The Added Value of Advanced Echocardiography for the Morpho-Functional and Prognostic Evaluation of the Right Heart in Dilated Cardiomyopathy: Do Not Forget about the Right Atrium.

(1) Introduction and Aims: Right ventricular (RV) remodeling significantly impacts the prognosis of dilated cardiomyopathy (DCM) patients, and right atrial (RA) size and function are still often neglected in DCM patients. Accordingly, our aims were to (i) evaluate right heart subclinical changes and (ii) the prognostic value of RA compared to left atrial (LA) size and function in patients with DCM by advanced echocardiography. (2) Materials and Methods: Sixty-eight patients with DCM (with a mean age of 60 years; 35 men) were evaluated by comprehensive transthoracic echocardiography, compared to 62 age- and sex-matched healthy controls (with a mean age of 61 years; 32 men), and followed up for 12.4 ± 5 months. (3) Results: DCM patients have RV and RA global longitudinal dysfunction by 2DSTE, higher RA minimum volumes and tricuspid annulus areas despite having normal RV volumes, ejection fractions, and RA maximum volumes by 3DE compared to the controls. The RA strain and RV strain are correlated with each other. The RA reservoir strain (with an AUC = 0.769) has an increased value for outcome prediction compared to that of the LA strain. (4) Conclusion: Patients with DCM have RV longitudinal dysfunction and decreased RA function, in the absence of clinical RV involvement or atrial arrhythmias, and the RA strain is associated with an increased risk of hospitalization and cardiac death.

Lower Limit of Normality of Segmental Multilayer Longitudinal Strain in Healthy Adult Subjects.

Speckle tracking echocardiography is an advanced imaging technique that allows for a more detailed assessment of cardiac global and regional function. Reference values for segmental longitudinal layered strain (subendocardial, mid-myocardial, and subepicardial) are scarce, limiting the clinical use of these measurements in clinical practice. Two hundred consecutive Caucasian healthy subjects (mean age = 37 ± 11 years) were enrolled in the study. The mean values of global longitudinal strain (GLS) for endocardial (Endo), mid-myocardial (Myo) and epicardial (Epi) layers were -22.9 ± 2.7, -20.0 ± 2.4 and -17.5 ± 2.1, respectively. The GLSEndo/GLSMyo ratio was 1.1 ± 0.05, while the GLSEndo/GLSEpi ratio was 1.3 ± 0.05. The apical strain-sparing ratio was >1 in 10% of the subjects (endocardium) and 7% (mid-myocardium). The lower limits for segmental LS were as follows: for endocardial LS, -10% (basal), -12% (mid), -14% (apical); for mid-myocardial LS, -10% -10% (basal), -10% (mid), -10% (apical); and for epicardial LS, -7% (basal), -8% (mid), -8% (apical). The findings of this study provide data regarding the lower limit of normality of LS for each LV segment and suggest, for practical considerations, that an LS value below 10% should be considered abnormal in any segment. Further larger studies are warranted to confirm these findings.

Dapagliflozin Ameliorates Neural Damage in the Heart and Kidney of Diabetic Mice.

(1) Background: Measures for the control of diabetes mellitus (DM) and, especially, for the control of its complications represent a main objective of the research carried out on this disease, since both mortality and morbidity relating to DM represent real problems for the health system worldwide. The aim of our study was to evaluate nervous tissue from the heart and kidneys of mice with diabetes induced by streptozotocin (STZ) in the presence or absence of dapagliflozin (DAPA) treatment. (2) Methods: For this purpose, we used 24 C 57Bl/6 male mice, aged between 8 and 10 weeks. The mice were divided into three groups: sham (DM-), control (DM+), and treated (DM+). Diabetes mellitus was induced by injecting a single intraperitoneal dose of STZ. The duration of diabetes in the mice included in our study was 12 weeks after STZ administration; then, the heart and kidneys were sampled, and nervous tissue (using the primary antibody PGP 9.5) from the whole heart, from the atrioventricular node, and from the kidneys was analyzed. (3) Results: The density of nerve tissue registered a significant decrease in animals from the control group (DM+), to a value of 0.0122 ± 0.005 mm2 nerve tissue/mm2 cardiac tissue, compared with the sham group (DM-), wherein the value was 0.022 ± 0.006 mm2 nervous tissue/mm2 cardiac tissue (p = 0.004). Treatment with dapagliflozin reduced the nerve tissue damage in the treated (DM+DAPA) group of animals, resulting in a nerve tissue density of 0.019 ± 0.004 mm2 nerve tissue/mm2 cardiac tissue; a statistically significant difference was noted between the control (DM+) and treated (DM+DAPA) groups (p = 0.046). The same trends of improvement in nerve fiber damage in DM after treatment with DAPA were observed both in the atrioventricular node and in the kidneys. (4) Conclusions. These data suggest that dapagliflozin, when used in streptozotocin-induced diabetes in mice, reduces the alteration of the nervous system in the kidneys and in the heart, thus highlighting better preservation of cardiac and renal homeostasis, independent of any reduction in the effects of hyperglycemia produced in this disease.

