Ante-mortem characterization of sudden deaths as first-manifestation in Italy.

PURPOSE: There is a relative paucity of data on ante-mortem clinical characteristics of young (age 1 to 35 years) sudden death (SD) victims. The aim of the study was to characterize ante-mortem characteristics of SD victims, in a selected national cohort identified by a web search. METHODS: A dataset of all SD (January 2010 and December 2015) was built from national forensic data and medical records, integrated with Google search model. Families were contacted to obtain consent for interviews. Data were obtained on ante-mortem symptoms. ECG characteristics and autopsy data were available. RESULTS: Out of 301 SD cases collected, medical and family history was available in 132 (43.9%). Twenty-eight (21.1%) had a positive family history for SD. SD occurred during sport/effort in 76 (57.6%). One hundred twelve (85%) SD cases had no prior reported symptoms. Autopsy data were available in 100/132 (75.8%) cases: an extra cardiac cause was identified in 20 (20%). Among the 61 cases with a cardiac diagnosis, 21 (34%) had hypertrophic cardiomyopathy. Among the 19 (19%) victims without structural abnormalities, molecular autopsy identified pathogenic variants for channelopathies in 9 cases. Ten (10%) victims had no identifiable cause. CONCLUSIONS: Most SD were due to cardiac causes and occurred in previously asymptomatic patients. SD events mainly occurred during strenuous activity. In a minority of cases, no cause was identified. The web-based selection criteria, and incomplete data retrieval, need to be carefully taken into account for data interpretation and reproducibility.

Myocardial Perfusion Defects in Hypertrophic Cardiomyopathy Mutation Carriers.

Background Impaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype-positive, left ventricular hypertrophy-negative). Methods and Results A single center, case-control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre-phenotypic features of HCM. Individuals with genotype-positive, left ventricular hypertrophy-negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH-fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype-positive, left ventricular hypertrophy-negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end-systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=<0.005; 3.01±0.96 versus 3.47±0.75, P=0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P=0.826). Conclusions Regional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.

Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy: Biomarker Variability and its Impact on Clinical Care.

OBJECTIVES: The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD). METHODS: A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death. RESULTS: MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk). CONCLUSIONS: Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.

Left atrial shape is independent predictor of arrhythmia recurrence after catheter ablation for atrial fibrillation: A shape statistics study.

BACKGROUND: Markers of left atrial (LA) shape may improve the prediction of postablation outcomes in atrial fibrillation (AF). Correlations to LA volume and AF persistence limit their incremental value over current clinical predictors. OBJECTIVE: To develop a shape score independent from AF persistence and LA volume using shape-based statistics, and to test its ability to predict postablation outcome. METHODS: Preablation computed tomography (CT) images from 141 patients with paroxysmal (57%) or persistent (43%) AF were segmented. Deformation of an average LA shape into each patient encoded patient-specific shape. Local analysis investigates regional differences between patient groups. Linear regression was used to remove shape variations related to LA volume and AF persistence, and to build a shape score to predict postablation outcome. Cross-validation was performed to evaluate its accuracy. RESULTS: Ablation failure rate was 23% over a median 12-month follow-up. Regions associated with ablation failure mostly consisted of a large area on posteroinferior LA, mitral isthmus, and left inferior vein. On univariate analysis, strongest predictors were AF persistence (P = .005), LA indexed volume (P = .02), and the proposed shape score (P = .001). On multivariate analysis, all 3 were independent predictors of ablation failure, with the LA shape score showing the highest predictive value (odds ratio [OR] = 6.2 [2.5-15.8], P < .001), followed by LA indexed volume (OR = 3.1 [1.2-7.9], P = .019) and AF persistence (OR = 2.9 [1.2-7.6], P = .022). CONCLUSION: Posteroinferior LA, mitral isthmus, and left inferior vein are the regions whose shape have the highest impact on outcome. LA shape predicts AF ablation failure independently from, and more accurately than, atrial volume and AF persistence.

High-Resolution Late Gadolinium Enhancement Magnetic Resonance for the Diagnosis of Myocardial Infarction With Nonobstructed Coronary Arteries.

