Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced electrocardiogram analysis.

AIMS: Typical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. The ECG is used as the gatekeeper to cardiac imaging for diagnosis. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM. METHODS AND RESULTS: Advanced ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM [n = 75 overt, n = 32 relative (<15 mm hypertrophy); a subgroup of which underwent cardiovascular magnetic resonance (n = 92)], and comparator subjects (n = 2449), including healthy volunteers (n = 1672), patients with coronary artery disease (n = 372), left ventricular electrical remodelling (n = 108), ischaemic (n = 114) or non-ischaemic cardiomyopathy (n = 57), and asymmetrical septal hypertrophy HCM (n = 126). Multivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy [area under the receiver operating characteristic (AUC) curve (bootstrapped 95% confidence interval) 0.982 (0.965-0.993)]. Linear discriminant analysis also diagnosed ApHCM with high accuracy [AUC 0.989 (0.986-0.991)]. CONCLUSION: Explainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting that future diagnostic and management strategies may incorporate both features.

Global longitudinal strain and plasma biomarkers for prognosis in heart failure complicated by diabetes: a prospective observational study.

BACKGROUND: Heart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes. METHODS: In this prospective, observational study, consecutive patients (n = 315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2), and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation. RESULTS: Compared to those without diabetes (n = 156), the diabetes group (n = 159) had a higher LGE prevalence (76 vs. 60%, p < 0.05), higher T1 (1285±42 vs. 1269±42ms, p < 0.001), and higher ECV (30.5±3.5 vs. 28.8±4.1%, p < 0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2, and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43-3.79], p < 0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02-1.07], p = 0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03-1.21], p = 0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p = 0.02). CONCLUSIONS: Compared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS by CMR is a powerful and independent prognostic marker in HF patients with diabetes.

ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy: The change of the paradigm.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.

Three-dimensional sector-wise golden angle-improved k-space uniformity after electrocardiogram binning.

PURPOSE: To develop and evaluate a 3D sector-wise golden-angle (3D-SWIG) profile ordering scheme for cardiovascular MR cine imaging that maintains high k-space uniformity after electrocardiogram (ECG) binning. METHOD: Cardiovascular MR (CMR) was performed at 1.5 T. A balanced SSFP pulse sequence was implemented with a novel 3D-SWIG radial ordering, where k-space was divided into wedges, and each wedge was acquired in a separate heartbeat. The high uniformity of k-space coverage after physiological binning can be used to perform functional imaging using a very short acquisition. The 3D-SWIG was compared with two commonly used 3D radial trajectories for CMR (i.e., double golden angle and spiral phyllotaxis) in numerical simulations. Free-breathing 3D-SWIG and conventional breath-held 2D cine were compared in patients (n = 17) referred clinically for CMR. Quantitative comparison was performed based on left ventricular segmentation. RESULTS: Numerical simulations showed that 3D-SWIG both required smaller steps between successive readouts and achieved better k-space sampling uniformity after binning than either the double golden angle or spiral phyllotaxis trajectories. In vivo evaluation showed that measurements of left ventricular ejection fraction calculated from a 48 heart-beat free-breathing 3D-SWIG acquisition were highly reproducible and agreed with breath-held 2D-Cartesian cine (mean ± SD difference of -3.1 ± 3.5% points). CONCLUSIONS: The 3D-SWIG acquisition offers a simple solution for highly improved k-space uniformity after physiological binning. The feasibility of the 3D-SWIG method is demonstrated in this study through whole-heart cine imaging during free breathing with an acquisition time of less than 1 min.

Immediate recruitment of dormant coronary collaterals can provide more than half of normal resting perfusion during coronary occlusion in patients with coronary artery disease.

