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Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

BACKGROUND Global physical inactivity pandemic is responsible for more than 5 million deaths annually through its effects on non-communicable diseases. This requires urgent intervention. The aim of this study was to investigate the associations of physical activity with cardiovascular fitness in a cross-sectional retrospective observational fashion. Data were collected for 21 years from 2530 healthy volunteers and athletes representing the entire spectrum of physical activity from the totally inactive sedentary persons to the highly trained national athletes. METHODS Cardiac fitness was investigated echocardiographically, which is characterized by reduced resting heart rate (RHR), increased relative left ventricular muscular mass (rLVMM), improved left ventricular diastolic function (characterized by the ratio of early to late ventricular peak velocities, E/A) and peak exercise oxygen consumption. RESULTS We found that even moderate exercise is associated with improved cardiac characteristics. With increasing exercise level, the RHR decreased from 69 to 63.3, 61.4, 58.6, 56.1, and 55.8/min in non-athletes, leisure athletes, lower class athletes, 2nd class athletes, 1st class athletes, and national athletes, respectively. While the rLVMM was increased from 64.6 to 70.7, 76.3, 78.5, 86.7, and 88.9 in the same groups. The E/A ratio also increased from 1.71 to 1.72, 1.85, 2.04 in the non-athletes, leisure athletes, lower class athletes, and 2nd class athletes, respectively, but then decreased to 1.92 and 1.98 in the 1st class athletes and national athletes. The largest exercise-induced improvement of cardiac fitness was observed between the inactive and the least active group, which did not increase further in the highly trained national athletes enduring up to 20 training hours per week. CONCLUSIONS Our findings indicate that cardiac fitness can be improved by moderate exercise in sedentary persons. This information would help physicians to encourage inactive patients, who find physical exercise intimidating, for doable and sustainable behavioral change.

Purpose To test whether signal intensity percent infarct mapping (SI-PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age. Materials and Methods Forty-five swine with reperfused MI underwent 1.5T late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) after bolus injection of 0.2 mmol/kg Gd(DTPA) on days 2–62 following MI. Animals were classified into acute, healing, and healed groups by pathology. Infarct volume (IV) and infarct fraction (IF) were determined by two readers, using binary techniques (including 2–5 standard deviations [SD] above the remote, and full-width at half-maximum) and the SI-PIM method. Triphenyl-tetrazolium-chloride staining (TTC) was performed as reference. Bias (percent under/overestimation of IV relative to TTC) of each quantification method was calculated. Bland–Altman analysis was done to test the accuracy of the quantification methods, while intraclass correlation coefficient (ICC) analysis was done to assess intra- and interobserver agreement. Results Bias of the MRI quantification methods do not depend on the age of the MI. Full-width at half-maximum (FWHM) and SI-PIM gave the best estimate of MI volume determined by the reference TTC (P-values for the FWHM and SI-PIM methods were 0.183, 0.26, 0.95, and 0.073, 0.091, 0.73 in Group 1, Group 2, and Group 3, respectively), while using any of the binary thresholds of 2–4 SDs above the remote myocardium showed significant overestimation. The 5 SD method, however, provided similar IV compared to TTC and was shown to be independent of the size and age of MI. ICC analysis showed excellent inter- and intraobserver agreement between the readers. Conclusion Our results indicate that the SI-PIM method can accurately determine MI volume regardless of the pathological stage of MI. Once tested, it may prove to be useful for the clinic. J. Magn. Reson. Imaging 2016;43:911–920

Background In coronary artery disease (CAD), body surface potential mapping (BSPM) may reveal minor electrical potential changes appearing in the depolarization phase even if pathological changes are absent on the conventional 12-lead ECG. We hypothesized that a simple BSPM parameter, Max/Min signifies successful percutaneous coronary intervention (PCI). Methods Ninety-two adult Caucasian patients with stable CAD and positive exercise test underwent coronary angiography. Seventy patients (age, 59 ± 8; 46 males) were revascularized by PCI (left anterior descending [LAD] in 38, right [RCA] in 17 and left circumflex [LCX] coronary artery in 15). Control groups contained 22 patients (age, 60 ± 8; 14 males) without intervention and 35 healthy subjects (age, 58 ± 2; 15 males). Left ventricular ejection fraction (LVEF, transthoracic echocardiography) and Max/Min BSPM parameter (63-lead Montreal system) were evaluated before and 4–40 days following coronary angiography. Max/Min was defined by the ratio of the highest maximum to the deepest minimum potential of all leads recorded by BSPM. Results Before PCI, Max/Min value of patients with LAD lesion (0.83 [0.74; 0.93]) was significantly lower while that with RCA lesion (1.63 [1.35; 1.99]) was significantly higher than that of healthy group (1.01 [0.970; 1.13]) (P < 0.05) and LVEF was significantly lower in LAD lesion (46.50% [43.00; 51.00]) than in the healthy group (55.00% [50.00; 58.75]) (P < 0.01). Max/Min value significantly increased from 0.83 [0.74; 0.93] to 0.92 [0.82; 0.99] (P < 0.01) following LAD PCI while significantly decreased from 1.63 [1.35; 1.98] to 1.35 [1.21; 1.43] (P < 0.01) post-RCA PCI. It did not vary significantly, however, either following LCX PCI or without intervention. LVEF significantly increased (from 46.50% [43.00; 51.00] to 49.00% [46.00; 51.00]) only after LAD PCI. Conclusion Max/Min parameter is suitable to follow patients after LAD and RCA PCI.

