Development and internal validation of a clinical score to predict neonatal hypoglycaemia in women with gestational diabetes.

INTRODUCTION: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. OBJECTIVES: To create a score to predict NH in women with GD. METHODS: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. RESULTS: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599-0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27-1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29-2.15), 2.24 (1.65-3.04), 2.83 (2.02-3.98), 3.08 (1.83-5.16), and 6.84 (4.34-10.77), respectively. CONCLUSION: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH.

Atrioventricular block secondary to transient causes and long-term recurrence after an index event.

BACKGROUND: Atrioventricular block (AVB) secondary to transient causes can recover with its correction. However, studies assessing predictors of recovery and long-term recurrence are lacking. METHODS: Patients with advanced or complete AVB who had a reversible cause admitted in a single expert center were retrospectively studied. Patients with AVB secondary to acute coronary syndromes were excluded from analysis. RESULTS: In a population of 162 patients, the main factors associated with recovery of rhythm without a permanent pacemaker (PPM) implantation were the presence of chronic kidney disease (CKD) on dialysis (OR 7.6; CI 95% 1.2-47.5 (p = .03)); greater serum potassium levels (OR 2.3; CI 95% 1.28-4.0 (p < .01)), higher dosage of bradycardic drugs (OR 2.2; CI 95% 1.13-4.4 (p = .02)), the association between different bradycardic drugs (OR 9.0; CI 95% 2.02-40.3 (p < .01)) and between drug therapy and hyperkaliemia (OR 5.2; CI 95% 1.8-15.1 (p < .01)). There was an overall high burden of conductions abnormalities which did not correlate with recovery of rhythm (OR 0.5; CI 95% 0.19-1.5 (p = .23)). In 29 patients (17.9%) there was a correction of the AVB. During a maximum follow-up of 130 months, 24 patients (82.8%) had a recurrence which warranted a PPM. In the overall cohort only five patients (3%) had sustained recovery of rhythm. CONCLUSIONS: Recovery of AVB was mainly observed with higher doses of drug therapy, higher serum potassium levels or a combination of factors and regardless of baseline conduction abnormalities. The high rate of recurrence during follow-up warrants a close follow-up or PPM implantation at index admission.

The challenging approach of a young patient with a primary intimal sarcoma of the heart: a case report.

Background: Primary intimal sarcomas of the heart are extremely rare and have a dismal prognosis. Their management represents a complex clinical challenge since complete surgical resection is the only reliable possibility of cure but is only possible in 50% of patients. In non-resectable disease, anthracycline-based therapy is the most effective treatment, but pazopanib may be used in patients unfit to receive anthracyclines. Case summary: A 38-year-old man presented with acute right heart failure symptoms due to a primary intimal sarcoma of the heart. A definite diagnosis was made after cardiac surgery. Multi-modality cardiac imaging showed early recurrence of disease with mitral valve and pulmonary veins' invasion, and the patient was deemed inoperable. Due to chronic kidney disease and previous heart failure symptoms, he was started on first-line pazopanib palliative treatment. After 11 months of chemotherapy, there was good clinical tolerance and no evidence of disease progression, which occurred after 13 months. Discussion: This case highlights the value of a multi-modality imaging approach for cardiac masses. Most importantly, it reports the successful treatment of a young patient with a primary intimal sarcoma of the heart who was started on palliative pazopanib, with a significantly higher progression-free survival than is reported in the literature. This finding may support pazopanib as a good alternative as first-line treatment when there is contraindication for anthracycline-based chemotherapy.

Association between foetal sex and adverse neonatal outcomes in women with gestational diabetes.

