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OBJECTIVES: Three-dimensional transesophageal echocardiography (TEE) is widely used to guide decision-making for mitral repair - relative impact of surgical mitral valve repair (MVr) and MitraClip on annular remodeling is unknown. The aim was to determine the impact of both mitral repair strategies on annular geometry, including the primary outcome of annular circumference and area. DESIGN: This was a retrospective observational study of patients who underwent mitral intervention between 2016 and 2020. SETTING: Weill Cornell Medicine, a single large academic medical center. PARTICIPANTS: The population comprised of 50 degenerative mitral regurgitation (MR) patients undergoing MVr. INTERVENTIONS: Elective MVr and transesophageal echocardiography (TEE) MEASUREMENTS AND MAIN RESULTS: MitraClip or surgical MVr patients were matched (1:1) for gender and CAD. Mitral annular geometry indices were quantified on intra-procedural 3D TEE. Mild or less MR on follow-up TTE defined optimal response. MitraClip patients were older (80±8 vs. 66±6;p

Objectives This study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR). Background AF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling. Methods Fifty-three patients with persistent AF and normal left ventricular ejection fraction were prospectively examined by means of 3-dimensional transesophageal echocardiography before, immediately after, and 6 weeks after electric cardioversion to sinus rhythm. Annular motion was assessed during AF and in sinus rhythm with the use of 3-dimensional analysis software, and the relationship with MR severity was explored. Results During AF and immediately after sinus rhythm restoration, the mitral annulus behaved relatively adynamically, with an overall change in annular area of 10.3% (95% CI: 8.7%-11.8%) and 12.2% (95% CI: 10.6%-13.8%), respectively. At follow-up, a significant increase in annular dynamics (19.0%; 95% CI: 17.4%-20.6%; P Conclusions Mitral annular dynamics are impaired in AF, with blunted presystolic narrowing that contributes to AFMR. Sinus rhythm restoration allows gradual recovery of presystolic annular dynamics. Improved annular dynamics decrease AFMR severity by optimizing annular-leaflet imbalance, regardless of LA remodeling.

The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Professor Sir Richard Doll, in collaboration with Professor Sir Austin Bradford Hill, were the first to quantitate the relationship of cigarette smoking with lung cancer.1 Later, Doll aptly stated, “Death in old age is inevitable, but death before old age is not.”1 The Richard Doll Building at the University of Oxford in Oxford, England, is inscribed with one of Doll's many impactful statements about cigarette smoking: In previous centuries, 70 years used to be regarded as humanity's allotted span of life, and only about one in five lived to such an age. Nowadays, however, for non-smokers in Western countries, the situation is reversed: only about one in five will die before 70, and the non-smoker death rates are still decreasing, offering the promise, at least in developed countries, of a world where death before 70 is uncommon.1 Despite this evidence-based optimism, cigarette smoking and the emerging clinical and public health challenges of overweight and obesity and physical inactivity are the leading avoidable causes of premature death in most industrialized nations. These risk factors are also emerging in the rest of the world, so that smoking, overweight and obesity, and physical inactivity are the major contributors to the reason that cardiovascular disease (CVD) has increased from number 5 to number 1 as the cause of mortality worldwide.2 In the United States during the past several decades (since 1965), the prevalence of cigarette smoking has decreased markedly.3 Nonetheless, in 2018, approximately 34.2 million Americans aged 18 years and older, or 13.7% of the population, were current cigarette smokers.3 Thus, the impact of cigarette smoking on avoidable and premature mortality remains alarmingly high. In the United States alone, smoking causes more than 480,000 deaths each year.3 These sobering statistics reflect, in major ways, the approximate 2-fold increased risk of CVD among current smokers and the approximate 20-fold increased risk of lung cancer among long-term smokers. Specifically, these relative increases translate to absolute increases of more than 150,000 deaths per year from CVD and 130,000 deaths per year from lung cancer among persons ≥35 years of age.4 Quitting smoking before age 40 years reduces the risk of dying from cigarette-related disease by approximately 90%.5 Specifically, smoking cessation significantly reduces the risks of CVD—beginning within a matter of months—and the risk of CVD among those who quit smoking equals that of lifelong nonsmokers within a few years, even among older adults.6 In contrast, reductions in mortality risk from lung cancer only begin to appear several years after quitting, and even by 10 years, the risk has been reduced to only approximately midway between continuing smokers and lifelong nonsmokers.7 In the United States in 2016, approximately 30 million hospital admissions occurred among persons 18+ years of age, with an average length of stay of 4.6 days.8 A 2009 study in San Francisco reported the prevalence of cigarette smoking among hospitalized patients to be 40%9 in contrast to the prevalence in the general population of 13.7%.3,10 This prevalence implies that up to 12 million inpatients in US hospitals are smokers. In this paper, we discuss effective and safe counseling and drug therapies that have the potential to prevent numerous premature deaths in the United States caused by cigarettes in hospitalized smokers.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard β = −0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard β = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling. NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

BACKGROUND: Evaluation of aortic stenosis (AS) requires calculation of the aortic valve area (AVA), which relies on the assumption of a circular-shaped left ventricular outflow tract (LVOT). However, the LVOT is often elliptical, and the circular assumption underestimates the true LVOT area. Biplane imaging using transthoracic echocardiography (TTE) allows for direct planimetry of the LVOT area. We aim to assess the feasibility of obtaining LVOT area by this technique, and its impact on the discordance between AVA and gradient criteria in AS grading. METHODS: We prospectively studied 134 patients (median age 80 years, interquartile range (IQR) 73–87 years; 39% female) with AS, including 82 (61%) with severe AS and 52 (39%) with mild or moderate AS. LVOT area was traced by direct planimetry (LVOTA(biplane)) and compared with LVOT area calculated by circular assumption (LVOTA(circ)). In a subset of patients who underwent cardiac computed tomography (CT), direct planimetry of LVOT area (LVOTA(CT)) was used as a reference standard. RESULTS: LVOTA(biplane) was significantly larger than LVOTA(circ) (4.20 cm(2) (IQR 3.66–4.90 cm(2)) vs 3.73 cm(2) (IQR 3.14–4.15 cm(2)), p < 0.001). Among 30 patients who underwent cardiac CT, LVOTA(biplane) had better agreement with LVOTA(CT) than LVOTA(circ) (mean bias −0.45 ± 0.63 cm(2) vs −1.02 ± 0.63 cm(2), p < 0.0001). Of 82 patients with severe AS (AVA ≤ 1 cm(2) using LVOTA(circ)), 40 (49%) had discordant mean gradient (MG < 40 mmHg). By using LVOTA(biplane), patients with discordant AVA and MG decreased from 49% to 27% (p = 0.004), and 29% of patients with severe AS were reclassified as moderate AS, with the highest percentage of reclassification in the low-gradient AS with preserved left ventricular ejection fraction group. CONCLUSIONS: Direct planimetry by biplane imaging avoids the inherent underestimation of LVOT area using the circular assumption. LVOT area obtained by biplane planimetry can lead to better concordance between AVA and MG, and classification of AS severity.

