BACKGROUND AND AIMS:High cholesterol absorption efficiency is determined by genetic variation in small intestinal sterol transporters and affects one-third of individuals. Their risk for atherosclerotic cardiovascular disease (ASCVD) is increased compared with low cholesterol absorbers, despite similar serum lipid concentrations. We investigated the association of cholesterol absorption efficiency with proatherogenic properties of low-density lipoproteins (LDLs). METHODS:The study cohort consisted of 90 middle-aged participants, 56 females and 34 males, without lipid-lowering therapy or ASCVD. They were divided into low (n = 45) and high (n = 45) cholesterol absorbers by the median value of serum cholestanol to cholesterol ratio. LDL aggregation susceptibility and binding of lipoproteins to proteoglycans were determined as biomarkers of lipoprotein atherogenicity. Nuclear magnetic resonance spectroscopy, mass spectrometry, and gas-liquid chromatography were used to determine lipoprotein subclass profile, LDL lipidome, and serum concentrations of cholesterol and noncholesterol sterols, respectively. RESULTS:Age, dietary cholesterol, and serum total cholesterol or lipoprotein cholesterol levels did not differ between the groups. In the high absorbers, LDL particles were larger, and LDL aggregation susceptibility and the binding of lipoproteins to proteoglycans were increased in the low absorbers. Of LDL surface lipids, sphingomyelin 42:3;O2, and phosphatidylcholine (PC) 32:0 correlated positively, whereas PC 32:1 correlated negatively with serum cholestanol levels. These LDL surface lipids were also associated with increased LDL aggregation susceptibility and proteoglycan-binding. CONCLUSIONS:The present findings suggest that increased proatherogenic properties in high cholesterol absorbers may contribute to increased ASCVD risk. REGISTRATION:https://clinicaltrials.gov/study/NCT01315964.

The AAMS open-label clinical study demonstrated the safety and feasibility of epicardial transplantation of autologous right atrial appendage micrografts (AAMs) during coronary artery bypass grafting (CABG) surgery. The study also provided the first indications of therapeutic efficacy of the AAMs, as delivered within an extracellular matrix patch, to reduce ischemic scar and increase viable ventricular wall thickness. To further evaluate the initial beneficial effects observed in the AAMS study, we designed the randomized, double-blinded, and placebo-controlled AAMS2 trial. Focusing on patients with ischemic heart disease (IHD) and myocardial scar, the AAMS2 trial aims to generate state-of-the-art structural and functional imaging data of the myocardium treated with an AAMs-patch during CABG. The AAMS2 trial recruits IHD patients who are set to undergo non-urgent CABG and present with an ischemic myocardial scar in preoperative cardiac magnetic resonance imaging (CMRI) with late gadolinium enhancement. Patients are randomized (1:1) to receive a collagen-based matrix patch (Hemopatch®), with or without AAMs, epicardially onto the scar border. The primary endpoint, assessed by CMRI preoperatively and at 6 months post-operative follow-up, focuses on the left ventricle scar mass. The secondary endpoints center on the change in scar mass by the AAMs-patch site and evaluation of therapy safety and feasibility as well as its effects on myocardial structure and function by echocardiography. Change in blood N-terminal-pro-BNP levels in the timeframe is the co-primary endpoint. Data from the AAMS2 trial provides the first randomized, blinded, and placebo-controlled evaluation of efficacy on epicardial AAMs transplantation for ischemic myocardial scar. This data will pave the road towards rational design of larger AAMs therapeutic efficacy-addressing trial(s). ClinicalTrials.gov, NCT05632432, registered 30 November 2022, https://clinicaltrials.gov/study/NCT05632432.

Aim We aimed to elucidate the potential role for thoracic outlet syndrome (TOS) and upper extremity deep venous thrombosis in the development of chronic thromboembolic pulmonary hypertension (CTEPH). Method Charts from 64 consecutive patients with CTEPH who underwent pulmonary endarterectomy in Helsinki University Hospital between 2015 and 2023 were analysed for baseline characteristics, risk factors for thrombosis, treatments, and outcome at 1 year. Results We found that seven patients with CTEPH (11%) had TOS with subclavian vein stenosis, impaired flow, and collaterals in provocation contrast venography. These patients with TOS CTEPH were younger (median 23 vs 59 years, p<0.001) and had more often distal (segmental 100% vs 38,6%, p<0.01) disease than other patients with CTEPH and had fewer risk factors for thrombosis (p<0.05). Functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk test and pulmonary vascular resistance (PVR) at baseline were similar. At 1 year postoperatively, there was a similar improvement in PVR (-45% vs -56%), NT-proBNP (-70.0% vs -71.8%), and functional class (improvement in 85.7% vs 91.5%) whereas 6-minute walk test increased more (247 vs 100 m, p<0.05) in patients with TOS. Patients with TOS were more often treated with balloon pulmonary angioplasty postoperatively (57.0 vs 10.5%, p<0.01). Treatment with pulmonary vasodilators did not differ significantly (42.9% vs 15.1%). TOS was later treated with thoracoscopic first-rib resection in three patients (43%). Conclusions CTEPH with upper extremity deep venous thrombosis and TOS represents a unique subgroup of patients who benefit from interventional therapies.

The aim of this study was to investigate whether cholesterol metabolism, especially high cholesterol absorption, affects atherosclerotic event risk in acute coronary syndrome (ACS) versus control patients without coronary artery disease (CAD). We set up a randomized, case-control substudy of a Corogene cohort (total cohort 5,295 consecutive patients admitted for coronary angiography because of stable or atypical chest pains and followed up for a median of 9.5 [interquartile range, 8.9-10.0] years). Of these, 200 ACS patients were matched by sex, age, BMI, LDL-C, and serum triglycerides to 200 patients without CAD. Blood samples were available in 363 cases (study population: ACS, n = 168; no CAD, n = 195) for analysis of serum biomarkers of relative cholesterol metabolism. High cholesterol absorption was associated with nonfatal and fatal acute CAD events in the ACS group but not in the no CAD group, whereas good compliance with statin treatment during the follow-up and low LDL-C concentration associated with good prognosis. Patients with high cholesterol absorption showed the worst survival probability during the follow-up, whereas individuals with low cholesterol absorption showed the best survival probability. In conclusion, high cholesterol absorption was associated with nonfatal and fatal acute CAD events in the ACS group in this exploratory clinical study. Individuals with high cholesterol absorption had more atherosclerotic events during the follow-up period, and their survival rate was worse than that of those with low cholesterol absorption. With therapy lowering both cholesterol absorption and LDL-C concentrations, cholesterol metabolism can be modified to become less atherogenic.

Treatment patterns of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Finland are unknown. Guidelines now recommend early escalation of treatment for PAH. We evaluated how well Finnish practice follows guidelines, and how treatment initiations and outcomes are related. The pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients in Finland cohort includes all PAH and CTEPH patients diagnosed between 2008 and 2020 in all Finnish university hospitals. Drug therapy was analysed in patients with medical/procedural history available, and changes in the 4-tier comparative, prospective registry of newly initiated therapies for pulmonary hypertension (COMPERA) 2.0 risk score were evaluated. PAH patients (n = 268) were initially treated with monotherapy (52%) or double therapy (24%). After year 2015, double therapy use increased to 39%. PAH treatment at 1 year after diagnosis included phosphodiesterase 5 inhibitors (71%), endothelin-receptor antagonist (48%), prostacyclin analogue (7%), calcium channel blocker (12%) and selexipag (1%). 35% achieved low risk at 1 year, increasing to 44% for patients diagnosed after 2015. Those remaining at intermediate-high (IH) or high risk (H) (28%) were not treated less aggressively than others but were older, had more comorbidities, and often history of smoking. CTEPH patients (n = 189) were treated with pulmonary endarterectomy (PEA) (27%), balloon pulmonary angioplasty (BPA) (11%) and medical therapy only (41%) within 1 year from diagnosis. 45% achieved low risk at 1 year. We present additional results on treatment of IH and H patients, patient characteristics preceding death, and treatment persistence. We found less treatment of PAH patients with double or triple therapies and of CTEPH patients with PEA and BPA than expected but with good results. Patients not reaching low or intermediate COMPERA 2.0 were old and had comorbidities.

Background. Elevated low-density lipoprotein (LDL) cholesterol causes atherosclerotic cardiovascular diseases. Variables of whole-body cholesterol metabolism, for example, high cholesterol absorption efficiency, might also be atherogenic, whereas the role of bile acids is controversial. Objectives. This post hoc study concerns the impact of cholesterol absorption on bile acid metabolism. The hypothesis was that cholesterol absorption efficiency interferes with bile acid metabolism. Methods. Cholesterol metabolism was studied using absolute and relative methods. Elimination of cholesterol from the body as bile acids and neutral sterols was assessed from 24-h faecal collections and analysed by gas-liquid chromatography. Cholesterol absorption efficiency was evaluated by a peroral continuous dual-isotope feeding method, and cholesterol synthesis by a sterol-balance technique. The relative methods included analyses of serum biomarkers of cholesterol absorption efficiency and cholesterol synthesis by gas-liquid chromatography. Results. Faecal bile acids, neutral sterols and cholesterol synthesis were lower in high- versus low-cholesterol absorbers. Elimination of cholesterol from the body as bile acids and neutral sterols was reduced in high- versus low-cholesterol absorbers. Serum and LDL cholesterol levels did not differ in low- versus high-cholesterol absorbers. Absolute and relative methods of cholesterol metabolism correlated with each other, suggesting that the results can be considered valid. Conclusion. In high-cholesterol absorbers, poor elimination of cholesterol from the body as bile acids and neutral sterols may indicate an increased risk of atherosclerosis. It can be prevented by decreasing cholesterol absorption and increasing reverse cholesterol transport by dietary means combined with ezetimibe and statin treatment, when needed.

Background: To assess characteristics, risk group distribution, and prognosis of patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Finland. Methods: Clinical chart review of patients with PAH or CTEPH recorded between 2008 and 2019 and linkage to official mortality data. Results: We identified 627 patients, with 502 (80%) diagnosed after 2008, yielding an incidence of PAH and CTEPH of 4.0 and 2.9/million/year, respectively. The median time from symptoms to diagnosis was 1 year. Mean age at diagnosis of PAH patients (n = 268) was 57 years, 73% were women, 40% had idiopathic PAH, 28% associated with connective tissue diseases, and 15% with congenital heart disease, 9% had ≥3 cardiovascular comorbidities. At 1 year, 34%/34%/24%/8% were at the low/intermediate-low/intermediate-high/high Compera 2.0 risk classification groups. Survival was 91.3%, 74.8%, and 62.6% at 1, 3, and 5 years, respectively, with an improving trend over calendar time. Ten PAH patients had a lung transplant. PAH subtype, cardiac output, and the presence of ischemic heart disease or type 2 diabetes predicted survival.CTEPH patients (n = 189) were 63 years (mean) at diagnosis and 49% were women. Of the CTEPH patients, 29% underwent pulmonary endarterectomy (PEA) and 22% were treated with balloon pulmonary angioplasty. Survival was 94.6%, 87.2%, and 79.4% at 1, 3, and 5 years, respectively. PEA patients were younger, had fewer comorbidities, and had longer survival than non-PEA patients. Conclusions: Incidence and survival of PAH and CTEPH patients in Finland were similar to previously presented data for other countries.

Background & aims: Increasing evidence suggests that high cholesterol absorption efficiency enhances the risk of atherosclerotic cardiovascular diseases. It is not known whether inhibiting cholesterol absorption has different metabolic effects in high- vs. low cholesterol absorbers. We evaluated the effects of phytostanol esters on serum lipids and cholesterol metabolism in a post hoc study of three randomized, double-blind, controlled trials. The participants were classified into low (n = 20) and high (n = 21) cholesterol absorbers by median cholesterol absorption efficiency based on the plasma cholesterol absorption marker cholestanol at baseline. Methods: The participants consumed mayonnaise or margarine without or with phytostanol esters for six to nine weeks without other changes in the diet or lifestyle. Serum cholesterol, cholestanol, lathosterol, and faecal neutral sterols and bile acids were analysed by gas-liquid chromatography. According to power calculations, the size of the study population (n = 41) was appropriate. Results: During the control period, cholesterol synthesis, and faecal neutral sterols and bile acids were lower in high- vs. low absorbers (p < 0.05 for all). Phytostanol esters reduced low-density lipoprotein cholesterol by 10-13% in both groups, and directly measured cholesterol absorption efficiency by 41 +/- 7% in low- and 47 +/- 5% in high absorbers (p < 0.001 for all) without side effects. Cholesterol synthesis and faecal neutral sterols (p < 0.01) increased in both groups, more markedly in the high vs. low absorbers (p < 0.01). Conclusions: Low cholesterol absorption combined with high faecal neutral sterol excretion are components of reverse cholesterol transport. Thus, high- vs. low absorbers had a more disadvantageous metabolic profile at baseline. In both groups, phytostanol esters induced favourable changes in serum, lipoprotein, and metabolic variables known to help in prevention of the development of atherosclerotic cardiovascular diseases. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods: We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up. Of 65 patients with SI-NETs, 54 patients underwent a prospective follow-up. In addition, survival was evaluated during the median follow-up of 6 years. Results: At baseline, three patients had CHD. During the median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg score, Spearman’s ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristic analysis with an AUC of 0.98 (95% CI: 0.94–1.00) and outperformed proBNP, chromogranin A (CgA), and individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. Regurgitation increased or decreased in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) were associated with increased mortality in SI-NET patients. Conclusions: Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are the strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was low among the SI-NET patients, probably reflecting successful treatment regimens.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

