Myocardial T1 mapping by cardiac magnetic resonance imaging shows early myocardial changes in treatment-naive patients with active rheumatoid arthritis and positive autoantibodies.

OBJECTIVES: We aimed to study whether myocardial changes are already detectable by cardiac magnetic resonance (CMR) imaging at the time of rheumatoid arthritis (RA) diagnosis. METHODS: This single-centre prospective study included 39 treatment-naive patients with early rheumatoid arthritis (ERA, symptom duration <1 year) without any history of heart disease, and 38 age- and sex-matched healthy volunteers. The disease severity was assessed with clinical evaluation (Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score) and serological testing (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)). The ERA patients were classified into group A (DAS28-CRP score ≥3.2, positive RF and ACPA; n=17) and group B (not fulfilling the group A criteria). The ERA patients and healthy controls underwent 1.5T CMR. RESULTS: Group A patients had significantly higher myocardial global T1 relaxation times than the healthy controls, 987 [965, 1003] ms vs. 979 [960, 991] ms (median [IQR]; p=0.041). A significant difference in T1 was found in the basal, mid inferior and mid anterolateral segments. In a multivariate analysis, prolonged global T1 relaxation time was independently associated with female sex (95% CI [5.62, 51.31] ms, p=0.016), and group A status (95% CI [4.65, 39.01] ms p=0.014). CONCLUSIONS: At the time of diagnosis, ERA patients with a higher disease activity (DAS28-CRP score ≥3.2) and both positive RF and ACPA showed prolonged T1 relaxation times in basal myocardial segments. These segments could be most susceptible to the development of myocardial fibrosis, and a segmental reporting style could be useful when estimating the first signs of myocardial fibrosis.

Safe Deferral of Coronary Computed Tomography Angiography for Patients With a Low Pretest Probability of Coronary Artery Disease in 2019 European Society of Cardiology Guidelines.

BACKGROUND: Coronary computed tomography angiography is increasingly used as the first-line test for suspected coronary artery disease. Its overuse in a low pretest probability (PTP) population may lead to low diagnostic yield without change in patient management. We evaluated the clinical consequences of the updated 2019 European Society of Cardiology (ESC) chronic coronary syndromes guidelines' PTP estimation and whether imaging could be safely deferred in patients with a low PTP. METHODS AND RESULTS: This retrospective cohort included all 1753 consecutive patients who underwent coronary computed tomography angiography for suspected coronary artery disease at Helsinki University Hospital between 2009 and 2017. PTP was calculated according to the 2013 and 2019 ESC guidelines. The overall mortality, cardiac deaths, myocardial infarctions, and hospitalizations for unstable angina were acquired from national registry data for 1 to 10 years of follow-up (median, 4 years). Updated 2019 ESC guidelines classified 72% of the patients as having low PTP, whose imaging could have been deferred. The revascularization rate (4.7%) and annual cardiac mortality (0.4%) were low in the 857 patients reclassified from the recommendation to test, according to the 2013 ESC guideline, to deferral of coronary computed tomography angiography, according to the new 2019 guideline. CONCLUSIONS: The updated 2019 ESC guideline PTP score aids clinicians in safely preventing the overuse of cardiac imaging in patients deemed at low PTP of coronary artery disease. Diagnostic yield, revascularization rate, and cardiac mortality are low in patients with low pretest risk.

DSP c.6310delA p.(Thr2104Glnfs*12) associates with arrhythmogenic cardiomyopathy, increased trabeculation, curly hair, and palmoplantar keratoderma.

