Left atrial expansion index measured with cardiovascular magnetic resonance estimates pulmonary capillary wedge pressure in dilated cardiomyopathy.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) assessment is fundamental for managing dilated cardiomyopathy (DCM) patients. Although cardiovascular magnetic resonance (CMR) has become the gold-standard imaging technique for evaluating cardiac chamber volume and function, PCWP is not routinely assessed with CMR. Therefore, this study aimed to validate the left atrial expansion index (LAEI), a LA reservoir function parameter able to estimate filling pressure with echocardiography, as a novel CMR-measured parameter for non-invasive PCWP estimation in DCM patients. METHODS: We performed a retrospective, single-center, cross-sectional study. We included electively admitted DCM patients referred to our tertiary center for further diagnostic evaluation that underwent a clinically indicated right heart catheterization (RHC) and CMR within 24 h. PCWP invasively measured during RHC was used as the reference. LAEI was calculated from CMR-measured LA maximal and minimal volumes as LAEI = ( (LAVmax-LAVmin)/LAVmin) × 100. RESULTS: We enrolled 126 patients (47 ± 14 years; 68% male; PCWP = 17 ± 9.3 mmHg) randomly divided into derivation (n = 92) and validation (n = 34) cohorts with comparable characteristics. In the derivation cohort, the log-transformed (ln) LAEI showed a strong linear correlation with PCWP (r = 0.81, p < 0.001) and remained a strong independent PCWP determinant over clinical and conventional CMR parameters. Moreover, lnLAEI accurately identified PCWP ≥ 15 mmHg (AUC = 0.939, p < 0.001), and the optimal cut-off identified (lnLAEI ≤ 3.85) in the derivation cohort discriminated PCWP ≥ 15 mmHg with 82.4% sensitivity, 88.2% specificity, and 85.3% accuracy in the validation cohort. Finally, the equation PCWP = 52.33- (9.17xlnLAEI) obtained from the derivation cohort predicted PCWP (-0.1 ± 5.7 mmHg) in the validation cohort. CONCLUSIONS: In this cohort of DCM patients, CMR-measured LAEI resulted in a novel and useful parameter for non-invasive PCWP evaluation.

Thyroid dysfunction on the heart: clinical effects, prognostic impact and management strategies.

Thyroid hormones have a considerable influence on cardiac function and structure. There are direct and indirect effects of thyroid hormone on the cardiovascular system, which are prominent in both hypothyroidism and hyperthyroidism. In this review, we discuss how thyroid dysfunction impacts cardiovascular pathophysiology and the underlying molecular mechanisms.

Indirect ultrasound evaluation of left ventricular outflow tract diameter implications for heart failure and aortic stenosis severity assessment.

BACKGROUND: Whereas dependency of left ventricular outflow tract diameter (LVOTD) from body surface area (BSA) has been established and a BSA-based LVOTD formula has been derived, the relationship between LVOTD and aortic root and LV dimensions has never been explored. This may have implications for evaluation of LV output in heart failure (HF) and aortic stenosis (AS) severity. METHODS: A cohort of 540 HF patients who underwent transthoracic echocardiography was divided in a derivation and validation subgroup. In the derivation subgroup (N = 340), independent determinants of LVOTD were analyzed to derive a regression equation, which was used for predicting LVOTD in the validation subgroup (N = 200) and compared with the BSA-derived formula. RESULTS: LVOTD determinants in the derivation subgroup were sinuses of Valsalva diameter (SVD, beta = 0.392, P < .001), BSA (beta = 0.229, P < .001), LV end-diastolic diameter (LVEDD, beta = 0.145, P = .001), and height (beta = 0.125, P = .037). The regression equation for predicting LVOTD with the aforementioned variables (LVOTD = 6.209 + [0.201 × SVD] + [1.802 × BSA] + [0.03 × LVEDD] + [0.025 × Height]) did not differ from (P = .937) and was highly correlated with measured LVOTD (R = 0.739, P < .001) in the validation group. Repeated analysis with LV end-diastolic volume instead of LVEDD and/or accounting for gender showed similar results, whereas BSA-derived LVOTD values were different from measured LVOTD (P < .001). CONCLUSION: Aortic root and LV dimensions affect LVOTD independently from anthropometric data and are included in a new comprehensive equation for predicting LVOTD. This should improve evaluation of LV output in HF and severity of AS when direct LVOTD measurement is difficult or impossible.

From left ventricular ejection fraction to cardiac hemodynamics: role of echocardiography in evaluating patients with heart failure.