BACKGROUND Cardiac sarcoidosis (CS) is a rare but potentially fatal inflammatory cardiomyopathy. OBJECTIVES The authors studied temporal changes in the incidence, characteristics, and outcome of CS. METHODS A retrospective analysis was made of a 30-year nationwide cohort of CS. RESULTS The cohort comprised 511 patients with a median age of 52 years and female preponderance (69%). Altogether 77, 166, and 268 cases of CS were diagnosed in years 1988 to 2009, 2010 to 2014, and 2015 to 2019, respectively; the 5-year count of 2015 to 2019 was 134-fold the count of 1990 to 1994 (268/2) and 18-fold the count of 2000 to 2004 (268/15). Prior to 2010, compared with the later periods, CS presented more often with ventricular tachycardia/fibrillation (prevalence 36% vs 19% in 2010-2014 and 11% in 2015-2019, P < 0.001), left ventricular ejection fraction <50% (49%, 35%, and 31%; P = 0.010), and elevation of natriuretic peptides (87%, 57%, and 49%; < 0.001). On magnetic resonance imaging, late gadolinium enhancement involved a median of 15% (IQR: 11%-22%) of left ventricular mass in studies of 1988 to 2009 (n = 16), 15% (IQR: 9%-22%) in studies of 2010 to 2014 (n = 87), and 11% (IQR: 5%-19%) in studies of 2015 to 2019 (n =150) (P = 0.031). The respective 5-year incidences of the composite of death, heart transplantation, left ventricular-assisted device implantation, or ventricular tachyarrhythmia were 40% (95% CI: 29%-51%), 32% (95% CI: 25%-39%), and 23% (95% CI: 16%-30%) (P = 0.002). The prognostic trend disappeared after adjustment for differences in the presenting phenotype. CONCLUSIONS Diagnoses of incident CS have increased exponentially in Finland. Concurrently, the phenotype has turned milder and prognosis better, suggesting detection of CS at an earlier stage of its course. (JACC Adv. 2024;3:101102) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

HomeCirculationVol. 149, No. 11End-Stage Heart Failure in Cardiac Sarcoidosis No AccessResearch ArticleRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessFull TextEnd-Stage Heart Failure in Cardiac Sarcoidosis Diana Velikanova, Pauli Pöyhönen, Jukka Lehtonen, Piia Simonen, Valtteri Uusitalo, Tapani Vihinen, Kari Kaikkonen, Petri Haataja, Tuomas Kerola, Tuomas T. Rissanen, Ville Vepsäläinen, Aleksi Alatalo, Päivi Pietilä-Effati and Markku Kupari Diana VelikanovaDiana Velikanova Heart and Lung Center (D.V., P.P., J.L., P.S., M.K.), Helsinki University Hospital and University of Helsinki, , Finland. , Pauli PöyhönenPauli Pöyhönen https://orcid.org/0000-0002-3031-5391 Heart and Lung Center (D.V., P.P., J.L., P.S., M.K.), Helsinki University Hospital and University of Helsinki, , Finland. Radiology (P.P., V.U.), Helsinki University Hospital and University of Helsinki, , Finland. , Jukka LehtonenJukka Lehtonen Correspondence to: Jukka Lehtonen, MD, Division of Cardiology, Heart and Lung Center, Helsinki University Hospital, 00029 HUS, Finland. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7637-6061 Heart and Lung Center (D.V., P.P., J.L., P.S., M.K.), Helsinki University Hospital and University of Helsinki, , Finland. , Piia SimonenPiia Simonen https://orcid.org/0000-0002-3394-6420 Heart and Lung Center (D.V., P.P., J.L., P.S., M.K.), Helsinki University Hospital and University of Helsinki, , Finland. , Valtteri UusitaloValtteri Uusitalo https://orcid.org/0000-0001-7345-7122 Radiology (P.P., V.U.), Helsinki University Hospital and University of Helsinki, , Finland. Physiology and Nuclear Medicine (V.U.), Helsinki University Hospital and University of Helsinki, , Finland. , Tapani VihinenTapani Vihinen Heart Center, Turku University Hospital, Finland (T.V.). , Kari KaikkonenKari Kaikkonen https://orcid.org/0000-0002-4939-0105 Medical Research Center Oulu, University and University Hospital of Oulu, Finland (K.K.). , Petri HaatajaPetri Haataja Heart Hospital, Tampere University Hospital, Finland (P.H.). , Tuomas KerolaTuomas Kerola Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland (T.K.). , Tuomas T. RissanenTuomas T. Rissanen https://orcid.org/0000-0002-1914-2282 Heart Center, North Karelia Central Hospital, Joensuu, Finland (T.T.R.). , Ville VepsäläinenVille Vepsäläinen Heart Centre, Kuopio University Hospital, Kuopio, Finland (V.V.). , Aleksi AlataloAleksi Alatalo South Ostrobothnia Central Hospital, Seinäjoki, Finland (A.A.). , Päivi Pietilä-EffatiPäivi Pietilä-Effati https://orcid.org/0000-0002-4502-8934 Vaasa Central Hospital, Vaasa, Finland (P.P-E.). and Markku KupariMarkku Kupari https://orcid.org/0000-0002-5813-3477 Heart and Lung Center (D.V., P.P., J.L., P.S., M.K.), Helsinki University Hospital and University of Helsinki, , Finland. Originally published11 Mar 2024https://doi.org/10.1161/CIRCULATIONAHA.123.066962Circulation. 2024;149:885–887FootnotesFor Sources of Funding and Disclosures, see page 887.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Jukka Lehtonen, MD, Division of Cardiology, Heart and Lung Center, Helsinki University Hospital, 00029 HUS, Finland. Email jukka.lehtonen@hus.fiREFERENCES1. Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis.Eur Heart J. 2023; 44:1495–1510. doi: 10.1093/eurheartj/ehad067CrossrefGoogle Scholar2. Kandolin R, Lehtonen J, Airaksinen J, Vihinen T, Miettinen H, Ylitalo K, Kaikkonen K, Tuohinen S, Haataja P, Kerola T, et al. Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study.Circulation. 2015; 131:624–632. doi: 10.1161/CIRCULATIONAHA.114.011522LinkGoogle Scholar3. Nordenswan HK, Pöyhönen P, Lehtonen J, Ekström K, Uusitalo V, Niemelä M, Vihinen T, Kaikkonen K, Haataja P, Kerola T, et al. Incidence of sudden cardiac death and life-threatening arrhythmias in clinically manifest cardiac sarcoidosis with and without current indications for an implantable cardioverter defibrillator.Circulation. 2022; 146:964–975. doi: 10.1161/CIRCULATIONAHA.121.058120LinkGoogle Scholar4. Birnie DH, Sauer WH, Bogun F, Cooper JM, Culver DA, Duvernoy CS, Judson MA, Kron J, Mehta D, Cosedis Nielsen J, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis.Heart Rhythm. 2014; 11:1305–1323. doi: 10.1016/j.hrthm.2014.03.043CrossrefMedlineGoogle Scholar5. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk.J Am Stat Assoc. 1999; 94:496–509. doi: 10.1080/01621459.1999.10474144CrossrefGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails March 12, 2024Vol 149, Issue 11 Advertisement Article InformationMetrics © 2024 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.123.066962PMID: 38466785 Originally publishedMarch 11, 2024 Keywordscardiomyopathyheart failuresarcoidosisPDF download Advertisement SubjectsCardiomyopathyHeart Failure

BACKGROUND Heart failure (HF) is the leading cause of hospitalization in individuals over 65 years of age. Identifying noninvasive methods to detect HF may address the epidemic of HF. Seismocardiography which measures cardiac vibrations transmitted to the chest wall has recently emerged as a promising technology to detect HF. OBJECTIVES In this multicenter study, the authors examined whether seismocardiography using commercially available smartphones can differentiate control subjects from patients with stage C HF. METHODS Both inpatients and outpatients with HF were enrolled from Finland and the United States. Inpatients with HF were assessed within 2 days of admission, and outpatients were assessed in the ambulatory setting. In a prespecified pooled data analysis, algorithms were derived using logistic regression and then validated using a bootstrap aggregation method. RESULTS A total of 217 participants with HF (174 inpatients and 172 outpatients) and 786 control subjects from cardiovascular clinics were enrolled. The mean age of participants with acute HF was 64 +/- 13 years, 64.9% were male, left ventricular ejection fraction was 39% +/- 15%, and median N -terminal pro -B-type natriuretic peptide was 5,778 ng/L (Q1Q3: 1,933 -6,703). The majority (74%) of participants with HF had reduced EF, and 38% had atrial fibrillation. Across both HF cohorts, the algorithms had an area under the receiver operating characteristic curve of 0.95 with a sensitivity of 85%, specificity of 90%, and accuracy of 89% for the detection of HF, with a decision threshold of 0.5. The positive and negative likelihood ratios were 8.50 and 0.17, respectively. The accuracy of the algorithms was not significantly different in subgroups based on age, sex, body mass index, and atrial fibrillation. CONCLUSIONS Smartphone-based assessment of cardiac function using seismocardiography is feasible and differentiates patients with HF from control subjects with high diagnostic accuracy. (Recognition of Heart Failure With Micro Electro-mechanical Sensors FI; NCT04444583; Recognition of Heart Failure With Micro Electro-mechanical Sensors [NCT04378179]; Detection of Coronary Artery Disease With Micro Electro-mechanical Sensors; NCT04290091) (c) 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.

AbstractThe risk of atherosclerotic cardiovascular diseases (ASCVDs) can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) concentrations. Nevertheless, ASCVDs still cause most deaths worldwide. Here, we discuss the prevention of ASCVD and the event risk with a focus on heart-healthy diets, i.e., low intakes of saturated and trans-fatty acids and cholesterol, and high intakes of unsaturated fatty acids, viscous fibre, and dietary phytostanols as fatty acid esters, according to international dyslipidaemia treatment guidelines. Calculations based on both FINRISK and Cholesterol Treatment Trialists’ Collaborators regression equations indicate that heart-healthy diets combined with phytostanol ester reduce LDL-C concentrations to such an extent that the 10-year estimated reduction in the incidence of coronary artery disease would be 23%. This information can be used, in particular, to prevent the development of subclinical atherosclerosis in healthy middle-aged populations and the progression of atherosclerosis to ASCVD. The outcome of simple and feasible dietary changes, and, when needed, combined with statins, can be significant: reduced mortality, an increased number of healthy life-years, and reduced healthcare costs.

Background and aims: Hydroxychloroquine (HCQ) has a variable effect on cholesterol synthesis. To clarify this, we assessed the effect of HCQ on the cholesterol-synthesis pathway in individuals with low and high cholesterol absorption efficiency. Method: A total of 53 acute myocardial infarction patients with a constant statin dose randomized to receive HCQ or placebo for six months in a double -blind manner, were classified further into low (n = 26) and high (n = 27) cholesterol absorbers based on the median baseline serum cholestanol level. Serum lipids and biomarkers of cholesterol synthesis (squalene, lanosterol, zymostenol, desmosterol, and lathosterol) and absorption efficiency (sitosterol and cholestanol), were measured at baseline and one-, six-, and 12-month follow-up visits. Results: In low cholesterol absorbers, serum cholesterol concentration and cholesterol synthesis and absorption biomarkers did not differ between the HCQ and placebo groups. At one month, high cholesterol absorbers with HCQ had lower serum cholesterol concentration and serum lanosterol to cholesterol ratio in comparison to the placebo group (HCQ 3.18 +/- 0.62 vs. placebo 3.71 +/- 0.65, p = 0.042, and HCQ 10.4 +/- 2.55 vs. placebo 13.1 +/- 2.36, p = 0.008, respectively). At 12 months, serum desmosterol to cholesterol ratio was lower in HCQ users (HCQ 47.1 +/- 7.08 vs. placebo 59.0 +/- 13.1, p = 0.011). Conclusions: HCQ affects the cholesterol-synthesis pathway in high cholesterol absorbers. It reduces serum lanosterol and desmosterol ratios and consequently serum cholesterol concentration possibly by inhibiting the activity of lanosterol synthase as described earlier in vitro studies. Trial registration: ClinicalTrials.gov Identifier: NCT02648464.

BACKGROUND:Factor Xa inhibitors (FXaI) are recommended for treatment of venous thromboembolism (VTE). However, in FXaI trials there is a 2-3% treatment failure rate. This observational study aimed to elucidate factors associated with recurrent VTE during coagulation FXaI treatment. METHODS:Ten consecutive FXaI failure cases were included. Various thrombosis risk scores were assessed, thrombophilia was screened, and coagulation activity was followed-up, to tailor individual anticoagulation strategies. RESULTS:Our patients were young (mean age 37.5 years, range 22-55), six being women. Index VTE was pulmonary embolism (PE) in eight patients, and upon recurrent PE, six of them developed chronic thromboembolic pulmonary hypertension (CTEPH). Although initially many patients appeared to have unprovoked VTE, all had major VTE risk factors. Seven patients had chronic venous obstruction: five subclavian (thoracic outlet syndrome, TOS) even though only two had upper extremity deep vein thrombosis at index thrombosis, plus one common iliac, and one with chronic paraplegia. Five patients had multiple VTE risk factors and four had thrombophilia. VTE risk scores varied from the lowest (TOS patients) to the highest risk (multiple risk factors/thrombophilia). FXaI failure occurred on average at 97 days of therapy (range 15-279) without evident noncompliance. D-dimer levels declined from the index thrombosis to FXaI failure, and re-thrombosis resisted further anticoagulation, low D-dimer referring to impaired fibrinolysis. The majority (8/10) of patients required mechanical/surgical interventions. CONCLUSIONS:Our results underline careful risk assessment upon PE and reoccurrence, with inclusion of TOS as a risk factor of VTE and CTEPH.

BACKGROUND:Cardiac sarcoidosis involves a significant but difficult-to-define risk of sudden cardiac death (SCD). Current guidelines recommend consideration of an implantable cardioverter defibrillator for patients with extensive or significant myocardial late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. However, extensive/significant LGE is not defined. METHODS:A nationwide cardiac sarcoidosis registry was screened for patients entered before 2020 with cardiac magnetic resonance imaging done before or <3 months after diagnosis. Available studies were re-analyzed for LGE mass as a percentage of left ventricular (LV) mass and the number of LGE-positive LV segments in a 17-segment model. The occurrence of fatal or aborted SCD and ventricular tachycardia (VT) prompting therapy was recorded until the end of 2020 and subjected to cumulative incidence analyses, including competing events (LV assist device implantations, heart transplantations, and fatalities other than SCD). The predictors of SCD/VT were assessed using Fine and Gray modeling and time-dependent receiver operating characteristic analysis. RESULTS:Altogether, 305 patients (66% women, median age 51) with clinically manifest, definite (45%) or probable cardiac sarcoidosis (55%) were analyzed. On follow-up (median, 4.0 years), 21 SCDs, 60 VTs, and 14 competing events were noted. Both LGE mass and the number of LGE segments predicted the composite of SCD/VT (P<0.001), with receiver operating characteristic analyses identifying LGE mass ≥9.9% and ≥6 LGE segments as discriminative thresholds. At presentation, 70 patients were free of class I and class IIa implantable cardioverter defibrillator indications unrelated to LGE. Their 5-year rate of SCD/VT was 6.3% (0.0-14.8%) with LGE mass <9.9% versus 21.5% (6.5-36.6%) with higher LGE mass, and 6.9% (0.0-16.3%) with <6 LGE segments versus 20.5% (5.9-35.2%) with ≥6 segments. CONCLUSIONS:In cardiac sarcoidosis, myocardial LGE making up ≥9.9% of LV mass or affecting ≥6 LV segments may suggest prognostically significant LV involvement and a high risk of SCD. However, prospective validation of the thresholds is needed.

Objectives:Given that pulmonary arterial hypertension (PAH) and chronic thromboembolic hypertension (CTEPH) are rare yet severe subtypes of pulmonary hypertension significantly impacting patients' lives, this study analyzed the total societal costs of these conditions in Finland. Methods:PAH (n = 247) and CTEPH (n = 177) patients diagnosed between 2008 and 2019 were analyzed for primary and specialty outpatient visits, emergency visits, hospitalizations, home and institutional care, sick leaves, disability pensions, and drug costs for 5 years before and after diagnosis. Results:In PAH and CTEPH, annual specialty care number of outpatient visits increased from 3.8 and 3.3 (5 years before diagnosis) to 13.8 and 9.5 one-year post-diagnosis, then decreased to 9.2 and 4.0 at 5 years post-diagnosis. Annual inpatient days rose from 2.8 and 2.7 to 16.1 and 19.7 pre-diagnosis, then fell to 10.2 and 3.5 post-diagnosis, respectively. Within 5 years post-diagnosis, in working-age 70 % PAH and 42 % CTEPH patients received disability pensions. Drug therapy accounted for most costs (67 % in PAH and 60 % in CTEPH), followed by inpatient care, disability pensions, and outpatient care. Total costs were significantly lower for CTEPH, especially after pulmonary endarterectomy. Among PAH subtypes, the highest costs were in patients with PAH associated with connective tissue diseases. Conclusions:PAH and CTEPH cause a significant economic burden on patients and society with considerable differences depending on the PAH subtype and whether the patient has undergone PEA operation or not.

Background Patent foramen ovale (PFO) closure is traditionally guided by transoesophageal echocardiography (TEE) under general anaesthesia, which prolongs procedure duration and increases costs and risks. A transnasal echocardiography with a microTEE-probe (microTNE) is tolerated under conscious sedation and offers an effective alternative to TEE. The aim of this study was to compare the feasibility, safety and time expenditure of PFO closure using conventional TEE versus microTNE guidance.Methods Consecutive patients assigned for PFO losure in Helsinki University Hospital from 2003 to 2021 were included in the study (n=336). TEE with general anaesthesia was used until November 2018 (n=167) while microTNE-guided PFO closure (n=169) under conscious sedation was the principal method thereafter. Patients were followed for 3 months after PFO closure.Results The microTNE-route success rate was 97.2% vs TEE 100% (p=0.06) and procedure success rate was 97.7% with microTNE and 96.0% with TEE-guidance (p=0.54). The procedure time was significantly shorter with microTNE 21±7 min than with TEE 30±13 min (p<0.001). At the beginning of microTNE era, nasal bleeding complication was quite frequent; however, overall complication rates were equal between the groups. However, C reactive protein (CRP) increase was significantly milder with microTNE than TEE 1.0±2.9 vs 3.0±4.0 mg/L (p<0.001). An increase in CRP was independently associated with procedure type (p=0.004) and time (p=0.003).Conclusions MicroTNE is a feasible and safe alternative for PFO closure guidance. MicroTNE under conscious sedation shortens procedure duration and induces a milder inflammatory reaction than conventional TEE under general anaesthesia.

Background:To assess characteristics, risk group distribution, and prognosis of patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Finland. Methods:Clinical chart review of patients with PAH or CTEPH recorded between 2008 and 2019 and linkage to official mortality data. Results:We identified 627 patients, with 502 (80%) diagnosed after 2008, yielding an incidence of PAH and CTEPH of 4.0 and 2.9/million/year, respectively. The median time from symptoms to diagnosis was 1 year. Mean age at diagnosis of PAH patients (n = 268) was 57 years, 73% were women, 40% had idiopathic PAH, 28% associated with connective tissue diseases, and 15% with congenital heart disease, 9% had ≥3 cardiovascular comorbidities. At 1 year, 34%/34%/24%/8% were at the low/intermediate-low/intermediate-high/high Compera 2.0 risk classification groups. Survival was 91.3%, 74.8%, and 62.6% at 1, 3, and 5 years, respectively, with an improving trend over calendar time. Ten PAH patients had a lung transplant. PAH subtype, cardiac output, and the presence of ischemic heart disease or type 2 diabetes predicted survival.CTEPH patients (n = 189) were 63 years (mean) at diagnosis and 49% were women. Of the CTEPH patients, 29% underwent pulmonary endarterectomy (PEA) and 22% were treated with balloon pulmonary angioplasty. Survival was 94.6%, 87.2%, and 79.4% at 1, 3, and 5 years, respectively. PEA patients were younger, had fewer comorbidities, and had longer survival than non-PEA patients. Conclusions:Incidence and survival of PAH and CTEPH patients in Finland were similar to previously presented data for other countries.