Right ventricular performance in patients with heart failure with mildly reduced ejection fraction: the forgotten ventricle.

Right ventricular (RV) function is a major determinant of prognosis and adverse outcomes in patients with heart failure (HF). It is largely unknown if HF with mildly reduced ejection fraction (HFmrEF) patients have some special characteristics in RV function (RVF) that may distinguish them from HF with reduced or preserved ejection fraction (HFrEF or HFpEF) patients. Standard echocardiography was performed to estimate RVF [tricuspid annular systolic velocity (TDSV), plane systolic excursion (TAPSE), TAPSE to pulmonary artery systolic pressure (TAPSE/PASP) and RV myocardial performance index (MPI-TEI index)] in a cross-sectional study. In 306 participants, the RV systolic function evaluated with TAPSE and TDSV was impaired in 39.1 and 24.2%, respectively. TAPSE, TAPSE/PASP and TDSV were lower in HFmrEF compared with HFpEF and higher compared with HFrEF (p < 0.001 for among-groups comparison). RV diastolic dysfunction varied between 12.6 and 43.8% depending on the echocardiographic parameter. Diastolic RVF determined by tricuspid inflow E/A wave ratio (Et/At) was impaired in less patients with HFmrEF compared with those with HFpEF or HFrEF (25.9% vs 48.4% vs 56.3%; p = 0.030, respectively). RV diastolic dysfunction by et'/at' (tissue Doppler tricuspid valve annulus e' and a' waves) was impaired in less patients with HFmrEF compared with HFrEF (11.8% vs 33.3%; p = 0.019). A multivariate regression analysis revealed a significant association between RV and LV systolic dysfunction. The present study shows a high prevalence of RV dysfunction in HFmrEF patients. Study findings provides some new insights on RV and LV systolic dysfunction coupling whereas RV diastolic dysfunction was not dependent on LV systolic dysfunction.

Female Sexual Dysfunction: A Problem Hidden in the Shadows.

BACKGROUND: Female sexual dysfunction (FSD) has been largely underdiagnosed and undertreated due to the lack of concrete definitions, validated assessment methods and efficient treatments. However, during the last few decades, there has been great progress in the clinical management and research of FSD. OBJECTIVE: The purpose of this review is to describe the pathophysiology of FSD, report the prevalence of the disease in the setting of cardiovascular (CV) risk factors and disease, and review current and under investigation treatment options. METHODS: A comprehensive review was performed to identify studies examining the association of FSD with CV risk factors and/or disease, as well studies reporting relevant management options. RESULTS: The prevalence of FSD is increased in the general population (approximately 40%) and is significantly higher in patients with hypertension, diabetes mellitus, and dyslipidemia. In patients with overt CV disease, FSD is even more prevalent (up to 90%). The cause of FSD is multifactorial and includes a variety of vascular, hormonal, interpersonal and psychological factors, which are all intertwined. Several treatment options exist that are efficient in improving female sexual function, while a cluster of other options has been shown to offer benefits. CONCLUSION: FSD is a major public health problem with great impact on the patients' quality of life. In the setting of increased CV burden, FSD is even more prevalent. Increased awareness is needed for the physician to establish a trustful environment with the patient, discuss such issues, and offer proper management options.

Erectile Dysfunction as a Cardiovascular Risk Factor: Time to Step Up?

BACKGROUND: Erectile dysfunction (ED) is a major health problem that affects a significant proportion of the general population, and its prevalence is even higher in patients with CV risk factors and/or disease. ED and cardiovascular (CV) disease share several common pathophysiological mechanisms, and thus, the potential role of ED as a predictor of CV events has emerged as a significant research aspect. OBJECTIVE: The purpose of this review is to present and critically discuss data assessing the relation between ED and CV disease and the potential predictive value of ED for CV events. METHODS: A comprehensive review of the literature has been performed to identify studies evaluating the association between ED and CV disease. RESULTS: Several cross-sectional and prospective studies have examined the association between ED and CV disease and found an increased prevalence of ED in patients with CV disease. ED was shown to independently predict future CV events. Importantly, ED was found to precede the development of overt coronary artery disease (CAD) by 3 to 5 years, offering a "time window" to properly manage these patients before the clinical manifestation of CAD. Phosphodiesterase type 5 inhibitors are the first-line treatment option for ED and were shown to be safe in terms of CV events in patients with and without CV disease. CONCLUSION: Accumulating evidence supports a strong predictive role of ED for CV events. Early identification of ED could allow for the optimal management of these patients to reduce the risk for a CV event to occur.

