Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models.

Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+ overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD-ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis.

Factors Associated with Disparities in Appropriate Statin Therapy in an Outpatient Inner City Population.

Lipid-lowering therapies are essential for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The aim of this study is to identify discrepancies between cholesterol management guidelines and current practice with a focus on statin treatment in an underserved population based in a large single urban medical center. Among 1042 reviewed records, we identified 464 statin-eligible patients. Age was 61.0 ± 10.4 years and 53.9% were female. Most patients were black (47.2%), followed by Hispanic (45.7%) and white (5.0%). In total, 82.1% of patients were prescribed a statin. An appropriate statin was not prescribed in 32.4% of statin-eligible patients who qualified based only on a 10-year ASCVD risk of ≥7.5%. After adjustment for gender and health insurance status, appropriate statin treatment was independently associated with age >55 years (OR = 4.59 (95% CI 1.09-16.66), p = 0.026), hypertension (OR = 2.38 (95% CI 1.29-4.38), p = 0.005) and chronic kidney disease (OR = 3.95 (95% CI 1.42-14.30), p = 0.017). Factors independently associated with statin undertreatment were black race (OR = 0.42 (95% CI 0.23-0.77), p = 0.005) and statin-eligibility based solely on an elevated 10-year ASCVD risk (OR = 0.14 (95% CI 0.07-0.25), p < 0.001). Hispanic patients were more likely to be on appropriate statin therapy when compared to black patients (86.8% vs. 77.2%). Statin underprescription is seen in approximately one out of five eligible patients and is independently associated with black race, younger age, fewer comorbidities and eligibility via 10-year ASCVD risk only. Hispanic patients are more likely to be on appropriate statin therapy compared to black patients.

Optimisation of diagnosis and treatment of heart failure in a primary care setting.

BACKGROUND: Heart failure (HF) is one of the leading causes of emergency department visits and hospital admissions in the USA. We identified a gap in the diagnosis and the use of guideline-directed medical therapy in patients with HF at the internal medicine clinic. AIM: To improve the diagnosis and treatment of HF, as well as to reduce emergency department visits and hospitalisation over 12 months in patients aged 40-75 years. METHODS: The multidisciplinary quality improvement (QI) team performed a root cause analysis and identified barriers to optimal guideline-directed medical therapy. Rates of patients on guideline-directed medical therapy with systolic HF diagnosis, emergency department visits and hospital admissions were the outcome measures. The process measures included echocardiogram order and completion rates, and rates of accurate classification of HF from the baseline rate of less than 10%. We used the focus, analyse, develop, execute and evaluate (FADE) model with five improvement cycles. The major components of interventions included (1) leveraging health information technology; (2) optimising teamwork; and (3) providing education to patients, physicians and internal medicine clinic staff. Data were analysed using statistical process control and run charts. RESULTS: We observed a reduction in the total number of emergency department visits (160 vs 108), hospital admissions (117 vs 114) and observation visits (22 vs 16) comparing the 1-year preproject and 1-year postproject periods. An increase in the use of ACE inhibitors or angiotensin receptor blockers occurred from the baseline rate of 20%-37% during the second half of the project and was sustained at 71.4% (median) during 6 months of the postproject period. CONCLUSIONS: We achieved a sustainable increase in the accurate diagnosis of HF and achieved 80% diagnosis during the 6-month poststudy period.

Superior safety of direct oral anticoagulants compared to Warfarin in patients with atrial fibrillation and underlying cancer: a national veterans affairs database study.

