Retinal Ischemic Perivascular Lesions in Individuals With Atrial Fibrillation.

Background We previously demonstrated that retinal ischemic perivascular lesions (RIPLs), which are indicative of ischemia in the middle retina, may be a biomarker of ischemic cardiovascular disease. In this study, we sought to determine the relationship between RIPLs and atrial fibrillation, a common source of cardiac emboli. Methods and Results In this case-control study, we identified individuals between the ages of 50 and 90 years who had undergone macular spectral domain optical coherence tomography imaging. Individuals with atrial fibrillation were identified, and age- and sex-matched individuals from the same pool, but without a diagnosis of atrial fibrillation, were selected as controls. Spectral domain optical coherence tomography scans were reviewed by 3 independent and masked observers for presence of RIPLs. The relationship between RIPLs and atrial fibrillation was analyzed using multivariable logistic regression models. There were 106 and 91 subjects with and without atrial fibrillation, respectively. The percentage of subjects with RIPLs was higher in the atrial fibrillation group compared with the control group (57.5% versus 37.4%; P=0.005). After adjusting for age, sex, smoking history, hypertension, diabetes, coronary artery disease, carotid stenosis, stroke, and myocardial infarction, the presence of RIPLs was significantly associated with atrial fibrillation, with an odds ratio of 1.91 (95% CI, 1.01-3.59). Conclusions RIPLs are significantly associated with atrial fibrillation, independent of underlying ischemic heart disease or cardiovascular risk factors. This association may inform the diagnostic cardiovascular workup for individuals with RIPLs incidentally detected on optical coherence tomography scan of the macula.

Role of Quantitation of Saline Bubble Studies in Patients with Liver Cirrhosis.

OBJECTIVE: Microbubble contrast echocardiography with a late positive signal enables the detection of intrapulmonary vascular dilation, including hepatopulmonary syndrome, in patients with end-stage liver disease. We assessed the relationship between the severity of bubble study and clinical outcome. METHODS: We retrospectively analyzed 163 consecutive patients with liver cirrhosis who underwent an echocardiogram with bubble study from 2018 to 2021. Patients who were diagnosed with a late positive signal were divided into three groups: grade 1 (1-9 bubbles), grade 2 (10-30 bubbles) and grade 3 (>30 bubbles). RESULTS: Fifty-six percent of the patients had a late positive bubble study (grade 1: 31%, grade 2: 23%, grade 3: 46%). Patients with grade 3 had a significantly higher international normalized ratio, model for end-stage liver disease score and Child-Pugh score and a lower peripheral oxygen saturation compared with patients with a negative study. In patients undergoing liver transplant (LT), survival rates were similar among the groups (3-mo: >87%, 1-y: >87%, 2-y: >83%). However, survival rate was lower in grade 3 patients without LT (3-mo: 81%, 1-y: 64%, 2-y: 39%). CONCLUSION: Patients with grade 3 had much worse mortality without LT compared with other groups. However, after LT, all grades had equal survival. Therefore, patients with grade 3 may be considered as higher priority for LT.

Retinal vein occlusion is associated with stroke independent of underlying cardiovascular disease.

BACKGROUND: Stroke is a leading cause of mortality and morbidity. Thus, identifying associated risk factors may lead to earlier interventions aimed at reducing the risk of stroke development. Since cardiovascular disease simultaneously increases the risk of stroke and retinal vein occlusion (RVO), we sought to determine whether RVO is associated with the risk of stroke independent of underlying cardiovascular co-morbidities. METHODS: In this cross-sectional study, we reviewed the records of 80,754 individuals who were evaluated by an ophthalmologist over a 6-year period. We identified individuals with RVO, stroke and cardiovascular diseases including hypertension, diabetes mellitus, carotid disease, coronary artery disease and atrial fibrillation. Multivariable logistic regression models were used to analyze odds ratios for RVO and stroke. RESULTS: After adjusting for age, sex, cardiovascular disease and other risk factors, we found that the presence of RVO was associated with an odds ratio for stroke of 1.73 (CI, 1.40-2.12, p < 0.001). The association between RVO and stroke, after adjusting for sex and cardiovascular co-morbidities, was significantly stronger in individuals younger than 50 years of age, with an odds ratio of having a stroke of 3.06 (1.34-6.25, p < 0.001), while the presence of RVO in individuals older than 85 years was not significantly associated with stroke 1.19 (0.77-1.79, p = 0.41). CONCLUSIONS: Our findings demonstrate that RVO is significantly associated with stroke, even after adjusting for underlying cardiovascular co-morbidities. This association was highly significant in younger subjects, while not significant in older individuals.

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.

Handheld ultrasonography in cardiovascular medicine, updates and controversies.

A variety of hand-held ultrasound (HHU) machines have recently become available and offer different capabilities and features. Despite the differences of the individual HHU devices, all offer the potential for faster diagnoses and are more sensitive than clinical assessment in identifying cardiovascular abnormalities. In addition, they provide enhanced transportability, can potentially reduce waiting time for full echocardiograms, and may save health-care resources. Significant potential for the growth of HHU as a tool to facilitate patient care exists when performed by well-trained and competent providers is anticipated. This paper presents the characteristics, benefits, limitations, and future perspectives of HHU devices.

