Myocardial strain of the left ventricle by speckle tracking echocardiography: From physics to clinical practice.

Speckle tracking echocardiography (STE) is a reliable imaging technique of recognized clinical value in several settings. This method uses the motion of ultrasound backscatter speckles within echocardiographic images to derive myocardial velocities and deformation parameters, providing crucial insights on several cardiac pathological and physiological processes. Its feasibility, reproducibility, and accuracy have been widely demonstrated, being myocardial strain of the various chambers inserted in diagnostic algorithms and guidelines for various pathologies. The most important parameters are Global longitudinal strain (GLS), Left atrium (LA) reservoir strain, and Global Work Index (GWI): based on large studies the average of the lower limit of normality are -16%, 23%, and 1442 mmHg%, respectively. For GWI, it should be pointed out that myocardial work relies primarily on non-invasive measurements of blood pressure and segmental strain, both of which exhibit high variability, and thus, this variability constitutes a significant limitation of this parameter. In this review, we describe the principal aspects of the theory behind the use of myocardial strain, from cardiac mechanics to image acquisition techniques, outlining its limitation, and its principal clinical applications: in particular, GLS have a role in determine subclinical myocardial dysfunction (in cardiomyopathies, cardiotoxicity, target organ damage in ambulatory patients with arterial hypertension) and LA strain in determine the risk of AF, specifically in ambulatory patients with arterial hypertension.

Induced myocardial ischemia in candidates to liver transplantation without evidence of heart disease.

BACKGROUND: Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether stress echocardiography and coronary computed tomography angiography (CCTA) could detect CAD in end-stage liver disease (ESLD) patients without previous evidence of heart disease. METHODS: LT candidates ≥30 years underwent a cardiovascular (CV) assessment through stress echocardiography. CCTA was performed in patients ≥50 years with two or more CV risk factors (e.g. diabetes, CAD family history, dyslipidaemia). Coronary angiography (CAG) was scheduled when stress echocardiography and/or CCTA were positive. Sensibility, specificity, positive and negative predictive values of stress echocardiography and CCTA were assessed by numbers of coronary revascularization (true positives) and lack of acute coronary events over a mean follow-up of 3 years (true negatives). RESULTS: Stress echocardiography was performed in 273 patients, CCTA in 34 and CAG in 41. Eight patients had critical coronary lesions, and 19 not-critical lesions. Sensitivity, specificity, positive and negative predictive values were 50.0%, 90.2%, 13.3% and 98.4% for stress echocardiography and 100%, 76.7%, 36.4% and 100% for CCTA. Among 163 patients who underwent LT (57.6%), 16 died and 5 had major adverse CV events over a mean follow-up of 3 years. CONCLUSIONS: A very low prevalence of CAD in a selected population of ESLD at intermediate to high CV risk was found. A screening based on stress echocardiography and CCTA resulted in low incidence of post-LT acute coronary events in ELSD patients. CAD has no impact on mid-term survival.

[Myocardial no-reflow phenomenon: recent knowledges]. / Sul fenomeno del "no-reflow miocardico" nei pazienti con infarto miocardico. Attuali concetti.

Early revascularization of the infarct-related artery by primary percutaneous coronary intervention (PPCI) has become the gold standard therapy in ST-segment elevation myocardial infarction (STEMI). However, in a number of patient undergoing PPCI, epicardial coronary artery reperfusion: does not translate into myocardial reperfusion: a phenomenon called as no-reflow. The no-reflow phenomenon has a multifactorial pathogenesis, including: distal embolization, ischemia-reperfusion injury, and individual predisposition of coronary microcirculation to injury. Angiographic and electrocardiographic indexes may be used for the diagnosis. Also, lack of ST-segment elevation resolution is considered an established marker of no-reflow. Importantly, the no-reflow phenomenon provides prognostic information in STEMI patients because it is associated with low ventricular ejection fraction, adverse left ventricular remodelling and mortality at follow-up. Various mechanical devices and pharmacological approaches have been proposed to prevent and to treat the phenomenon: the assessment of mechanisms of no-reflow might guide the development of personalized form of treatment. This paper will be focused on the postulated mechanisms of the phenomenon, modalities for the diagnosis, and the main treatment options.

Left atrial appendage occlusion in patients with atrial fibrillation and large prevalence of prior intracranial bleeding.

