Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation in a preclinical model.

Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations (i.e. age of treatment) seen clinically. Rabbits were exposed to CoA resulting in peak-to-peak blood pressure gradient (BPGpp) severities of ≤ 10, 10-20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid-structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions from experimentally measured data. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Experimental results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.

Developing small-diameter vascular grafts with human amniotic membrane: long-term evaluation of transplantation outcomes in a small animal model.

While current clinical utilization of large vascular grafts for vascular transplantation is encouraging, tissue engineering of small grafts still faces numerous challenges. This study aims to investigate the feasibility of constructing a small vascular graft from decellularized amniotic membranes (DAMs). DAMs were rolled around a catheter and each of the resulting grafts was crosslinked with (a) 0.1% glutaraldehyde; (b) 1-ethyl-3-(3-dimethylaminopropyl) crbodiimidehydro-chloride (20 mM)-N-hydroxy-succinimide (10 mM); (c) 0.5% genipin; and (d) no-crosslinking, respectively. Our results demonstrated the feasibility of using a rolling technique followed by lyophilization to transform DAM into a vessel-like structure. The genipin-crosslinked DAM graft showed an improved integrated structure, prolonged stability, proper mechanical property, and superior biocompatibility. After transplantation in rat abdominal aorta, the genipin-crosslinked DAM graft remained patent up to 16 months, with both endothelial and smooth muscle cell regeneration, which suggests that the genipin-crosslinked DAM graft has great potential to beimplementedas a small tissue engineered graft for futurevasculartransplantation.

Diagnostic accuracy of bicuspid aortic valve by echocardiography.

BACKGROUND: Echocardiography is regarded as the gold standard for diagnosis of bicuspid aortic valve (BAV), yet diagnostic accuracy has been evaluated previously only in single-center studies. We systematically evaluated the accuracy of BAV diagnosis in a large healthcare system of multiple echocardiography laboratories. METHODS AND RESULTS: Aurora Health Care is a multihospital, multi-clinic system across the state of Wisconsin encompassing 33 inpatient and outpatient echocardiography laboratories with 39 cardiologist readers and 72 sonographers. As all laboratories store echocardiograms in one database, we queried all patients with "bicuspid aortic valve" diagnosis on echocardiography. Echocardiograms were classified as "BAV" or "possible BAV" based on initial reader confidence. An expert review panel categorized each as BAV, no BAV, or Indeterminate. Of the 745 cases identified, 589 (79.1%, initial reader interpretation: n = 494 "BAV," n = 95 "possible") were BAV. A high level of agreement (84%) was present in BAV diagnosis. There were 156 (20.9%) echocardiograms that were no BAV (8.4%) or Indeterminate (12.4%). We identified three common reasons for misdiagnosis: poor image quality (n = 70, 44.9%), leaflet calcium (n = 44, 28.2%), and oblique axis imaging (n = 33, 21.1%). A clear reason for misclassification was not elucidated in nine cases (n = 9, 5.7%). CONCLUSIONS: This is the first study to evaluate BAV accuracy across a community health system with multiple echocardiography laboratories and a heterogeneous group of readers and sonographers. We establish a high degree of accuracy of echocardiography in BAV diagnosis and draw attention to common echocardiographic pitfalls that lead to BAV misclassification, highlighting opportunities for education and quality improvement.

Marked respiratory-related fluctuations in left ventricular outflow tract gradients in hypertrophic obstructive cardiomyopathy: an observational study.

