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Truncating variants in titin (TTNtv) are the most prevalent genetic etiology of dilated cardiomyopathy (DCM). Although TTNtv has been associated with atrial fibrillation, it remains unknown whether and how left atrial (LA) function differs between patients with DCM with and without TTNtv. We aimed to determine and compare LA function in patients with DCM with and without TTNtv and to evaluate whether and how left ventricular (LV) function affects the LA using computational modeling. Patients with DCM from the Maastricht DCM registry that underwent genetic testing and cardiovascular magnetic resonance (CMR) were included in the current study. Subsequent computational modeling (CircAdapt model) was performed to identify potential LV and LA myocardial hemodynamic substrates. In total, 377 patients with DCM (n = 42 with TTNtv, n = 335 without a genetic variant) were included (median age 55 years, interquartile range [IQR] 46–62 years, 62% men). Patients with TTNtv had a larger LA volume and decreased LA strain compared with patients without a genetic variant (LA volume index 60 mLm−2 [IQR 49–83] vs 51 mLm−2 [IQR 42–64]; LA reservoir strain 24% [IQR 10–29] vs 28% [IQR 20–34]; LA booster strain 9% [IQR 4–14] vs 14% [IQR 10–17], respectively; all P <.01). Computational modeling suggests that while the observed LV dysfunction partially explains the observed LA dysfunction in the patients with TTNtv, both intrinsic LV and LA dysfunction are present in patients with and without a TTNtv. Patients with DCM with TTNtv have more severe LA dysfunction compared with patients without a genetic variant. Insights from computational modeling suggest that both intrinsic LV and LA dysfunction are present in patients with DCM with and without TTNtv. Higher LV and LA volumes on CMR are observed in patients with TTNtv with DCM compared with those without a TTNtv, accompanied by lower LA strain values. Simulating the observed LV values using computational modeling does not provide the observed LA values, indicating that intrinsic LA dysfunction contributes to the observed LA myopathy in addition to the well-known LV myopathy. CMR = cardiac magnetic resonance; LA = left atrial; LV = left ventricular; TTNtv = truncating variants in titin. [Display omitted] [ABSTRACT FROM AUTHOR]

The left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. The goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM. Patients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize. A total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro–B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05). LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]

This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF). DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection. A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >−21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization. A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006). Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death. [ABSTRACT FROM AUTHOR]

Background: Echocardiographic determination of ejection fraction (EF) by manual tracing of endocardial borders is time consuming and operator dependent, whereas visual assessment is inherently subjective. Objectives: This study tested the hypothesis that a novel, fully automated software using machine learning-enabled image analysis will provide rapid, reproducible measurements of left ventricular volumes and EF, as well as average biplane longitudinal strain (LS). Methods: For a total of 255 patients in sinus rhythm, apical 4- and 2-chamber views were collected from 4 centers that assessed EF using both visual estimation and manual tracing (biplane Simpson's method). In addition, datasets were saved in a centralized database, and machine learning-enabled software (AutoLV, TomTec-Arena 1.2, TomTec Imaging Systems, Unterschleissheim, Germany) was applied for fully automated EF and LS measurements. A reference center reanalyzed all datasets (by visual estimation and manual tracking), along with manual LS determinations. Results: AutoLV measurements were feasible in 98% of studies, and the average analysis time was 8 ± 1 s/patient. Interclass correlation coefficients and Bland-Altman analysis revealed good agreements among automated EF, local center manual tracking, and reference center manual tracking, but not for visual EF assessments. Similarly, automated and manual LS measurements obtained at the reference center showed good agreement. Intraobserver variability was higher for visual EF than for manual EF or manual LS, whereas interobserver variability was higher for both visual and manual EF, but not different for LS. Automated EF and LS had no variability. Conclusions: Fully automated analysis of echocardiography images provides rapid and reproducible assessment of left ventricular EF and LS. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate whether left ventricular (LV) lead position in cardiac resynchronization therapy (CRT) can be determined by myocardial deformation imaging during LV pacing and to compare imaging techniques for analysis of LV lead position. Background: LV lead position has a significant impact on effectiveness of CRT, but clinically applicable methods to determine LV lead position are less defined. Methods: In 56 patients (53 ± 5 years, 34 men) undergoing CRT, fluoroscopy and 2 myocardial deformation imaging–based approaches were applied to determine the LV lead position. Myocardial deformation imaging–based techniques were used to determine 1) the segment with maximal temporal difference of peak circumferential strain before and while on biventricular CRT; and 2) the segment with earliest peak systolic circumferential strain during pure LV pacing. Twelve-month echocardiography was performed to determine LV remodeling and improvement in function. Optimal LV lead position was defined as concordance or immediate neighboring of the determined LV lead position to the segment with latest systolic strain prior to CRT. Results: LV lead position determined during LV pacing correlated to the position determined by fluoroscopy (kappa = 0.761). Patients with optimal LV lead position had greater improvement in LV ejection fraction and decrease in end-diastolic volume than those with nonoptimal LV lead position (12 ± 4% vs. 7 ± 3%, p < 0.001, and 28 ± 13 ml vs. 14 ± 8 ml, p < 0.001, respectively). Determination of the LV lead position based on myocardial deformation imaging during LV pacing showed greater discriminatory power for improvement of ejection fraction (difference optimal vs. nonoptimal lead position group: 4.64 ± 1.01 ml; p < 0.001) than deformation imaging with biventricular pacing (3.03 ± 1.08 ml; p = 0.007) and fluoroscopy (2.22 ± 1.12 ml; p = 0.053). Conclusions: Myocardial deformation imaging during LV pacing allows determination of the LV lead position in CRT. Improvement in LV function and remodeling as indicators of optimal LV lead position can be best predicted by LV lead position analysis during LV pacing. (Left Ventricular Lead Position in Cardiac Resynchronization Therapy; NCT00748735) [Copyright &y& Elsevier]

Abstract: Background: Cardioversion (CV) success of atrial fibrillation (AF) inversely correlates to the size of the left atrium (LA). Atrial fibrillation and its most important risk factor, congestive heart failure (CHF), both induce atrial structural enlargement and fibrosis. To investigate the effect of AF and CHF on atrial dilatation and fibrosis, and to estimate whether echocardiographically determined atrial size may be used as a marker for atrial fibrosis. Methods: In six dogs, pacemakers were implanted followed by HIS bundle ablation. After 4 weeks of rapid ventricular stimulation (185 bpm) for CHF induction, additional rapid atrial stimulation (500 bpm) was maintained for 7 weeks to induce AF. Serial determinations of echocardiographic atrial size were performed. Seven dogs with sinus rhythm served as histological controls. Postmortem tissue was obtained to determine the degree and composition of atrial fibrosis. Results: While the ejection fraction of the AF/CHF dogs decreased significantly from 57±5% to 19±7% (P<.01), an increased degree of atrial fibrosis was found (right atrium [RA], 4.9±2.0% to 19.9±5.4%; LA, 4.4±1.6% to 22.2±3.2%; P<.01), accompanied by a significant increase of atrial volumes (LA: 21±4 to 44±4 mm3; P<.01; RA: 10±3 to 18±6 mm3; P<.05) and LA diameters (34±4 to 43±2 mm, P<.05). Atrial fibrosis and size significantly correlated. Conclusions: Atrial fibrillation/CHF leads to a significant atrial fibrosis and dilation. The increased echocardiographic size correlates to the degree of atrial fibrosis and may be used as clinical marker for atrial fibrosis. The fibrosis accompanying atrial dilatation may also explain why LA size, as determined by echocardiography, is a strong predictor of CV success. [Copyright &y& Elsevier]

Abstract: Introduction: Increasing duration of ventricular fibrillation (VF) is associated with a higher risk of ineffective resuscitation. In addition, precountershock chest compression can influence defibrillation success. Transesophageal defibrillation may increase defibrillation success because of the proximity of the esophagus to the heart. We evaluated the efficacy of transesophageal defibrillation compared with standard transthoracic defibrillation after long episodes of VF. Methods: Defibrillation success after 10 minutes of untreated VF was evaluated in 12 sheep randomized into 2 groups: (group A) in 6 sheep, up to 3 transthoracic shocks were applied, followed by up to 3 transesophageal shocks (first shock: 150 J, second and third shocks: 200 J). (group B) In 6 sheep, 2 minutes of precountershock chest compression preceded the defibrillation shocks. Truncated biphasic shocks were delivered between a sternal and an apical patch electrode for transthoracic defibrillation and between an esophageal and a cutaneous patch electrode for transesophageal defibrillation. Results: In group A with no precountershock chest compression, external defibrillation failed despite shocks with maximum energy (200 J) in all 6 sheep. Transesophageal defibrillation was successful in 3 sheep (50%). In group B with precountershock chest compression, external defibrillation failed in all 6 sheep. Transesophageal defibrillation was successful with the first shock in all 6 sheep. Conclusions: Transesophageal defibrillation may terminate VF of long duration that is refractory to standard defibrillation. Precountershock chest compression may increase transesophageal defibrillation success. [Copyright &y& Elsevier]