OBJECTIVES: To explore temporal trends and geographic variations in mortality from prescription opioids from 1999 to 2016. METHODS: Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death files were used to calculate age-adjusted rates and 95% confidence intervals (CIs) and create spatial cluster maps. RESULTS: From 1999 to 2016, counties in West Virginia experienced the highest overall mortality rates in the United States from prescription opioids. Specifically, from 1999 to 2004, the highest rate in West Virginia of 24.87/100,000 (95% CI 17.84–33.73) was the fourth highest in the United States. From 2005 to 2009, West Virginia experienced the highest rate in the United States, 60.72/100,000 (95% CI 47.33–76.71). From 2010 to 2016, West Virginia also experienced the highest rate in the United States, which was 90.24/100,000 (95% CI 73.11–107.36). As such, overall, West Virginia experienced the highest rates in the United States and the largest increases overall of ~3.6-fold between 1999 and 2004 and 2010 and 2016. From 1999 to 2004, Florida had no “hot spots,” but from 2006 to 2010 they did appear, and from 2011 to 2016, they disappeared. CONCLUSIONS: These data show markedly divergent temporal trends and geographic variations in mortality rates from prescription opioids, especially in the southern United States. Specifically, although initial rates were high and continued to increase alarmingly in West Virginia, they increased but then decreased in Florida. These descriptive data generate hypotheses requiring testing in analytic epidemiological studies. Understanding the divergent patterns of prescription opioid-related deaths, especially in West Virginia and Florida, may have important clinical and policy implications.

The highly productive northern Bering and Chukchi marine shelf ecosystem has long been dominated by strong seasonality in sea-ice and water temperatures. Extremely warm conditions from 2017 into 2019—including loss of ice cover across portions of the region in all three winters—were a marked change even from other recent warm years. Biological indicators suggest that this change of state could alter ecosystem structure and function. Here, we report observations of key physical drivers, biological responses and consequences for humans, including subsistence hunting, commercial fishing and industrial shipping. We consider whether observed state changes are indicative of future norms, whether an ecosystem transformation is already underway and, if so, whether shifts are synchronously functional and system wide or reveal a slower cascade of changes from the physical environment through the food web to human society. Understanding of this observed process of ecosystem reorganization may shed light on transformations occurring elsewhere. Exceptionally warm years in 2017–2019 have caused changes in the physical and biological characteristics of the Pacific Arctic Ocean. What these changes mean for the ecosystem and societal consequences will depend on if they are evidence of a transformation or anomalies in the system.

Background Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain. Methods The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE. Results Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p 2/m2 [CI 1.19–3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m2 [CI 1.02–1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m2 [CI 0.95–30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p p mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028). Conclusions MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.

Objectives To determine the cause of sudden brief unilateral tapering tinnitus (SBUTTs). Patients Five adults evaluated at a tertiary tinnitus referral center. Intervention Dry needling of lateral pterygoid muscle of one patient; jaw maneuvers in two patients. Main outcome measures Halting of SBUTTs. Results Trauma to the region of the lateral pterygoid muscle is associated with ipsilateral SBUTTs. Dry needling of the lateral pterygoid muscles abolishes SBUTTs. Some SBUTTs can be heard by others. Conclusions Some, if not all, SBUTTs appear to be closely related to trigger points within the lateral pterygoid muscle. SBUTTs may be generated by a local twitch response from trigger points within the lateral pterygoid muscle.

Introduction Our initial study reported consecutive patients with constant cardiac synchronous subjective tinnitus (pulsatile tinnitus without an identifiable acoustic source (P)) all of whom could suppress their pulsations with head and neck intense muscle contractions ("somatic testing" (ST)). The term somatosensory pulsatile tinnitus syndrome (SSPT) was coined to refer to this type of P. With now more than a decade of clinical experience with P, herein are reported (a) other ways P can present, beside SSPT, (b) how P is related to the somatosensory system and recumbency, and (c) what treatments have been effective. Methods Retrospective case series of 58 adults with P encountered in an outpatient clinic or through telemedicine. Results P could be constant or intermittent, with or without non-pulsatile tinnitus (nP). 90% of cases could suppress their pulsations with ST; 9% could not. In 7 of 11 cases that had no P at time of testing, ST elicited P. The most common type of P was SSPT (constant pulsatile tinnitus suppressible by ST) (60%). Treatment of head and neck muscle dysfunction (muscle dry needling and Botulinum toxin injection) has abolished P; auricular electrical stimulation was effective in 2 cases. Conclusion Suppression of pulsations by ST, eliciting P by ST, and abolishment of P by head and neck muscle treatments all support a major role of the craniocervical somatosensory system in the etiology of most, if not all, cases of P. Three mechanisms are proposed: (A) somatosensory afferents causing dysfunction of the CNS mechanisms that normally suppress self-generated cardiac and vascular sounds, (B) cardiac synchronous disinhibition of the auditory CNS by somatosensory afferents and (C) some combination of A and B.