BACKGROUND: Studies evaluating safety of warfarin and direct oral anticoagulants (DOACs) for prevention of stroke in patients with atrial fibrillation (AF) are lacking. METHODS & RESULTS: All patients (n = 196,521) receiving care at veteran's affairs with active cancer and AF from 2010-2015 were included. One-year mortality was significantly higher in unadjusted analysis with warfarin (44.9%) compared to dabigatran (25%, P < 0.001), rivaroxaban (24.4%, P < 0.001) and apixaban (30%, P < 0.001) and after adjusting for age, sex and type of cancer mortality (OR = 2.66, 95% CI: 2.52-2.82, P < 0.001). Risk of ischemic stroke (13.5% vs. 11.1%, 12.0%, 14.0%) was similar, however risk of hemorrhagic stroke was significantly higher among patients receiving warfarin (1.2%) compared to patients receiving dabigatran (0.5%), rivaroxaban (0.7%) and apixaban (0.8%) respectively, P = 0.04. CONCLUSIONS: We demonstrated the superior safety profile of DOACs compared to warfarin among patients with underlying cancer and AF. Warfarin was associated with higher mortality, similar ischemic stroke risk but higher risk of hemorrhagic stroke.

Inter- and Intraoperator Variability in Measurement of On-Site CT-derived Fractional Flow Reserve Based on Structural and Fluid Analysis: A Comprehensive Analysis.

PURPOSE: To measure the inter- and intraobserver variability among operators of varying expertise in conducting CT-derived fractional flow reserve (CT FFR) measurements on-site by using structural and fluid analysis and to evaluate differences in reproducibility between two different training methods for end users. MATERIALS AND METHODS: This retrospective analysis of the prospectively enrolled cohort included 22 symptomatic patients who underwent both 320-detector row coronary CT angiography and catheter-derived fractional flow reserve (FFR) within 90 days. Thirteen operators of varying expertise were assigned to one of two training arms: arm 1, on-site training by a specialist in CT FFR technology; arm 2, self-training through use of written materials. After the training, all 13 operators reviewed the CT data and measured CT FFR in 24 vessels in 22 patients. Inter- and intraoperator variability and agreements between CT FFR and catheter-derived FFR measurements were evaluated. RESULTS: The overall intraclass correlation coefficient (ICC) among operators was 0.71 (95% confidence interval: 0.58, 0.83) with a mean absolute difference (± standard deviation) of 0.027 ± 0.022. The operators in arm 2 showed greater interoperator differences than those in arm 1 (0.031 ± 0.024 vs 0.023 ± 0.018; P = .024). Among operators who recalculated CT FFR, the mean CT FFR value did not significantly differ between the first and second calculations (ICC, 0.66; 95% confidence interval: 0.46, 0.87), with the medical specialists producing the lowest intraoperator variability (0.053 ± 0.060). The overall correlation coefficient between CT FFR and catheter FFR was r = 0.61, with a mean absolute difference of 0.096 ± 0.089. CONCLUSION: Good reproducibility of CT FFR values calculated on-site on the basis of structural and fluid analysis was observed among operators of varying expertise. Face-to-face training sessions may cause less variability.© RSNA, 2019Supplemental material is available for this article.

Prognostic value of frontal QRS-T angle in predicting survival after primary percutaneous coronary revascularization/coronary artery bypass grafting for ST-elevation myocardial infarction.

BACKGROUND: Frontal QRS-T angle (FQRST) has previously been correlated with mortality in patients with stable coronary artery disease, but its role as survival predictor after ST-elevation myocardial infarction (STEMI) remains unknown. METHODS: We evaluated 267 consecutive patients with STEMI undergoing reperfusion or coronary artery bypass grafting. Data assessed included demographics, clinical presentation, electrocardiograms, medical therapy, and one-year mortality. RESULTS: Of 267 patients, 187 (70%) were males and most (49.4%) patients were Caucasian. All-cause mortality was significantly higher among patients with the highest (101-180°) FQRST [28% vs. 15%, p = 0.02]. Patients with FQRST 1-50° had higher survival (85.6%) compared with FQRST = 51-100° (72.3%) and FQRST = 101-180° (67.9%), [log rank, p = 0.01]. Adjusting for significant variables identified during univariate analysis, FQRST (OR = 2.04 [95% CI: 1.31-13.50]) remained an independent predictor of one-year mortality. FQRST-based risk score (1-50° = 0 points, 51-100° = 2 points, 101-180° = 5 points) had excellent discriminatory ability for one-year mortality when combined with Mayo Clinic Risk Score (C statistic = 0.875 [95%CI: 0.813-0.937]. A high (>4 points) FQRST risk score was associated with greater mortality (32% vs. 19%, p = 0.02) and longer length of stay (6 vs. 2 days, p < 0.001). CONCLUSION: FQRST represents a novel independent predictor of one-year mortality in patients with STEMI undergoing reperfusion. A high FQRST-based risk score was associated with greater mortality and longer length of stay and, after combining with Mayo Clinic Risk Score, improved discriminatory ability for one-year mortality.

