Cardiovascular assessment after treatment for retinopathy of prematurity: a comparative study between anti-VEGF agent (aflibercept) and laser.

OBJECTIVE: The aim of this study was to compare the cardiac effects and aortic arterial indices following intravitreal aflibercept treatment or diode laser photocoagulation for the treatment of retinopathy of prematurity (ROP) in infants. METHODS: This single-centre, retrospective study was conducted in infants who were administered laser photocoagulation (LPC) or intravitreal aflibercept (IVA) treatment as initial treatment and had completed at least one year of corrected age. The patients were evaluated in terms of aortic elastic parameters, right and left ventricular systolic and diastolic function using conventional, pulsed Doppler and tissue Doppler imaging (TDI) echocardiographic parameters. RESULTS: Fifteen infants were in the LPC group, 16 in the IVA group, and 20 in the control group. Although there were some statistically significant differences in terms of pulsed and TDI echocardiographic parameters between the treatment and control groups, these values could not clearly be adopted as a diastolic dysfunction and myocardial performance indices were not influenced. The aortic elastic parameters were impaired in both LPC and IVA groups compared to the control group. Consequently, we observed only minor differences between the treatment groups, which may suggest subtle changes due to the anti-angiogenic treatment. CONCLUSIONS: Although favourable and promising outcomes were obtained with intravitreal injection of anti-vascular endothelial growth factor agents for the treatment of ROP, concerns have been raised about potential systemic side effects, including potential cardiovascular side effects caused by these agents. The small reduction in right ventricular Doppler velocities could probably be explained by the use of anti-angiogenic or laser treatment in infants.

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0.91 ± 0.15 ( p < 0.01), respectively. Conclusion Ultrasound-accelerated catheter-directed thrombolysis is a safe and efficacious treatment for submassive pulmonary embolism. It reduces pulmonary hypertension and improves right ventricular function in patients with submassive pulmonary embolism.

Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study.

BACKGROUND: There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab. METHODS: Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters. RESULTS: Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17). CONCLUSION: In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.

Assessment of biventricular systolic strain derived from the two-dimensional and three-dimensional speckle tracking echocardiography in lymphoma patients after anthracycline therapy.

The aim of this study was to investigate the usefulness of three-dimensional (3D) speckle tracking echocardiography (STE) for assessment of both left and right ventricular systolic function in patients with lymphoma after anthracycline chemotherapy, compared with two-dimensional (2D) STE. Totally eighty-nine patients undergoing anthracycline containing chemotherapy were studied. Echocardiographic assessment included 2D and 3D left ventricular (LV) global longitudinal strain (GLS), global circumferential strain (GCS) and right ventricular (RV) GLS. All the parameters were analyzed at baseline, after the completion of four cycles and at the end of the regimen respectively. The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic parameters to discriminate between before and after chemotherapy. Compared with those at baseline, the 3D GLS and GCS of LV and GLS of RV decreased significantly after four cycles of the therapy (all p < 0.01). At the end of the treatment, 2D GLS and GCS of LV deteriorated markedly (both p < 0.05). The area under the curve for GLS, GCS of LV and GLS of RV derived by 3D were 0.81, 0.66 and 0.78, respectively. The cutoff value with -20.4% of LV GLS by 3D had sensitivity of 81% and specificity of 66% for differentiating patients after therapy from baselines. The cutoff value with -21.9% of RV GLS by 3D had sensitivity of 71% and specificity of 74% fordifferentiating patients after therapy from baselines. The data from this study demonstrated that both 2D and 3D STE can be conducted to evaluate the slight myocardial damage for lymphoma patients after anthracycline chemotherapy. 3D STE could examine subclinical biventricular dysfunction in earlier point than 2D STE.

Echocardiographic assessment of right ventricular systolic function in conscious healthy dogs following a single dose of pimobendan versus atenolol.

