15 weeks of soccer training increases left ventricular mass and improves indices of left ventricular diastolic function in previously sedentary, mildly hypertensive, middle-aged women.

PURPOSE: To investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women. METHODS: Hypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.6 kg; body fat: 43.3 ± 5.2%) were randomized to soccer training (SOC, n = 21) or control (CON, n = 20). SOC performed three weekly training sessions for 15 weeks, whereas CON had no training or lifestyle changes during the same period. Cardiac structure and function were assessed by echocardiography pre-intervention and post-intervention. RESULTS: Soccer training increased (P = 0.001) left ventricular mass index by 10% [95% CI 4; 15], while no changes occurred in CON (time × group interaction, P = 0.005). In addition, only SOC demonstrated a within-group increase (P = 0.01) of 8% [95% CI 2; 14] in left ventricular septum diameter. For markers of right ventricular remodelling, a within-group increase (P = 0.02) occurred for tricuspid annulus plane systolic excursion of 8% [95% CI 1; 14] in SOC only. Left atrial diameter index increased (P < 0.001) by 6% [95% CI 3; 10] after SOC, while it was unaffected in CON (time × group interaction, P = 0.02). For makers of diastolic function, SOC demonstrated a within-group increase (P = 0.02) in the average early diastolic mitral annulus velocity of 10% [95% CI 2; 19]. In addition, a reduction (P < 0.001) in mitral valve A velocity of - 19% [95% CI - 29; - 10] was observed following soccer training, which manifested in increased (P < 0.001) mitral valve E/A ratio of 34% [95% CI 16; 53] in SOC. No within-group changes were apparent in CON. CONCLUSION: In sedentary, mildly hypertensive, middle-aged women, 15 weeks of soccer training increases left ventricular mass and left atrial diameter and improves indices of left ventricular diastolic function.

Scar border zone mass and presence of border zone channels assessed with cardiac magnetic resonance imaging are associated with ventricular arrhythmia in patients with ST-segment elevation myocardial infarction.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (CMR) permits characterization of left ventricular ischaemic scars. We aimed to evaluate if scar core mass, border zone (BZ) mass, and BZ channels are risk markers for subsequent ventricular arrhythmia (VA) in ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A sub-study of the DANish Acute Myocardial Infarction-3 multi-centre trial and Danegaptide phase II proof-of-concept clinical trial in which a total of 843 STEMI patients had a 3-month follow-up CMR. Of these, 21 patients subsequently experienced VA during 100 months of follow-up and were randomly matched 1:5 with 105 controls. A VA event was defined as: ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. Ischaemic scar characteristics were automatically detected by specialized software. We included 126 patients with a median left ventricular ejection fraction of 51.0 ± 11.6% in cases with VA vs. 55.5 ± 8.5% in controls (P = 0.10). Cases had a larger mean BZ mass and more often BZ channels compared to controls [BZ mass: 17.2 ± 10.3 g vs. 10.3 ± 6.0 g; P = 0.0002; BZ channels: 17 (80%) vs. 44 (42%); P = 0.001]. A combination of ≥17.2 g BZ mass and the presence of BZ channels was five times more prevalent in cases vs. controls (P ≤ 0.00001) with an odds ratio of 9.40 (95% confidence interval 3.26-27.13; P ≤ 0.0001) for VA. This identified cases with 52% sensitivity and 90% specificity. CONCLUSION(S): Scar characterization with CMR indicates that a combination of ≥17.2 g BZ mass and the presence of BZ channels had the strongest association with subsequent VA in STEMI patients. CLINICALTRIALS.GOV: Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER), NCT01960933 (DANAMI 3-PRIMULTI), and NCT01977755 (Danegaptide).

Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial.

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations. METHODS: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO3) or ACE inhibitor (ACEi: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention. RESULTS: Forty-eight participants (nACEi = 23, nPLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACEi (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus. CONCLUSION: Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.

Rubidium-82 PET imaging is feasible in a rat myocardial infarction model.

