Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy-An Animal and In-Human Comparative Study.

ApoE abnormality represents a well-known risk factor for cardiovascular diseases. Beyond its role in lipid metabolism, novel studies demonstrate a complex involvement of apoE in membrane homeostasis and signaling as well as in nuclear transcription. Due to the large spread of apoE isoforms in the human population, there is a need to understand the apoE's role in pathological processes. Our study aims to dissect the involvement of apoE in heart failure. We showed that apoE-deficient rats present multiple organ damages (kidney, liver, lung and spleen) besides the known predisposition for obesity and affected lipid metabolism (two-fold increase in tissular damages in liver and one-fold increase in kidney, lung and spleen). Heart tissue also showed significant morphological changes in apoE-/- rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE-/- rats fed a high-fat diet showed more damage and affected collagen content (~60% less total collagen content and double increase in collagen1/collagen3 ratio) compared with the left ventricle (no significant differences in total collagen content or collagen1/collagen3 ratio). In patients, we were able to find a correlation between the presence of ε4 allele and cardiomyopathy (χ2 = 10.244; p = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 ± 2.63 mm in ε4-allele-presenting patients vs. 19.8 ± 3.58 mm if the ε4 allele is absent, p < 0.0001*) and increased in systolic pulmonary artery pressure (50.44 ± 16.47 mmHg in ε4-allele-presenting patients vs. 40.68 ± 15.94 mmHg if the ε4 allele is absent, p = 0.0019). Our results confirm that the presence of the ε4 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the ε4 allele is associated with right ventricle dysfunction, implying different regulatory mechanisms of fibroblasts and the extracellular matrix in both ventricles. This is essential to be considered and thoroughly investigated before the design of therapeutical strategies for patients with heart failure.

Testosterone and quality of life in patients with dilated cardiomyopathy.

BACKGROUND: Testosterone is an important factor that influences the quality of life in men. The purpose of this study is to evaluate how testosterone level impacts the quality of life in patients with dilated cardiomyopathy. METHODS: This cross-sectional single-center included 97 male patients with dilated cardiomyopathy, in whom serum testosterone was measured. Health-related quality of life was measured using the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). We used correlation and multivariable regression to assess the association between KCCQ-12 score, serum testosterone level, and clinical and paraclinical variables. RESULTS: The mean age of study participants was 58 (range 29-88). The mean LVEF was 25 ±8.61%. The average total serum testosterone level was 3.13 ±2.72 (range 0.19-13.5 ng/ml). The median global KCCQ-12 score was 44.8 (6.2-90.6) representing a poor to fair impairment in quality of life. There was an inverse correlation between the KCCQ-12 score and NYHA class (Pearson coefficient r = 0.847 p<0.001) and a direct correlation with LVEF (r=0.445, p<0.001). Also, the KCCQ-12 score correlated with hemoglobin level (r=0.214, p=0.037) and plasmatic creatinine level (r=-0.296 p= 0.004). In multivariable regression, the independent predictors of health-related quality of life were testosterone, LVEF, and NYHA class. CONCLUSIONS: The results of this study showed for the first time a significant direct relationship between serum testosterone levels and quality of life in patients with dilated cardiomyopathy.

Isorhythmic atrioventricular dissociation in an adult with levo-transposition of the great arteries.

A 36-year-old woman with levo-transposition of the great arteries presented for a programmed visit. She was asymptomatic and the clinical examination showed no signs of decompensated heart failure. Standard 12-lead ECG showed isorhythmic atrioventricular dissociation. A 24-hour ambulatory recording demonstrated sinus rhythm with intermittent periods of isorhythmic dissociation. This case highlights the association between two rare conditions.

Subacute effusive-constrictive pericarditis in a patient with COVID-19.

We report the case of a previously healthy young woman, who developed a severe form of COVID-19 with massive pneumonia and acute pericarditis in whom constrictive physiology developed rapidly. To our knowledge, this represents the second reported case of SARS-CoV-2 constrictive pericarditis, a rare, but severe cardiac complication.

Testosterone, cardiomyopathies, and heart failure: a narrative review.