In clinical practice heart failure (HF) patients are generally classified on the basis of left ventricular (LV) ejection fraction. This approach, however, has important limitations. According to the definition of HF as a clinical syndrome that results from any impairment of LV filling or ejection of blood, a more articulated hemodynamic categorization of HF patients taking into account both LV forward flow and filling pressure would be desirable. However, the reliability of hemodynamic measures using echocardiographic techniques, which are the most used in current clinical practice for evaluation of HF patients, needs to be clarified. The aim of this article, therefore, is to verify whether echocardiography has acceptable feasibility, accuracy and reproducibility for the noninvasive evaluation of LV hemodynamics. This evaluation is necessary to progress to a hemodynamic characterization of HF patients that would ultimately overcome the HF classification based on ejection fraction.

Current Role of Echocardiography in Cardiac Resynchronization Therapy: from Cardiac Mechanics to Flow Dynamics Analysis.

PURPOSE OF REVIEW: The aim of this review is to summarily explain what LV synchrony, coordination, myocardial work, and flow dynamics are, trying to clarify their advantages and limitations in the treatment of heart failure patients undergoing or with implanted cardiac resynchronization therapy (CRT). RECENT FINDINGS: CRT is an established treatment for patients with heart failure and left ventricular systolic dysfunction. In the current guidelines, CRT implant indications rely only on electrical dyssynchrony, but in the last years, many aspects of cardiac mechanics (including contractile synchrony, coordination, propagation, and myocardial work) and flow dynamics have been studied using echocardiographic techniques to better characterize patients undergoing or with implanted CRT. However, the concepts, limits, and potential applications of all these echocardiographic evaluations are unclear to most clinicians. The use of left ventricular dyssynchrony and discoordination indices may help to identify those significant mechanical alterations whose correction may increase the probability of a favorable CRT response. Assessment of myocardial work and intracardiac flow dynamics may overcome some limitations of the conventional evaluation of cardiac mechanics but more investigations are needed before extensive clinical application.

Sex differences in anthracycline-induced cardiotoxicity: the benefits of estrogens.

Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.

Intracardiac flow analysis in cardiac resynchronization therapy: A new challenge?

In the past years, assessment of cardiac function has become possible through the analysis of intracardiac flow dynamics, performed noninvasively using phase-contrast cardiac magnetic resonance and contrast and noncontrast ultrasound techniques. From 2013 to 2019, 9 echocardiographic investigations have considered 215 patients with cardiac resynchronization therapy (CRT) as a model for assessing flow dynamics within the left ventricle. Preliminary results have been reported about the acute hemodynamic effects of CRT and programming of the CRT device, showing the potential of an approach based on analysis of intracardiac flows. At present, there are only scarce data on the capability of intracardiac flow dynamics to predict LV remodeling after CRT and no information on clinical outcome prediction. Future investigations should be aimed at clarifying the mechanisms and impact of maladaptive intracardiac vortex dynamics on progressive LV remodeling as well as the prognostic meaning of implanted CRT device based on cardiac flow analysis.

Angina and left ventricular dysfunction: can we 'reduce' it?

Despite the evolution in pharmacology and devices, recurrent and persistent angina still represent a frequent issue in clinical practice. A 69-year-old Caucasian female patient has history of surgical aortic valve replacement with a bioprosthesis for severe aortic stenosis with subsequent transcatheter valve-in-valve implantation for bioprosthesis degeneration and single coronary artery bypass graft with left internal mammary artery on left anterior descending (LAD). After transcatheter aortic valve implantation, she started to complain angina [Canadian Cardiovascular Society (CCS) Class III], effectively treated with bisoprolol uptitration and ivabradine 5 b.i.d. addition. After 6 months, she had a non-ST segment elevated myocardial infarction with evidence of left main occlusion and good functioning aortic bioprosthesis. A retrograde drug-eluting balloon percutaneous coronary intervention (PCI) on LAD (in-stent restenosis) was performed. However, the patient continued to complain angina (CCS Class II-III), even after further ivabradine increase to 7.5 mg b.i.d. After 4 months, the patient underwent Reducer implantation. After 2 months, angina started to improve and the patient is currently angina free. In the last decades, PCI materials and stents greatly improved. Medical therapy (such as ß-blockers) has been shown not only to improve symptoms but also to add a prognostic benefit in patients with reduced ejection fraction (EF). Ivabradine showed additional benefits in patients with angina and reduced EF. However, still a relevant portion of patients complain refractory angina. The COSIRA trial showed that a coronary sinus Reducer was associated with greater angina relief than the sham procedure and could be a further step in angina treatment.

Potential cardiac risk of immune-checkpoint blockade as anticancer treatment: What we know, what we do not know, and what we can do to prevent adverse effects.

