Barbara Lichodziejewska

Mean Platelet Volume Predicts Early Death in Acute Pulmonary Embolism

Background Recently, mean platelet volume (MPV) was reported to predict venous thromboembolism. Moreover, MPV correlates with platelet reactivity and indicates poor outcome in acute coronary syndromes. Objective To examine the hypothesis that in acute pulmonary embolism (APE) MPV is elevated and may predict mortality. Methods and results The study included consecutive 192 patients with APE, (79M/113F, 64±18 years) and 100 controls matched for age, sex and concomitant diseases. On admission blood samples were collected for MPV and troponin measurements. Although MPV did not differ between patients with APE and controls (10.0±1.2 vs 10.1±0.8 fl), it differed between low- and intermediate- or high-risk APE (9.4±1.2 fl, 10.3±1.1 fl, 10.3±1.8 fl; respectively, p<0.0001). Eighteen (9%) patients with APE died during the 30-day observation. MPV was higher in non-survivors than survivors (10.7±1.4 fl vs 9.9±1.2fl, p<0.01). The areas under receiver operating characteristic curves of MPV were 0.658 (95% CI 0.587 to 0.725) for predicting 30-day mortality, and 0.712 (95% CI 0.642 to 0.775) for 7-day mortality. MPV >10.9 fl, showed sensitivity, specificity, positive predictive value and negative predictive value for death within 30 days (39%, 81%, 18%, 93%, respectively) and for 7-day mortality (54%, 82%, 18%, 96%). Multivariable analysis showed that MPV was an independent mortality predictor for 7- and 30-day all-cause mortality (HR=2.0 (95% CI 1.3 to 3.0), p<0.001)) and 1.7 (95% CI 1.2 to 2.5), p<0.01)), respectively). MPVs were higher in patients with myocardial injury than in those without troponin elevation (10.2±1.1 fl vs 9.8±1.2 fl; p=0.02). There were correlations between MPV and right ventricular diameter and right ventricular dysfunction (r=0.28, p<0.01 and r=0.19, p<0.02, respectively). Conclusion MPV is an independent predictor of early death in APE. Moreover, MPV in APE is associated with right ventricular dysfunction and myocardial injury.

Prognostic Value of Echocardiography in Normotensive Patients With Acute Pulmonary Embolism

OBJECTIVES The goal of the study was to evaluate the prognostic value of echocardiographic indices of right ventricular dysfunction (RVD) for prediction of pulmonary embolism-related 30-day mortality or need for rescue thrombolysis in initially normotensive patients with acute pulmonary embolism (APE). BACKGROUND There is no generally accepted echocardiographic definition of RVD used for prognosis in APE. METHODS We studied the prognostic value of a set of echocardiographic parameters in 411 consecutive patients (234 women, age 64 ± 18 years) with APE hemodynamically stable at admission. RESULTS Thirty-day APE-related mortality was 3% (14 patients), all-cause mortality was 5% (21 patients). Nine patients received thrombolysis as a result of hemodynamic deterioration, and 7 of them survived. The clinical endpoint (CE), which included APE-related death or thrombolysis, occurred in 21 patients. At univariable Cox analysis, the hazard ratio (HR) for CE of the right ventricular (RV)/left ventricular (LV) ratio was 7.3 (95% confidence interval [CI]: 2.0 to 27.3; p = 0.003). However, multivariable analysis showed that tricuspid annulus plane systolic excursion (TAPSE) was the only independent predictor (HR: 0.64, 95% CI: 0.54 to 0.7; p < 0.0001). Moreover, the area under the curve (AUC) in receiver-operating characteristic analysis for TAPSE (0.91, 95% CI: 0.856 to 0.935; p = 0.0001) in CE prediction was higher (p < 0.001) than AUC of RV/LV ratio (0.638, 95% CI: 0.589 to 0.686; p = 0.001). TAPSE ≤15 mm had a HR of 27.9 (95% CI: 6.2 to 124.6; p < 0.0001) and a positive predictive value (PPV) of 20.9% for CE with a 99% negative predictive value (NPV), whereas TAPSE ≤20 mm had a PPV of 9.2 with a 100% NPV. RV/LV ratios of >0.9 and >1.0 had a PPV of 13.2% and 14.4% and a NPV of 97% and 94.3%, respectively. CONCLUSIONS TAPSE is preferable to the RV/LV ratio for risk stratification in initially normotensive patients with APE. TAPSE ≤15 mm identifies patients with an increased risk of 30-day APE-related mortality, whereas TAPSE >20 mm can be used for identification of a very low-risk group.

