José Luis Zamorano

Normal reference values of left ventricular strain using three-dimensional speckle tracking echocardiography: results from a multicentre study

AIMS Three-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population. METHODS AND RESULTS A total of 303 healthy subjects (156 males [51%], between 18 and 82 years of age, ejection fraction [EF] 61 ± 3%), stratified to provide approximately equal proportions of healthy subjects of 18-30, 31-40, 41-50, 51-60, and >60 years of age, underwent 3DSTE. Data were analysed for LV volumes, EF, mass, and global and regional circumferential, longitudinal, radial, and area strain. Significant but small differences between men and women were found for longitudinal and area strains, as well as between different age groups for all LV strain parameters. However, large differences in normal values were observed between different segments, walls, and levels of the LV for radial and longitudinal strains, whereas circumferential and area strains demonstrated generally consistent normal ranges across the LV. CONCLUSIONS Normal ranges of global and regional LV strain using 3DSTE have been established for clinical use. Differences in the magnitude of LV strain are present between men and women as well as different age groups. Moreover, there are differences between different segments, walls, and levels as part of the functional non-uniformity of the normal LV that necessitates the use of segment-specific normal ranges for radial and longitudinal strains. Circumferential and area strains demonstrate the most consistent normal ranges overall.

Incidence, angiographic features and outcomes of patients presenting with subtle ST-elevation myocardial infarction

BACKGROUND Borderline electrocardiograms represent a challenge in ST-segment elevation myocardial infarction (STEMI) management and are associated with inappropriate discharges and delays to intervention. OBJECTIVES To assess angiographic characteristics and outcomes of patients presenting with subtle ST-elevation (STE) myocardial infarction. METHODS A total of 504 consecutive patients with suspected STEMI treated by systematic primary percutaneous coronary intervention were prospectively included. Subtle STE was defined as a maximal preinterventional STE of 0.1 to 1 mm. Angiograms were interpreted by investigators unaware of the electrocardiographic data. RESULTS The proportion of patients with subtle STE was 18.3%, 86% of them presented with Thrombolysis In Myocardial Infarction flow grade 0/1 and 91% underwent percutaneous coronary intervention. Despite having smaller infarcts, subtle STE patients associated more frequent multivessel disease (57% vs 44%, P = .02) and larger delays to reperfusion. During a follow-up of 19.0 ± 4.9 months, the rates of death or reinfarction were similar among groups (10.0% vs 12.6%, P = .467). Subtle STE was not associated with better outcomes neither in univariate nor after adjustment in a multivariate analysis (adjusted hazard ratio 0.79, 95% CI 0.37-1.69, P = .546). CONCLUSIONS Subtle STEMI is frequent in clinical practice and is usually associated with acute total coronary occlusion. Therefore, it should be diagnosed and treated in the same expeditiously manner as marked STEMI.

Erişkin hipertansiyonunda ekokardiyografi kullanimi özerine öneriler: Avrupa Kardiyovasköler Göröntöleme Birliǧi (EACVI) ve Amerikan Ekokardiyografi Derneǧi (ASE) raporu

Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment.

EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction.

Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to Control and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs Control: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs Control 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury.

Preclinical models of atherosclerosis. The future of Hybrid PET/MR technology for the early detection of vulnerable plaque

Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.

Frailty is an independent prognostic marker in elderly patients with myocardial infarction

Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age.

ESC sudden-death risk model in hypertrophic cardiomyopathy: Incremental value of quantitative contrast-enhanced CMR in intermediate-risk patients

Hypertrophic cardiomyopathy (HCM) remains the most common cause of sudden cardiac death (SCD) in the young; however, current strategies do not identify all HCM patients at risk. A novel validated algorithm was proposed by the last European Society of Cardiology guidelines to guide implantable cardioverter‐defibrillator (ICD) therapy. Recently, extensive myocardial fibrosis was independently associated with increased risk of SCD events. This study aimed to establish the relation between myocardial fibrosis (late gadolinium enhancement [LGE] extension) and the novel SCD risk‐prediction model in a real population of HCM to evaluate its potential additional value in the different risk groups.

Prognostic Significance of Right Heart Thrombi in Patients With Acute Symptomatic Pulmonary Embolism: Systematic Review and Meta-analysis

Background: For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity. Methods: We performed a meta‐analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography‐detectable RHT for the primary outcome of short‐term all‐cause mortality and the secondary outcome of short‐term PE‐related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms “right heart thrombi,” “pulmonary embolism,” and “prognos.*” A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity. Results: Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography‐detectable RHT died (16.7% [95% CI, 13.8–19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0–4.7]). RHT had a significant association with short‐term all‐cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I2 = 20%) and with PE‐related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0–11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7–13.6]; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I2 = 0%) studies. Conclusions: In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis. Trial Registry: PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/

Cardiac resynchronization therapy: do patient selection and implant practice vary depending on the volume a center handles?

The annual volume of implants may condition and determine many aspects of cardiac resynchronization therapy (CRT).

Effects of Ivabradine on Heart Rate and Hemodynamic Parameters in a Swine Model of Cardiogenic Shock

Cardiogenic shock (CS) after myocardial infarction is associated with elevated mortality. There are few specific treatment options. Catecholamine administration may worsen tachycardia because decreased tissue perfusion may lead to reduced ventricular efficiency and increased oxygen consumption. Preliminary data indicate that ivabradine may offer a benefit in situations of severe tachycardia and shock, probably as a result of lower oxygen consumption and oxidative stress, although the hemodynamic effects of the drug in this context are unknown. For this reason, prior to administration of the drug in a clinical setting, we deemed it appropriate to study whether ivabradine administration may induce hemodynamic changes in a porcine model of CS after myocardial infarction. Ten female large white pigs (mean weight, 32.8 [2.2] kg) were included. The animals were anesthetized with propofol and fentanyl and the anterior descending artery was occluded for 45 minutes by inflation of an angioplasty balloon. To simulate CS after infarction, noradrenalin, dobutamine, and saline solution were administered until a postreperfusion heart rate (HR) of 90 bpm and a pulmonary wedge pressure > 18 mmHg were achieved. Amiodarone was also administered at the same dose in both study groups to prevent ventricular fibrillation, which is a frequent occurrence in porcine models of acute ischemia. Hemodynamic parameters (blood pressure, HR, cardiac output, pulmonary artery pressure, pulmonary wedge pressure, and central venous pressure) were monitored with Swan-Ganz catheters inserted into the aorta via the carotid and jugular approach. After balloon deflation, each animal was stabilized for 15 minutes prior to subsequent open-label randomization to the control group (n = 5) or ivabradine group (n = 5). Ivabradine was administered intravenously as a slow intravenous bolus at a dose of 0.3 mg/kg and was diluted in distilled water at a concentration 12 mg/mL. The placebo group received the equivalent volume of saline solution. The aforementioned hemodynamic parameters were then measured at 15-minute intervals after infusion of drug/placebo. The study variables are expressed as mean SD. The means were compared with the Student t test for independent data with a normal distribution and with the Fisher-Pitman test for independent variables with a nonparametric distribution. Ivabradine administration was associated with a significant decrease in HR (Figure 1; median [confidence interval] absolute reduction in HR at 15 minutes, 21 [21 to 25] vs –1 [–5 to 0] bpm; P = .04), with no change in blood pressure, pulmonary artery pressure, or cardiac output. Tidal volume significantly increased in the ivabradine group (Figure 2; tidal volume at 15 minutes, 63.7 [5.7] vs 43.7 [7.5] mL; P < .01). However, the decrease in HR was not accompanied by a reduction in pulmonary wedge pressure, and an increase in central venous pressure was observed compared with the control group (Figure 1). The numerical differences recorded in the 2 groups before administration of the study drug were not significant for any variables. Although findings indicative of the efficacy and safety of ivabradine in acute heart failure after infarction have been reported, the hemodynamic impact of reducing HR in CS is not known. Our results are in agreement with those of Bakkehaug et al. in a porcine model of CS. The model used by those authors, however, was more invasive than ours—medial sternotomy was performed—and is thus less readily applicable in clinical practice. An additional consideration, at least as important as the type of model, is that the animals in that study were not randomized; rather, the animals were their own control. An effect of spontaneous improvement occurring after induction of ischemia and reperfusion of the infarction cannot therefore be ruled out. In conclusion, ivabradine administered in a porcine model of CS induced by ischemia/reperfusion can reduce HR without significantly compromising cardiac output and can therefore increase tidal volume. However, this reduction in HR does not appear to reduce filling pressures. Before randomized clinical studies are conducted, we believe broader knowledge is required, in particular with a view to establishing whether this pharmacological strategy is of any value in reducing oxidative stress and myocardial damage in CS after myocardial infarction.