OBJECTIVE: To quantify drug-induced changes in right ventricular (RV) systolic function after administration of pimobendan and atenolol. ANIMALS: 80 healthy privately-owned dogs. METHODS: Using a prospective, blinded, fully-crossed study design with randomized drug administration, RV systolic function was determined twice at two time periods; before and 3 h after administration of pimobendan (0.25 mg/kg PO) or atenolol (1 mg/kg PO). Indices of RV systolic function included tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulsed-wave tissue Doppler-derived systolic myocardial velocity of the lateral tricuspid annulus (S'), and speckle-tracking-derived global longitudinal RV free wall strain and strain rate. The effect of treatment on percent change from baseline RV function was analyzed with a linear mixed model including the covariates heart rate, body weight, age, gender, drug sequence, and time period. RESULTS: All indices showed a significant (p < 0.0001) increase and decrease from baseline following pimobendan and atenolol, respectively. Significant differences from baseline were attributed to drug treatment (p < 0.0001); whereas, effects of other covariates were not significant. The greatest percent changes, but also highest variability, were observed for S' and strain rate (p < 0.0001). Post-atenolol, a significantly greater proportion of dogs exceeded the repeatability coefficient of variation for FAC and S' compared to TAPSE (p ≤ 0.007). CONCLUSIONS: Echocardiographic indices in healthy dogs tracked expected changes in RV systolic function following pimobendan and atenolol and warrant study in dogs with cardiovascular disease.

Assessment of right ventricular responses to therapy in pulmonary hypertension.

Irrespective of its cause, pulmonary hypertension (PH) leads to an increase in pulmonary vascular resistance (PVR). Failing adaption of the right ventricle (RV) to the increased afterload is the main cause of death in PH patients and therefore monitoring RV function during treatment is essential. However, consensus on the optimal method for serial assessment of RV function is lacking and therefore the major clinical trials on PH-specific therapies have not provided clear answers with respect to the response of the RV to treatment. This short review will give an overview of the most important load-dependent and load-independent parameters for assessing RV response to therapy in PH patients.

Sample size and cost analysis for pulmonary arterial hypertension drug trials using various imaging modalities to assess right ventricular size and function end points.

BACKGROUND: Placebo-controlled trials for pulmonary arterial hypertension are no longer acceptable because new therapies must show clinically significant effects on top of standard treatment. The purpose of this study was to estimate sample sizes and imaging costs for the planning of a hypothetical pulmonary arterial hypertension drug trial using imaging to detect changes in right ventricular size and function in response to combined therapy. METHODS AND RESULTS: Same-day cardiovascular MR (CMR) and 2-dimensional (2D) and 3D transthoracic echocardiography (2DTTE and 3DTTE) were performed in 22 patients with pulmonary arterial hypertension (54±13 years of age) twice, 6 months apart. Short-axis CMR cines and full-volume 3DTTE data sets of the right ventricle were used to measure end-diastolic volume and ejection fraction. Fractional area change was obtained from 2DTTE. Sample size calculations used a 2-sample t test model incorporating differences between baseline and 6-month measurements. Cost estimates were made using the Medicare fee schedule. No significant differences were noted between baseline and follow-up measurements. Large SDs reflected variable progression of disease in individual patients on standard therapy and measurement variability. These sources of variability resulted in intertechnique differences in sample sizes: to detect a change of 5% to 15% in 3DTTE-derived right ventricular ejection fraction and fractional area change or change of 15 to 30 mL in 3DTTE right ventricular end-diastolic volume; sample sizes were 2× to 2.5× those required by CMR. As a result, the total cost of a trial using complete TTE was greater than CMR, which was greater than limited TTE. CONCLUSIONS: Because of lower measurement variability, CMR is more cost saving in pulmonary arterial hypertension drug trials than echocardiography, unless limited TTE is used.

[Echocardiographic assessment of circulation system in patients during and 3-5 years after all therapy in childhood]. / Echokardiograficzna ocena ukladu krazenia w trakcie i po uplywie 3-5 lat od zakonczenia leczenia ostrej bialaczki limfoblastycznej w wieku dzieciecym.

Circulatory disturbances may occur during and after the treatment of acute lymphoblastic leukemia (ALL). The reasons are: leukemic infiltrations of the heart, anaemia, renal disturbances, infections, cardiotoxic drugs, especially anthracyclines (Atc). The aim of the study was echocardiographic assessment of circulatory system in patients during and 3-5 years after ALL therapy in childhood. The study group (group B) consisted of 20 children, aged 1-16 years, who underwent Atc treatment with cumulative doses 155.8-330 mg/m2 and cardioprotective agent--dexrazoxane. In this group echocardiography was performed before the treatment as well as after 1, 6, 12 months and 3 years. The retrospective group (R) consisted of 36 persons aged 12-24 years, examined 3-5 years after the completion of ALL treatment, who had undergone the treatment with Atc in doses 148.6-416.7 mg/m2 without cardioprotection. The control group (K) consisted of 28 healthy volunteers, aged 9-25 years. In all subjects echocardiography was performed, standard measurements taken, systolic and diastolic indices of left ventricle (LV) function calculated. In patients during and 3-5 years after the treatment neither LV dilatation nor abnormal wall-thickness was found. The systolic indices remained normal. In the group B echocardiographic indices did not change significantly during 3 years of treatment and did not correlate with growing cumulative Atc doses. In this group isovolumetric relaxation time (IVRT) was significantly longer, what emphasized the need of further clinical and echocardiographic follow-up.

Right ventricular performance and contractile reserve in patients with severe heart failure. Assessment by pressure-area relations and association with outcome.

BACKGROUND: Right ventricular (RV) performance appears to be important in patients with severe heart failure. Although clinical assessments of RV function previously have been limited to load-dependent ejection phase indices, a new method has been developed using the relatively load-insensitive concepts of pressure-volume relations with automated echocardiographic measures of RV cross-sectional area as a surrogate for volume. METHODS AND RESULTS: Sixteen patients with New York Heart Association functional class IV heart failure and group mean left ventricular ejection fraction of 20 +/- 5% were studied. RV pressure-area loops were recorded on-line from echocardiographic measures of RV area and high-fidelity pressure during transient inferior, vena caval balloon occlusions. RV contractile reserve was assessed as its functional response to an increase in dobutamine from 5.7 +/- 4.1 to 13.1 +/- 4.7 micrograms/kg per minute. Complete data sets were available in 13 patients. Group mean RV end-systolic elastance (E'es) and maximal elastance (E'max) increased with augmented dobutamine infusion (2.9 +/- 1.5 to 5.5 +/- 3.3 mm Hg/cm2 and 3.3 +/- 1.6 to 6.4 +/- 3.9 mm Hg/cm2, respectively; P < .01 versus baseline), although individual responses were variable. During a 30-day follow-up, 9 patients remained unstable, requiring continuous intravenous inotropic therapy; 6 of these had profound deterioration requiring mechanical circulatory support. The remaining 4 patients had a comparatively good short-term outcome with clinical stability. A 100% increase in RV E'es or E'max was associated with a good short-term outcome (P < .05). CONCLUSIONS: RV performance can be assessed by pressure-area relations in patients with heart failure. RV contractile reserve in response to increases in dobutamine was associated with a good short-term outcome and may be of prognostic value in patients with severe heart failure.

Evaluation of right ventricular function by assessment of cardiac efficiency: influence of induction of anaesthesia in coronary artery bypass grafting patients.

Considering the heart as a physical pump cardiac efficiency is calculated from the ratio of cardiac work performed to the maximum level of energy of the heart. The aim of the study was to compare cardiac efficiency with cardiac output and right ventricular ejection fraction. Nine patients scheduled for coronary artery bypass grafting were investigated. A femoral arterial and a right ventricular ejection fraction pulmonary artery catheter were placed in the awake state. Anaesthesia was induced with eltanolone and fentanyl. Cardiac output, pulmonary artery and central venous pressures, and right ventricular ejection fraction were measured in the awake state (baseline), 2 min after induction of anaesthesia and 1 and 5 min after intubation. Cardiac efficiency was calculated by dividing the stroke work by the maximum energy of the heart as calculated from the pressure volume diagram. An analysis of variance was carried out for cardiac efficiency, cardiac output and right ventricular ejection fraction. Cardiac efficiency was significantly (p < 0.05) reduced 1 min after intubation from 28 +/- 11 to 14 +/- 5%. In contrast the right ventricular ejection fraction (from 48 +/- 10 to 35 +/- 13%) and cardiac output (from 6.5 +/- 1.5 to 5.3 +/- 1.2 L/min) did not change significantly during the induction of anaesthesia. Cardiac efficiency was found to be a more sensitive parameter to describe changes in the right ventricular function than the ejection fraction and cardiac output during induction of anaesthesia with eltanolone and fentanyl which was used as a model to vary cardiac performance and afterload.

Radionuclide assessment of right ventricular contractile reserve after acute myocardial infarction.