OBJECTIVES: The aim of this study was to assess the diagnostic yield of cardiac magnetic resonance (CMR) including high-resolution (HR) late gadolinium enhancement (LGE) imaging using a 3-dimensional respiratory-navigated method in patients with myocardial infarction with nonobstructed coronary arteries (MINOCA). BACKGROUND: CMR plays a pivotal role for the diagnosis of patients with MINOCA. However, the diagnosis remains inconclusive in a significant number of patients, the results of CMR being either negative or uncertain (i.e., compatible with multiple diagnoses). METHODS: Consecutive patients categorized as having MINOCA after blood testing, electrocardiography, coronary angiography, and echocardiography underwent conventional CMR, including cine, T2-weighted, first-pass perfusion, and conventional breath-held LGE imaging. HR LGE imaging using a free-breathing method allowing improved spatial resolution (voxel size 1.25 × 1.25 × 2.5 mm) was added to the protocol when the results of conventional CMR were inconclusive and was optional otherwise. Diagnoses retained after reviewing conventional CMR were compared with those retained after the addition of HR LGE imaging. RESULTS: From 2013 to 2016, 229 patients were included (mean age 56 ± 17 years, 45% women). HR LGE imaging was performed in 172 patients (75%). In this subpopulation, definite diagnoses were retained after conventional CMR in 86 patients (50%): infarction in 39 (23%), myocarditis in 32 (19%), takotsubo cardiomyopathy in 13 (8%), and other diagnoses in 2 (1%). In the remaining 86 patients (50%), results of CMR were inconclusive: negative in 54 (31%) and consistent with multiple diagnoses in 32 (19%). HR LGE imaging led to changes in final diagnosis in 45 patients (26%) and to a lower rate of inconclusive final diagnosis (29%) (p < 0.001). In particular, HR LGE imaging could reveal or ascertain the diagnosis of infarction in 14% and rule out the diagnosis of infarction in 12%. HR LGE imaging was particularly useful when the results of transthoracic echocardiography, ventriculography, and conventional CMR were negative, with a 48% rate of modified diagnosis in this subpopulation. CONCLUSIONS: HR LGE imaging has high diagnostic value in patients with MINOCA and inconclusive findings on conventional CMR. This has major diagnostic, prognostic, and therapeutic implications.

Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy.

OBJECTIVE: In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We measured MBF using cardiovascular magnetic resonance fully quantitative perfusion mapping to determine the relationship between perfusion, hypertrophy and late gadolinium enhancement (LGE) in HCM. METHODS: 101 patients with HCM with unobstructed epicardial coronary arteries and 30 controls (with matched cardiovascular risk factors) underwent pixel-wise perfusion mapping during adenosine stress and rest. Stress, rest MBF and the myocardial perfusion reserve (MPR, ratio of stress to rest) were calculated globally and segmentally and then associated with segmental wall thickness and LGE. RESULTS: In HCM, 79% had a perfusion defect on clinical read. Stress MBF and MPR were reduced compared with controls (mean±SD 1.63±0.60 vs 2.30±0.64 mL/g/min, p<0.0001 and 2.21±0.87 vs 2.90±0.90, p=0.0003, respectively). Globally, stress MBF fell with increasing indexed left ventricle mass (R2 for the model 0.186, p=0.036) and segmentally with increasing wall thickness and LGE (both p<0.0001). In 21% of patients with HCM, MBF was lower during stress than rest (MPR <1) in at least one myocardial segment, a phenomenon which was predominantly subendocardial. Apparently normal HCM segments (normal wall thickness, no LGE) had reduced stress MBF and MPR compared with controls (mean±SD 1.88±0.81 mL/g/min vs 2.32±0.78 mL/g/min, p<0.0001). CONCLUSIONS: Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker.

Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy.

AIMS: The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM. METHODS AND RESULTS: We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73-0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06-3.68; P = 0.03). CONCLUSION: PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.