Existing models of aortic stenosis (AS) are limited to inducing left ventricular pressure overload. As they have reduced control over the severity of aortic constriction, the clinical relevance of these models is largely hindered by their inability to mimic AS hemodynamics and recapitulate flow patterns associated with congenital valve defects, responsible for the accelerated onset and progression of AS. Here we report the development of a highly tunable bio-inspired soft robotic tool that enables the recapitulation of AS in a porcine model, in which customization of actuation patterns allows hemodynamic mimicry of AS and congenital aortic valve defects. In vitro and computational tools including lumped-parameter, finite element, and computational fluid dynamics platforms were developed to predict the hemodynamics induced by the bio-inspired soft robotic sleeve. The controllability of our in vivo model and its ability to replicate flow patterns of AS and congenital defects were demonstrated in swine through echocardiography, left ventricular catheterization, and magnetic resonance imaging. This work supports the use of soft robotics to simulate human physiology and disease, while paving the way towards the development of patient-specific models of AS and congenital defects that can guide clinical decisions to improve the management and treatment of these patients.

Nonautoimmune hyperthyroidism caused by activating mutations in the GNAS gene is a rare condition. In this study, we report a five-year-old girl diagnosed with nonautoimmune hyperthyroidism and tall stature harboring a somatic mosaic gain-of-function mutation in the GNAS gene (NM_080425.3: c.2530C>T;p.Arg844Cys previously reported as NM_000516.5:c.601C>T;p.Arg201Cys) and referred to thereafter as R201C, in three of four quadrants of the thyroid gland. Provision of a molecular diagnosis may avoid unnecessary complete ablation of the thyroid gland.

Objectives (a) Update previous descriptions of trends in ASSB; (b) determine if factors previously associated with ASSB are replicated by updated data; and (c) generate new hypotheses about the occurrence of ASSB and racial inequalities in ASSB mortality. Methods National Center for Health Statistics files (International Classification of Diseases, Tenth Edition) Code W75 to describe race-ethnicity-specific ASSB occurrence. Results (a) ASSB mortality continues to increase significantly; for 1999-2016, 4.4-fold for NHB girls (45.8 per 100,000 in 2016), 3.5-fold for NHB boys (53.8), 2.7-fold for NHW girls (15.8) and 4.0-fold for NHW boys (25.9); (b) F actors previously associated with ASSB (unmarried mothers and mothers with low educational attainment, low infant birth weight, low gestational age, lack of prenatal care, male infant, multiple birth, high birth order) continue to be associated with both overall ASSB and inequalities adversely affecting NHB; (c) (1) geographic differences and similarities in ASSB occurrence support hypotheses related to positive deviance; (2) lower ASSB mortality for births attended by midwives as contrasted to physicians generate hypotheses related to both medical infrastructure and maternal engagement; (3) high rates of ASSB among infants born to teenage mothers generate hypotheses related to the possibility that poor maternal health may be a barrier to ASSB prevention based on education, culture and tradition. Conclusions for Practice These descriptive data may generate new hypotheses and targets for interventions for reducing both ASSB mortality and racial inequalities. Analytic epidemiologic studies designed a priori to do so are required to address these hypotheses.

Objectives This study hypothesized that compensatory mitral leaflet area (MLA) adaptation occurs in patients with persistent atrial fibrillation (AF) without left ventricular (LV) dysfunction but has limitations that augment mitral regurgitation (MR). The study also explored whether asymmetrical annular dilation is matched by relative leaflet enlargement. Background Functional MR occurs in patients with AF and isolated annular dilation, but the relationship of MLA adaptation with annular area (AA) is unknown. Methods Three-dimensional echocardiographic images were acquired from 86 patients with quantified MR: 53 with nonvalvular persistent AF (23 MR+ with moderate or greater MR, 30 MR−) without LV dysfunction or dilation and 33 normal controls. Comprehensive 3-dimensional analysis included total diastolic MLA, adaptation ratios of MLA to annular area and MLA to leaflet closure area, and annular and tenting geometry. Results Total MLA was 22% larger in patients with AF than in controls, thus paralleling the increased AA. However, as AA increased, adaptive indices (MLA/AA ratio and ratio of MLA to closure area) plateaued, becoming lowest in MR+ patients (ratio of MLA to closure area = 1.63 ± 0.17 controls, 1.60 ± 0.11 MR−, 1.32 ± 0.10 MR+; p Conclusions MLA adaptively increases in AF with isolated annular dilation and normal LV function. This compensatory enlargement becomes insufficient with greater annular dilation, and the leaflets fail to match asymmetrical annular remodeling, thereby increasing MR. These findings can potentially help optimize therapeutic options and motivate basic studies of adaptive growth processes.

The mechanism of reduced stroke volume index (SVi) in paradoxical low-flow, low-pressure gradient (PLFLPG) aortic stenosis (AS) remains unclarified. Guyton et al. ( 21 ) demonstrated that SVi is determined by whole body O2 consumption (V̇o2) in many subjects, including patients with heart disease. We hypothesized that reduced SVi in PLFLPG AS is associated with reduced V̇o2 by the whole body. This study investigated the relationship between V̇o2, SVi, and AS severity in patients with AS to examine the association between reduced V̇o2 and PLFLPG AS. In 59 patients (24 men and 35 women, mean age: 78 ± 7 yr old) with severe AS, SVi, AS severity, and type were evaluated by echocardiography, and V̇o2 was measured by the fraction of O2 in expired gases. SVi and V̇o2 were significantly decreased in 20 patients with PLFLPG AS compared with 39 patients with non-PLFLPG AS (30 ± 4 vs. 41 ± 7 ml/m2 and 2.4 ± 0.5 vs. 3.0 ± 0.5 ml·min−1·kg−1, respectively, P < 0.01). The SVi-to-V̇o2 ratio was not different between the two groups (13.1 ± 2.6 vs. 13.6 ± 2.1, not significant). SVi was independently correlated with V̇o2 ( r = 0.74, P < 0.01) but not with the aortic valve area index. Categorized PLFLPG AS was also significantly associated with reduced V̇o2 ( P < 0.001). PLFLPG AS is associated with reduced V̇o2 by the whole body, which may offer insights into the mechanism of PLFLPG AS. NEW & NOTEWORTHY Paradoxical low-flow, low-pressure gradient severe aortic stenosis (PLFLPG AS) is an important and problematic subtype, and its central pathophysiology with reduced stroke volume is yet to be clarified. We hypothesized and subsequently clarified that reduced stroke volume in PLFLPG AS is associated with reduced O2 consumption by the whole body. This study suggests important insights into the mechanism of PLFLPG AS and may further promote studies to investigate further mechanisms and novel treatment.