Transesophageal Overdrive Pacing in a Patient with Atrial Tachycardia and ß -Thalassemia Major. A Challenging Simplicity.

INTRODUCTION: Transesophageal overdrive pacing is an accepted method for the diagnosis and treatment of supraventricular tachycardias, although is not used frequently in clinical practice. CASE REPORT: A 47 years old woman is reported with a medical history of ß -Thalassemia Major admitted to our hospital with atrial tachycardia of recent onset and successfully converted using a transesophageal overdrive atrial pacing. CONCLUSION: Transesophageal overdrive atrial pacing is a low cost, simple and safe procedure that can be performed at the bedside, especially in patients, as those with ß -Thalassemia Major, whose health status makes difficult the usage of medicines that could possibly aggravate their general health status.

Macrovascular Complications of Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has emerged as a pandemic. It has different complications, both microvascular and macrovascular. OBJECTIVE: The purpose of this review is to summarize the different types of macrovascular complications associated with T2DM. METHODS: A comprehensive review of the literature was performed to identify clinical studies, which determine the macrovascular complications associated with T2DM. RESULTS: Macrovascular complications of T2DM include coronary heart disease, cardiomyopathy, arrhythmias and sudden death, cerebrovascular disease and peripheral artery disease. Cardiovascular disease is the primary cause of death in diabetic patients. Many clinical studies have shown a connection between T2DM and vascular disease, but almost always other risk factors are present in diabetic patients, such as hypertension, obesity and dyslipidaemia. CONCLUSION: T2DM causes a variety of macrovascular complications through different pathogenetic pathways that include hyperglycaemia and insulin resistance. The association between T2DM and cardiovascular disease is clear, but we need more clinical studies in order to identify the pure effect of T2DM.

Glycemic efficacy and safety of glucagon-like peptide-1 receptor agonist on top of sodium-glucose co-transporter-2 inhibitor treatment compared to sodium-glucose co-transporter-2 inhibitor alone: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). The purpose of this meta-analysis was to provide precise effect estimates regarding the safety and efficacy of the addition of a GLP-1RA on top of SGLT-2i treatment. RESEARCH DESIGN AND METHODS: PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration ≥ 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. We also used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the credibility of our summary estimates. RESULTS: We identified three eligible RCTs, pooling data retrieved from 1,042 patients with T2DM in total. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in significant decrease in HbA1c by 0.91% (95% CI; -1.41 to -0.42) [GRADE: moderate], in body weight by 1.95 kg (95% CI; -3.83 to -0.07) [GRADE: moderate], in fasting plasma glucose by 1.53 mmol/L (95% CI; -2.17 to -0.88) [GRADE: moderate] and in systolic blood pressure levels by 3.64 mm Hg (95% CI -6.24 to -1.03). No significant effects on lipid profile and diastolic blood pressure were demonstrated. A significant increase in the risk for any hypoglycemia (RR: 2.62, 95% CI; 1.15-5.96, I2 = 33%) [GRADE: moderate] and for nausea (RR: 3.21, 95% CI; 1.36-7.54, I2 = 63%) [GRADE: moderate] and a non-significant increase in the risk for diarrhoea (RR: 1.64, 95% CI; 0.98-2.75, I2 = 0%) [GRADE: low] were documented. No other safety issues were identified. CONCLUSIONS: This meta-analysis suggests that a GLP-1RA/SGLT-2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.

