Multimodality imaging for pre-clinical assessment of Fabry's cardiomyopathy.

Anderson Fabry's disease (AFD) is a rare but underdiagnosed intracellular lipid disorder which can cause left ventricular hypertrophy (LVH). Pre-clinical diagnosis of Fabry's disease is important as it permits early stratification for enzyme replacement therapy, improving the patient's long-term prognosis, avoiding progression to irreversible fibrosis, and preventing cardiovascular complications. Combinations of imaging modalities that integrate the strengths of each modality and at the same time eliminate weaknesses of an individual modality can offer improved diagnostics, therapeutic monitoring, and pre-clinical assessment of Fabry's disease. This review discusses the advantages and challenges in developing multimodality imaging systems of Fabry's cardiomyopathy, highlights some successful combinations that are now routinely used in the clinic and in research, and discusses recent advances in multimodality instrumentation that may offer new opportunities for pre-clinical assessment of this disease.

Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator.

BACKGROUND: Prosthetic valve thrombosis during pregnancy is life-threatening for mother and fetus, and the treatment of this complication is unclear. Cardiac surgery in pregnancy is associated with very high maternal and fetal mortality and morbidity. Thrombolytic therapy has rarely been used in these patients. The aim of this study is to evaluate the safety and efficacy of low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator for the treatment of prosthetic valve thrombosis in pregnant women. METHODS AND RESULTS: Between 2004 and 2012, tissue-type plasminogen activator was administered to 24 consecutive women in 25 pregnancies with 28 prosthetic valve thrombosis episodes (obstructive, n=15; nonobstructive, n=13). Mean age of the patients was 29±6 years. Thrombolytic therapy sessions were performed under transesophageal echocardiography guidance. The mean dose of tissue-type plasminogen activator used was 48.7±29.5 mg (range, 25-100 mg). All episodes resulted in complete thrombus lysis after thrombolytic therapy. One patient had placental hemorrhage with preterm live birth at the 30th week, and 1 patient had minor bleeding. CONCLUSIONS: Low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed is an effective therapy with an excellent thrombolytic success rate for the treatment of prosthetic valve thrombosis in pregnant women. This protocol also seems to be safer than cardiac surgery or any alternative medical strategies published to date. Thrombolytic therapy should be considered first-line therapy in pregnant patients with prosthetic valve thrombosis.

Real-time three-dimensional transesophageal echocardiography in the assessment of mechanical prosthetic mitral valve ring thrombosis.

Although 2-dimensional (2D) transesophageal echocardiography (TEE) is the gold standard for the diagnosis of prosthetic valve thrombosis, nonobstructive clots located on mitral valve rings can be missed. Real-time 3-dimensional (3D) TEE has incremental value in the visualization of mitral prosthesis. The aim of this study was to investigate the utility of real-time 3D TEE in the diagnosis of mitral prosthetic ring thrombosis. The clinical outcomes of these patients in relation to real-time 3D transesophageal echocardiographic findings were analyzed. Of 1,263 patients who underwent echocardiographic studies, 174 patients (37 men, 137 women) with mitral ring thrombosis detected by real-time 3D TEE constituted the main study population. Patients were followed prospectively on oral anticoagulation for 25 ± 7 months. Eighty-nine patients (51%) had thrombi that were missed on 2D TEE and depicted only on real-time 3D TEE. The remaining cases were partially visualized with 2D TEE but completely visualized with real-time 3D TEE. Thirty-seven patients (21%) had thromboembolism. The mean thickness of the ring thrombosis in patients with thromboembolism was greater than that in patients without thromboembolism (3.8 ± 0.9 vs 2.8 ± 0.7 mm, p <0.001). One hundred fifty-five patients (89%) underwent real-time 3D TEE during follow-up. There were no thrombi in 39 patients (25%); 45 (29%) had regression of thrombi, and there was no change in thrombus size in 68 patients (44%). Thrombus size increased in 3 patients (2%). Thrombosis was confirmed surgically and histopathologically in 12 patients (7%). In conclusion, real-time 3D TEE can detect prosthetic mitral ring thrombosis that could be missed on 2D TEE and cause thromboembolic events.

Electrical plasticity and cardioprotection in myocardial ischemia--role of selective sodium channel blockers.

