Impact of new task force criteria in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that can lead to sudden cardiac death. The diagnostic criterion has recently been revised and through the use of cardiac magnetic resonance (CMR) imaging this study aimed to assess the clinical impact of comparing the original 1994 task force (TF) criterion to the revised 2010 criterion. METHODS: We evaluated 173 consecutive CMR scans of patients referred with clinical suspicion of ARVC between 2008 and 2011. We then compared the prevalence of major and minor CMR criteria by applying the two criteria. RESULTS: Using the 1994 TF criterion, 13 (7.5%) patients had definite, 11 (6.4%) had borderline, and 39 (22.5%) had possible ARVC. Using the 2010 TF criterion, 10 (5.8%) patients had definite, 1 had borderline, and 7 had (0.04%) possible ARVC. With the 1994 criterion, 81 patients satisfied CMR criterion, of which 36 (44%) had major and 45 (56%) had minor criteria. Upon reclassification with the revised criterion, 61 of the 81 patients were not assigned any criteria, even though many patients had significant risk factors. The negative predictive values (NPV) for both CMR criteria were 100% but the positive predictive values (PPV) for combined CMR major or minor criteria improved from 23% to 55%. CONCLUSIONS: Revision of the criterion has enhanced the diagnostic capabilities of CMR but has resulted in a large cohort of patients not classified. In these patients, there is presently no official consensus on imaging or clinical strategy for surveillance of the evolution of pathology over time.

Right-ventricular failure following left ventricle assist device implantation.

PURPOSE OF REVIEW: To review recent insights on right-ventricular failure (RVF) following left-ventricular assist device (LVAD) implantation. RECENT FINDINGS: Even with the availability of new generation continuous mechanical assist devices, RVF after implantation of LVAD is still associated with high morbidity and mortality. Recent studies have tried to better define the risk of RVF using combined clinical scores and measures of right-ventricular function or strain. Small exploratory studies have also investigated the role of pulmonary vasodilators and phosphodiesterase inhibitors in selected patients receiving LVAD implantation. SUMMARY: Measure of right-ventricular function could improve the risk stratification of RVF following LVAD implantation. Future multicenter studies are needed to validate right-ventricular risk scores and to develop evidence-guided preventive and therapeutic strategies.

Right ventricular failure in idiopathic pulmonary arterial hypertension is associated with inefficient myocardial oxygen utilization.

BACKGROUND: In idiopathic pulmonary arterial hypertension (IPAH), increased right ventricular (RV) power is required to maintain cardiac output. For this, RV O2 consumption (MVO2) must increase by augmentation of O2 supply and/or improvement of mechanical efficiency-ratio of power output to MVO2. In IPAH with overt RV failure, however, there is evidence that O2 supply (perfusion) reserve is reduced, leaving only increase in either O2 extraction or mechanical efficiency as compensatory mechanisms. We related RV mechanical efficiency to clinical and hemodynamic parameters of RV function in patients with IPAH and associated it with glucose metabolism. METHODS AND RESULTS: The patients included were in New York Heart Association (NYHA) class II (n=8) and class III (n=8). They underwent right heart catheterization, MRI, and H2(15)O-, (15)O2-, C(15)O-, and 18FDG-PET. RV power and O2 supply were similar in both groups (NYHA class II versus class III: 0.54±0.14 versus 0.47±0.12 J/s and 0.109±0.022 versus 0.128±0.026 mL O2/min per gram, respectively). RV O2 extraction was near-significantly lower in NYHA class II compared with NYHA class III (63±17% versus 75±16%, respectively, P=0.10). As a result, MVO2 was significantly lower (0.066±0.012 versus 0.092±0.010 mL O2/min per gram, respectively, P=0.006). RV efficiency was reduced in NYHA class III (13.9±3.8%) compared with NYHA class II (27.8±7.6%, P=0.001). Septal bowing, measured by MRI, correlated with RV efficiency (r = -0.59, P=0.020). No relation was found between RV efficiency and glucose uptake rate. RV mechanical efficiency and ejection fraction were closely related (r=0.81, P<0.001). CONCLUSIONS: RV failure in IPAH was associated with reduced mechanical efficiency that was partially explained by RV mechanical dysfunction but not by a metabolic shift.

Characteristics and prognosis of patients with decompensated right ventricular failure during the course of pulmonary hypertension.