Quantitative Myocardial Perfusion in Fabry Disease.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease resulting in tissue accumulation of sphingolipids. Key myocardial processes that lead to adverse outcomes in FD include storage, hypertrophy, inflammation, and fibrosis. These are quantifiable by multiparametric cardiovascular magnetic resonance. Recent developments in cardiovascular magnetic resonance perfusion mapping allow rapid in-line perfusion quantification permitting broader clinical application, including the assessment of microvascular dysfunction. We hypothesized that microvascular dysfunction in FD would be associated with storage, fibrosis, and edema. METHODS: A prospective, observational study of 44 FD patients (49 years, 43% male, 24 [55%] with left ventricular hypertrophy [LVH]) and 27 healthy controls with multiparametric cardiovascular magnetic resonance including vasodilator stress perfusion mapping. Myocardial blood flow (MBF) was measured and its associations with other processes investigated. RESULTS: Compared with LVH- FD, LVH+ FD had higher left ventricular ejection fraction (73% versus 68%), more late gadolinium enhancement (85% versus 15%), and a lower stress MBF (1.76 versus 2.36 mL/g per minute). The reduction in stress MBF was more pronounced in the subendocardium than subepicardium. LVH- FD had lower stress MBF than controls (2.36 versus 3.00 mL/g per minute; P=0.002). Across all FD, late gadolinium enhancement and low native T1 were independently associated with reduced stress MBF. On a per-segment basis, stress MBF was independently associated with wall thickness, T2, extracellular volume fraction, and late gadolinium enhancement. CONCLUSIONS: FD patients have reduced perfusion, particularly in the subendocardium with greater reductions with LVH, storage, edema, and scar. Perfusion is reduced even without LVH suggesting it is an early disease marker.

Focal scar and diffuse myocardial fibrosis are independent imaging markers in repaired tetralogy of Fallot.

AIMS: To identify the correlates of focal scar and diffuse fibrosis in patients with history of tetralogy of Fallot (TOF) repair. METHODS AND RESULTS: Consecutive patients with prior TOF repair underwent electrocardiogram, 24-h Holter, transthoracic echocardiography, exercise testing, and cardiac magnetic resonance (CMR) including cine imaging to assess ventricular volumes and ejection fraction, T1 mapping to assess left ventricular (LV) and right ventricular (RV) diffuse fibrosis, and free-breathing late gadolinium-enhanced imaging to quantify scar area at high spatial resolution. Structural imaging data were related to clinical characteristics and functional imaging markers. Cine and T1 mapping results were compared with 40 age- and sex-matched controls. One hundred and three patients were enrolled (age 28 ± 15 years, 36% women), including 36 with prior pulmonary valve replacement (PVR). Compared with controls, TOF showed lower LV ejection fraction (LVEF) and RV ejection fraction (RVEF), and higher RV volume, RV wall thickness, and native T1 and extracellular volume values on both ventricles. In TOF, scar area related to LVEF and RVEF, while LV and RV native T1 related to RV dilatation. On multivariable analysis, scar area and LV native T1 were independent correlates of ventricular arrhythmia, while RVEF was not. Patients with history of PVR showed larger scars on RV outflow tract but shorter LV and RV native T1. CONCLUSION: Focal scar and biventricular diffuse fibrosis can be characterized on CMR after TOF repair. Scar size relates to systolic dysfunction, and diffuse fibrosis to RV dilatation. Both independently relate to ventricular arrhythmias. The finding of shorter T1 after PVR suggests that diffuse fibrosis may reverse with therapy.