BACKGROUND: Dormant coronary collaterals are highly prevalent and clinically beneficial in cases of coronary occlusion. However, the magnitude of myocardial perfusion provided by immediate coronary collateral recruitment during acute occlusion is unknown. We aimed to quantify collateral myocardial perfusion during balloon occlusion in patients with coronary artery disease (CAD). METHODS: Patients without angiographically visible collaterals undergoing elective percutaneous transluminal coronary angioplasty (PTCA) to a single epicardial vessel underwent two scans with 99mTc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT). All subjects underwent at least three minutes of angiographically verified complete balloon occlusion, at which time an intravenous injection of the radiotracer was administered, followed by SPECT imaging. A second radiotracer injection followed by SPECT imaging was performed 24 h after PTCA. RESULTS: The study included 22 patients (median [interquartile range] age 68 [54-72] years. The perfusion defect extent was 19 [11-38] % of the LV, and the collateral perfusion at rest was 64 [58-67]% of normal. CONCLUSION: This is the first study to describe the magnitude of short-term changes in coronary microvascular collateral perfusion in patients with CAD. On average, despite coronary occlusion and an absence of angiographically visible collateral vessels, collaterals provided more than half of the normal perfusion.

Electrocardiographic parameters associated with pacemaker induced cardiomyopathy.

BACKGROUND: Chronic right ventricular (RV) pacing can induce left ventricular (LV) dyssynchrony and cause pacemaker induced cardiomyopathy (PiCM). Identifying which patients are at risk for PiCM is limited. METHODS: Patients receiving RV-only permanent pacemakers (PPMs) at Duke University Medical Center between 2011 and 2017 who had normal baseline ejection fractions (EFs) were identified. Patients who developed a subsequent decrease in EF, died, or underwent cardiac resynchronization therapy, left ventricular assist device, or heart transplant without a competing cause were considered as the primary endpoint. Pre-PPM and post-PPM electrocardiograms (ECGs) were analyzed to extract scalar measurements including the lead one ratio (LOR) as well as advanced-ECG (A-ECG) features to identify predictors of PiCM. Traditional and penalized Cox regression were used to identify variables predictive of the primary endpoint. RESULTS: Pre-PPM ECGs were evaluated for 404 patients of whom 140 (35%) experienced the primary endpoint. Predictors included female sex (hazard ratio [HR] 1.14), a T' wave in V6 (HR 1.31), a P' wave in aVL (HR 0.88), and estimated glomerular filtration rate (HR 0.88). Post-PPM ECGs were evaluated for 228 patients for whom 94 (41%) experienced the primary endpoint. Predictors included female sex (HR 0.50), age (HR 1.06), and a history of congestive heart failure (HR 1.63). Neither LOR nor A-ECG parameters were strong predictors of the primary endpoint. CONCLUSIONS: Baseline and paced ECG data provide limited insight into which patients are at high risk for developing PiCM.

ISE/ISHNE Expert Consensus Statement on ECG Diagnosis of Left Ventricular Hypertrophy: The Change of the Paradigm. The joint paper of the International Society of Electrocardiology and the International Society for Holter Monitoring and Noninvasive Electrocardiology.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria, i.e. the increased QRS complex amplitude in defined leads. The classical ECG diagnostic paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces. These increased forces are reflected in the augmented QRS amplitude in the corresponding leads. However, the clinical observations document increased QRS amplitude only in the minority of patients with LVH. The low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm.

Looking for the Right Diagnosis? Cardiovascular Magnetic Resonance Imaging Can Help Differentiate Cardiomyopathies.

Differentiating cardiomyopathies is a common clinical quandary in cardiology. Getting the right diagnosis is important for guiding patient management and providing prognosis. Incorrect or uncertain diagnoses can lead to further unnecessary investigations and/or treatment decisions applied inappropriately, which can have consequences for both the patient and health care costs. Cardiovascular magnetic resonance (CMR) imaging offers strength here due to its precision and breadth in assessing cardiac function and tissue characterisation. This review aims to raise awareness among cardiologists and physicians of the important insights provided by CMR-insights that can improve diagnosis and guide management, as well as aid in risk stratification, in different cardiomyopathies.

Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume.

BACKGROUND: Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. METHODS: Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). RESULTS: Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to - 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (- 2 ± 7%). CONCLUSIONS: CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV.

Generalization of three-dimensional golden-angle radial acquisition to reduce eddy current artifacts in bSSFP CMR imaging.