BACKGROUND: New therapies for pulmonary arterial hypertension have prolonged survival but simultaneously increased the number of hospital admissions because of decompensated right heart failure (DRHF). The optimal approach in DRHF has not been established yet. AIM: Analysis of clinical course of DRHF in a group of patients with pulmonary hypertension treated in a single referral centre. METHODS: We retrospectively analysed 60 episodes of DRHF in 37 patients (29 females, mean age 44+/-17 years) with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension admitted to our hospital between 2005 and 2007. We assessed the cause of decompensation, vital signs at admission, functional class and laboratory values. We classified all episodes into four haemodynamic profiles using the value of systolic blood pressure together with presence of peripheral perfusion abnormalities (profile cold vs. warm) and symptoms of venous congestion (profile wet vs. dry). Primary end-point was in-hospital mortality. RESULTS: The most common causes of DRHF were infection (27%), drug noncompliance (20%), and pulmonary embolism (3%). In 48% no causative factor was indentified. There were 19 (32%) in-hospital deaths. The highest mortality was observed among patients with connective tissue disease (61%). The haemodynamic profile 'warm-wet' was the most common (48%) and the profile 'cold-dry' was the rarest but was associated with a 100% mortality. Patients who died had higher value of functional class (3.84+/-0.38 vs. 3.51+/-0.55, p=0.01) and higher activity of aspartate transaminase (61+/-61 vs. 42+/-78 U/l, p=0.02) compared with those who survived. In multivariate analysis higher dopamine dose (RR 2.0/1 microg/kg/min, 95% CI 1.00-5.00, p <0.001) was an independent factor of in-hospital death. In contrast 'rescue therapy' with iloprost or treprostinil decreased mortality (RR 0.09, 95% CI 0.01-0.99, p=0.04). Mortality in patients receiving dopamine was higher (60 vs. 18%, p=0.001) than in patients treated without dopamine. CONCLUSION: Mortality in patients with pulmonary hypertension and DRHF remains very high and seems to be related to haemodynamic profile on admission. The newly introduced therapy with parenteral prostanoids may be more beneficial than dopamine infusion.

A proposed functional clinical classification predicts in-hospital and long-term survival in the setting of acute right ventricular infarction.

BACKGROUND: The objectives of the present investigation were to validate the prognostic role of a proposed Clinical Classification [CC], to evaluate the TIMI risk score [RS] and to establish whether the TIMI-RS should incorporate points for patients with acute right ventricular infarction [TIMI-RS-RVI]. METHODS AND RESULTS: A total of 523 RVI patients were classified on clinical and functional basis as: A, without right ventricular failure [RVF], B with RVF and C with cardiogenic shock. The CC was evaluated prospectively among 98 patients with RVI and retrospectively in 425 RVI patients. The TIMI-RS was evaluated prospectively among 622 patients with STEMI [anterior:277, inferior:247, RVI:98], and retrospectively in 425 RVI patients. The CC established differences among the 3-RVI Classes for in-hospital mortality [prospectively and retrospectively; p<0.01, p<0.001, respectively] that were maintained at 8 years [p < 0.001]. Patients with anterior and inferior STEMI, but not those with RVI revealed an association between outcome and TIMI-RS [p<0.001]. Testing for TIMI-RS-RVI did not result a good prognostic tool [ROC=0.9; excellent discrimination, but with a very poor "clinical calibration"]. CONCLUSIONS: The proposed CC allowed prediction of mortality at short- and long-term in the setting of acute RVI. The role of the TIMI-RS should be reevaluated prospectively as a prognostic tool in the scenario of RVI patients.

The systolic to diastolic duration ratio in children with hypoplastic left heart syndrome: a novel Doppler index of right ventricular function.

