A review of the pivotal role of cardiac MRI in mitral valve regurgitation.

Cardiac imaging is the cornerstone of defining the etiology, quantification, and management of mitral regurgitation (MR). This continues to be even more so the case with emerging transcatheter techniques to manage MR. Transthoracic echocardiography remains the first-line imaging modality to assess MR but has limitations. Cardiac MRI(CMR) provides the advantages of quantitative nonvisual estimation, 3D volumetric data, late gadolinium, T1, and extracellular volume measurements to comprehensively assess mitral valvular pathology, cardiac remodeling, and the prognostic impact of therapies. This review describes the superiority, technical aspects and growing evidence behind CMR, and lays the roadmap for the future of CMR in MR.

Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator.

BACKGROUND: The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was "non-MRI-conditional" (i.e., not approved by the Food and Drug Administration for MRI scanning). METHODS: Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. RESULTS: MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. CONCLUSIONS: In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).

The use of contrast-enhanced transthoracic echocardiography for spiral-variant hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is a common heritable cardiomyopathy with various clinical phenotypes. A rare spiral variant has been recently reported that has been associated with adverse outcomes and has traditionally been diagnosed using cardiac magnetic resonance. We report a case of the rare variant spiral hypertrophic cardiomyopathy where we used transthoracic echocardiography with an ultrasound enhancing agent to demonstrate the geometry of spiral hypertrophic cardiomyopathy and compared to simultaneous cardiac MRI images. The use of echocardiography with ultrasound enhancing agents may prove to be a valuable tool in identifying the geometry of hypertrophic cardiomyopathy variants in selected patients.

Calcified mass in the right atrium extending into the inferior vena cava with pulmonary artery embolization. Typical or atypical myxoma?

Cardiac masses are divided into neoplastic and non-neoplastic. They usually represent a diagnostic challenge given their relative rarity, their infrequent symptoms, and the overall difficulty with dynamic imaging of the heart. While echocardiography is useful in the initial evaluation of a suspected mass, cardiac magnetic resonance (CMR) imaging is the best imaging modality to characterize cardiac tumors due to its superior tissue characterization and its higher contrast resolution. For neoplastic, primary cardiac tumors are rare (0.05%). Atrial myxoma is the most common cardiac (50%) mass. About 75%-80% of myxoma are seen in the left atrium. Atypical myxoma is a term describing myxoma arising in other nonleft atrial locations. 20%-25% myxomas arise from the right atrium and 5% or less from the ventricles. We present a case of a 59-year-old female patient presenting with severe dyspnea. Her chest noncontrast CT showed a calcified mass lesion in the right atrium extending into the inferior vena cava. She underwent cardiac MRI for better tissue characterization. The cardiac MRI revealed a very irregular, highly spiculated, heavily calcified, heterogeneous, and nonenhancing lesion within the right atrium extending into the inferior vena cava. Via dynamic imaging, no evidence of mobile components was present. Via T1, T2 along with pre- and postcontrast imaging, the mass was confirmed to be calcified without a fibrotic component or evidence of thrombus. The above findings raised the possibility of atypical myxoma.

Right Heart Function in Critically Ill Patients at Risk for Acute Right Heart Failure: A Description of Right Ventricular-Pulmonary Arterial Coupling, Ejection Fraction and Pulmonary Artery Pulsatility Index.

BACKGROUND: The gold standard for right heart function is the assessment of right ventricular-pulmonary arterial coupling defined as the ratio of arterial to end-systolic elastance (Ea/Emax). This study demonstrates the use of the volumetric pulmonary artery (PA) catheter for estimation of Ea/Emax and describes trends of Ea/Emax, right ventricular ejection fraction (RVEF), and pulmonary artery pulsatility index (PAPi) during initial 48hours of resuscitation in the trauma surgical intensive care unit (ICU). METHODS: Review of prospectively collected data for 32 mechanically ventilated adult trauma and emergency general surgery patients enrolled within 6hours of admission to the ICU. Haemodynamics, recorded every 12hours for 48hours, were compared among survivors and non-survivors to hospital discharge. RESULTS: Mean age was 49±20 years, 69% were male, and 84% were trauma patients. Estimated Ea/Emax was associated with pulmonary vascular resistance and inversely related to pulmonary arterial capacitance and PA catheter derived RVEF. Seven (7) trauma patients did not survive to hospital discharge. Non-survivors had higher estimated Ea/Emax, suggesting right ventricular-pulmonary arterial uncoupling, with a statistically significant difference at 48hours (2.3±1.7 vs 1.0±0.58, p=0.018). RVEF was significantly lower in non-survivors at study initiation and at 48hours. PAPi did not show a consistent trend. CONCLUSIONS: Estimation of Ea/Emax using volumetric PA catheter is feasible. Serial assessment of RVEF and Ea/Emax may help in early identification of right heart dysfunction in critically ill mechanically ventilated patients at risk for acute right heart failure.

Provocative maneuvers to improve patent foramen ovale detection: A brief review of the literature.

Patent foramen ovale (PFO) is the most common type of inter-atrial shunt, with prevalence as high as 30%. Detection of PFO has implications in patients with stroke, peripheral embolism, decompression illness, and other conditions. Transesophageal echo (TEE) with saline contrast injection is the current standard for PFO detection, but even with TEE, PFOs are sometimes missed. With advances in percutaneous PFO closure therapies and proven long-term benefit of closure, accurate PFO detection takes on cardinal importance. Various provocative maneuvers to enhance PFO detection are in clinical use and have been studied. The Valsalva maneuver has long-held position as the ideal provocation to unmask PFO, but other maneuvers such as cough, sniff, Müller's, and more have gained relevance. In this article, we will examine various maneuvers and discuss their utility in PFO detection.

Cardio-hepatic risk assessment by CMR imaging in liver transplant candidates.

BACKGROUND: The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof-of-concept study the value of a one-stop-shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one-stop-shop CMR approach. METHODS: In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination. RESULTS: Over 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event-free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC. CONCLUSIONS: This study further defines the population suitable for the one-stop-shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions.

Echocardiography and cardiovascular MRI entwined within the imaging domain; uniting the two. A compendium for the echocardiographer.

A review of the unique and complementary roles echocardiography and cardiovascular MRI provide to the clinician. A focus on the physics of each modality as well as imaging of the left ventricle.

Left atrial appendage myxofibrosarcoma: A rare masquerader of myxoma and thrombus-"all that glitters is not gold".

Left atrial appendage mass can occasionally pose a serious challenge to physicians to identify the nature of the mass with the aid of imaging techniques. We present a case of 67-year-old man, who was evaluated for suspected left atria myxoma. Transesophageal echocardiography revealed a heterogeneous density originating from left atrial appendage, thought to be most consistent with a myxoma. Cardiac magnetic resonance imaging, uncharacteristically, gave an equivocal picture, suggesting the mass to be a myxoma on initial imaging and a thrombus with evidence of liquefaction necrosis following postcontrast enhancement. Surprisingly, histopathology of the mass following its surgical excision yielded a rare diagnosis of myxofibrosarcoma.

Can cardiovascular MRI be used to more definitively characterize cardiac masses initially identified using echocardiography?

