Electrophysiological Characterization of Subclinical and Overt Hypertrophic Cardiomyopathy by Magnetic Resonance Imaging-Guided Electrocardiography.

BACKGROUND: Ventricular arrhythmia in hypertrophic cardiomyopathy (HCM) relates to adverse structural change and genetic status. Cardiovascular magnetic resonance (CMR)-guided electrocardiographic imaging (ECGI) noninvasively maps cardiac structural and electrophysiological (EP) properties. OBJECTIVES: The purpose of this study was to establish whether in subclinical HCM (genotype [G]+ left ventricular hypertrophy [LVH]-), ECGI detects early EP abnormality, and in overt HCM, whether the EP substrate relates to genetic status (G+/G-LVH+) and structural phenotype. METHODS: This was a prospective 211-participant CMR-ECGI multicenter study of 70 G+LVH-, 104 LVH+ (51 G+/53 G-), and 37 healthy volunteers (HVs). Local activation time (AT), corrected repolarization time, corrected activation-recovery interval, spatial gradients (GAT/GRTc), and signal fractionation were derived from 1,000 epicardial sites per participant. Maximal wall thickness and scar burden were derived from CMR. A support vector machine was built to discriminate G+LVH- from HV and low-risk HCM from those with intermediate/high-risk score or nonsustained ventricular tachycardia. RESULTS: Compared with HV, subclinical HCM showed mean AT prolongation (P = 0.008) even with normal 12-lead electrocardiograms (ECGs) (P = 0.009), and repolarization was more spatially heterogenous (GRTc: P = 0.005) (23% had normal ECGs). Corrected activation-recovery interval was prolonged in overt vs subclinical HCM (P < 0.001). Mean AT was associated with maximal wall thickness; spatial conduction heterogeneity (GAT) and fractionation were associated with scar (all P < 0.05), and G+LVH+ had more fractionation than G-LVH+ (P = 0.002). The support vector machine discriminated subclinical HCM from HV (10-fold cross-validation accuracy 80% [95% CI: 73%-85%]) and identified patients at higher risk of sudden cardiac death (accuracy 82% [95% CI: 78%-86%]). CONCLUSIONS: In the absence of LVH or 12-lead ECG abnormalities, HCM sarcomere gene mutation carriers express an aberrant EP phenotype detected by ECGI. In overt HCM, abnormalities occur more severely with adverse structural change and positive genetic status.

Long-Term Outcomes Following Heart Team Revascularization Recommendations in Complex Coronary Artery Disease.

Background The Heart Team ( HT ) comprises integrated interdisciplinary decision making. Current guidelines assign a Class Ic recommendation for an HT approach to complex coronary artery disease ( CAD ). However, there remains a paucity of data in regard to hard clinical end points. The aim was to determine characteristics and outcomes in patients with complex CAD following HT discussion. Methods and Results This observational study was conducted at St Thomas' Hospital (London, UK). Case mixture included unprotected left main, 2-vessel (including proximal left anterior descending artery) CAD , 3-vessel CAD , or anatomical and/or clinical equipoise. HT strategy was defined as optimal medical therapy ( OMT ) alone, OMT +percutaneous coronary intervention ( PCI ), or OMT +coronary artery bypass grafting. From April 2012 to 2013, 51 HT meetings were held and 398 cases were discussed. Patients tended to have multivessel CAD (74.1%), high SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) scores (median, 30; interquartile range, 23-39), and average age 69±11 years. Multinomial logistic regression analysis performed to determine variables associated with HT strategy demonstrated decreased likelihood of undergoing PCI compared with OMT in older patients with chronic kidney disease and peripheral vascular disease. The odds of undergoing coronary artery bypass grafting compared with OMT decreased in the presence of cardiogenic shock and left ventricular dysfunction and increased in younger patients with 3-vessel CAD . Three-year survival was 60.8% (84 of 137) in the OMT cohort, 84.3% (107 of 127) in the OMT + PCI cohort, and 90.2% in the OMT +coronary artery bypass grafting cohort (92 of 102). Conclusions In our experience, the HT approach involved a careful selection process resulting in appropriate patient-specific decision making and good long-term outcomes in patients with complex CAD .

The impact of catheter ablation for atrial fibrillation in heart failure.

Atrial fibrillation (AF) commonly co-exists with systolic heart failure (SHF) and its presence is associated with a worse prognosis. Despite this, a rhythm control approach using antiarrhythmic drugs (AADs) to reduce AF burden has demonstrated no prognostic benefit. Catheter ablation (AFA) is more effective than AADs at reducing AF burden. We performed a meta-analysis to evaluate the impact of AFA on outcomes in SHF. Electronic databases were systematically searched. We included only randomized controlled trials that examined the impact of AFA on clinical outcomes in patients with SHF (LVEF <50%). We included studies with any ablation strategy that incorporated pulmonary vein isolation and any control group. Seven studies (n = 858) were included with a mean follow-up of 6-38 months. In comparison to controls, AFA was associated with significant reductions in all-cause mortality (relative risk [RR] 0.52, P = 0.0009) and unplanned or heart failure hospitalization (RR 0.58, P < 0.00001). Compared to controls, AFA was also associated with significant improvements in LVEF (mean difference 6.30%, P < 0.00001), Minnesota Living with Heart Failure Questionnaire score (mean difference 9.58, P = 0.0003), 6-minute walk distance (mean difference 31.78 m, P = 0.003) and VO 2 max (mean difference 3.17, P = 0.003). However, major procedure-related complications occurred in 2.4%-15% of ablation patients. In patients with AF and SHF, catheter ablation has significant benefits. Further work is needed to establish the role of ablation in the routine treatment of SHF patients with AF.

Risk classification in primary prevention of CVD according to QRISK2 and JBS3 'heart age', and prevalence of elevated high-sensitivity C reactive protein in the UK cohort of the EURIKA study.

Objectives: This study assessed cardiovascular disease (CVD) risk classification according to QRISK2, JBS3 'heart age' and the prevalence of elevated high-sensitivity C reactive protein (hsCRP) in UK primary prevention patients. Method: The European Study on Cardiovascular Prevention and Management in Usual Daily Practice (EURIKA) (NCT00882336) was a cross-sectional study conducted in 12 European countries. 673 UK outpatients aged ≥50 years, without clinical CVD but with at least one conventional CVD risk factor, were recruited. 10-year CVD risk was calculated using QRISK2. JBS3 'heart age' and hsCRP level were assessed according to risk category. Results: QRISK2 and JBS3 heart age was calculated for 285 of the 305 patients free from diabetes mellitus and not receiving a statin. QRISK2 classified 28%, 39% and 33% of patients as low (<10%), intermediate (10% to <20%) and high (≥20%) risk, respectively. Two-thirds of low-risk patients and half of intermediate-risk patients had a heart age ≥5 years and ≥10 years higher than their chronological age, respectively. Half of low-risk patients had hsCRP levels ≥2 mg/L and approximately 40% had levels ≥3 mg/L. Approximately 80% of low-risk patients had both elevated hsCRP and heart age relative to their chronological age. Conclusions: Almost 40% more patients in this 'at risk' group would be eligible for statin therapy following the lowering of the National Institute for Health and Care Excellence treatment threshold to ≥10% 10-year risk. Of patients falling below this treatment threshold, almost all were at increased lifetime risk as measured by JBS3, and of these, the majority had elevated hsCRP levels. These patients with high absolute risk may benefit from early primary CVD prevention.

Temporal Trends in Identification, Management, and Clinical Outcomes After Out-of-Hospital Cardiac Arrest: Insights From the Myocardial Ischaemia National Audit Project Database.

BACKGROUND: There is wide variation in survival rates from out-of-hospital cardiac arrest (OHCA) and overall survival remains poor. There is an expert consensus that early reperfusion therapy in ST-elevation reduces mortality. The management of patients without ST-elevation, however, is controversial. METHODS AND RESULTS: The Myocardial Ischaemia National Audit Project database is a national registry of all hospital admissions in England and Wales treated as an acute coronary syndrome (ACS). We examined temporal trends, over a 5-year period, of OHCAs identified by Myocardial Ischaemia National Audit Project, admitted to hospital and treated as ACS, the interventional management of these patients and clinical outcomes. Four hundred ten thousand four hundred sixty-two patients were admitted to hospital in England and Wales with ACS. Of these, 9421 presented with OHCA (2.30%). There was an increase in OHCA cases as a proportion of ACS between 2009 and 2013 (1.79% in 2009 versus 2.74% in 2013; Ptrend<0.001). The rate of coronary angiography+percutaneous coronary intervention increased in ACS patients presenting with OHCA (54.9% in 2009 [876/1595] versus 66.3% in 2013 [884/1334]; Ptrend<0.001). Cox proportional hazards model with time-varying exposure to coronary angiography demonstrated a significant reduction in mortality in both the ST-elevation (hazard ratio, 0.30; 95% confidence interval, 0.28-0.32; P<0.05) and non-ST-elevation cohort (hazard ratio, 0.44; 95% confidence interval, 0.42-0.46; P<0.001). Predictors of favorable outcome were synonymous with the selection criteria for patients undergoing coronary angiography±percutaneous coronary intervention. CONCLUSIONS: This observational study showed that selection for coronary angiography±percutaneous coronary intervention was associated with reduced mortality in OHCA patients diagnosed with ACS. These data support the need for a randomized controlled trial.