BACKGROUND: Right ventricular (RV) function is an important determinant of clinical status in children with hypoplastic left heart syndrome (HLHS). However, assessment of RV function remains challenging because of its complex morphology. We investigated the S/D duration ratio in children with HLHS as a novel index of global RV function. METHODS: We measured systolic (S) and diastolic (D) duration using tricuspid regurgitation duration from Doppler flow, to calculate the S/D ratio in 33 children with HLHS and 33 control subjects matched for age and sex. We compared the S/D ratio between patients with HLHS and control subjects, between patients with HLHS and normal and abnormal RV function, and between patients with HLHS at different stages of palliation. We further correlated the S/D ratio with catheterization data. RESULTS: Patients and control subjects were well matched for age (3.12 +/- 4.5 vs 3 +/- 4.5 years, not significant) sex, and heart rate (cycle length 524 +/- 179 vs 575 +/- 162 milliseconds, not significant). Patients with HLHS had a significantly higher S/D ratio than control subjects (1.65 +/- 0.85 vs 0.85 +/- 0.2, P < .0001). The S/D ratio became increasingly elevated in HLHS at higher heart rates, but not in control subjects. The S/D ratio was significantly higher in patients with HLHS and decreased RV function as compared with patients with HLHS and normal RV function (2.2 +/- 0.7 vs 1.5 +/- 0.47, P = .006), and significantly increased in patients with Norwood stage 1 versus patients with Norwood stages 2 and 3 HLHS (2.16 vs 1.4 and 1.32, respectively, P < .01 and P < .001, respectively). The S/D ratio did not correlate with catheterization-derived RV end-D pressure or cardiac index. CONCLUSIONS: Patients with HLHS have an increased S/D ratio as a result of a shortened D and prolonged S. Measurement of the S/D duration ratio using Doppler flow is a novel method to augment assessment of global RV function in HLHS.

Left and right ventricular diastolic dysfunction as predictors of difficult separation from cardiopulmonary bypass.

PURPOSE: As the evaluation of diastolic function can be complex in the setting of a busy cardiac operating room, its assessment may benefit from an algorithmic approach using transesophageal echocardiography. We developed a diagnostic algorithm which was then applied in a series of cardiac surgery patients to determine whether moderate to severe left ventricular diastolic dysfunction (LVDD) and right ventricular diastolic dysfunction (RVDD) can predict difficult separation from cardiopulmonary bypass (DSB). METHODS: An algorithm using pulsed-wave Doppler interrogation of the mitral and tricuspid valve, the pulmonary and hepatic venous flow, and tissue Doppler interrogation of the mitral and tricuspid annulus was developed. The study was divided in two phases involving two groups of patients undergoing cardiac surgery. In phase I, echocardiographic evaluations of patients (n = 74) were used to test the reproducibility of the algorithm and to evaluate inter-observer variability using Cohen's kappa values which were calculated in three specific periods. In phase II, the algorithm was applied to a second group of patients (validation group, n = 179) to explore its prognostic significance. The primary end-point in phase II was DSB. RESULTS: In phase I, the kappa coefficients for LVDD and RVDD algorithms were 0.77 and 0.82, respectively. In phase II, moderate or severe degrees of LVDD were observed in 29 patients (16%) and moderate to severe RVDD was observed in 18 patients (10%) before cardiac surgery. Both moderate and severe LVDD (P = 0.017) and RVDD (P = 0.049) before surgery were observed more frequently in patients with DSB. CONCLUSION: Moderate and severe LVDD and RVDD can be identified with very good reproducibility, and both degrees of diastolic dysfunction are associated with DSB.

Sequence of echocardiographic changes during development of right ventricular failure in rat.

BACKGROUND: The temporal relations between the onset of echocardiographic changes and clinical diagnosis of right ventricular (RV) failure are unresolved. We have characterized such relations in a rat monocrotaline (MCT) model of RV failure. METHODS: Eight-week-old male Wistar rats were injected with MCT (60 mg/kg) or vehicle and underwent serial echocardiography. RV free-wall thickness (RVWT), pulmonary artery acceleration time normalized to cycle length (PAAT/CL), RV end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE) were measured. RESULTS: Significant differences in echocardiographic parameters between MCT-treated and control rats were found as early as 14 days before RV failure for RVWT, 10 days for PAAT/CL, and 7 days for RVEDD and TAPSE. The time intervals between the onset of changes in RVWT, PAAT/CL, RVEDD, and TAPSE and diagnosis of RV failure were 11.3 +/- 0.8, 10.9 +/- 0.7, 6.5 +/- 0.5, and 5.4 +/- 0.7 days, respectively. The sequence of echocardiographic changes was consistent in all animals during development of RV failure. CONCLUSIONS: Pulmonary hypertension (assessed by PAAT/CL) and RV free-wall thickening (characterized by RVWT) precede RV dilation and RV systolic dysfunction (measured by RVEDD and TAPSE, respectively). Echocardiographic analysis permits accurate determination of the stage of disease development in MCT-induced RV failure.

Quantitative measures of right ventricular dysfunction by echocardiography in the diagnosis of acute nonmassive pulmonary embolism.

