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.

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 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.

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.

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.

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.

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.

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.

Frequency and angiographic characteristics of coronary microvascular dysfunction in stable angina: a hybrid imaging study.

AIMS: Coronary microvascular dysfunction (CMD) can cause angina in the absence of obstructive coronary artery disease (CAD). We studied the frequency and angiographic characteristics of CMD in symptomatic patients with suspected stable CAD and identified CMD as diffusely abnormal coronary vasodilator capacity by positron emission tomography (PET) perfusion imaging. METHODS AND RESULTS: We recruited prospectively 189 patients with intermediate pre-test probability of CAD who underwent coronary computed tomography angiography and quantitative 15O-water PET perfusion imaging followed by invasive coronary angiography, and assessment of fractional flow reserve when feasible. Prevalence of obstructive epicardial CAD was 37%. Absolute myocardial blood flow was diffusely reduced (<2.4 mL/g/min) within the left ventricle during adenosine stress in 32 (17%) patients. In 15 (8%) patients, this was explained by three-vessel obstructive CAD, whereas the remaining 17 (9%) were diagnosed with CMD. Of these, 2 (1% of all patients) had no coronary atherosclerosis, 5 (3% of all patients) had non-obstructive atherosclerosis, and in 10 (5% of all patients) CMD co-existed with obstructive CAD. Atypical angina or non-anginal chest pain (53%) was the most common presentation. Older age and male sex were associated with CMD, but other risk factors of CAD were equally common in patients with or without CMD. CONCLUSION: Coronary microvascular dysfunction exists in 9% of symptomatic stable patients with suspected CAD. However, the prevalence of microvascular dysfunction without any coronary atherosclerosis is low (1%) in this population.

Prognostic Value of Coronary CT Angiography With Selective PET Perfusion Imaging in Coronary Artery Disease.

OBJECTIVES: The purpose of this study was to evaluate the prognostic value of sequential hybrid imaging strategy in which positron emission tomography (PET) perfusion imaging is performed selectively in patients with suspected obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA). BACKGROUND: Coronary CTA is an accurate diagnostic test for excluding obstructive CAD. However, the positive predictive value is suboptimal. METHODS: We investigated 864 consecutive symptomatic patients with intermediate probability of CAD who adhered to the sequential imaging approach. PET myocardial perfusion imaging using 15O-labeled water during adenosine stress was performed when suspected obstructive stenosis was present on coronary CTA. The major adverse events (AEs) including all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP) were recorded. RESULTS: During a median follow-up of 3.6 years, 16 deaths, 10 MIs, and 5 UAPs occurred. Obstructive CAD was excluded by coronary CTA in 462 (53%) patients who had significantly lower annual AE rate than did patients with suspected obstructive stenosis on coronary CTA (0.4% vs. 1.5%; p = 0.003). The latter underwent PET study, on which 195 (49%) had normal and 207 had abnormal perfusion. The annual rate of AEs was 5 times higher in those with abnormal perfusion than with normal perfusion (2.5% vs. 0.5%; p = 0.004). Patients with normal perfusion had AE rate comparable to patients without obstructive CAD on coronary CTA (p = 0.77). CONCLUSIONS: In patients with suspected CAD obstructive disease can be excluded in 53% of patients by coronary CTA, and these patients have good outcome. About one-half (49%) of the remaining patients have normal perfusion and event rate comparable to patients without obstructive CAD on coronary CTA while patients with ischemia have clearly worse outcome. Sequential approach utilizing anatomical imaging by coronary CTA followed by selective functional perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected CAD.