The concept of electrical protection of the ischemic myocardium is in constant evolution and has recently been supported by experimental and clinical studies. Historically, antiplatelet agents, angiotensin-converting enzyme inhibitors, ß-blockers, and statins have been all proposed as drugs conferring anti-ischemic cardioprotection. This was supported by the evidence consistently indicating that all these drugs were capable of reducing mortality and the risk of repeat myocardial infarction. The electrical plasticity paradigm is, however, a novel concept that depicts the benefits of improved sodium channel blockade with drugs such as ranolazine and cariporide. Although it has been hypothesized that the protective role of ranolazine depends on decreased fatty acid ß-oxidation affecting preconditioning, we speculate against such a hypothesis, because inhibition of ß-oxidation requires higher concentrations of the drug, above the therapeutic range. Rather, we discuss the key role of calcium overload reduction through inhibition of the late sodium current (I(Na)). Mechanisms driving cardioprotection involve the block of a cascade of complex ionic exchanges that can result in intracellular acidosis, excess cytosolic calcium, myocardial cellular dysfunction, and eventually cell injury and death. In this review we discuss the studies that demonstrate how electrical plasticity through sodium channel blockers can promote cardioprotection against ischemia in coronary heart disease.

Comparison of different TEE-guided thrombolytic regimens for prosthetic valve thrombosis: the TROIA trial.

OBJECTIVES: The aim of this prospective study was to identify the most effective and safest regimen among different thrombolytic treatment strategies. BACKGROUND: The best treatment strategies for prosthetic valve thrombosis have been controversial. METHODS: Transesophageal echocardiography-guided thrombolytic treatment was administered to 182 consecutive patients with prosthetic valve thrombosis in 220 different episodes (156 women; mean age, 43.2 ± 13.06 years) between 1993 and 2009 at a single center. These regimens chronologically included rapid (Group I), slow (Group II) streptokinase, high-dose (100 mg) tissue plasminogen activator (t-PA) (Group III), a half-dose (50 mg) and slow infusion (6 h) of t-PA without bolus (Group IV), and a low dose (25 mg) and slow infusion (6 h) of t-PA without bolus (Group V). The endpoints were thrombolytic success, in-hospital mortality, and nonfatal complication rates. RESULTS: The overall success rate in the whole series was 83.2%; it did not differ significantly among Groups I through V (68.8%, 85.4%, 75%, 81.5%, and 85.5%, respectively; p = 0.46). The overall complication rate in the whole series was 18.6%. Although the overall complication rate was similar among Groups I through IV (37.5%, 24.4 %, 33.3%, and 29.6%, respectively; p > 0.05 for each comparison), it was significantly lower in Group V (10.5%, p < 0.05 for each). The combined rates of mortality and nonfatal major complications were also lower in Group V than in the other groups, with all differences significant except for comparison of Groups IV and V. By multivariate analysis, the predictors of combined mortality plus nonfatal major complications were any thrombolytic therapy regimen other than Group V (odds ratios for Groups I through IV: 8.2, 3.8, 8.1, and 4.1, respectively; p < 0.05 for each) and a history of stroke/transient ischemic attack (odds ratio: 3.5, p = 0.011). In addition, there was no mortality in Group V. CONCLUSIONS: Low-dose slow infusion of t-PA repeated as needed without a bolus provides effective and safe thrombolysis in patients with prosthetic valve thrombosis. (Comparison of Different TRansesophageal Echocardiography Guided thrOmbolytic Regimens for prosthetIc vAlve Thrombosis; NCT01451320).

Left ventricular assist devices and gastrointestinal bleeding: a narrative review of case reports and case series.

BACKGROUND: The use of left ventricular assist devices (LVADs) has become a state-of-the-art therapy for advanced cardiac heart failure; however, multiple reports in the literature describe an increased risk for gastrointestinal (GI) bleeding in these patients. We characterized this association by reviewing recent studies on this topic. HYPOTHESIS: GI bleeding occurs frequently in patients with LVADs, especially with devices with nonpulsatile flow patterns. METHODS: We performed a comprehensive literature review to identify articles that reported GI bleeding in patients with LVADs. Databases used included PubMed, EMBASE, Scopus, Web of Knowledge, and Ovid. Baseline and outcome data were then ed from these reports. RESULTS: We identified 10 case reports and 22 case series with 1543 patients. The mean age was 54.2 years. Most patients had nonpulsatile LVADs (1316, 85.3%). Three hundred and seventeen patients (20.5%) developed GI bleeding; this occurred more frequently in patients with nonpulsatile LVADs. Multiple procedures were performed without complications but often did not identify a definite bleeding site. Suspect lesions occurred throughout the GI tract but were more frequent in the upper GI tract. Many patients had arteriovenous malformations. All patients received medical therapy. None of the patients had their LVAD replaced. The use of anticoagulation did not appear to predispose these patients to more GI bleeding episodes. CONCLUSIONS: Patients with LVADs have frequent GI bleeds, especially from arteriovenous malformations, which can occur throughout the GI tract. Most diagnostic and therapeutic interventions can be used safely in these patients. The pathogenesis of the GI bleeding in these patients may involve the use of anticoagulant medications, the formation of arteriovenous malformations, loss of von Willebrand factor activity, and mucosal ischemia.

