Role of cardiac CT in the diagnostic evaluation and risk stratification of patients with myocardial infarction and non-obstructive coronary arteries (MINOCA): rationale and design of the MINOCA-GR study.

INTRODUCTION: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 5%-15% of all patients with acute myocardial infarction. Cardiac MR (CMR) and optical coherence tomography have been used to identify the underlying pathophysiological mechanism in MINOCA. The role of cardiac CT angiography (CCTA) in patients with MINOCA, however, has not been well studied so far. CCTA can be used to assess atherosclerotic plaque volume, vulnerable plaque characteristics as well as pericoronary fat tissue attenuation, which has not been yet studied in MINOCA. METHODS AND ANALYSIS: MINOCA-GR is a prospective, multicentre, observational cohort study based on a national registry that will use CCTA in combination with CMR and invasive coronary angiography (ICA) to evaluate the extent and characteristics of coronary atherosclerosis and its correlation with pericoronary fat attenuation in patients with MINOCA. A total of 60 consecutive adult patients across 4 participating study sites are expected to be enrolled. Following ICA and CMR, patients will undergo CCTA during index hospitalisation. The primary endpoints are quantification of extent and severity of coronary atherosclerosis, description of high-risk plaque features and attenuation profiling of pericoronary fat tissue around all three major epicardial coronary arteries in relation to CMR. Follow-up CCTA for the evaluation of changes in pericoronary fat attenuation will also be performed. MINOCA-GR aims to be the first study to explore the role of CCTA in combination with CMR and ICA in the underlying pathophysiological mechanisms and assisting in diagnostic evaluation and prognosis of patients with MINOCA. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at national meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT4186676.

The Interplay between Myocardial Fibrosis, Strain Imaging and Collagen Biomarkers in Adults with Repaired Tetralogy of Fallot.

BACKGROUND: We sought to assess the interplay between right ventricle (RV) fibrosis, biventricular dysfunction based on global longitudinal strain (GLS) analysis, and biomarkers such as Galectin-3 (Gal-3), procollagen type III (PCIII), and NTproBNP. METHODS: We studied 35 adult patients with rToF. All patients underwent a cardiac magnetic resonance (CMR) scan including feature tracking for deformation imaging. Blood biomarkers were measured. RESULTS: LGE RV was detected in all patients, mainly at surgical sites. Patients with the highest RV LGE scoring had greater RV dilatation and dysfunction whereas left ventricular (LV) function was preserved. LV GLS correlated with RV total fibrosis score (p = 0.007). A LV GLS value of -15.9% predicted LGE RV score > 8 (AUC 0.754 (p = 0.02)). Neither RV GLS nor biomarker levels were correlated with the extent of RV fibrosis. A cut-off value for NTproBNP of 145.25 pg/mL predicted LGE RV score > 8 points (AUC 0.729, (p = 0.03)). A cut-off value for Gal-3 of 7.42 ng/mL predicted PR Fraction > 20% [AUC 0.704, (p = 0.05)]. CONCLUSIONS: A significant extent of RV fibrosis was mainly detected at surgical sites of RV, affecting RV performance. CMR-FT reveals subtle LV dysfunction in rToF patients, due to decreased performance of the fibrotic RV. Impaired LV function and elevated NTproBNP in rToF reflect a dysfunctional fibrotic RV.

Micro-CT-Based Quantification of Extracted Thrombus Burden Characteristics and Association With Angiographic Outcomes in Patients With ST-Elevation Myocardial Infarction: The QUEST-STEMI Study.

