Anomalous Origin of All Coronary Arteries from Right Sinus of Valsalva.

Anomalous coronary arteries are rare and often incidental findings. Most variants are benign. We present the case of a 75-year-old man with exertional dyspnea in whom the left anterior descending coronary artery arose from the right sinus of Valsalva, and the left circumflex coronary artery originated from the distal right coronary artery and supplied the obtuse marginal branch. No arteries originated from the left sinus of Valsalva. The patient was prescribed optimal medical therapy for atherosclerotic stenosis in his ramus intermedius. His symptoms were stable 3 years later.

Spontaneous coronary artery dissection with left ventricular thrombus.

Spontaneous coronary artery dissection (SCAD) is a rare, nonatherosclerotic cause of acute coronary syndrome. The etiology is unclear, and optimal treatment for SCAD remains undefined. We describe a patient with significant cardiovascular risk factors who presented with SCAD resulting in anterior wall acute myocardial infarction with left ventricular thrombus. The patient was managed conservatively with anticoagulant and antiplatelet therapy.

Pulmonary artery catheter entrapment in cardiac surgery: a simple percutaneous solution.

Pulmonary artery catheter entrapment is a reported complication after cardiac surgery from inadvertent suturing of the catheter to the vena-caval wall during surgery. This article reports a simple percutaneous technique to retrieve the trapped catheter.

Tumor necrosis factor receptor-associated factor 2 signaling provokes adverse cardiac remodeling in the adult mammalian heart.

BACKGROUND: Tumor necrosis factor superfamily ligands provoke a dilated cardiac phenotype signal through a common scaffolding protein termed tumor necrosis factor receptor-associated factor 2 (TRAF2); however, virtually nothing is known about TRAF2 signaling in the adult mammalian heart. METHODS AND RESULTS: We generated multiple founder lines of mice with cardiac-restricted overexpression of TRAF2 and characterized the phenotype of mice with higher expression levels of TRAF2 (myosin heavy chain [MHC]-TRAF2(HC)). MHC-TRAF2(HC) transgenic mice developed a time-dependent increase in cardiac hypertrophy, left ventricular dilation, and adverse left ventricular remodeling, and a significant decrease in LV+dP/dt and LV-dP/dt when compared with littermate controls (P<0.05 compared with littermate). During the early phases of left ventricular remodeling, there was a significant increase in total matrix metalloproteinase activity that corresponded with a decrease in total myocardial fibrillar collagen content. As the MHC-TRAF2(HC) mice aged, there was a significant decrease in total matrix metalloproteinase activity accompanied by an increase in total fibrillar collagen content and an increase in myocardial tissue inhibitor of metalloproteinase-1 levels. There was a significant increase in nuclear factor-κB activation at 4 to 12 weeks and jun N-terminal kinases activation at 4 weeks in the MHC-TRAF2(HC) mice. Transciptional profiling revealed that >95% of the hypertrophic/dilated cardiomyopathy-related genes that were significantly upregulated genes in the MHC-TRAF2(HC) hearts contained κB elements in their promoters. CONCLUSIONS: These results show for the first time that targeted overexpression of TRAF2 is sufficient to mediate adverse cardiac remodeling in the heart.

Digoxin treatment in heart failure--unveiling risk by cluster analysis of DIG data.

