Early Experience With New Transcatheter Mitral Valve Replacement

Background

Transcatheter mitral valve replacement (TMVR) is a potential therapy for patients with symptomatic, severe mitral regurgitation (MR). The feasibility of this therapy remains to be defined.

Age-Related Outcomes After Transcatheter Mitral Valve Repair in Patients With Heart Failure: Analysis From COAPT

ObjectivesThe aim of this study was to assess the impact of age on outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial.BackgroundIn the COAPT trial, TEER with the MitraClip device in patients with heart failure (HF) and moderate to severe or severe secondary mitral regurgitation (SMR) reduced the risk for HF hospitalization (HFH) and all-cause mortality compared with maximally tolerated guideline-directed medical therapy (GDMT) alone. There are limited data regarding the effectiveness of MitraClip therapy in elderly patients.MethodsPatients (n = 614) were grouped by median age at randomization (74 years) and by MitraClip treatment vs GDMT alone. The primary endpoint was the 2-year rate of death or HFH assessed by multivariable Cox regression.ResultsDeath or HFH within 2 years occurred less frequently after treatment with the MitraClip vs GDMT alone in patients <74 years of age (37.3% vs 64.5%; adjusted HR: 0.41; 95% CI: 0.29-0.59) and ≥74 years of age (51.7% vs 69.6%; adjusted HR: 0.58; 95% CI: 0.42-0.81) (P_int = 0.17). Mortality was also consistently reduced with MitraClip treatment in young and elderly patients (P_int = 0.42). In contrast, elderly patients treated with the MitraClip vs GDMT alone tended to have a lesser reduction of HFH than younger patients (P_int = 0.03). Younger and older patients had similar improvements in quality of life after treatment with the MitraClip compared with GDMT alone.ConclusionsIn the COAPT trial, MitraClip treatment of moderate to severe and severe SMR reduced the composite risk for death or HFH and improved survival and quality of life regardless of age. As such, young and elderly patients with HF and severe SMR benefit from TEER, although elderly patients may not have as great a benefit from the MitraClip device in reducing HFH.     

End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension

OBJECTIVES: Primary pulmonary hypertension (PPH) is a pulmonary vasculopathy resulting in exercise intolerance, usually due to dyspnea. We hypothesized that ventilation is increased during exercise in PPH relative to normal because the ventilated lung is underperfused, cardiac output increase is restricted, and arterial hypoxemia may develop. Our aim was to determine the size of the reduction in end-tidal Pco(2) (Petco(2)) as a reflection of the abnormality in ventilatory efficiency and ventilatory drive in PPH patients. METHODS: We performed cardiopulmonary exercise testing (CPET) in 52 PPH patients. All had hemodynamic measurements to confirm the diagnosis of PPH. A subgroup of 29 patients who underwent right-heart catheterization within 50 days of CPET were studied to compare their CPET responses to resting hemodynamics. Nine healthy volunteers matched for age and gender served as CPET control subjects. RESULTS: In PPH patients, the percentage of predicted peak oxygen uptake (Vo(2)) correlated significantly with mean pulmonary artery pressure (mPAP) [r = - 0.59, p = 0.0007, n = 29]. Petco(2) values at rest, anaerobic threshold (AT), and peak Vo(2) were proportionately reduced as percentage of predicted peak Vo(2) decreased (r = 0.66 to 0.72, p < 0.0001, n = 52). Petco(2) values at rest, AT, and peak Vo(2) were also reduced as mPAP increased (r = - 0.51 to - 0.53, p < 0.005, n = 29). In contrast to normal subjects in whom Petco(2) increased from rest to AT, Petco(2) decreased in PPH patients, except for two patients with mild PPH in whom there was no change. Also, Petco(2) increased rather than decreased further at the start of recovery, in contrast to normal. Although usually normal at rest, oxyhemoglobin saturation decreased during exercise in most PPH patients. CONCLUSIONS: In patients with PPH, Petco(2) at rest and exercise is significantly reduced in proportion to physiologic disease severity. The range of values is unusually low. Furthermore, the directional changes of Petco(2) during exercise and early recovery are in the opposite direction of normal.     

Increased threat of tropical cyclones and coastal flooding to New York City during the anthropogenic era