Purpose The purpose of this work was to determine the pro-and anti-inflammatory properties of the single-cell organism Euglena gracilis (EG) and various fractions of its whole biomass. Methods Heterotrophically grown EG was tested, along with its aqueous fraction (E-AQ), the intact linear β-glucan paramylon granules (PAR), and alkaline-solubilized paramylon. Peripheral blood mononuclear cell cultures were treated with the test products and analyzed for a variety of cellular responses. Immune cell activation was evaluated by flow cytometry detection of CD69 levels on CD3-CD56+ NK cells, CD3+CD56+ NKT cells, and monocytes, and cytokines were analyzed from the cell culture supernatants. Antioxidant capacity was measured by Folin-Ciocalteu assay and cellular antioxidant protection and MTT assays. Results EG and E-AQ were the most effective in driving immune cell responses as measured by CD69 upregulation on NK and NKT cells and proinflammatory (tumor necrosis factor, IL-6, IL-1β) cytokine production. None of the test products effectively stimulated monocyte. EG and PAR inhibited reactive oxygen species under conditions of oxidative stress. E-AQ contained antioxidants capable of providing cellular antioxidant protection from oxidative damage and protection of mitochondrial function under inflammatory conditions. Conclusion The effects of EG on immune function are only partially attributable to the content of the β-glucan, paramylon. The regulation of additional cellular responses, such a reactive oxygen species production and resistance to oxidative stress, is likely mediated by currently unknown molecules found in the EG cell.

OBJECTIVES To assess impact of left ventricular (LV) chamber remodeling on MitraClip (MClp) response. BACKGROUND MitraClip is the sole percutaneous therapy approved for mitral regurgitation (MR) but response varies. LV dilation affects mitral coaptation; determinants of MClp response are uncertain. METHODS LV and mitral geometry were quantified on pre- and post-procedure two-dimensional (2D) transthoracic echocardiography (TTE) and intra-procedural three-dimensional (3D) transesophageal echocardiography (TEE). Optimal MClp response was defined as ≤mild MR at early (1-6 month) follow-up. RESULTS Sixty-seven degenerative MR patients underwent MClp: Whereas MR decreased ≥1 grade in 94%, 39% of patients had optimal response (≤mild MR). Responders had smaller pre-procedural LV end-diastolic volume (94 ± 24 vs. 109 ± 25 mL/m2 , p = 0.02), paralleling smaller annular diameter (3.1 ± 0.4 vs. 3.5 ± 0.5 cm, p = 0.002), and inter-papillary distance (2.2 ± 0.7 vs. 2.5 ± 0.6 cm, p = 0.04). 3D TEE-derived annular area correlated with 2D TTE (r = 0.59, p

Objectives To evaluate the impact of a 12-month multi-modal public health intervention programme for treating and preventing anaemia among children aged 6 months to 4 years in an underserved community in Peru. Methods The intervention included nutritional education, use of a Lucky Iron Fish® cooking tool, and dietary supplementation. The primary outcome measure was anaemia resolution. Secondary outcomes included absolute changes in haemoglobin, change in knowledge survey scores and adherence to interventions. Chi-square test and Mann-Whitney U-test were employed to identify associations between anaemia and intervention-related measures. Variables found to be significantly associated in bivariate analysis or of clinical importance were included in a logistic regression model. Results Of the 406 children enrolled, 256 (63.1%) completed the programme. Of those, 34.0% had anaemia at baseline; this decreased to 13.0% over 12 months. The mean haemoglobin for all ages at baseline was 11.3 g/dL (SD 0.9). At 12 months, the mean was 11.9 g/dL (SD 0.8), with a mean increase of 0.5 g/dL (95% CI 0.4-0.6). Children with anaemia at baseline saw an increase of 1.19 g/dL at the 12-month follow-up (95% CI 1.12-1.37). Parents correctly answered 79.0% of knowledge assessment questions at baseline, which increased to 86.6% at 12 months. Conclusions We observed a reduction in the prevalence of mild to moderate anaemia among study participants in this vulnerable population and conclude that multi-modal intervention programmes providing nutrition education in conjunction with low-cost iron supplementation and easy-to-use Lucky Iron Fish® cooking tools may reduce and prevent anaemia in children.

The purpose of this prospective study was to evaluate the success rates and prosthetic complications of implants with a modified sandblasted and acid-etched (SLA) surface inserted for posterior single-implant crown restorations. Final crowns were placed 3 to 4 weeks after surgery, and patient follow-up spanned 10 years in a private practice setting. A total of 22 patients (8 women, 14 men) with 25 posterior implants placed (16 mandible, 9 maxilla) were selected, including only implants for posterior single-implant crowns with insertion torque values of ≥ 35 Ncm at placement. Twenty-one implants passed the reverse torque test at 3 to 4 weeks after implant placement, and final restorations were placed. Three patients (4 implants) had "spinners," and there was one patient dropout after completion of the final restoration. All patients were recalled for clinical exams, digital periapical radiographs, and clinical photos at short-term (≤ 5 years) and long-term (> 5 years) follow-up appointments. The Community Periodontal Index of Treatment Needs was also determined at the initial and follow-up visits. Crestal bone level was measured at crown placement (T1), short-term follow-up (T2; mean: 29.4 months), and long-term follow-up appointments (T3; mean: 114.4 months). Twenty patients (23 implants) returned for examination at T2, and 15 (18 implants) were available at T3. For the 17 implants available at all evaluations, statistically significant bone loss was found from T1 to T2 (0.23 ± 0.30 mm), and the mean crestal bone level appeared stable from T2 to T3. Based on clinical and radiographic findings, the success rate for the implants and restorations at T2 and T3 was graded as 100%. Therefore, it can be stated that an early loading protocol of 3 to 4 weeks using a modified SLA surface at premolar/molar single-tooth locations can result in favorable clinical and radiographic long-term results.