PURPOSE: We propose a novel generalization of the three-dimensional double-golden-angle profile ordering, which allows for whole-heart volumetric imaging with retrospective binning and reduced eddy current artifacts. METHODS: A novel theory bridging the gap between the three-dimensional double golden-angle trajectory, and the two-dimensional tiny-golden-angle trajectory is presented. This enables a class of double golden-angle profile orderings with a smaller angular distance between successive k-space readouts. The novel profile orderings were evaluated through simulations, phantom experiments, and in vivo imaging. Comparisons were made to the original double-golden-angle trajectory. Image uniformity and off-resonance sensitivity were evaluated using phantom measurements, and qualitative image quality was assessed using in vivo images acquired in a healthy volunteer. RESULTS: The proposed theory successfully reduced the angular step while maintaining image uniformity after binning. Simulations revealed a slow degradation with decreasing angular steps and an increasing number of physiological bins. The phantom images showed a definite improvement in image uniformity and increased robustness to off-resonance, and in vivo imaging corroborated those findings. CONCLUSION: Reducing the angular step in cardio-respiratory-binned golden-angle imaging shows potential for overcoming eddy current-induced image artifacts associated with 3D golden-angle radial imaging.

Predicting peri-operative troponin elevation by advanced electrocardiography.

BACKGROUND: Peri-operative mortality remains a global problem and an improved pre-operative risk assessment identifying those at highest risk for peri-operative myocardial injury might improve postsurgical outcomes. AIMS: To determine whether pre-operative measures of advanced electrocardiography (A-ECG) could predict elevated serum troponin T (TnT) in patients undergoing elective, major non-cardiac surgery. MATERIAL AND METHODS: This observational cohort study included 257 surgical patients who underwent elective major non-cardiac surgery between the years 2012-2013 and 2015-2016 at Karolinska University Hospital. All selected patients were ≥ 18 years of age [median age 70 (63-75) years], had a pre-operative digital 12­lead ECG < 6 months prior to the procedure and a postoperative high-sensitivity cardiac TnT (hs-cTnT) sample. A-ECG confounders including atrial fibrillation or flutter, abundant premature atrial or ventricular contractions, bundle branch blocks, QRS duration >110 ms, heart rate > 100 beats/min and paced rhythms were excluded. Previously validated A-ECG diagnostic scores that detect cardiovascular pathologies were calculated and compared in patients with and without peri-operative myocardial injury, defined as hs-cTnT >14 ng l-1. RESULTS: Pre-operative left ventricular systolic dysfunction by A-ECG was more probable in patients with than without peri-operative myocardial injury (p = 0.03). CONCLUSIONS: While a pre-operative A-ECG score for LVSD was able to differentiate between patients with versus without elevated peri-operative TnT levels, it did not add any further utility to standard clinical parameters for predicting troponin-related events in the studied population.

Sector-wise golden-angle phase contrast with high temporal resolution for evaluation of left ventricular diastolic dysfunction.

PURPOSE: To develop a high temporal resolution phase-contrast pulse sequence for evaluation of diastolic filling patterns, and to evaluate it in comparison to transthoracic echocardiography. METHODS: A phase-contrast velocity-encoded gradient-echo pulse sequence was implemented with a sector-wise golden-angle radial ordering. Acquisitions were optimized for myocardial tissue (TE/TR: 4.4/6.8 ms, flip angle: 8º, velocity encoding: 30 cm/s) and transmitral flow (TE/TR: 4.0/6.6 ms, flip angle: 20º, velocity encoding: 150 cm/s). Shared velocity encoding was combined with a sliding-window reconstruction that enabled up to 250 frames per cardiac cycle. Transmitral and myocardial velocities were measured in 35 patients. Echocardiographic velocities were obtained with pulsed-wave Doppler using standard methods. RESULTS: Myocardial velocity showed a low difference and good correlation between MRI and Doppler (mean ± 95% limits of agreement 0.9 ± 3.7 cm/s, R2 = 0.63). Transmitral velocity was underestimated by MRI (P < .05) with a difference of -11 ± 28 cm/s (R2 = 0.45). The early-to-late ratio correlated well (R2 = 0.66) with a minimal difference (0.03 ± 0.6). Analysis of interobserver and intra-observer variability showed excellent agreement for all measurements. CONCLUSIONS: The proposed method enables the acquisition of phase-contrast images during a single breath-hold with a sufficiently high temporal resolution to match transthoracic echocardiography, which opens the possibility for many clinically relevant variables to be assessed by MRI.

Lead one ratio in left bundle branch block predicts poor cardiac resynchronization therapy response.