Relationship between atrial scar on cardiac magnetic resonance and pulmonary vein reconnection after catheter ablation for paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary vein (PV) reconnection is frequent in patients showing atrial fibrillation (AF) recurrence after PV isolation (PVI). Its detection with cardiac magnetic resonance (CMR) may help predict outcome and guide redo procedures. We assessed the relationship between scar on CMR and PV reconnection after catheter ablation for paroxysmal AF. METHODS AND RESULTS: Fifty-one patients with paroxysmal AF underwent CMR before PVI using either a conventional single-electrode catheter (N = 28) or a circular multielectrode catheter (N = 23). At 3 months, a second CMR study was performed, followed by a systematic electrophysiological procedure to look for PV reconnection, regardless of AF recurrence. Preablation fibrosis and postablation scar were quantified and mapped from late gadolinium-enhanced CMR. CMR results were compared to the distribution and extent of PV reconnection. CMR and electrophysiological findings were compared between catheter types. Three months after successful PVI, scar gaps were found in 39 (76%) patients, and 78 (39%) veins. Electrical PV reconnection was detected in 45 (88%) patients, and 99 (50%) veins. The extent of PV reconnection related closely to the number of gaps (R = 0.55; P < .001), and to scar burden (R = -0.63; P < .001). However, the agreement was only fair for the localization of PV reconnection (k = 0.37; P < .001), scar gaps particularly lacking sensitivity in areas of pre-existing fibrosis. The circular catheter was associated with shorter procedures (P < .001), more scar (P = .01), less gaps (P = .01), and less reconnected veins (P = .03). CONCLUSION: PV reconnection is extremely frequent after PVI. CMR scar imaging accurately predicts its extent, but poorly predicts its location. Multielectrode circular catheters induce more complete ablation.

Quantitative myocardial perfusion in coronary artery disease: A perfusion mapping study.

BACKGROUND: Cardiac MR stress perfusion remains a qualitative technique in clinical practice due to technical and postprocessing challenges. However, automated inline perfusion mapping now permits myocardial blood flow (MBF, ml/g/min) quantification on-the-fly without user input. PURPOSE: To investigate the diagnostic performance of this novel technique in detecting occlusive coronary artery disease (CAD) in patients scheduled to undergo coronary angiography. STUDY TYPE: Prospective, observational. SUBJECTS: Fifty patients with suspected CAD and 24 healthy volunteers. FIELD STRENGTH: 1.5T. SEQUENCE: "Dual" sequence multislice 2D saturation recovery. ASSESSMENT: All patients underwent cardiac MR with perfusion mapping and invasive coronary angiography; the healthy volunteers had MR with perfusion mapping alone. STATISTICAL TESTS: Comparison between numerical variables was performed using an independent t-test. Receiver operator characteristic (ROC) curves were generated for transmyocardial, endocardial stress MBF, and myocardial perfusion reserve (MPR, the stress:rest MBF ratio) to diagnose severe (>70%) stenoses as measured by 3D quantitative coronary angiography (QCA). ROC curves were compared by the method of DeLong et al. RESULTS: Compared with volunteers, patients had lower stress MBF and MPR even in vessels with <50% stenosis (2.00 vs. 3.08 ml/g/min, respectively). As stenosis severity increased (<50%, 50-70%, >70%), MBF and MPR decreased. To diagnose occlusive (>70%) CAD, endocardial and transmyocardial stress MBF were superior to MPR (area under the curve 0.92 [95% CI 0.86-0.97] vs. 0.90 [95% CI 0.84-0.95] and 0.80 [95% CI 0.72-0.87], respectively). An endocardial threshold of 1.31 ml/g/min provided a per-coronary artery sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90%, 82%, 50%, and 98%, with a per-patient diagnostic performance of 100%, 66%, 57%, and 100%, respectively. DATA CONCLUSION: Perfusion mapping can diagnose occlusive CAD with high accuracy and, in particular, high sensitivity and NPV make it a potential "rule-out" test. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:756-762.

Two-Minute k-Space and Time-accelerated Aortic Four-dimensional Flow MRI: Dual-Center Study of Feasibility and Impact on Velocity and Wall Shear Stress Quantification.

PURPOSE: To investigate the two-center feasibility of highly k-space and time (k-t)-accelerated 2-minute aortic four-dimensional (4D) flow MRI and to evaluate its performance for the quantification of velocities and wall shear stress (WSS). MATERIALS AND METHODS: This cross-sectional study prospectively included 68 participants (center 1, 11 healthy volunteers [mean age ± standard deviation, 61 years ± 15] and 16 patients with aortic disease [mean age, 60 years ± 10]; center 2, 14 healthy volunteers [mean age, 38 years ± 13] and 27 patients with aortic or cardiac disease [mean age, 78 years ± 18]). Each participant underwent highly accelerated 4D flow MRI (k-t acceleration, acceleration factor of 5) of the thoracic aorta. For comparison, conventional 4D flow MRI (acceleration factor of 2) was acquired in the participants at center 1 (n = 27). Regional aortic peak systolic velocities and three-dimensional WSS were quantified. RESULTS: k-t-accelerated scan times (center 1, 2:03 minutes ± 0:29; center 2, 2:06 minutes ± 0:20) were significantly reduced compared with conventional 4D flow MRI (center 1, 12:38 minutes ± 2:25; P < .0001). Overall good agreement was found between the two techniques (absolute differences ≤15%), but proximal aortic WSS was significantly underestimated in patients by using k-t-accelerated 4D flow when compared with conventional 4D flow (P ≤ .03). k-t-accelerated 4D flow MRI was reproducible (intra- and interobserver intraclass correlation coefficient ≥0.98) and identified significantly increased peak velocities and WSS in patients with stenotic (P ≤ .003) or bicuspid (P ≤ .04) aortic valves compared with healthy volunteers. In addition, k-t-accelerated 4D flow MRI-derived velocities and WSS were inversely related to age (r ≥-0.53; P ≤ .03) over all healthy volunteers. CONCLUSION: k-t-accelerated aortic 4D flow MRI providing 2-minute scan times was feasible and reproducible at two centers. Although consistent healthy aging- and disease-related changes in aortic hemodynamics were observed, care should be taken when considering WSS, which can be underestimated in patients.© RSNA, 2019See also the commentary by François in this issue.

Predictors of future onset of atrial fibrillation in hypertrophic cardiomyopathy.

BACKGROUND: Novel predictors of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) are desirable. AIM: To detect new multimodality imaging variables predictive of de novo AF in HCM. METHODS: Consecutive patients with HCM underwent clinical assessment and 48-hour Holter electrocardiography to detect AF episodes. Left ventricular (LV) morphology, function and fibrosis, and the left atrium (LA) were characterized by cardiac magnetic resonance. Mitral valve, systolic pulmonary artery pressure, LV filling and maximum gradients were assessed by echocardiography. Patients with no previous history of AF were followed with Holter recordings. RESULTS: Two hundred and nine patients were included (mean age 53±16 years; 140 men), 46 (22%) of whom had a history of AF and a longer duration from HCM diagnosis, more frequent use of heart failure medication, a higher systolic pulmonary artery pressure, a lower LV ejection fraction, a higher extent of LV fibrosis and prevalence of fibrosis on right ventricular (RV)-LV insertions, a higher LA volume and lower LA phasic function. Patients with no AF at inclusion were followed for 26 (17-42) months, and 15 (9%) developed de novo AF. Among clinical characteristics, New York Heart Association class was the only significant AF predictor in the multivariable analysis (hazard ratio 2.65 per class, 95% confidence interval [CI] 1.15-6.10; P=0.02). Among imaging characteristics, two independent predictors were identified: myocardial fibrosis on RV insertions (hazard ratio 2.8, 95% CI 1.3-5.9; P=0.008); and LA volume (hazard ratio 1.03 per mL/m2, 95% CI 1.01-1.06; P=0.006). CONCLUSIONS: AF in HCM is predicted by New York Heart Association class, LA volume and LV fibrosis on RV-LV insertions on cardiac magnetic resonance imaging. The mechanisms relating the ventricular phenotype to AF should be clarified in future studies.

Influence of contact force on voltage mapping: A combined magnetic resonance imaging and electroanatomic mapping study in patients with tetralogy of Fallot.