Papillary thyroid carcinoma (PTC) is the most common histologic type of thyroid carcinoma worldwide. Lymph node (LN) metastases are common, and microscopic LN metastases occur in the majority of patients who have PTC. 1 LN metastases are associated with an increased risk of local or regional recurrence of cancer, and they can be a negative prognostic indicator with respect to survival. 2 , 3 , 4 LN metastases may necessitate more extensive surgery, with increased risks, and a longer period of recovery, as well as an increased use of postoperative radioactive iodine. To facilitate development of an appropriate presurgical plan to clear all macroscopic disease during the initial surgery, a thorough examination of LNs with preoperative radiographic mapping is essential.

Introduction: Acute rheumatic fever (ARF) results from autoimmune responses to group A streptococcus. ARF can cause chronic rheumatic heart valve disease (RHVD), a major public health burden in low- and middle-income countries. Although ARF affects both sexes equally, females have a higher prevalence of RHVD. We identified a target protein, ProTα, that may contribute to pathophysiology of and gender predisposition in RHVD. Estradiol regulates ProTα, which influences transcriptional activity of the estrogen receptor (ER). Methods: Human heart valves (n=120) obtained from heart transplantation and valve replacement surgeries, including non-diseased mitral and aortic valves (NDMV and NDAV, n=17/group), rheumatic mitral and aortic valves (RMVD, n=45; RAVD, n=8) and calcifying valves from patients with calcific aortic valve disease (CAVD, n=33) underwent proteomic and network analyses, and immunohistochemical assessment of CD68, CD4, CD8 and ProTα. ProTα levels were measured in plasma and peripheral mononuclear cells (PBMCs) from RHVD patients and healthy donors (n=14/group) by ELISA and flow cytometry. Results: A comparison of proteomes from NDMV and NDAV established the baseline differences between valve types. 12 proteins were enriched (q Conclusion: We propose that ProTα is a novel contributor to the immunopathogenesis of RHVD and may regulate sex predisposition in this disease.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets. MV annulus systolic expansion, PMs’ systolic superior shift, and MV leaflets’ systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP. PMs’ superior shift, MV leaflets’ lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m(2), 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m(2), 6.8 ± 2.5 versus 5.7 ± 1.0 cm(2)/m(2) and 1.6 ± 0.8 versus 0.1 ± 0.5 cm(2)/m(2), P < 0.001, respectively). Multivariate analysis identified MV leaflets’ lengthening and PMs’ superior shift as independent factors associated with MV annular expansion. CONCLUSIONS: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets’ lengthening and PMs’ superior shift.

Mixed venous oxygen (O(2)) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O(2) consumption (V̇o(2)), while clinical use is limited to the required invasive catheterization. According to Fick’s equation, V̇o(2) (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] − [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O(2) saturation). Because V̇o(2), CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O(2) saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] (r = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was −2.2% (95% confidence interval, −3.2 to −1.1%) with limits of agreement from −9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O(2) saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism. NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick’s equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

OBJECTIVES: The aims of this study were to test the magnitude of agreement between echocardiography- (echo) and cardiac magnetic resonance (CMR)-derived left atrial (LA) strain and to study their relative diagnostic performance in discriminating diastolic dysfunction (DD) and predicting atrial fibrillation (AF). BACKGROUNDS: Peak atrial longitudinal strain (PALS) is a novel performance index. Utility of echo-quantified LA strain has yet to be prospectively tested in relation to current DD guidelines or compared to CMR. METHODS: The study population comprised 257 post-myocardial infarction (MI) patients undergoing echo and CMR, including prospective derivation (n = 157) and clinical validation (n = 100) cohorts. DD was graded on echo using established consensus guidelines blinded to strain results. RESULTS: PALS on both echo and CMR was nearly 2-fold lower among patients with versus no DD (p < 0.001) and was significantly different in those with mild versus no DD (p < 0.01). In contrast, LA geometric parameters including echo- and CMR-derived volumes were significantly different between advanced versus no DD groups (p < 0.001) but not between groups with mild versus no DD (all p > 0.05). Echo and CMR PALS yielded small differences irrespective of orientation and similar diagnostic performance for DD in the derivation (area under the curve: 0.70 to 0.78) and validation (area under the curve 0.75 to 0.78) cohorts. Impaired PALS on both modalities was independently associated with MI size (p < 0.001). During 4.4 ± 3.8 years of follow-up in the derivation cohort, 8% developed AF. Both 2-chamber echo- and CMR-derived PALS stratified arrhythmic risk (p = 0.004 and p = 0.02, respectively), including a 4-fold difference among patients in the Lowest versus remainder of quartiles of echo-derived PALS (24% vs. 6%). Similarly, echo and CMR PALS were Lower (both p < 0.05) among patients with subsequent heart failure hospitalizations. CONCLUSIONS: Echo-derived PALS parallels results of CMR, yields incremental diagnostic utility versus LA geometry for stratifying presence and severity of DD, and improves prediction of AF and congestive heart failure after MI.

Aims The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR). Methods and results The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3–5 mmHg, n = 3927), mid (5–10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P Conclusion In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3–5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.

The Miller McEntire Periodontal Prognostic Index (MMPPI) is a simple, powerful, evidenced-based, statistically validated, and accurate motivational tool which can be used daily in clinical practice with all patients. Its usage is not limited to patients presenting with periodontitis but is routinely used with periodontally healthy patients. In other words, the MMPPI can be used for all patients. The benefits to the patient are that they better understand their long-term periodontal prognosis of 15 and 30 years. It also encourages patients to make lifestyle changes to improve their overall health including smoking cessation, blood sugar control, and compliance to their recommended preventative periodontal maintenance frequency. Accurate prognosis can be determined by scoring the most periodontally involved molar that you plan to keep. The strength of the MMPPI is that it translates clinical outcomes into patient value.

