Atrial septal defect patients have an elevated risk for infective endocarditis.

Background. It has been unclear whether simple atrial septal defect (ASD) is an independent risk factor for infective endocarditis (IE). This study aimed to untangle the risk of endocarditis in a large nationwide cohort. Methods. We acquired data from the Finnish hospital discharge register on all individuals with ASD diagnosis from 1969 to 2019. Patients with complex congenital cardiac abnormalities were ruled out. Five individualized controls from the general population were matched to the ASD patient's birth year, sex, and residence at the index date. All the patients with ICD-8, -9, or -10 diagnosis codes for IE were gathered from the hospital discharge registry. Results. Altogether, 8322 patients with ASD and 39,237 individualized controls were enrolled in the study. Median follow-up was 21.6 years (IQR 11.8-36.9) from the first hospital contact. In total, 24 (16 male) cases of infective endocarditis among ASD patients and 10 (8 male) cases among controls were diagnosed during the follow-up. The incidence of endocarditis was 0.11 per 1000 person-years in the patients with ASD and 0.011 per 1000 person-years in the controls. The adjusted risk ratio for endocarditis was 13.51 (95% CI: 6.20-29.46) in patients with ASD compared to the control cohort. Patients with ASD and endocarditis had higher long-term mortality than individualized control patients (MRR 2.25, 95% CI: 1.23-4.11). Conclusions. The incidence of IE in patients with ASD was higher than in the general population. Mortality associated with IE was higher in patients with ASD compared to controls.

Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy.

BACKGROUND: Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS: We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS: Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS: hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Determining optimal noninvasive parameters for the prediction of left ventricular remodeling in chronic ischemic patients.

OBJECTIVES: DOPPLER-CIP aims to determine the optimal noninvasive parameters (myocardial function, perfusion, ventricular blood flow, cell integrity) and methodology (ergometry, echocardiography, scintigraphy, MRI) in a given ischemic substrate that best predicts the impact of an intervention (or the lack thereof) on adverse morphological ventricular remodeling and functional recovery. Moreover, the relative predictive value of each of these parameters, in respect to the cost of extracting this information in order to enable optimization of cost-effectiveness for improved health care, will be determined by this project. DESIGN: DOPPLER-CIP is a multi-center registry study. All patients with ischemic heart disease included in this study undergo at least two noninvasive stress imaging examinations at baseline. The presence/or absence of left ventricular (LV) remodeling will be assessed after a follow-up of 2 years, during which all cardiac events will be registered. RESULTS: 676 patients were included. Currently, baseline data analysis is almost finished and the follow-up is ongoing. CONCLUSIONS: After completion, DOPPLER-CIP will provide evidence-based guidelines toward the most effective use of cardiac imaging in the chronically ischemic heart disease patient. The study will generate information, knowledge, and insight into the new imaging methodologies and into the pathophysiology of chronic ischemic heart disease.

[Can strokes be prevented by cardiac catheterization procedures?]. / Voidaanko aivoverenkierron häiriöitä estää sydämen katetritoimenpiteillä?

Most strokes associated with atrial fibrillation are caused by thrombi generated at the left auricle of the heart. Anticoagulation effectively prevents strokes associated with atrial fibrillation, but may in some patients cause severe bleeding complications that lead to cessation of therapy. Catheter closure of the left auricle of the heart is an effective but technically demanding treatment alternative in cases where severe bleedings prevent anticoagulation therapy and the patient carries a high risk of developing stroke. Some strokes of unknown origin may also be caused by a patent foramen ovale.

Intrapericardial, but not extrapericardial, fat is an independent predictor of impaired hyperemic coronary perfusion in coronary artery disease.