Life-course risk factor levels and coronary artery calcification. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Risk factors measured in early life have been shown to predict coronary artery calcium (CAC) in adulthood. However, limited data exist on when risk factor profiles of those who develop CAC diverge from those who do not. We investigated the associations of coronary heart disease risk factor trajectories beginning in adolescence and CAC measured at middle-age. METHODS: CAC was measured among 589 participants aged 39-45years in whom cardiovascular risk factors (serum lipids, blood pressure, body mass index, physical activity, smoking habits, and fruit, vegetable, fish, and butter intake) had been collected in 1980, 1983, 1986, 2001, and 2007 as part of the Cardiovascular Risk in Young Finns Study. RESULTS: Mean levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol, apolipoprotein B (Apo-B), and systolic blood pressure (SBP) levels across the 27-year period were significantly higher among those with CAC vs. those without. The difference between the groups was 0.25mmol/l (95% confidence interval, 95%CI, 0.079-0.41) for LDL-C, 0.26mmol/l (95%CI 0.080-0.44) for total cholesterol, 0.05mmol/l (95%CI 0.0085-0.091) for Apo-B and 1.92mmHg (95%CI 0.10-3.74) for SBP after adjustment for other risk factors. Those with CAC at age 39-45years had higher serum lipid levels already in adolescence or early adulthood compared with those without CAC, with these differences becoming more pronounced during the life-course. CONCLUSIONS: Long-time risk factor exposure to higher LDL-C, total cholesterol and Apo-B levels already starting in adolescence and higher SBP levels in adulthood is associated with CAC at middle-age.

Incidence of persistent renal dysfunction after contrast enhanced coronary CT angiography in patients with suspected coronary artery disease.

Contrast-induced nephropathy (CIN) is a potentially serious complication of contrast agents used in computed tomography angiography (CTA). The aim of this study was to evaluate whether persistent renal dysfunction occurs in patients undergoing coronary CTA for suspected stable coronary artery disease (CAD). From a cohort of 957 patients undergone coronary CTA, we identified 402 patients with plasma creatinine levels collected before and within 6 months after CTA. According to the definition of CIN, patients with a ≥25 % increase in plasma creatinine after CTA were evaluated. The post-CTA measurements in 402 patients (195 men, age 62.9 ± 9.3 years) were performed at a median of 99 days after CTA. On average, there was no change in plasma creatinine level between the pre- and post-CTA measurements (75.8 ± 16.0 and 75.7 ± 16.4 µmol/L, respectively; P = 0.63) but both increases and decreases were commonly detected. Fourteen (3.5 %) patients had a ≥25 % increase in plasma creatinine levels after CTA. A more detailed evaluation of these patients revealed that in 4 patients the increase was explained by other morbidities, whereas in 9 patients the creatinine level returned to the previous levels at later follow-up (median time to normalization: 311 days). Only in 1 (0.2 %) remaining patient, there was a persistent increase in plasma creatinine level, possibly related to the iodine contrast agent exposure. Alterations in plasma creatinine concentration occur frequently. Persistent renal dysfunction attributable to iodine contrast agent exposure is rare in patients referred to coronary CTA for suspected CAD.

Childhood Psychosocial Factors and Coronary Artery Calcification in Adulthood: The Cardiovascular Risk in Young Finns Study.

IMPORTANCE: There is increasing evidence supporting the importance of psychosocial factors in the pathophysiology of atherosclerotic disease. They have been shown to be associated with the population attributable risk for myocardial infarction. OBJECTIVE: To determine if a score of favorable childhood psychosocial factors would be associated with decreased coronary artery calcification in adulthood. DESIGN, SETTING, AND PARTICIPANTS: The analyses were performed in 2015 using data gathered in 1980 and 2008 within the longitudinal Cardiovascular Risk in Young Finns Study. The data source consisted of 311 individuals who had psychosocial factors measured at ages 12 years to 18 years and coronary artery calcification measured 28 years later in adulthood. The summary measure of psychosocial factors in childhood comprised measures of socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. MAIN OUTCOMES AND MEASURES: Coronary artery calcification at ages 40 years to 46 years. RESULTS: Of the 311 participants, 48.2% were men. Of the participants, 55 (17.7%) had some calcium observed in their coronary arteries. A 1-SD increase in a favorable summary score of childhood psychological factors was associated with an adulthood coronary artery calcification probability of 0.85 (95% CI, 0.76-0.95) (P = .006). This inverse relationship remained significant after adjustment for age, sex, and conventional childhood risk factors (0.85; 95% CI, 0.74-0.97; P = .02) or for age, sex, adulthood conventional cardiovascular risk factors, socioeconomic status, social support, and depressive symptoms (0.83; 95% CI, 0.71-0.97; P = .02). CONCLUSIONS AND RELEVANCE: In this longitudinal study, we observed an independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood. A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.

Coronary heart disease risk factors, coronary artery calcification and epicardial fat volume in the Young Finns Study.

AIMS: We investigated associations of pre-clinical coronary heart disease (CHD), adolescence and adulthood CHD risk factors, and epicardial fat volume (EFV), which is thought to influence CHD pathology. METHODS AND RESULTS: EFV and coronary calcium scores were quantified using computed tomography imaging for 557 subjects from the Cardiovascular Risk in Young Finns Study in 2007. CHD risk marker levels were assessed repeatedly from 1980 to 2007. Carotid intima-media thickness (cIMT), carotid distensibility, and brachial flow-mediated dilatation were measured by vascular ultrasound in 2007. Increased EFV was cross-sectionally associated with male sex, increased waist circumference, body-mass index (BMI), cIMT, metabolic syndrome prevalence, levels of apolipoprotein B, total cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, blood pressure, insulin, and fasting glucose, as well as ever smoking, alcoholic intake, and lower high-density lipoprotein cholesterol (HDL-C), carotid distensibility and physical activity in adulthood. In BMI-adjusted analyses, only apolipoprotein B, ever smoking, alcohol intake and metabolic syndrome prevalence were independently associated with EFV. In adolescence, skinfold thickness, BMI, and insulin levels were higher and HDL-C lower with increasing EFV. Subjects in the lowest vs. highest quarter of EFV had consistently lower BMI across the early life-course. CONCLUSION: Associations of CHD risk markers with EFV were attenuated after multivariable adjustment. We found no evidence of increased EFV being independently associated with pre-clinical atherosclerosis. EFV was most strongly associated with BMI and waist circumference. Subjects with higher EFV had consistently higher BMI from age 12 suggesting that life-long exposure to higher BMI influences the development of EFV.

Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

AIMS: Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. METHODS AND RESULTS: We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). CONCLUSION: Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD.

Absolute flow or myocardial flow reserve for the detection of significant coronary artery disease?

OBJECTIVES: We compared the accuracy of quantified myocardial flow reserve and absolute stress myocardial blood flow (MBF) alone in the detection of coronary artery disease (CAD). BACKGROUND: Myocardial flow reserve, i.e. ratio of stress and rest flow, has been commonly used to detect CAD with many imaging modalities. However, it is not known whether absolute stress flow alone is sufficient for detection of significant CAD. METHODS: We enrolled 104 patients with moderate (30-70%) pre-test likelihood of CAD without previous myocardial infarction. MBF was measured by positron emission tomography and O-15-water at rest and during the adenosine stress in the regions of the left anterior descending, left circumflex, and right coronary artery. All the patients underwent invasive coronary angiography including the measurement of fractional flow reserve when appropriate. RESULTS: Quantified myocardial flow reserve (optimal cut-off value 2.5) detected significant coronary stenosis with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 81, 87, 66 and 94%, respectively. When compared with flow reserve, absolute MBF at stress (optimal cut-off value of 2.4 mL/min/g) was more accurate in detecting significant coronary stenosis [area under the curve (AUC) 0.94 vs. 0.90, P = 0.02] with sensitivity, specificity, PPV, and NPV of 95% (P = 0.03 vs. flow reserve), 90, 73, and 98%, respectively. An absolute increase of MBF from rest to stress by <1.5 mL/g/min had also similar accuracy in detecting CAD (AUC: 0.95). The results were comparable in patients who did and did not receive i.v. beta-blockers prior imaging. CONCLUSIONS: Absolute stress perfusion alone was superior to perfusion reserve in the detection of haemodynamically significant CAD and allows shorter imaging protocols with smaller radiation dose.

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.

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial.

BACKGROUND: Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging. METHODS/DESIGN: This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry. DISCUSSION: AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative 'advanced' imaging technologies. TRIAL REGISTRATION: NCT01288560.