Established and emerging roles for ultrasound enhancing agents (contrast echocardiography).

The ability to opacify the left ventricle and delineate the endocardium after intravenous injection of microbubble ultrasound enhancing agents is of established value to quantify volumes and function in suboptimal unenhanced images, particularly in stress echocardiograms. However, applications other than quantitation of left ventricle structure and function exist for contrast enhanced left ventricular opacification. Contrast agents enable recording of Doppler velocity signals in patients with poor ultrasound transmission, providing estimates of aortic stenosis gradient and pulmonary artery pressures. Contrast echo is of value in detecting apical hypertrophic cardiomyopathy and accompanying apical aneurysms. Most importantly, ultrasound enhancing agents can identify apical and left atrial masses when they cannot be visualized in unenhanced images, and can distinguish thrombi from tumors by visualizing the vascularity inherent in tumors. Contrast agents distinguish trabecular from compacted myocardium in noncompaction syndrome, and hypertrabeculation with other abnormal conditions. A major potential application of ultrasound enhancing agents is myocardial opacification, which can assist in identifying nonviable myocardium. Also, the delayed reappearance of myocardial perfusion after microbubble destruction identifies impaired contrary flow and can diagnose coronary stenosis. Innovative applications of ultrasound contrast agents currently under investigation, include visualizing the vaso vasorum to identify plaques and assess their vulnerability, and theranostic agents to deliver drugs and biologists and to assist in sonothrombolysis. It is anticipated that the role of ultrasound contrast agents will continue to increase in the future.

Trends in testing and prevalence of elevated Lp(a) among patients with aortic valve stenosis.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is causally associated with aortic valve stenosis (AS) but Lp(a) testing among AS patients is not broadly incorporated into clinical practice. We evaluated trends in Lp(a) testing in an academic medical center. METHODS: Educational efforts and adding Lp(a) to the lipid panel on the electronic medical record (EMR) and pre-procedure order sets were used to increase awareness of Lp(a) as a risk factor in AS. Medical records at University of California San Diego Health (UCSDH) were analyzed from 2010 to 2020 to define the yearly frequency of first time Lp(a) testing in patients with diagnosis codes for AS or undergoing transcatheter aortic valve replacement (TAVR). RESULTS: Lp(a) testing for any indication increased over 5-fold from 2010 to 2020. A total of 3808 patients had a diagnosis of AS and 417 patients had TAVR. Lp(a) levels >30 mg/dL were present in 37% of AS and 35% of TAVR patients. The rates of Lp(a) testing in AS and TAVR were 14.0% and 65.7%, respectively. In AS, Lp(a) testing increased over time from 8.5% in 2010, peaking at 24.2% in 2017, and declining to 13.9% in 2020 (p < 0.001 for trend). Following implementation of EMR order-sets in 2016, Lp(a) testing in TAVR cases increased to a peak of 88.5% in 2018. CONCLUSIONS: Elevated Lp(a) is prevalent in AS and TAVR patients. Implementation of educational efforts and practice pathways resulted in increased Lp(a) testing in patients with AS. This study represents a paradigm that may allow increased global awareness of Lp(a) as a risk factor for AS.

Mitral Valve Prolapse-The Role of Cardiac Imaging Modalities.

Mitral valve prolapse (MVP) is the most common nonischemic mitral regurgitation etiology and mitral abnormality requiring surgery in the Western world. There is an increasing awareness that pathological findings in MVP are not confined to the valve tissue; rather, it is a complex disease, involving the mitral valve apparatus, cardiac hemodynamics, and cardiac structure. Imaging has played a fundamental role in the understanding of the diagnosis, prevalence, and consequences of MVP. The diagnosis of MVP by imaging is based upon demonstrating valve leaflets ascending into the left atrium through the saddle-shaped annulus. Transthoracic and transesophageal echocardiography are the primary modalities in the diagnosis and assessment of MVP patients and must include careful assessment of the leaflets, annulus, chords, and papillary muscles. High-spatial-resolution imaging modalities such as cardiac magnetic resonance images and cardiac computed tomography play a secondary role in this regard and can demonstrate the anatomical relation between the mitral valve annulus and leaflet excursion for appropriate diagnosis. Ongoing development of new methods of cardiac imaging can help us to accurately understand the mechanism, diagnose the disease, develop an appropriate treatment plan, and estimate the risk for sudden death. Recently, several new observations with respect to prolapse have been derived from cardiac imaging including three-dimensional echocardiography and tissue-Doppler imaging. The aim of this article is to present these new imaging-derived insights for the diagnosis, risk assessment, treatment, and follow-up of patients with MVP.

Myocardial Strain and Association With Clinical Outcomes in Danon Disease: A Model for Monitoring Progression of Genetic Cardiomyopathies.

Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD. Regression analyses were performed to evaluate for an association of global longitudinal strain (GLS) and ejection fraction with the composite outcome (death, ventricular assist device, heart transplantation, and implantable cardioverter defibrillator for secondary prevention). A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis. Absolute GLS was reduced with a mean of 12.2% with an apical-sparing pattern observed. Univariable regression for GLS and composite outcome showed an odds ratio of 1.32 (95% CI, 1.02-1.71) with P=0.03. For receiver operating characteristic analysis, the areas under the curve for GLS and ejection fraction were 0.810 (P=0.02) and 0.605 (P=0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate of 85.7% and false positive rate of 13.3%. Conclusions In this cohort of patients with DD, GLS may be a useful assessment of myocardial function and may predict clinical outcomes. This study highlights the potential use of myocardial strain phenotyping to monitor disease progression and potentially to predict clinical outcomes in DD and other genetic cardiomyopathies.

Optimal Quantification of Functional Mitral Regurgitation: Comparison of Volumetric and Proximal Isovelocity Surface Area Methods to Predict Outcome.

Background Effective orifice area (EOA) ≥0.2 cm2 or regurgitant volume (Rvol) ≥30 mL predicts prognostic significance in functional mitral regurgitation (FMR). Both volumetric and proximal isovelocity surface area (PISA) methods enable calculation of these metrics. To determine their clinical value, we compared EOA and Rvol derived by volumetric and PISA quantitation upon outcome of patients with FMR. Methods and Results We examined the outcome of patients with left ventricular ejection fraction <35% and moderate to severe FMR. All had a complete echocardiogram including EOA and Rvol by both standard PISA and volumetric quantitation using total stroke volume calculated by left ventricular end-diastolic volume×left ventricular ejection fraction and forward flow by Doppler method: EOA=Rvol/mitral regurgitation velocity time integral. Primary outcome was all-cause mortality or heart transplantation. We examined 177 patients: mean left ventricular ejection fraction 25.2% and 34.5% with ischemic cardiomyopathy. Echo measurements were greater by PISA than volumetric quantitation: EOA (0.18 versus 0.11 cm2), Rvol (24.7 versus 16.9 mL), and regurgitant fraction (61 versus 37 %) respectively (all P value <0.001). During 3.6±2.3 years' follow-up, patients with EOA ≥0.2 cm2 or Rvol ≥30 mL had a worse outcome than those with EOA <0.2 cm2 or Rvol <30 mL only by volumetric (log rank P=0.003 and 0.004) but not PISA quantitation (log rank P=0.984 and 0.544), respectively. Conclusions Volumetric and PISA methods yield different measurements of EOA and Rvol in FMR; volumetric values exhibit greater prognostic significance. The echo method of quantifying FMR may affect the management of this disorder.

Clinical and Echocardiographic Predictors of Reduced Survival in Patient with Functional Mitral Regurgitation.

Functional mitral regurgitation (FMR) is associated with a poor outcome in patients with reduced left ventricular ejection fraction (LVEF). Two recent studies of percutaneous mitral valvular repair therapy reported disparate results, likely due in part to variable risk among FMR patients. The aim of this study is to define echocardiographic factors of prognostic significance in FMR patients, and particularly to compare ischemic and nonischemic FMR. We followed three hundred sixteen consecutive patients (age 60 ± 14 years, men 70%) with FMR and LVEF ≤ 35% between January 2010 and December 2015 (mean follow-up 3.7 years). Patients were categorized into ischemic (39.6%) and nonischemic (60.4%). MR was graded according to the American Society of Echocardiography guidelines. Although echo findings were similar between ischemic and nonischemic patient, the incidence of death, heart transplantation (HT), or LVAD implantation was higher in ischemic than in nonischemic patients (Log rank p = 0.001). In age and gender adjusted multivariate (11 variables) Cox regression analysis, left atrium volume index (LAVI) was associated with death, HT, or LVAD with hazard ratio of 2.1 for patients with FMR (p = 0.003). LAVI greater than 48.7 mL/m2 predicts adverse outcome in both nonischemic and ischemic FMR (AUC 0.62, p < 0.001). Combined ischemic FMR with LAVI ≥ 48.7 mL/m2 had the highest incident rate of all groups. In conclusion, despite similar LV function and MR severity, ischemic FMR patients had higher mortality than nonischemic patients. Of all echocardiographic parameters, an LAVI ≥ 48.7 mL/m2 predicted adverse clinical outcome.

Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model.

A first-in-man clinical study on a myocardial-derived decellularized extracellular matrix hydrogel suggested the potential for efficacy in chronic myocardial infarction (MI) patients. However, little is understood about the mechanism of action in chronic MI. In this study, the authors investigated the efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a rat chronic MI model. Assessment of cardiac function via magnetic resonance imaging demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent further negative LV remodeling in the chronic MI model through modulation of the immune response, down-regulation of pathways involved in heart failure progression and fibrosis, and up-regulation of genes important for cardiac muscle contraction.