OBJECTIVE: To measure intrapericardial fat (IPF), extrapericardial fat (EPF), and myocardial perfusion (MBF) in patients with and without coronary artery disease (CAD), hypothesizing that perfusion is more strongly associated with IPF because it is in direct anatomic contiguity with the myocardium or coronary arteries. METHODS AND RESULTS: Fat surrounding the heart may increase the risk of CAD and calcification, but little is known about the role of MBF in this relationship. The study included 107 patients with an intermediate likelihood of CAD. Positron emission tomography/computed tomography was used to measure IPF and EPF volumes and coronary artery calcium level, together with MBF at rest and during adenosine-induced hyperemia. Subsequently, all subjects underwent coronary angiography and were grouped for presence/absence of CAD and severity of myocardial hypoperfusion. IPF and EPF levels were higher in men and in patients with CAD (n=85) than in those without CAD (n=22) (P<0.001). EPF was increased regardless of the degree of stenoses (n=45), whereas IPF was selectively increased in subjects with obstructive stenoses (n=40). IPF and EPF levels were both associated with coronary artery calcium scores (R=0.25 and R=0.26, respectively; P<0.02), coronary flow reserve (R=-0.37 and R=-0.38, respectively; P<0.001), and hyperemic MBF (R=-0.36 and R=-0.44, respectively; P<0.0005). Male sex was a strong negative predictor of MBF. After discounting for confounders, myocardial hyperemic perfusion was predicted independently by sex, coronary artery calcium score, and IPF, but not EPF. CONCLUSIONS: CAD is accompanied by augmented fat depots surrounding the heart, which are negatively related to coronary flow hyperemia. Among fat depots, IPF was the only independent predictor of hyperemic MBF, supporting the hypothesis of a direct paracrine/vasocrine effect.

Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome.

BACKGROUND: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. METHODS: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. RESULTS: We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. CONCLUSION: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

Recent advances in cardiac imaging for patients with heart failure.

PURPOSE OF REVIEW: Transthoracic echocardiography (ECHO) and single-photon emission computed tomography (SPECT) are routine in many heart failure patients. Recently, other imaging tests have emerged in heart failure management: cardiovascular magnetic resonance (CMR), positron emission tomography (PET) and computed tomography (CT). This article reviews recent developments in heart failure imaging. RECENT FINDINGS: Longitudinal left ventricular systolic strain on ECHO speckle tracking imaging detects subclinical cardiomyopathy and predicts survival in symptomatic heart failure. Late gadolinium enhancement for myocardial scar is an independent predictor of death or transplantation in ischemic and nonischemic cardiomyopathy. In contrast to earlier reports, both ECHO and CMR contrast have a negligible risk of adverse outcomes. Stress perfusion imaging (SPECT or PET) and PET flow quantification have prognostic value in ischemic cardiomyopathy. F-2-fluoro-2-deoxyglucose (FDG) PET directed management can impact outcome. Abnormal myocardial neuronal activity on I-metaiodobenzylguanidine (MIBG) imaging is associated with increased risk of ventricular arrhythmias and death. Cardiac CT potentially could assess heart failure etiology through coronary angiography and myocardial tissue characterization but its precise role remains undetermined. SUMMARY: There have been several exciting developments in all imaging modalities. Large multicenter trials such as IMAGE heart failure are required to standardize measures and establish benefit before widespread use in heart failure can be recommended.

Computed tomography coronary angiography for patients with heart failure (CTA-HF): a randomized controlled trial (IMAGE-HF 1C).

AIMS: This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. Invasive coronary angiography (ICA) is used to investigate HF patients. CCTA may be a non-invasive cost-effective alternative to ICA. This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. METHODS AND RESULTS: This multicentre, international trial enrolled patients with HF of unknown aetiology. The primary outcome was the cost of CCTA vs. ICA strategies at 12 months. Clinical outcomes were also collected. An 'intention-to-diagnose' analysis was performed and a secondary 'as-tested' analysis was based on the modality received. Two hundred and forty-six patients were randomized (age = 57.8 ± 11.0 years, ejection fraction = 30.1 ± 10.1%). The severity of coronary artery disease was similar in both groups. In the 121 CCTA patients, 93 avoided ICA. Rates of downstream ischaemia and viability testing were similar for both arms. There were no significant differences in the composite clinical outcomes or quality of life measures. The cost of CCTA trended lower than ICA [CDN -$871 (confidence interval, CI -$4116 to $3028)]. Using an 'as-tested' analysis, CCTA was associated with a decrease in healthcare costs (CDN -$2932, 95% CI -$6248 to $746). CONCLUSION: In patients with HF of unknown aetiology, costs were not statistically different between the CCTA and ICA strategies. CLINICAL TRIALS.GOV: NCT01283659.

Real-world clinical diagnostics of heart failure patients with reduced or preserved ejection fraction.