Testosterone exerts an important regulation of cardiovascular function through genomic and nongenomic pathways. It produces several changes in cardiomyocytes, the main actor of cardiomyopathies, which are characterized by pathological remodeling, eventually leading to heart failure. Testosterone is involved in contractility, in the energy metabolism of myocardial cells, apoptosis, and the remodeling process. In myocarditis, testosterone directly promotes the type of inflammation that leads to fibrosis, and influences viremia with virus localization. At the same time, testosterone exerts cardioprotective effects that have been observed in different studies. There is increasing evidence that low endogenous levels of testosterone have a negative impact in some cardiomyopathies and a protective impact in others. This review focuses on the interrelationships between testosterone and cardiomyopathies and heart failure.

Heart function assessment during aging in apolipoprotein E knock-out mice.

BACKGROUND: Apolipoprotein (apo) E isoforms have strong correlations with metabolic and cardiovascular diseases. However, it is not clear if apoE has a role in development of non-ischemic cardiomyopathy. Our study aims to analyze the involvement of apoE in non-ischemic cardiomyopathy. METHODS AND RESULTS: Serial echo-cardiographic measurements were performed in old wildtype and apoE deficient (apoE-/-) mice. Morphological and functional cardiac parameters were in normal range in both groups at the age of 12 month. At the age of 18 months, both groups had shown ventricular dilation and increased heart rates. However, the apoE-/- mice presented signs of diastolic dysfunction by hypertrophic changes in left ventricle, due probably to arterial hypertension. The right ventricle was not affected by age or genotype.  CONCLUSION: Even in the absence of high fat diet, apoE deficiency in mice induces mild changes in the cardiac function of the left ventricle during aging, by developing diastolic dysfunction, which leads to heart failure with preserved ejection fraction. However, further studies are necessary to conclude over the role of apoE in cardiac physiology and its involvement in development of heart failure.

Spinal cord infarction caused by extensive aortic intramural hematoma.

We report the case of a 62-year-old Caucasian man, an ex-smoker, who presented to the emergency room complaining of intense lower back pain followed by immediate bilateral loss of inferior limbs motor function. Clinical examination showed complete paralysis and paranesthesia in both legs, while pain and temperature sensory examination revealed a sensory level at dermatome T6, with normal touch, vibration, and position senses. His blood pressure was 190∕100 mmHg. Computed tomography demonstrated dilated thoracic aorta (maximum diameter 44 mm) and abdominal aorta (maximum 58 mm), with extended intramural hematoma (IMH), thus establishing the diagnosis of type A aortic IMH complicated with paraplegia through spinal perfusion deficit. Due to the extension of the lesions, surgical intervention for aortic repair was considered at high risk while cerebrospinal fluid drainage was not recommended by the neurologist. The patient remained stable while hospitalized and was released from the hospital with mild improvement of neurological deficiencies.

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.

Native valve endocarditis with Staphylococcus warneri.

We report a rare case of native valve endocarditis caused by Staphylococcus warneri in an immunocompetent 79-year-old man with known degenerative valvular heart disease but no previous risk factors such as recent invasive treatment or medical implant. The patient presented with heart failure, due to perforation of the mitral valve, and lacked any signs of infection. The diagnosis of endocarditis with S. warneri was established by echocardiography and positive blood cultures.

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.

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.

Right atrium floating thrombus and bilateral pulmonary embolism in a patient with pancreatic pseudocyst.

Pulmonary embolism in the context of pancreatitis is a rare condition and even fewer cases of pulmonary embolism associated with pancreatic pseudocyst and chronic pancreatitis have been reported in the literature. We present the case of a patient diagnosed with chronic pancreatitis due to alcohol ingestion complicated with pancreatic pseudocyst, with no classic thrombogenic risk factors, who developed right atrial thrombus and massive bilateral pulmonary embolism. .

Apolipoprotein E in Cardiovascular Diseases: Novel Aspects of an Old-fashioned Enigma.

The presence of different APOE isoforms represents a well-known risk factor for cardiovascular diseases. Besides the pleiotropic effects of APOE polymorphism on heart and neurological diseases, this review summarizes the less-known functions of APOE and the possible implications for cardiovascular disorders. Beyond the role as lipid transporting protein, its involvement in lipid membrane homeostasis and signaling, as well as its nuclear transcriptional effects suggests a more complex role of APOE, receiving great interest from researchers and physicians from all medical fields. Due to the presence of different APOE isoforms in human population, understanding APOE's role in pathological processes represents not only a challenge, but a demand for further development of therapeutic strategies for cardiovascular diseases.