In a changing climate, future inundation of the United States’ Atlantic coast will depend on both storm surges during tropical cyclones and the rising relative sea levels on which those surges occur. However, the observational record of tropical cyclones in the North Atlantic basin is too short (A.D. 1851 to present) to accurately assess long-term trends in storm activity. To overcome this limitation, we use proxy sea level records, and downscale three CMIP5 models to generate large synthetic tropical cyclone data sets for the North Atlantic basin; driving climate conditions span from A.D. 850 to A.D. 2005. We compare pre-anthropogenic era (A.D. 850–1800) and anthropogenic era (A.D.1970–2005) storm surge model results for New York City, exposing links between increased rates of sea level rise and storm flood heights. We find that mean flood heights increased by ∼1.24 m (due mainly to sea level rise) from ∼A.D. 850 to the anthropogenic era, a result that is significant at the 99% confidence level. Additionally, changes in tropical cyclone characteristics have led to increases in the extremes of the types of storms that create the largest storm surges for New York City. As a result, flood risk has greatly increased for the region; for example, the 500-y return period for a ∼2.25-m flood height during the pre-anthropogenic era has decreased to ∼24.4 y in the anthropogenic era. Our results indicate the impacts of climate change on coastal inundation, and call for advanced risk management strategies.Tropical cyclones (TCs) and their associated storm surges are the costliest natural hazards to impact the U.S. Atlantic coast (1–3). For example, Hurricane Sandy caused an estimated $50 billion of damage and destroyed at least 650,000 houses in 2012, largely because of flooding from a 3- to 4-m storm surge and large waves (4). A storm surge is the anomalous rise of water above predicted astronomical tides, and its height is driven primarily by wind patterns, storm track, and coastal geomorphology forcing water onshore, with a smaller contribution from reduced atmospheric pressure allowing the ocean surface to rise. The financial cost and human impact of future storm surges will be controlled by the TC climate (frequency, intensity, size, duration, and location) and the rate of relative sea level rise (RSLR), which is the base water level upon which storm surges occur (5, 6). The flood height attained during a given storm is determined by combining storm surge, tides, and relative sea level. Therefore, as sea level rises through time, coastal inundation risk from storm surges rises as well. Thus, it is useful to conduct a long-term analysis of the impact of changing TC climates and RSLR on flood heights (7).The observational record of TCs in the North Atlantic Ocean basin spans A.D. 1851 to the present, but is too short (8) and potentially unreliable (9) to accurately assess long-term trends in TC frequency, intensity, and storm surge height, particularly for the largest events and for locations that rarely experience landfalling TCs (e.g., refs. 8–13). As an alternative to the observational record of TCs in the North Atlantic Ocean basin, ref. 8 developed a long-term synthetic TC data set, downscaled from the National Center for Atmospheric Research Climate System Model version 1.4 spanning the past millennium, which allows for more accurate assessment of low-frequency variability in TC activity over long periods of time. This process creates a long-term synthetic TC data set consistent with a reasonable past climate (8, 13), and is described in detail in refs. 14 and 15. Here we generate long-term synthetic TC data sets downscaled from the newer, state-of-the-art Coupled Model Intercomparison Project Phase 5 (CMIP5) models. To perform our analysis, we use an interdisciplinary approach that combines TCs with simulated storm surges and proxy relative sea level reconstructions of the last two millennia from southern New Jersey (Fig. 1) (16).Open in a separate windowFig. 1.Relative sea level reconstruction compiled for southern New Jersey using reconstructions from two sites [Leeds Point and Cape May Courthouse (6)]. Samples dated from the pre-anthropogenic era are shown in blue. Samples shown in black are from the interim time period between the pre-anthropogenic and anthropogenic time periods. Samples dated from the anthropogenic era are shown in red. A light blue dashed line shows the best fit line for the pre-anthropogenic era data, and a pink dashed line shows the best fit line for the anthropogenic era data. Equations of the best fit lines are given on the figure. Horizontal error bars represent the 2σ uncertainty, in calendar years, of the year associated with each point. Vertical error bars represent the approximate 1σ uncertainty, in meters, of the sea level associated with each point.We examine changes in coastal flooding in New York City (NYC) using two time periods to provide a paleoclimate perspective of coastal flooding events such as Hurricane Sandy. We define the anthropogenic era to be a time period in which anthropogenic forcing can be assumed to be dominant (A.D. 1970–2005); we choose the pre-anthropogenic era to be a time period in which anthropogenic forcing can be assumed to be minimal (A.D. 850–1800). Our definition of the end of the time period for the pre-anthropogenic era is consistent with several previous studies (17–19).     

Two-dimensional echocardiographic identification of pulmonary artery branch stenosis

Pulmonary artery branch stenosis is a not uncommon congenital lesion, noted in approximately 4% of children at the time of cardiac catheterization. Real-time 2-dimensional echocardiography was used to examine 10 patients with angiographically documented pulmonary branch stenosis. Five cases of pulmonary artery branch narrowing were identified by echocardiography without prior knowledge of angiographic findings. In 5 other patients whose angiographic results were known, the narrowings were identified in 4 of 5 cases. These results demonstrate the feasibility of evaluating pulmonary branch stenosis with the nonionizing, noninvasive method of 2-dimensional echocardiography.     