BACKGROUND: A low electrocardiogram (ECG) lead one ratio (LOR) of the maximum positive/negative QRS amplitudes is associated with lower left ventricular ejection fraction (LVEF) and worse outcomes in left bundle branch block (LBBB); however, the impact of LOR on cardiac resynchronization therapy (CRT) outcomes is unknown. We compared clinical outcomes and echocardiographic changes after CRT implantation by LOR. METHODS: Consecutive CRT-defibrillator recipients with LBBB implanted between 2006 and 2015 at Duke University Medical Center were included (N = 496). Time to heart transplant, left ventricular assist device (LVAD) implantation, or death was compared among patients with LOR <12 vs ≥12 using Cox-proportional hazard models. Changes in LVEF and LV volumes after CRT were compared by LOR. RESULTS: Baseline ECG LOR <12 was associated with an adjusted hazard ratio (HR) of 1.69 (95% CI: 1.12-2.40, P = .01) for heart transplant, LVAD, or death. Patients with LOR <12 had less reduction of LV end diastolic volume (ΔLVEDV -4 ± 21 vs -13 ± 23%, P = .04) and LV end systolic volume (ΔLVESV -9 ± 27 vs -22 ± 26%, P = .03) after CRT. In patients with QRS duration (QRSd) ≥150 ms, LOR <12 was associated with an adjusted HR of 2.01 (95% CI 1.21-3.35, P = .008) for heart transplant, LVAD, or death, compared with LOR ≥12. CONCLUSIONS: Baseline ECG LOR <12 portends worse outcomes after CRT implantation in patients with LBBB, specifically among those with QRSd ≥150 ms. This ECG ratio may identify patients with a class I indication for CRT implantation at high risk for poor postimplantation outcomes.

Diastolic function and its association with diabetes, hypertension and age in an outpatient population with normal stress echocardiography findings.

BACKGROUND: Diastolic dysfunction can be caused by hypertension or diabetes mellitus, and it is also often found with increasing age. In a given patient, the cause of diastolic dysfunction is therefore not always obvious. We sought to study the interplay of these risk factors for diastolic dysfunction in an outpatient population with a low likelihood of ischemic heart disease. METHODS: Consecutive patients referred for stress echocardiography were included retrospectively. Exclusion criteria included pathological stress response, atrial arrhythmia, left ventricular ejection fraction < 55%, and more than mild valvular disease. Standard diastolic parameters were recorded in all patients. In a subset of patients, mechanistic analysis of early filling was performed using the parameterized diastolic filling (PDF) method. RESULTS: We included 726 patients (median [interquartile range] age 56 (44-65) years, 57% male). The prevalence of diabetes and hypertension was 43 and 49%, respectively. In multiple linear regression modeling, the presence of diabetes, hypertension, sex and increasing age explained a moderate amount of the variance in e' velocities, E/A ratio and E/e' (R2 = 0.31-0.48, p < 0.001), and a low amount of the variance in left atrial volume index (LAVI) and the PDF parameters (n = 446, R2 = 0.05-0.17, p < 0.001). Sex was only related to LAVI and E/e' for the conventional parameters (beta - 0.94, p = 0.04, and beta - 0.91, p < 0.001, respectively). CONCLUSIONS: Diabetes, hypertension, increasing age, and to a lesser extent sex, explain a moderate amount of the variance in conventional diastolic parameters related to myocardial tissue velocities and E/A ratio in a healthy outpatient population. The effect of these risk factors was substantially less pronounced on left atrial volume index and the PDF parameters.

Mechanistic validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging Guidelines for the assessment of diastolic dysfunction in heart failure with reduced ejection fraction.

BACKGROUND: The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling. AIMS: We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD. METHODS: Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism. RESULTS: Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s2, p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15-24] vs 11 [8-14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = - 0.39, p = 0.005). CONCLUSIONS: Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.

Cardiovascular magnetic resonance 4D flow analysis has a higher diagnostic yield than Doppler echocardiography for detecting increased pulmonary artery pressure.