Utility of the NavX® Electroanatomic Mapping System for Permanent Pacemaker Implantation in a Pregnant Patient with Chagas Disease.

Chagas disease is a highly prevalent zoonosis in Mexico, Central, and South America. Early cardiac involvement is one of the most serious complications of this disease, and conduction disturbances may occur at an early age. We describe a young pregnant woman with Chagas disease and a high degree atrioventricular block, who required implantation of a permanent dual chamber pacemaker. Using an electroanatomic navigation EnSite NavX® system the pacemaker was successfully implanted with minimal fluoroscopic exposure. This case demonstrates the safety and feasibility of using an electroanatomic navigation system to guide permanent pacemaker implantation minimizing x-ray exposure in pregnant patients.

No harmful effect of dialysis-induced hypotension on the myocardium in patients who have normal ejection fraction and a negative exercise test.

BACKGROUND: We investigated the effects of dialysis-induced hypotension (DIH) on the myocardium of patients who have a normal ejection fraction and normal treadmill stress tests. METHODS: This study included 26 end-stage renal disease (ESRD) patients with DIH, 30 ESRD patients without DIH (non-DIH), and 30 control subjects. Mitral-myocardial systolic velocity (MSV), the mitral E'/A' ratio, the left ventricle filling pressure index (E/E' ratio), tricuspid-MSV, and the tricuspid E'/A' ratio were calculated. RESULTS: Biventricular systolic and diastolic functions were impaired in dialysis patients. The mitral and tricuspid MSV were similar between DIH and non-DIH patients (8.03 ± 0.90 cm/s vs. 8.31 ± 1.68 cm/s, p = 0.896, and 13.27 ± 2.97 cm/s vs. 13.15 ± 2.37 cm/s, p = 0.980). Mitral and tricuspid E'/A' were similar between DIH and non-DIH patients. (1.30 ± 0.53 vs. 1.16 ± 0.56, p = 0.695, and 0.70 ± 0.24 vs. 0.68 ± 0.33, p = 0.976). Likewise, the E/E' ratio was similar between DIH and non-DIH patients (8.20 ± 2.83 vs. 8.28 ± 2.53, p = 0.990). CONCLUSION: Although biventricular systolic and diastolic function is impaired in dialysis patients compared to controls, DIH episodes did not have an adverse effect on the myocardial functions.

Transthoracic echocardiography of the HeartWare left ventricular assist device.

BACKGROUND: The unique findings on transthoracic echocardiography of the HeartWare left ventricular assist device (LVAD) have not been previously described. METHODS AND RESULTS: HeartWare LVADs were implanted in 19 patients from May 2009 through December 2010; 152 comprehensive transthoracic echocardiograms (TTEs) performed postoperatively on these patients were retrospectively analyzed for device component visualization, inlet cannula/outflow conduit flow velocities, and imaging artifacts. The inlet cannula was adequately visualized in 66% of studies, incompletely visualized in 14%, and not visualized in 20%. Spectral Doppler interrogation of inlet cannula flow velocity was always uninterpretable due to artifact. Standard parasternal long-axis and apical views always included the inlet cannula in the imaging sector, resulting in a prominent "waterfall" color Doppler artifact obscuring the mitral valve. Inclusion of the inlet cannula in the imaging sector also precluded spectral Doppler interrogation of the mitral valve owing to artifact. The outflow conduit was partially visualized and interrogated by spectral Doppler in 68% of studies, and the average measured peak flow velocity was 1.4 m/s (range 1.0-1.9 m/s). CONCLUSIONS: The HeartWare LVAD inlet cannula and outflow conduit are both readily visualized by TTE in a majority of patients. However, significant color and spectral Doppler artifacts occur when the inlet cannula is visualized in the imaging sector, necessitating routine off-axis Doppler interrogation of the mitral valve.

Multiple left ventricular thrombi in a patient with left ventricular noncompaction.

The major clinical features of myocardial noncompaction are heart failure, arrhythmias, and thromboembolic events. Prominent myocardial trabeculae and deep recesses characteristic of myocardial noncompaction can cause stagnant blood flow and the formation of left ventricular clots. We describe the case of a 62-year-old woman who presented with symptoms of heart failure secondary to left ventricular noncompaction. Transthoracic and transesophageal echocardiography revealed multiple left ventricular thrombi, which had formed despite the patient's long-term therapy with aspirin. Anticoagulative therapy should be considered for patients with myocardial noncompaction who also have risk factors for thromboembolism, such as atrial fibrillation, a history of systemic embolism, or severe left ventricular systolic dysfunction. However, chronic antiplatelet therapy may not sufficiently prevent clot formation in patients who have myocardial noncompaction and severe left ventricular systolic dysfunction.

Percutaneous stenting to treat pulmonary vein stenosis after single-lung transplantation.

Pulmonary vein stenosis after lung transplantation is rare. Untreated, it can cause transplant failure and death. We describe the case of a 56-year-old man in whom pulmonary vein stenosis developed after single-lung transplantation. He was successfully treated with angioplasty and stent implantation guided by intravascular ultrasonography. To our knowledge, this is the first report of using this method to evaluate the pulmonary vein after lung transplantation, to confirm the diagnosis of pulmonary vein stenosis, and to guide the sizing and positioning of a stent. In lung-transplant recipients, percutaneous stent implantation may preclude reoperation and salvage the transplanted lung when used as treatment for pulmonary vein stenosis.

Medical literature searches: a comparison of PubMed and Google Scholar.

BACKGROUND: Medical literature searches provide critical information for clinicians. However, the best strategy for identifying relevant high-quality literature is unknown. OBJECTIVES: We compared search results using PubMed and Google Scholar on four clinical questions and analysed these results with respect to article relevance and quality. METHODS: Abstracts from the first 20 citations for each search were classified into three relevance categories. We used the weighted kappa statistic to analyse reviewer agreement and nonparametric rank tests to compare the number of citations for each article and the corresponding journals' impact factors. RESULTS: Reviewers ranked 67.6% of PubMed articles and 80% of Google Scholar articles as at least possibly relevant (P = 0.116) with high agreement (all kappa P-values < 0.01). Google Scholar articles had a higher median number of citations (34 vs. 1.5, P < 0.0001) and came from higher impact factor journals (5.17 vs. 3.55, P = 0.036). CONCLUSIONS: PubMed searches and Google Scholar searches often identify different articles. In this study, Google Scholar articles were more likely to be classified as relevant, had higher numbers of citations and were published in higher impact factor journals. The identification of frequently cited articles using Google Scholar for searches probably has value for initial literature searches.

The role of hypervirulent Staphylococcus aureus infections in the development of deep vein thrombosis.

Patients with sepsis frequently have activated coagulation pathways triggered by tissue factor, reduced levels of anticoagulation factors, reduced fibrinolysis, activated endothelial surfaces, and activated platelets. These processes result in disseminated intravascular coagulation and microthrombus formation and contribute to multi-organ system failure. S aureus surface proteins and exotoxins can contribute to thrombus formation through effects on the coagulation pathway and on anticoagulation factors. In addition, S aureus can activate endothelial surfaces and platelets. Some exotoxins such as the Panton-Valentine leukocidin can cause leukocyte lysis and additional injury to endothelial surfaces. These events can cause microthrombosis and deep venous thrombosis. Several case series have described an association between acute hematogenous osteomyelitis secondary to S aureus and the development of deep venous thrombosis in extremities. In addition, a recent clinical case review of staphylococcal community-acquired pneumonia demonstrated that patients who died secondary to these infections frequently had deep venous thrombosis. These observations support the idea that S aureus can contribute to thrombus formation. We recently cared for a patient who developed splanchnic vein thrombosis during an episode of staphylococcal cellulitis associated with bacteremia and multi-organ system failure. The pathogenesis of splenic vein thrombosis differs from the pathogenesis of deep venous thrombosis in the extremities in some, but not all, respects. Clearly the presence of circulating staphylococci and associated proteins could contribute to the formation of thrombi in the splanchnic circulation. Patients with hypervirulent staphylococcal infections require evaluation for deep venous thrombosis in extremities and in unusual sites. The development of these clots has a potentially significant impact on management and outcome. This review considers the pathogenesis of deep vein thrombosis in patients with sepsis, the potential contributions of Staphylococcus aureus in this process, and clot formation in unusual locations which greatly increases the complexity of patient care.

Isolated left ventricular noncompaction in a 90-year-old man.

