Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure.

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of ß-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.

Quality of life and functional status after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: A Swedish single-center study.

Little is known about long-term quality of life (QOL) and functional status after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). We investigated QOL and functional status late after PEA. All patients who underwent PEA for CTEPH 1993-2020 at one Swedish center were included. Baseline characteristics and data from right heart catheterization, 6-min walk test, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) were obtained from patient charts and national registers. The RAND 36-Item Health Survey was sent by post, and Karnofsky Performance Status (KPS) was evaluated by telephone. A total of 110 patients were included. The survey was completed by 49/66 (74%) patients who were alive in 2020. In all domains except for bodily pain, QOL was slightly lower than that of an age-matched reference population. The KPS score was obtained from 42/49 (86%) patients; of these, 31 patients (74%) had a KPS score of ≥80% (able to carry on normal activity). All 42 patients were able to live at home and care for personal needs. The median postoperative CAMPHOR scores were: 4 for symptoms, 4 for activity, and 2.5 for QOL. We observed that QOL after PEA approached the expected QOL in a reference population and that CAMPHOR scores were comparable to those of a large UK cohort after PEA. Functional status improved when assessed late after PEA. Three-quarters of the study population were able to conduct normal activities at late follow-up. Our findings suggest that many patients enjoy satisfactory QOL and high functional status late after PEA.

Extracellular vesicles in heart failure - A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting.

Aims: Extracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype. Materials and methods: Patients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function (n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)]. Results: Median concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups. Conclusion: Con43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.

Association of residual pulmonary hypertension with survival after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

This study investigated whether residual pulmonary hypertension (PH), defined as early postoperative mean pulmonary artery pressure (mPAP) of ≥30 mmHg, after undergoing pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) was associated with long-term survival. All patients who underwent PEA for CTEPH at two Scandinavian centers were included in this study. Baseline characteristics and vital statuses were obtained from patient charts and national health-data registers. The patients were then categorized based on residual PH measured via right heart catheterization within 48 h after undergoing PEA. Crude and weighted flexible parametric survival models were used to estimate the association between residual PH and all-cause mortality and to quantify absolute survival differences. From 1992 to 2020, 444 patients underwent surgery. We excluded 6 patients who died on the day of surgery and 12 patients whose early postoperative pulmonary hemodynamic data was unavailable. Of the total study population (n = 426), 174 (41%) and 252 (59%) patients had an early postoperative mPAP <30 and ≥30 mmHg, respectively. After weighting, there was a significant association between residual PH and all-cause mortality (hazard ratio: 2.49; 95% confidence interval [CI]: 1.60-3.87), and the absolute survival difference between the groups at 10 and 20 years was -22% (95% CI: -32% to -12%) and-32% (95% CI: -47% to -18%), respectively. A strong and clinically relevant association of residual PH with long-term survival after PEA for CTEPH was found. After accounting for differences in baseline characteristics, the absolute survival difference at long-term follow-up was clinically meaningful and imply careful surveillance to improve clinical outcomes in these patients. Early postoperative right heart catheter measurements of mPAP seem to be helpful for prognostication following PEA for CTEPH.

Sex and survival following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: a Scandinavian observational cohort study.

Studies have suggested sex-related survival differences in chronic thromboembolic pulmonary hypertension (CTEPH). Whether long-term prognosis differs between men and women following pulmonary endarterectomy for CTEPH remains unclear. We investigated sex-specific survival after pulmonary endarterectomy for CTEPH. We included all patients who underwent pulmonary endarterectomy for CTEPH at two Scandinavian centers and obtained baseline characteristics and vital statuses from patient charts and national health-data registers. Propensity scores and weighting were used to account for baseline differences. Flexible parametric survival models were employed to estimate the association between sex and all-cause mortality and the absolute survival differences. The expected survival in an age-, sex-, and year of surgery matched general population was obtained from the Human Mortality Database, and the relative survival was used to estimate cause-specific mortality. A total of 444 patients were included, comprising 260 (59%) men and 184 (41%) women. Unadjusted 30-day mortality was 4.2% in men versus 9.8% in women (p = 0.020). In weighted analyses, long-term survival did not differ significantly in women compared with men (hazard ratio: 1.36; 95% confidence interval: 0.89-2.06). Relative survival at 15 years conditional on 30-day survival was 94% (79%-107%) in men versus 75% (59%-88%) in women. In patients who underwent pulmonary endarterectomy for CTEPH, early mortality was higher in women compared with men. After adjustment for differences in baseline characteristics, female sex was not associated with long-term survival. However, relative survival analyses suggested that the observed survival in men was close to the expected survival in the matched general population, whereas survival in women deviated notably from the matched general population.