BACKGROUND: Pulmonary hypertension is definitively diagnosed by the measurement of mean pulmonary artery (PA) pressure (mPAP) using right heart catheterization. Cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow analysis can estimate mPAP from blood flow vortex duration in the PA, with excellent results. Moreover, the peak systolic tricuspid regurgitation (TR) pressure gradient (TRPG) measured by Doppler echocardiography is commonly used in clinical routine to estimate systolic PA pressure. This study aimed to compare CMR and echocardiography with regards to quantitative and categorical agreement, and diagnostic yield for detecting increased PA pressure. METHODS: Consecutive clinically referred patients (n = 60, median [interquartile range] age 60 [48-68] years, 33% female) underwent echocardiography and CMR at 1.5 T (n = 43) or 3 T (n = 17). PA vortex duration was used to estimate mPAP using a commercially available time-resolved multiple 2D slice phase contrast three-directional velocity encoded sequence covering the main PA. Transthoracic Doppler echocardiography was performed to measure TR and derive TRPG. Diagnostic yield was defined as the fraction of cases in which CMR or echocardiography detected an increased PA pressure, defined as vortex duration ≥15% of the cardiac cycle (mPAP ≥25 mmHg) or TR velocity > 2.8 m/s (TRPG > 31 mmHg). RESULTS: Both CMR and echocardiography showed normal PA pressure in 39/60 (65%) patients and increased PA pressure in 9/60 (15%) patients, overall agreement in 48/60 (80%) patients, kappa 0.49 (95% confidence interval 0.27-0.71). CMR had a higher diagnostic yield for detecting increased PA pressure compared to echocardiography (21/60 (35%) vs 9/60 (15%), p < 0.001). In cases with both an observable PA vortex and measurable TR velocity (34/60, 56%), TRPG was correlated with mPAP (R2 = 0.65, p < 0.001). CONCLUSIONS: There is good quantitative and fair categorical agreement between estimated mPAP from CMR and TRPG from echocardiography. CMR has higher diagnostic yield for detecting increased PA pressure compared to echocardiography, potentially due to a lower sensitivity of echocardiography in detecting increased PA pressure compared to CMR, related to limitations in the ability to adequately visualize and measure the TR jet by echocardiography. Future comparison between echocardiography, CMR and invasive measurements are justified to definitively confirm these findings.

Substantial prevalence of subclinical cardiovascular diseases in patients with hemophilia A evaluated by advanced electrocardiography.

BACKGROUND: Patients with hemophilia A (PWHA) have reportedly lower mortality due to cardiovascular disease (CVD) compared to the general population. AIM: To evaluate signs of CVD in asymptomatic PWHA using advanced electrocardiography (A-ECG). METHODS: PWHA (n = 29, median [interquartile range] age 57 [47-70] years) and age-matched male controls (n = 29, 59 [48-68] years) were evaluated. Digital resting 12­lead ECGs were retrospectively analysed using both conventional and A-ECG techniques including derived vectorcardiography and waveform complexity. Previously validated multivariate A-ECG scores designed to detect: 1) cardiac disease in general, 2) left ventricular systolic dysfunction (LVSD), 3) coronary artery disease or coronary microvascular disease (CAD/CMVD), or 4) left ventricular hypertrophy defined as left ventricular electrical remodelling (LVH/LVER), were quantified and compared between PWHA and controls. RESULTS: Compared to controls, PWHA had a higher probability of having cardiac disease (median [interquartile range] 84.6 [32.5-99.5] vs. 0.6 [0.2-8.2]%), LVSD (4.1 [1.3-12.9] vs. 0.9 [0.5-3.2]%), CAD/CMVD (84.3 [35.6-96.6] vs. 6.7 [0.8-24.4]%), and LVH/LVER (17 [5/29] vs. 0 [0/29]%). Compared to patients with non-severe HA (n = 20), patients with severe HA (n = 9) showed a non-significant trend towards lower probability of cardiac disease, CAD/CMVD, LVSD and LVH/LVER. CONCLUSION: In PWHA, A-ECG exhibits changes more indicative of overt or subclinical CVD compared to controls, and there is a tendency for lower scores for CVD in patients with severe compared to non-severe HA. These results suggest that PWHA ≥ 40 years could be at higher risk for CVD than age-matched controls and that A-ECG could potentially be used for early detection.

The electrical determinants of increased wall thickness and mass in left ventricular hypertrophy.

INTRODUCTION: Left ventricular hypertrophy (LVH), defined as an increased left ventricular mass (LVM), can manifest as increased wall thickness, ventricular dilatation, or both. Existing LVH criteria from the electrocardiogram (ECG) have poor sensitivity. However, it is unknown whether changes in wall thickness and mass, respectively, can be separately detected by the ECG. METHODS: Patients undergoing cardiovascular magnetic resonance and resting 12-lead ECG were included. Exclusion criteria were clinical confounders that might influence the ECG, including myocardial scar. Advanced ECG (A-ECG) analysis included conventional ECG measures and amplitudes, derived vectorcardiographic and polarcardiographic measures, and singular value decomposition of waveform complexity. A-ECG scores for 1) increased LVM index (LVMI), and 2) increased global wall thickness index (GTI) beyond the upper limit of normal in healthy volunteers, respectively, were derived using multivariable logistic regression. The area under the curve (AUC) and its bootstrapped confidence interval (CI) for each score were compared to those of conventional ECG-LVH criteria including Cornell voltage, Cornell product, and Sokolow-Lyon voltage criteria. RESULTS: Out of 485 patients (median [interquartile range] age 51 [38-61] years, 54% female), 51 (11%) had increased LVMI and 65 (13%) had increased GTI. The A-ECG scores for increased LVMI (AUC [95% CI] 0.84 [0.78-0.90]), and increased GTI (0.80 [0.74-0.85]) differed, and had a higher AUC than the conventional ECG-LVH criteria (p < 0.001 for all). CONCLUSIONS: Increased LVMI differed from increased GTI in its electrocardiographic manifestation by A-ECG. New A-ECG scores outperform conventional ECG criteria for LVH in determining increased LVMI and GTI, respectively.

Cardiovascular Magnetic Resonance Imaging of Inherited Heart Conditions.

Imaging modalities are central to diagnosis and prognostication of confirmed or suspected inherited cardiomyopathies. The availability and use of cardiovascular magnetic resonance imaging (CMR) to supplement traditional modalities has increased substantially and has several advantages over traditional imaging techniques. CMR is unique in its ability to easily acquire images in any plane. Moreover, advances in CMR sequences have begun to enable characterisation of the myocardium without the need for invasive biopsy and has provided a major step forward in the understanding of inherited heart disease pathology and genotype-phenotype interactions. This review summarises the current role of CMR in inherited cardiomyopathies depending on their genotype and phenotype status, using arrhythmogenic right ventricular dysplasia/cardiomyopathy and hypertrophic cardiomyopathy as prototypical examples.

Low lead one ratio predicts clinical outcomes in left bundle branch block.

INTRODUCTION: We evaluated the association between a novel electrocardiographic (ECG) marker of late, rightward electrocardiographic forces (termed the lead one ratio [LOR]), and left ventricular ejection fraction (LVEF), myocardial scar, and clinical outcomes in patients with left bundle branch block (LBBB). METHODS AND RESULTS: LOR was calculated in patients with LBBB from a derivation cohort (n = 240) and receiver operator characteristic curves identified optimal threshold values for predicting myocardial scar and LVEF less than 35%. An independent validation cohort of patients with LBBB (n = 196) was used to test the association of LOR with the myocardial scar, LVEF, and the likelihood of death, heart transplant or left ventricular assist device (LVAD) implantation. The optimal thresholds in the derivation cohort were LOR less than 13.7 for identification of scar (sensitivity 55%, specificity 80%), and LOR less than 12.1 for LVEF less than 35% (sensitivity 49%, specificity 80%). In the validation cohort, LOR less than 13.7 was not associated with scar size or presence (P > 0.05 for both). LOR less than 12.1 was associated with lower LVEF (30 [20-40] versus 40 [25-55]%; P = 0.002) and predicted LVEF less than 35% in univariable (odds ratio [OR], 2.2 [1.2-4.1]; P = 0.01) and multivariable analysis (OR, 2.2 [1.2-4.3]; P = 0.02). LOR less than 12.1 was associated with scar presence when patients with nonischemic cardiomyopathy were excluded (OR = 7.2 [1.5-33.2]; P = 0.002). LOR less than 12.1 had an adjusted hazard ratio of 1.53 ([1.05-2.21]; P = 0.03) for death, transplant or LVAD implantation. CONCLUSIONS: In conclusion, ECG LOR less than 12.1 predicts reduced-LV systolic function and poorer prognosis in patients with LBBB.