Beyond the Initial Insult: Clinical Characteristics and Prognosis of Heart Failure with Improved Ejection Fraction.

INTRODUCTION: Heart failure with improved ejection fraction (HFimpEF) is a recently defined subtype of HF, characterized by an increase in ejection fraction (EF) after a prior diagnosis of reduced EF. There are limited data on the characteristics and outcome of this patient subset. The study aimed to investigate the clinical profile and prognosis of this patient group. METHODS: HFimpEF patients from a large echocardiography database with comprehensive clinical and outcome data were evaluated for clinical characteristics and outcomes including mortality and cardiovascular hospitalizations. HFimpEF was defined as prior HF diagnosis with EF ≤40% followed by an EF increase of ≥10% to >40%. RESULTS: The study included 2,883 patients with an EF ≤40%. 27% (777) fulfilled criteria of HFimpEF. Non-ischemic cardiomyopathy, female sex, and smaller left ventricular dimensions were associated with EF improvement. Median follow-up duration was 1,346 days. Patients with HFimpEF had a significantly improved prognosis compared to those without EF improvement. Patients with a significant improvement in the EF (≥50%) experienced a 30% lower mortality rate (HR: 0.70, 95% CI: 0.57-0.86, p < 0.001) and a decreased risk of cardiovascular hospitalizations. CONCLUSIONS: HFimpEF is a distinct clinical entity observed in 27% of patients with initially reduced EF and conveys a better prognosis. However, even with improvement, EF in most patients does not fully recover, and clinical events can still occur.

Unraveling the relationship among insulin resistance, IGF-1, and amyloid-beta 1-40: Is the definition of type 3 diabetes applicable in the cardiovascular field?

The concept of "type 3 diabetes" has emerged to define alterations in glucose metabolism that predispose individuals to the development of Alzheimer's disease (AD). Novel evidence suggests that changes in the insulin/insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis, which are characteristic of Diabetes Mellitus, are one of the major factors contributing to excessive amyloid-beta (Aß) production and neurodegenerative processes in AD. Moreover, molecular findings suggest that insulin resistance and dysregulated IGF-1 signaling promote atherosclerosis via endothelial dysfunction and a pro-inflammatory state. As the pathophysiological role of Aß1-40 in patients with cardiovascular disease has attracted attention due to its involvement in plaque formation and destabilization, it is of great interest to explore whether a paradigm similar to that in AD exists in the cardiovascular field. Therefore, this review aims to elucidate the intricate interplay between insulin resistance, IGF-1, and Aß1-40 in the cardiovascular system and assess the applicability of the type 3 diabetes concept. Understanding these relationships may offer novel therapeutic targets and diagnostic strategies to mitigate cardiovascular risk in patients with insulin resistance and dysregulated IGF-1 signaling.

Why do women with cardiac symptoms delay seeking medical help? Insights from a qualitative study among Jewish Israeli women.

BACKGROUND: The delay time from onset of symptoms of a myocardial infarction to seeking medical assistance can have life-threatening consequences. Women delay significantly more often than men do in calling for medical help, once symptoms of a myocardial infarction occur. OBJECTIVES: The current qualitative study's main aim was to explore psychosocial factors that contribute to Israeli women's delaying calls for medical assistance and, by contrast, the motivational factors that encourage them to do so. DESIGN: A qualitative study. METHOD: In total, 12 women were interviewed shortly after experiencing a myocardial infarction. Qualitative data were subjected to thematic analysis. RESULTS: Two major themes emerged describing barriers to seeking help: (1) the use of denial as a defense mechanism and (2) the need for control. The motivational factor which enhanced help-seeking was "fear of death." CONCLUSION: These findings may help in designing gender-sensitive interventions with the aim of minimizing the symptom onset to call time and thus preventing irreversible and life-threatening health damage.

Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression.

