Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Implications of the Hemodynamic Optimization Approach Guided by Right Heart Catheterization in Patients with Severe Heart Failure

OBJECTIVE: To report the hemodynamic and functional responses obtained with clinical optimization guided by hemodynamic parameters in patients with severe and refractory heart failure. METHODS: Invasive hemodynamic monitoring using right heart catheterization aimed to reach low filling pressures and peripheral resistance. Frequent adjustments of intravenous diuretics and vasodilators were performed according to the hemodynamic measurements. RESULTS: We assessed 19 patients (age = 48±12 years and ejection fraction = 21±5%) with severe heart failure. The intravenous use of diuretics and vasodilators reduced by 12 mm Hg (relative reduction of 43%) pulmonary artery occlusion pressure (P<0.001), with a concomitant increment of 6 mL per beat in stroke volume (relative increment of 24%, P<0.001). We observed significant associations between pulmonary artery occlusion pressure and mean pulmonary artery pressure (r=0.76; P<0.001) and central venous pressure (r=0.63; P<0.001). After clinical optimization, improvement in functional class occurred (P< 0.001), with a tendency towards improvement in ejection fraction and no impairment to renal function. CONCLUSION: Optimization guided by hemodynamic parameters in patients with refractory heart failure provides a significant improvement in the hemodynamic profile with concomitant improvement in functional class. This study emphasizes that adjustments in blood volume result in imme-diate benefits for patients with severe heart failure.

Lowering Pulmonary Wedge Pressure after Heart Transplant: Pulmonary Compliance and Resistance Effect

AbstractBackground:Right ventricular (RV) afterload is an important risk factor for post-heart transplantation (HTx) mortality, and it results from the interaction between pulmonary vascular resistance (PVR) and pulmonary compliance (CPA). Their product, the RC time, is believed to be constant. An exception is observed in pulmonary hypertension because of elevated left ventricular (LV) filling pressures.Objective:Using HTx as a model for chronic lowering of LV filling pressures, our aim was to assess the variations in RV afterload components after transplantation.Methods:We retrospectively studied 159 patients with right heart catheterization before and after HTx. The effect of Htx on hemodynamic variables was assessed.Results:Most of the patients were male (76%), and the mean age was 53 ± 12 years. HTx had a significant effect on the hemodynamics, with normalization of the LV and RV filling pressures and a significant increase in cardiac output and heart rate (HR). The PVR decreased by 56% and CPA increased by 86%. The RC time did not change significantly, instead of increasing secondary to pulmonary wedge pressure (PWP) normalization after HTx as expected. The expected increase in RC time with PWP lowering was offset by the increase in HR (because of autonomic denervation of the heart). This effect was independent from the decrease of PWP.Conclusion:The RC time remained unchanged after HTx, notwithstanding the fact that pulmonary capillary wedge pressure significantly decreased. An increased HR may have an important effect on RC time and RV afterload. Studying these interactions may be of value to the assessment of HTx candidates and explaining early RV failure after HTx.

The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension.

BACKGROUND: Pulmonary vascular diseases are increasingly recognised as important clinical conditions. Pulmonary hypertension associated with a range of aetiologies is difficult to treat and associated with progressive morbidity and mortality. Current therapies for pulmonary hypertension include phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, or prostacyclin mimetics. However, none of these provide a cure and the clinical benefits of these drugs individually decline over time. There is, therefore, an urgent need to identify new treatment strategies for pulmonary hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the PPARbeta/delta agonist GW0742 induces vasorelaxation in systemic and pulmonary vessels. Using tissue from genetically modified mice, we show that the dilator effects of GW0742 are independent of the target receptor PPARbeta/delta or cell surface prostacyclin (IP) receptors. In aortic tissue, vascular relaxant effects of GW0742 were not associated with increases in cGMP, cAMP or hyperpolarisation, but were attributed to inhibition of RhoA activity. In a rat model of hypoxia-induced pulmonary hypertension, daily oral dosing of animals with GW0742 (30 mg/kg) for 3 weeks significantly reduced the associated right heart hypertrophy and right ventricular systolic pressure. GW0742 had no effect on vascular remodelling induced by hypoxia in this model. CONCLUSIONS/SIGNIFICANCE: These observations are the first to show a therapeutic benefit of 'PPARbeta/delta' agonists in experimental pulmonary arterial hypertension and provide pre-clinical evidence to favour clinical trials in man.

Right heart ischemia in cases of sepsis.