Isolated ventricular myocardial noncompaction is a cardiomyopathy that is being diagnosed more frequently in patients of all ages because of increased awareness and improvements in imaging methods. It is an extremely rare cause of heart failure in nonagenarians. We describe the case of a man who presented with heart failure for the first time at 90 years of age. The diagnosis was isolated left ventricular noncompaction. Transthoracic echocardiography showed a trabeculated, sponge-like appearance of the left ventricular apical and inferolateral segments. After medical management, the patient was asymptomatic at the 3-month follow-up examination. Knowledge of ventricular noncompaction is increasing within the cardiology community. Patients who have isolated noncompaction with a limited number of involved ventricular segments can live beyond normal life expectancy without developing heart failure. In addition to discussing our patient's case, we briefly review the relevant medical literature.

Segmental diastolic compression of circumflex coronary artery secondary to pericardial constriction: an uncommon cause of angina pectoris.

Diastolic segmental compression of a native coronary artery is an uncommon cause of chest pain. Here we describe a 24-year-old woman with constrictive pericarditis who had retrosternal chest pain, progressive dyspnea, tachycardia, and bilateral leg edema. She was diagnosed with compression of the first and second obtuse marginal branches of left circumflex coronary artery secondary to constrictive pericarditis. She underwent pericardiectomy and her symptoms were relieved following surgery.

Percutaneous ventricular assist device in hypertrophic obstructive cardiomyopathy with cardiogenic shock: bridge to myectomy.

We present the case of a 69-year-old woman with end-stage hypertrophic obstructive cardiomyopathy who developed cardiogenic shock. She underwent emergent placement of a percutaneous left ventricular assist device (TandemHeart) in the catheterization lab as a bridge support device until a septal myectomy could be performed as definitive treatment. This case suggests a novel and promising use of the TandemHeart as a bridge to myectomy.

Aortic stenosis and angiodysplastic gastrointestinal bleeding: Heyde's disease.

Obscure gastrointestinal (GI) bleeding can be a perplexing and difficult problem in elderly patients, especially if they are hemodynamically unstable. If aortic stenosis is also present, the cause of the GI bleeding may be explained. We present a 66-year-old man with a medical history of coronary artery disease who presented with acute GI bleeding. During his hospital course, the patient had a colonoscopy showing diffuse angiodysplasia and an echocardiogram showing severe aortic stenosis. This combination of angiodysplasia and aortic stenosis is known as Heyde's syndrome. It has been hypothesized that the aortic stenosis causes an acquired von Willebrand factor deficiency that leads to GI bleeding. Aortic valve replacement, when possible, can prevent recurrent GI bleeding in these cases, but medical decisions in these cases are complex and difficult.

Epicardial fat thickness is associated with non-dipper blood pressure pattern in patients with essential hypertension.

OBJECTIVE: Epicardial fat tissue reflects visceral adiposity and is a suggested cardiometabolic risk factor. Patients with abdominal obesity have an increased prevalence of the non-dipper blood pressure (BP) pattern, but it is unclear whether the same is true of patients with increased epicardial fat thickness (EFT). The association between EFT and circadian BP changes in patients with recently diagnosed essential hypertension was examined. METHODS: Sixty hypertensive patients underwent echocardiography, treadmill stress testing, and 24 hours of ambulatory BP monitoring. Epicardial fat thickness and left ventricular mass (LVM) index were measured by using transthoracic echocardiography. The patients were categorized into two groups according to their BP pattern (group 1, non-dippers; group 2, dippers). RESULTS: The mean EFT and LVM of patients in group 1 (n = 24) (EFT, 7.6 ± 2.1 mm; LVM, 130 ± 31.2 g/m(2)) were significantly greater than those of group 2 (n = 36) (EFT, 5.5 ± 1.2 mm, P = .0001; LVM, 107 ± 23.7 g/m(2), P = .002). The average systolic BP over 24 hours (BP(s) 24) and average diastolic BP over 24 hours (BP(d) 24) of group 1 (BP(s) 24, 151.1 ± 17.6 mm Hg; BP(d) 24, 94.1 ± 16.5 mm Hg) were significantly higher than those of group 2 (BP(s) 24, 136.7 ± 11.9 mm Hg, P = .0001; BP(d) 24, 84.6 ± 10.6 mm Hg; P = .008). Multivariate backward logistic regression analysis demonstrated that the non-dipper BP pattern was associated with EFT (standardized ß coefficient = 0.87, P = .005) and LVM (standardized ß coefficient = 0.43, P = .016). An EFT ≥ 7 mm was associated with the non-dipper BP pattern with 44% sensitivity and 94% specificity (receiver operating characteristic area under curve of 0.72, 95% CI [0.59-0.83], P = .0007). CONCLUSIONS: Epicardial fat thickness was above average in newly diagnosed, untreated hypertensive patients with non-dipper BP pattern. The echocardiographic measurement of EFT may be used to indicate increased risk of hypertension-related adverse cardiovascular events.