Echocardiographic diastolic ventricular abnormality in hypertensive heart disease: Atrial emptying index

To analyze changes in left ventricular diastolic properties in hypertensive heart disease, the atrial emptying index was used to assess the rapid phase of diastolic filling of the left ventricle. Ten normal subjects (Group 1), 11 hypertensive patients without evidence of cardiac involvement (Group 2) and 10 hypertensive patients with echocardiographic evidence of left ventricular hypertrophy (Group 3) were compared using M mode echocardiography and systemic hemodynamic data. Where as cardiac index (dye-dilution method) and rate of circumferential fiber shortening (echocardiogram) were normal in all three groups, there was a progressive increase in left atrial index (p <0.001, Group 1 versus Group 2 and versus Group 3) and a progressive decrease in the atrial emptying index (p <0.001, Group 1 versus Group 2 and versus Group 3). No correlation existed between the atrial emptying index and the left atrial index, mean arterial pressure or total peripheral resistance in any of the three groups. These data suggest that rapid filling of the left ventricle is reduced early in hypertension, even before electrocardiographic or systolic echocardiographic abnormalities are detectable. The atrial emptying index therefore appears to be an early indicator of abnormalities of left ventricular diastolic compliance in uncomplicated hypertension.     

Effects of prazosin on serum lipids in patients with essential hypertension: a review of the findings presented at the Satellite Symposium on coronary heart disease: hypertension and other risk factors, Milan, 1983

Accumulated evidence has indicated that the failure of blood pressure control with antihypertensive therapy to reduce the incidence of myocardial infarction may be due to unfavorable effects of drug therapy on other cardiovascular risk factors, particularly lipid concentrations. Several studies have demonstrated that beta-blocking drugs increase serum triglyceride concentration and reduce high-density lipoprotein cholesterol concentration, both of which are risk factors for coronary artery disease. However, several investigators have reported that prazosin, an alpha-adrenergic blocking agent, does not cause adverse changes in those lipid parameters or in the cholesterol ratio. If one considers the net effect of antihypertensive therapy to be the reduction of blood pressure plus the alterations in lipid metabolism, the metabolic response to a drug may be an important determinant of the overall effectiveness of treatment and a deciding factor in the choice among available antihypertensive agents.     

Effects of castration on adipose tissue growth and regrowth in the male rat

Adipose tissue has been found to regrow in the male rat following surgical removal (lipectomy) of inguinal subcutaneous depots, but the degree of regrowth has varied widely across experiments. It is possible that at least part of the disparity of previous findings occurred because of differences among the experiments in the testicular integrity of experimental animals. To address this possibility, the present study examined effects of castration on adipose tissue regrowth in rats treated either as weanlings or as young adults. Male Sprague-Dawley rats, at either 4 or 15 weeks of age, were subjected to one of four surgical procedures: bilateral lipectomy of the inguinal subcutaneous depots; castration; lipectomy and castration; or sham surgery. Adipose tissue mass and cellularity were examined 6 months later. Castration reduced body weight gain, but castrated rats achieved a higher ratio of adipose weight to body weight than noncastrated rats. In rats lipectomized but not castrated at 15 weeks of age, partial regeneration and a small increase in growth of noninguinal subcutaneous adipose tissue combined to produce substantial restoration of adipose mass. The same surgery in 4-week-old rats did not result in significant restoration because growth of noninguinal subcutaneous adipose tissue was reduced. In rats that were both castrated and lipectomized, regrowth of adipose tissue was substantial regardless of age at time of surgery. Thus, castration is seen to impede body weight gain while sparing ordinary growth of adipose tissue and facilitating regrowth of adipose tissue following lipectomy. Since adipose tissue regrowth varied with age only in noncastrated rats, it appears to be facilitated as well by testicular maturation.     

Radioimmunoassay of posterior pituitary peptides: a review

The available data regarding the radioimmunoassay of vasopressin, oxytocin, and neurophysin have been reviewed. Because of the very recent development of most of these assays, much of the data are available only in the form of abstracts. While it is therefore difficult to compare methodology, some conclusions do seem warranted. The assays for both vasopressin and oxytocin are likely to continue to involve some extraction step. The vasopressin assays are relatively consistent from laboratory to laboratory and in general have conformed with classic concepts of vasopressin secretion and with the previously published bioassy data. Oxytocin has been little studied by radioimmunoassay, and while the animal data have been in line with previous concepts of oxytocin secretion and bioassay data, the discrepant results in the assay of oxytocin in the human are as yet unexplained. The assay of neurophysin appears to be considerably easier to accomplish than that of either of the peptide hormones. However, the early promise in animals that neurophysin would be a reliable indicator of vasopressin and oxytocin release, and further that there might be a specific neurophysin for each of these hormones, has not been realized in the assays so far reported in man. Whether subsequent improvement of the human neurophysin assay and development of specific assays for the various human neurophysins will demonstrate a specific relationship between neurophysin and oxytocin and vasopressin, remains to be seen. Enough is already known, however, to suggest that a complete assessment of posterior pituitary function must henceforth include radioimmunoassays for one or more neurophysins in addition to those for vasopressin and oxytocin.