PICM is not uncommon in patients receiving PPM for CHB with preserved LVEF and is strongly associated with RV pacing burden >20%. CRT response rate is high in PICM, but is perhaps underutilized.
OBJECTIVES
Our goal was to prospectively compare the accuracy of real-time three-dimensional (3D) color Doppler vena contracta (VC) area and two-dimensional (2D) VC diameter in an in vitro model and in the clinical assessment of mitral regurgitation (MR) severity.
BACKGROUND
Real-time 3D color Doppler allows direct measurement of VC area and may be more accurate for assessment of MR than the conventional VC diameter measurement by 2D color Doppler.
METHODS
Using a circulatory loop with an incorporated imaging chamber, various pulsatile flow rates of MR were driven through 4 differently sized orifices. In a clinical study of patients with at least mild MR, regurgitation severity was assessed quantitatively using Doppler-derived effective regurgitant orifice area (EROA), and semiquantitatively as recommended by the American Society of Echocardiography. We describe a step-by-step process to accurately identify the 3D-VC area and compare that measure against known orifice areas (in vitro study) and EROA (clinical study).
RESULTS
In vitro, 3D-VC area demonstrated the strongest correlation with known orifice area (r = 0.92, p < 0.001), whereas 2D-VC diameter had a weak correlation with orifice area (r = 0.56, p = 0.01). In a clinical study of 61 patients, 3D-VC area correlated with Doppler-derived EROA (r = 0.85, p < 0.001); the relation was stronger than for 2D-VC diameter (r = 0.67, p < 0.001). The advantage of 3D-VC area over 2D-VC diameter was more pronounced in eccentric jets (r = 0.87, p < 0.001 vs. r = 0.6, p < 0.001, respectively) and in moderate-to-severe or severe MR (r = 0.80, p < 0.001 vs. r = 0.18, p = 0.4, respectively).
CONCLUSIONS
Measurement of VC area is feasible with real-time 3D color Doppler and provides a simple parameter that accurately reflects MR severity, particularly in eccentric and clinically significant MR where geometric assumptions may be challenging.
Germline mutations involving small mothers against decapentaplegic-transforming growth factor-β (SMAD-TGF-β) signaling are an important but rare cause of pulmonary arterial hypertension (PAH), which is a disease characterized, in part, by vascular fibrosis and hyperaldosteronism (ALDO). Here, we developed and analyzed a fibrosis protein-protein network (fibrosome) in silico, which predicted that the SMAD3 target neural precursor cell expressed developmentally down-regulated 9 (NEDD9) is a critical ALDO-regulated node underpinning pathogenic vascular fibrosis. Bioinformatics and microscale thermophoresis demonstrated that oxidation of Cys18 in the SMAD3 docking region of NEDD9 impairs SMAD3-NEDD9 protein-protein interactions in vitro. This effect was reproduced by ALDO-induced oxidant stress in cultured human pulmonary artery endothelial cells (HPAECs), resulting in impaired NEDD9 proteolytic degradation, increased NEDD9 complex formation with Nk2 homeobox 5 (NKX2–5), and increased NKX2–5 binding to COL3A1. Upregulation of NEDD9-dependent collagen III expression corresponded to changes in cell stiffness measured by atomic force microscopy. HPAEC-derived exosomal signaling targeted NEDD9 to increase collagen I/III expression in human pulmonary artery smooth muscle cells, identifying a second endothelial mechanism regulating vascular fibrosis. ALDO-NEDD9 signaling was not affected by treatment with a TGF-β ligand trap, and, thus, was not contingent on TGF-β-signaling. Colocalization of NEDD9 with collagen III in HPAECs was observed in fibrotic pulmonary arterioles from PAH patients. Furthermore, NEDD9 ablation or inhibition prevented fibrotic vascular remodeling and pulmonary hypertension in animal models of PAH in vivo. These data identify a critical TGF-β-independent post-translational modification that impairs SMAD3-NEDD9 binding in HPAECs to modulate vascular fibrosis and promote PAH.
For the left ventricle (LV) to function as an effective pump it must be able to fill from a low left atrial pressure. However, this ability is lost in patients with heart failure. We investigated LV filling by imaging the cardiac blood flow using 2D phase contrast magnetic resonance imaging and quantified the intraventricular pressure gradients and the strength and location of vortices. In normal subjects, blood flows towards the apex prior to the mitral valve opening, and the mitral annulus moves rapidly away after the valve opens, with both effects enhancing the vortex ring at the mitral valve tips. Instead of being a passive by-product of the process as was previously believed, this ring facilitates filling by reducing convective losses and enhancing the function of the LV as a suction pump. The virtual channel thus created by the vortices may help insure efficient mass transfer for the left atrium to the LV apex. Impairment of this mechanism contributes to diastolic dysfunction, with LV filling becoming dependent on left atrial pressure, which can lead to eventual heart failure. Better understanding of the mechanics of this progression may lead to more accurate diagnosis and treatment of this disease.
early diastolic flow propagation occurs with an initial rapid velocity that abruptly decelerates to a terminal velocity. With diastolic dysfunction, the initial velocity is slower and the deceleration point occurs closer to the mitral annulus than with normal filling. A new parameter that combines these 2 effects (Vs) provides a more accurate assessment of diastolic function than the conventional propagation velocity.
The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE
Many patients with acute heart failure have marked hypertension and preserved left ventricular ejection fraction. In these patients, the heart failure usually does not result from transient systolic dysfunction or valvular abnormalities but rather results from diastolic dysfunction. Treatment of this condition includes control of hypertension, cautious diuresis, and, if necessary, ventilatory support. Further workup after the acute phase should be directed by the overall clinical picture. Other potential contributing factors, such as renal artery stenosis, valvular heart disease, and ischemia, should be strongly considered. Unfortunately, chronic therapy for diastolic heart failure has not yet been standardized due to the paucity of clinical trial data. Strict control of hypertension appears to be of paramount importance. Angiotensin-converting enzyme inhibitors or receptor blockers may be of benefit in preventing repeat hospitalizations.
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