Abstract: Background: Left ventricular lead implantation for cardiac resynchronization therapy (CRT) usually requires a pre- or intraprocedural occlusion contrast venography of the coronary sinus (CS) in order to identify tributaries to the lateral wall. As many patients undergo a preprocedural coronary angiogram, we investigated the diagnostic accuracy of venous phase imaging of the CS in patients prior to CRT implantation. The aim of this study was to assess the quality of venous phase coronary sinus angiography. Methods: In 24 CRT patients retrograde occlusion venography and venous phase coronary sinus angiography obtained during coronary angiography were compared with respect to image quality, vessel diameters and the ability to identify a coronary sinus side branch suitable for left ventricular lead placement. Results: Suitable target vessels for left ventricular lead implantation were identified in all patients irrespective of the method (retrograde occlusion venography or venous phase coronary sinus angiography). There was a high concordance in vessel diameters between venous phase and retrograde angiography. Visibility was superior in retrograde venography. Conclusions: In heart failure patients who are scheduled for coronary angiograms venous phase coronary sinus angiography is a time-saving and easy to perform alternative imaging modality. Radiation exposure and the amount of contrast medium needed is reduced as compared to coronary sinus occlusion angiography. The information obtained thereby may be used to plan subsequent CRT implantation without the need for retrograde coronary sinus angiography. [Copyright &y& Elsevier]

Background: Transesophageal echocardiography (TEE) is routinely used to exclude atrial thrombus prior to cardioversion of atrial fibrillation (AF). Because the TEE probe lies adjacent to the atria, cardioversion using an electrode attached to the TEE probe should allow for immediate low-energy transesophageal cardioversion. Objective: The purpose of this study was to evaluate a cardioversion electrode sheath that can be affixed to conventional TEE probes for simultaneous thrombus exclusion and cardioversion of AF. Methods: A thin electrode was integrated into a latex or polyurethane sheath covering a conventional TEE probe. TEE thrombus exclusion and biphasic transesophageal cardioversion using a step-up protocol were performed during deep sedation. Esophagoscopy was performed immediately after cardioversion and after 1 week. Results: TEE was performed in 27 patients. One patient showed left atrial thrombi. Transesophageal cardioversion was successful in 25 of the remaining 26 patients. Mean atrial cardioversion threshold was 63 +/- 48 J. Transesophageal cardioversion restored sinus rhythm in two patients with unsuccessful transthoracic cardioversion. Transesophageal cardioversion in deep sedation was well tolerated. Esophagoscopy revealed slight mucosal damage in three patients at the site of shock application; two of these patients showed signs of gastroesophageal reflux disease. Mucosal damage unrelated to the site of shock delivery was noted in three patients. Conclusion: Atrial thrombus exclusion and transesophageal cardioversion of AF via a disposable cardioversion sheath offers the opportunity to perform transesophageal cardioversion and TEE thrombus exclusion during one sedation. It may not be suitable for use in patients with gastroesophageal reflux disease. Transesophageal cardioversion may establish sinus rhythm in selected patients refractory to transthoracic cardioversion. [ABSTRACT FROM AUTHOR]

Background: Pre-interventional three-dimensional (3D) reconstruction of the heart by CT or MRI provides important information on cardiac anatomy for electrophysiological interventions. However, updates of 3D-imaging modalities with high soft-tissue contrast are not available during ablation procedures. Objective: We describe the development and first clinical testing of a close to real-time visualization of cardiac anatomy by intracardiac echocardiography (ICE). Methods: An electronic phased-array 5-10 MHz ICE-catheter (AcuNav/Siemens/64 elements) was inserted via a straightened femoral vein sheath (12F) and placed in the right atrium in 5 pigs. A custom-made prototype stepper motor allowed automatic rotation around the longitudinal axis from 90 degrees to 360 degrees in 2-5 degrees steps. For every plane 2D images of a complete cardiac cycle were acquired, triggered by respiration and ECG. The ultrasound images were digitized and 3D-reconstruction was performed by a prototype software. After experimental validation the system was tested in 6 patients during electrophysiological studies. Results: From a single location in the right atrium, 3D-acquisition and reconstruction of both atria and ventricles with good image quality were achieved within 3-5 minutes. Doppler-mode facilitated identification of the great vessels including the pulmonary veins and their entry into the heart. 3D-visualization of ablation catheters was also possible in all patients and pigs. Conclusion: Semi-automated 3D intracardiac echocardiography from a single site inside the right atrium provides the electrophysiologist with a detailed image of both atria and ventricles with repeated updates of the cardiac anatomy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Because of the proximity of the esophagus to the heart, transesophageal defibrillation might increase defibrillation success. We assessed the defibrillation threshold (DFT) of transesophageal defibrillation compared with standard transthoracic defibrillation. Methods: Defibrillation success and DFTs were determined in 22 female pigs with high (68 ± 4 kg, n = 12) or low body weight (39 ± 1 kg, n = 10). After induction of ventricular fibrillation, biphasic shocks were delivered between two cutaneous patch electrodes (sternal and apical position) or between an esophageal and two cutaneous patch electrodes in a sternal and apical position. The esophageal electrode was integrated into a latex sheath covering a standard transesophageal echocardiography probe. Results: In 5 of 12 pigs with high body weight, external defibrillation failed despite 3 consecutive 200-J shocks, whereas subsequent transesophageal defibrillation was successful with the first shock. In the remaining 7 pigs, a more than 50% reduction in DFT was obtained with transesophageal defibrillation compared with standard biphasic external defibrillation (67 ± 27 vs 164 ± 23 J, P < .001). Pigs with lower body weight were successfully defibrillated by both transthoracic and transesophageal shocks. The DFT in pigs with low body weight was significantly lower using transesophageal defibrillation compared with transthoracic shocks (65 ± 15 vs 99 ± 38 J, P < .05). Conclusions: In this animal model, nonresponders to standard external defibrillation could successfully be defibrillated via an esophageal-cutaneous electrode configuration. Overall, an almost 50% DFT reduction was achieved by transesophageal defibrillation. Transesophageal defibrillation may provide an additional tool for terminating VF, which is refractory to external defibrillation, eg, in patients with very high body weight. [Copyright &y& Elsevier]

