious compared with the transfemoral approach for a range of lesion subtypes. Nevertheless, there remains a need for improvements in peripheral device and catheter technology to decrease transradial failure rates.

Post mortem study of the depth and circumferential location of sympathetic nerves in human renal arteries--implications for renal denervation catheter design.

OBJECTIVES: The aims of this study were to examine human renal arteries and to accurately characterize their sympathetic innervation and location using CD-56 immunohistochemistry stains to highlight Neural Cell Adhesion Molecules (N-CAM). BACKGROUND: Porcine models have often formed the basis for design of denervation technology, with only a limited number of human studies available to detail the complex microarray of renal sympathetic nerves. METHODS: Post-mortem renal arteries (N = 14) were harvested and prepared into three sections (proximal, mid, and distal), and then stained using Hematoxylin and Eosin, followed by immunohistochemistry to characterize the expression of CD-56 renal neural tissue. Digital micro calipers were then used to measure the nerve distances and locations within the vessels. RESULTS: (i) Approximately 77% of nerves are located between 0.5 and 2.5 mm from the tunica intima layer, with 22.5% occurring in the 2.5-5.0 mm range, (ii) nerve bundles occur in 3-dimensional arborized arrays, (iii) the nerve bundles are evenly distributed throughout the proximal and distal vessel in this human study. Thickness of vessel wall correlated with proximity of the nerve bundles (r = 0.74, P < 0.01), and nerve bundle thickness (r = 0.62, P = 0.04). The larger the internal and external diameters and areas of the vessel were, the further the distance to the nearest nerve bundles were (r = 0.752, P =<0.01). CONCLUSIONS: In human renal arteries with larger diameters and thicker vessel parenchyma, the innervation is found further from the lumen, and the nerves increase in thickness. This has implications for catheter and system design, as well as depth and duration of energy required for effective ablations. Effective percutaneous transluminal denervation procedures in this population would need to be circumferential rather than interrupted, and to mediate tissue damage to depths beyond 2.5 mm from the tunica intima.

Double trouble: hypertrophic cardiomyopathy coexistent with malignant anomalous right coronary artery.

A 40-year-old man with no cardiac history was admitted for evaluation of atypical chest pain of 1-month duration. On investigation he was found to have hypertrophic cardiomyopathy and an anomalous right coronary artery arising from the left sinus of Valsalva. This is of great clinical significance as both these conditions are independently associated with sudden cardiac death. Following extensive risk assessment and detailed discussion with the patient, he was discharged on medical therapy, comprising bisoprolol, aspirin and rosuvastatin. He has remained free of symptoms for 1 year. This report describes the rare coexistence of these two distinct clinical entities, examines the various treatment options and provides support for medical management as an acceptable treatment strategy in appropriately selected cases.

Detection of high-sensitivity troponin in outpatients with stable pulmonary hypertension identifies a subgroup at higher risk of adverse outcomes.

BACKGROUND: The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting. METHODS AND RESULTS: We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90). CONCLUSIONS: Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance.

A Comparison of Traditional and Novel Definitions (RIFLE, AKIN, and KDIGO) of Acute Kidney Injury for the Prediction of Outcomes in Acute Decompensated Heart Failure.

AIMS: To determine if newer criteria for diagnosing and staging acute kidney injury (AKI) during heart failure (HF) admission are more predictive of clinical outcomes at 30 days and 1 year than the traditional worsening renal function (WRF) definition. METHODS: We analyzed prospectively collected clinical data on 637 HF admissions with 30-day and 1-year follow-up. The incidence, stages, and outcomes of AKI were determined using the following four definitions: KDIGO, RIFLE, AKIN, and WRF (serum creatinine rise ≥0.3 mg/dl). Receiver operating curves were used to compare the predictive ability of each AKI definition for the occurrence of adverse outcomes (death, rehospitalization, dialysis). RESULTS: AKI by any definition occurred in 38.3% (244/637) of cases and was associated with an increased incidence of 30-day (32.3 vs. 6.9%, χ(2) = 70.1; p < 0.001) and 1-year adverse outcomes (67.5 vs. 31.0%, χ(2) = 81.4; p < 0.001). Most importantly, there was a stepwise increase in primary outcome with increasing stages of AKI severity using RIFLE, KDIGO, or AKIN (p < 0.001). In direct comparison, there were only small differences in predictive abilities between RIFLE and KDIGO and WRF concerning clinical outcomes at 30 days (AUC 0.76 and 0.74 vs. 0.72, χ(2) = 5.6; p = 0.02) as well as for KDIGO and WRF at 1 year (AUC 0.67 vs. 0.65, χ(2) = 4.8; p = 0.03). CONCLUSION: During admission for HF, the benefits of using newer AKI classification systems (RIFLE, AKIN, KDIGO) lie with the ability to identify those patients with more severe degrees of AKI who will go on to experience adverse events at 30 days and 1 year. The differences in terms of predictive abilities were only marginal.

Percutaneous atrial septostomy with modified butterfly stent and intracardiac echocardiographic guidance in a patient with syncope and refractory pulmonary arterial hypertension.

PURPOSE: Syncope is associated with poor prognosis in patients with pulmonary hypertension. Atrial septostomy improves cardiac index and functional class in appropriately selected patients with pulmonary hypertension, and has been shown to improve syncope. One of the major challenges to its effectiveness is maintaining septostomy patency. We report the case of percutaneous deployment of a modified peripheral stent to create an atrial septostomy in a man with severe pulmonary hypertension and syncope, initially intolerant of medical therapy. PROCEDURES: Percutaneous butterfly stent deployment across the interatrial septum using intracardiac echocardiography and fluoroscopy. FINDINGS: The patient improved in all clinical parameters (BNP, six-minute walk test, dyspnoea score), and was subsequently able to tolerate targeted pulmonary hypertension therapies. PRINCIPAL CONCLUSIONS: Atrial septostomy using butterfly stents to maintain patency may play a role in the treatment of patients with advanced pulmonary hypertension who do not respond to targeted therapy.

Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy.

AIMS: The aim of this study was to investigate the frequency of corrected QT interval (QTc) prolongation in a methadone maintenance therapy (MMT) population, and to examine potential associations between this QTc interval and methadone dose as well as concurrent use of opiates, cocaine and benzodiazepines. DESIGN: Cross-sectional study of patients attending a specialist drug treatment clinic from July 2008 to January 2009. SETTING: Single-centre inner-city specialist drug treatment clinic, Ireland. PARTICIPANTS: A total of 180 patients on stable MMT attending for daily methadone doses, over a 6-month period, where a total of 376 patients were attending during the study period. MEASUREMENTS: All patients agreeing to participate in the study underwent 12-lead electrocardiograms and QTc analysis, as well as analysis of urine toxicology screen results for opiates, benzodiazepines and cocaine. ECGs were carried out prior to methadone dose being received, regardless of time of day (trough ECG). FINDINGS: The average age was 32.6 ± 7.1 years, with mean [standard deviation (SD)] methadone dose 80.4 ± 27.5 mg. The mean (SD) QTc was 420.9 ± 21.1 ms, range 368-495 ms. Patients who had a positive toxicology screen for opiates were receiving significantly lower doses of methadone (77.8 ± 23.5 mg versus 85.0 ± 21.4 mg, P = 0.04). No significant association was noted between QTc interval prolongation and presence of cocaine metabolites in the urine (P = 0.13) or methadone dose (P = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450 ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450 ms. CONCLUSIONS: Drug-induced corrected QT interval prolongation is evident (ranging from 8.8-11.1%, depending on definition applied) in patients receiving relatively low daily doses of methadone therapy, with no evidence of a dose-response relationship. The presence of cocaine metabolites in urine does not appear to be associated with increased corrected QT interval. Increased awareness of cardiac safety guidelines, including relevant clinical and family history, baseline and trough dose ECG monitoring, should be incorporated into methadone maintenance therapy protocols.