BACKGROUND: Small-animal myocardial infarct models are frequently used in the assessment of new cardioprotective strategies. A validated quantification of perfusion using a non-cyclotron-dependent PET tracer would be of importance in monitoring response to therapy. We tested whether myocardial PET perfusion imaging is feasible with Rubidium-82 (82Rb) in a small-animal scanner using a rat myocardial infarct model. METHODS: 18 Sprague-Dawley rats underwent permanent coronary artery ligation (infarct group), and 11 rats underwent ischemia-reperfusion (reperfusion group) procedure. 82Rb-PET and magnetic resonance imaging (MRI) were conducted before and after the intervention. Perfusion was compared to both left ventricle ejection fraction (LVEF) and infarct size assessed by MRI. RESULTS: Follow-up global 82Rb-uptake correlated significantly with infarct size (infarct group: r = -0.81, P < 0.001 and reperfusion group: r = -0.61, P = 0.04). Only 82Rb-uptake in the infarct group correlated with LVEF. At follow-up, a higher segmental 82Rb-uptake in the infarct group was associated with better wall motion (ß = 0.034, CI [0.028;0.039], P < 0.001, R2 = 0.30), and inversely associated with scar transmurality (ß = -2.4 [-2.6; -2.2], P < 0.001, R2 = 0.59). The associations were similar for the reperfusion group. CONCLUSION: 82Rb-PET is feasible in small animal scanners despite the long positron range and enables fast and time-efficient myocardial perfusion imaging in rat models.

Subacute cardiac rubidium-82 positron emission tomography (82Rb-PET) to assess myocardial area at risk, final infarct size, and myocardial salvage after STEMI.

BACKGROUND: Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR). METHODS: Twelve STEMI patients were injected with 99mTc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index. RESULTS: SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78). CONCLUSIONS: 82Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population.

Blood pooling in extrathoracic veins after glossopharyngeal insufflation.

PURPOSE: Trained breath-hold divers hyperinflate their lungs by glossopharyngeal insufflation (GPI) to prolong submersion time and withstand lung collapse at depths. Pulmonary hyperinflation leads to profound hemodynamic changes. METHODS: Thirteen divers performed preparatory breath-holds followed by apnea with GPI. Filling of extrathoracic veins was determined by ultrasound and magnetic resonance imaging and peripheral extravasation of fluid was assessed by electrical impedance. Femoral vein diameter was measured by ultrasound throughout the easy-going and struggle phase of apnea with GPI in eight divers in a sub-study. RESULTS: After GPI, pulmonary volume increased by 0.8 ± 0.6 L above total lung capacity. The diameter of the superior caval (by 36 ± 17%) and intrathoracic part of the inferior caval vein decreased (by 21 ± 16%), while the diameters of the internal jugular (by 53 ± 34%), hepatic (by 28 ± 40%), abdominal part of the inferior caval (by 28 ± 28%), and femoral veins (by 65 ± 50%) all increased (P < 0.05). Blood volume of the internal jugular, the hepatic, the abdominal part of the inferior caval vein, and the combined common iliac and femoral veins increased by 145 ± 115, 80 ± 88, 61 ± 60, and 183 ± 197%, respectively. In the sub-study, femoral vein diameter increased by 44 ± 33% in the easy-going phase of apnea with GPI, subsequently decreasing by 20 ± 16% during the struggle phase. Electrical impedance remained unchanged over the thigh and forearm, thus excluding peripheral fluid extravasation. CONCLUSIONS: GPI leads to heart and pulmonary vessel compression, resulting in redistribution of blood to extrathoracic capacitance veins proximal to venous valves. This is partially reversed by the onset of involuntary breathing movements.

Organ perfusion during voluntary pulmonary hyperinflation; a magnetic resonance imaging study.

Pulmonary hyperinflation is used by competitive breath-hold divers and is accomplished by glossopharyngeal insufflation (GPI), which is known to compress the heart and pulmonary vessels, increasing sympathetic activity and lowering cardiac output (CO) without known consequence for organ perfusion. Myocardial, pulmonary, skeletal muscle, kidney, and liver perfusion were evaluated by magnetic resonance imaging in 10 elite breath-hold divers at rest and during moderate GPI. Cardiac chamber volumes, stroke volume, and thus CO were determined from cardiac short-axis cine images. Organ volumes were assessed from gradient echo sequences, and organ perfusion was evaluated from first-pass images after gadolinium injection. During GPI, lung volume increased by 5.2 ± 1.5 liters (mean ± SD; P < 0.001), while spleen and liver volume decreased by 46 ± 39 and 210 ± 160 ml, respectively (P < 0.05), and inferior caval vein diameter by 4 ± 3 mm (P < 0.05). Heart rate tended to increase (67 ± 10 to 86 ± 20 beats/min; P = 0.052) as right and left ventricular volumes were reduced (P < 0.05). Stroke volume (107 ± 21 to 53 ± 15 ml) and CO (7.2 ± 1.6 to 4.2 ± 0.8 l/min) decreased as assessed after 1 min of GPI (P < 0.01). Left ventricular myocardial perfusion maximum upslope and its perfusion index decreased by 1.52 ± 0.15 s(-1) (P < 0.001) and 0.02 ± 0.01 s(-1) (P < 0.05), respectively, without transmural differences. Pulmonary tissue, spleen, kidney, and pectoral-muscle perfusion also decreased (P < 0.05), and yet liver perfusion was maintained. Thus, during pulmonary hyperinflation by GPI, CO and organ perfusion, including the myocardium, as well as perfusion of skeletal muscles, are reduced, and yet perfusion of the liver is maintained. Liver perfusion seems to be prioritized when CO decreases during GPI.

The decrease of cardiac chamber volumes and output during positive-pressure ventilation.

Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml (P < 0.001) and from 265 (±17) ml to 212 (±16) ml (P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min (P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by -146 (±32) and -187 (±64) ml/s (P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.

The Incidence and Impact of Permanent Right Ventricular Infarction on Left Ventricular Infarct Size in Patients With Inferior ST-Segment Elevation Myocardial Infarction.

Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (ß = -0.0; p = 0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17 LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16.

Effect of angiotensin-converting enzyme inhibition on cardiovascular adaptation to exercise training.

Angiotensin-converting enzyme (ACE) activity may be one determinant of adaptability to exercise training, but well-controlled studies in humans without confounding conditions are lacking. Thus, the purpose of the present study was to investigate whether ACE inhibition affects cardiovascular adaptations to exercise training in healthy humans. Healthy participants of both genders (40 ± 7 years) completed a randomized, double-blind, placebo-controlled trial. Eight weeks of exercise training combined with placebo (PLA, n = 25) or ACE inhibitor (ACEi, n = 23) treatment was carried out. Before and after the intervention, cardiovascular characteristics were investigated. Mean arterial blood pressure was reduced (p < 0.001) by -5.5 [-8.4; -2.6] mmHg in ACEi , whereas the 0.7 [-2.0; 3.5] mmHg fluctuation in PLA was non-significant. Maximal oxygen uptake increased (p < 0.001) irrespective of ACE inhibitor treatment by 13 [8; 17] % in ACEi and 13 [9; 17] % in PLA. In addition, skeletal muscle endurance increased (p < 0.001) to a similar extent in both groups, with magnitudes of 82 [55; 113] % in ACEi and 74 [48; 105] % in PLA. In contrast, left atrial volume decreased (p < 0.05) by -9 [-16; -2] % in ACEi , but increased (p < 0.01) by 14 [5; 23] % in PLA. Total hemoglobin mass was reduced (p < 0.01) by -3 [-6; -1] % in ACEi , while a non-significant numeric increase of 2 [-0.4; 4] % existed in PLA. The lean mass remained constant in ACEi but increased (p < 0.001) by 3 [2; 4] % in PLA. In healthy middle-aged adults, 8 weeks of high-intensity exercise training increases maximal oxygen uptake and skeletal muscle endurance irrespective of ACE inhibitor treatment. However, ACE inhibitor treatment counteracts exercise training-induced increases in lean mass and left atrial volume. ACE inhibitor treatment compromises total hemoglobin mass.

Conductance artery stiffness impairs atrio-ventriculo-arterial coupling before manifestation of arterial hypertension or left ventricular hypertrophic remodelling.

As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV.

Life-Threatening Necrotizing Pneumonia with Panton-Valentine Leukocidin-Producing, Methicillin-Sensitive Staphylococcus aureus in a Healthy Male Co-Infected with Influenza B.

A previously healthy male was rushed into a hospital critically ill with confusion, sepsis, and acute respiratory distress syndrome only 43 h after having a normal chest X-ray and with blood samples showing only minimally elevated C-reactive protein. Two days earlier, the patient had returned to his home country, the Faroe Islands, from a 10-day work trip aboard a Scandinavian ship in Colombia. The diagnosis turned out to be an influenza B infection and necrotizing pneumonia with Panton-Valentine leukocidin (PVL)-producing methicillin-sensitive Staphylococcus aureus (MSSA). It was influenza season in Colombia but not in the Faroe Islands. The frequency of MSSA with PVL-encoding genes among pediatric infection patients is very low in the Kingdom of Denmark and Faroe Islands and very high in Colombia, and the frequency generally varies highly by region. The patient in this case now suffers severe sequelae from the infection. With this case, we would like to remind clinicians of this rare but severe condition. PVL-producing S. aureus pneumonia should be considered in critically ill, previously healthy patients, especially during influenza season and if the patient has been traveling in countries with high frequencies of PVL-producing S. aureus.

Impact of age on reperfusion success and long-term prognosis in ST-segment elevation myocardial infarction - A cardiac magnetic resonance imaging study.

BACKGROUND: Coronary collateral circulation and conditioning from remote ischemic coronary territories may protect culprit myocardium in the elderly, and younger STEMI patients could suffer from larger infarcts. We evaluated the impact of age on myocardial salvage and long-term prognosis in a contemporary STEMI cohort. METHODS: Of 1603 included STEMI patients 807 underwent cardiac magnetic resonance. To assess the impact of age on infarct size and left ventricular ejection fraction (LVEF) as well as the composite endpoint of death and re-hospitalization for heart failure we stratified the patients by an age cut-off of 60 years. RESULTS: Younger STEMI patients had smaller final infarcts (10% vs. 12%, P = 0.012) and higher final LVEF (60% vs. 58%, P = 0.042). After adjusting for multiple potential confounders age did not remain significantly associated with infarct size and LVEF. During 4-year follow-up, the composite endpoint occurred less often in the young (3.2% vs. 17.2%; P < 0.001) with a univariate hazard ratio of 5.77 (95% CI, 3.75-8.89; p < 0.001). Event estimates of 4 subgroups (young vs. elderly and infarct size beyond vs. below median) showed a gradual increase in the occurrence of the composite endpoint depending on both age and acute infarct size (log-rank p < 0.001). CONCLUSION: Having a STEMI after entering the seventh decade of life more than quadrupled the risk of future death or re-hospitalization for heart failure. Risk of death and re-hospitalization depended on both advanced age and infarct size, albeit no substantial difference was found in infarct size, LVEF and salvage potential between younger and elderly patients with STEMI.

Ischemia From Nonculprit Stenoses Is Not Associated With Reduced Culprit Infarct Size in Patients with ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: In patients with ST-segment-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention, reperfusion injury accounts for a significant fraction of the final infarct size, which is directly related to patient prognosis. In animal studies, brief periods of ischemia in noninfarct-related (nonculprit) coronary arteries protect the culprit myocardium via remote ischemic preconditioning. Positive fractional flow reserve (FFR) documents functional significant coronary nonculprit stenosis, which may offer remote ischemic preconditioning of the culprit myocardium. The aim of the study was to investigate the association between functional significant, multivessel disease (MVD) and reduced culprit final infarct size or increased myocardial salvage (myocardial salvage index [MSI]) in a large contemporary cohort of STEMI patients. METHODS: Cardiac magnetic resonance was performed in 610 patients with STEMI at day 1 and 3 months after primary percutaneous coronary intervention. Patients were stratified into 3 groups according to FFR measurements in nonculprit stenosis (if any): angiographic single vessel disease (SVD), FFR nonsignificant MVD (functional SVD), or FFR-significant, functional MVD. RESULTS: A total of 431 (71%) patients had SVD, 35 (6%) had functional SVD, and 144 (23%) had functional MVD. There was no difference in final infarct size (mean infarct size [%left ventricular mass] SVD, 9±3%; functional SVD, 9±3%; and functional MVD, 9±3% [P=0.82]) or in MSI between groups (mean MSI [%left] SVD, 66±23%; functional SVD, 68±19%; and functional MVD, 69±19% [P=0.62]). In multivariable analyses, functional MVD was not associated with larger MSI (P=0.56) or smaller infarct size (P=0.55). CONCLUSIONS: Functional MVD in nonculprit myocardium was not associated with reduced culprit final infarct size or increased MSI following STEMI. This is important knowledge for future studies examining a cardioprotective treatment in patients with STEMI, as a possible confounding effect of FFR-significant, functional MVD can be discarded. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

Bone Geometry, Density, and Microarchitecture in the Distal Radius and Tibia in Adults With Marfan Syndrome Assessed by HR-pQCT.

Marfan syndrome (MFS) is a hereditary disorder of connective tissue caused by mutations in the fibrillin-1 gene. Studies have shown that patients with MFS have lower bone mass, but little is known about the other constituents of bone strength. We hypothesize that patients with MFS will have larger bone area and compromised cortical microarchitecture compared with non-MFS individuals. A total of 74 adult patients with MFS and 145 age- and sex-matched non-MFS reference individuals were included in this study. High-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and dual-energy X-ray absorptiometry of total hip and the lumbar spine were performed, and bone turnover and sex hormones were measured. Patients with MFS had significantly lower areal bone mineral density (BMD) at the total spine (-13%) and total hip (-7%) when compared with the reference group. Patients with MFS had significantly larger total bone area at both the radius (+27%) and tibia (+34%). Volumetric BMD at both measured sites showed significantly reduced total, trabecular, and cortical volumetric BMD in patients with MFS compared with the reference group. The microarchitectural parameters at the radius and tibia were compromised in patients with MFS with significantly reduced trabecular number and thickness, leading to a higher trabecular separation and significantly reduced cortical thickness and increased cortical porosity compared with the reference group. The differences in bone density, geometry, or microarchitecture were not explained by increased bone turnover markers or circulating levels of sex hormones. We conclude patients with MFS have altered bone geometry, altered bone microstructure, and lower bone mass (lower areal BMD and volumetric BMD at all sites) compared with healthy reference individuals. Future studies should focus on fracture rates and fracture risk in adult and aging patients with MFS. © 2020 American Society for Bone and Mineral Research (ASBMR).

Infarct size following loading with Ticagrelor/Prasugrel versus Clopidogrel in ST-segment elevation myocardial infarction.

BACKGROUND: Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI. METHODS AND RESULTS: Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001). CONCLUSIONS: Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI.

Fractional flow reserve-guided PCI in patients with and without left ventricular hypertrophy: a DANAMI-3-PRIMULTI substudy.

AIMS: The aim of this substudy was to investigate the correlation between fractional flow reserve (FFR) and diameter stenosis in patients with STEMI with and without left ventricular hypertrophy (LVH), and the influence of LVH on complete FFR-guided revascularisation versus culprit only, in terms of risk of clinical outcome. METHODS AND RESULTS: In this DANAMI-3-PRIMULTI substudy, 279 patients with STEMI had cardiac magnetic resonance (CMR) imaging for assessment of left ventricular mass index. Ninety-six patients had FFR evaluation of a non-culprit lesion. Diameter stenosis of the non-culprit lesion was determined with two-dimensional quantitative coronary analysis. The diameter stenosis (56.9% vs 54.3%, p=0.38) and FFR value (0.83 vs 0.85, p=0.34) were significantly correlated in both groups (Spearman's ρ=-0.40 and -0.41 without LVH and with LVH, respectively; p<0.001) but were not different between patients without and with LVH (p for interaction=0.87). FFR-guided complete revascularisation was associated with reduced risk of death, myocardial infarction or ischaemia-driven revascularisation both for patients without LVH (HR 0.42, 95% CI: 0.20-0.85) and for patients with LVH (HR 0.50, 95% CI: 0.17-1.47), with no interaction between the FFR-guided complete revascularisation and LVH (p for interaction=0.82). CONCLUSIONS: LVH did not interact with the correlation between diameter stenosis and FFR and did not modify the impact of complete revascularisation on the occurrence of subsequent clinical events.

Usefulness of High Sensitivity Troponin T to Predict Long-Term Left Ventricular Dysfunction After ST-Elevation Myocardial Infarction.

Guidelines recommend the use of transthoracic echocardiography (TTE) and clinical scores to risk stratify patients after ST-elevation myocardial infarction (STEMI). High sensitivity troponin T (hs-cTnT) is predictive of outcome after STEMI but the predictive value of hs-cTnT relative to other risk assessment tools has not been established. We aimed to compare the predictive value of hs-cTnT to other risk assessment tools in patients with STEMI. A subset of 578 patients with STEMI were included in this post-hoc study from the Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction trial. Patients underwent cardiac magnetic resonance imaging (CMR) during index hospitalization as well as TTE at 1 year after their STEMI. The predictive value of hs-cTnT was compared with CKMB, infarct size (IS)/left ventricular ejection fraction (LVEF) assessed with CMR, LVEF assessed at discharge with TTE and the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk-scores. The primary outcome was LV systolic dysfunction defined as LVEF ≤40% after 1 year on TTE. The area under the receiver operating characteristic curve analyses showed no significant difference between hs-cTnT and early CMR-assessed IS or LVEF in predicting subsequent LVEF ≤40%. Area under the curve for hs-cTnT was 0.82, 0.85 for IS (p = 0.22), and 0.87 for LVEF (p = 0.23). For predischarge TTE-assessed LVEF, the value was 0.85 (p = 0.45), 0.63 for creatine kinase-MB (p <0.001), 0.61 for the GRACE score (p <0.001), and 0.70 for the TIMI score (p = 0.02). A peak hs-cTnT value <3,500 ng/L ruled out LVEF ≤40% with probability of 98%. In conclusion, in patients presenting with STEMI undergoing PCI, hs-cTnT level strongly predicted long-term LV dysfunction and could be used as a clinical risk stratification tool to identify patients at high risk of progressing to LV dysfunction due to its general availability and high-predictive accuracy.

Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction: A DANAMI-3 sub-study.

AIMS: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47-36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07-50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27-47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83-328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. CONCLUSION: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.

Cardiac function and incidence of unexplained myocardial scarring in patients with primary carnitine deficiency - a cardiac magnetic resonance study.

Primary carnitine deficiency (PCD) not treated with L-Carnitine can lead to sudden cardiac death. To our knowledge, it is unknown if asymptomatic patients treated with L-Carnitine suffer from myocardial scarring and thus be at greater risk of potentially serious arrhythmia. Cardiac evaluation of function and myocardial scarring is non-invasively best supported by cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). The study included 36 PCD patients, 17 carriers and 17 healthy subjects. A CMR cine stack in the short-axis plane were acquired to evaluate left ventricle (LV) systolic and diastolic function and a similar LGE stack to evaluate myocardial scarring and replacement fibrosis. LV volumes and ejection fraction were not different between PCD patients, carriers and healthy subjects. However, LV mass was higher in PCD patients with the severe homozygous mutation, c.95 A > G (p = 0.037; n = 17). Among homozygous PCD patients there were two cases of unexplained myocardial scarring and this is in contrast to no myocardial scarring in any of the other study participants (p = 0.10). LV mass was increased in PCD patients. L-carnitine supplementation is essential in order to prevent potentially lethal cardiac arrhythmia and serious adverse cardiac remodeling.