AIMS: Foetal male sex is associated with adverse perinatal outcomes. However, studies evaluating the impact of foetal sex on perinatal outcomes in women with gestational diabetes (GDM) are scarce. We studied whether male new-born sex is associated with neonatal outcomes, in women with GDM. METHODS: This is a retrospective study based on the national Portuguese register of GDM. All women with live-born singleton pregnancies between 2012 and 2017 were eligible for study inclusion. Primary endpoints under analysis were neonatal hypoglycaemia, neonatal macrosomia, respiratory distress syndrome (RDS) and neonatal intensive care unit (NICU) admission. We excluded women with missing data on the primary endpoint. Pregnancy data and neonatal outcomes between female and male new-borns were compared. Multivariate logistic regression models were built. RESULTS: We studied 10,768 new-borns in mothers with GDM, 5635 (52.3%) male, 438 (4.1%) had neonatal hypoglycaemia, 406 (3.8%) were macrosomic, 671 (6.2%) had RDS, and 671 (6.2%) needed NICU admission. Male new-borns were more frequently small or large for gestational age. No differences were observed on maternal age, body mass index, glycated haemoglobin, anti-hyperglycaemic treatment, pregnancy complications or gestational age at delivery. In the multivariate regression analysis, male sex was independently associated with neonatal hypoglycaemia [OR 1.26 (IC 95%: 1.04-1.54), p = 0.02], neonatal macrosomia [1.94 (1.56-2.41), p < 0.001], NICU admission [1.29 (1.07-1.56), p = 0.009], and RDS [1.35 (1.05-1.73, p = 0.02]. CONCLUSIONS: Male new-borns have an independent 26% higher risk of neonatal hypoglycaemia, 29% higher risk of NICU admission, 35% higher risk of RDS, and almost twofold higher risk of macrosomia, compared to female new-borns.

Underuse of reperfusion therapy with systemic thrombolysis in high-risk acute pulmonary embolism in a Portuguese center.

INTRODUCTION: Reperfusion therapy is generally recommended in acute high-risk pulmonary embolism (HR-PE), but several population-based studies report that it is underused. Data on epidemiology, management and outcomes of HR-PE in Portugal are scarce. OBJECTIVE: To determine the reperfusion rate in HR-PE patients, the reasons for non-reperfusion, and how it influences outcomes. METHODS: In this retrospective cohort study of consecutive HR-PE patients admitted to a thromboembolic disease referral center between 2008 and 2018, independent predictors for non-reperfusion were assessed by multivariate logistic regression. PE-related mortality and long-term MACE (cardiovascular mortality, PE recurrence and chronic thromboembolic disease) were calculated according to the Kaplan-Meier method. Differences stratified by reperfusion were assessed using the log-rank test. RESULTS: Of 1955 acute PE patients, 3.8% presented with hemodynamic instability. The overall reperfusion rate was 50%: 35 patients underwent systemic thrombolysis, one received first-line percutaneous embolectomy and one rescue endovascular treatment. Independent predictors of non-reperfusion were: age, with >75 years representing 12 times the risk of non-treatment (OR 11.9, 95% CI 2.7-52.3, p=0.001); absolute contraindication for thrombolysis (31.1%), with recent major surgery and central nervous system disease as the most common reasons (OR 16.7, 95% CI 3.2-87.0, p<0.001); and being hospitalized (OR 7.7, 95% CI 1.4-42.9, p=0.020). At a mean follow-up of 2.5±3.3 years, the survival rate was 33.8%. Although not reaching statistical significance for hospital mortality, mortality in the reperfusion group was significantly lower at 30 days, 12 months and during follow-up (relative risk reduction of death of 64% at 12 months, p=0.013). Similar results were found for MACE. CONCLUSIONS: In this population, the recommended reperfusion therapy was performed in only 50% of patients, with advanced age and absolute contraindications to fibrinolysis being the main predictors of non-reperfusion. In this study, thrombolysis underuse was associated with a significant increase in short- and long-term mortality and events.

Prevalence and predictors of chronic thromboembolic pulmonary hypertension following severe forms of acute pulmonary embolism.