BACKGROUND: Left atrial appendage occlusion (LAAO) represents an alternative approach for the prevention of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF) and contraindication for oral anticoagulation (OAC). The aim of our study was to analyse the outcomes in patients treated with LAAO, with a focus on cases with previous intracranial bleeding. METHODS: Sixty patients with NVAF underwent LAAO (75.4 ±â€Š9 years); mean CHA2DS2-VASc was 4.4 ±â€Š1.7, mean HAS-BLED 3.2 ±â€Š0.9. Thirty-two patients (53.3%) reported previous intracranial bleeding. Ischaemic and bleeding events recorded during follow-up were compared with expected event rates according to CHA2DS2-VASc and HAS-BLED scores. RESULTS: Device implantation was successful in 58 patients (96.7%). The antiplatelet therapy was tailored according to patients' bleeding risk. During follow-up (2.32 ±â€Š1.5 years) 3 ischaemic strokes and 1 transient ischaemic attack occurred, versus 13 total expected thromboembolic events (P = 0.033); 5 major bleedings were observed, versus 7 expected ones, if the patients were under OAC. Considering the combined endpoint (thromboembolic and major bleeding events) 9 events were observed versus 20 expected major events (P = 0.031). In the prespecified subgroup of patients with previous intracranial bleeding, two ischaemic strokes and one transient ischaemic attack were observed during follow-up versus six total expected thromboembolic events; no intracranial bleeding recurrence was recorded. Regarding the combined endpoint four major events were recorded versus nine expected ones. CONCLUSION: LAAO is an efficient and safe option for the prevention of cardioembolic stroke in patients with NVAF, high thromboembolic risk and contraindication to OAC, particularly in patients with previous intracranial bleeding.

Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention.

AIMS: Thromboxane A2 (TXA2) is a key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction. We sought to investigate whether baseline plasma levels of TXA2 are associated with coronary no-reflow after primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS: A total of 47 consecutive patients (age, 62.5 +/- 12.7; male sex, 76.6%) admitted to our hospital for a first ST-segment elevation myocardial infarction and undergoing PPCI within 12 h of onset of symptoms were enrolled. Admission TXA2 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Angiographic no-reflow was defined as a final TIMI flow of

Concordance of angiographic and electrocardiographic indexes of microvascular obstruction: myocardial haemorrhage role.

BACKGROUND: Angiographic and electrocardiographic (ECG) indexes of microvascular obstruction (MVO) have been described. We aimed at assessing by cardiac magnetic resonance (CMR) anatomical features underlying concordance between them. METHODS: Forty-one patients were enrolled. Patients presented with neither angiographic nor ECG indexes of MVO (without MVO) (44%), with either angiographic or ECG indexes of MVO (discordant with MVO) (22%) or with both angiographic and ECG indexes of MVO (concordant with MVO) (34%). All patients underwent in-hospital CMR. Echocardiographic data obtained after 6 months were compared with those obtained in hospital. RESULTS: Concordant patients with MVO had larger infarct size, lower myocardial salvage index and higher rate of myocardial haemorrhage (all assessed by CMR) [33% (25-41%), 15% (10-29%) and 88%, respectively] as compared with patients without MVO [12% (9-16%), 66% (52-79%) and 0%; Bonferroni-adjusted P < 0.001, Bonferroni-adjusted P < 0.001 and P < 0.001, respectively], or with discordant ones [25% (21-39%), 35% (20-48%) and 7%; Bonferroni-adjusted P = 0.03, Bonferroni-adjusted P = 0.002 and P = 0.04, respectively]. After 6 months, ejection fraction significantly decreased in concordant patients with MVO (P < 0.001) without significant changes in the other groups. CONCLUSIONS: Concordance of angiographic and ECG indexes of MVO reflects more severe myocardial damage translating into unfavourable left ventricular remodelling.

No-reflow: incidence and detection in the cath-lab.