BACKGROUND: Transthoracic echocardiography (TTE) is used in the risk assessment of patients with pulmonary embolism (PE), but the incremental diagnostic information from quantitative measures of right ventricular (RV) size, pressure, and function by TTE has yet to be fully evaluated. METHODS: In 300 consecutive patients with suspected first nonmassive PE, TTE and ventilation/perfusion scintigraphy were performed. RESULTS: Among measures of RV anatomy, RV pressure estimates, and estimates of global and regional RV function with significant diagnostic information in a logistic regression analysis, the acceleration time of RV outflow less than 89 milliseconds, the ratio of RV to left ventricular diameter greater than 0.78, RV outflow tract fractional shortening less than 35%, and signs of RV strain on electrocardiogram had independent, incremental diagnostic information (area under the receiver operating characteristics curve = 0.81). If D-dimer greater than 4.1 mmol/L was included, the area under the curve increased to 0.88. The negative and positive predictive values if any 2 of 3 factors in the final model were present were 88% and 70%, respectively. CONCLUSION: TTE is able to identify differential diagnoses and enhance pretest probability of PE significantly. TTE could therefore be considered as an integral part of the initial diagnostic workup of patients suspected of PE, especially if definitive diagnostic imaging has limited availability.

Right ventricular dyssynchrony in patients with pulmonary hypertension is associated with disease severity and functional class.

BACKGROUND: Abnormalities in right ventricular function are known to occur in patients with pulmonary arterial hypertension. OBJECTIVE: Test the hypothesis that chronic elevation in pulmonary artery systolic pressure delays mechanical activation of the right ventricle, termed dyssynchrony, and is associated with both symptoms and right ventricular dysfunction. METHODS: Fifty-two patients (mean age 46 +/- 15 years, 24 patients with chronic pulmonary hypertension) were prospectively evaluated using several echocardiographic parameters to assess right ventricular size and function. In addition, tissue Doppler imaging was also obtained to assess longitudinal strain of the right ventricular wall, interventricular septum, and lateral wall of the left ventricle and examined with regards to right ventricular size and function as well as clinical variables. RESULTS: In this study, patients with chronic pulmonary hypertension had statistically different right ventricular fractional area change (35 +/- 13 percent), right ventricular end-systolic area (21 +/- 10 cm2), right ventricular Myocardial Performance Index (0.72 +/- 0.34), and Eccentricity Index (1.34 +/- 0.37) than individuals without pulmonary hypertension (51 +/- 5 percent, 9 +/- 2 cm2, 0.27 +/- 0.09, and 0.97 +/- 0.06, p < 0.005, respectively). Furthermore, peak longitudinal right ventricular wall strain in chronic pulmonary hypertension was also different -20.8 +/- 9.0 percent versus -28.0 +/- 4.1 percent, p < 0.01). Right ventricular dyssynchrony correlated very well with right ventricular end-systolic area (r = 0.79, p < 0.001) and Eccentricity Index (r = 0.83, p < 0.001). Furthermore, right ventricular dyssynchrony correlates with pulmonary hypertension severity index (p < 0.0001), World Health Organization class (p < 0.0001), and number of hospitalizations (p < 0.0001). CONCLUSION: Lower peak longitudinal right ventricular wall strain and significantly delayed time-to-peak strain values, consistent with right ventricular dyssynchrony, were found in a small heterogeneous group of patients with chronic pulmonary hypertension when compared to individuals without pulmonary hypertension. Furthermore, right ventricular dyssynchrony was associated with disease severity and compromised functional class.

[Right ventricle insufficiency in pulmonary arterial hypertension. Physiopathologic considerations]. / Insuficiencia ventricular derecha en la hipertensión arterial pulmonar. Consideraciones fisiopatológicas.

The present review is focused on chronic RV pressure overload or Cor Pulmonale as it may occur in the setting of two distinct disorders: those associated with abnormal pulmonary gas exchange (hypoxemia and/or hypercapnia) where chronic obstructive pulmonary disease (COPD) is the leading cause, and those associated with pulmonary vascular obstruction where primary pulmonary hypertension (PDDH) is the representative example. The clinical curse, prognostic, implications, and therapeutic strategies differ considerably in these two clinical entities. Right ventricular failure (RVF) may adversely influence the natural history and prognosis of patients with diverse cardiopulmonary disorders. It has been long established that right ventricular (RV) ischemia, RV overload, and RV pressure overload, alone or in combination, are the main factors involved in the pathogenesis of RVF. From the pathophysiologic point of view, RVF of COPD is more a congestive type of failure, in which activation of renin-angiotensin system is involved. In PPH, a low cardiac output state is predominant and the precise mechanism of RVF remains unknown. Current evidence in favor of the pathogenetic role of ischemia, adrenergic overdrive, and genetic determination are all reviewed during the course.