INTRODUCTION AND OBJECTIVES: The true prevalence of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) in the Portuguese population remains unknown. We aimed to assess the prevalence and predictors of CTEPH two years after a symptomatic high- (HR) or intermediate-high risk (IHR) PE. METHODS: We conducted a retrospective cohort study of patients admitted with PE between 2014 and 2019 to a Portuguese referral center for pulmonary hypertension. RESULTS: In this single-center registry of 969 patients admitted with PE (annual incidence of 46/100000 population), 194 had HR (5.4%) and IHR (14.7%) PE. After excluding patients who died or had no follow-up in the first three months, 129 patients were included in the analysis. The overall prevalence of suspected CTEPH by clinical assessment, Doppler echocardiography and V/Q lung scan was 6.2% (eight patients). CTEPH was confirmed by right heart catheterization in four of these (3.1%). Increased pulmonary artery systolic pressure (PASP) at admission (OR 1.12; 95% CI 1.04-1.22; p=0.005) and the presence of varicose veins in the lower limbs (OR 7.47; 95% CI 1.53-36.41; p=0.013) were predictors of CTEPH. PASP >60 mmHg at admission identified patients with CTEPH at follow-up with sensitivity and specificity of 83.3% and 76.3%, respectively. All patients diagnosed with CTEPH had at least two radiological findings suggestive of CTEPH at the index event. CONCLUSIONS: In our cohort, the prevalence of CTEPH in survivors of severe forms of acute PE was 6.2%. PASP above 60 mmHg and supporting radiological findings on the index computed tomography scan are highly suggestive of acute-on-chronic CTEPH.

Percutaneous versus surgical revascularization of unprotected left main coronary artery: Data from the Portuguese Registry of Acute Coronary Syndromes (ProACS).

BACKGROUND: In acute coronary syndromes (ACS), the optimal revascularization strategy for unprotected left main coronary artery (ULMCA) culprit lesion has been under-investigated. Therefore, we compared clinical characteristics and short- and medium-term outcomes of percutaneous and surgical revascularization in ACS. METHODS AND RESULTS: Of 31886 patients enrolled in a multicenter, national, prospective registry study between October 2010 and December 2020, 246 (0.8%) had ULMCA as a culprit lesion and underwent percutaneous coronary intervention (PCI) alone (n=133, 54%) or coronary artery bypass grafting (CABG) alone (n=113, 46%). Patients undergoing PCI presented more frequently ongoing chest pain (68% versus 41%, p<0.001) and cardiogenic shock (25% versus 1%, p<0.001). Time from admission to revascularization was higher in surgical group with a median time to CABG of 4.5 days compared to 0 days to PCI (p<0.001). Angiographic success rate was 93.2% in patients who underwent PCI. Primary endpoint (all-cause death, non-fatal reinfarction and/or non-fatal stroke during hospitalization) occurred in 15.9% of patients and was more frequent in the PCI group (p<0.001). After adjustment, surgical revascularization was associated with better in-hospital prognosis (odds ratio (OR) 0.164; 95% confidence interval (CI), 0.04-0.64; p=0.009). Similar results were achieved after propensity score matching. No difference was found at one-year all-cause death. CONCLUSION: Percutaneous coronary intervention was the most common revascularization strategy in the ACS with ULMCA culprit lesion. PCI was preferred in unstable patients and presented a high angiographic success. CABG was often delayed and preferred in low-risk patients. At one-year follow-up, PCI and CABG conferred a similar prognosis. The two approaches appear complementary in this high risk cohort.

Maternal height as a predictor of glucose intolerance in the postpartum and its relationship with maternal pre-gestational weight.

PURPOSE: Short stature predicts higher risk of developing type 2 diabetes. We studied the association between height and glucose intolerance in women with gestational diabetes mellitus (GDM) and whether this association differed according to body mass index (BMI). METHODS: Retrospective study of the Portuguese GDM registry. EXCLUSION CRITERIA: missing data on postpartum oral glucose tolerance test (OGTT) or BMI. ENDPOINT: postpartum glucose intolerance (diabetes mellitus or prediabetes on the 6-8 weeks postpartum OGTT). Women were divided by mean height and compared. A multivariate logistic regression was used, and the analysis was stratified by BMI (cut-off: 30 kg/m2) and interaction was tested. RESULTS: We included 7402 women; mean height was 161.9 ± 6.2 cm. Taller women had lower BMI and lower rates of glucose intolerance (6.8 vs. 8.8%, p = 0.002). Women with BMI < 30 kg/m2 were taller than those with obesity. Height associated with glucose intolerance. The multivariate adjusted OR of glucose intolerance was 0.98 (95% CI 0.96-0.99), p = 0.001, per 1 cm increase in height. This association was only observed in women with BMI < 30 kg/m2: OR 0.97 (95% CI 0.95-0.99), < 0.001. There was no such association in women with BMI ≥ 30 kg/m2: OR 0.99 (95% CI 0.97-1.02), p = 0.65. P for interaction between BMI and height was 0.09. CONCLUSIONS: In non-obese pre-gestational women, height is inversely associated with postpartum glucose intolerance. Per 1 cm increase in height, women present a 3% decrease in the risk of developing diabetes mellitus or prediabetes.

Chronic management of pulmonary embolism in thromboangiitis obliterans.

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare small vessel vasculitis that is associated with an increased risk of arterial occlusion. Although venous thromboembolism has been described, the risk of its recurrence and the best long-term anticoagulation management is not known. Considering this, we would like to share our experience with two patients admitted to our hospital with recurrent pulmonary embolism and previous diagnosis of TAO, aiming to discuss the indication for indefinite anticoagulation in this population.

Large free-floating right atrial mass presenting as intermediate-high risk pulmonary embolism: is reperfusion a better definite strategy?

We present a woman in her 60s diagnosed with an intermediate-high risk acute pulmonary embolism and a large, non-serpiginous right atrial (RA) mass. Conservative therapy with unfractionated heparin was started and further assessment of the mass with cardiac MRI suggested thrombus as the most likely diagnosis. Despite 1 month of anticoagulation, mass size remained stable and surgical RA embolectomy and left pulmonary endarterectomy was performed. Histopathology confirmed thrombus. The patient died 10 weeks after surgery.

First trimester fasting glucose and glycated haemoglobin cut-offs associated with abnormal glucose homeostasis in the post-partum reclassification in women with hyperglycaemia in pregnancy.

Hyperglycaemia first detected during pregnancy is either gestational diabetes mellitus (GDM) or previous undiagnosed diabetes. We aimed to study if there were a first trimester fasting glycaemia (FTG) and a glycated haemoglobin (HbA1c) cut-off values associated with type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis (AGH) at the post-partum oral glucose tolerance test (OGTT) reclassification. We retrospectively studied a group of pregnant women from the Portuguese National Registry of GDM. Receiver-operating characteristic (ROC) curves were used to determine the best FTG and HbA1c cut-offs to predict T2DM and AGH. We studied 4068 women. The area under the ROC curves (AUC) for the association with T2DM was 0.85 (0.80-0.90) for FTG and 0.85 (0.80-0.91) for HbA1c. The best FTG cut-off for association with T2DM was 99 mg/dL: sensitivity 77.4%, specificity 74.3%, positive predictive value (PPV) 4.8%, and negative predictive value (NPV) 99.5%. The best HbA1c cut-off for association with T2DM was 5.4%: sensitivity 79.0%, specificity 80.1%, PPV 5.7%, and NPV 99.6%. The AUC for the association of FTG and HbA1c with AGH were 0.73 (0.70-0.76) and 0.71 (0.67-0.74), respectively. The best FTG cut-off for predicting AGH was 99 mg/dL: sensitivity 59.4%, specificity 76.2%, PPV 17.0%, and NPV 95.8%. The best HbA1c cut-off was 5.4%: sensitivity 48.7%, specificity 81.5%, PPV 17.8%, and NPV 95.1%. We suggest an FTG of 99 mg/dL and an HbA1c of 5.4% as the best cut-offs below which T2DM is unlikely to be present. Almost all patients with FTG < 99 mg/dL and HbA1c < 5.4% did not reclassify as T2DM. These early pregnancy cut-offs might alert the physician for the possibility of a previous undiagnosed diabetes and alert them to the importance of testing for it after delivery.