BACKGROUND: Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. We used cluster analysis to delineate the clinical characteristics of HF patients in whom digoxin therapy was associated with improved or worsened clinical outcomes. METHODS: The Digitalis Investigation Group (DIG) database was partitioned into 20 clusters. Multivariate Cox regression analyses was used, to identify clusters in which digoxin was associated with either an increase (Mortality(dig)HR>1), decrease (Mortality(dig)HR<1), or no association with all cause mortality (Mortality(dig)HR-NS); and separately, with an increase (HFA(dig)HR>1), decrease (HFA(dig)HR<1), or no association (HFA(dig)HR-NS) with HF admissions (HFA). RESULTS: We identified 938 patients in the Mortality(dig)HR>1 group, 6818 patients in the Mortality(dig)HR-NS group, and none in Mortality(dig)HR<1 group. The Mortality(dig)HR>1 group had a higher prevalence of females, diabetes mellitus, hypertension, higher age, systolic blood pressure (SBP), heart rate and ejection fraction (EF), compared to the Mortality(dig)HR-NS group. Similarly, 6325 patients clustered in the HFA(dig)HR<1 group, 1431 patients in the HFA(dig)HR-NS group, and none in the HFA(dig)HR>1 group. The HFA(dig)HR-NS group had a higher prevalence of females and hypertension, higher SBP, body mass index and EF; and lower prevalence of peripheral edema and third heart sound, compared with the HFA(dig)HR<1 group. CONCLUSION: Thus, the baseline characteristics of patients who did not have reduction in HF hospitalization or who had increased mortality were very similar and included females with hypertension, higher EF and higher SBP. Thus, use of digoxin in patients with this profile may need to be avoided.

Hepcidin in anemia of chronic heart failure.

Anemia is a common finding among patients with chronic heart failure (HF). Although comorbidities, such as kidney failure, might contribute to the pathogenesis of anemia, many patients with HF do not have any other obvious etiology for their anemia. We investigated whether anemia in HF is associated with an elevation in hepcidin concentration. We used time-of-flight mass spectrometry to measure hepcidin concentration in urine and serum samples of patients with HF and in control subjects. We found that the concentration of hepcidin was lower in urine samples of patients with HF compared with those of control subjects. Serum hepcidin was also reduced in HF but was not significantly lower than that in controls. There were no significant differences between hepcidin levels in patients with HF and anemia compared with patients with HF and normal hemoglobin level. We concluded that hepcidin probably does not play a major role in pathogenesis of anemia in patients with chronic HF.

A case of Brugada syndrome presenting with incessant polymorphic ventricular tachycardia.

Brugada syndrome, an inherited arrhythmogenic cardiac disease, manifests with ST-segment changes in the right precordial leads, right bundle block pattern, and susceptibility to ventricular tachyarrhythmias and sudden death. The only established therapy for this disease is prevention of sudden death by implantation of a defibrillator. Herein we describe a case of a patient who presented with incessant ventricular tachycardia (VT) and syncope and who had a type 1 Brugada pattern on ECG. The patient was successfully treated with quinidine, after which the classically described type 2 and 3 patterns emerged.

Adaptive and maladptive effects of SMAD3 signaling in the adult heart after hemodynamic pressure overloading.

BACKGROUND: Previous studies suggest that transforming growth factor-beta provokes cardiac hypertrophy and myocardial fibrosis; however, it is unclear whether the deleterious effects of transforming growth factor-beta signaling are conveyed through SMAD-dependent or SMAD-independent signaling pathways. METHODS AND RESULTS: To determine the contribution of SMAD-dependent signaling to cardiac remodeling, we performed transaortic constriction in SMAD3 null (SMAD3(-/-)) and littermate control mice (age, 10 to 12 weeks). Cumulative survival 20 days after transaortic constriction was significantly less in the SMAD3(-/-) mice when compared with littermate controls (43.6% versus 90.9%, P<0.01). Transaortic constriction resulted in a significant increase in cardiac hypertrophy in the SMAD3(-/-) mice, denoted by an increase in the heart weight to tibial length ratio and increased myocyte cross-sectional area. Loss of SMAD3 signaling also resulted in a significant 60% decrease in myocardial fibrosis (P<0.05). A microRNA microarray showed that 55 microRNAs were differentially expressed in littermate and SMAD3(-/-) mice and that 10 of these microRNAs were predicted to bind to genes that regulate the extracellular matrix. Of these 10 candidate microRNAs, both miR-25 and miR-29a were sufficient to decrease collagen gene expression when transfected into isolated cardiac fibroblasts in vitro. CONCLUSIONS: The results suggest that SMAD3 signaling plays dual roles in the heart: one beneficial role by delimiting hypertrophic growth and the other deleterious by modulating myocardial fibrosis, possibly through a pathway that entails accumulation of microRNAs that decrease collagen gene expression.

The emerging role of microRNAs in cardiac remodeling and heart failure.

Recent studies have suggested a potentially important role for a family of tiny regulatory RNAs, known as microRNAs (miRNAs or miRs), in the control of diverse aspects of cardiac function in health and disease. Although the field of miRNA biology is relatively new, there is emerging evidence that miRNAs may play an important role in the pathogenesis of heart failure through their ability to regulate the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodeling. Here, we review the biology of miRNAs in relation to their role in modulating various aspects of the process of cardiac remodeling, as well as discuss the potential application of miRNA biology to the field of heart failure.

Admission hyperglycemia and length of hospital stay in patients with diabetes and heart failure: a prospective cohort study.

The authors assessed the relationship between glycemia and length of hospital stay (LOS) in a prospective cohort study of patients with diabetes mellitus and heart failure (HF). Of 212 patients with acute HF exacerbation, 119 (56%) also had diabetes. The mean age of the cohort was 63+/-0.87 years, and the mean body mass index was 29.3 kg/m2. Diabetic patients had significantly longer LOS compared with the nondiabetics (5.0+/-0.29 vs 3.4+/-0.19; P<.001). In patients with diabetes, the mean glycated hemoglobin A1c was 8.3%, admission blood glucose (BG) was 169+/-7.7 mg/dL, and average BG was 196+/-8.1 mg/dL. After adjusting for age, sex, weight, hypertension, renal function, and anemia, LOS was significantly correlated with admission BG (r=0.31; P<.001) and average BG (r=0.34; P=.001). In patients with acute HF exacerbation, diabetes significantly prolonged LOS. Hyperglycemia correlated with LOS.

Transforming growth factor-beta receptor antagonism attenuates myocardial fibrosis in mice with cardiac-restricted overexpression of tumor necrosis factor.

The mechanisms that are responsible for the development of myocardial fibrosis in inflammatory cardiomyopathy are unknown. We have previously generated lines of transgenic mice with cardiac-restricted overexpression of tumor necrosis factor (MHCsTNF mice), a pro-inflammatory cytokine. The MHCsTNF mice develop a heart failure phenotype that is characterized by progressive myocardial fibrosis, as well as increased levels transforming growth factor-beta (TGF-beta)(mRNA and protein. In order to determine whether TGF-beta-mediated signaling was responsible for the myocardial fibrosis observed in the MHCsTNF mice, we treated MHCsTNF and littermate control mice from 4 to 12 weeks of age with a novel orally available TGF-beta receptor antagonist (NP-40208). At the time of terminal study, myocardial collagen content was determined using the picrosirius red technique, and left ventricular (LV) systolic and diastolic function were determined using the Langendorff method. Treatment with NP-40208 resulted in a significant (P < 0.05) 65% decrease in nuclear translocation of Smad 2/3, a significant (P < 0.05), decrease in the heart-weight to body-weight ratio from 6.5 to 5.7, a approximately 37% decrease in fibrillar collagen content (P < 0.01) and a significant (P < 0.05) decrease in the LV chamber stiffness by approximately 25% in the MHCsTNF mice when compared to diluent-treated controls. Treatment with NP-40208 had no discernable effect on LV systolic function, nor any effect on cardiac myocyte size or fetal gene expression in the MHCsTNF mice. Taken together, these observations suggest that sustained pro-inflammatory signaling in the adult heart is associated with a pro-fibrotic phenotype that arises, at least in part, from TGF-beta-mediated signaling, with resultant activation of Smad 2/3, leading to increased myocardial fibrosis and increased LV diastolic chamber stiffness.

Bedside ultrasound diagnosis of aortic dissection in a cocaine abuser.

Aortic dissection and myocardial infarction are two well-known and well-reported complications of cocaine abuse. This case report describes a patient with cocaine-induced myocardial infarction who was also found to have a type A aortic dissection. Interestingly, this potentially fatal complication was detected by a bedside 2D echocardiogram.