The primary goal in patients with ST-elevation myocardial infarction (STEMI) is the restoration of myocardial tissue-level perfusion. In a variable proportion of patients with STEMI, however, microcirculatory impairment may persist after epicardial coronary artery recanalization. This phenomenon is known as "myocardial no-reflow". Of note, no-reflow is associated with a worse prognosis both at short- and long-term follow-up. Depending on the population under study and the diagnostic technique used for its detection, the incidence of no-reflow ranges from 5 to 50%. No-reflow can be directly assessed in the cath-lab in several ways, including angiographic Thrombolysis in Myocardial Infarction (TIMI) flow grade assessment and more complex angiographic indexes, such as TIMI frame count, TIMI perfusion grade, myocardial blush grade, or by direct invasive assessment of coronary flow. After the cath-lab, both the evaluation of electrocardiographic ST-segment resolution and imaging techniques, as myocardial contrast echocardiography or cardiac magnetic resonance, are able to monitor no-reflow evolution, with imaging playing a crucial role in its quantification. In this article, we review indexes of no-reflow used both in the cath-lab and thereafter.

New strategies for the management of no-reflow after primary percutaneous coronary intervention.

The myocardial no-reflow phenomenon is characterized by a reduced antegrade myocardial blood flow despite an open infarct-related artery in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Importantly, no-reflow is known to be associated with unfavorable clinical outcome and prognosis. It is a complex phenomenon and is caused by the variable combination of four pathogenetic components: distal atherothrombotic embolization, ischemic injury, reperfusion injury and susceptibility of coronary microcirculation to injury. As a consequence, appropriate strategies to prevent or treat each of these components are expected to reduce the occurrence of no-reflow. Mechanical and pharmacological approaches performed before, during and after performing myocardial revascularization have been investigated in recent studies, in order to reduce the rate of no-reflow. In this article, we concentrate on the major preventive and therapeutic approaches currently available for the management of the no-reflow phenomenon.

Angiographic patterns of myocardial reperfusion after primary angioplasty and ventricular remodeling.

BACKGROUND: No reflow after primary percutaneous coronary intervention is a dynamic process and its reversibility may affect left ventricular (LV) remodeling. We aimed at assessing in-hospital evolution of angiographic no reflow, predictors of its reversibility, and its impact on LV function at follow-up (FU). METHODS: Fifty-three consecutive patients (age, 60±10 years; male sex, 79%) presenting with ST-elevation myocardial infarction and undergoing primary percutaneous coronary intervention within 12 h of symptom onset were enrolled. No reflow was defined as a final thrombolysis in myocardial infarction (TIMI) flow of 2 or final TIMI flow of 3 with myocardial blush grade (MBG) of less than 2. The evolution of angiographic no reflow was assessed by repeat in-hospital coronary angiography. Patients with no reflow found to have an improvement of TIMI and/or MBG leading to a final TIMI 3 and MBG of greater than or equal to 2 were classified as reversible no reflow; the remaining patients were classified as sustained no reflow. Variables predicting the patterns of no reflow, recorded on admission, were assessed among clinical, angiographic and laboratory data. FU echocardiographic data (at 6 months) were compared with those obtained in-hospital according to no reflow evolution. RESULTS: Thirty-six patients (68%) exhibited myocardial reperfusion; 17 patients (32%) showed no reflow. Among these, six patients (age, 58±10 years; male sex, 83%) showed sustained no reflow, whereas 11 patients (age, 55±8 years; male sex, 82%) showed reversible no reflow. Patients with sustained no reflow had longer time to percutaneous coronary intervention (261±80 min) compared with those with myocardial reperfusion (216±94 min) or reversible no reflow (237±76 min; P=0.008 and 0.05, respectively). Moreover, patients with sustained no reflow had a higher peak troponin-T levels (14.5 ng/ml; range, 7.5-20.2 ng/ml) compared with those presenting with myocardial reperfusion (3.9 ng/ml; range, 3.3-9.1 ng/ml) and reversible no reflow (7.7 ng/ml; range, 3.6-29.9 ng/ml; P=0.03 and 0.07, respectively). At multivariate ordinal logistic regression, time pre-PCI retained its statistical significant association with angiographic no reflow evolution (odds ratio=2.54; 95% confidence interval: 1.45-6.53; P=0.04), with troponin T levels showing a borderline statistical significance (odds ratio=3.12; 95% confidence interval: 1.07-6.23; P=0.09). Finally, in patients with sustained no reflow only both end-diastolic and end-systolic volumes significantly increased at FU (P<0.001 and 0.001, respectively). CONCLUSION: Sustained no reflow is associated with a longer ischemic time and predicts worse LV remodeling. No reflow, however, shows an in-hospital reversibility calling for therapeutic interventions when its prevention fails.

CD4+CD28 null T lymphocytes are expanded in young women with polycystic ovary syndrome.

Women affected by polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. We demonstrated that women with PCOS showed an expansion of CD4(+)CD28(null) T cells, an aggressive population of T lymphocytes that has been recently associated with recurrent coronary instability and type 2 diabetes mellitus. This sheds new light on possible mechanisms responsible for the higher rate of cardiovascular disease among women with PCOS.

Prevention and treatment of no-reflow.

No-reflow phenomenon occurs frequently during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and it has a strong negative impact on outcome. Prevention of no-reflow has to be defined as any attempt to prevent its occurrence prior to or during the recanalization procedure. Strategy of prevention may be pharmacological or device based. Among drugs, abciximab is indicated by European Society of Cardiology (ESC) guidelines for prevention of no-reflow (class of recommendation IIa and level of evidence B). Among devices used for preventing no-reflow, manual thrombus aspiration only has been associated with a reduction of no-reflow and lower mortality at follow-up and is currently indicated in the ESC guidelines (class IIa of recommendation and level B of evidence). Treatment of no-reflow has to be defined as any attempt to treat its occurrence after coronary recanalization. Strategy of treatment may be pharmacological or device based. Adenosine and verapamil are indicated by ESC guidelines for treatment of no-reflow (class of recommendation IIb and level of evidence B and C, respectively). Serial assessment of myocardial perfusion showed that in up to 50% of patients no-reflow is spontaneously reversible. This finding may open new scenarios, as mechanisms of reversibility may become future therapeutic targets.

Effect of chronic Aspirin therapy on angiographic thrombotic burden in patients admitted for a first ST-elevation myocardial infarction.

Myocardial no-reflow may negate the benefit of urgent coronary revascularization in patients with acute ST-elevation myocardial infarction (STEMI). Among its pathogenetic mechanisms, distal embolization is of prominent importance and several studies have shown that a high coronary thrombotic burden is associated with distal embolization. We aimed at assessing predictors of angiographic thrombus grade in patients undergoing primary percutaneous coronary intervention. Ninety-one patients (62 +/- 12 years old, 79% men) presenting for a first STEMI and undergoing urgent coronary angiography within 12 hours from onset of symptoms were consecutively included in the study. Thrombus grade was evaluated by angiography according to the Gibson score and patients were allocated to the high thrombus grade (HTG; score 4 to 5) group or to the low thrombus grade (score 0 to 3) group. Variables predicting angiographic thrombus grade were assessed among clinical, angiographic, procedural, and laboratory data. Sixty-four patients (61 +/- 12 years old, 78% men) presented with HTG, whereas 27 patients (63 +/- 10 years old, 80% men) presented with low thrombus grade. Patients an HTG showed a significantly higher white blood cell count (12.5 +/- 4.8 vs 10.5 +/- 2.9, p = 0.015). Aspirin and beta-blocker therapy before admission were less frequently taken in the HTG group (5% vs 26% and 7% vs 23%, respectively, p = 0.01 and p = 0.03). At multivariate analysis, lack of previous therapy with aspirin was the only independent predictor of an HTG (odds ratio 6.14, 95% confidence interval 1.09 to 34.67, p = 0.04). In conclusion, previous aspirin therapy is associated with a decrease in angiographic thrombus grade in patients with STEMI treated with primary percutaneous coronary intervention, thus further priming efforts for appropriate use of aspirin in primary prevention of a first STEMI.

Baseline von Willebrand factor plasma levels and no-reflow phenomenon after primary percutaneous coronary intervention for ST segment elevation myocardial infarction.

No-reflow phenomenon is associated with a poor prognosis and its underlying mechanisms are still poorly understood. von Willebrand Factor (vWF) is a central molecule in haemostasis which plays an important role in acute coronary syndromes. However its possible role in no-reflow has not been assessed prior to this study. Quantitative baseline vWF plasma antigen was measured by immunoturbidometric assay in 54 consecutive patients with a first ST segment elevation acute myocardial infarction, treated by primary percutaneous coronary intervention within 12 h of symptom onset. Definitions of no-reflow were (1) angiographic: final TIMI flow ≤2 or final TIMI flow 3 with a myocardial blush grade <2; (2) electrocardiographic: lack of ST segment resolution (≤50% reduction of ST segment elevation at 90 min). Angiographic and electrocardiographic no-reflow was observed in 32 (59%) and 30 (56%) patients, respectively (only 9 patients had both type of no-reflow). Plasma levels of vWF were significantly higher in patients with angiographic no-reflow but not in those with electrocardiographic no-reflow. Also, vWF was the most powerful independent predictors of angiographic no-reflow (OR 3.8, 95% CI 1.1-12.9, p=0.033). Our results provide new insights into no-reflow pathophysiology with appealing therapeutic implications.

Randomized evaluation of intracoronary nitroprusside vs. adenosine after thrombus aspiration during primary percutaneous coronary intervention for the prevention of no-reflow in acute myocardial infarction: the REOPEN-AMI study protocol.

BACKGROUND: Thrombus aspiration improves microvascular obstruction in patients with acute myocardial infarction treated by percutaneous coronary intervention. However, drugs such as nitroprusside and adenosine have not yet been tested as adjuncts to thrombus aspiration. Therefore, we designed a placebo-controlled, randomized, open-label, blind-examination, multicenter trial assessing the effects of intracoronary nitroprusside or adenosine on microvascular obstruction in patients undergoing primary or rescue percutaneous coronary intervention and thrombus aspiration. METHODS AND RESULTS: Six hospitals in Italy participate in the REOPEN-AMI study. Two hundred and forty consecutive patients with acute myocardial infarction undergoing primary or rescue percutaneous coronary intervention and thrombus aspiration are randomly allocated 1: 1: 1 to receive either intracoronary nitroprusside, adenosine or placebo. The primary end-point is the incidence of ST resolution greater than 70% on surface ECG at 90 min after the procedure. Secondary end-points are: incidence of angiographic no-reflow (thrombolysis in myocardial infarction flow < or =2 or 3 with a myocardial blush grade <2); changes of left ventricular volumes at follow-up (at bidimensional echocardiography); rate of major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization and heart failure requiring hospitalization). CONCLUSIONS: REOPEN-AMI will provide important data on the efficacy and safety of intracoronary nitroprusside and adenosine as an adjunctive treatment to percutaneous coronary intervention after thrombus aspiration for patients with acute myocardial infarction.

Baseline systemic inflammatory status and no-reflow phenomenon after percutaneous coronary angioplasty for acute myocardial infarction.

BACKGROUND: Systemic inflammation is involved in several pathological cardiovascular processes. However, whether it plays a role in the no-reflow phenomenon occurring in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is unknown. METHODS: We studies 60 consecutive patients (59.5+/-12 years, 82% males) with a first ST-segment elevation AMI, treated by primary or rescue PCI within 6 h of symptom onset. Angiographic indexes of no-reflow, evaluated at the end of the procedure, included coronary TIMI flow grading, corrected TIMI frame count (c-TFC) and myocardial blush grade (MBG). ECG indexes of no-reflow included the lack of ST segment resolution (defined as a reduction <50% of the measured ST-segment elevation at 90 min, compared to the admission ECG), as analyzed both in the single lead with the maximal ST elevation and in all leads showing ST elevation on admission. Patients were divided into two groups according to baseline high-sensitivity C-reactive protein (CRP) serum levels measured on admission: high CRP group (CRP>5 mg/L) and low CRP group (CRP<5 mg/L). RESULTS: A similar prevalence of final TIMI flow<3 and MBG<3 was observed in patients with high and low CRP serum levels (30% vs. 12%, p=0.1, and 50% vs. 53%, p=1.0, respectively), and c-TFC was also similar in the two groups (26+/-4.5 vs. 24+/-6, p=0.5). Accordingly, the prevalence of lack of ST-segment resolution in the two groups was similar, both by the single-lead method (25% vs. 25%, p=1.0) and the multiple-lead method (29% vs. 19%, p=0.4). CONCLUSION: In this study we failed to demonstrate any significant association between CRP serum levels on admission and coronary no-reflow, as assessed by both angiographic and ECG parameters in AMI patients treated by successful primary or rescue PCI within 6 h of chest pain onset.