Right Ventricular Function and Sexual Function: Exploring Shadows in Male and Female Patients With Heart Failure.

INTRODUCTION: Sexual health plays an important role in heart failure (HF) patients, and the relationship between HF and sexual dysfunction is well established; however, the role of right ventricular function in sexual dysfunction has not been investigated sufficiently. AIM: To investigate the potential association between right ventricular dysfunction and sexual dysfunction in both male and female patients with HF. METHODS: Patients with a clinical diagnosis of HF were evaluated in a cross-sectional study. Patients from the whole spectrum of HF were included in the study, regardless of cause, duration, and classification of HF. Sexual function in men was evaluated with the International Index of Erectile Function and in women with the Female Sexual Functioning Index. MAIN OUTCOME MEASURES: We demonstrate that right ventricular dysfunction is associated with worse sexual function in both men and women. RESULTS: 306 consecutive patients with HF participated in the study. Right ventricular systolic dysfunction ranged from 24.2-39.1% and right ventricular diastolic dysfunction from 16.1-83.1%, depending on the echocardiographic parameter that was assessed. Right ventricular systolic dysfunction assessed by tricuspid annular plane systolic excursion (TAPSE), TAPSE/pulmonary artery systolic pressure ratio, and right ventricular basal diameter was associated with a lower International Index of Erectile Function score (P = .031, P = .009, and P < .001, respectively). Multiple linear regression analysis revealed that erectile function was independently associated only with TAPSE/pulmonary artery systolic pressure ratio and tricuspid late tricuspid diastolic flow velocity wave (ß = 32.84, P = .006; and ß = -0.47, P = .026, respectively), whereas female sexual function was independently associated only with the early tricuspid diastolic flow velocity/late tricuspid diastolic flow velocity ratio (ß= -0.47, P = .026). CLINICAL IMPLICATIONS: Our study demonstrates that right ventricular dysfunction in patients with HF reflects an impaired sexual function status. Physicians should be aware of this association and closely evaluate those patients for sexual dysfunction. STRENGTHS & LIMITATIONS: We innovatively assessed the correlation between right ventricular dysfunction and sexual function using validated questionnaires. The main limitation is the relatively small sample size. CONCLUSIONS: Our study provides some new insights into the relationship between sexual dysfunction and right ventricular systolic and diastolic dysfunction in HF patients, also suggesting potential interventions to improve sexual and right ventricular function and prognosis in this population. Koutsampasopoulos K, Vogiatzis I, Ziakas A, et al. Right Ventricular Function and Sexual Function: Exploring Shadows in Male and Female Patients With Heart Failure. J Sex Med 2019;16:1199-1211.

Role of PCSK9 Inhibitors in High Risk Patients with Dyslipidemia: Focus on Familial Hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is characterized by substantially increased Low-Density Lipoprotein Cholesterol (LDL-C) levels. Patients with FH have a significantly higher risk for Cardiovascular (CV) events, and the timely reduction of LDL-C is of paramount importance to ameliorate the risk for CV disease. Among the available lipid-lowering therapies, the novel Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors have emerged as a very promising class of drugs for the management of such patients. OBJECTIVE: The purpose of this review is to present available data on the efficacy and safety of the two available PCSK9 inhibitors in patients with FH, and importantly to discuss potential differences between the two drugs. METHODS: A comprehensive literature search was performed to identify available data from clinical studies evaluating the impact of evolocumab or alirocumab on lipid and CV parameters in patients with FH. RESULTS: Several studies have assessed the lipid-lowering profile of PCSK9 inhibitors in patients with FH. Both evolocumab and alirocumab were found to significantly reduce LDL-C by more than 50-60% in FH patients. Furthermore, data also support a lower rate of lipid apheresis in FH patients receiving a PCSK9 inhibitor. In terms of CV outcomes, both drugs were found to possess CV-ameliorating effects of the same extent in patients with CV disease. However, alirocumab reduced all-cause mortality, as well, a finding not observed with evolocumab. Several differences in the study population characteristics might explain this and other mild differences observed in the CV trials of these drugs. CONCLUSION: Available evidence suggests similar potency of alirocumab and evolocumab in reducing lipids and CV events.