Data from the literature suggest that cases of sepsis complicated by right ventricular (RV) dysfunction have poorer prognosis. In these cases progressive hypoperfusion associated to increasing, injury-related, pulmonary vascular resistance account for RV ischemia. In the present analysis, we wanted to evaluate whether prevalent RV cardiac ischemic damage could be detected in a series of fatal sepsis cases. We retrospectively investigated 20 cases of sepsis that underwent forensic autopsy (study group-11♀, 9♂, mean age 57 years) and compared them to a group of 20 cases of hanging (hanging group-4 ♀, 16 ♂, mean age 44 years) as well as to a group of 20 cases of myocardial infarction (MI group-9 ♀, 11 ♂, mean age 65 years), as examples of cardiac damage due to global hypoxia during agony and ischemic damage, respectively. We performed immunohistochemistry with the antibodies anti-fibronectin and C5b-9. The reactions were semiquantitively classified and the groups were compared. In 30% of the cases of sepsis prevalent RV ischemic damage could be detected with the antibody anti-fibronectin. This expression was significantly different from that observed in cases of MI (p=0.028) and hanging (p<0.001). Our study showed that, in cases of fatal sepsis, prevalent RV ischemic damage occurred in a substantial minority of cases.

Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease

Recent studies have recognised the importance of pulmonary hypertension (PH) in sickle cell disease (SCD). The aim of this study was to determine the prevalence and prognostic impact of PH and its features in patients with SCD. 80 patients with SCD underwent baseline clinical evaluation, laboratory testing, 6-min walk tests (6MWTs) and echocardiography. Patients with a peak tricuspid regurgitant jet velocity (TRV) of >= 2.5 m.s(-1) were further evaluated through right heart catheterisation (RHC) to assure the diagnosis of PH. Our study evidenced a 40% prevalence of patients with elevated TRV at echocardiography. RHC (performed in 25 out of 32 patients) confirmed PH in 10% (95% CI 3.4-16.5%) of all patients, with a prevalence of post-capillary PH of 6.25% (95% CI 0.95-11.55%) and pre-capillary PH of 3.75% (95% CI -0.4-7.9%). Patients with PH were older, had worse performance in 6MWTs, and more pronounced anaemia, haemolysis and renal dysfunction. Survival was shorter in patients with PH. Our study reinforced the use of echocardiography as a screening tool for PH in SCD and the mandatory role of RHC for proper diagnosis. Our findings confirmed the prognostic significance of PH in SCD as its association to pronounced haemolytic profile.

A rare cause of fatal right heart failure

Microscopic pulmonary tumor embolism (MPTE) is an uncommon cause of dyspnea in patients with cancer and one of the most difficult to diagnose. MPTE is a syndrome that is pathologically characterized by the occlusion of small pulmonary arteries and arterioles by aggregates of tumor cells. Because the clinical picture resembles that of thromboembolic disease, it is rarely recognized before death. The most common clinical symptom is subacute progressive dyspnea over weeks to months. We recently observed a case of MPTE of exceptional interest as the patient was under aggressive anticoagulant treatment and developed fulminant pulmonary hypertension with fatal right heart failure.

[Rare cause of right heart failure: two cases]

Two asylum seekers (patient A, 30 year old man from Mongolia; patient B, 18 year old woman from the Sudan) were referred to our outpatient clinic because of acute and chronic deterioration of their general condition and shortness of breath. Both patients presented with a clear clinical picture of systemic venous hypertension and moderate pulmonary congestion. Patient B had a paradoxical pulse compatible to cardiac tamponade.

Non-invasive detection of acute cell-mediated graft rejection in paediatric heart transplant recipients: the role of cardiovascular magnetic resonance

Background and Aim: Acute cardiac rejection is currently diagnosed by endomyocardial biopsy (EMB), but multiparametric cardiac magnetic resonance (CMR) may be a non-invasive alternative by its capacity for myocardial structure and function characterization. Our primary aim was to determine the utility of multiparametric CMR in identifying acute graft rejection in paediatric heart transplant recipients. The second aim was to compare textural features of parametric maps in cases of rejection versus those without rejection. Methods: Fifteen patients were prospectively enrolled for contrast-enhanced CMR followed by EMB and right heart catheterization. Images were acquired on a 1,5 Tesla scanner including T1 mapping (modified Look-Locker inversion recovery sequence – MOLLI) and T2 mapping (modified GraSE sequence). The extracellular volume (ECV) was calculated using pre- and post-gadolinium T1 times of blood and myocardium and the patient’s hematocrit. Markers of graft dysfunction including hemodynamic measurements from echocardiography, catheterization and CMR were collated. Patients were divided into two groups based on degree of rejection at EMB: no rejection with no change in treatment (Group A) and acute rejection requiring new therapy (Group B). Statistical analysis included student’t t test and Pearson correlation. Results: Acute rejection was diagnosed in five patients. Mean T1 values were significantly associated with acute rejection. A monotonic, increasing trend was noted in both mean and peak T1 values, with increasing degree of rejection. ECV was significantly higher in Group B. There was no difference in T2 signal between two groups. Conclusion: Multiparametric CMR serves as a noninvasive screening tool during surveillance encounters and may be used to identify those patients that may be at higher risk of rejection and therefore require further evaluation. Future and multicenter studies are necessary to confirm these results and explore whether multiparametric CMR can decrease the number of surveillance EMBs in paediatric heart transplant recipients.

Cardiopulmonary Manifestations of Hepatosplenic Schistosomiasis

Background -Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. Methods and Results -All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). Conclusions -Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease. (Circulation. 2009; 119: 1518-1523.)

Concordancia de presión sistólica pulmonar estimada por ultrasonografía y cateterismo cardíaco derecho en pacientes candidatos a trasplante cardíaco

Introducción: A los pacientes con Insuficiencia Cardíaca (IC) estadio D candidatos a trasplante cardiaco se les realiza la determinación de las presiones de la arteria pulmonar por CCD considerada como prueba de oro. Se decidió conocer si la medición de las presión de la arteria pulmonar obtenidas por ECO TT tenían concordancia con las obtenidas por el CCDen estos paciente que fueron evaluados para trasplante cardiaco. Metodología: Se realizó una recolección retrospectiva de los datos consignados en las historias clínicas de todos los pacientes que fueron receptores de un trasplante cardiaco en la FCI-IC desde septiembre del 2005 hasta Mayo del 2013 y se determinó la concordancia entre la presión sistólica pulmonar evaluado por ECO TT y CCD. Resultados: Se incluyeron 46 pacientes. El 76,1% son hombres y con edad promedio de 46,4 ± 13,1. La PSAP estimada por CCD fue 48,3 ± 13,1 mmHg Vs 45,1 ± 12,1 mmHg por ECO TT. La fracción de eyección fue 15,1 ± 4,06% (IC: 13,95-16,36). El 75,9% de los pacientes tenían HTP moderada y severa. La concordancia entre la PSAP determinada por ambos métodos fue 0,475 (I,C: 0.256 - 0.694), y el coeficiente de correlación intraclase fue de 0,090, indicando una baja concordancia entre los dos métodos. Discusión: La determinación de las presiones pulmonares determinada por ECO TT tiene mala concordancia con las obtenidas por CCD. No se debe usar este estudio para excluir los pacientes candidatos a trasplante cardiaco ni para evaluar las variaciones de las misma en la evolución de la enfermedad.

Variación de volumen sistólico como predictor de hipovolemia en pacientes pediátricos con choque séptico

El compromiso del sistema cardiovascular es frecuente en los pacientes en estado crítico, por tanto la monitorización hemodinámica es esencial para un tratamiento apropiado dirigido a objetivos terapéuticos en este grupo de pacientes. La monitorización hemodinámica del gasto cardíaco y la estimación del volumen intravascular son fundamentales para el manejo de los pacientes pediátricos en estado crítico, la medición del gasto cardíaco es uno de los principales elementos para evaluar la situación hemodinámica y la perfusión tisular de un paciente ayudando a dirigir el tratamiento y a monitorizar la respuesta clínica en pacientes con choque séptico. La hipovolemia es una causa común para la falla circulatoria en pacientes en condición crítica, el encontrar un método confiable para medición de precarga es importante para guiar la administración de líquidos. Tradicionalmente se han utilizado medidas de la volemia asociadas como la presión venosa central (PVC), frecuencia cardiaca (FC), presión arterial (PA) y el gasto urinario. Estos indicadores tienen grandes factores de distracción que hacen que su valor sea limitado y por tanto se tengan que buscar alternativas más confiables. En años recientes se han postulado parámetros dinámicos para la evaluación de la precarga, entre ellos uno de los mas ampliamente estudiado es la medición de la variabilidad de Volumen sistólico (VVS); Este valor se basa en el concepto de que durante la inspiración, la disminución del retorno venoso produce una disminución del Volumen sistólico, lo cual se manifiesta como una disminución en la onda de pulso; Por tanto en una situación de hipovolemia esta diferencia será mayor, dado que será más evidente la disminución del volumen al final de la diástole. En adultos este parámetro se ha convertido en una herramienta útil para evaluar estado de volumen de los pacientes que se encuentran en estado crítico y ha demostrado su utilidad para predecir respuesta a administración de fluidos en diferentes poblaciones de pacientes. En la actualidad no hay estudios en niños que comparen la medición de VVS contra dichas medidas tradicionales de volemia.