Cancer immunotherapy has become a well-established treatment option for some cancers after the development of a family of drugs targeting the so-called immune checkpoints, such as CTLA4 and PD-1 with PD-L1. These co-receptors/ligands inhibit the activation of T-cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint-blocking drugs is to awake an immune response primarily directed against cancer cells. Nonetheless, as the immune response elicited by these drugs is not completely tumor-specific, their use may actually cause several adverse effects, including adverse cardiovascular effects. In this review, we will discuss the principles and potentiality of immunotherapy for cancer treatment, the experimental and clinical data on the role of CTLA4 and PD-1 with PD-L1 as immune-checkpoints in the cancer environment and in the cardiovascular system, and strategies aimed at preventing possible cardiovascular adverse effects of immune-checkpoint blockers.

Urgent Myocardial Revascularization in Non ST-Segment Elevation Acute Myocardial Infarction Guided by Speckle Tracking Echocardiography: A Challenging Interventional Decision-Making.

A 68-year-old man with a non-ST elevation myocardial infarction (NSTEMI) presented with a low risk profile indicating invasive revascularization within 72 h. However, left ventricular (LV) global longitudinal strain (GLS) calculated by two-dimensional speckle tracking echocardiography (2D-STE) in the Emergency Room showed substantial myocardial infarction. Therefore, urgent reperfusion therapy was decided and delivered within 30 min from hospital admission. LV GLS fully recovered after the invasive procedure and the final infarct size was 7%. This case shows that very early revascularization in NSTEMI patients can be guided by 2D-STE and might be considered for those patients with substantial LV myocardial infarction.

Echocardiographic evaluation of cardiac dyssynchrony: Does it still matter?

Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure and left ventricular systolic dysfunction. For many years, cardiac mechanical dyssynchrony assessed by echocardiography has been considered as a key evaluation to characterize CRT candidates and predict CRT response. In current guidelines, however, CRT implant indications rely only on electrical dyssynchrony. The aim of this article was to clarify whether and how the evaluation of cardiac mechanical dyssynchrony should be performed today by echocardiography.

Speckle tracking analysis in intensive care unit: A toy or a tool?

The use of conventional echocardiography in the intensive care unit (ICU) is today established to assess left and right ventricular systolic function, for preload determination and procedural guidance. Next step in ICU echocardiography could be the use of novel ultrasound techniques such as strain echocardiography to assist in the management of patients with acute coronary syndrome, heart failure, or pulmonary embolism. This review has gathered the available evidence supporting the incremental value of strain in the diagnostic workup of cardiac diseases treated in ICU.

Right heart-pulmonary circulation unit and cardiac resynchronization therapy.

Clinical response to cardiac resynchronization therapy (CRT) has been known for years to be highly variable, with a spectrum of responses from no change or even deterioration of cardiac function to spectacular improvements. In the plethora of clinical, echocardiographic, biohumoral, and electrophysiological predictors of response to CRT and postimplant issues besides patient selection, the role of right ventricular (RV) function has been largely overlooked. In reviewing current evidence, we noticed conflicting results between observational studies and randomized trials not only concerning the impact of baseline RV function on CRT efficacy but also on the effects of CRT on RV size and function. Hence, we aimed to provide a critical reappraisal of current knowledge and unresolved issues on the reciprocal interactions between RV function and CRT, shifting the spotlight on the concept of right heart pulmonary circulation unit and on the clinical and prognostic significance of impaired ventricular-arterial coupling reserve. In this viewpoint, we propose that (1) CRT should not be denied to potential candidate because of "isolated" RV dysfunction and (2) assessment of baseline right heart pulmonary circulation unit and its dynamic response to pharmacological stress should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors.

Current role of echocardiography in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure and left ventricular systolic dysfunction. Patients are usually assessed by echocardiography, which provides a number of anatomical and functional information used for cardiac dyssynchrony assessment, prognostic stratification, identification of the optimal site of pacing in the left ventricle, optimization of the CRT device, and patient follow-up. Compared to other cardiac imaging techniques, echocardiography has the advantage to be non-invasive, repeatable, and safe, without exposure to ionizing radiation or nefrotoxic contrast. In this article, we review current evidence about the role of echocardiography before, during, and after the implantation of a CRT device.

Left ventricular hypertrophy or storage disease? the incremental value of speckle tracking strain bull's-eye.

Left ventricular hypertrophy (LVH) develops in response to a variety of physical, genetic, and biochemical stimuli and represents the early stage of ventricular remodeling. In patients with LVH, subclinical left ventricular (LV) dysfunction despite normal ejection fraction (EF) may be present before the onset of symptoms, which portends a dismal prognosis. Strain measurement with two-dimensional speckle tracking echocardiography (STE) represents a highly reproducible and accurate alternative to LVEF determination. The present review focuses on current available evidence that supports the incremental value of STE in the diagnostic and prognostic workup of LVH. When assessing the components of LV contraction, STE has an incremental value in differentiating between primary and secondary LVH and in the differential diagnosis with storage diseases. In addition, STE provides unique information for the stratification of patients with LVH, enabling to detect intrinsic myocardial dysfunction before LVEF reduction.