Quality of life outcomes in transcatheter aortic valve replacement patients requiring pacemaker implantation.

BACKGROUND: Permanent pacemaker implantation is the most common complication after Transcatheter aortic valve replacement (TAVR) and is associated with worse outcomes and mortality. However, its impact on quality-of-life (QoL) outcomes remains unknown. METHODS: We included 383 consecutive patients undergoing TAVR from January 2012 to 2016 who completed a baseline Kansas City Cardiomyopathy Questionnaire (KCCQ-12) health survey. The clinical, laboratory, angiographic, QoL, mortality, and occurrence of poor outcomes (KCCQ-12 score < 45 or KCCQ decrease of ≥10 points) were obtained. RESULTS: The mean age was 83 ± 8 years, 51% were men, and majority were Caucasians (n = 364, 95%). Permanent pacemaker (PPM) was implanted in 11.5% of patients post-TAVR. PPM patients were more likely to have prior conduction disease including RBBB (25% vs 12%, P = .02) and PQ interval >250 ms (11% vs 5%, P = .07). One-month median KCCQ-12 scores were significantly lower among PPM patients (84.7 vs 68.8, P = .04), but did not differ significantly at 1-year (86.5 vs 90.6, P = .5) post-TAVR. Occurrence of poor outcomes did not differ significantly among those with or without PPM at 1 month (11% vs 7%, P = .39) and 1 year (13% vs 9%, P = .45), respectively. However, patients with poor QoL outcomes at 1 month post-TAVR also had significantly worse mortality during follow-up in unadjusted (31.3% vs 4.5%, P < .001) and adjusted (HR = 5.30, 95% [CI: 1.85-15.22, P = .002])analyses, respectively. CONCLUSION: Permanent pacemaker implantation is associated with short-term reduction in QoL without long-term implications post-TAVR. Patients with poor QoL post-TAVR also have significantly higher mortality.

Optimisation of lipids for prevention of cardiovascular disease in a primary care.

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines focus on atherosclerotic cardiovascular disease (ASCVD) risk reduction, using a Pooled Cohort Equation to calculate a patient's 10-year risk score, which is used to guide initiation of statin therapy. We identified a gap of evidence-based treatment for hyperlipidaemia in the Internal Medicine Clinic. Therefore, the aim of this study was to increase calculation of ASCVD risk scores in patients between the ages of 40 and 75 years from a baseline rate of less than 1% to 10%, within 12 months, for primary prevention of ASCVD. Root cause analysis was performed to identify materials/methods, provider and patient-related barriers. Plan-Do-Study-Act cycles included: (1) creation of customised workflow in electronic health records for documentation of calculated ASCVD risk score; (2) physician education regarding guidelines and electronic health record workflow; (3) refresher training for residents and a chart alert and (4) patient education and physician reminders. The outcome measures were ASCVD risk score completion rate and percentage of new prescriptions for statin therapy. Process measures included lipid profile order and completion rates. Increase in patient wait time, and blood test and medications costs were the balanced measures. We used weekly statistical process control charts for data analysis. The average ASCVD risk completion rate was 14.2%. The mean ASCVD risk completion rate was 4.0%. In eligible patients, the average lipid profile completion rate was 18%. ASCVD risk score completion rate was 33% 1-year postproject period. A team-based approach led to a sustainable increase in ASCVD risk score completion rate. Lack of automation in ASCVD risk score calculation and physician prompts in electronic health records were identified as major barriers. Furthermore, the team identified multiple barriers to lipid blood tests and treatment of increased ASCVD risk based on ACC/AHA guidelines.

Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes.

OBJECTIVES: To determine if fractional flow reserve guided percutaneous coronary intervention (FFR-guided PCI) is associated with reduced ischemic myocardium compared with angiography-guided PCI. BACKGROUND: Although FFR-guided PCI has been shown to improve outcomes, it remains unclear if it reduces the extent of ischemic myocardium at risk compared with angiography-guided PCI. METHODS: We evaluated 380 patients (190 FFR-guided PCI cases and 190 propensity-matched controls) who underwent PCI from 2009 to 2014. Clinical, laboratory, angiographic, stress testing, and major adverse cardiac events [MACE] (all-cause mortality, recurrence of MI requiring PCI, stroke) data were collected. RESULTS: Mean age was 63 ± 11 years; the majority of patients were males (76%) and Caucasian (77%). Median duration of follow up was 3.4 [Range: 1.9, 5.0] years. Procedural complications including coronary dissection (2% vs. 0%, P = .12) and perforation (0% vs. 0%, P = 1.00) were similar between FFR-guided and angiography-guided PCI patients. FFR-guided PCI patients had lower unadjusted (14.7% vs. 23.2%, P = .04) and adjusted [OR = 0.58 (95% CI: 0.34-0.98)] risk of repeat revascularization at one year. FFR-guided PCI patients were less likely (23% vs. 32%, P = .02) to have ischemia and had lower (5.9% vs. 21.1%, P < .001) ischemic burden (moderate-severe ischemia) on post-PCI stress testing. Presence of ischemia post-PCI remained a strong predictor of MACE [OR = 2.14 (95%CI: 1.28-3.60)] with worse survival compared to those without ischemia (HR = 1.63 (95% CI: 1.06-2.51). CONCLUSION: Compared with angiography-guided PCI, FFR-guided PCI results in less repeat revascularization and a lower incidence of post PCI ischemia translating into improved survival, without an increase in complications.

Neutrophil-to-lymphocyte ratio predicts heart failure readmissions and outcomes in patients undergoing transcatheter aortic valve replacement.

OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR) has prognostic value in acute coronary syndromes. We investigated its utility for predicting heart failure (HF) admissions and major adverse cardiac outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Data on clinical, laboratory, procedural, HF admissions, and major adverse cardiac events (MACEs) (all-cause mortality, recurrence of myocardial infarction requiring intervention, stroke) for 298 consecutive patients who underwent TAVR between 2012 and 2016 in our tertiary center were collected. RESULTS: Analysis included 298 patients. The mean age was 83 ± 8 years, 51% were males, and 95% were Caucasians. The median Society of Thoracic Surgeons risk score was 9 (interquartile range: 6.3-11.8). Receiver-operating curve analysis identified a cutoff value of NLR of 4.0 for MACE after TAVR and sensitivity of 68% and specificity of 68% {area under the curve [AUC] = 0.65 [95% confidence interval (CI): 0.51-0.79], p = 0.03}. An NLR of 4.0 for HF hospitalizations after TAVR and sensitivity of 60% and specificity of 57% [AUC = 0.61 (95% CI: 0.53-0.69), p = 0.01]. NLR ≥4.0 before TAVR significantly predicted MACE after TAVR (68.4% vs. 31.6%, p = 0.02) and HF hospitalizations (58.3% vs. 41.7%, p = 0.03). NLR with TAVR risk score increased the predictive value for MACE after TAVR from AUC = 0.61 (95% CI: 0.50-0.72, p = 0.06) to AUC = 0.69 (95% CI: 0.57-0.80, p = 0.007). CONCLUSION: NLR predicts all-cause mortality, MACE, and HF hospitalization 1 year after TAVR. NLR with TAVR risk score improved predictability for MACE. Further studies for prognostication using NLR are warranted.

Temporal Trends, Complications, and Predictors of Outcomes Among Nonagenarians Undergoing Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: The aim of this study was to determine temporal trends, in-laboratory complications, mortality, and predictors of mortality among nonagenarians undergoing percutaneous coronary intervention (PCI). BACKGROUND: Nonagenarians (patients 90 years of age or older) undergoing PCI are often underrepresented in clinical trials, and their management remains challenging and controversial. METHODS: All veterans undergoing PCI with data recorded in the Veterans Affairs Clinical Assessment, Reporting, and Tracking program from 2005 to 2014 were evaluated. Temporal trends in the use of PCI, occurrence of in-laboratory complications, and 30-day and 1-year mortality were assessed. Using a frailty model, predictors of 30-day and 1-year mortality in nonagenarians were evaluated. RESULTS: Among all veterans undergoing PCI (n = 67,148) between 2005 and 2014, 274 (0.4%) were nonagenarians. The proportion of nonagenarians increased from 0.25% in 2008 to 0.58% in 2014. Compared with younger patients, nonagenarians had a greater risk for acute cardiogenic shock post-procedure (0.73% vs. 0.12%; p = 0.04) and no reflow (2.9% vs. 1.0%; p = 0.02). Unadjusted (10.6% vs. 1.4%; p < 0.0001) and adjusted 30-day mortality (odds ratio: 2.14; 95% confidence interval [CI]: 1.42 to 3.22) and unadjusted (16.3% vs. 4.2%; p < 0.0001) and adjusted 1-year mortality (odds ratio: 1.82; 95% CI: 1.27 to 2.62) were higher among PCI patients who were nonagenarians. The National Cardiovascular Data Registry risk score was highly predictive of both 30-day (hazard ratio: 2.29; 95% CI: 1.86 to 2.82) and 1-year (hazard ratio: 1.43; 95% CI: 1.07 to 1.90) mortality among nonagenarians. CONCLUSIONS: Nonagenarians were a small but growing population with worse 30-day and 1-year mortality. The National Cardiovascular Data Registry risk score was a strong predictor of mortality in these patients.

The Tpeak - Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: A systematic review and meta-analysis.

BACKGROUND: The Tpeak - Tend interval (the interval from the peak to the end of the T wave), an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death in different clinical settings. OBJECTIVE: This systematic review and meta-analysis evaluated the significance of the Tpeak - Tend interval in predicting arrhythmic and/or mortality end points. METHODS: PubMed, Embase, Cochrane Library, and CINAHL Plus databases were searched through November 30, 2016. RESULTS: Of the 854 studies identified initially, 33 observational studies involving 155,856 patients were included in our meta-analysis. Tpeak - Tend interval prolongation (mean cutoff value 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio [OR] 1.14; 95% confidence interval [CI] 1.11-1.17; P < .001). When different end points were analyzed, the ORs were as follows: VT/VF, 1.10 (95% CI 1.06-1.13; P < .0001); sudden cardiac death, 1.27 (95% CI 1.17-1.39; P < .0001); cardiovascular death, 1.40 (95% CI 1.19-1.64; P < .0001); and all-cause mortality, 4.56 (95% CI 0.62-33.68; P < .0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR 5.68; 95% CI 1.57-20.53; P < .01), followed by hypertension (OR 1.52; 95% CI 1.26-1.85; P < .0001), heart failure (OR 1.07; 95% CI 1.04-1.11; P < .0001), and ischemic heart disease (OR 1.06; 95% CI 1.02-1.10; P = 0.001). CONCLUSION: The Tpeak - Tend interval is a useful risk stratification tool in different diseases and in the general population.