Exertional dyspnea after myocardial infarction: thinking beyond the diagnosis of heart failure.

INTRODUCTION: We herein present an unusual case of a pseudoaneurysm of the left ventricular myocardium, which is a rare and fatal complication of myocardial infarction. CASE REPORT: A 64-year-old man with a history of bipolar disorder and arterial hypertension was hospitalized for delayed presentation ST-elevation myocardial infarction. He was admitted to our hospital 24 hours after symptom onset. Diagnostic coronary angiography revealed 95% stenosis at the distal third of the right coronary artery, and he underwent a primary percutaneous coronary intervention to the culprit lesion. Despite administration of a diuretic and optimization of other pharmaceutical treatment, his heart failure deteriorated. Electrocardiography showed a sinus rhythm with Q-wave formation in the inferior wall leads (II, III, aVF), T-wave inversion in the same leads, and borderline QT prolongation (QTc of 490 ms). No ST elevation suggestive of left ventricular aneurysm formation was noticed. Forty days later, cardiac ultrasound revealed a dyskinetic cavity (pseudoaneurysm) in continuity with the posterior-inferior wall of the myocardium, resulting in severe mitral valve regurgitation. Unfortunately, the patient died while awaiting surgical treatment. CONCLUSION: Although most patients with left ventricular pseudoaneurysm have a relatively benign outcome, those with symptoms of heart failure must be urgently diagnosed and treated.

Mineralocorticoid Receptor Antagonists in Primary Aldosteronism.

BACKGROUND: Primary aldosteronism is the most common causes of secondary hypertension. Patients suffering from this clinical syndrome have an increased cardiovascular risk and target organ damage. Mineralocorticoid receptor antagonists are the optimal pharmaceutical option for the management of such patients. OBJECTIVES: The study aimed to assess the effects of mineralocorticoid receptor antagonist in the treatment of patients with primary aldosteronism. METHOD: We conducted an in-depth review of the literature and comprehensive identification of the clinical studies investigating the efficacy of mineralocorticoid receptor antagonists in individuals with primary aldosteronism. RESULTS: Mineralocorticoid receptor antagonists result in significant improvement in blood pressure and serum potassium level among patients with primary aldosteronism. Moreover, mineralocorticoid receptor antagonists reverse left ventricular hypertrophy, albuminuria, and carotid intima-media thickness. However, a high risk for atrial fibrillation remains among subject with primary aldosteronism in such agents. CONCLUSION: Mineralocorticoid receptor antagonists are recommended as the first-line treatment in patients with bilateral primary aldosteronism. In patients with unilateral aldosterone-producing adenoma, adrenalectomy should be preferred. However, existing data presents significant limitations and is rather inconclusive. Future randomized control trials are required in order to illustrate the field.

Neuroendocrine tumor in the liver of a patient with isolated polycystic liver disease: A case report and review of the literature.

Neuroendocrine tumors (NETs) frequently metastasize to the liver, but it is rare to find them there as primary tumors. Isolated polycystic liver disease (PCLD) is a rare autosomal dominant disease. There is no known association between polycystic liver disease and neuroendocrine or other tumors. We report a case of a 64-year-old female with a past medical history of isolated PCLD who presented with increasing abdominal pain over a two-week period. Our patient underwent open surgical biopsy one month after presentation. The histological examination and immunohistochemical findings suggested an intermediate grade neuroendocrine tumor. A 24-h delayed whole-body scintigraphy technique was utilized for the identification and localization of neuroendocrine tumors via the administration of In-111-labeled OctreoScan; however, no extrahepatic accumulation was observed. No previous studies in the literature describe a patient with PCLD and a primary or metastatic neuroendocrine tumor of the liver.