AIMS: The study aimed at investigating the use of guideline-recommended diagnostic tools and medication in patients with heart failure (HF) in specialty care in Southwest Finland. We also compared the characteristics of the diagnosed and undiagnosed patients as well as laboratory tests, procedures, and treatments in everyday clinical practice. METHODS AND RESULTS: Patients diagnosed with HF, cardiomyopathy, or hypertension-induced heart disease (n = 20 878, primary cohort) or not diagnosed with HF but having a record of elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) (>125 ng/L, n = 24 321, secondary cohort) were included in the study from the specialty care patient register of the Hospital District of Southwest Finland during the years 2005-2017. Among patients with an International Classification of Diseases, Tenth Revision (ICD-10) code for HF, only 50% had ejection fraction (EF) data to be found by data mining from the electronic health records. Of these patients, 39% (n = 4042) had EF ≤ 40% [HF with reduced EF (HFrEF)] and 61% (n = 6347) had EF > 40%. Elevated NT-proBNP together with EF > 40% narrowed down the number to 4590 patients, a population defined as HF with preserved EF (HFpEF) patients. HFpEF patients were further stratified into HF with mildly reduced EF (HFmrEF; EF 41-50%, n = 1468) and EF > 50% patients (n = 3122) to compare clinical characteristics. NT-proBNP was higher within the HFrEF patients vs. HFpEF {4580 [inter-quartile range (IQR): 2065-9765] vs. 2900 [2065-9765] ng/L, P < 0.001}. Baseline co-morbidities differed between HFpEF and HFrEF groups. Further, HFpEF patients had more procedures and lab tests taken prior to diagnosis than had HFrEF patients. HFmrEF patients were found to resemble more HFrEF than EF > 50% patients. In 70% (n = 17 156) of patients in the secondary cohort, the NT-proBNP concentrations were >300 ng/L, median was 1090 (IQR 551-2558) ng/L and EF 58.4 ± 12.1% (n with EF available = 6845). Reduced EF was present in 6.8% of patients lacking HF diagnosis. CONCLUSIONS: Half of the patients with ICD-10 code for HF did not have EF data available after a visit at specialty care. In particular, the diagnosis of HFpEF seems challenging, reflected as an increase in procedures and laboratory test preceding diagnosis compared with those in HFrEF patients. Also, a large proportion of patients did not have HF diagnosis, yet they presented elevated NT-proBNP concentrations and clinical characteristics resembling those of HFpEF patients.

Recurrent hospitalizations are associated with increased mortality across the ejection fraction range in heart failure.

AIMS: The proportion of patients hospitalized for heart failure (HF) with preserved left ventricular ejection fraction (LVEF) is rising, but no approved treatment exists, in part owing to incomplete characterization of this particular HF phenotype. In order to better define the characteristics of HF phenotypes in Finland, a large cohort with 12 years' follow-up time was analysed. METHODS AND RESULTS: Patients diagnosed between 2005 and 2017 at the Hospital District of Southwest Finland were stratified according to LVEF measure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. For this retrospective registry study, previously diagnosed HF patients were defined as follows: patients with reduced ejection fraction (HFrEF; LVEF ≤ 40%; n = 4042), mid-range ejection fraction (HFmrEF; LVEF > 40-50% and NT-proBNP ≥ 125 pg/mL; n = 1468), and preserved ejection fraction (HFpEF; LVEF > 50% and NT-proBNP ≥ 125 pg/mL; n = 3122) and followed up for 15 022, 4962, and 10 097 patient-years, respectively. Cardiovascular (CV) hospitalization and mortality, influence of pre-selected covariates on hospitalization and mortality, and the proportion of HFpEF and HFmrEF patients with a drop in LVEF to HFrEF phenotype were analysed. All data were extracted from the electronic patient register. HFrEF patients were rehospitalized slightly earlier than HFpEF/HFmrEF patients, but the second, third, and fourth rehospitalization rates did not differ between the subgroups. Female gender and better kidney function were associated with reduced rehospitalizations in HFmrEF and HFrEF, with a non-significant trend in HFpEF. Each additional hospitalization was associated with a two-fold increased risk of death and 2.2- to 2.3-fold increased risk of CV death. All-cause mortality was higher in patients with HFpEF. Although CV mortality was less frequent in HFpEF patients, it was associated with increased NT-proBNP concentrations at index in all patient groups. During the 10 years following the index date, 26% of HFmrEF patients and 10% of HFpEF patients progressed to an HFrEF phenotype. CONCLUSIONS: These findings suggest that disease progression, in terms of increased frequency of hospitalizations, and the relationship between increased number of hospitalizations and mortality are similar by LVEF phenotypes. These data highlight the importance of effective treatments that can reduce hospitalizations and suggest a role for monitoring NT-proBNP levels in the management of HFpEF patients in particular.

Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy.

BACKGROUND: The anti-ischemic agent trimetazidine improves ejection fraction in heart failure that is hypothetically linked to inhibitory effects on cardiac free fatty acid (FFA) oxidation. However, FFA oxidation remains unmeasured in humans. We investigated the effects of trimetazidine on cardiac perfusion, efficiency of work, and FFA oxidation in idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Nineteen nondiabetic patients with idiopathic dilated cardiomyopathy on standard medication were randomized to single-blind trimetazidine (n=12) or placebo (n=7) for 3 months. Myocardial perfusion, FFA, and total oxidative metabolism were measured using positron emission tomography with [(15)O]H(2)O, [(11)C]acetate, and [(11)C]palmitate. Cardiac function was assessed echocardiographically; insulin sensitivity was assessed by the homeostasis model assessment index. Trimetazidine increased ejection fraction from 30.9+/-8.5% to 34.8+/-12% (P=0.027 versus placebo). Myocardial FFA uptake was unchanged, and beta-oxidation rate constant decreased only 10%. Myocardial perfusion, oxidative metabolism, and work efficiency remained unchanged. Trimetazidine decreased insulin resistance (glucose: 5.9+/-0.7 versus 5.5+/-0.6 mmol/L, P=0.047; insulin: 10+/-6.9 versus 7.6+/-3.6 mU/L, P=0.031; homeostasis model assessment index: 2.75+/-2.28 versus 1.89+/-1.06, P=0.027). The degree of beta-blockade and trimetazidine interacted positively on ejection fraction. Plasma high-density lipoprotein concentrations increased 11% (P<0.001). CONCLUSIONS: In idiopathic dilated cardiomyopathy with heart failure, trimetazidine increased cardiac function and had both cardiac and extracardiac metabolic effects. Cardiac FFA oxidation modestly decreased and myocardial oxidative rate was unchanged, implying increased oxidation of glucose. Trimetazidine improved whole-body insulin sensitivity and glucose control in these insulin-resistant idiopathic dilated cardiomyopathy patients, thus hypothetically countering the myocardial damage of insulin resistance. Additionally, the trimetazidine-induced increase in ejection fraction was associated with greater beta1-adrenoceptor occupancy, suggesting a synergistic mechanism.

The effect of right ventricular pacing on myocardial oxidative metabolism and efficiency: relation with left ventricular dyssynchrony.

PURPOSE: Right ventricular (RV) apical pacing induces dyssynchrony by a left bundle branch block type electrical activation sequence in the heart and may impair left ventricular (LV) function. Whether these functional changes are accompanied by changes in myocardial perfusion, oxidative metabolism and efficiency, and the relation with the induction of LV dyssynchrony are unknown. Our study was designed to investigate the acute effects of RV pacing on these parameters. METHODS: Ten patients with normal LV ejection fraction and VVI/DDD pacemaker were studied during AAI pacing/sinus rhythm without RV pacing (pacing-OFF) and with RV pacing (pacing-ON) at the same heart rate. Dynamic [15O]water and [11C]acetate positron emission tomography was used to measure perfusion and oxidative metabolism (kmono) of the LV. An echocardiographic examination was used to assess LV stroke volume (SV) and LV dyssynchrony. Myocardial efficiency of forward work was calculated as systolic blood pressure × cardiac output/LV mass/kmono. RESULTS: RV pacing decreased SV in all subjects (mean decrease 13%, from 76 ± 7 to 66 ± 7 ml, p = 0.004), but global perfusion and kmono were unchanged. The efficiency tended to be lower with pacing-ON (70 ± 20 vs 81 ± 21 mmHg l/g, p = 0.066). In patients with dyssynchrony during pacing (n = 6) efficiency decreased by 23% (from 78 ± 25 to 60 ± 14 mmHg l/g, p = 0.02), but in patients without dyssynchrony no change in efficiency was detected. Accordingly, heterogeneity in myocardial perfusion and oxidative metabolism was detected during pacing in patients with dyssynchrony but not in those without dyssynchrony. CONCLUSION: RV pacing resulted in a significant decrease in SV. However, deleterious effects on LV oxidative metabolism and efficiency were observed only in patients with dyssynchrony during RV pacing.

Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas).

PURPOSE: Carimas (Cardiac Image Analysis System) is a new software package developed at the Turku PET Centre for the quantitation of PET studies of the heart with a broad range of tracers. The goal of this study was to assess the reproducibility of results the package provides for myocardial perfusion (MP) quantitation using (15)O-labelled water. METHODS: Four observers with various levels of experience in nuclear medicine independently analysed 20 MP studies (10 rest flow: "rest", 10 adenosine-induced hyperaemia: "stress"). Each study was analysed twice. The linear mixed model for repeated measures was fitted to the data to calculate intraclass correlation coefficients (ICC), differences between the repeats (the intraobserver differences) and differences between the observers (the interobserver differences). Also, Pearson correlation coefficients (r) were calculated and Bland-Altman plots were drawn. The reproducibility of MP was assessed on global, regional and segmental levels. Thereafter, this analysis was applied in 48 consecutive clinical patients with suspected coronary heart disease (CHD). RESULTS: For the experienced observer the Pearson r for all segments was 0.974 at rest and 0.978 at stress (p < 0.0001), and the repeatability coefficients were 0.145 ml/g per min (15.5% of the average) and 0.389 ml/g per min (14.9%), correspondingly. The ICC reflected very good overall reproducibility. The intraobserver and interobserver differences were small, and the difference between the most and the least experienced observers at stress was 8.5% for the global MP. The clinical accuracy of the perfusion in the detection of CHD was excellent (positive predictive value 91% and negative predictive value 88%) against invasive angiography. CONCLUSION: The results demonstrate high reproducibility of myocardial perfusion quantitation with (15)O-labelled water PET using Carimas. The results support the feasibility of robust analysis and good clinical accuracy.

Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction.

AIMS: To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2-6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3-6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound. At 6 months, BMC group had a greater absolute increase of global LVEF than placebo group, measured either by angiography (mean +/- SD increase 7.1 +/- 12.3 vs. 1.2 +/- 11.5%, P = 0.05) or by 2-D echocardiography (mean +/- SD increase 4.0 +/- 11.2 vs. -1.4 +/- 10.2%, P = 0.03). No differences were observed between the groups in the adverse clinical events, arrhythmia risk variables, or the minimal lumen diameter of the stented coronary lesion. CONCLUSION: Intracoronary BMC therapy is associated with an improvement of global LVEF and neutral effects on arrhythmia risk profile and restenosis of the stented coronary lesions in patients after thrombolytic therapy of STEMI.

Heart failure in Finland: clinical characteristics, mortality, and healthcare resource use.

AIMS: The aims of this study were to describe patient characteristics of the adult chronic heart failure (HF) population and to estimate the prevalence, incidence, healthcare resource utilization (HCRU), and mortality associated with HF in Southwest Finland. METHODS AND RESULTS: This was a retrospective biobank and clinical registry study. Adult patients with an HF diagnosis (International Statistical Classification of Diseases and Related Health Problems (ICD) code I50) during 2004-2013 in secondary care were included in the study and compared with age-matched and gender-matched control patients without an I50 diagnosis. HF patients were stratified in groups by left ventricular ejection fraction (LVEF) as follows: LVEF < 40% [HF with reduced ejection fraction (HFrEF)]; LVEF ≥ 40% [HF with preserved ejection fraction (HFpEF)]; or unknown (LVEF unknown). HCRU was stratified by inpatient, outpatient, and emergency room visits. In 2013, the incidence of HF was 3.2/1000, and the prevalence was 13.9/1000 inhabitants (n = 15 594). In the stratified analysis of HF patients (n = 8833, average ± SD age 77.1 ± 11.2), 1115 (12.6%) patients had HFrEF (female 31.3%), 1449 (16.4%) had HFpEF (female 50.9%), and 6269 (71%) had unknown LVEF (female 52.1%). The most common co-morbidities were essential hypertension (58%), chronic elevated serum creatinine (57.3%), atrial fibrillation and flutter (55.1%), and chronic ischaemic heart disease (46.4%). Patients with HF diagnosis had higher HCRU compared with that of age-matched and gender-matched controls (3.7 more days per year at the hospital for HF patients compared with the controls). The total 5 year mortality was 62.6% for HF patients and 28.3% for controls, with higher age being the strongest predictor of mortality. Moreover, multivariable Cox regression analysis showed that patients with HFrEF had a 13% (95% confidence interval 2.7-25%) increased risk of mortality compared with HFpEF patients. CONCLUSIONS: The high mortality rate and HCRU among the studied HF patients highlight the severity of the disease and the economic and social burden on both patients and society. This calls for improved methods of care for this large patient population.

Is ventilatory efficiency (VE/VCO(2) slope) associated with right ventricular oxidative metabolism in patients with congestive heart failure?

BACKGROUND: The relationship between minute ventilation and the rate of CO2 elimination (VE/VCO2 slope) is associated with mortality in patients with congestive heart failure (CHF). The VE/VCO2 slope > or =34 denotes a poor prognosis and has been proposed to reflect abnormalities in pulmonary perfusion. AIMS: To study whether increased VE/VCO2 slope is associated with elevated right ventricular (RV) oxidative metabolism relative to the left ventricle (LV). METHODS: 21 patients with stable NYHA II-III CHF underwent symptom limited cardiopulmonary exercise testing. Dynamic [(11)C]acetate positron emission tomography (PET) was used to measure oxidative metabolism (k(mono)) of the LV and RV. Corrected RV oxidative metabolism (RVOx) was calculated as RV/LV k(mono) ratio. RESULTS: Peak VO2 was 16.2+/-4.1 ml/min/kg and the VE/VCO2 slope was 33.4+/-6.1. LV and RV k(mono) were 0.046+/-0.009 and 0.037+/-0.007 min(-1), respectively, with a RVOx of 0.83+/-0.17. There was a good correlation between RVOx and the VE/VCO2 slope (r=0.61, p=0.0034). RVOx was 0.77+/-0.16 in patients with a VE/VCO2 slope <34 and 0.93+/-0.16 in patients with VE/VCO2 slope > or =34 (p=0.047). CONCLUSION: RVOx correlates with VE/VCO2 slope in CHF patients. This supports the hypothesis that pulmonary vascular resistance is a determinant of the VE/VCO2 slope.

Effects of CRT on myocardial innervation, perfusion and metabolism.

Heart failure leads to specific changes in cardiac perfusion, metabolism, and innervation. Typically, in the early phase of heart failure, left ventricular (LV) efficiency of forward work is compromised and right ventricular oxidative metabolism increased while resting myocardial perfusion is normal. With advancing disease, LV perfusion and especially the perfusion reserve and oxidative metabolism also become compromised. In addition to the abnormalities linked with the heart failure itself, commonly co-existing left bundle branch block leads to striking, mainly regional imbalance in these parameters. Recent studies have documented that cardiac resynchronization therapy (CRT) has prominent effects on myocardial perfusion, metabolism, and innervation. Cardiac resynchronization therapy normalizes many of these parameters and these changes can be considered to be the signs of successful resynchronization. In contrast, a significant number of patients do not respond to CRT. Some of the metabolic parameters, such as existing glucose metabolism as a marker of viability as well as those related to right ventricle function, may also be linked to the response to CRT.

Myocardial fatty acid metabolism and cardiac performance in heart failure.

It is well established that cardiac metabolism is abnormal in heart failure (HF). Experimental studies suggest that in severe HF, cardiac metabolism reverts to a more fetal-like substrate use characterized by enhanced glucose and downregulated free fatty acid (FFA) metabolism. Correspondingly, in humans, when FFA levels are similar, myocardial glucose metabolism is increased, and FFA metabolism is decreased. However, depression of left ventricular function and insulin resistance induces a shift back to greater FFA uptake and oxidation by increasing circulating FFA availability. Myocardial insulin resistance may further impair myocardial glucose uptake and lead to an energy depletion state. Experimental and preliminary clinical studies suggest that metabolic modulators enhancing myocardial glucose oxidation may improve cardiac function in patients with chronic HF. However, it has been found that acute FFA deprivation is harmful to the cardiac performance. Optimizing myocardial energy metabolism may serve as an additional approach for managing HF, but further studies are warranted.