Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a Prospective, Non-randomized Study of Patients With Cirrhosis.

BACKGROUND & AIMS: Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time. METHODS: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient. RESULTS: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P = .015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls). CONCLUSIONS: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective.

Rheolityc thrombectomy in acute myocardial infarction: Effect on microvascular obstruction, infarct size, and left ventricular remodeling.

OBJECTIVES: We sought to analyze whether rheolytic thrombectomy (RT) in comparison with manual thrombus aspiration (MTA) may reduce microvascular obstruction (MVO), infarct size (IS), and left ventricular (LV) remodeling in ST-elevation myocardial infarction (STEMI). BACKGROUND: Conflicting results have been reported as to whether MTA reduces MVO and IS. METHODS AND RESULTS: Eighty STEMI reperfused by primary angioplasty and abciximab were randomly allocated (1:1) to RT or MTA. Cardiac magnetic resonance imaging (MRI) was performed in 37 patients (19 RT) and after 1 year in 19 (9 RT); baseline, 1- and 6-month 2D-echo was performed in all patients. MVO and IS were measured 8 min after gadolinium injection with late enhancement sequences and were analyzed quantitatively at a core laboratory blinded to randomization. At baseline TIMI thrombus grade were similar (RT: 4.47 ± 0.84 vs. MTA: 4.67 ± 0.76, P = 0.453). After thrombectomy, thrombus grade decreased to 1.11 ± 1.04 in RT vs. 2.17 ± 1.29 in MTA arm (P = 0.009). RT compared with MTA did not reduced significantly myocardial IS [12.2% (6.4-22.1) vs. 19.0% (7-28.5), P = 0.224] as well as the extent of MVO [0.0% (0.0-0.17) vs. 0.6% (0.0-1.4), P = 0.117], but a trend toward a lower incidence of MVO (16% vs. 44%, P = 0.056) and a less LV remodeling rate were found in RT arm (11% vs. 24%, P < 0.140). CONCLUSION: RT in comparison with MTA was more effective in thrombus removal, but it did not reduced significantly the IS and the extent of MVO. However, a trend toward a lower incidence of MVO and a better preservation of LV volumes were found in RT arm. © 2015 Wiley Periodicals, Inc.

Paradoxical embolization in TIPS: take a closer look to the heart.

No definitive indications are provided in the literature for pre-TIPS patient workup, which is often limited to prevent the incidence of refractory hepatic encephalopathy or unacceptable deterioration of liver function. Concerning cardiologic workup, efforts are generally limited at excluding ventricular failure or porto pulmonary hypertension. The cases presented herein focus the attention of the readers on the possible occurrence of post-TIPS paradoxical embolization in the presence of a patent foramen ovale, frequently recognized in adult population. In conclusion, although this complication has been already reported in literature, in the present manuscript we concentrate on possible additional risk factors which may allow to identify a subset of patients with a higher likelihood to experience paradoxical embolization following TIPS. Another important line of information presented herein is the feasibility of percutaneous closure of a patent foramen ovale before TIPS deployment in the presence of portal vein thrombosis and possibly with additional risk factors.

Pattern and degree of left ventricular remodeling following a tailored surgical approach for hypertrophic obstructive cardiomyopathy.

Background The role of a tailored surgical approach for hypertrophic cardiomyopathy (HCM) on regional ventricular remodelling remains unknown. The aims of this study were to evaluate the pattern, extent and functional impact of regional ventricular remodelling after a tailored surgical approach. Methods From 2005 to 2008, 44 patients with obstructive HCM underwent tailored surgical intervention. Of those, 14 were ineligible for cardiac magnetic resonance (CMR) studies. From the remainder, 14 unselected patients (42±12 years) underwent pre- and post-operative CMR studies at a median 12 months post-operatively (range 4-37 months). Regional changes in left ventricular (LV) thickness as well as global LV function following surgery were assessed using CMR Tools (London, UK). Results Pre-operative mean echocardiographic septal thickness was 21±4 mm and mean LV outflow gradient was 69±32 mmHg. Following surgery, there was a significant degree of regional regression of LV thickness in all segments of the LV, ranging from 16% in the antero-lateral midventricular segment to 41% in the anterior basal segment. Wall thickening was significantly increased in basal segments but showed no significant change in the midventricular or apical segments. Globally, mean indexed LV mass decreased significantly after surgery (120±29g/m2 versus 154±36g/m2; p<0.001). There was a trend for increased indexed LV end-diastolic volume (70±13 mL versus 65±11 mL; p=0.16) with a normalization of LV ejection fraction (68±7% versus 75±9%; p<0.01). Conclusion Following a tailored surgical relief of outflow obstruction for HCM, there is a marked regional reverse LV remodelling. These changes could have a significant impact on overall ventricular dynamics and function.