Noninvasive evaluation of right hemodynamics in carcinoid heart disease: A case report.

We report the case of a 67-year-old woman with a carcinoid tumor of midgut origin who developed carcinoid heart disease and died because of bowel perforation. Echocardiography allowed the diagnosis, recognizing the typical abnormalities of tricuspid and pulmonary valve leaflets. The sonographic examination also evidenced peculiar alterations of the right heart hemodynamics: end-diastolic reversal of flow at the level of the pulmonary valve, reduced respiratory excursion without enlargement of the inferior vena cava, and biphasic hepatic venous flow without respiratory variation. Echocardiography allowed both the diagnosis and the accurate assessment of the hemodynamic consequences of the disease. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:355-361, 2017.

Current views on anthracycline cardiotoxicity.

Anthracyclines are well established and effective anticancer agents used to treat a variety of adult and pediatric cancers. Unfortunately, these drugs are also among the commonest chemotherapeutic agents that have been recognized to cause cardiotoxicity. In the last years, several experimental and clinical investigations provided new information and perspectives on anthracycline-related cardiotoxicity. In particular, molecular mechanisms of cardiotoxicity have been better elucidated, early diagnosis has improved through the use of advanced noninvasive cardiac imaging techniques, and emerging data indicate a genetic predisposition to develop anthracycline-related cardiotoxicity. In this article, we review established and new knowledge about anthracycline cardiotoxicity, with special focus on recent advances in cardiotoxicity diagnosis and genetic profiling.

Echocardiographic assessment of left ventricular systolic function: from ejection fraction to torsion.

Assessment of left ventricular (LV) systolic function is the cornerstone of the echocardiographic examination. There are many echocardiographic parameters that can be used for clinical and research purposes, each one with its pros and cons. The LV ejection fraction is the most used one due to its feasibility and predictability, but it also has many limits, related to both the imaging technique used for calculation and to the definition itself. LV longitudinal function is expression of subendocardial fibers contraction. Because the subendocardium is often involved early in many pathological processes, its analysis has been a fertile field for the development of sensitive parameters. Longitudinal function can be evaluated in many ways, such as M-mode echocardiography, tissue Doppler imaging, and speckle tracking echocardiography. This latter is a relatively new tool to assess LV function through measurement of myocardial strain, with a high temporal and spatial resolution and a better inter- and intra-observer reproducibility compared to Doppler strain. It is angle independent, not affected by translation cardiac movements, and can assess simultaneously the entire myocardium along all the three-dimensional geometrical (longitudinal, circumferential, and radial) axes. Speckle tracking echocardiography also allows the analysis of LV torsion. The aim of this paper was to review the main echocardiographic parameters of LV systolic function and to describe its pros and cons.

Longitudinal strain of left ventricular basal segments and E/e' ratio differentiate primary cardiac amyloidosis at presentation from hypertensive hypertrophy: an automated function imaging study.

BACKGROUND: Longitudinal strain is an early marker of left ventricular (LV) dysfunction in several cardiac diseases. Our aim was to differentiate cardiac amyloidosis (CA) at diagnosis from hypertensive LV hypertrophy (LVH) by analysis of longitudinal myocardial deformation. METHODS: Thirty healthy controls (C), 30 newly diagnosed, never treated hypertensives with LVH (H-LVH), and 33 patients with CA at diagnosis underwent echo Doppler including speckle tracking-based automated function imaging (AFI). Averaged peak systolic global longitudinal strain (GLS, 18 segments) and basal, middle, and apical longitudinal strain (BLS, MLS, and ALS, respectively, six segments each) were calculated. RESULTS: Left ventricular mass index, relative wall thickness, and ejection fraction did not differ between H-LVH and CA. E/e' ratio was higher in CA than in H-LVH (P<.001) and C (P<.0001). GLS was lower in CA than in C (P<.0001), without difference with H-LVH. ALS did not differ among the three groups, MLS was significantly lower in both CA and H-LVH than in C but BLS was lower in CA compared to both H-LVH and C (both P<.0001). In the pooled population, E/e' was independently associated with BLS (ß=-0.54, P<.0001). At receiver operating curve analysis, CA was predicted by BLS≤-11.3% (sensitivity=63.3%, specificity=100%) and E/e'≥12.3 (sensitivity=69.7%, specificity=83.3%). The best AUC (=0.819) was obtained by the combination E/e'+BLS. CONCLUSIONS: Our findings highlight a real difference of E/e' ratio and longitudinal strain of LV basal segments between hypertensive LVH and CA, which could be used to differentiate the two diseases.

Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection.

Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies.