Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing.

BACKGROUND: Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here, we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently, we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. RESULTS: Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women's buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. CONCLUSIONS: SRD5A1/5α reductase-1 responds epigenetically to the environment and its downregulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs.

Medical decisions in organ donors and heart transplant candidates with history of COVID-19 infection: An international practice survey.

BACKGROUND: A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection. METHODS: An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021. RESULTS: There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID-19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID-19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID-19 infection, or who died of COVID-19 or its complications. The timing of candidate reactivation on the waiting list after COVID-19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty-one percent of the respondents felt COVID-19 vaccine should be mandatory before transplant, but this rate varied by geographic region. CONCLUSION: Our results reflect evolving experience of the heart transplant field at a time of lack of high-quality evidence. In the absence of longer-term outcome data for donors and transplant candidates with history of COVID-19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID-19.

Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

BACKGROUND: Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. RESULTS: Overall, 190 active cancer patients were included, with a mean age of 58 ± 15 years and a female predominance (78%). During a median follow-up of 243 days (interquartile ranges [IQR]: 164-401 days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789 days (IQR: 521-968 days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P = .015). CONCLUSION: Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

Prognostic Implication of Tricuspid Regurgitation in ST-segment Elevation Myocardial Infarction Patients.

BACKGROUND: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients. OBJECTIVES: To investigate the possible implication of TR among STEMI patients. METHODS: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded. RESULTS: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06-5.6, P = .036) for patients with moderate to severe TR. CONCLUSIONS: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate.

Prognostic Implication of Tricuspid Regurgitation in ST-segment Elevation Myocardial Infarction Patients.

BACKGROUND: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients. OBJECTIVES: To investigate the possible implication of TR among STEMI patients. METHODS: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded. RESULTS: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06-5.62; P = 0.036) for patients with moderate-severe TR. CONCLUSIONS: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate.

Forced diuresis with matched hydration during transcatheter aortic valve implantation for Reducing Acute Kidney Injury: a randomized, sham-controlled study (REDUCE-AKI).

AIMS: Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) and is associated with increased risk for short- and long-term mortality. In patients undergoing percutaneous coronary intervention (PCI), forced diuresis with matched hydration has been shown to reduce the incidence of AKI by ∼50%. The aim of the present study was to evaluate whether forced diuresis with matched intravenous hydration reduces AKI in patients undergoing TAVI. METHODS AND RESULTS: Reducing Acute Kidney Injury (REDUCE-AKI) was a single-centre, prospective, randomized, double-blind sham-controlled clinical trial, designed to examine the effect of an automated matched saline infusion with urine output for the prevention of AKI in patients undergoing TAVI. A total of 136 TAVI patients were randomized, 68 in each group. Mean age was 83.9 ± 5 years and 41.2% were males. There were no differences in baseline characteristics between the two groups. The rate of AKI was not statistically different between the groups (25% in the active group vs. 19.1% in the sham group, P = 0.408). There was a significant increase in long-term mortality in the active group (27.9% vs. 13. 2% HR 3.744, 95% CI 1.51-9.28; P = 0.004). The study was terminated prematurely by the Data Safety Monitoring Board for futility and a possible signal of harm. CONCLUSIONS: Unlike in PCI, forced diuresis with matched hydration does not prevent AKI in patients undergoing TAVI, and might be associated with increased long-term mortality. Future studies should focus on understanding the mechanisms behind these findings. CLINICALTRIALS.GOV REGISTRATION: NCT01866800, 30 April 2013.

Shift Work and the Risk of Coronary Artery Disease: A Cardiac Computed Tomography Angiography Study.

AIMS: Shift work disrupts the normal circadian rhythm and is associated with risk factors for coronary artery disease (CAD) and a higher incidence of CAD morbidity and mortality. Cardiac computed tomography angiography (CCTA) is a robust noninvasive modality for assessing the presence, extent, and severity of CAD. We sought to investigate whether shift workers are prone to a higher burden of CAD compared to non-shift workers. METHODS: We conducted a historically prospective study in consecutive patients who underwent CCTA and answered a telephonic questionnaire. Due to significant differences in age and gender, we compared 89 well-matched pairs of shift workers and non-shift workers with the use of propensity scores. RESULTS: Our cohort consisted of 349 participants, of whom 94 (26.9%) were shift workers. The mean age was 50.7 years, and 62.5% were males. After pairing, we showed that shift workers had a higher prevalence of CAD than non-shift workers (74.2 vs. 53.9%, respectively, p = 0.01), and a lower prevalence of coronary calcium scores of zero (46.8 vs. 63.4%, respectively, p = 0.034). Stenosis >50% was more prevalent in shift workers than in non-shift workers (20.2 vs. 11.2%, respectively, p = 0.006), and the extent of CAD (defined as the presence of ≥1-vessel disease) tended to be higher in shift workers than in non-shift workers (25.8 vs. 13.5%, respectively, p = 0.06). CONCLUSIONS: In this CCTA study, we showed in a well-matched cohort of consecutive patients that shift workers had a higher prevalence and extent of CAD than non-shift workers.

New formula for defining "normal" and "prolonged" QT in patients with bundle branch block.

OBJECTIVES: To predict the QT interval in the presence of normal QRS for patients with left bundle branch block (LBBB). BACKGROUND: There is no acceptable method for simple and reliable QT correction for patients with bundle branch block (BBB). METHODS: We measured the QT interval in patients with new onset LBBB who had a recent electrocardiogram with narrow QRS for comparison. 48 patients who developed in-hospital LBBB were studied. Patients who had similar heart rate before and after LBBB were included. We used linear regression, the Bogossian method, and our new fixed QRS replacement method to evaluate the most reliable correction method. RESULTS: JTc (QTc-QRS) interval was preserved before and after LBBB (328.9 ±â€¯25.4 ms before LBBB vs. 327.3 ms post LBBB (p = 0.550). Mean predicted preLBBB QTc difference was 1.3 ms, -21.3 ms and 1.6 ms for the three methods respectively (p < 0.001 for Bogossian comparison with the other methods). Coefficients of correlation (R) between actual preLBBB QTc with predicted preLBBB QTc were 0.707, 0.683 and 0.665 respectively (p > 0.3 for R comparisons between all methods). The average absolute difference in preLBBB QTc was 15.5 ms and 16.7 ms for the regression and fixed-gender methods (p value between the two = 0.321) and 25.5 ms for the Bogossian method, which was found to be significantly underperforming. CONCLUSIONS: In patients with LBBB, replacing of the QRS duration after deriving the QTc interval with a fixed value of 88 ms for female and 95 ms for male provides a simple and reliable method for predicting the QTc before the development of LBBB.

Impact of carotid atherosclerosis on the risk of adverse cardiac events in patients with and without coronary disease.

BACKGROUND AND PURPOSE: Carotid atherosclerosis (CA) is reportedly a strong predictor of imminent cardiac events even in the absence of established coronary artery disease (CAD). We examined the differential impact of CA on the risk of major adverse cardiovascular events in patients with and without CAD diagnosed angiographically. METHODS: We conducted a follow-up survey of 1391 patients who underwent clinically driven coronary angiography and a same-day carotid ultrasound and Doppler study. Definitions of CAD, CA, and carotid artery stenosis were in accordance with current practice guidelines. RESULTS: Of 1391 patients, angiographic CAD was present in 1105 (79%) patients. Mean and median follow-up was 1574 and 1702 days, respectively. Rates of the primary composite major adverse cardiovascular event end point were higher among patients with CAD compared with those without CAD (48% versus 20%; P<0.001), whereas the rates of all-cause mortality (10% versus 9%; P=0.81) and stroke (7% versus 5%; P=0.3) did not differ significantly between both groups. Carotid artery stenosis and CA were associated with an increased risk of the composite major adverse cardiovascular event end point among patients without CAD (hazard ratio=3.17 [95% confidence interval, 1.52-6.60]; P<0.01; and hazard ratio=1.69 [0.95-3.01]; P=0.07, respectively) though not in patients with CAD. Carotid artery stenosis was associated with an increased risk of all-cause mortality among patients without CAD (hazard ratio=2.93 [1.09-7.87]; P=0.03]) though not among those with CAD. CONCLUSIONS: CA and carotid artery stenosis are independent predictors of major adverse cardiovascular event in patients undergoing coronary angiography. The prognostic implications of carotid disease are imparted predominantly in patients without pre-existent CAD.

Prediction of recurrent heart failure hospitalizations and mortality using the echocardiographic Killip score.

AIM: Examine the performance of a simple echocardiographic "Killip score" (eKillip) in predicting heart failure (HF) hospitalizations and mortality after index event of decompensated HF hospitalization. METHODS: HF patients hospitalized at our facility between 03/2019-03/2021 who underwent an echocardiography during their index admission were included in this retrospective analysis. The cohort was divided into 4 classes of eKillip according to: stroke volume index (SVI) < 35ml/m2 > and E/E' ratio < 15 > . An eKillip Class I was defined as SVI ≥ 35ml/m2 and E/E' ≤ 15 and was used as reference. RESULTS: Included 751 patients, median age 78.1 (IQR 69.3-86) years, 59% men, left ventricular ejection fraction 45 (IQR 30-60)%, brain natriuretic peptide levels 634 (IQR 331-1222)pg/ml. Compared with eKillip Class I, a graded increase in the combined endpoint of 30-day mortality and rehospitalizations rates was noted: (Class II: HR 1.77, CI 0.95-3.33, p = 0.07; Class III: HR 1.94, CI 1.05-3.6, p = 0.034; Class IV: HR 2.9, CI 1.64-5.13, p < 0.001 respectively), which overall persisted after correction for clinical (Class II: HR 1.682, CI 0.9-3.15, p = 0.105; Class III: HR 2.104, CI 1.13-3.9, p = 0.019; Class IV: HR 2.74, CI 1.54-4.85, p = 0.001 respectively) or echocardiographic parameters (Class II: HR 1.92, CI 1.02-3.63, p = 0.045; Class III: HR 1.54, CI 0.81-2.95, p = 0.189; Class IV: HR 2.04, CI 1.1-3.76, p = 0.023 respectively). Specifically, the eKillip Class IV group comprised one-third of the patient population and persistently showed increased risk of 30-day HF hospitalizations or mortality following multivariate analysis. CONCLUSION: A simple echocardiographic score can assist identifying high-risk decompensated HF patients for recurrent hospitalizations and mortality.

Srd5a1 is Differentially Regulated and Methylated During Prepubertal Development in the Ovary and Hypothalamus.

5α-reductase-1 catalyzes production of various steroids, including neurosteroids. We reported previously that expression of its encoding gene, Srd5a1, drops in murine ovaries and hypothalamic preoptic area (POA) after early-life immune stress, seemingly contributing to delayed puberty and ovarian follicle depletion, and in the ovaries the first intron was more methylated at two CpGs. Here, we hypothesized that this CpG-containing locus comprises a methylation-sensitive transcriptional enhancer for Srd5a1. We found that ovarian Srd5a1 mRNA increased 8-fold and methylation of the same two CpGs decreased up to 75% between postnatal days 10 and 30. Estradiol (E2) levels rise during this prepubertal stage, and exposure of ovarian cells to E2 increased Srd5a1 expression. Chromatin immunoprecipitation in an ovarian cell line confirmed ESR1 binding to this differentially methylated genomic region and enrichment of the enhancer modification, H3K4me1. Targeting dCas9-DNMT3 to this locus increased CpG2 methylation 2.5-fold and abolished the Srd5a1 response to E2. In the POA, Srd5a1 mRNA levels decreased 70% between postnatal days 7 and 10 and then remained constant without correlation to CpG methylation levels. Srd5a1 mRNA levels did not respond to E2 in hypothalamic GT1-7 cells, even after dCas9-TET1 reduced CpG1 methylation by 50%. The neonatal drop in POA Srd5a1 expression occurs at a time of increasing glucocorticoids, and treatment of GT1-7 cells with dexamethasone reduced Srd5a1 mRNA levels; chromatin immunoprecipitation confirmed glucocorticoid receptor binding at the enhancer. Our findings on the tissue-specific regulation of Srd5a1 and its methylation-sensitive control by E2 in the ovaries illuminate epigenetic mechanisms underlying reproductive phenotypic variation that impact life-long health.

Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing.

Background: We aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET). Methods: Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex. Results: One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction). Conclusions: Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.

Successful conservative management of left ventricular assist device candidates.

AIMS: Clinical trials comparing LVADs vs. conservative therapy were performed before the availability of novel medications or used suboptimal medical therapy. This study aimed to report that long-term stabilization of patients entering a left ventricular assist device (LVAD) programme is possible with the use of aggressive conservative therapy. This is important because the excellent clinical stabilization provided by LVADs comes at the expense of significant complications. METHODS AND RESULTS: This study was a single-centre prospective evaluation of consecutive patients with advanced heart failure (HF) fulfilling criteria for LVAD implantation based on clinical and echocardiographic characteristics, cardiopulmonary exercise test, and right heart catheterization results. Their initial therapy included inotropes, thiamine, beta-blockers, digoxin, spironolactone, hydralazine, and nitrates followed by the introduction of novel HF therapies. Coronary revascularization and cardiac resynchronization therapy were performed when indicated, and all patients were closely followed at our outpatient clinic. During the study period, 28 patients were considered suitable for LVAD implantation (mean age 63 ± 10.8 years, 92% men, 78% ischaemic, median HF duration 4 years). Clinical stabilization was achieved and maintained in 21 patients (median follow-up 20 months, range 9-38 months). Compared with baseline evaluation, cardiac index increased from 2.05 (1.73-2.28) to 2.88 (2.63-3.55) L/min/m2 , left ventricular end-diastolic diameter decreased from 65.5 (62.4-66) to 58.3 (53.8-62.5) mm, and maximal oxygen consumption increased from 10.1 (9.2-11.3) to 16.1 (15.3-19) mL/kg/min. Three patients died and only four ultimately required LVAD implantation. CONCLUSIONS: Notwithstanding the small size of our cohort, our results suggest that LVAD implantation could be safely deferred in the majority of LVAD candidates.

Repetitive milrinone therapy in ambulatory advanced heart failure patients.

BACKGROUND: Advanced heart failure (HF) patients usually poorly tolerate guideline-directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short-term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up-titrate GDMT and improve functional class. HYPOTHESIS: Repetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients. METHODS: Advanced HF patients treated with beta-blockers and implanted with defibrillators were initiated with repetitive, intermittent short-term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B-natriuretic peptide (BNP) levels, and echocardiography parameters. RESULTS: The cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286-3768] to 631 [278-1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV (p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change. CONCLUSIONS: In this small cohort of advanced HF, repetitive, intermittent, short-term milrinone therapy was found to be safe and potentially efficacious.

Intermittent inotropic therapy with levosimendan vs. milrinone in advanced heart failure patients.

AIMS: Routine, intermittent inotropic therapy (IIT) is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life (QOL), despite limited evidence to support its' use. Given recent reports of improved QOL and reduced HF hospitalization, with levosimendan compared with placebo in advanced HF patients, we aimed to assess the effects of switching a small group of milrinone-treated patients to levosimendan. This was performed as part of a protocol for changing our ambulatory HF clinic milrinone-based IIT to levosimendan. METHODS AND RESULTS: Single-centre study of consecutive ambulatory advanced HF patients that received ≥4 cycles of once-weekly milrinone IIT at our HF outpatient clinic, who were switched to levosimendan IIT. All patients had left ventricular ejection fraction ≤35%, elevated B-natriuretic peptide (BNP), and were in New York Heart Association Classes III-IV despite maximally tolerated guideline directed medical therapy. Patients were evaluated using BNP levels, echocardiography, cardio-pulmonary exercise test, and HF QOL questionnaire before and after 4 weeks of levosimendan IIT. The cohort included 11 patients, 10 (91%) were male and the mean age was 76 ± 12 years. After 4 weeks of levosimendan therapy, maximal O2 consumption improved in 8/9 (89%) by a mean of 2.28 mL/kg [95% CI -0.22-3.38, P = 0.05]. BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L [261-1035] to 719 ng/L [294-739], (P < 0.01). QOL as measure by the EQ-5D-5L questionnaire improved in 8/11 (82%) patients after levosimendan IIT, by a median of two points [95% CO -4.14-0.37, P = 0.09]. On echocardiography, peak systolic annular velocity (S') increased after levosimendan IIT by an average of 3 cm/s [95% CI 0.16-2.10, P = 0.03]. CONCLUSIONS: In this small-scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.

Characteristics of Patients With Pulmonary Arterial Hypertension in a Pulmonary Hypertension Association-Accredited Comprehensive Care Center: A Contrast in Features When Compared With US National Registry Data.

Background Since the initial description in the 1980s, our understanding of the diversity of pulmonary arterial hypertension (PAH) has continued to evolve. In this study, we report the characteristics of patients seen in an academic medical center for PAH from August 2020 through November 2021 and contrast those with nationally reported data from the United States Pulmonary Hypertension Scientific Registry (USPHSR).  Study Design Investigators at the University of Utah Pulmonary Hypertension Program prospectively enrolled adult patients diagnosed with WHO Group 1 PAH, who were evaluated between August 2020 and November 2021 in a program-specific registry. Patient exposure and health histories were collected through structured interviews and questionnaires, along with clinical data and medication use. A total of 242 patients were enrolled in the University of Utah Pulmonary Hypertension Registry (UUPHR).  Results Of the 242 enrolled patients, the most common etiology was associated PAH (APAH), accounting for 71.1% of the population. The second largest etiology was idiopathic PAH (IPAH) at 26.4%. The remaining patients were distributed between familial PAH (FPAH), pulmonary veno-occlusive disease (PVOD), and others. Of the total population classified as APAH, 39% of cases were noted as secondary to connective tissue disease (CTD) and 33% as toxin-induced. These represented 28% and 24% of the total population, respectively.  Conclusions In this US-based accredited academic medical center, the etiology of PAH in our patient population contrasts with national registry data. In the UUPHR, APAH, specifically CTD-PAH and toxin-associated PAH, accounts for the majority of patients with PAH. This contrasts with IPAH, which nationally is the most reported cause of PAH. Differences in our population may reflect the regional variation of the referral site, but it is noteworthy for its contrast with historically reported phenotypes.

A Contact-Free Optical Device for the Detection of Pulmonary Congestion-A Pilot Study.

BACKGROUND: The cost of heart failure hospitalizations in the US alone is over USD 10 billion per year. Over 4 million Americans are hospitalized every year due to heart failure (HF), with a median length of stay of 4 days and an in-hospital mortality rate that exceeds 5%. Hospitalizations of patients with HF can be prevented by early detection of lung congestion. Our study assessed a new contact-free optical medical device used for the early detection of lung congestion. METHODS: The Gili system is an FDA-cleared device used for measuring chest motion vibration data. Lung congestion in the study was assessed clinically and verified via two cardiologists. An algorithm was developed using machine learning techniques, and cross-validation of the findings was performed to estimate the accuracy of the algorithm. RESULTS: A total of 227 patients were recruited (101 cases vs. 126 controls). The sensitivity and specificity for the device in our study were 0.91 (95% CI: 0.86-0.93) and 0.91 (95% CI: 0.87-0.94), respectively. In all instances, the observed estimates of PPVs and NPVs were at least 0.82 and 0.90, respectively. The accuracy of the algorithm was not affected by different covariates (including respiratory or valvular conditions). CONCLUSIONS: This study demonstrates the efficacy of a contact-free optical device for detecting lung congestion. Further validation of the study results across a larger and precise scale is warranted.