Characterization of Löeffler eosinophilic myocarditis by means of real time three-dimensional contrast-enhanced echocardiography.

Löeffler endocarditis is a rare myocardial disease often due to eosinophil leukemia or idiopathic hypereosinophilic syndrome. Degranulation of eosinophils within the eosinophil infiltrated myocardium is associated with myocardial necrosis due to the release of toxic cationic proteins, and with mural thrombi formation, which can occur anywhere in the ventricles. Thrombus formed on denuded myocardium is replaced by fibrosis as the final pathological stage of the disease, eventually leading to restrictive cardiomyopathy. We describe a multimodality imaging approach to the diagnosis and follow-up evaluation of Löeffler disease complicated by thrombus formation and neoangiogenesis of LV apex.

[Clinical and genetic features of left ventricular noncompaction: a continuum in cardiomyopathies]. / Clinica e genetica del ventricolo sinistro non compatto: conferma di un continuum nelle cardiomiopatie.

Isolated left ventricular non-compaction (LVNC) is a rare genetic form of cardiomyopathy (CM) characterized by prominent left ventricular wall trabeculation and intertrabecular recesses communicating with the ventricular cavity. Clinical signs are variable, ranging from lack of symptoms to severe manifestations including heart failure, sustained ventricular arrhythmias, cardioembolism and sudden death. The diagnosis of LVNC is frequently missed, due to limited awareness in the medical community. Contemporary diagnostic sensitivity has been enhanced by the introduction of specific morphologic criteria by high resolution echocardiography and cardiac magnetic resonance. As a consequence, LVNC has been diagnosed more frequently in association with other disorders such as congenital heart disease or genetic CM. The clinical relevance of regional non-compaction in the context of other cardiac diseases is still uncertain. Recent evidence points to an overlapping genetic background encompassing LVNC, hypertrophic and dilated CM, suggesting a continuum of disease associated with sarcomere protein gene mutations. This concept may prove relevant to the understanding of common pathogenetic mechanisms of CM and offer novel research opportunities.

The many faces of hypertrophic cardiomyopathy: from developmental biology to clinical practice.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterized by complex pathophysiology, heterogeneous morphology, and variable clinical manifestations over time. Besides cardiac hypertrophy, the HCM phenotype is characterized by a host of manifestations, including mitral valve and subvalvar abnormalities, subaortic and mid-ventricular left ventricular (LV) obstruction, microvascular dysfunction, myocardial fibrosis, disarray, atrial remodeling, myocardial bridging of epicardial coronary arteries, LV apical aneurysms, and autonomic nervous system abnormalities. Such heterogeneous phenotype still lacks a comprehensive explanation, which cannot be accounted solely by genetic heterogeneity, despite the large number of genes and mutations involved. It is likely that pre-natal and acquired features deriving from the primary genetic defect interact with the environment to produce the final result evident in each patient. Based on novel insights provided by cardiac developmental biology, a common lineage ancestry of several HCM manifestations might be traced back to the pluripotent epicardium-derived cells, which early during heart development differentiate into interstitial fibroblasts, coronary smooth muscle cells, and atrio-ventricular endocardial cushions as mesenchymal cells. To date, the different faces of HCM have not been sufficiently liked or explained. We here attempt to address these issues by describing the various components of the disease, their origin, interaction, and clinical significance.

Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

OBJECTIVES: Our aim was to assess the distribution and clinical significance of left ventricular (LV) mass in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Hypertrophic cardiomyopathy is defined echocardiographically by unexplained left ventricular wall thickening. Left ventricular mass, quantifiable by modern cardiovascular magnetic resonance techniques, has not been systematically assessed in this disease. METHODS: In 264 HCM patients (age 43 +/- 18 years; 75% men), LV mass by cardiovascular magnetic resonance was measured, indexed by body surface area, and compared with that in 606 healthy control subjects. RESULTS: The LV mass index in HCM patients significantly exceeded that of control subjects (104 +/- 40 g/m(2) vs. 61 +/- 10 g/m(2) in men and 89 +/- 33 g/m(2) vs. 47 +/- 7 g/m(2) in women; both p < 0.0001). However, values were within the normal range (< or = mean +2 SDs for control subjects) in 56 patients (21%), and only mildly increased (mean +2 to 3 SDs) in 18 (16%). The LV mass index showed a modest relationship to maximal LV thickness (r(2) = 0.38; p < 0.001), and was greater in men (104 +/- 40 g/m(2) vs. 89 +/- 33 g/m(2) in women; p < 0.001) and in patients with resting outflow obstruction (121 +/- 43 g/m(2) vs. 96 +/- 37 g/m(2) in nonobstructives; p < 0.001). During a 2.6 +/- 0.7-year follow-up, markedly increased LV mass index proved more sensitive in predicting outcome (100%, with 39% specificity), whereas maximal wall thickness >30 mm was more specific (90%, with 41% sensitivity). CONCLUSIONS: In distinction to prior perceptions, LV mass index was normal in about 20% of patients with definite HCM phenotype. Therefore, increased LV mass is not a requirement for establishing the clinical diagnosis of HCM. The LV mass correlated weakly with maximal wall thickness, and proved more sensitive in predicting outcome.

Spatial relationship between coronary microvascular dysfunction and delayed contrast enhancement in patients with hypertrophic cardiomyopathy.

UNLABELLED: To clarify the spatial relationship between coronary microvascular dysfunction and myocardial fibrosis in hypertrophic cardiomyopathy (HCM), we compared the measurement of hyperemic myocardial blood flow (hMBF) by PET with the extent of delayed contrast enhancement (DCE) detected by MRI. METHODS: In 34 patients with HCM, PET was performed using (13)N-labeled ammonia during hyperemia induced by intravenous dipyridamole. DCE and systolic thickening were assessed by MRI. Left ventricular myocardial segments were classified as with DCE, either transmural (DCE-T) or nontransmural (DCE-NT), and without DCE, either contiguous to DCE segments (NoDCE-C) or remote from them (NoDCE-R). RESULTS: In the group with DCE, hMBF was significantly lower than in the group without DCE (1.81 +/- 0.94 vs. 2.13 +/- 1.11 mL/min/g; P < 0.001). DCE-T segments had lower hMBF than did DCE-NT segments (1.43 +/- 0.52 vs. 1.91 +/- 1 mL/min/g, P < 0.001). Similarly, NoDCE-C segments had lower hMBF than did NoDCE-R (1.98 +/- 1.10 vs. 2.29 +/- 1.10 mL/min/g, P < 0.01) and had no significant difference from DCE-NT segments. Severe coronary microvascular dysfunction (hMBF in the lowest tertile of all segments) was more prevalent among NoDCE-C than NoDCE-R segments (33% vs. 24%, P < 0.05). Systolic thickening was inversely correlated with percentage transmurality of DCE (Spearman rho = -0.37, P < 0.0001) and directly correlated with hMBF (Spearman rho = 0.20, P < 0.0001). CONCLUSION: In myocardial segments exhibiting DCE, hMBF is reduced. DCE extent is inversely correlated and hMBF directly correlated with systolic thickening. In segments without DCE but contiguous to DCE areas, hMBF is significantly lower than in those remote from DCE and is similar to the value obtained in nontransmural DCE segments. These results suggest that increasing degrees of coronary microvascular dysfunction might play a causative role for myocardial fibrosis in HCM.

Performance of Doppler ultrasound in the prediction of severe portal hypertension in hepatitis C virus-related chronic liver disease.

PURPOSE: To evaluate the correlation between hepatic vein pressure gradient measurement and Doppler ultrasonography (DUS) in patients with chronic liver disease (CLD). PATIENTS AND METHODS: Sixty-six patients with fibrotic to cirrhotic hepatitis C virus-related CLD, were consecutively included upon referral to our haemodynamic laboratory. Superior mesenteric artery pulsatility index (SMA-PI), right interlobar renal and intraparenchymal splenic artery resistance indices, were determined, followed by hepatic venous pressure gradient (HVPG) measurement. RESULTS: A correlation was found between HVPG and intraparenchymal splenic artery resistance index (SA-RI) (r=0.50, P<0.0001), SMA-PI (r=-0,48, P<0.0001), right interlobar renal artery resistance index (RRA-RI) (r=0.51, P<0.0001) in the whole patient population. However, dividing patients according to the presence/absence of severe portal hypertension (i.e. HVPG > or =12 mmHg), a correlation between HVPG and intraparenchymal SA-RI (r=0.70, P<0.0001), SMA-PI (r=-0.49, P=0.02), RRA-RI (r=0.66, P=0.0002) was observed only for HVPG values <12 mmHg. HVPG but not DUS correlated with the presence of esophageal varices (P<0.0001). CONCLUSIONS: Superior mesenteric artery pulsatility index, intraparenchymal splenic and right interlobar renal artery resistance indices do not adequately predict severe portal hypertension.

Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis.

UNLABELLED: Measurement of hepatic venous pressure gradient (HVPG) is a standard method for the assessment of portal pressure and correlates with the occurrence of its complications. Liver stiffness measurement (LSM) has been proposed as a noninvasive technique for the prediction of the complications of cirrhosis. In this study, we evaluated the ability of LSM to predict severe portal hypertension compared with that of HVPG in 61 consecutive patients with HCV-related chronic liver disease. A strong relationship between LSM and HVPG measurements was found in the overall population (r=0.81, P<0.0001). However, although the correlation was excellent for HVPG values less than 10 or 12 mm Hg (r=0.81, P=0.0003 and r=0.91, P<0.0001, respectively), linear regression analysis was not optimal for HVPG values>or=10 mm Hg (r2=0.35, P<0.0001) or>or=12 mm Hg (r2=0.17, P=0.02). The AUROC for the prediction of HVPG>or=10 and >or=12 mm Hg were 0.99 and 0.92, respectively and at LSM cutoff values of 13.6 kPa and 17.6 kPa, sensitivity was 97% and 94%, respectively. In patients with cirrhosis, LSM positively correlated with the presence of esophageal varices (P=0.002), although no correlation between LSM and esophageal varices size was detected. The area under the ROC for the prediction of EV was 0.76 and at a LSM cutoff value of 17.6 kPa sensitivity was 90%. CONCLUSION: LSM represents a non-invasive tool for the identification of chronic liver disease patients with clinically significant or severe portal hypertension and could be employed for screening patients to be subjected to standard investigations including upper GI endoscopy and hemodynamic studies.

Identification of the ischemic etiology of heart failure by cardiovascular magnetic resonance imaging: diagnostic accuracy of late gadolinium enhancement.

BACKGROUND: A large proportion of patients with heart failure (HF) have a large and poorly contracting left ventricle. The noninvasive recognition of the ischemic etiology of such patients is difficult, and for this purpose, usually patients undergo coronary angiography. It has been shown that cardiovascular magnetic resonance (CMR) imaging can detect myocardial scarring by evaluating late gadolinium enhancement (LGE). The diagnostic accuracy of such method in differentiating the etiology of HF has not been previously tested in an unselected HF ambulatory population. METHODS: We studied 60 ambulatory patients consecutively enrolled from a specialized HF clinic. We included HF patients who were found to have increased left ventricular (LV) dimensions and reduced function. CMR was performed in these patients by operators who were unaware of patients' history and clinical conditions. LV dimensions and global and regional function, as well as the pattern of LGE, were obtained in each subject. Coronary angiography was subsequently performed in all the patients. The diagnostic accuracy of clinical history and electrocardiographic patterns, as well as regional wall motion abnormalities, wall thinning, and LGE, in differentiating coronary artery disease (CAD) from non-CAD patients were evaluated. RESULTS: The majority of CAD patients (98%) showed LV contrast hyperenhancement with respect to non-CAD HF subjects (16%). The detection of LGE by CMR had a sensitivity of 98% and a specificity of 84% and an overall accuracy of 93% in detecting CAD etiology among HF patients. CONCLUSIONS: LGE is able to accurately differentiate CAD from non-CAD etiology of HF and may represent a clinically useful noninvasive tool for this purpose. As it provides relevant functional information as well as insight into the etiology, CMR may be included among the most important diagnostic tools in the workup of patients with HF.

Detection and assessment of coronary artery anomalies by three-dimensional magnetic resonance coronary angiography.

BACKGROUND: Coronary artery anomalies (CAAs) are a relatively rare condition usually diagnosed in vivo by conventional angiography. In the past few years Magnetic resonance coronary angiography (MRCA) has been used to detect CAAs and found to be highly accurate. No data is available regarding the ability of MRCA to detect previously not suspected anomalies. METHODS: We prospectively analyzed the origin and course of 336 patients undergoing a diagnostic Cardiovascular magnetic resonance (CMR) study. After the completion of a standard examination a navigator-echo 3D-MRCA low-quality scan was used in all the cases to rule out CAAs. The high-quality MRCA was applied only if an abnormal coronary arterial tree was seen. RESULTS: Nineteen patients with CAAs (12 men, 7 women; mean age, 53+/-18 years) were identified by MRCA. Six out of the 19 CAAs subjects had already been detected by other means (coronary angiography in 5, and transesophageal echocardiography in 1 case). However in none of them a complete anatomical assessment was achieved. In 13 patients CAAs were an unexpected and new finding. MRCA was able to assess the origin and proximal course of the anomalous artery in all the cases. CONCLUSIONS: MRCA is able to detect the presence and anomalous course of CAAs. Besides offering precise information about already suspected CAAs, MRCA can identify anomalies previously not suspected. This study suggests a potential role for MRCA as a screening tool for CAAs in young patients with angina, ventricular arrhythmias, or unexplained syncope as well as in highly competitive athletes.

Small diameter H-graft porta-caval shunt performed at different stages of liver disease.

BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and occlusion). To further investigate these assumptions, we retrospectively reviewed the results of partial porta-caval shunts performed at different stages of liver disease. METHODS: Twenty-nine cirrhotic patients underwent a partial porta-caval shunt with a ringed polytetrafluoroethylene interposition prosthesis of 8-mm (20 patients) or 10-mm (9 patients) in diameter. Pre and post-shunt porta-caval pressure was measured in all patients. Twelve patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%). Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively. Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval pressure gradient, reduced significantly using either 8- or 10-mm prosthesis. The overall early mortality and morbidity were 13.8% and 48% respectively. The early mortality and morbidity were different between patients of Child A and B when compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No patient re-bled early from varices. The overall late mortality and morbidity were 40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8% of the two groups of patients respectively; variceal re-bleeding occurred in 4 patients (16%). Encephalopathy occurred postoperatively in 5 patients (20%), acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at 3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate that partial porta-caval shunt with a small diameter interposition H-graft is an effective procedure for the treatment of variceal bleeding, as well as for the prevention of re-bleeding in patients of Child A and those of Child B, as an elective or emergency/urgency procedure, with a low rate of complications and encephalopathy. This technique could be used safely in patients with good liver function but they should be monitored closely because of the risk of shunt occlusion.

Diagnostic work up of arrhythmogenic right ventricular cardiomyopathy by cardiovascular magnetic resonance (CMR). Consensus statement.

Cardiovascular Magnetic Resonance (CMR) has become a widespread diagnostic tool. Since its introduction CMR has been used to image patients with known or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC). Several abnormalities have been found and described by CMR and at present this diagnostic tool is considered very important for the diagnosis. However, the diagnosis of ARVC relies upon the fulfillment of both clinical and functional criteria and CMR can provide several but not all the information useful for the diagnosis. Furthermore, some findings such as evidence of right ventricular epicardial fat once considered a peculiar marker of ARVC, have been shown to possess a low specificity. This document was prepared by representatives of the three Italian official Organizations involved in CMR. Its main scope is to highlight the problems encountered when studying patients with suspected ARVC by CMR, to indicate the basic technical equipment needed, to recommend a proper imaging protocol and to offer a consensus on the main diagnostic features relevant for the diagnosis.

Diagnostic work-up of arrhythmogenic right ventricular cardiomyopathy by cardiovascular magnetic resonance.

Cardiovascular magnetic resonance (CMR) has become a widespread diagnostic tool. Since its introduction, CMR has been used to image patients with a known or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC). Several abnormalities have been found and described by CMR and at present this diagnostic tool is considered very important for the diagnosis. However, the diagnosis of ARVC relies upon the fulfillment of both clinical and functional criteria and CMR can provide several but not all the information useful for the diagnosis. Furthermore, some findings such as evidence of right ventricular epicardial fat, once considered a peculiar marker of ARVC, have been shown to possess a low specificity. This document was prepared by representatives of the three Italian official Organizations involved in CMR. Its main scope is to highlight the problems encountered when studying patients with suspected ARVC at CMR, to indicate the basic technical equipment needed, to recommend a proper imaging protocol and to offer a consensus on the main features relevant for the diagnosis.