Background The no-flow region (NF) visualised by magnetic resonance imaging (MRI) in myocardial infarction (MI) has been explained as the product of reperfusion-injury-induced microvascular obstruction. However, a similar MRI phenomenon occurs in non-reperfused MI. Accordingly, our purpose was to compare the MRI and histopathologic characteristics of the NF in reperfused and non-reperfused MIs. Methods Reperfused (n = 7) and non-reperfused MIs (n = 7) were generated in swine by percutaneous balloon occlusion and microsphere embolisation techniques. Four days post-MI, animals underwent myocardial T2-mapping, early and serial late gadolinium enhancement MRI. MI and NF were compared between the models using the independent samples t test. Serial measurements were analysed using repeated measures analysis of variance. Triphenyltetrazolium chloride (TTC) macroscopic and microscopic histopathologic assessment was also performed. Results The MI size in the reperfused and non-reperfused groups was 17.1 ± 3.4 ml and 19.4 ± 8.1 ml, respectively (p = 0.090), in agreement with TTC assessment (p = 0.216; p = 0.484), and the NF size was 7.7 ± 2.4 ml and 8.1 ± 1.9 ml, respectively (P = 0.211). Compared to the reference 2-min post-contrast measurement, the NF size was significantly reduced at 20 min in the reperfused group and at 25 min in the non-reperfused group (both p 0.326). Histopathologic assessment revealed extensive calcification and hemosiderin deposition in the NF of the reperfused MI, but not in the non-reperfused MI. Conclusions The NF in non-reperfused and reperfused MIs have similar characteristics on MRI despite the different pathophysiologic and underlying histopathologic conditions, indicating that the presence of the NF alone cannot differentiate between these two types of MI.

A substantial, common shortcoming of the currently used semiautomated techniques for the quantification of myocardial infarct with delayed enhancement magnetic resonance imaging is the assumption that the whole myocardial slab that corresponds to the hyperenhanced tomographic area is 100% nonviable. This assumption is, however, incorrect. To resolve this conflict, we have recently proposed the signal intensity percent-infarct mapping method and validated it in an ex vivo, canine experiment. The purpose of the current study has been the validation of the signal intensity percent-infarct mapping method in vivo, using a porcine model of reperfused myocardial infarct.In swines (n=6), reperfused myocardial infarct was generated occluding for 90 min by an angioplasty balloon either the left anterior descending or the left circumflex coronary artery. To obtain DE images, Gd(DTPA) enhanced inversion-recovery fast gradient-echo acquisitions were carried out on day 28 after myocardial infarction. Scanning started 15 min after intravenous injection of 0.2 mmol/kg Gd(DTPA). At the end of the MRI session, the animal was sacrificed and 2,3,5-triphenyltetrazolium chloride staining was used to validate the existence and to determine the accurate size of the myocardial infarct. Tissue samples were taken and stained with hematoxylin-eosin and Masson's trichrome for histological assessment of the infarct and the periinfarct zone. The signal intensity percent-infarct mapping data were compared with corresponding data from the delayed enhancement images analyzed with SI(remote+2S.D.) thresholding, and with corresponding triphenyltetrazolium-chloride staining data using Friedman's repeated measure analysis of variance on ranks.The infarct volume determined by the triphenyltetrazolium chloride, SI(remote+2S.D.) and signal intensity percent-infarct mapping methods was 3.04 ml [2.74, 3.45], 13.62 ml [9.06, 18.45] and 4.27 ml [3.45, 6.33], respectively. Median infarct volume determined by SI(remote+2S.D.) significantly differed from that determined by triphenyltetrazolium chloride (P.05). The Bland-Altman overall bias was 12.49% of the volume of the left ventricle. Median infarct volume determined by signal intensity percent-infarct mapping, however, did not differ significantly (NS) from that obtained by triphenyltetrazolium chloride. Signal intensity percent-infarct mapping yielded only a 1.99% Bland-Altman overall bias of the left ventricular volume.This in vivo study in the porcine reperfused myocardial infarct model demonstrates that signal intensity percent-infarct mapping is a highly accurate method for the determination of the extent of myocardial infarct. MRI images for signal intensity percent-infarct mapping are obtained with the pulse sequence of conventional delayed enhancement imaging and are acquired within clinically acceptable scanning time. This makes signal intensity percent-infarct mapping a practical method for clinical implementation.

To determine the infarct affinity of a low molecular weight contrast agent, Gd(ABE-DTTA), during the subacute phase of myocardial infarct (MI). Dogs (n = 7) were examined, using a closed-chest, reperfused MI model. MI was generated by occluding for 180 min the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon. DE-MRI images with Gd(ABE-DTTA) were obtained on days 4, 14, and 28 after MI. Control DE-MRI by Gd(DTPA) was carried out on day 27. T2-TSE images were acquired on day 3, 13 and 27. Triphenyltetrazolium chloride (TTC) histomorphometry validated postmortem the existence of infarct. Gd(ABE-DTTA) highlighted the infarct on day 4, but not at all on day 14 or on day 28, following MI. On day 4, the mean ± SD signal intensity (SI) of infarcted myocardium in the presence of Gd(ABE-DTTA) significantly differed from that of healthy myocardium (45 ± 6.0 vs. 10 ± 5.0, P < 0.05), but it did not on day 14 (11 ± 9.4 vs. 10 ± 5.7, P = NS), nor on day 28 (7 ± 1.5 vs. 7 ± 2.4, P = NS). The mean ± SD signal intensity enhancement (SIE) induced by Gd(ABE-DTTA) was 386 ± 165% on day 4, significantly different from mean SIE on day 14 (9 ± 20%), and from mean SIE on day 28 (12 ± 18%), following MI (P < 0.05). The last two mean values did not differ significantly (P = NS) from each other. As control, Gd(DTPA) was used and it did highlight the infarct on day 27, inducing a mean SIE value of 312 ± 40%. The mean SIE on day 3, 13, or 27 did not vary significantly (P = NS) on the T2-TSE images (114 ± 41%, 123 ± 41%, and 150 ± 79%, respectively). Post mortem, the existence of infarcts was confirmed by TTC staining. The infarct affinity of Gd(ABE-DTTA) vanishes in the subacute phase of scar healing, allowing its use for infarct age differentiation early on, immediately following the acute phase.

Patients with peripheral arterial disease often have coronary heart disease, as well. However, their assessment with classical noninvasive cardiology methods is often non-diagnostic or limited. The aim of this study was to analyze the feasibility and the risks of dobutamine stress cardiovascular MRI for cardiac evaluation of patients with peripheral arterial disease. 21 patients with peripheral artery disease (mean±SD age 64.3±7.7 years) were studied prospectively with dobutamine stress cardiovascular MRI. The protocol was completed by all of 21 patients. The target heart rate was attained in 95.2% of the studies. No serious adverse event occurred. The image quality scores (1-4) for all ventricular wall segments were high (median, interquartile range) (4 [4-4]). Five patients (23.8%) have inducible wall motion abnormality. Interobserver agreement was almost perfect for wall motion scores (κ = 0.87, p

To test whether signal intensity percent infarct mapping (SI-PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age.Forty-five swine with reperfused MI underwent 1.5T late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) after bolus injection of 0.2 mmol/kg Gd(DTPA) on days 2-62 following MI. Animals were classified into acute, healing, and healed groups by pathology. Infarct volume (IV) and infarct fraction (IF) were determined by two readers, using binary techniques (including 2-5 standard deviations [SD] above the remote, and full-width at half-maximum) and the SI-PIM method. Triphenyl-tetrazolium-chloride staining (TTC) was performed as reference. Bias (percent under/overestimation of IV relative to TTC) of each quantification method was calculated. Bland-Altman analysis was done to test the accuracy of the quantification methods, while intraclass correlation coefficient (ICC) analysis was done to assess intra- and interobserver agreement.Bias of the MRI quantification methods do not depend on the age of the MI. Full-width at half-maximum (FWHM) and SI-PIM gave the best estimate of MI volume determined by the reference TTC (P-values for the FWHM and SI-PIM methods were 0.183, 0.26, 0.95, and 0.073, 0.091, 0.73 in Group 1, Group 2, and Group 3, respectively), while using any of the binary thresholds of 2-4 SDs above the remote myocardium showed significant overestimation. The 5 SD method, however, provided similar IV compared to TTC and was shown to be independent of the size and age of MI. ICC analysis showed excellent inter- and intraobserver agreement between the readers.Our results indicate that the SI-PIM method can accurately determine MI volume regardless of the pathological stage of MI. Once tested, it may prove to be useful for the clinic.

To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary [2 or 5 standard deviation (SD)], SI-PIM and R1-PIM methods. Infarct fraction (IF), and infarct-involved voxel fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure.

OBJECTIVE To demonstrate the feasibility of using multidetector computed tomography with gadolinium contrast (Gd-MDCT) for the quantification of myocardial infarct (MI). MATERIALS AND METHODS MI was induced in male swine (n = 6). One week later, the animals received 0.2-mmol/kg gadopentetate dimeglumine and were sacrificed. On the excised hearts, Gd-MDCT with several tube voltages (80, 120, and 140 kV), late gadolinium enhancement MRI (LGE-MRI), and triphenyl-tetrazolium-chloride staining were then conducted. We used a 2-SD threshold for the CT images and several threshold limits (2, 3, 4, 5, 6 SD, and full width at half-maximum [FWHM]) for the LGE-MRI images to delineate the infarct area. Total infarct volume and infarct fraction of each heart were calculated. RESULTS MI size measured by MDCT at 140 kV showed good correlation with the reference triphenyl-tetrazolium-chloride value. Applying an 80-kV tube voltage, however, significantly underestimated MI size. In our study, the LGE-MRI method, using the 6-SD threshold, provided the most accurate determination of MI size. LGE-MRI, using the 2- and 3-SD threshold limits, significantly overestimated infarct size. CONCLUSIONS The Gd-MDCT technique has been found suitable for the evaluation of MI in an ex vivo experimental setting. Gd-MDCT has the ability to detect MI even at low kV settings, but accuracy is limited by a high image noise because of reduced photon flux.

Background Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older myocardial infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older myocardial infarct using myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent. Dogs (n = 6) were studied in a closed-chest, reperfused, double myocardial infarct model. Myocardial infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second myocardial infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABE-DTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Masson's trichrome staining provided histologic evaluation of infarcts. Results Gd(ABE-DTTA) or Gd(DTPA) highlighted the acute infarct, whereas the four-week old infarct was visualized by Gd(DTPA), but not by Gd(ABE-DTTA). With Gd(ABE-DTTA), the mean ± SD signal intensity enhancement (SIE) was 366 ± 166% and 24 ± 59% in the acute infarct and the four-week old infarct, respectively (P < 0.05). The latter did not differ significantly from signal intensity in healthy myocardium (P = NS). Gd(DTPA) produced signal intensity enhancements which were similar in acute (431 ± 124%) and four-week old infarcts (400 ± 124%, P = NS), and not statistically different from the Gd(ABE-DTTA)-induced SIE in acute infarct. The existence and localization of both infarcts were confirmed by triphenyltetrazolium chloride (TTC). Histologic evaluation demonstrated coagulation necrosis, inflammation, and multiple foci of calcification in the four day old infarct, while the late subacute infarct showed granulation tissue and early collagen deposition. Conclusions Late enhancement CMR with separate administrations of standard extracellular contrast agent, Gd(DTPA), and the new low molecular weight contrast agent, Gd(ABE-DTTA), differentiates between acute and late subacute infarct in a reperfused, double infarct, canine model.

In a 53-year-old male admitted with acutely developing symptoms of right-sided hemiparesis and dysarthria revealed an extensive ischaemic infarct involving the left posterior cerebral artery territory. ECG showed right bundle branch block and significant anterior ST-segment elevation ( Panel A ). In addition, elevated cardiac enzyme levels suggested acute myocardial infarction (MI). Immediate transthoracic echocardiography showed a homogenous mass involving …

Until Titus's destruction of Jerusalem in 70 CE, the national and religious life of Palestinian Jewry was organized around the cultic system of the Temple. Despite many changes in the political status of the nation and of Jerusalem itself, the Temple continued to serve as the seat of the priesthood, the destination of sacred pilgrimage, and the instrument of cultic expiation. Other places and forms of worship are attested during the second commonwealth, and by the advent of the common era groups such as the Qumran community had turned away from Jerusalem altogether. Yet there can be little doubt that the Temple was perceived as the preeminent symbol of Israel's God. Excavations of first-century Palestinian synagogues have revealed a basic architectural design of orientation toward the sanctuary. Although geographically and religiously remote from the Temple, the Jews of the diaspora continued, writes Philo of Alexandria (ca. 20 BCE–50 CE), to “hold the Holy City where stands the sacred Temple of the most high God to be their mother city.”

Methods: Dogs (n=6) were studied in closed-chest, reperfused, double MI model. MIs were generated by occluding the Left Anterior Descending coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumfex coronary artery. Inversion-recovery gradient-echo (IR-GRE) delayed enhancement (DE) images were obtained on day 3 and day 4 after second MI, using Gd(DTPA) and Gd(ABE-DTTA), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Masson’s trichrome staining provided histologic evaluation of infarcts.