Conflicting data have been reported about the implications of a decreased right ventricular (RV) contractile reserve (i.e., a < 5% stress-induced increase in ejection fraction [EF]). If a reduced reserve corresponds to ischemia, it will probably be associated with an electrocardiographic marker of RV ischemia, stress-induced ST-segment elevation (increases ST) in leads V3R to V6R. To test this hypothesis, 98 asymptomatic postinfarction patients (27 with RV infarction) were assigned to a dobutamine stress test (maximal dose 40 micrograms/kg/min) with equilibrium radionuclide angiography and electrocardiographic study, including leads V3R to V6R. All but 11 patients underwent coronary angiography. A dobutamine-induced increases ST in VR leads was seen in 24 patients with and in 8 without RV infarction. This electrocardiographic sign was 75% sensitive and 84% specific for the diagnosis of proximal right coronary artery disease. It was 61% sensitive and 74% specific for the detection of reduced RV contractile reserve. Patients with RV infarction had reduced RVEF at rest (38 +/- 9%), but the mean contractile reserve was normal (12 +/- 12%). The contractile reserve was significantly smaller in patients with proximal versus distal or no right coronary artery disease. It was also smaller (P < 0.01) in patients with increased ST versus no increased ST. In conclusion, high doses of dobutamine are useful in assessing RV contractile reserve after acute myocardial infarction. In these patients, a reduced RV contractile reserve is related to proximal right coronary artery disease and is associated with stress-induced increased ST in VR leads.

Assessment of right ventricle dimensions with microsonometry in anesthetized rabbits.

Dimension measurements of the right ventricle are difficult to obtain because of its complex geometry, thus we evaluated a method of right ventricular dimension measurements. Crystals were placed on the ventral and dorsal side of the right ventricular free wall, approximately one-fourth of the right ventricular semicircle away from the septum, in the middle of a cranio-caudal axis of the ventricles. The effects of an increased (infusion of 20 mL/kg of 5% glucose for 3 min into seven rabbits), as well as decreased preload (nitroglycerin, 5 micrograms/kg/min i.v. n = 6) were measured and compared with changes during a placebo infusion (n = 6). The change in shortening of the right ventricle wall segment correlated with changes in both atrial natriuretic factor (ANF) plasma concentration (r = 0.89, p < 0.05) and central venous pressure (CVP) (r = 0.94, p < 0.05), respectively. Both these variables are influenced by right ventricular function and dimensions in healthy animals. Dimension measurements obtained across the free wall of the right ventricle appear to reflect right ventricular function well and should be useful in assessing the effects of drugs intended for the treatment of angina pectoris or heart failure.

Doppler assessment of right ventricular filling dynamics during volume loading in ischemic heart disease.

To assess the effects of volume loading on right ventricular (RV) filling dynamics, the RV inflow pattern was recorded using pulsed Doppler echocardiography (PDE) during dextran infusion in 7 normal subjects (Group I) and 24 patients with ischemic heart disease. The patients with ischemic heart disease were divided into three groups according to the left ventricular (LV) and RV ejection fractions (EF). Group II consisted of 11 patients whose LVEF and RVEF exceeded 50%. Group III consisted of 7 patients whose LVEF was lower than 50% and RVEF was higher than 50%. Group IV was comprised of 6 patients whose LVEF and RVEF were lower than 50%. Peak flow velocity of the RV rapid filling wave in early diastole [R(T)] and that of the atrial contraction wave [A(T)] were measured, and the ratio of A(T) to R(T) [A(T)/R(T)] in each cardiac cycle was calculated. In some of the subjects, simultaneous right-sided cardiac catheterization was performed with a Swan-Ganz thermodilution catheter. The LV and RV function during volume loading were calculated according to the following formulae: delta Stroke volume index (SVI)/delta pulmonary artery wedge pressure (PAWP) and delta SVI/delta right atrial pressure (RAP), respectively. After dextran infusion, R(T) increased significantly in Groups I, II, and III, but not in Group IV. The A(T) and A(T)/R(T) ratio remained unchanged in all groups. The percent change of the R(T) correlated well with delta SVI/delta RAP (r = 0.56, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulsed Doppler echocardiography assessment of acute hemodynamic effects of nifedipine on pulmonary hypertension in chronic obstructive lung disease].

To observe acute hemodynamic effects of pulmonary hypertension in chronic obstructive lung disease by nifedipine, we studied 16 patients with pulsed doppler ultrasound. Pulsed doppler ultrasonogram was employed to measure hemodynamic parameters before and 45 minutes after nifedipine 20 mg (give po) in 16 patients. Results indicate that PAMP decreased significantly (P less than 0.01) from 5.5 +/- 1.6 to 4.0 +/- 1.5 kPa. We conclude that nifedipine reduces pulmonary artery pressure, at least acutely, in patients with hypoxic pulmonary hypertension.