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17ß-estradiol (E2) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of IL-1α, IL-6, Mmp9, Mmp12, Col1α1, and Col3α1 was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with Col1α1 and Col3α1 expression 1-week post-surgery (r = -0.79 p < 0.001; r = -0.6 p = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while Col1α1, Col3α1, IL-1α, IL-6, Tnfα, Mmp12, and FasL gene expression was significantly lower in E2- compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with Col3α1 in T12/OVX/ E2 (r = -0.56 p = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E2 replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status.

Dimensionless index and outcome in patients with aortic valve disease.

PURPOSE: Assessment of aortic stenosis (AS) is based on aortic valve (AV) gradients and calculation of aortic valve area (AVA). These parameters are influenced by flow and dependent on geometric assumptions. The dimensionless index (DI), the ratio of the LVOT time-velocity integral to that of the AV jet, is simple to perform, and is less susceptible to error but has only been examined in small selected groups of AS patients. The objective of this study was to assess the DI and prognosis in a large cohort. METHODS: All subjects who underwent echocardiography with an assessment of the AV that included DI were included. Association between AV parameters including mean gradient, AVA, DI and AV resistance and mortality and cardiovascular hospitalizations was examined. RESULTS: A total of 9393 patients (mean age 71 ± 16 years; 53% male) were included. 731 (7.7%) patients had DI less than .25. Increasing age and a diagnosis of heart failure were significantly associated with lower DI. Subjects with low DI had significantly lower ventricular function, a higher incidence of mitral and tricuspid regurgitation, worse diastolic function and more elevated pulmonary pressures. Decreasing DI was associated with significantly decreased survival and event-free survival which remained highly significant on multivariate analysis. CONCLUSIONS: In a large population of patients with AV disease, decreased DI, was associated with increased mortality and decreased event-free survival. The easily obtained DI identifies a broad range of AS subjects with worse prognosis and should be integrated into the assessment of these complex patients.

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO), predicts future major adverse cardiovascular events after myocardial infarction.

OBJECTIVE: Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome. METHODS AND RESULTS: Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events), including all-cause mortality, re-infarction, or heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge (respectively, 7.81 [3.47-19.98] vs 3.45 [2.3-4.78] µM, p < 0.001). After estimating the 3.45 µM TMAO cut-off with the analysis of the continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% of patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p = 0.05). At multivariable Cox analysis, patients from the HH/LH group had more than two times higher risk of MACE during the follow-up than the LL/HL group (HR = 2.15 [95% CI, 1.03-4.5], p = 0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function. CONCLUSION: In patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.

Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice.

INTRODUCTION: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. METHODS: AN-like model was established through dietary restriction (DR). On days 1-25, mice were on DR, and on days 26-31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. RESULTS: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. CONCLUSION: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."

Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.

Variable clinical expression of a novel FLNC truncating variant in a large family.

BACKGROUND: Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family. METHODS: Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases. RESULTS: Seventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late­gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall. CONCLUSION: This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.

A Pregnant Woman With Severe Symptomatic Aortic Stenosis: How Should We Treat?

A 31-year-old woman with end-stage kidney disease and with a bicuspid aortic valve presented with acute heart failure in the second trimester of pregnancy. The patient received a diagnosis of severe aortic stenosis and chose to continue the pregnancy against medical advice. Following a multidisciplinary team consultation, she underwent urgent transcatheter aortic valve replacement.

Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort.

BACKGROUND: Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed. OBJECTIVES: The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655). METHODS: After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms. RESULTS: Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: -35.6 ± 32.6 mm Hg; Valsalva: -45.3 ± 35.9 mm Hg), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (median: -480 ng/L; Q1-Q3: -1,104 to -179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events. CONCLUSIONS: Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.

Perceptions of Barriers and Facilitators to Reducing Exposure to Secondhand Smoke in the Home: A Qualitative Study With Palestinian-Arab Women in Israel.