Clinical Symptoms of Mitral Valve Prolapse Are Related to Hypomagnesemia and Attenuated by Magnesium Supplementation

Mitral valve prolapse syndrome (MVP) is a frequent disorder characterized by a number of complaints which lessen the quality of life. The pathogenesis of MVP symptoms has not been fully elucidated. Hyperadrenergic activity and magnesium deficiency have been suggested. This study was designed to verify the concept that heavily symptomatic MVP is accompanied by hypomagnesemia and to elucidate whether magnesium supplementation alleviates the symptoms and influences adrenergic activity. We assessed serum magnesium in 141 subjects with heavily symptomatic primary MVP and in 40 healthy controls. Decreased serum magnesium was found in 60% of patients and in 5% of controls (p <0.0001). Patients with low serum magnesium were subjected to magnesium or placebo supplementation in a double-blind, crossover fashion. Typical symptoms of MVP (n = 13), intensity of anxiety, and daily excretion of catecholamines were determined. After 5 weeks, the mean number of symptoms per patient decreased from 10.4 +/- 2.1 to 5.6 +/- 2.5 (p <0.0001), and a significant reduction in weakness, chest pain, dyspnea, palpitations, and anxiety was observed. Increased noradrenaline excretion before and after magnesium was seen in 63% and 17% of patients, respectively (p <0.01). Mean daily excretion of noradrenaline and adrenaline was significantly diminished after magnesium. It is concluded that many patients with heavily symptomatic MVP have low serum magnesium, and supplementation of this ion leads to improvement in most symptoms along with a decrease in catecholamine excretion.

Refined balloon pulmonary angioplasty driven by combined assessment of intra-arterial anatomy and physiology – Multimodal approach to treated lesions in patients with non-operable distal chronic thromboembolic pulmonary hypertension – Technique, safety and efficacy of 50 consecutive angioplasties

BACKGROUND/OBJECTIVES Balloon pulmonary angioplasty (BPA) is an emerging therapeutic method in CTEPH. We aimed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy (IVUS/OCT) and physiology (pulmonary pressure ratio, PPR) in non-operable distal CTEPH. METHODS 11 pts (mean age 76, 59–84, 7 males) were enrolled in the BPA program according to the following inclusion criteria: 1. Non-operable CTEPH; 2. RHC with mPAP > 30 mm Hg; 3. At least one segmental perfusion defect at lung scintigraphy; 4. WHO class > II. Overall, 9 pts underwent 27 BPA sessions (mean 3 sessions per patient, range 1–5), 50 pulmonary arteries were dilated (mean 6 vessels per patient, range 3–9; 2.03 dilated arteries per session). All the angioplasties were performed according to an algorithm, which incorporated anatomical and functional assessment of targeted lesions. RESULTS We performed BPA of 32 web lesions, 5 ring-like stenosis and 13 complete obstructions. BPA resulted in clinical and hemodynamic improvement. WHO class improved from pre-BPA to post-BPA (p = 0.018), and 6 MWD increased from 304 m to 384 m (p = 0.03), NT-proBNP dropped from 1248 pg/ml to 730 pg/ml (p < 0.001). Mean PAP and PVR decreased (p = 0.01), while CO and CI increased (p = 0.01). All dilated arteries were patent at angiographic reassessment. No significant complications occurred and all treated patients are still alive. Insignificant transient reperfusion pulmonary oedema occurred in only 2 patients, who responded well to supplemental oxygen. CONCLUSIONS Refined BPA with assessment of intrapulmonary physiology using a pressure wire and precise evaluation of anatomy with IVUS and OCT provides hemodynamic and functional improvement, with minimal complications in distal non-operable CTEPH. This observation requires further validation in a large prospective study.