In diagnosing cardiac and paracardiac masses, cardiac MRI (CMR) has gained acceptance as the gold standard. CMR has been observed to be superior to echocardiography in characterizing soft-tissue structures and, specifically, in classifying cardiac masses. The aim of our study was to evaluate the association between mortality and cardiac or paracardiac masses initially identified by echocardiography (ECHO) and confirmed by CMR. Between January 2002 and August 2007, a total of 158 patients underwent both ECHO and CMR for the evaluation of cardiac masses that were equivocal or undefined by ECHO. The primary study endpoints were 5-year all-cause mortality and 5-year cardiac mortality. Causes of death as of April 1, 2015 were obtained from medical records or the National Death Index. Patients were analyzed according to mass type determined by CMR using the Kruskal-Wallis test, Kaplan-Meier curves, and the log-rank test. Over a mean duration of follow-up of 10.4 ± 2.9 years (range: 0.01-12 years) post-CMR, the overall all-cause mortality rate was 25.9% (41/158). Median age at death was 76 years and there were 21 females (51.2%). Mortality rates in the different classifications of cardiac masses by CMR were as follows: 20% (1/5) in patients with a Nondiagnostic CMR; 20% (1/5) in Other Diagnoses; 17.9% (7/39) in No Masses (includes Normal Anatomical Variants); 16.7% (3/18) in Benign Masses; 23.8% (15/63) in Fat; 50% (5/10) in Thrombus; and 61.5% (8/13) in Malignant Mass. The mean survival time in patients with No Mass (n = 39) was not significantly longer than patients with any type of cardiac mass (n = 114) (P = .16). No significant difference was found in age at death between patients when grouped by CMR classification (P = .40). However, among CMR-confirmed masses, there were some significant differences by mass classification type (P = .006). During the follow-up period, 26% (41/158) of patients died and 22% (9/41) of the deaths were cardiovascular related; there was no significant difference in mean survival times with respect to cause of mortality (P = .23). In patients with cardiac masses, dually confirmed by ECHO and CMR, significant differences in survival time were observed based upon CMR classified type of mass while CMR was instrumental in obviating invasive biopsy.

PI3K/mTOR Dual Inhibitor, LY3023414, Demonstrates Potent Antitumor Efficacy Against Esophageal Adenocarcinoma in a Rat Model.

OBJECTIVE: The purpose of the current study is to determine the efficacy of a PI3K/mTOR dual inhibitor, LY3023414, on established EAC in an in vivo model. BACKGROUND: Esophageal adenocarcinoma (EAC) is a highly lethal cancer with limited treatment options. The PI3K/mTOR pathway is upregulated in EAC and may be a target for novel therapies. METHODS: Esophagojejunostomy was performed on Sprague-Dawley rats to induce carcinogenesis, and LY3023414 was cyclically administered intraperitoneally between 32 and 40 weeks postsurgery to treatment animals. Magnetic resonance imaging (MRI) and histology were used to determine clinical response. Immunohistochemistry, immunofluorescence, and Western blot were used to validate apoptosis by cleaved caspase-3, proliferation by Ki67, and pathway inhibition, respectively. RESULTS: Mean MRI tumor volume increased by 109.2% in controls (n = 32) and decreased by 56.8% in treatment animals (n=17) (P < 0.01). Treatment with LY3023414 demonstrated tumor volume increase in 0% (control = 46.4%) (P < 0.01), decrease in 58.8% (control = 7.1%) (P < 0.01), and stable volume in 41.2% (control = 46.4%) (P = 0.77). EAC prevalence in controls increased by 25%; whereas, prevalence in treatment animals decreased by 29.4% (P < 0.01). Approximately, 75% of treatment animals presenting with residual masses on MRI had a histological response >50%. Increased apoptosis by cleaved caspase-3 (P = 0.03) and decreased proliferation by Ki67 (P < 0.01) were demonstrated in the treatment arm, when compared with the control arm. On Western blot analysis of pathway checkpoints, p-mTOR (p=0.03) and PI3K-α (P = 0.04) were downregulated in treatment responsive residual tumors, when compared with controls. CONCLUSIONS: LY3023414 demonstrates efficacy against EAC in a preclinical model, establishing the rationale for clinical testing.

Management of an asymptomatic patient with the apical variant of hypertrophic cardiomyopathy.

Healthcare professionals are faced with challenging decisions regarding patient evaluation and management on a daily basis. Once a diagnosis is made, additional challenges include how to proceed with the management. Here, we present an eighty-two-year-old female who was incidentally diagnosed with the apical variant of hypertrophic cardiomyopathy on a transthoracic echocardiogram. She was found to have newly diagnosed atrial fibrillation, but was otherwise asymptomatic from a cardiomyopathy standpoint. No specific guidelines exist for this patient population. Therefore, how does one proceed with the management of an asymptomatic patient with the apical variant of hypertrophic cardiomyopathy?

Incremental value of contrast echocardiography in the evaluation of a cardiac thrombus.

A 52-year-old man presented with altered mental status and report of prior complaint of chest pain. On electrocardiography, anterolateral ST-segment elevations with Q-waves in the septal leads were seen. Initial echocardiography images demonstrated a thickened anteroseptum. Further imaging showed the presence of a well-attached laminated apical thrombus. Contrast echocardiography images showed that the thrombus had minimal attachment to the endocardial surface. CT head subsequently showed the presence of acute stroke. The case demonstrates the additional value of contrast echocardiography in the evaluation of cardiac masses despite the certainty in the diagnosis of a thrombus.

Preclinical Study of AUY922, a Novel Hsp90 Inhibitor, in the Treatment of Esophageal Adenocarcinoma.

OBJECTIVE: To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. BACKGROUND: EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. METHODS: In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. RESULTS: In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (control = 9.4%), increase in 9.1% (control = 37.5%), and stable disease in 54.5% (control = 43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90ß, and CDK4, and upregulation of Hsp72. CONCLUSIONS: AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.

Cardiac computed tomography of an asymptomatic 48-year-old woman with ALCAPA syndrome.

Untreated ALCAPA cases most often die in infancy. Adults with untreated ALCAPA commonly present with mitral regurgitation, severe left ventricular dysfunction, and sometimes myocardial infarction. Herein, we present an asymptomatic adult female with ALCAPA recognized through cardiac computed tomography (CT). In ALCAPA, like other coronary anomalies, cardiac CT is often instrumental in providing unique noninvasive and clinically relevant evaluation. Herein, we present an atypical presentation of an asymptomatic middle-aged adult female with ALCAPA.

Gargantuan left atrium: a sequela of mitral regurgitation and mitral stenosis.

Cardiac magnetic resonance imaging and echocardiography revealed a gargantuan left atrium measuring 18.9 cm × 15.7 cm × 11.3 cm in a 56-year-old patient diagnosed with severe rheumatic mitral stenosis, severe pulmonary hypertension, and permanent atrial fibrillation. A chest x-ray also revealed a cardiothoracic ratio approaching 1.0 and a transthoracic echocardiogram measured diameters as large as 19.2 cm. The patient then underwent mitral valve replacement and left atrial reduction surgery and has had no further admissions or complications.

Routine cine-CMR for prosthesis-associated mitral regurgitation: a multicenter comparison to echocardiography.

BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is an important complication after prosthetic mitral valve (PMV) implantation. Transthoracic echocardiography is widely used to screen for native MR, but can be limited with PMV. Cine-cardiac magnetic resonance (CMR) holds the potential for the non-invasive assessment of regurgitant severity based on MR-induced inter-voxel dephasing. The study aim was to evaluate routine cine-CMR for the visual assessment of PMV-associated MR. METHODS: Routine cine-CMR was performed at nine sites. A uniform protocol was used to grade MR based on jet size in relation to the left atrium (mild < 1/3, moderate 1/3-2/3, severe > 2/3). MR was graded in each long-axis orientation, with overall severity based on cumulative grade. Cine-CMR was also scored for MR density and pulmonary vein systolic flow reversal (PVSFR). Visual interpretation was compared to quantitative analysis in a single-center (derivation) cohort, and to transesophageal echocardiography (TEE) in a multicenter (validation) cohort. RESULTS: The population comprised 85 PMV patients (59% mechanical valves, 41% bioprostheses). Among the derivation cohort (n = 25), quantitative indices paralleled visual scores, with stepwise increases in jet size and density in relation to visually graded MR severity (both p = 0.001). Patients with severe MR had an almost three-fold increase in quantitative jet area (p = 0.002), and a two-fold increase in density (p = 0.04) than did other patients. Among the multicenter cohort, cine-CMR and TEE (Δ =. 2 ± 3 days) demonstrated moderate agreement (κ = 0.44); 64% of discordances differed by ≤ 1 grade (Δ = 1.2 ± 0.5). Using a TEE reference, cine-CMR yielded excellent diagnostic performance for severe MR (sensitivity, negative predictive value = 100%). Patients with visually graded severe MR also had more frequent PVSFR (p < 0.001), denser jets (p < 0.001), and larger left atria (p = 0.01) on cine-CMR. CONCLUSION: Cine-CMR is useful for the assessment of PMV-associated MR, which manifests concordant quantitative and qualitative changes in size and density of inter-voxel dephasing. Visual MR assessment based on jet size provides an accurate non-invasive means of screening for TEE-evidenced severe MR.