INTRODUCTION: Smoking is a collective and complex problem in the Palestinian-Arab community in Israel, where women and children are particularly vulnerable to exposure to secondhand smoke (SHS), especially in the home. AIMS AND METHODS: We undertook this study to better understand women's experiences with SHS exposure in the home and to identify pathways for intervention. Using the grounded theory approach, seven focus groups were conducted with 66 women in different localities across Israel. Purposive and snowball sampling techniques were applied to recruit women who have currently or previously been exposed to smoking in the home. Focus groups were audio-recorded and transcribed verbatim, and data were then coded and analyzed using the constant comparison analysis method to identify emergent themes and subthemes. RESULTS: Three core themes emerged from the discussions. These include women's perceptions of smoking among men and exposure to SHS in the home, the implications of smoking on spousal and social relationships, and the women's experiences in coping with this situation and their suggestions for interventions. We identified additional sub-themes, including the consequences to women's and children's health, as well as the complex interaction between smoking in the home and women's social position, agency, and home ownership. CONCLUSIONS: Women exposed to SHS in the home experience consequences that affect their health and their spousal and social relationships. They also face several personal and societal challenges in tackling this issue. Culturally tailored interventions targeting both communities and households can raise awareness and impact smoking behaviors in the home. IMPLICATIONS: The findings of this study demonstrate the far-reaching consequences of SHS exposure in the home among women who are exposed. The findings contribute to our understanding of smoking contingencies among men and smoking behaviors in the home. This study lays the groundwork for future community and household-based research and interventions. We suggest several critical junctures that may increase response to smoking cessation interventions and to reduce smoking in the home, such as at the time of marriage when the home policy is set, and the adverse effects of exposure on children and other family members, especially those with illness.

The impact of aging on cardiac remodeling in chronic mitral regurgitation.

BACKGROUND: Chronic mitral regurgitation (MR) is a volume overload state that causes dilatation of the left sided cardiac chambers. The presence of significant dilatation is considered an indication for mitral valve intervention, however, aging may affect left ventricular (LV) remodeling independently of valvular disease. The objective of this study was to examine age-related changes in cardiac remodeling in a broad population of patients with chronic MR. METHODS: Consecutive subjects that underwent echocardiography examinations recorded in the echocardiography database of a university-affiliated laboratory were retrieved. Subjects were categorized into none/mild, moderate or severe MR. For purposes of analysis of differences with aging, the population was divided into groups above and below 70 years of age and standard echocardiographic measurements were compared between the groups. RESULTS: A total of 3492 subjects with at least moderate MR (mean age: 76 years, 52% female) were included in the study and compared to 18,250 subjects with none or mild MR. Older patients had significantly smaller LV end-diastolic diameters and volumes and significantly larger left atrial (LA) volumes when compared to the younger group. LA volume index increased in both age groups as MR severity increased, while LV end-diastolic volume increased with increasing MR only in the younger population. CONCLUSIONS: Cardiac remodeling in chronic MR is significantly influenced by age. Guideline based recommendations of timing of mitral valve interventions in asymptomatic MR patients, based on assessment of LA and LV remodeling, may need to take age into account.

Novel N-Acylethanolamide Derivatives Affect Body Weight and Energy Balance.

