A Case Report of Systemic Sclerosis Complicated by Biventricular Heart Failure, Pulmonary Hypertension and Review of Literature

Background: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder whose aetiology is not fully understood. Skin fibrosis and visceral organs involvement are the hallmarks, and the heart could be disproportionately or subtly involved. Cardiovascular manifestations could include arrhythmias, pericarditis, myocardial fibrosis, pulmonary hypertension and congestive heart failure. Pulmonary involvement could cause lung fibrosis, arteriolar thickening, and pulmonary hypertension. The presence of these manifestations confers a poor prognosis. Case Report: The case report presents a 50-year-old male patient with generalized skin sclerosis, hypo and hyperpigmented skin lesions, dyspnoea at rest, displaced apical impulse, tachycardia and pan-systolic murmur at the apex radiating to the axilla. Echo cardiography features showed ejection fraction of 33.3% with dilated atrial and ventricular chambers. Conclusions: We present a case systemic sclerosis complicated by biventricular heart failure and pulmonary hypertension

Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

INTRODUCTION: Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. METHODS: Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up. RESULTS: Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. CONCLUSIONS: A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases

Statins and the vasculopathy of systemic sclerosis: potential therapeutic agents?

It has been postulated that endothelial cell injury is the initiating event in the pathogenesis of systemic sclerosis, causing attraction, attachment, migration and infiltration of activated T-cells and subsequent production of cytokines and growth factors. As a result of the action of these cytokines and growth factors, chemoattraction of fibroblasts into the vessel wall and transdifferentiation of resident fibroblasts and smooth muscle cells into myofibroblasts occur leading to fibrosis and exaggerated collagen deposition in the vessel wall. To date, the therapeutic options for the vasculopathy of systemic sclerosis have been limited to drugs that cause vasodilation and inhibit platelet aggregation and only a few agents have shown vascular remodeling effects. Therapeutic agents that could potentially modify the course of this vasculopathy may have a disease-modifying effect, particularly, if instituted in the early stages of the disease. Extensive recent studies have shown that statins display numerous effects independent of their well-established lipid-lowering effect that may be of potential benefit in preventing vascular injury and ischemic vascular events. Here, we review the current literature, which suggests that statins may have a modifying effect on the vasculopathy of systemic sclerosis

Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group

Introduction: Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. Method: This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. Results: Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. Conclusions: Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

&lt;b&gt;Background&lt;/b&gt; Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Cardiotoxicity with vascular endothelial growth factor inhibitor therapy

Angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway (VSP) have been important additions in the therapy of various cancers, especially renal cell carcinoma and colorectal cancer. Bevazicumab, the first VSP to receive FDA approval in 2004 targeting all circulating isoforms of VEGF-A, has become one of the best-selling drugs of all times. The second wave of tyrosine kinase inhibitors (TKIs), which target the intracellular site of VEGF receptor kinases, began with the approval of sorafenib in 2005 and sunitinib in 2006. Heart failure was subsequently noted, in 2–4% of patients on bevacizumab and in 3–8% of patients on VSP-TKIs. The very fact that the single-targeted monoclonal antibody bevacizumab can induce cardiotoxicity supports a pathomechanistic role for the VSP and the postulate of the “vascular” nature of VSP inhibitor cardiotoxicity. In this review we will outline this scenario in greater detail, reflecting on hypertension and coronary artery disease as risk factors for VSP inhibitor cardiotoxicity, but also similarities with peripartum and diabetic cardiomyopathy. This leads to the concept that any preexisting or coexisting condition that reduces the vascular reserve or utilizes the vascular reserve for compensatory purposes may pose a risk factor for cardiotoxicity with VSP inhibitors. These conditions need to be carefully considered in cancer patients who are to undergo VSP inhibitor therapy. Such vigilance is not to exclude patients from such prognostically extremely important therapy but to understand the continuum and to recognize and react to any cardiotoxicity dynamics early on for superior overall outcomes

Quantitative and Qualitative Analysis on Sex and Gender in Preparatory Material for National Medical Examination in Germany and the United States

Background: Sex- and gender-based medicine (SGBM) should be a mandatory part of medical education. We compared the quantity and quality of sex- and gender-related content of e-learning materials commonly used by German and American medical students while preparing for national medical examinations. Methods: Quantitative, line-by-line analysis of the preparatory materials AMBOSS 2017 and USMLE Step 1 Lecture Notes (2017) by KAPLAN MEDICAL was performed between April and October 2017. Subjects were allocated to one of the three main fields: clinical subjects, behavioral and social science, and pharmacology. Qualitative analysis comprised binary categorization into sex- and gender-based aspects and qualification with respect to the presence of a pathophysiological explanation for the sex or gender difference. Results: In relation to the total content of AMBOSS and KAPLAN, the sex- and gender-based share of the clinical subjects content was 26.8% (±8.2) in AMBOSS and 21.1% (±10.2) in KAPLAN. The number of sex- and gender-based aspects in the behavioral and social science learning material differed significantly for AMBOSS and KAPLAN (4.4% ± 3.1% vs 10.7% ± 7.5%; P = .044). Most of the sex- and gender-related content covered sex differences. Most learning cards and texts did not include a detailed pathophysiological explanation for sex- or gender-based aspects. The knowledge provided in the preparatory documents represents only a small part of facts that are already known about sex and gender differences. Conclusions: The preparatory materials focused almost exclusively on biological sex differences and the sociocultural dimension in particular is underrepresented. A lot more evidence-based facts are known and should be integrated into the materials to reflect the importance of SGBM as an integral component of patient-centered medicine

Bosentan for digital ulcers prevention does not worsen cardiopulmonary exercise test parameters in SSc patients with interstitial lung disease

Bosentan for digital ulcers prevention does not worsen cardiopulmonary exercise test parameters in SSc patients with interstitial lung diseas