The Value of Multimodal Imaging in Early Phenotyping of Cardiomyopathies: A Family Case Report.

Cardiomyopathies are structural and functional myocardial disorders that are not caused by other specific conditions such as coronary artery disease, arterial hypertension, valvular disease or congenital heart diseases. They are grouped into specific morphological and functional phenotypes, and sub-classified into familial and non-familial forms, with the dilated phenotype being the most frequent. However, there are many overlapping features between these phenotypes, complicating the diagnosis and management of patients. We report here the case of three related patients with different types of cardiomyopathies, emphasizing the importance of a multimodal approach to diagnosis.

The Dysfunctional Right Ventricle in Dilated Cardiomyopathies: Looking from the Right Point of View.

Dilated cardiomyopathies (DCMs) are a heterogenous group of primary myocardial diseases, representing one of the leading causes of heart failure, and the main indication for heart transplantation. While the degree of left ventricular dilation and dysfunction are two key determinants of adverse outcomes in DCM patients, right ventricular (RV) remodeling and dysfunction further negatively influence patient prognosis. Consequently, RV functional assessment and diagnosing RV involvement by using an integrative approach based on multimodality imaging is of paramount importance in the evaluation of DCM patients and provides incremental prognostic and therapeutic information. Transthoracic echocardiography remains the first-line imaging modality used for the assessment of the RV, and newer techniques such as speckle-tracking and three-dimensional echocardiography significantly improve its diagnostic and prognostic accuracy. Nonetheless, cardiac magnetic resonance (CMR) is considered the gold standard imaging modality for the evaluation of RV size and function, and all DCM patients should be evaluated by CMR at least once. Accordingly, this review provides a comprehensive overview of the anatomy and function of the RV, and the pathophysiology, diagnosis, and prognostic value of RV dysfunction in DCM patients, based on traditional and novel imaging techniques.

Increased QRS duration and dispersion are associated with mechanical dyssynchrony in patients with permanent right ventricular apical pacing.

BACKGROUND: Permanent right ventricular apical pacing may have negative effects on ventricular function and contribute to development of heart failure. We aimed to assess intra- and interventricular mechanical dyssynchrony in patients with permanent right ventricular apical pacing, and to establish electrocardiographic markers of dyssynchrony. METHODS: 84 patients (46:38 male:female) who required permanent pacing were studied. Pacing was done from right ventricular apex in all patients. We measured QRS duration and dispersion on standard 12-lead ECG. Intra- and interventricular mechanical dyssynchrony and left ventricular ejection fraction were assessed by transthoracic echocardiography. Patients were followed-up for 24 months.  Results: Six months after implantation, QRS duration increased from 128.02 ms to 132.40 ms, p≤0.05. At 24 months, QRS dispersion increased from 43.26 ms to 46.13 ms, p≤0.05. Intra- and interventricular dyssynchrony increased and left ventricular ejection fraction decreased during follow-up. A QRS dispersion of 47 ms predicted left ventricular dysfunction and long-term electromechanical dyssynchrony with a sensitivity of 80% and a specificity of 76%.  Conclusion: In patients with permanent right ventricular apical pacing there is an increased duration and dispersion of QRS related to dyssynchrony and decreased left ventricular ejection fraction. This study shows that QRS dispersion could be a better predictive variable than QRS duration for identifying left ventricular ejection fraction worsening in patients with permanent right ventricular apical pacing. The electrocardiogram is a simple tool for predicting systolic function worsening in these patients and can be used at the bedside for early diagnosis in the absence of clinical symptoms, allowing adjustments of medical treatment to prevent progression of heart failure and improve the patient's quality of life.

An unusual case of aortic metastasis from lung cancer.