[Chronic thromboembolic pulmonary hypertension may be cured with surgery]. / Kronisk lungembolism kan botas med kirurgi.

Chronic thromboembolic pulmonary hypertension is a subtype of pulmonary hypertension that affects 0,5-4% of patients who have had a pulmonary embolism. Emboli in the pulmonary arteries lead to fibrosis, obstruction and remodeling of the pulmonary arteries which causes increased pulmonary arterial blood pressure and increased pulmonary vascular resistance. Cardiac ultrasound is used as initial screening in order to identify high pulmonary artery pressures and right heart dysfunction. Lung scintigraphy, computed tomography, and pulmonary angiography are used to verify and describe disease severity. Surgical treatment entails circulatory arrest with endarterectomy starting proximal in the pulmonary arteries and continuing distally throughout the pulmonary arterial tree. Removal of obstruction leads to decreased pulmonary artery pressure and pulmonary vascular resistance, resulting in improved quality of life and near normal life expectancy.

Life expectancy after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: a Swedish single-center study.

Pulmonary endarterectomy is the guideline recommended treatment for chronic thromboembolic pulmonary hypertension, in addition to life-long anticoagulation therapy. The aim was to analyze long-term relative survival after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. We included all patients who underwent pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at Karolinska University Hospital between 1997 and 2018 (n = 100). We obtained baseline characteristics and vital status from patient charts and national health-data registers. The expected survival from the general Swedish population matched by age, sex, and year of surgery was obtained from the Human Mortality Database. The relative survival was used as an estimate of cause-specific mortality. The mean age of the patients was 62 years and 39% were women. Most patients were severely symptomatic (95% in New York Heart Association functional class III-IV), and mean preoperative systolic/diastolic (mean) pulmonary artery pressure was 78/27 (45) mmHg. The mean and maximum follow-up time was 7.2 and 22.1 years, respectively. Early (30-day) mortality was 7%. The 15-year observed, expected, and relative survival was 55% (95% confidence interval, 40%-68%), 71%, and 77% (95% confidence interval, 56%-95%), respectively. The 15-year relative survival conditional on 30-day survival was 83% (95% confidence interval, 60%-100%). Although the life expectancy following pulmonary endarterectomy was shorter compared to the general population, the difference was small in those who survived the operation and the early postoperative period. Patients with chronic thromboembolic pulmonary hypertension who are surgical candidates should undergo pulmonary endarterectomy to improve prognosis.

Synthetic tracheal grafts seeded with bone marrow cells fail to generate functional tracheae: First long-term follow-up study.

OBJECTIVE: Synthetic tracheal grafts seeded with autologous bone marrow-mononuclear cells (BM-MNCs) have been described as becoming living and functional grafts representing a promising option for tracheal replacement for pathologies unamenable by segmental resection or autologous repair. This study aimed to present the first long-term follow-up of these procedures in humans. METHODS: We retrospectively analyzed 3 patients who received synthetic tracheal grafts seeded with BM-MNCs implanted. RESULTS: Patient 1 was a 37-year-old man with mucoepidermoid carcinoma, the first-ever human to receive a synthetic tracheal graft seeded with BM-MNCs. Patient 2 was a 30-year-old man with adenoid cystic carcinoma, and patient 3 was a 22-year-old woman with an iatrogenic tracheal injury. All patients developed graft-related complications necessitating multiple surgical reinterventions. Patient 1 was hospitalized for 8 months before dying from respiratory failure secondary to graft dehiscence 32 months after implantation. Patient 2 died 3.5 months after implantation from undisclosed causes. Patient 3 received a second synthetic tracheal graft after 11 months and an allogeneic trachea and lung transplantation 45 months after the primary implantation. Patient 3 underwent 191 surgical interventions after the primary implantation and spent 55 months in the intensive care unit before dying from airway bleeding. All patients' bronchoscopic, histologic, and radiologic investigations demonstrated graft-associated complications, including anastomotic fistulae and obstructive granulation tissue, without graft vascularization, mucosal lining, or integration into adjacent tissues. CONCLUSIONS: Synthetic tracheal grafts seeded with BM-MNCs do not become living functional tracheal grafts and lead to debilitating complications and death.