Electrocardiographic criteria of left ventricular hypertrophy in patients with morbid obesity.

Background: Obesity is frequently accompanied by systemic hypertension complicated by left ventricular hypertrophy (LVH). Standard electrocardiography (ECG) is generally accepted screening tool for LVH in systemic hypertension. The aim was to assess currently used ECG criteria in the diagnosis of LVH in morbidly obese patients.

Heart diastolic dysfunction in patients with systemic sclerosis

Introduction There are limited data on left (LV) and right ventricular (RV) diastolic function in systemic sclerosis (SSc) patients especially in relation to biomarkers of matrix remodeling. The aim of the study was to analyze LV and RV myocardial diastolic function in SSc patients at baseline and after at least 1 year of follow-up and its relation to serum tissue inhibitors of metalloproteinase 1 (TIMP-1) level. Material and methods We prospectively studied 111 SSc patients (101 female, 10 male, age 54.2 ±13.8 years) and 21 age-matched controls (18 female, 3 male, age 49.3 ±10.5 years). After at least 1 year of observation (3.0 ±1.1 years) we reevaluated 69 of the SSc patients. Transthoracic echocardiography (Philips, iE33) for assessment of LV and RV diastolic function was performed and TIMP-1 serum level was measured. Results Impaired LV relaxation was observed in 38 (34%) SSc patients and in 1 (5%) of the controls (p < 0.001). The mean E/A ratio was lower in patients with SSc than in controls (p = 0.002) and significantly decreased after the follow-up period (p = 0.02). Impaired RV relaxation was detected in 25 (22.5%) SSc patients and in 1 (5%) control subject (p < 0.001) but did not deteriorate after follow-up. Mean serum level of TIMP-1 was significantly elevated in the follow-up group compared to baseline examination (p = 0.0001). Serum TIMP-1 level correlated positively with E/E’, both septal and lateral (r = 0.4, p = 0.002 and r = 0.32, p = 0.01). Conclusions The LV and RV relaxation is impaired in SSc patients. Moreover, left ventricular diastolic function deteriorated after the follow-up period. The TIMP-1 serum levels correlate with echocardiographic parameters, providing a potent link for LV diastolic function and matrix remodeling in patients with SSc.

Refined balloon pulmonary angioplasty—A therapeutic option in very elderly patients with chronic thromboembolic pulmonary hypertension

INTRODUCTION/OBJECTIVES Balloon pulmonary angioplasty (BPA) is a developing treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, to our knowledge there are no published data on BPA in CTEPH subjects aged 75 or over. The aim of the study was to analyze clinical and hemodynamic outcomes of sequential BPA in very elderly patients disqualified from pulmonary endarterectomy (PEA). PATIENTS AND METHODS We enrolled 10 patients (4 male, 6 female, median age 81 [75-88]) with confirmed CTEPH, mPAP > 30 mmHg, and WHO class > II, disqualified from PEA. Overall, 10 patients underwent 39 BPA sessions (mean 3.9 sessions per patient, range 1-9), and 70 pulmonary arteries were dilated, (mean 6.5 vessels per patient, range 1-14). RESULTS Pulmonary angioplasty resulted in significant clinical and hemodynamic improvement in every patient: 6 MWT distance increased from a median of 221 m (80-320) to 345 (230-455) and plasma NT-proBNP levels decreased (P < 0.01). Sequential BPA resulted in normalization of mPAP (<25 mmHg) in 6 of 10 patients and mPAP decreased to 25-30 mmHg in three others. In the whole group mPAP decreased from 41 (31-53) mmHg to 23 (17-33) mmHg (P < 0.01). Overall, mean PAP and PVR decreased significantly in all cases, while CO and CI increased (P < 0.01). No severe complications occurred during BPA and over a median follow-up of 553 days (range 81-784), and all patients are still alive and in good general health. CONCLUSION This study demonstrated the safety and efficacy of refined BPA in CTEPH patients aged 75 or over, disqualified from PEA. Refined BPA may emerge as an alternative therapeutic strategy in very elderly CTEPH patients who are suitable for surgery, but this requires further validation in a large prospective study.

Acute pulmonary embolism treatment with rivaroxaban results in a shorter duration of hospitalisation compared to standard therapy: an academic centre experience.

BACKGROUND Depending on the severity of clinical condition, acute pulmonary embolism (APE) is treated with unfraction-ated heparin (UFH), low-molecular weight heparin (LMWH), oral anticoagulants or, in the most severe form, with fibrinolytic agents. Following APE, patients require prolonged anticoagulant therapy for 3-6 months or in some cases indefinitely. Treatment options in this period include vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOAC) including rivaroxaban. The most recent European Society of Cardiology guidelines on the diagnosis and management of APE recommend use of NOAC in patients at a low-to-moderate risk of early mortality (a class I B recommendation). Rivaroxaban may be used in haemodynamically stable patients since the first day of therapy and was approved for this indication in Poland in December 2012. AIM To evaluate the rate of rivaroxaban use, characterise patients with APE treated with rivaroxaban, and evaluate potential reduction of the duration of hospitalisation in patients treated with rivaroxaban compared to those receiving VKA. METHODS We evaluated hospital and postdischarge treatment in 215 consecutive APE patients (105 men, 110 women) at the mean age of 65.0 (range: 19.5-91.9) years. The study included patients hospitalised from January 2013 to November 2014, i.e. in the period immediately following approval of rivaroxaban for the treatment of APE in Poland. In the acute phase, patients were treated with LMWH, UFH, or rivaroxaban, and the treatment was continued with VKA, LMWH, or rivaroxaban. The timing of initiation of oral therapy depended on the haemodynamic stability of the patient. RESULTS Our study group of 215 APE patients included 157 (73%) moderate-risk patients, 51 (24%) low-risk, and 7 (3.3%) high-risk patients. Treatment was initiated with UFH or LMWH in 208 (96.7%) patients, and with rivaroxaban in 7 (3.3%) patients. In 33 (16.5%) patients, rivaroxaban was started after up to 3 days of heparin therapy. Chronic therapy prescribed at discharge in-cluded VKA in 64 (30.5%) patients, rivaroxaban in 82 (39%) patients, and LMWH in 64 (30.5%) patients. Five patients died during hospital, for the total mortality of 2.3%. Acute high-risk PE was diagnosed on admission in 2 of these patients, and moderate-risk PE in 3 patients. Treatment in this group included enoxaparin in 4 patients and UFH in 1 patient. Patients who were discharged on rivaroxaban stayed in hospital for a significantly shorter time compared to patients discharged on VKA (6 [2-22] vs. 8 [2-17] days, p = 0.0005). Duration of hospital stay was significantly shorter in APE patients with sPESI of 0 who were treated with rivaroxaban compared to those with sPESI of 0 treated with VKA (5 [2-11] vs. 6 [2-12] days, p = 0.002). A significant difference in the duration of hospital stay was also noted in patients with sPESI of ≥ 1 treated with rivaroxaban compared to those treated with VKA (7 [3-22] vs. 9 [3-17] days, p = 0.015). Patients with sPESI of ≥ 1 treated with rivaroxaban were hospitalised for a sig-nificantly longer time compared to those with sPESI of 0 treated with rivaroxaban (7 [3-22] vs. 5 [2-11] days, p = 0.00005). CONCLUSIONS Rivaroxaban therapy is a useful therapeutic option in patients with APE. Compared to standard therapy, use of rivaroxaban has been associated with a significant reduction of the duration of hospital stay.

Tricuspid annulus plane systolic excursion (TAPSE) has superior predictive value compared to right ventricular to left ventricular ratio in normotensive patients with acute pulmonary embolism

Introduction Right ventricular dysfunction (RVD) is an indicator of poor prognosis in normotensive patients with acute pulmonary embolism (APE). The aim of this study was to compare right ventricular (RV)/left ventricular (LV) ratio measured by echocardiography and multidetector computed tomography (MDCT) with tricuspid annulus plane systolic excursion (TAPSE) as a prognostic factor of APE-related 30-day mortality. Material and methods We examined 76 patients with confirmed APE, hemodynamically stable at admission. We evaluated the prognostic value of RV/LV ratio in the apical 4-chamber view and TAPSE measured at echocardiography and the MDCT RV/LV ratio. Results Thirty-day APE-related mortality was 10.5% (8 patients). The area under the curve (AUC) for TAPSE in the prediction of APE-related mortality was higher (p < 0.00001) (0.905, 95% CI: 0.828–0.983) than the AUC of the echo RV/LV ratio (0.427, 95% CI: 0.183–0.672) and MDCT RV/LV ratio (0.371, 95% CI: 0.145–0.598). In univariable Cox analysis, TAPSE was the only significant mortality predictor, with hazard ratio (HR) 0.73 (95% CI: 0.62–0.87, p = 0.0004). In multivariable Cox analysis TAPSE was the only significant mortality predictor, with HR 0.62 (95% CI: 0.46–0.85; p = 0.003), while age, heart rate, and RV/LV ratio in echo or MDCT were non-significant. TAPSE ≤ 15 mm was a significant predictor of APE-related mortality, with HR 26.2 (95% CI: 3.2–214.1; p = 0.002), PPV 44% and NPV 98%. Conclusions The TAPSE is preferable to echo and MDCT RV/LV ratio for risk stratification in initially normotensive patients with APE. The TAPSE ≤ 15 mm identifies patients with an increased risk of 30-day APE-related mortality.

Patent foramen ovale increases the risk of acute ischemic stroke in patients with acute pulmonary embolism leading to right ventricular dysfunction

BACKGROUND Patent foramen ovale (PFO) is an established risk factor for ischemic stroke. Since acute right ventricular dysfunction (RVD) observed in patients with PE can lead to right-to-left inter-atrial shunt via PFO, we hypothesized that PFO is a risk factor for ischemic stroke in PE with significant right ventricular dysfunction. METHODS 55 patients (31 F, 24M), median age 49 years (range 19-83 years) with confirmed PE underwent echocardiography for RVD and PFO assessment. High risk acute PE was diagnosed in 3 (5.5%) patients, while 16 (29%) hemodynamically stable with RVD patients formed a group with intermediate-risk PE. PFO was diagnosed in 19 patients (34.5%). Diffusion-weighted MRI of the brain for acute ischemic stroke (AIS) was performed in all patients 4.91 ± 4.1 days after admission. RESULTS AIS was detected by MRI in 4 patients (7.3%). Only one stroke was clinically overt and resulted in hemiplegia. All 4 AIS occurred in the PFO positive group (4 of 19 patients), and none in subjects without PFO (21.0% vs 0%, p=0.02). Moreover, all AIS occurred in patients with RVD and PFO, and none in patients with PFO without RVD (50% vs 0%, p=0.038). CONCLUSION Our data suggest that acute pulmonary embolism resulting in right ventricular dysfunction may lead to acute ischemic stroke in patients with patent foramen ovale. However, the clinical significance of such lesions remains to be determined.