Arrhythmogenic right ventricular cardiomyopathy: a survey of the investigations at the University of Padua.

The purpose of this paper is to review the history of the clinico-pathologic investigations performed at the University of Padua on an old morbid entity ("parchment heart"), which, in the 1960s, led to the clinical description of the disease, in the 1980s to the revival of the scientific interest, and in the mid 1990s to the understanding of the genetic background. All the steps of the progressive knowledge are reviewed: necropsy of young people who died suddenly, in vivo diagnosis by ECG, echocardiography, angiocardiography, endomyocardial biopsy, nuclear magnetic resonance, and diagnostic criteria. Familial occurrence with autosomic dominant transmission and various penetrance was documented. Gene defects were recently mapped both to chromosome 14q23-q24 and 1q42-q43, thus providing evidence for genetic heterogeneity. The pathologic substrates of arrhythmogenic right ventricular cardiomyopathy pointed to an acquired progressive myocardial atrophy with fibro-fatty replacement of dying myocytes. Nowadays the disease is definitively regarded as a primary myocardial disorder and it has been included in the revised WHO classification of cardiomyopathies.

[Outcome of arrhythmogenic right ventricular dysplasia. Apropos of 4 cases]. / Modalités évolutives de la dysplasie ventriculaire droite arythmogène. A propos de 4 observations.

The authors propose a classification of the outcome of arrhythmogenic right ventricular dysplasia with reference to 4 selected cases with a follow-up period of over 9 years. In type I, the left ventricular ejection fraction is normal (EF > 50%) and the risk, exclusively arrhythmic, can be controlled by appropriate antiarrhythmic therapy. This is the commonest form of arrhythmogenic right ventricular dysplasia with different varieties according to the degree of dilatation of the right ventricle. In type II, there is a variable degree of left ventricular involvement (30 < EF < 50%) either by extension of a comparable disease process as observed in the right ventricle or by an isolated or superimposed phenomenon of myocarditis. This form is stable and may remain stable for many years providing the arrhythmias are correctly treated. In type III, progressive degradation of the myocardium is observed over a period of about 10 years with a clinical presentation comparable to that of certain arrhythmogenic dilated cardiomyopathies which are often hereditary. In this case, the patients have an arrhythmic risk associated with that of cardiac failure which becomes progressively irreversible. The histology shows interstitial fibrosis with biventricular lymphocytic infiltration suggesting an autoimmune phenomenon. Therefore, the classification of cases of arrhythmogenic right ventricular dysplasia depends on the potential evolutivity of the lesions. When the patient is seen in the early stages of the disease, the prognosis should be garded, especially in a hereditary form.

Análisis funcional del ventrículo derecho (Suficiencia- Insuficiencia)

Históricamente se ha visto en ventrículo derecho como una estructura mucho menos importante que el ventrículo izquierdo lo que no es una situación fortuita, ya que estudios considerados como clásicos (1,2) demostraron experimentalmente que en casos de ablación de la pared libre del ventrículo derecho el compromiso circulatorio era mínimo y que el elemento clave en la propia eyección ventricular derecha era la función izquierda. La afirmación del Dr. Bernheim (3) válida pero desafortunada para el estudio del ventrículo derecho, de que la causa más importante de falla ventricular derecha era la falla ventricular izquierda, obstaculizó por mucho tiempo los esfuerzos por comprender mejor el funcionamiento de esta cámara, además de su compleja geometría que en sí la hace de muy difícil análisis. En vista de estas dificultades, hasta hace relativamente poco tiempo se ha estudiado el ventrículo derecho con base en las mismas consideraciones teóricas que para el izquierdo, esta situación también ha dificultado su entendimiento. Con el advenimiento de nueva biotecnología que permitió una mejor monitorización y sobrevivida en entidades tales como SDRA, EPOC e IAM se renovó el interés tanto en lo relacionado con el ventrícilo derecho como tal, como en la interacción corazón-pulmón. Deviniendo en tema de estudio y análisis para neumólogos, cardiólosgos e intensivistas. El propósito primordial de este artículo es plantear en tono de discusión algunas características fisiológicas sobresalientes del corazón derecho para con base en estas consideraciones hacer una aproximación fisiopatológica de la insuficiencia de esta cámara cardíaca