Aims: Left ventricular outflow (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM) is dynamic and sensitive to many variables that affect left ventricular preload, afterload, and contractility. The haemodynamic effect of normal respiration on LVOT obstruction has not been described. Methods and results: We examined 20 patients with HCM who were noted to have phasic respiratory variation of LVOT obstruction on initial transthoracic 2D echocardiogram and Doppler examination. LVOT gradients were re-examined with simultaneous recording of a respirometer. LVOT gradients varied widely during the respiratory cycle; peak gradients were uniformly lowest during inspiration (50.8 mmHg + 25.6) and highest during expiration (90.1 mmHg + 41.8). On average, there was 82.4% ± 39.1 (P ≤ 0.0001) incremental change from inspiration to expiration, in the severity of LVOT obstruction. In 11 patients with mitral annulus inflow, LV inflow (preload) was decreased during inspiration. In 16 patients with isovolumic relaxation time and ejection time measurements, decreased left atrial filling pressure was noted during inspiration, consistent with decreased LVOT obstruction. When compared with a control group of 20 HCM patients who did not have respiratory variation, the study group patients were more overweight (mean body mass index cases 35.1 ± 7.3 vs. control group 29.1 ± 5.1, P = 0.0045) and more likely to have sleep-disordered breathing (n = 15 study group, n = 5 control group). Conclusions: Counterintuitive respiratory-related fluctuations in LVOT gradients were observed in this case series of 20 HCM patients. These findings challenge traditional haemodynamic teaching and demonstrate the contribution of LV transmural pressure to LVOT obstruction in certain HCM patients.

Malignant cardiac phenotypic expression of Danon disease (LAMP2 cardiomyopathy).

INTRODUCTION: Danon disease is an X-linked lysosomal condition that causes a deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. It is characterized clinically by a triad of skeletal myopathy, cardiomyopathy, and intellectual disability. METHODS: We examined clinical, echocardiographic, and genetic data on 5 patients with Danon disease, highlighting their clinical course and outcomes. RESULTS: All patients presented phenotypically with hypertrophic cardiomyopathy and later developed systolic dysfunction. The mean age at diagnosis was 19years (11-31years). All patients had diastolic dysfunction (mean e' of 5cm/s [3.5-6cm/s], mean E/e' of 17 [15-21]). Three patients required cardiac transplantation (ages 15, 27, and 42). Of the two deaths in this group, both were in women. CONCLUSION: We highlight the aggressive cardiac phenotype of Danon disease in our clinical experience with rapid progression to end-stage cardiomyopathy; this progression occurred in both men and women. A timely diagnosis and an early referral for cardiac transplantation is crucial for improved outcomes.

Ventricular Septal Dissection Complicating Inferior Wall Myocardial Infarction.

Postmyocardial infarction ventricular septal defect is an increasingly rare mechanical complication of acute myocardial infarction. We present a case of acute myocardial infarction from right coronary artery occlusion that developed hypotension and systolic murmur 12 hours after successful percutaneous coronary intervention. Although preoperative imaging suggested a large ventricular septal defect and a pseudoaneurysm, intraoperative findings concluded a serpiginous dissection of the ventricular septum. The imaging technicalities are discussed.

A great imitator in adult cardiology practice: congenitally corrected transposition of the great arteries.

INTRODUCTION: Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital disease that frequently remains undiagnosed until adulthood, especially when there is an absence of other congenital anomalies. Adults with ccTGA may remain asymptomatic and their diagnosis could be missed on initial evaluation, or it could be diagnosed incidentally as an evaluation of murmur. We aim to report the different presentations of ccTGA in eight adult patients and review the key features required to suspect the diagnosis during an initial visit. CASES: We present some illustrative cases of ccTGA patients who had diverse presentations ranging from being completely asymptomatic to presenting with an acquired heart disease resulting in sudden cardiac arrest. Overall, most of these patients had isolated ccTGA with no other significant associated cardiac anomalies and were either undiagnosed or lost to follow-up until adulthood. These case illustrations represent the challenges confronted in adult practices when patients with unrecognized ccTGA present during an initial visit. CONCLUSIONS: Congenitally corrected transposition of the great arteries poses a challenge in the adult cardiology practice because of its diverse clinical presentation. It is crucial that internists, cardiologists, and sonographers maintain a high degree of suspicion after meticulous physical examination for the early recognition of ccTGA, and thus avoid associated morbidities. Through some case examples, we provide clues to the key diagnostic features that could help them to be vigilant in making a diagnosis.