Background: Pathogenic variants in DSP associate with cardiac and cutaneous manifestations including arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, curly or wavy hair, and palmoplantar keratoderma (PPK). Episodes of myocardial inflammation associated with DSP cardiomyopathy might be confused in clinical work with myocarditis of other etiologies such as viral. Cardiac magnetic resonance imaging (CMR) may help in differential diagnosis. Methods and results: This study comprised 49 Finnish patients: 34 participants from families with suspected DSP cardiomyopathy (9 index patients and 25 family members) and 15 patients with myocarditis. All 34 participants underwent genetic testing and cardiac evaluation, and 29 of them also underwent CMR. Participants with the DSP variant, numbering 22, were dermatologically examined. The 15 patients with myocarditis underwent CMR and were evaluated during their hospitalization.A heterozygous truncating DSP c.6310delA p.(Thr2104Glnfs*12) variant was confirmed in 29 participants. Only participants with the DSP variant had pacemakers and life-threatening ventricular arrhythmias. Of the participants with the DSP variant, 24% fulfilled cardiomyopathy criteria, and the median age at diagnosis was 53. Upon CMR, myocardial edema was found to be more common in patients with myocarditis. Both groups had a substantial percentage of late gadolinium enhancement (LGE). A ring-like LGE and increased trabeculation were observed only in participants with the DSP variant. All the studied participants with the DSP variant had PPK and curly or wavy hair. Hyperkeratosis developed before the age of 20 in most patients. Conclusions: The DSP c.6310delA p.(Thr2104Glnfs*12) variant associates with curly hair, PPK, and arrhythmogenic cardiomyopathy with increased trabeculation. Cutaneous symptoms developing in childhood and adolescence might help recognize these patients at an earlier stage. CMR, together with dermatologic characteristics, may help in diagnosis.

Cardiac magnetic resonance -detected myocardial injury is not associated with long-term symptoms in patients hospitalized due to COVID-19.

BACKGROUND: Long-term symptoms are frequent after coronavirus disease 2019 (COVID-19). We studied the prevalence of post-acute myocardial scar on cardiac magnetic resonance imaging (CMR) in patients hospitalized due to COVID-19 and its association with long-term symptoms. MATERIALS AND METHODS: In this prospective observational single-center study, 95 formerly hospitalized COVID-19 patients underwent CMR imaging at the median of 9 months after acute COVID-19. In addition, 43 control subjects were imaged. Myocardial scar characteristic of myocardial infarction or myocarditis were noted from late gadolinium enhancement images (LGE). Patient symptoms were screened using a questionnaire. Data are presented as mean ± standard deviation or median (interquartile range). RESULTS: The presence of any LGE was higher in COVID-19 patients (66% vs. 37%, p<0.01) as was the presence of LGE suggestive of previous myocarditis (29% vs. 9%, p = 0.01). The prevalence of ischemic scar was comparable (8% vs. 2%, p = 0.13). Only two COVID-19 patients (7%) had myocarditis scar combined with left ventricular dysfunction (EF <50%). Myocardial edema was not detected in any participant. The need for intensive care unit (ICU) treatment during initial hospitalization was comparable in patients with and without myocarditis scar (47% vs. 67%, p = 0.44). Dyspnea, chest pain, and arrhythmias were prevalent in COVID-19 patients at follow-up (64%, 31%, and 41%, respectively) but not associated with myocarditis scar on CMR. CONCLUSIONS: Myocardial scar suggestive of possible previous myocarditis was detected in almost one-third of hospital-treated COVID-19 patients. It was not associated with the need for ICU treatment, greater symptomatic burden, or ventricular dysfunction at 9 months follow-up. Thus, post-acute myocarditis scar on COVID-19 patients seems to be a subclinical imaging finding and does not commonly require further clinical evaluation.

Peak flow measurements in patients with severe aortic stenosis: a prospective comparative study between cardiovascular magnetic resonance 2D and 4D flow and transthoracic echocardiography.

