Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

The Doppler assessment of diastolic dysfunction (DD) is not part of a standard comprehensive intraoperative echocardiographic examination. Although the reasons may be many, the lack of a simplified algorithm for the assessment of DD specific to the perioperative arena, the implications of this diagnosis on clinical care, and the absence of therapeutic options are some of the commonly cited reasons. In this article, the authors address these possible reasons for the lack of routine application of Doppler indices to assess perioperative DD. The authors have chosen to highlight some of the most common conceptual questions, which often have been raised by anesthesiologists, and attempted to suggest answers. Drawing from their experience and data, the authors propose a simplified algorithm for the application of Doppler to assess and diagnose DD with an individualized and a mechanistic approach. The proposed algorithm is from within the premise of the published guidelines and attempts to simplify the perioperative approach. The authors hope this approach will be simple enough for routine application to affect therapy and a tangible change in outcome. The authors suggest that knowledge of left atrial size is valuable as a marker for persistently increased left ventricular end-diastolic pressure and its possible role in risk stratification.

BACKGROUND AND AIM OF THE STUDY: Intraoperative real-time three-dimensional transesophageal echocardiography (RT-3D TEE) was used to examine the geometric changes that occur in the mitral annulus immediately after aortic valve replacement (AVR). METHODS: A total of 35 patients undergoing elective surgical AVR under cardiopulmonary bypass was enrolled in the study. Intraoperative RT-3D TEE was used prospectively to acquire volumetric echocardiographic datasets immediately before and after AVR. The 3D echocardiographic data were analyzed offline using TomTec Mitral Valve Assessment software to assess changes in specific mitral annular geometric parameters. RESULTS: Datasets were successfully acquired and analyzed for all patients. A significant reduction was noted in the mitral annular area (-16.3%, p 0.001), circumference (-8.9%, p 0.001) and the anteroposterior (-6.3%, p = 0.019) and anterolateral-posteromedial (-10.5%, p 0.001) diameters. A greater reduction was noted in the anterior annulus length compared to the posterior annulus length (10.5% versus 6.2%, p 0.05) after AVR. No significant change was seen in the non-planarity angle, coaptation depth, and closure line length. During the period of data acquisition before and after AVR, no significant change was noted in the central venous pressure or left ventricular end-diastolic diameter. CONCLUSION: The mitral annulus undergoes significant geometric changes immediately after AVR. Notably, a 16.3% reduction was observed in the mitral annular area. The anterior annulus underwent a greater reduction in length compared to the posterior annulus, which suggested the existence of a mechanical compression by the prosthetic valve.

Neuropeptide Y is one of the most abundant neurotransmitters in the myocardium, and is known to influence cardiovascular remodeling. We hypothesized that diabetic neuropathy could possibly be associated with altered neuropeptide Y and its receptor expression levels in myocardium and plasma. Plasma neuropeptide Y levels in diabetic (n=24, HgbA1c 7.9 ± 1.1%) and non-diabetic (n=27, HgbA1c 5.8 ± 0.5%) patients undergoing cardiac surgery utilizing cardiopulmonary bypass were analyzed. Right atrial tissue of these patients was used to determine the expression of neuropeptide Y, the receptors 1-5, and leptin by immunoblotting, real-time PCR and immunofluorescence. Apoptosis signaling and endostatin and angiostatin were measured to determine the effects of leptin. Plasma neuropeptide Y levels were significantly increased in patients with Type II diabetes mellitus as compared to non-diabetic patients (P=0.026). Atrial tissue neuropeptide Y mRNA levels were lower in diabetic patients (P=0.036). There was a significant up-regulation of myocardial Y(2) and Y(5) receptors (P=0.009, P=0.01 respectively) in the diabetic patients. Leptin, involved with apoptosis and angiogenesis, was down regulated in diabetic patients (P=0.05). The levels of caspase-3, endostatin and angiostatin were significantly elevated in diabetic patients (P=0.003, P=0.008, P=0.01 respectively). Y(1) receptors were more likely to be localized within the nuclei of cardiomyocytes and vascular smooth muscle cells. Neuropeptide expression is altered differentially in the serum and myocardium by diabetes. Altered regulation of this system in diabetics may be in part responsible for the decreased angiogenesis, increased apoptosis, and increased vascular smooth muscle proliferation leading to coronary artery disease and heart failure in this patient population.