Massive Accumulation of Myofibroblasts in the Critical Isthmus Is Associated With Ventricular Tachycardia Inducibility in Post-Infarct Swine Heart.

OBJECTIVES: In this study the authors determined the extent of cellular infiltration and dispersion, and regional vascularization in electrophysiologically (EP) defined zones in post-myocardial infarction (MI) swine ventricle. BACKGROUND: The critical isthmus (CI) in post-MI re-entrant ventricular tachycardia (VT) is a target for catheter ablation. In vitro evidence suggests that myofibroblasts (MFB) within the scar border zone (BZ) may increase the susceptibility to slow conduction and VT, but whether this occurs in vivo remains unproven. METHODS: Six weeks after mid-left anterior descending coronary artery occlusion, EP catheter-based mapping was used to assess susceptibility to VT induction. EP data were correlated with detailed cellular profiling of ventricular zones using immunohistochemistry and spatial distribution analysis of cardiomyocytes, fibroblasts, MFB, and vascularization. RESULTS: In pigs with induced sustained monomorphic VT (mean cycle length: 353 ± 89 ms; n = 6) the area of scar that consisted of the BZ (i.e., between the normal and the low-voltage area identified by substrate mapping) was greater in VT-inducible hearts (iVT) than in noninducible hearts (non-VT) (p < 0.05). Scar in iVT hearts was characterized by MFB accumulation in the CI (>100 times that in normal myocardium and >5 times higher than that in the BZ in non-VT hearts) and by a 1.7-fold increase in blood vessel density within the dense scar region extending towards the CI. Sites of local abnormal ventricular activity potentials exhibited cellularity and vascularization that were intermediate to the CI in iVT and BZ in non-VT hearts. CONCLUSIONS: The authors reported the first cellular analysis of the VT CI following an EP-based zonal analysis of iVT and non-VT hearts in pigs post-MI. The data suggested that VT susceptibility was defined by a remarkable number of MFB in the VT CI, which appeared to bridge the few remaining dispersed clusters of cardiomyocytes. These findings define the cellular substrate for the proarrhythmic slow conduction pathway.

A rare case of a giant saphenous vein graft aneurysm with right atrial fistula formation.

A 57-year-old hypertensive and dyslipidaemic man with a history of coronary artery bypass graft 19 years previously, presented with severe exertional angina and dyspnoea despite optimal anti-ischaemic pharmacological therapy and previous percutaneous coronary intervention to the left circumflex artery. CT revealed an aneurysm of the saphenous vein graft to the posterior left ventricular branch of the right coronary artery. The aneurysm had formed a fistulous connection with the right atrium. Initially, luminal reconstruction with serial stents was deemed the most appropriate treatment strategy. However, the procedure was abandoned due to the inability to visualise the graft distal to the aneurysm and the significant shunt to the right atrium. Surgical correction of the right atrial wall defect and replacement of the diseased grafts led to complete resolution of the patient's symptoms.

Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients.

BACKGROUND: High on treatment platelet reactivity (HTPR) is common in patients receiving clopidogrel following an acute coronary syndrome (ACS); it's also associated with increased morbidity and mortality. More potent and predictable antiplatelet drugs have addressed this issue at the expense of increased bleeding. Identification of HTPR and the targeted use of more potent antiplatelet drugs has, so far, broadly failed. We investigate this approach in terms of the timing of platelet function testing and how this can impact on the ability of these bedside tests to predict HTPR around the time of coronary intervention. METHODS: High risk ACS patients treated with 5 days of clopidogrel had platelet function assessed using the multiple electrode aggregometry system (MEA) pre, post and 24 h following percutaneous coronary intervention (PCI). Simultaneous detailed analysis of platelet status was undertaken with quantification of platelet bound and soluble p-selectin and mass spectrometry quantification of the eicosanoid 12-HETE. RESULTS: As assessed by MEA 40.5% of patients had HTPR pre-PCI; mean aggregation units (AU) in response to ADP were 499.1 ± 46.3 pre-PCI, 407.6 ± 37.7 post-PCI and 269.1 ± 24.6 AU 24 h post-PCI (pre to post PCI p > 0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet reactivity was contrasted with on-going expression of platelet bound p-selectin, increased soluble p-selectin and rising 12-HETE concentrations. CONCLUSIONS: This study outlines significant changes in ex-vivo platelet aggregation that occur within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there were no changes in antiplatelet therapy during the study period its clear that timing is crucial when assessing high on treatment residual platelet activity.