BACKGROUND: Aortic valve stenosis (AS) is the most prevalent valvular disease in the developed countries. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is an emerging imaging technique, which has been suggested to improve the evaluation of AS severity compared to two-dimensional (2D) flow and transthoracic echocardiography (TTE). We investigated the reliability of CMR 2D flow and 4D flow techniques in measuring aortic transvalvular peak systolic flow in patients with severe AS. METHODS: We prospectively recruited 90 patients referred for aortic valve replacement due to severe AS (73.3 ± 11.3 years, aortic valve area 0.7 ± 0.1 cm2, and 54/36 tricuspid/bicuspid), and 10 non-valvular disease controls. All the patients underwent echocardiography and 2D flow and 4D flow CMR. Peak flow velocity measurements were compared using Wilcoxon signed rank sum test and Bland-Altman analysis. RESULTS: 4D flow underestimated peak flow velocity in the AS group when compared with TTE (bias - 1.1 m/s, limits of agreement ± 1.4 m/s) and 2D flow (bias - 1.2 m/s, limits of agreement ± 1.6 m/s). The differences between values obtained by TTE (median 4.3 m/s, range 2.7-6.1 m/s) and 2D flow (median 4.5 m/s, range 2.9-6.5 m/s) compared to 4D flow (median 3.1 m/s, range 1.7-5.1 m/s) were significant (p < 0.001). The difference between 2D flow and TTE were insignificant (bias 0.07 m/s, limits of agreement ± 1.5 m/s). In non-valvular disease controls, peak flow velocity was measured higher by 4D flow than 2D flow (1.4 m/s, 1.1-1.7 m/s and 1.3 m/s, 1.1-1.5 m/s, respectively; bias 0.2 m/s, limits of agreement ± 0.16 m/s). CONCLUSIONS: CMR 4D flow significantly underestimates systolic peak flow velocity in patients with severe AS. 2D flow, in turn, estimated the AS velocity accurately, with measured peak flow velocities comparable to TTE.

Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome.

BACKGROUND: Several clinical risk estimation tools have established their role in the prediction of recurrence of acute coronary syndrome (ACS), but the value of genetic risk scores (GRSs) remains unclear. We examined how well 2 different GRSs estimate recurrent ACS and whether clinical factors are associated with GRSs. METHODS AND RESULTS: A cohort of 2090 consecutive patients with ACS who underwent coronary angiography between July 2006 and March 2008 in a single tertiary center was genotyped and prospectively followed up for a median of 5.5 years. We formed 2 partially overlapping GRSs: GRS47 of 47 single-nucleotide polymorphisms with previously reported significant association with coronary artery disease and GRS153 of 153 single-nucleotide polymorphisms with significant or suggestive association with coronary artery disease. GRS47 showed association with recurrent ACS independent of clinical factors (P=0.037; hazard ratio, 1.17; 95% confidence interval, 1.01-1.36). GRS153 had no association with either recurrent ACS or composite of recurrent ACS or death. Also, GRS47 was associated inversely with smoking and ST-segment-elevation myocardial infarction (P=0.004; odds ratio, 0.22; 95% confidence interval, 0.08-0.62 and P=0.041; odds ratio, 0.36; 95% confidence interval, 0.13-0.96, respectively). CONCLUSIONS: GRSs combined of 47 known coronary artery disease risk single-nucleotide polymorphisms were associated with recurrent ACS after multivariable adjustments in a heterogenic ACS population for the first time. Smoking and ST-segment-elevation myocardial infarction had an inverse association with the GRSs. The significance of smoking in relation to genetic coronary artery disease predisposition may merit further evaluation in patients with ACS.

Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population.

Myocardial infarction (MI) is divided into either ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI), differing in a number of clinical characteristics. We sought to identify genetic variants conferring risk to NSTEMI or STEMI by conducting a genome-wide association study (GWAS) of MI stratified into NSTEMI and STEMI in a consecutive sample of 1,579 acute MI cases with 1,576 controls. Subsequently, we followed the results in an independent population-based sample of 562 cases and 566 controls, a partially independent prospective cohort (N = 16,627 with 163 incident NSTEMI cases), and examined the effect of disease-associated variants on gene expression in 513 healthy participants. Genetic variants on chromosome 1p13.3 near the damage-regulated autophagy modulator 2 gene DRAM2 associated with NSTEMI (rs656843; odds ratio 1.57, P = 3.11 × 10(-10)) in the case-control analysis with a consistent but not statistically significant effect in the prospective cohort (rs656843; hazard ratio 1.13, P = 0.43). These variants were not associated with STEMI (rs656843; odds ratio, 1.11, P = 0.20; hazard ratio 0.97, P = 0.87), appearing to have a pronounced effect on NSTEMI risk. A majority of the variants at 1p13.3 associated with NSTEMI were also associated with the expression level of DRAM2 in blood leukocytes of healthy controls (top-ranked variant rs325927, P = 1.50 × 10(-12)). The results suggest that genetic factors may in part influence whether coronary artery disease results in NSTEMI rather than STEMI.

Differences in ST-elevation and T-wave amplitudes do not reliably differentiate takotsubo cardiomyopathy from acute anterior myocardial infarction.

BACKGROUND: Previous efforts to distinguish acute anterior ST-elevation myocardial infarction (anterior-STEMI) from various forms of takotsubo cardiomyopathy (TTC) by electrocardiography (ECG) have produced differing results. METHODS: We performed a retrospective comparison of acute ECGs between 48 apical and 9 mid-ventricular TTC patients, with 96 anterior-STEMI patients. ECG was recorded in acute phase (<24h from onset of pain), and analyzed for ST-changes, negative T-waves, abnormal Q-waves and QT-interval duration. Time from onset of pain to ECG was gathered from patient records. RESULTS: Anterior-STEMI patients had ST-elevation in lead V1 more frequently than apical (70% vs 15%, p<0.0001) or mid-ventricular TTC patients (70% vs 0%, p<0.0001), and higher ST-elevation amplitudes in leads V2-V5 (p<0.02). Lack of ST-elevation in lead V1 and ST-elevation amplitude <2mm in lead V2 distinguished TTC from anterior-STEMI patients with 63% sensitivity and 93% specificity, with 79% predictive value. CONCLUSIONS: In patients with anterior ST-elevation and acute chest pain, lack of ST-elevation in lead V1 and ST-elevation amplitude <2mm in lead V2 suggests a TTC diagnosis. However, this criterion is not reliable enough in clinical practice to distinguish between TTC and anterior-STEMI patients.

Mortality rate increases steeply with nonadherence to statin therapy in patients with acute coronary syndrome.

BACKGROUND: In a prospective cohort of consecutive acute coronary syndrome (ACS) patients, we compared the adherence rate of statin usage and mortality rate during a median follow-up of 23 months. HYPOTHESIS: Adherence to statin therapy after acute coronary syndrome affects mortality rate. METHODS: We analyzed ACS patients (N = 1969; age, 65.9 ± 11.8 years; female 30.4%) who underwent angiography between March 2006 and March 2008. The postdischarge usage of statins was based on the purchase register of the Social Insurance Institution of Finland. The death rate was verified from Statistics Finland. RESULTS: At discharge, the rate of statin prescription to patients was 95.4% (n = 1878). When comparing adherent patients (n = 1200; 61.7%), who purchased the medication systematically until the end of the median 23-month follow-up, with nonadherent patients (n = 94; 4.8%), who did not use the medication at all, there was a vast difference in absolute death rate between the groups: 4.9% vs 14.9%, respectively (P < 0.001). We conducted Cox proportional hazards model with ACS type, cerebrovascular attack, diabetes, age, 3-artery disease, and cancer as adjusted confounders. Compared with regular statin users, nonusers were associated with a >2× increased hazard ratio of mortality (hazard ratio: 2.70, 95% confidence interval: 1.49-4.90, P = 0.001). CONCLUSIONS: Statin medication is essential for discharged ACS patients. They should be strongly encouraged to purchase and use it.

Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population.

OBJECTIVE: The effect of polymorphisms of the vitamin D receptor (VDR) gene on susceptibility to type 1 diabetes has recently been investigated extensively. Several findings on positive disease associations have been observed and, in addition, a protective effect of vitamin D supplementation has been reported. DESIGN: We studied the effect of three vitamin D receptor gene polymorphisms (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control series (more than 2000 controls and about 1000 patients) from the Finnish population. METHODS: A combination of case-control and affected-family based approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction. RESULTS: A few borderline significant associations were observed with both approaches used. In the case-control association analyses we found significant differences between cases and controls in frequencies of VDRB (P=0.024, all subjects and P=0.016, HLA DQB1*0302-positive subjects) and VDRF (P=0.0063, Turku cohort). In the total family set a decreased (39.3%) transmission of the VDRA-VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1-2 to sons was seen (P=0.0059 and P=0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P=0.022). Interestingly, we also observed significant differences in allele frequencies of the polymorphisms studied between populations from three different regions in Finland. CONCLUSIONS: All these differences disappeared after correction for multiple testing. We conclude that the single nucleotide polymorphisms analysed are unlikely to be associated with type 1 diabetes in the Finnish population.