In patients with cardiovascular events, such as myocardial infarction or aortic dissection without known risk factors for cardiovascular disease, neoplastic disease should be considered as a differential diagnosis. In this report, we present a case of a 51-year old man with previously undiagnosed non-small lung cancer leading to fatal cardiovascular complications due to hemovascular spread, diagnosed post-mortem. This case illustrates the value of autopsy in unexpected deaths.

NT-proBNP and Echocardiographic Parameters in Liver Cirrhosis - Correlations with Disease Severity.

determined. Liver disease severity in patients with cirrhosis was established by Child-Pugh class, MELD score and presence/absence of ascites. Results: Plasma levels of NT-proBNP were significantly higher in cirrhotic patients than in the healthy subjects. NT-proBNP levels were also significantly elevated in Child-Pugh class C patients compared to those in class B and A. Left atrium size, diastolic function, left ventricular wall thickness and left ventricular ejection fraction were significantly altered in cirrhotic patients compared to controls. Advanced cirrhosis and high levels of NT-proBNP were significantly associated with increased left atrium volume and signs of cardiac diastolic dysfunction. We also observed significant differences between quartile groups of MELD score for the following: NT-proBNP, Troponin I, left atrium volume, left ventricle wall thickness, lateral wall and septum systolic tissue doppler velocities and global longitudinal strain. Conclusion: NT-proBNP is increased in patients with cirrhosis and is correlated with the severity of liver disease as established by Child-Pugh class, MELD score and presence of ascites.

Longitudinal strain analysis allows the identification of subclinical deterioration of right ventricular function in patients with cancer therapy-related left ventricular dysfunction.

BACKGROUND: This study was designed to assess right ventricular systolic function in cancer patients. METHODS AND RESULTS: 68 consecutive patients receiving potentially cardiotoxic agents were followed for 6 months in a single-center, observational, cohort-study. Left ventricle and free-wall right ventricular longitudinal strain were analyzed prior and after 6 months of treatment, using a vendor-independent software, together with left ventricle ejection fraction, tricuspid annulus plane systolic excursion and right ventricular fractional area change. Cancer therapy-related cardiac dysfunction was defined as a left ventricle ejection fraction drop of >10% to <53%. Both left ventricle ejection fraction (59±7% vs. 55±8%, p<0.0001) and left ventricle longitudinal strain (-19.7±2.5% vs. -17.1±2.6%, p<0.0001) were reduced at follow up, along with free-wall right ventricular longitudinal strain (-24.9±4.5% vs. -21.6±4.9%, p<0.0001). Cancer therapy-related cardiac dysfunction was detected in 20 patients (29%). In 15 out of these 20 patients (75%), a concomitant relative reduction in free-wall right ventricular longitudinal strain magnitude by 17±7% was detected. Moreover, there was a significant correlation between left ventricle and free-wall right ventricular longitudinal strain at follow-up examinations (r=0.323, p<0.0001). A relative drop of right ventricular longitudinal strain >17% had a sensitivity of 55% and a specificity of 70% (AUC=0.75, 0.7-0.8, 95% CI) to identify patients with cancer treatment related cardiac dysfunction. Neither tricuspid annulus plane systolic excursion (24±5 vs. 23±4 mm, p=0.07), nor right ventricular fractional area change (45±8% vs. 44±7%, p=0.6) showed any significant change between examinations. CONCLUSIONS: Longitudinal strain analysis allows the identification of subclinical right ventricular dysfunction appearing in the course of cancer treatment when conventional indices of right ventricular dysfunction function are unaffected.

A rare case of familial restrictive cardiomyopathy, with mutations in MYH7 and ABCC9 genes.

Restrictive cardiomyopathy is the least common type of cardiomyopathy, being defined by diastolic dysfunction and often unimpaired systolic function. Restrictive cardiomyopathies can be classified as familial or non-familial. Patients with familial restrictive cardiomyopathy can develop signs and symptoms of this condition anytime from childhood to adulthood. The evolution of the disease is towards signs and symptoms of pulmonary and systemic congestion and, without treatment, there is a five-year mortality rate of approximately 30% in these patients. We discuss the case of a 43-year-old patient diagnosed with familial restrictive cardiomyopathy with positive genetic tests for mutations of MYH7 gene and ABCC9 gene, who was first hospitalized in 2011 for palpitations. The echocardiography performed in evolution showed a continuous alteration of right ventricle function, without important differences of left ventricular function.  She developed heart failure symptoms six years after diagnosis and she had seven hospitalizations in the past two years, currently with an increasing need of diuretics and persistent hepatic dysfunction. Cardiac transplantation or left ventricular assist device therapy should be considered in patients with severe heart failure symptoms and no longer effective treatment. However, elevated pulmonary vascular resistance excludes the patient from cardiac transplantation.

Variability of right ventricular global and segmental longitudinal strain measurements.

OBJECTIVES: We evaluated intra-observer, test-retest, and inter-observer reproducibility of right ventricular (RV) longitudinal strain (LS) measurements derived from two-dimensional speckle tracking echocardiography. BACKGROUND: The assessment of RV deformation has demonstrated to hold valuable prognostic and diagnostic data in clinical practice. Data about the reproducibility of the measurements, however, are missing. METHODS: In 200 subjects, apical modified four-chamber view focused on the right ventricle (RV) was obtained. In 150 subjects (75%), a second set of images was acquired for test-retest analysis. Global RV LS (RVGLS-4C), free wall strain (RVFW-4C), and segmental maximum peak strain (base, mid, and apex) were calculated (EchoPac vBT13, GE Vingmed Ultrasound, Horten, Norway). Additionally, the reliability and feasibility of RV free wall strain derived from single wall tracking (RVFW-SWT) were tested. The absolute difference between repeated measurements and inter-class correlation coefficients (ICC) for consistency was calculated. RESULTS: RVGLS-4C and RVFW-4C measurement could be obtained in all subjects. RVGLS-4C demonstrated lower intra-observer, test-retest, and inter-observer absolute difference compared to RVFW-4C (1.4 ± 1.2%, 1.8 ± 1.5%, and 1.7 ± 1.9%, respectively, vs 2.4 ± 2.4, 2.2 ± 1.9, and 2.6 ± 3.0, respectively, P < 0.01). ICC ranged between 0.83 and 0.90 for RVGLS-4C measurements and between 0.76 and 0.79 for RVFW-4C measurements. RVFW-SWT was feasible in 82.5% of the subjects and showed noninferior reproducibility compared to RVFW-4C. Basal and apical segments demonstrating the highest variability. CONCLUSIONS: The measurement of RVGLS-4C appears to be reliable in clinical practice and demonstrates better reproducibility compared to RV free wall LS measurements. Segmental LS measurements presented high variability and such parameters should be interpreted with caution.

Left and right ventricular morphology and function in athletes with elevated pulmonary systolic arterial pressure.

OBJECTIVES: The objective of the study was to evaluate the prevalence and potential impact of elevated pulmonary arterial systolic pressure (PASP) on left and right cardiac morphology and function in young elite athletes. METHODS: In total, 85 professional athletes (40 endurance, 20 strength, and 25 mixed training, mean age 17.8 ± 4.0) and 50 sedentary controls (mean age 18.6 ± 3.3) underwent transthoracic echocardiographic examination. Two-dimensional measurements of the right (RV) and left ventricle (LV) were obtained. PASP was estimated from the peak tricuspid regurgitant velocity (TRV). Speckle tracking-derived longitudinal LV and RV strain measurements (RV_LS) were calculated for function estimation. RESULTS: Maximum TRV (2.2 ± 0.3 vs 2.0 ± 0.2 m/s, P < .01) and PASP (26 ± 5 vs 22 ± 5 mm Hg, P < .01) were higher in athletes compared to controls. PAPS above 30 mm Hg (35 ± 3 mm Hg, range 31-40 mm Hg) was identified in 11 athletes (12.9%). Athletes with elevated PASP demonstrated higher LV mass (P < .01), LV stroke volume indexed (P < .01), larger RV-end-systolic area (ESAi), RV-end-diastolic area (EDAi), right atrium ES volume and ED volume, and decreased RV fractional area change (FAC) (P < .01) when compared to matched controls and higher RV-EDAi (13.0 ± 1.6 vs 11.1 ± 1.5, P < .01), RV-ESAi (8.2 ± 1.5 vs 6.1 ± 0.9, P < .01), and significantly reduced RV FAC (38.1 ± 5.8 vs 44.6 ± 2.5, P < .01) when compared to matched athletes. LV global longitudinal strain and RV_LS showed no differences between the groups. CONCLUSIONS: Pulmonary arterial systolic pressure elevation in young athletes is associated with pronounced right ventricular enlargement, even when compared to matched athletes. Conventional and speckle tracking echocardiography showed preserved right ventricular function.