Background: Angiographic detection of thrombus in STEMI is associated with adverse outcomes. However, routine thrombus aspiration failed to demonstrate the anticipated benefit. Hence, management of high coronary thrombus burden remains challenging. We sought to assess for the first time extracted thrombotic material characteristics utilizing micro-computed tomography (micro-CT). Methods: One hundred thirteen STEMI patients undergoing thrombus aspiration were enrolled. Micro-CT was undertaken to quantify retrieved thrombus volume, surface, and density. Correlation of these indices with angiographic and electrocardiographic outcomes was performed. Results: Mean aspirated thrombus volume, surface, and density (±standard deviation) were 15.71 ± 20.10 mm3, 302.89 ± 692.54 mm2, and 3139.04 ± 901.88 Hounsfield units, respectively. Aspirated volume and surface were significantly higher (p < 0.001) in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were reference vessel diameter (RVD) (p = 0.011), right coronary artery (RCA) (p = 0.039), and smoking (p = 0.027), whereas RVD (p = 0.018) and RCA (p = 0.019) were predictive for thrombus surface. Thrombus volume and surface were independently associated with distal embolization (p = 0.007 and p = 0.028, respectively), no-reflow phenomenon (p = 0.002 and p = 0.006, respectively), and angiographically evident residual thrombus (p = 0.007 and p = 0.002, respectively). Higher thrombus density was correlated with worse pre-procedural TIMI flow (p < 0.001). Patients with higher aspirated volume and surface developed less ST resolution (p = 0.042 and p = 0.023, respectively). Conclusions: Angiographic outcomes linked with worse prognosis were more frequent among patients with larger extracted thrombus. Despite retrieving larger thrombus load in these patients, current thrombectomy devices fail to deal with thrombotic material adequately. Further studies of novel thrombus aspiration technologies are warranted to improve patient outcomes. Clinical Trial Registration: QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered.

How Should I Get Prepared for and Treat Rota Burr Entrapment in a Focally Underexpanded and Restenosed Stent: A Case Report.

Although high-speed rotational atherectomy has been successfully used in selected cases of stent underexpansion secondary to heavy peri-stent calcification, a higher risk of burr entrapment demands extreme caution and surgical back-up on site. The main cause of this complication is the lack of diamond dust on the back end of the burr, which prevents backward ablation of tissues when retracted. To date, only few reports of successful burr retrieval using percutaneous bailout techniques have been published. We report a case of burr entrapment within a previously implanted left circumflex artery stent which was successfully recaptured using the dual catheter technique; following the retrieval the patient underwent routine percutaneous coronary intervention.

Calcification of coronary arteries and aortic valve and circulating a-klotho levels in patients with chronic kidney disease.

BACKGROUND: Evidence suggests that the anti-aging protein a-Klotho is a central modulator of mineral homeostasis. Circulating a-Klotho exerts endocrine activity and has been implicated in the process of vascular calcification, which is accelerated in patients with chronic kidney disease (CKD) and portends an unfavorable overall prognosis. However, the role of a-Klotho in this process remains unclear. The purpose of this study was to investigate the possible interaction between a-Klotho and the calcification of the aortic valve and coronary arteries in patients with CKD. METHODS: In this study we enrolled a total of 60 adult patients with CKD. Group 1 included 30 participants with CKD stage V and group 2 included 30 participants with CKD stage III. RESULTS: Participants in group 1 had lower levels of circulating a-Klotho compared to group 2 (390; 280-590 vs. 722; 501-897 pg/mL; P=0.001), were of younger age (55.5; 45-63 vs. 69; 62-74 years; P<0.001), had lower body mass index (25.6; 23.8-27.5 vs. 28.2; 25.7-31.1 kg/m2; P=0.036), higher serum phosphate (4.75; 4-5.6 vs. 3.35; 2.9-3.8 mg/dL; P<0.001), higher calcium-phosphate product (41; 35.1-49.2 vs. 31.5; 28.6-35 mg2/dL2; P<0.001), and higher parathyroid hormone (PTH) levels (28.4; 15-44.6 vs. 7.05; 4.3-10.2 pmol /L; P<0.001). CONCLUSIONS: No statistically significant difference was found between the two groups in terms of coronary arteries and aortic valve calcification. Calcitonin, PTH and phosphate were identified as predictors for circulating a-Klotho levels whereas, only hyperlipidemia was identified as predictor for coronary artery calcification. In conclusion, circulating a-Klotho is found to decrease with worsening CKD severity but no correlation was found between the levels of a-Klotho and severity of coronary arteries and aortic valve calcification.

Torsades de Pointes and Prolonged Self-Terminating Ventricular Fibrillation Induced by Amiodarone.

A 71-year-old man with a recent diagnosis of pneumonia developed paroxysmal atrial fibrillation and was admitted to the cardiology service. Amiodarone was administered intravenously to restore sinus rhythm. Significant prolongation of the QT interval (QTc = 640ms) was noted and an exceedingly prolonged (over 3 minutes), self-terminating, episode of ventricular flutter/fibrillation occurred during bedside monitoring. The event was terminated without first converting to a more organized ventricular rhythm and without any adverse neurological sequelae. Apart from the long duration of ventricular fibrillation and its spontaneous termination, our case highlights the importance of the continuous heart rhythm monitoring in patients with extreme QT interval prolongation.

Quality of Life is Related to Haemodynamics in Precapillary Pulmonary Hypertension.

BACKGROUND: Precapillary pulmonary hypertension (PH) is characterised by compromised functional capacity and impaired quality of life. Assessment of haemodynamics is routinely used for initial diagnosis, follow-up, and risk stratification in these patients. The purpose of this study was to investigate the relation of health-related quality of life (HRQoL) as assessed by emPHasis-10 score, a self-assessment questionnaire assessing breathlessness, fatigue, control, and confidence, to haemodynamic and neurohormonal indices in patients with precapillary PH. METHOD: This was a prospective cross-sectional study which included stable patients with precapillary PH. All patients underwent right heart catheterisation, 6-minute walk test, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, and assessment of HRQoL with the emPHasis-10 scale. RESULTS: Overall, 54 patients were included (32 women; mean age, 58.4 ± 14.6 yr). Mean emPHasis-10 score was 19.2 ± 12.0. EmPHasis-10 score correlated with World Health Organization functional class (r = 0.52, p < 0.001), 6-minute walk distance (r=-0.56, p < 0.001), and log10(NT-proBNP) (r = 0.41, p < 0.01). A positive correlation of emPHasis-10 score with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) and a negative correlation with mixed venous oxygen saturation and cardiac index was observed, after adjustment for age, sex, body mass index, and PH group. In a subgroup analysis of patients with pulmonary arterial hypertension (n = 34) there was a stronger correlation of emPHasis-10 score with mPAP (r = 0.86, p < 0.001) and PVR (r = 0.69, p < 0.01), but no correlation with cardiac index and mixed venous oxygen saturation. CONCLUSIONS: Self-assessment of quality of life with the use of the emPHasis-10 score reflects functional capacity and is correlated with haemodynamic and neurohormonal indices of right heart dysfunction in patients with precapillary PH.

Duration of interventricular septal shift toward the left ventricle is associated with poor clinical outcome in precapillary pulmonary hypertension: A cardiac magnetic resonance study.

BACKGROUND: Right ventricular pressure overload results in interventricular septal shift toward the left ventricle in patients with precapillary pulmonary hypertension (PH). We aimed to investigate the predictive role of the duration of septal curvature configuration during the cardiac cycle, as expressed by the novel marker curvature duration index (CDi) in precapillary PH. METHODS: This was a prospective study. All patients underwent cardiac magnetic resonance (CMR). CDi was defined by the number of CMR frames in which septal curvature configuration toward left ventricle is observed *100/total number of frames per cardiac cycle. Time from enrollment to first clinical failure event (death, hospitalization due to PH, and disease progression) was recorded. RESULTS: The study included 36 patients with precapillary PH. During a median follow-up of 20 months (IQR 4-37 months), 14 clinical failure events were observed. Survival ROC analysis showed that the optimal cutoff value of CDi, which predicted clinical failure, was 67%. Kaplan-Meier survival analysis showed that CDi≥67% was associated with a 9.4-fold increase in the risk for clinical failure. Addition of CDi to baseline models including six-minute walk test distance (c-statistic = 0.65 vs. c-statistic = 0.79), NT-proBNP (c-statistic = 0.72 vs. c-statistic = 0.83), and WHO functional class (c-statistic = 0.76 vs. c-statistic = 0.81) improved risk stratification. CONCLUSION: Ventricular septal shift toward the left ventricle lasting for more than the two thirds of the cardiac cycle is associated with worse prognosis in precapillary PH.

Massive coronary artery air embolism due to an unusual cause.

A 46-year-old man underwent angioplasty of a restenotic bifurcation lesion of the circumflex artery. The procedure required repeated balloon exchanges and during the last balloon inflation, no balloon was visualized. A test injection revealed a massive coronary air embolism due to expulsion of air that had accumulated in the guiding catheter shaft. The patient was rapidly resuscitated from electromechanical dissociation with intracoronary injection of adrenaline and atropine and forceful intracoronary saline injections. Inspection of the balloon revealed a defect and scratch marks at the junction of the wire part and shaft of the monorail balloon, a location that places the air leakage inside the guiding catheter. This is the first report of massive intracoronary air embolism due to an undetectable damage to the shaft of a balloon angioplasty catheter. Recognition of the problem and immediate intervention is vital in limiting the duration of cardiac dysfunction.

Right Atrial Function Predicts Clinical Outcome in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Although the primary role of right atrial (RA) size in the diagnosis and risk stratification of precapillary pulmonary hypertension (PH) has been studied, little is known about the clinical significance of RA function. In line with studies assessing left atrial function in heart failure, the aim of this study was to introduce the RA function index (RAFi) and to explore its prognostic power in precapillary PH. METHODS: RA emptying fraction was calculated as (RA end-systolic volume - RA end-diastolic volume) × 100/(RA end-systolic volume). RAFi was calculated as (RA emptying fraction × right ventricular outflow tract velocity-time integral)/(RA end-systolic volume index). Patients were followed for the end point of clinical failure, which was defined as death, hospitalization because of PH, or disease progression. RESULTS: In total, 47 patients with precapillary PH were included. Mean RAFi was 16.1 ± 22.3%. Over a median follow-up period of 25 months (interquartile range, 9.5-41.1 months), 29 patients experienced clinical failure. Univariate Cox proportional-hazard analysis showed that RAFi was a predictor of clinical failure (hazard ratio, 0.935; 95% CI, 0.890-0.981; P = .007). Addition of RAFi to established predictors of outcomes, including 6-minute walk distance, N-terminal pro-B-type natriuretic peptide, and RA area, improved their prognostic power. CONCLUSIONS: RAFi is an easily assessed echocardiographic parameter, which is strongly predictive of clinical outcomes in patients with precapillary PH. Further studies are needed to validate RAFi and define its role in clinical practice.

Data on diagnostic performance of stress perfusion cardiac magnetic resonance for coronary artery disease detection at the vessel level.

Stress perfusion cardiac magnetic resonance (CMR) has been proposed as an important gatekeeper for invasive coronary angiography (ICA) and percutaneous coronary interventions (PCI) in patients evaluated for possible coronary artery disease (CAD) (Fihn et al., 2012; Montalescot et al., 2013) [1], [2]. Several meta-analyses have evaluated the accuracy of stress perfusion CMR to diagnose CAD at the vessel level (Danad et al., 2017; Dai et al., 2016; Jiang et al., 2016; Takx et al., 2015; Li et al., 2015; Desai and Jha, 2013; Jaarsma et al. 2012; Hamon et al., 2010; Nandalur et al. 2007) [3], [4], [5], [6], [7], [8], [9], [10], [11]. However, they included in the same analysis studies with different definitions of significant CAD (i.e. fractional flow reserve [FFR] < 0.75 and < 0.80 or coronary stenosis ≥ 50% and ≥ 70%), magnetic field strength (1.5 or 3 Tesla [T]), and study protocol (integration or not of late gadolinium enhancement [LGE] into stress perfusion protocol). Data of 34 studies (6091 arteries) have been pooled with the aim of analyzing the accuracy of stress perfusion CMR for the diagnosis of ischemic heart disease at the vessel level according to different definitions of significant CAD, magnetic field strength and study protocol (Arnold et al., 2010; Bettencourt et al., 2013; Cheng et al., 2007; Chiribiri et al., 2013; Cury et al., 2006; De Mello et al., 2012; Donati et al., 2010; Ebersberger et al., 2013; Gebker et al., 2008; Greulich et al., 2015; Hussain et al., 2016; Ishida et al., 2005, 2003; Kamiya et al., 2014; Kitagawa et al., 2008; Klein et al., 2008; Klem et al., 2006; Klumpp et al., 2010; Krittayaphong et al., 2009; Lockie et al., 2011; Ma et al., 2012; Merkle et al., 2007; Meyer et al., 2008; Mor-Avi et al., 2008; Pan et al., 2015; Papanastasiou et al., 2016; Pons Lladó et al., 2004; Sakuma et al., 2005; Salerno et al., 2014; Scheffel et al., 2010; van Werkhoven et al., 2010; Walcher et al., 2013; Watkins et al., 2009; Yun et al., 2015) [12-45]. This article describes data related article titled "Diagnostic Performance of Stress Perfusion Cardiac Magnetic Resonance for the Detection of Coronary Artery Disease" (Kiaos et al., submitted for publication) [46].

A case of sarcoidosis-associated pulmonary hypertension masquerading as chronic thromboembolic pulmonary hypertension.

Occlusive vasculopathy due to the development and accumulation of granulomas at the level of intima of large vessels, as well as mediastinal lymph nodes and fibrosing mediastinitis secondary to sarcoidosis, causing extrinsic compression of mediastinal vascular structure are uncommon mechanisms of sarcoidosis-associated pulmonary hypertension. We present a case of a 62-year-old woman with a rare manifestation of sarcoidosis, which was misclassified and treated as chronic thromboembolic pulmonary hypertension for a long period. Fluorine-18-fluorodeoxyglucose positron emission tomography played a major role in accessing final diagnosis. Mechanisms that lead to development of pulmonary hypertension, the contribution of novel imaging modalities, and treatment options are discussed.

Pregnancy outcome in women with congenital heart disease: A single-center experience.

OBJECTIVE: Pregnancies in patients with adult congenital heart disease (ACHD) are often complicated. We aimed to highlight the nature and the rate of these complications in a single-center patient population. METHODS: We retrospectively studied all the pregnancies of women who presented on an outpatient basis, and all pregnancies were reviewed for maternal and fetal outcomes. RESULTS: Of 117 pregnancies from 52 ACHD patients (age at pregnancy 28.3 ± 6.6 years), 10 were therapeutically aborted. A proportion of 41.1% of the remaining 107 pregnancies were complicated either with cardiac (3.7%), obstetric (15.0%), or fetal/neonatal (11.2%) adverse events or with spontaneous abortion (17.8%). Hospitalization during pregnancy was required in 10 patients. Elective cesarean sections were initially planned for 31% of the 87 pregnancies, which were finally completed, while 8% required an emergency cesarean section, mostly for obstetric reasons. NYHA class deterioration after pregnancy was detected in 9.3% of our cohort. Modified WHO class III/IV, prior medication use, and higher body mass index (BMI) were related to cardiac complications during pregnancy or NYHA deterioration. CONCLUSION: Pregnancies in ACHD patients are at high risk for complications. Advanced modified WHO class, prior medication use, and high BMI were related to adverse cardiac events.

Diagnostic performance of stress perfusion cardiac magnetic resonance for the detection of coronary artery disease: A systematic review and meta-analysis.

INTRODUCTION: The purpose of this study was to investigate the accuracy of qualitative stress perfusion cardiac magnetic resonance (CMR) to diagnose ischemia-causing lesions according to different definitions of significant coronary artery disease (CAD), and magnetic field strength. METHODS: We searched PubMed, Web of Science, and the Cochrane Library for studies evaluating diagnostic performance of qualitative stress perfusion CMR for diagnosis of CAD versus coronary angiography or fractional flow reserve (FFR) from inception to 10 September 2017. We used hierarchical models to synthesize the available data. RESULTS: Sixty-seven studies (7113 patients) met the inclusion criteria. The patient-based analysis of studies using FFR as the reference standard demonstrated a mean sensitivity of 0.90 (95% confidence interval [CI], 0.85-0.93) and a mean specificity of 0.85 (95% CI, 0.80-0.89). The patient-based analyses for detecting coronary stenosis ≥50% and coronary stenosis ≥70% at 1.5T and for detecting coronary stenosis ≥50% and coronary stenosis ≥70%, at 3T, demonstrated a mean sensitivity of 0.82 (95% CI, 0.79-0.84), 0.86 (95% CI, 0.83-0.89), 0.90 (95% CI, 0.82-0.95), and 0.91 (95% CI, 0.79-0.96), respectively; with a mean specificity of 0.75 (95% CI, 0.71-0.80), 0.77 (95% CI, 0.71-0.81), 0.79 (95% CI, 0.69-0.86), and 0.74 (95% CI, 0.59-0.85). CONCLUSION: Qualitative stress perfusion CMR has high accuracy for the diagnosis of CAD, irrespective of the reference standard and the magnet strength. Studies using FFR as the reference standard had higher diagnostic accuracy on a patient level compared to studies using coronary angiography, with a notable difference in specificity.

Epidemiology and management of chronic thromboembolic pulmonary hypertension: experience from two expert centers.

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, and therefore, there is a lack of data regarding its clinical presentation, diagnosis, and management at a national basis. We aimed to describe the demographics and management of patients with CTEPH in Northern Greece. METHODS: We conducted a retrospective, observational study by a joint collaboration between two pulmonary hypertension expert centers in Greece, and the study included patients diagnosed with CTEPH. The patient population was divided into two groups depending on their operability. RESULTS: Overall, 27 consecutive patients were included (59% female, mean age 59.3±15.1 years). Dyspnea and fatigue were the most common presenting symptoms. History of pulmonary embolism was present in 82%. Of patients, 18 (67%) were assessed as operable, of whom 10 (55%) finally underwent pulmonary endarterectomy (PEA). There were no differences in symptoms, WHO functional class, 6-min walking test distance, and hemodynamics between the operable and nonoperable groups. At the end of follow-up, all non-operable and operable patients who did not receive surgical treatment were treated with at least one pulmonary hypertension-specific drug. CONCLUSION: This is the first report that presents data of patients diagnosed with CTEPH in Greece. The percentage of patients who underwent surgical treatment is lower but approaches the reported rates in large registries. Considering that PEA is a relatively safe and potentially curative surgical procedure, we emphasize the need for establishing a designated PEA center in Greece.

Iatrogenic Lutembacher Syndrome after Percutaneous Mitral Commissurotomy.

Atrial septal defects (ASDs) are common immediately after percutaneous mitral commissurotomy (PMC). They are usually small, hemodynamically insignificant, and tend to decrease or disappear within 6 to 12 months. Herein, a case is described of persistent ASD in a patient with mitral valve stenosis who had undergone successful PMC three years previously. The patient had signs and symptoms of right heart failure and severe tricuspid regurgitation (TR) with borderline right ventricular systolic function on echocardiography, in addition to the ASD. Cardiac magnetic resonance (CMR) imaging played a significant role in decision-making by clarifying the anatomy of the ASD and severity of the shunt, measuring right ventricular systolic function, and providing absolute quantification for TR. The right ventricular systolic function was normal on CMR, rendering the patient suitable for surgical treatment. Persistent iatrogenic ASDs have become an increasingly common finding after invasive procedures requiring trans-septal puncture and the manipulation of catheters. Multimodality imaging can provide significant aid in the management of patients with valvular heart disease complicated by iatrogenic shunts.