Somatostatin receptors in fibrotic myocardium.

A patient with a neuroendocrine tumor and history of coronary artery disease underwent PET with 68Ga-DOTATATE PET tracer for tumor visualization. Analysis of the scan showed uptake of 68Ga-DOTATATE in the left ventricle corresponding to previous myocardial infarct. 68Ga-DOTATATE binds by somatostatin receptors (SSTR) and it has been proposed that it may be useful for the detection of cardiac inflammatory lesions. We aimed to test whether SSTR could be upregulated in cardiac fibrotic scar. We analyzed SSTR in cardiac samples from patients with end-stage ischemic cardiomyopathy (ICM, n = 8) and control hearts (n = 5). In mature ICM tissue, SSTR1 and SSTR2 expression was unchanged and SSTR5 expression was significantly decreased in ICM samples vs. control. Immunohistochemistry showed increased SSTR1 and SSTR2 in ICM. Areas with SSTR1 or SSTR2 staining were often adjacent to fibrotic areas. The majority of SSTR1 and SSTR2 staining localized in cardiomyocytes in fibrotic scar-rich areas where CD68 macrophage staining was not present. SSTR are occasionally upregulated in cardiac fibrotic areas. When using 68Ga-DOTATATE PET tracer to detect cardiac sarcoidosis or atherosclerotic plaque, the possibility of tracer uptake in fibrotic areas should be considered.

Rheumatic Heart Disease in the Developing World.

Despite recent public policy initiatives, rheumatic heart disease (RHD) remains a major source of morbidity worldwide. Rheumatic heart disease occurs as a sequela of Streptococcus pyogenes (group A streptococcal [GAS]) infection in patients with genetic susceptibility. Strategies for prevention of RHD or progression of RHD include prevention of GAS infection with community initiatives, effective treatment of GAS infection, and secondary prophylaxis with intramuscular penicillin. The cardiac surgical community has attempted to improve the availability of surgery in RHD-endemic areas with some success, and operative techniques and outcomes of valve repair continue to improve, potentially offering patients a safer, more durable operation. Innovation offers hope for a more scalable solution with improved biomaterials and transcatheter delivery technology; however, cost remains a barrier.

Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT-/- mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor ß1 (TGFß1) and collagen (COL1A1) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

Correction to: Routine Sildenafil Does Not Improve Clinical Outcomes After Fontan Operation.

The original version of this article unfortunately contained a mistake. The presentation of Table 2 was incorrect .The corrected table is given below.

Routine Sildenafil Does Not Improve Clinical Outcomes After Fontan Operation.

Fontan operation can be complicated by persistent chest tube output (CTO) leading to prolonged hospital length of stay (LOS). Postoperative sildenafil administration has been shown to improve clinical outcomes in selected patients after Fontan. We initiated a practice change utilizing intravenous (IV) sildenafil in early postoperative period in all patients undergoing Fontan operation with aim to decrease LOS and CTO. Nineteen patients (February 2014-May 2016) received 0.35 mg/kg sildenafil IV (three doses) followed by enteral, 1 mg/kg every eight hours until hospital discharge. Clinical outcomes were compared to 84 pre-protocol controls. Vital signs were recorded after second sildenafil dose. Demographics were similar between groups. Sildenafil group had longer median LOS [9 (7, 11) vs. 13 (8, 25) days, p = 0.016]. CTO days were longer [6 (5, 8) vs. 8 (6, 13) days, p = 0.011]. Sildenafil group had longer mechanical ventilation [6.9 (3.5, 11.1) vs. 4 (2, 7) h, p = 0.045] and longer oxygen therapy [99 (52, 225) vs. 14.5 (14, 56) h, p = 0.001]. There was a trend towards more albumin 5% resuscitation in first 24 h [17 (1, 30) vs. 21 (10, 40) ml/kg, p = 0.069]. There was no difference in inotrope score at 24 h, maximum lactate, or fluid balance. Readmission rates were similar. There was no mortality. IV sildenafil was well tolerated, and no doses were held. Routine early administration of sildenafil after Fontan operation is not associated with an improvement in any measured clinical outcome, including postoperative CTO, LOS, colloid administration, or duration of mechanical ventilation.

Central Venous to Arterial CO2 Difference After Cardiac Surgery in Infants and Neonates.

OBJECTIVES: Venous to arterial CO2 difference correlates with cardiac output in critically ill adults, but its utility in pediatric patients is unclear. We sought to correlate venous to arterial CO2 difference with other cardiac output surrogates (arteriovenous oxygen saturation difference, central venous oxygen saturation, and lactate) and investigate its capacity to predict poor outcomes associated with low cardiac output (low cardiac output syndrome) in infants after cardiac surgery with cardiopulmonary bypass. DESIGN: Retrospective chart review. Poor outcome was defined as any inotrope score greater than 15; death, cardiac arrest, extracorporeal membrane oxygenation; and unplanned surgical reintervention. SETTING: Pediatric cardiovascular ICU. PATIENTS: One hundred thirty-nine infants less than 90 days who underwent cardiopulmonary bypass, from October 2012 to May 2015. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-six arterial and venous blood gas pairs from admission (n = 139), 6 (n = 62), 12 (n = 73), and 24 hours (n = 22) were included in analysis. For all pairs, venous to arterial CO2 difference was moderately correlated with arteriovenous oxygen saturation difference (R = 0.53; p < 0.01) and central venous oxygen saturation (R = -0.43; p < 0.01), but not lactate. At admission, venous to arterial CO2 difference was also moderately correlated with central venous oxygen saturation (R = -0.40; p < 0.01) and arteriovenous oxygen saturation difference (R = 0.55; p < 0.01), but not lactate. Thirty-four of 139 neonates (24.5%) had poor outcome. Median admission venous to arterial CO2 difference was 5.9 mm Hg (3.8-9.2 mm Hg). Patients with poor outcome had median admission venous to arterial CO2 difference 8.3 (5.6-14.9) versus 5.4 mm Hg (3.0-8.4 mm Hg) in those without poor outcome. Venous to arterial CO2 difference (area under the curve = 0.69; p < 0.01), serum lactate (area under the curve = 0.64; p = 0.02), and central venous oxygen saturation (area under the curve = 0.74; p < 0.01) were predictive of poor outcome. After controlling for covariates, admission venous to arterial CO2 difference remained significantly associated with poor outcome (odds ratio, 1.3; 95% CI, 1.1-1.45), including independent association with mortality (odds ratio, 1.2; 95% CI, 1.07-1.31). CONCLUSIONS: Venous to arterial CO2 difference is correlated with important surrogates of cardiac output, and is associated with poor outcome and mortality related to low cardiac output syndrome after cardiac surgery in infants. Prospective validation of these findings, including confirmation that venous to arterial CO2 difference can identify low cardiac output syndrome in real time, is warranted.