A novel contact-free atrial fibrillation monitor: a pilot study.

Aims: Atrial fibrillation (AF) is a major cause of morbidity and mortality. Current guidelines support performing electrocardiogram (ECG) screenings to spot AF in high-risk patients. The purpose of this study was to validate a new algorithm aimed to identify AF in patients measured with a recent FDA-cleared contact-free optical device. Methods and results: Study participants were measured simultaneously using two devices: a contact-free optical system that measures chest motion vibrations (investigational device, 'Gili') and a standard reference bed-side ECG monitor (Mindray®). Each reference ECG was evaluated by two board certified cardiologists that defined each trace as: regular rhythm, AF, other irregular rhythm or indecipherable/missing. A total of 3582, 30-s intervals, pertaining to 444 patients (41.9% with a history of AF) were made available for analysis. Distribution of patients with active AF, other irregular rhythm, and regular rhythm was 16.9%, 29.5%, and 53.6% respectively. Following application of cross-validated machine learning approach, the observed sensitivity and specificity were 0.92 [95% confidence interval (CI): 0.91-0.93] and 0.96 (95% CI: 0.95-0.96), respectively. Conclusion: This study demonstrates for the first time the efficacy of a contact-free optical device for detecting AF.

Validation of a novel contact-free heart and respiratory rate monitor.

There is a growing need for remote monitoring of patients due to a lack of resources and infection control. Current systems use sensors that require constant physical contact with the user, which may result in discomfort or lack of adherence. In the present study, we evaluated the accuracy of a new contact-free system to monitor heart and respiratory rate. Study participants were measured simultaneously using two devices: a contact-free optical system that measures nano-vibrations and movements (investigational device, "Gili Pro BioSensor") and a standard reference bed-side monitor, inclusive of an electrocardiogram and capnograph modules (Mindray®). Co-primary endpoints included HR and RR accuracy in subjects without active arrhythmias for HR, and for all study populations for RR (i.e., for subjects with and without active arrhythmias). Confirmatory secondary endpoints included HR scored continuously for all study populations, inclusive of subjects with arrhythmias. The present study included 115 patients who completed study procedures. Mean age was 66 ± 14.6 (range 29-93) with 60% males, 31% obese patients (i.e., BMI > 30 kg/m2, range 17-44) and 56% measured in a chair. For the dichotomised accuracy analysis, both co-primary endpoint for HR and RR resulted in 100% accuracy (95% CI: HR 98.8-100%; RR 98.9-100%), whereas for the confirmatory secondary analysis, 99.1% of the HR measurements across subjects with and without active arrhythmias were deemed accurate (95% CI: 97.4-99.8%). The current study demonstrated over 99% accuracy in detecting heart and respiratory rate using a novel contact-free optical system.

Automated external defibrillator use and outcomes after out-of-hospital cardiac arrest: an Israeli cohort study.

BACKGROUND: Out-of-hospital cardiac arrests (OHCA) are a serious healthcare situation with low survival rates. Application of an automated external defibrillator (AED) by bystanders shortens time to defibrillation and increases survival. In Israel, a regulation ensuring the presence of AED in public places was issued and implemented since 2014. We investigated whether this regulation had an impact on the outcomes of OHCA patients. METHODS: We performed a retrospective, single-center observational study. Included in the cohort were patients who were admitted to the department of intensive care cardiac unit with OHCA. Patients were stratified into two groups according to the year the regulation was introduced: group 1 (2009-2013) and group 2 (2014-2018). RESULTS: A total of 77 patients were included in group 1 and 61 in group 2. The utilization of AED was significantly higher in group 2 compared to group 1 (42% vs. 27%; P = 0.04). Compared to group 1 patients, group 2 had lower 48 h (0% vs. 8%; P = 0.02) and 30-day mortality (28% vs. 42%; P = 0.02). Cognitive damage following recovery was less frequent in group 2 (55% vs. 81%; P = 0.01). CONCLUSION: Deployment of AEDs in public places by mandatory regulations increased utilization for OHCA and may improve outcomes.