Spiral hypertrophic cardiomyopathy as detected by cardiac magnetic resonance.

Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease; characterized by left ventricular hypertrophy (LVH). Spiral HCM is described as having a counterclockwise rotation pattern of hypertrophy along with variable degrees of fibrosis. A 34-year-old female presented with symptoms suggestive of heart failure. Echocardiography showed concentric LVH with normal contractility. Cardiac MRI showed asymmetric septal hypertrophy with mid-cavity obliteration and a spiral pattern of variably increasing wall thickness. Late gadolinium enhancement (LGE) demonstrated several areas of abnormal postgadolinium uptake. We report a case of spiral HCM. We should consider cardiovascular magnetic resonance (CMR) as the reference standard for diagnosing HCM.

Novel use of dynamic MR hydrography to rule out esophageal perforation post atrial fibrillation ablation in a patient with anaphylaxis to gadolinium.

Esophageal thermal injury is one of the most devastating complications of atrial radiofrequency ablation, and its diagnosis can be challenging. In this report, we highlight the novel use of free water as a contrast material to better visualize the esophageal lumen in a patient with anaphylaxis to Iodinated contrast media and Gadolinium who recently underwent atrial fibrillation ablation. This becomes particularly handy in patients with contrast allergy, and further emphasizes the role of multimodality imaging.

Is there an alternative explanation to post-myocardial infarction emergence of mitral regurgitation? A CMR-LGE observational study.

BACKGROUND AND AIM OF THE STUDY: Post-myocardial infarction (MI) mitral regurgitation (MR) is thought to be due to a passive, rather than active, remodeling of the mitral valve apparatus and its relationship with other cardiac structures that contribute to MR. Standard contrast-enhanced magnetic resonance (CMR) late gadolinium enhancement (LGE) may be sensitive to non-myocardial pathology involving the mitral valve leaflets. It was hypothesized that the presence of mitral valve enhancement (MVE) on LGE imaging in post-MI patients would be associated with an increased incidence of MR. METHODS: The presence or absence of MVE was noted in patients presenting for CMR with MI and non-MI indications requiring LGE. A chi-square analysis was performed for non-contiguous variables; SPSS (Chicago) software was utilized for the statistical analysis. RESULTS: Eighty-seven patients (54 males, 33 females) underwent LGE-CMR studies utilizing a 1.5 T GE scanner with MultiHance gadolinium contrast administration. LGE+ (present) was noted in 68 patients, and LGE- (absent) in 19 patients. Post-MI patterns of LGE+ were noted in 51 patients and LGE-in 36 patients; MVE+ was noted in 39 patients and MVE- in 48; and MR+ was present in 67 patients and absent (MR-) in 20 patients. MVE was observed chiefly in post-MI patients (33/51; 65%) and infrequently in non-post-MI patients (6/36; 17%; chi2 = 17.8, p < 0.001, power = 0.995). Further, MR was present more frequently in patients with MVE (36/39; 92%) compared to patients without MVE (31/48; 65%; chi2 = 7.8, p = 0.005, power = 0.814). CONCLUSION: MVE is present in a large number of post-MI patients but rarely in non-post-MI patients. Post-MI patients with, rather than without, MVE are far more likely to have MR. These observations suggest a specific but as-yet unknown reactive process that may contribute to mitral leaflet remodeling in post-MI patients, potentially contributing to an increased incidence of MR in post-MI patients.