The utility of prolactin serial sampling and the best prolactin cut-offs associated with persistent hyperprolactinemia.

BACKGROUND: A single prolactin sampling is recommended for the diagnosis of hyperprolactinemia. We aimed to study the utility of the prolactin serial sampling and to determine the best cut-offs associated with persistent hyperprolactinemia. METHODS: Retrospective study of hyperprolactinemic patients [referral prolactin (rPRL)] that underwent prolactin serial samplings. Prolactin at 0 minutes (PRL0'), 20 to 30, and 40 to 60 minutes. The lowest of these last 2 was defined as nadir prolactin (nPRL). Persistent hyperprolactinemia was defined as nPRL above normal. We excluded patients under dopamine receptor agonists. Receiver-operating characteristic (ROC) curves were used to determine the best rPRL and PRL0' cut-offs predicting persistent hyperprolactinemia. RESULTS: We studied 53 patients (3 males). Median rPRL 48.0 ng/mL (39.5-72.5), PRL0' 34.3 ng/mL (18.0-50.8) and nPRL 29.5 ng/mL (11.4-44.4). PRL0' was elevated in 35 (66.0%) patients and in 7 of them a normal nPRL was reached; therefore 28 (52.8%) had persistent hyperprolactinemia. The area under curve (AUC) for the association between rPRL and persistent hyperprolactinemia was 0.70 (95%CI: 0.56-0.84); best cut-off: 53.4 ng/mL [sensitivity 53.6%, specificity 80.0%, positive predictive value (PPV) 75.0%, and negative predictive value (NPV) 60.6%]. In the 35 patients with elevated PRL0', the AUC was 0.92 (95%CI: 0.81-1.00); best cut-off: 35.2 ng/mL (sensitivity 85.7%, specificity 85.7%, PPV 60.0%, and NPV 96.0%). CONCLUSIONS: Approximately 1/3 of the patients reached a normal PRL0'. In an additional 20%, prolactin normalized after serial samplings. Patients with rPRL >53.4 ng/mL had 75% probability of having persistent hyperprolactinemia and those with PRL0' <35.2 ng/mL had a 96% probability of not having persistent hyperprolactinemia.

Metformin combined with insulin in women with gestational diabetes mellitus: a propensity score-matched study.

AIM: Metformin use in gestational diabetes (GDM) is a common practice. Although its use in combination with insulin might be advantageous, it was never formally tested. We studied whether combined treatment was associated with better obstetric or neonatal outcomes compared to insulin alone. METHODS: This is a retrospective study, using the Portuguese National Registry of GDM (2012-2017), of women treated with insulin ± metformin. Primary endpoints were obstetric and neonatal complications. Secondary endpoints were gestational weight gain (GWG) and insulin dose. A propensity score-matched analysis was performed to balance the distribution of age, BMI, insulin treatment duration, HbA1c, first trimester diagnosis of GDM and previous GDM or macrosomia. Women treated with metformin plus insulin and insulin only were then compared. RESULTS: A total of 4034 women were treated with insulin or insulin plus metformin (10.2%). After propensity score matching, we studied two groups of 386 patients. Obstetric and neonatal complications were similar. Women treated with metformin plus insulin had 201 (52.1%) obstetric complications versus 184 (47.7%) in insulin-only group, p = 0.22; and 112 (29.0%) neonatal complications versus 96 (24.9%), p = 0.19. Patients treated with metformin plus insulin had similar GWG, excessive weight gain and insulin dose compared to the insulin-only group. CONCLUSIONS: Women with GDM treated with insulin plus metformin had similar obstetric and neonatal complications, weight gained and insulin dose compared to those only treated with insulin.