OBJECTIVE Describe southern US homicide rates in whites and blacks between 1999 and 2015. METHODS The Centers for Disease Control and Prevention Multiple Cause of Death Files provided mortality rates and 95% confidence intervals (CIs) for non-Hispanic whites (NHW) as well as non-Hispanic blacks and African Americans (NHB). RESULTS Overall, age-adjusted (1 to ≥85 years) homicide was significantly higher in the South (7.6/100,000, 95% CI 7.6-7.7) than the rest of the United States (4.9/100,000, 95% CI 4.8-4.9) even though the southern rate among NHB (18.7/100,000, 95% CI 18.5-18.8) was lower than the rest of the United States (23.3/100,000, 95% CI 23.1-23.5). The overall southern NHB:NHW mortality rate ratio was 5.1 and 10.6 in the rest of the nation. Homicide rates among NHW men were higher in the South than in each of the other US Census areas, whereas corresponding rates among NHB men were lower. For both men and women the NHB:NHW mortality rate ratio was lower in the South than in any other region. In addition, homicide rates among NHB women in the South were equal to or lower than corresponding rates in the West and Midwest. Finally, higher rates for NHW in metropolitan areas led to overall higher NHW mortality rates and relatively low NHB:NHW rates. Southern NHW had a higher percentage of firearms-related homicides (58.4%) than the corresponding percentage in the rest of the United States (49.8%; P < 0.001). Southern NHB used firearms for 78.8% of homicides compared with 83.9% in the rest of the United States (P < 0.001). CONCLUSIONS The overall high homicide rates in the southern United States were attributable to relatively higher NHW rates than those found in the rest of the country. Further research targeting the role of firearms as well as cultural and other issues could further the understanding of the interrelations of homicide with complex regional and cultural factors.

BACKGROUND: Conventional hemodynamic parameters may not accurately predict symptomatic improvement after percutaneous mitral valvuloplasty (PMV). Changes in left heart chamber compliance following adequate relief o0066 mitral stenosis (MS) may be useful in determining functional capacity after PMV. This study aims to determine the acute effects of PMV on compliance of the left heart and whether its changes relate to the patient’s functional capacity. METHODS: One-hundred thirty-seven patients with severe MS undergoing PMV were enrolled. Left atrial (C(a)) and left ventricular (C(v)) compliance were invasively estimated and net atrioventricular compliance (C(av)) was calculated before and immediately after the procedure. B-type natriuretic peptide (BNP) levels were obtained before and 24 hr after the procedure. The primary endpoint was functional status at 6-month follow-up, and the secondary endpoint was a composite of death, mitral valve (MV) replacement, repeat PMV, new onset of atrial fibrillation, or stroke in patients in whom PMV was successful. RESULTS: The mean age was 43 ± 12 years, and 119 patients were female (87%). After PMV, C(a) and C(av) improved significantly from 5.3 [IQR 3.2–8.2] mL/mmHg to 8.7 [5.3–19.2] mL/mmHg (P < 0.001) and 2.2 [1.6–3.4] to 2.8 [2.1–4.1] mL/mmHg (P < 0.001), respectively, whereas C(v) did not change (4.6 [3.2–6.8] to 4.4 [3.1–5.6]; P = 0.637). Plasma BNP levels significantly decreased after PMV, with no correlation between its variation and changes in left chamber compliance. At 6-month follow-up, NYHA functional class remained unchanged in 32 patients (23%). By multivariable analyses, changes in C(a) immediately after PMV (adjusted OR 1.42; 95% CI 95% 1.02 to 1.97; P = 0.037) and younger age (adjusted OR 0.95; CI 95% 0.92–0.98; P = 0.004), predicted improvement in functional capacity at 6-month follow-up, independent of postprocedural data. The secondary endpoint were predicted by post-PMV mean gradient (adjusted HR 1.363; 95% CI 95% 1.027–1.809; P = 0.032), and lack of functional improvement at 6-month follow-up (adjusted HR 4.959; 95% 1.708–14.403; P = 0.003). CONCLUSIONS: C(a) and C(av) increase significantly after PMV with no change in C(v). The improvement of C(a) is an important predictor of functional status at 6-month follow up, independently of other hemodynamic data. Postprocedural mean gradient and lack of short-term symptomatic improvement were predictors of adverse outcome.

Levine, Robert S., Jason L. Salemi, Maria C. Mejia de Grubb, Sarah K. Wood, Lisa Gittner, Hafiz Khan, Michael A. Langston, Baqar A. Husaini, George Rust, and Charles H. Hennekens. Altitude and variable effects on infant mortality in the United States. High Alt Med Biol. 19:265-271, 2018.To explore whether altitude has different effects on infant mortality from newborn respiratory distress, nontraumatic intracranial hemorrhage, and necrotizing enterocolitis.Infants born in the US Mountain Census Division (AR, CO, ID, NV, NM, UT, and WY) had lower mortality from newborn respiratory distress (p 0.001, mortality rate ratios [MRR] = 0.5 for non-Hispanic blacks and non-Hispanic whites and 0.6 for Hispanic whites) relative to infants born elsewhere in the United States, while Mountain Division non-Hispanic white infants had significantly higher mortality from nontraumatic intracranial hemorrhage (MRR = 1.3 [1.1, 1.6] p 0.001). After adjustment for state average birth weight, gestational age, and income inequality, a statistically significant, inverse association remained between state average altitude and non-Hispanic white infant mortality from newborn respiratory distress. County altitude (3058 counties in 9 categories from ≤0 to ≥7000 feet) was negatively correlated with newborn respiratory distress (r = -0.91, p 0.001) and necrotizing enterocolitis (r = -0.81, p = 0.006) at ≤0 to ≥7000 feet and positively correlated with nontraumatic intracranial hemorrhage at ≤0 to 6000-6999 feet (r = 0.78, p = 0.02).These data show variable cause-specific effects of altitude on infant mortality. Analytic epidemiologic research is needed to confirm or refute the hypotheses generated by these descriptive data.

Background Aortic valve area (AVA) ≤1.0 cm2 is a defining characteristic of severe aortic stenosis (AS). AVA can be underestimated at low transvalvular flow rate. Yet, the impact of flow rate on prognostic value of AVA ≤1.0 cm2 is unknown and is not incorporated into AS assessment. Objectives This study aimed to evaluate the effect of flow rate on prognostic value of AVA in AS. Methods In total, 1,131 patients with moderate or severe AS and complete clinical follow-up were included as part of a longitudinal database. The effect of flow rate (ratio of stroke volume to ejection time) on prognostic value of AVA ≤1.0 cm2 for time to death was evaluated, adjusting for confounders. Sensitivity analysis was performed to identify the optimal cutoff for prognostic threshold of AVA. The findings were validated in a separate external longitudinal cohort of 939 patients. Results Flow rate had a significant effect on prognostic value of AVA. AVA ≤1.0 cm2 was not prognostic for mortality (p = 0.15) if AVA was measured at flow rates below median (≤242 ml/s). In contrast, AVA ≤1.0 cm2 was highly prognostic for mortality (p = 0.003) if AVA was measured at flow rates above median (>242 ml/s). Findings were irrespective of multivariable adjustment for age, sex, and surgical/transcatheter aortic valve replacement (as time-dependent covariates); comorbidities; medications; and echocardiographic features. AVA ≤1.0 cm2 was also not an independent predictor of mortality below median flow rate in the validation cohort. The optimal flow rate cutoff for prognostic threshold was 210 ml/s. Conclusions Transvalvular flow rate determines prognostic value of AVA in AS. AVA measured at low flow rate is not a good prognostic marker and therefore not a good diagnostic marker for truly severe AS. Flow rate assessment should be incorporated into clinical diagnosis, classification, and prognosis of AS.

Aims Secondary mitral regurgitation (MR) drives adverse remodelling towards late heart failure stages. Little is known about the evolution of MR under guideline-directed therapy (GDT) and its relation to cardiac remodelling and outcome. We therefore aimed to assess incidence, impact, and predictors of progressive secondary MR in patients under GDT. Methods and results We prospectively enrolled 249 patients with chronic heart failure and reduced ejection fraction receiving GDT in this long-term observational study. Of patients with non-severe MR at baseline 81% remained stable whereas 19% had progressive MR. Those patients were more symptomatic (P

OBJECTIVES: The aim of Working Group 3 was to focus on three topics that were assessed using patient-reported outcome measures (PROMs). These topics included the following: (a) the aesthetics of tooth and implant-supported fixed dental prostheses focusing on partially edentulous patients, (b) a comparison of fixed and removable implant-retained prostheses for edentulous populations, and (c) immediate versus early/conventional loading of immediately placed implants in partially edentate patients. PROMs include ratings of satisfaction and oral health-related quality of life (QHRQoL), as well as other indicators, that is, pain, general health-related quality of life (e.g., SF-36). MATERIALS AND METHODS: The Consensus Conference Group 3 participants discussed the findings of the three systematic review manuscripts. Following comprehensive discussions, participants developed consensus statements and recommendations that were then discussed in larger plenary sessions. Following this, any necessary modifications were made and approved. RESULTS: Patients were very satisfied with the aesthetics of implant-supported fixed dental prostheses and the surrounding mucosa. Implant neck design, restorative material, or use of a provisional restoration did not influence patients' ratings. Edentulous patients highly rate both removable and fixed implant-supported prostheses. However, they rate their ability to maintain their oral hygiene significantly higher with the removable prosthesis. Both immediate provisionalization and conventional loading receive positive patient-reported outcomes. CONCLUSIONS: Patient-reported outcome measures should be gathered in every clinical study in which the outcomes of oral rehabilitation with dental implants are investigated. PROMs, such as patients' satisfaction and QHRQoL, should supplement other clinical parameters in our clinical definition of success. ispartof: CLINICAL ORAL IMPLANTS RESEARCH vol:29 pages:270-275 ispartof: location:Denmark status: published

Mitral valve prolapse (MVP) is a common heritable valvulopathy affecting approximately 2.4% of the population. It is the most important cause of primary mitral regurgitation (MR) requiring surgery. MVP is characterized by fibromyxomatous changes and displacement of one or both mitral leaflets into the left atrium. Echocardiography represents the primary diagnostic modality for assessment of MVP. Accurate quantitation of ventricular volumes and function for surgical planning in asymptomatic severe MR can be provided with both echocardiography and cardiac magnetic resonance. In addition, assessment of myocardial fibrosis using late gadolinium enhancement and T1 mapping allows better understanding of the impact of MVP on the myocardium. Imaging in MVP is important not only for diagnostic and prognostic purposes, but is also essential for detailed phenotyping in genetic studies. Genotype-phenotype studies in MVP pedigrees have allowed the identification of milder, non-diagnostic MVP morphologies by echocardiography. Such morphologies represent early expression of MVP in gene carriers. This review focuses on multimodality imaging and the phenotypic spectrum of MVP. Moreover, the review details the recent genetic discoveries that have increased our understanding of the pathophysiology of MVP, with clues to mechanisms and therapy.

Background Myocardial strain provides a novel means of quantifying subtle alterations in contractile function; incremental utility post-MI is unknown. Objectives To test longitudinal—quantified by postprocessing routine echo—for assessment of MI size measured by cardiac magnetic resonance (CMR) and conventional methods, and assess regional and global strain (GLS) as markers of LV thrombus. Methods The population comprised of patients with anterior ST-segment MI who underwent echo and CMR prospectively. Preexisting echoes were retrieved, re-analyzed for strain, and compared to conventional MI markers as well as CMR-evidenced MI, function, and thrombus. Results Seventy-four patients underwent echo and CMR 4 ± 1 weeks post-MI; 72% had abnormal GLS. CMR-quantified MI size was 2.5-fold larger and EF lower among patients with abnormal GLS, paralleling 2.6–3.1 fold differences in Q-wave size and CPK (all P ≤ .002). GLS correlated with CMR-quantified MI (r = .66), CPK (r = .52) and Q-wave area (r = .44; all P ≤ .001): Regional strain was lower in the base, mid, and apical LV among patients with CMR-defined transmural MI in each territory (P

Objectives Rheumatic mitral stenosis (MS) is a progressive disease, and risk of death may persist despite relief of the obstruction. Net atrioventricular compliance (C n ) modulates the overall haemodynamic burden of the MS and may be useful in predicting cardiovascular death after percutaneous mitral valvuloplasty (PMV). Methods A total of 427 patients (mean age 50±16 years, 84% female) with severe MS undergoing PMV were enrolled. Doppler-derived C n was estimated at baseline using a previously validated equation. The primary endpoint was late cardiovascular death, and the secondary endpoint was a composite of all-cause mortality, mitral valve (MV) replacement or repeat PMV over a median follow-up of 31 months (IQR: 7.8–49.2 months). Results At baseline, 209 patients (49%) were in New York Heart Association (NYHA) functional class III or IV. During follow-up, 49 patients died (41 cardiovascular deaths), 50 underwent MV replacement and 12 required repeat PMV, with an overall incidence of cardiac mortality and adverse events of 4.1 deaths and 11.1 events per 100 patient-years, respectively. Low baseline C n was a strong predictor of both cardiac death (adjusted HR 0.70, 95% CI 0.49 to 0.86) and composite endpoint (adjusted HR 0.81, 95% CI 0.67 to 0.91) after adjusting for clinical factors, baseline pulmonary artery pressure, tricuspid regurgitation severity, right ventricular function and immediate procedural haemodynamic data. The inclusion of C n in a model with conventional parameters resulted in improvement in 5-year cardiovascular mortality risk prediction. Conclusions Baseline C n is a strong predictor of cardiovascular death in patients with MS undergoing PMV, independent of other prognostic markers of decreased survival in MS, including baseline patient characteristics and postprocedural data. C n assessment therefore has potential value in evaluation of cardiovascular mortality risk in the setting of MS.

Objectives. To assess state-level progress on eliminating racial disparities in infant mortality. Methods. Using linked infant birth–death files from 1999 to 2013, we calculated state-level 3-year rolling average infant mortality rates (IMRs) and Black–White IMR ratios. We also calculated percentage improvement and a projected year for achieving equality if current trend lines are sustained. Results. We found substantial state-level variation in Black IMRs (range = 6.6–13.8) and Black–White rate ratios (1.5–2.7), and also in percentage relative improvement in IMR (range = 2.7% to 36.5% improvement) and in Black–White rate ratios (from 11.7% relative worsening to 24.0% improvement). Thirteen states achieved statistically significant reductions in Black–White IMR disparities. Eliminating the Black–White IMR gap would have saved 64 876 babies during these 15 years. Eighteen states would achieve IMR racial equality by the year 2050 if current trends are sustained. Conclusions. States are achieving varying levels of progress in reducing Black infant mortality and Black–White IMR disparities. Public Health Implications. Racial equality in infant survival is achievable, but will require shifting our focus to determinants of progress and strategies for success.

Background The American Cancer Society estimates that about 25% of all US cancer deaths will be due to lung cancer – more than from cancers of the colon, breast, and prostate combined. Methods We ascertained county-level age-adjusted and age-specific death rates and 95% confidence intervals from the Centers for Disease Control and Prevention Compressed Mortality File. Multiple regression analyses were used to estimate the strength and direction of relationships between county poverty, smoking, fine particulate matter (PM2.5) air pollution, and US Census divisions and race- and sex-specific lung cancer deaths. Results Poverty, smoking, and particulate matter air pollution were positively and significantly related to lung cancer deaths among white men, but of these, only poverty and smoking were significantly associated with lung cancer deaths among white women. Residence in the South Atlantic, East South Central, and West South Central US Census divisions at the time of death was significantly associated with lung cancer deaths for both white men and white women. As with white men, poverty and smoking were associated with lung cancer deaths among black men, but of these, only adult smoking had a statistically significant association among black women. Conclusions The results support the need for further research, particularly in high-risk areas, to better differentiate factors specific to race and sex and to understand the impact of local risk factors.

Secondary mitral valve regurgitation (MR) remains a challenging problem in the diagnostic workup and treatment of patients with heart failure. Although secondary MR is characteristically dynamic in nature and sensitive to changes in ventricular geometry and loading, current therapy is mainly focused on resting conditions. An exercise-induced increase in secondary MR, however, is associated with impaired exercise capacity and increased mortality. In an era where a multitude of percutaneous solutions are emerging for the treatment of patients with heart failure, it becomes important to address the dynamic component of secondary MR during exercise as well. A critical reappraisal of the underlying disease mechanisms, in particular the dynamic component during exercise, is of timely importance. This review summarizes the pathophysiological mechanisms involved in the dynamic deterioration of secondary MR during exercise, its functional and prognostic impact, and the way current treatment options affect the dynamic lesion and exercise hemodynamics in general.

Describe trends in non-Hispanic black infant mortality (IM) in the New York City (NYC) counties of Bronx, Kings, Queens, and Manhattan and correlations with gun-related assault mortality.Linked Birth/Infant Death data (1999-2013) and Compressed Mortality data at ages 1 to ≥85 years (1999-2013). NYC and United States (US) Census data for income inequality and poverty. Pearson coefficients were used to describe correlations of IM with gun-related assault mortality and other causes of death.In NYC, the risk of non-Hispanic black IM in 2013 was 49% lower than in 1995 (rate ratio: 0.51; 95% CI: 0.43, 0.61). Yearly declines between 1999 and 2013 were significantly correlated with declines in gun-related assault mortality (correlation coefficient (r) = 0.70, p = 0.004), drug-related mortality (r = 0.59, p = 0.020), major heart disease and stroke (r = 0.85, p 0.001), malignant neoplasms (r = 0.57, p = 0.026), diabetes mellitus (r = 0.63, p = 0.011), and pneumonia and influenza (r = 0.78, p 0.001). There were no significant correlations of IM with chronic lower respiratory or liver disease, non-drug-related accidental deaths, and non-gun-related assault. Yearly IM (1995-2012) was inversely correlated with income share of the top 1% of the population (r = -0.66, p = 0.007).In NYC, non-Hispanic black IM declined significantly despite increasing income inequality and was strongly correlated with gun-related assault mortality and other major causes of death. These data are compatible with the hypothesis that activities related to overall population health, including those pertaining to gun-related homicide, may provide clues to reducing IM. Analytic epidemiological studies are needed to test these and other hypotheses formulated from these descriptive data.