Cardiac Arrest Prior to Venoarterial Extracorporeal Membrane Oxygenation: Risk Factors for Mortality.

OBJECTIVES: Mortality after cardiac arrest remains high despite initiation of venoarterial extracorporeal membrane oxygenation. We aimed to identify pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality in patients with witnessed cardiac arrest and with greater than or equal to 1 minute of cardiopulmonary resuscitation before venoarterial extracorporeal membrane oxygenation. The association between preimplant variables and all-cause mortality at 90 days was analyzed with multivariable logistic regression. DESIGN: Retrospective observational cohort study. SETTING: Tertiary medical center. PATIENTS: Seventy-two consecutive patients with cardiac arrest prior to venoarterial extracorporeal membrane oxygenation cannulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median age was 56 years (interquartile range, 43-56 yr), 75% (n = 54) were men. Out-of-hospital cardiac arrest occurred in 12% (n = 9) of the patients. Initial cardiac rhythm was nonshockable in 57% (n = 41) and shockable in 43% (n = 31) of patients. Median cardiopulmonary resuscitation duration was 21 minutes (interquartile range, 10-73 min; range, 1-197 min]. No return of spontaneous circulation was present in 64% (n = 46) and postarrest cardiogenic shock in 36% (n = 26) of the patients at venoarterial extracorporeal membrane oxygenation cannulation. Median duration of venoarterial extracorporeal membrane oxygenation was 5 days (interquartile range, 2-12 d). The 90-day overall mortality and in-hospital mortality were 57% (n = 41), 53% (n = 38) died during venoarterial extracorporeal membrane oxygenation, and 43% (n = 31) were successfully weaned. All survivors had Cerebral Performance Category score 1-2 at discharge to home. Multivariable logistic regression analysis identified initial nonshockable cardiac arrest rhythm (odds ratio, 12.2; 95% CI, 2.83-52.7; p = 0.001), arterial lactate (odds ratio per unit, 1.15; 95% CI, 1.01-1.31; p = 0.041), and ischemic heart disease (7.39; 95% CI, 1.57-34.7; p = 0.011) as independent risk factors of 90-day mortality, whereas low-flow duration, return of spontaneous circulation, and age were not. CONCLUSIONS: In 72 patients with cardiac arrest before venoarterial extracorporeal membrane oxygenation initiation, nonshockable rhythm, arterial lactate, and ischemic heart disease were identified as independent pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality. The novelty of this study is that the metabolic state, expressed as level of lactate just before venoarterial extracorporeal membrane oxygenation initiation seems more predictive of outcome than cardiopulmonary resuscitation duration or absence of return of spontaneous circulation.

Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction.

Heart failure affects 2-3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction ≥45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.

Human Fetal Cardiac Mesenchymal Stromal Cells Differentiate In Vivo into Endothelial Cells and Contribute to Vasculogenesis in Immunocompetent Mice.

Mesenchymal stromal cells (MSCs) have shown great potential as a treatment for systemic inflammatory diseases, but their local regenerative properties are highly tissue- and site specific. Previous studies have demonstrated that adult human MSCs respond to inflammatory cytokines through the release of paracrine factors that stimulate angiogenesis, but they do not themselves differentiate into vascular structures in vivo. In this study, we used human fetal cardiac MSCs (hfcMSCs) harvested during the first trimester of heart development and injected them into the subcutaneous tissue of normal immunocompetent mice treated with short-term costimulation blockade for tolerance induction. When hfcMSCs were transplanted subcutaneously together with Matrigel matrix, they contributed to vasculogenesis through differentiation into endothelial cells and generation of the basal membrane protein Laminin α4. These characteristics of hfcMSCs are similar to the mesodermal progenitors giving rise to the developing heart and they may be useful for treatment of ischemic injuries.

VA-ECMO Support in Nonsurgical Patients With Refractory Cardiogenic Shock: Pre-Implant Outcome Predictors.

Refractory cardiogenic shock (RCS) is associated with a high mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as acute cardiopulmonary support but selection of VA-ECMO candidates remains challenging. There are limited data on which pre-VA-ECMO variables that predict outcome. The aim of this study was to identify pre-VA-ECMO predictors of 90-day mortality. We retrospectively analyzed 76 consecutive patients (median age 52; interquartile range [IQR]: 37-60) supported with VA-ECMO due to RCS. The association between pre-implant variables and all-cause mortality at 90 days was analyzed with multivariable logistic regression. Main etiologies of RCS were acute myocardial infarction 51% and other AHF etiologies 49%. Cardiopulmonary resuscitation was performed in 54% of patients before initiation of VA-ECMO. Median duration of VA-ECMO was 5 days (IQR: 2-11). The 90-day overall mortality was 49% and in-hospital mortality was 50%; 46% died on VA-ECMO, 37% were successfully weaned, 13% were bridged to heart transplantation, and 4% to left ventricular assist device. Multivariable logistic regression analysis identified arterial lactate (odds ratio [OR] per mmol/L: 1.15; 95% confidence interval [CI]: 1.06-1.24; P = 0.001) and number of inotropes and vasopressors (OR per agent: 2.14; 95% CI: 1.26-3.63; P = 0.005) as independent predictors of 90-day mortality. In RCS patients arterial lactate level and number of inotropes and vasopressors were identified as independent pre-VA-ECMO predictors of 90-day mortality. Thus, the severity of cardiogenic shock expressed as levels of lactate and vasoactive agents just before start of VA-ECMO may be more predictive of outcome than the specific etiology of cardiogenic shock.

Venoarterial extracorporeal membrane oxygenation for postcardiotomy shock: Risk factors for mortality.

OBJECTIVES: Refractory postcardiotomy cardiogenic shock is associated with a high mortality, and venoarterial extracorporeal membrane oxygenation can offer acute cardiopulmonary life support. The aim of this study was to identify pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality. METHODS: We retrospectively analyzed 105 consecutive patients supported with venoarterial extracorporeal membrane oxygenation due to refractory postcardiotomy cardiogenic shock. The association between preimplant variables and all-cause mortality at 90 days was analyzed with univariable and multivariable logistic regression. RESULTS: Main surgical subgroups were single noncoronary artery bypass grafting (29%), isolated coronary artery bypass grafting (20%), and 2 and 3 concomitant surgical procedures (31% and 20%, respectively). The median age of patients was 62 years (interquartile range, 52-68 years), and 76% were men. Cardiopulmonary resuscitation was performed in 30% of patients before venoarterial extracorporeal membrane oxygenation initiation. The median duration of venoarterial extracorporeal membrane oxygenation was 7 days (interquartile range, 3-14). The 90-day overall mortality was 57%, and in-hospital mortality was 56%. Forty-seven percent of patients died on venoarterial extracorporeal membrane oxygenation, 51% of patients were successfully weaned, 1% of patients were bridged to heart transplantation, and 1% of patients were bridged to left ventricular assist device. Multivariable logistic regression analysis identified arterial lactate (odds ratio per unit, 1.22; 95% confidence interval, 1.07-14.0; P = .004) and ischemic heart disease (odds ratio, 7.87; 95% confidence interval, 2.55-24.3; P < .001) as independent risk factors of 90-day mortality. CONCLUSIONS: In patients with postcardiotomy cardiogenic shock, ischemic heart disease and level of arterial lactate before venoarterial extracorporeal membrane oxygenation initiation were identified as independent pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality. These risk factors are easily available for pre-venoarterial extracorporeal membrane oxygenation risk prediction and may improve patient selection for this resource-intensive therapy.

Spatial detection of fetal marker genes expressed at low level in adult human heart tissue.

Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS: In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION: The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING: Biosensors, Aarhus University Hospital, and participating sites.

Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants.

AIMS: Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF (https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). METHODS: Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. CONCLUSIONS: In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF.