Ahmet Güner

Mechanical dispersion and global longitudinal strain by speckle tracking echocardiography: Predictors of appropriate implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy

In this study, we investigated whether mechanical dispersion which reflects electrical abnormality and other echocardiographic and clinic parameters predict appropriate ICD shock in patients undergone ICD implantation for hypertrophic cardiomyopathy.

Status of the Epicardial Coronary Arteries in Non-ST Elevation Acute Coronary Syndrome in Patients with Mechanical Prosthetic Heart Valves (from the TROIA-ACS Trial)

Coronary thromboembolism (CE) is a rare cause of prosthetic valve derived complications. This study investigates the diagnosis and treatment strategies for non-ST elevation acute coronary syndrome (NSTEACS) in patients with prosthetic heart valves. Forty-eight NSTEACS patients with prosthetic heart valves (mitral:27; aortic:14; mitral+aortic:7) were included in this study. All patients underwent transthoracic and transesophageal echocardiographic examination and coronary angiography. Normal coronary angiographic findings, or visible trombus in one of the coronary arteries, international normalized ratio <2, concomitant prosthetic valve thrombosis (PVT) and absence of multivessel atherosclerotic disease favored CE rather than atherothrombosis. Thrombolytic therapy (TT) with low-dose slow-infusion of tissue type plasminogen activator was used in patients with suspected CE and/or PVT. Coronary angiography demonstrated normal coronary arteries in 26 patients, CE in 16 patients and coronary atherosclerosis in 6 patients. Transesophageal echocardiography revealed obstructive PVT in 9 and nonobstructive PVT in 28 patients whereas 11 patients had normally functioning prostheses. TT was administered to 24 patients with PVT and/or CE. In these patients, TT was successful in 19 patients, partially successful in 4 patients and failed in 1 patient. In conclusion, NSTEACS in patients with prosthetic heart valves is more likely to be associated with PVT derived CE rather than atherosclerosis. TT with low-dose slow infusion of type plasminogen activator has proved its efficacy and safety in patients with CE and/or PVT.

The relationship between heparanase levels, thrombus burden and thromboembolism in patients receiving unfractionated heparin treatment for prosthetic valve thrombosis

INTRODUCTION Procoagulant activity of heparanase has been recently described in several arterial and venous thrombotic disorders. In this study, we aimed to investigate the role of heparanase with regard to thrombus burden, thromboembolism, and treatment success with unfractionated heparin (UFH) in patients with prosthetic valve thrombosis (PVT). METHODS This study enrolled 79 PVT patients who received UFH for PVT and 82 controls. Plasma samples which were collected from patients both at baseline and after the UFH treatment and from controls at baseline only, were tested for heparanase levels by heparanase enzyme-linked immunosorbent assay. RESULTS The PVT group included 18 obstructive and 61 non-obstructive PVT patients who received UFH infusions for a median duration of 15 (7-20) days. The UFH treatment was successful in 37 (46.8%) patients. Baseline heparanase levels were significantly higher in the patient group than in the controls [0.29 (0.21-0.71) vs. 0.25 (0.17-0.33) ng/mL; p = 0.002]. Baseline heparanase levels were significantly higher in obstructive PVT patients. There was a significant increase in heparanase levels after UFH treatment. Post-UFH heparanase levels were higher in patients who experienced treatment failure compared to successfully treated group. Baseline and post-UFH heparanase levels were significantly higher in patients with a thrombus area ≥1 cm2 and with a recent history of thromboembolism. CONCLUSIONS Increased heparanase levels may be one of the esoteric causes for PVT. UFH treatment may trigger an increase in heparanase levels which may affect the treatment success. Increased heparanase levels may be associated with high risk of thromboembolism and increased thrombus burden in PVT patients.

What is the importance of real-time three dimensional transesophageal echocardiography and time in therapeutic range in patients with prosthetic valve thrombosis?

We have recently read with great interest the article reported by Cınar et al. which was published in the last issue of the Journal of Thrombosis and Thrombolysis [1]. We appreciate the authors for their report describing the predictive value of CHA2DS2-VASc with mitral prosthetic valve thrombosis (PVT). On the other hand, we believe that there are several drawbacks that need to be addressed. PVT is the most frequent etiology in patients with prosthetic heart valves with inadequate anticoagulation being the most common underlying cause. Traditionally, vitamin K antagonists (VKAs) have been the mainstay of oral anticoagulant therapy in patients with mechanical heart valves, but the coagulation status should be monitored carefully to avoid major hemorrhagic and ischemic complications. A target international normalized ratio (INR) range of 2.5–4.0 is the current recommendation for patients with mechanical mitral valve replacement. An INR < 2.5 is associated with an increased risk of stroke, and the INR > 4 is associated with an increased risk of major bleeding. The proportion of time in the therapeutic range (TTR) thus provides a useful and reliable measure of the quality of anticoagulation management. Increased TTR is associated with a lower risk of thromboembolic events and bleeding in patients using VKA. This parameter is a major determinant of the efficacy and safety of VKAs, with maximum benefits evident when the TTR is > 70% [2]. Despite the importance of maintaining an acceptable INR, it has been estimated in randomized controlled trials that patients spend more than one-third of their time outside the TTR [3], and the TTR value may be low throughout the patients’ anticoagulation therapy, even though the INR value of the patients at admission is within the acceptable range. For this reason, the lack of evaluation of TTR values of the patients in this study can be seen as a major drawback of this study. Transesophageal echocardiography (TEE) shows usually accurate imaging capabilities and is effective in distinguishing thrombus from pannus and vegetation in patients with mechanical heart valves. It is also a powerful tool in evaluating thrombus size, mobility and location [4]. Real time three-dimensional (RT-3D) TEE has emerged as an important clinical tool in the assessment of PVT more than 10 years. RT-3D TEE has higher spatial resolution, resulting in images with unparalleled anatomic detail when compared with 2D imaging. The detection of nonobstructive PVT can be challenging, particularly when Doppler parameters are within normal limits and clinical findings are subtle. Hence, nonobstructive PVT can be even missed with 2D imaging. Briefly, diagnostic accuracy for detecting PVT was improved after introduction of RT-3D TEE, especially for those on mitral position [5–9]. In conclusion, RT-3D TEE is a complementary imaging tool to 2D TEE in the diagnosis and evaluation of PVT. Furthermore, assessment of TTR in patients with mechanical heart valves under VKA therapy is crucial.

How to perform and manage low-dose and slow/ultra-slow tissue type plasminogen activator infusion regimens in patients with prosthetic valve thrombosis

Over the last two decades, thrombolytic therapy (TT) has become an alternative to surgery as a first-line therapy in patients with thrombosed mechanical valves [1–3]. In TROIA Trial, low dose (25 mg)—slow infusion (6 h) of tissue type plasminogen activator (t-PA) has been found to be an effective and safe regimen in the management of prosthetic valve thrombosis (PVT) [4]. Accelerated and high dose TT regimens were associated with higher complication and mortality rates. 2014 AHA/ACC guideline for the management of patients with valvular heart disease had recommended emergency surgery for patients with left-sided PVT with NYHA Class III-IV (Class 1-B) and large, mobile thrombus(> 0.8 cm2) (Class 2a). Additionaly, TT was reasonable for patients with a thrombosed left-sided prosthetic heart valve, recent onset (< 14 days) of NYHA class I to II symptoms, and a small thrombus (< 0.8 cm2)(Class 2a) [5]. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease now recommends urgent initial treatment with either slow-infusion low-dose TT or emergency surgery for obstructive PVT as first-line treatment strategies with class 1-B indication [6]. Based on our experience regarding TT [3, 4, 7], low dose and ultra-slow infusion (25 mg/25 h) of the TT regimen could be associated with lower complication rates. Recently, the ultra-slow PROMETEE Trial has demonstrated that ultra-slow (25 h) infusion of low dose (25 mg) t-PA without bolus appears to be associated with quite low non-fatal complications and mortality for PVT patients without loss of effectiveness, except for those with NYHA class-IV [8].

A successful catheter ablation of a ventricular fibrillation

Malignant ventricular arrhythmias are challenging to manage, requiring a multidisciplinary approach. The mechanism, which triggers ventricular fibrillation (VF) associated with ventricular extrasystoles has not been clarified yet, however, abolishing ventricular extrasystoles may stop ventricular fibrillation in these patients. By this case presentation, we aimed to present a successful treatment of an electrical storm (ES), which developed after an acute myocardial infarction, by catheter ablation.

Two-dimensional and real-time three-dimensional transesophageal echocardiography-guided thrombolytic therapy for prosthetic valve thrombosis is crucial

We have read with great interest the article by Kathirvel et al which was recently published in the Indian Heart Journal.1 We commend the authors for this important report describing clinical outcomes with tenecteplase (TNK) versus streptokinase thrombolytic therapy (TT) in patients with mitral prosthetic valve thrombosis (PVT). However, at the same time, we would like to highlight some important issues that need to be addressed. First, TNK, a tissue-type plasminogen activator modified by 3 amino acids from alteplase, has the potential to deliver this kind of performance. It has greaterfibrin specificity resulting in no evidence of systemicfibrinogendepletion and resistance to plasminogen activator inhibitor resulting in an initial serum half-life of 20 min and a mean terminal half-life of 100 min, such that it can be conveniently given as a bolus dose (over 5 s) on aweight-adjusted basis. At a dose of 0.5 mg/kg, it has been a standard of care for treating acute STsegment elevation myocardial infarction for 15 years.2 In this study, 12 of the 52 patients with PVT were treated with a 24-h infusion of TNK. According to the manufacturers guidelines, the reconstituted solution should be diluted with sterile water for injection up to a maximal concentration of 5mg TNK perml, and it should be administered as an intravenous single bolus dose over 5 s. The remaining TNK solution, if needed, may be kept in the vial for up to 8 h, but at 2e8 C temperature.3 How were the biological stability and efficiency of reconstituted solution ensured during the 24-h infusion? Second, transthoracic echocardiography (TTE) usually offers inadequate images in making differential diagnosis of thrombus, pannus, and vegetation due to acoustic shadowing and low resolution caused byprostheticmaterial. On the otherhand, transesophageal echocardiography (TEE) with its high resolution may differentiate thrombus from pannus formation and vegetation in patients with PVT. Furthermore, TEE is also of great value with regard to the assessment of mobility, location, and thrombus size; this may assist in the decision regarding surgery, anticoagulation, or TT. In addition, a large residual nonobstructive PVTmay be present in some patients who have experienced successful TT, but it may be missed during TTE study. The detection of nonobstructive PVT can be challenging, particularly when Doppler parameters are within normal limits and clinical findings are subtle. Hence, nonobstructive PVT can even be missed with conventional 2D imaging. In comparison, real-time threedimensional (RT-3D) TEE, over the last decade, has emerged as an important clinical tool in the assessment of PVT. RT-3DTEE has higher spatial resolution, resulting in images with unparalleled anatomic detail when compared with 2D imaging. The diagnostic accuracy for detecting PVThas improved after the introductionof RT-3DTEE, especially for those inmitralposition 4e6. _ It is understood that cinefluoroscopy is effective at detecting abnormality of leaflet mobility, and TTE may provide data regarding changes in valve area and transvalvular gradients. Nevertheless, these imaging tools are complementary to TEE, which offers a fundamental roadmap for TT in patients with PVT. Third, patients with thrombus with size >1 cm2 were included in the trial. It is surprising why these patients were not given TT and were excluded from the trial. _ It is noteworthy that the recent 2017 American Heart Association (AHA)/American College Cardiology (ACC) focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease now recommends urgent initial treatment with either slow-infusion lowdose fibrinolytic therapy or emergency surgery for obstructive PVT as first-line treatment strategies with class 1-B indication.7 In conclusion, during TT in patients with PVT, continuous TEE guidance is crucial. Moreover, RT-3D TEE is a complementary imaging tool to 2D TEE in the diagnosis and evaluation of PVT. Finally, if TEE had been performed on all the patients in the study both before and after TT, the unexpected results would not have been the same.

