Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Amiodarone accumulates two cholesterol precursors in myocardium: A controlled clinical study.

BACKGROUND: Amiodarone is an effective antiarrhythmic drug, which interferes with cholesterol synthesis. In the human body, it inhibits two enzymes in the cholesterol-synthesis pathway, followed by increases especially in serum desmosterol and zymostenol concentrations and a decrease in that of serum lathosterol. OBJECTIVES: We explored whether desmosterol and zymostenol accumulate also in myocardial tissue during amiodarone treatment. METHODS: Thirty-three patients admitted for cardiac transplantation volunteered for the study. Ten patients were on amiodarone treatment (AD group) and 23 were not (control group). The groups were matched as regards demographic and clinical variables. Myocardial samples were obtained from the removed hearts from 31 patients. Cholesterol, non-cholesterol sterols and squalene were quantified by means of gas-liquid chromatography. RESULTS: In serum and myocardium, desmosterol was 19- and 18-fold higher and zymostenol 4- and 2-fold higher in the AD group versus the control group (p < 0.001 for all). In contrast, myocardial cholesterol, squalene and lathosterol levels were lower in the AD group than in the control group (p < 0.05 for all). Levels of phytosterols and cholestanol were similar in the serum and myocardium in the two groups. Levels of myocardial and serum desmosterol, zymostenol, lathosterol and phytosterols correlated with each other in both groups (p < 0.05 for all). CONCLUSION: Amiodarone treatment caused the accumulation of desmosterol and zymostenol in myocardium. In particular, myocardial desmosterol concentrations were substantially elevated, which may play a part in some of the therapeutic and adverse effects of amiodarone treatment.

Long-term improvement of symptoms of angina pectoris after successful revascularization of coronary artery chronic total occlusions.

Objectives. To compare long-term angina pectoris relief of successful versus failed percutaneous coronary intervention of chronic total occlusions (CTO PCI). Background. Previous studies demonstrate better short-term angina pectoris relief of CTO PCI than with optimal medical treatment (OMT), however, data on the long-term effects are lacking. Methods. 295 patients undergoing CTO PCI were analyzed retrospectively, with a follow-up evaluation of symptoms of angina pectoris and all-cause death one to four years after the intervention. The primary outcome was long-term relief of symptoms of angina pectoris. Secondary outcomes included a composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and later target vessel revascularization (TVR). At follow-up, patients were interviewed for symptoms of angina pectoris at 1, 6, 12, and 22 to 48 months after the intervention. Results. CTO PCI was successful in 225 (76%) patients and failed in 70 (24%) patients. Short-term (six months) relief of angina pectoris was observed in both groups, but only the successful CTO PCI group showed long-term relief. The Kaplan-Meier curves of all-cause death did not differ between the groups (p = .715). The final follow-up was a mean (range) of 37 (25 to 44) months after the intervention in the successful CTO PCI group, and 33 (28 to 48) months in the failed CTO PCI group. Conclusions. Successful CTO PCI is associated with better long-term relief of symptoms of angina pectoris compared to failed CTO PCI.

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.

A method for measuring the angle between left atrial and left ventricular long axes using 3D echocardiography.

BACKGROUND: Left ventricle (LV) optimized views are routinely used for left atrial (LA) volume and strain measurements on 2D echocardiography. This might be a source of the error because of the variation of the angle between the left atrial and left ventricle long axes (LA-LV angle), leading to foreshortening of the LA. METHODS: We investigated two novel parameters: the angle between the left atrial and left ventricle long axes (LA-LV angle) and its deviation from the 4-chamber plane. To accurately measure the angles in 3D space, these measurements were performed using 3D echocardiography. We developed a method for the measurement based on marking anatomic points of reference in the 3D echocardiogram and measuring the angles between these points. We used three types of phantoms made of wood and agar-agar to investigate the repeatability and reproducibility of these measurements and performed measurements on human subjects. RESULTS: The ultrasound measurements were in excellent agreement with the true angles of the phantoms: LA-LV angle bias was .5 degrees (95% CI -1.8 to +2.7) in the wooden phantoms and 1.2 degrees (-.7 to +3.1) in the agar-agar phantoms, while the angle deviation from the 4-chamber plane was -.9 degrees (-4.3 to +4.1) in the wooden phantoms and .0 degrees (-3.3 to +3.3) in the agar-agar phantoms. The measurements demonstrated good repeatability and reproducibility (Pearson correlation coefficients ranging from .91 to .99). The measurements from human hearts showed good repeatability (Pearson correlation was .81 for repeated LA-LV angle measurements and .97 for repeated measurements of the deviation from the 4-chamber plane). CONCLUSION: The measurement of the LA-LV angle is a feasible tool to investigate one eventual error of 2D echocardiography.

Statin use improves survival of patients with known or suspected lower extremity artery disease on all ankle brachial index levels.

Background: Statin medication improves the prognosis of patients with lower extremity artery disease (LEAD). Research has previously focused on patients with a lowered ankle brachial index (ABI) excluding patients with a normal or elevated ankle brachial index. The aim of this study was to analyze the impact of statin use on survival and cardiovascular mortality in patients with LEAD of different severity depicted by the ABI level. Patients and methods: 4128 ABI measurements by trained and experienced nurses between 2000 and 2009 were combined with medication data from the Social Insurance Institution and causes of death data from the national causes of death registry. End of follow-up was set at the end of 2014. The data of statin use included all statin medication with the Anatomical Therapeutic Chemical (ATC) classification codes between C10AA01 and C10AA08. Results: 1956 (47.4%) patients had statin medication. Statin use was associated with improved overall survival and amputation free survival (AFS) on all ABI levels. When adjusted for age, sex and diabetes the greatest overall survival benefit from statin use was for the patients with ABI>1.3 (hazard ratio, HR: 0.67, 95% CI: 0.48-0.94, p=0.020, reference group statin non-users) and ABI 0.9-1.3 (HR: 0.78, 95% CI: 0.65-0.94, p=0.008). In propensity score matched pairs statin treatment was associated with significantly lower all-cause mortality (p<0.0001), cardiovascular mortality (p=0.034), cerebrovascular mortality (p=0.003) and embolic stroke related mortality (p=0.001) in patients with ABI >1.3 or <0.9. Overall survival benefit was significant in females with ABI<0.5 and in males across several ABI levels. Conclusions: According to our study, statins seem to improve overall and amputation free survival regardless of ABI level. Statin use was associated with lower mortality from cerebrovascular disease, overall mortality and in the propensity score matched patients with ABI<0.9 or >1.3 with cardiovascular mortality.

MiR-185-5p regulates the development of myocardial fibrosis.

BACKGROUND: Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis. METHODS AND RESULTS: Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p. Analysis of resident cardiac cells from mice subjected to experimental cardiac fibrosis model showed induction of miR-185-5p expression specifically in cardiac fibroblasts. In vitro, augmenting miR-185-5p induced collagen production and profibrotic activation in cardiac fibroblasts, whereas inhibition of miR-185-5p attenuated collagen production. In vivo, targeting miR-185-5p in mice abolished pressure overload induced cardiac interstitial fibrosis. Mechanistically, miR-185-5p targets apelin receptor and inhibits the anti-fibrotic effects of apelin. Finally, analysis of left ventricular tissue from patients with severe cardiomyopathy showed an increase in miR-185-5p expression together with pro-fibrotic TGF-ß1 and collagen I. CONCLUSIONS: Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial.

BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. OBJECTIVE: The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). METHODS AND ANALYSIS: Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. CONCLUSIONS: The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

Magnetic resonance imaging safety in patients with abandoned or functioning epicardial pacing leads.

OBJECTIVES: The European Society of Cardiology Guidelines on cardiac pacing from 2021 allow magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices (CIEDs) but do not recommend MRI in patients with epicardial pacing leads. The clinical dilemma remains whether performing an MRI in patients with CIED and epicardial leads is safe. We aimed to evaluate the safety of performing an MRI in patients with CIED and abandoned or functioning epicardial pacing leads. METHODS: We included all adult patients who underwent clinically indicated MRIs with CIED and functioning or abandoned epicardial leads in a single tertiary hospital between November 2011 and October 2019. The data were retrospectively collected. RESULTS: Twenty-six MRIs were performed on 17 patients with functioning or abandoned epicardial pacing leads. Sixty-nine percent of the MRI scans (18/26) were conducted on patients with functioning epicardial pacing leads. A definite adverse event occurred in one MRI scan. This was a transient elevation of the pacing threshold in a patient with a functioning epicardial ventricular pacing lead implanted 29 years previously. An irreversible atrial pacing lead impedance elevation was detected 6 months after the MRI in another patient; the association with the previous MRI remained unclear. No adverse events were detected in MRIs performed on patients with modern (implanted in 2000 or later) functioning epicardial leads. CONCLUSIONS: MRIs in patients with CIED and modern functioning epicardial pacing leads were performed without detectable adverse events. Further large-scale studies are necessary to confirm MRI safety in patients with epicardial pacing leads. KEY POINTS: • Currently, MRI in patients with cardiac implantable electronic devices (CIEDs) and functioning or abandoned epicardial pacing leads is not recommended. • MRIs in patients with CIED and modern functioning epicardial leads (implanted in 2000 or later) were performed without detectable adverse events in our patient cohort. • Allowing MRI in patients with epicardial pacing leads may significantly improve the diagnostic work-up, especially in specific patient groups, such as patients with congenital heart disease.

Orientation of the Atrial Septum to the Inferior Vena Cava May Contribute to the Persistent Patency of the Foramen Ovale.

PURPOSE: There is growing evidence that paradoxical embolism through patent foramen ovale (PFO) is a cause for cryptogenic stroke. However, it is still unclear why the foramen ovale fails to close after birth. We studied whether the 3D relations between the atrial septum (AS) and the inferior vena cava (IVC) are associated with PFO. METHODS: We recruited 30 patients (18-49 years) with a first-ever cryptogenic stroke and 30 age- and sex-matched stroke-free controls. Using cardiac magnetic resonance, an approach to evaluate the 3D relations between the AS and the IVC was developed. The presence of interatrial right-to-left shunt was evaluated with transesophageal echocardiography (TEE) in patients and transcranial Doppler in controls. RESULTS: Of 30 patients, 29 underwent successful TEE, of which 12 (41%) had a shunt. Patients with a shunt had a greater mean 3D angle (γ) between the atrial septal plane and the vector from the orifice of the IVC to the middle of the AS compared with patients without a shunt (45 ± 9° vs. 36 ± 8°, p = 0.017). Of 30 controls, 12 (40%) had a shunt and a greater mean γ compared with controls without a shunt (47 ± 8° vs. 37 ± 10°, p = 0.007). In a pooled analysis, 24 (41%) of 59 subjects with a shunt had a mean γ of 46 ± 9° compared with subjects without a shunt of 37 ± 9° (p < 0.001). CONCLUSIONS: More perpendicular orientation of the atrial septal plane to the orifice of the IVC is associated with PFO, possibly by directing the IVC flow to PFO.

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease.

BACKGROUND: Clinical implications of different types of vascular calcification are poorly understood. The two most abundant forms of calcification, nodular and sheet calcification, have not been quantitatively analyzed in relation to the clinical presentation of lower extremity arterial disease (LEAD). METHODS: The study analyzed 51 femoral artery plaques collected during femoral endarterectomy, characterized by the presence of > 90% stenosis. Comprehensive clinical data was obtained from patient records, including magnetic resonance angiography (MRA) images, toe pressure and ankle brachial index measurements and laboratory values. The plaques were longitudinally sectioned, stained with Hematoxylin and Eosin and digitized in a deep learning platform for quantification of the relative area of nodular and sheet calcification to the plaque section area. A deep learning artificial intelligence algorithm was designed and independently validated to reliably quantify nodular calcification and sheet calcification. Vessel measurements and quantity of each calcification category was compared to the risk factors and clinical presentation. RESULTS: On average, > 90% stenosed vessels contained 22.4 ± 12.3% of nodular and 14.5 ± 11.8% of sheet calcification. Nodular calcification area proportion in lesions with > 90% stenosis is associated with reduced risk of critically low toe pressure (< 30 mmHg) (OR = 0.910, 95% CI = 0.835-0.992, p < 0.05), severely lowered ankle brachial index (< 0.4) (OR = 0.912, 95% CI = 0.84-0.986, p < 0.05), and semi-urgent operation (OR = 0.882, 95% CI = 0.797-0.976, p < 0.05). Sheet calcification did not show any significant association. CONCLUSIONS: Large amount of nodular calcification is associated with less severe LEAD. Patients with nodular calcification may have better flow reserves despite local obstruction.

Salivary IgA antibody to malondialdehyde-acetaldehyde associates with mild periodontal pocket depth.

OBJECTIVE: Oxidized epitopes such as malondialdehyde-acetaldehyde (MAA) play a crucial role in the progression of atherosclerosis through activation of the humoral immune response. The exact mechanism of the association between atherosclerosis and periodontal diseases is not fully understood. The aim of the current study is to evaluate the association of oral humoral immune response to oxidized epitopes with parameters of periodontal disease. MATERIALS AND METHODS: The Parogene cohort consist of patients who have undergone coronary angiography due to cardiac symptoms. In this study, 423 patients were randomly selected for an extensive oral examination. Salivary Immunoglobulin A to oxidized epitopes and bacterial antigens was determined by chemiluminescence immunoassay. RESULTS: In a binary logistic regression model adjusted with periodontal disease confounders, periodontal pocket depth (PPD) 4-5 mm associated with salivary IgA antibodies to MAA-LDL (p = 0.034), heat shock protein 60 of Aggregatibacter actinomycetemcomitans (p = 0.045), Porphyromonas gingivalis (p = 0.045), A. actinomycetemcomitans (p = 0.005), P. intermedia (p = 0.020), and total IgA (p = 0.003). CONCLUSIONS: The current study shows the association of salivary IgA to MAA-LDL with PPD 4-5 mm in a cohort of patients with chronic coronary artery disease. Humoral immune cross-reactivation to oxidized epitopes such MAA-LDL could partly explain the link of periodontitis with systemic diseases.

Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure.

Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the expression and activation of TNKSs in myocardium of IHF patients and MI rats. We explored the cardioprotective effect of TNKS inhibition in an isoproterenol-induced zebrafish HF model. In IHF patients, we observed elevated TNKS2 and DICER and concomitant upregulation of miR-34a-5p and miR-21-5p in non-infarcted myocardium. In a rat MI model, we found augmented TNKS2 and DICER in the border and infarct areas at the early stage of post-MI. We also observed consistently increased TNKS1 in the border and infarct areas and destabilized AXIN in the infarct area from 4 weeks onward, which in turn triggered Wnt/ß-catenin signaling. In an isoproterenol-induced HF zebrafish model, inhibition of TNKS activity with XAV939, a TNKSs-specific inhibitor, protected against ventricular dilatation and cardiac dysfunction and abrogated overactivation of Wnt/ß-catenin signaling and dysregulation of miR-34a-5p induced by isoproterenol. Our study unravels a potential role of TNKSs in the pathogenesis of IHF by regulating Wnt/ß-catenin signaling and possibly modulating miRNAs and highlights the pharmacotherapeutic potential of TNKS inhibition for prevention of IHF.

Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study.

BACKGROUND AND PURPOSE: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. METHODS: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. RESULTS: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). CONCLUSIONS: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Toe pressure should be part of a vascular surgeon's first-line investigation in the assessment of lower extremity artery disease and cardiovascular risk of a patient.

OBJECTIVE: Toe pressure (TP) is an accurate indicator of the peripheral vascular status of a patient and thus cardiovascular risk, with less susceptibility to errors than ankle-brachial index (ABI). This study aimed to analyze how ABI and TP measurements associate with overall survival and cardiovascular death and to analyze the TP of patients with ABI of 0.9 to 1.3. METHODS: The first ABI and TP measurements of a consecutive 6784 patients treated at the Helsinki University Hospital vascular surgery clinic between 1990 and 2009 were analyzed. Helsinki University Vascular Registry and the national Cause of Death Registry provided the data. RESULTS: The poorest survival was in patients with ABI >1.3 (10-year survival, 15.3%; hazard ratio, 2.2; 95% confidence interval, 1.9-2.6; P < .0001; reference group, ABI 0.9-1.3), followed by the patients with TP <30 mm Hg (10-year survival, 19.6%; hazard ratio, 2.0; 95% confidence interval, 1.7-2.2; P < .0001; reference group, TP ≥80 mm Hg). The best 10-year survival was in patients with TP ≥80 mm Hg (43.9%). Of the 642 patients with normal ABI (0.9-1.3), 18.7% had a TP <50 mm Hg. The highest cardiovascular death rate (64.6%) was in the patients with TP <30 mm Hg, and it was significantly lower than for the patients with TP >50 mm Hg. CONCLUSIONS: Low TP is associated significantly with survival and cardiovascular mortality. Patients with a normal ABI may have lower extremity artery disease (LEAD) and a considerable risk for a cardiovascular event. If only the ABI is measured in addition to clinical examination, a substantial proportion of patients may be left without LEAD diagnosis or adequate treatment of cardiovascular risk factors. Thus, especially if ABI is normal, LEAD is excluded only if TPs are also measured and are normal.

Revisiting left atrial volumetry by magnetic resonance imaging: the role of atrial shape and 3D angle between left ventricular and left atrial axis.

BACKGROUND: Accurate measurement of left atrial (LA) volumes is needed in cardiac diagnostics and the follow up of heart and valvular diseases. Geometrical assumptions with 2D methods for LA volume estimation contribute to volume misestimation. In this study, we test agreement of 3D and 2D methods of LA volume detection and explore contribution of 3D LA axis orientation and LA shape in introducing error in 2D methods by cardiovascular magnetic resonance imaging. METHODS: 30 patients with prior first-ever ischemic stroke and no known heart disease, and 30 healthy controls were enrolled (age 18-49) in a substudy of a prospective case-control study. All study subjects underwent cardiac magnetic resonance imaging and were pooled for this methodological study. LA volumes were calculated by biplane area-length method from both conventional long axis (LAVAL-LV) and LA long axis-oriented images (LAVAL-LA) and were compared to 3D segmented LA volume (LAVSAX) to assess accuracy of volume detection. 3D orientation of LA long axis to left ventricular (LV) long axis and to four-chamber plane were determined, and LA 3D sphericity indices were calculated to assess sources of error in LA volume calculation. Shapiro-Wilk test, Bland-Altman analysis, intraclass and Pearson correlation, and Spearman's rho were used for statistical analysis. RESULTS: Biases were - 9.9 mL (- 12.5 to - 7.2) for LAVAL-LV and 13.4 (10.0-16.9) for LAVAL-LA [mean difference to LAVSAX (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 ± 6.2° [mean ± SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 ± 18.0°. 3D orientation of LA axis or 3D sphericity were not correlated to error in LA volume calculation. CONCLUSIONS: Calculated LA volume accuracy did not improve by using LA long axis-oriented images for volume calculation in comparison to conventional method. We present novel data on LA axis orientation and a novel metric of LA sphericity and conclude that these measures cannot be utilized to assess error in LA volume calculation. TRIAL REGISTRATION: Main study Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) has been registered previously.

Evidence of subtle left ventricular systolic dysfunction in cryptogenic stroke in the young.

INTRODUCTION: Ischemic stroke in young patients often remains cryptogenic, that is, no underlying reason can be found. Some of these strokes may originate in the heart. Left ventricular (LV) dynamic volumetry and strain analysis are relatively new and promising methods for evaluating LV function. METHODS: In this pilot study, we recruited 30 young (18-50 years) patients with cryptogenic ischemic stroke and 30 age- and sex-matched controls from the SECRETO study (NCT01934725). The LV systolic function was assessed by LV volumetry (ejection fraction, peak emptying rate, and time to peak emptying rate). The longitudinal systolic function was assessed by speckle tracking strain and strain rate imaging, and by tissue velocity imaging derived MAD (mitral annular displacement) and septal S'. RESULTS: Stroke patients had less vigorous global longitudinal strain (median -18.9, interquartile range 3.3), compared to healthy controls (median -20.0, interquartile range 2.8), P = .010. There was no statistically significant differences in septal S', MAD, global longitudinal strain rate, or dynamic volumetry-derived parameters between the two groups. CONCLUSIONS: Young cryptogenic stroke patients have subtly altered systolic function compared to healthy controls, found merely with longitudinal strain analysis. This infers that the heart may play a role in the pathogenesis of cryptogenic ischemic stroke.

The value of myocardial perfusion imaging in screening coronary artery disease before kidney transplantation.

The value of myocardial single-photon emission computed tomography (SPECT) in pre-transplant evaluation of kidney transplant recipients is controversial. We assessed whether myocardial SPECT predicts major adverse cardiac events (MACE) and determined whether SPECT findings affected transplant recipients' medical and invasive treatment. We analyzed 301 patients referred for myocardial SPECT before kidney transplantation and combined the results with information from patient files and the Transplantation Registry. During the median follow-up time of 96 months (IQR 70.75-118.25 months), the incidence of MACE was higher in patients (n = 37) with severely abnormal SPECT (>10% reversible perfusion defect) than in patients (n = 35) with mildly abnormal or normal SPECT (51.4%, 29.4%, and 27.0%, respectively, P = .011). Severely abnormal SPECT findings predicted long-term MACE in a univariable analysis but not after adjusting for other risk factors. Following SPECT, 29 patients (9.6%) underwent coronary angiography and 14 (4.6%) were revascularized. New antithrombotic or statin medication was prescribed to 7.3% of patients with ischemia in SPECT. Kidney transplantation patients are at high long-term risk of MACE even with normal preoperative myocardial SPECT. Abnormal SPECT did not predict MACE when adjusted for other risk factors. Minority of the patients underwent coronary revascularization or had changes in preventive medication before transplantation.

Lower ST-elevation myocardial infarction incidence during COVID-19 epidemic in Northern Europe.

We compared the ST elevation myocardial infarction (STEMI) incidence during COVID-19 pandemic (March 2020) to January-February 2020 and to same time period in earlier years 2017-2019 in five Nordic-Baltic tertiary centers. During 2017-2019, there were no marked differences in STEMI incidence between January, February and March. During 2020, there was an average drop of 32% in STEMI incidence in March. The isolation measures may decrease the risk for respiratory virus infection and contribute to the lower STEMI incidence and that we might benefit from firmer suggestions on hand hygiene and social distancing during flu season at least among high-risk individuals.