Introduction - The obesity pandemic is multifactorial. Nutritional, pharmacologic and surgical interventions are limited in reach and efficacy, raising need for new therapeutics. Aims - Characterization of anorexigenic and cognitive effect and central mechanism of action of novel N-acylethanolamide derivatives. Methods - Sabra mice divided to similar experimental groups, injected IP with: oleyl-L-leucinolamide (1 A), linoleyl-L-leucinolamide (4 A), linoleyl-L-valinolamide (5 A), oleyl-oxycarbonyl-L-valinolamide (1 B), oleyl-oxycarbonyl-D-valinolamide (2 B), oleylamine-carbonyl-L-valinolamide (3 B), oleylamine-carbonyl-D-valinolamide (4 B), and oleyl-L-hydroxyvalineamide (5 B). Control group with vehicle. Body weight and food consumption followed for 39 days. Motor activity and cognitive function by open field test and eight-arm maze. Mice sacrificed and mechanism of action investigated by qPCR. The genes analyzed involved in energy balance and regulation of appetite. Catecholamines and serotonin evaluated. Results - Compounds 1 A, 5 A, 1 B-4 B, caused significant weight loss of 4.2-5.6 % and 5 A, 1 B-4 B, improved cognitive function following 8 i. p. injections of 1 mg/kg during 39 days, by different mechanisms. 5 A, 3 B and 4 B decreased food consumption, whereas 1 A, 5 A and 2 B increased motor activity. 1 A, 4 A, 1 B and 3 B elevated SIRT-1, associated with survival. POMC upregulated by 1 B and 2 B, CART by 1 B, 2 B and 1 A. NPY and CAMKK2 downregulated by 5 A. 4 B enhanced 5-HT levels. 4 A, 5 A, 1 B, 4 B, 5 B decreased FAAH, showing long lasting effect. Conclusions - These new compounds might be developed for the treatment of obesity and for improved cognitive function.

Exploring physician gender bias in the initiation of prescribing cascades for older men and women: a qualitative clinical vignette study protocol.

INTRODUCTION: A prescribing cascade occurs when a drug is prescribed to manage the often unrecognised side effect of another drug; these cascades are of particular concern for older adults who are at heightened risk for drug-related harm. It is unknown whether, and to what extent, gender bias influences physician decision-making in the context of prescribing cascades. The aim of this transnational study is to explore the potential impact of physician implicit gender biases on prescribing decisions that may lead to the initiation of prescribing cascades in older men and women in two countries, namely: Canada and Italy. METHODS AND ANALYSIS: Male and female primary care physicians at each site will be randomised 1:1 to a case vignette that features either a male or female older patient who presents with concerns consistent with the side effect of a medication they are taking. During individual interviews, while masked to the true purpose of the study, participants will read the vignette and use the think-aloud method to describe their ongoing thought processes as they consider the patient's concerns and determine a course of action. Interviews will be recorded, transcribed verbatim and thematic analysis will be conducted to highlight differences in decisions in the interviews/transcripts, using a common analytical framework across the sites. ETHICS AND DISSEMINATION: This study has received ethics approval at each study site. Verbal informed consent will be received from participants prior to data collection and all data will be deidentified and stored on password-protected servers. Results of this study will be disseminated through peer-reviewed journal articles and presented at relevant national and international conferences.

The association between myocardial contraction fraction assessed by echocardiography and mortality.

BACKGROUND: Left ventricular ejection fraction (EF) is the most commonly used echocardiographic measurement of LV systolic function. Myocardial contraction fraction (MCF) may be a more accurate assessment of LV systolic function than EF. Limited data are available regarding the prognostic value of MCF compared to EF in a population referred for echocardiography. OBJECTIVES: To assess whether MCF was predictive of all-cause mortality in a population referred for echocardiography. METHODS: All consecutive subjects undergoing echocardiography in a university-affiliated laboratory during a 5-year period were retrieved for analysis. MCF was calculated by dividing LV stroke volume (LV end diastolic volume-LV end systolic volume) by LV myocardial volume and multiplied by 100. All cause mortality was the primary endpoint. Multivariate Cox proportional hazards regression analysis was used to evaluate independent variables associated with survival. RESULTS: 18,149 continuous subjects (median age 60 years, 53% male) were included. Median MCF in the cohort was 52% (interquartile range 40-64) while median EF was 64% (56-69). Any reduction in MCF from a value of 60 was significantly associated with survival on multivariable analysis. When echo parameters including EF, e:e', elevated TR gradient and significant MR were added to the model, MCF less than 50% remained significantly associated with mortality. MCF was also independently associated with both death and cardiovascular hospitalization. The AUC for MCF was .66 (95% confidence interval (CI): .65-.67) while for EF the AUC was only .58 (95% CI: .57-.59), a statistically significant difference (p < .0001). CONCLUSIONS: Reduced MCF is independently associated with mortality in a large population referred for echocardiography.

Mild Tricuspid Regurgitation: A Marker of Disease Burden Independently Associated with Increased Mortality.

INTRODUCTION: Tricuspid regurgitation (TR) is a common finding which appears to be associated with a worse prognosis. There are conflicting data regarding the prognostic impact of mild TR. We examined the clinical characteristics and echocardiographic properties of subjects with TR and its impact on clinical outcome with particular emphasis on subjects with mild TR. METHODS: Consecutive echocardiography examinations during 5 years were evaluated for TR severity and outcome including mortality and cardiovascular hospitalizations. RESULTS: The study included 21,429 subjects; 45% of the subjects had mild TR, 15% had moderate TR, and 6.5% had severe TR. Primary organic TR was evident in 7% of the subjects, a percentage that increased with increasing TR severity. TR severity was incrementally associated with older subjects with an increasing number of comorbidities and echocardiographic abnormalities. 29% of the subjects died at a median follow-up duration of 8.7 years. Increasing severity of TR was independently and incrementally associated with mortality. Subjects with mild TR had a 25% increased mortality rate compared to subjects with minimal TR (HR 1.25, 95% CI: 1.12-1.39, p < 0.001) after adjustment for significant clinical parameters. TR severity was also an independent incrementally graded predictor of cardiovascular hospitalization and mortality (mild TR: HR 1.23, 95% CI: 1.12-1.34, p < 0.001). CONCLUSIONS: TR is associated with older and sicker patients with numerous comorbidities. TR severity is a predictor of a worse clinical outcome. Mild TR was independently associated with decreased survival. TR should be considered a marker of a disease burden with a poor prognosis.

The obesity paradox in patients with acute coronary syndromes over 2 decades - the ACSIS registry 2000-2018.

BACKGROUND: Obesity is a worldwide epidemic which is associated with major cardiovascular (CV) risk factors. Nevertheless, substantial distant data, mostly published more than a decade ago, have demonstrated an obesity paradox, where obese patients generally have a better short- and long-term prognosis than do their leaner counterparts with the same CV profile. Nonetheless, it is not fully elucidated whether the obesity paradox is still relevant in the contemporary cardiology era among patients with acute coronary syndrome (ACS). We aimed to examine temporal trends in the clinical outcomes of ACS patients by their BMI status. METHODS: Data from the ACSIS registry including all patients with calculated BMI data between the years 2002-2018. Patients were stratified by BMI groups to underweight, normal, overweight and obese. Clinical endpoints included 30d major cardiovascular events (MACE), and 1-year mortality. Temporal trends were examined in the late (2010-2018) vs. the early period (2002-2008). Multivariable models examined factors associated with clinical outcomes by BMI status. RESULTS: Among the 13,816 patients from the ACSIS registry with available BMI data, 104 were underweight, 3921 were normal weight, 6224 were overweight and 3567 were obese. 1-year mortality was highest among underweight patients (24.8%), as compared to normal weight patients (10.7%) and lowest among overweight and obese patients (7.1% and 7.5% respectively; p for trend <0.001). 30-day MACE rates followed a similar pattern (24.3% for underweight, 13.6% for normal weight, 11.6% for overweight, and 11.7% for obese; p for trend<0.001). Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in all BMI groups, but unchanged in patients who were underweight. Similarly, 1-year mortality has decreased in normal weight and obese patients but remained similarly high in underweight patients. CONCLUSIONS: In ACS patients, during 2-decades, 30-day MACE and 1-year mortality were lower among overweight and obese patients compared to underweight and even normal weight patients. Temporal trends revealed that 30-day MACE and 1-year mortality have decreased among all BMI groups other than the underweight ACS patients, among whom the adverse CV rates were consistently high. Our findings suggest that the obesity paradox is still relevant in ACS patients in the current cardiology era.