The PROMETEE protocol is safe and efficient in patients with prosthetic valve thrombosis

To the Editor, We have recently read with great interest the article by Altay et al1 entitled “Successful thrombolysis of a subacute prosthetic valve thrombosis with modified ultraslow thrombolytic therapy’’. The authors reported a case of mitral prosthetic valve thrombosis (PVT), which was successfully treated with the socalled modified ultraslow thrombolytic therapy. Low dose, ultraslow infusion of tissuetype plasminogen activator (tPA) was administered along with continuous intravenous unfractioned heparin (UFH) infusion. We congratulate the authors for achieving a successful outcome in such a highrisk patient. However, we believe the modification of thrombolytic therapy (TT) protocol that the authors proposed requires addressing. Firstly, we totally disagree with the authors about simultaneous heparin infusion during TT administration. The primary goal of reducing the dose of tPA and slowering the infusion rate is to reduce the major bleeding. Other measures that we have proposed to reduce bleeding in the TROIA and the ultraslow PROMETEE Trials were omitting bolus dose and avoiding concomittant anticoagulant use.2,3 Such a strategy resulted in quite low rates of major and minor bleeding (1.7% and 2.5%, respectively, in the ultraslow PROMETEE Trial).3 Secondly, the timing of abandoning the lone tPA protocol and switching to simultaneous heparin plus tPA regime seems arbitrary and unnecessary. The authors have decided to intensify the lytic effect by this strategy after 2 lone tPA sessions. However, we have observed in the PROMETEE trial that, lone TT is efficacious in only 60% of patients after completion of 2 sessions. The success rate increases up to 90% after 8 successive infusions. Indeed, most patients required multiple successive tPA infusions in the trials that we have previously reported.3 Hence, claiming a causal relationship between switching the regime to simultaneous tpa plus heparin and treatment success does not seem reasonable. Moreover, premature efforts to replace the safest regime with aggressive strategies to force lysis may potentially cause unnecessary adverse events. Clinicians should be cautious or preferably avoid premature withdrawal of evidencebased treatments or overuse of regimes beyond the reported safety measures.

ST-segment elevation myocardial infarction possibly caused by thromboembolism from left atrial appendage thrombus after incomplete surgical ligation

Coronary embolism (CE) is the underlying cause of 3% of acute coronary syndromes but is frequently overlooked in the differential diagnoses of acute coronary syndromes. The CE may be direct (left sided from the native or prosthetic heart valve, the left atrium, left atrial appendage or pulmonary venous bed), paradoxical (from the venous circulation through a patent foramen ovale, atrial septal defect, ventricular septal defects, cyanotic congenital heart defects or pulmonary arteriovenous malformations), or iatrogenic (following cardiac interventions. In patients with atrial fibrillation (AF), left atrial appendage (LAA) ligation during mitral valve surgery has long been recommended to decrease the future risk of embolic events such as myocardial infarction or ischemic stroke. Recently, Aryana et al reported that in patients with AF who underwent surgical ligation of LAA, the presence of incomplete ligation was associated with a significantly higher risk of stroke/systemic embolization than complete ligation (24% vs 2%).

A rare cause of retinal artery embolism: Accessory mitral valve tissue

A 42‐year‐old female patient was referred our clinic for investigation of a history of acute retinal artery occlusion. Transthoracic echocardiography showed a cyst‐like, mobile formation on posterior mitral valve leaflet. 2D and real time 3D transesophageal echocardiography showed a flexible circular mobile structure which was attached to posterior mitral valve leaflet. Echocardiographic appearance and morphological characteristics were suggestive of accessory mitral valve tissue.