Diffusely Increased Myocardial Extracellular Volume With or Without Focal Late Gadolinium Enhancement: Prevalence and Associations With Left Ventricular Size and Function.

PURPOSE: Myocardial extracellular volume fraction (ECV) using cardiovascular magnetic resonance (CMR) can identify diffuse lesions not detected by late gadolinium enhancement (LGE). We aimed to determine the prevalence of increased ECV and its relation to other CMR findings. MATERIALS AND METHODS: Consecutive patients (n=609, age median [interquartile range] 53 [39 to 66] y, 62% male) underwent CMR at 1.5 T. Focal lesions on LGE images were noted. ECV in regions without focal LGE findings defined diffuse changes. Pronounced increases in left ventricular (LV) end-diastolic volume index and LV mass index, and pronounced decreases in LV ejection fraction were defined as >3 SD from the sex-specific mean in healthy volunteers. RESULTS: Of 609 patients without amyloidosis or hypertrophic cardiomyopathy, 8% had diffusely increased ECV and 5% of all patients had diffusely increased ECV without any focal LGE findings. Multivariate analysis showed that a pronounced increase in the LV end-diastolic volume index was associated with increased ECV (P=0.001), but not LGE (P=0.52). A pronounced decrease in LV ejection fraction was associated with the presence of LGE (P<0.001), but not with increased ECV (P=0.41). CONCLUSIONS: Eight percent of patients in this clinical cohort with known or suspected heart disease had diffusely increased ECV and 60% of these lacked focal LGE findings. LV size is independently associated with increased ECV, whereas systolic dysfunction is independently associated with LGE. This image-based clinical study demonstrates that ECV-CMR provides additional information negligibly related to the results of LGE imaging, and thereby increases the diagnostic yield of CMR.

COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.

SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.

Stationary tissue background correction increases the precision of clinical evaluation of intra-cardiac shunts by cardiovascular magnetic resonance.

We aimed to evaluate the clinical utility of stationary tissue background phase correction for affecting precision in the measurement of Qp/Qs by cardiovascular magnetic resonance (CMR). We enrolled consecutive patients (n = 91) referred for CMR at 1.5T without suspicion of cardiac shunt, and patients (n = 10) with verified cardiac shunts in this retrospective study. All patients underwent phase contrast flow quantification in the ascending aorta and pulmonary trunk. Flow was quantified using two semi-automatic software platforms (SyngoVia VA30, Vendor 1; Segment 2.0R4534, Vendor 2). Measurements were performed both uncorrected and corrected for linear (Vendor 1 and Vendor 2) or quadratic (Vendor 2) background phase. The proportion of patients outside the normal range of Qp/Qs was compared using the McNemar's test. Compared to uncorrected measurements, there were fewer patients with a Qp/Qs outside the normal range following linear correction using Vendor 1 (10% vs 18%, p < 0.001), and Vendor 2 (10% vs 18%, p < 0.001), and following quadratic correction using Vendor 2 (7% vs 18%, p < 0.001). No patient with known shunt was reclassified as normal following stationary background correction. Therefore, we conclude that stationary tissue background correction reduces the number of patients with a Qp/Qs ratio outside the normal range in a consecutive clinical population, while simultaneously not reclassifying any patient with known cardiac shunts as having a normal Qp/Qs. Stationary tissue background correction may be used in clinical patients to increase diagnostic precision.

Solitary contralateral adrenal metastasis of renal cell carcinoma 15 years following radical nephrectomy: A case report and review of literature.

INTRODUCTION: Renal cell carcinoma (RCC) is known to metastasize to almost every organ. A well-recognized phenomenon in RCC is late metastatic recurrence after nephrectomy which is arbitrarily defined as more than 10 years. The incidence of solitary ipsilateral and contralateral adrenal metastasis is 3% and 0.7% respectively in patients who have underwent radical nephrectomy. CASE REPORT: A57-year-old female presented with an incidental ultrasonic finding of a right adrenal mass 15 years after radical nephrectomy for left side renal cell carcinoma. Further evaluation with abdominal contrast enhanced CT scan revealed a right adrenal mass suggestive of metastatic lesion. The results of laboratory examinations showed the mass to be nonfunctional. Open right adrenalectomy was performed. She was discharged home on 4th postoperative day. Pathological examination revealed morphological and immunohistochemical findings in line with metastatic renal cell carcinoma of the left kidney. During the last 2 years she has being on regular follow up, neither local recurrence nor distant metastasis anywhere have been detected by whole body Positron Emission Tomography(PET) scan. DISCUSSION: Late metastatic contralateral adrenal recurrence from RCC is very rare and to the best of our knowledge, 5 similar cases have been reported 10 years after radical nephrectomy. Early diagnosis of adrenal metastasis is challenging because they are usually silent both anatomically and functionally. CONCLUSION: Solitary contralateral adrenal metastatic recurrence of RCC is extremely rare event. Surgical removal is a wise option in these cases that may improve survival.

Thrombo-embolic complications in takotsubo syndrome: Review and demonstration of an illustrative case.

Thrombo-embolism is one of the serious complications of takotsubo syndrome (TS) in addition to heart failure, pulmonary edema, cardiogenic shock, cardiac arrest, life-threatening arrhythmias, left ventricular outlet tract obstruction, mitral regurgitation, cardiac rupture, and death. The most common cardio-embolic events in TS are cerebral, renal, and peripheral embolism. Approximately, one-third of patients with left ventricular thrombus (LVT) in TS develop embolic complications. Cardio-embolism in TS may occur with or without the presence of detectable LVT. In the present report, the thrombo-embolic complications in TS with the emphasis on the association of TS to both acute coronary syndrome (ACS) including coronary embolism and ischemic stroke including cerebral embolism are reviewed. This serious complication is elucidated by demonstration of the case of a 67-year-woman with mid-apical TS complicated by LVT, left anterior descending artery (LAD) and left middle cerebral artery (segment M2) thrombo-embolic occlusions. The cerebral artery thrombotic occlusion was treated successfully with endovascular thrombectomy with complete resolution of the neurological deficits. There was spontaneous recanalization of the apical LAD occlusion verified by cardiac computed tomography angiography.

Synthetic late gadolinium enhancement cardiac magnetic resonance for diagnosing myocardial scar.

OBJECTIVES: Late gadolinium enhancement (LGE) is the in vivo reference standard for assessing focal myocardial fibrosis. Post-contrast T1-mapping by Modified Look-Locker Inversion recovery (MOLLI) can be used to generate synthetic late gadolinium enhancement (SynLGE) images with an image contrast similar to conventional LGE images. We hypothesized that SynLGE has an accuracy that approaches conventional LGE for diagnosing focal myocardial fibrosis. METHODS: Consecutive patients (n = 109, mean ± SD age 50 ± 16 years, 63% male) referred for clinical cardiac magnetic resonance imaging underwent LGE and post-contrast MOLLI starting 10-15 and 20-25 minutes post contrast, respectively. A cardiac short-axis stack and three long-axis views were acquired for SynLGE and LGE. SynLGE were generated from post-contrast T1-maps. Only LGE and SynLGE images were analyzed by two blinded observers for agreement regarding localization and origin of focal myocardial fibrosis on a per-patient basis. RESULTS: Consensus identified focal fibrosis by LGE in 44/109 (40%) patients. Compared to LGE, SynLGE yielded a diagnostic sensitivity of 34/44 (77%), specificity of 64/65 (98%), positive predictive value of 34/35 (97%), negative predictive value of 64/74 (86%), and an overall accuracy of 98/109 (90%). In cases where SynLGE missed focal fibrosis (n = 10), these were either small non-ischemic focal fibrosis (n = 8) or infarction in a thin myocardial wall (n = 2). In one case, SynLGE identified midmural non-ischemic focal fibrosis not identified by LGE. DISCUSSION: Overall, SynLGE showed good agreement with LGE. SynLGE derived from post-contrast T1-maps may provide the complementary ability to increase confidence in assessment of LGE images for focal myocardial fibrosis.

Blood correction reduces variability and gender differences in native myocardial T1 values at 1.5 T cardiovascular magnetic resonance - a derivation/validation approach.

BACKGROUND: Myocardial native T1 measurements are likely influenced by intramyocardial blood. Since blood T1 is both variable and longer compared to myocardial T1, this will degrade the precision of myocardial T1 measurements. Precision could be improved by correction, but the amount of correction and the optimal blood T1 variables to correct with are unknown. We hypothesized that an appropriate correction would reduce the standard deviation (SD) of native myocardial T1. METHODS: Consecutive patients (n = 400) referred for CMR with known or suspected heart disease were split into a derivation cohort for model construction (n = 200, age 51 ± 18 years, 50% male) and a validation cohort for assessing model performance (n = 200, age 48 ± 17 years, 50% male). Exclusion criteria included focal septal abnormalities. A Modified Look-Locker inversion recovery sequence (MOLLI, 1.5 T Siemens Aera) was used to acquire T1 and T1* maps. T1 and T1* maps were used to measure native myocardial T1, and blood T1 and T1*. A multivariate linear regression correction model was implemented using blood measurement of R1 (1/T1), R1* (1/T1*) or hematocrit. The correction model from the derivation cohort was applied to the validation cohort, and assessed for reduction in variability with the F-test. RESULTS: Blood [LV + RV] mean R1, mean R1* and hematocrit correlated with myocardial T1 (Pearson's r, range 0.37 to 0.45, p < 0.05 for all) in both the derivation and validation cohorts respectively, suggesting that myocardial T1 measurements are influenced by intramyocardial blood. Mean myocardial native T1 did not differ between the derivation and validation cohorts (1030 ± 42.6 ms and 1023 ± 45.2 ms respectively, p = 0.07). In the derivation cohort, correction using blood mean R1 and mean R1* yielded a decrease in myocardial T1 SD (45.2 ms to 36.6 ms, p = 0.03). When the model from the derivation cohort was applied to the validation cohort, the SD reduction was maintained (39.3 ms, p = 0.049). This 13% reduction in measurement variability leads to a 23% reduction in sample size to detect a 50 ms difference in native myocardial T1. CONCLUSIONS: Correcting native myocardial T1 for R1 and R1* of blood improves the precision of myocardial T1 measurement by ~13%, and could consequently improve disease detection and reduce sample size needs for clinical research.

Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients.

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve ≥15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.