Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Treatment of Left Ventricular Thrombi-Insights from a Swiss Multicenter Registry.

Current guidelines recommend vitamin K antagonists (VKAs) for the treatment of a left ventricular thrombus (LVT). However, direct oral anticoagulants (DOACs) show superior safety and efficacy compared with VKAs in most thromboembolic disorders. Nevertheless, DOACs remain poorly investigated for the treatment of LVT. To describe the thrombus resolution rate and clinical efficacy of DOACs versus VKAs in patients with LVT, we analyzed consecutive patients with confirmed LVT from a multicenter echocardiography database. Echocardiograms and clinical end points were evaluated independently. The thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen. In total, 101 patients were included (17.8% women, mean age 63.3 ± 13.2 years), 50.5% had recently experienced a myocardial infarction. The mean left ventricular ejection fraction was 36.6 ± 12.2%. DOACs versus VKAs were used in 48 and 53 patients, respectively. The median follow-up was 26.6 (interquartile range 11.8;41.2) months. Among patients receiving VKAs compared with DOACs, the thrombus resolved more rapidly within the first month in those taking VKAs (p = 0.049). No differences were seen between the 2 groups with respect to major bleedings, strokes, and other thromboembolic events. In each group, LVT recurred in 3 of the subjects (a total of 6) after discontinuation of anticoagulation. In conclusion, DOACs appear to be a safe and effective alternative to VKAs for the treatment of LVTs, but the rate of thrombus dissolution within 1 month after initiation of anticoagulation appears to be higher with VKAs. A sufficiently powered randomized trial is required to definitively define the role of DOACs in the treatment of LVT.

Effects of sinus rhythm maintenance on left heart function after electrical cardioversion of atrial fibrillation: implications for tachycardia-induced cardiomyopathy.

BACKGROUND: The role of tachycardia-induced cardiomyopathy vs tachycardia-related short diastolic filling period and reduced atrial contraction in decline of left ventricular ejection fraction (LVEF) in atrial fibrillation (AF) is uncertain. We aimed to characterize left heart changes over time in patients with AF who undergo electrical cardioversion (ECV). METHODS: Consecutive AF patients who were to undergo ECV were enrolled. Patients with unstable or acute heart failure, severe valvular diseases, recent open-heart surgery, major disorders, or an unsuccessful ECV were excluded. Transthoracic echocardiography, including 3-dimensional left atrial and ventricular volume acquisitions, was performed 1-2 hours before and after ECV, and 4-6 weeks later. RESULTS: In 73 patients (77% male, 66 ± 11 years), ECV resulted in an immediate increase in LVEF (from 43 [interquartile range (IQR), 33-50%] to 48 [IQR, 40-53%]; P < 0.0001). Four to 6 weeks after ECV, ejection fraction increased further in patients who remained in sinus rhythm (SR) (n = 55) to 55 (IQR, 44-62)%; P < 0.001. In patients with AF relapse, LVEF returned to values comparable to pre-ECV (n = 18) (44 [IQR, 32-51]%; P = 0.03). The atrial emptying fraction did not significantly change immediately after ECV (n = 69; from 20 [IQR, 13-25]% to 20 [IQR, 15-28]%; P = 0.14). Only patients who remained in SR showed an increase in atrial emptying fraction after 4-6 weeks (n = 51; to 37 [IQR, 26-48]%; P < 0.0001 vs post-ECV). CONCLUSIONS: Immediate improvement in LVEF after ECV explains approximately 50% of total LVEF increase over time. However, in SR, LVEF, and atrial function continuously increase over 4-6 weeks after ECV. This might be attributable to recovery of tachycardia-induced cardiomyopathy.

Twelve-lead electrocardiography in the young: physiologic and pathologic abnormalities.

UNLABELLED: BACKGROUND/ OBJECTIVE: The purpose of the present study was to analyze the prevalence of physiologic and pathologic ECG abnormalities in a cohort of young conscripts that represents the whole young generation of today. METHODS: ECGs of all Swiss citizens who underwent conscription for the army during a 29-month period were analyzed manually. RESULTS: ECGs of 43,401 conscripts (mean age 19.2 ± 1.1 years) were analyzed; 158 conscripts were female. Incomplete right bundle branch block was found in 5870 (13.5%) and left anterior fascicular block in 360 (0.83%). First-degree AV block was present in 329 (0.8%) and Mobitz type I (Wenckebach) second-degree AV block in 3 (0.01%). Early repolarization was observed in 1035 (2.4%), T-wave inversion in 39 (0.09%), and minor T-wave changes in 182 (0.42%). Brugada-like abnormalities were observed in 6 (0.01%). None of the conscripts had atrial fibrillation or flutter. CONCLUSION: ECG abnormalities can be found in a relatively large proportion of young individuals. Incomplete right bundle branch block, left fascicular block, and first-degree AV block are the most frequent findings. No conscript presented with atrial fibrillation or flutter.

T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis.

AIMS: The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. METHODS AND RESULTS: Immunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 ± 0.90 ng/mL, n = 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 ± 2.61 ng/mL, n = 63) and patients with chronic coronary artery disease (6.93 ± 1.31 ng/mL, n = 162). In both patient groups there was a significant (P = 0.043) dependency of T-cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T-cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of-function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic-based interactions. CONCLUSION: Our findings reveal a novel mechanism of T-cad-dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction.

Cryoballoon versus radiofrequency catheter ablation of paroxysmal atrial fibrillation: biomarkers of myocardial injury, recurrence rates, and pulmonary vein reconnection patterns.

BACKGROUND: Cryoballoon ablation has emerged as a novel treatment strategy for patients with atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to compare pulmonary vein isolation (PVI) using cryoballoon ablation versus RF ablation with regard to myocardial injury, pulmonary vein (PV) reconnection patterns, and outcome. METHODS: Fifty patients (age 59 ± 9 years, ejection fraction 0.59 ± 0.06, left atrial size 41 ± 5 mm) with paroxysmal AF were studied. Twenty-five patients underwent PVI using a 28-mm cryoballoon. A control group of 25 patients underwent PVI using an open-irrigation RF ablation catheter. Myocardial injury was determined by measuring troponin T (TnT). PV reconnection patterns were studied in case of repeat procedures. RESULTS: Procedure duration was 166 ± 32 minutes in the cryoballoon group versus 197 ± 52 minutes in the RF group (P = .014), with similar ablation times (cryoballoon: 45 minutes [interquartile range 40-52.5 minutes]; RF: 47 minutes [interquartile range 44-65 minutes], P = .17). Postprocedural TnT in the RF group was 1.29 ± 0.41 µg/L versus 0.76 ± 0.55 µg/L in the cryoballoon group (P = .002). In 12 patients who underwent repeat ablation, 74% of PV reconnection sites were inferiorly located in the cryoballoon group compared to 17% in the RF group (P = .0004). With 1.2 ± 0.4 and 1.3 ± 0.6 procedures per patient, 88% of patients in the cryoballoon group and 92% in the RF group were in stable sinus rhythm after follow-up of 12 ± 3 months (P = NS). CONCLUSION: Differences in the extent of myocardial injury and patterns of PV reconnection were observed between cryoballoon ablation and RF ablation of paroxysmal AF.

Cryoballoon ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

Cryoballoon ablation has emerged as a novel treatment option for drug-refractory atrial fibrillation (AF). The purpose of this manuscript is to report the initial experience of a Swiss centre performing cryoballoon ablation, and to provide a critical review of the literature. Fourteen patients (age 59 +/- 10 years, LVEF 57 +/- 5%, left atrial size 41 +/- 3 mm) with paroxysmal AF were studied. After transseptal puncture, a 28 mm cryoballoon catheter was inserted into the left atrium. After balloon positioning at the antrum of each pulmonary vein (PV), cryoballoon ablation was performed (5 minutes/application). The endpoint of the ablation was pulmonary vein isolation (PVI). Eighty-four percent of all PVs could be isolated with the cryoballoon alone. There was no specific distribution of the PVs requiring additional non-balloon ablation. The mean procedure time was 199 +/- 56 minutes. One patient developed tamponade requiring drainage. No phrenic nerve palsies occurred. After a period of follow-up of 12 +/- 3 months, 10/14 patients (71%) were in sinus rhythm without antiarrhythmic drugs. A review of AF ablation procedures performed at our centre during a one-year period showed that documentation of persistent AF or other arrhythmias were the causes for not using the cryoballoon in 49% of patients because additional linear lesions may be required in these cases. Cryoballoon ablation is an interesting new tool for PVI. The success rate of 71% after a 1-year follow-up is not higher when compared to radiofrequency ablation. Furthermore, data on long-term outcomes are lacking. Randomised comparisons with radiofrequency catheter ablation are needed.

Differences in coronary artery plaques between target and non-target vessels.

OBJECTIVE: We used intravascular ultrasound (IVUS) and virtual histology (VH) to assess the differences of plaque burden and composition between target coronary arteries containing the culprit lesion and non-target coronary arteries. METHODS: Sixty patients referred for acute (n = 19) or elective (n = 41) coronary angiography were included. The target vessel containing the culprit lesion was identified by angiography. A non-target coronary artery was chosen for comparison. The first 4 cm of each vessel were analyzed with IVUS and VH. RESULTS: Total plaque burden was higher in the target vessel compared to the non-target vessel (52.4% vs. 45.9%, a relative difference of 14.2%; p < 0.001). The plaque composition of the target vessel correlated strongly with the plaque composition of the non-target vessel, but the relative amount of necrotic core was significantly higher in the target vessels (21.7% vs 19.2%; p = 0.028), whereas the amount of fibrolipidic material was significantly greater in non-target vessels (10.6% vs. 12.7%; p = 0.035). CONCLUSIONS: We conclude that in patients with relevant coronary artery disease, plaque burden and the amount of necrotic core material are greater in the target vessel. There is a strong correlation of plaque composition between target and non-target coronary arteries.

Intravascular ultrasound-based left main coronary artery assessment: comparison between pullback from left anterior descending and circumflex arteries.

OBJECTIVE: We compared continuous pullback from the left anterior descending artery (LAD) with pullback from the circumflex artery (CX) for the assessment of the left main coronary artery (LMCA) by intravascular ultrasound (IVUS). BACKGROUND: Gray-scale IVUS and virtual histology by IVUS (IVUS-VH) overcome many shortcomings of contrast angiography in diagnostic assessment of the LMCA. IVUS of LCMA can be acquired by continuous pullback from LAD or CX. Equivalence of the two pullback methods has not been investigated. METHODS: LMCA morphology was assessed by IVUS in 65 patients referred for elective or rescue coronary angiography. In each patient IVUS was performed once using pullback from the LAD and once using pullback from the CX. Intraclass correlation coefficients (ICC) were calculated to measure the degree of reliability. RESULTS: The mean age of patients was 60.4 +/- 9.5 years (range 40-84). The IVUS-determined degree of stenosis in the LMCA was a mean of 30% +/- 8% (range 15-52%). The ICC showed excellent reliability (ICC > 0.8) for volume measurements within the plaque (lipid volume, fibrolipidic volume, lipid core volume and calcified volume) and for the measurement of large or averaged diameters (maximal vessel diameter, average vessel diameter, average lumen diameter). The ICC was intermediate (ICC 0.5-0.8) for the measurement of small diameters (minimal vessel diameter, minimal lumen diameter, maximal lumen diameter) and for area calculations (minimal lumen area) based on small diameters. CONCLUSIONS: Overall, there was excellent reliability between IVUS-based LMCA morphology assessment using pullback from either the LAD or the CX.

"Apical ballooning" - what is the cause?

The pathophysiology of takotsubo cardiomyopathy remains enigmatic. Here we attempted to define the link between the coronary arteries and the histopathological involvement of the left ventricle. We observed similarities and discrepancies between patients. All patients experienced stress prior to the event. We found a reduced coronary flow reserve in all patients and signs of hibernating myocardium on biopsy specimen. This raises a strong suspicion of stress-induced endothelial dysfunction with hibernating myocardium in the pathogenesis of this cardiomyopathy.

Effects of the heart-lung machine on melatonin metabolism and mood disturbances.

OBJECTIVE: Cardiothoracic surgery using the heart-lung machine (HLM) provokes a pronounced endocrine-metabolic response leading to circadian rhythm disturbances that affect postoperative morbidity. Focus has been laid on changes in melatonin metabolism. The effects of an extra-corporal artificial circulation have not been adequately addressed. METHODS: Seventeen patients scheduled for open heart surgery using the HLM were compared with 15 patients undergoing major surgery without cardiopulmonary bypass (non-HLM). Late afternoon and night urinary 6-sulfatoxymelatonin were measured at baseline, immediately after the operation and on return to the normal ward. Mood disturbances were assessed at baseline and final sampling times using a standardized questionnaire (arbitrary units). RESULTS: Vital signs were comparable between groups. The difference (delta) between day and night melatonin levels was similar at baseline (HLM group 1.1 ng/ml, non-HLM group 1.4 ng/ml, p=0.25). Immediately following surgery melatonin day-night deltas were unchanged to baseline (HLM 1.0 ng/ml, p=0.67; non-HLM 0.8 ng/ml, p=0.46) but at final sampling normal circadian melatonin profile was abolished (-0.3 ng/ml, p=0.001 and 0.0 ng/ml, p=0.07). However, this effect was not different between the two studied groups (p=0.17). No mood disorders were detectable at baseline (HLM 8.0 vs non-HLM 7.0, p=0.97) and no changes occurred after surgery (7.0 vs 6.5, p=0.33). Overall, patients with a worsening psychological score had pronounced postoperative washout of afternoon-night melatonin delta (p=0.04). CONCLUSIONS: We found no relevant influence of the HLM on perioperative circadian melatonin profiles. Additionally, no alterations in mood assessment before and after surgery were observed. However, worsening of psychological score was associated with a pronounced disruption of the normal circadian melatonin profile.