Background. There is controversy about the role of decreased resting blood flow as the pathophysiologic correlate of hibernating myocardium. The aim of this study was an absolute quantification of volumetric myocardial blood flow (MBFvol) in dysfunctional myocardium with different viability conditions as defined by fluorine 18 deoxyglucose (FDG) positron emission tomography (PET) while taking into consideration the functional recovery after revascularization. The impact of MBFvol in the diagnosis of functional recovery was also investigated. Methods and Results. Forty-two patients with severe coronary artery disease and dysfunctional myocardium underwent resting oxygen 15 water PET, as well as FDG PET and technetium 99m tetrofosmin single photon emission computed tomography, all attenuation-corrected. Relative FDG and Tc-99m tetrofosmin uptake (normalized to the segment with 100% Tc-99m tetrofosmin uptake), as well as MBFvol (myocardial blood flow multiplied by the water-perfusable tissue fraction to account for the flow to the entire segment volume), were determined in 18 myocardial segments per patient. Viability in dysfunctional segments (estimated by ventriculography) with reduced Tc-99m tetrofosmin uptake of 70% or lower was classified as viable (FDG >70%, mismatch) or nonviable (FDG ≤70%,match). Fifteen patients underwent revascularization and were followed up. Mismatch segments with improved function were classified as hibernating myocardium. Mean MBFvol in viable myocardium was slightly reduced (0.60 ± 0.02 mL · min-1 · mL-1) compared with that in normokinetic myocardium (0.64 ± 0.01 mL · min-1 · mL-1) ( P = .036) and was significantly higher than in nonviable myocardium (0.36 ± 0.01 mL · min-1 · mL-1) ( P < .001). Receiver operating characteristic analysis confirmed an FDG uptake greater than 70% as the optimal threshold to predict functional recovery (diagnostic accuracy [ACC], 76%). MBFvol in hibernating myocardium (0.62 ± 0.04 mL · min-1 · mL-1) was not significantly reduced compared with that in normokinetic myocardium (0.66 ± 0.02 mL · min-1 · mL-1) and was significantly higher than in persistently dysfunctional myocardium (0.51 ± 0.04 mL · min-1 · mL-1) ( P < .05). The ACC of MBFvol greater than 0.40 mL · min-1 · mL-1 as the threshold to predict functional recovery was 61% but did not improve the accuracy of FDG PET by itself. Conclusions. In patients with severe coronary artery disease and dysfunctional myocardium, MBFvol as determined with O–15 water differs significantly between viable and nonviable myocardium as determined by FDG PET and is not significantly reduced in hibernating compared with normokinetic myocardium. Therefore chronically reduced resting blood flow appears unlikely to be the pathophysiologic correlate of the functional state of hibernation. However, MBFvol does not improve the ACC of FDG PET by itself. (J Nucl Cardiol 2003;10:34-45.) [ABSTRACT FROM AUTHOR]

Abstract: Mitral valve prolapse usually has a good prognosis. However, an association between mitral valve prolapse and atrial and ventricular arrhythmias has been described. This case presents a patient who was admitted after cardiac resuscitation due to ventricular fibrillation. A severe mitral valve prolapse was the only pathology found. [Copyright &y& Elsevier]