David Rodriguez

A systematic review of genetic mutations in pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9.MethodsTo provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests.ResultsOur results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH.ConclusionOur systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.

Venous thromboembolism: thrombosis, inflammation, and immunothrombosis for clinicians

Venous thromboembolism (VTE) is a worldwide disease related with mortality, cardiovascular disability, impaired quality of life and, cause major long-term complications. Clinicians related to the acute and long-term patients care must be involved in the molecular mechanisms of thrombosis. The vessel wall and its inner lining of the endothelium are critical to the maintenance of a patent vasculature. After endothelial disruption, collagen (first line of endothelial defense) and intravascular tissue factor (second line of endothelial defense) are exposed to blood flow, starting the formation of a thrombus. Anticoagulant endovascular proteins and endogenous fibrinolysis have an active role in hemostasis. Currently, the process of coagulation is a cell surface-based model that includes three overlapping phases: initiation, amplification, and propagation. From a simple view, inflammation is one of the first responses of the immune system to infection; inflammation is driven by eicosanoids and cytokines, which are released by injured or infected cells. Common cytokines, which regulate inflammatory response, include interleukins (mainly interleukin-6) that are responsible for communication among white blood cells, chemokines that promote chemotaxis, and interferons that have anti-viral effects. Acute infections have been associated with a transient increase in the risk of myocardial infarction, stroke and recently with venous thrombosis, supporting the notion that systemic and respiratory infections increase the risk of thromboembolic events. Recently, immunothrombosis, another thrombosis mechanism that includes innate immune mechanisms, the neutrophil extracellular genetic traps, and the immunothrombosis dysregulation, could explain some cases of “unprovoked” VTE especially in elderly, a high-risk population for thrombosis.

Ischaemic stroke from a large mitral vegetation as clinical presentation of infective endocarditis

Neurological complications appear in 20–40% of patients with left-side infective endocarditis; one-half of them correspond to ischaemic stroke, 20% to cerebral haemorrhage, and 30% to other complications (transient ischaemic attack, meningitis, infectious aneurysm, brain abscess). A 45-year-old woman presented with right-sided hemiparesis and dysarthria. She had a 5-day history of intermittent fever, malaise, and polyarthralgia. Patient denied …

Stress Transient Hypertrophic Cardiomyopathy and B-Type Natriuretic Peptide Role

This report describes a transient hypertrophic cardiomyopathy with right-ventricle outlet tract obstruction (RVOTO) induced by perinatal stress due to a major surgical procedure in a female newborn with congenital abnormalities. On day 10, she presented with heart failure, abnormal B-type natriuretic peptide (BNP), and an echocardiogram showing normal wall thickness. An in-hospital follow-up echocardiogram showed biventricular hypertrophy and RVOTO. At discharge, the infant was asymptomatic, with a normal echocardiogram and BNP. Transient RVOTO triggered by surgical stress and abnormal BNP have not been reported previously. Pathophysiology, the role of BNP, and clinical characteristics are discussed.

The use of cardiac CT as a roadmap for resolving coronary stent dislodgement

Stent dislodgement of an unexpanded stent is a rare and potentially severe complication of percutaneous coronary interventions that can result in emergent coronary artery bypass graft surgery, embolization, or death. Several approaches have been used to identify and resolve this unusual complication; however, the best strategy, as well as the role of cardiac computed tomography (CT) in this clinical scenario, remains unknown. We report the case of an 83-year-old male with the previous history of ischemic heart disease, paroxysmal atrial fibrillation, and stroke. The patient underwent failed percutaneous coronary intervention of a proximal heavily calcified lesion in the left anterior descending coronary artery, which resulted in the dislodgment of a 2.5 mm × 2.5 mm unexpanded stent. The initial

Giant coronary ectasia and athlete's heart mimicking an acute coronary syndrome

Coronary artery ectasia is observed in 0.3--5% of diagnostic angiograms; >50% of cases are related to coronary atherosclerosis, 20--30% are congenital and up to 20% are related to connective tissue or inflammatory diseases. The impact of strenuous exercise on the left ventricle’s structure has been demonstrated. Studies with ECGs and echocardiography discovered a high prevalence of increased cardiac voltage, suggestive of left ventricle enlargement and hypertrophy respectively. Coronary artery anomalies have been described in 14% of athletes. A 37-year-old man, a retired professional football soccer player with history of syncope upon exertion, presented to the ED with ischemic acute chest pain at rest. On admission, his pulse was 70 beats/min, blood pressure 146/85 mmHg. Physical examination was normal. ECG revealed ST dynamic changes and negative deep T waves on anterior-lateral region (Fig. 1A and B). Laboratory tests revealed normal values of cardiac biomarkers.

B-type natriuretic peptide reference interval of newborns from healthy and pre-eclamptic women: a prospective, multicentre, cross-sectional study

Objective To define and compare the reference interval of B-type natriuretic peptide (BNP) in healthy newborns (HN) from healthy mothers and with severe pre-eclampsia. Design Prospective, multicentre, cross-sectional study. Setting Four obstetric wards of second-level academic hospitals. Participants 167 HN, from 146 healthy and 21 severe pre-eclamptic women. We included newborns from healthy mothers with full-term pregnancies (38 to 42 gestational weeks), who received adequate prenatal care and who had Apgar scores ≥7 at 0 and 5 min. Newborns with chromosomopathies identified during prenatal consultations, those with respiratory distress and those with cardiac or pulmonary disease detected in the first paediatric evaluation were excluded from this study. In the group of pre-eclamptic women, we considered the same inclusion criteria, but the patients also had to meet the diagnostic criteria for pre-eclampsia with severity features, according to the American College of Obstetricians and Gynaecologists guidelines. The same exclusion criteria used for the healthy group were applied to the pre-eclampsia-associated newborn. Interventions A single blood sample from the umbilical cord artery after delivery (vaginal or caesarean section). Primary outcome Reference level of BNP in HN. Results In the HN group, the median BNP was 12.15 pg/mL (IQR 7.7–16.8 pg/mL) and in the pre-eclamptic group 20.8 pg/mL (IQR 5.8–46.5 pg/mL). The reference interval for BNP in HN was 5pg/mL (95% CI 5 to 5) to 34 pg/mL (95% CI 28.4 to 38.8). We identified higher expression of BNP in newborns from pre-eclamptic women overall (p=0.037, r=0.16) and in newborns exposed to stress conditions, such as complications during labour and delivery (p=0.004, r=0.33). Conclusions In HN, BNP concentrations at birth were lower than reported in other similar populations. In neonates with stress conditions, the higher expression of this biomarker establishes another possible link between stress and the cardiovascular response. Trial registration number NCT02574806; Pre-results.

Factor Xa inhibition and sPESI failure in intermediate-high-risk pulmonary embolism

We report the case of a 61-year-old man who presented at the Emergency Department (ED), complaining of sudden-onset dyspnea and chest pain after a long flight from Tokyo to Houston. Considering his clinical stability and sPESI 0, enoxaparin 1 mg/kg BID was started for 24 h, and the patient was then considered for early discharge with apixaban 10 mg BID. Direct-factor Xa inhibition did not improve extensive thrombus burden and right ventricular dysfunction despite D-dimer measurement reduction. Because of the treatment failure, we considered thrombolysis. Currently, recommendations to use thrombolysis in patients under non-vitamin K antagonist oral anticoagulants (NOACs) do not exist. Hence, the one dose of apixaban was stopped, and 12 h later, we performed successful thrombolysis. A systematic review from 2007 to 2017 did not identify any cases related to NOACs failure to reduce thrombus burdens in patients with PE and persistent right ventricular dysfunction. We also did not find any evidence of cases that reported strategies for urgent thrombolysis in PE patients on NOACs. To the best of our knowledge, apixabans failure to reduce thrombus burden, persistent right ventricular dysfunction, and a NOACs-thrombolysis bridge in patients with PE on apixaban has not been previously described. Both the bedside risk stratification and the therapeutic failures should alert clinicians in the ED to the potential limitations of low-molecular-weight heparin, NOACs therapy, and sPESI in the setting of intermediate-high-risk PE.

Inferior vena cava filters in pulmonary embolism: A historic controversy.

OBJECTIVE Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. METHODS Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. RESULTS IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. CONCLUSION Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.