BACKGROUND: Voltage criteria for ventricular mapping have been obtained from small series of patients and prioritizing high specificity. OBJECTIVE: The purpose of this study was to analyse the potential influence of contact force (CF) on voltage mapping and to define voltage cutoff values for right ventricular (RV) scar using the tetralogy of Fallot as a model of transmural RV scar and magnetic resonance imaging (MRI) as reference. METHODS: Fourteen patients (age 32.6 ± 14.3 years; 5 female) with repaired tetralogy of Fallot underwent high-resolution cardiac MRI (1.25 × 1.25 × 2.5 mm). Scar, defined as pixels with intensity >50% maximum, was mapped over the RV geometry and merged within the CARTO system to RV endocardial voltage maps acquired using a 3.5-mm ablation catheter with CF technology (SmartTouch, Biosense Webster). RESULTS: In total, 2446 points were analyzed, 915 within scars and 1531 in healthy tissue according to MRI. CF correlated to unipolar (ρ = 0.186; P <.001) and bipolar voltage in healthy tissue (ρ = 0.245; P <.001) and in scar tissue. Receiver operating characteristic curve analysis excluding points with very low CF (<5g) identified optimal voltage cutoffs of 5.19 mV for unipolar voltage and 1.76 mV for bipolar voltage, yielding sensitivity/specificity of 0.89/0.85 and 0.9/0.9, respectively. CONCLUSION: CF is an important factor to be taken into account for voltage mapping. If good CF is applied, unipolar and bipolar voltage cutoffs of 5.19 mV and 1.76 mV are optimal for identifying RV scar on endocardial mapping with the SmartTouch catheter. Data on the diagnostic accuracy of different voltage cutoff values are provided.

Left atrial appendage patency and device-related thrombus after percutaneous left atrial appendage occlusion: a computed tomography study.

Aims: Transoesophageal echocardiography studies have reported frequent peri-device leaks and device-related thrombi (DRT) after percutaneous left atrial appendage (LAA) occlusion. We assessed the prevalence, characteristics and correlates of leaks and DRT on cardiac computed tomography (CT) after LAA occlusion. Methods and results: Consecutive patients underwent cardiac CT before LAA occlusion to assess left atrial (LA) volume, LAA shape, and landing zone diameter. Follow-up CT was performed after >3 months to assess device implantation criteria, device leaks and DRT. CT findings were related to patient and device characteristics, as well as to outcome during follow-up. One-hundred and seventeen patients (age 74 ± 9, 37% women, CHA2DS2VASc 4.4 ± 1.3, and HASBLED 3.5 ± 1.0) were implanted with Amplatzer cardiac plug (ACP)/Amulet (71%) or Watchman (29%). LAA patency was detected in 44% on arterial phase CT images and 69% on venous phase images. The most common leak location was postero-inferior. LAA patency related to LA dilatation, left ventricular ejection fraction impairment, non-chicken wing LAA shape, large landing zone diameter, incomplete device lobe thrombosis, and disc/lobe misalignment in patients with ACP/Amulet. DRT were detected in 19 (16%), most being laminated and of antero-superior location. DRT did not relate to clinical or imaging characteristics nor to implantation criteria, but to total thrombosis of device lobe. Over a mean 13 months follow-up, stroke/transient ischaemic attack occurred in eight patients, unrelated to DRT or LAA patency. Conclusion: LAA patency on CT is common after LAA occlusion, particularly on venous phase images. Leaks relate to LA/LAA size at baseline, and device malposition and incomplete thrombosis at follow-up. DRT is also quite common but poorly predicted by patient and device-related factors.

High-resolution three-dimensional late gadolinium-enhanced cardiac magnetic resonance imaging to identify the underlying substrate of ventricular arrhythmia.

Aims: Cardiac magnetic resonance (CMR) is recommended as a second-line method to diagnose ventricular arrhythmia (VA) substrate. We assessed the diagnostic yield of CMR including high-resolution late gadolinium-enhanced (LGE) imaging. Methods and results: Consecutive patients with sustained ventricular tachycardia (VT), non-sustained VT (NSVT), or ventricular fibrillation/aborted sudden death (VF/SCD) underwent a non-CMR diagnostic workup according to current guidelines, and CMR including LGE imaging with both a conventional breath-held and a free-breathing method enabling higher spatial resolution (HR-LGE). The diagnostic yield of CMR was compared with the non-CMR workup, including the incremental value of HR-LGE. A total of 157 patients were enrolled [age 54 ± 17 years; 75% males; 88 (56%) sustained VT, 52 (33%) NSVT, 17 (11%) VF/SCD]. Of these, 112 (71%) patients had no history of structural heart disease (SHD). All patients underwent electrocardiography and echocardiography, 72% coronary angiography, and 51% exercise testing. Pre-CMR diagnoses were 84 (54%) no SHD, 39 (25%) ischaemic cardiomyopathy (ICM), 11 (7%) non-ischaemic cardiomyopathy (NICM), 3 (2%) arrhythmogenic right ventricular cardiomyopathy (ARVC), 2 (1%) hypertrophic cardiomyopathy (HCM), and 18 (11%) other. CMR modified these diagnoses in 48 patients (31% of all and 43% of those with no SHD history). New diagnoses were 9 ICM, 28 NICM, 8 ARVC, 1 HCM, and 2 other. CMR modified therapy in 19 (12%) patients. In patients with no SHD after non-CMR tests, SHD was found in 32 of 84 (38%) patients. Eighteen of these patients showed positive HR-LGE and negative conventional LGE. Thus, HR-LGE significantly increased the CMR detection of SHD (17-38%, P < 0.001). Conclusion: CMR including HR-LGE imaging has high diagnostic value in patients with VAs. This has major prognostic and therapeutic implications, particularly in patients with negative pre-CMR workup.

Microparticles and microRNAs: new players in the complex field of coagulation.

Atherosclerosis is a complex process that begins with endothelial dysfunction, and continues with several inflammatory processes leading, eventually, to plaque rupture and formation of arterial thrombus. Increased platelet reactivity and classical coagulation pathways are not the only players of the whole thrombotic process: microparticles (MPs), irregularly shaped small vesicles released from the plasma membrane after cell activation, apoptosis, or exposure to shear stress have been demonstrated to be involved in such a process. MicroRNAs (MiRs), small-non-coding single-strand RNAs acting as post-transcriptional modulator of target gene expression are expressed in the large majority of eukaryotes. MiRs are implicated in several phenomena: control of metabolism, control of cell-differentiation, control of cell-proliferation and control of cell-apoptosis, therefore contributing to physiologic and pathogenic processes in hematologic, genetic, infective and cardiac diseases. Microparticles operate as a delivery system of MiRs, playing an active and important role in processes such as coagulation and thrombosis. These novel findings also suggest MPs and, in particular MIRs, as possible and promising therapeutic targets.

Immediate evidence of the benefit of distal protection in vein graft intervention.

Percutaneous intervention carries a higher risk of distal embolization and fatal outcome in saphenous vein grafts (SVG) than in native coronary vessels. Most of these adverse clinical events, predominantly myocardial infarction and reduced antegrade flow (no reflow phenomenon), are due to distal embolization of atherothrombotic debris and distal microvascular occlusion. For this reason, in current interventional practice, the use of distal protection devices is mandatory. Our case report provides direct and dramatic evidence of the usefulness of a low-profile filter device in the setting of massively thrombotic SVG.

Clopidogrel-induced neutropenia after coronary stenting: is cilostazol a good alternative?

Dual antiplatelet therapy with aspirin plus thienopyridines has become the standard treatment of patients undergoing coronary stenting. Clopidogrel has mostly replaced the use of ticlopidine due to its more favourable adverse event profile. However, also the use of clopidogrel is not without side effects. Clopidogrel major adverse events are represented by marrow suppression, manifesting with aplastic anaemia, thrombocytopenia and neutropenia. When clopidogrel toxicity occurs, there are few and unsubstantiated alternative treatments and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced bone marrow toxicity manifesting with severe neutropenia in a patient treated with multiple coronary stents and provide suggestions for an alternative treatment.

Left anterior descending artery percutaneous coronary intervention from the right radial access via the left internal mammary artery: a case report.

BACKGROUND: Trans-radial access in coronary intervention has gained popularity as it grants advantages in patients with higher risk of haemorrhage, especially those with non-cardiac conditions and those treated with oral anticoagulant therapy. CASE REPORT: We report a case of percutaneous coronary intervention (PCI) of the left anterior descending (LAD) artery distal to left internal mammary artery (LIMA) anastomosis from the usually contraindicated right radial approach, in an actively bleeding patient affected by gastric cancer and chronic atrial fibrillation, and with no other available low-risk route. CONCLUSION: LAD trans-LIMA PCI via right radial access can be attempted in selected cases with suitable anatomy.